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Sample records for 1-day fzp-withdrawn rats

  1. The hepatic Igf2/H19 locus is not altered in 1-day old pups born to obese-prone Sprague-Dawley rats fed a low protein diet containing adequate folic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gong et al. (Epigenetics, 2010) found, using diets low in folic acid, that compared to an 18% protein diet a 9% protein diet fed to pregnant Sprague-Dawley rats resulted in increased Igf2 and H19 gene expression in the liver of day 0 male offspring. In addition DNA methylation in the Imprinting Cont...

  2. Spinal neuronal plasticity is evident within 1 day after a painful cervical facet joint injury.

    PubMed

    Crosby, Nathan D; Weisshaar, Christine L; Winkelstein, Beth A

    2013-05-10

    Excessive stretch of the cervical facet capsular ligament induces persistent pain and spinal plasticity at later time points. Yet, it is not known when such spinal modifications are initiated following this painful injury. This study investigates the development of hyperalgesia and neuronal hyperexcitability in the spinal cord after a facet joint injury. Behavioral sensitivity was measured in a model of painful C6/C7 facet joint injury in the rat, and neuronal hyperexcitability in the spinal cord was evaluated at 6h and 1 day after injury or a sham procedure, in separate groups. Extracellular recordings of C6/C7 dorsal horn neuronal activity (229 neurons) were used to quantify spontaneous and evoked firing. Rats exhibited no change in sensitivity to mechanical stimulation of the forepaw at 6h, but did exhibit increased sensitivity at 1 day after injury (p=0.012). At 6h, both spontaneous neuronal activity and firing evoked by light brushing, pinch, and von Frey filaments (1.4-26g) applied at the forepaw were not different between sham and injury. At 1 day, spontaneous firing was noted in a greater number of neurons after injury than sham (p<0.04). Evoked firing was also increased 1 day after injury compared to normal and sham (p<0.03). Dorsal horn hyperexcitability and increased spontaneous firing developed between 6 and 24h after painful facet injury, suggesting that the development of hyperalgesia parallels dorsal horn hyperexcitability following mechanical facet joint injury, and these spinal mechanisms are initiated as early as 1 day after injury.

  3. SUR1-Associated Mechanisms Are Not Involved in Ischemic Optic Neuropathy 1 Day Post-Injury

    PubMed Central

    Nicholson, James D.; Guo, Yan; Bernstein, Steven L.

    2016-01-01

    Ischemia-reperfusion injury after central nervous system (CNS) injury presents a major health care challenge with few promising treatments. Recently, it has become possible to reduce edema after CNS injury by antagonizing a sulfonylurea receptor 1 (SUR1) regulated ion channel expressed after injury. SUR1 upregulation after injury is a necessary precondition for the formation of this channel, and has been implicated in white matter injury after clinical spinal cord trauma. Glibenclamide, an SUR1 antagonist, appears to have neuroprotective effect against cerebral stroke in an open-label small clinical trial and great effectiveness in reducing damage after varied experimental CNS injury models. Despite its importance in CNS injuries, SUR1 upregulation appears to play no part in rodent anterior ischemic optic neuropathy (rAION) injury as tested by real-time PCR and immunohistochemical staining of rAION-injured rat optic nerve (ON). Furthermore, the SUR1 antagonist glibenclamide administered immediately after rAION injury provided no protection to proximal ON microvasculature 1 day post-injury but may reduce optic nerve head edema in a manner unrelated to ON SUR1 expression. Our results suggest that there may be fundamental differences between rAION optic nerve ischemia and other CNS white matter injuries where SUR1 appears to play a role. PMID:27560494

  4. Multiple Family Groups for Adult Cancer Survivors and Their Families: A 1-Day Workshop Model

    PubMed Central

    STEINGLASS, PETER; OSTROFF, JAMIE S.; STEINGLASS, ABBE STAHL

    2015-01-01

    With marked advances in early detection and aggressive multimodality treatment, many adult cancers are now associated with good prognoses for disease-free survival. A burgeoning literature examining posttreatment quality-of-life issues has highlighted the numerous challenges experienced by patients and families in the aftermath of cancer treatment, further underscoring a need for new family-based psychosocial support interventions for cancer survivors and their families. This paper describes the clinical protocol for one such intervention, a 1-day “workshop” version of a multiple family group (MFG) for head and neck cancer survivors and their families. Data are reported from our experiences in running five 1-day workshops. Families uniformly reported that they were highly satisfied with their MFG participation, leading us to conclude that the abbreviated 1-day MFG model we are advocating is a promising family-focused support intervention for cancer survivors and their families. PMID:21884077

  5. Basic Training: A 1-Day Education Module for New Clientele in the Turf Industry

    ERIC Educational Resources Information Center

    Patton, Aaron J.; Reicher, Zachary J.

    2011-01-01

    It is important that Extension education programs be directed at clientele new to the turfgrass industry. A 1-day Basic Training: Turf Management seminar was created in 2006 to provide education to those new to the turfgrass industry. The seminar covered the basics of turfgrass management including growth, physiology, fertilization, cultural…

  6. Effects of a 1-Day Environmental Education Intervention on Environmental Attitudes and Connectedness with Nature

    ERIC Educational Resources Information Center

    Sellmann, Daniela; Bogner, Franz X.

    2013-01-01

    Besides cognitive learning effects, short-term environmental education (EE) is often regarded as ineffective in intervening with participants' environmental attitudes and behaviour. However, in Germany, school classes often participate in such 1-day EE programmes because they better match the school curriculum in contrast to longer (residential)…

  7. GENE EXPRESSION PATTERNS OF CD-1 DAY-8 EMBRYO CULTURES EXPOSED TO BROMOCHLORO ACETIC ACID

    EPA Science Inventory

    Gene expression patterns of CD-1 day-8 embryo cultures exposed to bromochloro acetic acid

    Edward D. Karoly?*, Judith E. Schmid* and E. Sidney Hunter III*
    ?Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina and *Reproductiv...

  8. Clinical response to 2 commonly used switch formulas occurs within 1 day.

    PubMed

    Berseth, Carol Lynn; Johnston, William H; Stolz, Suzanne I; Harris, Cheryl L; Mitmesser, Susan Hazels

    2009-01-01

    Very fussy or extremely fussy infants were randomized to receive: soy-based formula (Soy: n = 82) or a partially hydrolyzed cow's milk protein (CMP), low-lactose formula (PHF: n = 77) in a multicenter, double-blind, randomized, parallel, prospective 28-day feeding trial. Body weight and infant formula tolerance were reported. Adverse events were recorded throughout the study. A significant reduction in mean scores of fussiness, gas, spit-up, and crying compared with baseline measures was observed in infants who received either Soy or PHF within 1 day of formula intake; improvement in symptoms was sustained by study end. Stool consistency remained constant through day 28 in the PHF group, whereas stools in the Soy group became more firm by day 2 and did not return to prestudy consistency. PHF, with a protein profile patterned more closely on human breast milk, improved symptoms of formula intolerance as well as soy-based formula.

  9. Do currently available blood glucose monitors meet regulatory standards? 1-day public meeting in Arlington, Virginia.

    PubMed

    Klonoff, David C; Reyes, Juliet S

    2013-07-01

    Blood glucose monitors (BGMs) are approved by regulatory agencies based on their performance during strict testing conducted by their manufacturers. However, after approval, there is uncertainty whether BGMs maintain the accuracy levels that were achieved in the initial data. The availability of inaccurate BGM systems pose a public health problem because their readings serve as a basis for treatment decisions that can be incorrect. Several articles have concluded that BGMs in the marketplace may not consistently provide accurate results in accordance with the regulatory standards that led to approval. To address this growing concern, Diabetes Technology Society organized and conducted a 1-day public meeting on May 21, 2013, in Arlington, VA, presided by its president, David Klonoff, M.D., FACP, Fellow AIMBE, to determine whether BGMs on the market meet regulatory standards. The meeting consisted of four sessions in which Food and Drug Administration diabetes experts as well as leading academic clinicians and clinical chemists participated: (1) How is BGM performance determined? (2) Do approved BGMs perform according to International Organization for Standardization standards? (3) How do approved BGMs perform when used by patients and health care professionals? (4) What could be the consequence of poor BGM performance?

  10. Filter-based pathogen enrichment technology for detection of multiple viable foodborne pathogens in 1 day.

    PubMed

    Murakami, Taku

    2012-09-01

    Conventional foodborne pathogen assays currently used in the food industry often require long culture enrichments to increase pathogen levels so they can be detected. Even using sensitive real-time PCR assays, culture enrichment at least overnight is necessary especially for detection of pathogens with slow growth rates such as Listeria monocytogenes. To eliminate this cumbersome enrichment step and detect minute amounts of pathogens within 1 day, filter-based pathogen enrichment technology was developed utilizing a unique combination of glass fiber depth filter and porous filter aid materials to efficiently separate pathogens from food homogenates and avoid filter clogging by food particles. After pathogen immobilization in depth filters, only viable pathogens were selectively collected in a small volume of growth medium via microbial multiplication and migration; nonviable pathogens remained inside the filters. By assaying viable pathogens using real-time PCRs, multiple species of foodborne pathogens were detected, including L. monocytogenes, Salmonella enterica, and Escherichia coli O157:H7, at around 1 CFU/ml or 1 CFU/g in various food samples. This filter-based pathogen enrichment technology is a unique bacterial enrichment alternative to the conventional culture enrichment step and can significantly shorten the time necessary to obtain assay results.

  11. Macroanatomical investigation of the aorticorenal ganglion in 1-day-old infant sheep.

    PubMed

    Klećkowska-Nawrot, J; Kaczyńska, K; Jakubowska, W

    2009-06-01

    The aorticorenal gland belongs to the paired splanchnic ganglion, which is the main component of the coeliac plexus. It lies near the renal artery and suprarenal gland. The research was conducted on 13 1-day-old infant sheep - eight males and five females. Based on the conducted studies, it was concluded that the aorticorenal ganglion is characterized by the variable location in relation to the abdominal aorta, renal artery, caudal vena cava and suprarenal gland (holotopy), the thoracic and lumbar segment of the vertebral column (skeletotopy) (between L(1) and L(3)) and also a different shape (elongated, round, triangular, oval) as well as variable length (the aorticorenal ganglion is longer on the left side of the body; 2.72 mm) and distance from the caudal end of the suprarenal gland (longer on the left side of the body; 8.34 mm). With regard to the sex of the animal, the ganglion is the longest on the left side in ewes (3.02 mm), while in rams it is the longest on the right side (2.68 mm). Regarding the division according to sex, the longest segment was observed on the right side in ewes (9.27 mm), and the shortest segment in rams was also on the right side (6.84 mm).

  12. Passive avoidance training enhances cell proliferation in 1-day-old chicks.

    PubMed

    Dermon, C R; Zikopoulos, B; Panagis, L; Harrison, E; Lancashire, C L; Mileusnic, R; Stewart, M G

    2002-10-01

    One-day-old domestic chicks were injected i.p. with bromodeoxyuridine (BrdU) before training on a one-trial passive avoidance task where the aversive experience was a bead coated with a bitter tasting substance, methyl anthranilate (MeA). Animals were tested 24 h later; those avoiding (if MeA-trained) or pecking if water (W)-trained (which they peck appetitively), along with a group of untrained naïve chicks, were used to determine cell proliferation either 24 h or 9 days post BrdU injection. In all three groups, BrdU positive cells were identified sparsely throughout the forebrain but labelling was pronounced around ventricular zone (VZ) surfaces at both 24 h and 9 days post-BrdU-injection. Double immunolabelling with neuronal specific antibodies, to either NeuN, or beta-tubulin III, confirmed that most BrdU labelled cells appeared to be neurons. Unbiased stereological analysis of labelled cells in selected forebrain areas 24 h post BrdU injection showed a significant MeA-training induced increase in labelled cells in both the dorsal VZ surface bordering the intermediate and medial hyperstriatum ventrale (IMHV) and the tuberculum olfactorium (TO). By 9 days post-BrdU-injection, there was a significantly greater number of BrdU labelled cells in MeA-trained birds within the IMHV, lobus parolfactorius (LPO) and TO. These results demonstrate that avoidance training in 1-day-old chicks has a marked effect on cell proliferation, in the LPO and IMHV, regions of the chick previously identified as a key loci of memory formation, and in a second region (TO), which has olfactory functions, but has not been previously investigated in relation to avoidance learning.

  13. Tuning the Field Trip: Audio-Guided Tours as a Replacement for 1-Day Excursions in Human Geography

    ERIC Educational Resources Information Center

    Wissmann, Torsten

    2013-01-01

    Educators are experiencing difficulties with 1-day field trips in human geography. Instead of teaching students how to apply theory in the field and learn to "sense" geography in everyday life, many excursions have degraded into tourist-like events where lecturers try to motivate rather passive students against a noisy urban backdrop.…

  14. Salmonella spp. infection in imported 1-day-old chicks, ducklings, and turkey poults: a public health risk.

    PubMed

    Osman, Kamelia M; Yousef, Ashgan M M; Aly, Mona M; Radwan, Moustafa I

    2010-04-01

    The occurrence of Salmonella in 750 birds was assessed. The samples included the internal organs (caecal pouches, yolk sac, liver, and lung) of imported 1-day-old chicks (n = 150), grandparent chicks (n = 150), breeder chicks (n = 150), ducklings (n = 150), and turkey poults (n = 150), and paper-lined boxes (n = 250). Salmonellae isolated from the internal organs and paper-lined box of 1-day-old chicks, ducklings, and poults were mostly evident from the paper-lined box followed by caecal samples. Imported 1-day-old grandparent flocks were Salmonella free. Although 23.3% of the imported breeder flocks were positive for Salmonella, the imported duckling flocks and day-old turkey poults exhibited 19.3% and 12.6%, respectively. The widest diversity in isolated salmonellae was from the 1-day-old chicks where Salmonella Newport, Salmonella Kentucky, Salmonella Enteritidis, Salmonella Shubra, Salmonella Saintpaul, and Salmonella Agona were isolated. On the other hand, two Salmonella serovars were isolated from the imported breeders, Salmonella Shubra and Salmonella Shipley, and from the imported ducklings, Salmonella Shubra and Salmonella Saintpaul. The three Salmonella serovars isolated from the imported day-old turkey poults were Salmonella Shubra, Salmonella Newport, and Salmonella Saintpaul. The high percentage and diversity of Salmonella isolation from the imported birds cause concern because of the zoonotic potential of this agent and its economical importance to the local commercial poultry breeding industry. From 80 samples investigated for Salmonella, the positivity of the standard microbiological technique method was 17.5% and of the polymerase chain reaction method (Salmonella-specific invA gene) was 22.5%. The concordance between the two methods was 90% (k = 0.850). Our results indicated that the polymerase chain reaction approach is better than culturing for detecting Salmonella in poultry samples when using the preenriched medium combinations used in this

  15. Day to day variability in fat oxidation and the effect after only 1 day of change in diet composition.

    PubMed

    Støa, Eva Maria; Nyhus, Lill-Katrin; Børresen, Sandra Claveau; Nygaard, Caroline; Hovet, Åse Marie; Bratland-Sanda, Solfrid; Helgerud, Jan; Støren, Øyvind

    2016-04-01

    Indirect calorimetry is a common and noninvasive method to estimate rate of fat oxidation (FatOx) during exercise, and test-retest reliability should be considered when interpreting results. Diet also has an impact on FatOx. The aim of the present study was to investigate day to day variations in FatOx during moderate exercise given the same diet and 2 different isoenergetic diets. Nine healthy, moderately-trained females participated in the study. They performed 1 maximal oxygen uptake test and 4 FatOx tests. Habitual diets were recorded and repeated to assess day to day variability in FatOx. FatOx was also measured after 1 day of fat-rich (26.8% carbohydrates (CHO), 23.2% protein, 47.1% fat) and 1 day of CHO-rich diet (62.6% CHO, 20.1% protein, 12.4% fat). The reliability test revealed no differences in FatOx, respiratory exchange ratio (RER), oxygen uptake, carbon dioxide production, heart rate, blood lactate concentration, or blood glucose between the 2 habitual diet days. FatOx decreased after the CHO-rich diet compared with the habitual day 2 (from 0.42 ± 0.15 to 0.29 ± 0.13 g·min(-1), p < 0.05). No difference was found in FatOx between fat-rich diet and the 2 habitual diet days. FatOx was 31% lower (from 0.42 ± 0.14 to 0.29 ± 0.13 g·min(-1), p < 0.01) after the CHO-rich diet compared with the fat-rich diet. Using RER data to measure FatOx is a reliable method as long as the diet is strictly controlled. However, even a 1-day change in macronutrient composition will likely affect the FatOx results.

  16. High-resolution analysis of 1 day extreme precipitation in a wet area centred over eastern Liguria

    NASA Astrophysics Data System (ADS)

    Bertolini, Andrea; Brunetti, Michele; Maugeri, Maurizio

    2016-04-01

    The north of Tuscany and eastern Liguria have experienced several exceptional precipitation episodes and floods during the last century, with serious damage to human life and the environment. In recent years, the damage related to these extreme events appears to increase. In this context, we perform a detailed investigation of observed 1-day precipitation extremes and their frequency distribution, based on a dense data set of high-quality, homogenized station records in 1951-2010. Our dataset is composed of about 800 precipitation series coming from the databases of various regional agencies of central and northern Italy (ARPA Emilia Romagna, ARPA Liguria, SIR Toscana and ARPA Piemonte). As well as for any other meteorological measure, physical signals in raw precipitation data series are often hidden behind measuring errors and non-climatic noise caused mainly by station relocation and changes in instruments, in the environment around the station or in the observing conventions. Therefore, we developed specific codes to control the possible outliers, identify periods of failure and malfunction of the weather station, and to control of the values recorded after periods of missing data (suspected cumulative values). Finally, we have subjected the longer series to the Craddock homogeneity test to verify the relative homogeneity of the records and, if necessary, we have homogenized them, to remove all signals of non-climatic origin. After this process of control and homogenization of the data, we have about 400 validated precipitation series available for the study area centred on the eastern Liguria (8.25°E - 43.50 °N to 11.00°E - 45.00 °N, of about 30.000 km2) that we use to estimate very high quantiles (return levels) corresponding to 10-, 50- and 100-year return periods, as predicted by a generalized extreme value distribution. Return level estimates are produced on a regular high-resolution grid (30 arcsec) using a variant of regional frequency analysis

  17. Differential expression of toll-like receptor genes: sepsis compared with sterile inflammation 1 day before sepsis diagnosis.

    PubMed

    Lissauer, Matthew E; Johnson, Steven B; Bochicchio, Grant V; Feild, Carinda J; Cross, Alan S; Hasday, Jeffrey D; Whiteford, Craig C; Nussbaumer, William A; Towns, Michael; Scalea, Thomas M

    2009-03-01

    Toll-like receptors (TLRs) are critical components of innate immunity. This study was designed to evaluate differential expression of genes for TLR and associated signal transduction molecules in critically ill patients developing sepsis compared with those with sterile inflammation. Uninfected critically ill patients with systemic inflammatory response syndrome were prospectively followed daily for development of sepsis. They were divided into two groups and compared in a case-control manner: (a) preseptic patients (n = 45) who subsequently developed sepsis, and (b) uninfected systemic inflammatory response syndrome patients (n = 45) who remained uninfected. Whole blood RNA was collected (PAXGene tube) at study entry and 1, 2, and 3 days before clinical sepsis diagnosis (or time-matched uninfected control) and analyzed via Affymetrix Hg_U133 Plus 2.0 microarrays. Genes were considered differentially expressed if they met univariate significance controlled for multiple comparisons at P < 0.005. Differentially expressed probes were uploaded into the Database for Annotation, Visualization and Integrated Discovery. The TLR pathway (Kyoto Encyclopedia of Genes and Genomes-KEGG) significance was determined via Expression Analysis Systematic Explorer (EASE) scoring. A total of 2,974 Affymetrix probes representing 2,190 unique genes were differentially expressed 1 day before sepsis diagnosis. Thirty-six probes representing 25 genes were annotated to the TLR pathway (KEGG) via the Database for Annotation, Visualization and Integrated Discovery with an EASE score at P < 0.0004. Notable TLR genes demonstrating increased expression include TLR-4 (median, 1.43-fold change), TLR-5 (2.08-fold change), and MAPK14 (1.90-fold change). An additional 11 unique genes were manually annotated into the TLR pathway based on known relevance such as TLR-8 (1.54-fold change). The total 36 genes contained 28 showing increased expression and 8 showing decreased expression. Differential gene

  18. High energy X-ray observations of CYG X-3 from from OSO-8: Further evidence of a 34.1 day period

    NASA Technical Reports Server (NTRS)

    Dolan, J. F.; Crannell, C. J.; Dennis, B. R.; Frost, K. J.; Orwig, L. E.

    1981-01-01

    The X-ray source Cyg X-3 (=4U2030+40) was observed with the high energy X-ray spectrometer on OSO-8 for two weeks in 1975 and in 1976 and for one week in 1977. No change in spectral shape and intensity above 23 keV was observed from year to year. No correlation is observed between the source's intensity and the phase of the 34.1 day period discovered by Molteni, et al. (1980). The pulsed fraction of the 4.8 hour light curve between 23 and 73 keV varies from week to week, however, and the magnitude of the pulsed fraction appears to be correlated with the 34.1 day phase. No immediate explanation of this behavior is apparent in terms of previously proposed models of the source.

  19. Reproductive biology, stem cells biotechnology and regenerative medicine: a 1-day national symposium held at Shahid Sadoughi University of Medical Sciences

    PubMed Central

    Akyash, Fatemeh; Tahajjodi, Somayyeh Sadat; Sadeghian-Nodoushan, Fatemeh; Aflatoonian, Abbas; Abdoli, Ali-Mohammad; Nikukar, Habib; Aflatoonian, Behrouz

    2016-01-01

    This paper summarizes the proceedings of a 1 day national symposium entitled “Reproductive biology, stem cells biotechnology and regenerative medicine” held at Shahid Sadoughi University of Medical Sciences, Yazd, Iran on 3rd March 2016. Here, we collected the papers that presented and discussed at this meeting by specialists that currently researched about the overlaps of the fields of reproductive biology and stem cells and their applications in regenerative medicine.

  20. Effects of selenium sources and levels on reproductive performance and selenium retention in broiler breeder, egg, developing embryo, and 1-day-old chick.

    PubMed

    Yuan, Dong; Zhan, XiuAn; Wang, YongXia

    2011-12-01

    An 8-week experiment was conducted using 540 48-week-old Lingnan Yellow broiler breeders to evaluate the effect of the sources and levels of selenium (Se) on reproduction and Se retention. After receiving basal diet for 8 weeks, breeders were randomly assigned to six dietary treatments and fed corn-soy-based diets supplemented with 0.15 or 0.30 mg/kg of Se from sodium selenite (SS) or from Se-enriched yeast (SY) or from selenomethionine (SM). The Se concentration of basal diet was 0.04 mg/kg of Se. With the increase of dietary Se level, hatchability decreased (P < 0.05), but the Se concentrations were elevated in liver, kidney, pancreas, and breast muscle of breeders, yolk and albumen, liver and breast muscle of developing embryos, and tissues (liver, kidney, pancreas, and breast muscle) of 1-day-old chicks (P < 0.01). Irrespective of the Se level, the Se concentrations in liver, kidney, pancreas, and breast muscle were greater (P < 0.01) in breeders fed SY or SM compared with breeders fed SS, and kidney from breeders fed SM had greater Se concentration than that from breeders fed SY (P < 0.01). Yolk and albumen from SM treatments also had the greatest Se concentrations (P < 0.01). The embryonic liver and breast muscle from SM treatments had higher (P < 0.01) Se concentrations than those of SS treatments. The Se concentrations in liver, kidney, and breast muscle of 1-day-old chicks were greater (P < 0.01) in SY or SM treatments compared with SS treatments, and there was a more significant increase in Se concentrations in kidney and breast muscle of 1-day-old chicks from SM treatments than those from SY treatments (P < 0.01). The results suggest that the Se retention efficiency of SM is higher than that of SY, which, in turn, is higher than that of SS for broiler breeders and their offspring.

  1. Characterization of the invasiveness of monophasic and aphasic Salmonella Typhimurium strains in 1-day-old and point-of-lay chickens.

    PubMed

    Martelli, Francesca; Gosling, Rebecca; Kennedy, Emma; Rabie, André; Reeves, Hannah; Clifton-Hadley, Felicity; Davies, Rob; La Ragione, Roberto

    2014-01-01

    Egg-related outbreaks of salmonellosis are a significant health concern. Although Salmonella Enteritidis (SE) is the major egg-associated serotype, Salmonella Typhimurium (ST) can also infect the hen's reproductive tract and contaminate eggs. Recently, monophasic and aphasic variants of ST have been reported with increased frequency in Europe, and the isolation of these variants from laying flocks triggers the same legislative restrictions associated with biphasic ST strains. However, little is known about the colonization, invasiveness and persistence of monophasic and aphasic ST strains in laying hens. In this study, seven groups of 1-day-old and point-of-lay commercial Hy-line chicken layers were separately challenged with four different strains of monophasic ST, one aphasic ST, one biphasic ST and one egg-invasive SE strain. Tissue samples and cloacal swabs (point-of-lay chickens only) were collected at regular intervals post challenge in order to recover the Salmonella challenge strains. In 1-day-old chicks, only the aphasic ST strain and the SE strain were recovered after direct plating, suggesting that the number of salmonellas colonizing the tissues of the chicks infected with the other strains was likely to be low. Interestingly, all of the strains colonized well in the point-of-lay chickens, and there was no statistical difference in the overall number of positive samples or Salmonella counts between the seven strains. Salmonella was recovered from the point-of-lay birds to the end of the study (20 days after challenge). Monophasic and aphasic ST strains colonized point-of-lay birds as efficiently as biphasic ST and SE strains. Further studies are necessary to estimate the invasiveness of these strains in naturally-infected vaccinated laying hens, and to assess the impact of natural infection on egg contamination.

  2. Resonance enhancement in the accelerator transmutation of 1.3-day {sup 232}Pa and 2.1-day {sup 238}Np

    SciTech Connect

    Moore, M. S.; Danon, Y.

    1995-09-15

    The suggestion that the transmutation of actinide waste into fission products might best be done with thermalized spallation neutrons and odd-odd target materials such as {sup 238}Np has been studied. During the 1993 LAMPF/PSR cycle, we measured the fission cross section of 1.3-day {sup 232}Pa and 2.1-day {sup 238}Np from 0.01 eV to 40 keV at the LANSCE facility, and have carried out a preliminary resonance analysis of the observed structure and of the thermal region, with a 1/v representation above a few eV. In the present study, we calculate the reaction rates of these two species and {sup 247}Cm in a 'resonance reactor', an accelerator-driven assembly whose slowing-down properties are well known. Our model is a 1.8 m{sup 3} block of lead with a helium-cooled tungsten target in the center, i.e., the Rensselaer Intense Neutron Source (RINS). We include the effects of adding moderator outside an idealized lead slowing-down assembly, giving resonance enhancement factors for {sup 232}Pa and {sup 238}Np, and present parameters for the accelerator required to drive such an assembly to accomplish actinide burnup of these species.

  3. Hypoglycemic Activity of Fumaria parviflora in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Fathiazad, Fatemeh; Hamedeyazdan, Sanaz; Khosropanah, Mohamad Karim; Khaki, Arash

    2013-01-01

    Purpose: Fumaria parviflora Lam (Fumariaceae) has been used in traditional medicine in the treatment of several diseases such as diabetes. The present work was designed to evaluate the hypoglycaemic effects of methanolic extract (ME) of F. parviflora in normal and streptozotocin-induced diabetic rats. Methods: The rats used were allocated in six (I, II, III, IV, V and VI) experimental groups (n=5). Group I rats served as ‘normal control’ animals received distilled water and group II rats served as ‘diabetic control’ animals. Diabetes mellitus was induced in groups II, V and VI rats by intraperitoneal single injection of streptozotocin (STZ, 55 mg kg-1). Group V and VI rats were addi-tionally treated with ME (150 mg kg-1 day-1 and 250 mg kg-1 day-1, i.p. respectively) 24 hour post STZ injection, for seven consecutive days. Groups III and IV rats received only ME 150 mg kg-1 day-1 and 250 mg kg-1 day-1, i.p. respectively for seven days. The levels of blood glucose were determined using a Glucometer. Results: Administra-tion of F. parviflora extract showed a potent glucose lowering effect only on streptozo-tocin (STZ) induced diabetic rats below 100 mg/dl (P<0.001). However, no significant differences in the blood glucose levels were recorded between diabetic rats received 125 or 250 mg/kg of plant extracts. Conclusion: The findings of the study indicated that F. parviflora has significant hypoglycemic effect on STZ-induced diabetic rats with no effects on blood glucose levels of normal rats. PMID:24312837

  4. The protective effects of silibinin in the treatment of streptozotocin-induced diabetic osteoporosis in rats.

    PubMed

    Wang, Te; Cai, Leyi; Wang, Yangyang; Wang, Qingqing; Lu, Di; Chen, Hua; Ying, Xiaozhou

    2017-03-05

    Diabetic osteoporosis (DO) is a complication of diabetes mellitus. Our previous study showed that silibinin can attenuate high glucose mediated human bone marrow stem cells dysfunction through antioxidant effect. However, no study has yet investigated the effect of silibinin in diabetic rats. Therefore, we assessed the effects of silibinin on bone characteristics in streptozotocin-induced diabetic rats. The aim of our study was to determine whether providing silibinin in the different supplementation could prevent bone loss in diabetic rats or not. Rats were randomly divided into four groups: (1) control group (CG) (n=10); (2) diabetic group (DG) (n=10); (3) diabetic group with 50mgkg(-1)day(-1) of silibinin orally (DG-50) (n=10); and (4) diabetic group with 100mgkg(-1)day(-1) of silibinin orally (DG-100) (n=10). 12 weeks after streptozotocin (STZ) injection, the femora from all rats were assessed and oxidative stress was evaluated. Bone mineral density was significantly decreased in diabetic rats; these effects were prevented by treatment with silibinin (100mgkg(-1)day(-1) orally). Similarly, in the DG and DG-50 groups, changes in microarchitecture of femoral metaphysis assessed by microcomputed tomography demonstrated simultaneous existence of diabetic osteoporosis; these impairments were prevented by silibinin (100mgkg(-1)day(-1) orally). In conclusion, silibinin supplementation may have potential use as a possible therapy for maintaining skeletal health and these results can enhance the understanding of diabetic osteoporosis induced by diabetes.

  5. Sentinel node detection using 99mTc-rhenium sulphide colloid in breast cancer patients: evaluation of 1 day and 2 day protocols, and a dose-finding study.

    PubMed

    Koizumi, M; Nomura, E; Yamada, Y; Takiguchi, T; Tanaka, K; Yoshimoto, M; Makita, M; Sakamoto, G; Kasumi, F; Ogata, E

    2003-06-01

    Sentinel node (SN) biopsy is a promising replacement for standard axillary lymph node dissection for the staging of early breast cancer, and various techniques have been studied to identify SNs with dye or radioactive colloid. This study assesses the effect of the dose of radioactivity and the time before biopsy in order to set standards for the use of 99mTc-rhenium sulphide for the detection of SNs in breast cancer patients. Sixty patients with stage T1-2 N0 M0 breast cancer underwent SN biopsy, which was immediately followed by standard axillary dissection to confirm the SN results. For SN biopsy, 99mTc-rhenium colloid was injected peritumorally. A 1 day (morning injection and afternoon surgery) or 2 day (day before afternoon injection and morning surgery) protocol was applied. A dose-finding study was performed simultaneously using 7.4-37 MBq for the 1 day protocol and 37-74 MBq for the 2 day protocol. A scintigram was taken at 2 h for the 1 day protocol and 16 h for the 2 day protocol. After the injection of blue dye, SN biopsy was performed with a gamma probe, followed by standard axillary node dissection. The radiation exposure received by the surgical team during the operation was monitored. Histopathological comparison between SNs and axillary nodes was performed. Patient characteristics that might affect the radiocolloid uptake by SNs were assessed. SNs were identified in all patients regardless of the dose or administration protocol used. Two patients showed false negative pathological SN results, and the negative predictive value was 96% and the positive predictive value was 100%. In addition, radiation exposure to the surgical team and the amount of radioactive surgical waste were low, especially at lower doses. Two groups of patient characteristics were related to SN uptake. One was the body mass index (BMI) and the other was the age or menopausal status. Patients with a larger BMI tended to take up a smaller amount of 99mTc colloid. Older or post

  6. The effects of adults' affective expression and direction of visual gaze on 12-month-olds' visual preferences for an object following a 5-minute, 1-day, or 1-month delay.

    PubMed

    Flom, Ross; Johnson, Sarah

    2011-03-01

    Between 12- and 14 months of age infants begin to use another's direction of gaze and affective expression in learning about various objects and events. What is not well understood is how long infants' behaviour towards a previously unfamiliar object continues to be influenced following their participation in circumstances of social referencing. In this experiment, we examined infants' sensitivity to an adult's direction of gaze and their visual preference for one of two objects following a 5-min, 1-day, or 1-month delay. Ninety-six 12-month-olds participated. For half of the infants during habituation (i.e., familiarization), the adults' direction of gaze was directed towards an unfamiliar object (look condition). For the remaining half of the infants during habituation, the adults' direction of gaze was directed away from the unfamiliar object (look-away condition). All infants were habituated to two events. One event consisted of an adult looking towards (look condition) or away from (look-away condition) an object while facially and vocally conveying a positive affective expression. The second event consisted of the same adult looking towards or away from a different object while conveying a disgusted affective expression. Following the habituation phase and a 5-min, 1-day, or 1-month delay, infants' visual preference was assessed. During the visual preference phase, infants saw the two objects side by side where the adult conveying the affective expression was not visible. Results of the visual preference phase indicate that infants in the look condition showed a significant preference for object previously paired with the positive affect following a 5-min and 1-day delay. No significant visual preference was found in the look condition following a 1-month delay. No significant preferences were found at any retention interval in the look-away condition. Results are discussed in terms of early learning, social referencing, and early memory.

  7. Acute Inhalation Toxicity Study of 1, 4-Dioxane in Rats (Rattus norvegicus)

    DTIC Science & Technology

    2012-07-01

    Control (C) vs. 100, 1600 and 3200 ppm; 2 Each cell identifies number of rats with lesions where n = 8 rats, except n = 7 for liver/1-day/female...F., Arcos , J. C., and Hochligeti, C. 1965. Studies on the carcinogenic activity of protein-denaturing agents: Hepatocarcinogenicity of dioxane...J Natl. Cancer Inst. 35:949-58. Argus, M. F., Sohal, R. S., Bryant, G. M., Hoch-Ligeti, C., and Arcos , J. C. 1973. Dose- response and

  8. Dental abnormalities in the osteopetrotic rat mutation microphthalmia blanc.

    PubMed

    Cielinski, M J; Iizuka, T; Marks, S C

    1994-11-01

    Dental manifestations of the mild, transient osteopetrosis in the rat mutation microphthalmia blanc (mib) were examined. Eruption of all teeth was delayed in mib rats compared to normal littermates. The delays ranged from 5 days for incisors to 3 and 2 days for the first and second molars. Normal rats had straight incisors in the sagittal plane that exhibited signs of wear, but in mib littermates the incisors were maloccluded, distorted, and showed no signs of wear. Radiographic and histological examination of the dentition of 1- and 4-week-old rats revealed that the apical end of incisors in mib rats failed to extend posteriorly to the third molar region as in normal siblings, but ended at the first molar. Histological examination of longitudinal sections of mandibles through the incisors of neonatal normal and mib rats showed that in 1-day-old mutants the incisor was closely surrounded by alveolar bone to which it was ankylosed. The incisor body in mib rats was also malformed, with an indented apical end. This ankylosis was temporary, being resolved by 3 days. These findings show that neonatal reductions in bone resorption cause incisor defects and delay the eruption of all teeth in mib rats. The malocclusion and distortion of incisors of mib rats are likely caused by temporary ankylosis of incisor matrices to alveolar bone. Taken together, these findings illustrate the concept that bone resorption is an essential and rate-limiting element of tooth eruption.

  9. Differential gene expression in the liver of the African lungfish, Protopterus annectens, after 6 months of aestivation in air or 1 day of arousal from 6 months of aestivation.

    PubMed

    Hiong, Kum C; Ip, Yuen K; Wong, Wai P; Chew, Shit F

    2015-01-01

    The African lungfish, Protopterus annectens, can undergo aestivation during drought. Aestivation has three phases: induction, maintenance and arousal. The objective of this study was to examine the differential gene expression in the liver of P. annectens after 6 months (the maintenance phase) of aestivation as compared with the freshwater control, or after 1 day of arousal from 6 months aestivation as compared with 6 months of aestivation using suppression subtractive hybridization. During the maintenance phase of aestivation, the mRNA expression of argininosuccinate synthetase 1 and carbamoyl phosphate synthetase III were up-regulated, indicating an increase in the ornithine-urea cycle capacity to detoxify ammonia to urea. There was also an increase in the expression of betaine homocysteine-S-transferase 1 which could reduce and prevent the accumulation of hepatic homocysteine. On the other hand, the down-regulation of superoxide dismutase 1 expression could signify a decrease in ROS production during the maintenance phase of aestivation. In addition, the maintenance phase was marked by decreases in expressions of genes related to blood coagulation, complement fixation and iron and copper metabolism, which could be strategies used to prevent thrombosis and to conserve energy. Unlike the maintenance phase of aestivation, there were increases in expressions of genes related to nitrogen, carbohydrate and lipid metabolism and fatty acid transport after 1 day of arousal from 6 months aestivation. There were also up-regulation in expressions of genes that were involved in the electron transport system and ATP synthesis, indicating a greater demand for metabolic energy during arousal. Overall, our results signify the importance of sustaining a low rate of waste production and conservation of energy store during the maintenance phase, and the dependence on internal energy store for repair and structural modification during the arousal phase, of aestivation in the liver

  10. Differential Gene Expression in the Liver of the African Lungfish, Protopterus annectens, after 6 Months of Aestivation in Air or 1 Day of Arousal from 6 Months of Aestivation

    PubMed Central

    Hiong, Kum C.; Ip, Yuen K.; Wong, Wai P.; Chew, Shit F.

    2015-01-01

    The African lungfish, Protopterus annectens, can undergo aestivation during drought. Aestivation has three phases: induction, maintenance and arousal. The objective of this study was to examine the differential gene expression in the liver of P. annectens after 6 months (the maintenance phase) of aestivation as compared with the freshwater control, or after 1 day of arousal from 6 months aestivation as compared with 6 months of aestivation using suppression subtractive hybridization. During the maintenance phase of aestivation, the mRNA expression of argininosuccinate synthetase 1 and carbamoyl phosphate synthetase III were up-regulated, indicating an increase in the ornithine-urea cycle capacity to detoxify ammonia to urea. There was also an increase in the expression of betaine homocysteine-S-transferase 1 which could reduce and prevent the accumulation of hepatic homocysteine. On the other hand, the down-regulation of superoxide dismutase 1 expression could signify a decrease in ROS production during the maintenance phase of aestivation. In addition, the maintenance phase was marked by decreases in expressions of genes related to blood coagulation, complement fixation and iron and copper metabolism, which could be strategies used to prevent thrombosis and to conserve energy. Unlike the maintenance phase of aestivation, there were increases in expressions of genes related to nitrogen, carbohydrate and lipid metabolism and fatty acid transport after 1 day of arousal from 6 months aestivation. There were also up-regulation in expressions of genes that were involved in the electron transport system and ATP synthesis, indicating a greater demand for metabolic energy during arousal. Overall, our results signify the importance of sustaining a low rate of waste production and conservation of energy store during the maintenance phase, and the dependence on internal energy store for repair and structural modification during the arousal phase, of aestivation in the liver

  11. ENVIRONMENTAL ANTIANDROGENS: LOW DOSES OF VINCLOZOLIN ALTER SEXUAL DIFFERENTIATION OF THE MALE RAT

    EPA Science Inventory

    In humans and rodents, exposure to antiandrogenic chemicals during sexual differentiation can produce malformations of the reproductive tract. Perinatal administration of 100 or 200 mg vinclozolin (V) kg-1 day-1 during sexual differentiation in rats induces female-like anogenital...

  12. Experimental allergic encephalomyelitis in pituitary-grafted Lewis rats

    PubMed Central

    Esquifino, Ana I; Cano, Pilar; Zapata, Agustín; Cardinali, Daniel P

    2006-01-01

    Treatment of susceptible rats with dopaminergic agonists that reduce prolactin release decreases both severity and duration of clinical signs of experimental allergic encephalomyelitis (EAE). To assess to what extent the presence of an ectopic pituitary (that produces an increase in plasma prolactin levels mainly derived from the ectopic gland) affects EAE, 39 male Lewis rats were submitted to pituitary grafting from littermate donors. Another group of 38 rats was sham-operated by implanting a muscle fragment similar in size to the pituitary graft. All rats received subcutaneous (s.c.) injections of complete Freund's adjuvant (CFA) plus spinal cord homogenate (SCH) and were monitored daily for clinical signs of EAE. Animals were killed by decapitation on days 1, 4, 7, 11 or 15 after immunization and plasma was collected for prolactin RIA. In a second experiment, 48 rats were immunized by s.c. injection of a mixture of SCH and CFA, and then received daily s.c. injections of bromocriptine (1 mg/kg) or saline. Groups of 8 animals were killed on days 8, 11 or 15 after immunization and plasma prolactin was measured. Only sham-operated rats exhibited clinical signs of the disease when assessed on day 15 after immunization. A progressive decrease in plasma prolactin levels was observed in pituitary-grafted rats, attaining a minimum 15 days after immunization, whereas plasma prolactin levels were increased during the course of the disease in sham-operated rats. Plasma prolactin levels were higher in pituitary-grafted rats than in sham-operated rats 1 day after immunization, but lower on days 7, 11 and 15 after immunogen injection. Further supporting a correlation of suppressed prolactin levels with absence of clinical signs of EAE, rats that were administered the dopaminergic agonist bromocriptine showed very low plasma prolactin levels and did not exhibit any clinical sign of EAE. These results indicate that low circulating prolactin levels coincide with absence of

  13. Alterations in Skeletal Muscle Microcirculation of Head-Down Tilted Rats

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.; Stepke, Bernhard; Fleming, John T.; Joshua, Irving G.

    1992-01-01

    In this study we assessed the function of microscopic blood vessels in skeletal muscle (cremaster muscle) for alterations which may contribute to the observed elevation of blood pressure associated with head-down tilted whole body suspension (HDT/WBS), a model of weightlessness. Arteriolar baseline diameters, vasoconstrictor responses to norepinephrine (NE) and vasodilation to nitroprusside (NP) were assessed in control rats, rats suspended for 7 or 14 day HDT/WBS rats, and rats allowed to recover for 1 day after 7 days HDT/WBS. Neither baseline diameters nor ability to dilate were influenced by HDT/WBS. Maximum vasoconstriction to norepinephrine was significantly greater in arterioles of hypertensive 14 day HDT/WBS rats. This first study of the intact microvasculature in skeletal muscle indicates that an elevated contractility of arterioles to norepinephrine in suspended rats, and suggests an elevated peripheral resistance in striated muscle may contribute to the increase in blood pressures among animals subjected to HDT/WBS.

  14. [Histochemical study of the digestive organs of rats after a flight on "Kosmos-605"].

    PubMed

    Shubich, M G; Goriacheva, L L; Dudetskiĭ, V I; Lutsenko, N M; Mogil'naia, G M

    1977-01-01

    The histochemical study of the stomach, small and large intestines and pancreas of rats flown aboard the biosatellite Cosmos-605 as well as of synchronous and vivarium controls demonstrated a significant decline in the mucine producing capacity of epithelial cells of the stomach of the flight rats on the R + 1 day. The study showed an increased content of sialo- and sulphosaccharides in goblet cells of cryptae of large intestine and a reduced content of free cation protein in the acinar cells of the pancreas of flight rats. The changes were transient and disappeared by the R + 26 day.

  15. Metallothionein metabolism in the streptozotocin-diabetic rat

    SciTech Connect

    Chen, M.L.; Failla, M.L.

    1986-03-05

    Earlier reports from their laboratory showed the induction of the insulin-deficient diabetic state in adult rats was associated with an accumulation of zinc, copper, and a metallothionein-like zinc and copper binding protein in the soluble fraction of liver and kidney. Based upon chromatographic and electrophoretic properties, -SH to metal ratio and amino acid composition, they now report that elevated concentrations of metallothioneins (MT)-I and -II are indeed present in diabetic rat liver and kidney cytosol. The relative rates of MT synthesis in tissues from diabetic and control rats were measured by comparing incorporation of /sup 35/S-cysteine into MT vs. total cytoplasmic proteins at 5 h after injection of the precursor. The relative rates of MT synthesis in livers from rats diabetic for 10 d and fed either chow or purified diet containing 13 or 35 ppm copper were 1.4, 2.3 and 2.8 times greater, respectively, than control rats fed the same diets. Higher relative rates of MT synthesis were also observed in kidneys from diabetic rats fed purified diets compared to controls. Maximal relative rates of MT synthesis in diabetic liver and kidney were observed at 4 and 10 d, respectively, after onset of diabetes. The half-lives of cytoplasmic MT in liver and kidney from diabetic (10 d) rats were 1.3 and 2.6 days, respectively; half-lives of MT in control liver and kidney were 5.0 and 2.1 days, respectively.

  16. Erythropoietin enhances neurogenesis and restores spatial memory in rats after traumatic brain injury.

    PubMed

    Lu, Dunyue; Mahmood, Asim; Qu, Changsheng; Goussev, Anton; Schallert, Timothy; Chopp, Michael

    2005-09-01

    Erythropoietin (EPO) is neuroprotective in models of stroke and traumatic brain injury (TBI) when administered prior to or within the first few hours after injury. We seek to demonstrate that EPO also has neurorestorative effects when administered late (i.e., 1 day) after TBI in the rat. Twelve rats were subjected to TBI. Six rats were treated with EPO daily for 14 days starting 1 day after injury, and an additional six rats were treated with saline. Bromodeoxyuridine (BrdU) was administered daily for 14 days. Memory tests using a Morris Water Maze were performed prior to and after injury and treatment. Animals were sacrificed at 15 days after TBI, and their brains were prepared for histological analysis of damage to the dentate gyrus (DG) and for evaluation of newly formed neurons using double labeling of BrdU and MAP-2. The data revealed a significant improvement in spatial memory and significant increase in the number of newly formed neurons with EPO treatment compared with control animals. These data suggest that EPO treatment initiated 1 day after TBI is neurorestorative by enhancing neurogenesis, as well as neuroprotective.

  17. Effect of total parenteral nutrition, systemic sepsis, and glutamine on gut mucosa in rats

    NASA Technical Reports Server (NTRS)

    Yoshida, S.; Leskiw, M. J.; Schluter, M. D.; Bush, K. T.; Nagele, R. G.; Lanza-Jacoby, S.; Stein, T. P.

    1992-01-01

    The effect of the combination of total parenteral nutrition (TPN) and systemic sepsis on mucosal morphology and protein synthesis was investigated. Rats were given a standard TPN mixture consisting of glucose (216 kcal.kg-1.day-1), lipid (24 kcal.kg-1.day-1), and amino acids (1.5 g N.kg-1.day-1) for 5 days. On the 5th day the rats (n = 37) were randomized into four groups according to diet as follows: 1) control nonseptic on standard TPN, 2) control nonseptic on TPN with glutamine, 3) septic on standard TPN, and 4) septic with the TPN supplemented with glutamine. Twenty hours after the injection of Escherichia coli, the rats were given a 4-h constant infusion of [U-14C]leucine to determine the mucosal fractional protein synthesis rates. The following results were obtained. 1) Histological examination showed that systemic sepsis caused tissue damage to the ileum and jejunum. 2) Glutamine supplementation attenuated these changes. 3) There were no visible changes to the colon either from glutamine supplementation or sepsis. 4) Sepsis was associated with an increase in mucosal protein synthesis and decreased muscle synthesis. 5) Addition of glutamine to the TPN mix further increased protein synthesis in the intestinal mucosa of septic rats.

  18. 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.…

  19. Eldecalcitol prevents endothelial dysfunction in postmenopausal osteoporosis model rats.

    PubMed

    Serizawa, Kenichi; Yogo, Kenji; Tashiro, Yoshihito; Takeda, Satoshi; Kawasaki, Ryohei; Aizawa, Ken; Endo, Koichi

    2016-02-01

    Postmenopausal women have high incidence of cardiovascular events as estrogen deficiency can cause endothelial dysfunction. Vitamin D is reported to be beneficial on endothelial function, but it remains controversial whether vitamin D is effective for endothelial dysfunction under the treatment for osteoporosis in postmenopausal women. The aim of this study was to evaluate the endothelial protective effect of eldecalcitol (ELD) in ovariectomized (OVX) rats. ELD (20  ng/kg) was orally administrated five times a week for 4 weeks from 1 day after surgery. After that, flow-mediated dilation (FMD) as an indicator of endothelial function was measured by high-resolution ultrasound in the femoral artery of living rats. ELD ameliorated the reduction of FMD in OVX rats. ELD inhibited the increase in NOX4, nitrotyrosine, and p65 and the decrease in dimer/monomer ratio of nitric oxide synthase in OVX rat femoral arteries. ELD also prevented the decrease in peroxisome proliferator-activated receptor gamma (PPARγ) in femoral arteries and cultured endothelial cells. Although PPARγ is known to inhibit osteoblastogenesis, ELD understandably increased bone mineral density of OVX rats without increase in PPARγ in bone marrow. These results suggest that ELD prevented the deterioration of endothelial function under condition of preventing bone loss in OVX rats. This endothelial protective effect of ELD might be exerted through improvement of endothelial nitric oxide synthase uncoupling, which is mediated by an antioxidative effect through normalization of vascular PPARγ/NF-κB signaling.

  20. Differentiation of rapid and slower-acting effects of insulin on mitochondrial processes in brown adipose tissue from streptozotocin-diabetic rats.

    PubMed Central

    Gualberto, A; Saggerson, E D

    1989-01-01

    Insulin treatment of streptozotocin-diabetic rats restores the depressed palmitoyl-group oxidation observed in brown-adipose-tissue mitochondria from diabetic rats. A relatively rapid effect of insulin (5 h) to increase carnitine-dependent oxidation of palmitoyl-CoA and to increase overt carnitine palmitoyltransferase activity is differentiated from a slower effect of the hormone (1 day) to increase palmitoylcarnitine oxidation. PMID:2649091

  1. Rat Cardiovascular Responses to Whole Body Suspension: Head-down and Non-Head-Down Tilt

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.; Steffen, Joseph M.; Dombrowski, Judy

    1992-01-01

    The rat whole body suspension technique mimics responses seen during exposure to microgravity and was evaluated as a model for cardiovascular responses with two series of experiments. In one series, changes were monitored in chronically catheterized rats during 7 days of Head-Down Tilt (HDT) or Non-Head-Down Tilt (N-HDT) and after several hours of recovery. Elevations of mean arterial (MAP), systolic, and diastolic pressures of approx. 20 % (P less than 0.05) in HDT rats began as early as day 1 and were maintained for the duration of suspension. Pulse pressures were relatively unaffected, but heart rates were elevated approx. 10 %. During postsuspension (2-7 h), most cardiovascular parameters returned to presuspension levels. N-HDT rats exhibited elevations chiefly on days 3 and 7. In the second series, blood pressure was monitored in 1- and 3-day HDT and N-HDT rats to evaluate responses to rapid head-up tilt. MAP, systolic and diastolic pressures, and HR were elevated (P less than 0.05) in HDT and N-HDT rats during head-up tilt after 1 day of suspension, while pulse pressures remained un changed. HDT rats exhibited elevated pretilt MAP and failed to respond to rapid head-up tilt with further increase of MAP on day 3, indicating some degree of deconditioning. The whole body suspended rat may be useful as a model to better understand responses of rats exposed to microgravity.

  2. Chronic psychological stress enhances nociceptive processing in the urinary bladder in high-anxiety rats.

    PubMed

    Robbins, M T; DeBerry, J; Ness, T J

    2007-08-15

    This study sought to determine whether acute and/or chronic psychological stress produce changes in urinary bladder nociception. Female Sprague-Dawley (SD; low/moderate anxiety) or Wistar-Kyoto (WK; high-anxiety) rats were exposed to either an acute (1 day) or a chronic (10 days) water avoidance stress paradigm or a sham stress paradigm. Paw withdrawal thresholds to mechanical and thermal stimuli and fecal pellet output, were quantified at baseline and after the final stress or sham stress exposure. Rats were then sedated, and visceromotor responses (VMRs) to urinary bladder distension (UBD) were recorded. While acute stress exposure did not significantly alter bladder nociceptive responses in either strain of rats, WK rats exposed to a chronic stress paradigm exhibited enhanced responses to UBD. These high-anxiety rats also exhibited somatic analgesia following acute, but not chronic, stress. Furthermore, WK rats had greater fecal pellet output than SD rats when stressed. Significant stress-induced changes in nociceptive responses to mechanical stimuli were observed in SD rats. That chronic psychological stress significantly enhanced bladder nociceptive responses only in high-anxiety rats provides further support for a critical role of genetics, stress and anxiety as exacerbating factors in painful urogenital disorders such as interstitial cystitis (IC).

  3. Cerebrospinal fluid from rats given hypoxic preconditioning protects neurons from oxygen-glucose deprivation-induced injury.

    PubMed

    Zhang, Yan-Bo; Guo, Zheng-Dong; Li, Mei-Yi; Li, Si-Jie; Niu, Jing-Zhong; Yang, Ming-Feng; Ji, Xun-Ming; Lv, Guo-Wei

    2015-09-01

    Hypoxic preconditioning activates endogenous mechanisms that protect against cerebral ischemic and hypoxic injury. To better understand these protective mechanisms, adult rats were housed in a hypoxic environment (8% O2/92% N2) for 3 hours, and then in a normal oxygen environment for 12 hours. Their cerebrospinal fluid was obtained to culture cortical neurons from newborn rats for 1 day, and then the neurons were exposed to oxygen-glucose deprivation for 1.5 hours. The cerebrospinal fluid from rats subjected to hypoxic preconditioning reduced oxygen-glucose deprivation-induced injury, increased survival rate, upregulated Bcl-2 expression and downregulated Bax expression in the cultured cortical neurons, compared with control. These results indicate that cerebrospinal fluid from rats given hypoxic preconditioning protects against oxygen-glucose deprivation-induced injury by affecting apoptosis-related protein expression in neurons from newborn rats.

  4. Cerebrospinal fluid from rats given hypoxic preconditioning protects neurons from oxygen-glucose deprivation-induced injury

    PubMed Central

    Zhang, Yan-bo; Guo, Zheng-dong; Li, Mei-yi; Li, Si-jie; Niu, Jing-zhong; Yang, Ming-feng; Ji, Xun-ming; Lv, Guo-wei

    2015-01-01

    Hypoxic preconditioning activates endogenous mechanisms that protect against cerebral ischemic and hypoxic injury. To better understand these protective mechanisms, adult rats were housed in a hypoxic environment (8% O2/92% N2) for 3 hours, and then in a normal oxygen environment for 12 hours. Their cerebrospinal fluid was obtained to culture cortical neurons from newborn rats for 1 day, and then the neurons were exposed to oxygen-glucose deprivation for 1.5 hours. The cerebrospinal fluid from rats subjected to hypoxic preconditioning reduced oxygen-glucose deprivation-induced injury, increased survival rate, upregulated Bcl-2 expression and downregulated Bax expression in the cultured cortical neurons, compared with control. These results indicate that cerebrospinal fluid from rats given hypoxic preconditioning protects against oxygen-glucose deprivation-induced injury by affecting apoptosis-related protein expression in neurons from newborn rats. PMID:26604909

  5. Creatine supplementation enhances endurance performance in trained rats.

    PubMed

    Malin, Steven K; Cotugna, Nancy

    2008-01-01

    Minimal evidence has shown creatine (Cr) supplementation to enhance endurance performance in either humans or rats. The purpose of this study was to examine the effects of Cr supplementation on endurance performance during high-intensity exercise in trained male rats. Endurance performance was defined as the distance run. Sixteen days of running were performed over 28 days. A cycle of 7 days consisted of 2 days of training, 1 day off, 2 days of training then 2 days off and this was repeated over a total of 28 days. Cr was administered on all 28 days. Treatment rats (n = 7) drank water containing Cr while the control rats drank water with no supplement (n = 6). The Cr group's average distance run increased significantly from baseline to exercise day 16 (baseline = 128.91 m ± 18.23 vs. exercise day 16 = 217.11m ± 18.11; p < 0.005), while the control groups did not (baseline = 137.24 m ± 10.14, exercise day 16 = 101.04 m ± 14.97; p > 0.05). Over the course of the study, the treatment group's running endurance improved by 81% compared to baseline (p < 0.001) and we conclude that Cr supplementation provided rats an increased ability to run farther demonstrating possible implications for improving endurance athletes' performances.

  6. Endotoxin-induced mortality in rats is reduced by nitrones

    SciTech Connect

    Hamburger, S.A.; McCay, P.B. )

    1989-12-01

    The goal of these investigations was to determine if nitrone spin-trapping agents can alter mortality associated with endotoxemia in the rat. Reactive free radicals attack nitrone spin-trapping agents forming relatively reactive, persistent free radical spin adducts. We administered 85 mM (10 ml/kg) of alpha-phenyl N-tert-butyl nitrone (PBN), alpha-4-pyridyl-N-oxide N-tert-butyl nitrone (4-POBN), 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), or vehicle (saline i.p.) 30 min before endotoxin (25 mg/kg i.p.) or vehicle to Sprague-Dawley (SD) or Holtzman virus-free (HVF) rats (n = 10-17/group). All vehicle-treated rats receiving endotoxin were dead by 1 day. At 7 days, 83% of PBN-treated SD, 42% of PBN- or POBN-treated HVF, and 25% of DMPO-treated HVF rats were alive. The difference in survival of PBN-treated animals between strains may reflect the higher susceptibility of HVF rats to endotoxin. The observed reduction in mortality may be related to the well-established capacity of spin-trapping agents to capture reactive free radicals that may be generated in target tissues in response to endotoxin, and that would otherwise react with cell components and produce tissue injury.

  7. Effect of L-carnitine treatment on lipid metabolism and cardiac performance in chronically diabetic rats.

    PubMed

    Rodrigues, B; Xiang, H; McNeill, J H

    1988-10-01

    The beneficial effects of L-carnitine administration were studied in vivo in isolated perfused working hearts from control and diabetic rats. Control and streptozocin-induced diabetic (STZ-D) rats were treated daily for 6 wk with high-dose L-carnitine (3 g.kg-1.day-1 i.p.). STZ-D results in loss of body weight and hypoinsulinemia. These effects were not altered by L-carnitine treatment. Myocardial free-carnitine levels were decreased in the untreated diabetic rats. L-Carnitine treatment of the diabetic rats increased myocardial free-carnitine levels, which were comparable with those of control rats. Six weeks after STZ administration, hearts from untreated diabetic animals exhibited depressed left ventricular developed pressure, cardiac contractility, and ventricular relaxation rates compared with control animals. However, this depression was not seen in the L-carnitine-treated diabetic animals. L-Carnitine treatment of diabetic rats significantly reduced plasma glucose and lipid levels but had no effect on control rats. Furthermore, thyroid hormone levels were higher in the L-carnitine-treated diabetic rats than in the untreated diabetic group. The data suggest that high-dose L-carnitine treatment may reduce the severity of diabetes and result in improved cardiac performance.

  8. Clearance of inhaled ceramic fibers from rat lungs.

    PubMed Central

    Yamato, H; Tanaka, I; Higashi, T; Kido, M

    1994-01-01

    Deposition, clearance, retention, and durability of inhaled particles in lung are important factors for induction of pulmonary fibrosis or lung cancer. To study the deposition and clearance of aluminium silicate ceramic fibers from the lung, male Wistar rats were exposed to ceramic fibers, with a mass median aerodynamic diameter (MMAD) of 3.7 microns, for 6 hr/day, 5 days/week for 2 weeks. The average exposure concentration was 27.2 mg/m3 (SD 9.0). The rats were killed at 1 day, 1 month, 3 months, and 6 months after the end of exposure, and the fiber numbers and dimensions were measured with a scanning electron microscope. No significant difference in length of residual ceramic fibers in the lungs was found among the groups. The geometric mean diameter and number of ceramic fibers, however, decreased according to the clearance period. These findings suggest that the fibers were dissolved at their surface. PMID:7882924

  9. Chronic trimethyltin chloride exposure and the development of kidney stones in rats.

    PubMed

    Ren, Xuefeng; Wu, Xin; Sui, Gang; Gong, Zhihong; Yawson, Emmanuel; Wu, Banghua; Lai, Guanchao; Ruan, Xiaolin; Gao, Hongbin; Zhou, Feng; Su, Bing; Olson, James R; Tang, Xiaojiang

    2015-05-01

    We recently reported that occupational exposure to trimethyltin (TMT) is a risk factor for developing kidney stones. To further examine the association between TMT exposure and the formation of kidney stones, we conducted a 180-day animal study and exposed the randomly grouped Sprague-Dawley (SD) rats to TMT in the drinking water at doses of 0, 8.2, 32.8 and 131.3 µg kg(-1) day(-1). Transient behavioral changes were observed in the high-dose group during the first 2 weeks of exposure. TMT exposure led to a significant dose-dependent inhibition of renal H(+)/K(+)-ATPase and an increase in urinary pH. In comparison to no kidney stones being identified in the control and the lowest dose group, 1 rat in the 32.8 µg kg(-1) day(-1) dose group and 3 out of 9 rats in the 131.3 µg kg(-1) day(-1) dose group were found to have stones in the kidney/urinary tract. Pathological analysis showed that more wide spread calcium disposition was observed in kidneys of rats with TMT exposure compared with the rats in the control group. However, X-ray diffraction (XRD) analysis found that the kidney stones were mainly composed of struvite with the formula: NH4MgPO4 6H2O, while calcium-containing components were also detected. Together, this study further demonstrates through animal studies that chronic exposure to a relatively low level of TMT induces nephrotoxicity and increases the risk for developing kidney stones.

  10. Pulmonary function in rats dying from long-term parenteral nutrition.

    PubMed

    Dahl, P E; Kjaeve, J C

    2003-01-01

    Infusion of Vamin or Intralipid causes death in a rat model of continuous parenteral nutrition. Morphological investigations have shown vascular injury and thrombus formation in the lungs. In this study, lung function in rats was examined before death due to parenteral nutrition. The rats were fed saline intravenously (group I); 100 mL kg(-1) day(-1) (controls); a 7% amino acid-glucose solution (Vamin-Glukos) (group II); 100 mL kg(-1) day(-1), or 20% fat emulsion (Intralipid) (group III); 40 mL kg(-1) day(-1). The infusion was stopped when the condition of the rats deteriorated. In a saline-perfused, isolated lung model, pulmonary arterial pressure (Ppa), transpulmonary pressure (Ptp), endothelial function, measured as inactivation of serotonin (bioassay), and the capillary filtration coefficient (CFC) were determined. Haematological parameters were also evaluated. Constant findings in group II and III were central thrombus formation, anaemia and thrombocytopenia. Ppa increased from 0.7 (0.04) kPa in group I to 1.4 (0.1) kPa and 1.7 (0.1) kPa in groups II and III, respectively (p<0.001). Inactivation of serotonin was reduced to 36% (2) in group II and 37% (2) in group III compared with 74% (5) in group I (p<0.002). CFC increased to 25 mg min(-1) (5) (group II) and 30 mg min(-1) (6) (group III) compared with 13 mg min(-1) (2) in controls (p=0.01). The study shows that major pulmonary hypertension and severe reduction of the endothelial function are present when rats deteriorate after infusion of parenteral nutrition substrates.

  11. Role of lipid peroxidation in biliary obstruction in the rat.

    PubMed

    Muriel, P; Suarez, O R

    1994-01-01

    There is poor evidence about the participation of lipoperoxidative processes in liver damage induced by biliary obstruction, thus the aim of this work was to study the role of lipid peroxidation in this model of liver injury. Biliary obstruction was induced in male Wistar rats by ligation of the common bile duct; control animals were sham operated. Rats were sacrificed at different times after surgery. Liver sections were used for glycogen and lipoperoxidation quantification. Markers of liver damage were determined in serum. All serum markers of liver damage increased after 1 day of biliary obstruction. Liver glycogen content decreased 1 day after surgery. On the other hand, lipoperoxidation increased later than markers of liver damage, suggesting that it is a consequence rather than the cause of liver injury. Moreover, administration of colchiceine (a good free-radical scavenger) or vitamin E prevented lipoperoxidation but not liver damage, confirming that lipoperoxidation does not play an important role in liver damage induced by biliary obstruction. This model of liver injury seems to be useful for testing hepatoprotective drugs that do not act as free-radical scavengers.

  12. Feeding history and obese-prone genotype increase survival of rats exposed to a challenge of food restriction and wheel running.

    PubMed

    Diane, Abdoulaye; Pierce, W David; Heth, C Donald; Russell, James C; Richard, Denis; Proctor, Spencer D

    2012-09-01

    We hypothesized that obese-prone genotype and history of food restriction confer a survival advantage to genetically obese animals under environmental challenge. Male juvenile JCR:LA-cp rats, obese-prone and lean-prone, were exposed to 1.5 h daily meals and 22.5-h voluntary wheel running, a procedure inducing activity anorexia (AA). One week before the AA challenge, obese-prone rats were freely fed (obese-FF), or pair fed (obese-PF) to lean-prone, free-feeding rats (lean-FF). Animals were removed from protocol at 75% of initial body weight (starvation criterion) or after 14 days (survival criterion). AA challenge induced weight loss in all rats, but percent weight loss was more rapid and sustained in lean-FF rats than in obese-FF or obese-PF animals (P < 0.04). Weight loss was significantly higher in obese-FF rats than obese-PF rats, 62% of which achieved survival criterion and stabilized with zero weight loss. Obese-PF rats survived longer, on average (12.0 ± 1.1 day) than obese-FF (8.2 ± 1.1 day) and lean-FF rats (3.5 ± 0.2 day) (P < 0.02). Wheel running increased linearly in all groups; lean-FF increased more rapidly than obese-FF (P < 0.05); obese-PF increased at an intermediate rate (P < 0.02), and those rats that survived stabilized daily rates of wheel running. Prior food restriction of juvenile obese-prone rats induces a survival benefit beyond genotype, that is related to achievement of homeostasis. This metabolic adaptive process may help explain the development of human obesity in the presence of an unstable food environment which subsequently transitions to an abundant food supply.

  13. 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

  14. Photodynamic therapy for the treatment of buccal candidiasis in rats.

    PubMed

    Junqueira, Juliana Campos; Martins, Joyce da Silva; Faria, Raquel Lourdes; Colombo, Carlos Eduardo Dias; Jorge, Antonio Olavo Cardoso

    2009-11-01

    The study objective was to evaluate the effects of photodynamic therapy on buccal candidiasis in rats. After experimental candidiasis had been induced on the tongue dorsum, 72 rats were distributed into four groups according to treatment: treated with laser and methylene blue photosensitizer (L+P+); treated only with laser (L+P-); treated only with photosensitizer (L--P+); not treated with laser or photosensitizer (L-P-). The rats were killed immediately, 1 day, or 5 days after treatment, for microscopic analysis of the tongue dorsum. Observation verified that the photodynamic therapy group (L+P+) exhibited fewer epithelial alterations and a lower chronic inflammatory response than the L-P- group. The group L+P- presented more intense epithelial alterations and chronic inflammatory response than the remaining groups. The L-P+ group showed tissue lesions similar to those of the L-P- group. In conclusion, rats treated with photodynamic therapy developed more discrete candidiasis lesions than did the remaining groups.

  15. Nitrogen sparing by 2-ketoisocaproate in parenterally fed rats

    SciTech Connect

    Yagi, M.; Matthews, D.E.; Walser, M. )

    1990-11-01

    In rats receiving total parenteral nutrition with or without sodium 2-ketoisocaproate (KIC; 2.48 g.kg-1.day-1), L-(1-{sup 13}C)leucine and (1-{sup 14}C)KIC were constantly infused for 6 h. CO{sub 2} production, {sup 14}CO{sub 2} production, {sup 13}CO{sub 2} enrichment, urinary urea nitrogen (N) plus ammonia N and total urinary N were measured. Whole body protein synthesis (S) was calculated in non-KIC-infused rats and also in unfed rats infused with (1-{sup 14}C)leucine from fractional oxidation of labeled leucine (1-F), where F is fractional utilization for protein synthesis, and urea N plus ammonia N excretion (C) as S = C x F/(1-F). Addition of KIC caused a significant reduction in N excretion and a significant improvement in N balance. Fractional oxidation of labeled KIC increased, whereas fractional utilization of labeled KIC for protein synthesis decreased, but the extent of incorporation of infused KIC into newly synthesized protein (as leucine) amounted to at least 40% of the total rate of leucine incorporation into newly synthesized whole body protein. We conclude that addition of KIC spares N in parenterally fed rats and becomes a major source of leucine for protein synthesis.

  16. Reboxetine Improves Auditory Attention and Increases Norepinephrine Levels in the Auditory Cortex of Chronically Stressed Rats

    PubMed Central

    Pérez-Valenzuela, Catherine; Gárate-Pérez, Macarena F.; Sotomayor-Zárate, Ramón; Delano, Paul H.; Dagnino-Subiabre, Alexies

    2016-01-01

    Chronic stress impairs auditory attention in rats and monoamines regulate neurotransmission in the primary auditory cortex (A1), a brain area that modulates auditory attention. In this context, we hypothesized that norepinephrine (NE) levels in A1 correlate with the auditory attention performance of chronically stressed rats. The first objective of this research was to evaluate whether chronic stress affects monoamines levels in A1. Male Sprague–Dawley rats were subjected to chronic stress (restraint stress) and monoamines levels were measured by high performance liquid chromatographer (HPLC)-electrochemical detection. Chronically stressed rats had lower levels of NE in A1 than did controls, while chronic stress did not affect serotonin (5-HT) and dopamine (DA) levels. The second aim was to determine the effects of reboxetine (a selective inhibitor of NE reuptake) on auditory attention and NE levels in A1. Rats were trained to discriminate between two tones of different frequencies in a two-alternative choice task (2-ACT), a behavioral paradigm to study auditory attention in rats. Trained animals that reached a performance of ≥80% correct trials in the 2-ACT were randomly assigned to control and stress experimental groups. To analyze the effects of chronic stress on the auditory task, trained rats of both groups were subjected to 50 2-ACT trials 1 day before and 1 day after of the chronic stress period. A difference score (DS) was determined by subtracting the number of correct trials after the chronic stress protocol from those before. An unexpected result was that vehicle-treated control rats and vehicle-treated chronically stressed rats had similar performances in the attentional task, suggesting that repeated injections with vehicle were stressful for control animals and deteriorated their auditory attention. In this regard, both auditory attention and NE levels in A1 were higher in chronically stressed rats treated with reboxetine than in vehicle

  17. Effect of chronic estradiol administration on the acute pressor response to aortic coarctation in conscious rats.

    PubMed

    Salgado, M C; Castania, J A; Ballejo, G; Salgado, H C

    1995-08-01

    We investigated the effect of chronic estradiol administration on the pressor response elicited by acute (45 min) partial aortic constriction in conscious Wistar rats and on vascular reactivity to angiotensin II and vasopressin in vitro. Estradiol (10 micrograms kg-1 day-1, sc) or vehicle was administered for 7 days to young castrated male and female rats and to female rats that had stopped cycling (14-16 months of age). In the acute experiment of aortic coarctation in conscious rats, carotid pressure was monitored continuously before and for 45 min after partial abdominal aortic coarctation. In ovariectomized females the mean carotid pressure and heart rate before aortic coarctation were significantly lower in estradiol-treated animals (107 +/- 3 vs 119 +/- 3 mmHg and 360 +/- 31 vs 494 +/- 12 bpm). Estradiol did not affect the pressor response (145-150 mmHg) to aortic coarctation of castrated male rats or ovariectomized female rats but blunted the reflex bradycardia of ovariectomized rats. The onset of the pressor response to aortic coarctation was delayed in aged female rats as compared to the other groups. While estradiol treatment significantly accelerated the onset of hypertension in aged rats, it did not affect the pressor response of castrated animals. Full dose-response curves to angiotensin II and vasopressin were constructed in vitro in the isolated mesenteric arterial bed obtained from similarly treated groups. Estradiol did not affect the vasopressin sensitivity or responsiveness of any group, but caused a significant increase in angiotensin II sensitivity in ovariectomized rats only.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. The contact allergen dinitrochlorobenzene (DNCB) and respiratory allergy in the Th2-prone Brown Norway rat.

    PubMed

    Kuper, C Frieke; Stierum, Rob H; Boorsma, Andre; Schijf, Marcel A; Prinsen, Menk; Bruijntjes, Joost P; Bloksma, Nanne; Arts, Josje H E

    2008-04-18

    All LMW respiratory allergens known to date can also induce skin allergy in test animals. The question here was if in turn skin allergens can induce allergy in the respiratory tract. Respiratory allergy was tested in Th2-prone Brown Norway (BN) rats by dermal sensitization with the contact allergen dinitrochlorobenzene (DNCB; 1%, day 0; 0.5%, day 7) and a head/nose-only inhalation challenge of 27mg/m3 of DNCB (15 min, day 21), using a protocol that successfully identified chemical respiratory allergens. Skin allergy to DNCB was examined in BN rats and Th1-prone Wistar rats in a local lymph node assay followed by a topical patch challenge of 0.1% DNCB. Sensitization of BN rats via the skin induced DNCB-specific IgG in serum, but not in all animals, and an increased number of CD4+ cells in the lung parenchyma. Subsequent inhalation challenge with DNCB did not provoke apneas or allergic inflammation (signs of respiratory allergy) in the BN rats. However, microarray analysis of mRNA isolated from the lung revealed upregulation of the genes for Ccl2 (MCP-1), Ccl4 (MIP-1beta), Ccl7 and Ccl17. Skin challenge induced considerably less skin irritation and allergic dermatitis in the BN rat than in the Wistar rat. In conclusion, the Th2-prone BN rat appeared less sensitive to DNCB than the Wistar rat; nevertheless, DNCB induced allergic inflammation in the skin of BN rats but even a relatively high challenge concentration did not induce allergy in the respiratory tract, although genes associated with allergy were upregulated in lung tissue.

  19. Efficacy of moclobemide in a rat model of neurotoxicant-induced edema.

    PubMed

    Girard, Philippe; Verniers, Danielle; Pansart, Yannick; Gillardin, Jean-Marie

    2007-05-01

    The potent antidepressant effect of moclobemide, a selective and reversible type A monoamine oxidase (MAO) inhibitor, is clinically established. In view of the ongoing debate on the neuroprotective properties of MAO inhibitors, the present study was undertaken to further define the protective effect of moclobemide in a rat model of neurotoxicant-induced edema. In this model, daily oral triethyltin (TET) administration for 5 consecutive days strongly perturbed the rat behaviour and induced a cerebral edema at the 5th day. Oral coadministration of moclobemide (2 x 100 mg.kg-1.day-1) with TET blocked the development of brain edema and the increase in the cerebral chloride content induced by TET. Moreover, moclobemide reduced the increase in the cerebral sodium content and attenuated the neurological deficit. In conclusion, moclobemide possesses potent protective properties in this rat model of cerebral edema, suggesting potential clinical utility as a neuroprotectant.

  20. Impairment of mitochondrial β-oxidation in rats under cold-hypoxic environment

    NASA Astrophysics Data System (ADS)

    Dutta, Arkadeb; Vats, Praveen; Singh, Vijay K.; Sharma, Yogendra K.; Singh, Som N.; Singh, Shashi B.

    2009-09-01

    Mitochondrial ß-oxidation of fatty acid provides a major source of energy in mammals. High altitude (HA), characterized by hypobaric hypoxia and low ambient temperatures, causes alteration in metabolic homeostasis. Several studies have depicted that hypoxic exposure in small mammals causes hypothermia due to hypometabolic state. Moreover, cold exposure along with hypoxia reduces hypoxia tolerance in animals. The present study investigated the rate of β-oxidation and key enzymes, carnitine palmitoyl transferase-I (CPT-I) and hydroxyacyl CoA dehydrogenase (HAD), in rats exposed to cold-hypobaric hypoxic environment. Male Sprague Dawley rats (190-220 g) were randomly divided into eight groups ( n = 6 rats in each group): 1 day hypoxia (H1); 7 days hypoxia (H7); 1 day cold (C1); 7 days cold (C7); 1 day cold-hypoxia (CH1); 7 days cold-hypoxia (CH7) exposed; and unexposed control for 1 and 7 days (UC1 and UC7). After exposure, animals were anaesthetized with ketamine (50 mg/kg body weight) and xylazine (10 mg/kg body weight) intraperitonialy and sacrificed. Mitochondrial CPT-I, HAD, 14C-palmitate oxidation in gastrocnemius muscle and liver, and plasma leptin were measured. Mitochondrial CPT-I was significantly reduced in muscle and liver in CH1 and CH7 as compared to respective controls. HAD activity was significantly reduced in H1 and CH7, and in H1, H7, CH1, and CH7 as compared to unexposed controls in muscle and liver, respectively. A concomitant decrease in 14C-palmitate oxidation was found. Significant reduction in plasma leptin in hypoxia and cold-hypoxia suggested hypometabolic state. It can be concluded that ß-oxidation of fatty acids is reduced in rats exposed to cold-hypoxic environment due to the persisting hypometabolic state in cold-hypoxia exposure.

  1. Peripheral and spinal GABAergic regulation of incisional pain in rats.

    PubMed

    Reichl, Sylvia; Augustin, Mirjam; Zahn, Peter K; Pogatzki-Zahn, Esther M

    2012-01-01

    Impairment of spinal GABAergic inhibition is demonstrated to contribute to pathologic chronic pain states. We investigated spinal and peripheral GABAergic regulation of incisional pain in rats. We found that intrathecal but not peripheral administration of muscimol (GABA-A receptor agonist) and baclofen (GABA-B receptor agonist) reduced mechanical and thermal hyperalgesia after plantar incision in rats. Nonevoked pain behavior after incision was unaffected by these agonists. Similarly, nociception in unincised rats was not reduced by the same dose of agonists. Thus, GABA-A and GABA-B receptors are involved in mediating incision-induced hyperalgesia (but not nonevoked pain). Intrathecal and systemic application of L-838,417, a subtype-selective benzodiazepine site agonist (α2, α3, α5), reduced mechanical and heat hyperalgesia after incision, indicating a role of these subunits in mediating incision-induced hyperalgesia. Interestingly, the effects of all agonists were more intense and prolonged on the day after surgery than on the day of incision. Similarly, spinally administered GABA-A and GABA-B antagonists increased pain behavior, again with a greater effect 1 day after incision. One possible explanation for this finding might be that an incision modulates GABA-mediated inhibition 1 day after incision. However, expression of GABA-A receptor subunits α2 and α3 and GABA-B receptor subunits within the dorsal horn of the spinal cord were unchanged after incision, indicating that receptor expression cannot explain a possible modulation of GABAergic inhibition after incision. Thus, other mechanisms need to be considered. In conclusion, GABA-A and GABA-B receptors are promising targets for postoperative, incisional pain in humans.

  2. The protective potential of Yucca schidigera (Sarsaponin 30) against nitrite-induced oxidative stress in rats.

    PubMed

    Cigerci, I Hakki; Fidan, A Fatih; Konuk, Muhsin; Yuksel, Hayati; Kucukkurt, Ismail; Eryavuz, Abdullah; Sozbilir, Nalan Baysu

    2009-07-01

    The present study was designed to determine the protective effects of Yucca schidigera (Ys) against oxidative damage induced by acute nitrite intoxication as well as the histopathological evaluation of Ys in rats. The rats were divided into three groups each containing 12 rats: control (C); nitrite intoxication (N); Ys + nitrite intoxication (NY). C and N groups were fed standard rat feed (SRF). The NY group was fed SRF + 100 ppm Ys powder for 4 weeks. Acute nitrite intoxication was induced by subcutaneous (s.c.) administration of sodium nitrite (60 mg/kg) 1 day after the feeding period. Fifty minutes after sodium nitrite administration, blood samples and tissues including lung, liver, and kidney were collected for clinical biochemistry and histopathological investigations. Ys treatment was found to decrease methemoglobin, blood and tissue malondialdehyde, and tissue nitric oxide concentrations, and to increase the glutathione in blood and various tissues. However, plasma nitric oxide, total antioxidant activity, beta-carotene, and vitamin A did not differ between N and NY groups. While the N group rats showed distinct pathology in various tissues (compared with controls), the NY group had similar lung and liver pathology to the control. Only moderate or mild hemorrhage and hyperemia were seen in kidneys of NY group rats. Consequently, the natural compounds found in Ys, such as polyphenols, steroidal saponins, and other phytonutrients, could be used to substantially protect the organism from nitrite-induced oxidative damage and its complications.

  3. Compensatory renal growth after unilateral nephrectomy in the new-born rat

    PubMed Central

    Dicker, S. E.; Shirley, D. G.

    1973-01-01

    1. The right kidney in a series of control rats aged between 5 days and 115 days was weighed. The kidney weight/body weight ratio was greater in young than in older rats, but decreased linearly with increasing age. 2. After unilateral nephrectomy of rats 5 days old, the remaining kidney underwent compensatory growth. The rate and extent of this growth were greater than in adult rats. 3. The concentrations of RNA and DNA in the renal cortex and medulla of rats 5 days old were higher than in adult animals. The concentrations of the two nucleic acids fell with age, and reached adult levels after approximately 6 weeks. 4. After unilateral nephrectomy of rats 5 days old, the concentrations of RNA and DNA in the medulla were not significantly different from those in control animals. In the cortex, however, there was a delayed increase in the RNA/DNA ratio, which reached a level some 12% higher than that in control rats. This increase was smaller than that observed in unilaterally nephrectomized adult rats. 5. The cortical QO2 of the remaining kidney of unilaterally nephrectomized new-born rats was elevated by some 20% within 1 day of unilateral nephrectomy. Cortical QO2's remained higher than those of control animals for 3-4 weeks. 6. Since after unilateral nephrectomy, the increase in renal mass in new-borns was greater than that in adults, whereas the degree of cortical cellular hypertrophy (as estimated by the RNA/DNA ratio) was smaller than in adults, it is likely that in new-born animals a significant contribution to compensatory growth comes from cellular hyperplasia. PMID:4686024

  4. Toxicity of lunar dust assessed in inhalation-exposed rats

    PubMed Central

    Lam, Chiu-wing; Scully, Robert R.; Zhang, Ye; Renne, Roger A.; Hunter, Robert L.; McCluskey, Richard A.; Chen, Bean T.; Castranova, Vincent; Driscoll, Kevin E.; Gardner, Donald E.; McClellan, Roger O.; Cooper, Bonnie L.; McKay, David S.; Marshall, Linda; James, John T.

    2015-01-01

    Humans will again set foot on the moon. The moon is covered by a layer of fine dust, which can pose a respiratory hazard. We investigated the pulmonary toxicity of lunar dust in rats exposed to 0, 2.1, 6.8, 20.8 and 60.6 mg/m3 of respirable-size lunar dust for 4 weeks (6 h/day, 5 days/week); the aerosols in the nose-only exposure chambers were generated from a jet-mill ground preparation of a lunar soil collected during the Apollo 14 mission. After 4 weeks of exposure to air or lunar dust, groups of five rats were euthanized 1 day, 1 week, 4 weeks or 13 weeks after the last exposure for assessment of pulmonary toxicity. Biomarkers of toxicity assessed in bronchoalveolar fluids showed concentration-dependent changes; biomarkers that showed treatment effects were total cell and neutrophil counts, total protein concentrations and cellular enzymes (lactate dehydrogenase, glutamyl transferase and aspartate transaminase). No statistically significant differences in these biomarkers were detected between rats exposed to air and those exposed to the two low concentrations of lunar dust. Dose-dependent histopathology, including inflammation, septal thickening, fibrosis and granulomas, in the lung was observed at the two higher exposure concentrations. No lesions were detected in rats exposed to ≤6.8 mg/m3. This 4-week exposure study in rats showed that 6.8 mg/m3 was the highest no-observable-adverse-effect level (NOAEL). These results will be useful for assessing the health risk to humans of exposure to lunar dust, establishing human exposure limits and guiding the design of dust mitigation systems in lunar landers or habitats. PMID:24102467

  5. Toxicity of lunar dust assessed in inhalation-exposed rats.

    PubMed

    Lam, Chiu-wing; Scully, Robert R; Zhang, Ye; Renne, Roger A; Hunter, Robert L; McCluskey, Richard A; Chen, Bean T; Castranova, Vincent; Driscoll, Kevin E; Gardner, Donald E; McClellan, Roger O; Cooper, Bonnie L; McKay, David S; Marshall, Linda; James, John T

    2013-10-01

    Humans will again set foot on the moon. The moon is covered by a layer of fine dust, which can pose a respiratory hazard. We investigated the pulmonary toxicity of lunar dust in rats exposed to 0, 2.1, 6.8, 20.8 and 60.6 mg/m(3) of respirable-size lunar dust for 4 weeks (6 h/day, 5 days/week); the aerosols in the nose-only exposure chambers were generated from a jet-mill ground preparation of a lunar soil collected during the Apollo 14 mission. After 4 weeks of exposure to air or lunar dust, groups of five rats were euthanized 1 day, 1 week, 4 weeks or 13 weeks after the last exposure for assessment of pulmonary toxicity. Biomarkers of toxicity assessed in bronchoalveolar fluids showed concentration-dependent changes; biomarkers that showed treatment effects were total cell and neutrophil counts, total protein concentrations and cellular enzymes (lactate dehydrogenase, glutamyl transferase and aspartate transaminase). No statistically significant differences in these biomarkers were detected between rats exposed to air and those exposed to the two low concentrations of lunar dust. Dose-dependent histopathology, including inflammation, septal thickening, fibrosis and granulomas, in the lung was observed at the two higher exposure concentrations. No lesions were detected in rats exposed to ≤6.8 mg/m(3). This 4-week exposure study in rats showed that 6.8 mg/m(3) was the highest no-observable-adverse-effect level (NOAEL). These results will be useful for assessing the health risk to humans of exposure to lunar dust, establishing human exposure limits and guiding the design of dust mitigation systems in lunar landers or habitats.

  6. EDU pretreatment decreases polymorphonuclear leukocyte migration into rat lung airways.

    PubMed

    Bassett, D J; Elbon, C L; Ishii, Y; Yang, H; Otterbein, L; Boswell, G A; Kerr, J S

    1994-07-01

    Pretreatment with the heterocyclic compound EDU (N-[2-(2-oxo-1-imidazolindinyl)ethyl]-N'-phenylurea) has previously been shown to reduce polymorphonuclear leukocyte (PMN) infiltration into the airways of ozone-exposed rats. The present study further examined the effects of 1 and 2 days EDU pretreatment on rat lung inflammatory responses by determining PMN infiltration in response to intratracheal instillation with the chemoattractant formyl-norleucine-leucine-phenylalanine (fNLP). Maximal recovery of PMNs by bronchoalveolar lavage was observed 4 hr after fNLP instillation with no alteration in the numbers of recoverable macrophages and lymphocytes. Although 1-day pretreatment with EDU did not affect PMN recovery from fNLP-instilled rat lungs, 2 days of EDU pretreatment prevented PMN infiltration as indicated by PMN recoveries that were similar to those obtained from saline-instilled lungs. Measurements of lung-marginated and interstitial pools of inflammatory cells using collagenase tissue digestion demonstrated no effect of 2 days EDU pretreatment. Although 2 days EDU pretreatment alone did not alter blood PMN content, lung permeability, and the lavage recoveries of inflammatory cells, blood PMN responses to chemotactic stimuli in vitro were impaired. In addition, EDU was shown to directly inhibit PMN chemotaxis and superoxide anion generation in vitro. These data demonstrated that EDU acts by interfering with PMN activation and migration rather than by decreasing PMN availability. EDU, by modulating the inflammatory response, represents a useful compound for preventing PMN-associated amplification of acute lung injuries.

  7. Dexamethasone treatment causes resistance to insulin-stimulated cellular potassium uptake in the rat.

    PubMed

    Rhee, Michael S; Perianayagam, Anjana; Chen, Pei; Youn, Jang H; McDonough, Alicia A

    2004-11-01

    Patients treated with glucocorticoids have elevated skeletal muscle ouabain binding sites. The major Na(+)-K(+)-ATPase (NKA) isoform proteins found in muscle, alpha2 and beta1, are increased by 50% in rats treated for 14 days with the synthetic glucocorticoid dexamethasone (DEX). This study addressed whether the DEX-induced increase in the muscle NKA pool leads to increased insulin-stimulated cellular K+ uptake that could precipitate hypokalemia. Rats were treated with DEX or vehicle via osmotic minipumps at one of two doses: 0.02 mg.kg(-1).day(-1) for 14 days (low DEX; n = 5 pairs) or 0.1 mg.kg(-1).day(-1) for 7 days (high DEX; n = 6 pairs). Insulin was infused at a rate of 5 mU.kg(-1).min(-1) over 2.5 h in conscious rats. Insulin-stimulated cellular K+ and glucose uptake rates were assessed in vivo by measuring the exogenous K+ infusion (K+(inf)) and glucose infusion (Ginf) rates needed to maintain constant plasma K+ and glucose concentrations during insulin infusion. DEX at both doses decreased insulin-stimulated glucose uptake as previously reported. Ginf (in mmol.kg(-1).h(-1)) was 10.2 +/- 0.6 in vehicle-treated rats, 5.8 +/- 0.8 in low-DEX-treated rats, and 5.2 +/- 0.6 in high-DEX-treated rats. High DEX treatment also reduced insulin-stimulated K+) uptake. K+(inf) (in mmol.kg(-1).h(-1)) was 0.53 +/- 0.08 in vehicle-treated rats, 0.49 +/- 0.14 in low-DEX-treated rats, and 0.27 +/- 0.08 in high-DEX-treated rats. DEX treatment did not alter urinary K+ excretion. NKA alpha2-isoform levels in the low-DEX-treated group, measured by immunoblotting, were unchanged, but they increased by 38 +/- 15% (soleus) and by 67 +/- 3% (gastrocnemius) in the high-DEX treatment group. The NKA alpha1-isoform level was unchanged. These results provide novel evidence for the insulin resistance of K+ clearance during chronic DEX treatment. Insulin-stimulated cellular K+ uptake was significantly depressed despite increased muscle sodium pump pool size.

  8. Inhaled environmental combustion particles cause myocardial injury in the Wistar Kyoto rat.

    PubMed

    Kodavanti, Urmila P; Moyer, Carolyn F; Ledbetter, Allen D; Schladweiler, Mette C; Costa, Daniel L; Hauser, Russ; Christiani, David C; Nyska, Abraham

    2003-02-01

    Epidemiologists have associated particulate matter (PM) air pollution with cardiovascular morbidity and premature mortality worldwide. However, experimental evidence demonstrating causality and pathogenesis of particulate matter (PM)-induced cardiovascular damage has been insufficient. We hypothesized that protracted, repeated inhalation by rats of oil combustion-derived, fugitive emission PM (EPM), similar in metal composition to selected sources of urban air PM, causes exposure duration- and dose-dependent myocardial injury in susceptible rat strains. Zinc was the only primary water-leachable/bioavailable element of this EPM. Male Sprague-Dawley (SD), Wistar Kyoto (WKY), and spontaneously hypertensive (SH) rats were exposed nose-only to EPM (2, 5, or 10 mg/m(3), 6 h/day for 4 consecutive days or 10 mg/m(3), 6 h/day, 1 day/week for 4 or 16 consecutive weeks). Two days following the last EPM exposure, cardiac and pulmonary tissues were examined histologically. The results showed that particle-laden alveolar macrophages were the only pulmonary lesions observed in all three rat strains. However, WKY rats exposed to EPM (10 mg/m(3) 6 h/day, 1 day/week for 16 weeks) demonstrated cardiac lesions with inflammation and degeneration. To further characterize the nature of EPM-associated lesions, more rigorous histopathological and histochemical techniques were employed for WKY and SD rats. We examined the hearts for myocardial degeneration, inflammation, fibrosis, calcium deposits, apoptosis, and the presence of mast cells. Decreased numbers of granulated mast cells, and multifocal myocardial degeneration, chronic-active inflammation, and fibrosis were present in 5 of 6 WKY rats exposed to EPM for 16 weeks. None of these lesions were present in WKY exposed to clean air. EPM-related cardiac lesions were indistinguishable from air-exposed controls in SD and SH rats. This study demonstrates that long-term inhalation exposures to environmentally relevant PM containing

  9. Embryonic mouse STO cell-derived xenografts express hepatocytic functions in the livers of nonimmunosuppressed adult rats.

    PubMed

    Zhang, Mingjun; Joseph, Brigid; Gupta, Sanjeev; Guest, I; Xu, Meng; Sell, Stewart; Son, Kyung-Hwa; Koch, Katherine S; Leffert, Hyam L

    2005-02-01

    Cells derived from embryonic mouse STO cell lines differentiate into hepatocytes when transplanted into the livers of nonimmunosuppressed dipeptidylpeptidase IV (DPPIV)-negative F344 rats. Within 1 day after intrasplenic injection, donor cells moved rapidly into the liver and were found in intravascular and perivascular sites; by 1 month, they were intrasinusoidal and also integrated into hepatic plates with approximately 2% efficiency and formed conjoint bile canaliculi. Neither donor cell proliferation nor host inflammatory responses were observed during this time. Detection of intrahepatic mouse COX1 mitochondrial DNA and mouse albumin mRNA in recipient rats indicated survival and differentiation of donor cells for at least 3 months. Mouse COX1 targets were also detected intrahepatically 4-9 weeks after STO cell injection into nonimmunosuppressed wild-type rats. In contrast to STO-transplanted rats, mouse DNA or RNA was not detectable in untreated or mock-transplanted rats or in rats injected with donor cell DNA. In cultured STO donor cells, DPPIV and glucose-6-phosphatase activities were observed in small clusters; in contrast, mouse major histocompatibility complex class I H-2Kq, H-2Dq, and H-2Lq and class II I-Aq markers were undetectable in vitro before or after interferon gamma treatment. Together with H-2K allele typing, which confirmed the Swiss mouse origin of the donor cells, these observations indicate that mouse-derived STO cell lines can differentiate along hepatocytic lineage and engraft into rat liver across major histocompatibility barriers.

  10. Intracerebral Glycine Administration Impairs Energy and Redox Homeostasis and Induces Glial Reactivity in Cerebral Cortex of Newborn Rats.

    PubMed

    Moura, Alana Pimentel; Parmeggiani, Belisa; Grings, Mateus; Alvorcem, Leonardo de Moura; Boldrini, Rafael Mello; Bumbel, Anna Paula; Motta, Marcela Moreira; Seminotti, Bianca; Wajner, Moacir; Leipnitz, Guilhian

    2016-11-01

    Accumulation of glycine (GLY) is the biochemical hallmark of glycine encephalopathy (GE), an aminoacidopathy characterized by severe neurological dysfunction that may lead to early death. In the present study, we evaluated the effect of a single intracerebroventricular administration of GLY on bioenergetics, redox homeostasis, and histopathology in brain of neonatal rats. Our results demonstrated that GLY decreased the activities of the respiratory chain complex IV and creatine kinase, induced reactive species generation, and diminished glutathione (GSH) levels 1, 5, and 10 days after GLY injection in cerebral cortex of 1-day-old rats. GLY also increased malondialdehyde (MDA) levels 5 days after GLY infusion in this brain region. Furthermore, GLY differentially modulated the activities of superoxide dismutase, catalase, and glutathione peroxidase depending on the period tested after GLY administration. In contrast, bioenergetics and redox parameters were not altered in brain of 5-day-old rats. Regarding the histopathological analysis, GLY increased S100β staining in cerebral cortex and striatum, and GFAP in corpus callosum of 1-day-old rats 5 days after injection. Finally, we verified that melatonin prevented the decrease of complex IV and CK activities and GSH concentrations, and the increase of MDA levels and S100β staining caused by GLY. Based on our findings, it may be presumed that impairment of redox and energy homeostasis and glial reactivity induced by GLY may contribute to the neurological dysfunction observed in GE.

  11. Deep sea minerals prolong life span of streptozotocin-induced diabetic rats by compensatory augmentation of the IGF-I-survival signaling and inhibition of apoptosis.

    PubMed

    Liao, Hung-En; Shibu, Marthandam Asokan; Kuo, Wei-Wen; Pai, Pei-Ying; Ho, Tsung-Jung; Kuo, Chia-Hua; Lin, Jing-Ying; Wen, Su-Ying; Viswanadha, Vijaya Padma; Huang, Chih-Yang

    2016-07-01

    Consumption of deep sea minerals (DSM), such as magnesium, calcium, and potassium, is known to reduce hypercholesterolemia-induced myocardial hypertrophy and cardiac-apoptosis and provide protection against cardiovascular diseases. Heart diseases develop as a lethal complication among diabetic patients usually due to hyperglycemia-induced cardiac-apoptosis that causes severe cardiac-damages, heart failure, and reduced life expectancy. In this study, we investigated the potential of DSM and its related cardio-protection to increase the life expectancy in diabetic rats. In this study, a heart failure rat model was developed by using streptozotocin (65 mg kg(-1) ) IP injection. Different doses of DSM-1× (37 mg kg(-1) day(-1) ), 2× (74 mg kg(-1) day(-1) ) and 3× (111 mg kg(-1) day(-1) ), were administered to the rats through gavages for 4 weeks. The positive effects of DSM on the survival rate of diabetes rats were determined with respect to the corresponding effects of MgSO4 . Further, to understand the mechanism by which DSM enhances the survival of diabetic rats, their potential to regulate cardiac-apoptosis and control cardiac-dysfunction were examined. Echocardiogram, tissue staining, TUNEL assay, and Western blotting assay were used to investigate modulations in the myocardial contractile function and related signaling protein expression. The results showed that DSM regulate apoptosis and complement the cardiomyocyte proliferation by enhancing survival mechanisms. Moreover DSM significantly reduced the mortality rate and enhanced the survival rate of diabetic rats. Experimental results show that DSM administration can be an effective strategy to improve the life expectancy of diabetic subjects by improving cardiac-cell proliferation and by controlling cardiac-apoptosis and associated cardiac-dysfunction. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 769-781, 2016.

  12. 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.

  13. Pathology of acute inhalation exposure to 3-methylfuran in the rat and hamster

    SciTech Connect

    Haschek, W.M.; Morse, C.C.; Boyd, M.R.; Hakkinen, P.J.; Witschi, H.P.

    1983-01-01

    The acute inhalation toxicity of 3-methylfuran (3MF) was investigated in SPF Fischer-derived and CD/CR rats, and golden Syrian hamsters by determination of the 2-week LC/sub 50/, and by histologic examination of animals killed 1, 3, and 14 days following a 1-hr exposure to 148 and 322 ..mu..mole 3MF/liter for CD/CR rats and hamsters, respectively. The Fischer-derived rat was more sensitive to 3MF-induced lethality than the CD/CR rat with an LC/sub 50/ in the male rat of 81 ..mu..mole/liter-1 hr as compared to 222 ..mu..mole/liter-1hr. No sex difference was found. The hamster was relatively resistant with no lethality at 322 ..mu..mole 3MF/liter-2 hr. Pulmonary damage was present in both species. In the hamster, selective necrosis of nonciliated bronchiolar epithelial (Clara) cells was seen at 1 day with virtually complete regeneration by 14 days whereas in the rat the bronchiolar epithelial damage was more extensive and was followed by scattered peribronchiolar fibrosis and epithelial mucous metaplasia suggestive of ''small airway disease'' of man. Relatively selective 3MF-induced necrosis of olfactory epithelium occurred in the nasal mucosa of both species. Resolution of this lesion was seen by 14 days in the hamster. In the rat, however, the necrosis was much more extensive and was followed by partially occlusive fibrosis of the nasal cavity as seen at 14 days. 3MF also induced centrilobular hepatic necrosis in both species. In the rat, lymphocyte necrosis in the thymus and spleen, and esophageal necrosis was also seen.

  14. Pathology of acute inhalation exposure to 3-methylfuran in the rat and hamster

    SciTech Connect

    Haschek, W.M.; Morse, C.C.; Boyd, M.R.; Hakkinen, P.J.; Witschi, H.P.

    1983-12-01

    The acute inhalation toxicity of 3-methylfuran (3MF) was investigated in SPF Fischer-derived and CD/CR rats, and golden Syrian hamsters by determination of the 2-week LC50, and by histologic examination of animals killed 1, 3, and 14 days following a 1-hr exposure to 148 and 322 mumole 3MF/liter for CD/CR rats and hamsters, respectively. The Fischer-derived rat was more sensitive to 3MF-induced lethality than the CD/CR rat with an LC50 in the male rat of 81 mumole/liter-1 hr as compared to 222 mumole/liter-1 hr. No sex difference was found. The hamster was relatively resistant with no lethality at 322 mumole 3MF/liter-2 hr. Pulmonary damage was present in both species. In the hamster, selective necrosis of nonciliated bronchiolar epithelial (Clara) cells was seen at 1 day with virtually complete regeneration by 14 days whereas in the rat the bronchiolar epithelial damage was more extensive and was followed by scattered peribronchiolar fibrosis and epithelial mucous metaplasia suggestive of ''small airway disease'' of man. Relatively selective 3MF-induced necrosis of olfactory epithelium occurred in the nasal mucosa of both species. Resolution of this lesion was seen by 14 days in the hamster. In the rat, however, the necrosis was much more extensive and was followed by partially occlusive fibrosis of the nasal cavity as seen at 14 days. 3MF also induced centrilobular hepatic necrosis in both species. In the rat, lymphocyte necrosis in the thymus and spleen, and esophageal necrosis was also seen.

  15. Effects of GSM-Frequency Electromagnetic Radiation on Some Physiological and Biochemical Parameters in Rats.

    PubMed

    Khirazova, E E; Baizhumanov, A A; Trofimova, L K; Deev, L I; Maslova, M V; Sokolova, N A; Kudryashova, N Yu

    2012-10-01

    Single exposure of white outbred rats to electromagnetic radiation with a frequency 905 MHz (GSM frequency) for 2 h increased anxiety, reduced locomotor, orientation, and exploration activities in females and orientation and exploration activities in males. Glucocorticoid levels and antioxidant system activity increased in both males and females. In addition to acute effects, delayed effects of radiation were observed in both males and females 1 day after the exposure. These results demonstrated significant effect of GSM-range radiation on the behavior and activity of stress-realizing and stress-limiting systems of the body.

  16. No evidence of rat hepatitis E virus excretion into urine of rats.

    PubMed

    Li, Tian-Cheng; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Johne, Reimar; Wakita, Takaji

    2016-08-31

    To investigate whether rat hepatitis E virus (rat HEV) is excreted into the urine of rats, we infected three Wistar and six nude rats with rat HEV and examined the rat HEV RNA in serum, fecal and urine samples. We detected rat HEV RNA in the serum and fecal samples of all rats but not in the urine. Our results suggest that in rats, rat HEV is not transmitted via urine.

  17. Cholecystokinin-8 activates myenteric neurons in 21- and 35-day old but not 4- and 14-day old rats.

    PubMed

    Washington, Martha C; Murry, Candace R; Raboin, Shannon J; Roberson, Allison E; Mansour, Mahmoud M; Williams, Carol S; Sayegh, Ayman I

    2011-02-01

    Cholecystokinin (CCK) activates the myenteric neurons of adult rats. The goal of this work is to determine the ontogeny of this activation by CCK-8 in the myenteric plexus of the duodenum (2cm immediately following the pyloric sphincter aborally) and compare it with that of the dorsal vagal complex (DVC) - which occurs in 1-day old pups. Despite the existence of both of the CCK receptors, CCK(1) and CCK(2), in 4, 14, 21 and 35 day old rats, CCK-8 (0, 5, 10, 20 and 40μg/kg, i.p.) increased Fos-like immunoreactivity (Fos-LI, a marker for neuronal activation) in the myenteric neurons of 21- and 35-day old rats but in the DVC of all age groups. As such, this belated activation of myenteric neurons by CCK-8 compared to the DVC may reflect a delayed role for these neurons in CCK-related functions.

  18. Effects of antenatal application of ambroxol and glucocorticoid on lung morphometry and signal transduction of bone morphogenetic protein in the fetal rat.

    PubMed

    Chen, Xiao-Qing; Wu, Sheng-Hua; Guo, Xi-Rong; Zhou, Xiao-Yu

    2012-07-01

    Antenatal ambroxol, dexamethasone (Dex) and betamethasone (Beta) are used to prevent neonate respiratory distress syndrome. The present study aimed to investigate the role of ambroxol, Dex and Beta administered antenatally on lung morphogenesis and signal transduction of bone morphogenetic protein (BMP) in rat embryo. Fetal lungs treated with ambroxol, 1-day Beta, 3-day Dex and 3-day Beta were more mature compared to the controls as determined by light microscopy and transmission electron microscopy. Expression of BMP4 and bone morphogenetic protein receptor II (BMPR‑II) mRNA was upregulated in the 1-day-Beta-, 3-day-Dex- and 3-day-Beta-treated animals. BMP4 and BMPR-II protein were significantly increased in the 1-day-Beta-, 3-day-Dex- and 3-day-Beta-treated animals. Ambroxol, Dex and Beta promoted the morphological development of rat fetal lung; Beta was more effective than Dex. A multi-dose of glucocorticoids exhited a more beneficial effect than a single dose. The effects of Beta and Dex may be mediated by regulation of BMP signal transduction in rat fetal lung.

  19. Voluntary wheel running attenuates ethanol withdrawal-induced increases in seizure susceptibility in male and female rats.

    PubMed

    Devaud, Leslie L; Walls, Shawn A; McCulley, Walter D; Rosenwasser, Alan M

    2012-11-01

    We recently found that voluntary wheel running attenuated ethanol withdrawal-induced increased susceptibility to chemoconvulsant-induced seizures in male rats. Since female rats recover from ethanol withdrawal (EW) more quickly than male rats across several behavioral measures, this study was designed to determine whether the effects of exercise on EW seizures also exhibited sex differences. Animals were maintained under no-wheel, locked-wheel or free-wheel conditions and ethanol was administered by liquid diet for 14 days with control animals pair-fed an isocaloric diet, after which seizure thresholds were determined at 1 day or 3 days of EW. Consistent with previous reports, females ran significantly more than males, regardless of diet condition. Introduction of the ethanol-containing liquid diet dramatically increased running for females during the day (rest) phase, with little impact on night phase activity. Consistent with previous reports, EW increased seizure susceptibility at 1 day in non-exercising males and females and at 3 days in males. These effects were attenuated by access to running wheels in both sexes. We also assessed the effects of sex, ethanol diet and exercise on ethanol clearance following an acute ethanol administration at 1 day EW in a separate set of animals. Blood ethanol concentrations at 30 min post-injection were lower in males, ethanol-exposed animals, and runners, but no interactions among these factors were detected. Interestingly, females displayed more rapid ethanol clearance than males and there were no effects of either diet or wheel access on clearance rates. Taken together, these data suggest that voluntary wheel running during ethanol administration provides protective effects against EW seizures in both males and females. This effect may be mediated, in part, in male, but not in female rat, by effects of exercise on early pharmacokinetic contributions. This supports the idea that encouraging alcoholics to exercise may

  20. Simulated systemic recurrent Mycoplasma infection in rats induces recurrent sickness responses without residual impairment in spatial learning and memory.

    PubMed

    Swanepoel, Tanya; Harvey, Brian H; Harden, Lois M; Laburn, Helen P; Mitchell, Duncan

    2012-02-01

    In spite of their prevalence and importance, recurrent acute infections seldom have been investigated in the laboratory. We set out to measure fever and sickness behaviour in simulated recurrent Mycoplasma infection; Mycoplasma is a common clinical cause of recurrent acute infection. Male Sprague-Dawley rats had radiotransponders implanted to measure abdominal temperature and cage activity. After recovery, rats received three intraperitoneal (I.P.) injections, 10 days apart, of either fibroblast-stimulating lipopeptide-1 (FLS-1), a pyrogenic moiety of Mycoplasma salivarium, at a dose of 500 μg.kg(-1) in 1 ml.kg(-1) phosphate-buffered saline (PBS), or vehicle (PBS, 1 ml.kg(-1)). Body mass and food intake were measured daily. For measurement of learning and memory, training in a Morris Water Maze commenced 10 days after the last of the three successive injections and continued daily for 4 days. Spatial memory was assessed on the following day. Hippocampal tissue of rats was collected on the day of the last exposure to the maze. Recurrent FSL-1 administration induced recurrent fevers (~1°C) for about 9h, recurrent lethargy (~40-60%) for 1 day, recurrent anorexia (~16-30%) for 1 day, and recurrent reductions in the rate of mass gain (~112%) for 1 day, but did not induce persistent stunting. Recurrent FSL-1 administration did not result in tolerance to fever, lethargy or anorexia. There was no residual histological damage to the hippocampus and no residual detrimental effect in learning or memory in rats. Though we cannot extrapolate our results directly to humans, clinical recurrent acute Mycoplasma infection may not impose a high risk of stunting or impaired spatial learning and memory.

  1. Spontaneous synaptic activity is required for the formation of functional GABAergic synapses in the developing rat hippocampus.

    PubMed

    Colin-Le Brun, Isabelle; Ferrand, Nadine; Caillard, Olivier; Tosetti, Patrizia; Ben-Ari, Yehezkel; Gaïarsa, Jean-Luc

    2004-08-15

    Here we examine the role of the spontaneous synaptic activity generated by the developing rat hippocampus in the formation of functional gamma-aminobutyric acid (GABA) synapses. Intact hippocampal formations (IHFs) were dissected at birth and incubated for 1 day in control or tetrodotoxin (TTX)-supplemented medium at 25 degrees C. After the incubation, miniature GABA(A)-mediated postsynaptic currents (mGABA(A)-PSCs) were recorded in whole-cell voltage-clamped CA3 pyramidal neurones from IHF-derived slices. After 1 day in vitro in control medium, the frequency of mGABA(A)-PSCs was similar to that recorded in acute slices obtained 1 day after birth, but significantly higher than the frequency recorded from acute slices just after birth. These results suggest that the factors required in vivo for the formation of functional GABAergic synapses are preserved in the IHFs in vitro. The frequency increase was prevented when IHFs were incubated for 1 day with TTX. TTX treatment affected neither the morphology of CA3 pyramidal neurones nor cell viability. The TTX effects were reproduced when IHFs were incubated in the presence of glutamatergic or GABAergic ionotropic receptor antagonists or in high divalent cationic medium. The present results indicate that the spontaneous synaptic activity generated by the developing hippocampus is a key player in the formation of functional GABAergic synapses, possibly via network events requiring both glutamatergic and GABAergic receptors.

  2. Spontaneous synaptic activity is required for the formation of functional GABAergic synapses in the developing rat hippocampus

    PubMed Central

    Colin-Le Brun, Isabelle; Ferrand, Nadine; Caillard, Olivier; Tosetti, Patrizia; Ben-Ari, Yehezkel; Gaïarsa, Jean-Luc

    2004-01-01

    Here we examine the role of the spontaneous synaptic activity generated by the developing rat hippocampus in the formation of functional γ-aminobutyric acid (GABA) synapses. Intact hippocampal formations (IHFs) were dissected at birth and incubated for 1 day in control or tetrodotoxin (TTX)-supplemented medium at 25°C. After the incubation, miniature GABAA-mediated postsynaptic currents (mGABAA-PSCs) were recorded in whole-cell voltage-clamped CA3 pyramidal neurones from IHF-derived slices. After 1 day in vitro in control medium, the frequency of mGABAA-PSCs was similar to that recorded in acute slices obtained 1 day after birth, but significantly higher than the frequency recorded from acute slices just after birth. These results suggest that the factors required in vivo for the formation of functional GABAergic synapses are preserved in the IHFs in vitro. The frequency increase was prevented when IHFs were incubated for 1 day with TTX. TTX treatment affected neither the morphology of CA3 pyramidal neurones nor cell viability. The TTX effects were reproduced when IHFs were incubated in the presence of glutamatergic or GABAergic ionotropic receptor antagonists or in high divalent cationic medium. The present results indicate that the spontaneous synaptic activity generated by the developing hippocampus is a key player in the formation of functional GABAergic synapses, possibly via network events requiring both glutamatergic and GABAergic receptors. PMID:15218067

  3. Spironolactone prevents alterations associated with cardiac hypertrophy produced by isoproterenol in rats: involvement of serum- and glucocorticoid-regulated kinase type 1.

    PubMed

    Martín-Fernández, Beatriz; de las Heras, Natalia; Miana, María; Ballesteros, Sandra; Valero-Muñoz, María; Vassallo, Dalton; Davel, Ana Paula; Rossoni, Luciana Venturini; Cachofeiro, Victoria; Lahera, Vicente

    2012-06-01

    Persistent β-adrenergic receptor stimulation with isoproterenol is associated with cardiac hypertrophy as well as cardiac synthesis of angiotensin II. Serum- and glucocorticoid-regulated kinase type 1 (SGK-1) is a key mediator in structural, functional and molecular cardiac effects of aldosterone in rats. This study was designed to investigate the cardiac effects of the mineralocorticoid receptor antagonist spironolactone on the response to isoproterenol treatment in rats, as well as the involvement of the main mediator of cellular aldosterone action, SGK-1, in the heart. Male Wistar rats received isoproterenol (3 mg kg(-1) day(-1)) or vehicle for 15 days. Half of the animals in each group were simultaneously treated with spironolactone (200 mg kg(-1) day(-1)). Systolic and diastolic blood pressures were not significantly different among groups. Treatment with spironolactone normalized the increased left ventricular end-diastolic pressure observed in isoproterenol-treated rats. Isoproterenol treatment induced cardiac hypertrophy and increased collagen content, both of which were normalized by spironolactone treatment. The mRNA levels of transforming growth factor β, connective tissue growth factor, matrix metalloprotease 2, matrix metalloprotease inhibitor 2, tumour necrosis factor α, interleukin 1β, p22phox and xanthine dehydrogenase were increased (P < 0.05) in isoproterenol-treated rats, and this effect was prevented by spironolactone (P < 0.05). Spironolactone also reduced the elevated SGK-1 expression in isoproterenol-treated rats. The observed reduction of the principal mediator of aldosterone cellular actions, SGK-1, by spironolactone in hearts from isoproterenol-treated rats suggests a role of mineralocorticoids in the cardiac hypertrophy, fibrosis, inflammation, oxidation and diastolic dysfunction induced by isoproterenol treatment in rats.

  4. Immuno-neutralization of circulating relaxin does not alter the breast cancer-protective action of parity in MNU-treated rats.

    PubMed

    Steinetz, Bernard G; Sherwood, O David; Lasano, Sally; Horton, Lori; Bosland, Maarten C

    2004-04-01

    Early pregnancy and childbirth protects women against future development of breast cancer by an unknown mechanism. Parity likewise reduces mammary cancer incidence in rats exposed to the carcinogen, N-methyl-N-nitrosourea (MNU), providing a model for the human phenomenon. We hypothesized that relaxin, a 6KD luteal mammotropic hormone of pregnancy, might be the anti-cancer pregnancy factor, and that induced relaxin deficiency during rat gestation would restore carcinogen sensitivity. Forty-one pregnant (age 50 days) and 25 age-matched virgin Sprague-Dawley rats were used. Relaxin deficiency was induced by injecting mouse monoclonal anti-rat relaxin antibody (MCA1) days 12-18 of gestation. Pregnant controls were injected with vehicle or mouse IgG on the same schedule. Because MCA1 disrupts parturition, all rats underwent cesarean section on day 22. At age 100 days, all rats were injected i.v. with MNU (50mg/Kg) and examined daily for tumors until euthanized at age 240 days. Mammary tumor incidence and frequency were significantly (p<0.01) reduced and tumor latency was increased (p<0.001) in primiparous as compared with virgin rats. However, tumor incidence, type, size and latency were similar in MCA1-treated and control primiparous rats. Thus, luteal relaxin does not appear to be the factor responsible for resistance to breast cancer.

  5. Limitation of adipose tissue enlargement in rats chronically treated with semicarbazide-sensitive amine oxidase and monoamine oxidase inhibitors.

    PubMed

    Carpéné, C; Abello, V; Iffiú-Soltész, Z; Mercier, N; Fève, Bruno; Valet, P

    2008-06-01

    Inhibition of semicarbazide-sensitive amine oxidases (SSAO) and monoamine oxidases (MAO) reduces fat deposition in obese rodents: chronic administration of the SSAO-inhibitor semicarbazide (S) in combination with pargyline (MAO-inhibitor) has been shown to reduce body weight gain in obese Zucker rats, while (E)-2-(4-fluorophenethyl)-3-fluoroallylamine, an SSAO- and MAO-B inhibitor, has been reported to limit weight gain in obese and diabetic mice. Our aim was to state whether such weight gain limitation could occur in non-obese, non-diabetic rats and to extend these observations to other amine oxidase inhibitors. Prolonged treatment of non-obese rats with a high dose of S (900 micromol kg(-1) day(-1)) reduced body weight gain and limited white adipose tissue enlargement. When chronically administered at a threefold lower dose, S also inhibited SSAO activity but not fat depot enlargement, suggesting that effects other than SSAO inhibition were involved in adipose tissue growth retardation. However, combined treatment of this lower dose of S with pargyline inhibited SSAO, MAO, energy intake, weight gain and fat deposition. Adipocytes from treated rats exhibited unchanged insulin responsiveness but impaired antilipolytic responses to amine oxidase substrates. Phenelzine clearly inhibited both MAO and SSAO when tested on adipocytes. Obese rats receiving phenelzine i.p. at 17 micromol kg(-1) day(-1) for 3 weeks, exhibited blunted MAO and SSAO activities in any tested tissue, diminished body weight gain and reduced intra-abdominal adipose tissue. Their adipocytes were less responsive to lipogenesis activation by tyramine or benzylamine. These observations suggest that SSAO inhibition is not sufficient to impair fat deposition. However, combined MAO and SSAO inhibition limits adiposity in non-obese as well as in obese rats.

  6. Rat Bite Fever

    MedlinePlus

    ... Ear Nose & Throat Emotional Problems Eyes Fever From Insects or Animals Genitals and Urinary Tract Glands & Growth ... Preventable Diseases Healthy Children > Health Issues > Conditions > From Insects or Animals > Rat Bite Fever Health Issues Listen ...

  7. Rat-bite fever

    MedlinePlus

    Streptobacillary fever; Streptobacillosis; Haverhill fever; Epidemic arthritic erythema; Spirillary fever; Sodoku ... Rat-bite fever can be caused by 2 different bacteria, Streptobacillus moniliformis or Spirillum minus. Both of these are found in ...

  8. 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...

  9. Sericin reduces serum cholesterol in rats and cholesterol uptake into Caco-2 cells.

    PubMed

    Limpeanchob, Nanteetip; Trisat, Kanittaporn; Duangjai, Acharaporn; Tiyaboonchai, Waree; Pongcharoen, Sutatip; Sutheerawattananonda, Manote

    2010-12-08

    A cholesterol lowering effect of sericin was investigated both in vivo and in vitro. Rats were dosed with cholesterol with and without sericin for 14 days. Non-high-density lipoprotein (HDL) and total serum cholesterols were reduced in rats fed high-cholesterol diet with all three tested doses of sericin (10, 100, and 1000 mg kg(-1) day(-1)). The potential mechanism of actions was determined by measuring the uptake of radiolabeled cholesterol into differentiated Caco-2 cells and cholesterol solubility in mixed lipid micelles. Concentration of sericin as low as 25 and 50 μg/mL inhibited 30% of cholesterol uptake into Caco-2 cells whereas no effect was found at higher concentration. Cholesterol micellar solubility was reduced in the presence of sericin. This study suggests the cholesterol lowering effect of sericin results from its inhibition of cholesterol absorption in intestinal cells and its reduction of cholesterol solubility in lipid micelles.

  10. Subdepressor dose of benidipine ameliorates diabetic cardiac remodeling accompanied by normalization of upregulated endothelin system in rats.

    PubMed

    Jesmin, Subrina; Hattori, Yuichi; Maeda, Seiji; Zaedi, Sohel; Sakuma, Ichiro; Miyauchi, Takashi

    2006-05-01

    We investigated whether benidipine, a long-acting calcium channel blocker (CCB), can normalize cardiac expression profiles of the endothelin (ET)-1 system in insulin-resistant diabetes. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of human Type 2 diabetes, were treated for 12 wk with vehicle or benidipine (3 mg.kg(-1).day(-1)). OLETF rats exhibited a significant increase in ET-1 in plasma and left ventricular (LV) tissues compared with nondiabetic controls. Expression of prepro-ET-1, ET-converting enzyme, and ET(A) and ET(B) receptors in LV tissues was also significantly higher in OLETF rats. The two MAPKs, JNK and p38MAPK, both of which are activated by ET-1, were more abundantly expressed in OLETF rat LV tissues. All these alterations were reversed to nondiabetic levels when OLETF rats were treated with the subdepressor dose of benidipine. Furthermore, benidipine therapy resulted in hindering cardiomyocyte hypertrophy and cardiac perivascular fibrosis in OLETF rats. The beneficial actions of benidipine at the subdepressor dose on cardiac remodeling in insulin-resistant diabetes may involve normalization of the upregulated ET-1 system.

  11. Prolongation of GFP-expressed skin graft after intrathymic injection of GFP positive splenocytes in adult rat

    NASA Astrophysics Data System (ADS)

    Hakamata, Yoji; Igarashi, Yuka; Murakami, Takashi; Kobayashi, Eiji

    2006-02-01

    GFP is a fluorescent product of the jellyfish Aequorea victoria and has been used for a variety of biological experiments as a reporter molecule. While GFP possesses advantages for the non-invasive imaging of viable cells, GFP-positive cells are still considered potential xeno-antigens. It is difficult to observe the precise fate of transplanted cells/organs in recipients without immunological control. The aim of this study was to determine whether intrathymic injection of GFP to recipients and the depletion of peripheral lymphocytes could lead to donor-specific unresponsiveness to GFP-expressed cell. LEW rats were administered intraperitoneally with 0.2 ml of anti-rat lymphocyte serum (ALS) 1 day prior to intrathymic injection of donor splenocytes or adeno-GFP vector. Donor cells and vector were non-invasively inoculated into the thymus under high frequency ultrasound imaging using an echo-guide. All animals subsequently received a 7 days GFP-expressed skin graft from the same genetic background GFP LEW transgenic rat. Skin graft survival was greater in rats injected with donor splenocytes (23.6+/-9.1) compared with adeno-GFP (13.0+/-3.7) or untreated control rats (9.5+/-1.0). Intrathymic injection of donor antigen into adult rats can induce donor-specific unresponsiveness. Donor cells can be observed for a long-term in recipients with normal immunity using this strategy.

  12. Longitudinal MR imaging study in the prediction of ischemic susceptibility after cerebral hypoperfusion in rats: Influence of aging and hypertension.

    PubMed

    Lee, J-T; Liu, H-L; Yang, J-T; Yang, S-T; Lin, J-R; Lee, T-H

    2014-01-17

    Our previous study has shown that aging and hypertension may alter apparent diffusion coefficient (ADC) and cerebral blood flow (CBF) and increase ischemic susceptibility in the non-ischemic rat brain. The present study wishes to further investigate whether aging and hypertension may influence cerebral diffusion/perfusion and increase ischemic susceptibility in the ischemic brain. Brain magnetic resonance (MR) imaging was examined 1day before and 1 and 7days after bilateral common carotid artery occlusion. Young and middle-aged normotensive Wistar-Kyoto rats and young and middle-aged spontaneously hypertensive rats (SHRs) were studied. Infarction occurred mainly in the parietal cortex and was larger in middle-aged SHRs than the other three groups (P<0.05). In pre-operation, ADC was higher and CBF was lower in middle-aged/hypertensive rats than young/normotensive rats (P<0.05). The ADC was higher in the parietal cortex of the rats with infarction at 7days when compared to the rats without infarction [receiver operating characteristic curve (ROC), P=0.001; binary logistic regression (BLR), P=0.006]. However, there was no difference in the hippocampus and thalamus. At day 1 post-operation, CBF reduced and ADC/CBF ratio elevated significantly in the parietal cortex of the rats with infarction when compared to the rats without infarction (CBF: ROC, P=0.002; BLR, P=0.017. ADC/CBF ratio: ROC, P=0.001; BLR, P=0.018). Our results demonstrated that pre-operation ADC and post-operation CBF and ADC/CBF ratio can be used as good MR markers in the prediction of ischemic susceptibility after cerebral hypoperfusion.

  13. Dietary inhibition of xanthine oxidase attenuates radiation-induced endothelial dysfunction in rat aorta.

    PubMed

    Soucy, Kevin G; Lim, Hyun Kyo; Attarzadeh, David O; Santhanam, Lakshmi; Kim, Jae Hyung; Bhunia, Anil K; Sevinc, Baris; Ryoo, Sungwoo; Vazquez, Marcelo E; Nyhan, Daniel; Shoukas, Artin A; Berkowitz, Dan E

    2010-05-01

    Radiation exposure is associated with the development of various cardiovascular diseases. Although irradiation is known to cause elevated oxidant stress and chronic inflammation, both of which are detrimental to vascular function, the molecular mechanisms remain incompletely understood. We previously demonstrated that radiation causes endothelial dysfunction and increased vascular stiffness by xanthine oxidase (XO) activation. In this study, we investigated whether dietary inhibition of XO protects against radiation-induced vascular injury. We exposed 4-mo-old rats to a single dose of 0 or 5 Gy gamma radiation. These rats received normal drinking water or water containing 1 mM oxypurinol, an XO inhibitor. We measured XO activity and superoxide production in rat aorta and demonstrated that both were significantly elevated 2 wk after radiation exposure. However, oxypurinol treatment in irradiated rats prevented aortic XO activation and superoxide elevation. We next investigated endothelial function through fluorescent measurement of nitric oxide (NO) and vascular tension dose responses. Radiation reduced endothelium-dependent NO production in rat aorta. Similarly, endothelium-dependent vasorelaxation in the aorta of irradiated rats was significantly attenuated compared with the control group. Dietary XO inhibition maintained NO production at control levels and prevented the development of endothelial dysfunction. Furthermore, pulse wave velocity, a measure of vascular stiffness, increased by 1 day postirradiation and remained elevated 2 wk after irradiation, despite unchanged blood pressures. In oxypurinol-treated rats, pulse wave velocities remained unchanged from baseline throughout the experiment, signifying preserved vascular health. These findings demonstrate that XO inhibition can offer protection from radiation-induced endothelial dysfunction and cardiovascular complications.

  14. The effect of sodium repletion on growth and protein turnover in sodium-depleted rats.

    PubMed

    Wassner, S J

    1991-07-01

    This study examines the consequences of sodium chloride supplementation to young rats previously made salt deficient by feeding them a sodium-deficient, chloride-replete diet. Salt-deficient rats received the test diet and distilled water for 10 days. As in our previous studies, rats cared for in this manner grew more slowly than rats fed the identical diet but allowed to drink 37 mM sodium chloride. On day 11, half of the salt-depleted animals received 37 mM sodium chloride in their drinking water. Sodium-deficient and supplemented rats were studied 1,2,5-6 and 11-12 days later. Urinary sodium rapidly rose from undetectable of 46 mEq/l urine within 1 day of supplementation and there was no further increase the next day, suggesting that extracellular fluid volumes were rapidly repleted. Food intake increased in the supplemented rats compared with the deficient animals but the difference in food intake equalled only 2.25 g/day for the first 2 days of supplementation. Over the last 12 days of the study, the slopes of both weight and length gains were equal in both the supplemented and the control group and significantly higher than those in the deficient rats. Over the course of the study, full catchup was not obtained in either length or weight. In addition to total weight and length gains, liver and kidney weights increased proportionately and by 5-6 days of supplementation were equivalent to the weights seen in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Effects of juice from Morinda citrifolia (Noni) on gastric emptying in male rats.

    PubMed

    Pu, Hsiao-Fung; Huang, Wei-Ju; Tseng, Wen-Min; Wang, Shyi-Wu; Liu, Yu-Wen; Doong, Ming-Long; Wang, Paulus S

    2004-12-31

    The effects of juice from Morinda citrifolia (noni) on gastric emptying, gastrointestinal transit, and plasma level of cholecystokinin (CCK) in rats were studied. Male rats were given noni by gavage at levels of 0.25, 1, or 4 ml/kg once per day for one or 7 days. The rats in the control group were given water, while the rats in the experimental group were fasted overnight before measurement of gastrointestinal motility. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal (10%) and Na251CrO4 (0.5 microCi/ml). Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Then, gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Finally, blood samples were collected for measurement of CCK by radioimmunoassay. The administration of noni at 0.25 ml/kg, but not at 1 ml/kg and 4 ml/kg, for 1 day significantly inhibited gastric emptying. In contrast, gastric emptying was significantly inhibited by oral noni (0.25, 1, or 4 ml/kg) for 7 days. Intraperitoneal injection of lorglumide (5 or 10 mg/kg), a selective CCK1 receptor antagonist, effectively attenuated the noni-induced inhibition of gastric emptying. The intestinal transit and body weight, food intake, water intake, urine volume as well as feces weight were not altered by the administration of noni either acutely or chronically, but the administration of oral noni (1 ml/kg) for 7 days increased the level of plasma CCK in male rats. These results suggest that oral noni inhibits gastric emptying in male rats via a mechanism involving stimulation of CCK secretion and CCK1 receptor activation.

  16. [MK-801 or DNQX reduces electroconvulsive shock-induced impairment of learning-memory and hyperphosphorylation of Tau in rats].

    PubMed

    Liu, Chao; Min, Su; Wei, Ke; Liu, Dong; Dong, Jun; Luo, Jie; Liu, Xiao-Bin

    2012-08-25

    This study explored the effect of the excitatory amino acid receptor antagonists on the impairment of learning-memory and the hyperphosphorylation of Tau protein induced by electroconvulsive shock (ECT) in depressed rats, in order to provide experimental evidence for the study on neuropsychological mechanisms improving learning and memory impairment and the clinical intervention treatment. The analysis of variance of factorial design set up two intervention factors which were the electroconvulsive shock (two level: no disposition; a course of ECT) and the excitatory amino acid receptor antagonists (three level: iv saline; iv NMDA receptor antagonist MK-801; iv AMPA receptor antagonist DNQX). Forty-eight adult Wistar-Kyoto (WKY) rats (an animal model for depressive behavior) were randomly divided into six experimental groups (n = 8 in each group): saline (iv 2 mL saline through the tail veins of WKY rats ); MK-801 (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats) ; DNQX (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats ); saline + ECT (iv 2 mL saline through the tail veins of WKY rats and giving a course of ECT); MK-801 + ECT (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats and giving a course of ECT); DNQX + ECT (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats and giving a course of ECT). The Morris water maze test started within 1 day after the finish of the course of ECT to evaluate learning and memory. The hippocampus was removed from rats within 1 day after the finish of Morris water maze test. The content of glutamate in the hippocampus of rats was detected by high performance liquid chromatography. The contents of Tau protein which included Tau5 (total Tau protein), p-PHF1(Ser396/404), p-AT8(Ser199/202) and p-12E8(Ser262) in the hippocampus of rats were detected by immunohistochemistry staining (SP) and Western blot. The results showed that ECT and the glutamate ionic receptor blockers (NMDA receptor antagonist MK-801 and

  17. Role of connective tissue growth factor in vascular and renal damage associated with hypertension in rats. Interactions with angiotensin II.

    PubMed

    de las Heras, Natalia; Ruiz-Ortega, Marta; Rupérez, Mónica; Sanz-Rosa, David; Miana, María; Aragoncillo, Paloma; Mezzano, Sergio; Lahera, Vicente; Egido, Jesus; Cachofeiro, Victoria

    2006-12-01

    We have evaluated the role of connective tissue growth factor (CTGF) in vascular and renal damage associated with hypertension and possible interactions with angiotensin II (Ang II). Spontaneously hypertensive rats (SHR) were treated with either the Ang II receptor antagonist candesartan (C;2 mg/Kg(-1)/day(-1)) or antihypertensive triple therapy (TT; in mg/Kg(-1)/day(-1);20 hydralazine +7 hydrochlorothiazide +0.15 reserpine) for 10 weeks. Wistar Kyoto rats were used as a normotensive control group. Hypertension was associated with an increase in aortic media area, media-to-lumen ratio and collagen density. Kidneys from SHR showed minimum renal alterations. Aorta and renal gene expression and immunostaining of CTGF were higher in SHR. Candesartan decreased arterial pressure, aortic media area, media-to-lumen ratio and collagen density. However, although arterial pressure decrease was comparable for both treatments, TT partially reduced these parameters. Candesartan-treated rats showed lower levels of vascular CTGF expression, aortic media area, media-to-lumen ratio and collagen density than TT-treated animals. Treatments improve renal damage and reduce renal gene expression and CTGF immunostaining in SHR in a similar manner. The results show that vascular and renal damage is associated with stimulation of CTGF gene and protein content. These results also might suggest that CTGF could be one downstream mediator of Ang II in hypertension-associated organ damage in SHR.

  18. Differential mRNA expression of acetylcholinesterase in the central nervous system of rats with acute and chronic exposure of sarin & physostigmine.

    PubMed

    Bansal, Iti; Waghmare, C K; Anand, T; Gupta, A K; Bhattacharya, B K

    2009-07-01

    A time-course study was carried out to measure the acetylcholinesterase (AChE) gene expression in the brain of female rats exposed to different doses of sarin and physostigmine. Short-term effects were studied with an acute single subcutaneous dose (s.c.) of 80 microg kg(-1) (0.5 x LD(50)) sarin. Cortex and cerebellum showed a significant decline in AChE mRNA expression at 2.5, 24 and 72 h. Biochemical studies showed that plasma butrylcholinesterase (BChE) and brain AChE activities were significantly decreased at 2.5 h, which came back to near control values by 24 h in both cases. For long-term chronic studies, three groups of female rats received daily doses of physostigmine (0.1 mg kg(-1) day(-1)) intramuscularly (i.m.), sarin (15 microg kg(-1) day(-1)) s.c. independently and a combined dose of physostigmine (i.m.) (0.1 mg kg(-1) day(-1)) followed by sarin (s.c.) (15 microg kg(-1) day(-1)) continuously for 30 days. Differential AChE mRNA levels in cortex and cerebellum of rat brain were observed after 30 days and after a lag period of another 30 days with no further administration. Plasma (BChE) and brain (AChE) showed irregular inhibition profile in biochemical studies at 30 days and returned to control levels after 60 days. The acute single subcutaneous administration of sarin for short-term as well as chronic long-term studies showed that AChE inhibition alone does not lead to observed changes in mRNA expression of AChE gene. These observations further suggest that route of administration as well as dose exposure regimen also contributes to the regulation of AChE mRNA expression.

  19. [Fatal rat bites].

    PubMed

    Yanai, O; Goldin, L; Hiss, J

    1999-04-15

    We present a rare case of infant death due to blood loss resulting from multiple rat bites. Domestic dogs and cats cause most animal bites. Bites of a house rat usually cause bacterial infection, successfully treated with antibiotics. There is little information about death due to house rat bites. Since the wounds they cause tend to occur post-mortem, they are usually wedged, clean and without subcutaneous bleeding. An 11-week-old, malnourished infant girl was bitten to death while sleeping in her mother's bed in a rat-infested home. The infant's clothing was covered with blood, parts of her face were missing and marks of gnawing were present on her neck and extremities. There was subcutaneous bleeding around the wounds indicating that they were inflicted while the child was alive. Autopsy findings revealed profound blood loss. We conclude that a combination of low socio-economic status, severe failure to thrive, and poor hygiene in a rat-infested environment contributed to the fatal outcome in this attack.

  20. Phosgene- and chlorine-induced acute lung injury in rats: comparison of cardiopulmonary function and biomarkers in exhaled breath.

    PubMed

    Luo, Sa; Trübel, Hubert; Wang, Chen; Pauluhn, Jürgen

    2014-12-04

    This study compares changes in cardiopulmonary function, selected endpoints in exhaled breath, blood, and bronchoalveolar lavage fluid (BAL) following a single, high-level 30-min nose-only exposure of rats to chlorine and phosgene gas. The time-course of lung injury was systematically examined up to 1-day post-exposure with the objective to identify early diagnostic biomarkers suitable to guide countermeasures to accidental exposures. Chlorine, due to its water solubility, penetrates the lung concentration-dependently whereas the poorly water-soluble phosgene reaches the alveolar region without any appreciable extent of airway injury. Cardiopulmonary endpoints were continually recorded by telemetry and barometric plethysmography for 20h. At several time points blood was collected to evaluate evidence of hemoconcentration, changes in hemostasis, and osteopontin. One day post-exposure, protein, osteopontin, and cytodifferentials were determined in BAL. Nitric oxide (eNO) and eCO2 were non-invasively examined in exhaled breath 5 and 24h post-exposure. Chlorine-exposed rats elaborated a reflexively-induced decreased respiratory rate and bradycardia whereas phosgene-exposed rats developed minimal changes in lung function but a similar magnitude of bradycardia. Despite similar initial changes in cardiac function, the phosgene-exposed rats showed different time-course changes of hemoconcentration and lung weights as compared to chlorine-exposed rats. eNO/eCO2 ratios were most affected in chlorine-exposed rats in the absence of any marked time-related changes. This outcome appears to demonstrate that nociceptive reflexes with changes in cardiopulmonary function resemble typical patterns of mixed airway-alveolar irritation in chlorine-exposed rats and alveolar irritation in phosgene-exposed rats. The degree and time-course of pulmonary injury was reflected best by eNO/eCO2 ratios, hemoconcentration, and protein in BAL. Increased fibrin in blood occurred only in chlorine

  1. Celecoxib, but not indomethacin, ameliorates the hypertensive and perivascular fibrotic actions of cyclosporine in rats: Role of endothelin signaling

    SciTech Connect

    El-Mas, Mahmoud M.; Helmy, Maged W.; Ali, Rabab M.; El-Gowelli, Hanan M.

    2015-04-01

    The immunosuppressant drug cyclosporine (CSA) is used with nonsteroidal antiinflammatory drugs (NSAIDs) in arthritic conditions. In this study, we investigated whether NSAIDs modify the deleterious hypertensive action of CSA and the role of endothelin (ET) receptors in this interaction. Pharmacologic, protein expression, and histopathologic studies were performed in rats to investigate the roles of endothelin receptors (ET{sub A}/ET{sub B}) in the hemodynamic interaction between CSA and two NSAIDs, indomethacin and celecoxib. Tail-cuff plethysmography measurements showed that CSA (20 mg kg{sup −1} day{sup −1}, 10 days) increased systolic blood pressure (SBP) and heart rate (HR). CSA hypertension was associated with renal perivascular fibrosis and divergent changes in immunohistochemical signals of renal arteriolar ET{sub A} (increases) and ET{sub B} (decreases) receptors. While these effects of CSA were preserved in rats treated concomitantly with indomethacin (5 mg kg{sup −1} day{sup −1}), celecoxib (10 mg kg{sup −1} day{sup −1}) abolished the pressor, tachycardic, and fibrotic effects of CSA and normalized the altered renal ET{sub A}/ET{sub B} receptor expressions. Selective blockade of ET{sub A} receptors by atrasentan (5 mg kg{sup −1} day{sup −1}) abolished the pressor response elicited by CSA or CSA plus indomethacin. Alternatively, BQ788 (ET{sub B} receptor blocker, 0.1 mg kg{sup −1} day{sup −1}) caused celecoxib-sensitive elevations in SBP and potentiated the pressor response evoked by CSA. Together, the improved renovascular fibrotic and endothelin receptor profile (ET{sub A} downregulation and ET{sub B} upregulation) mediate, at least partly, the protective effect of celecoxib against the hypertensive effect of CSA. Clinically, the use of celecoxib along with CSA in the management of arthritic conditions might provide hypertension-free regimen. - Highlights: • Chronic CSA causes hypertension and renal perivascular fibrosis in rats.

  2. Neuronal network disturbance after focal ischemia in rats

    SciTech Connect

    Kataoka, K.; Hayakawa, T.; Yamada, K.; Mushiroi, T.; Kuroda, R.; Mogami, H. )

    1989-09-01

    We studied functional disturbances following left middle cerebral artery occlusion in rats. Neuronal function was evaluated by (14C)2-deoxyglucose autoradiography 1 day after occlusion. We analyzed the mechanisms of change in glucose utilization outside the infarct using Fink-Heimer silver impregnation, axonal transport of wheat germ agglutinin-conjugated-horseradish peroxidase, and succinate dehydrogenase histochemistry. One day after occlusion, glucose utilization was remarkably reduced in the areas surrounding the infarct. There were many silver grains indicating degeneration of the synaptic terminals in the cortical areas surrounding the infarct and the ipsilateral cingulate cortex. Moreover, in the left thalamus where the left middle cerebral artery supplied no blood, glucose utilization significantly decreased compared with sham-operated rats. In the left thalamus, massive silver staining of degenerated synaptic terminals and decreases in succinate dehydrogenase activity were observed 4 and 5 days after occlusion. The absence of succinate dehydrogenase staining may reflect early changes in retrograde degeneration of thalamic neurons after ischemic injury of the thalamocortical pathway. Terminal degeneration even affected areas remote from the infarct: there were silver grains in the contralateral hemisphere transcallosally connected to the infarct and in the ipsilateral substantia nigra. Axonal transport study showed disruption of the corticospinal tract by subcortical ischemia; the transcallosal pathways in the cortex surrounding the infarct were preserved. The relation between neural function and the neuronal network in the area surrounding the focal cerebral infarct is discussed with regard to ischemic penumbra and diaschisis.

  3. Cardioprotective effect of cannabidiol in rats exposed to doxorubicin toxicity.

    PubMed

    Fouad, Amr A; Albuali, Waleed H; Al-Mulhim, Abdulruhman S; Jresat, Iyad

    2013-09-01

    The potential protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against doxorubicin cardiotoxicity in rats. Cardiotoxicity was induced by six equal doses of doxorubicin (2.5mgkg(-1) i.p., each) given at 48h intervals over two weeks to achieve a total dose of 15mgkg(-1). Cannabidiol treatment (5mgkg(-1)/day, i.p.) was started on the same day of doxorubicin administration and continued for four weeks. Cannabidiol significantly reduced the elevations of serum creatine kinase-MB and troponin T, and cardiac malondialdehyde, tumor necrosis factor-α, nitric oxide and calcium ion levels, and attenuated the decreases in cardiac reduced glutathione, selenium and zinc ions. Histopathological examination showed that cannabidiol ameliorated doxorubicin-induced cardiac injury. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in cardiac tissue of doxorubicin-treated rats. These results indicate that cannabidiol represents a potential protective agent against doxorubicin cardiac injury.

  4. Erdosteine prevents doxorubicin-induced cardiotoxicity in rats.

    PubMed

    Yagmurca, Murat; Fadillioglu, Ersin; Erdogan, Hasan; Ucar, Muharrem; Sogut, Sadik; Irmak, M Kemal

    2003-10-01

    The clinical use of doxorubicin (Dxr) is limited by its cardiotoxic effects which are mediated by oxygen radicals. The purpose of this study was to investigate in vivo protective effects of erdosteine, an antioxidant agent because of its secondary active metabolites in vivo, against the cardiotoxicity induced by Dxr in rats. Three groups of male Sprague-Dawley rats (60 days old) were used. Group 1 was untreated group used as control; the other groups were treated with Dxr (single i.p. dosage of 20 mg kg(-1) b.wt.) or Dxr plus erdosteine (10 mg kg(-1) day(-1), orally), respectively. Erdosteine or oral saline treatment was done starting 2 days before Dxr for 12 days. The analyses were done at the 10th day of Dxr treatment. The protein carbonyl content, the activities of myeloperoxidase, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK) as well as heart rate and blood pressures were significantly increased in Dxr group in comparison with the other groups. However, pulse pressure was decreased in Dxr group. The body and heart weights were decreased in both Dxr administered groups in comparison with control group. Disorganization of myocardial histology, picnotic nuclei, edema, and increase in collagen content around vessels were seen in the slides of Dxr group, whereas normal myocardial microscopy was preserved in Dxr plus erdosteine group. Collectively, these in vivo hemodynamic, enzymatic and morphologic studies provide an evidence for a possible prevention of cardiac toxicity in Dxr-treated patients.

  5. Effects of fluoxetine on memory under forced treadmill exercise conditions in male rats

    PubMed Central

    Jafary, Leila; Reisi, Parham; Naghsh, Nooshin

    2015-01-01

    Background: Studies show inconsistent effects of forced exercise on cognitive processes. These differences are probably due to the stress of coercion in forced exercise. Because fluoxetine is used to treat complications caused by stress, this study aimed to evaluate the effects of fluoxetine on memory in rats under forced treadmill exercise. Materials and Methods: Experimental groups were the control, the control exercise, the fluoxetine, and the fluoxetine exercise. The exercise program was treadmill running at 22 m/min, 0° inclination for 50 min/day, 6 days/week, for 4 weeks. Fluoxetine (5 mg/kg) was injected 30 min before treadmill. Morris water maze and passive avoidance learning tests were used for evaluation of memory. Acquisition phase of both tests were performed before interventions and memory was evaluated 1-day and 1-week after the last session of exercise and treatments. Results: Our data showed that forced exercise impaired performance in passive avoidance learning test (P < 0.05 and P < 0.01, 1-day and 1-week after the last session of exercise and treatments, respectively). Spatial memory was only impaired after 1-week in the exercise group. Fluoxetine improved spatial memory after 1-day in the control group. However, it had no significant effects on memory in the exercise group. Conclusion: The data correspond to the possibility that forced treadmill exercise can cause stress, and thereby cause damage to memory. The present results suggest that although fluoxetine may improve memory in intact rats but it cannot prevent damages that are caused by forced exercise. PMID:26645020

  6. Assessment of pulmonary toxicity of MgO nanoparticles in rats.

    PubMed

    Gelli, Kiranmai; Porika, Mahendar; Anreddy, Rama Narsimha Reddy

    2015-03-01

    In this study, we have evaluated the pulmonary toxicity of MgO nanoparticles (MgO NPs) in rats following their exposure. NPs in phosphate buffered saline + 1% Tween 80 were exposed via intratracheal instillation at a doses of 1 mg/kg or 5 mg/kg into rat lungs and evaluated for various tissue damage markers like alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid and histopathology of lungs at 1, 7, and 30 days of post-exposure intervals. A dose-dependant increase in ALP and LDH activity was observed in BAL fluids of rat lungs than sham control at all post-exposure periods (P <0.05), and a dose-dependant infiltration of interstitial lymphocytes, peribronchiolar lymphocytic infiltration, and dilated and/or congested vessels at 1 day post-exposure period, worsened at 1 week period, and were reduced at 1 month at histology, indicating the pulmonary toxicity of MgO NPs. In conclusion, MgO NPs exposure produced a dose-dependent pulmonary toxicity in rats and was comparable with that of Quartz particles.

  7. Gene Expression Profiling in Lung Tissues from Rat Exposed to Lunar Dust Particles

    NASA Technical Reports Server (NTRS)

    Zhang, Ye; Lam, Chiu-Wing; Zalesak, Selina M.; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Scully, Robert R.; Williams, Kyle; Wu, Honglu; James, John T.

    2014-01-01

    The Moon's surface is covered by a layer of fine, reactive dust. Lunar dust contain about 1-2% of very fine dust (< 3 micron), that is respirable. The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues from rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m(exp 3) of lunar dust. Five rats per group were euthanized 1 day, and 3 months after the last inhalation exposure. The total RNAs were isolated from lung tissues after being lavaged. The Agilent Rat GE v3 microarray was used to profile global gene expression (44K). The genes with significant expression changes are identified and the gene expression data were further analyzed using various statistical tools.

  8. Triamcinolone acetonide protects the rat retina from STZ-induced acute inflammation and early vascular leakage.

    PubMed

    Kim, Y H; Choi, M Y; Kim, Y S; Park, C H; Lee, J H; Chung, I Y; Yoo, J M; Choi, W S; Cho, G J; Kang, S S

    2007-09-15

    Streptozotocin (STZ) has been commonly used to induce in vivo and in vitro hyperglycemic diabetes and its toxicity leads to inflammation and vascular injury. Triamcinolone acetonide (TA), as an anti-angiogenic/anti-inflammatory drug, is clinically used to improve the visual acuity in neovascular and edematous ocular diseases. The aim of this study was to investigate the effect of TA on early inflammation and vascular leakage in the retina of STZ-induced hyperglycemic rats. Hyperglycemia was induced in 8-week-old male Sprague-Dawley (SD) rats by a single intraperitoneal injection of STZ (65 mg/kg); only rats with blood glucose levels >13.9 mmol/l 1 day after STZ injection were included in STZ-hyperglycemic group. Sex- and age-matched SD rats injected with buffer were used as the control group. One day before STZ and buffer injection, 2 microl TA (4 mg/ml in saline) and 2 microl saline were intravitreal-injected into the right and the left eyes of rats, respectively. Retinal vascular leakage was measured using the Evans-blue method. Changes in pro-inflammatory target genes, such as tumor necrotic factor (TNF)-alpha, intracellular adhesion molecule (ICAM)-1, and vascular endothelial growth factor (VEGF) were assessed by immunoblottings, immunostaining, and ELISA analyses. Vascular hyperleakage and up-regulation of most pro-inflammatory genes peaked within a few days after STZ injection and had recovered. However, these changes were blocked by TA pretreatment. Our data suggest that TA controls STZ-induced early vascular leakage and temporary pro-inflammatory signals in the rat retina.

  9. Anodal transcranial direct current stimulation relieves the unilateral bias of a rat model of Parkinson's disease.

    PubMed

    Li, Yiyan; Tian, Xulong; Qian, Long; Yu, Xuehong; Jiang, Weiwei

    2011-01-01

    The unilaterally lesioned rat model of Parkinson's disease which fails to orient to the food stimuli presented on the contralateral side of its preferential side of body could be induced by the injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB). We employed transcranial direct current stimulation (tDCS, current intensity: 80 μA, and 40 μA; anodal electrode area: 3.14 mm(2); stimulation time: 30 minutes) over the M1 area to relieve the ipsilateral bias in the rat model. A corridor test was set to count the ipsilateral bias of the rats. In this experiment, 30 Sprague-Dawley rats (80 μA: n = 8, 40 μA: n = 8, sham: n = 7, healthy control: n = 7) were chosen for the corridor test and the tDCS session. The lesioned rats exhibited increased ipsilateral bias 4 weeks after the lesion surgery (P < 0.01), and the anodal tDCS with the active electrode on the lesioned side relieved the ipsilateral bias significantly (P < 0.01) immediately after the surgery and the improvement lasted for nearly 1 day. The rats in the group of 80 μA exhibited more significant changes than the 40 μA group after one day. After all the experiments, the histological process showed no neurotrauma led by the tDCS. In conclusion, the modulatory function of the cortical excitability of the tDCS may awaken the compensatory mechanisms and the response mechanisms which modulate the loss of the brain function. Further studies should be done to provide more evidence about the assumption.

  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. The fate of dienochlor administered orally and dermally to rats.

    PubMed

    Quistad, G B; Mulholland, K M; Skinner, W S

    1986-09-15

    Within four days of receiving a single oral dose (1 mg/kg) of [U-ring-14C]dienochlor [bis(pentachloro-2,4-cyclopentadien-1-yl)] female rats excreted 2 and 88% of the applied 14C in urine and feces, respectively. Metabolites could not be identified and the preponderance of the fecal radioactivity consisted of unextractable 14C-labeled residues. Within 1 day virtually all of the dienochlor had been degraded by rats, with only traces of parent dienochlor in excreta and tissues. After four days only 2% of the applied dose remained in tissues (mainly kidney, liver, and gastrointestinal tract). Pharmacokinetic studies with blood plasma and bile showed dienochlor (and/or its metabolites) to be poorly absorbed. Rats were exposed dermally for 24 hr to [14C]dienochlor formulated as Pentac WP miticide both as an aqueous suspension and as an undiluted wettable powder. Half of the dose adhered to the skin and the other half was found in gauze patches used to protect the treated skin. After a 24-hr exposure over 60% of the radiolabel that adhered to skin was removed by washing with an aqueous soap solution and 86% of this rinsing solution was unmetabolized dienochlor. The dienochlor and its metabolites were transported inefficiently from the application site; only 1% of the applied dose was detected in urine plus feces and less than or equal to 0.2% in tissues. With application rates that simulate field exposure by humans, the actual residue of dienochlor and metabolites in skin (i.e., not removable by washing) is about thirteen times higher following exposure to dienochlor as undiluted wettable powder than as an aqueous suspension.

  12. Fate of avermectin B sub 1a in rats

    SciTech Connect

    Maynard, M.S.; Halley, B.A.; Green-Erwin, M.; Alvaro, R.; Gruber, V.F.; Hwang, Shuchen; Bennett, B.W.; Wislocki, P.G. )

    1990-03-01

    Male and female rats were administered ({sup 3}H)avermectin B{sub 1a} or a mixture of ({sup 3}H)- and ({sup 14}C)avermectin B{sub 1a} as a single oral dosage at 1.4 or 0.14 mg/kg. Most of the dose (69-82%) was recovered in the feces, with 1% or less found in the urine. The total residue levels in liver, kidney, muscle, and fat tissues were <5.3 ppm at 1 day after dosing and essentially depleted within 7 days after dosing. For all tissues analyzed, the depletion half-life of the total radioactive residue was approximately 1.2 days, while the half-life of avermectin B{sub 1a} was between 0.6 and 1.0 day. The tissue residue was shown to be qualitatively similar between the tissue type, dose, sex, pretreatment with or without unlabeled avermectin B{sub 1a}, and label ({sup 3}H or {sup 14}C). A major metabolite (3{double prime}-desmethyl) and a minor metabolite (24-hydroxymethyl) isolated and identified from rat liver microsomal incubations of avermectin B{sub 1a} were identified in the rat tissues. These two metabolites and avermectin B{sub 1a} accounted for > 85% of the tissue residue. The fate of ({sup 3}H)avermectin B{sub 1a} was the same as the fate of ({sup 14}C)avermectin B{sub 1a}, demonstrating the stability of the {sup 3}H label on avermectin B{sub 1a} and the validity of its use in animal metabolism studies.

  13. Erdosteine modulates radiocontrast-induced hepatotoxicity in rat.

    PubMed

    Yesildağ, Ahmet; Ozden, Ahmet; Yilmaz, H Ramazan; Uz, Efkan; Ağackiran, Yetkin; Yesildağ, Mihrican; Yilmaz, Nigar; Sirmali, Rana; Vural, Hüseyin; Naziroğlu, Mustafa

    2009-04-01

    It has been suggested that reactive oxygen species (ROS) plays an important role in radio contrast media (RCM)-induced ischemia reperfusion tissue injury although antioxidants may have protective effects on the injury. We investigated the effects of erdosteine as an antioxidant agent on RCM-induced liver toxicity in rats by evaluation of lipid peroxidation (as TBARS), catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) values and histological evaluation. Twenty-one rats were equally divided into three groups as follows: control, RCM, and RCM plus erdosteine. RCM was intraperitoneally administered for 1 day. Erdosteine was administered orally for 2 days after RCM administration. Liver samples were taken from the rats and they homogenized in a motor-driven tissue homogenizer. TBARS levels were significantly (p < 0.005) higher in RCM group than in control although SOD activities significantly (p < 0.05) decreased in RCM group. TBARS levels were lower in RCM plus erdosteine group than in control although SOD activity and GSH level increased (p < 0.05) in liver as compared to RCM alone. Erdosteine showed also histopathological protection (p < 0.0001) against RCM induced hepatotoxicity. GSH-Px and CAT activities were not statistically changed by the erdosteine. According to our results, it can be concluded that radiocontrast media can induce oxidative stress in liver as suggested by previous studies. Erdosteine seems to be protective agent on the radiocontrast media-induced liver toxicity by inhibiting the production of ROS via the enzymatic antioxidant system.

  14. Beneficial effects of ventromedial hypothalamus (VMH) lesioning on function and morphology of the liver after hepatectomy in rats.

    PubMed

    Lee, Eun Young; Inoue, Shuji; Senoo, Akira; Shimizu, Hiroyuki; Suzuki, Yoko; Ishizuka, Noriko; Imazeki, Nobuo; Sasaki, Kahoru; Kako, Masako; Osaka, Toshimasa; Miki, Takashi

    2011-11-03

    Liver has a high regenerative capacity and restores its mass and function shortly after partial hepatectomy through increased proliferation and metabolic modification of hepatocytes. The proliferation of hepatocytes can be triggered by its mass reduction after hepatectomy or by the neural factors including lesioning of the ventromedial hypothalamus (VMH). In the present study, we examined the effect of VMH lesioning on liver regeneration in hepatectomized rats by evaluating liver function and morphology. We found that functional deficits caused by partial hepatectomy [prolonged prothrombin time (PT), increased indocyanine green (ICG) retention, and decrease in PAS (periodic Acid-Schiff staining)-positive hepatocytes] were restored by VMH lesioning at 1 week after the surgery, whereas these alterations disappeared at 4 weeks. Morphologically, lipid microdroplets, which are considered to be important for maintaining contiguous liver function via supplying fuel for cell proliferation, were found to accumulate in hepatocytes of the hepatectomized rats at early period (1 day) after partial hepatectomy. Interestingly, such lipid microdroplets were also detected in the VMH lesioned rats and the more abundantly in the VMH lesioned, hepatectomized rats up to 1 week after the surgery. In conclusion, our results suggest that VMH lesioning in rats promotes recovery of liver anatomically and functionally after partial hepatectomy by promoting cell proliferation process.

  15. Effects of grape seed polyphenols on oxidative damage in liver tissue of acutely and chronically exercised rats.

    PubMed

    Belviranlı, Muaz; Gökbel, Hakkı; Okudan, Nilsel; Büyükbaş, Sadık

    2013-05-01

    The objective of the present study was to investigate the effects of grape seed extract (GSE) supplementation on oxidative stress and antioxidant defense markers in liver tissue of acutely and chronically exercised rats. Rats were randomly assigned to six groups: Control (C), Control Chronic Exercise (CE), Control Acute Exercise (AE), GSE-supplemented Control (GC), GSE-supplemented Chronic Exercise(GCE) and GSE-supplemented Acute Exercise (GAE). Rats in the chronic exercise groups were subjected to a six-week treadmill running and in the acute exercise groups performed an exhaustive running. Rats in the GSE supplemented groups received GSE (100 mg.kg(-1) .day(-1) ) in drinking water for 6 weeks. Liver tissues of the rats were taken for the analysis of malondialdehyde (MDA), nitric oxide (NO) levels and total antioxidant activity (AOA) and xanthine oxidase (XO) activities. MDA levels decreased with GSE supplementation in control groups but increased in acute and chronic exercise groups compared to their non-supplemented control. NO levels increased with GSE supplementation. XO activities were higher in AE group compared to the CE group. AOA decreased with GSE supplementation. In conclusion, while acute exercise triggers oxidative stress, chronic exercise has protective role against oxidative stress. GSE has a limited antioxidant effect on exercise-induced oxidative stress in liver tissue.

  16. The effect of sevoflurane anesthesia on cognitive function and the expression of Insulin-like Growth Factor-1 in CA1 region of hippocampus in old rats.

    PubMed

    Peng, Sheng; Zhang, Yan; Sun, Da-Peng; Zhang, Deng-Xin; Fang, Qiang; Li, Guo-Jun

    2011-02-01

    To investigate the effects of sevoflurane on cognitive function in old Sprague-Dawley (SD) rats and the expression of insulin-like growth factor-1 (IGF-1) in CA1 region of hippocampus. Forty Sprague-Dawley rats of 12 months old were randomly divided into five groups: the normal control group; 1.5% sevoflurane I group (be tested after received 1.5% sevoflurane for 1 day); 1.5% sevoflurane II group (be tested after received 1.5% sevoflurane for 7 day); 3.0% sevoflurane I group (be tested after received 3.0% sevoflurane for 1 day) and 3.0% sevoflurane II group (be tested after received 3.0% sevoflurane for 7 day). All SD rats were received 1.5 or 3.0% sevoflurane in a special glass anesthesia box for 2 h respectively, except for the normal control group. Y-maze was used to test the ability of learning and memory after being received sevoflurane for 1 or 7 days at the same moment portion. The altered expression level of IGF-1 in the hippocampus was tested to compare its transcripts by RT-PCR analysis. The results showed that 3% sevoflurane induced the decline of cognitive function and significantly deceased the IGF-1 expression at mRNA levels at 1 day in the 3.0% sevoflurane I group when compared with the normal control group. However, there were no significant difference among the other groups when compared with normal control group. Therefore, administration of sevoflurane might temporally affect the ability of cognitive function of rats through suppressing the IGF-1 expression at mRNA levels in hippocampus.

  17. 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.

  18. Culturing rat hippocampal neurons.

    PubMed

    Audesirk, G; Audesirk, T; Ferguson, C

    2001-01-01

    Cultured neurons are widely used to investigate the mechanisms of neurotoxicity. Embryonic rat hippocampal neurons may be grown as described under a wide variety of conditions to suit differing experimental procedures, including electrophysiology, morphological analysis of neurite development, and various biochemical and molecular analyses.

  19. 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

    2015-09-28

    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.

  20. 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

  1. Expression of tranferrin receptors in the pineal gland of postnatal and adult rats and its alteration in hypoxia and melatonin treatment.

    PubMed

    Kaur, C; Sivakumar, V; Ling, E A

    2007-02-01

    Transferrin receptors (Tfrc) are membrane bound glycoproteins which function to mediate cellular uptake of iron from transferrin. We examined expression of Tfrc in the pineal gland of rats of different ages from 1 day to 12 weeks. The mRNA and protein expression of Tfrc increased up to 6 weeks of age and decreased in 12 week rats. Tfrc immunoreactivity was observed on pinealocytes and macrophages/microglia. By immunoelectron microscopy, the immunoreaction in pinealocytes was observed in the cytosol, on mitochondria and plasma membrane whereas in macrophages/microglia it was localized on the plasma membrane in 1-day to 2-week old rats. In older rats, the immunoreaction product in pinealocytes was associated with the plasma membrane and mitochondria only. Iron localization was observed in pinealocytes as well as macrophages/microglia. It is suggested that Tfrc are required for uptake of iron for cell proliferation and maturation in the pineal gland upto 6 weeks of age. The significance of Tfrc expression on mitochondria is speculative. They may be involved in iron transport to the mitochondria or for regulation of the secretory activity of pinealocytes. The TfrcmRNA and protein expression increased significantly in response to hypoxia in 12-week rats and this coincided with intense iron staining of the pinealocytes and macrophages/microglia. It is concluded that increased expression of Tfrc in response to hypoxia leads to excess cellular uptake of iron which may be damaging to the cells. Melatonin administration in hypoxic rats may prove to be beneficial as it reduced the Tfrc expression.

  2. Increases in the density of parvalbumin-immunoreactive neurons in anterior cingulate cortex of amphetamine-withdrawn rats: evidence for corticotropin-releasing factor in sustained elevation.

    PubMed

    Mohila, Carrie Ann; Onn, Shao-Pii

    2005-03-01

    We previously reported synchronization of pyramidal neurons within prefrontal cortex of rats repeatedly exposed to amphetamine (AMPH). To test the hypothesis that cortical synchronization may be related to changes in local GABA signaling, we used antibodies specific for parvalbumin (PV), calbindin D28k (CB) and calretinin (CR) as selective labels for three distinct GABA interneuron classes in the anterior cingulate cortex (ACC) of similarly treated rats. We observed a selective increase in the density of PV-immunoreactive (ir), but not CB-ir or CR-ir, neurons in the ACC of AMPH-treated rats at both 1 day and 7 day withdrawal. Increased density of PV-ir GABA interneurons in the ACC at 1 day withdrawal was reproduced in rats repeatedly injected with apomorphine or with SKF-38393. Thus, the critical role of DA receptors during AMPH exposure is evident. However, DA receptor activation did not appear to account for the PV up-regulation in AMPH-treated rats at 7 day withdrawal. Significantly higher numbers of pericellular basket-like puncta immunoreactive for corticotropin-releasing factor (CRF) were observed in the ACC of AMPH rats at 7 day withdrawal. Combined dual immunofluorescence and confocal microscopy further revealed that CRF-ir puncta made possible pericellular contacts on PV-ir (not CB-, CR- or glutamate-ir) cell bodies. A potential cellular mechanism seems to emerge that CRF-ir terminals, that may be underdetected under normal conditions due to low activity levels, may be functionally activated during psychostimulant withdrawal, thereby altering local GABAergic signaling.

  3. Effect of Black maca (Lepidium meyenii) on one spermatogenic cycle in rats.

    PubMed

    Gonzales, G F; Nieto, J; Rubio, J; Gasco, M

    2006-10-01

    Lepidium meyenii (Maca) grows exclusively between 4000 and 4500 m above sea level in the Peruvian central Andes. The hypocotyls of this plant are traditionally used in the Andean region for their supposed fertility-enhancing properties. The hypocotyls have different colours. Of these, Black maca has better effects on spermatogenesis. The present study aimed to test the hypothesis that Black maca has early effects during a spermatogenic cycle (12 days) of male rats. For this, testicular spermatid, epididymal sperm and vas deferens sperm counts were measured after 1, 3, 5, 7 and 12 days of treatment with Black maca. Aqueous extract of Black maca was given orally by daily gavage at a dose of 2 g kg(-1). In a spermatogenic cycle, compared with day 1, daily sperm production (DSP) was lower at day 7 (control), whereas with Black maca, the difference was observed at day 12. Epididymal sperm count was higher in rats treated with Black maca at days 1, 3 and 7, but similar to controls at days 5 and 12; similarly sperm counts in vas deferens was higher in rats treated with Black maca in days 3, 5 and 7, but similar to controls at days 1 and 12. From this, it is suggested that first action of Black maca was at epididymal level increasing sperm count after 1 day of treatment, whereas an increase in sperm count was observed in vas deferens at day 3 of treatment. Finally, an increase in DSP was observed after 7 days of treatment with Black maca. Testicular testosterone was not affected after 7 days treatment with Black maca. In conclusion, Black maca affects sperm count as early as 1 day after beginning of treatment.

  4. Intermittent access to beer promotes binge-like drinking in adolescent but not adult Wistar rats.

    PubMed

    Hargreaves, Garth A; Monds, Lauren; Gunasekaran, Nathan; Dawson, Bronwyn; McGregor, Iain S

    2009-06-01

    Teenagers are more likely than adults to engage in binge drinking and could be more vulnerable to long-term brain changes following alcohol abuse. We investigated the possibility of excessive adolescent drinking in a rodent model in which beer (4.44% ethanol vol/vol) is presented to adult and adolescent male Wistar rats. Experiment 1 tracked ad libitum beer and water consumption in group-housed rats from postnatal day (PND) 28-96. Rats consumed an average of 7.8 g/kg/day of ethanol during adolescence (PND 34-55) and this gradually declined to a lower level of intake in adulthood (PND 56-93) of 3.9 g/kg/day. In Experiment 2, beer was made available to both adolescent (PND 29+) and adult (PND 57+) rats for 2h each day in a custom-built "lickometer" apparatus over 75 days. Access to beer was provided either 1 day out of every 3 ("intermittent" groups) or every day ("daily" groups). Relative to body weight, adolescent rats consumed more beer than adult rats in these limited access sessions. Adolescents with intermittent access consumed more than adolescents with daily access, a "binge"-like effect that was not observed in adult groups and that disappeared in adulthood. After 3 months of daily or intermittent alcohol consumption, the preference for beer versus sucrose was assessed. Rats previously kept under an intermittent schedule displayed a higher preference for beer relative to 3% sucrose, but only when testing occurred after 2 days of abstinence. In Experiment 3, adolescent (PND 30-37) and adult (PND 58-65) rats were given 20-min access to beer and their blood alcohol concentrations (BACs) were assessed. Adolescent groups consumed more alcohol than adults and showed higher BACS that were typical of human "binge" drinking (>80 mg/dL). Despite this, the correlation between BAC and beer intake was similar in both age groups. Together these results show that the intermittent presentation of alcohol itself appears to have subtle long-lasting effects on the motivation

  5. Increased expression of histone deacetylases 2 in temporal lobe epilepsy: a study of epileptic patients and rat models.

    PubMed

    Huang, Yuanyuan; Zhao, Fenghua; Wang, Liang; Yin, Huan; Zhou, Chunlei; Wang, Xuefeng

    2012-02-01

    Histone deacetylases 2 (HDAC2) is expressed in the central nervous system; it has multiple functions in neural plasticity. However, we do not know if HDAC2 is also involved in the pathology of epilepsy. Here we report that HDAC2 was expressed in the brain tissues of both control and temporal lobe epilepsy (TLE) patients. Results from immunofluorescence and immunohistochemistry showed that HDAC2 was primarily located in the nucleus and that TLE patients exhibit significantly more HDAC2 positive cells than control. Western blotting showed that HDAC2 protein levels were significantly higher in TLE than in control brain. Moreover, in the rat model of TLE, there was a sustained enhancement of HDAC2 expression in rat models of TLE. HDAC2 was significantly increased in both the acute (1 day) and chronic (60 days) animals compared with control group. These results suggest that HDAC2 play an important role in the pathogenesis of human TLE.

  6. Pulmonary toxicity of methylcyclopentadienyl manganese tricarbonyl: nonciliated bronchiolar epithelial (Clara) cell necrosis and alveolar damage in the mouse, rat, and hamster

    SciTech Connect

    Hakkinen, P.J.; Haschek, W.M.

    1982-01-01

    Methylcyclopentadienyl manganese tricarbonyl manganese tricarbonyl (MMT) was administered ip to young female BALB/c mice (120 mg MMT/kg), S/A albino rats (5 mg MMT/kg), or LV/sub 6//LAK Syrian hamsters (180 mg MMT/kg). This administration resulted in lung cell damage followed by cellular proliferation, which was quantified by measuring increases in thymidine incorporation into DNA (mouse, rat, and hamster) and by labeling indices (LI) determined from cell kinetic studies (mouse and rat). Thymidine incorporation into pulmonary DNA was significantly elevated within 1 to 2 days following MMT treatment in all three species, with peak incorporation occurring on Day 2 in the rat and hamster, and Day 4 in the mouse. Both bronchiolar and parenchymal LI were elevated at this time. Alveolar damage and nonciliated bronchiolar epithelial (Clara) cell necrosis were evident within 1 day of injection. This finding was followed by type II epithelial and Clara cell proliferation. Ultrastructurally, in the mouse, mitochondrial swelling and degeneration preceded Clara cell necrosis. Bronchiolar damage was most severe in the mouse, whereas parenchymal damage was most severe in the rat. These results suggest that the mouse, rat, and hamster have different susceptibilities to MMT-induced injury.

  7. Response of rats to low levels of sarin.

    PubMed

    Henderson, Rogene F; Barr, Edward B; Blackwell, Walter B; Clark, Connie R; Conn, Carole A; Kalra, Roma; March, Thomas H; Sopori, Mohan L; Tesfaigzi, Yohannes; Ménache, Margaret G; Mash, Deborah C

    2002-10-15

    The purpose of this study was to determine whether exposure to levels of sarin causing no overt clinical signs would cause more subtle, adverse health effects that persisted after the exposure ended. Inhalation exposures of male Fischer 344 rats to 0, 0.2, or 0.4 mg/m(3) of sarin for 1 h/day for 1, 5, or 10 days under normal (25 degrees C) and heat-stressed (32 degrees C) conditions were completed and observations were made at 1 day and 1 month after the exposures. The sarin exposures had no observed effects on body weight, respiration rate, and minute volume during exposure nor in body temperature and activity during the 30-day recovery period. There was no evidence of cellular changes in brain determined by routine histopathology nor of any increase in apoptosis. Brain mRNA for interleukin (IL)-1beta, tumor necrosis factor-alpha, and IL-6 was increased in a dose-dependent manner. Autoradiographic studies demonstrated that M1 cholinergic receptor site densities were unchanged at 1 day after repeated exposures with or without heat stress. At 30 days, there was a decrease in M1 receptors in the olfactory tubercle (with and without heat), and, with heat stress, M1 sites also decreased in a dose-dependent manner in the frontal cortex, anterior olfactory nucleus, and hippocampus. M3 receptor sites were not affected by sarin exposure alone. In the presence of heat stress, there was an upregulation in binding site densities in the frontal cortex, olfactory tubercle, anterior nucleus, and striatum immediately after exposure, and these effects persisted at 30 days. Although red blood cell acetylcholinesterase (AChE) was not greatly inhibited by the 1-day exposure, there were 30 and 60% inhibitions after repeated exposures at the low and high doses, respectively. Histochemical staining for AChE demonstrated that sarin exposure alone reduced AChE in the cerebral cortex, striatum, and olfactory bulb. Sarin exposure under heat stress reduced AChE staining in the hippocampus

  8. 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.

  9. Pregnancy suppresses neuropathic pain induced by chronic constriction injury in rats through the inhibition of TNF-α

    PubMed Central

    Onodera, Yoshiko; Kanao-Kanda, Megumi; Kanda, Hirotsugu; Sasakawa, Tomoki; Iwasaki, Hiroshi; Kunisawa, Takayuki

    2017-01-01

    Purpose Pregnancy-induced analgesia develops during late pregnancy, but it is unclear whether this analgesia is effective against neuropathic pain. The detailed molecular mechanisms underlying pregnancy-induced analgesia have not been investigated. We examined the antinociceptive effect of pregnancy-induced analgesia in a neuropathic pain model and the expression of tumor necrosis factor (TNF)-α, glial fibrillary acidic protein (GFAP), Iba-1, and c-Fos in the spinal dorsal horn just before parturition. Materials and methods Female Sprague Dawley rats (200–250 g) were randomly assigned to one of four groups (pregnant + chronic constriction injury [CCI]; pregnant + sham injury; not pregnant + CCI; and not pregnant + sham injury). Separate groups were used for the behavioral and tissue analyses. CCI of the left sciatic nerve was surgically induced 3 days after confirming pregnancy in the pregnancy group or on day 3 in the not pregnant group. The spinal cord was extracted 18 days after CCI. TNF-α, GFAP, Iba-1, and c-Fos expression levels in the spinal dorsal horn were measured by Western blot analysis. Mechanical threshold was tested using von Frey filaments. Results The lowered mechanical threshold induced by CCI was significantly attenuated within 1 day before parturition and decreased after delivery. TNF-α expression in CCI rats was decreased within 1 day before parturition. Further, GFAP, Iba-1, and c-Fos expression in the spinal dorsal horn was reduced in the pregnant rats. Serum TNF-α in all groups was below measurable limits. Conclusion Our findings indicate that pregnancy-induced analgesia suppresses neuropathic pain through reducing spinal levels of TNF-α, GFAP, Iba-1, and c-Fos in a rat model of CCI. PMID:28331359

  10. Povidone-iodine-induced cell death in cultured human epithelial HeLa cells and rat oral mucosal tissue.

    PubMed

    Sato, So; Miyake, Masao; Hazama, Akihiro; Omori, Koichi

    2014-07-01

    Although povidone-iodine (PVP-I) has been used as a gargle since 1956, its effectiveness and material safety have been remained controversial. The aim of this study was to investigate the toxicity of PVP-I to epithelial cells in a concentration range significantly lower than that used clinically. Study design was in vitro laboratory investigations and in vivo histological and immunologic analysis. We examined the effects of PVP-I at concentrations of 1 × 10(-2) to 1 × 10(3) μM and 1 × 10(-4) to 1 × 10 μM on HeLa cells as a model of epithelial cells and rat oral mucosa, respectively, after 1 or 2 days of exposure. Annexin V/FLUOS was used to distinguish live, apoptotic and necrotic cells. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method was also used to observe whether apoptotic epithelial cells exist in rat oral mucosa after 1 day of exposure of PVP-I. HeLa cells developed concentration-dependent cytotoxicity, and epithelium of rat oral mucosa was thinned in a concentration-dependent manner. HeLa cell apoptosis increased after 1 × 10(0) μM of PVP-I exposure for 2 days. In the TUNEL method, many apoptotic epithelial cells were observed in the rat oral mucosa after 1 day of exposure to diluted 1 × 10(-2) μM of PVP-I, but minimal apoptotic epithelial cells were observed using 1 × 10(-3) μM of PVP-I. Our findings suggest that exposure to PVP-I, of which concentrations are even lower than those used clinically, causes toxicity in epithelial cells. This knowledge would help us better understand the risk of the use of PVP-I against mucosa.

  11. 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

  12. Rat Endovascular Perforation Model

    PubMed Central

    Sehba, Fatima A.

    2014-01-01

    Experimental animal models of aneurysmal subarachnoid hemorrhage (SAH) have provided a wealth of information on the mechanisms of brain injury. The Rat endovascular perforation model (EVP) replicates the early pathophysiology of SAH and hence is frequently used to study early brain injury following SAH. This paper presents a brief review of historical development of the EVP model, details the technique used to create SAH and considerations necessary to overcome technical challenges. PMID:25213427

  13. Basic science; repetitive mild non-contusive brain trauma in immature rats exacerbates traumatic axonal injury and axonal calpain activation: a preliminary report.

    PubMed

    Huh, Jimmy W; Widing, Ashley G; Raghupathi, Ramesh

    2007-01-01

    Infants who experience inflicted brain injury (shaken-impact syndrome) present with subdural hematoma, brain atrophy, and ventriculomegaly, pathologic features that are suggestive of multiple incidences of brain trauma. To develop a clinically relevant model of inflicted brain injury in infants, the skulls of anesthetized 11-day-old rat pups were subjected to one, two, or three successive mild impacts. While skull fractures were not observed, a single impact to the intact skull resulted in petechial hemorrhages in the subcortical white matter, and double or triple impacts led to hemorrhagic tissue tears at 1 day postinjury. Whereas the singly impacted brain did not exhibit overt damage at 7 days, two impacts resulted in an enlarged ventricle and white matter atrophy; three impacts to the brain led to similar pathology albeit at 3 days postinjury. By 7 days, cortical atrophy was observed following three impacts. Reactive astrocytes were visible in the deep cortical layers below the impact site after two impacts, and through all cortical layers after three impacts. Swellings were observed in intact axons in multiple white matter tracts at 1 day following single impact and progressed to axonal disconnections by 3 days. In contrast, double or triple impacts resulted in axonal disconnections by 1 day postinjury; in addition, three impacts led to extensive axonal injury in the dorsolateral thalamus by 3 days. Calpain activation was observed in axons in subcortical white matter tracts in all brain-injured animals at 1 day and increased with the number of impacts. Despite these pathologic alterations, neither one nor two impacts led to acquisition deficits on the Morris water maze. While indicative of the graded nature of the pathologic response, these data suggest that repetitive mild brain injury in the immature rat results in pathologic features similar to those following inflicted brain injuries in infants.

  14. Methamphetamine regulation of sulfotransferase 1A1 and 2A1 expression in rat brain sections.

    PubMed

    Zhou, Tianyan; Huang, Chaoqun; Chen, Yue; Xu, Jiaojiao; Shanbhag, Preeti Devaraya; Chen, Guangping

    2013-01-01

    Sulfotransferase catalyzed sulfation regulates the biological activities of various neurotransmitters/hormones and detoxifies xenobiotics. Rat sulfotransferase rSULT1A1 catalyzes the sulfation of neurotransmitters and xenobiotic phenolic compounds. rSULT2A1 catalyzes the sulfation of hydroxysteroids and xenobiotic alcoholic compounds. In this work, Western blot and real-time RT-PCR were used to investigate the effect of methamphetamine on rSULT1A1 and rSULT2A1 protein and mRNA expression in rat cerebellum, frontal cortex, hippocampus, and striatum. After 1-day treatment, significant induction of rSULT1A1 was observed only in the cerebellum; rSULT2A1 was induced significantly in the cerebellum, frontal cortex, and hippocampus. After 7 days of exposure, rSULT1A1 was induced in the cerebellum, frontal cortex, and hippocampus, while rSULT2A1 was induced significantly in all four regions. Western blot results agreed with the real-time RT-PCR results, suggesting that the induction occurred at the gene transcriptional level. Results indicate that rSULT1A1 and rSULT2A1 are expressed in rat frontal cortex, cerebellum, striatum, and hippocampus. rSULT1A1 and rSULT2A1are inducible by methamphetamine in rat brain sections in a time dependable manner. rSULT2A1 is more inducible than rSULT1A1 by methamphetamine in rat brain sections. Induction activity of methamphetamine is in the order of cerebellum>frontal cortex, hippocampus>striatum. These results suggest that the physiological functions of rSULT1A1 and rSULT2A1 in different brain regions can be affected by methamphetamine.

  15. Isoflavonoid compounds extracted from Pueraria lobata suppress alcohol preference in a pharmacogenetic rat model of alcoholism.

    PubMed

    Lin, R C; Guthrie, S; Xie, C Y; Mai, K; Lee, D Y; Lumeng, L; Li, T K

    1996-06-01

    The extract from an edible vine, Pueraria lobata, has long been used in China to lessen alcohol intoxication. We have previously shown that daidzin, one of the major components from this plant extract, is efficacious in lowering blood alcohol levels and shortens sleep time induced by alcohol ingestion. This study was conducted to test the antidipsotropic effect of daidzin and two other major isoflavonoids, daidzein and puerarin, from Pueraria lobata administered by the oral route. An alcohol-preferring rat model, the selectively-bred P line of rats, was used for the study. All three isoflavonoid compounds were effective in suppressing voluntary alcohol consumption by the P rats. When given orally to P rats at a dose of 100 mg/kg/day, daidzein, daidzin, and puerarin decreased ethanol intake by 75%, 50%, and 40%, respectively. The decrease in alcohol consumption was accompanied by an increase in water intake, so that the total fluid volume consumed daily remained unchanged. The effects of these isoflavonoid compounds on alcohol and water intake were reversible. Suppression of alcohol consumption was evident after 1 day of administration and became maximal after 2 days. Similarly, alcohol preference returned to baseline levels 2 days after discontinuation of the isoflavonoids. Rats receiving the herbal extracts ate the same amounts of food as control animals, and they gained weight normally during the experiments. When administered orally, none of these compounds affected the activities of liver alcohol dehydrogenase and aldehyde dehydrogenase. Therefore, the reversal of alcohol preference produced by these compounds may be mediated via the CNS. Data demonstrate that isoflavonoid compounds extracted from Pueraria lobata is effective in suppressing the appetite for alcohol when taken orally, raising the possibility that other constituents of edible plants may exert similar and more potent actions.

  16. Effects of cerulein and epidermal growth factor on pancreatic growth in the reserpinized rat model.

    PubMed

    Bérubé, F L; Benrezzak, O; Vanier, M; Morisset, J

    1993-07-01

    This study was undertaken to determine the effect of reserpine on rat pancreatic growth, to evaluate if reserpine-caused alterations can be prevented by epidermal growth factor (EGF) and/or cerulein treatment, to evaluate the time course of rat pancreas recovery after reserpine, and to determine if EGF and/or cerulein treatment can accelerate such a recovery. In the first experiment, three groups of male Sprague-Dawley rats (250-265 g) were used. Ad libitum-fed control animals received the reserpine vehicle, and one experimental group received reserpine (1 mg kg-1 day-1 for 7 days) while the other, pair-fed group received the reserpine vehicle with a reduced amount of food to result in malnourishment. Rats from each of these three groups were also assigned to one of four treatments consisting of saline, EGF (10 micrograms kg-1), cerulein (1 microgram kg-1), or a combination (same doses) twice a day for 7 days. In the morning of the 8th day, after an overnight fat, rats were killed. In the second experiment, rats were selected and treated with reserpine or the vehicle as described in experiment 1; after the 7-day treatment, a first cohort of animals was allowed a 30-day recovery period. Three other groups (an ad libitum-fed control, a pair-fed, and a reserpine group) were allowed a 6-day recovery period during which they were treated subcutaneously, twice a day, with either saline, EGF (10 micrograms kg-1), cerulein (1 microgram kg-1), or a combination (same doses). On the morning of the 31st or 7th day, after an overnight fat, rats were killed. After death, all pancreata were examined for weight and protein, amylase, chymotrypsinogen, RNA, and DNA content. In the ad libitum-fed control group, EGF caused pancreatic hypertrophy, whereas cerulein was associated with hypertrophy and hyperplasia. In the pair-fed malnourished group, the EGF effect was limited to slight increases in pancreatic weight and cell mass whereas cerulein caused hypertrophy; EGF plus cerulein

  17. ET-receptor antagonism, myocardial gene expression, and ventricular remodeling during CHF in rats.

    PubMed

    Oie, E; Bjønerheim, R; Grogaard, H K; Kongshaug, H; Smiseth, O A; Attramadal, H

    1998-09-01

    Both myocardial and plasma endothelin-1 (ET-1) are elevated in congestive heart failure (CHF). However, the role played by endogenous ET-1 in the progression of CHF remains unknown. The aim of the present study was to investigate and correlate myocardial gene expression programs and left ventricular (LV) remodeling during chronic ET-receptor antagonism in CHF rats. After ligation of the left coronary artery, rats were randomized to oral treatment with a nonselective ET-receptor antagonist (bosentan, 100 mg . kg-1 . day-1, n = 11) or vehicle (saline, n = 13) for 15 days, starting 24 h after induction of myocardial infarction. Bosentan substantially attenuated LV dilatation during postinfarction failure as evaluated by echocardiography. Furthermore, bosentan decreased LV systolic and end-diastolic pressures and increased fractional shortening. Myocardial expression of preproET-1 mRNA and a fetal gene program characteristic of myocardial hypertrophy were increased in the CHF rats and were not affected by bosentan. Consistently, right ventricular-to-body weight ratios, diameters of cardiomyocytes, and echocardiographic analysis demonstrated a sustained hypertrophic response and a normalized relative wall thickness after intervention with bosentan. Thus the modest reduction of preload and afterload provided by bosentan substantially attenuates LV dilatation, causing improved pressure-volume relationships. However, the compensatory hypertrophic response was not altered by ET-receptor antagonism. Therefore, ET-1 does not appear to play a crucial role in the mechanisms of myocardial hypertrophy during the early phase of postinfarction failure.

  18. Circadian rhythm of catecholamine excretion in rats after phase shift of light-dark cycle.

    PubMed

    Sudo, A; Miki, K

    1995-01-01

    To clarify the time course of circadian rhythm adaptation to a phase shift of the light-dark (LD) cycle, urinary excretion of catecholamines was measured in rats before and after a 12-hour or 6-hour phase delay of a 12-hour light and 12-hour dark schedule. In rats under a basal condition, distinct circadian rhythms in catecholamine excretion were observed, especially in adrenaline excretion. During the 1st and 2nd days after a 12-hour phase delay, the acrophase and amplitude of adrenaline rhythm remained almost unchanged, but thereafter the acrophase was retarded and the amplitude was reduced. The acrophase once again became constant after 5 or 6 days, but the ratio of amplitude to mesor in the circadian rhythm of adrenaline excretion and the ratio of light-period to 24-hour noradrenaline excretion were readjusted to the new LD schedule on 11th or 12th day. IN the 6-hour phase delay of the LD cycle, similar findings were observed, and the results suggested adaptation on the 5-6th day. It is considered that the circadian rhythms of the sympathetic adrenomedullary function are restored, at the latest, 12 days after a 12-hour delay of the LD cycle, and 6 days after a 6-hour delay, suggesting that rats need approximately 1 day to adapt to a 1-hour phase shift.

  19. Subchronic urinary bladder toxicity evaluation of N-Nitrosodiphenylamine in Fischer 344 rats.

    PubMed

    Dodd, Darol E; Pluta, Linda J; Sochaski, Mark A; Funk, Kathleen A; Thomas, Russell S

    2013-05-01

    Female Fischer 344 (F344) rats were exposed to N-nitrosodiphenylamine (NDPA) by dietary feed at concentrations of 0, 250, 1000, 2000, 3000 or 4000 ppm for 5 days, 2, 4 and 13 weeks duration. Endpoints evaluated included clinical observations, body weights, urinary bladder weights, blood NDPA, gross pathology and urinary bladder histopathology. There were no NDPA exposure-related clinical signs of toxicity. The mean body weight decreased 3% to 5% compared with the control in the 4000 ppm group during study weeks 2 through to 13. Statistically significant increases in urinary bladder weight were observed as early as after 5 days exposure and were concentration dependent at ≥ 3000 ppm. NDPA-related urinary bladder microscopic alterations consisted of mixed cell infiltrates, increased mitosis, increased necrosis of epithelial cells, diffuse and/or nodular transitional epithelial hyperplasia and squamous metaplasia of transitional epithelium. These changes affected only rats exposed to NDPA concentrations ≥ 2000 ppm. Blood NDPA concentrations were negligible in animals exposed to ≤ 1000 ppm and ranged from 0.12 to 0.19 µg ml(-1) in rats of the ≥ 2000 ppm groups at the 5 days and 2 weeks time points. A no observable adverse effect level (NOAEL) of 1000 ppm NDPA (60 mg kg(-1) day(-1) ) was selected based on the absence of urinary bladder histopathology.

  20. Extended Exposure to Environmental Cues, but not to Sucrose, Reduces Sucrose Cue-reactivity in Rats

    PubMed Central

    Harkness, John H.; Wells, Jason; Webb, Sierra; Grimm, Jeffrey W.

    2015-01-01

    The present study examined the effect of extinction of sucrose-predictive contextual cues and/or sucrose satiation on the expression of sucrose cue-reactivity in a rat model of relapse. Context extinction was imposed by housing rats in their home cage or in the operant conditioning chamber for 17 hours prior to testing. For sucrose satiation, rats were allowed unlimited access to water or sucrose for 17 hours prior to testing. Cue-reactivity was assessed after either 1 (Day 1) or 30 (Day 30) days of forced abstinence from sucrose self-administration. An abstinence-dependent increase in sucrose cue-reactivity was observed in all conditions (“incubation of craving”). Context extinction dramatically reduced lever responding on both Day 1 and Day 30. Sucrose satiation had no significant effect on cue-reactivity in any condition. These results demonstrate that the context in which self-administration occurred maintains a powerful influence over cue-reactivity even after extended forced abstinence. In contrast, the primary reinforcer has little control over cue-reactivity. These findings highlight the important role of conditioned contextual cues in driving relapse behavior. PMID:26169836

  1. The effects of intermittent high asbestos exposure (peak dose levels) on the lungs of rats.

    PubMed Central

    Davis, J. M.; Beckett, S. T.; Bolton, R. E.; Donaldson, K.

    1980-01-01

    Four groups of rats were treated by inhalation with the UICC preparations of amosite or chrysotile in order to explore the effects of intermittent high dust concentrations (peak dosing). For each of the 2 asbestos types one group of rats was treated for 5 days each week, 7 h a day, for 1 year. Two other groups were treated with amosite or chrysotile at 5 times the previous dose for 1 day each week for 1 year. Results showed that the lung dust levels of both chrysotile or amosite in the lungs of rats after the 12-month inhalation period were similar regardless of whether "peak" or "even" dosing had been used. During the following 6 months, asbestos was cleared from the "peak" chrysotile group more slowly than the "even" chrysotile group but clearance from the "peak" amosite group was faster than that found after "even" dosing with amosite. Levels of early peribronchial fibrosis were generally lower for the "peak" dosing groups than for "even" dosing although levels of interstitial fibrosis were slightly higher following "peak" dosing. The incidence of pulmonary neoplasms did not differ between the "peak"-dosing and "even"-dosing experiments. These findings therefore give no indication that short periods of high dust exposure in an asbestos factory would result in a significantly greater hazard than would be indicated by the raised overall dust counts for the day in question. Images Fig. 3 PMID:7426382

  2. Rat hippocampal alterations could underlie behavioral abnormalities induced by exposure to moderate noise levels.

    PubMed

    Uran, S L; Aon-Bertolino, M L; Caceres, L G; Capani, F; Guelman, L R

    2012-08-30

    Noise exposure is known to affect auditory structures in living organisms. However, it should not be ignored that many of the effects of noise are extra-auditory. Previous findings of our laboratory demonstrated that noise was able to induce behavioral alterations that are mainly related to the cerebellum (CE) and the hippocampus (HC). Therefore, the aim of this work was to reveal new data about the vulnerability of developing rat HC to moderate noise levels through the assessment of potential histological changes and hippocampal-related behavioral alterations. Male Wistar rats were exposed to noise (95-97 dB SPL, 2h daily) either for 1 day (acute noise exposure, ANE) or between postnatal days 15 and 30 (sub-acute noise exposure, SANE). Hippocampal histological evaluation as well as short (ST) and long term (LT) habituation and recognition memory assessments were performed. Results showed a mild disruption in the different hippocampal regions after ANE and SANE schemes, along with significant behavioral abnormalities. These data suggest that exposure of developing rats to noise levels of moderate intensity is able to trigger changes in the HC, an extra-auditory structure of the Central Nervous System (CNS), that could underlie the observed behavioral effects.

  3. Maturation of the inhibitory response of growth hormone secretion to ether stress in postnatal rat.

    PubMed

    Strbák, V; Jurcovicová, J; Vigas, M

    1985-05-01

    To study the maturation of inhibitory influences on growth hormone (GH) secretion the effect of ether stress on plasma GH levels was studied during postnatal ontogenesis in female rats. Ether stress did not affect plasma GH levels in 1-day-old pups. A distinct decrease of plasma GH was found in 3- and 9-day-old pups, and the response was prevented by treatment of 3-day-old animals with somatostatin antiserum. No effect of ether stress on plasma GH was noted in 12-, 15-, 18- and 21-day-old rats. Treatment of intact 12-day-old pups with the somatostatin antiserum increased plasma GH level under basal conditions. The inhibitory effect of ether stress on plasma GH was noted again at the age 30 days and in adult animals. It is concluded that the hypothalamus of 3-day-old rats is able to release enough somatostatin to inhibit GH secretion after stress. At the period 12-18 days a phase of pituitary refractoriness was noted: ether stress as well as TRH injection (our previous observation) fail to affect plasma GH in female pups, probably due to high somatostatin secretion under basal conditions and (or) low capacity of pituitary to release GH. It is suggested that regulation of GH secretion is not mature until after the 21st day of life.

  4. Effect of reserpine on the histochemical and biochemical properties of rat intestinal mucin

    SciTech Connect

    Forstner, J.; Roomi, N.; Khorasani, R.; Kuhns, W.; Forstner, G. )

    1991-04-01

    Biochemical and histochemical parameters of intestinal mucins were examined in control and reserpine-treated rats. An assay for intestinal mucin sulfotransferase was developed and the activity shown to increase 3.4 times over control levels in rats given intraperitonal reserpine (0.5 mg/kg body wt) daily for 7 days. Histochemical staining of intestinal sections revealed an increase in sulfomucins in goblet cells of reserpine-treated rats. The effects were prominent as early as 1 day following injection, particularly in the distal third of the small intestine, and during the next 6 days these changes spread progressively to the middle and proximal thirds. After 3 days of treatment mucins were purified from each intestinal segment and compared to control mucins with respect to composition and (35S)NaSO{sub 4} incorporation. Although individual amino acid and carbohydrate molar ratios were unchanged, the total carbohydrate and sulfate content of mucins in treated animals was elevated (two to three times above control) in the middle and distal thirds of the intestine. In vivo ({sup 35}S)SO{sub 4} incorporation into these mucins was also proportionaltely elevated, and was targetted to O-linked oligosaccharide side chains. These findings are consistent with an action of reserpine causing an increased production of mucin which is enriched in glycoprotein components bearing sulfated oligosaccharide chains. The relevance of these findings to the production of hypersulfated and hyperglycosylated mucins in cystic fibrosis is discussed.

  5. Protective effects of erdosteine against doxorubicin-induced cardiomyopathy in rats.

    PubMed

    Fadillioğlu, Ersin; Erdoğan, Hasan; Söğüt, Sadik; Kuku, Irfan

    2003-01-01

    The usefulness of doxorubicin (DXR) is limited by its cardiotoxicity. In order to improve future DXR therapy by using a new antioxidant agent, an experimental study was designed. This study was undertaken to determine whether DXR-induced cardiotoxicity is prevented by erdosteine, a mucolytic agent showing antioxidant properties. Three groups of male Sprague-Dawley rats (60 days old) were used: one group was untreated as a control; the other groups were treated with DXR (single i.p. dosage of 20 mg kg(-1) body wt.) or DXR plus erdosteine (10 mg kg(-1) day(-1), orally), respectively. The DXR treatment without erdosteine increased antioxidant enzyme activities and also increased lipid peroxidation in myocardial tissue. The rats treated with DXR plus erdosteine produced a significant decrease in lipid peroxidation in comparison with control and DXR groups. Furthermore, erdosteine administration led to an increase in antioxidant enzyme activities in comparison with the control group. Erdosteine treatment also increased the activities of catalase (CAT) and glutathione peroxidase (GSH-Px) in comparison with the DXR group. There was no significant difference in lipid peroxidation of myocardial tissue between control and DXR plus erdosteine-treated rats. It was concluded that erdosteine caused an increase in the activities of antioxidant enzymes, especially GSH-Px and CAT, protecting the heart tissue sufficiently from oxidative damage to membrane lipids and other cellular components induced by DXR.

  6. Different alcohol exposures induce selective alterations on the expression of dynorphin and nociceptin systems related genes in rat brain.

    PubMed

    D'Addario, Claudio; Caputi, Francesca F; Rimondini, Roberto; Gandolfi, Ottavio; Del Borrello, Elia; Candeletti, Sanzio; Romualdi, Patrizia

    2013-05-01

    Molecular mechanisms of adaptive transformations caused by alcohol exposure on opioid dynorphin and nociceptin systems have been investigated in the rat brain. Alcohol was intragastrically administered to rats to resemble human drinking with several hours of exposure: water or alcohol (20% in water) at a dose of 1.5 g/kg three times daily for 1 or 5 days. The development of tolerance and dependence were recorded daily. Brains were dissected 30 minutes (1- and 5-day groups) or 1, 3 or 7 days after the last administration for the three other 5-day groups (groups under withdrawal). Specific alterations in opioid genes expression were ascertained. In the amygdala, an up-regulation of prodynorphin and pronociceptin was observed in the 1-day group; moreover, pronociceptin and the kappa opioid receptor mRNAs in the 5-day group and both peptide precursors in the 1-day withdrawal group were also up-regulated. In the prefrontal cortex, an increase in prodynorhin expression in the 1-day group was detected. These data indicate a relevant role of the dynorphinergic system in the negative hedonic states associated with multiple alcohol exposure. The pattern of alterations observed for the nociceptin system appears to be consistent with its role of functional antagonism towards the actions of ethanol associated with other opioid peptides. Our findings could help to the understanding of how alcohol differentially affects the opioid systems in the brain and also suggest the dynorphin and nociceptin systems as possible targets for the treatment and/or prevention of alcohol dependence.

  7. Dissociation between biochemical and functional effects of the aldose reductase inhibitor, ponalrestat, on peripheral nerve in diabetic rats.

    PubMed Central

    Cameron, N. E.; Cotter, M. A.

    1992-01-01

    1. The aim of the study was to examine the effects in rats of two different doses of the aldose reductase inhibitor, ponalrestat, on functional measures of nerve conduction and sciatic nerve biochemistry. 2. After 1 month, streptozotocin-induced diabetes produced 22%, 23% and 15% deficits in conduction velocity of sciatic nerves supplying gastrocnemius and tibialis anterior muscles and saphenous sensory nerve respectively compared to controls. These deficits were maintained over 2 months diabetes. 3. Slower-conducting motor fibres supplying the interosseus muscles of the foot did not show a diabetic deficit compared to onset controls, however, there was a 13% reduction in conduction velocity after 2 months diabetes relative to age-matched controls, indicating a maturation deficit. 4. Resistance to hypoxic conduction failure was investigated for sciatic nerve trunks in vitro. There was an increase in the duration of hypoxia necessary for an 80% reduction in compound action potential amplitude with diabetes. This was progressive; after 1 month, hypoxia time was increased by 22% and after 2 months by 57%. 5. The effect of 1-month treatment with the aldose reductase inhibitor, ponalrestat, on the abnormalities caused by an initial month of untreated diabetes was examined. Two doses of ponalrestat were employed, 8 mg kg-1 day-1 (which is equivalent to, or greater than, the blockade employed in clinical trials), and 100 mg kg-1 day-1. 6. Sciatic nerve sorbitol content was increased 7 fold by diabetes. Both doses were effective in reducing this; 70% for 8 mg kg-1 day-1, and to within the control range for 100 mg kg-1 day-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1467842

  8. 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…

  9. Chronic administration of oxprenolol and metoprolol attenuate sympathetic cardiovascular responses only in non-adrenalectomized pithed rats.

    PubMed

    Vila, E; Badia, A

    1995-10-01

    1. Oxprenolol and metoprolol (30 mg kg-1) were injected intraperitoneally (i.p.) for 1 day (acute treatment) and 6 weeks (chronic treatment) to Sprague-Dawley rats. 2. Increases of mean blood pressure and heart rate to noradrenaline (0.1-10 micrograms kg-1) and to electrical stimulation (0.5 msec, supramax V, 0.25-5 Hz) of the entire sympathetic outflow were measured in non-adrenalectomized (acute and chronic) and adrenalectomized (chronic) pithed rats. 3. Acute beta-adrenoceptor antagonist administration was without effect on mean blood pressure and heart rate increases to noradrenaline and electrical stimulation. 4. Chronic administration with oxprenolol significantly diminished the stimulation-induced increases of mean blood pressure and heart rate in non-adrenalectomized pithed rats. 5. Increases in heart rate, elicited by stimulation of the entire sympathetic outflow in non-adrenalectomized but not in adrenalectomized pithed rats, were decreased by metoprolol treatment. Both treatments were without effect on noradrenaline responses. 6. These results indicate that chronic beta-adrenoceptor antagonist treatment is associated with a reduction in the cardiovascular responses to sympathetic nerve-stimulation. However, this mechanism only operates when adrenomedullary adrenaline is present to facilitate the noradrenaline release through activation of presynaptic beta 2-adrenoceptors.

  10. The protective activity of Urtica dioica leaves on blood glucose concentration and beta-cells in streptozotocin-diabetic rats.

    PubMed

    Golalipour, Mohammad Jafar; Khori, Vahid

    2007-04-15

    This study was done to determine the protective activity of the hydroalcholic extract of Urtica dioica leaves on Hyperglycemia and beta-cells in hyperglycemic rats. Thirty Wistar rats were allocated in groups of normal, Diabetic and treatment. Hyperglycemia in Rats induced by 80 mg kg(-1) streptozotocin. In treatment group, animals received hydroalcholic extract of Urtica dioica 100 mg kg(-1) day(-1) for five days, intraperitoneally and then hyperglycemia induced by streptozotocin. The blood glucose concentration was measured by using a Glucometer in 1st, 3rd and 5th weeks. In the end of 5th weeks the animals in each group were sacrificed by anesthesia and whole pancreas in three groups extracted and fixed in bouin's fluid and stained by chromealum hematoxiline-phloxine and beta cells were counted in three groups by Olympus microscope. Mean +/- SE of blood glucose concentrations in the end of fifth weeks were 99.4 +/-5.0, 454.7 +/- 34.5 and 303.6 +/- 100.6 in control, diabetic and treatment groups, respectively (p < 0.05). The percentages of beta-cells in control, diabetic and treatment groups were 73.6, 1.9 and 22.9%, respectively. The percentage of beta-cells in treatment group comparing with diabetic group was significant (p < 0.05). This study showed that the protective administration of hydroalcholic extract of Urtica dioica has hypoglycemic effect and protective activity of beta-cells of langerhans in hyperglycemic rats.

  11. Artemisinin induces hormonal imbalance and oxidative damage in the erythrocytes and uterus but not in the ovary of rats.

    PubMed

    Farombi, E O; Abolaji, A O; Adedara, I A; Maduako, I; Omodanisi, I

    2015-01-01

    Artemisinin is an antimalarial drug previously reported to induce neurotoxicity and embryotoxicity in animal models. This study investigated the erythrocytes and reproductive toxicity potentials of artemisinin in female rats. Animals were randomly divided into four study groups of eight rats each. The control group (group I) received corn oil, the vehicle, while groups II-IV were orally exposed to 7, 35 and 70 mg kg(-1) day(-1) of artemisinin, respectively, by gastric intubation for 7 consecutive days. Subsequently, we evaluated the impact of artemisinin on the endocrine environment and selected markers of oxidative damage and antioxidant status of the erythrocytes, ovary and uterus. Artemisinin significantly increased hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels and decreased catalase, glutathione peroxidase and superoxide dismutase activities in erythrocytes and uterus of rats compared with control group (p < 0.05). However, artemisinin did not alter ovarian MDA, H2O2, glutathione levels and catalase activity, while ovarian and uterine histological assessment revealed absence of visible lesions. Moreover, artemisinin significantly decreased follicle-stimulating hormone and increased progesterone levels compared with control (p < 0.05). Thus, these data suggest that in the absence of malarial parasite infection, artemisinin induced hormonal imbalance and oxidative damage in the erythrocytes and uterus but spared the ovary of rats.

  12. Effects of evening primrose oil treatment on sciatic nerve blood flow and endoneurial oxygen tension in streptozotocin-diabetic rats.

    PubMed

    Cameron, N E; Cotter, M A

    1994-12-01

    Evening primrose oil (EPO) is rich in the omega-6 essential fatty acid component, gamma-linolenic acid. The aim of the investigation was to determine whether EPO treatment prevented a reduction in sciatic nerve perfusion and oxygenation in streptozotocin-diabetic rats. Rats were treated from diabetes induction with 10 g EPO kg-1 day-1. Sciatic blood flow was measured by microelectrode polarography and hydrogen clearance. Diabetes caused 47.7% +/- 3.4% (P < 0.001) and 58.8% +/- 4.8% (P < 0.001) reduction in the nutritive (capillary) and the non-nutritive (large vessel) components of endoneurial blood flow, respectively, which were prevented by EPO. Treatment had no significant effect on nutritive flow in non-diabetic rats; however, the rate of non-nutritive flow increased by 97.7% +/- 38.9% (P < 0.01). Sciatic endoneurial oxygen tension was measured by microelectrode polarography. Diabetes resulted in a 44.7% +/- 3.4% reduction in mean oxygen tension (P < 0.001), which was largely (82.3% +/- 10.2%) prevented by EPO treatment (P < 0.001). Thus, EPO prevents impairment of blood flow and endoneurial oxygenation in experimental diabetes. It is likely that this neurovascular action accounts for the beneficial effects of treatment on nerve function in diabetic rats and patients.

  13. A 28-day repeated dose toxicity study of ultraviolet absorber 2-(2'-hydroxy-3',5'-di-tert-butylphenyl) benzotriazole in rats.

    PubMed

    Hirata-Koizumi, Mutsuko; Watari, Nobuaki; Mukai, Daisuke; Imai, Toshio; Hirose, Akihiko; Kamata, Eiichi; Ema, Makoto

    2007-01-01

    To examine the possible repeated-dose toxicity of an ultraviolet absorber, 2-(2'-hydroxy-3',5'-di-tert-butylphenyl)benzotriazole (HDBB), CD(SD)IGS rats were administered HDBB by gavage at a dose of 0 (vehicle: corn oil), 0.5, 2.5, 12.5, or 62.5 mg kg(-1) day(-1) for 28 days. At the completion of the administration period, a decrease in red blood cells, hemoglobin, and hematocrit was noted only in males at 2.5 mg/kg and more. Blood biochemical changes were noted at 0.5 mg/kg and more in males and at 62.5 mg/kg in females. Histopathologic changes were observed principally in the liver (vacuolar degeneration and hypertrophy of hepatocytes, bile duct proliferation, etc.) and in the heart (degeneration and hypertrophy of myocardium and cell infiltration). These changes were noted at 0.5 mg/kg and more in males and at 12.5 mg/kg and more in females. At higher doses, hypertrophy of tubular epithelium in the kidneys and diffuse follicular cell hyperplasia in the thyroids in both sexes and increased severity of basophilic tubules in the kidneys and extramedullary hematopoiesis in the spleen in males were also detected. After the 14-day recovery period, these changes mostly recovered in females but not in males. Based on these findings, no observed adverse effect level (NOAEL) was concluded to be less than 0.5 mg kg(-1) day(-1) in male rats and 2.5 mg kg(-1) day(-1) in female rats.

  14. Do rats have orgasms?

    PubMed Central

    Pfaus, James G.; Scardochio, Tina; Parada, Mayte; Gerson, Christine; Quintana, Gonzalo R.; Coria-Avila, Genaro A.

    2016-01-01

    Background Although humans experience orgasms with a degree of statistical regularity, they remain among the most enigmatic of sexual responses; difficult to define and even more difficult to study empirically. The question of whether animals experience orgasms is hampered by similar lack of definition and the additional necessity of making inferences from behavioral responses. Method Here we define three behavioral criteria, based on dimensions of the subjective experience of human orgasms described by Mah and Binik, to infer orgasm-like responses (OLRs) in other species: 1) physiological criteria that include pelvic floor and anal muscle contractions that stimulate seminal emission and/or ejaculation in the male, or that stimulate uterine and cervical contractions in the female; 2) short-term behavioral changes that reflect immediate awareness of a pleasurable hedonic reward state during copulation; and 3) long-term behavioral changes that depend on the reward state induced by the OLR, including sexual satiety, the strengthening of patterns of sexual arousal and desire in subsequent copulations, and the generation of conditioned place and partner preferences for contextual and partner-related cues associated with the reward state. We then examine whether physiological and behavioral data from observations of male and female rats during copulation, and in sexually-conditioned place- and partner-preference paradigms, are consistent with these criteria. Results Both male and female rats display behavioral patterns consistent with OLRs. Conclusions The ability to infer OLRs in rats offers new possibilities to study the phenomenon in neurobiological and molecular detail, and to provide both comparative and translational perspectives that would be useful for both basic and clinical research. PMID:27799081

  15. 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

  16. Protective effect of naringenin against gentamicin-induced nephrotoxicity in rats.

    PubMed

    Fouad, Amr A; Albuali, Waleed H; Zahran, Ahmed; Gomaa, Wafaey

    2014-09-01

    The protective effect of naringenin, a flavonoid compound isolated from citrus fruits, was investigated against nephrotoxicity induced by gentamicin (80mgkg(-1)/day, i.p., for eight days) in rats. Naringenin treatment (50mgkg(-1)/day, p.o.) was administered for eight days, starting on the same day of gentamicin administration. Gentamicin caused significant elevations of serum creatinine, and kidney tissue levels of malondialdehyde, nitric oxide, and interleukin-8, and a significant decrease in renal glutathione peroxidase activity. Naringenin treatment significantly ameliorated the changes in the measured biochemical parameters resulted from gentamicin administration. Also, naringenin markedly attenuated the histopathological renal tissue injury observed with gentamicin. Immunohistochemical examinations showed that naringenin significantly reduced the gentamicin-induced expression of kidney injury molecule-1, vascular endothelial growth factor, inducible nitric oxide synthase, and caspase-9, and increased survivin expression in the kidney tissue. It was concluded that naringenin, through its antioxidant and anti-inflammatory effects, may represent a therapeutic option to protect against gentamicin nephrotoxicity.

  17. Enhancement of aphrodisiac activity in male rats by ethanol extract of Kaempferia parviflora and exercise training.

    PubMed

    Chaturapanich, G; Chaiyakul, S; Verawatnapakul, V; Yimlamai, T; Pholpramool, C

    2012-05-01

    This study aimed to investigate the effects of Kaempferia parviflora extract (KD) and exercise training on reproductive function in male rats. Sexually mature males were assigned to four groups: control, KD70 (received 70 mg kg(-1) day(-1) for 4 weeks), Ex (exercise training for 4 weeks), Ex + KD70 (exercise training with KD 70 mg kg(-1) day(-1)). At the end of treatment regimes, sexual behaviours including mount latency (ML), mount frequency (MF), ejaculation latency (EL), post-ejaculation latency (PEL), number of mount within 30 min (MF(30)) and number of ejaculation (NEL) were assessed by a video camera, and fertility was tested by natural mating. Results showed that KD had no effect on the weights of reproductive organs, liver, kidneys and levator ani muscle. On the other hand, the weights of epididymis, seminal vesicles, prostate gland and levator ani muscle were significantly increased in the Ex and Ex+KD70 groups. ML and EL were shortened in all treatment groups, but PEL was decreased only in KP70 group. Only Ex and Ex + KD70 groups exhibited lower MF and higher NEL whilst MF(30) were not changed in all groups. None of the treatments altered male fertility. It is concluded that KD enhanced sexual motivation whereas exercise training promoted both sexual motivation and performance.

  18. Radiation injury in rat lung: I. Prostacyclin (PGI/sub 2/) production, arterial perfusion, and ultrastructure

    SciTech Connect

    Ts'ao, C.; Ward, W.F.; Port, C.D.

    1983-11-01

    Pulmonary prostacyclin (PGI/sub 2/) production, arterial perfusion, and ultrastructure were correlated in rats sacrificed from 1 day to 6 months after a single exposure of 25 Gy of gamma rays to the right hemithorax. PGI/sub 2/ production by the irradiated lung decreased to approximately half the normal value 1 day after irradiation (P < 0.05), then increased steadily throughout the study. By 6 months postirradiation, the right lung produced two to three times as much PGI/sub 2/ as did either shielded left lung or sham-irradiated lungs (P < 0.05). Perfusion scans revealed hyperemia of the right lung from 1 to 14 days after irradiation. From its peak at 14 days postirradiation, however, perfusion of the irradiated lung decreased steadily, then reached a plateau from 3 to 6 months at less than half that in the shielded left lung. Electron micrographs of the right lung revealed perivascular edema from 1 to 30 days after irradiation. The right lung then exhibited changes typical of radiation pneumonitis followed by progressive interstitial fibrosis. Platelet aggregates were not observed at any time. Thus, decreased PGI/sub 2/ production is an immediate but transient response of the lung to radiation injury. Then from 2 to 6 months after irradiation, the fibrotic, hypoperfused lung produces increasing amounts of the potent vasodilator and antithrombotic agent, PGI/sub 2/. Pulmonary PGI/sub 2/ production and arterial perfusion are inversely correlated for at least 6 months after hemithoracic irradiation.

  19. Blood-brain barrier after resuscitation from 10-min clinical death in rats.

    PubMed

    Kapuściński, A; Kapuściński, P

    1995-01-01

    In rats 10-min clinical death was induced by intrathoracic compression of the cardiac vessel bundle. The animals were sacrificed from 15 min to 7 days after resuscitation. They were decapitated 15 sec after intracarotid injection of mixture of L-[U-14C]glutamic acid and tritiated water. Using by the dual label method the brain uptake index (BUI) and percent of injected dose of amino acid in the cerebral hemisphere were calculated. In 45% of animals an increase of amino acid transfer and rise of BUI revealed the blood-brain barrier (BBB) alterations. The most pronounced changes developed after 120 min and 1 day after resuscitation. The impaired vs. normal BBB state depends probably on uneven recovery of cerebral circulation in individual animals after resuscitation.

  20. The effects of thyroid hormones on myelination in the developing rat brain.

    PubMed

    Freundl, K; Van Wynsberghe, D M

    1978-01-01

    Rats radiothyroidectomized 1 day after birth received daily subcutaneous injections of 1 microgram/10 g body weight of thyroxine (T4) or an equimolar amount of triiodothyroacetic acid (T3AC) from day 6 through day 25. The number of myelinated axons, myelinated axon area, and area of the myelin sheath in the corpus striatum were investigated. Hypothyroid neonates demonstrated a normal number of myelinated axons with a decrease in the area of these axons. T4 treatment resulted in an increased number of smaller axons while T3AC treatment produced fewer but larger axons than the T4 treatment. The myelin area changed as the axon area changed with the myelin thickness remaining constant in all groups.

  1. Dopaminergic control of prolactin mRNA accumulation in the pituitary of the male rat.

    PubMed

    Brocas, H; van Coevorden, A; Seo, H; Refetoff, S; Vassart, G

    1981-04-01

    Dopaminergic control of the expression of the prolactin gene was investigated by administration of bromoergocryptine (CB154) to male rats. The effects of the drug on the following parameters were measured: (i) circulating levels of GH and PRL; (ii) synthesis of GH and PRl measured by pulse labeling pituitary fragments in vitro; (iii) GH and PRL mRNA activities; and (iv) content of PRL and mRNA. After 1 day of CB154 administration, serum PRL fell to undetectable levels whereas it took 3 days to observe a 50% reduction in PRL synthesis. This effect was accounted for by a parallel decrease in PRL mRNA activity and content. GH synthesis and GH mRNA were not affected by the treatment. Our results show that the dopaminergic inhibition of PRL production involves regulation at a pre-translational level.

  2. Postural development in rats.

    PubMed

    Lelard, T; Jamon, M; Gasc, J-P; Vidal, P-P

    2006-11-01

    Mammals adopt a limited number of postures during their day-to-day activities. These stereotyped skeletal configurations are functionally adequate and limit the number of degrees of freedom to be controlled by the central nervous system. The temporal pattern of emergence of these configurations in altricial mammals is unknown. We therefore carried out an X-ray study in unrestrained rats from birth (P0) until postnatal day 23 (P23). The X-rays showed that many of the skeletal configurations described in adult rodents were already present at birth. By contrast, limb placement changed abruptly at around P10. These skeletal configurations, observed in anesthetized pups, required the maintenance of precise motor control. On the other hand, motor control continued to mature, as shown by progressive changes in resting posture and head movements from P0 to P23. We suggest that a few innate skeletal configurations provide the necessary frames of reference for the gradual construction of an adult motor repertoire in altricial mammals, such as the rat. The apparent absence of a requirement for external sensorial cues in the maturation of this repertoire may account for the maturation of postural and motor control in utero in precocial mammals (Muir et al., 2000 for a review on the locomotor behavior of altricial and precocial animals).

  3. Male rat sexual behavior.

    PubMed

    Agmo, A

    1997-05-01

    The male rat's sexual behavior constitutes a highly ordered sequence of motor acts involving both striate and smooth muscles. It is spontaneously displayed by most adult made rats in the presence of a sexually receptive female. Although the behavior is important for the survival of the species it is not necessary for survival of the individual. In that way it is different from other spontaneous behaviors such as eating, drinking, avoidance of pain, respiration or thermoregulation. Among other things, this means that it is difficult to talk about sexual deprivation or need. Nevertheless, studies of male sex behavior distinguish sexual motivation (the ease by which behavior is activated, "libido") from the execution of copulatory acts (performance, "potency") (Meisel, R.L. and Sachs, B.D., The physiology of male sexual behavior. In: E. Knobil and J.D. Neill (Eds.), The Physiology of Reproduction, 2nd Edn., Vol. 2, Raven Press, New York, 1994, pp. 3-105 [13]). The hormonal control of male sexual behavior has been extensively studied. It is clear that steroid hormones, androgens and estrogens, act within the central nervous system, modifying neuronal excitability. The exact mechanism by which these hormones activate sex behavior remains largely unknown. However, there exists a considerable amount of knowledge concerning the brain structures important for sexual motivation and for the execution of sex behavior. The modulatory role of some non-steroid hormones is partly known, as well as the consequences of manipulations of several neurotransmitter systems.

  4. 17β-Estradiol and vitamin E modulates oxidative stress-induced kidney toxicity in diabetic ovariectomized rat.

    PubMed

    Ulas, Mustafa; Cay, Mehmet

    2011-12-01

    The aim of this study was to investigate the effects of vitamin E (alpha-tocopherol) and 17β-estradiol (E(2)) supplementation on malondialdehyde (MDA), glutathione (GSH), vitamin A, beta carotene, selenium-dependent glutathione peroxidase (GSH-Px), zinc-dependent superoxide dismutase (SOD), and copper/zinc-dependent catalase (CAT) values in the kidney of ovariectomized (OVX) diabetic rats. Forty-two female rats were randomly divided into seven equal groups as follows: group I, control; group II, OVX; group III, OVX+E(2); group IV, OVX+E(2)+alpha-tocopherol; group V, OVX+diabetic; group VI, OVX+diabetic+E(2); and group VII, OVX+diabetic+E(2)+alpha-tocopherol. E(2) (40 μg kg(-1)/day) and alpha-tocopherol (100 μg kg(-1)/day) were given. Bilateral ovariectomy was performed in all groups except group I. After 4 weeks, antioxidant and MDA levels in the kidney for all groups were analyzed. GSH-Px, CAT, SOD, GSH levels, vitamin A, and beta carotene levels were decreased in OVX group compared to those in the control group but MDA level was elevated via ovariectomy. However, E(2) and E(2)+alpha-tocopherol supplementations in OVX group was associated with an increase in the GSH-Px, GSH, CAT and Zn-SOD values, vitamin A, and beta carotene levels but a decrease in MDA levels in kidney. The MDA levels in the kidney of diabetic OVX rats were found higher than those in the control and OVX groups. However, GSH, GSH-Px, CAT, SOD, vitamin A, and beta carotene levels in kidney were lower in OVX diabetic rats. On the other hand, E(2) and E(2)+alpha-tocopherol supplementations to OVX diabetic rats have caused an increase in GSH-Px, CAT and SOD, GSH, vitamin A, and beta carotene levels but a decrease in MDA levels. In conclusion, the E(2) and E(2)+alpha-tocopherol supplementations to diabetic OVX and OVX rats may strengthen the antioxidant defense system by reducing lipid peroxidation, and therefore they may play a role in preventing renal disorders.

  5. Interactions of testosterone and all-trans retinoic acid in regulation of androgen receptor expression in rat lacrimal gland.

    PubMed

    Ubels, John L; Veenstra, Eric; Ditlev, Jonathon; Ingersoll, Kyle

    2003-12-01

    All-trans retinoic acid down-regulates androgen receptor (AR) expression in lacrimal gland acinar cells in culture. The goal of this study was to determine if retinoic acid inhibits androgen-stimulated up-regulation of AR protein and AR mRNA expression in lacrimal glands of orchiectomized rats in vivo. Delivery of androgens to orchiectomized rats was accomplished by subcutaneous implantation of a 25 or 50 mg 21-day slow-release testosterone pellet. Rats were treated with retinoic acid by gastric gavage at 20 mg kg(-1) day(-1). After 7 days of treatment lacrimal glands were removed, AR protein expression in frozen sections was determined by immunohistochemistry and total RNA was probed for AR mRNA expression. Serum testosterone was measured by ELISA and serum retinoic acid was detected by HPLC. Orchiectomy decreases serum testosterone to 17 +/- 8 ng dl(-1), compared to 143 +/- 27 ng dl(-1) in normal rats, and reduces the number of lacrimal acinar cell nuclei expressing ARs to less than 30% of normal. Implantation of testosterone pellets restored lacrimal AR expression, but increased serum testosterone to more than 10 times the normal levels. Retinoic acid failed to inhibit AR expression in rats with high serum testosterone. Therefore a dose-response study was conducted in which testosterone was delivered by injection of a single dose of Depotestosterone at 2.5-200 mg kg(-1). Treatment of orchiectomized rats with a dose of testosterone as low as 2.5 mg kg(-1) resulted in serum testosterone levels of 62 +/- 17 ng dl(-1) and significantly increased lacrimal gland AR expression. Delivery of retinoic acid at 20 or 50 mg kg(-1) day(-1) simultaneously with a 2.5 mg kg(-1) testosterone injection prevented restoration of lacrimal gland AR expression and significantly reduced AR mRNA expression. A pharmacologic dose of retinoic acid inhibits AR expression in lacrimal gland acinar cells in vivo, as well as in vitro. This indicates that effects of retinoic acid and testosterone

  6. An Overview on the Respiratory Stimulant Effects of Caffeine and Progesterone on Response to Hypoxia and Apnea Frequency in Developing Rats.

    PubMed

    Bairam, Aida; Uppari, NaggaPraveena; Mubayed, Sébastien; Joseph, Vincent

    2015-01-01

    The respiratory stimulant caffeine is the most frequently used xanthine (theophylline or aminophylline) for the treatment of apnea in premature infants. It decreases but does not eliminate apnea. In most cases such decreases is insufficient to prevent the use of artificial ventilation. Progesterone is a respiratory stimulant in adult mammals including human, and it decreases sleep apnea in menopausal women. Whether progesterone as an adjunct to caffeine therapy could be effective in further reducing the frequency of apnea in premature infants is not known because its respiratory effect in newborns has not been well studied. Using rat pups at different postnatal ages, we first determined whether the respiratory stimulant effects of acute caffeine (10 mg/kg, i.p.) or progesterone (4 mg/kg i.p.) are age dependent. These studies showed that caffeine enhances the ventilatory response to hypoxia in 1 and 4 days-old rats while it decreases apnea frequency in 12-days-old. In contrast, progesterone enhances the ventilatory response to hypoxia in less than 7-days-old but decreases apnea in 1-day-old rats. Preliminary experiments show that administration of progesterone (4 mg/kg i.p.) to newborn rats that are chronically treated with caffeine (mimicking its clinical uses - 7.5 mg/kg once/day by gavage) enhances the respiratory stimulant effects of caffeine. Surprisingly, acute injection of progesterone enhances apnea frequency and reduces hypoxic ventilatory response in 12-day-old rats.

  7. The role of peripheral 5HT2A and 5HT1A receptors on the orofacial formalin test in rats with persistent temporomandibular joint inflammation.

    PubMed

    Okamoto, K; Imbe, H; Tashiro, A; Kimura, A; Donishi, T; Tamai, Y; Senba, E

    2005-01-01

    The role of peripheral serotonin (5HT) 2A and 5HT1A receptors on the orofacial nocifensive behavioral activities evoked by the injection of formalin into the masseter muscle was evaluated in the rats with persistent temporomandibular joint (TMJ) inflammation evoked by Complete Freund's Adjuvant (CFA). The orofacial nocifensive behavioral activities evoked by the injection of formalin into masseter muscle were significantly enhanced at 1 day (CFA day 1 group) or 7 days (CFA day 7 group) during TMJ inflammation. Pretreatment with local administration of 5HT2A receptor antagonist, ketanserin (0.01, 0.1 mg/rat) into the masseter muscle or systemic administration of ketanserin via i.p. injection (1 mg/kg) reduced the orofacial nocifensive behavioral activities of the late phase evoked by formalin injection into masseter muscle on the side of TMJ inflammation (CFA day 7 group). However, local (0.001-0.1 mg/rat) or systemic (1 mg/kg) administration of 5HT1A receptor antagonist, propranolol, into masseter muscle did not produce the antinociceptive effect in CFA day 7 group. Moreover, local administration of ketanserin (0.1 mg) or propranolol (0.1 mg) into masseter muscle did not inhibit nocifensive orofacial behavior in rats without TMJ inflammation. These data suggest that persistent TMJ inflammation causes the elevation of the orofacial nocifensive behavior, and peripheral 5HT2A receptors play an important role in mediating the deep craniofacial tissue nociception in rats with TMJ inflammation.

  8. Traffic Noise Exposure Increases Gastric Pepsin Secretion in Rat.

    PubMed

    Moslehi, Azam; Nabavizadeh, Fatemeh; Keshavarz, Mansoor; Rouhbakhsh, Nematollah; Sotudeh, Masoud; Salimi, Ehsan; Barzegar Behrooz, Amir

    2016-03-01

    Noise is considered as one of the most severe sources of environmental and workplace constraints. Many noise effects are well known on immune function, hormonal levels, cardiovascular and respiratory systems. In this study, our aim is to evaluate the effects of traffic noise exposure on basal and stimulated gastric pepsin secretion. 48 male rats were exposed to traffic noise (86 dB) for a short term of (8h/day for 1 day) and a long term of (8h/day for 7, 14, 21 and 28 days) as well as a control group. The gastric contents were collected by the wash-out technique. Pepsin secretion was measured by employing the Anson method. Histological studies were carried out on the epithelial layer. The corticosteroid hormone was measured in the serum for the stress augmentation. The present finding indicated no changes in pepsin secretion content in the short term, but in the 14 and 21 days traffic noise exposure, basal gastric pepsin secretion increased markedly compared to the control group. Histological results showed that the number of oxyntic glands and cell nuclei decreased in comparison with the control group while the thickness of the epithelial layer increases. In addition, the corticosterone levels increase in all groups in comparison with the control. It seems that the increase of gastric pepsin secretion is due to the description and translation processes in the peptic cells and needs enough time for completion.

  9. Protective effect of cannabidiol against cadmium hepatotoxicity in rats.

    PubMed

    Fouad, Amr A; Al-Mulhim, Abdulruhman S; Gomaa, Wafaey

    2013-10-01

    The protective effect of cannabidiol, the non-psychoactive component of Cannabis sativa, against liver toxicity induced by a single dose of cadmium chloride (6.5 mgkg(-1) i.p.) was investigated in rats. Cannabidiol treatment (5 mgkg(-1)/day, i.p.) was applied for five days starting three days before cadmium administration. Cannabidiol significantly reduced serum alanine aminotransferase, and suppressed hepatic lipid peroxidation, prevented the depletion of reduced glutathione and nitric oxide, and catalase activity, and attenuated the elevation of cadmium level in the liver tissue resulted from cadmium administration. Histopathological examination showed that cadmium-induced liver tissue injury was ameliorated by cannabidiol treatment. Immunohistochemical analysis revealed that cannabidiol significantly decreased the cadmium-induced expression of tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB, caspase-3, and caspase-9, and increased the expression of endothelial nitric oxide synthase in liver tissue. It was concluded that cannabidiol may represent a potential option to protect the liver tissue from the detrimental effects of cadmium toxicity.

  10. Influence of Particle Size on Persistence and Clearance of Aerosolized Silver Nanoparticles in the Rat Lung

    PubMed Central

    Anderson, Donald S.; Patchin, Esther S.; Silva, Rona M.; Uyeminami, Dale L.; Sharmah, Arjun; Guo, Ting; Das, Gautom K.; Brown, Jared M.; Shannahan, Jonathan; Gordon, Terry; Chen, Lung Chi; Pinkerton, Kent E.; Van Winkle, Laura S.

    2015-01-01

    The growing use of silver nanoparticles (AgNPs) in consumer products raises concerns about potential health effects. This study investigated the persistence and clearance of 2 different size AgNPs (20 and 110 nm) delivered to rats by single nose-only aerosol exposures (6 h) of 7.2 and 5.4 mg/m3, respectively. Rat lung tissue was assessed for silver accumulations using inductively-coupled plasma mass spectrometry (ICP-MS), autometallography, and enhanced dark field microscopy. Involvement of tissue macrophages was assessed by scoring of silver staining in bronchoalveolar lavage fluid (BALF). Silver was abundant in most macrophages at 1 day post-exposure. The group exposed to 20 nm AgNP had the greatest number of silver positive BALF macrophages at 56 days post-exposure. While there was a significant decrease in the amount of silver in lung tissue at 56 days post-exposure compared with 1 day following exposure, at least 33% of the initial delivered dose was still present for both AgNPs. Regardless of particle size, silver was predominantly localized within the terminal bronchial/alveolar duct junction region of the lung associated with extracellular matrix and within epithelial cells. Inhalation of both 20 and 110 nm AgNPs resulted in a persistence of silver in the lung at 56 days post-exposure and local deposition as well as accumulation of silver at the terminal bronchiole alveolar duct junction. Further the smaller particles, 20 nm AgNP, produced a greater silver burden in BALF macrophages as well as greater persistence of silver positive macrophages at later timepoints (21 and 56 days). PMID:25577195

  11. Joint immobilization induced hypoxic and inflammatory conditions in rat knee joints.

    PubMed

    Yabe, Yutaka; Hagiwara, Yoshihiro; Suda, Hideaki; Ando, Akira; Onoda, Yoshito; Tsuchiya, Masahiro; Hatori, Kouki; Itoi, Eiji

    2013-01-01

    The purpose of this study was to examine the hypoxic and inflammatory conditions after immobilization in the joint capsule of rat knees. The unilateral knee joints of adult male rats were immobilized with an internal fixator (Im group) for 1 day, 3 days, and 1, 2, 4, 8, and 16 weeks. Sham-operated animals had holes drilled in the femur and tibia and screws inserted without a plate (control group). The number of cells and blood vessels in the capsule were histologically examined. The hypoxic condition in the capsule was histologically examined with a Hypoxyprobe™-1. The gene expressions related to the hypoxic (hypoxia inducible factor-1α, vascular endothelial growth factor, and fibroblast growth factor 2) and inflammatory conditions [interleukin-6 (IL-6), IL-1α, IL-1β, tumor necrosis factor-α, and tumor necrosis factor-β] were evaluated by quantitative reverse transcription polymerase chain reaction. The number of cells was unchanged at 1 day in the two groups; however, the number significantly increased at 3 days in the Im group. The number of blood vessels in the Im group gradually decreased. Strong immunostaining of Hypoxyprobe™-1 around the blood vessels was observed in the Im group. The gene expressions of hypoxia inducible factor-1α and fibroblast growth factor 2 were significantly higher in the Im group compared with those in the control group. The gene expressions of IL-6, IL-1α, IL-1β, and tumor necrosis factor-β were significantly higher in the Im group compared with those in the control group. These data indicated that joint immobilization induced hypoxic and inflammatory conditions in the joint capsule, which might be an initiating factor for joint contracture.

  12. Effect of D-penicillamine on rat lung elastin cross-linking during the perinatal period.

    PubMed

    Koçtürk, Semra; Oktay, Gülgün; Güner, Gül; Pekçetin, Cetin; Güre, Ataman

    2006-01-01

    This study was designed to clarify the effects of D-penicillamine (DPA), a drug used for treatment of various pathological events, on lung elastin formation and maturation of the newborn in the perinatal period. The investigation was conducted on 20 newborn rats bred from 40 female and six male rats. DPA doses 400 mg kg(-1) day(-1) and physiological saline were given intraperitoneally (i.p) to experimental and control groups. To assess newborn maturation, their body and lung weights were determined. Serum Cu levels were measured by atomic absorption spectroscopy and ceruloplasmin (Cp) activities were measured spectrophotometrically. Newborn lung tissue elastin, desmosine (DES) and isodesmosine (IDES) levels were measured by HPLC. The results showed that DPA treatment caused loss of skin elasticity and reduction in body and lung weight in newborns of the experimental group. The serum Cu levels and Cp activity were found to be significantly lower in both maternal and newborn of the experimental groups compared with the control group. The lung DES, IDES and elastin values of newborns in the experimental group were decreased compared with the control group. In conclusion, our results indicate that 400 mg kg(-1) day(-1) DPA, a dose that is used in the treatment of Wilson's disease, rheumatoid arthritis and cystinuria, caused the retardation of newborn maturation, a decrease in DES-IDES cross-links and levels of lung elastin of offspring in the perinatal period. Another conclusion to be drawn from this study is that even low levels of Cu depletion due to DPA administration induces a change in cross-linking in lung elastin during the perinatal period.

  13. Pathogenesis and Transmission of Kilham Rat Virus Infection in Rats

    PubMed Central

    Novotny, James F.; Hetrick, Frank M.

    1970-01-01

    The Kilham rat virus (RV) was found to produce mortality in newborn rats after intracerebral, intravenous, or subcutaneous administration of virus. Both infectious virus and viral hemagglutinins were detected in a variety of tissues and in the blood and urine of experimentally infected rats. Contact control rats housed with infected littermates did not develop disease but did produce antibody to RV. Horizontal virus transmission was also evidenced by the seroconversion of antibody-negative mothers whose litters were infected with RV. The level of maternal antibody was found to be the determining factor in the susceptibility or refractiveness of newborn rats to RV infection. If the mother had no detectable hemagglutination-inhibiting (HI) antibody titer (less than 10) or a low antibody titer (10 or 20), her offspring were highly susceptible to RV. However, the litters of rats with HI titers of 40 or greater were afforded protection when challenged with RV; the higher the maternal antibody level the more solid was the protection conferred. Vertical transmission of RV was also demonstrated. Litters born of mothers infected with RV several days before delivery died within 7 to 9 days of a disease identical to that seen in infected newborns and virus was recovered from a variety of tissues. Results of mother-litter exchange experiments also indicated vertical transmission (rather than transmission through milk) occurs, since litters of infected mothers developed the disease when nursed by normal mothers, whereas litters of normal mothers remained normal although they were nursed by infected mothers. PMID:16557835

  14. AT1 receptors are necessary for eccentric training-induced hypertrophy and strength gains in rat skeletal muscle.

    PubMed

    McBride, Todd A

    2006-03-01

    This study was undertaken to measure the response of skeletal muscle to eccentric contractions (EC) in the presence of the angiotensin type 1 (AT1) receptor blocker, losartan. It was hypothesized that blocking AT1 receptors prior to an initial bout of EC would prevent the muscle from developing the normal adaptation to EC as demonstrated by the repeated bout effect. It was also hypothesized that continuous AT1 receptor blockade during EC training would significantly reduce muscle hypertrophy and strength gains that occur with repeated EC. Rats received losartan in their drinking water at either a low dose (20 mg (kg body weight)-1 day-1) or a high dose (40 mg (kg body weight)-1 day-1). Each bout of EC consisted of a total of 24 contractions. Rats were assigned to four groups: a single acute bout of EC (n=6); two bouts of EC separated by 14 days (n=8); and 4 weeks of training twice a week on the low dose (n=5) or the high dose (n=9). There was no effect of AT1 receptor blockade on the initial loss of function following a single acute bout of EC, or on the repeated bout effect following a second exposure to EC. AT1 receptor blockade did alter the results of EC training, in both the low and high dose groups. Losartan treatments prevented EC training-induced increases in muscle wet and dry weights compared to untreated rats. Finally, the low and high dose losartan treatments also prevented an increase in muscle contractile force following EC training compared to the untreated group. Functional AT1 receptors are therefore not necessary for an acute adaptation to EC as demonstrated by the repeated bout effect, but are necessary for muscle hypertrophy and increased contractile force associated with EC training.

  15. Systematic analysis of axonal damage and inflammatory response in different white matter tracts of acutely injured rat spinal cord.

    PubMed

    Gomes-Leal, W; Corkill, D J; Picanço-Diniz, C W

    2005-12-20

    The mechanisms of white matter (WM) damage during secondary degeneration are a fundamental issue in the pathophysiology of central nervous system (CNS) diseases. Our main goal was to describe the pattern of an acute inflammatory response and secondary damage to axons in different WM tracts of acutely injured rat spinal cord. Adult rats were deeply anesthetized and injected with 20 nmol of NMDA into the spinal cord ventral horn on T7. Animals were perfused after survival times of 1 day, 3 days and 7 days. Ten micrometer sections were submitted to immunocytochemical analysis for activated macrophages/microglia, neutrophils and damaged axons. There were inflammatory response and progressive tissue destruction of ventral WM (VWM) with formation of microcysts in both VWM and lateral WM (LWM). In the VWM, the number of beta-amyloid precursor protein (beta-APP) end-bulbs increased from 1 day with a peak at 3 days, decreasing by 7 days following the injection. APP end-bulbs were present in the dorsal WM (DWM) at 3 days survival time but were not in the LWM. Electron microscopic analysis revealed different degrees of myelin disruption and axonal pathology in the vacuolated WM up to 14 mm along the rostrocaudal axis. Quantitative analysis revealed a significant loss of medium and large axons (P < 0.05), but not of small axons (P > 0.05). Our results suggest that bystander axonal damage and myelin vacuolation are important secondary component of the pathology of WM tracts following rat SCI. Further studies are needed to understand the mechanisms of these pathological events.

  16. Online tools for understanding rat physiology

    PubMed Central

    2010-01-01

    Rat models have been used to investigate physiological and pathophysiological mechanisms for decades. With the availability of the rat genome and other online resources, tools to identify rat models that mimic human disease are an important step in translational research. Despite the large number of papers published each year using rat models, integrating this information remains a problem. Resources for the rat genome are continuing to grow rapidly, while resources providing access to rat phenotype data are just emerging. An overview of rat models of disease, tools to characterize strain by phenotype and genotype, and steps being taken to integrate rat physiological data is presented in this article. Integrating functional and physiological data with the rat genome will build a solid research platform to facilitate innovative studies to unravel the mechanisms resulting in disease. PMID:20056729

  17. 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.

  18. Cardiovascular effects in rats after intratracheal instillation of metal welding particles

    PubMed Central

    Zheng, Wen; Antonini, James M.; Lin, Yen-Chang; Roberts, Jenny R.; Kashon, Michael L.; Castranova, Vincent; Kan, Hong

    2015-01-01

    Studies have indicated that pulmonary exposure to welding fumes can induce a series of adverse effects in the respiratory system, including infection, bronchitis, siderosis and decreased pulmonary function. Recent clinical and epidemiological studies have found that pulmonary exposure to welding fumes is also associated with a higher incidence of cardiovascular events. However, there is insufficient evidence to confirm a direct effect of welding fumes on the cardiovascular system. The present study investigated the effects of pulmonary exposure to welding fumes on the heart and the vascular system in rats. Two chemically distinct welding fumes generated from manual metal arc-hard surfacing (MMA-HS) and gas metal arc-mild steel (GMA-MS) welding were tested. Three groups of rats were instilled intratracheally with MMA-HS (2 mg/rat), GMA-MS (2 mg/rat) or saline as control once a week for seven weeks. On days 1 and 7 after the last treatment, basal cardiovascular function and the cardiovascular response to increasing doses of adrenoreceptor agonists were assessed. MMA-HS treatment reduced the basal levels of left ventricle end-systolic pressure and dP/dtmax at 1 day post-treatment, and decreased dP/dtmin in response to isoproterenol (ISO) at 7 days post-treatment. Unlike MMA-HS, GMA-MS only affected left ventricular end-diastolic pressure in response to ISO at 7 days post-treatment. Treatment with MMA-HS or GMA-MS did not alter heart rate and blood pressure. Our findings suggest that exposure to different welding fumes can induce different adverse effects on the cardiovascular system, and that cardiac contractility may be a sensitive indicator of cardiovascular dysfunction. PMID:25600139

  19. Rapid plasticity follows whisker pairing in barrel cortex of the awake rat.

    PubMed

    Sellien, Heike; Ebner, Ford F

    2007-02-01

    Synaptic plasticity can be induced easily throughout life in the rodent somatic sensory cortex. Trimming all but two whiskers on one side of an adult rat's face, called 'whisker pairing', causes the active (intact) whiskers to develop a stronger drive on cortical cells in their respective barrel columns, while inactive (trimmed) whisker efficacy is down-regulated. To date, this type of activity-dependent plasticity has been induced by trimming all but two whiskers, letting the rats explore their environment from 1 day to 1 month, after which cortical responses were analyzed physiologically under anesthesia. Such studies have enhanced our understanding of cortical plasticity, but the anesthesia complicates the examination of changes that occur in the first few hours after whisker trimming. Here we assayed the short-term changes that occur in alert, active animals over a period of hours after whisker trimming. The magnitude of barrel cortex evoked responses was measured in response to stimulation of the cut and paired whiskers of rats under several conditions: (a) whisking in air (control), (b) active whisking of an object by the rat, and (c) epochs of passive whisker stimulation to identify the onset of whisker pairing plasticity changes in cortex. The main difference between whisking in air without contact and passive whisker stimulation is that the former condition induces an increased response to stimulation of inactive cut whiskers, while the latter condition increases the responses to the stimulated whiskers. The results support the conclusion that whisker pairing plasticity in barrel cortex occurs within 4 h after whisker trimming in an awake, alert animal.

  20. A cross-fostering analysis of bromine ion concentration in rats that inhaled 1-bromopropane vapor

    PubMed Central

    Ishidao, Toru; Fueta, Yukiko; Ueno, Susumu; Yoshida, Yasuhiro; Hori, Hajime

    2016-01-01

    Objective: Inhaled 1-bromopropane decomposes easily and releases bromine ion. However, the kinetics and transfer of bromine ion into the next generation have not been clarified. In this work, the kinetics of bromine ion transfer to the next generation was investigated by using cross-fostering analysis and a one-compartment model. Methods: Pregnant Wistar rats were exposed to 700 ppm of 1-bromopropane vapor for 6 h per day during gestation days (GDs) 1-20. After birth, cross-fostering was performed between mother exposure groups and mother control groups, and the pups were subdivided into the following four groups: exposure group, postnatal exposure group, gestation exposure group, and control group. Bromine ion concentrations in the brain were measured temporally. Results: Bromine ion concentrations in mother rats were lower than those in virgin rats, and the concentrations in fetuses were higher than those in mothers on GD20. In the postnatal period, the concentrations in the gestation exposure group decreased with time, and the biological half-life was 3.1 days. Conversely, bromine ion concentration in the postnatal exposure group increased until postnatal day 4 and then decreased. This tendency was also observed in the exposure group. A one-compartment model was applied to analyze the behavior of bromine ion concentration in the brain. By taking into account the increase of body weight and change in the bromine ion uptake rate in pups, the bromine ion concentrations in the brains of the rats could be estimated with acceptable precision. PMID:27108641

  1. Cardiovascular effects in rats after intratracheal instillation of metal welding particles.

    PubMed

    Zheng, Wen; Antonini, James M; Lin, Yen-Chang; Roberts, Jenny R; Kashon, Michael L; Castranova, Vincent; Kan, Hong

    2015-01-01

    Studies have indicated that pulmonary exposure to welding fumes can induce a series of adverse effects in the respiratory system, including infection, bronchitis, siderosis and decreased pulmonary function. Recent clinical and epidemiological studies have found that pulmonary exposure to welding fumes is also associated with a higher incidence of cardiovascular events. However, there is insufficient evidence to confirm a direct effect of welding fumes on the cardiovascular system. The present study investigated the effects of pulmonary exposure to welding fumes on the heart and the vascular system in rats. Two chemically distinct welding fumes generated from manual metal arc-hard surfacing (MMA-HS) and gas metal arc-mild steel (GMA-MS) welding were tested. Three groups of rats were instilled intratracheally with MMA-HS (2 mg/rat), GMA-MS (2 mg/rat) or saline as control once a week for seven weeks. On days 1 and 7 after the last treatment, basal cardiovascular function and the cardiovascular response to increasing doses of adrenoreceptor agonists were assessed. MMA-HS treatment reduced the basal levels of left ventricle end-systolic pressure and dP/dt(max) at 1 day post-treatment, and decreased dP/dt(min) in response to isoproterenol (ISO) at 7 days post-treatment. Unlike MMA-HS, GMA-MS only affected left ventricular end-diastolic pressure in response to ISO at 7 days post-treatment. Treatment with MMA-HS or GMA-MS did not alter heart rate and blood pressure. Our findings suggest that exposure to different welding fumes can induce different adverse effects on the cardiovascular system, and that cardiac contractility may be a sensitive indicator of cardiovascular dysfunction.

  2. Neonatal hyperleptinaemia programmes adrenal medullary function in adult rats: effects on cardiovascular parameters.

    PubMed

    Trevenzoli, I H; Valle, M M R; Machado, F B; Garcia, R M G; Passos, M C F; Lisboa, P C; Moura, E G

    2007-04-15

    Epidemiological studies have shown a strong correlation between stressful events (nutritional, hormonal or environmental) in early life and development of adult diseases such as obesity, diabetes and cardiovascular failure. It is known that gestation and lactation are crucial periods for healthy growth in mammals and that the sympathoadrenal system is markedly influenced by environmental conditions during these periods. We previously demonstrated that neonatal hyperleptinaemia in rats programmes higher body weight, higher food intake and hypothalamic leptin resistance in adulthood. Using this model of programming, we investigated adrenal medullary function and effects on cardiovascular parameters in male rats in adulthood. Leptin treatment during the first 10 days of lactation (8 microg 100 g(-1) day(-1), s.c.) resulted in lower body weight (6.5%, P < 0.05), hyperleptinaemia (10-fold, P < 0.05) and higher catecholamine content in adrenal glands (18.5%, P < 0.05) on the last day of treatment. In adulthood (150 days), the rats presented higher body weight (5%, P < 0.05), adrenal catecholamine content (3-fold, P < 0.05), tyrosine hydroxylase expression (35%, P < 0.05) and basal and caffeine-stimulated catecholamine release (53% and 100%, respectively, P < 0.05). Systolic blood pressure and heart rate were also higher in adult rats (7% and 6%, respectively, P < 0.05). Our results show that hyperleptinaemia in early life increases adrenal medullary function in adulthood and that this may alter cardiovascular parameters. Thus, we suggest that imprinting factors which increase leptin and catecholamine levels during the neonatal period could be involved in development of adult chronic diseases.

  3. 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.

  4. Spatial integration with rats.

    PubMed

    Chamizo, V D; Rodrigo, T; Mackintosh, N J

    2006-11-01

    Rats were trained to find the hidden platform in a Morris pool, whose location was defined by reference to a small number of landmarks around the circumference of the pool. In each of three experiments, an experimental group was trained on alternate trials with two different subsets of three of the available landmarks, with the two subsets sharing one landmark in common. When tested with landmarks drawn from both of their training configurations, but without the landmark common to the two sets, they had no difficulty in locating the platform. In Experiment 1, they performed at least as well as a group trained with all the available landmarks present on every trial. In Experiment 2, they performed significantly better than a group trained with two different subsets of landmarks that shared no one landmark in common.

  5. The rat adrenal medulla.

    PubMed

    Tischler, A S

    1989-01-01

    Adult adrenal medullary cells, in many strains of rats, develop diffuse and nodular hyperplasia and neoplasia under a variety of conditions. Both endogenous and exogenous factors affect the development of these proliferative changes. The former include the animals' strain, age, and sex. The latter include drugs and other environmental agents, diet, and perhaps stress. Adrenal medullary neoplasms which arise under diverse circumstances often closely resemble each other both morphologically and functionally, and exhibit characteristics of immature chromaffin cells. Recent data indicate that normal, mature-appearing epinephrine- and norepinephrine-type chromaffin cells are able to divide, and suggest that signals which regulate chromaffin cell function also regulate cell proliferation. Prolongation of these signals or superimposed abnormalities might initiate pathological proliferative states. It remains to be determined whether the mechanisms which promote or prevent cell proliferation in the adult adrenal are related to those involved in normal development.

  6. Iodothyronine Metabolism in Rat Liver Homogenates

    PubMed Central

    Kaplan, Michael M.; Utiger, Robert D.

    1978-01-01

    To investigate mechanisms of extrathyroidal thyroid hormone metabolism, conversion of thyroxine (T4) to 3,5,3′-triiodothyronine (T3) and degradation of 3,3′,5′-triiodothyronine (rT3) were studied in rat liver homogenates. Both reactions were enzymatic. For conversion of T4 to T3, the Km of T4 was 7.7 μM, and the Vmax was 0.13 pmol T3/min per mg protein. For rT3 degradation, the Km of rT3 was 7.5 nM, and the Vmax was 0.36 pmol rT3/min per mg protein. Production of rT3 or degradation of T4 or T3 was not detected under the conditions employed. rT3 was a potent competitive inhibitor of T4 to T3 conversion with a Ki of 4.5 nM; 3,3′-diiodothyronine was a less potent inhibitor of this reaction. T4 was a competitive inhibitor of rT3 degradation with a Ki of 10.2 μM. Agents which inhibited both reactions included propylthiouracil, which appeared to be an allosteric inhibitor, 2,4-dinitrophenol, and iopanoic acid. Sodium diatrizoate had a weak inhibitory effect. No inhibition was found with α-methylparatyrosine, Fe+2, Fe+3, reduced glutathione, β-hydroxybutyrate, or oleic acid. Fasting resulted in inhibition of T4 to T3 conversion and of rT3 degradation by rat liver homogenates which was reversible after refeeding. Serum T4, T3, and thyrotropin concentrations fell during fasting, with no decrease in serum protein binding as assessed by a T3-charcoal uptake. There was no consistent change in serum rT3 concentrations. Dexamethasone had no effect in vitro. In vivo dexamethasone administration resulted in elevated serum rT3 concentrations after 1 day, and after 5 days, in inhibition of T4 to T3 conversion and rT3 degradation without altering serum T4, T3, or thyrotropin concentrations. Endotoxin treatment had no effect of iodothyronine metabolism in liver homogenates. In kidney homogenates the reaction rates and response to propylthiouracil in vitro were similar to those in liver. No significant T4 to T3 conversion or rT3 production or degradation could be detected

  7. Social facial touch in rats.

    PubMed

    Wolfe, Jason; Mende, Carolin; Brecht, Michael

    2011-12-01

    We know much about how rats use their whiskers to discriminate simple tactile properties, but little about how they are used in natural settings. Here we studied whisker motion during social interactions between rats in order to gain a better understanding of natural whisker use in this model system for sensorimotor integration. In the first set of experiments, an intruder was placed in a second rat's home cage. Anogenital sniffing immediately ensued; later in the trial, facial interactions occurred at least as frequently. Whereas much previous work has focused on the importance of anogenital sniffing during social interactions, these facial interactions were accompanied by some of the most intense whisker behaviors described to date. Whisker trimming increased biting but reduced boxing. In addition, whiskers were more protracted and whisking amplitude was larger in aggressive than in nonaggressive interactions. In a second set of experiments, rats interacted facially across a gap. As rats approached each other, whisking amplitude decreased and whiskers were more protracted. Whisker trimming disrupted facial alignment and reduced the frequency of interactions, indicating that whisker use, and possibly whisker protraction, is important for rats to orient themselves with respect to one another. We also found that females whisked with smaller amplitude when interacting with males than with females, and that they held their whiskers less protracted than males. The natural whisker use described here should further our understanding of this important somatosensory system during social interactions.

  8. Management of an outbreak of rat theilovirus.

    PubMed

    Dyson, Melissa C

    2010-05-01

    Rat theilovirus is a commonly reported infection in research rat colonies. The author's institution experienced an outbreak of rat theilovirus in a breeding colony of unique outbred rats. To manage this outbreak, the institution chose to use a 'test and cull' strategy because this approach is reported to be successful in mouse colonies infected with Theiler's murine encephalomyelitis virus, a related virus. Here the author describes the outbreak and subsequent management of rat theilovirus. The strategy successfully cleared the virus from the rat colony.

  9. Expression of semaphorin 3A in the rat corneal epithelium during wound healing

    SciTech Connect

    Morishige, Naoyuki; Ko, Ji-Ae; Morita, Yukiko; Nishida, Teruo

    2010-05-14

    The neural guidance protein semaphorin 3A (Sema3A) is expressed in corneal epithelial cells of the adult rat. We have now further investigated the localization of Sema3A in the normal rat corneal epithelium as well as changes in its expression pattern during wound healing after central corneal epithelial debridement. The expression pattern of Sema3A was compared with that of the tight-junction protein zonula occludens-1 (ZO-1), the gap-junction protein connexin43 (Cx43), or the cell proliferation marker Ki67. Immunofluorescence analysis revealed that Sema3A was present predominantly in the membrane of basal and wing cells of the intact corneal epithelium. The expression of Sema3A at the basal side of basal cells was increased in the peripheral epithelium compared with that in the central region. Sema3A was detected in all layers at the leading edge of the migrating corneal epithelium at 6 h after central epithelial debridement. The expression of Sema3A was markedly up-regulated in the basal and lateral membranes of columnar basal cells apparent in the thickened, newly healed epithelium at 1 day after debridement, but it had largely returned to the normal pattern at 3 days after debridement. The expression of ZO-1 was restricted to superficial epithelial cells and remained mostly unchanged during the wound healing process. The expression of Cx43 in basal cells was down-regulated at the leading edge of the migrating epithelium but was stable in the remaining portion of the epithelium. Ki67 was not detected in basal cells of the central epithelium at 1 day after epithelial debridement, when Sema3A was prominently expressed. Immunoblot analysis showed that the abundance of Sema3A in the central cornea was increased 1 day after epithelial debridement, whereas that of ZO-1 or Cx43 remained largely unchanged. This increase in Sema3A expression was accompanied by up-regulation of the Sema3A coreceptor neuropilin-1. Our observations have thus shown that the expression of

  10. Characterization of a shortened model of diet alternation in female rats: effects of the CB1 receptor antagonist rimonabant on food intake and anxiety-like behavior

    PubMed Central

    Blasio, Angelo; Rice, Kenner C; Sabino, Valentina; Cottone, Pietro

    2014-01-01

    The prevalence of eating disorders and obesity in Western societies is epidemic and increasing in severity. Preclinical research focused on the development of animal models which can mimic the maladaptive patterns of food intake observed in certain forms of eating disorders and obesity. This study was aimed at characterizing a recently established model of palatable diet alternation in female rats. For this purpose, females rats were fed either continuously with a regular chow diet (Chow/Chow) or intermittently with a regular chow diet for 2 days and a palatable, high-sucrose diet for 1 day (Chow/Palatable). Following diet cycling, rats were administered rimonabant (0, 0.3, 1, 3 mg/kg i.p.) during access to either palatable diet or chow diet and were assessed for food intake and body weight. Finally, rats were pretreated with rimonabant (0 – 3 mg/kg, i.p.) and tested in the elevated plus maze during withdrawal from the palatable diet. Female rats with alternating access to palatable food cycled their intake, overeating during access to the palatable diet, and under-eating upon returning to the regular chow diet. Rimonabant treatment resulted in increased chow hypophagia and anxiety-like behavior in Chow/Palatable rats. No effect of drug treatment was observed on the compulsive eating of palatable food in the diet cycled rats. The results of this study suggest that withdrawal from alternating access to the palatable diet makes individuals vulnerable to the anxiogenic effects of rimonabant and provide etiological factors potentially responsible for the emergence of severe psychiatric side-effects following rimonabant treatment in obese patients. PMID:25011007

  11. Characterization of a shortened model of diet alternation in female rats: effects of the CB1 receptor antagonist rimonabant on food intake and anxiety-like behavior.

    PubMed

    Blasio, Angelo; Rice, Kenner C; Sabino, Valentina; Cottone, Pietro

    2014-10-01

    The prevalence of eating disorders and obesity in western societies is epidemic and increasing in severity. Preclinical research has focused on the development of animal models that can mimic the maladaptive patterns of food intake observed in certain forms of eating disorders and obesity. This study was aimed at characterizing a recently established model of palatable diet alternation in female rats. For this purpose, females rats were fed either continuously with a regular chow diet (Chow/Chow) or intermittently with a regular chow diet for 2 days and a palatable, high-sucrose diet for 1 day (Chow/Palatable). Following diet cycling, rats were administered rimonabant (0, 0.3, 1, 3 mg/kg intraperitoneally) during access to either palatable diet or chow diet and were assessed for food intake and body weight. Finally, rats were pretreated with rimonabant (0, 3 mg/kg, intraperitoneally) and tested in the elevated plus maze during withdrawal from the palatable diet. Female rats with alternating access to palatable food cycled their intake, overeating during access to the palatable diet and undereating upon returning to the regular chow diet. Rimonabant treatment resulted in increased chow hypophagia and anxiety-like behavior in Chow/Palatable rats. No effect of drug treatment was observed on the compulsive eating of palatable food in the diet-cycled rats. The results of this study suggest that withdrawal from alternating access to the palatable diet makes individuals vulnerable to the anxiogenic effects of rimonabant and provides etiological factors potentially responsible for the emergence of severe psychiatric side-effects following rimonabant treatment in obese patients.

  12. Vitamin A Supplementation in Early Life Enhances the Intestinal Immune Response of Rats with Gestational Vitamin A Deficiency by Increasing the Number of Immune Cells

    PubMed Central

    Liu, Xia; Cui, Ting; Li, Yingying; Wang, Yuting; Wang, Qinghong; Li, Xin; Bi, Yang; Wei, Xiaoping; Liu, Lan; Li, Tingyu; Chen, Jie

    2014-01-01

    Vitamin A is a critical micronutrient for regulating immunity in many organisms. Our previous study demonstrated that gestational or early-life vitamin A deficiency decreases the number of immune cells in offspring. The present study aims to test whether vitamin A supplementation can restore lymphocyte pools in vitamin A-deficient rats and thereby improve the function of their intestinal mucosa; furthermore, the study aimed to identify the best time frame for vitamin A supplementation. Vitamin A-deficient pregnant rats or their offspring were administered a low-dose of vitamin A daily for 7 days starting on gestational day 14 or postnatal day 1, day 14 or day 28. Serum retinol concentrations increased significantly in all four groups that received vitamin A supplementation, as determined by high-performance liquid chromatography. The intestinal levels of secretory immunoglobulin A and polymeric immunoglobulin receptor increased significantly with lipopolysaccharide challenge in the rats that received vitamin A supplementation starting on postnatal day 1. The rats in this group had higher numbers of CD8+ intestinal intraepithelial lymphocytes, CD11C+ dendritic cells in the Peyer's patches and CD4+CD25+ T cells in the spleen compared with the vitamin A-deficient rats; flow cytometric analysis also demonstrated that vitamin A supplementation decreased the number of B cells in the mesenteric lymph nodes. Additionally, vitamin A supplementation during late gestation increased the numbers of CD8+ intestinal intraepithelial lymphocytes and decreased the numbers of B lymphocytes in the mesenteric lymph nodes. However, no significant differences in lymphocyte levels were found between the rats in the other two vitamin A supplement groups and the vitamin A-deficient group. In conclusion, the best recovery of a subset of lymphocytes in the offspring of gestational vitamin A-deficient rats and the greatest improvement in the intestinal mucosal immune response are achieved when

  13. Environmental lead exposure during early life alters granule cell neurogenesis and morphology in the hippocampus of young adult rats.

    PubMed

    Verina, T; Rohde, C A; Guilarte, T R

    2007-03-30

    Exposure to environmentally relevant levels of lead (Pb(2+)) during early life produces deficits in hippocampal synaptic plasticity in the form of long-term potentiation (LTP) and spatial learning in young adult rats [Nihei MK, Desmond NL, McGlothan JL, Kuhlmann AC, Guilarte TR (2000) N-methyl-D-aspartate receptor subunit changes are associated with lead-induced deficits of long-term potentiation and spatial learning. Neuroscience 99:233-242; Guilarte TR, Toscano CD, McGlothan JL, Weaver SA (2003) Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure. Ann Neurol 53:50-56]. Other evidence suggests that the performance of rats in the Morris water maze spatial learning tasks is associated with the level of granule cell neurogenesis in the dentate gyrus (DG) [Drapeau E, Mayo W, Aurousseau C, Le Moal M, Piazza P-V, Abrous DN (2003) Spatial memory performance of aged rats in the water maze predicts level of hippocampal neurogenesis. Proc Natl Acad Sci U S A 100:14385-14390]. In this study, we examined whether continuous exposure to environmentally relevant levels of Pb(2+) during early life altered granule cell neurogenesis and morphology in the rat hippocampus. Control and Pb(2+)-exposed rats received bromodeoxyuridine (BrdU) injections (100 mg/kg; i.p.) for five consecutive days starting at postnatal day 45 and were killed either 1 day or 4 weeks after the last injection. The total number of newborn cells in the DG of Pb(2+)-exposed rats was significantly decreased (13%; P<0.001) 1 day after BrdU injections relative to controls. Further, the survival of newborn cells in Pb(2+)-exposed rats was significantly decreased by 22.7% (P<0.001) relative to control animals. Co-localization of BrdU with neuronal or astrocytic markers did not reveal a significant effect of Pb(2+) exposure on cellular fate. In Pb(2+)-exposed rats, immature granule cells immunolabeled with doublecortin (DCX) displayed aberrant dendritic morphology

  14. Assessment of effect of Zhu-tan Tong-luo decoction on CYP450 isoforms activity of rats.

    PubMed

    Jin, Yongxi; Shao, Lingjiu; Li, Gaowen; Shao, Mengmeng; Zhi, Yinghao; Zhu, Wenzong

    2015-01-01

    In order to investigate the effects of Zhu-tan Tong-luo decoction on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of CYP2B6, CYP2C19, CYP1A2, CYP3A4, CYP2C9, CYP2D6. The rats were randomly divided into acute Zhu-Tan Tong-Luo decoction group (Low, High), chronic Zhu-Tan Tong-Luo decoction group (Low, High) and control group. The acute group rats were given 0.6, 1.2 g/kg (Low, High) Zhu-tan Tong-luo decoction by intragastric administration for 1 day, and the chronic group for 14 days. Six probe drugs bupropion, omeprazole, phenacetin, testosterone, tolbutamide, and metroprolol were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. There statistical pharmacokinetics differences for omeprazole, phenacetin, testosterone, tolbutamide, and metroprolol in rats were observed by comparing acute Zhu-tan Tong-luo decoction group with control group; and statistical pharmacokinetics differences for bupropion, omeprazole, phenacetin, testosterone, tolbutamide, and metroprolol were observed by comparing chronic Zhu-Tan Tong-Luo decoction group with control group. After intragastric administration of Zhu-Tan Tong-Luo decoction may slightly induce the activities of CYP2B6, CYP2C19, CYP1A2, CYP3A4, CYP2C9, CYP2D6 of rats. Induction of drug metabolizing enzyme by Zhu-Tan Tong-Luo decoction would reduce the efficacy of other drug. Additional, there no statistical difference for biochemical results after 1 or 14 intragastric administration of Zhu-Tan Tong-Luo decoction.

  15. Foetal proglucagon processing in relation to adult appetite control: lessons from a transplantable rat glucagonoma with severe anorexia.

    PubMed

    Jensen, P B; Larsen, P J; Karlsen, C; Jensen, H I; Holst, J J; Madsen, O D

    2011-10-01

    We have previously reported severe anorexia abruptly induced in rats 2-3 weeks after they have been transplanted subcutaneously with the glucagonoma MSL-G-AN. Vagotomy did not affect the time of onset and severity of anorexia, and the anorectic state resembles hunger with strongly elevated neuropeptide Y (NPY) mRNA levels in the nucleus arcuatus. We now show that circulating levels of bioactive glucagon-like peptide-1 (GLP-1) (7-36amide) start to increase above control levels exactly at the time of onset of anorexia. At this time-point, bioactive glucagon as well as total glucagon precursors and GLP-1 metabolites are already vastly elevated compared to controls. We further show that intravenous administration of very high concentrations of GLP-1 to hungry schedule-fed rats causes anorexia in a dose-dependent manner, which is blocked by the GLP-1 receptor antagonist exendin (9-39). GLP-1 (7-36amide) has a well-characterized anorectic effect but also causes taste aversion when administered centrally. The anorectic effect is blocked in rats treated neonatally by monosodium glutamate (MSG). We show that MSG treatment does not prevent the MSL-G-AN-induced anorexia, thereby suggesting a different type of anorectic function. We show a very strong component of taste aversion as anorectic rats, when presented to novel or known alternative food items, will resume normal feeding for 1 day, and then redevelop anorexia. We hypothetize that the anorexia in MSL-G-AN tumour-bearing rats correlates with a foetal processing pattern of proglucagon to both glucagon and GLP-1 (7-36amide), and is due to taste aversion. The sudden onset is characterized by a dramatic increase in circulating levels of biologically active GLP-1 (7-36amide), suggesting eventual saturation of proteolytic inactivation of its N-terminus.

  16. Assessment of effect of Zhu-tan Tong-luo decoction on CYP450 isoforms activity of rats

    PubMed Central

    Jin, Yongxi; Shao, Lingjiu; Li, Gaowen; Shao, Mengmeng; Zhi, Yinghao; Zhu, Wenzong

    2015-01-01

    In order to investigate the effects of Zhu-tan Tong-luo decoction on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of CYP2B6, CYP2C19, CYP1A2, CYP3A4, CYP2C9, CYP2D6. The rats were randomly divided into acute Zhu-Tan Tong-Luo decoction group (Low, High), chronic Zhu-Tan Tong-Luo decoction group (Low, High) and control group. The acute group rats were given 0.6, 1.2 g/kg (Low, High) Zhu-tan Tong-luo decoction by intragastric administration for 1 day, and the chronic group for 14 days. Six probe drugs bupropion, omeprazole, phenacetin, testosterone, tolbutamide, and metroprolol were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. There statistical pharmacokinetics differences for omeprazole, phenacetin, testosterone, tolbutamide, and metroprolol in rats were observed by comparing acute Zhu-tan Tong-luo decoction group with control group; and statistical pharmacokinetics differences for bupropion, omeprazole, phenacetin, testosterone, tolbutamide, and metroprolol were observed by comparing chronic Zhu-Tan Tong-Luo decoction group with control group. After intragastric administration of Zhu-Tan Tong-Luo decoction may slightly induce the activities of CYP2B6, CYP2C19, CYP1A2, CYP3A4, CYP2C9, CYP2D6 of rats. Induction of drug metabolizing enzyme by Zhu-Tan Tong-Luo decoction would reduce the efficacy of other drug. Additional, there no statistical difference for biochemical results after 1 or 14 intragastric administration of Zhu-Tan Tong-Luo decoction. PMID:26629097

  17. Amelioration of cisplatin-induced nephrotoxicity in rats by tetramethylpyrazine, a major constituent of the Chinese herb Ligusticum wallichi.

    PubMed

    Ali, B H; Al-Moundhri, M; Eldin, M Tag; Nemmar, A; Al-Siyabi, S; Annamalai, K

    2008-07-01

    Nephrotoxicity of the anticancer drug, cisplatin (CP) involves enhanced renal generation of reactive oxygen metabolites and lipid peroxidation caused by decreased levels of antioxidants and antioxidant enzymes. Tetramethylpyrazine (TMP) is known to act as a strong antioxidant. Therefore, in the present work, we aimed at testing the possible protective or palliative effect of TMP on CP nephrotoxicity in rats. TMP was given orally at a dose of 80 mg . kg(- 1) . day(- 1) for 7 days. Some of these rats were given a single intraperitoneal injection of CP (or vehicle) at a dose of 6 mg/kg on Day 6 of treatment. Animals were sacrificed 6 days after CP (or vehicle) treatment, and blood, urine, and kidneys were obtained. Nephrotoxicity was assessed biochemically by measuring creatinine and urea in serum, reduced glutathione (GSH) concentration in renal cortex, by urinalysis, and histopathologically by light microscopy. CP significantly increased the concentration of urea and creatinine (P < 0.05) by about 128% and 170%, respectively; increased urine volume and N-acetyl-beta-D-glucosaminidase (NAG) activity; and significantly decreased osmolality and protein concentrations. CP treatment reduced GSH by about 34% (P < 0.05) and superoxide dismutase (SOD) and total antioxidant activity (TOX) by about 28% and 21%, respectively (P < 0.05). TMP pretreatment significantly mitigated all of these effects. Sections from saline- and TMP-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly reduced when CP was given after pretreatment with TMP. CP cortical concentration was not significantly altered by TMP treatment. The results suggest that TMP ameliorated the histological, physiological, and biochemical indices of nephrotoxicity in rats. Pending further pharmacological and toxicological studies, TMP may potentially be useful as a nephroprotective agent.

  18. Ovarian hormones ameliorate memory impairment, cholinergic deficit, neuronal apoptosis and astrogliosis in a rat model of Alzheimer's disease

    PubMed Central

    HU, ZHIYING; YANG, YANG; GAO, KEQIANG; RUDD, JOHN A.; FANG, MARONG

    2016-01-01

    Ovarian hormones, including progesterone (P4) and 17 β-estradiol (E2), have been shown to affect memory functions; however, the underlying mechanism whereby ovarian hormone replacement therapy may decrease the risk of Alzheimer's disease (AD) is currently unclear. The present study aimed to investigate the effects of P4 and E2 on spatial and learning memory in an ovariectomized rat model of AD. β-amyloid (Aβ) or saline were stereotaxically injected into the hippocampus of the rats and, after 1 day, ovariectomy or sham operations were performed. Subsequently, the rats were treated with P4 alone, E2 alone, or a combination of P4 and E2. Treatment with E2 and/or P4 was shown to improve the learning and memory functions of the rats, as demonstrated by the Morris water maze test. In addition, treatment with E2 and P4 was associated with increased expression levels of choline acetyltransferase and 5-hydroxytryptamine receptor 2A (5-HT2A), and decreased expression levels of the glial fibrillary acidic protein in the hippocampus of the rats. Furthermore, E2 and P4 treatment significantly attenuated neuronal cell apoptosis, as demonstrated by terminal deoxynucleotidyl transferase dUTP nick end labeling assays; thus suggesting that the ovarian hormones were able to protect against Aβ-induced neuronal cell toxicity. The results of the present study suggested that the neuroprotective effects of P4 and E2 were associated with amelioration of the cholinergic deficit, suppression of apoptotic signals and astrogliosis, and upregulation of 5-HT2A expression levels. Therefore, hormone replacement therapy may be considered an effective strategy for the treatment of patients with cognitive disorders and neurodegenerative diseases. PMID:26889223

  19. Nicotine and elevated body temperature reduce the complexity of the genioglossus and diaphragm EMG signals in rats during early maturation

    NASA Astrophysics Data System (ADS)

    Akkurt, David; Akay, Yasemin M.; Akay, Metin

    2009-10-01

    In this paper, we examined the effect of nicotine exposure and increased body temperature on the complexity (dynamics) of the genioglossus muscle (EMGg) and the diaphragm muscle (EMGdia) to explore the effects of nicotine and hyperthermia. Nonlinear dynamical analysis of the EMGdia and EMGg signals was performed using the approximate entropy method on 15 (7 saline- and 8 nicotine-treated) juvenile rats (P25-P35) and 19 (11 saline- and 8 nicotine-treated) young adult rats (P36-P44). The mean complexity values were calculated over the ten consecutive breaths using the approximate entropy method during mild elevated body temperature (38 °C) and severe elevated body temperature (39-40 °C) in two groups. In the first (nicotine) group, rats were treated with single injections of nicotine enough to produce brain levels of nicotine similar to those achieved in human smokers (2.5 (mg kg-1)/day) until the recording day. In the second (control) group, rats were treated with injections of saline, beginning at postnatal 5 days until the recording day. Our results show that warming the rat by 2-3 °C and nicotine exposure significantly decreased the complexity of the EMGdia and EMGg for the juvenile age group. This reduction in the complexity of the EMGdia and EMGg for the nicotine group was much greater than the normal during elevated body temperatures. We speculate that the generalized depressive effects of nicotine exposure and elevated body temperature on the respiratory neural firing rate and the behavior of the central respiratory network could be responsible for the drastic decrease in the complexity of the EMGdia and EMGg signals, the outputs of the respiratory neural network during early maturation.

  20. Fluoxetine, desipramine, and the dual antidepressant milnacipran reduce alcohol self-administration and/or relapse in dependent rats.

    PubMed

    Simon O'Brien, Emmanuelle; Legastelois, Rémi; Houchi, Hakim; Vilpoux, Catherine; Alaux-Cantin, Stéphanie; Pierrefiche, Olivier; André, Etienne; Naassila, Mickaël

    2011-06-01

    A few clinical studies have shown that dual antidepressants (serotonergic (5-HT) and noradrenergic (NE) transporter inhibitors, SNRIs) may be effective in alcoholism treatment. We studied the effect of the dual antidepressant milnacipran on ethanol operant self-administration in acutely withdrawn ethanol-dependent and in -non-dependent Wistar rats, and used fluoxetine and desipramine to dissect both 5-HT and NE components, respectively, in the effect of milnacipran. Milnacipran was also tested for relapse after protracted abstinence and on ethanol-induced (1.0 g/kg) conditioned place preference in control rats and ethanol-induced locomotor sensitization in DBA/2J female mice. Milnacipran dose dependently (5-40 mg/kg) attenuated the increased ethanol self-administration observed during early withdrawal and was more potent in preventing reinstatement in dependent rats after protracted abstinence as compared with non-dependent rats. Desipramine and fluoxetine (10 mg/kg) blocked ethanol self-administration during early withdrawal, and recovery was delayed in dependent animals, indicating a potent effect. Ethanol self-administration was also reduced 1 day after treatment with desipramine and fluoxetine but not with milnacipran. Finally, milnacipran prevented ethanol-induced place preference in ethanol-naive rats and reduced the magnitude of ethanol-induced sensitization associated with a delayed induction in mice. Desipramine (20 mg/kg) countered sensitization development and reduced its expression at 1 week after treatment; fluoxetine (10 mg/kg) reduced sensitization expression. Thus, 5-HT and NE transmissions during sensitization expression may mediate the effect of milnacipran on sensitization induction. These results support that SNRIs may have a potential use in alcoholism treatment.

  1. Changes in the activity levels of glutamine synthetase, glutaminase and glycogen synthetase in rats subjected to hypoxic stress

    NASA Astrophysics Data System (ADS)

    Vats, P.; Mukherjee, A. K.; Kumria, M. M. L.; Singh, S. N.; Patil, S. K. B.; Rangnathan, S.; Sridharan, K.

    Exposure to high altitude causes loss of body mass and alterations in metabolic processes, especially carbohydrate and protein metabolism. The present study was conducted to elucidate the role of glutamine synthetase, glutaminase and glycogen synthetase under conditions of chronic intermittent hypoxia. Four groups, each consisting of 12 male albino rats (Wistar strain), were exposed to a simulated altitude of 7620 m in a hypobaric chamber for 6 h per day for 1, 7, 14 and 21 days, respectively. Blood haemoglobin, blood glucose, protein levels in the liver, muscle and plasma, glycogen content, and glutaminase, glutamine synthetase and glycogen synthetase activities in liver and muscle were determined in all groups of exposed and in a group of unexposed animals. Food intake and changes in body mass were also monitored. There was a significant reduction in body mass (28-30%) in hypoxia-exposed groups as compared to controls, with a corresponding decrease in food intake. There was rise in blood haemoglobin and plasma protein in response to acclimatisation. Over a three-fold increase in liver glycogen content was observed following 1 day of hypoxic exposure (4.76+/-0.78 mg.g-1 wet tissue in normal unexposed rats; 15.82+/-2.30 mg.g-1 wet tissue in rats exposed to hypoxia for 1 day). This returned to normal in later stages of exposure. However, there was no change in glycogen synthetase activity except for a decrease in the 21-days hypoxia-exposed group. There was a slight increase in muscle glycogen content in the 1-day exposed group which declined significantly by 56.5, 50.6 and 42% following 7, 14, and 21 days of exposure, respectively. Muscle glycogen synthetase activity was also decreased following 21 days of exposure. There was an increase in glutaminase activity in the liver and muscle in the 7-, 14- and 21-day exposed groups. Glutamine synthetase activity was higher in the liver in 7- and 14-day exposed groups; this returned to normal following 21 days of exposure

  2. 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…

  3. Adenohypophysitis in rat pituitary allografts

    PubMed Central

    Rotondo, Fabio; Quintanar-Stephano, Andres; Asa, Sylvia L; Lombardero, Matilde; Berczi, Istvan; Scheithauer, Bernd W; Horvath, Eva; Kovacs, Kalman

    2010-01-01

    The histological, immunohistochemical and ultrastructural alterations in 81 pituitary allografts from Lewis rats transplanted beneath the renal capsule of Wistar rats were investigated. Intrasellar pituitaries of rats bearing allografts were also examined. Recipient rats were sacrificed at various time points after transplantation. Two days after transplantation, the central portion of the allografts demonstrated ischaemic necrosis. A week later, massive mononuclear cell infiltrates consisting primarily of lymphocytes and to a lesser extent, macrophages, plasma cells and granulocytes became prominent. At about three to four weeks after transplantation, the mononuclear cell infiltrate diminished; the surviving adenohypophysial cells, mainly prolactin (PRL) cells, increased in number and necrosis was replaced by connective tissue. No histological changes were noted in the intrasellar pituitaries of rats bearing allografts. Immunohistochemistry demonstrated that the surviving adenohypophysial cells were mainly PRL-producing cells. Electron microscopy revealed adenohypophysial cell destruction, a spectrum of inflammatory cells and, in late phase, accumulation of fibroblasts and collagen fibres. PRL cells were the prominent cell types; they increased in number. It appears that pituitary allografts are ‘foreign’ and evoke an immune response, suggesting that they may be used as an experimental animal model for morphological investigation of the development and progression of adenohypophysitis, a rare disease occurring mainly in young women often associated with pregnancy. PMID:20586813

  4. 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…

  5. Angiotensin II receptor subtypes are coupled with distinct signal-transduction mechanisms in neurons and astrocytes from rat brain

    SciTech Connect

    Sumners, C.; Wei Tang; Zelezna, B.; Raizada, M.K. )

    1991-09-01

    Both neurons and astrocytes contain specific receptors for angiotensin II (AII). The authors used selective ligands for the AT{sub 1} and AT{sub 2} types of AII receptors to investigate the expression of functional receptor subtypes in astrocyte cultures and neuron cultures from 1-day-old (neonatal) rat brain. In astrocyte cultures, competition of {sup 125}I-labeled AII ({sup 125}I-AII) specific binding with AT{sub 1} (DuP753) or AT{sub 2} {l brace}PD123177, CGP42112A, (Phe(p-NH{sub 2}){sup 6})AII{r brace} selective receptor ligands revealed a potency series of AII > DuP753 > > > CGP42112A > (Phe(p-NH{sub 2}){sup 6})AII > PD123177. These results suggest a predominance of the AT{sub 1} receptor subtype in neonatal astrocytes. {sup 125}I-AII specific binding to neonate neuronal cultures was reduced 73-84% by 1 {mu} MPD123177, and the residual {sup 125}I-AII specific binding was eliminated by DuP753. The results suggest that astrocyte cultures from neonatal rat brains contain predominantly AT{sub 1} receptors that are coupled to a stimulation of inositophospholipid hydrolysis. In contrast, neuron cultures from neonatal rat brain contain mostly AT{sub 2} receptors that are coupled to a reduction in basal cGMP levels, but a smaller population of AT{sub 1} receptors is also present in these neurons.

  6. Early constraint-induced movement therapy promotes functional recovery and neuronal plasticity in a subcortical hemorrhage model rat.

    PubMed

    Ishida, Akimasa; Misumi, Sachiyo; Ueda, Yoshitomo; Shimizu, Yuko; Cha-Gyun, Jung; Tamakoshi, Keigo; Ishida, Kazuto; Hida, Hideki

    2015-05-01

    Constraint-induced movement therapy (CIMT) promotes functional recovery of impaired forelimbs after hemiplegic strokes, including intracerebral hemorrhage (ICH). We used a rat model of subcortical hemorrhage to compare the effects of delivering early or late CIMT after ICH. The rat model was made by injecting collagenase into the globus pallidus near the internal capsule, and then forcing rats to use the affected forelimb for 7 days starting either 1 day (early CIMT) or 17 days (late CIMT) after the lesion. Recovery of forelimb function in the skilled reaching test and the ladder stepping test was found after early-CIMT, while no significant recovery was shown after late CIMT or in the non-CIMT controls. Early CIMT was associated with greater numbers of ΔFosB-positive cells in the ipsi-lesional sensorimotor cortex layers II-III and V. Additionally, we found expression of the growth-related genes brain-derived neurotrophic factor (BDNF) and growth-related protein 43 (GAP-43), and abundant dendritic arborization of pyramidal neurons in the sensorimotor area. Similar results were not detected in the contra-lesional cortex. In contrast to early CIMT, late CIMT failed to induce any changes in plasticity. We conclude that CIMT induces molecular and morphological plasticity in the ipsi-lesional sensorimotor cortex and facilitates better functional recovery when initiated immediately after hemorrhage.

  7. Soluble epoxide hydrolase inhibition does not prevent cardiac remodeling and dysfunction after aortic constriction in rats and mice.

    PubMed

    Morgan, Lisa A; Olzinski, Alan R; Upson, John J; Zhao, Shufang; Wang, Tao; Eisennagel, Stephen H; Hoang, Bao; Tunstead, James R; Marino, Joseph P; Willette, Robert N; Jucker, Beat M; Behm, David J

    2013-04-01

    Epoxyeicosatrienoic acids, substrates for soluble epoxide hydrolase (sEH), exhibit vasodilatory and antihypertrophic activities. Inhibitors of sEH might therefore hold promise as heart failure therapeutics. We examined the ability of sEH inhibitors GSK2188931 and GSK2256294 to modulate cardiac hypertrophy, fibrosis, and function after transverse aortic constriction (TAC) in rats and mice. GSK2188931 administration was initiated in rats 1 day before TAC, whereas GSK2256294 treatment was initiated in mice 2 weeks after TAC. Four weeks later, cardiovascular function was assessed, plasma was collected for drug and sEH biomarker concentrations, and left ventricle was isolated for messenger RNA and histological analyses. In rats, although GSK2188931 prevented TAC-mediated increases in certain genes associated with hypertrophy and fibrosis (α-skeletal actin and connective tissue growth factor), the compound failed to attenuate TAC-induced increases in left ventricle mass, posterior wall thickness, end-diastolic volume and pressure, and perivascular fibrosis. Similarly, in mice, GSK2256294 did not reverse cardiac remodeling or systolic dysfunction induced by TAC. Both compounds increased the sEH substrate/product (leukotoxin/leukotoxin diol) ratio, indicating sEH inhibition. In summary, sEH inhibition does not prevent cardiac remodeling or dysfunction after TAC. Thus, targeting sEH seems to be insufficient for reducing pressure overload hypertrophy.

  8. Urogastrone-epidermal growth factor and aspects of sexual maturation in female rats as a function of age at treatment.

    PubMed

    da Silva, V A; Smart, J L; McLean, A E

    1991-05-01

    The effect of epidermal growth factor (EGF) on sexual maturation of female rats was studied. A within-litter experimental design was employed, so that in each litter each female received four daily injections of EGF (E, 500 ng/g body weight s.c.) or vehicle (V), at one of three ages: days 0-3 (E1, V1), days 8-11 (E2, V2), days 16-19 (E3, V3). Body weight, pinna detachment, incisor eruption, eye opening, auditory startle, visual placing, vaginal opening and first cytological oestrus were assessed. Neonatal treatment with EGF (E1) delayed pinna detachment and the appearance of the auditory startle, but accelerated eye opening. Also, E1, but not E2 and E3, resulted in lower body weight at weaning. Treatment E3 advanced sexual maturation, as indicated by vaginal opening and first cytological oestrus, by 5-6 days. E1 and E2 had no such effect. Hence the sensitive period for the effect of EGF on female rat sexual maturation is later than that for effects on other developmental characteristics and body weight. In a second experiment, ovary and uterus weights were found not to differ between E3 and V3 females killed on the day of vaginal opening of the E3 rats, suggesting that the effect of EGF may be specifically on the perineal epithelium and not on sexual maturation generally.

  9. Isolated rat cortical progenitor cells are maintained in division in vitro by membrane-associated factors.

    PubMed

    Temple, S; Davis, A A

    1994-04-01

    Ventricular zone cells in the developing CNS undergo extensive cell division in vivo and under certain conditions in vitro. The culture conditions that promote cell division have been studied to determine the role that contact with cell membrane associated factors play in the proliferation of these cells. Progenitor cells have been taken from the ventricular zone of developing rat cerebral cortex and placed into microwells. Small clusters of these cells can generate large numbers of neurons and non-neuronal progeny. In contrast, single progenitor cells largely cease division, approximately 90% acquiring neuron-like characteristics by 1 day in vitro. DiI-labeled, single cells from embryonic day 14 cortex plated onto clusters of unmarked progenitor cells have a significantly higher probability (approximately 3-fold) of maintaining a progenitor cell phenotype than if plated onto the plastic substratum around 100 microns away from the clusters. Contact with purified astrocytes also promotes the progenitor cell phenotype, whereas contact with meningeal fibroblasts or balb3T3 cells promotes their differentiation. Membrane homogenates from cortical astrocytes stimulate significantly more incorporation of BrdU by E14 cortical progenitor cells than membrane homogenates from meningeal fibroblasts. These data indicate that the proliferation of rat cortical progenitor cells can be maintained by cell-type specific, membrane-associated factors.

  10. Local administration of AAV-BDNF to subventricular zone induces functional recovery in stroke rats.

    PubMed

    Yu, Seong-Jin; Tseng, Kuan-Yin; Shen, Hui; Harvey, Brandon K; Airavaara, Mikko; Wang, Yun

    2013-01-01

    Migration of new neuroprogenitor cells (NPCs) from the subventricular zone (SVZ) plays an important role in neurorepair after injury. Previous studies have shown that brain derived neurotrophic factor (BDNF) enhances the migration of NPCs from SVZ explants in neonatal mice in vitro. The purpose of this study was to identify the role of BDNF in SVZ cells using AAV-BDNF in an animal model of stroke. BDNF protein production after AAV-BDNF infection was verified in primary neuronal culture. AAV-BDNF or AAV-RFP was injected into the left SVZ region of adult rats at 14 days prior to right middle cerebral artery occlusion (MCAo). SVZ tissues were collected from the brain and placed in Metrigel cultures 1 day after MCAo. Treatment with AAV-BDNF significantly increased the migration of SVZ cells in the stroke brain in vitro. In another set of animals, AAV-GFP was co-injected with AAV-BDNF or AAV-RFP to label cells in left SVZ prior to right MCAo. Local administration of AAV-BDNF significantly enhanced recovery of locomotor function and migration of GFP-positive cells from the SVZ toward the lesioned hemisphere in stroke rats. Our data suggest that focal administration of AAV-BDNF to the SVZ increases behavioral recovery post stroke, possibly through the enhancement of migration of cells from SVZ in stroke animals. Regional manipulation of BDNF expression through AAV may be a novel approach for neurorepair in stroke brains.

  11. Evaluation of Cisplatin Neurotoxicity in Cultured Rat Dorsal Root Ganglia via Cytosolic Calcium Accumulation

    PubMed Central

    Erol, Kevser; Yiğitaslan, Semra; Ünel, Çiğdem; Kaygısız, Bilgin; Yıldırım, Engin

    2016-01-01

    Background: Calcium homeostasis is considered to be important in antineoplastic as well as in neurotoxic adverse effects of cisplatin. Aims: This study aimed to investigate the role of Ca2+ in cisplatin neurotoxicity in cultured rat dorsal root ganglia (DRG) cells. Study Design: Cell culture study. Methods: DRG cells prepared from 1-day old Sprague-Dawley rats were used to determine the role of Ca2+ in the cisplatin (10–600 μM) neurotoxicity. The cells were incubated with cisplatin plus nimodipine (1–3 μM), dizocilpine (MK-801) (1–3 μM) or thapsigargin (100–300 nM). Toxicity of cisplatinon DRG cells was determined by the MTT assay. Results: The neurotoxicity of cisplatin was significant when used in high concentrations (100–600 μM). Nimodipine (1 μM) but not MK-801 or thapsigargin prevented the neurotoxic effects of 200 μM of cisplatin. Conclusion: Voltage-dependent calcium channels may play a role in cisplatin neurotoxicity. PMID:27403382

  12. Bone marrow cells repair cigarette smoke-induced emphysema in rats.

    PubMed

    Huh, Jin Won; Kim, Sun-Yong; Lee, Ji Hyun; Lee, Jin-Seok; Van Ta, Quang; Kim, Mijung; Oh, Yeon-Mok; Lee, Yun-Song; Lee, Sang-Do

    2011-09-01

    The therapeutic potential of stem cells in chronic obstructive pulmonary disease is not well known although stem cell therapy is effective in models of other pulmonary diseases. We tested the capacities of bone marrow cells (BMCs), mesenchymal stem cells (MSCs), and conditioned media of MSCs (MSC-CM) to repair cigarette smoke-induced emphysema. Inbred female Lewis rats were exposed to cigarette smoke for 6 mo and then received BMCs, MSCs, or MSC-CM from male Lewis rats. For 2 mo after injection, the BMC treatment gradually alleviated the cigarette smoke-induced emphysema and restored the increased mean linear intercept. The BMC treatment significantly increased cell proliferation and the number of small pulmonary vessels, reduced apoptotic cell death, attenuated the mean pulmonary arterial pressure, and inhibited muscularization in small pulmonary vessels. However, only a few male donor cells were detected from 1 day to 1 mo after BMC administration. The MSCs and cell-free MSC-CM also induced the repair of emphysema and increased the number of small pulmonary vessels. Our data show that BMC, MSCs, and MSC-CM treatment repaired cigarette smoke-induced emphysema. The repair activity of these treatments is consistent with a paracrine effect rather than stem cell engraftment because most of the donor cells disappeared and because cell-free MSC-CM also induced the repair.

  13. Respiratory effects of sectioning the carotid sinus glossopharyngeal and abdominal vagal nerves in the awake rat.

    PubMed Central

    Martin-Body, R L; Robson, G J; Sinclair, J D

    1985-01-01

    Normoxic and hypoxic respiration has been measured in awake rats after denervation procedures designed to eliminate the regulatory input from the carotid bodies, from all chemosensory tissue supplied by the glossopharyngeal nerve (n. IX), and from abdominal chemoreceptors. Studies were made 1 day after section of the carotid sinus nerve (c.s.n.), n. IX (at a level including c.s.n.), the abdominal vagus (n. Xa) and combinations of these nerves. Results were compared with those found in normal controls. C.s.n. section led to hypoventilation in both normoxia and hypoxia, reductions in respiratory frequency being consistent and substantial, and reductions in tidal volume varying with the degree of hypoxia. By comparison, section of n. IX produced significantly greater reductions of both normoxic and hypoxic ventilation. Section of n. Xa produced no significant change in normoxic ventilation but in hypoxia produced a significant small reduction in ventilation, mostly from an effect on tidal volume. Denervation of all the associated chemosensory tissue by combined section of n. IX and n. Xa demonstrated a summation of effects but left two distinct residual responses, one to mild hypoxia, and one to severe hypoxia, both associated mainly with increases of tidal volume. The experiments demonstrate that glomus tissues at different sites in the rat produce significant and distinct contributions to respiratory regulation. Denervation of all known receptors shows that significant ventilatory responses to hypoxia are still produced, either by unrevealed peripheral chemoreceptors, or by central neural mechanisms. PMID:3989730

  14. Demonstration of direct lineage between hepatocytes and hepatocellular carcinoma in diethylnitrosamine-treated rats.

    PubMed

    Bralet, Marie-Pierre; Pichard, Virginie; Ferry, Nicolas

    2002-09-01

    The question whether hepatocellular carcinoma (HCC) arises from dedifferentiation of mature hepatocytes or from proliferation of liver stem cells is still debated. In the present study, we used retroviral-mediated genetic labeling to investigate the fate of mature hepatocytes in rats after administration of diethylnitrosamine (DEN). Mature hepatocytes were genetically labeled by intravenous injection of retroviral vectors containing the Escherichia coli beta-galactosidase gene coupled to a nuclear localization signal (nls-LacZ) 1 day after partial hepatectomy. Liver biopsies performed after completion of hepatic regeneration showed that 18.3% of hepatocytes expressed the nls-LacZ transgene. Rats were then treated with DEN in drinking water for 12 weeks and sacrificed between 98 and 151 days after the onset of DEN administration. Clones of beta-galactosidase positive cells were observed, half of which (53%) also expressed the placental form of glutathione-S-transferase (GSTp), a marker of preneoplastic cells. HCCs of various sizes expressing GSTp were present in all animals. Careful examination of 90 HCCs revealed that 16 (17.7%) also expressed nls-LacZ. This figure precisely matched the proportion of labeled hepatocytes before DEN treatment (18.3%). In conclusion, a random clonal origin of HCC from mature hepatocytes is seen in the DEN model of hepatocarcinogenesis.

  15. Polyphenols from Camellia sinenesis attenuate experimental cholestasis-induced liver fibrosis in rats.

    PubMed

    Zhong, Zhi; Froh, Matthias; Lehnert, Mark; Schoonhoven, Robert; Yang, Liu; Lind, Henrik; Lemasters, John J; Thurman, Ronald G

    2003-11-01

    Accumulation of hydrophobic bile acids during cholestasis leads to generation of oxygen free radicals in the liver. Accordingly, this study investigated whether polyphenols from green tea Camellia sinenesis, which are potent free radical scavengers, decrease hepatic injury caused by experimental cholestasis. Rats were fed a standard chow or a diet containing 0.1% polyphenolic extracts from C. sinenesis starting 3 days before bile duct ligation. After bile duct ligation, serum alanine transaminase increased to 760 U/l after 1 day in rats fed a control diet. Focal necrosis and bile duct proliferation were also observed after 1-2 days, and fibrosis developed 2-3 wk after bile duct ligation. Additionally, procollagen-alpha1(I) mRNA increased 30-fold 3 wk after bile duct ligation, accompanied by increased expression of alpha-smooth muscle actin and transforming growth factor-beta and the accumulation of 4-hydroxynenonal, an end product of lipid peroxidation. Polyphenol feeding blocked or blunted all of these bile duct ligation-dependent changes by 45-73%. Together, the results indicate that cholestasis due to bile duct ligation causes liver injury by mechanisms involving oxidative stress. Polyphenols from C. sinenesis scavenge oxygen radicals and prevent activation of stellate cells, thereby minimizing liver fibrosis.

  16. Differential expression of prostaglandin E receptor subtype EP2 in rat uterus during early pregnancy.

    PubMed

    Shi, J J; Ma, X H; Diao, H L; Ni, H; Xu, L B; Zhu, H; Yang, Z M

    2005-10-01

    PGE2 is essential for mammalian female reproduction. This study was to examine the expression of EP2 gene in the rat uterus during early pregnancy, delayed implantation and artificial decidualization by in situ hybridization and immunohistochemistry. There was no detectable EP2 mRNA expression in the uterus from days 1 to 4 of pregnancy (day 1 = day of vaginal sperm). A low level of EP2 immunostaining was observed in the luminal and glandular epithelium from days 1 to 4 of pregnancy. Both EP2 mRNA and protein expression were highly detected in the luminal epithelium at implantation sites on day 6 of pregnancy. EP2 expression decreased from day 7 of pregnancy and was undetectable on days 8 and 9 of pregnancy. After delayed implantation was terminated by estrogen treatment and the embryo implanted, both EP2 mRNA and protein expression were strongly observed in the luminal epithelium at the implantation site. There was no detectable EP2 expression in both control and decidualized uteri. In conclusion, these data suggest that EP2 expression at implantation site may play an important role during embryo implantation in rats.

  17. Evaluation of kidney injury biomarkers in rat amniotic fluid after gestational exposure to cadmium.

    PubMed

    Jacobo-Estrada, Tania; Cardenas-Gonzalez, Mariana; Santoyo-Sánchez, Mitzi; Parada-Cruz, Benjamín; Uria-Galicia, Esther; Arreola-Mendoza, Laura; Barbier, Olivier

    2016-09-01

    Cadmium is a well-characterized nephrotoxic agent that is also capable of accumulating and diffusing across the placenta; however, only a few studies have addressed its effects over fetal kidneys and none of them has used a panel of sensitive and specific biomarkers for the detection of kidney injury. The goal of this study was to determine cadmium renal effects in rat fetuses by the quantification of early kidney injury biomarkers. Pregnant Wistar rats were exposed by inhalation to an isotonic saline solution or to CdCl2 solution (DDel =1.48 mg Cd kg(-1) day(-1) ) during gestational days (GD) 8-20. On GD 21, dams were euthanized and samples obtained. Kidney injury biomarkers were quantified in amniotic fluid samples and fetal kidneys were microscopically evaluated to search for histological alterations. Our results showed that cadmium exposure significantly raised albumin, osteopontin, vascular endothelial growth factor and tissue inhibitor of metalloproteinases-1 levels in amniotic fluid, whereas it decreased creatinine. Clusterin, calbindin and IFN-inducible protein 10 did not show any change. Accordingly, histological findings showed tubular damage and precipitations in the renal pelvis. In conclusion, gestational exposure to cadmium induces structural alterations in fetal renal tissue that can be detected by some kidney injury biomarkers in amniotic fluid samples. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Elemental imaging of kidneys of adult rats exposed to uranium acetate

    NASA Astrophysics Data System (ADS)

    Homma-Takeda, S.; Terada, Y.; Nakata, A.; Sahoo, S. K.; Yoshida, S.; Ueno, S.; Inoue, M.; Iso, H.; Ishikawa, T.; Konishi, T.; Imaseki, H.; Shimada, Y.

    2009-06-01

    Concern about the toxicity of depleted uranium for military use has increased recently. Renal toxicity is the hallmark effect of uranium exposure. However, the dynamics and distribution of uranium in the kidney are not well understood. Here, we determined the precise distribution of uranium and essential elements in the rat kidney using microbeam scanning particle-induced X-ray emission (micro-PIXE) and synchrotron radiation X-ray fluorescence (SR-XRF). Uranium accumulation in the rat kidney reached a maximum at 1 day after the subcutaneous (s.c.) administration of 2 mg U/kg of uranium acetate and then gradually decreased. At 3 h after administration, uranium was distributed mainly in the proximal tubules of the inner zone of the cortex and in the outer stripe of the outer medulla, and absorbed by the proximal tubule epithelium. Iron was localized more in the inside of the outer medulla than uranium, while phosphorus, potassium, sulfur and zinc were equally distributed in the cortex and the outer stripe of the outer medulla. At 3 days after administration, the number of apoptotic cells increased and cells were lost from the proximal tubules. Uranium was detectable mainly in the outer stripe of the outer medulla at 15 days, suggesting that the renal distribution of uranium is site-selective and causes site-specific renal lesions.

  19. Spatiotemporal expression of postsynaptic density 95 in rat retina after optic nerve injury.

    PubMed

    Li, Chen; Zhou, Yi; Liu, ZhiQiang; Tuo, JingSheng; Hu, Nan; Guan, HuaiJin

    2012-03-01

    Postsynaptic density protein 95 (PSD95) contains three PSD95/Drosophilia disk large/ZO-1[PDZ] homology domains and links neuronal nitric oxide synthase (nNOS) with the N-methyl-D: -aspartic acid receptor. Previous studies showed that the assembly of PSD95/nNOS signaling played an important role in rat ischemic brain injury. In this study, we aimed to elucidate the changes of PSD95 expression and location in retina after optic nerve crush. The optic nerve injury model of rats was created by crushing optic nerve at 2 mm retrobulbarly. Real-time PCR and Western blot analysis were used to analyze mRNA and protein expression of PSD95. The spatial distribution of PSD95 were evaluated by immunohistochemistry. Immunofluorescence was performed to observe the co-localization of PSD95. The PSD95 expression diminished at 1 day and elevated and peaked on the 7th day of post-injury. The mRNA and protein levels of PSD95 underwent the similar change. The association of PSD95 and rhodopsin was detected by immunofluorescence double staining. The injury-induced expression of PSD95 was physically co-existed with active caspase-3 (apoptotic marker) and nNOS. The spatiotemporal changes of PSD95 expression suggests that this protein likely to play a role in the degenerative process of never cells induced by optic nerve injury in the retina.

  20. Comparison of the neuropsychological mechanisms of 2,6-diisopropylphenol and N-methyl-D-aspartate receptor antagonist against electroconvulsive therapy-induced learning and memory impairment in depressed rats

    PubMed Central

    LIU, GANG; LIU, CHAO; NING-ZHANG, XUE

    2015-01-01

    The present study aimed to examine the neurophysiological mechanisms of the 2,6-diisopropylphenol and N-methyl-D-aspartate (NMDA) receptor antagonist against learning and memory impairment, induced by electroconvulsive therapy (ECT). A total of 48 adult depressed rats without olfactory bulbs were randomly divided into six experimental groups: i) saline; ii) 10 mg/kg MK-801; iii) 10 mg/kg MK-801 and a course of ECT; iv) 200 mg/kg 2,6-diisopropylphenol; v) 200 mg/kg 2,6-diisopropylphenol and a course of ECT; and vi) saline and a course of ECT. The learning and memory abilities of the rats were assessed using a Morris water maze 1 day after a course of ECT. The hippocampus was removed 1 day after assessment using the Morris water maze assessment. The content of glutamate in the hippocampus was detected using high-performance liquid chromatography. The expression levels of p-AT8Ser202 and GSK-3β1H8 in the hippocampus were determined using immunohistochemical staining and western blot analysis. The results demonstrated that the 2,6-diisopropylphenol NMDA receptor antagonist, MK-801 and ECT induced learning and memory impairment in the depressed rats. The glutamate content was significantly upregulated by ECT, reduced by 2,6-diisopropylphenol, and was unaffected by the NMDA receptor antagonist in the hippocampus of the depressed rats. Tau protein hyperphosphorylation in the hippocampus was upregulated by ECT, but was reduced by 2,6-diisopropylphenol and the MK-801 NMDA receptor antagonist. It was also demonstrated that 2,6-diisopropylphenol prevented learning and memory impairment and reduced the hyperphosphorylation of the Tau protein, which was induced by eECT. GSK-3β was found to be the key protein involved in this signaling pathway. The ECT reduced the learning and memory impairment, caused by hyperphosphorylation of the Tau protein, in the depressed rats by upregulating the glutamate content. PMID:25998151

  1. 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.

  2. 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.

  3. Voluntary Sleep Loss in Rats

    PubMed Central

    Oonk, Marcella; Krueger, James M.; Davis, Christopher J.

    2016-01-01

    Study Objectives: Animal sleep deprivation (SDEP), in contrast to human SDEP, is involuntary and involves repeated exposure to aversive stimuli including the inability of the animal to control the waking stimulus. Therefore, we explored intracranial self-stimulation (ICSS), an operant behavior, as a method for voluntary SDEP in rodents. Methods: Male Sprague-Dawley rats were implanted with electroencephalography/electromyography (EEG/EMG) recording electrodes and a unilateral bipolar electrode into the lateral hypothalamus. Rats were allowed to self-stimulate, or underwent gentle handling-induced SDEP (GH-SDEP), during the first 6 h of the light phase, after which they were allowed to sleep. Other rats performed the 6 h ICSS and 1 w later were subjected to 6 h of noncontingent stimulation (NCS). During NCS the individual stimulation patterns recorded during ICSS were replayed. Results: After GH-SDEP, ICSS, or NCS, time in nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep increased. Further, in the 24 h after SDEP, rats recovered all of the REM sleep lost during SDEP, but only 75% to 80% of the NREM sleep lost, regardless of the SDEP method. The magnitude of EEG slow wave responses occurring during NREM sleep also increased after SDEP treatments. However, NREM sleep EEG slow wave activity (SWA) responses were attenuated following ICSS, compared to GH-SDEP and NCS. Conclusions: We conclude that ICSS and NCS can be used to sleep deprive rats. Changes in rebound NREM sleep EEG SWA occurring after ICSS, NCS, and GH-SDEP suggest that nonspecific effects of the SDEP procedure differentially affect recovery sleep phenotypes. Citation: Oonk M, Krueger JM, Davis CJ. Voluntary sleep loss in rats. SLEEP 2016;39(7):1467–1479. PMID:27166236

  4. 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.

  5. 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.

  6. In vivo tropisms and kinetics of rat theilovirus infection in immunocompetent and immunodeficient rats.

    PubMed

    Drake, Michael T; Besch-Williford, Cindy; Myles, Matthew H; Davis, Justin W; Livingston, Robert S

    2011-09-01

    Rat theilovirus (RTV) is a cardiovirus related to Theiler's murine encephalomyelitis virus. While RTV is a prevalent viral pathogen of rats used in biomedical research, the pathogenesis and characterization of RTV infections is not well understood. In the studies reported herein, we used immunohistochemistry to identify viral antigens in enterocytes of the small intestines of Sprague-Dawley (SD) rats. Fecal viral shedding in immunocompromised and immunocompetent rats following oral gavage with RTV1 was high for the first 2 weeks of infection with persistent shedding of high viral loads being observed in immunocompromised nude rats but not in immunocompetent rats. RTV was also detected in mesenteric lymph nodes and spleen of immunocompromised rats but not immunocompetent rats. In addition, the magnitude of serum antibody responses differed between immunocompetent rat strains with Brown Norway and SD rats having a significantly higher antibody response than CD or Fischer 344 rats. These data suggest that RTV1 has a tropism for the epithelial cells of the small intestine, immunocompetent rats have differing serum antibody responses to RTV infection, and sustained fecal shedding and extraintestinal dissemination of RTV1 occurs in rats deficient in T cell-dependent adaptive immunity. RTV infection in immunocompromised and immunocompetent rats has merit as a model for further studies of theilovirus pathogenesis following oral viral exposure.

  7. 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.

  8. Impact of Environmental Enrichment on Perineuronal Nets in the Prefrontal Cortex following Early and Late Abstinence from Sucrose Self-Administration in Rats

    PubMed Central

    Slaker, Megan; Barnes, Jesse; Sorg, Barbara A.; Grimm, Jeffrey W.

    2016-01-01

    Perineuronal nets (PNNs) are aggregates of extracellular matrix that form structures surrounding a subset of GABAergic interneurons. The staining intensity of PNNs appears to be related to plasticity. Environmental enrichment (EE) influences plasticity during adulthood: EE decreases the rewarding effects of drugs of abuse and diminishes both drug- and sucrose-seeking behavior. We determined the impact of EE on PNN intensity in the medial prefrontal cortex (mPFC) in rats trained to self-administer sucrose. We examined the number and intensity of PNNs within the prelimbic (PL), infralimbic (IL), and orbitofrontal (OF) regions of the mPFC of adult Long-Evans rats that were trained for sucrose self-administration followed by acute or chronic EE during abstinence and a cue-induced reinstatement test. Rats exposed to EE prior to a cue-induced reinstatement of sucrose seeking had an increase in PNN staining compared with rats in standard housing. Conversely, naïve rats given 1 day of EE had a decrease in PNN intensity in the PL, no change in the IL, and an increase in the OF. Our findings demonstrate that EE increases PNN intensity in the mPFC after sucrose training, suggesting that training enhances the ability of EE to increase PNN intensity. We further demonstrate an interaction between time of abstinence, duration of EE exposure, and cue-induced reinstatement. Our results suggest that increased PNN intensity after EE may alter the excitatory/inhibitory balance of mPFC neurons such that rats are less responsive to a sucrose cue. PMID:27977779

  9. Characterization and comparison of post-natal rat Achilles tendon-derived stem cells at different development stages.

    PubMed

    Chen, Jialin; Zhang, Wei; Liu, Zeyu; Zhu, Ting; Shen, Weiliang; Ran, Jisheng; Tang, Qiaomei; Gong, Xiaonan; Backman, Ludvig J; Chen, Xiao; Chen, Xiaowen; Wen, Feiqiu; Ouyang, Hongwei

    2016-03-14

    Tendon stem/progenitor cells (TSPCs) are a potential cell source for tendon tissue engineering. The striking morphological and structural changes of tendon tissue during development indicate the complexity of TSPCs at different stages. This study aims to characterize and compare post-natal rat Achilles tendon tissue and TSPCs at different stages of development. The tendon tissue showed distinct differences during development: the tissue structure became denser and more regular, the nuclei became spindle-shaped and the cell number decreased with time. TSPCs derived from 7 day Achilles tendon tissue showed the highest self-renewal ability, cell proliferation, and differentiation potential towards mesenchymal lineage, compared to TSPCs derived from 1 day and 56 day tissue. Microarray data showed up-regulation of several groups of genes in TSPCs derived from 7 day Achilles tendon tissue, which may account for the unique cell characteristics during this specific stage of development. Our results indicate that TSPCs derived from 7 day Achilles tendon tissue is a superior cell source as compared to TSPCs derived from 1 day and 56 day tissue, demonstrating the importance of choosing a suitable stem cell source for effective tendon tissue engineering and regeneration.

  10. Effects of TRPV1 on the hippocampal synaptic plasticity in the epileptic rat brain.

    PubMed

    Saffarzadeh, Fatemeh; Eslamizade, Mohammad J; Ghadiri, Tahereh; Modarres Mousavi, Sayed Mostafa; Hadjighassem, Mahmoudreza; Gorji, Ali

    2015-07-01

    Temporal lobe epilepsy is often presented by medically intractable recurrent seizures due to dysfunction of temporal lobe structures, mostly the temporomesial structures. The role of transient receptor potential vaniloid 1 (TRPV1) activity on synaptic plasticity of the epileptic brain tissues was investigated. We studied hippocampal TRPV1 protein content and distribution in the hippocampus of epileptic rats. Furthermore, the effects of pharmacologic modulation of TRPV1 receptors on field excitatory postsynaptic potentials have been analyzed after induction of long term potentiation (LTP) in the hippocampal CA1 and CA3 areas after 1 day (acute phase) and 3 months (chronic phase) of pilocarpine-induced status epilepticus (SE). A higher expression of TRPV1 protein in the hippocampus as well as a higher distribution of this channel in CA1 and CA3 areas in both acute and chronic phases of pilocarpine-induced SE was observed. Activation of TRPV1 using capsaicin (1 µM) enhanced LTP induction in CA1 region in non-epileptic rats. Inhibition of TRPV1 by capsazepine (10 µM) did not affect LTP induction in non-epileptic rats. In acute phase of SE, activation of TRPV1 enhanced LTP in both CA1 and CA3 areas but TRPV1 inhibition did not affect LTP. In chronic phase of SE, application of TRPV1 antagonist enhanced LTP induction in CA1 and CA3 regions but TRPV1 activation had no effect on LTP. These findings indicate that a higher expression of TRPV1 in epileptic conditions is accompanied by a functional impact on the synaptic plasticity in the hippocampus. This suggests TRPV1 as a potential target in treatment of seizure attacks.

  11. Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

    NASA Technical Reports Server (NTRS)

    Yeshitla, Samrawit A.; Lam, Chiu-Wing; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Wu, Honglu; James, John T.; Meyers, Valerie E.; Zhang, Ye

    2014-01-01

    The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose-dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

  12. Animal Models of Rheumatoid Arthritis (I): Pristane-Induced Arthritis in the Rat

    PubMed Central

    Tuncel, Jonatan; Haag, Sabrina; Hoffmann, Markus H.; Yau, Anthony C. Y.; Hultqvist, Malin; Olofsson, Peter; Bäcklund, Johan; Nandakumar, Kutty Selva; Weidner, Daniela; Fischer, Anita; Leichsenring, Anna; Lange, Franziska; Haase, Claus; Lu, Shemin; Gulko, Percio S.; Steiner, Günter; Holmdahl, Rikard

    2016-01-01

    Background To facilitate the development of therapies for rheumatoid arthritis (RA), the Innovative Medicines Initiative BTCure has combined the experience from several laboratories worldwide to establish a series of protocols for different animal models of arthritis that reflect the pathogenesis of RA. Here, we describe chronic pristane-induced arthritis (PIA) model in DA rats, and provide detailed instructions to set up and evaluate the model and for reporting data. Methods We optimized dose of pristane and immunization procedures and determined the effect of age, gender, and housing conditions. We further assessed cage-effects, reproducibility, and frequency of chronic arthritis, disease markers, and efficacy of standard and novel therapies. Results Out of 271 rats, 99.6% developed arthritis after pristane-administration. Mean values for day of onset, day of maximum arthritis severity and maximum clinical scores were 11.8±2.0 days, 20.3±5.1 days and 34.2±11 points on a 60-point scale, respectively. The mean frequency of chronic arthritis was 86% but approached 100% in long-term experiments over 110 days. Pristane was arthritogenic even at 5 microliters dose but needed to be administrated intradermally to induce robust disease with minimal variation. The development of arthritis was age-dependent but independent of gender and whether the rats were housed in conventional or barrier facilities. PIA correlated well with weight loss and acute phase reactants, and was ameliorated by etanercept, dexamethasone, cyclosporine A and fingolimod treatment. Conclusions PIA has high incidence and excellent reproducibility. The chronic relapsing-remitting disease and limited systemic manifestations make it more suitable than adjuvant arthritis for long-term studies of joint-inflammation and screening and validation of new therapeutics. PMID:27227821

  13. Chronic deep brain stimulation of the rat ventral medial prefrontal cortex disrupts hippocampal-prefrontal coherence.

    PubMed

    Insel, Nathan; Pilkiw, Maryna; Nobrega, José N; Hutchison, William D; Takehara-Nishiuchi, Kaori; Hamani, Clement

    2015-07-01

    Deep brain stimulation (DBS) of the subgenual cingulate gyrus (SCG) has been used to treat patients with treatment-resistant depression. As in humans, DBS applied to the ventromedial prefrontal cortex of rats induces antidepressant-like responses. Physiological interactions between structures that play a role in depression and antidepressant treatment are still unknown. The present study examined the effect of DBS on inter-region communication by measuring the coherence of local field potentials in the rat infralimbic cortex (IL; homologue of the SCG) and one of its major afferents, the ventral hippocampus (VH). Rats received daily IL DBS treatment (100 μA, 90 μs, 130 Hz; 8h/day). Recordings were conducted in unrestrained, behaving animals on the day before treatment, after 1 and 10 days of treatment, and 10 days stimulation offset. VH-IL coherence in the 2-4 Hz range was reduced in DBS-treated animals compared with shams after 10 days, but not after only 1 day of treatment. No effect of DBS was observed in the 6-10 Hz (theta) range, where coherence was generally high and could be further evoked with a loud auditory stimulus. Finally, coherence was not affected by fluoxetine (10mg/kg), suggesting that the effects of DBS were not likely mediated by increased serotonin levels. While these data support the hypothesis that DBS disrupts communication between regions important for expectation-based control of emotion, they also suggest that lasting physiological effects require many days of treatment and, furthermore, may be specific to lower-frequency patterns, the nature and scope of which await further investigation.

  14. A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development

    PubMed Central

    Zambrano, E; Rodríguez-González, GL; Guzmán, C; García-Becerra, R; Boeck, L; Díaz, L; Menjivar, M; Larrea, F; Nathanielsz, PW

    2005-01-01

    Nutrient restriction during pregnancy and lactation impairs growth and development. Recent studies demonstrate long-term programming of function of specific organ systems resulting from suboptimal environments during fetal life and development up to weaning. We determined effects of maternal protein restriction (50% control protein intake) during fetal development and/or lactation in rats on the reproductive system of male progeny. Rats were fed either a control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. After delivery mothers received either C or R diet until weaning to provide four groups: CC, RR, CR and RC. We report findings in male offspring only. Maternal protein restriction increased maternal serum corticosterone, oestradiol and testosterone (T) concentrations at 19 days gestation. Pup birth weight was unchanged but ano-genital distance was increased by maternal protein restriction (P < 0.05). Testicular descent was delayed 4.4 days in RR, 2.1 days in CR and 2.2 days in RC and was not related to body weight. Body weight and testis weight were reduced in RR and CR groups at all ages with the exception of CR testis weight at 270 days postnatal age (PN). At 70 days PN luteinizing hormone and T concentrations were reduced in RR, CR and RC. mRNA for P450 side chain cleavage (P450scc) was reduced in RR and CR at 21 days PN but was unchanged at 70 days PN. Fertility rate was reduced at 270 days PN in RC and sperm count in RR and RC. We conclude that maternal protein delays sexual maturation in male rats and that some effects only emerge in later life. PMID:15611025

  15. Cloning of rat homeobox genes

    SciTech Connect

    Sakoyama, Yasuhiko; Mizuta, Ikuko; Ogasawara, Naotake

    1994-10-01

    We report the isolation of nine rat cognates of mouse homeoboxes within the four Hox gene clusters and a rat homologue of mouse IPF1 homeobox, RHbox No. 13A. The sequences of nine cloned homeoboxes are highly similar to those of the mouse and human homeoboxes in the Hox clusters. The restriction enzyme sites and map distances between each of the homeoboxes on the rat genome are nearly identical to those of mouse and human. Thus, we conclude that the isolated homeoboxes are the rat homologues of mouse homeoboxes within the four Hox clusters. A novel homeobox RHbox No. 13A is different from the Drosophila Antennapedia (Antp) sequence but is highly similar to the XlHbox8 (Xenopus laevis) and HtrA2 (Helobdella triserialis) homeoboxes. Forty-two amino acids of the last two-thirds of the RHbox No. 13A, XlHbox8, and mouse IPF1 homeodomains completely matched. In addition, these four homeodomains contain a unique His residue in the recognition helix of a helix-turn-helix DNA-binding motif. This His residue is not found in any of the previously published mammalian homeodomain sequences except mouse IPF1. 24 refs., 4 figs.

  16. 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

  17. Attenuation by creatine of myocardial metabolic stress in Brattleboro rats caused by chronic inhibition of nitric oxide synthase.

    PubMed Central

    Constantin-Teodosiu, D.; Greenhaff, P. L.; Gardiner, S. M.; Randall, M. D.; March, J. E.; Bennett, T.

    1995-01-01

    1. The present experiment was undertaken to investigate: (a) the effect of nitric oxide synthase (NOS) inhibition, mediated by oral supplementation of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on measures of myocardial energy metabolism and function: (b) the effect of oral creatine supplementation on these variables, in the absence and presence of L-NAME. 2. In one series of experiments, 4 weeks oral administration of L-NAME (0.05 mg ml-1 day-1 in the drinking water) to Brattleboro rats caused significant reductions in myocardial ATP, creatine, and total creatine concentrations and an accumulation of tissue lactate when compared with control animals. Administration of creatine (0.63 mg ml-1 day-1 in the drinking water) for 4 weeks elevated myocardial creatine and total creatine concentrations and reduced lactate accumulation, but did not significantly affect ATP or phosphocreatine (PCr). Concurrent treatment with creatine and L-NAME prevented the reduction in creatine and total creatine concentrations, and significantly attenuated the accumulation of lactate and the reduction in ATP seen with L-NAME alone. 3. In a second series of experiments, 4 weeks treatment with L-NAME and creatine plus L-NAME increased mean arterial blood pressure in conscious Brattleboro rats. Hearts isolated from these animals showed decreased coronary flow and left ventricular developed pressure (LVDP), and total mechanical performance. Treatment with creatine alone had no measurable effect on either mean arterial blood pressure or coronary flow in isolated hearts. However, there was an increase in LVDP, but not in total mechanical performance, because there was a bradycardia. 4. These results indicate that creatine supplementation can attenuate the metabolic stress associated with L-NAME administration and that this effect occurs as a consequence of the action of creatine on myocardial energy metabolism. PMID:8719809

  18. Translocation and biokinetic behavior of nanoscaled europium oxide particles within 5 days following an acute inhalation in rats.

    PubMed

    Creutzenberg, Otto; Kock, Heiko; Schaudien, Dirk

    2016-03-01

    Nanoscaled europium oxide (Eu2O3) particles were inhaled by rats after acute exposure and the potential translocation of particles followed by chemical analysis and transmission electron microscopy (TEM) was investigated. An aqueous dispersion (phosphate buffer/bovine serum albumin) of a commercially available Eu2O3 particle fraction consisting partially of nanoscaled particles was aerosolized with pressurized air. After rapid evaporation, rats inhaled the dry aerosol for 6 h in a single exposure resulting in an alveolar calculated dose of approximately 39.5 μg Eu2O3. Using chemical analysis, 36.8 μg Eu2O3 was detected 1 h after lung inhalation. The amount declined slightly to 34.5 μg after 1 day and 35.0 μg after 5 days. The liver showed an increase of Eu2O3 from 32.3 ng 1 h up to 294 ng 5 days after inhalation. Additionally, lung-associated lymph nodes, thymus, kidneys, heart and testis exhibited an increase of europium over the period investigated. In the blood, the highest amount of europium was found 1 h after treatment whereas feces, urine and mesenteric lymph nodes revealed the highest amount 1 day after treatment. Using TEM analysis, particles could be detected only in lungs, and in the liver, no particles were detectable. In conclusion, the translocation of Eu2O3 within 5 days following inhalation could be determined very precisely by chemical analysis. A translocation of Eu2O3 particulate matter to liver was not detectable by TEM analysis; thus, the overproportional level of 0.8% of the lung load observed in the liver after 5 days suggests a filtering effect of dissolved europium with accumulation.

  19. Significant improvement of survival by intrasplenic hepatocyte transplantation in totally hepatectomized rats.

    PubMed

    Vogels, B A; Maas, M A; Bosma, A; Chamuleau, R A

    1996-01-01

    The effect of intrasplenic hepatocyte transplantation (HTX) was studied in an experimental model of acute liver failure in rats with chronic liver atrophy. Rats underwent a portacaval shunt operation on Day -14 to induce liver atrophy, and underwent total hepatectomy on Day 0 as a start of acute liver failure. Intrasplenic hepatocyte or sham transplantation was performed on Day -7,-3, or -1 (n = 4 to 6 per group). During the period following hepatectomy, mean arterial blood pressure was maintained above 80 mm Hg and hypoglycaemia was prevented. Severity of hepatic encephalopathy was assessed by clinical grading and EEG spectral analysis, together with determination of blood ammonia and plasma amino acid concentrations, and "survival" time. Histological examination of the spleen and lungs was performed after sacrifice. Intrasplenic hepatocyte transplantation resulted in a significant improvement in clinical grading in all transplanted groups (p < 0.05), whereas a significant improvement in EEG left index was seen only in the group with transplantation on Day -1 (p < 0.05). In contrast to hepatocyte transplantation 1 day before total hepatectomy, rats with hepatocyte transplantation 3 and 7 days before total hepatectomy showed a significant 3- and 2-fold increase in "survival" time compared to sham transplanted controls: HTX at Day -1: 7.5 +/- 0.3 h vs. 5.9 +/- 0.6 h (p > 0.05), HTX at Day -3: 19.7 +/- 3.7 h vs. 6.5 +/- 0.3 h (p < 0.05), and HTX at Day -7: 13.8 +/- 3.2 h vs. 6.3 +/- 0.3 h (p < 0.05). Furthermore, rats with hepatocyte transplantation on Day -3 and -7 showed significantly lower blood ammonia concentrations after total hepatectomy (p < 0.0001). Histological examination of the spleens after sacrifice showed clusters of hepatocytes in the red pulp. Hepatocytes present in the spleen for 3 and 7 days showed bile accumulation and spots of beginning necrosis. The present data show that in a hard model of complete liver failure in portacaval shunted rats

  20. Role of miR-145 in chronic constriction injury in rats

    PubMed Central

    Pang, Xiaolin; Tang, Yuanzhang; Zhang, Dongya

    2016-01-01

    The present study aims to investigate the effects and underlying mechanisms of miRNA-145 (miR-145) in rat models of chronic constriction injury (CCI). Rats were randomly divided into control, sham, CCI, agomiRNA (agomiR)-normal control (NC) and agomiR-145 groups (n=25 in each group); in addition, 30 rats with CCI were divided into small hairpin (sh)RNA-NC and shRNA-ras responsive element binding protein 1 (RREB1) groups. Paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) were detected. Reverse transcription-quantitative polymerase chain reaction was used to detect miR-145 expression levels, and western blotting was performed to measure RREB1 and phosphorylated-protein kinase B (p-AKT) expression levels. In addition, a dual luciferase reporter assay was conducted to identify the target gene of miR-145. PWMT and PWTL were decreased in CCI rats and this decrease was alleviated by miR-145 injection. At 1, 3, 5 and 7 days after CCI, miR-145 expression level in the spinal cord tissue of rats in the CCI group was significantly decreased compared with 1 day before CCI (P<0.05). Compared with the CCI group, miR-145 expression level in the agomiR-145 group was significantly higher (P<0.05). In addition, expression levels of RREB1 and p-AKT were significantly increased in the CCI group and significantly decreased in the agomiR-145 group (P<0.05). Furthermore, knockdown of RREB1 expression by shRNA-RREB1 significantly increased values of PWMT and PWTL, decreased expression levels of RREB1 and p-AKT, and increased miR-145 expression levels (P<0.05). Further investigation demonstrated that miR-145 can bind with RREB1 mRNA. In conclusion, miR-145 may be involved in the development of CCI through regulating the expression of RREB1. PMID:28105140

  1. Fate and toxic effects of inhaled ultrafine cadmium oxide particles in the rat lung.

    PubMed

    Takenaka, S; Karg, E; Kreyling, W G; Lentner, B; Schulz, H; Ziesenis, A; Schramel, P; Heyder, J

    2004-01-01

    Female Fischer 344 rats were exposed to ultrafine cadmium oxide particles, generated by spark discharging, for 6 h at a concentration of 70 microg Cd/m(3) (1 x 10(6)/cm(3)) (40 nm modal diameter). Lung morphology and quantification of Cd content/concentration by inductively coupled plasma (ICP)-mass spectrometry were performed on days 0, 1, 4, and 7 after exposure. Cd content in the lung on day 0 was 0.53 +/- 0.12 microg/lung, corresponding to 19% of the estimated total inhaled cumulative dose, and the amount remained constant throughout the study. In the liver no significant increase of Cd content was found up to 4 days. A slight but statistically significant increase was observed in the liver on day 7. We found neither exposure-related morphological changes of lungs nor inflammatory responses in lavaged cells. Another group of rats were exposed to a higher concentration of ultrafine CdO particles (550 microg Cd/m(3) for 6 h, 51 nm modal diameter). The rats were sacrificed immediately and 1 day after exposure. The lavage study performed on day 0 showed an increase in the percentage of neutrophils. Multifocal alveolar inflammation was seen histologically on day 0 and day 1. Although the Cd content in the lung was comparable between day 0 and day 1 (3.9 microg/lung), significant elevation of Cd levels in the liver and kidneys was observed on both days. Two of 4 rats examined on day 0 showed elevation of blood cadmium, indicating systemic translocation of a fraction of deposited Cd from the lung in this group. These results and comparison with reported data using fine CdO particles indicate that inhalation of ultrafine CdO particles results in efficient deposition in the rat lung. With regard to the deposition dose, adverse health effects of ultrafine CdO and fine CdO appear to be comparable. Apparent systemic translocation of Cd took place only in animals exposed to a high concentration that induced lung injury.

  2. Effect of chromium supplementation on the diabetes induced-oxidative stress in liver and brain of adult rats.

    PubMed

    Refaie, Fawzia M; Esmat, Amr Y; Mohamed, Aly F; Aboul Nour, Wael H

    2009-12-01

    This study was designed to investigate the susceptibility of liver and brain tissues, as insulinin-dependent tissues, of normal adult male rats to the oxidative challenge of subchronic supplementation with chromium picolinate (CrPic) at low (human equivalent) and high doses (2.90 and 13.20 μg Cr kg(-1) day(-1), respectively). Also, the modulative effect of CrPic administration on the enhanced oxidative stress in the liver and brain tissues of alloxan-diabetic rats was studied. Fasting serum glucose level was not modified in normal rats but significantly reduced in diabetic rats that had received CrPic supplement. A mild oxidative stress was observed in the liver and brain of CrPic-supplemented normal rats confirmed by the dose-dependent reductions in the levels of hepatic and cerebral free fatty acids, superoxide dismutase and glutathione peroxidase activities, and in contrast increased tissue malondialdehyde concentration. On the other hand, hepatic and cerebral catalase activity was reduced in the high dose group only. CrPic supplementation did not act as a peroxisome proliferator confirmed by the significant reductions in liver and brain peroxisomal palmitoyl CoA oxidase activity. The non significant alterations in liver protein/DNA and RNA/DNA ratios indicate that CrPic did not affect protein synthesis per cell, and that mild elevations in hepatic total protein and RNA concentrations might be due to block or decrease in the export rate of synthesized proteins from the liver to the plasma. In diabetic rats, elevated levels of hepatic and cerebral free fatty acids and malondialdehyde, and in contrast the overwhelmed antioxidant enzymes, were significantly modulated in the low dose group and near-normalized in the high dose group. The significant increases observed in liver total protein and RNA concentrations, as well as protein/DNA and RNA/ DNA ratios in diabetic rats supplemented with the high dose of Cr, compared to untreated diabetics, may be related to the

  3. Desert RATS 2011: Near-Earth Asteroid Human Exploration Operations

    NASA Technical Reports Server (NTRS)

    Abercromby, Andrew; Gernhardt, Michael L.; Chappel, Steve

    2012-01-01

    The Desert Research and Technology Studies (D-RATS) 2011 field test involved the planning and execution of a series of exploration scenarios under operational conditions similar to those that would be expected during a human exploration mission to a near-Earth asteroid (NEA). The focus was on understanding the operations tempo during simulated NEA exploration and the implications of communications latency and limited data bandwidth. Anchoring technologies and sampling techniques were not evaluated due to the immaturity of those technologies and the inability to meaningfully test them at D-RATS. Reduced gravity analogs and simulations are being used to fully evaluate Multi-Mission Space Exploration Vehicle (MMSEV) and extravehicular (EVA) operations and interactions in near-weightlessness at a NEA as part of NASA s integrated analogs program. Hypotheses were tested by planning and performing a series of 1-day simulated exploration excursions comparing test conditions all of which involved a single Deep Space Habitat (DSH) and either zero, one, or two MMSEVs; three or four crewmembers; one of two different communications bandwidths; and a 100-second roundtrip communications latency between the field site and Houston. Excursions were executed at the Black Point Lava Flow test site with a Mission Control Center and Science Support Room at Johnson Space Center (JSC) being operated with 100-second roundtrip communication latency to the field. Crews were composed of astronauts and professional field geologists and teams of Mission Operations, Science, and Education & Public Outreach (EPO) experts also supported the mission simulations each day. Data were collected separately from the Crew, Mission Operations, Science, and EPO teams to assess the test conditions from multiple perspectives. For the operations tested, data indicates practically significant benefits may be realized by including at least one MMSEV and by including 4 versus 3 crewmembers in the NEA exploration

  4. The antigonadotropic action of testosterone but not 7alpha-methyl-19-nortestosterone is attenuated through the 5alpha-reductase pathway in the castrated male rat pituitary gland.

    PubMed

    Bandivdekar, A H; Karp, R; Sundaram, K; Kumar, N

    2000-01-01

    The enzyme 5alpha-reductase plays a significant role in the prostate to amplify the action of testosterone (T) by converting it to a more potent androgen, dihydrotestosterone (DHT). The role of 5alpha-reductase in the testosterone feedback inhibition of gonadotropin secretion from the pituitary has not been elucidated. Therefore, we investigated the role of 5alpha-reductase on T action in in vitro and in vivo models. Castration has been reported to increase the 5alpha-reductase activity in pituitary glands. Hence, the effect of castration duration on the conversion of T to DHT by pituitary homogenates and the responsiveness of pituitary monolayer cell cultures to gonadotropin-releasing hormone (GnRH) challenge exposure were investigated. Incubation of [3H]-T with pituitary homogenates showed that the conversion of T to 5alpha-reduced metabolites was two- to threefold greater in pituitaries from rats who had been castrated for 14 days compared with those castrated for 1 day. In addition, the GnRH-stimulated release of LH from monolayer cell cultures of pituitaries from rats castrated for 1 day was twofold greater, whereas that from rats castrated for 2 weeks was six- to sevenfold greater compared with basal luteinizing hormone (LH) release. Hence we used rats castrated for 2 weeks to elucidate the role of 5alpha-reductase in T feedback inhibition. The inhibitory effects of the androgens T, 19-nortestosterone (19-NT), and 7alpha-methyl-19-nortestosterone (MENT) at 3 different concentrations (10(-9), 10(-7), and 10(-5) mol/L) on GnRH-stimulated LH release from monolayer cell cultures of pituitaries from rats castrated for 2 weeks were examined. All 3 androgens showed dose-dependent inhibition of LH release. MENT showed the greatest inhibition, followed by 19-NT and T. In the presence of finasteride (a 5alpha-reductase inhibitor), the inhibition of LH released by T and 19-NT were significantly greater. The inhibitory effect of MENT, which does not undergo 5alpha

  5. Dithiobiuret toxicity in the rat

    SciTech Connect

    Williams, K.D.

    1985-01-01

    Raising the daily dose of dithiobiuret (DTB) in male rats from 0.5 to 1 to 5 mg/kg shortened the latency to the onset of flaccid muscle tone and associated diminished performance in a treadmill test from 7 to 5 to 3 days, respectively. Concomitant with the development of flaccid muscle tone gastrocnemius muscle contractions elicited by high frequency motor nerve stimulation were lower in peak tension and tended to fade more rapidly in DTB-treated rats than in control rats. Remarkably, rats treated with highly daily doses (10-16 mg/kg) of DTB were resistant to the expected development of DTB-induced flaccid muscle tone, and tetanic contractile abnormalities but a corresponding refractoriness to body weight loss, decreased fed and water intake, diuresis, and depression in water balance was not present. This nonselectivity of the refractory responses supported the results of a histopathological study indicating that DTB-induced neuromuscular toxicity was unlikely to be secondary to effect on other organ systems. It is not known whether the ultimate neurotoxin is DTB or a metabolite. In this regard, two pathways for the metabolism of DTB were proposed based on the results of thin-layer chromatography of urine samples from rats treated with either /sup 14/C- or /sup 35/S-DTB. One pathway involved the reversible oxidation of DTB to the disulfide-containing compound thiuret, and the other involved the replacement of a sulfur atom with oxygen to form monothiobiuret. Thiuret, but not monothiobiuret, possessed comparable toxicity to STB. This further suggested that redox cycling between DTB and thiuret could be an important contributing factor to the toxicity of DTB.

  6. Sexual dimorphism in hybrids rats.

    PubMed

    Garcia-Falgueras, Alicia; Pinos, Helena; Fernández, Rosa; Collado, Paloma; Pasaro, Eduardo; Segovia, Santiago; Guillamon, Antonio

    2006-12-06

    Laboratory rat strains descend from Wistar rats as a consequence of artificial selection. Previously we reported that the medial posterior division of the bed nucleus of the stria terminalis (BSTMP) was sexually dimorphic in Wistar and Long-Evans strains while the medial anterior division (BSTMA) and the locus coeruleus (LC) only showed sex differences in the ancestor Wistar strain. The lateral posterior division (BSTLP) was isomorphic in both strains. The present work studies the number of neurons in the BSTMP, BSTMA, BSTLP and LC of male and female Wistar and Long-Evans rats (F(0)) and their hybrid F(1) and F(2) generations. The BSTMP is sexually dimorphic in the F(0), F(1) and F(2) generations while sex differences in the LC are only seen in F(0) Wistar rats but not in the F(0) Long-Evans or the F(1) and F(2) hybrid generations. Sex differences in the BSTMA are seen in F(0) Wistar but not in F(0) Long-Evans rats and completely disappear in the F(2) generations. The number of neurons in the LC of both males and females decreased in heterozygotic individuals (F(1)) but increased in homozygotic (F(2)). However, the number of neurons in the BSTMP changes significantly over the generations, although the ratio of neurons (female/male) is stable and unaffected in homo- or heterozygosis. Thus, the mechanism that regulates the neuronal female/male ratio would be different from the one that controls the number of neurons. The facts that sex differences in the BSTMP are not affected by homo- or heterozygosis and that they are seen in several mammalian orders suggest the existence of a "fixed" type of brain sex differences in the Mammalia Class.

  7. 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.

  8. 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.

  9. Effects of concentrated ambient particles on normal and hypersecretory airways in rats.

    PubMed

    Harkema, Jack R; Keeler, Gerald; Wagner, James; Morishita, Masako; Timm, Edward; Hotchkiss, Jon; Marsik, Frank; Dvonch, Timothy; Kaminski, Norbert; Barr, Edward

    2004-08-01

    in southwestern Detroit during the summer months when particulate air pollution is usually high (July and September 2000). We monitored the outdoor air pollution in this community daily, and exposed normal and compromised rats to concentrated PM2.5 from this local urban atmosphere. Rats in the inhalation studies were exposed for 1 day or for 4 or 5 consecutive days (10 hours/day) to either filtered air (controls) or concentrated ambient particles (CAPs) delivered by a Harvard ambient fine particle concentrator. Rats were killed 24 hours after the end of the exposure. Biochemical, morphometric, and molecular techniques were used to identify airway epithelial and inflammatory responses to CAPs. Lung lobes were also either intratracheally lavaged with saline to determine cellular composition and protein in bronchoalveolar lavage fluid (BALF) or removed for analysis by inductively coupled plasma-mass spectrometry (ICPMS) to detect retention of ambient PM2.5--derived trace elements. The Harvard concentrator effectively concentrated the fine ambient particles from this urban atmosphere (10-30 times) without significantly changing the major physicochemical features of the atmospheric particles. Daily CAPs mass concentrations during the 10-hour exposure period (0800-1800) in July ranged from 16 to 895 microg/m3 and in September ranged from 81 to 755 microg/m3. In general, chemical characteristics of ambient particles were conserved through the concentrator into the exposure chamber. Single or repeated exposures to CAPs did not cause adverse effects in the nasal or pulmonary airways of healthy F344 or BN rats. In addition, CAPs-related toxicity was not observed in F344 rats pretreated with bacterial endotoxin. Variable airway responses to CAPs exposure were observed in BN rats with preexisting allergic airway disease induced by OVA sensitization and challenge. Only OVA-challenged BN rats exposed to CAPs for 5 consecutive days in September 2000 had significant increases in

  10. Loxoribine pretreatment reduces Salmonella Enteritidis organ invasion in 1-day-old chickens.

    PubMed

    Swaggerty, C L; He, H; Genovese, K J; Duke, S E; Kogut, M H

    2012-04-01

    Young poultry exhibit a transient colonization by some food-borne pathogens, including Salmonella, during the first week of life that stems from immature innate and acquired defense mechanisms. Consequently, modulation of the hosts' natural immune response is emerging as an important area of interest for food animal producers, including the poultry industry. Toll-like receptor (TLR) agonists have been shown to boost the innate immune response in young chickens and increase their resistance to colonization by Salmonella enterica serovar Enteritidis. The objective of the present study was to determine if pretreatment with loxoribine, a TLR7 agonist and immune modulator, protects young chicks from Salmonella Enteritidis organ invasion. Loxoribine (0-100 μg) was administered intra-abdominally to 1-d-old broiler chicks, and 4 h later, the birds were challenged orally with Salmonella Enteritidis. Twenty-four hours postchallenge, birds were euthanized and the liver and spleen aseptically removed and cultured for Salmonella Enteritidis. This was carried out on 3 separate occasions using 26 to 50 chicks per dose per experiment. Pretreatment of chicks with loxoribine (6.25-25 μg) significantly (P ≤ 0.05) reduced liver and spleen organ invasion by Salmonella Enteritidis. Higher doses (50-100 μg) of loxoribine had no effect. The results obtained in this study indicate that there is a potential application for using loxoribine to increase protection of young chicks when they are most susceptible to infections with Salmonella.

  11. Assessing of IDF curves for hydrological design by simple scaling of 1-day precipitation totals

    NASA Astrophysics Data System (ADS)

    Bara, M.; Kohnová, S.; Szolgay, J.; Gaál, L.; Hlavčová, K.

    2010-09-01

    In this paper the scaling properties of short term extreme rainfall in Slovakia were investigated. The simple scaling theory was applied to the intensity-duration-frequency (IDF) characteristics of a short duration rainfall. This method allows for the estimation of the design values of rainfall of selected recurrence intervals and durations shorter than a day by using only the daily data. The scaling behavior of rainfall intensities was examined, and the possibility of using simple scaling in Slovakia was verified. The methodology for the simple scaling of rainfall is demonstrated using an example of the meteorological station in Ilava.

  12. Testing gridded NWS 1-Day observed precipitation analysis in a daily irrigation scheduler

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One of the inputs required by daily irrigation schedulers is the amount of water supplied by rainfall. In-field measurements of daily precipitation are expensive or laborious, while measurements from gauges within a few kilometers are frequently not representative due to the high spatiotemporal vari...

  13. Loxoribine pretreatment reduces Salmonella enteritidis organ invasion in 1-day-old chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Young poultry exhibit a transient susceptibility to some infectious diseases, including Salmonella, during the first week of life that stems from immature innate and acquired defense mechanisms. Consequently, stimulation or modulation of the hosts’ natural immune response is emerging as an importan...

  14. 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.

  15. 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

  16. Wound Healing Delay in the ZDSD Rat

    PubMed Central

    A. SUCKOW, MARK; A. GOBBETT, TROY; G. PETERSON, RICHARD

    2017-01-01

    Animal models of diabetic delayed wound healing are essential to the development of strategies to improve clinical approaches for human patients. The Zucker diabetic Sprague Dawley (ZDSD) rat has proved to be an accurate model of diet-induced obesity and diabetes and we evaluated the utility of the ZDSD rat as a model for delayed wound healing associated with diabetes and obesity. Groups of ZDSD and Sprague Dawley (SD) rats were placed on a diabetogenic diet and evaluated two weeks later for hyperglycemia, as a sign of diabetes. Rats with blood glucose levels of >300 mg/dl were considered diabetic and those with blood glucose of <180 mg/dl were considered non-diabetic. All SD rats were non-diabetic. A full-thickness excisional skin wound was created in anesthetized rats using a punch biopsy and wound diameter measured on days 1, 4, 7, 9 and 11. Blood glucose levels and body weights were measured periodically before and after wounding. Diabetic ZDSD rats had significantly greater blood glucose levels than non-diabetic ZDSD and SD rats within 10 days of being placed on the diabetogenic diet. Furthermore, diabetic ZDSD rats initially weighed more than non-diabetic ZDSD and SD rats, however, by the end of the study there was no significant difference in body weight between the ZDSD groups. By day nine, wounds in ZDSD rats were significantly larger than those in SD rats and this persisted until the end of the study at day fourteen. Wounds from all groups were characterized histologically by abundant fibroblast cells, collagen deposition and macrophages. These results demonstrate delayed wound healing in both diabetic and non-diabetic ZDSD rats and suggest that obesity or metabolic syndrome are important factors in wound healing delay. PMID:28064221

  17. Green tea attenuates diabetes induced Maillard-type fluorescence and collagen cross-linking in the heart of streptozotocin diabetic rats.

    PubMed

    Babu, Pon Velayutham Anandh; Sabitha, Kuruvimalai Ekambaram; Srinivasan, Periasamy; Shyamaladevi, Chennam Srinivasulu

    2007-05-01

    The enhanced myocardial collagen content, collagen glycation and the resulting advanced glycation end products (AGE) which exhibit the characteristics of increased cross-linking are proposed for the stiffness of myocardium in diabetes. To explore the cardioprotective effect of green tea in diabetes, we study the effect of green tea extract on myocardial collagen characteristics in streptozotocin diabetic rats. The effect of green tea on marker enzymes in serum and cardiac tissues were also assayed to understand the extent of protection. Six weeks after the diabetes induction, diabetic rats were treated with green tea extract [300 mg (kg body weight)(-1)day(-1)] for 4 weeks. AGE were determined by fluorescence assay and cross-linking of collagen by solubility measurement while collagen content was measured by biochemical assay. The activities of aspartate transaminase (AST), lactate dehydrogenase (LDH) and creatine kinase (CPK) were measured by biochemical assay. The increase in blood glucose, glycated hemoglobin and systolic blood pressure in diabetic rats were reduced upon green tea treatment. The activities of AST, LDH and CPK were significantly increased in serum whereas decreased in cardiac tissues in diabetic rats representing the cardiac damage. Administration of green tea to diabetic rats significantly ameliorates these enzyme activities. There was no significant difference in the myocardial collagen content among the experimental rats. A significant (P<0.05) increase in collagen linked Maillard-type fluorescence and decrease in collagen solubility in the myocardium of diabetic rats as compared to control rats (0.955+/-0.02 versus 0.683+/-0.04 and 30+/-1.41 versus 45.17+/-1.17, respectively) indicates the increase in advanced glycation end products formation and degree of collagen cross-linking. Green tea administration to diabetic rats significantly (P<0.05) decreased the fluorescence (0.73+/-0.02) whereas increased the solubility of collagen (41

  18. [Effect of long-term exposure to low dose gamma-irradiation on the rat thyroid status].

    PubMed

    Nadol'nik, L I; Netsetskaia, Z V; Vinogradov, V V

    2004-01-01

    The effect of long-term exposure to low-dose external radiation on the rat thyroid status was studied. The experiments were carried out on Wistar female rats. The single doses absorbed were 0.1; 0.25; 0.5 Gy. The rats were irradiated 20 times (5 days x 4 weeks). The animals were decapitated after 1, 30 and 180 days following the last irradiation. Blood serum was assayed for content of thyroxin (T4) and triiodothyronine (T3) radioimmunologically. The liver was spectrophotometrically assayed for thyroid-induced NADP-malatedehydrogenase (NADP-MDH). It was shown that the long-term 0.5-Gy irradiation of the animals induced a decrease in blood T4 and T3 concentrations 1.34-1.71-fold and 1.24-1.43-fold after 1, 30 and 180 days, respectively. The T3 level was diminished most pronouncedly after 1 day, whereas that of T4--after 30 days following the exposure. With the doses of 0.1 and 0.25 Gy absorbed, the T4 and T3 concentration remained unchanged throughout all the periods studied. The activity of NADP-MDH was decreased 1.55-2.46-fold in all the experimental animals, and it was held decreased after 180 days (1.43-1.50-fold) in 0.25- and 0.5-Gy-irradiated groups, which indicates a disturbance in thyroid hormone metabolism in rats exposed chronically to low-dose radiation. After 180 days, the experimental animals experienced an elevation of thyroid gland weight on 15-20%. The thyroid status disturbance seemed to be due to both inhibited T4 and T3 biosynthesis in thyroid and disturbed hormone peripheral metabolism under radiation exposure.

  19. Leptin extends the anorectic effects of chronic PYY(3-36) administration in ad libitum-fed rats.

    PubMed

    Unniappan, Suraj; Kieffer, Timothy J

    2008-07-01

    Acute administration of peptide YY(3-36) [PYY(3-36)] results in a reduction in food intake in several different vertebrates. However, long-term continuous administration of PYY(3-36) causes only a transient reduction in food intake, thus potentially limiting its therapeutic efficacy. We hypothesized that a fall in leptin levels associated with reduced food intake could contribute to the transient anorectic effects of continuous PYY(3-36) infusion and thus that leptin replacement might prolong the anorectic effects of PYY(3-36). Seven-day administration of 100 microg x kg body wt(-1) x day(-1) PYY(3-36) using osmotic minipumps caused a significant reduction in food intake of ad libitum-fed rats, but only for the first 2 days postimplantation. Circulating levels of leptin were reduced 1 day following continuous infusion of PYY(3-36), and combined leptin infusion at a dose of leptin that had no anorectic effects on its own (100 microg x kg body wt(-1) x day(-1)) prolonged the anorectic actions of PYY(3-36) in ad libitum-fed rats for up to 6 days postimplantation and yielded reduced weight gain compared with either peptide alone. The inhibitory effects of 100 microg x kg body wt(-1) x day(-1) PYY(3-36) on food intake were absent in rats refed after a 24-h fast and substantially reduced at a dose of 1,000 microg x kg body wt(-1) x day(-1) PYY(3-36). Leptin replacement was unable to recover the anorectic effects of PYY(3-36) in fasted rats. Our results suggest that an acute fall in leptin levels is not solely responsible for limiting duration of action of chronic PYY(3-36) infusion, yet chronic coadministration of a subanorectic dose of leptin can extend the anorectic effects of PYY(3-36).

  20. Depletion of brain histamine produces regionally selective protection against thiamine deficiency-induced lesions in the rat.

    PubMed

    Langlais, Philip J; McRee, Robert Carter; Nalwalk, Julia A; Hough, Lindsay B

    2002-09-01

    Breakdown of the blood brain barrier and the subsequent accumulation of free radicals, lactate, and glutamate appear to be the immediate causes of thiamine deficiency (TD)-induced damage to thalamus. The mechanisms triggering these events are unknown but recent evidence suggests an important role of histamine. We therefore studied the effects of histamine depletion on thalamic lesions in the pyrithiamine-induced thiamine deficient (PTD) rat. Chronic intracerebroventricular (i.c.v., 7 days) infusion of alpha-fluoromethylhistidine (FMH), combined with bilateral ibotenate destruction of the histamine-containing neurons in the tuberomammillary (TM) nucleus and bolus i.c.v. infusion of 48/80, a potent mast cell degranulating agent, was used to deplete brain histamine levels. PTD rats receiving combined FMH + 48/80 + TM lesions developed acute neurological symptoms, including spontaneous seizures, approximately 1 day earlier than PTD rats treated with i.c.v. infusion of vehicle and sham lesions of the TM. When examined 1 week after restoration of thiamine, the PTD vehicle + sham lesion animals contained severe neuronal loss and gliosis in midline, intralaminar, ventral, lateral, and posterior nuclei. PTD animals treated with FMH + 48/80 + TM lesions had little evidence of neuronal loss or microglial proliferation in thalamus except in the gelatinosus and anteroventral nuclei, in which there was complete neuronal loss. These data demonstrate a significant and regionally selective role of histamine in the development of thalamic lesions in a rat model of Wernicke's encephalopathy. Furthermore, these data suggest either a dissociation between seizures and thalamic lesions or a significant role of histamine in seizure-related damage to the thalamus.

  1. Intraocular injection of dibutyryl cyclic AMP promotes axon regeneration in rat optic nerve.

    PubMed

    Monsul, Nicholas T; Geisendorfer, Abram R; Han, Paul J; Banik, Rudrani; Pease, Mary Ellen; Skolasky, Richard L; Hoffman, Paul N

    2004-04-01

    The optic nerve is a CNS pathway containing molecules capable of inhibiting axon elongation. The growth program in embryonic retinal ganglion cell (RGC) neurons enables axons to regenerate in the optic nerve through at least two mechanisms. Namely, high cyclic AMP (cAMP) levels abrogate the ability of CNS molecules to inhibit elongation, and the pattern of gene expression enables axons to undergo rapid, sustained, and lengthy elongation. In adult mammals, recovery of visual function after optic nerve injury is limited by both the death of most RGC neurons and the inability of surviving axons to regenerate. We now report that a single intraocular injection of the membrane-permeable cAMP analogue dibutyryl cAMP (db cAMP) promotes the regeneration of RGC axons in the optic nerves of adult rats, but does not prevent the death of RGC neurons. This regeneration in optic nerves crushed within the orbit (2 mm from the eye) was equally effective either 1 day before or 1 day after db cAMP injection. The number of regenerating axons, which was maximal 14 days after crush, declined with increasing time after injury (i.e., 28, 56, and 112 days) and distance beyond the crush site (i.e., 0.25, 0.5, and 1.0 mm). Thus, db cAMP promotes optic nerve regeneration without increasing the survival of axotomized RGC neurons. Furthermore, since db cAMP does not enable axons to undergo rapid, sustained, and lengthy elongation, strategies that increase survival and promote these changes in elongation may critically complement the ability of db cAMP to promote regeneration.

  2. 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.

  3. 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.

  4. Hyperammonemia in anorectic tumor-bearing rats.

    PubMed

    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.

  5. 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.

  6. 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.

  7. 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

  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. Immunochemistry of Rat Lung Tumorigenesis

    DTIC Science & Technology

    1983-01-01

    Memorial Institute 1640 (RPMI) tissue culture medium. The extra tissue surrounding the organs is dissected free and discarded; this procedure is done in a...concentration of 0.5 x 106 cells/ml in a total volume of 3 ml/culture using the following medium: Roswell Park Memorial Institute 1640 (RPMI 1640...test tubes containing sterile Roswel] Park Memorial Institute (RPMI) tissue culture medium 1640. Lymphocytes from rat spleens were isolated, counted and

  10. Methanethiol metabolism in the rat

    SciTech Connect

    Derr, R.F.; Draves, K.

    1983-03-01

    Methanethiol is associated with hepatic failure in humans and the synergistic action of methanethiol, ammonia and octanoate is sufficient to account for the coma of experimental hepatic necrosis. The sulfur atom of methanethiol is eliminated from the body as urinary sulfate at a rate which is approximated by a hyperbola such that 94% is excreted within 21 h after administration. Rats in octanoate or hepatic coma excreted only little sulfate in their urine.

  11. Comparative effects of continuous infusion of mCPP, Ro 60-0175 and d-fenfluramine on food intake, water intake, body weight and locomotor activity in rats.

    PubMed

    Vickers, S P; Benwell, K R; Porter, R H; Bickerdike, M J; Kennett, G A; Dourish, C T

    2000-07-01

    1. The aim of the study was to compare the effects of 14 day subcutaneous infusion of the 5-HT(2C) receptor agonists, m-chlorophenylpiperazine (mCPP, 12 mg kg(-1) day(-1)) and Ro 60-0175 (36 mg kg(-1) day(-1)) and the 5-HT releasing agent and re-uptake inhibitor, d-fenfluramine (6 mg kg(-1) day(-1)), on food and water intake, body weight gain and locomotion in lean male Lister hooded rats. 2. Chronic infusion of all three drugs significantly reduced food intake and attenuated body weight gain. In contrast, drug infusion did not lead to significant reductions in locomotor activity in animals assessed 2 and 13 days after pump implantation. 3. In a subsequent 14 day study that was designed to identify possible tolerance during days 7 - 14, animals were given a subcutaneous infusion of mCPP (12 mg kg(-1) day(-1)) or d-fenfluramine (6 mg kg(-1) day(-1)) for either 7 or 14 days. During the first 7 days both drugs significantly reduced body weight gain compared to saline-infused controls; however, from day 7 onwards animals withdrawn from drug treatment exhibited an increase in body weight such that by day 14 they were significantly heavier than their 14-day drug-treated counterparts. 4. Both mCPP and d-fenfluramine reduced daily food intake throughout the infusion periods. For 14-day treated animals this hypophagia was marked during the initial week of the study but only minor during the second week. In light of the sustained drug effect on body weight, the data suggest that weight loss by 5-HT(2C) receptor stimulation may be only partly dependent on changes in food consumption and that 5-HT(2C) receptor agonists may have effects on thermogenesis. 5. These data suggest tolerance does not develop to the effects of d-fenfluramine, mCPP and Ro 60-0175 on rat body weight gain.

  12. Do rats learn conditional independence?

    PubMed Central

    Timberlake, William

    2017-01-01

    If acquired associations are to accurately represent real relevance relations, there is motivation for the hypothesis that learning will, in some circumstances, be more appropriately modelled, not as direct dependence, but as conditional independence. In a serial compound conditioning experiment, two groups of rats were presented with a conditioned stimulus (CS1) that imperfectly (50%) predicted food, and was itself imperfectly predicted by a CS2. Groups differed in the proportion of CS2 presentations that were ultimately followed by food (25% versus 75%). Thus, the information presented regarding the relevance of CS2 to food was ambiguous between direct dependence and conditional independence (given CS1). If rats learnt that food was conditionally independent of CS2, given CS1, subjects of both groups should thereafter respond similarly to CS2 alone. Contrary to the conditionality hypothesis, subjects attended to the direct food predictability of CS2, suggesting that rats treat even distal stimuli in a CS sequence as immediately relevant to food, not conditional on an intermediate stimulus. These results urge caution in representing indirect associations as conditional associations, accentuate the theoretical weight of the Markov condition in graphical models, and challenge theories to articulate the conditions under which animals are expected to learn conditional associations, if ever. PMID:28386451

  13. Pathophysiology of the Belgrade rat

    PubMed Central

    Veuthey, Tania; Wessling-Resnick, Marianne

    2014-01-01

    The Belgrade rat is an animal model of divalent metal transporter 1 (DMT1) deficiency. This strain originates from an X-irradiation experiment first reported in 1966. Since then, the Belgrade rat’s pathophysiology has helped to reveal the importance of iron balance and the role of DMT1. This review discusses our current understanding of iron transport homeostasis and summarizes molecular details of DMT1 function. We describe how studies of the Belgrade rat have revealed key roles for DMT1 in iron distribution to red blood cells as well as duodenal iron absorption. The Belgrade rat’s pathology has extended our knowledge of hepatic iron handling, pulmonary and olfactory iron transport as well as brain iron uptake and renal iron handling. For example, relationships between iron and manganese metabolism have been discerned since both are essential metals transported by DMT1. Pathophysiologic features of the Belgrade rat provide us with a unique and interesting animal model to understand iron homeostasis. PMID:24795636

  14. Effect of two GABA-ergic drugs on the cognitive functions of rapid eye movement in sleep-deprived and recovered rats

    PubMed Central

    Bao, Lidao; Si, Lengge; Wang, Yuehong; Wuyun, Gerile; Bo, Agula

    2016-01-01

    Rapid eye movement (REM) sleep is closely associated with nervous functions. The present study aimed to evaluate the effects of gabazine and tiagabine on the cognitive functions (CF) of REM sleep-deprived and sleep recovered rats. Rats were divided into REM sleep deprivation, blank control (CC) and environmental groups. The REM sleep deprivation group was further divided into non-operation (nonOP), sham-operated (Sham), gabazine (SR) and tiagabine groups. Each group was evaluated over five time points: Sleep deprived for 1 day (SD 1 day), SD 3 day, SD 5 day, sleep recovery 6 h (RS 6 h) and RS 12 h. A rat model of REM sleep deprivation was established by a modified multi-platform water method, with CF assessed by Morris water maze. Hypothalamic γ-aminobutyric acid (GABA) and glutamic acid contents were measured via high performance liquid chromatography. The number and morphology of hypocretin (Hcrt) neurons and Fos in the hypothalamus, and GABAARα1-induced integral optical density were detected by immunofluorescence. Compared to the CC group, the nonOP and Sham group rats CF were significantly diminished, Fos-positive and Fos-Hcrt double positive cells were significantly increased, and GABA content and GABAARα1 expression levels were significantly elevated (P<0.05). The tiagabine and CC groups exhibited similar results at three time points. The CF of rats in the SR group were diminished and the number of Fos-positive and Fos-Hcrt double positive cells were significantly increased (P<0.05) at RS 6 h and RS l2 h. GABA content and GABAARα1 expression levels were significantly increased in the SR group at all time points (P<0.05), whereas only GABAARα1 expression levels were significantly increased in the tiagabine group at SD 5 day (P<0.05). The results of the present study indicated that REM sleep deprivation diminished CF, increased the number of Hcrt neurons, GABA content and GABAARα1 expression. Furthermore, all alterations were positively correlated with

  15. Effect of two GABA-ergic drugs on the cognitive functions of rapid eye movement in sleep-deprived and recovered rats.

    PubMed

    Bao, Lidao; Si, Lengge; Wang, Yuehong; Wuyun, Gerile; Bo, Agula

    2016-08-01

    Rapid eye movement (REM) sleep is closely associated with nervous functions. The present study aimed to evaluate the effects of gabazine and tiagabine on the cognitive functions (CF) of REM sleep-deprived and sleep recovered rats. Rats were divided into REM sleep deprivation, blank control (CC) and environmental groups. The REM sleep deprivation group was further divided into non-operation (nonOP), sham-operated (Sham), gabazine (SR) and tiagabine groups. Each group was evaluated over five time points: Sleep deprived for 1 day (SD 1 day), SD 3 day, SD 5 day, sleep recovery 6 h (RS 6 h) and RS 12 h. A rat model of REM sleep deprivation was established by a modified multi-platform water method, with CF assessed by Morris water maze. Hypothalamic γ-aminobutyric acid (GABA) and glutamic acid contents were measured via high performance liquid chromatography. The number and morphology of hypocretin (Hcrt) neurons and Fos in the hypothalamus, and GABAARα1-induced integral optical density were detected by immunofluorescence. Compared to the CC group, the nonOP and Sham group rats CF were significantly diminished, Fos-positive and Fos-Hcrt double positive cells were significantly increased, and GABA content and GABAARα1 expression levels were significantly elevated (P<0.05). The tiagabine and CC groups exhibited similar results at three time points. The CF of rats in the SR group were diminished and the number of Fos-positive and Fos-Hcrt double positive cells were significantly increased (P<0.05) at RS 6 h and RS l2 h. GABA content and GABAARα1 expression levels were significantly increased in the SR group at all time points (P<0.05), whereas only GABAARα1 expression levels were significantly increased in the tiagabine group at SD 5 day (P<0.05). The results of the present study indicated that REM sleep deprivation diminished CF, increased the number of Hcrt neurons, GABA content and GABAARα1 expression. Furthermore, all alterations were positively correlated with

  16. Exercise affects memory acquisition, anxiety-like symptoms and activity of membrane-bound enzyme in brain of rats fed with different dietary fats: impairments of trans fat.

    PubMed

    Teixeira, A M; Pase, C S; Boufleur, N; Roversi, K; Barcelos, R C S; Benvegnú, D M; Segat, H J; Dias, V T; Reckziegel, P; Trevizol, F; Dolci, G S; Carvalho, N R; Soares, F A A; Rocha, J B T; Emanuelli, T; Bürger, M E

    2011-11-10

    Here we evaluated the influence of physical exercise on behavior parameters and enzymatic status of rats supplemented with different dietary fatty acids (FA). Male Wistar rats fed diets enriched with soybean oil (SO), lard (L), or hydrogenated vegetable fat (HVF) for 48 weeks were submitted to swimming (30 min/d, five times per week) for 90 days. Dietary FA per se did not cause anxiety-like symptoms in the animals, but after physical exercise, SO group showed a better behavioral performance than L and the HVF groups in elevated plus maze (EPM). In Barnes maze, HVF group showed impaired memory acquisition as compared to L group, and exercise reversed this effect. SO-fed rats showed an improvement in memory acquisition after 1 day of training, whereas lard caused an improvement of memory only from day 4. HVF-fed rats showed no improvement of memory acquisition, but this effect was reversed by exercise in all training days. A lower activity of the Na(+)K(+)-ATPase in brain cortex of rats fed lard and HVF was observed, and this effect was maintained after exercise. Similarly, the HVF diet was related to lower activity of hippocampal Na(+)K(+)-ATPase, and exercise reduced activity of this enzyme in the SO and L groups. Our findings show influences of dietary FA on memory acquisition, whereas regular exercise improved this function and was beneficial on anxiety-like symptoms. As FA are present in neuronal membrane phospholipids and play a critical role in brain function, our results suggest that low incorporation of trans FA in neuronal membranes may act on cortical and hippocampal Na(+)K(+)-ATPase activity, but this change appears to be unrelated to the behavioral parameters primarily harmed by consumption of trans and less so by saturated FA, which were reversed by exercise.

  17. Voluntary exercise partially reverses neonatal alcohol-induced deficits in mPFC layer II/III dendritic morphology of male adolescent rats.

    PubMed

    Hamilton, G F; Criss, K J; Klintsova, A Y

    2015-08-01

    Developmental alcohol exposure in humans can produce a wide range of deficits collectively referred to as fetal alcohol spectrum disorders (FASD). FASD-related impairments in executive functioning later in life suggest long-term damage to the prefrontal cortex (PFC). In rodent neonates, moderate to high levels of alcohol exposure decreased frontal lobe brain size and altered medial PFC pyramidal neuron dendritic morphology. Previous research in our lab demonstrated that neonatal alcohol exposure decreased basilar dendritic complexity but did not affect spine density in Layer II/III pyramidal neurons in 26- to 30-day-old rats. The current study adds to the literature by evaluating the effect of neonatal alcohol exposure on mPFC Layer II/III basilar dendritic morphology in adolescent male rats. Additionally, it examines the potential for voluntary exercise to mitigate alcohol-induced deficits on mPFC dendritic complexity. An animal model of binge drinking during the third trimester of pregnancy was used. Rats were intubated with alcohol (alcohol-exposed, AE; 5.25 g kg(-1) day(-1)) on postnatal days (PD) 4-9; two control groups were included (suckle control and sham-intubated). Rats were anesthetized and perfused with heparinized saline solution on PD 42, and brains were processed for Golgi-Cox staining. Developmental alcohol exposure decreased spine density and dendritic complexity of basilar dendrites of Layer II/III neurons in the medial PFC (mPFC) compared to dendrites of control animals. Voluntary exercise increased spine density and dendritic length in AE animals resulting in elimination of the differences between AE and SH rats. Thus, voluntary exercise during early adolescence selectively rescued alcohol-induced morphological deficits in the mPFC.

  18. Effects of different intermittent peptide YY (3-36) dosing strategies on food intake, body weight, and adiposity in diet-induced obese rats.

    PubMed

    Reidelberger, Roger D; Haver, Alvin C; Chelikani, Prasanth K; Buescher, James L

    2008-08-01

    Chronic administration of anorexigenic substances to experimental animals by injections or continuous infusion typically produces either no effect or a transient reduction in food intake and body weight. Our aim here was to identify an intermittent dosing strategy for intraperitoneal infusion of peptide YY(3-36) [PYY(3-36)] that produces a sustained reduction in daily food intake and adiposity in diet-induced obese rats. Rats (665+/-10 g body wt, 166+/-7 g body fat) with intraperitoneal catheters tethered to infusion swivels had free access to a high-fat diet. Vehicle-treated rats (n=23) had relatively stable food intake, body weight, and adiposity during the 9-wk test period. None of 15 PYY(3-36) dosing regimens administered in succession to a second group of rats (n=22) produced a sustained 15-25% reduction in daily food intake for >5 days, although body weight and adiposity were reduced across the 9-wk period by 12% (594+/-15 vs. 672+/-15 g) and 43% (96+/-7 vs. 169+/-9 g), respectively. The declining inhibitory effect of PYY(3-36) on daily food intake when the interinfusion interval was >or=3 h appeared to be due in part to an increase in food intake between infusions. The declining inhibitory effect of PYY(3-36) on daily food intake when the interinfusion interval was <3 h suggested possible receptor downregulation and tolerance to frequent PYY(3-36) administration; however, food intake significantly increased when PYY(3-36) treatments were discontinued for 1 day following apparent loss in treatment efficacies. Together, these results demonstrate the development of a potent homeostatic response to increase food intake when PYY(3-36) reduces food intake and energy reserves in diet-induced obese rats.

  19. The Effect of GCSB-5 a New Herbal Medicine on Changes in Pain Behavior and Neuroglial Activation in a Rat Model of Lumbar Disc Herniation

    PubMed Central

    Cho, Hee Kyung; Kim, So-Yeon; Choi, Mi Jung; Baek, Seung Ok; Kwak, Sang Gyu

    2016-01-01

    Objective Lumbar disc herniation can induce sciatica by mechanical compression and/or chemical irritation. The aim of this study was to compare the effects of GCSB-5 (Shinbaro®) and NSAIDs on pain-related behavior and on the expressions of microglia, astrocytes, CGRP, TRPV1, IL-6, and CX3CL1 in a rat model of lumbar disc herniation. Methods 112 male Sprague-Dawley rats underwent implantation of nucleus pulposus to a dorsal root ganglion (DRG). Rats were divided into five groups as follows; a saline group (the vehicle control group) (n=27), a 10 mg/kg aceclofenac group (the aceclofenac group) (n=22), and 100, 300 or 600 mg/kg GCSB-5 groups (the GCSB-5 100, 300, or 600 groups) (n=21 for each group). Rats were tested for mechanical allodynia at 3 days after surgery and at 1 day, 3 days, 7 days, 14 days, 21 days, 28 days, 35 days, 42 days, 49 days, and 56 days after treatment commencement. Immunohistochemical staining of microglia (Iba1), astrocytes (GFAP), CGRP, and TRPV1, and PCR for IL-6 and CX3CL1 were performed on spinal dorsal horns and DRGs at 56 days after medication commencement. Results After 56 days of GCSB-5 300 administration, mechanical withdrawal thresholds were significantly increased (p<0.05), and immunohisto-chemical expressions of Iba1, GFAP, CGRP, and TRPV1 were reduced than other groups, but this difference was not statistically significant. Conclusion These results indicate GCSB-5 reduces mechanical allodynia and downregulates neuroglial activity and the expressions of CGRP and TRPV1 in the spinal segments of a rat model of lumbar disc herniation. PMID:26962414

  20. Rimonabant-mediated changes in intestinal lipid metabolism and improved renal vascular dysfunction in the JCR:LA-cp rat model of prediabetic metabolic syndrome.

    PubMed

    Russell, James C; Kelly, Sandra E; Diane, Abdoulaye; Wang, Ye; Mangat, Rabban; Novak, Susan; Vine, Donna F; Proctor, Spencer D

    2010-08-01

    Rimonabant (SR141716) is a specific antagonist of the cannabinoid-1 receptor. Activation of the receptor initiates multiple effects on central nervous system function, metabolism, and body weight. The hypothesis that rimonabant has protective effects against vascular disease associated with the metabolic syndrome was tested using JCR:LA-cp rats. JCR:LA-cp rats are obese if they are cp/cp, insulin resistant, and exhibit associated micro- and macrovascular disease with end-stage myocardial and renal disease. Treatment of obese rats with rimonabant (10 mg.kg(-1).day(-1), 12-24 wk of age) caused transient reduction in food intake for 2 wk, without reduction in body weight. However, by 4 wk, there was a modest, sustained reduction in weight gain. Glycemic control improved marginally compared with controls, but at the expense of increased insulin concentration. In contrast, rimonabant normalized fasting plasma triglyceride and reduced plasma plasminogen activator inhibitor-1 and acute phase protein haptoglobin in cp/cp rats. Furthermore, these changes were accompanied by reduced postprandial intestinal lymphatic secretion of apolipoprotein B48, cholesterol, and haptoglobin. While macrovascular dysfunction and ischemic myocardial lesion frequency were unaffected by rimonabant treatment, both microalbuminuria and glomerular sclerosis were substantially reduced. In summary, rimonabant has a modest effect on body weight in freely eating obese rats and markedly reduces plasma triglyceride levels and microvascular disease, in part due to changes in intestinal metabolism, including lymphatic secretion of apolipoprotein B48 and haptoglobin. We conclude that rimonabant improves renal disease and intestinal lipid oversecretion associated with an animal model of the metabolic syndrome that appears to be independent of hyperinsulinemia or macrovascular dysfunction.

  1. Inhibition by memantine of the development of persistent oral dyskinesias induced by long-term haloperidol treatment of rats.

    PubMed Central

    Andreassen, O. A.; Aamo, T. O.; Jøorgensen, H. A.

    1996-01-01

    1. Tardive dyskinesia (TD) is a serious side-effect of long-term treatment with neuroleptics. To investigate if neuroleptic-induced excessive stimulation of striatal glutamate receptors may underlie TD development, the effect of the NMDA antagonist, memantine (1-amino-3,5-dimethyladamantane), was studied in a rat model of TD. 2. In an acute experiment, six groups of rats were treated daily for 1 week with either vehicle or memantine 20 or 40 mg kg-1 day-1, and on the seventh day they received one injection of either haloperidol 1.0 mg kg-1 i.p. or saline i.p. In a subsequent long-term experiment lasting 20 weeks, the same treatment was continued, except that haloperidol was injected i.m. as decanoate (38 mg kg-1 every 4 weeks) and control rats received sesame oil. The behaviour was videotaped and scored at intervals during both experiments, and for 16 weeks after cessation of the long-term treatment. 3. In the acute experiment, haloperidol decreased motor activity and memantine increased moving and tended to attenuate the immobility induced by haloperidol. Memantine also enhanced the haloperidol-induced increase in the putative TD-analogue vacuous chewing movements (VCM). 4. In the long-term experiment, the most marked effect of haloperidol was a gradual increase in VCM and the increase persisted significantly for 12 weeks after cessation of treatment. Memantine dose-dependently increased VCM and moving during long-term treatment. However, only one week after stopping treatment, both these effects of memantine disappeared. In contrast to rats previously treated with haloperidol alone, rats co-treated with memantine (both doses) and haloperidol had VCM at the level of controls two weeks after stopping treatment. The blood levels of drugs were within the therapeutic range achieved in human subjects. 5. These results suggest that long-lasting changes induced by haloperidol are prevented by memantine, which supports the theory that excessive NMDA receptor stimulation

  2. Changing sensitivity of neonatal rats to tumorigenic effects of N-nitroso-N-ethylurea and X-radiation, given singly or combined

    SciTech Connect

    Knowles, J.F.

    1985-04-01

    After neonatal injection of rats with 10 mg N-nitroso-N-ethylurea (ENU)/kg body weight, whole-body X-irradiation with 1.25 Gy X-radiation caused a reduction in induced neurogenic tumors which was dependent on the interval between the two treatments. The reduction was greatest when radiation was given 1 day after ENU and progressively decreased with irradiation at 5 and 30 days. Changes in radiosensitivity in the neonatal period were also seen for ovarian tumors and squamous cell carcinomas of the mouth. Ovarian tumors were induced by 1.25 Gy X-rays alone, with a higher incidence occurring after irradiation at 5 days than at 30 days of age. Squamous cell carcinomas of the mouth have a high spontaneous incidence in this strain of rat, but 1.25 Gy X-radiation caused a significant reduction which was greater after irradiation at 5 than at 30 days of age. Pituitary tumors occurred in untreated and treated rats with a higher incidence in females. Only in males was there any suggestion of an effect of the various treatments on pituitary tumor incidence.

  3. "Warming yang and invigorating qi" acupuncture alters acetylcholine receptor expression in the neuromuscular junction of rats with experimental autoimmune myasthenia gravis.

    PubMed

    Huang, Hai-Peng; Pan, Hong; Wang, Hong-Feng

    2016-03-01

    Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction. "Warming yang and invigorating qi" acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis. However, few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction. Here, we used confocal laser scanning microscopy to examine the area and density of immunoreactivity for an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction in the phrenic nerve of rats with experimental autoimmune myasthenia gravis following "warming yang and invigorating qi" acupuncture therapy. Needles were inserted at acupressure points Shousanli (LI10), Zusanli (ST36), Pishu (BL20), and Shenshu (BL23) once daily for 7 consecutive days. The treatment was repeated after 1 day of rest. We found that area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve was significantly increased following acupuncture treatment. This outcome of the acupuncture therapy was similar to that of the cholinesterase inhibitor pyridostigmine bromide. These findings suggest that "warming yang and invigorating qi" acupuncture treatment increases acetylcholine receptor expression at the neuromuscular junction in a rat model of autoimmune myasthenia gravis.

  4. Iron porphyrinate Fe(TPPS) reduces brain cell damage in rats intrastriatally lesioned by quinolinate.

    PubMed

    González-Cortés, Carolina; Salinas-Lara, Citlaltepetl; Gómez-López, Marcos Artemio; Tena-Suck, Martha Lilia; Pérez-De La Cruz, Verónica; Rembao-Bojórquez, Daniel; Pedraza-Chaverrí, José; Gómez-Ruiz, Celedonio; Galván-Arzate, Sonia; Ali, Syed F; Santamaría, Abel

    2008-01-01

    It has been recently demonstrated that the reactive nitrogen species (RNS) peroxynitrite (ONOO(-)) is involved in the neurotoxic pattern produced by quinolinic acid in the rat brain [V. Pérez-De La Cruz, C. González-Cortés, S. Galván-Arzate, O.N. Medina-Campos, F. Pérez-Severiano, S.F. Ali, J. Pedraza-Chaverrí, A. Santamaría, Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington's disease in rats: protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III), Neuroscience 135 (2005) 463-474.]. The aim of this work was to investigate whether ONOO(-) can also be responsible for morphological alterations and inflammatory events in the same paradigm. For this purpose, we evaluated the effect of a pre-treatment with the iron porphyrinate Fe(TPPS), a well-known ONOO(-) decomposition catalyst (10 mg/kg, i.p., 120 min before lesion), on the quinolinate-induced striatal cell damage and immunoreactivities to glial-fibrilar acidic protein (GFAP), interleukin 6 (IL-6) and inducible nitric oxide synthase (iNOS), one and seven days after the intrastriatal infusion of quinolinate (240 nmol/microl) to rats. The striatal tissue from animals lesioned by quinolinate showed a significant degree of damage and enhanced immunoreactivities to GFAP, IL-6 and iNOS, both at 1 and 7 days post-lesion. Pre-treatment of rats with Fe(TPPS) significantly attenuated or prevented all these markers at both post-lesion times tested, except for GFAP immunoreactivity at 7 days post-lesion and iNOS immunoreactivity at 1 day post-lesion. Altogether, our results suggest that ONOO(-) is actively participating in triggering inflammatory events and morphological alterations in the toxic model produced by quinolinate, since the use of agents affecting its formation, such as Fe(TPPS), are effective experimental tools to reduce the brain lesions associated to excitotoxic and oxidative damage.

  5. JP-8 jet fuel can promote auditory impairment resulting from subsequent noise exposure in rats.

    PubMed

    Fechter, Laurence D; Gearhart, Caroline; Fulton, Sherry; Campbell, Jerry; Fisher, Jeffrey; Na, Kwangsam; Cocker, David; Nelson-Miller, Alisa; Moon, Patrick; Pouyatos, Benoit

    2007-08-01

    We report on the transient and persistent effects of JP-8 jet fuel exposure on auditory function in rats. JP-8 has become the standard jet fuel utilized in the United States and North Atlantic Treaty Organization countries for military use and it is closely related to Jet A fuel, which is used in U.S. domestic aviation. Rats received JP-8 fuel (1000 mg/m(3)) by nose-only inhalation for 4 h and half of them were immediately subjected to an octave band of noise ranging between 97 and 105 dB in different experiments. The noise by itself produces a small, but permanent auditory impairment. The current permissible exposure level for JP-8 is 350 mg/m(3). Additionally, a positive control group received only noise exposure, and a fourth group consisted of untreated control subjects. Exposures occurred either on 1 day or repeatedly on 5 successive days. Impairments in auditory function were assessed using distortion product otoacoustic emissions and compound action potential testing. In other rats, tissues were harvested following JP-8 exposure for assessment of hydrocarbon levels or glutathione (GSH) levels. A single JP-8 exposure by itself at 1000 mg/m(3) did not disrupt auditory function. However, exposure to JP-8 and noise produced an additive disruption in outer hair cell function. Repeated 5-day JP-8 exposure at 1000 mg/m(3) for 4 h produced impairment of outer hair cell function that was most evident at the first postexposure assessment time. Partial though not complete recovery was observed over a 4-week postexposure period. The adverse effects of repeated JP-8 exposures on auditory function were inconsistent, but combined treatment with JP-8 + noise yielded greater impairment of auditory function, and hair cell loss than did noise by itself. Qualitative comparison of outer hair cell loss suggests an increase in outer hair cell death among rats treated with JP-8 + noise for 5 days as compared to noise alone. In most instances, hydrocarbon constituents of the fuel

  6. Pharmacological inhibition of S-nitrosoglutathione reductase improves endothelial vasodilatory function in rats in vivo

    PubMed Central

    Chen, Qiumei; Sievers, Richard E.; Varga, Monika; Kharait, Sourabh; Haddad, Daniel J.; Patton, Aaron K.; Delany, Christopher S.; Mutka, Sarah C.; Blonder, Joan P.; Dubé, Gregory P.; Rosenthal, Gary J.

    2013-01-01

    Nitric oxide (NO) exerts a wide range of cellular effects in the cardiovascular system. NO is short lived, but S-nitrosoglutathione (GSNO) functions as a stable intracellular bioavailable NO pool. Accordingly, increased levels can facilitate NO-mediated processes, and conversely, catabolism of GSNO by the regulatory enzyme GSNO reductase (GSNOR) can impair these processes. Because dysregulated GSNOR can interfere with processes relevant to cardiovascular health, it follows that inhibition of GSNOR may be beneficial. However, the effect of GSNOR inhibition on vascular activity is unknown. To study the effects of GSNOR inhibition on endothelial function, we treated rats with a small-molecule inhibitor of GSNOR (N6338) that has vasodilatory effects on isolated aortic rings and assessed effects on arterial flow-mediated dilation (FMD), an NO-dependent process. GSNOR inhibition with a single intravenous dose of N6338 preserved FMD (15.3 ± 5.4 vs. 14.2 ± 6.3%, P = nonsignificant) under partial NO synthase inhibition that normally reduces FMD by roughly 50% (14.1 ± 2.9 vs. 7.6 ± 4.4%, P < 0.05). In hypertensive rats, daily oral administration of N6338 for 14 days reduced blood pressure (170.0 ± 5.3/122.7 ± 6.4 vs. 203.8 ± 1.9/143.7 ± 7.5 mmHg for vehicle, P < 0.001) and vascular resistance index (1.5 ± 0.4 vs. 3.2 ± 1.0 mmHg·min·l−1 for vehicle, P < 0.001), and restored FMD from an initially impaired state (7.4 ± 1.7%, day 0) to a level (13.0 ± 3.1%, day 14, P < 0.001) similar to that observed in normotensive rats. N6338 also reversed the pathological kidney changes exhibited by the hypertensive rats. GSNOR inhibition preserves FMD under conditions of impaired NO production and protects against both microvascular and conduit artery dysfunction in a model of hypertension. PMID:23349456

  7. Sorafenib inhibits liver regeneration in rats

    PubMed Central

    Andersen, Kasper Jarlhelt; Knudsen, Anders Riegels; Kannerup, Anne-Sofie; Sasanuma, Hideki; Nyengaard, Jens Randel; Hamilton-Dutoit, Stephen; Ladekarl, Morten; Mortensen, Frank Viborg

    2013-01-01

    Background Sorafenib is a multikinase inhibitor with antiangiogenic and antiproliferative properties, approved for the treatment of hepatocellular carcinoma. The effect of Sorafenib on liver regeneration in healthy rats was investigated. Methods Sixty Wistar rats received either Sorafenib (group S; 15 mg/kg) or placebo for 14 days prior to resection and until sacrifice. After a 70% partial hepatectomy, the rats were euthanized on post-operative days (POD) 2, 4 or 8. Hepatocyte proliferation was estimated by immunohistochemistry for Ki-67 antigen using stereological methods on sections prepared by systematic uniform random sampling. Results Seven animals (12%) died after surgery. Death rates were similar in treated rats and controls. At hepatectomy, the body weight was significantly lower in group S rats. The liver weight and regeneration rates were lower in group S rats on PODs 2, 4 and 8. Hepatocyte proliferation was significantly lower in group S animals on PODs 2 and 4. Alanine aminotransferase ALAT was significantly higher in the Sorafenib-treated group on PODs 2, 4 and 8. Alkaline phosphatase ALP and bilirubin levels were similar in the two groups, although bilirubin was elevated in group S rats on POD 8. Conclusion In this rat model, Sorafenib did not increase post-hepatectomy mortality, but was associated with a significant impaired liver weight gain, regeneration rates and hepatocyte proliferation. PMID:23461776

  8. 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...

  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. 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…

  11. The rat cortex in stereotaxic coordinates.

    PubMed

    Schober, W

    1986-01-01

    On the basis of Nissl-preparations the cortex of albino rats has been mapped cytoarchitectonically. 13 frontal sections through the cortex are illustrated with coordinates. Therewith exists a stereotaxic atlas of the cortex of the rat and one can realize exactly experimental investigations in the different cortical areas.

  12. Anticariogenic effects of tea in rats.

    PubMed

    Rosen, S; Elvin-Lewis, M; Beck, F M; Beck, E X

    1984-05-01

    Teas varying in fluoride and tannin concentration were evaluated in rats for anticariogenic activity. There was a direct correlation between fluoride in tea and the inhibition of sulcal caries in rats, whereas no relationship was observed between tannin and this type of lesion. Teas also had a significant effect on caries progression and imparted a black stain to the teeth.

  13. Delayed administration of the GLP-1 receptor agonist liraglutide improves metabolic and functional recovery after cerebral ischemia in rats.

    PubMed

    Dong, Wenbin; Miao, Yunping; Chen, Aiying; Cheng, Min; Ye, Xiaodi; Song, Fahuan; Zheng, Gaoli

    2017-02-22

    Glucagon-like peptide 1 receptor (GLP-1R) agonists administered before or immediately after induction of experimental stroke have been shown to provide acute neuroprotection. Here, we determined whether delayed treatment with a GLP-1R agonist could improve metabolic and functional recovery after stroke. Rats were subjected to middle cerebral artery occlusion (MCAO) and given the well-established GLP-1R agonist liraglutide (50, 100, or 200μg/kg) or normal saline (NS) daily for 4 weeks, starting 1 day after MCAO. Cerebral glucose metabolism and neurological deficits were evaluated using (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) imaging and modified neurological severity score (mNSS) test. Levels of neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), von Willebrand factor (vWF), and GLP-1R were assessed by immunohistochemical staining and Western blot analysis. PET imaging showed that animals treated with liraglutide had significantly higher (18)F-FDG accumulation in the cerebral infarction compared with animals treated with NS. Liraglutide significantly reduced the mNSS score. It also greatly increased the expression of NeuN, GFAP, vWF, and GLP-1R in the cerebral ischemic area at postoperative week 4. These results demonstrated metabolic and functional recovery after delayed treatment with liraglutide in a rat model of cerebral ischemia.

  14. Effects of Hibiscus rosa sinensis L (Malvaceae) on wound healing activity: a preclinical study in a Sprague Dawley rat.

    PubMed

    Shivananda Nayak, B; Sivachandra Raju, S; Orette, F A; Chalapathi Rao, A V

    2007-06-01

    Hibiscus rosa sinensis (H rosa sinensis), a plant product, has been used for the treatment of a variety of diseases as well as to promote wound healing. The wound-healing activity of the ethanol extract of H rosa sinensis flower was determined in rats, using excision, incision, and dead space wound models and is presented in this report. The animals were randomly divided into 2 groups of 6 each in all the models. Test group animals in each model were treated with the ethanol extract of H rosa sinensis orally by mixing in drinking water (120 mg kg(-1) day(-1)), and the control group animals were maintained with plain drinking water. Healing was assessed by the rate of wound contraction, period of epithelialization, tensile strength (skin breaking strength), granulation tissue weight, and hydroxyproline content. The antimicrobial activity of the flower extract against selected microorganisms that infect the wounds was also assessed. Animals treated with the extract exhibited an 86% reduction in the wound area compared with controls, who exhibited a 75% reduction. The extract-treated animals were found to epithelize their wounds significantly faster than controls (P < .002) and have shown significantly higher skin-breaking strength than controls (P < .002). The dry and wet weight of granulation tissue and hydroxyproline content were also increased significantly when compared with controls. The reported observations suggest H rosa sinensis aids wound healing in the rat model.

  15. Protective Effects of Cannabidiol against Seizures and Neuronal Death in a Rat Model of Mesial Temporal Lobe Epilepsy

    PubMed Central

    Do Val-da Silva, Raquel A.; Peixoto-Santos, Jose E.; Kandratavicius, Ludmyla; De Ross, Jana B.; Esteves, Ingrid; De Martinis, Bruno S.; Alves, Marcela N. R.; Scandiuzzi, Renata C.; Hallak, Jaime E. C.; Zuardi, Antonio W.; Crippa, Jose A.; Leite, Joao P.

    2017-01-01

    The present study reports the behavioral, electrophysiological, and neuropathological effects of cannabidiol (CBD), a major non-psychotropic constituent of Cannabis sativa, in the intrahippocampal pilocarpine-induced status epilepticus (SE) rat model. CBD was administered before pilocarpine-induced SE (group SE+CBDp) or before and after SE (group SE+CBDt), and compared to rats submitted only to SE (SE group), CBD, or vehicle (VH group). Groups were evaluated during SE (behavioral and electrophysiological analysis), as well as at days one and three post-SE (exploratory activity, electrophysiological analysis, neuron density, and neuron degeneration). Compared to SE group, SE+CBD groups (SE+CBDp and SE+CBDt) had increased SE latency, diminished SE severity, increased contralateral afterdischarge latency and decreased relative powers in delta (0.5–4 Hz) and theta (4–10 Hz) bands. Only SE+CBDp had increased vertical exploratory activity 1-day post SE and decreased contralateral relative power in delta 3 days after SE, when compared to SE group. SE+CBD groups also showed decreased neurodegeneration in the hilus and CA3, and higher neuron density in granule cell layer, hilus, CA3, and CA1, when compared to SE group. Our findings demonstrate anticonvulsant and neuroprotective effects of CBD preventive treatment in the intrahippocampal pilocarpine epilepsy model, either as single or multiple administrations, reinforcing the potential role of CBD in the treatment of epileptic disorders. PMID:28367124

  16. Functional connectivity changes during consolidation of inhibitory avoidance memory in rats: a manganese-enhanced MRI study.

    PubMed

    Chen, Ke-Hsin; Chen, Der-Yow; Liang, K C

    2013-10-31

    Consolidation of memory involves transfer of encoded information into a durable neural representation, but how this is transacted in the nervous system remains elusive. It has been proposed that memory consolidation is subserved by formation of a cell assembly due to coincidence of pre- and post-synaptic activity therein after learning. To capture such off-line changes, manganese-enhanced magnetic resonance imaging (MEMRI) was used to trace brain activity during the memory consolidation period. Male Wistar rats were trained on the one-trial inhibitory avoidance task and received intraventricular infusion of manganese ion shortly after training. The MEMRI taken 1 day later showed that brain areas including the prelimbic, insular and anterior pirifrom cortices of the learning group had significantly lower memory-related MEMRI signal than those of the control group. The functional network was revealed by correlating the MEMRI signals among regions followed by graph theoretical analysis. Learning sculpted the non-discriminative connectivity among many brain regions in the controls into a network in the trained rats with selected connectivity among regions implicated in inhibitory avoidance learning. The network could be organized into three clusters presumably subserving different functions. The results suggest that the brain prunes excessive functional connectivity in a cell assembly to consolidate new memory.

  17. Quantitative determination of total methamphetamine and active metabolites in rat tissue by liquid chromatography with tandem mass spectrometric detection.

    PubMed

    Hendrickson, Howard; Laurenzana, Elizabeth; Owens, S Michael

    2006-11-22

    High-throughput liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) methodology for the determination of methamphetamine (METH), amphetamine (AMP), 4-hydroxymethamphetamine (4-OH-METH), and 4-hydroxyamphetamine (4-OH-AMP) was developed and validated using simple trichloroacetic acid sample treatment. The method was validated in rat serum, brain, and testis. Lower limits-of-quantitation (LOQ) for METH and AMP were 1 ng x mL(-1) using positive ion electrospray tandem mass spectrometry (MS/MS). The accuracy of the method was within 25% of the actual values over a wide range of analyte concentrations. The within-assay precision was better than 12% (coefficient of variation). The method was linear over a wide dynamic range (0.3-1000 ng x mL(-1)). Quantitation was possible in all 3 matrices using only serum standards because of minimal matrix-associated ion effects or the use of an internal standard. Finally, the LC-MS/MS method was used to determine serum, brain, and testis METH and AMP concentrations during a subcutaneous infusion (5.6 mg kg(-1) day(-1)) of METH in rats. Concentrations of 4-OH-AMP and 4-OH-METH were below the LOQ in experimental samples. The bias introduced by using serum calibrators for the determination of METH and AMP concentrations in testis and brain was less than 8% and insignificant relative to the interanimal variability.

  18. Tissue Kim-1 and urinary clusterin as early indicators of cisplatin-induced acute kidney injury in rats.

    PubMed

    Vinken, Petra; Starckx, Sofie; Barale-Thomas, Erio; Looszova, Adriana; Sonee, Manisha; Goeminne, Nick; Versmissen, Loes; Buyens, Kristel; Lampo, Ann

    2012-10-01

    The kidney is one of the main targets of drug toxicity, and early detection of renal damage is critical in preclinical drug development. A model of cisplatin-induced nephrotoxicity in male Sprague Dawley rats treated for 1, 3, 5, 7, or 14 days at 1 mg/kg/day was used to monitor the spatial and temporal expression of various indicators of kidney toxicity during the progression of acute kidney injury (AKI). As early as 1 day after cisplatin treatment, positive kidney injury molecule-1 (Kim-1) immunostaining, observed in the outer medulla of the kidney, and changes in urinary clusterin indicated the onset of proximal tubular injury in the absence of functional effects. After 3 days of treatment, Kim-1 protein levels in urine increased more than 20-fold concomitant with a positive clusterin immunostaining and an increase in urinary osteopontin. Tubular basophilia was also noted, while serum creatinine and blood urea nitrogen levels were elevated only after 5 days, together with tubular degeneration. In conclusion, tissue Kim-1 and urinary clusterin were the most sensitive biomarkers for detection of cisplatin-induced kidney damage. Thereafter, urinary Kim-1 and osteopontin, as well as clusterin immunostaining accurately correlated with the histopathological findings. When AKI is suspected in preclinical rat studies, Kim-1, clusterin, and osteopontin should be part of urinalysis and/or IHC can be performed.

  19. Beneficial effects of quercetin on renal injury and oxidative stress caused by ciprofloxacin in rats: A histological and biochemical study.

    PubMed

    Elbe, H; Dogan, Z; Taslidere, E; Cetin, A; Turkoz, Y

    2016-03-01

    Ciprofloxacin is a broad-spectrum quinolone antibiotic commonly used in clinical practice. Quercetin is an antioxidant belongs to flavonoid group. It inhibits the production of superoxide anion. In this study, we aimed to evaluate the effects of quercetin on renal injury and oxidative stress caused by ciprofloxacin. Twenty-eight female Wistar albino rats were divided into four groups: control, quercetin (20 mg kg(-1) day(-1) gavage for 21 days), ciprofloxacin (20 mg kg(-1) twice a day intraperitoneally for 10 days), and ciprofloxacin + quercetin. Samples were processed for histological and biochemical evaluations. Malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD), and catalase (CAT) activities were measured in kidney tissue. The ciprofloxacin group showed histopathological changes such as infiltration, dilatation in tubules, tubular atrophy, reduction of Bowman's space, congestion, hemorrhage, and necrosis. In the ciprofloxacin + quercetin group, these histopathological changes markedly reduced. MDA levels increased in the ciprofloxacin group and decreased in the ciptofloxacin + quercetin group. SOD and CAT activities and GSH levels significantly decreased in the ciprofloxacin group. On the other hand, in the ciprofloxacin + quercetin group, SOD and CAT activities and GSH levels significantly increased with regard to the ciprofloxacin group. We concluded that quercetin has antioxidative and therapeutic effects on renal injury and oxidative stress caused by ciprofloxacin in rats.

  20. A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype.

    PubMed

    Hirata, Hiroaki; Yurube, Takashi; Kakutani, Kenichiro; Maeno, Koichiro; Takada, Toru; Yamamoto, Junya; Kurakawa, Takuto; Akisue, Toshihiro; Kuroda, Ryosuke; Kurosaka, Masahiro; Nishida, Kotaro

    2014-03-01

    The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell types-notochordal cells (NCs) and non-notochordal chondrocyte-like cells. In human discs, NCs are lost during adolescence, which is also when discs begin to show degenerative signs. However, little evidence exists regarding the link between NC disappearance and the pathogenesis of disc degeneration. To clarify this, a rat tail disc degeneration model induced by static compression at 1.3 MPa for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days. Radiography, MRI, and histomorphology showed degenerative disc findings in response to the compression period. Immunofluorescence displayed that the number of DAPI-positive NP cells decreased with compression; particularly, the decrease was notable in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, identified as NCs. The proportion of TUNEL-positive cells, which predominantly comprised non-NCs, increased with compression. Quantitative PCR demonstrated isolated mRNA up-regulation of ADAMTS-5 in the 1-day loaded group and MMP-3 in the 7-day loaded group. Aggrecan-1 and collagen type 2α-1 mRNA levels were down-regulated in both groups. This rat tail temporary static compression model, which exhibits decreased NC phenotype, increased apoptotic cell death, and imbalanced catabolic and anabolic gene expression, reproduces different stages of intervertebral disc degeneration.

  1. Involvement of the Nonneuronal Cholinergic System in Bone Remodeling in Rat Midpalatal Suture after Rapid Maxillary Expansion

    PubMed Central

    Guo, Jie; Wang, Lue; Miao, Cong; Ge, Lihua; Tian, Zhenchuan; Wang, Jianhong

    2016-01-01

    Few studies sought to analyze the expression and function of the nonneuronal acetylcholine system in bone remodeling in vivo due to the lack of suitable models. We established a rat maxilla expansion model in which the midline palatine suture of the rat was rapidly expanded under mechanical force application, inducing tissue remodeling and new bone formation, which could be a suitable model to investigate the role of the nonneuronal acetylcholine system in bone remodeling in vivo. During the expansion, the expression pattern changes of the nonneuronal cholinergic system components and the mRNA levels of OPG/RANKL were detected by immunohistochemistry or real-time PCR. The value of the RANKL/OPG ratio significantly increased after 1 day of expansion, indicating dominant bone resorption induced by the mechanical stimulation; however after 3 days of expansion, the value of the RANKL/OPG ratio significantly decreased, suggesting a dominant role of the subsequent bone formation process. Increasing expression of Ach was detected after 3 days of expansion which indicated that ACh might play a role in bone formation. The mRNA expression levels of other components also showed observable changes during the expansion which confirmed the involvement of the nonneuronal cholinergic system in the process of bone remodeling in vivo. Further researches are still needed to figure out the detailed functions of the nonneuronal cholinergic system and its components. PMID:27478838

  2. [Electrolyte makeup of the blood plasma and skeletal muscles of rats after a flight on the Kosmos-690 biosatellite].

    PubMed

    Nesterov, V P; Tigranian, R A

    1979-01-01

    Measurements of Na+, K+, Mg2+ and Ca2+ concentrations in the functionally different muscles (soleus, plantaris, diaphragm muscles) and plasma of the rats flown for 20.5 days aboard the biosatellite Cosmos-690 did not show any significant changes as compared with the controls. At the same time a decrease of the K+/Na+ ratio and a similar shift of Mg2+ and Ca2+ concentrations in plasma of irradiated rats as compared with these of non-irradiated animals demonstrated that the combined effects of space flight factors and gamma-irradiation influenced the system of ionic homeostasis in the blood. In the animals sacrificed on the R + 1 day the K+/Na+ ratio in the soleus muscle changed in favor of Na+ and in the plantaris muscle in favor of K+, and remained essentially unchanged in the diaphragm. The comparison of the flight experiments with the ground-based controls showed that ion changes in muscles occurred due to ionizing radiation rather than due to weightlessness.

  3. Neuroprotective effect of hyperbaric oxygen therapy in a juvenile rat model of repetitive mild traumatic brain injury

    PubMed Central

    Huang, Lei; Obenaus, Andre; Hamer, Mary; Zhang, John H.

    2016-01-01

    Repetitive mild traumatic brain injury (rmTBI) is an important medical concern for adolescent athletes that can lead to long-term disabilities. Multiple mild injuries may exacerbate tissue damage resulting in cumulative brain injury and poor functional recovery. In the present study, we investigated the increased brain vulnerability to rmTBI and the effect of hyperbaric oxygen treatment using a juvenile rat model of rmTBI. Two episodes of mild cortical controlled impact (3 days apart) were induced in juvenile rats. Hyperbaric oxygen (HBO) was applied 1 hour/day × 3 days at 2 atmosphere absolute consecutively, starting at 1 day after initial mild traumatic brain injury (mTBI). Neuropathology was assessed by multi-modal magnetic resonance imaging (MRI) and tissue immunohistochemistry. After repetitive mTBI, there were increases in T2-weighted imaging-defined cortical lesions and susceptibility weighted imaging-defined cortical microhemorrhages, correlated with brain tissue gliosis at the site of impact. HBO treatment significantly decreased the MRI-identified abnormalities and tissue histopathology. Our findings suggest that HBO treatment improves the cumulative tissue damage in juvenile brain following rmTBI. Such therapy regimens could be considered in adolescent athletes at the risk of repeated concussions exposures. PMID:28217290

  4. Cryopreservation and orthotopic transplantation of rat ovaries.

    PubMed

    Dorsch, Martina; Wedekind, Dirk

    2010-01-01

    The number of rat strains increased considerably in the last decade and will increase continuously during the next years. This requires enough space for maintaining vital strains and techniques for cryobanking, which can be applied not only in specialised rat resource centres but also in regular animal houses. Here we describe an easy and fast method for the cryopreservation and transplantation of frozen-thawed ovaries of the rat. With dimethyl sulfoxide as cryoprotectant rat ovaries can be stored at -196 degrees C for unlimited time. For revitalisation thawed ovaries have to be orthotopically transplanted into appropriate ovarectomised recipients. Reestablishment of the reproductive cycle in the recipients can be confirmed by vaginal cytology shortly after transplantation. The recipients are able to produce 2-3 litters after mating with males of an appropriate strain. Cyropreservation of ovaries thus can be considered a reliable method to preserve scientifically and economically important stocks and strains of rats that are currently not required.

  5. Experimental oxalate urolith formation in rats.

    PubMed

    McIntosh, G H; Belling, G B; Bulman, F H

    1979-06-01

    Urinary calculi composed of calcium oxalate were produced in male hooded Wistar rats fed a vitamin B6 deficient diet over 16 weeks. This basic diet was modified by doubling the phosphate content or loading with vitamin C or D3 in three treatment groups. The number of rats developing oxalate stones was not altered by the addition of vitamin D3 or phosphate, but there was a significant increase in total weight of stone formed and histological evidence of extensive renal damage in rats on the high vitamin D3 diet. The addition of vitamin C to the vitamin B6 deficient rats resulted in a reduction in the number of rats with uroliths and a fall in urinary oxalate excretion, while similarly loaded vitamin B6 supplemented controls were free of oxalate calculi. It is concluded that the oxalate urolithiasis induced by vitamin B6 deficiency was exacerbated by added vitamin D3 and reduced by vitamin C.

  6. 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.

  7. Identity Matching-to-Sample with Olfactory Stimuli in Rats

    ERIC Educational Resources Information Center

    Pena, Tracy; Pitts, Raymond C.; Galizio, Mark

    2006-01-01

    Identity matching-to-sample has been difficult to demonstrate in rats, but most studies have used visual stimuli. There is evidence that rats can acquire complex forms of olfactory stimulus control, and the present study explored the possibility that identity matching might be facilitated in rats if olfactory stimuli were used. Four rats were…

  8. Rat Control Lesson Plan for Fourth, Fifth and Sixth Grades.

    ERIC Educational Resources Information Center

    Media Learning Corp., Rochester, NY.

    This teacher guide was developed to assist teachers of elementary children in their preparation to teach some lessons on rat control. The overall objectives include determining the level of student understanding about rats, developing student attitudes toward rats, developing the student's ability to identify the rat's weapons, identifying those…

  9. 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.

  10. 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

  11. Mitochondrial DNA phylogeography of the Norway rat.

    PubMed

    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.

  12. Variation in rat sciatic nerve anatomy: implications for a rat model of neuropathic pain.

    PubMed

    Asato, F; Butler, M; Blomberg, H; Gordh, T

    2000-03-01

    We discovered a variation of rat sciatic nerve anatomy as an incidental finding during the anatomical exploration of the nerve lesion site in a rat neuropathic pain model. To confirm the composition and distribution of rat sciatic nerve, macroscopic anatomical investigation was performed in both left and right sides in 24 adult Sprague-Dawley rats. In all rats, the L4 and L5 spinal nerves were fused tightly to form the sciatic nerve. However, the L6 spinal nerve did not fuse with this nerve completely as a part of the sciatic nerve, but rather sent a thin branch to it in 13 rats (54%), whereas in the remaining 11 rats (46%), L6 ran separately along with the sciatic nerve. Also, the L3 spinal nerve sent a thin branch to the L4 spinal nerve or sciatic nerve in 6 rats (25%). We conclude that the components of sciatic nerve in Sprague-Dawley rats vary from L3 to L6; however, the major components are L4 and L5 macroscopically. This finding is in contrast to the standard textbooks of rat anatomy which describe the sciatic nerve as having major contributions from L4, L5, and L6.

  13. Naturally occurring anti-tissue antibodies in rat sera

    PubMed Central

    Weir, D. M.; Pinckard, R. N.; Elson, C. J.; Suckling, Deirdre E.

    1966-01-01

    Seventy per cent of normal rat sera have been shown to contain heat labile serum component(s) active against various rat organ homogenates as demonstrated by haemolytic complement fixation and passive haemagglutination tests. The main antigenic activity in rat liver has been found in the mitochondrial fractions. It was also demonstrated by the indirect fluorescent antibody technique that both guinea-pig complement and high molecular weight rat globulins were fixed to rat organ sections. Chemotactic activity has also been observed with rat serum and rat liver mitochondria and it is suggested that these naturally occurring antibodies may be implicated in the removal of tissue breakdown products. PMID:5338951

  14. Hepatotoxicity of acetaldehyde in rats.

    PubMed

    Strubelt, O; Younes, M; Urch, T; Breining, H; Pentz, R

    1987-11-01

    The ability of acetaldehyde to initiate hepatotoxicity as evidenced by enzyme leakage, hepatic fat accumulation and histological alterations was studied in rats. Neither oral nor intraperitoneal treatment with acetaldehyde had any hepatotoxic effect, even following aldehyde dehydrogenase inhibition by disulfiram. This is probably due to the inability of exogenously added acetaldehyde to penetrate liver cell membranes. In contrast, acetaldehyde derived metabolically from ethanol was capable of inducing moderate hepatotoxicity when it accumulated upon pretreatment with disulfiram. Acetaldehyde may thus be partly responsible for alcohol-induced liver damage.

  15. Experimental mammary carcinogenesis - Rat models.

    PubMed

    Alvarado, Antonieta; Faustino-Rocha, Ana I; Colaço, Bruno; Oliveira, Paula A

    2017-03-15

    Mammary cancer is one of the most common cancers, victimizing more than half a million of women worldwide every year. Despite all the studies in this field, the current therapeutic approaches are not effective and have several devastating effects for patients. In this way, the need to better understand the mammary cancer biopathology and find effective therapies led to the development of several rodent models over years. With this review, the authors intended to provide the readers with an overview of the rat models used to study mammary carcinogenesis, with a special emphasis on chemically-induced models.

  16. Combination therapy with acipimox enhances the effect of growth hormone treatment on linear body growth in the normal and small-for-gestational-age rat.

    PubMed

    Vickers, M H; Hofman, P L; Gluckman, P D; Lobie, P E; Cutfield, W S

    2006-12-01

    Growth hormone (GH) therapy is often associated with adverse side effects, including impaired insulin sensitivity. GH treatment of children with idiopathic short stature does not lead to an optimized final adult height. It has been demonstrated that FFA reduction induced by pharmacological antilipolysis can stimulate GH secretion per se in both normal subjects and those with GH deficiency. However, to date, no investigation has been undertaken to establish efficacy of combination treatment with GH and FFA regulators on linear body growth. Using a model of maternal undernutrition in the rat to induce growth-restricted offspring, we investigated the hypothesis that combination treatment with GH and FFA regulators can enhance linear body growth above that of GH alone. At postnatal day 28, male offspring of normally nourished mothers (controls) and offspring born with low birth weight [small for gestational age (SGA)] were treated with saline, GH, or GH (5 mg.kg(-1).day(-1)) in combination with acipimox (GH + acipimox, 20 mg.kg(-1).day(-1)) or fenofibrate (GH + fenofibrate, 30 mg.kg(-1).day(-1)) for 40 days. GH plus acipimox treatment significantly enhanced linear body growth in the control and SGA animals above that of GH, as quantified by tibial and total body length. Treatment with GH significantly increased fasting plasma insulin, insulin-to-glucose ratio, and plasma volumes in control and SGA animals but was not significantly different between saline and GH-plus-acipimox-treated animals. GH-induced lipolysis was blocked by GH plus acipimox treatment in both control and SGA animals, concomitant with a significant reduction in fasting plasma FFA and insulin concentrations. This is the first study to show that GH plus acipimox combination therapy, via pharmacological blocking of lipolysis during GH exposure, can significantly enhance the efficacy of GH in linear growth promotion and ameliorate unwanted metabolic side effects.

  17. Erythropoietin inhibits liver gelatinases during galactosamine-induced hepatic damage in rats.

    PubMed

    Madro, Agnieszka; Kurzepa, Jacek; Czechowska, Grazyna; Słomka, Maria; Celiński, Krzysztof; Szymonik-Lesiuk, Stanisława

    2009-01-01

    Matrix metalloproteinase (MMP)-2 and -9 (gelatinases) participate in extracellular protein remodeling. Moreover, they are involved in the development of hepatic fibrosis. The goal of this study was to evaluate liver gelatinase activities after erythropoietin (Epo) treatment (1U/dose, sc) in experimentally damaged livers of rats treated with D-galactosamine (Gal, 800 mg/kg/dose, ip). Sixty rats were divided into six equal groups: I - received 5 doses of Epo and a single dose of Gal [the experiment duration (ED): 10 days]; II - received 5 doses of Epo and 3 doses of Gal (ED: 14 days); III - received only 5 doses of Epo (ED: 9 days); IV - received 3 doses of Gal (ED: 5 days);V - received a single dose of Gal (ED: 1 day); VI - control group (ED: 9 days). The animals were sacrificed and the livers were collected 48 h after the last drug administration. The activity of gelatinases was measured using gelatin zymography. No fluctuations in gelatinase activities were observed after the administration of a single dose of Gal in comparison to the control group. However, a significant increase in gelatinase activities was observed after treatment with three doses of Gal. Five doses of Epo administrated before Gal treatment prevented elevated gelatinase activities: MMP-9 activity was comparable to control, and MMP-2 activity was decreased (group II). The gelatinase activities was lower in group I and II in comparison to the control group. These results revealed that Epo decreases MMP-2 and MMP-9 activity, suggesting that it is a hepatoprotective agent against hepatic damage induced by galactosamine injection.

  18. Functional observational battery and motor activity in rats after single administration of two NHE 1 inhibitors.

    PubMed

    Hübler, Nicole; Gottschling, Barbara; Jacobs, Maren; von Landenberg, Friedrich; Hewicker-Trautwein, Marion

    2005-11-01

    Two tests, a functional observational battery (FOB) and measurement of motor activity, have been used to screen the two NHE inhibitors EMD 96785 and EMD 125021 for neurobehavioral effects. These two NHE inhibitors, which exhibit a marked selectivity for the NHE 1 isoform, are under development in the research laboratories of Merck KGaA. NHE inhibitors are developed for the treatment of acute myocardial infarction and chronic heart failure. In prior studies with EMD 96785 and EMD 125021, clinical symptoms, such as uncoordinated movements and weakness of the hindlimbs, were detected in rats. The aim of this study was the evaluation of clinical findings in more detail using a FOB and measurement of motor activity in 96 female rats. The time course and reversibility of the adverse effects were investigated. The animals were treated with EMD 96785 or EMD 125021 by intravenous injection at a single dose of 100 mg/kg and four different time points (2 h, 1 day, 7 days and 21 days after treatment) were chosen for the clinical examination. This neurobehavioral test battery clearly detected neurological activity and defined time-course characteristics after treatment with EMD 96785 or EMD 125021. The various clinical parameters were grouped into functional-related domains and most alterations were seen in the domains of central nervous system and neuromuscular system. The most prominent clinical findings were seen with the pharmacologically more potent NHE inhibitor EMD 125021 when compared to EMD 96785. The clinical symptoms were proven to be reversible by 7 days after the single treatment for both compounds.

  19. Inhibition of Protease-activated Receptor 1 Ameliorates Intestinal Radiation Mucositis in a Preclinical Rat Model

    SciTech Connect

    Wang, Junru; Kulkarni, Ashwini; Chintala, Madhu; Fink, Louis M.; Hauer-Jensen, Martin

    2013-01-01

    Purpose: To determine, using a specific small-molecule inhibitor of protease-activated receptor 1 (PAR1) signaling, whether the beneficial effect of thrombin inhibition on radiation enteropathy development is due to inhibition of blood clotting or to cellular (PAR1-mediated) thrombin effects. Methods and Materials: Rats underwent fractionated X-irradiation (5 Gy Multiplication-Sign 9) of a 4-cm small-bowel segment. Early radiation toxicity was evaluated in rats receiving PAR1 inhibitor (SCH602539, 0, 10, or 15 mg/kg/d) from 1 day before to 2 weeks after the end of irradiation. The effect of PAR1 inhibition on development of chronic intestinal radiation fibrosis was evaluated in animals receiving SCH602539 (0, 15, or 30 mg/kg/d) until 2 weeks after irradiation, or continuously until termination of the experiment 26 weeks after irradiation. Results: Blockade of PAR1 ameliorated early intestinal toxicity, with reduced overall intestinal radiation injury (P=.002), number of myeloperoxidase-positive (P=.03) and proliferating cell nuclear antigen-positive (P=.04) cells, and collagen III accumulation (P=.005). In contrast, there was no difference in delayed radiation enteropathy in either the 2- or 26-week administration groups. Conclusion: Pharmacological blockade of PAR1 seems to reduce early radiation mucositis but does not affect the level of delayed intestinal radiation fibrosis. Early radiation enteropathy is related to activation of cellular thrombin receptors, whereas platelet activation or fibrin formation may play a greater role in the development of delayed toxicity. Because of the favorable side-effect profile, PAR1 blockade should be further explored as a method to ameliorate acute intestinal radiation toxicity in patients undergoing radiotherapy for cancer and to protect first responders and rescue personnel in radiologic/nuclear emergencies.

  20. Mitogenic effect of erythropoietin on neonatal rat cardiomyocytes: signal transduction pathways.

    PubMed

    Wald, M R; Borda, E S; Sterin-Borda, L

    1996-06-01

    The mitogenic effect of recombinant human erythropoietin (rHuEpo) on primary cultures of neonatal rat cardiac myocytes was observed. rHuEpo triggered a dose-dependent increase in myocyte proliferation. The hormone effect over optimally grown control culture 1 day after addition was maximum with 0.5 U/ml and was inhibited with anti-rHuEpo. Inhibitors of enzymatic pathways known to be involved in the cytokines intracellular mechanism such as genistein (tyrosine kinase inhibitor), 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (phospholipase C [PLC] inhibitor), and 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (protein kinase C [PKC] inhibitor) prevented the mitogenic action of rHuEpo. Also the inhibition of Na(+)-K(+)-ATPase activity by ouabain blunted the stimulatory action of rHuEpo on cell proliferation. The mitogenic action of the hormone was correlated with cardiac membrane paranitrophenylphosphatase (pNPPase) and PKC activity, since concentrations of rHuEpo that stimulate DNA synthesis increased pNPPase and PKC activity. Moreover, the enzymatic inhibition of tyrosine kinase, PLC, and PKC attenuated the stimulatory action of rHuEpo upon cardiac pNPPase activity. In this paper we demonstrate a non-hematopoietic action of rHuEpo showing both mitogenic and enzymatic effect upon primary myocyte cell culture and on pNPPase activity of neonatal rat heart. These effects are related to the capacity of rHuEpo to stimulate Na(+)-K(+)-ATPase activity and appear to be secondary to the activation of tyrosine kinase and PKC, indicating that in the rHuEpo mediated mitogenic action on cardiomyocytes involves the activation of the same enzymatic pathways that have been described by other cytokines in different tissues.

  1. Daily rhythm and regulation of clock gene expression in the rat pineal gland.

    PubMed

    Simonneaux, V; Poirel, V-J; Garidou, M-L; Nguyen, D; Diaz-Rodriguez, E; Pévet, P

    2004-01-05

    Rhythms in pineal melatonin synthesis are controlled by the biological clock located in the suprachiasmatic nuclei. The endogenous clock oscillations rely upon genetic mechanisms involving clock genes coding for transcription factors working in negative and positive feedback loops. Most of these clock genes are expressed rhythmically in other tissues. Because of the peculiar role of the pineal gland in the photoneuroendocrine axis regulating biological rhythms, we studied whether clock genes are expressed in the rat pineal gland and how their expression is regulated.Per1, Per3, Cry2 and Cry1 clock genes are expressed in the pineal gland and their transcription is increased during the night. Analysis of the regulation of these pineal clock genes indicates that they may be categorized into two groups. Expression of Per1 and Cry2 genes shows the following features: (1) the 24 h rhythm persists, although damped, in constant darkness; (2) the nocturnal increase is abolished following light exposure or injection with a beta-adrenergic antagonist; and (3) the expression during daytime is stimulated by an injection with a beta-adrenergic agonist. In contrast, Per3 and Cry1 day and night mRNA levels are not responsive to adrenergic ligands (as previously reported for Per2) and daily expression of Per3 and Cry1 appears strongly damped or abolished in constant darkness. These data show that the expression of Per1 and Cry2 in the rat pineal gland is regulated by the clock-driven changes in norepinephrine, in a similar manner to the melatonin rhythm-generating enzyme arylalkylamine N-acetyltransferase. The expression of Per3 and Cry1 displays a daily rhythm not regulated by norepinephrine, suggesting the involvement of another day/night regulated transmitter(s).

  2. Adenosine triphosphate-induced photoreceptor death and retinal remodeling in rats.

    PubMed

    Vessey, Kirstan A; Greferath, Ursula; Aplin, Felix P; Jobling, Andrew I; Phipps, Joanna A; Ho, Tracy; De Iongh, Robbert U; Fletcher, Erica L

    2014-09-01

    Many common causes of blindness involve the death of retinal photoreceptors, followed by progressive inner retinal cell remodeling. For an inducible model of retinal degeneration to be useful, it must recapitulate these changes. Intravitreal administration of adenosine triphosphate (ATP) has recently been found to induce acute photoreceptor death. The aim of this study was to characterize the chronic effects of ATP on retinal integrity. Five-week-old, dark agouti rats were administered 50 mM ATP into the vitreous of one eye and saline into the other. Vision was assessed using the electroretinogram and optokinetic response and retinal morphology investigated via histology. ATP caused significant loss of visual function within 1 day and loss of 50% of the photoreceptors within 1 week. At 3 months, 80% of photoreceptor nuclei were lost, and total photoreceptor loss occurred by 6 months. The degeneration and remodeling were similar to those found in heritable retinal dystrophies and age-related macular degeneration and included inner retinal neuronal loss, migration, and formation of new synapses; Müller cell gliosis, migration, and scarring; blood vessel loss; and retinal pigment epithelium migration. In addition, extreme degeneration and remodeling events, such as neuronal and glial migration outside the neural retina and proliferative changes in glial cells, were observed. These extreme changes were also observed in the 2-year-old P23H rhodopsin transgenic rat model of retinitis pigmentosa. This ATP-induced model of retinal degeneration may provide a valuable tool for developing pharmaceutical therapies or for testing electronic implants aimed at restoring vision.

  3. High virulence in hamsters of four dominant Leptospira serovars isolated from rats in the Philippines.

    PubMed

    Villanueva, Sharon Y A M; Saito, Mitsumasa; Tsutsumi, Yutaka; Segawa, Takaya; Baterna, Rubelia A; Chakraborty, Antara; Asoh, Tatsuma; Miyahara, Satoshi; Yanagihara, Yasutake; Cavinta, Lolita L; Gloriani, Nina G; Yoshida, Shin-ichi

    2014-02-01

    Leptospirosis is caused by pathogenic species of Leptospira. The aim of this study was to determine and characterize the pathogenicity of four dominant Leptospira isolates prevailing among rats in the Philippines. The isolates were Leptospira interrogans serovar Manilae strain K64, L. interrogans serovar Losbanos strain K37, L. interrogans serovar Ratnapura strain K5 and Leptospira borgpetersenii serovar Javanica strain K6. Pathogenicities were studied using hamsters, which reproduce severe human leptospirosis. The minimum lethal doses were 10(0) ( = 1) leptospires for K64, K37 and K5, and 10(1) leptospires for K6. Weight loss amongst the Leptospira-infected hamsters was observed from 1 day before death (K64-, K37- and K5-infected hamsters) to as much as 1 week before death for K6-infected hamsters. Similar and varied gross and microscopic lesions were observed amongst infected hamsters, even for strains belonging to the same species (i.e. L. interrogans). The most significant and common histopathological findings were congestion of the glomerulus, disarrangement of hepatic cords and erythrophagocytosis. Other findings were foamy splenic macrophages for K6, severe petechial pulmonary haemorrhage for K64, and hematuria and severe pulmonary congestion for K37. Immunostaining and culture revealed the presence of leptospires in different organs of the infected hamsters. Based on these results, Leptospira isolates from rats in the Philippines were shown to be highly virulent, causing pulmonary haemorrhage, severe hepato-renal damage and death in hamsters even at lower doses. The present findings on experimental leptospirosis support clinical data showing that patients with severe manifestations of leptospirosis, such as pulmonary haemorrhage, are increasing in the Philippines. These findings may serve as a basis to strengthen the early diagnosis and treatment of human leptospirosis.

  4. Adenosine triphosphate-induced photoreceptor death and retinal remodeling in rats

    PubMed Central

    Vessey, Kirstan A; Greferath, Ursula; Aplin, Felix P; Jobling, Andrew I; Phipps, Joanna A; Ho, Tracy; De Iongh, Robbert U; Fletcher, Erica L

    2014-01-01

    Many common causes of blindness involve the death of retinal photoreceptors, followed by progressive inner retinal cell remodeling. For an inducible model of retinal degeneration to be useful, it must recapitulate these changes. Intravitreal administration of adenosine triphosphate (ATP) has recently been found to induce acute photoreceptor death. The aim of this study was to characterize the chronic effects of ATP on retinal integrity. Five-week-old, dark agouti rats were administered 50 mM ATP into the vitreous of one eye and saline into the other. Vision was assessed using the electroretinogram and optokinetic response and retinal morphology investigated via histology. ATP caused significant loss of visual function within 1 day and loss of 50% of the photoreceptors within 1 week. At 3 months, 80% of photoreceptor nuclei were lost, and total photoreceptor loss occurred by 6 months. The degeneration and remodeling were similar to those found in heritable retinal dystrophies and age-related macular degeneration and included inner retinal neuronal loss, migration, and formation of new synapses; Müller cell gliosis, migration, and scarring; blood vessel loss; and retinal pigment epithelium migration. In addition, extreme degeneration and remodeling events, such as neuronal and glial migration outside the neural retina and proliferative changes in glial cells, were observed. These extreme changes were also observed in the 2-year-old P23H rhodopsin transgenic rat model of retinitis pigmentosa. This ATP-induced model of retinal degeneration may provide a valuable tool for developing pharmaceutical therapies or for testing electronic implants aimed at restoring vision. J. Comp. Neurol. 522:2928–2950, 2014. © 2014 Wiley Periodicals, Inc. PMID:24639102

  5. The effects of chronic imidazoline drug treatment on glial fibrillary acidic protein concentrations in rat brain.

    PubMed Central

    Olmos, G.; Alemany, R.; Escriba, P. V.; García-Sevilla, J. A.

    1994-01-01

    1. The concentration of the astrocytic marker, glial fibrillary acidic protein (GFAP) was quantitated by immunoblotting (western blotting) in the rat brain after treatment with various imidazoline drugs and other agents. 2. Chronic (7 days) but not acute (1 day) treatment with the imidazoline drugs, cirazoline (1 mg kg-1, i.p.) and idazoxan (10 mg kg-1, i.p.), but not with the structurally related alpha 2-adrenoceptor antagonists, RX821002 (2-methoxy idazoxan) (10 mg kg-1, i.p.) and efaroxan (10 mg kg-1, i.p.), markedly increased (45%) GFAP immunoreactivity in the rat cerebral cortex. Chronic treatment (7 days) with yohimbine (10 mg kg-1, i.p.), a non-imidazoline alpha 2-adrenoceptor antagonist, did not significantly modify GFAP immunoreactivity in the cerebral cortex. 3. Chronic treatment (7 days) with cirazoline and idazoxan did not alter the density of brain monoamine oxidase (MAO)-B sites labelled by [3H]-Ro 19-6327 (lazabemide), another relevant astroglial marker. Moreover, these imidazoline drug treatments did not modify the levels of alpha-tubulin in the cerebral cortex. These negative results reinforced the specificity of the effects of imidazoline drugs on GFAP. 4. Irreversible inactivation of brain alpha 2-adrenoceptors (and other neurotransmitters receptors) after treatment with an optimal dose of the peptide-coupling agent EEDQ (1.6 mg kg-1, i.p., for 6-24 h) did not alter GFAP immunoreactivity in the cerebral cortex. These results further disproved the involvement of these receptors on astroglial cells in the tonic control of GFAP levels.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 4 PMID:8032628

  6. Geraniol attenuates hydrogen peroxide-induced liver fatty acid alterations in male rats

    PubMed Central

    Ozkaya, Ahmet; Sahin, Zafer; Gorgulu, Ahmet Orhan; Yuce, Abdurrauf; Celik, Sait

    2017-01-01

    Background: Hydrogen peroxide (H2O2) is an oxidant agent and this molecule naturally occurs in the body as a product of aerobic metabolism. Geraniol is a plant-derived natural antioxidant. The aim of this study was to determine the role of geraniol on hepatic fatty acids alterations following H2O2-induced oxidative stress in male rats. Methods: After randomization, male Wistar rats were divided into four groups (n = 7 each group). Geraniol (50 mg/kg, dissolved in corn oil) and H2O2 (16 mg/kg, dissolved in distilled water) were administered by an intraperitoneal injection. Administrations were performed during 30 days with 1-day interval. Results: Administration of H2O2 resulted with a significant increase in malondialdehyde (MDA) and a significant decrease in glutathione (GSH) peroxidase glutathione level; geraniol restored its effects on liver. However, hepatic catalase (CAT) activities were significantly higher in H2O2, geraniol, and geraniol+H2O2 groups than control group. The ratio of hepatic total saturated fatty acids increased in H2O2-treated animals compared with control. In addition, hepatic total unsaturated fatty acids reduced in H2O2 group compared with control. The percentages of both hepatic total saturated and unsaturated fatty acids were not different between geraniol+H2O2 and control groups. Conclusions: H2O2-induced oxidative stress may affect fatty acid composition in liver and body. Geraniol can partly restore oxidative hepatic damage because it cannot completely reverse the H2O2-induced increase in hepatic CAT activities. Moreover, this natural compound can regulate hepatic total saturated and unsaturated fatty acids percentages against H2O2-induced alterations. PMID:28163957

  7. Effects of naloxone and nalmefene in rat spinal cord injury induced by the ventral compression technique.

    PubMed

    Benzel, E C; Khare, V; Fowler, M R

    1992-03-01

    The neural injury prevention capabilities of narcotic antagonists have previously been reported. Of the available narcotic antagonists, naloxone has been the most widely studied. Other agents with higher potency, longer half-lives, and greater specificity, however, may be more desirable for the prevention of the "secondary injury" following a primary neural insult. The relative neural injury prevention efficacies of the various narcotic antagonists is not known. The establishment of the relative effectiveness of these drugs is warranted and is of potential clinical importance. Therefore, a study was undertaken to compare the effects of the two narcotic antagonists, naloxone and nalmefene, with respect to their neuro-protective efficacy following experimental spinal cord injury (SCI) in rats. Ninety adult Sprague-Dawley rats were divided into three groups--control; naloxone (2 mg/kg i.p., 45 min following injury); and nalmefene (0.1 mg/kg i.p., 45 min following injury)--following lesioning with the ventral SCI technique. Results were evaluated by the inclined-plane technique and neurologic examination at 1 day and 1 week following injury. Histomorphological evaluation of the injured segment of spinal cord was performed following euthanasia at 1 week following injury. A significant improvement (compared with the control group) was noted in both treatment groups. This was observed with respect to neurological examination and inclined-plane scores in both treatment groups at 24 h and 1 week following lesioning (with a significance level of at least p less than 0.001; analysis of variance). The nalmefene group demonstrated a greater level of function than the naloxone group at both 24 h and 1 week following injury (not significant; p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Neurotoxic lesions of the dorsal hippocampus and Pavlovian fear conditioning in rats.

    PubMed

    Maren, S; Aharonov, G; Fanselow, M S

    1997-11-01

    Electrolytic lesions of the dorsal hippocampus (DH) produce deficits in both the acquisition and expression of conditional fear to contextual stimuli in rats. To assess whether damage to DH neurons is responsible for these deficits, we performed three experiments to examine the effects of neurotoxic N-methyl-D-aspartate (NMDA) lesions of the DH on the acquisition and expression of fear conditioning. Fear conditioning consisted of the delivery of signaled or unsignaled footshocks in a novel conditioning chamber and freezing served as the measure of conditional fear. In Experiment 1, posttraining DH lesions produced severe retrograde deficits in context fear when made either 1 or 28, but not 100, days following training. Pretraining DH lesions made 1 week before training did not affect contextual fear conditioning. Tone fear was impaired by DH lesions at all training-to-lesion intervals. In Experiment 2, posttraining (1 day), but not pretraining (1 week), DH lesions produced substantial deficits in context fear using an unsignaled shock procedure. In Experiment 3, pretraining electrolytic DH lesions produced modest deficits in context fear using the same signaled and unsignaled shock procedures used in Experiments 1 and 2, respectively. Electrolytic, but not neurotoxic, lesions also increased pre-shock locomotor activity. Collectively, this pattern of results reveals that neurons in the DH are not required for the acquisition of context fear, but have a critical and time-limited role in the expression of context fear. The normal acquisition and expression of context fear in rats with neurotoxic DH lesions made before training may be mediated by conditioning to unimodal cues in the context, a process that may rely less on the hippocampal memory system.

  9. Functional observational battery and motor activity in rats after single administration of two NHE 1 inhibitors

    SciTech Connect

    Huebler, Nicole; Gottschling, Barbara . E-mail: barbara.gottschling@merck.de; Jacobs, Maren; Landenberg, Friedrich von; Hewicker-Trautwein, Marion

    2005-11-01

    Two tests, a functional observational battery (FOB) and measurement of motor activity, have been used to screen the two NHE inhibitors EMD 96785 and EMD 125021 for neurobehavioral effects. These two NHE inhibitors, which exhibit a marked selectivity for the NHE 1 isoform, are under development in the research laboratories of Merck KGaA. NHE inhibitors are developed for the treatment of acute myocardial infarction and chronic heart failure. In prior studies with EMD 96785 and EMD 125021, clinical symptoms, such as uncoordinated movements and weakness of the hindlimbs, were detected in rats. The aim of this study was the evaluation of clinical findings in more detail using a FOB and measurement of motor activity in 96 female rats. The time course and reversibility of the adverse effects were investigated. The animals were treated with EMD 96785 or EMD 125021 by intravenous injection at a single dose of 100 mg/kg and four different time points (2 h, 1 day, 7 days and 21 days after treatment) were chosen for the clinical examination. This neurobehavioral test battery clearly detected neurological activity and defined time-course characteristics after treatment with EMD 96785 or EMD 125021. The various clinical parameters were grouped into functional-related domains and most alterations were seen in the domains of central nervous system and neuromuscular system. The most prominent clinical findings were seen with the pharmacologically more potent NHE inhibitor EMD 125021 when compared to EMD 96785. The clinical symptoms were proven to be reversible by 7 days after the single treatment for both compounds.

  10. 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.

  11. Propranolol improves cutaneous wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Romana-Souza, Bruna; Nascimento, Adriana P; Monte-Alto-Costa, Andréa

    2009-06-02

    Sympathetic nerve failure has been proposed as a contributing factor in impaired cutaneous wound healing in diabetes mellitus. Nevertheless, no studies have shown whether beta-adrenoceptor blockade through beta-blocker (e.g., propranolol) administration may alter healing of diabetic cutaneous lesions. This study evaluated macro- and microscopically the effects of propranolol administration on cutaneous wound healing in streptozotocin-induced diabetic rats. Acute diabetes was induced by a single intraperitoneal injection of streptozotocin 14 days before wounding. Animals were treated with propranolol (50 mg/kg) dissolved in drinking water; controls received water only. Administration of beta-receptor antagonist began 1 day before wounding and was continued daily until euthanasia. A full-thickness excisional lesion (1 cm(2)) was created. The wound area was measured weekly and the animals were killed 14 days after wounding. Lesions and adjacent skin were formalin-fixed and paraffin-embedded. Sections were stained with hematoxylin-eosin, Sirius red, and toluidine blue, and immunostained for CD-68, alpha-smooth muscle actin and proliferating cell nuclear antigen. The wound area was significantly smaller in the propranolol-treated group than in the control group 7 and 14 days after wounding. Inflammatory cell numbers and metalloproteinase-9 levels were reduced in the propranolol-treated group compared to the control group 14 days after wounding. Cell proliferation, mast cell number, collagen deposition, blood vessel density, and nitric oxide levels were increased in the propranolol-treated group compared to the control group 14 days after wounding. Propranolol administration improves cutaneous wound healing of hyperglycemic diabetic rats by reducing the local inflammatory response and improving subsequent phases of the repair process.

  12. 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.

  13. Analysis of vkorc1 polymorphisms in Norway rats using the roof rat as outgroup

    PubMed Central

    2010-01-01

    Background Certain mutations in the vitamin K epoxide reductase subcomponent 1 gene (vkorc1) mediate rodent resistance to warfarin and other anticoagulants. Testing for resistance often involves analysis of the vkorc1. However, a genetic test for the roof rat (Rattus rattus) has yet to be developed. Moreover, an available roof rat vkorc1 sequence would enable species identification based on vkorc1 sequence and the evaluation of natural selection on particular vkorc1 polymorphisms in the Norway rat (R. norvegicus). Results We report the coding sequence, introns and 5' and 3' termini for the vkorc1 gene of roof rats (R. r. alexandrinus and R. r. frugivorus) from Uganda, Africa. Newly designed PCR primers now enable genetic testing of the roof rat and Norway rat. Only synonymous and noncoding polymorphisms were found in roof rats from Uganda. Both nominal subspecies of roof rats were indistinguishable from each other but were distinct from R. losea and R. flavipectus; however, the roof rat also shares at least three coding sequence polymorphisms with R. losea and R. flavipectus. Many of recently published vkorc1 synonymous and non-synonymous single nucleotide polymorphisms (SNPs) in Norway rats are likely SNPs from roof rats and/or other Rattus species. Tests applied to presumably genuine Norway rat vkorc1 SNPs are consistent with a role for selection in two populations carrying the derived Phe63Cys and Tyr139Cys mutations. Conclusion Geographic mapping of vkorc1 SNPs in roof rats should be facilitated by our report. Our assay should be applicable to most species of Rattus, which are intermediate in genetic distance from roof and Norway rats. Vkorc1-mediated resistance due to non-synonymous coding SNPs is not segregating in roof rats from Uganda. By using the roof rat sequence as a reference vkorc1, SNPs now can be assigned to the correct rat species with more confidence. Sampling designs and genotyping strategies employed so far have helped detect candidate mutations

  14. Pro-social 50-kHz ultrasonic communication in rats: post-weaning but not post-adolescent social isolation leads to social impairments—phenotypic rescue by re-socialization

    PubMed Central

    Seffer, Dominik; Rippberger, Henrike; Schwarting, Rainer K. W.; Wöhr, Markus

    2015-01-01

    Rats are highly social animals and social play during adolescence has an important role for social development, hence post-weaning social isolation is widely used to study the adverse effects of juvenile social deprivation and to induce behavioral phenotypes relevant to neuropsychiatric disorders, like schizophrenia. Communication is an important component of the rat's social behavior repertoire, with ultrasonic vocalizations (USV) serving as situation-dependent affective signals. High-frequency 50-kHz USV occur in appetitive situations and induce approach behavior, supporting the notion that they serve as social contact calls; however, post-weaning isolation effects on the behavioral changes displayed by the receiver in response to USV have yet to be studied. We therefore investigated the impact of post-weaning isolation on socio-affective information processing as assessed by means of our established 50-kHz USV radial maze playback paradigm. We showed that post-weaning social isolation specifically affected the behavioral response to playback of pro-social 50-kHz but not alarm 22-kHz USV. While group-housed rats showed the expected preference, i.e., approach, toward 50-kHz USV, the response was even stronger in short-term isolated rats (i.e., 1 day), possibly due to a higher level of social motivation. In contrast, no approach was observed in long-term isolated rats (i.e., 4 weeks). Importantly, deficits in approach were reversed by peer-mediated re-socialization and could not be observed after post-adolescent social isolation, indicating a critical period for social development during adolescence. Together, these results highlight the importance of social experience for affiliative behavior, suggesting a critical involvement of play behavior on socio-affective information processing in rats. PMID:25983681

  15. Leucine-Enriched Essential Amino Acids Augment Mixed Protein Synthesis, But Not Collagen Protein Synthesis, in Rat Skeletal Muscle after Downhill Running

    PubMed Central

    Kato, Hiroyuki; Suzuki, Hiromi; Inoue, Yoshiko; Suzuki, Katsuya; Kobayashi, Hisamine

    2016-01-01

    Mixed and collagen protein synthesis is elevated for as many as 3 days following exercise. Immediately after exercise, enhanced amino acid availability increases synthesis of mixed muscle protein, but not muscle collagen protein. However, the potential for synergic effects of amino acid ingestion with exercise on both mixed and collagen protein synthesis remains unclear. We investigated muscle collagen protein synthesis in rats following post-exercise ingestion of leucine-enriched essential amino acids. We determined fractional protein synthesis rates (FSR) at different time points following exercise. Mixed protein and collagen protein FSRs in skeletal muscle were determined by measuring protein-bound enrichments of hydroxyproline and proline, and by measuring the intracellular enrichment of proline, using injections of flooding d3-proline doses. A leucine-enriched mixture of essential amino acids (or distilled water as a control) was administrated 30 min or 1 day post-exercise. The collagen protein synthesis in the vastus lateralis was elevated for 2 days after exercise. Although amino acid administration did not increase muscle collagen protein synthesis, it did lead to augmented mixed muscle protein synthesis 1 day following exercise. Thus, contrary to the regulation of mixed muscle protein synthesis, muscle collagen protein synthesis is not affected by amino acid availability after damage-inducing exercise. PMID:27367725

  16. Leucine-Enriched Essential Amino Acids Augment Mixed Protein Synthesis, But Not Collagen Protein Synthesis, in Rat Skeletal Muscle after Downhill Running.

    PubMed

    Kato, Hiroyuki; Suzuki, Hiromi; Inoue, Yoshiko; Suzuki, Katsuya; Kobayashi, Hisamine

    2016-06-28

    Mixed and collagen protein synthesis is elevated for as many as 3 days following exercise. Immediately after exercise, enhanced amino acid availability increases synthesis of mixed muscle protein, but not muscle collagen protein. However, the potential for synergic effects of amino acid ingestion with exercise on both mixed and collagen protein synthesis remains unclear. We investigated muscle collagen protein synthesis in rats following post-exercise ingestion of leucine-enriched essential amino acids. We determined fractional protein synthesis rates (FSR) at different time points following exercise. Mixed protein and collagen protein FSRs in skeletal muscle were determined by measuring protein-bound enrichments of hydroxyproline and proline, and by measuring the intracellular enrichment of proline, using injections of flooding d₃-proline doses. A leucine-enriched mixture of essential amino acids (or distilled water as a control) was administrated 30 min or 1 day post-exercise. The collagen protein synthesis in the vastus lateralis was elevated for 2 days after exercise. Although amino acid administration did not increase muscle collagen protein synthesis, it did lead to augmented mixed muscle protein synthesis 1 day following exercise. Thus, contrary to the regulation of mixed muscle protein synthesis, muscle collagen protein synthesis is not affected by amino acid availability after damage-inducing exercise.

  17. Carbohydrate-conditioned odor preferences in rats.

    PubMed

    Lucas, F; Sclafani, A

    1995-06-01

    The effectiveness of odor cues to support nutrient-conditioned flavor preferences in rats was studied. When the rats drank fluid, the CS+ odor was paired with intragastric (IG) infusions of Polycose, and the CS- odor with IG water. In Experiment 1, rats trained with almond and anise odors presented with plain drinking water failed to acquire a CS+ odor preference. In contrast, rats in Experiment 2 formed a strong aversion to anise (or almond) paired with lithium chloride, which indicated that the odors were distinguishable to the rats. Experiment 3 showed that providing unique tastes (bitter or sour) in combination with the odors during training potentiated odor conditioning. The rats displayed a strong preference for the odor+taste CS+ and for the odor component alone. Experiment 4 showed that with another pair of odor (peppermint and vanilla), CS+ preferences could be conditioned in the absence of taste cues during training. These results demonstrate that rats can acquire strong nutrient-conditioned odor preferences.

  18. Cardiac lesions in rats fed rapeseed oils.

    PubMed Central

    Charlton, K M; Corner, A H; Davey, K; Kramer, J K; Mahadevan, S; Sauer, F D

    1975-01-01

    Fully refined rapeseed oils containing different amounts of erucic acid (1.6%, 4.3% and 22.3%) were fed, at 20% by weight of diet, to weanling male and female Sprague-Dawley rats for periods up to 112 days. Transient myocardial lipidosis characterized by accumulation of fat droplets in myocardial fibers was marked in male and female rats fed oxidized and unoxidized rapeseed oil containing 22.3% erucic acid, moderate with rapeseed oil containing 4.3% erucic acid and very slight in rats fed rapeseed oil containing 1.6% erucic acid. Peak intensity of myocardial lipidosis occurred at three to seven days and regressed thereafter. Focal myocardial necrosis and fibrosis occurred in male rats fed rapeseed oils containing different levels of erucic acid for 112 days. The incidence of myocardial necrosis and fibrosis was markedly lower in female rats, and the incidence of these lesions in either sex was not affected by the state of oxidation of these oils. In a second experiment, male rats were fed diets containing crude, partially refined or fully refined rapeseed oils. There was no correlation between the number of foci of myocardial necrosis and fibrosis and the state of refinement of the oils, but there were generally fewer lesions in rats fed those oils having the lowest levels of erucic acid. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. PMID:1170010

  19. Grapefruit juice modulates bone quality in rats.

    PubMed

    Deyhim, Farzad; Mandadi, Kranthi; Faraji, Bahram; Patil, Bhimanagouda S

    2008-03-01

    Hypogonadism and oxidative stress increase the risk for developing osteoporosis. The objective of this research was to evaluate the efficacy of drinking grapefruit juice on bone quality in orchidectomized (ORX) and non-ORX rats. Fifty-six 90-day-old male Sprague-Dawley rats were equally divided into four groups--non-ORX rats (sham), sham + grapefruit juice, ORX, and ORX + grapefruit juice--and treated for 60 days. Thereafter, all rats were sacrificed to determine the plasma antioxidant status, insulin-like growth factor I (IGF-I), and indices of bone turnover, bone quality, and calcium and magnesium concentrations in the bone, urine, and feces. Orchidectomy decreased (P < .05) antioxidant status, bone quality, and bone mineral contents and increased (P < .05) indices of bone turnover, urinary deoxypridinoline, calcium, and magnesium, and fecal calcium excretions. In contrast to the ORX group, ORX rats that drank grapefruit juice had an increase (P < .05) in antioxidant status, bone density, and bone mineral contents, delayed femoral fracture, and slowed down (P < .05) bone turnover rate and tended to have a decrease (P = .08) in urinary deoxypridinoline. In sham-treated animals, drinking grapefruit juice increased (P < .05) bone density and tended to increase the femoral strength. The concentration of IGF-I in the plasma was not affected across treatments. In conclusion, drinking grapefruit juice positively affected bone quality by enhancing bone mineral deposition in ORX rats and by improving bone density in non-ORX rats via an undefined mechanism.

  20. 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.

  1. Oestrogen changed cardiomyocyte contraction and beta-adrenoceptor expression in rat hearts subjected to ischaemia-reperfusion.

    PubMed

    Wu, Qin; Zhao, Zhi; Sun, Hong; Hao, Yan-ling; Yan, Chang-dong; Gu, Shu-ling

    2008-09-01

    Women with functional ovaries have a lower cardiovascular risk than men and postmenopausal women. However, oestrogen replacement therapy remains controversial. This study examined the effect of ovarian hormone deficiency and oestrogen replacement on ventricular myocyte contractile function and expression of beta-adrenoceptors (beta-ARs). Female Sprague-Dawley rats were subjected to bilateral ovariectomy (OVX) or sham operation (Sham). A subgroup of OVX rats received oestrogen (E2) replacement (40 microg kg(-1) day(-1)) for 4 weeks. Cardiomyocyte shortening was evaluated in basal conditions and in the presence of isoprenaline (ISO). The expression of beta-ARs was assessed by Western blotting. The presence of lactate dehydrogenase (LDH) activity in the coronary effluent was determined. Ovariectomy promoted body weight gain associated with reduced serum E2 and uterine weight, all of which were abolished by treatment with E2. Ovariectomy increased the amplitude of both basal and ISO-stimulated contractions, increased LDH release, upregulated beta1-AR expression and downregulated beta2-AR expression, all of which were restored by treatment with E2. A beta1-AR antagonist, CGP20712A, but not a beta2-AR antagonist, ICI118,551, significantly decreased the amplitude of ventricular myocyte shortening. Oestrogen decreased cardiomyocyte contraction and the expression of beta1-AR, and increased expression of beta2-AR, and all these effects were abolished by the E2 receptor antagonist, ICI182,780. These data suggest that oestrogen plays a cardioprotective role in female rat hearts subjected to ischaemia-reperfusion injury, and the effects of oestrogen are associated with decreased cardiomyocyte contraction and expression of beta1-AR, and increased expression of beta2-AR.

  2. Defining a therapeutic dosage window for transmeatal-LLLT applied to the rats with NIHL to Ameliorate NIHL

    NASA Astrophysics Data System (ADS)

    Rhee, ChungKu; Song, Kevin; Chang, So-Young; Jung, Jae Yun; Lim, Sung-Kyoo; Chung, Phil-Sang; Suh, Myung-Whan

    2015-02-01

    Aim: The LLLT was found to recover NIHL and ototoxicity induced hearing loss in rats but the optimal LLLT laser dosage to treat NIHL needs to be determined. The aim of this study was to find the optimal laser dosage to recover a NIHL with transmeatal-LLLT. Methods: Bilateral ears of rats were exposed to noise (narrow band noise, 120 dB, 16 kHz, 6 h). Left ears of the rats were irradiated with transmeatal-LLLT (830 nm) of 50, 100, 150, 200, 250, 300 mW for 60 minutes per day for 12 days, starting 1 day post induction of NIHL. Right ears were not irradiated and used as control ears. The hearing levels were measured at each frequency of 8, 12, and 32 kHz before the noise exposure, 1, 3, 8, and 12 days post noise exposure. The differences of hearing levels between left treated ear and right controlled ear at each frequency of different laser dosages (50 - 300 mW) were compared to see the most effective laser dosages to treat NIHL. Results: Hearing levels were most improved by 150 mW, slightly improved by 200 mW, not improved by 50 and 250 mW, and became worse by 300 mW. Conclusion: The results of this study suggest that most effective therapeutic laser dosage window to treat NIHL with transmeatal-LLLT was 150 mW for 12 days and it was not effective by 50, 250, and 300 mW.

  3. Age- and hormone-regulation of opioid peptides and synaptic proteins in the rat dorsal hippocampal formation.

    PubMed

    Williams, Tanya J; Mitterling, Katherine L; Thompson, Louisa I; Torres-Reveron, Annelyn; Waters, Elizabeth M; McEwen, Bruce S; Gore, Andrea C; Milner, Teresa A

    2011-03-16

    Circulating estrogen levels and hippocampal-dependent cognitive functions decline with aging. Moreover, the responses of hippocampal synaptic structure to estrogens differ between aged and young rats. We recently reported that estrogens increase levels of post-synaptic proteins, including PSD-95, and opioid peptides leu-enkephalin and dynorphin in the hippocampus of young animals. However, the influence of ovarian hormones on synaptic protein and opioid peptide levels in the aging hippocampus is understudied. Here, young (3- to 5-month-old), middle-aged (9- to 12-month-old), and aged (about 22-month-old) female rats were ovariectomized and then, 4 weeks later, subcutaneously implanted with a silastic capsule containing vehicle or 17β-estradiol. After 48 h, rats were subcutaneously injected with progesterone or vehicle and sacrificed 1 day later. Coronal sections through the dorsal hippocampus were processed for quantitative peroxidase immunohistochemistry of leu-enkephalin, dynorphin, synaptophysin, and PSD-95. With age, females showed opposing changes in leu-enkephalin and dynorphin levels in the mossy fiber pathway, particularly within the hilus, and regionally specific changes in synaptic protein levels. 17β-estradiol, with or without progesterone, altered leu-enkephalin levels in the dentate gyrus and synaptophysin levels in the CA1 of young but not middle-aged or aged females. Additionally, 17β-estradiol decreased synaptophysin levels in the CA3 of middle-aged females. Our results support and extend previous findings indicating 17β-estradiol modulation of hippocampal opioid peptides and synaptic proteins while demonstrating regional and age-specific effects. Moreover, they lend credence to the "window of opportunity" hypothesis during which hormone replacement can modulate hippocampal structure and circuitry to improve cognitive outcomes.

  4. Effect of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis in adult rat hippocampus and spatial learning.

    PubMed

    Ueda, S; Sakakibara, S; Yoshimoto, K

    2005-01-01

    The dentate gyrus of the hippocampal formation produces new neurons throughout adulthood in mammalian species. Several experimental statuses and factors regulating to neurogenesis have been identified in the adult dentate gyrus. For example, exposure to an enriched environment enhances neurogenesis in the dentate gyrus and improves hippocampus-dependent spatial learning. Furthermore, serotonin is known to influence adult neurogenesis, and learning and memory. However, the effects of long-lasting depletion of serotonin over the developing period on neurogenesis have not been investigated. Thus, we examined the influence of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis and spatial memory performance. As reported previously, environmental enrichment significantly increased new neurons in the dentate gyrus. However, there was no improvement of the spatial learning test in adult rats in standard and in environmental enrichment housings. Intracisternal administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine, on postnatal day 3 apparently reduced serotonin content in the adult hippocampus without regeneration. This experimental depletion of serotonin in the hippocampus of rats housed in an enriched environment had no effect on spatial memory performance, but produced significant decreases in the number of bromodeoxyuridine-labeled new cells in the dentate gyrus. These findings indicate that newly generated cells stimulated by environmental enrichment are not critical for improvements in hippocampus-dependent learning. Furthermore, numbers of bromodeoxyuridine-labeled cells in the dentate gyrus of 5,7-dihydroxytryptamine-injected rats did not differ between 1 day and 4 weeks after bromodeoxyuridine injection. These data suggest that survival of newly generated dentate gyrus cells remains relatively constant under long-lasting serotonin depletion.

  5. Photoperiodic response in the male laboratory rat.

    PubMed

    Wallen, E P; DeRosch, M A; Thebert, A; Losee-Olson, S; Turek, F W

    1987-08-01

    Normally photoperiodic laboratory rats can be induced to respond reproductively to a change in the length of the day by various experimental manipulations. One such paradigm that results in significant gonadal regression involves the treatment of rats with exogenous testosterone during exposure to short days. Studies were undertaken to assess various aspects of this model system including 1) the testicular response of testosterone-treated rats exposed to various photoperiods, 2) the time course for testicular regression under a short photoperiod, and 3) the role of the pineal gland as a mediator of the effects of day length on the neuroendocrine-gonadal axis. Photoperiods ranging in length from 2 to 22 h/24 h had no effect on testicular size in untreated rats. In contrast, while near normal testicular weights were maintained in laboratory rats treated with testosterone and exposed to 10 or more h of light per day, testicular regression occurred in rats implanted with testosterone-filled capsules and exposed to photoperiods of 8 or fewer h of light per day. Maximal testicular regression was reached in about 9 wk in testosterone-treated rats exposed to 6L:18D. Removal of the pineal gland totally blocked the inhibitory effects of exposure to short day lengths in testosterone-treated rats. These studies define some of the characteristics of an extant, but dormant, system for photoperiodic time measurement in the common laboratory rat and implicate a role for the pineal gland in this system. These experiments offer evidence that neuroendocrine factors that regulate continuous vs. seasonal reproductive patterns are malleable. Such flexibility in the photoperiodic response may also contribute to the evolution of seasonal to non-seasonal species and vice versa.

  6. Antidepressant effect of taurine in diabetic rats.

    PubMed

    Caletti, Greice; Olguins, Danielly B; Pedrollo, Elis F; Barros, Helena M T; Gomez, Rosane

    2012-10-01

    Clinical and preclinical studies have shown that diabetic individuals present more depressive behaviors than non-diabetic individuals. Taurine, one of the most abundant free amino acids in the central nervous system, modulates a variety of biological functions and acts as an agonist at GABAA receptors. Our objective was to assess the antidepressant effect of taurine in diabetic rats. Additionally, we studied the effect of taurine on weight gain, water and food intake, and blood glucose levels in diabetic and non-diabetic rats. Male Wistar rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were administered daily 0, 25, 50 or 100 mg/kg of taurine (n = 10 per subgroup) intraperitoneally. After 28 days of treatment, the animals were exposed to the forced swimming test, and their behaviors were recorded. Weight gain, water and food intake, and blood glucose levels were measured weekly. Our results showed that STZ rats had a higher immobility duration than CTR rats, and taurine decreased this depressive-like behavior in STZ rats at doses of 25 and 100 mg/kg. Both of these doses of taurine also decreased water intake and improved weight gain in STZ rats. All doses of taurine decreased the water intake in CTR rats. Taurine, at a dose of 100 mg/kg, decreased food intake and blood glucose levels in STZ rats. Because taurine is a GABA agonist and both amino acids are lower in the plasma of diabetic and depressive individuals, we hypothesize that taurine may represent a new adjuvant drug for the treatment of depression in diabetic individuals.

  7. Temporal Changes in Rat Liver Gene Expression after Acute Cadmium and Chromium Exposure

    PubMed Central

    Madejczyk, Michael S.; Baer, Christine E.; Dennis, William E.; Minarchick, Valerie C.; Leonard, Stephen S.; Jackson, David A.; Stallings, Jonathan D.; Lewis, John A.

    2015-01-01

    U.S. Service Members and civilians are at risk of exposure to a variety of environmental health hazards throughout their normal duty activities and in industrial occupations. Metals are widely used in large quantities in a number of industrial processes and are a common environmental toxicant, which increases the possibility of being exposed at toxic levels. While metal toxicity has been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify candidate biomarkers, rats were exposed via a single intraperitoneal injection to three concentrations of CdCl2 and Na2Cr2O7, with livers harvested at 1, 3, or 7 days after exposure. Cd and Cr accumulated in the liver at 1 day post exposure. Cd levels remained elevated over the length of the experiment, while Cr levels declined. Metal exposures induced ROS, including hydroxyl radical (•OH), resulting in DNA strand breaks and lipid peroxidation. Interestingly, ROS and cellular damage appeared to increase with time post-exposure in both metals, despite declines in Cr levels. Differentially expressed genes were identified via microarray analysis. Both metals perturbed gene expression in pathways related to oxidative stress, metabolism, DNA damage, cell cycle, and inflammatory response. This work provides insight into the temporal effects and mechanistic pathways involved in acute metal intoxication, leading to the identification of candidate biomarkers. PMID:25993096

  8. Acute and subacute toxicity evaluation of ethanolic extract from fruits of Schinus molle in rats.

    PubMed

    Ferrero, Adriana; Minetti, Alejandra; Bras, Cristina; Zanetti, Noelia

    2007-09-25

    Ethanolic and hexanic extracts from fruits and leaves of Schinus molle showed ability to control several insect pests. Potential vertebrate toxicity associated with insecticidal plants requires investigation before institutional promotion. The aim of the present study was to evaluate the acute and subacute toxicity of ethanolic extracts from fruits of Schinus molle in rats. The plant extract was added to the diet at 2g/kg body weight/day during 1 day to evaluate acute toxicity and at 1g/kg body weight/day during 14 days to evaluate subacute toxicity. At the end of the exposure and after 7 days, behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed. Finally, histopathological examinations were conducted on several organs. In both exposures, an increase in the arousal level was observed in experimental groups. Also, the landing foot splay parameter increased in the experimental group after acute exposure. Only the subacute exposure produced a significant increase in the motor activity in the open field. All these changes disappeared after 7 days. None of the exposures affected the different organs evaluated. Our results suggest that ethanolic extracts from fruits and leaves of Schinus molle should be relatively safe to use as insecticide.

  9. RUNX2 expression during early healing of tooth-extraction wounds in rats.

    PubMed

    Sato, Hirotaka; Takaoka, Yutaka

    2015-01-01

    Determining the molecular mechanisms involved in the healing of wounds created by tooth extraction will likely increase understanding of jawbone healing after dental surgery. Runt-related transcription factor 2 (RUNX2) is required for mesenchymal stem cells to differentiate to osteoprogenitor cells. Therefore, we used a rat model to analyze RUNX2 expression during wound-socket healing after tooth extraction. Immunohistochemical analyses of wound tissue immediately after tooth extraction revealed RUNX2 expression in monocytic cells in the coagulum and, to a lesser extent, in remnants of the periodontal ligament. Shortly thereafter, fibroblastic cells proliferated in the coagulum and large polymorphic cells were enclosed within the newly formed bone matrix. Western blot analysis showed that RUNX2 expression peaked from 12 h to 1 day after extraction and then rapidly declined. These findings indicate that the osteogenic commitment of cells derived from hematopoietic tissue in the extraction wound was greater than that of cells in remnants of the periodontal ligament. Thus, cells derived mainly from hematopoietic tissue and RUNX2 expression are essential in the differentiation of mesenchymal stem cells to osteoprogenitor cells immediately after tooth extraction.

  10. Elevated hydrostatic pressure activates sodium/hydrogen exchanger-1 in rat optic nerve head astrocytes.

    PubMed

    Mandal, Amritlal; Shahidullah, Mohammad; Delamere, Nicholas A; Terán, Marcos A

    2009-07-01

    Optic nerve head astrocytes become abnormal in eyes that have elevated intraocular pressure, and cultured astrocytes display altered protein expression after being subjected for > or = 1 days to elevated hydrostatic pressure. Here we show that 2-h elevated hydrostatic pressure (15 or 30 mmHg) causes phosphorylation of ERK1/2, ribosomal S6 protein kinase (p90(RSK)), and Na/H exchanger (NHE)1 in cultured rat optic nerve head astrocytes as judged by Western blot analysis. The MEK/ERK inhibitor U0126 abolished phosphorylation of NHE1 and p90(RSK) as well as ERK1/2. To examine NHE1 activity, cytoplasmic pH (pH(i)) was measured with BCECF and, in some experiments, cells were acidified by 5-min exposure to 20 mM ammonium chloride. Although baseline pH(i) was unaltered, the rate of pH(i) recovery from acidification was fourfold higher in pressure-treated astrocytes. In the presence of either U0126 or dimethylamiloride (DMA), an NHE inhibitor, hydrostatic pressure did not change the rate of pH(i) recovery. The findings are consistent with NHE1 activation due to phosphorylation of ERK1/2, p90(RSK), and NHE1 that occurs in response to hydrostatic pressure. These responses may precede long-term changes of protein expression known to occur in pressure-stressed astrocytes.

  11. Fucoidan attenuates the existing allodynia and hyperalgesia in a rat model of neuropathic pain.

    PubMed

    Hu, Chuanyin; Zhang, Guoping; Zhao, Yun-Tao

    2014-06-13

    Fucoidan is an active constituent found in brown seaweeds, which have potential neuroprotection. The current study aimed to investigate the effects of fucoidan on the maintenance of neuropathic pain induced by L5 spinal nerve ligation (SNL) and the underlying mechanism related to the spinal neuroimmune responses. Animals were randomized into 5 groups: sham-operation with vehicle and SNL with vehicle or fucoidan (15, 50, and 100mg/kg). Different doses of fucoidan or vehicle were administered intrathecally once daily from postoperative day (POD) 11-20. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) was measured on 1 day before operation and days 10, 20, 22, 24, 26, 28, 30 after operation. Glial activation markers such as glial fibrillary acidic protein (GFAP) and macrophage antigen complex-1 (mac-1), inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 activation, and extracellular signalregulated protein kinase (ERK) activation in the lumbar spinal cord were determined on day 30 after operation. The results showed that fucoidan caused dose-dependently attenuation of mechanical allodynia and thermal hyperalgesia. Furthermore, fucoidan could markedly inhibit neuroimmune activation characterized by glial activation, production of cytokines as well as ERK activation. The analgesic effect of intrathecal fucoidan in rats receiving SNL might partly attribute to the inhibition of neuroimmune activation associated with the maintenance of neuropathic pain.

  12. Calcium transients in single fibers of low-frequency stimulated fast-twitch muscle of rat.

    PubMed

    Carroll, S; Nicotera, P; Pette, D

    1999-12-01

    Ca(2+) transients were investigated in single fibers isolated from rat extensor digitorum longus muscles exposed to chronic low-frequency stimulation for different time periods up to 10 days. Approximately 2.5-fold increases in resting Ca(2+) concentration ([Ca(2+)]) were observed 2 h after stimulation onset and persisted throughout the stimulation period. The elevated [Ca(2+)] levels were in the range characteristic of slow-twitch fibers from soleus muscle. In addition, we noticed a transitory elevation of the integral [Ca(2+)] per pulse with a maximum ( approximately 5-fold) after 1 day. Steep decreases in rate constant of [Ca(2+)] decay could be explained by an immediate impairment of Ca(2+) uptake and, with longer stimulation periods, by an additional loss of cytosolic Ca(2+) binding capacity resulting from a decay in parvalbumin content. A partial recovery of the rate constant of [Ca(2+)] decay in 10-day stimulated muscle could be explained by an increasing mitochondrial contribution to Ca(2+) sequestration.

  13. Termination of pseudopregnancy in rats by silastic-PVP-PGF2 alpha tube.

    PubMed

    Lau, I F; Lemarbre, P M; Chauvin, C; Saksena, S K

    1979-05-01

    The efficacy of a one-end or both-end open Silastic-polyvinyl-pyrrolidone (Silastic-PVP) tube containing 600 microgram prostaglandin-F2 alpha (PGF2 alpha) and placed subcutaneously on day-6 of pseudopregnancy (PSP) in the induction of premature termination of PSP was compared. A both-end open Silastic-PVP-PGF2 alpha tube was more efficacious in inducing an early termination of PSP with a mean duration of 7.8 days. By contrast, PSP females receiving a one-end open Silastic-PVP-PGF2 alpha tube showed a mean duration of PSP of 9.9 days. The shortened duration of PSP in both these treatment groups was significantly different from the control value of 13.1 days. The significant drop in progesterone (delta 4P) but rise in 20 alpha-dihydroprogesterone (20 alpha-DHP) occurred 24 hr after treatment in PSP rats treated with both-end open Silastic-PVP-PGF2 alpha tube, whereas similar changes in delta 4P and 20 alpha-DHP took place 48-72 hr after the deposition of a one-end open Silastic-PVP PGF2 alpha tube. It is concluded than an initial larger amount of circulating PGF2 alpha is needed to induce an early premature termination of PSP. The exposure of corpus luteum to a more sustained but lower level of PGF2 alpha leads to a slower response.

  14. Analysis of gene expression profiles in healing rat fractures treated with nail and plate fixation.

    PubMed

    Wang, S D; Li, X L; Liu, H P

    2014-10-20

    To compare fracture healing therapies, the gene expression profiles of rat fracture samples treated with nail and plate fixation were analyzed at 1 day, 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks after surgery. The gene expression profiles GSE1685, which include 19 samples, were downloaded from the Gene Expression Omnibus database. After preprocessing, the gene expression profiles were subjected to time series analysis using the Short Time-series Expression Miner software, and the significantly differentially expressed gene (DEG) sets were selected. Further, the distributions of those DEG sets on the corresponding chromosomes were identified using the functional classification tool. Finally, the DEGs were subjected to function and pathway enrichment analysis. DEG analysis indicated that the number of DEGs (854 genes) from nail fixation was significantly lower than that of DEGs (1029 genes) from plate fixation. The DEGs were mainly enriched in cell proliferation, cellular localization, and response to wounding functions. Several critical DEGs expressed during the fracture healing process were screened, and 2 common pathways were enriched for the DEGs in the nail fixation and plate fixation. These DEGs and pathways may be potential targets or predictive markers during fracture healing.

  15. Coping style and stress hormone responses in genetically heterogeneous rats: comparison with the Roman rat strains.

    PubMed

    Díaz-Morán, Sira; Palència, Marta; Mont-Cardona, Carme; Cañete, Toni; Blázquez, Gloria; Martínez-Membrives, Esther; López-Aumatell, Regina; Tobeña, Adolf; Fernández-Teruel, Alberto

    2012-03-01

    The purpose of the present study was to evaluate for the first time the stress-induced hypothalamus-pituitary-adrenal (HPA), adrenocorticotropic hormone (ACTH), corticosterone and prolactin responses of the National Institutes of Health genetically heterogeneous rat stock (N/Nih-HS rats) in comparison with responses of the relatively high and low stress-prone Roman Low- (RLA-I) and High-Avoidance (RHA-I) rat strains. The same rats were also compared (experiment 1) with respect to their levels of unconditioned anxiety (elevated zero-maze test), novelty-induced exploratory behavior, conditioned fear and two-way active avoidance acquisition. In experiment 2, naive rats from these three strains/stocks were evaluated for "depressive-like" behavior in the forced swimming test. N/Nih-HS and RLA-I rats showed significantly higher post-stress ACTH, corticosterone and prolactin levels than RHA-I rats. N/Nih-HS rats also presented the highest context-conditioned freezing responses, extremely poor two-way avoidance acquisition and very low novelty-induced exploratory behavior. Experiment 2 showed that, compared to RHA-I rats, N/Nih-HS and RLA-I rats displayed significantly less struggling (escape-directed) and increased immobility responses in the forced swimming test. Factor analysis of data from experiment 1 showed associations among behavioral and hormonal responses, with a first factor comprising high loadings of elevated zero-maze variables and lower loadings of conditioned fear, two-way avoidance acquisition and hormonal measures, while a second factor mainly grouped conditioned fear and two-way avoidance acquisition with novelty-induced exploration and post-stress prolactin. Thus, regarding their anxiety/fearfulness, passive coping style, "depressive-like" and stress-induced hormonal responses the N/Nih-HS rats resemble the phenotype profiles of the relatively high-anxious and stress-prone RLA-I rat strain.

  16. 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.

  17. Origins of blood acetate in the rat.

    PubMed Central

    Buckley, B M; Williamson, D H

    1977-01-01

    A novel enzymimc cycling assay for the determination of acetate in biological material is described. Measurements of the acetate concentration in blood and liver samples from rats of various ages and nutritional states with this assay are reported. The contribution of the intestine, the liver and the rest of the body to maintaining the concentration of acetate in the circulation is examined. Evidence is presented that the gut flora constitute the main source of acetate in blood of fed adult rats, though endogenous production of acetate is of significance in other situations. The streptozotocin-diabetic rat has an elevated blood acetate concentration. PMID:597244

  18. Hypothalamic thermosensitivity in capsaicin-desensitized rats.

    PubMed Central

    Cormarèche-Leydier, M; Shimada, S G; Stitt, J T

    1985-01-01

    In rats, we tested the hypothesis that capsaicin desensitization reduces hypothalamic warm thermosensitivity. We locally heated and cooled the hypothalamus using water-perfused thermodes while observing thermoregulatory variables. In untreated rats, a small dose of capsaicin had profound effects on thermoregulation. However, desensitizing rats to capsaicin had no effect on hypothalamic thermosensitivity for metabolic rate or changes in body temperature due to displacements of hypothalamic temperature. Contrary to current opinion, we conclude that capsaicin desensitization does not alter hypothalamic thermosensitivity to warm or cold. PMID:4020699

  19. Malignant neoplasms in rats fed lasiocarpine.

    PubMed Central

    Rao, M. S.; Reddy, J. K.

    1978-01-01

    Lasiocarpine, a pyrrolizidine alkaloid, was fed at a dietary concentration of 50/10(6) for 55 weeks, to 20 male F-344 rats. Malignant tumours developed in 17/20 animals between 48 and 59 weeks. Forty-five percent (9/20) developed angiosarcomas of the liver and 35% (7/20) had hepatocellular carcinomas. Other tumours included malignant adnexas tumour of the skin (1 rat) and lympohoma (1 rat). Lung metastases were observed in 4 animals with angiosarcoma of the liver and one animal with hepatocellular carcinoma. From one animal, angiosarcoma was successfully transplanted through 4 generations. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:204322

  20. Vitamin C Prevents Sleep Deprivation-induced Elevation in Cortisol and Lipid Peroxidation in the Rat Plasma.

    PubMed

    Olayaki, L A; Sulaiman, S O; Anoba, N B

    2015-12-20

    Sleep deprivation (SD) is biological stressor that alters metabolic parameters, induced oxidative stress and lipid peroxidation. Previous studies have shown that antioxidants substances such as melatonin, tryptophan, vitamin E and vitamin C improved stress tolerance in laboratory animals. In this study, we examined the potential protective effects of administration of vitamin C on acute and chronic sleep deprivation-induced metabolic derangement. In addition, possible processes involved in vitamin C effects on acute and chronic sleep deprivation-induced metabolic derangement were determined. Thirty-five rats (120-250g) were used. The rats were divided into 7 groups of 5 rats each as Control (CTRL), Acute sleep deprived untreated with vitamin C (AC), Acute sleep deprived treated with vitamin C (AWC), Chronic sleep deprived untreated with vitamin C (CC), Chronic sleep deprived treated with vitamin C (CWC), Chronic sleep deprived + Recovery untreated with vitamin C (RC), and Chronic sleep deprived + Recovery treated with vitamin C (RWC). The SD was carried out for 20h for 1 day on the acute groups, and for 20h/day for 5 days on the chronic group, using the Multiple Modified Platforms (MMP) after oral administration of 300mg/kg of vitamin C to all vitamin C-treated groups. The recovery groups were further observed for five days after SD. The control group were treated with vitamin C and without stress in their home cages. At the end of the experiment, the animals were sacrificed and blood was collected for estimation of plasma glucose, insulin, cortisol and malondialdehyde (MDA). The results showed that acute and chronic SDs significantly  increased MDA and cortisol levels, while significantly reduced the levels of insulin. Treatment with vitamin C reversed the changes in the MDA, cortisol and plasma insulin levels. Additionally, allowing the rats to recover for 5 days after sleep deprivation corrected the observed changes. Plasma glucose was significantly

  1. Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

    SciTech Connect

    Zhu, Changlian; Gao, Jianfeng; Li, Qian; Huang, Zhiheng; Zhang, Yu; Li, Hongfu; Kuhn, Hans-Georg; Blomgren, Klas

    2011-01-07

    Research highlights: {yields} The effect of MRI on the developing brain is a matter of debate. {yields} Repeated exposure to MRI did not affect neurogenesis. {yields} Memory function was not affected by repeated MRI during development. {yields} Neither late gestation nor young postnatal brains were affected by MRI. {yields} Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 {sup o}C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.

  2. 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.

  3. Derivation of embryonic stem cells from Brown Norway rats blastocysts.

    PubMed

    Zhao, Xiaoyang; Lv, Zhuo; Liu, Lei; Wang, Liu; Tong, Man; Zhou, Qi

    2010-07-01

    Knockout Brown Norway (BN) rat could be a useful disease model for human disorders, however, a failure to derive embryonic stem (ES) cells disturbs the further development of the model. In this study, we reported a case of successful derivation of the BN rat ES cells with the derivation efficiency comparable to that of Sprague Dawley (SD) rats. The BN rat ES cells expressed the key transcription factors, and were able to form embryonic bodies (EBs) when being differentiated in vitro. After injecting the BN rat ES cells into the SD rat blastocysts, high-contribution chimeric rats were generated and could survive to their adulthood. Our success in generating pluripotent rat ES cells will benefit the generation of the knockout rats in the future.

  4. Milk composition of rats feeding restricted litters.

    PubMed Central

    Grigor, M R; Allan, J; Carne, A; Carrington, J M; Geursen, A

    1986-01-01

    Milk samples were taken from rats feeding ten pups and from both the suckled and non-suckled glands of rats feeding two pups. The lipid, protein and lactose concentrations were similar in the milks from the secreting glands, but the fluid from the non-suckled glands contained less lactose and lipid but significantly higher total protein and transferrin concentrations. The fatty acid compositions of the milk from the three sources were very similar. The mammary tissue from the rats feeding ten pups had a higher DNA content/g wet wt. than either the suckled or non-suckled mammary tissue of the rats feeding two pups. The specific activities of several lipogenic enzymes were significantly lower in the non-suckled mammary tissue. PMID:3707536

  5. 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.

  6. 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.

  7. 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...

  8. 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

  9. 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...

  10. The Therapeutic Effect of Vitamin C in an Animal Model of Complex Regional Pain Syndrome Produced by Prolonged Hindpaw Ischemia-Reperfusion in Rats.

    PubMed

    Kim, Jae Hun; Kim, Yong Chul; Nahm, Francis Sahngun; Lee, Pyung Bok

    2017-01-01

    Objectives: It is known that increased free radicals from oxidative stress are one of the major causes of complex regional pain syndrome (CRPS). In this study, we tested the hypothesis that vitamin C has a dose-related treatment effect in a chronic post-ischemic pain (CPIP) model. Methods: A total of 49 male rats weighing 250 to 350 g were used. The 4 treatment groups were control (no medication), group 1.0 (administration of 1 mg/day for vitamin C for 5 days), group 2.5 (administration of 2.5 mg/day vitamin C for 5 days), and group 7.5 (administration of 7.5 mg/day vitamin C for 5 days). The 50% mechanical withdrawal threshold and total blood antioxidant status (TAS) were measured before and after administration of vitamin C. Results: Twenty-eight CPIP model rats were generated from 49 rats. Seven rats were randomly allocated to each group. The 50% mechanical withdrawal threshold of group 2.5 (after the administration of vitamin C) was higher than that of the control group and group 1.0 (P < 0.05). At 1 day of the administration of vitamin C, the 50% mechanical withdrawal threshold of group 1.0 was higher than that of the control group and the blood levels of TAS in groups 2.5 and 7.5 were higher than that in control group (P < 0.05). Twelve days after the administration of vitamin C, the blood levels of TAS in groups 2.5 and 7.5 were lower than that of the control group (P < 0.05). Discussion: The administration of a proper dose of vitamin C can reduce oxidative stress, increase antioxidants, and recover the threshold for mechanical allodynia in the CPIP model.

  11. The Therapeutic Effect of Vitamin C in an Animal Model of Complex Regional Pain Syndrome Produced by Prolonged Hindpaw Ischemia-Reperfusion in Rats

    PubMed Central

    Kim, Jae Hun; Kim, Yong Chul; Nahm, Francis Sahngun; Lee, Pyung Bok

    2017-01-01

    Objectives: It is known that increased free radicals from oxidative stress are one of the major causes of complex regional pain syndrome (CRPS). In this study, we tested the hypothesis that vitamin C has a dose-related treatment effect in a chronic post-ischemic pain (CPIP) model. Methods: A total of 49 male rats weighing 250 to 350 g were used. The 4 treatment groups were control (no medication), group 1.0 (administration of 1 mg/day for vitamin C for 5 days), group 2.5 (administration of 2.5 mg/day vitamin C for 5 days), and group 7.5 (administration of 7.5 mg/day vitamin C for 5 days). The 50% mechanical withdrawal threshold and total blood antioxidant status (TAS) were measured before and after administration of vitamin C. Results: Twenty-eight CPIP model rats were generated from 49 rats. Seven rats were randomly allocated to each group. The 50% mechanical withdrawal threshold of group 2.5 (after the administration of vitamin C) was higher than that of the control group and group 1.0 (P < 0.05). At 1 day of the administration of vitamin C, the 50% mechanical withdrawal threshold of group 1.0 was higher than that of the control group and the blood levels of TAS in groups 2.5 and 7.5 were higher than that in control group (P < 0.05). Twelve days after the administration of vitamin C, the blood levels of TAS in groups 2.5 and 7.5 were lower than that of the control group (P < 0.05). Discussion: The administration of a proper dose of vitamin C can reduce oxidative stress, increase antioxidants, and recover the threshold for mechanical allodynia in the CPIP model. PMID:28138314

  12. Manganese-enhanced magnetic resonance imaging (MEMRI) of rat brain after systemic administration of MnCl₂: hippocampal signal enhancement without disruption of hippocampus-dependent behavior.

    PubMed

    Jackson, Stewart J; Hussey, Rosalind; Jansen, Maurits A; Merrifield, Gavin D; Marshall, Ian; MacLullich, Alasdair; Yau, Joyce L W; Bast, Tobias

    2011-01-01

    Manganese (Mn(2+))-enhanced magnetic resonance (MR) imaging (MEMRI) in rodents offers unique opportunities for the longitudinal study of hippocampal structure and function in parallel with cognitive testing. However, Mn(2+) is a potent toxin and there is evidence that it can interfere with neuronal function. Thus, apart from causing adverse peripheral side effects, Mn(2+) may disrupt the function of brain areas where it accumulates to produce signal enhancement and, thereby, Mn(2+) administration may confound cognitive testing. Here, we examined in male adult Lister hooded rats if a moderate systemic dose of MnCl₂ (200 μmol/kg; two intraperitoneal injections of 100 μmol/kg separated by 1 h) that produces hippocampal MR signal enhancement would disrupt hippocampal function. To this end, we used a delayed-matching-to-place (DMP) watermaze task, which requires rapid allocentric place learning and is highly sensitive to interference with hippocampal function. Tested on the DMP task 1 h and 24 h after MnCl₂ injection, rats did not show any impairment in indices of memory performance (latencies, search preference) or any sensorimotor effects. However, MnCl₂ injection caused acute peripheral effects (severe ataxia and erythema, i.e. redness of paws, ears, and nose) which subsided over 30 min. Additionally, rats injected with MnCl₂ showed reduced weight 1 day after injection and failed to reach the normal weight-growth curve of control rats within the 16 days monitored. Our results indicate that 200 μmol/kg MnCl₂ produces hippocampal MR signal enhancement without disrupting hippocampus-dependent behavior on a rapid place learning task, even though attention must be paid to peripheral side effects.

  13. Effects of ethanol during adolescence on the number of neurons and glia in the medial prefrontal cortex and basolateral amygdala of adult male and female rats

    PubMed Central

    Koss, W.A.; Sadowski, R.N.; Sherrill, L.K.; Gulley, J.M.; Juraska, J.M.

    2012-01-01

    Human adolescents often consume alcohol in a binge-like manner at a time when changes are occurring within specific brain structures, such as the medial prefrontal cortex (mPFC) and the basolateral nucleus of the amygdala (BLN). In particular, neuron and glia number are changing in both of these areas in the rat between adolescence and adulthood (Markham et al., 2007; Rubinow and Juraska, 2009). The current study investigated the effects of ethanol exposure during adolescence on the number of neurons and glia in the adult mPFC and BLN in Long-Evans male and female rats. Saline or 3 g/kg ethanol was administered between postnatal days (P) 35–45 in a binge-like pattern, with 2 days of injections followed by 1 day without an injection. Stereological analyses of the ventral mPFC (prelimbic and infralimbic areas) and the BLN were performed on brains from rats at 100 days of age. Neuron and glia densities were assessed with the optical disector and then multiplied by the volume to calculate the total number of neurons and glia. In the adult mPFC, ethanol administration during adolescence resulted in a decreased number of glia in males, but not females, and had no effect on the number of neurons. Adolescent ethanol exposure had no effects on glia or neuron number in the BLN. These results suggest that glia cells in the prefrontal cortex are particularly sensitive to binge-like exposure to ethanol during adolescence in male rats only, potentially due to a decrease in proliferation in males or protective mechanisms in females. PMID:22627163

  14. 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.

  15. 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.

  16. The rat brain hippocampus proteome.

    PubMed

    Fountoulakis, Michael; Tsangaris, George T; Maris, Antony; Lubec, Gert

    2005-05-05

    The hippocampus is crucial in memory storage and retrieval and plays an important role in stress response. In humans, the CA1 area of hippocampus is one of the first brain areas to display pathology in Alzheimer's disease. A comprehensive analysis of the hippocampus proteome has not been accomplished yet. We applied proteomics technologies to construct a two-dimensional database for rat brain hippocampus proteins. Hippocampus samples from eight months old animals were analyzed by two-dimensional electrophoresis and the proteins were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The database comprises 148 different gene products, which are in the majority enzymes, structural proteins and heat shock proteins. It also includes 39 neuron specific gene products. The database may be useful in animal model studies of neurological disorders.

  17. Neptunium-237 inhalation in rats.

    PubMed

    Sullivan, M F; Ruemmler, P S; Buschbom, R L

    1986-12-01

    Groups of rats were exposed to aerosols of 237Np nitrate to determine clearance rates, retention and distribution at various intervals after inhalation. Initial lung burdens (ILB) after 237Np inhalation by three treatment groups were 0.12, 0.19 and 0.37 mu Ci/kg, respectively. Radiochemical analyses of animals killed at 4, 8, 14, 28 and 90 d, as well as data for others maintained until they became moribund, showed that their lung clearance followed a three-compartment model, clearance half-times for which were 1, 35, and 10,000 d, respectively. Only 3% of the ILB was retained after 90 d; 12% of that burden had translocated to the skeleton at 750 d; the half-time for skeletal retention was 2500 d. A single tumor was the only malignancy detected in the lungs of the 35 animals allowed to survive the early phase of the study.

  18. 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.

  19. 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.

  20. Ultrasonic Vocalizations by Adult Rats (Rattus norvegicus)

    DTIC Science & Technology

    1991-12-01

    during aggression in rats and some other myomorph species (e.g., Acomys cahirinus, Apcdemus sylvati- cus). Other species (e.g., MusM muau_...which occur when the young are handled. The author reports that, unlike rats, other rodent species (e.g., lab mice, Acomys cahirinus, Clethrionomys gajj... Acomys was removed from the mother’s cage, and during exploratory behavior in Apodemus gyiL vaticus. i1 Sewell, G.D. Ultrasonic signals from rodents

  1. 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

  2. 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.

  3. Hindlimb unweighting affects rat vascular capacitance function

    NASA Technical Reports Server (NTRS)

    Dunbar, S. L.; Tamhidi, L.; Berkowitz, D. E.; Shoukas, A. A.

    2001-01-01

    Microgravity is associated with an impaired stroke volume and, therefore, cardiac output response to orthostatic stress. We hypothesized that a decreased venous filling pressure due to increased venous compliance may be an important contributing factor in this response. We used a constant flow, constant right atrial pressure cardiopulmonary bypass procedure to measure total systemic vascular compliance (C(T)), arterial compliance (C(A)), and venous compliance (C(V)) in seven control and seven 21-day hindlimb unweighted (HLU) rats. These compliance values were calculated under baseline conditions and during an infusion of 0.2 microg*kg(-1)*min(-1) norepinephrine (NE). The change in reservoir volume, which reflects changes in unstressed vascular volume (DeltaV(0)) that occurred upon infusion of NE, was also measured. C(T) and C(V) were larger in HLU rats both at baseline and during the NE infusion (P < 0.05). Infusion of NE decreased C(T) and C(V) by 20% in both HLU and control rats (P < 0.01). C(A) was also significantly decreased in both groups of rats by NE (P < 0.01), but values of C(A) were similar between HLU and control rats both at baseline and during the NE infusion. Additionally, the NE-induced DeltaV(0) was attenuated by 53% in HLU rats compared with control rats (P < 0.05). The larger C(V) and attenuated DeltaV(0) in HLU rats could contribute to a decreased filling pressure during orthostasis and thus may partially underlie the mechanism leading to the exaggerated fall in stroke volume and cardiac output seen in astronauts during an orthostatic stress after exposure to microgravity.

  4. Intraglomerular basement membrane translocation of immune complex (IC) in the development of passive in situ IC nephritis of rats.

    PubMed Central

    Fujigaki, Y.; Nagase, M.; Honda, N.

    1993-01-01

    A study was performed to elucidate the mechanisms of charge-based immune complex nephritis. A chronological observation after induction of nephritis was made by immunoelectron microscopy to clarify whether antigen (Ag) remains in association with antibody (Ab) and C3 during the translocation through the glomerular basement membrane (GBM). Fifteen minutes after intrarenal perfusion with cationized ferritin (pI > 10.0) as Ag, followed by injection of rabbit anti-ferritin Ab, deposition of subendothelial Ag-Ab-C3 complexes was observed. Between 2 hours and 1 day, a large number of Ag in close association with Ab was noted in the lamina densa, but only a small amount of C3 was detectable. During this time Ag and Ab in the subendothelial region gradually decreased. However, C3 reappeared in the subepithelial region together with the Ag-Ab complex after 1 day, and the subendothelial C3 significantly decreased. At 2 hours and day 1, the distributions of Ag and Ab in the GBM were similar in immersion-fixed kidneys regardless of the preperfusion with phosphate-buffered saline. On the other hand, the passage of Ag across the lamina densa was delayed in the experimental rats as compared with the controls. Significant albuminuria also appeared on day 1. Despite the general concept that Ab binding to cationized Ag results in low avidity immune complex, cationized Ag translocated across the GBM in close association with Ab. The complement was activated biphasically in the subendothelial and in the subepithelial space. The subendothelial complement activation may have contributed to the translocation of immune complex. Images Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8456943

  5. 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.

  6. Interpretation of male rat renal tubule tumors.

    PubMed Central

    Rodgers, I S; Baetcke, K P

    1993-01-01

    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 2u-globulin (alpha 2u-g), a low molecular weight protein, in the male rat kidney. The alpha 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 2u-g accumulation and to select appropriate procedures for estimating human risks under such circumstances. PMID:7517352

  7. Oxalate metabolism in magnesium-deficient rats.

    PubMed

    Rattan, V; Thind, S K; Jethi, R K; Sidhu, H; Nath, R

    1993-06-01

    Male weanling rats were maintained on magnesium-deficient diet for 30 d and compared with pair-fed control rats fed magnesium-supplemented diet. Magnesium deficiency led to slow growth and finally to a significant decrease in body weight (P < 0.001) accompanied by a significant hypomagnesaemia, hypomagnesuria and hyperoxaluria (P < 0.001 in each case) in experimental rats as compared to the control rats. Magnesium deficiency altered the glyoxylate metabolism in the liver and kidney mitochondria by significantly decreasing glyoxylate oxidation (by 26 per cent in liver and 17 per cent in kidney) and activity of alpha-ketoglutarate:glyoxylate carboligase enzyme (by 35 per cent in liver and 27 per cent in kidney) in the experimental animals. A significant increase in the specific activities of glycolic acid oxidase (P < 0.001) and glycolic acid dehydrogenase (P < 0.01) and a significant decrease in alanine transaminase (P < 0.01) was also observed in magnesium-deficient rats. No change in liver and kidney lactate dehydrogenase was observed. Thus magnesium deficiency in rats leads to accumulation of glyoxylate in the tissues, a part of which is converted into oxalate, thereby promoting hyperoxaluria.

  8. Sexually Dimorphic Risk Mitigation Strategies in Rats

    PubMed Central

    Pellman, Blake A.; Schuessler, Bryan P.

    2017-01-01

    Abstract The scientific understanding of fear and anxiety—in both normal and pathological forms—is presently limited by a predominance of studies that use male animals and Pavlovian fear conditioning-centered paradigms that restrict and assess specific behaviors (e.g., freezing) over brief sampling periods and overlook the broader contributions of the spatiotemporal context to an animal’s behavioral responses to threats. Here, we use a risky “closed economy” system, in which the need to acquire food and water and the need to avoid threats are simultaneously integrated into the lives of rats, to examine sex differences in mitigating threat risk while foraging. Rats lived for an extended period (∼2 months) in enlarged chambers that consisted of a safe, bedded nest and a risky foraging area where footshocks could be delivered unpredictably. We observed that male and female rats used different strategies for responding to the threat of footshock. Whereas male rats increased the size of meals consumed to reduce the overall time spent foraging, female rats sacrificed their metabolic needs in order to avoid shocks. Ovarian hormone fluctuations were shown to exert slight but reliable rhythmic effects on risky decision-making in gonadally intact female rats. However, this did not produce significant differences in approach–avoidance trade-offs between ovariectomized and intact female groups, suggesting that male–female sex differences are not due to the activational effects of gonadal hormones but, rather, are likely to be organized during early development. PMID:28197550

  9. 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

  10. 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.

  11. 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.

  12. Impact of dietary nitrate supplementation via beetroot juice on exercising muscle vascular control in rats.

    PubMed

    Ferguson, Scott K; Hirai, Daniel M; Copp, Steven W; Holdsworth, Clark T; Allen, Jason D; Jones, Andrew M; Musch, Timothy I; Poole, David C

    2013-01-15

    Dietary nitrate (NO(3)(-)) supplementation, via its reduction to nitrite (NO(2)(-)) and subsequent conversion to nitric oxide (NO) and other reactive nitrogen intermediates, reduces blood pressure and the O(2) cost of submaximal exercise in humans. Despite these observations, the effects of dietary NO(3)(-) supplementation on skeletal muscle vascular control during locomotory exercise remain unknown. We tested the hypotheses that dietary NO(3)(-) supplementation via beetroot juice (BR) would reduce mean arterial pressure (MAP) and increase hindlimb muscle blood flow in the exercising rat. Male Sprague-Dawley rats (3-6 months) were administered either NO(3)(-) (via beetroot juice; 1 mmol kg(-1) day(-1), BR n = 8) or untreated (control, n = 11) tap water for 5 days. MAP and hindlimb skeletal muscle blood flow and vascular conductance (radiolabelled microsphere infusions) were measured during submaximal treadmill running (20 m min(-1), 5% grade). BR resulted in significantly lower exercising MAP (control: 137 ± 3, BR: 127 ± 4 mmHg, P < 0.05) and blood [lactate] (control: 2.6 ± 0.3, BR: 1.9 ± 0.2 mm, P < 0.05) compared to control. Total exercising hindlimb skeletal muscle blood flow (control: 108 ± 8, BR: 150 ± 11 ml min(-1) (100 g)(-1), P < 0.05) and vascular conductance (control: 0.78 ± 0.05, BR: 1.16 ± 0.10 ml min(-1) (100 g)(-1) mmHg(-1), P < 0.05) were greater in rats that received BR compared to control. The relative differences in blood flow and vascular conductance for the 28 individual hindlimb muscles and muscle parts correlated positively with their percentage type IIb + d/x muscle fibres (blood flow: r = 0.74, vascular conductance: r = 0.71, P < 0.01 for both). These data support the hypothesis that NO(3)(-) supplementation improves vascular control and elevates skeletal muscle O(2) delivery during exercise predominantly in fast-twitch type II muscles, and provide a potential mechanism by which NO(3)(-) supplementation improves metabolic control.

  13. Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus

    PubMed Central

    Jugé, Lauriane; Pong, Alice C.; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E.; Cheng, Shaokoon

    2016-01-01

    Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied

  14. Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus.

    PubMed

    Jugé, Lauriane; Pong, Alice C; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E; Cheng, Shaokoon

    2016-01-01

    Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied

  15. 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

  16. 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.

  17. Effects of BCL-2 over-expression on B cells in transgenic rats and rat hybridomas.

    PubMed

    Iscache, Anne-Laure; Ménoret, Séverine; Tesson, Laurent; Rémy, Séverine; Usal, Claire; Pedros, Christophe; Saoudi, Abdelhadi; Buelow, Roland; Anegon, Ignacio

    2011-10-01

    The rat is an important biomedical experimental model that benefited from the recent development of new transgenic and knockout techniques. With the goal to optimize rat mAb production and to analyze the impact of Bcl-2 on B-cell development, we generated bcl-2 transgenic rats. Transgenic rats showed Bcl-2 over-expression in B cells, increased B cell numbers in lymphoid organs, elevated production of immunoglobulins (Igs) and prolonged B-cell survival in vitro. Transgenic rats remained healthy, reproduced normally and did not develop autoimmunity. Fusions with bcl-2 transgenic splenocytes did not result in increased hybridoma generation. A comparison of on- and off-rates of 39 mAbs generated with bcl-2 transgenic and wild-type animals revealed no significant differences. Over-expression of Bcl-2 in hybridomas did not change cell proliferation but resulted in increased Ig production. Bcl-2 transgenic rats will be a useful tool for the generation of rat mAbs, the analysis of B cells in different pathophysiological models, such as autoimmunity, cancer or organ transplantation, and the study of rat B-cell biology.

  18. Endothelial dysfunction in cold-induced hypertensive rats.

    PubMed

    Zhu, Zhiming; Zhu, Shanjun; Zhu, Jijun; van der Giet, Markus; Tepel, Martin

    2002-02-01

    Endothelial dysfunction can be observed in preatherosclerotic conditions. However, its pathogenetic role in hypertension is still controversial. Endothelial-dependent changes of blood pressure (BP) and expression of endothelial nitric oxide synthase (eNOS) were evaluated in cold-induced hypertensive rats. Wistar rats were exposed to cold stress for 8 weeks. Exposure to cold stress significantly increased the systolic BP in rats. The infusion of acetylcholine significantly lowered mean arterial BP in control rats by 48 +/- 2% and by 32 +/- 1% in cold-induced hypertensive rats. The acetylcholine-induced reduction of mean arterial BP was significantly attenuated in cold-induced hypertensive rats (control rats, 45 +/- 2 mm Hg; cold-induced hypertensive rats, 34 +/- 3 mm Hg; P < .05). Administration of N(G)-nitro-L-arginine-methyl ester for 1 week significantly increased BP in control rats, whereas no effect could be observed in cold-induced hypertensive rats. In cold-induced hypertensive rats eNOS in aortic vessels was significantly reduced compared to control rats. In this nongenetic, nonsurgical animal model of cold-induced hypertensive rats an endothelial dysfunction can be observed due to reduced eNOS.

  19. Social Structure Predicts Genital Morphology in African Mole-Rats

    PubMed Central

    Seney, Marianne L.; Kelly, Diane A.; Goldman, Bruce D.; Šumbera, Radim; Forger, Nancy G.

    2009-01-01

    Background African mole-rats (Bathyergidae, Rodentia) exhibit a wide range of social structures, from solitary to eusocial. We previously found a lack of sex differences in the external genitalia and morphology of the perineal muscles associated with the phallus in the eusocial naked mole-rat. This was quite surprising, as the external genitalia and perineal muscles are sexually dimorphic in all other mammals examined. We hypothesized that the lack of sex differences in naked mole-rats might be related to their unusual social structure. Methodology/Principal Findings We compared the genitalia and perineal muscles in three African mole-rat species: the naked mole-rat, the solitary silvery mole-rat, and the Damaraland mole-rat, a species considered to be eusocial, but with less reproductive skew than naked mole-rats. Our findings support a relationship between social structure, mating system, and sexual differentiation. Naked mole-rats lack sex differences in genitalia and perineal morphology, silvery mole-rats exhibit sex differences, and Damaraland mole-rats are intermediate. Conclusions/Significance The lack of sex differences in naked mole-rats is not an attribute of all African mole-rats, but appears to have evolved in relation to their unusual social structure and reproductive biology. PMID:19829697

  20. Rat leucocyte response to the bites of rat fleas (Siphonaptera: Pulicidae).

    PubMed

    Vaughan, J A; Jerse, A E; Azad, A F

    1989-09-01

    The host response to bites of the oriental rat flea, Xenopyslla cheopis Rothschild, was investigated by examining rat blood leucocyte kinetics, histopathology, and the effect that the host response had upon subsequent flea feeding and longevity. Test rats were subjected to controlled exposures of fleas, and leucocyte data from test rats were compared to those of unexposed controls. Of the five leucocyte types examined, only the basophil appeared to play a role in the host blood response to flea bites. Significant increases in blood basophil levels occurred 2-3 d after exposure but subsided to control levels within a week. However, flea feeding did not produce histopathology at the flea feeding sites nor did the basophilic blood response of rats affect subsequent feeding or longevity of the fleas.

  1. Reduced T cell response in carcinogen-sensitive Donryu rats compared with carcinogen-resistant DRH rats.

    PubMed

    Mise-Omata, S; Sugiura, T; Higashi, K; Yamashita, U

    1999-12-01

    Carcinogen-resistant DRH rats were developed from carcinogen-sensitive Donryu rats, which showed a high incidence of hepatic tumors when they were exposed to 3'-methyl-4-dimethyl-amino-azobenzene (3'-MeDAB4) or other aminoazo hepatocarcinogens. In order to study the mechanism of the difference of carcinogenesis, we studied the immunological competence of Donryu rats compared with that of DRH rats. Anti-keyhole limpet hemocyanin (KLH) antibody and KLH-specific delayed hypersensitivity (DTH) responses after immunization with KLH were reduced in Donryu rats compared with DRH rats. Proliferative responses of spleen cells to KLH and nonspecific mitogens such as conconavalin A (Con A) and phytohemagglutinin (PHA) were significantly lower in Donryu rats than in DRH rats. Upon the cross-linking of T cell receptor (TCR) complex using anti-CD3 monoclonal antibody (Mab), spleen cells from Donryu rats proliferated poorly. Two other strains of rats, SD and Wistar, exhibited high responsiveness, comparable to that of DRH rats, indicating that the responsiveness of Donryu rats was impaired. The production of interleukin-2 (IL-2) upon stimulation with Con A and the responsiveness of Con A blasts to exogenous IL-2 were also attenuated in Donryu rats. In contrast to T cell responsiveness, natural killer (NK) cell activity of spleen was increased in Donryu rats. Flow cytometric analysis revealed that the expression of CD4 and CD8 on T cells was decreased in Donryu rats, though the expression of other T cell markers such as CD2, CD3 and CD5 was not different. These results indicate that Donryu rats, which have been used in many years for cancer research in Japan, have impaired immunological surveillance mechanisms. This is likely to be one of the factors accounting for the high sensitivity to chemical carcinogens and the high susceptibility to transplanted tumor cells of Donryu rats.

  2. National BioResource Project-Rat and related activities.

    PubMed

    Serikawa, Tadao; Mashimo, Tomoji; Takizawa, Akiko; Okajima, Ryoko; Maedomari, Naoki; Kumafuji, Kenta; Tagami, Fumi; Neoda, Yuki; Otsuki, Mito; Nakanishi, Satoshi; Yamasaki, Ken-ichi; Voigt, Birger; Kuramoto, Takashi

    2009-07-01

    In order to establish a system to facilitate the systematic collection, preservation, and provision of laboratory rats (Rattus norvegicus) and their derivates, the National BioResource Project-Rat (NBRP-Rat) was launched in July 2002. By the end of 2008, more than 500 rat strains had been collected and preserved as live animals, embryos, or sperm. These rat resources are supplied to biomedical scientists in Japan as well as in other countries. This review article introduces NBRP-Rat and highlights the phenome project, recombinant inbred strains, BAC clone libraries, and the ENU-mutant archive, named the Kyoto University Rat Mutant Archive (KURMA). The future direction of rat resources are also discussed.

  3. 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.

  4. Expression of oxytocin receptor in diabetic rat penis.

    PubMed

    Li, M; Wang, T; Guo, S; Rao, K; Liu, J; Ye, Z

    2012-05-01

    Oxytocin receptor (OTR) expressed in the rat penis and mediated the contractility of the corpus cavernosum smooth muscle both in vitro and in vivo, and OTR could maintain penile detumescence; however, the expression of OTR in diabetic rat penis remains unknown. In the present study, we investigated the expression of OTR in diabetic rat penis. The experimental rats were randomly divided into control group and STZ-diabetic rats group. The expressions of mRNA and protein were examined by real-time quantitative PCR, Western blotting and immunohistochemistry respectively. Erectile function was evaluated by measuring intracavernous pressure following electrostimulation of the cavernous nerves. mRNA and protein expression of OTR significantly increased in diabetic rats group compared with the control group. Erectile function of diabetic rats group significantly decreased compared with the control group. Our data showed that the expression of OTR significantly increased in diabetic rats group and OTR may involve in the development of diabetic erectile dysfunction.

  5. Expression pattern of Mical-1 in the temporal neocortex of patients with intractable temporal epilepsy and pilocarpine-induced rat model.

    PubMed

    Luo, Jing; Xu, Yali; Zhu, Qiong; Zhao, Fenghua; Zhang, Ying; Peng, Xi; Wang, Wei; Wang, Xuefeng

    2011-11-01

    Mical-1 is a novel F-actin-disassembly factor that is critical in actin reorganization. It provides a molecular conduit through which actin reorganizes-a hallmark of cell morphological changes, including axon navigation. However, whether Mical-1 is involved in the epileptogenesis remains unknown. Here, we investigate Mical-1 expression pattern in patients with intractable temporal lobe epilepsy (TLE) and pilocarpine-induced rat model. We used double-labeled immunoflurescence, immunohistochemistry, and Western blotting to assess the location and expression of Mical-1 in temporal neocortex of patients with intractable TLE, and the expression pattern of Mical-1 at different time point in the hippocampus and temporal lobe cortex of the pilocarpine-induced rat model. Double-labeled immunofluorescence showed that Mical-1 was coexpressed with neuron-specific enolase (NSE) in the cytoplasm of neurons in temporal neocortex of patients with TLE and hippocampus of rat model. Faint and scattered immunoreactivity for Mical-1 in the neuron of temporal neocortex in TLE group, but strong immunoreactivity for Mical-1 was shown in control subjects. To quantitatively evaluate the Mical-1 immunoreactivity, we measured the mean optical density (OD) of Mical-1. In the hippocampus of pilocarpine-induced rat model, the OD values transient increased at 6 h after seizure then decreased from 1 day to 14 days, and returned to a subnormal level at 60 days. The lowest level of Mical-1 expression occurred at 14 days after seizure in the hippocampus. In the temporal lobe cortex of rat model, the OD values decreased at all time point after kindling compared to the normal group. Furthermore, our Western blot analysis confirmed these expression patterns of Mical-1 from latent stage to chronic stage. Our results indicate that in patients with TLE and pilocarpine-induced rat model, the expression of Mical-1 were followed a downtrend from the latent stage to chronic stage after seizure evoke. Thus, as

  6. Pulmonary effects of ultrafine and fine ammonium salts aerosols in healthy and monocrotaline-treated rats following short-term exposure.

    PubMed

    Cassee, F R; Arts, J H E; Fokkens, P H B; Spoor, S M; Boere, A J F; van Bree, L; Dormans, J A M A

    2002-12-01

    In the present study the effects of a 3-day inhalation exposure to model compounds for ambient particulate matter were investigated: ammonium bisulfate, ammonium ferrosulfate, and ammonium nitrate, all components of the secondary aerosol fraction of ambient particulate matter (PM), and carbon black (CB, model aerosol for primary PM). The objective of this study was to test the hypothesis that secondary model aerosols exert acute pulmonary adverse effects in rats, and that rats with pulmonary hypertension (PH), induced by monocrotaline (MCT), are more sensitive to these components than normal healthy animals. An additional aim was to test the hypothesis that fine particles exert more effects than ultrafines. Healthy and PH rats were exposed to ultrafine (mass median diameter [MMD] approximate, equals 0.07-0.10 microm; 4 x 10(5) particles/cm(3)) and fine (MMD approximate, equals 0.57-0.64 micro;m; 9 x 10(3) particles/cm(3)) ammonium aerosols during 4 h/day for 3 consecutive days. The mean mass concentrations ranged from 70 to 420 microg/m(3), respectively, for ultrafine ammonium bisulfate, nitrate, and ferrosulfate and from 275 to 410 microg/m(3) for fine-mode aerosols. In an additional experiment, simultaneous exposure to a fine CB aerosol (0.6 microm; 2-9 mg/m(3)) and ammonium nitrate (0.4-18 mg/m(3)) was performed. Bronchoalveolar lavage fluid (BALF) analysis and histopathological examination were performed on animals sacrificed 1 day after the last exposure. Histopathology of the lungs did not reveal test atmosphere-related abnormalities in either healthy or PH rats exposed to the ammonium salts, or to a combination of CB + nitrate. Alveolar macrophages in rats exposed to CB only revealed the presence of black material in their cytoplasm. There were no signs of cytotoxicity due to the aerosol exposures (as measured with lactate dehydrogenase [LDH], protein, and albumin contents in BALF). Macrophages were not activated after MCT treatment or the test atmospheres

  7. 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.

  8. The Metabolism of Tetralin in Fischer 344 Rats

    DTIC Science & Technology

    1986-04-01

    would die from the disease. The relevance of nephropathy observed in male rats exposed to various hydrocarbons to the occurrence of renal neoplasia in man...hydrocarbons develop dose-related nephropathies which are not observed in female rats and control rats or in the males and females of other animal...then held for long-term, post-exposure evaluation revealed tubular degeneration consistent with "old-rat nephropathy " (explained below). C. Chronic

  9. Behavioral Toxicological Studies of Pesticides in Laboratory Rats,

    DTIC Science & Technology

    Behavior, *Toxicology, *Pesticides, *Rats, Symposia, Laboratory tests, Toxicity, Insecticides, Exposure( General ), Dosage, Perception, Motor reactions, Learning, Military psychology , Military medicine

  10. 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

  11. Microdialysis of triamcinolone acetonide in rat muscle.

    PubMed

    Rojas, Cioli; Nagaraja, Nelamangala V; Webb, Alistair I; Derendorf, Hartmut

    2003-02-01

    The objective of this study was to compare plasma and muscle concentrations of triamcinolone acetonide (TA) in the rat by microdialysis. Microdialysis experiments were carried out at steady state in rats after an initial I.V. bolus 50 mg/kg of the phosphate ester of TA (TAP) followed by 23 mg/kg/h infusion. In vivo recovery was calculated by retrodialysis. The concentration determined at steady state in microdialysate, corrected for recovery, was 2.73 +/- 0.42 microg/mL compared to 21.9 +/- 2.3 microg/mL in plasma. The pharmacokinetics of TA in plasma was described by an open two-compartment model with a terminal half-life of 2.7 h. The clearance of TA in rats determined by compartmental analysis was 0.94 L/h/kg. The measured microdialysate levels of TA in muscle, corrected for recovery, were comparable to the predicted free drug levels in the peripheral compartment. Protein binding in rat plasma, measured by ultrafiltration, was 90.1%. The microdialysis in vivo recovery in muscle was similar to the in vitro recovery under stirred conditions. The results show the applicability of microdialysis to measure free tissue concentrations of TA in rats.

  12. 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.

  13. 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.

  14. The queer life of a lab rat.

    PubMed

    Pettit, Michael

    2012-08-01

    The laboratory rat is an important, if neglected, actor in the history of sexuality. From the 1920s and 1940s, a series of reports emerged from American psychology laboratories detailing instances of spontaneous "reversals" in sexual behavior within their rat colonies. Frank Beach, then at the American Museum of Natural History, developed a model for the "nature" of sexuality that stressed that all organisms had the neurological capacity to perform behavior of either sex. Beach enrolled his emerging specialty, behavioral endocrinology, in support of Alfred Kinsey's controversial findings. Both scientists highlighted the multitude of potential sexual outlets pursued by organisms and the prevalence of nonprocreative sexual behaviors. This article draws on elements of queer theory to elucidate how the landscape of the comparative psychologist's rat colony with its organisms, apparatus, practices, and rituals served an integral function in the redefinition of sex in the 20th century. Queer theory calls into question easy proclamations about what counts as natural or normal by drawing attention to the presumed binaries that frequently govern the classification of sex. The maintenance of the colony required the careful management of sex with its obstruction devices, hypersexualized indicator animals, segregation cages, and castrated rats injected with hormones. Moreover, Beach's own writings indicate how his own domestic life became entangled with the sex lives of the rats. An irony animates this Rockefeller-funded sexology: Research funded to elucidate the mechanisms underlying heterosexuality came to question its innateness and universality. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  15. 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

  16. 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.

  17. 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

  18. Distal interstitial epididymitis in young rats.

    PubMed

    Hoffmann, Guenther; Belote, Duane A; Suttie, Andrew W; Buetow, Bernard S; Muhumuza, Luke

    2015-04-01

    A sporadic, diffuse, interstitial mixed cell epididymitis of unknown etiology was noted in the epididymal cauda and distal corpus of young control Sprague-Dawley (SD) rats. Rats from 2 different suppliers were examined as part of routine toxicology studies. The incidence of this finding was 5/5 (study 1), 2/7 (study 2), and 2/7 (study 3). Although 2 of these studies partially overlapped temporally, none of the affected animals from any study was maintained concurrently with affected animals from any of the other 2 studies, and infectious causes, control article toxicity, or autoimmune processes were considered unlikely etiologies. Inflammation similar to that noted in the epididymides of these young rats was not present in other tissues and was not noted in study cohorts sacrificed at ages older than approximately 11 weeks or in rats of similar age from other concurrent studies. Similar findings were noted sporadically in historical control data, and consequently an age-related finding of unknown etiology and occurring in sporadic clusters is reported in SD rats ≤11 weeks old.

  19. Thalidomide decreases intrahepatic resistance in cirrhotic rats.

    PubMed

    Yang, Ying-Ying; Huang, Yi-Tsau; Lin, Han-Chieh; Lee, Fa-Yauh; Lee, Kuei-Chuan; Chau, Ga-Yang; Loong, Che-Chuan; Lai, Chiung-Ru; Lee, Shou-Dong

    2009-03-13

    Increased intrahepatic resistance (IHR) within cirrhotic liver is caused by increased endotoxemia, cytokines tumor necrosis factor-alpha (TNF-alpha), vasoconstrictor thromboxane A(2) (TXA(2)), and disrupted microvasculatures. We evaluated the effects of thalidomide-related inhibition of TNF-alpha upon the hepatic microcirculation of cirrhosis in rats. Portal venous pressure (PVP), hepatic TNF-alpha, expression of thromboxane synthase (TXS), and leukocyte common antigen (LCA) were measured in bile-duct-ligated (BDL) rats receiving 1 month of thalidomide (BDL-thalido rats). Portal perfusion pressure (PPP), IHR, and hepatic TXA(2) production were measured in the isolated liver perfusion system. Intravital microscopy was used to examine hepatic microvascular disruptions. In BDL-thalido rats, PVP, PPP, IHR, hepatic TXA(2) and TNF-alpha, hydroxyproline content, expression of TXS and LCA, and LPS-induced leukocyte recruitment were significantly decreased. Conversely, hepatic microvascular density and perfused sinusoids were significantly increased. Thalidomide decreased PVP and IHR by reducing hepatic TXA(2) and improving hepatic microvascular disruptions in rats with biliary cirrhosis.

  20. Diabetic rat testes: morphological and functional alterations.

    PubMed

    Ricci, G; Catizone, A; Esposito, R; Pisanti, F A; Vietri, M T; Galdieri, M

    2009-12-01

    Reproductive dysfunction is a consequence of diabetes, but the underlying mechanisms are poorly understood. This study investigated the histological and molecular alterations in the testes of rats injected with streptozotocin at prepuperal (SPI rats) and adult age (SAI rats) to understand whether diabetes affects testicular tissue with different severity depending on the age in which this pathological condition starts. The testes of diabetic animals showed frequent abnormal histology, and seminiferous epithelium cytoarchitecture appeared altered as well as the occludin distribution pattern. The early occurrence of diabetes increased the percentage of animals with high number of damaged tubules. The interstitial compartment of the testes was clearly hypertrophic in several portions of the organs both in SPI and SAI rats. Interestingly, fully developed Leydig cells were present in all the treated animals although abnormally distributed. Besides the above-described damages, we found a similar decrease in plasma testosterone levels both in SPI and SAI rats. Oxidative stress (OS) is involved in the pathogenesis of various diabetic complications, and in our experimental models we found that manganese superoxide dismutase was reduced in diabetic animals. We conclude that in STZ-induced diabetes, the altered spermatogenesis, more severe in SPI animals, is possibly due to the effect of OS on Leydig cell function which could cause the testosterone decrease responsible for the alterations found in the seminiferous epithelium of diabetic animals.

  1. Left ventricular volumetric conductance catheter for rats.

    PubMed

    Ito, H; Takaki, M; Yamaguchi, H; Tachibana, H; Suga, H

    1996-04-01

    Left ventricular (LV) volume (V) is an essential parameter for assessment of the cardiac pump function. Measurement of LVV in situ by a conductance catheter method has been widely used in dogs and humans but not yet in small experimental animals such as rats. We instituted a miniaturized six-electrode conductance catheter (3-F) for rat LVV measurement and its signal processing apparatus. We compared stroke volumes (SVs) simultaneously measured with this conductance catheter introduced into the LV through the apex and an electromagnetic flow probe placed on the ascending aorta during gradual decreases in LVV by an inferior vena caval occlusion. A high and linear correlation (r = 0.982) was obtained between these differently measured by SVs pooled from six rats. In another group of three rats, LV pressure was simultaneously measured with a 3-F catheter-tip micromanometer introduced into the LV through the apex. We obtained the slope of the end-systolic pressure-volume (P-V) relationship (Emax) by a gradual ascending aortic occlusion. After administration of propranolol, Emax obviously decreased with no change in volume intercept of the P-V relationship. The conductance volumetry proved to be useful in rats.

  2. Photoperiodic control of reproduction in olfactory-bulbectomized rats.

    PubMed

    Nelson, R J; Zucker, I

    1981-05-01

    30-day-old male rats were (1) sham-operated or subjected to (2) removal of the olfactory bulbs, (3) olfactory bulbectomy and blinding (4) olfactory bulbectomy and pinealectomy or (5) olfactory bulbectomy, blinding and pinealectomy. Animals were exposed from 30 to 110 days of age to long-day (14 h of light per day) or short-day (8 h of light per day) photoperiods. The reproductive system of neurologically-intact rats was not affected by exposure to short days. Nor did bulbectomy affect the reproductive system of rats exposed to long days. However, bulbectomized, short-day rats had significantly lower body weights, reduced testicular and seminal vesicle weights and lower plasma testosterone levels than did bulbectomized, long-day rats. The effects of short-day exposure on bulbectomized rats were prevented by pinealectomy. Short-day exposure and blinding exerted similar effects in bulbectomized rats. The testes of rats from all groups contained elongated spermatids; blinding and short-day treatment had no effect on spermatogenesis. Neither mating behavior nor the number of young sired was influenced by photoperiod in bulbectomized or intact rats. Removal of the olfactory bulbs unmasks photoperiodic responsiveness in rats; the antigonadal effects of short-day exposure are mediated by the pineal gland in bulbectomized rats as in species traditionally designated photoperiodic. The mechanisms by which bulbectomy renders rats responsive to short days are considered.

  3. 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.

  4. 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/...

  5. INORGANIC CATIONS IN RAT KIDNEY

    PubMed Central

    Tandler, C. J.; Kierszenbaum, A. L.

    1971-01-01

    For localization of pyroantimonate-precipitable cations, rat kidney was fixed by perfusion with a saturated aqueous solution of potassium pyroantimonate (pH about 9.2, without addition of any conventional fixative). A remarkably good preservation of the tissue and cell morphology was obtained as well as a consistent and reproducible localization of the insoluble antimonate salts of magnesium, calcium, and sodium. All proximal and distal tubules and glomeruli were delimited by massive electron-opaque precipitates localized in the basement membrane and, to a lesser extent, in adjacent connective tissue. In the intraglomerular capillaries the antimonate precipitate was encountered in the basement membranes and also between the foot processes. In addition to a more or less uniform distribution in the cytoplasm and between the microvilli of the brush border, antimonate precipitates were found in all cell nuclei, mainly between the masses of condensed chromatin. The mitochondria usually contained a few large antimonate deposits which probably correspond to the so-called "dense granules" observed after conventional fixations. PMID:4106544

  6. Chronotoxicity of nedaplatin in rats.

    PubMed

    Cui, Yimin; Sugimoto, Koh-Ichi; Kawai, Yoshiko; Sudoh, Toshiaki; Gemba, Munekazu; Fujimura, Akio

    2004-07-01

    Chronotoxicologic profiles of nedaplatin, a platinum compound, were evaluated in rats maintained under a 12 light/12 dark cycle with light from 07:00h to 19:00 h. Nedaplatin (5 mg/kg) was injected intravenously, once a week for 5 weeks at 08:00h or 20:00h. The suppression of body weight gain and reduction of creatinine clearance were significantly greater with the 20:00h than 08:00h treatment. Accumulation of nedaplatin in the renal cortex and bone marrow were also greater with 20:00 h treatment. There were significant relationships between the nedaplatin content in the kidney and bone marrow and degree of injury to each. These results suggest that the nedaplatin-induced toxicity depends on its dosing-time, and it is greater with treatment at 20:00 h, during the active phase. The dosing-time dependency in the accumulation of nedaplatin in the tissue of the organs might be involved in this chronotoxicologic phenomenon.

  7. Establishment of rat embryonic stem cells and making of chimera rats.

    PubMed

    Ueda, Shinobu; Kawamata, Masaki; Teratani, Takumi; Shimizu, Taku; Tamai, Yoshitaka; Ogawa, Hiromasa; Hayashi, Katsuyuki; Tsuda, Hiroyuki; Ochiya, Takahiro

    2008-07-30

    The rat is a reference animal model for physiological studies and for the analysis of multigenic human diseases such as hypertension, diabetes, neurological disorders, and cancer. The rats have long been used in extensive chemical carcinogenesis studies. Thus, the rat embryonic stem (rES) cell is an important resource for the study of disease models. Attempts to derive ES cells from various mammals, including the rat, have not succeeded. Here we have established two independent rES cells from Wister rat blastocysts that have undifferentiated characters such as Nanog and Oct3/4 genes expression and they have stage-specific embryonic antigen (SSEA) -1, -3, -4, and TRA-1-81 expression. The cells were successfully cultured in an undifferentiated state and can be possible over 18 passages with maintaining more than 40% of normal karyotype. Their pluripotent potential was confirmed by the differentiation into derivatives of the endoderm, mesoderm, and ectoderm. Most importantly, the rES cells are capable of producing chimera rats. Therefore, we established pluripotent rES cell lines that are widely used to produce genetically modified experimental rats for study of human diseases.

  8. Origins of albino and hooded rats: implications from molecular genetic analysis across modern laboratory rat strains.

    PubMed

    Kuramoto, Takashi; Nakanishi, Satoshi; Ochiai, Masako; Nakagama, Hitoshi; Voigt, Birger; Serikawa, Tadao

    2012-01-01

    Albino and hooded (or piebald) rats are one of the most frequently used laboratory animals for the past 150 years. Despite this fact, the origin of the albino mutation as well as the genetic basis of the hooded phenotype remained unclear. Recently, the albino mutation has been identified as the Arg299His missense mutation in the Tyrosinase gene and the hooded (H) locus has been mapped to the ∼460-kb region in which only the Kit gene exists. Here, we surveyed 172 laboratory rat strains for the albino mutation and the hooded (h) mutation that we identified by positional cloning approach to investigate possible genetic roots and relationships of albino and hooded rats. All of 117 existing laboratory albino rats shared the same albino missense mutation, indicating they had only one single ancestor. Genetic fine mapping followed by de novo sequencing of BAC inserts covering the H locus revealed that an endogenous retrovirus (ERV) element was inserted into the first intron of the Kit gene where the hooded allele maps. A solitary long terminal repeat (LTR) was found at the same position to the ERV insertion in another allele of the H locus, which causes the so called Irish (h(i)) phenotype. The ERV and the solitary LTR insertions were completely associated with the hooded and Irish coat patterns, respectively, across all colored rat strains examined. Interestingly, all 117 albino rat strains shared the ERV insertion without any exception, which strongly suggests that the albino mutation had originally occurred in hooded rats.

  9. Effects of corticotropin releasing factor on spontaneous burst activity in the piriform-amygdala complex of in vitro brain preparations from newborn rats.

    PubMed

    Fujii, Tomoko; Onimaru, Hiroshi; Homma, Ikuo

    2011-10-01

    The amygdala is an important higher regulatory center of the autonomic nervous system, involved in respiratory and cardiovascular control, and it also plays a role in the formation of emotions. Corticotropin-releasing factor (CRF) is a neuropeptide involved in stress responses. We have examined the effects of CRF on the spontaneous burst activity in the piriform-amygdala complex of rat brain preparations in vitro. Limbic-brainstem-spinal cord preparations of 0- to 1-day-old Wistar rats were isolated under deep ether anesthesia, and were superperfused in a modified Krebs solution. Bath application of 50nM CRF substantially increased the frequency of burst activity in the piriform-amygdala complex, whereas this polypeptide exerted only minor effects on C4 inspiratory activity. The excitatory effect of CRF on the amygdala burst was effectively blocked by the CRF1 antagonist, antalarmin, but not the CRF2 antagonist, astressin-2B, suggesting that CRF1 mediated the excitatory effect. The spatio-temporal pattern of the burst activity according to optical recordings was basically identical to the controls; the burst activity initially appeared in the piriform cortex and then propagated to the amygdala. The present experimental model could be useful for the study of role of the limbic system, including the amygdala, in stress responses.

  10. Spontaneous oscillatory burst activity in the piriform-amygdala region and its relation to in vitro respiratory activity in newborn rats.

    PubMed

    Onimaru, H; Homma, I

    2007-01-05

    The amygdala is important for the formation of emotions that are affected by olfactory information. The piriform cortex is involved in information processing related to olfaction. To investigate functional interactions between the piriform cortex and amygdala and their relation to medullary respiratory activity, we developed a novel in vitro preparation including the limbic system, brainstem, and spinal cord of newborn rats. With the use of optical and electrophysiologic recordings, we analyzed spontaneous neuronal activity in the piriform-amygdala complex in limbic-brainstem-spinal cord preparations from 0- to 1-day-old rats. For optical recordings, the preparation was stained with a voltage-sensitive dye, and inspiratory activity was monitored from the fourth cervical (C4) ventral root. Spontaneous oscillatory burst activity (up to 10/min) was detected from the rostral cut surface of limbic and para-limbic regions including the piriform cortex and amygdala. The burst activity initially appeared in the piriform cortex and then propagated to the amygdala. We averaged the imaging data in the limbic area with the use of C4 inspiratory activity as a trigger signal. The results suggest functional coupling of the rhythmic burst activity in the piriform-amygdala complex to medullary inspiratory activity, which was confirmed electrophysiologically by cross-correlation analysis of these signals. This rhythmic burst activity may be involved in the development of neuronal circuits that process information related to olfaction, emotion, and respiration.

  11. In vivo cell lineage analysis during chemical hepatocarcinogenesis in rats using retroviral-mediated gene transfer: evidence for dedifferentiation of mature hepatocytes.

    PubMed

    Gournay, Jérôme; Auvigne, Isabelle; Pichard, Virginie; Ligeza, Catherine; Bralet, Marie-Pierre; Ferry, Nicolas

    2002-06-01

    Feeding adult rats with a diet containing 2-acetylaminofluorene (2-AAF) results in suppression of hepatocyte proliferation and stimulation of oval cell proliferation. Although oval cells may be facultative liver stem cells, the actual relationship between oval cells and liver cancer has not been clearly established in vivo. Our goal was to label hepatic cells in vivo using retroviral vectors and follow their fate during the early steps of chemically induced hepatocarcinogenesis. Oval cell proliferation was induced by continuous feeding with a carcinogenic diet containing 2-AAF. We used two different strategies to genetically label hepatic cells: (a) labeling of proliferating cells in rats fed 2-AAF by injecting recombinant retroviral vectors containing the beta-galactosidase gene either in a peripheral vein or in the common bile duct at the peak of oval cell proliferation and (b) prelabeling of hepatocytes by intravenously injecting recombinant vectors 1 day after partial hepatectomy and 1 week before subsequent administration of 2-AAF. Using the first strategy, transgene expression occurred in both oval cells and hepatocytes. Using the second strategy, we could selectively label, and hence study the fate of, differentiated hepatocytes. In the latter case, we observed clusters of beta-galactosidase-positive hepatocytes, some of them also expressing preneoplastic markers such as gamma-glutamyl transpeptidase as well as the placental form of glutathione-S-transferase. These results demonstrate that preneoplastic foci can originate from mature hepatocytes and are consistent with the hypothesis that dedifferentiation of mature hepatocytes may occur during the course of carcinogenic regimen.

  12. Activation of mammalian target of rapamycin contributes to pain nociception induced in rats by BmK I, a sodium channel-specific modulator.

    PubMed

    Jiang, Feng; Hua, Li-Ming; Jiao, Yun-Lu; Ye, Pin; Fu, Jin; Cheng, Zhi-Jun; Ding, Gang; Ji, Yong-Hua

    2014-02-01

    The mammalian target of rapamycin (mTOR) pathway is essential for maintenance of the sensitivity of certain adult sensory neurons. Here, we investigated whether the mTOR cascade is involved in scorpion envenomation-induced pain hypersensitivity in rats. The results showed that intraplantar injection of a neurotoxin from Buthus martensii Karsch, BmK I (10 μg), induced the activation of mTOR, as well as its downstream molecules p70 ribosomal S6 protein kinase (p70 S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), in lumbar 5-6 dorsal root ganglia neurons on both sides in rats. The activation peaked at 2 h and recovered 1 day after injection. Compared with the control group, the ratios of p-mTOR/p-p70 S6K/p-4EBP1 in three types of neurons changed significantly. The cell typology of p-mTOR/p-p70 S6K/p-4E-BP1 immuno-reactive neurons also changed. Intrathecal administration of deforolimus, a specific inhibitor of mTOR, attenuated BmK I-induced pain responses (spontaneous flinching, paroxysmal pain-like behavior, and mechanical hypersensitivity). Together, these results imply that the mTOR signaling pathway is mobilized by and contributes to experimental scorpion sting-induced pain.

  13. Gonadotropin-releasing hormone treatment improves locomotor activity, urinary function and neurofilament protein expression after spinal cord injury in ovariectomized rats.

    PubMed

    Calderón-Vallejo, Denisse; Quintanar, J Luis

    2012-05-02

    It was reported that the hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH) produces neurotrophic effects and that the spinal cord possesses GnRH receptors. The aim of the present study was to determine whether administration of GnRH improves locomotor activity, urinary function and neurofilament (NFs) protein expression after spinal cord injury (SCI) in ovariectomized rats. SCI was induced by balloon inflation model resulting in paraplegia. Locomotion was evaluated according to the Basso, Beattie, and Bresnahan Scale. Rats were subjected to bladder compression, twice daily until bladder reflex was established. NFs of 68, 160 and 200 kDa from spinal cords were analyzed by electrophoresis. GnRH (60 μg/kg) or physiologic NaCl solution was administered at 1 day after SCI and then daily for 15 days and the functional evaluation was realized for 5 weeks. Our results indicate that locomotor activity, restoration of urinary dysfunction and NFs expression of 160 and 200 kDa were improved in SCI animals given GnRH compared to those without treatment. These findings suggest that GnRH acts as a neurotrophic factor and may be used as a potential therapeutic agent for treatment of SCI.

  14. The effect of short-term and long-term femoral artery ligation on rat calf muscle oxygen tension, blood flow, metabolism and function.

    PubMed

    Angersbach, D; Jukna, J J; Nicholson, C D; Ochlich, P; Wilke, R

    1988-01-01

    The effect of short-term (1 day-1 week) and long-term (6-12 weeks) femoral artery ligation on the oxygen tension (pO2), blood flow, metabolism and function of rat gastrocnemius muscle has been examined. Femoral artery ligation reduced resting blood flow, pO2 and pH. Concomitantly, the concentration of high energy phosphates was reduced and the muscle lactate concentration increased. The fatigue developed by the gastrocnemius/plantaris muscle, during a 10 min period of isometric exercise, was increased and the associated hyperaemia was attenuated. The surgery, performed to ligate the artery, induced an increase in the plasma fibrinogen concentration and whole blood viscosity. As the time interval increased after the femoral artery ligation there was a progressive reduction of the magnitude of the effects. Ten weeks after ligation resting muscle concentrations of high energy phosphates and lactate, whole blood viscosity and muscle pH had normalized. However, resting muscle blood flow, pO2, ability to sustained isometric exercise and the exercise induced hyperaemia were still reduced compared to intact animals. Comparison with literature data reveals that the changes produced by chronic femoral artery ligation in rat calf muscle mimic those seen in man with intermittent claudication.

  15. 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)

  16. 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.

  17. 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

  18. Circadian rhythms of pineal function in rats.

    PubMed

    Binkley, S A

    1983-01-01

    In pineal glands melatonin is synthesized daily. Melatonin synthesis in rats kept in most light-dark cycles occurs during the subjective night. This rhythm, which persists in constant dark, is a circadian rhythm which may be a consequence of another circadian rhythm in the pineal gland, of N-acetyltransferase activity (NAT). The NAT rhythm has been studied extensively in rats as a possible component of the system timing circadian rhythms. The NAT rhythm is driven by neural signals transmitted to the pineal gland by the sympathetic nervous system. Environmental lighting exerts precise control over the timing of the NAT rhythm. In rats, there is enough data to describe a daily time course of events in the pineal gland and to describe a pineal "life history." Hypothetical schemes for generation of the NAT rhythm and for its control by light are presented.

  19. Promotion of rat hepatocarcinogenesis by praziquantel.

    PubMed

    Shirai, T; Joong, K D; Hakoi, K; Thamavit, W; Pairojkul, C; Hoshiya, T; Hasegawa, R; Ito, N

    1991-10-01

    Praziquantel, the widely used anti-helminthic agent, was investigated for hepatocarcinogenesis-promoting potential using a medium-term liver bioassay system for carcinogens. F344 male rats were given a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg) and then starting 2 weeks later, received praziquantel in the diet at concentrations of 1.5 or 0.5%, or intragastrically at a dose of 1,500 mg/kg once a week for 6 weeks. Control groups received DEN or praziquantel alone. All rats were subjected to two-thirds partial hepatectomy at week 3 and killed at week 8. Development of glutathione S-transferase placental form-positive foci in the liver was significantly increased in terms of both number and area with the 1.5% dose, while only area was affected by the 0.5% dose. The results thus indicate that praziquantel at high dose has promoting potential in rat hepatocytic tumorigenesis.

  20. Toxicological studies on tienilic acid in rats.

    PubMed

    Oker-Blom, C; Mäkinen, J; Gothoni, G

    1980-07-01

    The subacute oral toxicity of tienilic acid in male and female Sprague--Dawley rats has been studied. Animals were given tienilic acid 0, 30, 120 and 480 mg/kg body weight as a 3% gum arabic suspension for 28 days. At 30 mg tienilic acid blood pressure and serum uric acid decreased. At the two higher dose-levels a slight decrease in hemoglobin and an increase in S-GPT was noticed and there was a significant increase in the liver weight and serum magnesium concentration of male rats, while the liver weight of female rats increased only slightly. On microscopic examination, unicellular necrosis of small groups of liver cells was noted, together with focal round-cell infiltration and some stasis of the two higher dose-levels in some animals. Tienilic acid had no noticeable effects on other organs or parameters.

  1. 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.

  2. Immunologically induced peliosis hepatis in rats.

    PubMed

    Husztik, E; Lázár, G; Szabó, E

    1984-06-01

    Peliosis hepatis has been induced immunologically with anti-rat glomerular basal membrane rabbit serum in rats pre-sensitized with a rare earth metal complex, neodymium pyrocatechin disulphonate (NPD). This is the first experimental evidence that peliosis hepatis may develop as a result of an immunological process. It is noteworthy that in this experimental form of peliosis hepatis and in that observed earlier in rats treated with basic polyglutamic acid derivatives, severe defibrination was detected and, as in most human cases, not only the liver but other organs were also involved in the peliotic lesions. Since the rare earth metal compounds, among them the pyrocatechin disulphonate complex of neodymium, depress the reticulo-endothelial activity, a role of the reticulo-endothelial system in the pathogenesis of this experimental form of peliosis hepatis is suggested.

  3. 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.

  4. Acclimation to decompression sickness in rats.

    PubMed

    Montcalm-Smith, E A; McCarron, R M; Porter, W R; Lillo, R S; Thomas, J T; Auker, C R

    2010-03-01

    Protection against decompression sickness (DCS) by acclimation to hyperbaric decompression has been hypothesized but never proven. We exposed rats to acclimation dives followed by a stressful "test" dive to determine whether acclimation occurred. Experiments were divided into two phases. Phase 1 rats were exposed to daily acclimation dives of hyperbaric air for 30 min followed by rapid decompression on one of the following regimens: 70 ft of seawater (fsw) for 9 days (L70), 70 fsw for 4 days (S70), 40 fsw for 9 days (L40), 40 fsw for 4 days (S40), or unpressurized sham exposure for 9 days (Control). On the day following the last exposure, all were subjected to a "test" dive (175 fsw, 60 min, rapid decompression). Both L70 and S70 rats had significantly lower incidences of DCS than Control rats (36% and 41% vs. 62%, respectively). DCS incidences for the other regimens were lower than in Control rats but without statistical significance. Phase 2 used the most protective regimen from phase 1 (L70); rats were exposed to L70 or a similar regimen with a less stressful staged decompression. Another group was exposed to a single acclimation dive (70 fsw/30 min) on the day before the test dive. We observed a nonsignificant trend for the rapidly decompressed L70 dives to be more protective than staged decompression dives (44% vs. 51% DCS incidence). The single acclimation dive regimen did not provide protection. We conclude that protection against DCS can be attained with acclimating exposures that do not themselves cause DCS. The deeper acclimation dive regimens (70 fsw) provided the most protection.

  5. Pinealectomy aggravates acute pancreatitis in the rat.

    PubMed

    Jaworek, Jolanta; Zwirska-Korczala, Krystyna; Szklarczyk, Joanna; Nawrot-Porąbka, Katarzyna; Leja-Szpak, Anna; Jaworek, Andrzej K; Tomaszewska, Romana

    2010-01-01

    Melatonin, a pineal indoleamine, protects the pancreas against acute damage; however, the involvement of the pineal gland in the pancreatoprotective action of melatonin is unknown. The primary aim of this study was to determine the effects of pinealectomy on the course of acute caerulein-induced pancreatitis (AP) in rats. AP was induced by a subcutaneous infusion of caerulein (25 μg/kg) into pinealectomized or sham-operated animals. Melatonin (5 or 25 mg/kg) was given via intraperitoneal (ip) injection 30 min prior to the induction of AP. The pancreatic content of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal (MDA + 4HNE) and the activity of an antioxidative enzyme, glutathione peroxidase (GSH-Px), were measured in each group of rats. Melatonin blood levels were measured by radioimmunoassay (RIA). In the sham-operated rats, AP was confirmed with histological examination and manifested as pancreatic edema and an increase in the blood lipase level (by 1,500%). In addition, the pancreatic content of MDA+ 4HNE was increased by 200%, and pancreatic glutathione peroxydase (GSH-Px) activity was reduced by 40%. Pinealectomy significantly aggravated the histological manifestations of AP, reduced the GSH-Px activity and markedly augmented the levels of MDA+ 4HNE in the pancreas of rats with or without AP as compared to sham-operated animals. Melatonin was undetectable in the blood of the pinealectomized rats with or without AP. Treatment with melatonin (25 mg/kg, ip) prevented the development of AP in the sham-operated rats and significantly reduced pancreatic inflammation in the animals previously subjected to pinealectomy. In conclusion, pineal melatonin contributes to the pancreatic protection through the activation of the antioxidative defense mechanism in pancreatic tissue as well as its direct antioxidant effects.

  6. [Berberine inhibits cardiac fibrosis of diabetic rats].

    PubMed

    Lu, Kun; Shen, Yongjie; He, Jinfeng; Liu, Guoling; Song, Wei

    2016-10-01

    Objective To explore the effect of berberine on cardiac fibrosis of diabetic rats by observing the expressions of serum transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) , collagen type 1 (Col1) and collagen type 3 (Col3) in myocardial tissues of diabetic rats after berberine treatment. Methods The diabetic model was induced by intraperitoneal injection of streptococci (STZ). Forty-three diabetic rats were randomly divided into diabetic model group (n=9), berberine treated groups of different doses [50, 100, 150 mg/(kg.d), gavage administration for 12 weeks; n=9, 9, 8 respectively], and metformin group as positive control (n=8); other 8 normal rats served as a negative control group. After the last administration, fasting blood glucose, left ventricular systolic pressure (LVSP) and left ventricular end diastolic pressure (LVEDP) were measured; rats' heart were taken to calculate the heart mass index (HMI); ELISA was used to detect the serum levels of TGF-β1 and CTGF; collagenous fibers in cardiac tissues were tested by Masson staining; collagen volume fraction (CVF) was measured by image analysis; Col1 and Col3 in cardiac tissues were determined by Western blotting. Results Compared with the normal control group, the fasting blood glucose, LVSP, LVEDP absolute value, HMI, the degree of cardiac fibrosis, the expressions of TGF-β1, CTGF, Col1 and Col3 significantly increased in the model group. All indexes mentioned above were reduced obviously in berberine treated groups of 100 and 150 mg/(kg.d). Conclusion Berberine improves cardiac fibrosis in diabetic rats through down-regulating the expressions of TGF-β1 and CTGF and reducing the synthesis and deposition of Col1 and Col3.

  7. 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.

  8. Disturbed patterns of behaviour in morphine tolerant and abstinent rats

    PubMed Central

    Kumar, R.; Mitchell, E.; Stolerman, I. P.

    1971-01-01

    1. Eating, drinking and spontaneous motor activity were studied in rats receiving large daily doses of morphine. These forms of behaviour were largely suppressed when the rats were made abstinent and were restored when morphine was given again. 2. Compensation for depressions of behaviour during abstinence did not seem sufficient to account for all the stimulant effects of morphine in tolerant rats. Morphine also had slight stimulant actions in non-tolerant rats. 3. In tolerant rats, the repeated pairing of the effects of morphine with the re-emergence of behaviour such as eating and drinking may intensify the rewarding value of the drug. PMID:5105387

  9. 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.

  10. Glycoconjugate in rat taste buds.

    PubMed

    Kano, K; Ube, M; Taniguchi, K

    2001-05-01

    The taste buds of the fungiform papillae, circumvallate papilla, foliate papillae, soft palate and epiglottis of the rat oral cavity were examined by lectin histochemistry to elucidate the relationships between expression of glycoconjugates and innervation. Seven out of 21 lectins showed moderate to intense staining in at least more than one taste bud. They were succinylated wheat germ agglutinin (s-WGA). Dolichos biflorus agglutinin (DBA), Bandeiraea simplicifolia lectin-I (BSL-I), Ricinus communis agglutinin-I (RCA-I), peanut agglutinin (PNA), Ulex europaeus agglutinin-I (UEA-I) and Phaseolus vulgaris agglutinin-L (PHA-L). UEA-I and BSL-I showed moderate to intense staining in all of the taste buds examined. They strongly stained the taste buds of the epiglottis, which are innervated by the cranial nerve X. UEA-I intensely stained the taste buds of the fungiform papillae and soft palate, both of which are innervated by the cranial nerve VII. The taste buds of circumvallate papilla and foliate papillae were innervated by the cranial nerve IX and strongly stained by BSL-I. Thus, UEA-I and BSL-I binding glycoconjugates, probably alpha-linked fucose and alpha-D-galactose, respectively, might be specific for taste buds. Although the expression of these glycoconjugates would be related to the innervation of the cranial nerve X, the differential expression of alpha-linked fucose and alpha-D-galactose might be related to the innervation of the cranial nerve VII and IX, respectively.

  11. Rat hepatitis E virus: geographical clustering within Germany and serological detection in wild Norway rats (Rattus norvegicus).

    PubMed

    Johne, Reimar; Dremsek, Paul; Kindler, Eveline; Schielke, Anika; Plenge-Bönig, Anita; Gregersen, Henrike; Wessels, Ute; Schmidt, Katja; Rietschel, Wolfram; Groschup, Martin H; Guenther, Sebastian; Heckel, Gerald; Ulrich, Rainer G

    2012-07-01

    Zoonotic hepatitis E virus (HEV) infection in industrialised countries is thought to be caused by transmission from wild boar, domestic pig and deer as reservoir hosts. The detection of HEV-specific antibodies in rats and other rodents has suggested that these animals may represent an additional source for HEV transmission to human. Recently, a novel HEV (ratHEV) was detected in Norway rats from Hamburg, Germany, showing the typical genome organisation but a high nucleotide and amino acid sequence divergence to other mammalian and to avian HEV strains. Here we describe the multiple detection of ratHEV RNA and HEV-specific antibodies in Norway rats from additional cities in north-east and south-west Germany. The complete genome analysis of two novel strains from Berlin and Stuttgart confirmed the association of ratHEV to Norway rats. The present data indicated a continuing existence of this virus in the rat populations from Berlin and Hamburg. The phylogenetic analysis of a short segment of the open reading frame 1 confirmed a geographical clustering of the corresponding sequences. Serological investigations using recombinant ratHEV and genotype 3 capsid protein derivatives demonstrated antigenic differences which might be caused by the high amino acid sequence divergence in the immunodominant region. The high amount of animals showing exclusively ratHEV RNA or anti-ratHEV antibodies suggested a non-persistent infection in the Norway rat. Future studies have to prove the transmission routes of the virus in rat populations and its zoonotic potential. The recombinant ratHEV antigen generated here will allow future seroepidemiological studies to differentiate ratHEV and genotype 3 infections in humans and animals.

  12. Cecal infusion of nutrients improves nutritional status of rats.

    PubMed

    Aghdassi, E; Raina, N; Allard, J P

    1995-11-01

    The role of colonic fermentation in providing energy was investigated in rats with small bowel transection (T) or 80% resection (SBR). Rats were randomized to receive for 12 d either saline (S) or the enteral solution (E) through a cecostomy to meet 30% of energy requirement; the rest (70%) was provided by parenteral nutrition. Although SBR-S rats lost weight significantly compared with d 1 of the study, SBR-E rats gained. Significantly greater carcass wet weight and fat were found in SBR-E and T-E rats compared with SBR-S and T-S rats. SBR-E and T-E rats had significantly greater colonic mucosal dry weight and protein compared with SBR-S and T-S rats. Cecal short-chain fatty acid (SCFA) contents were also significantly higher in SBR-E and T-E rats compared with SBR-S and T-S rats. There was no significant effect of surgery (T vs. SBR) on any of the variables studied. These results suggest that the products of fermentation of an enteral solution infused through a cecostomy contribute substantially to energy requirement, maintenance of body composition and nutritional status of rats.

  13. Renal Function and Hemodynamic Study in Obese Zucker Rats

    PubMed Central

    Park, Sung Kwang; Kang, Sung Kyew

    1995-01-01

    Objectives To investigate the renal function and hemodynamic changes in obesity and hyperinsulinemia which are characteristics of type II diabetes. Methods Studies were carried out in two groups of female Zucker rats. Group 1 rats were obese Zucker rats with hereditary insulin resistance. Group 2 rats were lean Zucker rats and served as controls. In comparison with lean Zucker rats, obese Zucker rats exhibited hyperinsulinemia but normoglycemia. Micropuncture studies and morphologic studies were performed in these rats. Results Functional studies showed that obese Zucker rats exhibited increases in kidney weight and GFR(obese Zucker, 1.23±.07)ml/min; lean Zucker, 0.93±.03ml/min). Micropuncture studies revealed that the increase in GFR in obese Zucker rats was attributable to the increases in the single nephron plasma flow rate and glomerular transcapillary hydraulic pressure. The glomerular ultrafiltration coefficient was the same in both groups. Morphologic studies revealed that the increase in GFR in obese Zucker rats was associated with an increase in glomerular volume. Conclusions These results suggest that obesity and hyperinsulinemia, which are the characteristics of type II diabetes, can be associated with glomerular hyperfiltration and glomerular capillary hypertension. PMID:7626557

  14. Quantification of tetrabromo benzoic acid and tetrabromo phthalic acid in rats exposed to the flame retardant Uniplex FPR-45.

    PubMed

    Silva, Manori J; Hilton, Donald; Furr, Johnathan; Gray, L Earl; Preau, James L; Calafat, Antonia M; Ye, Xiaoyun

    2016-03-01

    The first withdrawal of certain polybrominated diphenyl ethers flame retardants from the US market occurred in 2004. Since then, use of brominated non-PBDE compounds such as bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEH-TEBP) and 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) in commercial formulations has increased. Assessing human exposure to these chemicals requires identifying metabolites that can potentially serve as their biomarkers of exposure. We administered by gavage a dose of 500 mg/Kg bw of Uniplex FRP-45 (>95 % BEH-TEBP) to nine adult female Sprague-Dawley rats. Using authentic standards and mass spectrometry, we positively identified and quantified 2,3,4,5-tetrabromo benzoic acid (TBBA) and 2,3,4,5-tetrabromo phthalic acid (TBPA) in 24-h urine samples collected 1 day after dosing the rats and in serum at necropsy, 2 days post-exposure. Interestingly, TBBA and TBPA concentrations correlated well (R (2) = 0.92). The levels of TBBA, a known metabolite of EH-TBB, were much higher than the levels of TBPA both in urine and serum. Because Uniplex FRP-45 was technical grade and EH-TBB was present in the formulation, TBBA likely resulted from the metabolism of EH-TBB. Taken together, our data suggest that TBBA and TBPA may serve as biomarkers of exposure to non-PBDE brominated flame retardant mixtures. Additional research can provide useful information to better understand the composition and in vivo toxicokinetics of these commercial mixtures.

  15. Differential gene expression from microarray analysis distinguishes woven and lamellar bone formation in the rat ul