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Sample records for rats dipodomys species

  1. Kangaroo rats: intraspecific variation in Dipodomys spectabilis Merriam and Dipodomys deserti Stephens

    National Research Council Canada - National Science Library

    Nader, Iyad A

    1978-01-01

    Twenty morpholoigcl characters in addition to color were studied throughout the geographic range of two species of kangaroo rats, the banner-tailed kangaroo rat Dipodomys spectabilis and the desert...

  2. The effects of thyroxine on metabolism and water balance in a desert-dwelling rodent, Merriam's kangaroo rat (Dipodomys merriami).

    Science.gov (United States)

    Banta, Marilyn R; Holcombe, Dale W

    2002-01-01

    Desert-dwelling mammals such as Merriam's kangaroo rat (Dipodomys merriani) need to conserve both energy and water to survive desert conditions characterized by aridity and low productivity. The thyroid hormone thyroxine increases both basal metabolic rate and urinary water loss in mammals. Increases in basal metabolism and urinary water loss are likely to be detrimental to D. merriami, therefore the regulation of this hormone may be important. To examine the effects of thyroxine in this species, we implanted adult kangaroo rats with pellets designed to release specific doses of thyroxine at a constant rate for 90 days or a placebo pellet. We measured plasma thyroxine concentration, basal metabolic rate, food consumption, urine concentration and water loss in all implanted animals. Thyroxine implants significantly increased both plasma thyroxine and basal metabolic rate in a relatively dose-dependent manner. In response to thyroxine. kangaroo rats increased food consumption only slightly, but this small increase was sufficient to compensate for their elevated metabolic rates. Neither urine concentration nor water loss varied among treatment groups. Thyroxine increased energy expenditure but not water loss in this species.

  3. Endangered Species Program Naval Petroleum Reserves in California

    International Nuclear Information System (INIS)

    1992-02-01

    The Naval Petroleum Reserves in California (NPRC) are operated by the US Department of Energy (DOE). Construction and development activities, which are conducted by DOE at Naval Petroleum Reserve number-sign 1 (NPR-1) to comply with the Naval Petroleum Reserves Production Act of 1976 (Public Law 94-258), potentially threaten the continued existence of four federally-listed endangered species: the San Joaquin kit fox, (Vulpes macrotis mutica), blunt-nosed leopard lizard (Gambelia silus), giant kangaroo rat (Dipodomys ingens), and Tipton kangaroo rat (Dipodomys nitratoides nitratoides). All four are protected under the Endangered Species Act of 1973. The major objective of the Endangered Species Program on NPR-1 and NPR-2 is to provide DOE with the scientific expertise and continuity of programs necessary for continued compliance with the Endangered Species Act. The specific objective of this report is to summarize progress and results of the Endangered Species Program made during Fiscal Year 1990 (FY90)

  4. Endangered Species Program Naval Petroleum Reserves in California

    International Nuclear Information System (INIS)

    1992-03-01

    The Naval Petroleum Reserves in California (NPRC) are operated by the US Department of Energy (DOE) and Chevron USA. (CUSA). Four federally-listed endangered animal species and one threatened plant species are known to occur on NPRC: the San Joaquin kit fox (Vulpes macrotis mutica), blunt-nosed leopard lizard (Gambelia), giant kangaroo rat (Dipodomys ingens), Tipton kangaroo rat (Dipodomys nitratoides nitratoides) and Hoover's Wooly-star (Eriastrum hooveri). All five are protected under the Endangered Species Act of 1973 (as amended) (Public Law 93-205), which declares that it is the policy of Congress that all Federal departments and agencies shall seek to conserve endangered and threatened species and shall utilize their authorities in furtherance of the purposes of the Act. DOE is also obliged to determine whether actions taken by their lessees on Naval Petroleum Reserve No. 2 (NPR-2) will have any effects on endangered species or their habitats. The major objective of the Endangered Species Program on NPR-1 and NPR-2 is to provide DOE with the scientific expertise and continuity of programs necessary for the continued compliance with the Endangered Species Act. The specific objective of this report is to summarize progress and results of the Endangered Species Program made during Fiscal Year 1991 (FY91)

  5. Endangered Species Program, Naval Petroleum Reserves in California

    International Nuclear Information System (INIS)

    1992-12-01

    Naval Petroleum Reserve No. 1 (NPR-1) is operated by the U. S. Department of Energy (DOE) and Chevron USA (CUSA). Four federally-listed endangered animal species and one federally-threatened plant species are known to occur on the Naval Petroleum Reserves in California (NPRC): the San Joaquin kit fox (Vulpes velox macrotis), blunt-nosed leopard lizard (Gambelia silus), giant kangaroo rat (Dipodomys ingens), Tipton kangaroo rat (Dipodomys nitratoides nitratoides), and Hoover's wooly-star (Eriastrum hooveri). All five are protected under the Endangered Species Act of 1973 (as amended) (Public Law 93-205), which declaresthat it is the policy of Congress that all Federal departments and agencies shall seek to conserve endangered and threatened species and shall utilize their authorities in furtherance of the purposes of the Act. DOE is also obliged to determine whether actions taken by their lessees on Naval Petroleum Reserve No. 2 (NPR-2) will have any effects on endangered species or their habitats. The major objective of the EG ampersand G Energy Measurements, Inc. Endangered Species Program on NPR-1 and NPR-2 is to provide DOE with the scientific expertise and continuity of programs necessary for continued compliance with the Endangered SpeciesAct. The specific objective of this report is to summarize progress and results of the Endangered Species Program made during Fiscal Year 1992 (FY92)

  6. Influence of small-scale disturbances by kangaroo rats on Chihuahuan Desert ants

    Science.gov (United States)

    R. L. Schooley; B. T. Bestelmeyer; J. F. Kelly

    2000-01-01

    Banner-tailed kangaroo rats (Dipodomys spectabilis) are prominent ecosystem engineers that build large mounds that influence the spatial structuring of fungi, plants, and some ground-dwelling animals. Ants are diverse and functionally important components of arid ecosystems; some species are also ecosystem engineers. We investigated the effects of...

  7. Environmental Impact Analysis Process. Environmental Impact Statement, Flight Operations in the Sells Airspace Overlying the Tohono O’Odham Indian Reservation & Organ Pipe Cactus National Monument, Southern Arizona. Revised Draft

    Science.gov (United States)

    1986-06-06

    al. 1970. Endocrine and metabolic effects of noise in normal, hypertensive and psychotic subjects. IN: Physiological Effects of Noise. Welch, B. L...Perognathus baileyi Bannertail Kangaroo Rat Dipodomys spectabilis Cactus Mouse Peromyscus eremicus Canyon Mousea Peromyscus crinitus Desert Kangaroo Rat...Dipodomys deserti Desert Pocket Mouse Perognathus penicillatus Desert Woodrat Neotoma lepida Merriam Kangaroo Rat Dipodomys merriami Merriam Mouse

  8. Wild rodents (Dipodomys merriami) used as biomonitors in contaminated mining sites.

    Science.gov (United States)

    Espinosa-Reyes, Guillermo; Torres-Dosal, Arturo; Ilizaliturri, Cesar; Gonzalez-Mille, Donaji; Diaz-Barriga, Fernando; Mejia-Saavedra, Jesus

    2010-01-01

    Mining is one of the most important industrial activities globally; however, mining processes have critical environmental impacts, as mining is a major source of metals and metalloids that contribute significantly to the pollution of soil, sediment, water and air. Heavy metals can impact the health of exposed human populations and nonhuman receptors. This study focused on arsenic because its genotoxicity is well-known. Previously, we proposed a methodology to evaluate and integrate risk from a single source affecting different biologic receptors. Here, we propose an alternative approach estimating arsenic exposure in children and kangaroo rats using probabilistic simulation with Monte Carlo modeling. The estimates are then associated to measured DNA damage and compared to both populations of children and rodents living in contaminated and in reference areas. Finally, based on the integrated analysis of the generated information, we evaluate the potential use of wild rodents (Dipodomys merriami) as a biomonitor at mining sites. Results indicate that the variation of genotoxicity in children of the reference site is approximately 2 units when compared to the children of the contaminated site. In the rodents we observed a variation of approximately 4 units between those of the reference site when compared to those living on the contaminated site. We propose that D. merriami can be used as a biomonitor organism in sites with mining activity, and that a non-lethal test can be used to evaluate risk from metal exposure.

  9. Rapid genetic restoration of a keystone species exhibiting delayed demographic response

    Science.gov (United States)

    Genetic founder effects are often expected when animals colonize restored habitat in fragmented landscapes, but empirical data on genetic responses to restoration are limited. We examined the genetic response of banner-tailed kangaroo rats (Dipodomys spectabilis) to landscape-scale grassland restor...

  10. Food habits of rodents inhabiting arid and semi-arid ecosystems of central New Mexico

    Science.gov (United States)

    Hope, Andrew G.; Parmenter, Robert R.

    2007-01-01

    In this study, we describe seasonal dietary composition for 15 species of rodents collected in all major habitats on the Sevilleta National Wildlife Refuge (Socorro County) in central New Mexico. A comprehensive literature review of food habits for these species from throughout their distribution also is provided. We collected rodents in the field during winter, spring and late summer in 1998 from six communities: riparian cottonwood forest; piñon-juniper woodland; juniper-oak savanna; mesquite savanna; short-grass steppe; and Chihuahuan Desert scrubland. Rodents included Spermophilus spilosoma (Spotted Ground Squirrel), Perognathus flavescens (Plains Pocket Mouse), Perognathus flavus (Silky Pocket Mouse), Dipodomys merriami (Merriam’s Kangaroo Rat), Dipodomys ordii (Ord’s Kangaroo Rat), Dipodomys spectabilis (Banner-tailed Kangaroo Rat), Reithrodontomys megalotis (Western Harvest Mouse), Peromyscus boylii (Brush Mouse), Peromyscus eremicus (Cactus Mouse), Peromyscus leucopus (White-footed Mouse), Peromyscus truei (Piñon Mouse), Onychomys arenicola (Mearn’s Grasshopper Mouse), Onychomys leucogaster (Northern Grasshopper Mouse), Neotoma albigula/leucodon (White-throated Woodrats), and Neotoma micropus (Southern Plains Woodrat). We collected stomach contents of all species, and cheek-pouch contents of heteromyids, and quantified them in the laboratory. We determined seasonal diets in each habitat by calculating mean percentage volumes of seeds, arthropods and green vegetation (plant leaves and stems) for each species of rodent. Seeds consumed by each rodent were identified to genus, and often species, and quantified by frequency counts. Comparisons of diets between and among species of rodents, seasons, and ecosystems were also examined. We provide an appendix of all plant taxa documented.

  11. Environmental Assessment: Base Realignment and Closure (BRAC) 2005 Mission Realignments to Vandenberg AFB

    Science.gov (United States)

    2007-02-01

    implied by altered connective tissue metabolism and altered pulmonary morphology in animals after long-term exposures and pulmonary function...addition to the wildlife found in chaparral, other species include mammals like Heerman’s kangaroo rat (Dipodomys heermanni), Broad-footed mole (Scapanus

  12. Effects of rodent species, seed species, and predator cues on seed fate

    Science.gov (United States)

    Sivy, Kelly J.; Ostoja, Steven M.; Schupp, Eugene W.; Durham, Susan

    2011-07-01

    Seed selection, removal and subsequent management by granivorous animals is thought to be a complex interaction of factors including qualities of the seeds themselves (e.g., seed size, nutritional quality) and features of the local habitat (e.g. perceived predator risk). At the same time, differential seed selection and dispersal is thought to have profound effects on seed fate and potentially vegetation dynamics. In a feeding arena, we tested whether rodent species, seed species, and indirect and direct predation cues influence seed selection and handling behaviors (e.g., scatter hoarding versus larder hoarding) of two heteromyid rodents, Ord's kangaroo rat ( Dipodomys ordii) and the Great Basin pocket mouse ( Perognathus parvus). The indirect cue was shrub cover, a feature of the environment. Direct cues, presented individually, were (1) control, (2) coyote ( Canis latrans) vocalization, (3) coyote scent, (4) red fox ( Vulpes vulpes) scent, or (5) short-eared owl ( Asio flammeus) vocalization. We offered seeds of three sizes: two native grasses, Indian ricegrass ( Achnatherum hymenoides) and bluebunch wheatgrass ( Pseudoroegneria spicata), and the non-native cereal rye ( Secale cereale), each in separate trays. Kangaroo rats preferentially harvested Indian ricegrass while pocket mice predominately harvested Indian ricegrass and cereal rye. Pocket mice were more likely to scatter hoard preferred seeds, whereas kangaroo rats mostly consumed and/or larder hoarded preferred seeds. No predator cue significantly affected seed preferences. However, both species altered seed handling behavior in response to direct predation cues by leaving more seeds available in the seed pool, though they responded to different predator cues. If these results translate to natural dynamics on the landscape, the two rodents are expected to have different impacts on seed survival and plant recruitment via their different seed selection and seed handling behaviors.

  13. Tooele Army Depot Revised Final Site-Wide Ecological Risk Assessment. Volume II (Appendices A through D).

    Science.gov (United States)

    1998-02-01

    diet of higher trophic level species, such as raptors. Ord’s Kangaroo Rat (Dipodomys ordii). The Ord’s kangaroo rat is chiefly a nocturnal mammal...sandy soils. The entrances of these burrow systems are plugged during the day to maintain humidity and coolness. The kangaroo rat can obtain...sufficient quantities of water from the metabolism of food in their diet, but will drink water when it is available. TSK 0003/SWERA/Rev Final Rpt/November

  14. Derivation of soil screening thresholds to protect chisel-toothed kangaroo rat from uranium mine waste in northern Arizona

    Science.gov (United States)

    Hinck, Jo E.; Linder, Greg L.; Otton, James K.; Finger, Susan E.; Little, Edward E.; Tillitt, Donald E.

    2013-01-01

    Chemical data from soil and weathered waste material samples collected from five uranium mines north of the Grand Canyon (three reclaimed, one mined but not reclaimed, and one never mined) were used in a screening-level risk analysis for the Arizona chisel-toothed kangaroo rat (Dipodomys microps leucotis); risks from radiation exposure were not evaluated. Dietary toxicity reference values were used to estimate soil-screening thresholds presenting risk to kangaroo rats. Sensitivity analyses indicated that body weight critically affected outcomes of exposed-dose calculations; juvenile kangaroo rats were more sensitive to the inorganic constituent toxicities than adult kangaroo rats. Species-specific soil-screening thresholds were derived for arsenic (137 mg/kg), cadmium (16 mg/kg), copper (1,461 mg/kg), lead (1,143 mg/kg), nickel (771 mg/kg), thallium (1.3 mg/kg), uranium (1,513 mg/kg), and zinc (731 mg/kg) using toxicity reference values that incorporate expected chronic field exposures. Inorganic contaminants in soils within and near the mine areas generally posed minimal risk to kangaroo rats. Most exceedances of soil thresholds were for arsenic and thallium and were associated with weathered mine wastes.

  15. Positive interactions between desert granivores: localized facilitation of harvester ants by kangaroo rats.

    Directory of Open Access Journals (Sweden)

    Andrew J Edelman

    Full Text Available Facilitation, when one species enhances the environment or performance of another species, can be highly localized in space. While facilitation in plant communities has been intensely studied, the role of facilitation in shaping animal communities is less well understood. In the Chihuahuan Desert, both kangaroo rats and harvester ants depend on the abundant seeds of annual plants. Kangaroo rats, however, are hypothesized to facilitate harvester ants through soil disturbance and selective seed predation rather than competing with them. I used a spatially explicit approach to examine whether a positive or negative interaction exists between banner-tailed kangaroo rat (Dipodomys spectabilis mounds and rough harvester ant (Pogonomyrmex rugosus colonies. The presence of a scale-dependent interaction between mounds and colonies was tested by comparing fitted spatial point process models with and without interspecific effects. Also, the effect of proximity to a mound on colony mortality and spatial patterns of surviving colonies was examined. The spatial pattern of kangaroo rat mounds and harvester ant colonies was consistent with a positive interspecific interaction at small scales (<10 m. Mortality risk of vulnerable, recently founded harvester ant colonies was lower when located close to a kangaroo rat mound and proximity to a mound partly predicted the spatial pattern of surviving colonies. My findings support localized facilitation of harvester ants by kangaroo rats, likely mediated through ecosystem engineering and foraging effects on plant cover and composition. The scale-dependent effect of kangaroo rats on abiotic and biotic factors appears to result in greater founding and survivorship of young colonies near mounds. These results suggest that soil disturbance and foraging by rodents can have subtle impacts on the distribution and demography of other species.

  16. Invasive rats on tropical islands: Their population biology and impacts on native species

    OpenAIRE

    Harper, Grant A.; Bunbury, Nancy

    2015-01-01

    The three most invasive rat species, black or ship rat Rattus rattus, brown or Norway rats, R. norvegicus and Pacific rat, R. exulans have been incrementally introduced to islands as humans have explored the world’s oceans. They have caused serious deleterious effects through predation and competition, and extinction of many species on tropical islands, many of which are biodiversity hotspots. All three rat species are found in virtually all habitat types, including mangrove and arid shrub la...

  17. Invasive rats on tropical islands: Their population biology and impacts on native species

    Directory of Open Access Journals (Sweden)

    Grant A. Harper

    2015-01-01

    Full Text Available The three most invasive rat species, black or ship rat Rattus rattus, brown or Norway rats, R. norvegicus and Pacific rat, R. exulans have been incrementally introduced to islands as humans have explored the world’s oceans. They have caused serious deleterious effects through predation and competition, and extinction of many species on tropical islands, many of which are biodiversity hotspots. All three rat species are found in virtually all habitat types, including mangrove and arid shrub land. Black rats tend to dominate the literature but despite this the population biology of invasive rats, particularly Norway rats, is poorly researched on tropical islands. Pacific rats can often exceed population densities of well over 100 rats ha−1 and black rats can attain densities of 119 rats ha−1, which is much higher than recorded on most temperate islands. High densities are possibly due to high recruitment of young although the data to support this are limited. The generally aseasonally warm climate can lead to year-round breeding but can be restricted by either density-dependent effects interacting with resource constraints often due to aridity. Apparent adverse impacts on birds have been well recorded and almost all tropical seabirds and land birds can be affected by rats. On the Pacific islands, black rats have added to declines and extinctions of land birds caused initially by Pacific rats. Rats have likely caused unrecorded extinctions of native species on tropical islands. Further research required on invasive rats on tropical islands includes the drivers of population growth and carrying capacities that result in high densities and how these differ to temperate islands, habitat use of rats in tropical vegetation types and interactions with other tropical species, particularly the reptiles and invertebrates, including crustaceans.

  18. Chronic Co-species Housing Mice and Rats Increased the Competitiveness of Male Mice.

    Science.gov (United States)

    Liu, Ying-Juan; Li, Lai-Fu; Zhang, Yao-Hua; Guo, Hui-Fen; Xia, Min; Zhang, Meng-Wei; Jing, Xiao-Yuan; Zhang, Jing-Hua; Zhang, Jian-Xu

    2017-03-01

    Rats are predators of mice in nature. Nevertheless, it is a common practice to house mice and rats in a same room in some laboratories. In this study, we investigated the behavioral and physiological responsively of mice in long-term co-species housing conditions. Twenty-four male mice were randomly assigned to their original raising room (control) or a rat room (co-species-housed) for more than 6 weeks. In the open-field and light-dark box tests, the behaviors of the co-species-housed mice and controls were not different. In a 2-choice test of paired urine odors [rabbit urine (as a novel odor) vs. rat urine, cat urine (as a natural predator-scent) vs. rabbit urine, and cat urine vs. rat urine], the co-species-housed mice were more ready to investigate the rat urine odor compared with the controls and may have adapted to it. In an encounter test, the rat-room-exposed mice exhibited increased aggression levels, and their urines were more attractive to females. Correspondingly, the levels of major urinary proteins were increased in the co-species-housed mouse urine, along with some volatile pheromones. The serum testosterone levels were also enhanced in the co-species-housed mice, whereas the corticosterone levels were not different. The norepinephrine, dopamine, and 5-HT levels in the right hippocampus and striatum were not different between the 2. Our findings indicate that chronic co-species housing results in adaptation in male mice; furthermore, it appears that long-term rat-odor stimuli enhance the competitiveness of mice, which suggests that appropriate predator-odor stimuli may be important to the fitness of prey animals. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Short interspersed elements (SINEs) of the Geomyoidea superfamily rodents.

    Science.gov (United States)

    Gogolevsky, Konstantin P; Kramerov, Dmitri A

    2006-05-24

    A new short interspersed element (SINE) was isolated from the genome of desert kangaroo rat (Dipodomys deserti) using single-primer PCR. This SINE consists of two monomers: the left monomer (IDL) resembles rodent ID element and other tRNAAla(CGC)-derived SINEs, whereas the right one (Geo) shows no similarity with known SINE sequences. PCR and hybridization analyses demonstrated that IDL-Geo SINE is restricted to the rodent superfamily Geomyoidea (families Geomyidea and Heteromyidea). Isolation and analysis of IDL-Geo from California pocket mouse (Chaetodipus californicus) and Botta's pocket gopher (Thomomys bottae) revealed some species-specific features of this SINE family. The structure and evolution of known dimeric SINEs are discussed.

  20. Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species

    Directory of Open Access Journals (Sweden)

    Irmgard eAmrein

    2014-05-01

    Full Text Available African mole-rats (family Bathyergidae are small to medium sized, long-lived and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of one year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin. Solitary Cape mole-rats (Georychus capensis, social highveld mole-rats (Cryptomys hottentotus pretoriae, and eusocial naked mole-rats (Heterocephalus glaber were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean

  1. Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species.

    Science.gov (United States)

    Amrein, Irmgard; Becker, Anton S; Engler, Stefanie; Huang, Shih-Hui; Müller, Julian; Slomianka, Lutz; Oosthuizen, Maria K

    2014-01-01

    African mole-rats (family Bathyergidae) are small to medium sized, long-lived, and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN) correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of 1 year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin). Solitary Cape mole-rats (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean rodents.

  2. Borrelia bissettiae sp. nov. and Borrelia californiensis sp. nov. prevail in diverse enzootic transmission cycles.

    Science.gov (United States)

    Margos, Gabriele; Lane, Robert S; Fedorova, Natalia; Koloczek, Johannes; Piesman, Joseph; Hojgaard, Andrias; Sing, Andreas; Fingerle, Volker

    2016-03-01

    Two species of the genus Borrelia , Borrelia bissettiae sp. nov. and Borrelia californiensis sp. nov., were first described by Postic and co-workers on the basis of genetic analyses of several loci. Multilocus sequence analysis of eight housekeeping loci confirmed that these two Borrelia genomospecies are distinct members of the Borrelia burgdorferi sensu lato complex. B. bissettiae sp. nov. was initially described in transmission cycles involving Neotoma fuscipes wood rats and Ixodes pacificus ticks in California, and Neotoma mexicana and Ixodes spinipalpis in Colorado. The preferred host of B. californiensis sp. nov. appears to be the California kangaroo rat, Dipodomys californicus ; Ixodes jellisoni , I. spinipalipis and I. pacificus ticks are naturally infected with it. Thus, the ecological associations of the two genomospecies and their genetic distance from all other known Borrelia genomospecies species justify their description as separate genomospecies: B. bissettiae sp. nov. (type strain DN127 T  = DSM 17990 T  =  CIP 109136 T ) and B. californiensis (type strain CA446 T  = DSM 17989 T  = ATCC BAA-2689 T ).

  3. Species differences in the localization and number of CNS beta adrenergic receptors: Rat versus guinea pig

    International Nuclear Information System (INIS)

    Booze, R.M.; Crisostomo, E.A.; Davis, J.N.

    1989-01-01

    The localization and number of beta adrenergic receptors were directly compared in the brains of rats and guinea pigs. The time course of association and saturability of [125I]cyanopindolol (CYP) binding to slide-mounted tissue sections was similar in rats (Kd = 17 pM) and guinea pigs (Kd = 20 pM). The beta-1 and beta-2 receptor subtypes were examined through the use of highly selective unlabeled receptor antagonists, ICI 118,551 (50 nM) and ICI 89,406 (70 nM). Dramatic species differences between rats and guinea pigs were observed in the neuroanatomical regional localization of the beta adrenergic receptor subtypes. For example, in the thalamus prominent beta-1 and beta-2 receptor populations were identified in the rat; however, the entire thalamus of the guinea pig had few, if any, beta adrenergic receptors of either subtype. Hippocampal area CA1 had high levels of beta-2 adrenergic receptors in both rats and guinea pigs but was accompanied by a widespread distribution of beta-2 adrenergic receptors only in rats. Quantitative autoradiographic analyses of 25 selected neuroanatomical regions (1) confirmed the qualitative differences in CNS beta adrenergic receptor localization, (2) determined that guinea pigs had significantly lower levels of beta adrenergic receptors than rats and (3) indicated a differential pattern of receptor subtypes between the two species. Knowledge of species differences in receptor patterns may be useful in designing effective experiments as well as in exploring the relationships between receptor and innervation patterns. Collectively, these data suggest caution be used in extrapolation of the relationships of neurotransmitters and receptors from studies of a single species

  4. Formation of reactive oxygen species in rat epithelial cells upon ...

    Indian Academy of Sciences (India)

    In our study, we investigated the influence of fly ash on the promotion of early inflammatory reactions like the formation of reactive oxygen species (ROS) in rat lung epithelial cells (RLE-6TN). Furthermore, we determined the formation of nitric oxide (NO). The cells show a clear dose-response relationship concerning the ...

  5. Alterations in the molecular species of rat liver lecithin by corn-oil feeding to essential fatty acid-deficient rats as a function of time

    NARCIS (Netherlands)

    Golde, L.M.G. van; Pieterson, W.A.; Deenen, L.L.M. van

    1968-01-01

    The present paper describes, as a function of time, the qualitative and quantitative alterations in the molecular species pattern of rat liver lecithin which are observed when corn oil is fed to essential fatty acid-deficient rats. One of the most important changes observed was a very rapid

  6. Density, movement, and transuranic tissue inventory of small mammals at a liquid-radioactive waste disposal area

    International Nuclear Information System (INIS)

    Halford, D.K.

    1987-01-01

    Linear movement, density, and transuranic radionuclide inventory were estimated for small mammals residing at a liquid radioactive waste disposal area in southeastern Idaho. Deer mice (Peromyscus maniculatus), kangaroo rats (Dipodomys ordii), western harvest mice (Reithrodontomys megalotis), and Great Basin pocket mice (Perognathus parvus) were the predominant species. The total small mammal population within the 3.0-ha waste area was estimated to be 93. The distance between consecutive captures for all species combined averaged 41 m and ranged from 7 to 201 m. About 30% of the rodents captured inside the waste area were also captured outside its boundaries. The total population inventory of 238 Pu, /sup 239,240/Pu, 241 Am, 242 Cm, and 244 Cm was 44 pCi, 30 pCi, 19 pCi, 21 pCi, and <1 pCi, respectively. One-third, or about 35 pCi of transuranics, could be removed from the waste area by small mammals during the summer of 1981. 16 references, 3 figures, 3 tables

  7. Rodent movements, densities and radionuclide concentrations at a liquid radioactive waste disposal area

    International Nuclear Information System (INIS)

    Halford, D.K.

    1983-01-01

    Movements and densities of rodents at a liquid radioactive waste disposal area were studied from June to September 1981 using trap line and assessment line techniques. The average distance between points of successive capture was 42 +- 25 (SD) m for deer mice (Peromyscus maniculatus) and 37 +- 21 m for kangaroo rats (Dipodomys ordii). Densities of deer mice averaged 10.2/ha with a population estimate of 57 within the area of rodent captures. The population estimate of 4 species of small mammals at the waste pond complex was 93. Radionuclide concentrations averaged 133 +- 97 pCi/g for rodents captured inside the disposal area boundary, 18 +- 22 pCi/g for those captured outside of the dispoal area fence and 0.50 +- 0.6 pCi/g for control animals. Species captured outside of the waste area boundary had significantly lower (P 137 Cs, 134 Cs, 60 Co and 65 Zn) in rodents at the liquid waste disposal area was estimated to be about 162 nCi

  8. Leptospira Species in Feral Cats and Black Rats from Western Australia and Christmas Island.

    Science.gov (United States)

    Dybing, Narelle A; Jacobson, Caroline; Irwin, Peter; Algar, David; Adams, Peter J

    2017-05-01

    Leptospirosis is a neglected, re-emerging bacterial disease with both zoonotic and conservation implications. Rats and livestock are considered the usual sources of human infection, but all mammalian species are capable of carrying Leptospira spp. and transmitting pathogenic leptospires in their urine, and uncertainty remains about the ecology and transmission dynamics of Leptospira in different regions. In light of a recent case of human leptospirosis on tropical Christmas Island, this study aimed to investigate the role of introduced animals (feral cats and black rats) as carriers of pathogenic Leptospira spp. on Christmas Island and to compare this with two different climatic regions of Western Australia (one island and one mainland). Kidney samples were collected from black rats (n = 68) and feral cats (n = 59) from Christmas Island, as well as feral cats from Dirk Hartog Island (n = 23) and southwest Western Australia (n = 59). Molecular (PCR) screening detected pathogenic leptospires in 42.4% (95% confidence interval 29.6-55.9) of cats and 2.9% (0.4-10.2) of rats from Christmas Island. Sequencing of cat- and rat-positive samples from Christmas Island showed 100% similarity for Leptospira interrogans. Pathogenic leptospires were not detected in cats from Dirk Hartog Island or southwest Western Australia. These findings were consistent with previous reports of higher Leptospira spp. prevalence in tropical regions compared with arid and temperate regions. Despite the abundance of black rats on Christmas Island, feral cats appear to be the more important reservoir species for the persistence of pathogenic L. interrogans on the island. This research highlights the importance of disease surveillance and feral animal management to effectively control potential disease transmission.

  9. Species difference between rat and hamster in tissue accumulation of mercury after administration of methylmercury

    International Nuclear Information System (INIS)

    Omata, Saburo; Kasama, Hidetaka; Hasegawa, Hiroshi; Hasegawa, Kazuhiro; Sugano, Hiroshi; Ozaki, Kunio

    1986-01-01

    The accumulation of mercury in tissues of the rat and hamster was determined after the administration of a single dose of 203 Hg-methylmercury chloride (10 mg/kg body weight). (1) On day 2, the mercury contents of hamster tissues were higher than those of rat tissues, except for red blood cells, in which the mercury content was about 6-fold higher in the rat than in the hamster. (2) After that time, the mercury content of hamster tissues decreased rather steeply and on day 16 it had reached 14-25% in nervous tissues and 7-15% in other tissues, of the levels on day 2. (3) In the rat, on the other hand, the mercury content of nervous tissues on day 16 was higher than that on day 2 (106-220%), except for dorsal roots and dorsal root ganglia, which showed slight decreases (75-94% of the levels on day 2). In non-neural tissues, the decreases up to day 16 were also small (71-92% of the levels on day 2). (4) Thus, both the uptake and elimination of mercury seem to be more rapid in the tissues of hamster compared with those of the rat. Similar trends of mercury accumulation and elimination were observed when animals received multiple injections of methylmercury that induced acute methylmercury intoxication. (5) Significant biotransmormation of the injected methylmercury to inorganic mercury was detected in the liver, kidney and spleen of both animal species. Although the percentages of inorganic mercury in these tissues wer not so different between the two species on day 2, they became exceedingly high in the tissues of hamster at the later stage, except in the kidney cytosol, in which the values were close in both animal species between day 2 and day 16. (orig.)

  10. Regional and Seasonal Diet of the Western Burrowing Owl in South-Central Nevada

    Energy Technology Data Exchange (ETDEWEB)

    Derek B. Hall, Paul D. Greger, Jeffrey R. Rosier

    2009-04-01

    We examined diets of Western Burrowing Owls (Athene cunicularia hypugaea) based on contents of pellets and large prey remains collected year-round at burrows in each of the 3 regions in south central Nevada (Mojave Desert, Great Basin Desert, and Transition region). The most common prey items, based on percent frequency of occurrence, were crickets and grasshoppers, beetles, rodents, sun spiders, and scorpions. The most common vertebrate prey was kangaroo rats (Dipodomys spp.). True bugs (Hemiptera), scorpions, and western harvest mice (Reithrodontomys megalotis) occurred most frequently in pellets from the Great Basin Desert region. Kangaroo rats (Dipodomys spp.) and pocket mice (Perognathinae) were the most important vertebrate prey items in the Transition and Mojave Desert regions, respectively. Frequency of occurrence of any invertebrate prey was high (>80%) in samples year-round but dropped in winter samples, with scorpions and sun spiders exhibiting the steepest declines. Frequency of occurrence of any vertebrate prey peaked in spring samples, was intermediate for winter and summer samples, and was lowest in fall samples. With the possible exception of selecting for western harvest mice in the Great Basin Desert region, Western Burrowing Owls in our study appeared to be opportunistic foragers with a generalist feeding strategy.

  11. Population ecology of small mammals on the radioactive waste management complex, Idaho National Engineering Laboratory

    International Nuclear Information System (INIS)

    Groves, C.R.; Keller, B.L.

    1983-01-01

    Species composition, diversity, biomass, population dynamics, absolute density, and movements of small mammal populations were examined on and adjacent to a solid radioactive waste disposal area in southeastern Idaho. The 15-month live-trapping study resulted in marking 2384 individuals representing 10 species of small mammals. Three vegetation types were sampled: crested wheatgrass (Agropyron cristatum) and Russian thistle (Salsola kali) habitats on the disposal area and native sagebrush (Artemisia tridentata) habitat surrounding the disposal area. The deer mouse (Peromyscus maniculatus) was the most common rodent in both disposal area habitats as well as the adjacent sagebrush habitat; Ord's kangaroo rat (Dipodomys ordii) was also an abundant rodent in all vegetation types. The montane vole (Microtus montanus) was common only in crested wheatgrass stands on the disposal area. The annual total small mammal biomass of 346 kg for the entire disposal area represents a potentially large vector for movement of radionuclides off the disposal area. However, the number of animals known to contact waste areas and traverse at least 50 m beyond the perimeter of the SDA appears to be small (8.7%)

  12. Invasive non-native species' provision of refugia for endangered native species.

    Science.gov (United States)

    Chiba, Satoshi

    2010-08-01

    The influence of non-native species on native ecosystems is not predicted easily when interspecific interactions are complex. Species removal can result in unexpected and undesired changes to other ecosystem components. I examined whether invasive non-native species may both harm and provide refugia for endangered native species. The invasive non-native plant Casuarina stricta has damaged the native flora and caused decline of the snail fauna on the Ogasawara Islands, Japan. On Anijima in 2006 and 2009, I examined endemic land snails in the genus Ogasawarana. I compared the density of live specimens and frequency of predation scars (from black rats [Rattus rattus]) on empty shells in native vegetation and Casuarina forests. The density of land snails was greater in native vegetation than in Casuarina forests in 2006. Nevertheless, radical declines in the density of land snails occurred in native vegetation since 2006 in association with increasing predation by black rats. In contrast, abundance of Ogasawarana did not decline in the Casuarina forest, where shells with predation scars from rats were rare. As a result, the density of snails was greater in the Casuarina forest than in native vegetation. Removal of Casuarina was associated with an increased proportion of shells with predation scars from rats and a decrease in the density of Ogasawarana. The thick and dense litter of Casuarina appears to provide refugia for native land snails by protecting them from predation by rats; thus, eradication of rats should precede eradication of Casuarina. Adaptive strategies, particularly those that consider the removal order of non-native species, are crucial to minimizing the unintended effects of eradication on native species. In addition, my results suggested that in some cases a given non-native species can be used to mitigate the impacts of other non-native species on native species.

  13. Assessing plague risk and presence through surveys of small mammal flea communities

    Science.gov (United States)

    M. M. Friggens; P. L. Ford; R. R. Parmenter; M. Boyden; K. Gage

    2011-01-01

    Plague, caused by the bacterium Yersinia pestis, remains a threat to human and wildlife populations in the Western United States (Gage and Kosoy 2005). Several rodent species have been implicated as important maintenance hosts in the U.S., including Peromyscus maniculatus and Dipodomys spp. Fleas are a critical component of plague foci (Gage and Kosoy 2005)....

  14. The induction of species-specific immunity against Schistosoma japonicum by exposure of rats to ultra-violet attenuated cercariae

    International Nuclear Information System (INIS)

    Moloney, N.A.; Webbe, G.; Hinchcliffe, P.

    1987-01-01

    Single percutaneous immunizations of Fischer rats with 1000 ultra-violet attenuated Schistosoma japonicum cercariae induced 52-88% resistance to challenge 4 weeks later. Increasing this to 3 immunizations induced 90% resistance to challenge, and this level of protection remained undiminished for up to 40 weeks after vaccination. Rats vaccinated with gamma-irradiated S. mansoni cercariae were resistant to challenge with S. mansoni but not S. japonicum. Similarly rats vaccinated with u.v.-attenuated S. japonicum cercariae were not resistant to heterologous challenge. Thus irradiated vaccines are species-specific in both permissive and non-permissive hosts. (author)

  15. Species selective resistance of cardiac muscle voltage gated sodium channels: characterization of brevetoxin and ciguatoxin binding sites in rats and fish.

    Science.gov (United States)

    Dechraoui, Marie-Yasmine Bottein; Wacksman, Jeremy J; Ramsdell, John S

    2006-11-01

    Brevetoxins (PbTxs) and ciguatoxins (CTXs) are two suites of dinoflagellate derived marine polyether neurotoxins that target the voltage gated sodium channel (VGSC). PbTxs are commonly responsible for massive fish kills and unusual mortalities in marine mammals. CTXs, more often noted for human intoxication, are suspected causes of fish and marine mammal intoxication, although this has never been reported in the field. VGSCs, present in the membrane of all excitable cells including those found in skeletal muscle, nervous and heart tissues, are found as isoforms with differential expression within species and tissues. To investigate the tissue and species susceptibility to these biotoxins, we determined the relative affinity of PbTx-2 and -3 and P-CTX-1 to native VGSCs in the brain, heart, and skeletal muscle of rat and the marine teleost fish Centropristis striata by competitive binding in the presence of [(3)H]PbTx-3. No differences between rat and fish were observed in the binding of PbTxs and CTX to either brain or skeletal muscle. However, [(3)H]PbTx-3 showed substantial lower affinity to rat heart tissue while in the fish it bound with the same affinity to heart than to brain or skeletal muscle. These new insights into PbTxs and CTXs binding in fish and mammalian excitable tissues indicate a species related resistance of heart VGSC in the rat; yet, with comparable sensitivity between the species for brain and skeletal muscle.

  16. Testosterone improves erectile function through inhibition of reactive oxygen species generation in castrated rats

    Directory of Open Access Journals (Sweden)

    Rui Li

    2016-05-01

    Full Text Available Testosterone is overwhelmingly important in regulating erectile physiology. However, the associated molecular mechanisms are poorly understood. The purpose of this study was to explore the effects and mechanisms of testosterone in erectile dysfunction (ED in castrated rats. Forty male Sprague-Dawley rats were randomized to four groups (control, sham-operated, castration and castration-with-testosterone-replacement. Reactive oxygen species (ROS production was measured by dihydroethidium (DHE staining. Erectile function was assessed by the recording of intracavernous pressure (ICP and mean arterial blood pressure (MAP. Protein expression levels were examined by western blotting. We found that castration reduced erectile function and that testosterone restored it. Nitric oxide synthase (NOS activity was decrease in the castrated rats, and testosterone administration attenuated this decrease (each p < 0.05. The testosterone, dihydrotestosterone, cyclic guanosine monophosphate (cGMP and cyclic adenosine monophosphate (cAMP concentrations were lower in the castrated rats, and testosterone restored these levels (each p < 0.05. Furthermore, the cyclooxygenase-2 (COX-2 and prostacyclin synthase (PTGIS expression levels and phospho-endothelial nitric oxide synthase (p-eNOS, Ser1177/endothelial nitric oxide synthase (eNOS ratio were reduced in the castrated rats compared with the controls (each p < 0.05. In addition, the p40phox and p67phox expression levels were increased in the castrated rats, and testosterone reversed these changes (each p < 0.05. Overall, our results demonstrate that testosterone ameliorates ED after castration by reducing ROS production and increasing the activity of the eNOS/cGMP and COX-2/PTGIS/cAMP signaling pathways.

  17. Reactive oxygen species scavengers ameliorate mechanical allodynia in a rat model of cancer-induced bone pain

    Directory of Open Access Journals (Sweden)

    Ya-Qun Zhou

    2018-04-01

    Full Text Available Cancer-induced bone pain (CIBP is a frequent complication in patients suffering from bone metastases. Previous studies have demonstrated a pivotal role of reactive oxygen species (ROS in inflammatory and neuropathic pain, and ROS scavengers exhibited potent antinociceptive effect. However, the role of spinal ROS remains unclear. In this study, we investigated the analgesic effect of two ROS scavengers in a well-established CIBP model. Our results found that intraperitoneal injection of N-tert-Butyl-α-phenylnitrone (PBN, 50 and 100 mg/kg and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol, 100 and 200 mg/kg significantly suppressed the established mechanical allodynia in CIBP rats. Moreover, repeated injection of PBN and Tempol showed cumulative analgesic effect without tolerance. However, early treatment with PBN and Tempol failed to prevent the development of CIBP. Naive rats received repetitive injection of PBN and Tempol showed no significant change regarding the nociceptive responses. Finally, PBN and Tempol treatment notably suppressed the activation of spinal microglia in CIBP rats. In conclusion, ROS scavengers attenuated established CIBP by suppressing the activation of microglia in the spinal cord. Keywords: Cancer-induced bone pain, Reactive oxygen species, PBN, Tempol

  18. Four Cases of Spontaneous Neoplasia in the Naked Mole-Rat (Heterocephalus glaber), A Putative Cancer-Resistant Species.

    Science.gov (United States)

    Taylor, Kyle R; Milone, Nicholas A; Rodriguez, Carlos E

    2017-01-01

    The naked mole-rat (Heterocephalus glaber) is widely acclaimed to be cancer-resistant and of considerable research interest based on a paucity of reports of neoplasia in this species. We have, however, encountered four spontaneous cases of neoplasia and one presumptive case of neoplasia through routine necropsy and biopsy of individuals in a zoo collection of nonhybrid naked mole-rats bred from a single pair. One case each of metastasizing hepatocellular carcinoma, nephroblastoma (Wilms' tumor), and multicentric lymphosarcoma, as well as presumptive esophageal adenocarcinoma (Barrett's esophagus-like) was identified postmortem among 37 nonautolyzed necropsy submissions of naked mole-rats over 1-year-old that were submitted for necropsy between 1998 and August 2015. One incidental case of cutaneous hemangioma was also identified antemortem by skin biopsy from one naked mole-rat examined for trauma. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Preliminary report of biological intrusion studies at the Idaho National Engineering Laboratory subsurface disposal area

    International Nuclear Information System (INIS)

    Reynolds, T.D.; Arthur, W.J.

    1983-01-01

    As part of a larger study on the effects of biological intrusion of plants and animals into the soil cover placed over low-level radioactive wastes stored at the Idaho National Engineering Laboratory Subsurface Disposal Area (SDA), research was initiated in the summer of 1982 to determine the burrow characteristics and movement patterns of several small mammal species, and the rooting depths of various plants. The depth, length, and volume of burrows were determined for four small mammal species: deer mouse (Peromyscus maniculatus), Ord's kangaroo rat (Dipodomys ordii), montane vole (Microtus montanus), and Townsend's ground squirrel (Spermophilis townsendii). The latter species excavated the greatest mean burrow depth (39 cm), length (404 cm), and volume (14.8 1). Movement patterns of three species were determined by radiotelemetry. The mean area of use for P. maniculatus, D. ordii, and M. montanus was 2.3, 1.5, and 1.2 ha respectively. Limited data on rooting depths of various native and introduced plant species at the SDA were obtained by literature review and excavation. During FY-83, experiments will be conducted, using the information obtained from the first year of this study, to evaluate the impact of burrowing mammals and root intrusion on the integrity of the soil cover currently existing at the SDA. Details of these experimental studies are presented

  20. Subchronic and Genetic Safety Assessment of a New Medicinal Dendrobium Species: Dendrobium Taiseed Tosnobile in Rats

    Directory of Open Access Journals (Sweden)

    Li-Chan Yang

    2018-01-01

    Full Text Available Dendrobium Taiseed Tosnobile is a new species of herba dendrobii (Shi-Hu that was developed by crossbreeding D. tosaense and D. nobile. Its pharmacological activity and active component have been reported, but its subchronic toxicity and genetic safety have not yet been investigated. This study assessed the 90-day oral toxicity and genetic safety of the aqueous extracts of D. Taiseed Tosnobile (DTTE in male and female Sprague-Dawley (SD rats. Eighty rats were divided into four groups, each consisting of ten male and ten female rats. DTTE was given orally to rats at 800, 1600, or 2400 mg/kg for 90 consecutive days, and distilled water was used for the control group. Genotoxicity studies were performed using a bacterial reverse mutation assay and in vivo mammalian cell micronucleus test in ICR mice and analyzed using flow cytometry. Throughout the study period, no abnormal changes were observed in clinical signs and body weight or on ophthalmological examinations. Additionally, no significant differences were found in urinalysis, hematology, and serum biochemistry parameters between the treatment and control groups. Necropsy and histopathological examination indicated no treatment-related changes. Based on results, the no-observed-adverse-effect level of DTTE is greater than 2400 mg/kg in SD rats.

  1. Permeability of roads to movement of scrubland lizards and small mammals

    Science.gov (United States)

    Brehme, Cheryl S.; Tracey, Jeff A.; McClenaghan, Leroy R.; Fisher, Robert N.

    2013-01-01

    A primary objective of road ecology is to understand and predict how roads affect connectivity of wildlife populations. Road avoidance behavior can fragment populations, whereas lack of road avoidance can result in high mortality due to wildlife-vehicle collisions. Many small animal species focus their activities to particular microhabitats within their larger habitat. We sought to assess how different types of roads affect the movement of small vertebrates and to explore whether responses to roads may be predictable on the basis of animal life history or microhabitat preferences preferences. We tracked the movements of fluorescently marked animals at 24 sites distributed among 3 road types: low-use dirt, low-use secondary paved, and rural 2-lane highway. Most data we collected were on the San Diego pocket mouse (Chaetodipus fallax), cactus mouse (Peromyscus eremicus), western fence lizard (Sceloporus occidentalis), orange-throated whiptail (Aspidoscelis hyperythra), Dulzura kangaroo rat (Dipodomys simulans) (dirt, secondary paved), and deer mouse (Peromyscus maniculatus) (highway only). San Diego pocket mice and cactus mice moved onto dirt roads but not onto a low-use paved road of similar width or onto the highway, indicating they avoidpaved road substrate. Both lizard species moved onto the dirt and secondary paved roads but avoided the rural 2-lane rural highway, indicating they may avoid noise, vibration, or visual disturbance from a steady flow of traffic. Kangaroo rats did not avoid the dirt or secondary paved roads. Overall, dirt and secondary roads were more permeable to species that prefer to forage or bask in open areas of their habitat, rather than under the cover of rocks or shrubs. However, all study species avoided the rural 2-lane highway. Our results suggest that microhabitat use preferences and road substrate help predict species responses to low-use roads,but roads with heavy traffic may deter movement of a much wider range of small animal

  2. Laboratory Investigations of African Pouched Rats (Cricetomys gambianus as a Potential Reservoir Host Species for Monkeypox Virus.

    Directory of Open Access Journals (Sweden)

    Christina L Hutson

    Full Text Available Monkeypox is a zoonotic disease endemic to central and western Africa, where it is a major public health concern. Although Monkeypox virus (MPXV and monkeypox disease in humans have been well characterized, little is known about its natural history, or its maintenance in animal populations of sylvatic reservoir(s. In 2003, several species of rodents imported from Ghana were involved in a monkeypox outbreak in the United States with individuals of three African rodent genera (Cricetomys, Graphiurus, Funisciurus shown to be infected with MPXV. Here, we examine the course of MPXV infection in Cricetomys gambianus (pouched Gambian rats and this rodent species' competence as a host for the virus. We obtained ten Gambian rats from an introduced colony in Grassy Key, Florida and infected eight of these via scarification with a challenge dose of 4X104 plaque forming units (pfu from either of the two primary clades of MPXV: Congo Basin (C-MPXV: n = 4 or West African (W-MPXV: n = 4; an additional 2 animals served as PBS controls. Viral shedding and the effect of infection on activity and physiological aspects of the animals were measured. MPXV challenged animals had significantly higher core body temperatures, reduced activity and increased weight loss than PBS controls. Viable virus was found in samples taken from animals in both experimental groups (C-MPXV and W-MPXV between 3 and 27 days post infection (p.i. (up to 1X108 pfu/ml, with viral DNA found until day 56 p.i. The results from this work show that Cricetomys gambianus (and by inference, probably the closely related species, Cricetomys emini can be infected with MPXV and shed viable virus particles; thus suggesting that these animals may be involved in the maintenance of MPXV in wildlife mammalian populations. More research is needed to elucidate the epidemiology of MPXV and the role of Gambian rats and other species.

  3. Unusual ratio between free thyroxine and free triiodothyronine in a long-lived mole-rat species with bimodal ageing.

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Henning

    Full Text Available Ansell's mole-rats (Fukomys anselli are subterranean, long-lived rodents, which live in eusocial families, where the maximum lifespan of breeders is twice as long as that of non-breeders. Their metabolic rate is significantly lower than expected based on allometry, and their retinae show a high density of S-cone opsins. Both features may indicate naturally low thyroid hormone levels. In the present study, we sequenced several major components of the thyroid hormone pathways and analyzed free and total thyroxine and triiodothyronine in serum samples of breeding and non-breeding F. anselli to examine whether a their thyroid hormone system shows any peculiarities on the genetic level, b these animals have lower hormone levels compared to euthyroid rodents (rats and guinea pigs, and c reproductive status, lifespan and free hormone levels are correlated. Genetic analyses confirmed that Ansell's mole-rats have a conserved thyroid hormone system as known from other mammalian species. Interspecific comparisons revealed that free thyroxine levels of F. anselli were about ten times lower than of guinea pigs and rats, whereas the free triiodothyronine levels, the main biologically active form, did not differ significantly amongst species. The resulting fT4:fT3 ratio is unusual for a mammal and potentially represents a case of natural hypothyroxinemia. Comparisons with total thyroxine levels suggest that mole-rats seem to possess two distinct mechanisms that work hand in hand to downregulate fT4 levels reliably. We could not find any correlation between free hormone levels and reproductive status, gender or weight. Free thyroxine may slightly increase with age, based on sub-significant evidence. Hence, thyroid hormones do not seem to explain the different ageing rates of breeders and non-breeders. Further research is required to investigate the regulatory mechanisms responsible for the unusual proportion of free thyroxine and free triiodothyronine.

  4. Unusual ratio between free thyroxine and free triiodothyronine in a long-lived mole-rat species with bimodal ageing.

    Science.gov (United States)

    Henning, Yoshiyuki; Vole, Christiane; Begall, Sabine; Bens, Martin; Broecker-Preuss, Martina; Sahm, Arne; Szafranski, Karol; Burda, Hynek; Dammann, Philip

    2014-01-01

    Ansell's mole-rats (Fukomys anselli) are subterranean, long-lived rodents, which live in eusocial families, where the maximum lifespan of breeders is twice as long as that of non-breeders. Their metabolic rate is significantly lower than expected based on allometry, and their retinae show a high density of S-cone opsins. Both features may indicate naturally low thyroid hormone levels. In the present study, we sequenced several major components of the thyroid hormone pathways and analyzed free and total thyroxine and triiodothyronine in serum samples of breeding and non-breeding F. anselli to examine whether a) their thyroid hormone system shows any peculiarities on the genetic level, b) these animals have lower hormone levels compared to euthyroid rodents (rats and guinea pigs), and c) reproductive status, lifespan and free hormone levels are correlated. Genetic analyses confirmed that Ansell's mole-rats have a conserved thyroid hormone system as known from other mammalian species. Interspecific comparisons revealed that free thyroxine levels of F. anselli were about ten times lower than of guinea pigs and rats, whereas the free triiodothyronine levels, the main biologically active form, did not differ significantly amongst species. The resulting fT4:fT3 ratio is unusual for a mammal and potentially represents a case of natural hypothyroxinemia. Comparisons with total thyroxine levels suggest that mole-rats seem to possess two distinct mechanisms that work hand in hand to downregulate fT4 levels reliably. We could not find any correlation between free hormone levels and reproductive status, gender or weight. Free thyroxine may slightly increase with age, based on sub-significant evidence. Hence, thyroid hormones do not seem to explain the different ageing rates of breeders and non-breeders. Further research is required to investigate the regulatory mechanisms responsible for the unusual proportion of free thyroxine and free triiodothyronine.

  5. High prevalence of Rickettsia typhi and Bartonella species in rats and fleas, Kisangani, Democratic Republic of the Congo

    NARCIS (Netherlands)

    Laudisoit, A.; Falay, D.; Amundala, N.; de Bellock, J.G.; van Houtte, N.; Breno, M.; Verheven, E.; Wilschut, Liesbeth; Parola, P.; Raoult, D.; C., Socolovschi

    2014-01-01

    The prevalence and identity of Rickettsia and Bartonella in urban rat and flea populations were evaluated in Kisangani, Democratic Republic of the Congo (DRC) by molecular tools. An overall prevalence of 17% Bartonella species and 13% Rickettsia typhi, the agent of murine typhus, was found in the

  6. Comparison of rat and rabbit embryo-fetal developmental ...

    Science.gov (United States)

    Regulatory non-clinical safety testing of human pharmaceutical compounds typically requires embryo fetal developmental toxicity (EFDT) testing in two species, (one rodent and one non-rodent, usually the rat and the rabbit). The question has been raised whether under some conditions EFDT testing could be limited to one species, or whether the need for testing in a second species could be decided on a case by case basis. As part of an RIVM/CBG-MEB/HESI/US EPA consortium initiative, we built and queried a database of 379 EFDT studies conducted for marketed and non-marketed pharmaceutical compounds. The animal models (rat and rabbit) were assessed for their potential for adverse developmental and maternal outcomes. The database was analyzed for the prevalence of EFDT incidence and the nature and severity of adverse findings in the two species. Some manifestation of EFDT in either one or both species (rat and rabbit) was demonstrated for 282 compounds (74%), and EFDT was detected in only one species (rat or rabbit) in almost a third (31%, 118 compounds), with approximately 58% rat and 42% rabbit studies identifying an EFDT signal among the 379 compounds tested. For 24 compounds (6%), fetal malformations were observed in one species (rat or rabbit) in the absence of any EFDT in the second species. In general, growth retardation, fetal variations, and malformations were more prominent in the rat, whereas embryo-fetal death was observed more often in the rabbit. Discor

  7. Laboratory investigations of African Pouched Rats (Cricetomys gambianus) as a potential reservoir host species for Monkeypox Virus

    Science.gov (United States)

    Hutson, Christina L.; Nakazawa, Yoshinori J.; Self, Joshua; Olson, Victoria A.; Regnery, Russell L.; Braden, Zachary; Weiss, Sonja; Malekani, Jean; Jackson, Eddie; Tate, Mallory; Karem, Kevin L.; Rocke, Tonie E.; Osorio, Jorge E.; Damon, Inger K.; Carroll, Darin S.

    2015-01-01

    Monkeypox is a zoonotic disease endemic to central and western Africa, where it is a major public health concern. Although Monkeypox virus (MPXV) and monkeypox disease in humans have been well characterized, little is known about its natural history, or its maintenance in animal populations of sylvatic reservoir(s). In 2003, several species of rodents imported from Ghana were involved in a monkeypox outbreak in the United States with individuals of three African rodent genera (Cricetomys, Graphiurus, Funisciurus) shown to be infected with MPXV. Here, we examine the course of MPXV infection in Cricetomys gambianus (pouched Gambian rats) and this rodent species’ competence as a host for the virus. We obtained ten Gambian rats from an introduced colony in Grassy Key, Florida and infected eight of these via scarification with a challenge dose of 4X104 plaque forming units (pfu) from either of the two primary clades of MPXV: Congo Basin (C-MPXV: n = 4) or West African (W-MPXV: n = 4); an additional 2 animals served as PBS controls. Viral shedding and the effect of infection on activity and physiological aspects of the animals were measured. MPXV challenged animals had significantly higher core body temperatures, reduced activity and increased weight loss than PBS controls. Viable virus was found in samples taken from animals in both experimental groups (C-MPXV and W-MPXV) between 3 and 27 days post infection (p.i.) (up to 1X108pfu/ml), with viral DNA found until day 56 p.i. The results from this work show that Cricetomys gambianus (and by inference, probably the closely related species, Cricetomys emini) can be infected with MPXV and shed viable virus particles; thus suggesting that these animals may be involved in the maintenance of MPXV in wildlife mammalian populations. More research is needed to elucidate the epidemiology of MPXV and the role of Gambian rats and other species.

  8. Place prioritization for biodiversity content using species ecological niche modeling

    Directory of Open Access Journals (Sweden)

    Víctor Sánchez-Cordero

    2005-01-01

    Full Text Available Place prioritization for biodiversity representation is essential for conservation planning, particularly in megadiverse countries where high deforestation threatens biodiversity. Given the collecting biases and uneven sampling of biological inventories, there is a need to develop robust models of species’ distributions. By modeling species’ ecological niches using point occurrence data and digitized environmental feature maps, we can predict potential and extant distributions of species in untransformed landscapes, as well as in those transformed by vegetation change (including deforestation. Such distributional predictions provide a framework for use of species as biodiversity surrogates in place prioritization procedures such as those based on rarity and complementarity. Beyond biodiversity conservation, these predictions can also be used for place prioritization for ecological restoration under current conditions and under future scenarios of habitat change (e.g., deforestation scenarios. To illustrate these points, we (1 predict distributions under current and future deforestation scenarios for the Mexican endemic mammal Dipodomys phillipsii, and show how areas for restoration may be selected; and (2 propose conservation areas by combining nonvolant mammal distributional predictions as biodiversity surrogates with place prioritization procedures, to connect decreed natural protected areas in a region holding exceptional biodiversity: the Transvolcanic Belt in central Mexico. La selección de áreas prioritarias de conservación es fundamental en la planeación sistemática de la conservación, particularmente en países de mega-diversidad, en donde la alta deforestación es una de las amenazas a la biodiversidad. Debido a los sesgos taxonómicos y geográficos de colecta de los inventarios biológicos, es indispensable generar modelos robustos de distribución de especies. Al modelar el nicho ecológico de especies usando localidades de

  9. Long-term multi-species Lactobacillus and Bifidobacterium dietary supplement enhances memory and changes regional brain metabolites in middle-aged rats.

    Science.gov (United States)

    O'Hagan, Caroline; Li, Jia V; Marchesi, Julian R; Plummer, Sue; Garaiova, Iveta; Good, Mark A

    2017-10-01

    Ageing is associated with changes in the gut microbiome that may contribute to age-related changes in cognition. Previous work has shown that dietary supplements with multi-species live microorganisms can influence brain function, including induction of hippocampal synaptic plasticity and production of brain derived neurotrophic factor, in both young and aged rodents. However, the effect of such dietary supplements on memory processes has been less well documented, particularly in the context of aging. The main aim of the present study was to examine the impact of a long-term dietary supplement with a multi-species live Lactobacillus and Bifidobacteria mixture (Lactobacillus acidophilus CUL60, L. acidophilus CUL21, Bifidobacterium bifidum CUL20 and B. lactis CUL34) on tests of memory and behavioural flexibility in 15-17-month-old male rats. Following behavioural testing, the hippocampus and prefrontal cortex was extracted and analysed ex vivo using 1 H nuclear magnetic resonance ( 1 H NMR) spectroscopy to examine brain metabolites. The results showed a small beneficial effect of the dietary supplement on watermaze spatial navigation and robust improvements in long-term object recognition memory and short-term memory for object-in-place associations. Short-term object novelty and object temporal order memory was not influenced by the dietary supplement in aging rats. 1 H NMR analysis revealed diet-related regional-specific changes in brain metabolites; which indicated changes in several pathways contributing to modulation of neural signaling. These data suggest that chronic dietary supplement with multi-species live microorganisms can alter brain metabolites in aging rats and have beneficial effects on memory. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Tributyltin chloride disrupts aortic vascular reactivity and increases reactive oxygen species production in female rats.

    Science.gov (United States)

    Ximenes, Carolina Falcão; Rodrigues, Samya Mere Lima; Podratz, Priscila Lang; Merlo, Eduardo; de Araújo, Julia Fernandez Puñal; Rodrigues, Lívia Carla Melo; Coitinho, Juliana Barbosa; Vassallo, Dalton Valentim; Graceli, Jones Bernardes; Stefanon, Ivanita

    2017-11-01

    Organotin compounds, such as tributyltin (TBT), are environment contaminants that induce bioaccumulation and have potential toxic effects on marine species and mammals. TBT have been banned by the International Maritime Organization in 2003. However, the assessment of butyltin and metal contents in marine sediments has demonstrated high residual levels of TBT in some cases exceeding 7000 ng Sn g -1 . The acceptable daily intake (ADI) level for TBT established by the World Health Organization is 0.5 μg/kg bw/day is based on genotoxicity, reproduction, teratogenicity, immunotoxicity, and mainly neurotoxicity. However, their effect on the cardiovascular system is not well understood. In this study, female rats were exposed to 0.5 μg/kg/day of TBT for 15 days with the goal of understanding the effect of TBT on vascular function. Female Wistar rats were treated daily by gavage and divided into control (n = 10) and TBT (n = 10) groups. The aortic rings were incubated with phenylephrine in both the presence and absence of endothelium. The phenylephrine concentration-response curves were generated by exposing endothelium-intact samples to N G -nitro-L-arginine methyl ester (L-NAME), apocynin, superoxide dismutase (SOD), catalase, tiron, and allopurinol. Acetylcholine (ACh) and sodium nitroprusside (SNP) were used to evaluate the relaxation response. Exposure to TBT reduced serum 17β-estradiol E 2 levels and increased vascular reactivity. After incubation with L-NAME, the vascular reactivity to phenylephrine was significantly higher. Apocynin, SOD, catalase, and tiron decreased the vascular reactivity to phenylephrine to a significantly greater extent in TBT-treated rats than in the control rat. The relaxation induced by ACh and SNP was significantly reduced in TBT rats. Exposure to TBT induced aortic wall atrophy and increased superoxide anion production and collagen deposition. These results provide evidence that exposing rats to the current ADI for TBT (0.5

  11. Experimental comparison of pathogenic potential of two sibling species Anisakis simplex s.s. and Anisakis pegreffii in Wistar rat.

    Science.gov (United States)

    del Carmen Romero, María; Valero, Adela; Navarro-Moll, María Concepción; Martín-Sánchez, Joaquina

    2013-08-01

    There are little data available on the pathology caused by the sibling species Anisakis simplex s.s. and Anisakis pegreffii. The differences shown in their ability to penetrate the muscle of fish may also be manifested in humans. The purpose of this study is to confirm possible differences in pathogenicity between A. simplex s.s. and A. pegreffii using an experimental model which simulates infection in humans. Female Wistar rats were infected with 190 Anisakis type I L3 larvae from the Iberian coastline. After the animal was sacrificed, these L3 larvae were then recovered and identified via PCR-RFLP of the ITS1-5.8S-ITS2. A logistic regression analysis was performed searching for association between experimental pathogenic potential and species. The distribution of A. simplex s.s. and A. pegreffii between Atlantic and Mediterranean waters of the Iberian Peninsula showed statistically significant differences (P  0.3). 21.6% showed pathogenic potential, interpreted as the capacity of the larvae to cause lesions, stick to the gastrointestinal wall or penetrate it. The species variable showed association with the pathogenic role of the larva (P = 0.008). Taking A. simplex s.s. as our reference, the OR for A. pegreffii is 0.351 (P = 0.028). Despite this difference, A. pegreffii is also capable of causing anisakiasis, being responsible for 14.3% of the penetrations of the gastric mucosa found in rats, which justifies both species being considered aetiologic agents of this parasitic disorder. © 2013 John Wiley & Sons Ltd.

  12. Differential effects of methylmercury on the synthesis of protein species in dorsal root ganglia of the rat

    International Nuclear Information System (INIS)

    Kasama, Hidetaka; Itoh, Kazuo; Omata, Saburo; Sugano, Hiroshi

    1989-01-01

    Dorsal root ganglia from control and methylmercury(MeHg)-treated rats were incubated in vitro with 35 S-methionine and the proteins synthesized were analyzed by two-dimensional electrophoresis. The double labelling method, in which proteins of control dorsal root ganglia labelled in vitro with 3 H-leucine were added to each of the two samples as an internal standard, was used to minimize unavoidable errors arising from the resolving procedure itself. The results obtained showed that the effect of MeHg on the synthesis of proteins in dorsal root ganglia was not uniform for individual protein species in the latent period of MeHg intoxication. Among 200 protein species investigated, 157 showed inhibition of synthesis close to that of the total proteins in the tissue (68% of the control). Among the remaining protein species, 20 showed real stimulation of synthesis, whereas 7 were moderately inhibited and 16 were inhibited more strongly than the total proteins in the tissue. These results suggest that the effect of MeHg on the synthetic rates for protein species in dorsal root ganglia differs with the species, and that unusual elevation or reduction of the synthesis of some protein species caused by MeHg may lead to impairment of normal nerve functions. (orig.)

  13. Permeability of roads to movement of scrubland lizards and small mammals.

    Science.gov (United States)

    Brehme, Cheryl S; Tracey, Jeff A; McClenaghan, Leroy R; Fisher, Robert N

    2013-08-01

    A primary objective of road ecology is to understand and predict how roads affect connectivity of wildlife populations. Road avoidance behavior can fragment populations, whereas lack of road avoidance can result in high mortality due to wildlife-vehicle collisions. Many small animal species focus their activities to particular microhabitats within their larger habitat. We sought to assess how different types of roads affect the movement of small vertebrates and to explore whether responses to roads may be predictable on the basis of animal life history or microhabitat preferences preferences. We tracked the movements of fluorescently marked animals at 24 sites distributed among 3 road types: low-use dirt, low-use secondary paved, and rural 2-lane highway. Most data we collected were on the San Diego pocket mouse (Chaetodipus fallax), cactus mouse (Peromyscus eremicus), western fence lizard (Sceloporus occidentalis), orange-throated whiptail (Aspidoscelis hyperythra), Dulzura kangaroo rat (Dipodomys simulans) (dirt, secondary paved), and deer mouse (Peromyscus maniculatus) (highway only). San Diego pocket mice and cactus mice moved onto dirt roads but not onto a low-use paved road of similar width or onto the highway, indicating they avoid paved road substrate. Both lizard species moved onto the dirt and secondary paved roads but avoided the rural 2-lane rural highway, indicating they may avoid noise, vibration, or visual disturbance from a steady flow of traffic. Kangaroo rats did not avoid the dirt or secondary paved roads. Overall, dirt and secondary roads were more permeable to species that prefer to forage or bask in open areas of their habitat, rather than under the cover of rocks or shrubs. However, all study species avoided the rural 2-lane highway. Our results suggest that microhabitat use preferences and road substrate help predict species responses to low-use roads, but roads with heavy traffic may deter movement of a much wider range of small animal

  14. Polycyclic hydrocarbon biomarkers confirm selective incorporation of petroleum in soil and kangaroo rat liver samples near an oil well blowout site in the western San Joaquin Valley, California

    International Nuclear Information System (INIS)

    Kaplan, I.; Lu, S.T.; Lee, R.P.; Warrick, G.

    1996-01-01

    Following an accidental oil well blow out at an oil field in the western part of the San Joaquin Valley, soil samples and specimens of Heermann's kangaroo rats (Dipodomys heermanni) were collected from two oil-impacted areas and one control area. Fingerprinting by GC-MS and quantitative evaluation of metabolized petroleum hydrocarbons was performed on oil, soil extracts, and rat livers. A liver from a domestically raised rabbit was used as an experimental control. The results show that there is no significant incorporation of PAHs or low molecular weight n-alkanes (C 13 --C 25 ) into the liver tissues. The C 25 --C 35 n-alkane range for all soil samples, kangaroo rat livers, and rabbit liver, is dominated by a high abundance of C 27 , C 29 , C 31 , and C 33 hydrocarbons typical of epicuticular plant waxes. In all liver tissue samples, squalene, the cholesterol precursor, is the dominant hydrocarbon. Although evidence is lacking for metabolism of PAHs and paraffinic petroleum hydrocarbons, very strong evidence is available for incorporation of a set of polycyclic hydrocarbons (biomarkers) belonging to the terpane, sterane, and monoaromatic and triaromatic sterane families, identified by ion monitoring at 191, 217, 253, and 231 m/z, respectively. Because these hydrocarbons are not known to exist in the biosphere, but are only synthesized during oil- and coal-forming processes, their presence in the liver samples constitutes proof for crude oil incorporation into tissues. This conclusion is further substantiated by the selective incorporation of only the 20S enantiomer of C 28 and C 29 steranes and aromatic steranes into the livers, with the exclusion of the 20R enantiomer. The results from the study conclusively demonstrate that polycyclic hydrocarbon biomarkers provide excellent indices for proof of petroleum exposure and metabolism in some terrestrial herbivores

  15. Molecular species analysis of phosphatidylinositol (PI), phosphatidic acid (PA) and diacylglycerol (DG) in rat mast cells

    International Nuclear Information System (INIS)

    Kennerly, D.A.

    1987-01-01

    The metabolism of DG, PA and PI were studied in purified rat mast cells to determine whether generally accepted pathways of PI metabolism could explain the pattern of fatty acids seen in these intermediates. A method was developed to separate and quantitate by mass (for DG) or endogenous labeling (for PA and PI) the different molecular species of each lipid that are defined by their component fatty acids. The resultant molecular species fingerprint for each lipid was examined to see if it was similar to other intermediates in the PI cycle. For each class of compounds the percent in a given subclass was recorded. Stimulation caused a reduction of more saturated subclasses and/or an increase in AA containing compounds in PA, PI and DG. The relative similarity of subclasses of 32 P-PA and 32 P-PI supports the view that they are metabolically related. The relative absence of AA-containing species of DG suggests that most of the stimulated increase of DG was not produced by PI hydrolysis

  16. Negligible senescence in the longest living rodent, the naked mole-rat: insights from a successfully aging species.

    Science.gov (United States)

    Buffenstein, Rochelle

    2008-05-01

    Aging refers to a gradual deterioration in function that, over time, leads to increased mortality risk, and declining fertility. This pervasive process occurs in almost all organisms, although some long-lived trees and cold water inhabitants reportedly show insignificant aging. Negligible senescence is characterized by attenuated age-related change in reproductive and physiological functions, as well as no observable age-related gradual increase in mortality rate. It was questioned whether the longest living rodent, the naked mole-rat, met these three strict criteria. Naked mole-rats live in captivity for more than 28.3 years, approximately 9 times longer than similar-sized mice. They maintain body composition from 2 to 24 years, and show only slight age-related changes in all physiological and morphological characteristics studied to date. Surprisingly breeding females show no decline in fertility even when well into their third decade of life. Moreover, these animals have never been observed to develop any spontaneous neoplasm. As such they do not show the typical age-associated acceleration in mortality risk that characterizes every other known mammalian species and may therefore be the first reported mammal showing negligible senescence over the majority of their long lifespan. Clearly physiological and biochemical processes in this species have evolved to dramatically extend healthy lifespan. The challenge that lies ahead is to understand what these mechanisms are.

  17. Fos expression in the suprachiasmatic nucleus in response to light stimulation in a solitary and social species of African mole-rat (family Bathyergidae).

    Science.gov (United States)

    Oosthuizen, M K; Bennett, N C; Cooper, H M

    2005-01-01

    Mole-rats are strictly subterranean rodents that are rarely exposed to environmental light. They are well adapted to their environment and have reduced eyes and a severely regressed visual system. It has been shown, however, that mole-rats do exhibit endogenous circadian rhythms that can be entrained, suggesting an intact and functional circadian system. To determine whether light is the entraining agent in these animals, Fos expression in response to light pulses at different circadian times was investigated to obtain phase response curves. Light is integrated effectively in the suprachiasmatic nucleus of the Cape mole-rat (Georychus capensis), and Fos expression is gated according to the phase of the circadian clock. The Fos response in the Cape mole-rat was comparable to that of aboveground rodents. In contrast, the highveld mole-rat (Cryptomys hottentotus pretoriae) was less sensitive to light and did not show a selective Fos response according to the phase of the circadian cycle. Social species appear to be less sensitive to light than their solitary counterparts, which compares well with results from locomotor activity studies.

  18. Propolis, a Constituent of Honey, Inhibits the Development of Sugar Cataracts and High-Glucose-Induced Reactive Oxygen Species in Rat Lenses

    Directory of Open Access Journals (Sweden)

    Teppei Shibata

    2016-01-01

    Full Text Available Purpose. This study investigated the effects of oral propolis on the progression of galactose-induced sugar cataracts in rats and the in vitro effects of propolis on high-glucose-induced reactive oxygen species (ROS and cell death in cultured rat lens cells (RLECs. Methods. Galactose-fed rats and RLECs cultured in high glucose (55 mM medium were treated with propolis or vehicle control. Relative lens opacity was assessed by densitometry and changes in lens morphology by histochemical analysis. Intracellular ROS levels and cell viability were measured. Results. Oral administration of propolis significantly inhibited the onset and progression of cataract in 15% and 25% of galactose-fed rats, respectively. RLECs cultured with high glucose showed a significant increase in ROS expression with reduced cell viability. Treatment of these RLECs with 5 and 50 μg/mL propolis cultured significantly reduced ROS levels and increased cell viability, indicating that the antioxidant activity of propolis protected cells against ROS-induced damage. Conclusion. Propolis significantly inhibited the onset and progression of sugar cataract in rats and mitigated high-glucose-induced ROS production and cell death. These effects may be associated with the ability of propolis to inhibit hyperglycemia-evoked oxidative or osmotic stress-induced cellular insults.

  19. Aboriginal and invasive rats of genus Rattus as hosts of infectious agents.

    Science.gov (United States)

    Kosoy, Michael; Khlyap, Lyudmila; Cosson, Jean-Francois; Morand, Serge

    2015-01-01

    From the perspective of ecology of zoonotic pathogens, the role of the Old World rats of the genus Rattus is exceptional. The review analyzes specific characteristics of rats that contribute to their important role in hosting pathogens, such as host-pathogen relations and rates of rat-borne infections, taxonomy, ecology, and essential factors. Specifically the review addresses recent taxonomic revisions within the genus Rattus that resulted from applications of new genetic tools in understanding relationships between the Old World rats and the infectious agents that they carry. Among the numerous species within the genus Rattus, only three species-the Norway rat (R. norvegicus), the black or roof rat (R. rattus), and the Asian black rat (R. tanezumi)-have colonized urban ecosystems globally for a historically long period of time. The fourth invasive species, R. exulans, is limited to tropical Asia-Pacific areas. One of the points highlighted in this review is the necessity to discriminate the roles played by rats as pathogen reservoirs within the land of their original diversification and in regions where only one or few rat species were introduced during the recent human history.

  20. Comparing rat and rabbit embryo-fetal developmental toxicity ...

    Science.gov (United States)

    A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental adverse effect level (dLOAEL). For the vast majority of cases (83% based on AUC of n=283), dLOAELs in rats and rabbits were within the same order of magnitude (less than 10-fold different) when compared based on available data on AUC and Cmax exposures. For 13.5% of the compounds the rabbit was more sensitive and for 3.5% of compounds the rat was more sensitive when compared based on AUC exposures. For 12% of the compounds the rabbit was more sensitive and for 1.3% of compounds the rat was more sensitive based on Cmax exposures. When evaluated based on human equivalent dose (HED) conversion using standard factors, the rat and rabbit were equally sensitive. The relative extent of embryo-fetal toxicity in the presence of maternal toxicity was not different between species. Overall effect severity incidences were distributed similarly in rat and rabbit studies. Individual rat and rabbit strains did not show a different general distribution of systemic exposure LOAELs as compared to all strains combined for each species. There were no apparent species differences in the occurrence of embryo-fetal variations. Based on power of detection and given differences in the nature of developmental effects betwe

  1. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

    International Nuclear Information System (INIS)

    Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L.; Vickers, Alison E.M.

    2014-01-01

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol

  2. Social structure predicts genital morphology in African mole-rats.

    Directory of Open Access Journals (Sweden)

    Marianne L Seney

    2009-10-01

    Full Text Available 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.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.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.

  3. Social structure predicts genital morphology in African mole-rats.

    Science.gov (United States)

    Seney, Marianne L; Kelly, Diane A; Goldman, Bruce D; Sumbera, Radim; Forger, Nancy G

    2009-10-15

    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. 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. 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.

  4. Relationship of leptin administration with production of reactive oxygen species, sperm DNA fragmentation, sperm parameters and hormone profile in the adult rat.

    Science.gov (United States)

    Abbasihormozi, Shima; Shahverdi, Abdolhossein; Kouhkan, Azam; Cheraghi, Javad; Akhlaghi, Ali Asghar; Kheimeh, Abolfazl

    2013-06-01

    Leptin, an adipose tissue-derived hormone, plays an important role in energy homeostasis and metabolism, and in the neuroendocrine and reproductive systems. The function of leptin in male reproduction is unclear; however, it is known to affect sex hormones, sperm motility and its parameters. Leptin induces mitochondrial superoxide production in aortic endothelia and may increase oxidative stress and abnormal sperm production in leptin-treated rats. This study aims to evaluate whether exogenous leptin affects sperm parameters, hormone profiles, and the production of reactive oxygen species (ROS) in adult rats. A total of 65 Sprague-Dawley rats were divided into three treated groups and a control group. Treated rats received daily intraperitoneal injections of 5, 10 and 30 μg/kg of leptin administered for a duration of 7, 15, and 42 days. Control rats were given 0.1 mL of 0.9 % normal saline for the same period. One day after final drug administration, we evaluated serum specimens for follicle-stimulating hormone (FSH), leutinizing hormone (LH), free testosterone (FT), and total testosterone (TT) levels. Samples from the rat epididymis were also evaluated for sperm parameters and motility characteristics by a Computer-Aided Semen Analysis (CASA) system. Samples were treated with 2',7'-dichlorofluorescein-diacetate (DCFH-DA) and analyzed using flow cytometry and TUNEL to determine the impact of leptin administration on sperm DNA fragmentation. According to CASA, significant differences in all sperm parameters in leptin-treated rats and their age-matched controls were detected, except for TM, ALH and BCF. Serum FSH and LH levels were significantly higher in rats that received 10 and 30 μg/kg of leptin compared to those treated with 5 μg/kg of leptin in the same group and control rats (P control group (P hormone profile modulation.

  5. The species translation challenge-a systems biology perspective on human and rat bronchial epithelial cells.

    Science.gov (United States)

    Poussin, Carine; Mathis, Carole; Alexopoulos, Leonidas G; Messinis, Dimitris E; Dulize, Rémi H J; Belcastro, Vincenzo; Melas, Ioannis N; Sakellaropoulos, Theodore; Rhrissorrakrai, Kahn; Bilal, Erhan; Meyer, Pablo; Talikka, Marja; Boué, Stéphanie; Norel, Raquel; Rice, John J; Stolovitzky, Gustavo; Ivanov, Nikolai V; Peitsch, Manuel C; Hoeng, Julia

    2014-01-01

    The biological responses to external cues such as drugs, chemicals, viruses and hormones, is an essential question in biomedicine and in the field of toxicology, and cannot be easily studied in humans. Thus, biomedical research has continuously relied on animal models for studying the impact of these compounds and attempted to 'translate' the results to humans. In this context, the SBV IMPROVER (Systems Biology Verification for Industrial Methodology for PROcess VErification in Research) collaborative initiative, which uses crowd-sourcing techniques to address fundamental questions in systems biology, invited scientists to deploy their own computational methodologies to make predictions on species translatability. A multi-layer systems biology dataset was generated that was comprised of phosphoproteomics, transcriptomics and cytokine data derived from normal human (NHBE) and rat (NRBE) bronchial epithelial cells exposed in parallel to more than 50 different stimuli under identical conditions. The present manuscript describes in detail the experimental settings, generation, processing and quality control analysis of the multi-layer omics dataset accessible in public repositories for further intra- and inter-species translation studies.

  6. The species translation challenge—A systems biology perspective on human and rat bronchial epithelial cells

    Science.gov (United States)

    Poussin, Carine; Mathis, Carole; Alexopoulos, Leonidas G; Messinis, Dimitris E; Dulize, Rémi H J; Belcastro, Vincenzo; Melas, Ioannis N; Sakellaropoulos, Theodore; Rhrissorrakrai, Kahn; Bilal, Erhan; Meyer, Pablo; Talikka, Marja; Boué, Stéphanie; Norel, Raquel; Rice, John J; Stolovitzky, Gustavo; Ivanov, Nikolai V; Peitsch, Manuel C; Hoeng, Julia

    2014-01-01

    The biological responses to external cues such as drugs, chemicals, viruses and hormones, is an essential question in biomedicine and in the field of toxicology, and cannot be easily studied in humans. Thus, biomedical research has continuously relied on animal models for studying the impact of these compounds and attempted to ‘translate’ the results to humans. In this context, the SBV IMPROVER (Systems Biology Verification for Industrial Methodology for PROcess VErification in Research) collaborative initiative, which uses crowd-sourcing techniques to address fundamental questions in systems biology, invited scientists to deploy their own computational methodologies to make predictions on species translatability. A multi-layer systems biology dataset was generated that was comprised of phosphoproteomics, transcriptomics and cytokine data derived from normal human (NHBE) and rat (NRBE) bronchial epithelial cells exposed in parallel to more than 50 different stimuli under identical conditions. The present manuscript describes in detail the experimental settings, generation, processing and quality control analysis of the multi-layer omics dataset accessible in public repositories for further intra- and inter-species translation studies. PMID:25977767

  7. The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and Macaque species.

    Directory of Open Access Journals (Sweden)

    Alan D Curtis

    Full Text Available Atypical models of experimental autoimmune encephalomyelitis (EAE are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS. Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG in complete Freund's adjuvant (CFA followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA. The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in

  8. The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and Macaque species.

    Science.gov (United States)

    Curtis, Alan D; Taslim, Najla; Reece, Shaun P; Grebenciucova, Elena; Ray, Richard H; Rosenbaum, Matthew D; Wardle, Robert L; Van Scott, Michael R; Mannie, Mark D

    2014-01-01

    Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund's adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and

  9. Possible mechanism for species difference on the toxicity of pivalic acid between dogs and rats

    International Nuclear Information System (INIS)

    Yamaguchi, Toshiro; Nakajima, Yoshitsugu; Nakamura, Yutaka

    2006-01-01

    In a high dose toxicity study of pivalic acid (PA), PA caused skeletal muscle disorder in dog, and a significant increase of pivaloyl carnitine (PC) was observed in canine muscle, but not in rat muscle. In order to understand species difference of the toxicity of PA, we compared the in vitro metabolism of PA among dog, rat and rabbit, especially focussing on the carnitine conjugate. Canine muscle showed low, but significant carnitine conjugating activity, while that of rat was negligible. Canine kidney mitochondria had significant activity in the pivaloyl CoA synthesis (7 nmol/mg protein/h), but muscle mitochondria showed only trace activity. Both kidney and muscle mitochondria displayed similar carnitine acyltransferase activity (2-3 nmol/mg protein/h) towards pivaloyl CoA. On the other hand, with respect to the activity of carnitine acyltransferase in the reverse direction using PC as substrate, canine muscle mitochondria showed higher activity than that of kidney mitochondria. This means that PC is not the final stable metabolite, but is converted easily to pivaloyl CoA in canine muscle. These results suggest one of the possible mechanisms for canine selective muscle disorder to be as follows. Only canine muscle can metabolize PA to its carnitine conjugate slowly, but significantly. In canine muscle, PC is not the final stable metabolite; it is easily converted to pivaloyl CoA. As carnitine conjugation is thought to be the only detoxification metabolic route in canine muscle, under certain circumstances such as carnitine deficiency, the risk of exposure with toxic pivaloyl CoA might increase and the CoASH pool in canine muscle might be exhausted, resulting in toxicity in canine muscle

  10. Species difference in metabolism of inhaled butadiene

    International Nuclear Information System (INIS)

    Sabourin, P.J.; Dahl, A.R.; Bechtold, W.E.; Henderson, R.F.; Burka, L.T.

    1991-01-01

    Chronic exposure of B6C3F 1 mice and Sprague-Dawley rats to butadiene (BD) produced a very high incidence of cancer in mice while the incidence in rats was much lower with different tissues affected. Studies at this institute indicate that for equivalent exposures, the blood BD epoxide concentrations in mice are 5-fold higher than in rats and > 10-fold higher than in Cynomolgus monkeys. In this study, the profiles of urinary metabolites of butadiene were determined in Cynomolgus monkeys, F344/N rats, Sprague Dawley rats, B6C3F 1 mice and Syrian hamsters, species containing widely divergent hepatic epoxide hydrolase (EH) activities. Animals were exposed for 2 hr to 8,000 ppm [ 14 C]BD and 24-hr urine samples were analyzed for metabolites. Two major urinary metabolites were identified, N-acetyl-S-(-1(or 2)-3-butene-2(or 1)-ol)cysteine (1) and N-acetyl-S-(-4-butane-1,2-diol)cysteine (2). Monkeys exposed by inhalation produced primarily metabolite 2, while rodent species produced 1-4 times as much of 1 compared to 2. The ratio of 2/1 formation was related to the hepatic epoxide hydrolase activity in different species. The high 2/1 ratio in monkeys was consistent with the lower blood epoxide levels in this species. If BD metabolism by humans is similar to that in the monkey, exposure of humans to BD may result in lower tissue concentrations of reactive metabolites than an equivalent exposure of rodents. This has important implications for assessing the risk to humans of BD exposure based on rodent studies

  11. Metabolic alterations by clofibric acid in the formation of molecular species of phosphatidylcholine in rat liver.

    Science.gov (United States)

    Mizuguchi, H; Kudo, N; Kawashima, Y

    2001-10-01

    The mechanism by which p-chlorophenoxyisobutyric acid (clofibric acid) induces striking changes in the proportion of the molecular species of phosphatidylcholine (PC) in rat liver was studied. Treatment of rats with clofibric acid strikingly increased the content of 1-palmitoyl-2-oleoyl (16:0-18:1) PC, but decreased the contents of 1-palmitoyl-2-docosahexaenoyl (16:0-22:6), 1-stearoyl-2-arachidonoyl (18:0-20:4), and 1-stearoyl-2-linoleoyl (18:0-18:2) PC; the drug did not change the content of 1-palmitoyl-2-arachidonoyl (16:0-20:4) PC. The mechanism underlying these changes has been investigated with regard to the in vivo formation of the molecular species of PC by: (i) de novo synthesis, (ii) reacylation, and (iii) methylation of phosphatidylethanolamine (PE). We found that (i) the incorporation of [3H]glycerol, which was injected intravenously, into 16:0-18:1 diacylglycerol (DG) and 16:0-18:1 PC was increased markedly by clofibric acid feeding without changing the substrate specificity of CDP-choline:DG cholinephosphotransferase, (ii) the in vivo formation of 16:0-18:1 and 16:0-20:4 PC from 1-16:0-[3H]glycerophosphocholine (GPC), which was injected intraportally, was increased markedly by clofibric acid feeding, and (iii) the incorporation of [14C]ethanolamine, which was injected intravenously into 16:0-22:6, 18:0-22:6, and 18:0-20:4 PC, was decreased by clofibric acid feeding; the extent of the decrease in 16:0-20:4 PC was less than that of 18:0-20:4 PC. It was concluded, therefore, that (i) clofibric acid selectively increased the content and proportion of 16:0-18:1 PC by enhancing both the CDP-choline pathway and the remodeling of the pre-existing PC molecule, and (ii) the drug kept the content of 16:0-20:4 PC unchanged by stimulating the remodeling of the pre-existing PC molecule, whereas the formation of other more long chain, polyunsaturated molecular species, such as 16:0-22:6, 18:0-22:6, and 18:0-20:4, was decreased owing to the suppression of PE

  12. Reactive oxygen species inactivation improves pancreatic capillary blood flow in caerulein-induced pancreatitis in rats

    Directory of Open Access Journals (Sweden)

    Meirelles Jr. Roberto Ferreira

    2003-01-01

    Full Text Available PURPOSE: Reactive oxygen species (ROS inactivation was studied to determine alterations in the pancreatic capillary blood flow (PCBF during caerulein-induced pancreatitis in rats. METHODS: A laser-Doppler flowmeter to measure PCBF and N-t-Butyl-Phenylnitrone (PBN compound to inactivate ROS were used. Forty rats were divided in groups: 1 control; 2 caerulein; 3 PBN; 4 caerulein+PBN. Serum biochemistry and histopathological analyses were performed. RESULTS: PCBF measured a mean of 109.08 ± 14.54%, 68.24 ± 10.47%, 102.18 ± 10.23% and 87.73 ± 18.72% in groups 1, 2, 3 and 4, respectively. PCBF in groups 2 and 4 decreased 31.75 ± 16.79% and 12.26 ± 15.24%, respectively. Serum amylase was 1323.70 ± 239.10 U/l, 2184.60 ± 700.46 U/l, 1379.80 ± 265.72 U/l and 1622.10 ± 314.60 U/l in groups 1, 2, 3 and 4, respectively. There was a significant difference in the PCBF and serum amylase when compared groups 2 and 4. Cytoplasmatic vacuolation was present in groups 2 and 4. Otherwise, no qualitative changes were seen. CONCLUSION: ROS inactivation improves PCBF and minimizes the serum amylase increase during caerulein-induced pancreatitis. ROS effect may be one of the leading causative events in this model of acute pancreatitis.

  13. The naked mole-rat response to oxidative stress: just deal with it.

    Science.gov (United States)

    Lewis, Kaitlyn N; Andziak, Blazej; Yang, Ting; Buffenstein, Rochelle

    2013-10-20

    The oxidative stress theory of aging has been the most widely accepted theory of aging providing insights into why we age and die for over 50 years, despite mounting evidence from a multitude of species indicating that there is no direct relationship between reactive oxygen species (ROS) and longevity. Here we explore how different species, including the longest lived rodent, the naked mole-rat, have defied the most predominant aging theory. In the case of extremely long-lived naked mole-rat, levels of ROS production are found to be similar to mice, antioxidant defenses unexceptional, and even under constitutive conditions, naked mole-rats combine a pro-oxidant intracellular milieu with high, steady state levels of oxidative damage. Clearly, naked mole-rats can tolerate this level of oxidative stress and must have mechanisms in place to prevent its translation into potentially lethal diseases. In addition to the naked mole-rat, other species from across the phylogenetic spectrum and even certain mouse strains do not support this theory. Moreover, overexpressing or knocking down antioxidant levels alters levels of oxidative damage and even cancer incidence, but does not modulate lifespan. Perhaps, it is not oxidative stress that modulates healthspan and longevity, but other cytoprotective mechanisms that allow animals to deal with high levels of oxidative damage and stress, and nevertheless live long, relatively healthy lifespans. Studying these mechanisms in uniquely long-lived species, like the naked mole-rat, may help us tease out the key contributors to aging and longevity.

  14. Small mammal density and movement on the SL-1 disposal area, Idaho National Engineering Laboratory

    International Nuclear Information System (INIS)

    Filipovich, M.A.; Keller, B.L.

    1983-01-01

    This study was initiated to examine the population composition, density and food habits of small mammals on a radioactive waste disposal area. Population parameters of small mammals were studied at 3-month intervals on and adjacent to the SL-1 radioactive waste disposal area (1.4 ha) and a 0.3 ha control area between August 1981 and February 1982 with mark-release methods. Both areas have crested wheatgrass (Agropyron cristatum) stands surrounded by sagebrush steppe. Species composition on the SL-1 and control area was similar to that found on the Subsurface Disposal Area at the Idaho National Engineering Laboratory. Considerable use by small mammals of the perimeter of the crested wheatgrass stands was found on both the SL-1 and control area. Additionally, deer mice (Peromyscus maniculatus) and Ord's kangaroo rats (Dipodomys ordii) that frequent the crested wheatgrass stands of the SL-1 and control area were often captured over 100 m from the crested wheatgrass stands. Thus, future research efforts will focus on examining the intensity of perimeter use and food habits of rodents residing on and adjacent to the SL-1. Results of this study will be used to evaluate ecological conditions that affect small mammal use of radioactive waste disposal areas

  15. Teratology studies in the rat.

    Science.gov (United States)

    Leroy, Mariline; Allais, Linda

    2013-01-01

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

  16. Metabolism of 14C-tris(2-chloroethyl) phosphate (TRCP) in rats and mice

    International Nuclear Information System (INIS)

    Sanders, J.M.; Herr, D.W.; Burka, L.T.; Matthews, H.B.

    1990-01-01

    TRCP, a flame retardant, has been demonstrated to produce a dose-, sex-, and species-dependent lesion in the hippocampal region of the brain, following subchronic oral administration. This lesion is more common and more severe in female F344 rats than in male F344 rats, and is not observed in B6C3F1 mice. The present investigation of the metabolism of TRCP was designed to detect sex and species variations that might account for differences in toxicity. Elimination of TRCP-derived radioactivity was more rapid in mice, which excreted >70% of an oral dose of 175 mg/kg in urine in 8 hr vs ∼40% for male or female rats. However, the metabolic profile of TRCP-derived radioactivity in urine was similar for both species. The major metabolite in urine of rats and mice was identified as bis(2-chloroethyl) carboxymethyl phosphate. Two additional metabolites common to both species were bis(2-chloroethyl) hydrogen phosphate and the glucuronide of bis(2-chloroethyl) 2-hydroxyethyl phosphate. The major sex-related variation consisted of up to 2-fold higher levels of TRCP present in plasma of female rats (vs male rats) 5-30 min following an oral dose of 175 mg/kg. TRCP metabolism in rats was not induced or inhibited by 9 daily 175 mg/kg doses. Toxicity, as evidenced by seizures, was potentiated in male rats pretreated with inhibitors of aldehyde dehydrogenase

  17. Xenograft survival in two species combinations using total-lymphoid irradiation and cyclosporine

    International Nuclear Information System (INIS)

    Knechtle, S.J.; Halperin, E.C.; Bollinger, R.R.

    1987-01-01

    Total lymphoid irradiation (TLI) has profound immunosuppressive actions and has been applied successfully to allotransplantation but not xenotransplantation. Cyclosporine (CsA) has not generally permitted successful xenotransplantation of organs but has not been used in combination with TLI. TLI and CsA were given alone and in combination to rats that were recipients of hamster or rabbit cardiac xenografts. Combined TLI and CsA prolonged survival of hamster-to-rat cardiac xenografts from three days in untreated controls to greater than 100 days in most recipients. TLI alone significantly prolonged rabbit to rat xenograft survival with doubling of survival time. However, combined treatment did not significantly prolong rabbit-to-rat cardiac xenograft survival compared with TLI alone. The hamster and rat are phylogenetically closely related. Transplants from hamsters to rat are concordant xenografts since the time course of unmodified rejection is similar to first-set rejection of allografts. Although the rabbit-to-rat transplant is also between concordant species (average survival of untreated controls: 3.2 days) the rabbit and rat are more distantly related. These results suggest that TLI is an effective immunosuppressant when applied to cardiac xenotransplants in these animal models; that the choice of species critically affects xenograft survival when TLI and/or CsA are used for immunosuppression; and that the closely related species combination tested has markedly prolonged (greater than 100 days) survival using combined TLI and CsA

  18. Exposure to Rats and Rat-Associated Leptospira and Bartonella Species Among People Who Use Drugs in an Impoverished, Inner-City Neighborhood of Vancouver, Canada.

    Science.gov (United States)

    McVea, David A; Himsworth, Chelsea G; Patrick, David M; Lindsay, L Robbin; Kosoy, Michael; Kerr, Thomas

    2018-02-01

    Rat infestations are common, particularly in impoverished, inner-city neighborhoods. However, there has been little research into the nature and consequences of rat exposure in these neighborhoods, particularly in Canada. In this study, we sought to characterize exposure to rats and rat-associated Leptospira interrogans and Bartonella tribocorum, as well as risk factors associated with exposure, in residents (n = 202) of the Downtown Eastside (DTES) neighborhood of Vancouver, Canada. There was no evidence of exposure to rat-associated L. interrogans but 6/202 (3.0%) of participants were exposed to B. tribocorum, which is known to be circulating among DTES rats. We also found that frequent and close rat exposure was common among DTES residents, and that this exposure was particularly associated with injection drug use and outdoor income-generating activities (e.g., drug dealing). These risk factors may be good targets for interventions geared toward effectively reducing rat exposure.

  19. In vitro comparison of rat and chicken brain neurotoxic esterase

    International Nuclear Information System (INIS)

    Novak, R.; Padilla, S.

    1986-01-01

    A systematic comparison was undertaken to characterize neurotoxic esterase (NTE) from rat and chicken brain in terms of inhibitor sensitivities, pH optima, and molecular weights. Paraoxon titration of phenyl valerate (PV)-hydrolyzing carboxylesterases showed that rat esterases were more sensitive than chicken to paraoxon inhibition at concentrations less than or equal to microM and superimposable with chicken esterases at concentrations of 2.5-1000 microM. Mipafox titration of the paraoxon-resistant esterases at a fixed paraoxon concentration of 100 microM (mipafox concentration: 0-1000 microM) resulted in a mipafox I50 of 7.3 microM for chicken brain NTE and 11.6 microM for rat brain NTE. NTE (i.e., paraoxon-resistant, mipafox-sensitive esterase activity) comprised 80% of chicken and 60% of rat brain paraoxon-resistant activity with the specific activity of chicken brain NTE approximately twice that of rat brain NTE. The pH maxima for NTE from both species was similar showing broad, slightly alkaline optima from pH 7.9 to 8.6. [ 3 H]Diisopropyl phosphorofluoridate (DFP)-labeled NTE from the brains of both species had an apparent mol wt of 160,000 measured by sodium dodecyl sulfate polyacrylamide gel electrophoresis. In conclusion, NTE from both species was very similar, with the mipafox I50 for rat NTE within the range of reported values for chicken and human NTE, and the inhibitor parameters of the chicken NTE assay were applicable for the rat NTE assay

  20. Increased Expression of Simple Ganglioside Species GM2 and GM3 Detected by MALDI Imaging Mass Spectrometry in a Combined Rat Model of Aβ Toxicity and Stroke.

    Directory of Open Access Journals (Sweden)

    Sarah Caughlin

    Full Text Available The aging brain is often characterized by the presence of multiple comorbidities resulting in synergistic damaging effects in the brain as demonstrated through the interaction of Alzheimer's disease (AD and stroke. Gangliosides, a family of membrane lipids enriched in the central nervous system, may have a mechanistic role in mediating the brain's response to injury as their expression is altered in a number of disease and injury states. Matrix-Assisted Laser Desorption Ionization (MALDI Imaging Mass Spectrometry (IMS was used to study the expression of A-series ganglioside species GD1a, GM1, GM2, and GM3 to determine alteration of their expression profiles in the presence of beta-amyloid (Aβ toxicity in addition to ischemic injury. To model a stroke, rats received a unilateral striatal injection of endothelin-1 (ET-1 (stroke alone group. To model Aβ toxicity, rats received intracerebralventricular (i.c.v. injections of the toxic 25-35 fragment of the Aβ peptide (Aβ alone group. To model the combination of Aβ toxicity with stroke, rats received both the unilateral ET-1 injection and the bilateral icv injections of Aβ25-35 (combined Aβ/ET-1 group. By 3 d, a significant increase in the simple ganglioside species GM2 was observed in the ischemic brain region of rats who received a stroke (ET-1, with or without Aβ. By 21 d, GM2 levels only remained elevated in the combined Aβ/ET-1 group. GM3 levels however demonstrated a different pattern of expression. By 3 d GM3 was elevated in the ischemic brain region only in the combined Aβ/ET-1 group. By 21 d, GM3 was elevated in the ischemic brain region in both stroke alone and Aβ/ET-1 groups. Overall, results indicate that the accumulation of simple ganglioside species GM2 and GM3 may be indicative of a mechanism of interaction between AD and stroke.

  1. Rat bite fever.

    NARCIS (Netherlands)

    Gaastra, W.; Boot, R.G.A.; Ho, H.; Lipman, L.J.A.

    2009-01-01

    Rat bite fever (RBF) is a bacterial zoonosis for which two causal bacterial species have been identified: Streptobacillis moniliformis and Spirillum minus. Haverhill fever (HF) is a form of S. moniliformis infection believed to develop after ingestion of contaminated food or water. Here the

  2. Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Marion, Tracy L., E-mail: tracylmarion@qualyst.com [Curriculum in Toxicology, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7270 (United States); Perry, Cassandra H., E-mail: cassandraperry@qualyst.com [Qualyst, Inc., Durham, NC 27713 (United States); St Claire, Robert L., E-mail: bobstclaire@qualyst.com [Qualyst, Inc., Durham, NC 27713 (United States); Brouwer, Kim L.R., E-mail: kbrouwer@unc.edu [Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, CB 7569 Kerr Hall, Chapel Hill, NC 27599-7569 (United States)

    2012-05-15

    Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH. Using B-CLEAR{sup ®} technology, BAs were measured in cells + bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells + bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3 ± 5.9 μM in CTL rat and 183 ± 56 μM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16 ± 0.21 μM in CTL rat SCH and 9.61 ± 6.36 μM in CTL human SCH. Treatment of cells for 24 h with 10 μM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Na{sup +}-taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account. -- Highlights: ► Bile acids (BAs) were measured in rat and human sandwich-cultured hepatocytes (SCH). ► Cell and medium BA

  3. Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

    International Nuclear Information System (INIS)

    Marion, Tracy L.; Perry, Cassandra H.; St Claire, Robert L.; Brouwer, Kim L.R.

    2012-01-01

    Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH. Using B-CLEAR ® technology, BAs were measured in cells + bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells + bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3 ± 5.9 μM in CTL rat and 183 ± 56 μM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16 ± 0.21 μM in CTL rat SCH and 9.61 ± 6.36 μM in CTL human SCH. Treatment of cells for 24 h with 10 μM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Na + -taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account. -- Highlights: ► Bile acids (BAs) were measured in rat and human sandwich-cultured hepatocytes (SCH). ► Cell and medium BA concentrations

  4. Inter-species investigation of the mechano-regulation of bone healing: comparison of secondary bone healing in sheep and rat.

    Science.gov (United States)

    Checa, Sara; Prendergast, Patrick J; Duda, Georg N

    2011-04-29

    Inter-species differences in regeneration exist in various levels. One aspect is the dynamics of bone regeneration and healing, e.g. small animals show a faster healing response when compared to large animals. Mechanical as well as biological factors are known to play a key role in the process. However, it remains so far unknown whether different animals follow at all comparable mechano-biological rules during tissue regeneration, and in particular during bone healing. In this study, we investigated whether differences observed in vivo in the dynamics of bone healing between rat and sheep are only due to differences in the animal size or whether these animals have a different mechano-biological response during the healing process. Histological sections from in vivo experiments were compared to in silico predictions of a mechano-biological computer model for the simulation of bone healing. Investigations showed that the healing processes in both animal models occur under significantly different levels of mechanical stimuli within the callus region, which could explain histological observations of early intramembranous ossification at the endosteal side. A species-specific adaptation of a mechano-biological model allowed a qualitative match of model predictions with histological observations. Specifically, when keeping cell activity processes at the same rate, the amount of tissue straining defining favorable mechanical conditions for the formation of bone had to be increased in the large animal model, with respect to the small animal, to achieve a qualitative agreement of model predictions with histological data. These findings illustrate that geometrical (size) differences alone cannot explain the distinctions seen in the histological appearance of secondary bone healing in sheep and rat. It can be stated that significant differences in the mechano-biological regulation of the healing process exist between these species. Future investigations should aim towards

  5. Species’ traits help predict small mammal responses to habitat homogenization by an invasive grass

    Science.gov (United States)

    Ceradini, Joseph P.; Chalfoun, Anna D.

    2017-01-01

    Invasive plants can negatively affect native species, however, the strength, direction, and shape of responses may vary depending on the type of habitat alteration and the natural history of native species. To prioritize conservation of vulnerable species, it is therefore critical to effectively predict species’ responses to invasive plants, which may be facilitated by a framework based on species’ traits. We studied the population and community responses of small mammals and changes in habitat heterogeneity across a gradient of cheatgrass (Bromus tectorum) cover, a widespread invasive plant in North America. We live-trapped small mammals over two summers and assessed the effect of cheatgrass on native small mammal abundance, richness, and species-specific and trait-based occupancy, while accounting for detection probability and other key habitat elements. Abundance was only estimated for the most common species, deer mice (Peromyscus maniculatus). All species were pooled for the trait-based occupancy analysis to quantify the ability of small mammal traits (habitat association, mode of locomotion, and diet) to predict responses to cheatgrass invasion. Habitat heterogeneity decreased with cheatgrass cover. Deer mouse abundance increased marginally with cheatgrass. Species richness did not vary with cheatgrass, however, pocket mouse (Perognathus spp.) and harvest mouse (Reithrodontomys spp.) occupancy tended to decrease and increase, respectively, with cheatgrass cover, suggesting a shift in community composition. Cheatgrass had little effect on occupancy for deer mice, 13-lined ground squirrels (Spermophilus tridecemlineatus), and Ord's kangaroo rat (Dipodomys ordii). Species’ responses to cheatgrass primarily corresponded with our a priori predictions based on species’ traits. The probability of occupancy varied significantly with a species’ habitat association but not with diet or mode of locomotion. When considered within the context of a rapid

  6. Exposure to cigarette smoke increases apoptosis in the rat gastric mucosa through a reactive oxygen species-mediated and p53-independent pathway.

    Science.gov (United States)

    Wang, H; Ma, L; Li, Y; Cho, C H

    2000-04-01

    Cigarette smoking is a major risk factor for gastric cancer and peptic ulcer. The aim of our study was to investigate the relationship between exposure to cigarette smoke and apoptosis in the rat gastric mucosa and the mechanism involved. Rats were exposed to different concentrations of cigarette smoke (0, 2, and 4%) once daily for a different number of 1 h periods (1, 3, 6, and 9 d). Apoptosis was identified by the terminal deoxy-transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) method and caspase-3 activity. The mucosal xanthine oxidase (XO) activity and p53 level were also measured. The results showed that exposure to cigarette smoke produced a time- and concentration-dependent increase in apoptosis in the rat gastric mucosa that was accompanied by an increase in XO activity. The increased apoptosis and XO activity could be detected after even a single exposure. In contrast, the level of p53 was elevated only in the later stage of cigarette smoke exposure. The apoptotic effect could be blocked by pretreatment with an XO inhibitor (allopurinol, 20 mg/kg intraperitoneally) or a hydroxyl free radical scavenger (DMSO, 0.2%, 1 ml/kg intravenously). However, neither of these treatments had any effect on the p53 level of the mucosa. In summary, we conclude that exposure to cigarette smoke can increase apoptosis in the rat gastric mucosa through a reactive oxygen species- (ROS) mediated and a p53-independent pathway.

  7. Differential anatomical expression of ganglioside GM1 species containing d18:1 or d20:1 sphingosine detected by MALDI Imaging Mass Spectrometry in mature rat brain

    Directory of Open Access Journals (Sweden)

    Nina eWeishaupt

    2015-12-01

    Full Text Available GM1 ganglioside plays a role in essential neuronal processes, including differentiation, survival and signaling. Yet, little is known about GM1 species with different sphingosine bases, such as the most abundant species containing 18 carbon atoms in the sphingosine chain (GM1d18:1, and the less abundant containing 20 carbon atoms (GM1d20:1. While absent in the early fetal brain, GM1d20:1 continues to increase throughout pre- and postnatal development and into old age, raising questions about the functional relevance of the GM1d18:1 to GM1d20:1 ratio. Matrix-assisted laser desorption/ionization (MALDI Imaging Mass Spectrometry is a novel technology that allows differentiation between these two GM1 species and quantification of their expression within an anatomical context. Using this technology, we find GM1d18:1/d20:1 expression ratios are highly specific to defined anatomical brain regions in adult rats. Thus, the ratio was significantly different among different thalamic nuclei and between the corpus callosum and internal capsule. Differential GM1d18:1/GM1d20:1 ratios measured in hippocampal subregions in rat brain complement previous studies conducted in mice. Across layers of the sensory cortex, opposing expression gradients were found for GM1d18:1 and GM1d20:1. Superficial layers demonstrated lower GM1d18:1 and higher GM1d20:1 signal than other layers, while in deep layers GM1d18:1 expression was relatively high and GM1d20:1 expression low. By far the highest GM1d18:1/d20:1 ratio was found in the amygdala. Differential expression of GM1 with d18:1- or d20:1-sphingosine bases in the adult rat brain suggests tight regulation of expression and points toward a distinct functional relevance for each of these GM1 species in neuronal processes.

  8. Unexpected consequences of control: competitive vs. predator release in a four-species assemblage of invasive mammals.

    Science.gov (United States)

    Ruscoe, Wendy A; Ramsey, David S L; Pech, Roger P; Sweetapple, Peter J; Yockney, Ivor; Barron, Mandy C; Perry, Mike; Nugent, Graham; Carran, Roger; Warne, Rodney; Brausch, Chris; Duncan, Richard P

    2011-10-01

    Invasive species are frequently the target of eradication or control programmes to mitigate their impacts. However, manipulating single species in isolation can lead to unexpected consequences for other species, with outcomes such as mesopredator release demonstrated both theoretically and empirically in vertebrate assemblages with at least two trophic levels. Less is known about the consequences of species removal in more complex assemblages where a greater number of interacting invaders increases the potential for selective species removal to result in unexpected changes in community structure. Using a replicated Before-After Control-Impact field experiment with a four-species assemblage of invasive mammals we show that species interactions in the community are dominated by competition rather than predation. There was no measurable response of two mesopredators (rats and mice) following control of the top predator (stoats), but there was competitive release of rats following removal of a herbivore (possums), and competitive release of mice following removal of rats. © 2011 Blackwell Publishing Ltd/CNRS.

  9. Characterization of murine hepatitis virus (JHM) RNA from rats with experimental encephalomyelitis.

    Science.gov (United States)

    Jackson, D P; Percy, D H; Morris, V L

    1984-09-01

    When Wistar Furth rats are inoculated intracerebrally with the murine hepatitis virus JHM they often develop a demyelinating disease with resulting hind leg paralysis. Using an RNA transfer procedure and hybridization kinetic analysis, the virus-specific RNA in these rats was characterized. The pattern of JHM-specific RNA varied with individual infections of Wistar Furth rats. However, two species of JHM-specific RNA, the nucleocapsid and a 2.1-2.4 X 10(6)-Da RNA species were generally present. A general decrease in JHM-specific RNA in brains and spinal cord samples taken later than 20 days postinoculation was observed; however, JHM-specific RNA persisted in the spinal cord longer than in the brain of these rats.

  10. Species-specific differences in peroxisome proliferation, catalase, and SOD2 upregulation as well as toxicity in human, mouse, and rat hepatoma cells induced by the explosive and environmental pollutant 2,4,6-trinitrotoluene.

    Science.gov (United States)

    Naumenko, Ekaterina Anatolevna; Ahlemeyer, Barbara; Baumgart-Vogt, Eveline

    2017-03-01

    2,4,6-Trinitrotoluene (TNT) has been widely used as an explosive substance and its toxicity is still of interest as it persisted in polluted areas. TNT is metabolized in hepatocytes which are prone to its toxicity. Since analysis of the human liver or hepatocytes is restricted due to ethical reasons, we investigated the effects of TNT on cell viability, reactive oxygen species (ROS) production, peroxisome proliferation, and antioxidative enzymes in human (HepG2), mouse (Hepa 1-6), and rat (H4IIEC3) hepatoma cell lines. Under control conditions, hepatoma cells of all three species were highly comparable exhibiting identical proliferation rates and distribution of their cell cycle phases. However, we found strong differences in TNT toxicity with the lowest IC 50 values (highest cell death rate) for rat cells, whereas human and mouse cells were three to sevenfold less sensitive. Moreover, a strong decrease in cellular dehydrogenase activity (MTT assay) and increased ROS levels were noted. TNT caused peroxisome proliferation with rat hepatoma cells being most responsive followed by those from mouse and human. Under control conditions, rat cells contained fivefold higher peroxisomal catalase and mitochondrial SOD2 activities and a twofold higher capacity to reduce MTT than human and mouse cells. TNT treatment caused an increase in catalase and SOD2 mRNA and protein levels in human and mouse, but not in rat cells. Similarly, human and mouse cells upregulated SOD2 activity, whereas rat cells failed therein. We conclude that TNT induced oxidative stress, peroxisome proliferation and mitochondrial damage which are highest in rat cells rendering them most susceptible toward TNT. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 989-1006, 2017. © 2016 Wiley Periodicals, Inc.

  11. Temperature controls oxidative phosphorylation and reactive oxygen species production through uncoupling in rat skeletal muscle mitochondria.

    Science.gov (United States)

    Jarmuszkiewicz, Wieslawa; Woyda-Ploszczyca, Andrzej; Koziel, Agnieszka; Majerczak, Joanna; Zoladz, Jerzy A

    2015-06-01

    Mitochondrial respiratory and phosphorylation activities, mitochondrial uncoupling, and hydrogen peroxide formation were studied in isolated rat skeletal muscle mitochondria during experimentally induced hypothermia (25 °C) and hyperthermia (42 °C) compared to the physiological temperature of resting muscle (35 °C). For nonphosphorylating mitochondria, increasing the temperature from 25 to 42 °C led to a decrease in membrane potential, hydrogen peroxide production, and quinone reduction levels. For phosphorylating mitochondria, no temperature-dependent changes in these mitochondrial functions were observed. However, the efficiency of oxidative phosphorylation decreased, whereas the oxidation and phosphorylation rates and oxidative capacities of the mitochondria increased, with increasing assay temperature. An increase in proton leak, including uncoupling protein-mediated proton leak, was observed with increasing assay temperature, which could explain the reduced oxidative phosphorylation efficiency and reactive oxygen species production. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Reactive oxygen species and fatigue-induced prolonged low-frequency force depression in skeletal muscle fibres of rats, mice and SOD2 overexpressing mice.

    Science.gov (United States)

    Bruton, Joseph D; Place, Nicolas; Yamada, Takashi; Silva, José P; Andrade, Francisco H; Dahlstedt, Anders J; Zhang, Shi-Jin; Katz, Abram; Larsson, Nils-Göran; Westerblad, Håkan

    2008-01-01

    Skeletal muscle often shows a delayed force recovery after fatiguing stimulation, especially at low stimulation frequencies. In this study we focus on the role of reactive oxygen species (ROS) in this fatigue-induced prolonged low-frequency force depression. Intact, single muscle fibres were dissected from flexor digitorum brevis (FDB) muscles of rats and wild-type and superoxide dismutase 2 (SOD2) overexpressing mice. Force and myoplasmic free [Ca(2+)] ([Ca(2+)](i)) were measured. Fibres were stimulated at different frequencies before and 30 min after fatigue induced by repeated tetani. The results show a marked force decrease at low stimulation frequencies 30 min after fatiguing stimulation in all fibres. This decrease was associated with reduced tetanic [Ca(2+)](i) in wild-type mouse fibres, whereas rat fibres and mouse SOD2 overexpressing fibres instead displayed a decreased myofibrillar Ca(2+) sensitivity. The SOD activity was approximately 50% lower in wild-type mouse than in rat FDB muscles. Myoplasmic ROS increased during repeated tetanic stimulation in rat fibres but not in wild-type mouse fibres. The decreased Ca(2+) sensitivity in rat fibres could be partially reversed by application of the reducing agent dithiothreitol, whereas the decrease in tetanic [Ca(2+)](i) in wild-type mouse fibres was not affected by dithiothreitol or the antioxidant N-acetylcysteine. In conclusion, we describe two different causes of fatigue-induced prolonged low-frequency force depression, which correlate to differences in SOD activity and ROS metabolism. These findings may have clinical implications since ROS-mediated impairments in myofibrillar function can be counteracted by reductants and antioxidants, whereas changes in SR Ca(2+) handling appear more resistant to interventions.

  13. Hydrogen-rich water inhibits glucose and α,β -dicarbonyl compound-induced reactive oxygen species production in the SHR.Cg-Leprcp/NDmcr rat kidney

    Directory of Open Access Journals (Sweden)

    Katakura Masanori

    2012-07-01

    Full Text Available Abstract Background Reactive oxygen species (ROS production induced by α,β-dicarbonyl compounds and advanced glycation end products causes renal dysfunction in patients with type 2 diabetes and metabolic syndrome. Hydrogen-rich water (HRW increases the H2 level in blood and tissues, thus reducing oxidative stress in animals as well as humans. In this study, we investigated the effects of HRW on glucose- and α,β-dicarbonyl compound-induced ROS generation in vitro and in vivo. Methods Kidney homogenates from Wistar rats were incubated in vitro with glucose and α,β-dicarbonyl compounds containing HRW, following which ROS levels were measured. In vivo animal models of metabolic syndrome, SHR.Cg-Leprcp/NDmcr rats, were treated with HRW for 16 weeks, following which renal ROS production and plasma and renal α,β-dicarbonyl compound levels were measured by liquid chromatograph mass spectrometer. Results HRW inhibited glucose- and α,β-dicarbonyl compound-induced ROS production in kidney homogenates from Wistar rats in vitro. Furthermore, SHR.Cg-Leprcp/NDmcr rats treated with HRW showed a 34% decrease in ROS production. Moreover, their renal glyoxal, methylglyoxal, and 3-deoxyglucosone levels decreased by 81%, 77%, and 60%, respectively. Positive correlations were found between renal ROS levels and renal glyoxal (r = 0.659, p = 0.008 and methylglyoxal (r = 0.782, p = 0.001 levels. Conclusion These results indicate that HRW inhibits the production of α,β-dicarbonyl compounds and ROS in the kidneys of SHR.Cg-Leprcp/NDmcr rats. Therefore, it has therapeutic potential for renal dysfunction in patient with type 2 diabetes and metabolic syndrome.

  14. Extended longevity of reproductives appears to be common in Fukomys mole-rats (Rodentia, Bathyergidae.

    Directory of Open Access Journals (Sweden)

    Philip Dammann

    Full Text Available African mole-rats (Bathyergidae, Rodentia contain several social, cooperatively breeding species with low extrinsic mortality and unusually high longevity. All social bathyergids live in multigenerational families where reproduction is skewed towards a few breeding individuals. Most of their offspring remain as reproductively inactive "helpers" in their natal families, often for several years. This "reproductive subdivision" of mole-rat societies might be of interest for ageing research, as in at least one social bathyergid (Ansell's mole-rats Fukomys anselli, breeders have been shown to age significantly slower than non-breeders. These animals thus provide excellent conditions for studying the epigenetics of senescence by comparing divergent longevities within the same genotypes without the inescapable short-comings of inter-species comparisons. It has been claimed that many if not all social mole-rat species may have evolved similar ageing patterns, too. However, this remains unclear on account of the scarcity of reliable datasets on the subject. We therefore analyzed a 20-year breeding record of Giant mole-rats Fukomys mechowii, another social bathyergid species. We found that breeders indeed lived significantly longer than helpers (ca. 1.5-2.2fold depending on the sex, irrespective of social rank or other potentially confounding factors. Considering the phylogenetic positions of F. mechowii and F. anselli and unpublished data on a third Fukomys-species (F. damarensis showing essentially the same pattern, it seems probable that the reversal of the classic trade-off between somatic maintenance and sexual reproduction is characteristic of the whole genus and hence of the vast majority of social mole-rats.

  15. Ecological role of the giant root-rat (Tachyoryctes macrocephalus) in the Afroalpine ecosystem.

    Science.gov (United States)

    Šklíba, Jan; Vlasatá, Tereza; Lövy, Matěj; Hrouzková, Ema; Meheretu, Yonas; Sillero-Zubiri, Claudio; Šumbera, Radim

    2017-07-01

    Rodents with prevailing subterranean activity usually play an important role in the ecosystems of which they are a part due to the combined effect of herbivory and soil perturbation. This is the case for the giant root-rat Tachyoryctes macrocephalus endemic to the Afroalpine ecosystem of the Bale Mountains, Ethiopia. We studied the impact of root-rats on various ecosystem features within a 3.5-ha study locality dominated by Alchemilla pasture, which represents an optimal habitat for this species, in 2 periods of a year. The root-rats altered plant species composition, reducing the dominant forb, Alchemilla abyssinica, while enhancing Salvia merjame and a few other species, and reduced vegetation cover, but not the fresh plant biomass. Where burrows were abandoned by root-rats, other rodents took them over and A. abyssinica increased again. Root-rat burrowing created small-scale heterogeneity in soil compactness due to the backfilling of some unused burrow segments. Less compacted soil tended to be rich in nutrients, including carbon, nitrogen and phosphorus, which likely affected the plant growth on sites where the vegetation has been reduced as a result of root-rat foraging and burrowing. © 2016 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  16. Rats do not eat alone in public: Food-deprived rats socialize rather than competing for baits.

    Directory of Open Access Journals (Sweden)

    Omri Weiss

    Full Text Available Limited resources result in competition among social animals. Nevertheless, social animals also have innate preferences for cooperative behavior. In the present study, 12 dyads of food-deprived rats were tested in four successive trials, and then re-tested as eight triads of food-deprived rats that were unfamiliar to each other. We found that the food-deprived dyads or triads of rats did not compete for the food available to them at regular spatially-marked locations that they had previously learnt. Rather, these rats traveled together to collect the baits. One rat, or two rats in some triads, lead (ran ahead to collect most of the baits, but "leaders" differed across trials so that, on average, each rat ultimately collected similar amounts of baits. Regardless of which rat collected the baits, the rats traveled together with no substantial difference among them in terms of their total activity. We suggest that rats, which are a social species that has been found to display reciprocity, have evolved to travel and forage together and to share limited resources. Consequently, they displayed a sort of 'peace economy' that on average resulted in equal access to the baits across trials. For social animals, this type of dynamics is more relaxed, tolerant, and effective in the management of conflicts. Rather than competing for the limited available food, the food-deprived rats socialized and coexisted peacefully.

  17. Fraction from human and rat liver which is inhibitory for proliferation of liver cells.

    Science.gov (United States)

    Chen, T S; Ottenweller, J; Luke, A; Santos, S; Keeting, P; Cuy, R; Lea, M A

    1989-01-01

    A comparative study was undertaken with human and rat liver of a fraction reported to have growth inhibitory activity when prepared from rat liver. Fractions which were soluble in 70% ethanol and insoluble in 87% ethanol were prepared from liver cytosols. Electrophoretic analysis under denaturing conditions indicated that there were several quantitative or qualitative differences in the fractions from the two species. Fractions from both human and rat liver were found to be inhibitory for the incorporation of 3H-thymidine into DNA of foetal chick hepatocytes. Under conditions in which the rat fraction inhibited precursor incorporation into DNA of rat liver epithelial cells there was not a significant inhibitory effect with the fraction from human liver. DNA synthesis in a rat hepatoma cell line was not significantly inhibited by preparations from either species. The data suggested that corresponding fractions from both rat and human liver could have inhibitory effects on precursor incorporation into DNA but the magnitude of the effects and target cell specificity may differ.

  18. Mast cells in the sheep, hedgehog and rat forebrain

    Science.gov (United States)

    MICHALOUDI, HELEN C.; PAPADOPOULOS, GEORGIOS C.

    1999-01-01

    The study was designed to reveal the distribution of various mast cell types in the forebrain of the adult sheep, hedgehog and rat. Based on their histochemical and immunocytochemical characteristics, mast cells were categorised as (1) connective tissue-type mast cells, staining metachromatically purple with the toluidine blue method, or pale red with the Alcian blue/safranin method, (2) mucosal-type or immature mast cells staining blue with the Alcian blue/safranin method and (3) serotonin immunopositive mast cells. All 3 types of brain mast cells in all species studied were located in both white and grey matter, often associated with intraparenchymal blood vessels. Their distribution pattern exhibited interspecies differences, while their number varied considerably not only between species but also between individuals of each species. A distributional left-right asymmetry, with more cells present on the left side, was observed in all species studied but it was most prominent in the sheep brain. In the sheep, mast cells were abundantly distributed in forebrain areas, while in the hedgehog and the rat forebrain, mast cells were less widely distributed and were relatively or substantially fewer in number respectively. A limited number of brain mast cells, in all 3 species, but primarily in the rat, were found to react both immunocytochemically to 5-HT antibody and histochemically with Alcian blue/safranin staining. PMID:10634696

  19. Effect of moderate exercise on peritoneal neutrophils from juvenile rats.

    Science.gov (United States)

    Braz, Glauber Ruda; Ferreira, Diorginis Soares; Pedroza, Anderson Apolonio; da Silva, Aline Isabel; Sousa, Shirley Maria; Pithon-Curi, Tania Cristina; Lagranha, Claudia

    2015-09-01

    Previous studies showed that moderate exercise in adult rats enhances neutrophil function, although no studies were performed in juvenile rats. We evaluated the effects of moderate exercise on the neutrophil function in juvenile rats. Viability and neutrophils function were evaluated. Moderate exercise did not impair the viability and mitochondrial transmembrane potential of neutrophils, whereas there was greater reactive oxygen species production (164%; p < 0.001) and phagocytic capacity (29%; p < 0.05). Our results suggest that moderate exercise in juvenile rats improves neutrophil function, similar to adults.

  20. Photic induction of Fos in the suprachiasmatic nucleus of African mole-rats: responses to increasing irradiance.

    Science.gov (United States)

    Oosthuizen, Maria K; Bennett, Nigel C; Cooper, Howard M

    2010-09-01

    African mole-rats (family Bathyergidae) are strictly subterranean rodent species that are rarely exposed to environmental light. Morphological and physiological adaptations to the underground environment include a severely reduced eye size and regressed visual system. Responses of the circadian system to light, however, appear to be intact, since mole-rats are able to entrain their circadian activity rhythms to the light-dark cycle and light induces Fos expression in the suprachiasmatic nucleus (SCN). Social organization varies from solitary species to highly elaborated eusocial structures, characterized by a distinct division of labor and in which one reproductive female regulates the behavior and reproductive physiology of other individuals in the colony. The authors studied light-induced Fos expression in the SCN to increasing light intensities in four mole-rat species, ranging from strictly solitary to highly social. In the solitary Cape mole-rat, light induces significant Fos expression in the SCN, and the number of Fos-immunopositive cells increases with increasing light intensity. In contrast, Fos induction in the SCN of social species was slightly greater than, but not statistically different from, the dark-control animals as is typical of most rodents. One species showed a trend for an increase in expression with increased light, whereas a second species showed no trend in expression. In the naked mole-rat, Fos expression appeared higher in the dark-controls than in the animals exposed to light, although the differences in Fos expression were not significant. These results suggest a gradient in the sensitivity of the circadian system to light in mole-rats, with a higher percentage of individuals that are unresponsive to light in correlation with the degree of sociality. In highly social species, such as the naked mole-rat that live in a relatively stable subterranean milieu in terms of food availability, temperature, constant darkness, and devoid of 24-h

  1. Comparison of nicotinic receptor binding and biotransformation of coniine in the rat and chick.

    Science.gov (United States)

    Forsyth, C S; Speth, R C; Wecker, L; Galey, F D; Frank, A A

    1996-12-31

    Coniine, an alkaloid from Conium maculatum (poison hemlock), is a known teratogen in many domestic species with maternal ingestion resulting in arthrogryposis of the offspring. We have previously shown that rats are not susceptible and rabbits only weakly susceptible to coniine-induced arthrogryposis. However, the chick embryo does provide a reproducible laboratory animal model of coniine-induced teratogenesis. The reason for this cross-species variation is unknown. The purpose of this study was to evaluate coniine binding to nicotinic receptors and to measure coniine metabolism in vitro between susceptible and non-susceptible species. Using the chick model, neither the peripheral nicotinic receptor antagonist d-tubocurarine chloride nor the central nicotinic receptor antagonist trimethaphan camsylate blocked the teratogenesis or lethality of 1.5% coniine (50 microliters/egg). Trimethaphan camsylate enhanced coniine-induced lethality in a dose-dependent manner. Neither nicotinic receptor blocker prevented nicotine sulfate-induced malformations but d-tubocurarine chloride did block lethality in a dose-dependent manner. Competition by coniine for [125I]-alpha-bungarotoxin to nicotinic receptors isolated from adult rat diaphragm and chick thigh muscle and competition by coniine for [3H]-cytisine to receptors from rat and chick brain were used to assess coniine binding to nicotinic receptors. The IC50 for coniine in rat diaphragm was 314 microM while that for chick leg muscle was 70 microM. For neuronal nicotinic receptors, the IC50s of coniine for maternal rat brain, fetal rat brain, and chick brain were 1100 microM, 820 microM, and 270 microM, respectively. There were no differences in coniine biotransformation in vitro by microsomes from rat or chick livers. Differences in apparent affinity of coniine for nicotinic receptors or differences in the quantity of the nicotinic receptor between the rat and chick may explain, in part, the differences in susceptibility of

  2. Comparison of food hoarding of two sympatric rodent species under interspecific competition.

    Science.gov (United States)

    Zhang, Yi-Feng; Tong, Lei; Ji, Wei-Hong; Lu, Ji-Qi

    2013-01-01

    Competition can greatly affect the food hoarding strategies of rodents and the fate of seeds hoarded. In order to understand the influence of interspecific competition on food caching behavior of sympatric rodents, we investigated food hoarding patterns of two sympatric rodent species, buff-breasted rat (Rattus flavipectus) and Chinese white-bellied rat (Niviventor confucianus), and compared their responses and adjustment in hoarding behavior under interspecific competition. The results showed that: (1) the buff-breasted rat larder hoarded seeds only, while Chinese white-bellied rat hoarded seeds in both larder and scatter forms; (2) two species of rodents both larder hoarded more seeds when competitors were present; and (3) the Chinese white-bellied rats adjusted their seed hoarding from scatter to larder when competitors were introduced, which reduced the seed availability. Therefore, we concluded that rodents would adjust their food hoarding strategy when interspecific competitors were present, and this may produce a different effect on the fate of seeds and the recruitment of plants. This article is part of a Special Issue entitled: insert SI title. Copyright © 2012. Published by Elsevier B.V.

  3. Single-species versus dual-species probiotic supplementation as an emerging therapeutic strategy for obesity.

    Science.gov (United States)

    Karimi, G; Jamaluddin, R; Mohtarrudin, N; Ahmad, Z; Khazaai, H; Parvaneh, M

    2017-10-01

    Recent studies have reported beneficial effects of specific probiotics on obesity. However, the difference in the anti-obesity effects of probiotics as single species and dual species is still uncertain. Therefore, we aimed to compare the efficacy of single and dual species of bacteria on markers of obesity in high-fat diet-induced obese rats. A total of 40 male Sprague-Dawley rats were assigned to one of five groups of varying diets as follows: standard diet, high fat diet (HFD), HFD supplemented with Lactobacillus casei strain Shirota, HFD supplemented with Bifidobacterium longum and HFD supplemented with a mixture of these two bacterial species. After 15 weeks of supplementation, the animals were examined for changes in body weight, body fat, total count of bacteria in fecal, blood serum lipid profile, leptin, adiponectin and inflammatory biomarkers. Histological analysis of the liver and adipose tissue was performed and the hepatic mRNA expression levels of genes related to lipid metabolism were measured. It was found that probiotic supplementation of either B. longum or a mixture of B. longum and LcS bacteria significantly reduced weight and triglycerides in the HFD groups. Supplementation of B. longum bacteria showed better results in terms of modulating leptin level, fat mass, adipocyte size and lipoprotein lipase expression, as well as increasing adiponectin and peroxisome proliferator-activated receptors-γ expression compared to dual species of bacteria. No significant differences were observed in the total count of fecal bacteria, glucose and inflammatory biomarker levels between supplemented groups. B. longum supplementation in obesity was more beneficial in metabolic profile changes than the mixture species. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B

  4. Comparative morphology and morphometry of alveolar macrophages from six mammalian species

    International Nuclear Information System (INIS)

    Haley, P.J.; Muggenburg, B.A.; Weissman, D.N.; Bice, D.E.

    1988-01-01

    Pulmonary alveolar macrophages (PAM) were collected from normal, healthy mice, rats, dogs, cynomolgus monkeys, chimpanzees and humans and evaluated for morphologic and morphometric characteristics. The PAM of mice, rats, and dogs were morphologically similar to one another and had statistically similar frequency distributions for PAM size. The range of cell size for these three species was narrow. The PAM of nonhuman primates and humans were morphologically heterogenous with increased cytoplasmic vacuolation, irregular cell outlines and increased numbers of multi nucleated cells as compared to the PAM of rodents and dogs. The mean size of human PAMs was statistically greater than that for all other species evaluated, including nonhuman primates. These data indicate that significant differences in PAM morphology and size exist among species and that such differences may be important when selecting species for studies of PAM. (author)

  5. Adaptive training diminishes distractibility in aging across species.

    Science.gov (United States)

    Mishra, Jyoti; de Villers-Sidani, Etienne; Merzenich, Michael; Gazzaley, Adam

    2014-12-03

    Aging is associated with deficits in the ability to ignore distractions, which has not yet been remediated by any neurotherapeutic approach. Here, in parallel auditory experiments with older rats and humans, we evaluated a targeted cognitive training approach that adaptively manipulated distractor challenge. Training resulted in enhanced discrimination abilities in the setting of irrelevant information in both species that was driven by selectively diminished distraction-related errors. Neural responses to distractors in auditory cortex were selectively reduced in both species, mimicking the behavioral effects. Sensory receptive fields in trained rats exhibited improved spectral and spatial selectivity. Frontal theta measures of top-down engagement with distractors were selectively restrained in trained humans. Finally, training gains generalized to group and individual level benefits in aspects of working memory and sustained attention. Thus, we demonstrate converging cross-species evidence for training-induced selective plasticity of distractor processing at multiple neural scales, benefitting distractor suppression and cognitive control. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Radiolabelled soman binding to sera from Rats, Guinea Pigs and Monkeys.

    Science.gov (United States)

    Lenz, David E; Cerasoli, Douglas; Maxwell, Donald M

    2018-02-01

    Soman is a highly toxic organophosphorus chemical warfare compound that binds rapidly and irreversibility to a variety of serine active enzymes, i.e., butyryl- and acetyl-cholinesterases and carboxylesterase. The in vivo toxicity of soman has been reported to vary significantly in different animal species, such as rats and guinea pigs or non-human primates. This species variation makes it difficult to identify appropriate animal models for therapeutic drug development under the US Food and Drug Administration (FDA) Animal Rule. Since species variation in soman toxicity has been correlated with species variation in serum carboxylesterase, we undertook to determine if serum from guinea pigs, rats and non-human primates bound different levels of soman in vitro in the presence of equimolar concentrations of soman. Our results demonstrated that the amount of soman bound in the serum of rats was 4 uM, but essentially null in guinea pigs or non-human primates. The results strongly correlate with the presence or absence of carboxylesterase in the serum of animals and the difference in the toxic dose of soman in various species. Our results support prior suggestions that guinea pigs and non-human primates may be better animal models for the development of antidotes under the FDA Animal Rule. Published by Elsevier B.V.

  7. Long-lived cancer-resistant rodents as new model species for cancer research

    Directory of Open Access Journals (Sweden)

    Jorge eAzpurua

    2013-01-01

    Full Text Available Most rodents are small and short-lived, but several lineages have independently evolved long lifespans without a concomitant increase in body mass. Most notably, the two subterranean species naked mole rat (NMR and blind mole rat (BMR which have maximum lifespans of 32 and 21 years respectively. The longevity of these species has sparked interest in the tumor suppression strategies that may have also evolved, because for many rodent species (including mice, rats, guinea pigs, gerbils and hamsters tumors are major source of late-life mortality. Here, we review the recent literature on anticancer mechanisms in long-lived rodents. Both NMR and BMR seem to have developed tumor defenses that rely on extra-cellular signals. However, while the NMR relies on a form of contact inhibition to suppress growth, the BMR evolved a mechanism mediated by the release of interferon and rapid necrotic cell death. Although both organisms ultimately rely on canonical downstream tumor suppressors (pRB and p53 the studies reveal species can evolve different strategies to achieve tumor-resistance. Importantly, studies of these cancer-resistant rodents may benefit human health if such mechanisms can be activated in human cells.

  8. Stomach nematodes (Mastophorus muris) in rats (Rattus rattus) are associated with coconut (Cocos nucifera) habitat at Palmyra Atoll.

    Science.gov (United States)

    Lafferty, Kevin D; Hathaway, Stacie A; Wegmann, Alex S; Shipley, Frank S; Backlin, Adam R; Helm, Joel; Fisher, Robert N

    2010-02-01

    Black rats ( Rattus rattus ) and their stomach nematodes (Mastophorus muris) were historically introduced to islets at Palmyra Atoll in the central Pacific Line Islands. To investigate patterns of parasitism, we trapped rats and quantified nematodes on 13 islets of various sizes and habitat types. Most rats were parasitized (59%) with an average of 12 worms per infected rat. Islet size did not greatly influence parasite population biology. Nematodes also did not appear to affect rat condition (weight to skull length). The only strong and consistent factor associated with the mean abundance of nematodes in rats was habitat (dominant cover and locally dominant plant species). Thus, nematodes were much more abundant in rats from sites dominated by coconut trees (Cocos nucifera). Coconut trees may also be an introduced species at Palmyra Atoll.

  9. Utilization of molecular species of diglycerides in the synthesis of lecithin

    NARCIS (Netherlands)

    Mudd, J.B.; Golde, L.M.G. van; Deenen, L.L.M. van

    1969-01-01

    1. 1. The synthesis of lecithin by rat liver microsomes was measured in the presence of [14C]CDP-choline and three molecular species of diglycerides derived from rat liver lecithin containing four, two and one double bond. The rate of synthesis of lecithin was the same regardless of the fatty acid

  10. Quantitation of species differences in albumin–ligand interactions for bovine, human and rat serum albumins using fluorescence spectroscopy: A test case with some Sudlow's site I ligands

    International Nuclear Information System (INIS)

    Poór, Miklós; Li, Yin; Matisz, Gergely; Kiss, László; Kunsági-Máté, Sándor; Kőszegi, Tamás

    2014-01-01

    Albumin, the most abundant plasma protein is an approximately 67 kDa sized water-soluble macromolecule. Since several drugs and xenobiotics circulate in the blood at least partially in albumin-bound form, albumin plays a key role in the pharmacokinetics/toxicokinetics of these chemicals. Most of the drugs and xenobiotics are Sudlow's site I ligands. In numerous studies, bovine serum albumin (BSA) is used for modeling albumin–ligand interactions and the results are extrapolated to human serum albumin (HSA). Furthermore, only limited information is available related to albumin–ligand interactions of different albumin species. Therefore, in our study, we have focused on the quantification of differences between bovine, human and rat serum albumin (RSA) using four Sudlow's site I ligands (luteolin, ochratoxin A, phenylbutazone and warfarin). Interactions were analyzed by fluorescence spectroscopy. Stability constants as well as competing capacities of the ligands were determined, and thermodynamic study was also performed. Our results highlight that there could be major differences between BSA, HSA and RSA in their ligand binding properties. Based on our observations we emphasize that in molecular aspects BSA behaves considerably differently from HSA or from albumins of other species therefore, it is strongly recommended to apply at least some confirmatory measurements when data obtained from other species are attempted to be extrapolated to HSA. -- Highlights: • Albumin–ligand interactions of human, bovine and rat albumins were studied. • Four Sudlow's site I ligands were tested by fluorescence spectroscopy. • Substantial differences were found in stability constants among albumin complexes. • Competing capacity of ligands showed major differences in the studied species. • Data obtained for BSA cannot be directly extrapolated to human albumin

  11. Comparison of plutonium systemic distribution in rats and dogs with published data in humans.

    Science.gov (United States)

    Melo, Dunstana R; Weber, Waylon; Doyle-Eisele, Melanie; Guilmette, Raymond A

    2014-11-01

    This manuscript compares the behavior of monomeric (239)Pu(4+)-citrate injected intravenously in rats and dogs with a comparison of available humans' data. The experimental design for these two studies consisted of eight groups sacrificed at predetermined time-points post exposure. All organs and tissues as well as daily urinary and fecal excretion were analyzed. Liver and skeleton were the organs with the highest (239)Pu uptake in both species; 76% in dogs and 70% in rats at 24 hours (h) post IV administration. By the end of the study (28 days, d), the activity in skeleton and liver was 85% in dogs and 65% in rats. The urinary excretion function seems to be similar for rats, dogs and humans but the daily fecal to urinary excretion ratio differs between species. A rapid clearance from the liver of rats was observed compared to dogs. Skeleton-to-liver ratios are variable between species. Urinary and fecal excretion patterns for dogs are consistent with human data, indicating that dogs seem to represent better the (239)Pu behavior in humans. The data confirm that the better animal model to evaluate the efficacy of (239)Pu chelating compounds is the canine model.

  12. Microscopic dose distribution around PuO2 particles in lungs of hamsters, rats and dogs

    International Nuclear Information System (INIS)

    Diel, J.H.; Mewhinney, J.A.; Guilmette, R.A.

    1982-01-01

    Syrian hamsters, Fischer-344 rats and Beagle dogs inhaled monodisperse aerosols of PuO 2 and were sacrificed 1 to 16 days after exposure. The microscopic distribution of dose and tissue-at-risk around individual particles in lung was studied using autoradiographs of the lungs. The dose pattern in dogs and rats was more diffuse than in hamsters, resulting in a calculation of about twice the tumor incidence in rats and dogs as in hamsters on the basis of dose pattern using the same dose-effect model for all three species. The tumorigenic effect of inhaled insoluble PuO 2 particles depends on the species inhaling the material; Syrian hamsters are much less susceptible than are rats or dogs. It has been suggested that a difference in dose distribution resulting from differences in particle distributions in the two species may contribute to the differences in susceptibility in Syrian hamsters and rats. The role of dose distribution in lung cancer production is explored in this study by measuring microscopic dose patterns in regions surrounding single PuO 2 particles in lung. The alveolar structures of the dog and rat are different than those of the hamster. Based on these measurements, particles of PuO 2 in lung are more likely to cause lung cancer in dogs and rats than in hamsters

  13. Substantial species differences in relation to formation and degradation of N-acyl-ethanolamine phospholipids in heart tissue

    DEFF Research Database (Denmark)

    Moesgaard, B.; Petersen, G.; Hansen, Harald S.

    2002-01-01

    beneficial effects on the heart, but in the literature there are indications of species differences in the activity of these enzymes. We have examined heart microsomes from rats, mice, guinea pigs, rabbits, frogs, cows, dogs, cats, mini pigs and human beings for activities of these two enzymes. N......-Acyl-transferase activity was very high in dogs and cats (>13 pmol/min/mg protein) whereas it was very low to barely detectable in the other species (45 pmol/min/mg protein) whereas it was 9 pmol/min/mg protein in frogs and below that in the other species. The ratio of activity between the two enzymes varied from 0.......002 to 15 in the investigated species. The activity of the two enzymes in rat hearts as opposed to rat brain did not change during development. These results indicate that there may be substantial species differences in the generation of anandamide and other NAEs as well as NAPEs in heart tissues....

  14. Endangered Species Program, Naval Petroleum Reserves in California. Annual report FY93

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-02-01

    The Naval Petroleum Reserves in California (NPRC) are operated by the US Department of Energy (DOE) and Chevron USA. Production Company (CPDN). Four federally-listed endangered animal species and one federally-threatened plant species are known to occur on NPRC: San Joaquin kit fox, blunt-nosed leopard lizard, giant kangaroo rat, Tipton kangaroo rat, and Hoover`s wooly-star. All five are protected under the Endangered Species Act of 1973, which declares that it is ``...the policy of Congress that all Federal departments and agencies shall seek to conserve endangered species and threatened species and shall utilize their authorities in furtherance of the purposes of the Act.`` DOE is also obliged to determine whether actions taken by their lessees on Naval Petroleum Reserve No. 2 will have any effects on endangered species or their habitats. The major objective of the EG&G Energy Measurements, Inc. Endangered Species Program on NPRC is to provide DOE with the scientific expertise necessary for compliance with the Endangered Species Act. The specific objective of this report is to summarize progress and results of the Endangered Species Program made during fiscal year 1993.

  15. Comparative metabonomics of differential hydrazine toxicity in the rat and mouse

    International Nuclear Information System (INIS)

    Bollard, Mary E.; Keun, Hector C.; Beckonert, Olaf; Ebbels, Tim M.D.; Antti, Henrik; Nicholls, Andrew W.; Shockcor, John P.; Cantor, Glenn H.; Stevens, Greg; Lindon, John C.; Holmes, Elaine; Nicholson, Jeremy K.

    2005-01-01

    Interspecies variation between rats and mice has been studied for hydrazine toxicity using a novel metabonomics approach. Hydrazine hydrochloride was administered to male Sprague-Dawley rats (30 mg/kg, n = 10 and 90 mg/kg, n = 10) and male B6C3F mice (100 mg/kg, n = 8 and 250 mg/kg, n = 8) by oral gavage. In each species, the high dose was selected to produce the major histopathologic effect, hepatocellular lipid accumulation. Urine samples were collected at sequential time points up to 168 h post dose and analyzed by 1 H NMR spectroscopy. The metabolites of hydrazine, namely diacetyl hydrazine and 1,4,5,6-tetrahydro-6-oxo-3-pyridazine carboxylic acid (THOPC), were detected in both the rat and mouse urine samples. Monoacetyl hydrazine was detected only in urine samples from the rat and its absence in the urine of the mouse was attributed to a higher activity of N-acetyl transferases in the mouse compared with the rat. Differential metabolic effects observed between the two species included elevated urinary β-alanine, 3-D-hydroxybutyrate, citrulline, N-acetylcitrulline, and reduced trimethylamine-N-oxide excretion unique to the rat. Metabolic principal component (PC) trajectories highlighted the greater degree of toxic response in the rat. A data scaling method, scaled to maximum aligned and reduced trajectories (SMART) analysis, was used to remove the differences between the metabolic starting positions of the rat and mouse and varying magnitudes of effect, to facilitate comparison of the response geometries between the rat and mouse. Mice followed 'biphasic' open PC trajectories, with incomplete recovery 7 days after dosing, whereas rats followed closed 'hairpin' time profiles, indicating functional reversibility. The greater magnitude of metabolic effects observed in the rat was supported by the more pronounced effect on liver pathology in the rat when compared with the mouse

  16. Effects of dose, species, and dosing vehicle on the disposition of methacrylonitrile (MAN) in male rats

    International Nuclear Information System (INIS)

    Sanchez, I.M.; Ghanayem, B.I.

    1991-01-01

    MAN is structurally similar to known carcinogen acrylontrile (AN), with nitriles having similar industrial uses. Current studies were designed to investigate the biological fate of 2- 14 C-MAN in rats. After gavage administration of 115, 11.5 or 1.15 mg MAN/kg in water, F344 male rats were placed in glass metabolism cages and urine, expired air and feces were collected. Rats were sacrificed at various times and concentration of MAN-derived radioactivity in tissues was determined. MAN was rapidly absorbed from the GI tract and distributed to all major tissues. Sixty-70% of the low and medium doses were exhaled as 14 CO 2 in 72 hr compared to 25% of the highest dose. While 40% of the highest dose was expired as organic volatiles in 72 hr, only 9-12% of the low and accounted for 20-30% of all doses within 72 hr after dosing. Comparison of MAN disposition in Sprague-Dawley (SD) and F344 rats at 115 mg/kg revealed that SD rats excreted a greater % of the dose as 14 CO 2 and in the urine than did F344 rats. Administration of 115 mg MAN/kg to SD male rats in safflower oil resulted in increased elimination of MAN-derived radioactivity as CO 2 , volatiles, and in the urine over that observed when administered in water. These results suggest that: (1) saturation of MAN metabolism occurs at high doses: (2) MAN metabolism and disposition differ with the strain of rats studied; (3) MAN disposition may vary with the dosing vehicle used; and (4) MAN metabolism and disposition is apparently different from that reported on AN

  17. Stomach nematodes (Mastophorus Muris) in rats (Rattus rattus) are associated with coconut (Cocos nucifera) Habitat at palmyra atoll

    Science.gov (United States)

    Lafferty, K.D.; Hathaway, S.A.; Wegmann, A.S.; Shipley, F.S.; Backlin, A.R.; Helm, J.; Fisher, R.N.

    2010-01-01

    Black rats (Rattus rattus) and their stomach nematodes (Mastophorus muris) were historically introduced to islets at Palmyra Atoll in the central Pacific Line Islands. To investigate patterns of parasitism, we trapped rats and quantified nematodes on 13 islets of various sizes and habitat types. Most rats were parasitized (59) with an average of 12 worms per infected rat. Islet size did not greatly influence parasite population biology. Nematodes also did not appear to affect rat condition (weight to skull length). The only strong and consistent factor associated with the mean abundance of nematodes in rats was habitat (dominant cover and locally dominant plant species). Thus, nematodes were much more abundant in rats from sites dominated by coconut trees (Cocos nucifera). Coconut trees may also be an introduced species at Palmyra Atoll. ?? American Society of Parasitologists 2010.

  18. Verbascumkurdistanicum (Scrophulariaceae), a new species from Hakkâri, Turkey.

    Science.gov (United States)

    Fırat, Mehmet

    2015-01-01

    Verbascumkurdistanicum Fırat (Scrophulariaceae), is described and illustrated as a new species that is located in Hakkâri, Turkey. In this study, diagnostic morphological characters of this and closely related species (Verbascumoreophilum K.Koch and Verbascumpyramidatum M. Bieb) are discussed. Furthermore, distribution maps for the three taxa are provided.

  19. Social status and sex effects on neural morphology in Damaraland mole-rats, Fukomys damarensis.

    Science.gov (United States)

    Anyan, Jeff J; Seney, Marianne L; Holley, Amanda; Bengston, Lynn; Goldman, Bruce D; Forger, Nancy G; Holmes, Melissa M

    2011-01-01

    We previously reported that in a eusocial rodent, the naked mole-rat (Heterocephalus glaber), traditional neural sex differences were absent; instead, neural dimorphisms were associated with breeding status. Here we examined the same neural regions previously studied in naked mole-rats in a second eusocial species, the Damaraland mole-rat (Fukomys damarensis). Damaraland mole-rats live in social groups with breeding restricted to a small number of animals. However, colony sizes are much smaller in Damaraland mole-rats than in naked mole-rats and there is consequently less reproductive skew. In this sense, Damaraland mole-rats may be considered intermediate in social organization between naked mole-rats and more traditional laboratory rodents. We report that, as in naked mole-rats, breeding Damaraland mole-rats have larger volumes of the principal nucleus of the bed nucleus of the stria terminalis and paraventricular nucleus of the hypothalamus than do subordinates, with no effect of sex on these measures. Thus, these structures may play special roles in breeders of eusocial species. However, in contrast to what was seen in naked mole-rats, we also found sex differences in Damaraland mole-rats: volume of the medial amygdala and motoneuron number in Onuf's nucleus were both greater in males than in females, with no significant effect of breeding status. Thus, both sex and breeding status influence neural morphology in Damaraland mole-rats. These findings are in accord with the observed sex differences in body weight and genitalia in Damaraland but not naked mole-rats. We hypothesize that the increased sexual dimorphism in Damaraland mole-rats relative to naked mole-rats is related to reduced reproductive skew. 2011 S. Karger AG, Basel.

  20. Assessment of impacts and evaluation of restoration methods on areas affected by a well blowout, Naval Petroleum Reserve No. 1, California

    Energy Technology Data Exchange (ETDEWEB)

    Warrick, G.D.; Kato, T.T.; Phillips, M.V. [and others

    1996-12-01

    In June 1994, an oil well on Naval Petroleum Reserve No. 1 blew-out and crude oil was deposited downwind. After the well was capped, information was collected to characterize the release and to assess effects to wildlife and plants. Oil residue was found up to 13.7 km from the well site, but deposition was relatively light and the oil quickly dried to form a thin crust on the soil surface. Elevated levels of hydrocarbons were found in livers collected from Heermann`s kangaroo rats (Dipodomys heermanni) from the oiled area but polycyclic aromatic hydrocarbons (known carcinogens or mutagens) were not detected in the livers. Restoration techniques (surface modification and bioremediation) and natural recovery were evaluated within three portions of the oiled area. Herbaceous cover and production, and survival and vigor of desert saltbush (Atriplex polycarpa) were also monitored within each trapping grid.

  1. Nonstructural Protein L* Species Specificity Supports a Mouse Origin for Vilyuisk Human Encephalitis Virus.

    Science.gov (United States)

    Drappier, Melissa; Opperdoes, Fred R; Michiels, Thomas

    2017-07-15

    Vilyuisk human encephalitis virus (VHEV) is a picornavirus related to Theiler's murine encephalomyelitis virus (TMEV). VHEV was isolated from human material passaged in mice. Whether this VHEV is of human or mouse origin is therefore unclear. We took advantage of the species-specific activity of the nonstructural L* protein of theiloviruses to track the origin of TMEV isolates. TMEV L* inhibits RNase L, the effector enzyme of the interferon pathway. By using coimmunoprecipitation and functional RNase L assays, the species specificity of RNase L antagonism was tested for L* from mouse (DA) and rat (RTV-1) TMEV strains as well as for VHEV. Coimmunoprecipitation and functional assay data confirmed the species specificity of L* activity and showed that L* from rat strain RTV-1 inhibited rat but not mouse or human RNase L. Next, we showed that the VHEV L* protein was phylogenetically related to L* of mouse viruses and that it failed to inhibit human RNase L but readily antagonized mouse RNase L, unambiguously showing the mouse origin of VHEV. IMPORTANCE Defining the natural host of a virus can be a thorny issue, especially when the virus was isolated only once or when the isolation story is complex. The species Theilovirus includes Theiler's murine encephalomyelitis virus (TMEV), infecting mice and rats, and Saffold virus (SAFV), infecting humans. One TMEV strain, Vilyuisk human encephalitis virus (VHEV), however, was isolated from mice that were inoculated with cerebrospinal fluid of a patient presenting with chronic encephalitis. It is therefore unclear whether VHEV was derived from the human sample or from the inoculated mouse. The L* protein encoded by TMEV inhibits RNase L, a cellular enzyme involved in innate immunity, in a species-specific manner. Using binding and functional assays, we show that this species specificity even allows discrimination between TMEV strains of mouse and of rat origins. The VHEV L* protein clearly inhibited mouse but not human RNase L

  2. Species differences in the effect of pregnancy on lymphocyte cytokine production between human and rat

    NARCIS (Netherlands)

    Faas, Marijke M.; Bouman, Annechien; Veenstra van Nieuwenhoven, Angelique L.; van der Schaaf, Gerda; Moes, Henk; Heineman, Maas Jan; de Vos, Paul

    2005-01-01

    In the present study, we evaluated whether lymphocyte cytokine production during human and rat pregnancy shifts toward T helper cell type 2 (Th2) cytokine production. Therefore, blood samples were taken during the follicular and luteal phase and during pregnancy in rats and humans. Whole blood was

  3. Transplacental absorption of 238Pu in rats and guinea pigs

    International Nuclear Information System (INIS)

    Sullivan, M.F.

    1980-01-01

    Pregnant rats and guinea pigs were injected intravenously with 238 Pu citrate to determine if the potential for in utero accumulation of 238 Pu by these two species is related to the stage of development at which immunity is gained. Although guinea pigs retained more 238 Pu after birth than rats, the difference was not significant

  4. Characterization of differential cocaine metabolism in mouse and rat through metabolomics-guided metabolite profiling.

    Science.gov (United States)

    Yao, Dan; Shi, Xiaolei; Wang, Lei; Gosnell, Blake A; Chen, Chi

    2013-01-01

    Rodent animal models have been widely used for studying neurologic and toxicological events associated with cocaine abuse. It is known that the mouse is more susceptible to cocaine-induced hepatotoxicity (CIH) than the rat. However, the causes behind this species-dependent sensitivity to cocaine have not been elucidated. In this study, cocaine metabolism in the mouse and rat was characterized through LC-MS-based metabolomic analysis of urine samples and were further compared through calculating the relative abundance of individual cocaine metabolites. The results showed that the levels of benzoylecgonine, a major cocaine metabolite from ester hydrolysis, were comparable in the urine from the mice and rats treated with the same dose of cocaine. However, the levels of the cocaine metabolites from oxidative metabolism, such as N-hydroxybenzoylnorecgonine and hydroxybenzoylecgonine, differed dramatically between the two species, indicating species-dependent cocaine metabolism. Subsequent structural analysis through accurate mass analysis and LC-MS/MS fragmentation revealed that N-oxidation reactions, including N-demethylation and N-hydroxylation, are preferred metabolic routes in the mouse, while extensive aryl hydroxylation reactions occur in the rat. Through stable isotope tracing and in vitro enzyme reactions, a mouse-specific α-glucoside of N-hydroxybenzoylnorecgonine and a group of aryl hydroxy glucuronides high in the rat were identified and structurally elucidated. The differences in the in vivo oxidative metabolism of cocaine between the two rodent species were confirmed by the in vitro microsomal incubations. Chemical inhibition of P450 enzymes further revealed that different P450-mediated oxidative reactions in the ecgonine and benzoic acid moieties of cocaine contribute to the species-dependent biotransformation of cocaine.

  5. Bacterial Flora Changes in Conjunctiva of Rats with Streptozotocin-Induced Type I Diabetes.

    Science.gov (United States)

    Yang, Chao; Fei, Yuda; Qin, Yali; Luo, Dan; Yang, Shufei; Kou, Xinyun; Zi, Yingxin; Deng, Tingting; Jin, Ming

    2015-01-01

    The microbiota of both humans and animals plays an important role in their health and the development of disease. Therefore, the bacterial flora of the conjunctiva may also be associated with some diseases. However, there are no reports on the alteration of bacterial flora in conjunctiva of diabetic rats in the literature. Therefore, we investigated the changes in bacterial flora in bulbar conjunctiva of rats with streptozotocin (STZ)-induced type I diabetes. A high dose of STZ (60 mg/kg, i.p.) was injected into Sprague-Dawley (SD) rats to induce type I diabetes mellitus (T1DM). The diabetic rats were raised in the animal laboratory and at 8 months post-injection of STZ swab samples were taken from the bulbar conjunctiva for cultivation of aerobic bacteria. The bacterial isolates were identified by Gram staining and biochemical features. The identified bacteria from both diabetic and healthy rats were then compared. The diabetic and healthy rats had different bacterial flora present in their bulbar conjunctiva. In total, 10 and 8 bacterial species were found in the STZ and control groups, respectively, with only three species (Enterococcus faecium, Enterococcus gallinarum and Escherichia coli) shared between the two groups. Gram-positive bacteria were common in both groups and the most abundant was Enterococcus faecium. However, after the development of T1DM, the bacterial flora in the rat bulbar conjunctiva changed considerably, with a reduced complexity evident. STZ-induced diabetes caused alterations of bacterial flora in the bulbar conjunctiva in rats, with some bacterial species disappearing and others emerging. Our results indicate that the conjunctival bacterial flora in diabetic humans should be surveyed for potential diagnostic markers or countermeasures to prevent eye infections in T1DM patients.

  6. Sociality and the telencephalic distribution of corticotrophin-releasing factor, urocortin 3, and binding sites for CRF type 1 and type 2 receptors: A comparative study of eusocial naked mole-rats and solitary Cape mole-rats.

    Science.gov (United States)

    Coen, Clive W; Kalamatianos, Theodosis; Oosthuizen, Maria K; Poorun, Ravi; Faulkes, Christopher G; Bennett, Nigel C

    2015-11-01

    Various aspects of social behavior are influenced by the highly conserved corticotrophin-releasing factor (CRF) family of peptides and receptors in the mammalian telencephalon. This study has mapped and compared the telencephalic distribution of the CRF receptors, CRF1 and CRF2 , and two of their ligands, CRF and urocortin 3, respectively, in African mole-rat species with diametrically opposed social behavior. Naked mole-rats live in large eusocial colonies that are characterized by exceptional levels of social cohesion, tolerance, and cooperation in burrowing, foraging, defense, and alloparental care for the offspring of the single reproductive female. Cape mole-rats are solitary; they tolerate conspecifics only fleetingly during the breeding season. The telencephalic sites at which the level of CRF1 binding in naked mole-rats exceeds that in Cape mole-rats include the basolateral amygdaloid nucleus, hippocampal CA3 subfield, and dentate gyrus; in contrast, the level is greater in Cape mole-rats in the shell of the nucleus accumbens and medial habenular nucleus. For CRF2 binding, the sites with a greater level in naked mole-rats include the basolateral amygdaloid nucleus and dentate gyrus, but the septohippocampal nucleus, lateral septal nuclei, amygdalostriatal transition area, bed nucleus of the stria terminalis, and medial habenular nucleus display a greater level in Cape mole-rats. The results are discussed with reference to neuroanatomical and behavioral studies of various species, including monogamous and promiscuous voles. By analogy with findings in those species, we speculate that the abundance of CRF1 binding in the nucleus accumbens of Cape mole-rats reflects their lack of affiliative behavior. © 2015 Wiley Periodicals, Inc.

  7. Rats, cats, and elephants, but still no unicorn: induced pluripotent stem cells from new species.

    Science.gov (United States)

    Trounson, Alan

    2009-01-09

    Two independent studies in this issue of Cell Stem Cell (Liao et al., 2009; Li et al., 2009) derive rat induced pluripotent stem cells (iPSCs). In one report, the method used results in rat and human iPSCs that exhibit phenotypic traits similar to mouse embryonic stem cells.

  8. Fecal microbiota variation across the lifespan of the healthy laboratory rat.

    Science.gov (United States)

    Flemer, Burkhardt; Gaci, Nadia; Borrel, Guillaume; Sanderson, Ian R; Chaudhary, Prem P; Tottey, William; O'Toole, Paul W; Brugère, Jean-François

    2017-09-03

    Laboratory rats are commonly used in life science research as a model for human biology and disease, but the composition and development of their gut microbiota during life is poorly understood. We determined the fecal microbiota composition of healthy Sprague Dawley laboratory rats from 3 weeks to 2 y of age, kept under controlled environmental and dietary conditions. Additionally, we determined fecal short-chain fatty acid profiles, and we compared the rat fecal microbiota with that of mice and humans. Gut microbiota and to a lesser extent SCFAs profiles separated rats into 3 different clusters according to age: before weaning, first year of life (12- to 26-week-old animals) and second year of life (52- to 104-week-old). A core of 46 bacterial species was present in all rats but its members' relative abundance progressively decreased with age. This was accompanied by an increase of microbiota α-diversity, likely due to the acquisition of environmental microorganisms during the lifespan. Contrastingly, the functional profile of the microbiota across animal species became more similar upon aging. Lastly, the microbiota of rats and mice were most similar to each other but at the same time the microbiota profile of rats was more similar to that of humans than was the microbiota profile of mice. These data offer an explanation as to why germ-free rats are more efficient recipients and retainers of human microbiota than mice. Furthermore, experimental design should take into account dynamic changes in the microbiota of model animals considering that their changing gut microbiota interacts with their physiology.

  9. Trading new neurons for status: Adult hippocampal neurogenesis in eusocial Damaraland mole-rats.

    Science.gov (United States)

    Oosthuizen, M K; Amrein, I

    2016-06-02

    Diversity in social structures, from solitary to eusocial, is a prominent feature of subterranean African mole-rat species. Damaraland mole-rats are eusocial, they live in colonies that are characterized by a reproductive division of labor and a subdivision into castes based on physiology and behavior. Damaraland mole-rats are exceptionally long lived and reproductive animals show delayed aging compared to non-reproductive animals. In the present study, we described the hippocampal architecture and the rate of hippocampal neurogenesis of wild-derived, adult Damaraland mole-rats in relation to sex, relative age and social status or caste. Overall, Damaraland mole-rats were found to have a small hippocampus and low rates of neurogenesis. We found no correlation between neurogenesis and sex or relative age. Social status or caste was the most prominent modulator of neurogenesis. An inverse relationship between neurogenesis and social status was apparent, with queens displaying the lowest neurogenesis while the worker mole-rats had the most. As there is no natural progression from one caste to another, social status within a colony was relatively stable and is reflected in the level of neurogenesis. Our results correspond to those found in the naked mole-rat, and may reflect an evolutionary and environmentally conserved trait within social mole-rat species. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Sleep in the Cape Mole Rat: A Short-Sleeping Subterranean Rodent.

    Science.gov (United States)

    Kruger, Jean-Leigh; Gravett, Nadine; Bhagwandin, Adhil; Bennett, Nigel C; Archer, Elizabeth K; Manger, Paul R

    2016-01-01

    The Cape mole rat Georychus capensis is a solitary subterranean rodent found in the western and southern Cape of South Africa. This approximately 200-gram bathyergid rodent shows a nocturnal circadian rhythm, but sleep in this species is yet to be investigated. Using telemetric recordings of the electroencephalogram (EEG) and electromyogram (EMG) in conjunction with video recordings, we were able to show that the Cape mole rat, like all other rodents, has sleep periods composed of both rapid eye movement (REM) and slow-wave (non-REM) sleep. These mole rats spent on average 15.4 h awake, 7.1 h in non-REM sleep and 1.5 h in REM sleep each day. Cape mole rats sleep substantially less than other similarly sized terrestrial rodents but have a similar percentage of total sleep time occupied by REM sleep. In addition, the duration of both non-REM and REM sleep episodes was markedly shorter in the Cape mole rat than has been observed in terrestrial rodents. Interestingly, these features (total sleep time and episode duration) are similar to those observed in another subterranean bathyergid mole rat, i.e. Fukomys mechowii. Thus, there appears to be a bathyergid type of sleep amongst the rodents that may be related to their environment and the effect of this on their circadian rhythm. Investigating further species of bathyergid mole rats may fully define the emerging picture of sleep in these subterranean African rodents. © 2016 S. Karger AG, Basel.

  11. Differential subnetwork of chemokines/cytokines in human, mouse, and rat brain cells after oxygen-glucose deprivation.

    Science.gov (United States)

    Du, Yang; Deng, Wenjun; Wang, Zixing; Ning, MingMing; Zhang, Wei; Zhou, Yiming; Lo, Eng H; Xing, Changhong

    2017-04-01

    Mice and rats are the most commonly used animals for preclinical stroke studies, but it is unclear whether targets and mechanisms are always the same across different species. Here, we mapped the baseline expression of a chemokine/cytokine subnetwork and compared responses after oxygen-glucose deprivation in primary neurons, astrocytes, and microglia from mouse, rat, and human. Baseline profiles of chemokines (CX3CL1, CXCL12, CCL2, CCL3, and CXCL10) and cytokines (IL-1α, IL-1β, IL-6, IL-10, and TNFα) showed significant differences between human and rodents. The response of chemokines/cytokines to oxygen-glucose deprivation was also significantly different between species. After 4 h oxygen-glucose deprivation and 4 h reoxygenation, human and rat neurons showed similar changes with a downregulation in many chemokines, whereas mouse neurons showed a mixed response with up- and down-regulated genes. For astrocytes, subnetwork response patterns were more similar in rats and mice compared to humans. For microglia, rat cells showed an upregulation in all chemokines/cytokines, mouse cells had many down-regulated genes, and human cells showed a mixed response with up- and down-regulated genes. This study provides proof-of-concept that species differences exist in chemokine/cytokine subnetworks in brain cells that may be relevant to stroke pathophysiology. Further investigation of differential gene pathways across species is warranted.

  12. Spatial variation in the parasite communities and genomic structure of urban rats in New York City.

    Science.gov (United States)

    Angley, L P; Combs, M; Firth, C; Frye, M J; Lipkin, I; Richardson, J L; Munshi-South, J

    2018-02-01

    Brown rats (Rattus norvegicus) are a globally distributed pest. Urban habitats can support large infestations of rats, posing a potential risk to public health from the parasites and pathogens they carry. Despite the potential influence of rodent-borne zoonotic diseases on human health, it is unclear how urban habitats affect the structure and transmission dynamics of ectoparasite and microbial communities (all referred to as "parasites" hereafter) among rat colonies. In this study, we use ecological data on parasites and genomic sequencing of their rat hosts to examine associations between spatial proximity, genetic relatedness and the parasite communities associated with 133 rats at five sites in sections of New York City with persistent rat infestations. We build on previous work showing that rats in New York carry a wide variety of parasites and report that these communities differ significantly among sites, even across small geographical distances. Ectoparasite community similarity was positively associated with geographical proximity; however, there was no general association between distance and microbial communities of rats. Sites with greater overall parasite diversity also had rats with greater infection levels and parasite species richness. Parasite community similarity among sites was not linked to genetic relatedness of rats, suggesting that these communities are not associated with genetic similarity among host individuals or host dispersal among sites. Discriminant analysis identified site-specific associations of several parasite species, suggesting that the presence of some species within parasite communities may allow researchers to determine the sites of origin for newly sampled rats. The results of our study help clarify the roles that colony structure and geographical proximity play in determining the ecology of R. norvegicus as a significant urban reservoir of zoonotic diseases. Our study also highlights the spatial variation present in urban

  13. Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat.

    Science.gov (United States)

    Omerbašić, Damir; Smith, Ewan St J; Moroni, Mirko; Homfeld, Johanna; Eigenbrod, Ole; Bennett, Nigel C; Reznick, Jane; Faulkes, Chris G; Selbach, Matthias; Lewin, Gary R

    2016-10-11

    The naked mole-rat is a subterranean rodent lacking several pain behaviors found in humans, rats, and mice. For example, nerve growth factor (NGF), an important mediator of pain sensitization, fails to produce thermal hyperalgesia in naked mole-rats. The sensitization of capsaicin-sensitive TRPV1 ion channels is necessary for NGF-induced hyperalgesia, but naked mole-rats have fully functional TRPV1 channels. We show that exposing isolated naked mole-rat nociceptors to NGF does not sensitize TRPV1. However, the naked mole-rat NGF receptor TrkA displays a reduced ability to engage signal transduction pathways that sensitize TRPV1. Between one- and three-amino-acid substitutions in the kinase domain of the naked mole-rat TrkA are sufficient to render the receptor hypofunctional, and this is associated with the absence of heat hyperalgesia. Our data suggest that evolution has selected for a TrkA variant that abolishes a robust nociceptive behavior in this species but is still compatible with species fitness. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Hypofunctional TrkA Accounts for the Absence of Pain Sensitization in the African Naked Mole-Rat

    Directory of Open Access Journals (Sweden)

    Damir Omerbašić

    2016-10-01

    Full Text Available The naked mole-rat is a subterranean rodent lacking several pain behaviors found in humans, rats, and mice. For example, nerve growth factor (NGF, an important mediator of pain sensitization, fails to produce thermal hyperalgesia in naked mole-rats. The sensitization of capsaicin-sensitive TRPV1 ion channels is necessary for NGF-induced hyperalgesia, but naked mole-rats have fully functional TRPV1 channels. We show that exposing isolated naked mole-rat nociceptors to NGF does not sensitize TRPV1. However, the naked mole-rat NGF receptor TrkA displays a reduced ability to engage signal transduction pathways that sensitize TRPV1. Between one- and three-amino-acid substitutions in the kinase domain of the naked mole-rat TrkA are sufficient to render the receptor hypofunctional, and this is associated with the absence of heat hyperalgesia. Our data suggest that evolution has selected for a TrkA variant that abolishes a robust nociceptive behavior in this species but is still compatible with species fitness.

  15. Population genetics, community of parasites, and resistance to rodenticides in an urban brown rat (Rattus norvegicus) population.

    Science.gov (United States)

    Desvars-Larrive, Amélie; Pascal, Michel; Gasqui, Patrick; Cosson, Jean-François; Benoît, Etienne; Lattard, Virginie; Crespin, Laurent; Lorvelec, Olivier; Pisanu, Benoît; Teynié, Alexandre; Vayssier-Taussat, Muriel; Bonnet, Sarah; Marianneau, Philippe; Lacôte, Sandra; Bourhy, Pascale; Berny, Philippe; Pavio, Nicole; Le Poder, Sophie; Gilot-Fromont, Emmanuelle; Jourdain, Elsa; Hammed, Abdessalem; Fourel, Isabelle; Chikh, Farid; Vourc'h, Gwenaël

    2017-01-01

    Brown rats are one of the most widespread urban species worldwide. Despite the nuisances they induce and their potential role as a zoonotic reservoir, knowledge on urban rat populations remains scarce. The main purpose of this study was to characterize an urban brown rat population from Chanteraines park (Hauts-de-Seine, France), with regards to haematology, population genetics, immunogenic diversity, resistance to anticoagulant rodenticides, and community of parasites. Haematological parameters were measured. Population genetics was investigated using 13 unlinked microsatellite loci. Immunogenic diversity was assessed for Mhc-Drb. Frequency of the Y139F mutation (conferring resistance to rodenticides) and two linked microsatellites were studied, concurrently with the presence of anticoagulant residues in the liver. Combination of microscopy and molecular methods were used to investigate the occurrence of 25 parasites. Statistical approaches were used to explore multiple parasite relationships and model parasite occurrence. Eighty-six rats were caught. The first haematological data for a wild urban R. norvegicus population was reported. Genetic results suggested high genetic diversity and connectivity between Chanteraines rats and surrounding population(s). We found a high prevalence (55.8%) of the mutation Y139F and presence of rodenticide residues in 47.7% of the sampled individuals. The parasite species richness was high (16). Seven potential zoonotic pathogens were identified, together with a surprisingly high diversity of Leptospira species (4). Chanteraines rat population is not closed, allowing gene flow and making eradication programs challenging, particularly because rodenticide resistance is highly prevalent. Parasitological results showed that co-infection is more a rule than an exception. Furthermore, the presence of several potential zoonotic pathogens, of which four Leptospira species, in this urban rat population raised its role in the maintenance

  16. Comparative study of activities in reactive oxygen species production/defense system in mitochondria of rat brain and liver, and their susceptibility to methylmercury toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Mori, N.; Hirayama, K. [Kumamoto University, School of Health Science, Kumamoto (Japan); Yasutake, A. [National Institute for Minamata Disease, Minamata (Japan)

    2007-11-15

    The involvement of oxidative stress has been suggested as a mechanism for neurotoxicity caused by methylmercury (MeHg), but the mechanism for MeHg selective toxicity in the central nervous system is still unclear. In this research, to clarify the mechanism of selective neurotoxicity caused by MeHg, the oxygen consumption levels, the reactive oxygen species (ROS) production rates and several antioxidant levels in mitochondria were compared among the cerebrum, cerebellum and liver of male Wistar rats. In addition, the alterations of these indexes were examined in MeHg-intoxicated rats (oral administration of 10 mg/kg day, for 5 days). Although the cerebrum and cerebellum in intact rats showed higher mitochondrial oxygen consumption levels and ROS production rates than the liver, glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities were much lower in the cerebrum and cerebellum than in the liver. Especially, the cerebellum showed the highest oxygen consumption and ROS production rate and the lowest mitochondrial glutathione (GSH) levels among the tissues examined. In the MeHg-treated rats, decrease in the oxygen consumption and increase in the ROS generation were found only in the cerebellum mitochondria, despite a lower Hg accumulation in the mitochondrial fraction compared to the liver. Since MeHg treatment produced an enhancement of ROS generation in cerebellum mitochondria supplemented with succinate substrates, MeHg-induced oxidative stress might affect the complex II-III mediated pathway in the electron transfer chain in the cerebellum mitochondria. Our study suggested that inborn factors, high production system activity and low defense system activity of ROS in the brain, would relate to the high susceptibility of the central nervous system to MeHg toxicity. (orig.)

  17. Comparison of Pu metabolism and pulmonary tumors in dogs and rats exposed to 239PuO2

    International Nuclear Information System (INIS)

    Mahaffey, J.A.; Sanders, C.L.; Dagle, G.E.; Park, J.F.

    The dose-effect relationships of dogs and rats exposed by inhalation to 239 PuO 2 were compared to evaluate parameters that may provide a better understanding for extrapolating these laboratory animal results to humans. Comparisons were made on animals with lifetime lung doses between 1400 and 11,000 rad. Parameters compared included survival; Pu clearance and translocation; and time of occurrence, incidence and histopathology of pulmonary tumors. The group means for lifetime dose to lung were not significantly different between dogs and rats, but when survival time was expressed as the percentage of maximum life expectancy (MLE), the mean survival time of dogs was 40% of MLE and of rats was 56% of MLE. Lung tumors were the causes of death in 84% of the dogs and 54% of the rats; the mean survival time to lung tumor was 44% of MLE for dogs, compared to 57% of MLE for rats. Whole-body clearance of plutonium was slower in dogs. More Pu translocated to the thoracic lymph nodes, liver, and skeleton in the dogs than in rats. Estimates of species differences in lung clearance were dependent on the methods of estimating initial lung burden. There were parameters with qualitative and quantitative similarities in dogs and rats. Quantitative differences between species, generally within a factor of two, suggested that more reliable dosimetry estimates are needed to make quantitative extrapolation between species

  18. Epithelial cell kinetics in mouse and rat skin irradiated with electrons

    International Nuclear Information System (INIS)

    McMaster-Schuyler, L.

    1984-02-01

    Experiments were performed to examine the kinetic responses of mouse and rat epidermal cells in vivo after single doses of ionizing radiation including responses of hair follicles at times after irradiation. The labeling indices in both species were reduced to 30 to 50% of control values immediately following irradiation at all the doses. In the rat, the labeling indices recovered and overshot control values within the first three days after 300 to 1200 rads. The mouse labeling indices continued to be suppressed for up to 10 days after 300 to 2400 rads. This indicated that rat G 1 phase epidermal cells recovered three times faster than those of the mouse with respect to the ability to maintain or increase control level cell proliferation after irradiation. After 1800 and 2400 rads, doses which produce skin ulceration, both species showed a reduction in their labeling indices for up to 7 days, indicating that a dose-dependent mechanism of recovery may be operable in the rat. 99 refs., 15 figs., 6 tabs

  19. Hepatobiliary Clearance Prediction: Species Scaling From Monkey, Dog, and Rat, and In Vitro-In Vivo Extrapolation of Sandwich-Cultured Human Hepatocytes Using 17 Drugs.

    Science.gov (United States)

    Kimoto, Emi; Bi, Yi-An; Kosa, Rachel E; Tremaine, Larry M; Varma, Manthena V S

    2017-09-01

    Hepatobiliary elimination can be a major clearance pathway dictating the pharmacokinetics of drugs. Here, we first compared the dose eliminated in bile in preclinical species (monkey, dog, and rat) with that in human and further evaluated single-species scaling (SSS) to predict human hepatobiliary clearance. Six compounds dosed in bile duct-cannulated (BDC) monkeys showed biliary excretion comparable to human; and the SSS of hepatobiliary clearance with plasma fraction unbound correction yielded reasonable predictions (within 3-fold). Although dog SSS also showed reasonable predictions, rat overpredicted hepatobiliary clearance for 13 of 24 compounds. Second, we evaluated the translatability of in vitro sandwich-cultured human hepatocytes (SCHHs) to predict human hepatobiliary clearance for 17 drugs. For drugs with no significant active uptake in SCHH studies (i.e., with or without rifamycin SV), measured intrinsic biliary clearance was directly scalable with good predictability (absolute average fold error [AAFE] = 1.6). Drugs showing significant active uptake in SCHH, however, showed improved predictability when scaled based on extended clearance term (AAFE = 2.0), which incorporated sinusoidal uptake along with a global scaling factor for active uptake and the canalicular efflux clearance. In conclusion, SCHH is a useful tool to predict human hepatobiliary clearance, whereas BDC monkey model may provide further confidence in the prospective predictions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  20. The Use of Cytochrome b Gene as a Specific Marker of the Rat Meat (Rattus norvegicus on Meat and Meat Products

    Directory of Open Access Journals (Sweden)

    C. Sumantri

    2012-04-01

    Full Text Available Falsification of the origin of livestock meat and its processed with rat meat is a problem that must be overcome to ensure food safety. One way that is often used to detect forgeries by using cytochrome b gene as a marker. The purpose of this study was to create a specific primer derived from cytochrome b sequences in rat (Rattus norvegicus as the DNA marker to detect any contamination of rat meat on fresh livestock meat and its processed meat products. Meatballs were made from beef meat with the addition of rat 1%-25%, and the meatballs were obtained from traditional markets. DNA extraction was conducted from seven species (goat, chicken, cattle, sheep, pig, horse, and rat by using phenol-chloroform. The highest success rate in detecting the presence of rat meat in a mixture of beef meatballs at concentration of 15% was 100%. The specific fragment of cytochrome b gene in R. norvegicus has no similarity with the cytochrome b gene from six other species, so it can be used as molecular markers to detect the presence of rat meat contamination in the processed of meat products. Amplified fragment length for goats, chickens, cattle, sheep, pigs, horses, and rats 157, 227, 274, 331, 398, 439 and 603 bp respectively. The amplification of cytochrome b gene in seven species of animals with different fragment length indicated the specificity of cytochrome b gene sequences among species.

  1. Perinatal L-arginine and antioxidant supplements reduce adult blood pressure in spontaneously hypertensive rats

    NARCIS (Netherlands)

    Racasan, S; Braam, B; van der Giezen, DM; Goldschmeding, R; Boer, P; Koomans, HA; Joles, JA

    Embryo cross-transplantation and cross-fostering between spontaneously hypertensive rats (SHR) and normotensive rats (WKY) suggest that perinatal environment modulates the genetically determined phenotype. In SHR the balance between NO and reactive oxygen species (ROS) is disturbed. We hypothesized

  2. Similarity of satellite DNA properties in the order Rodentia

    Energy Technology Data Exchange (ETDEWEB)

    Mazrimas, J A; Hatch, F T

    1977-09-01

    We have characterized satellite DNAs from 9 species of kangaroo rat (Dipodomys) and have shown that the HS-..cap alpha.. and HS-..beta.. satellites, where present, are nearly identical in all species as to melting transition midpoint (Tm), and density in neutral CsCl, alkaline CsCl, and Cs/sub 2/SO/sub 4/-Ag/sup +/ gradients. However, the MS satellites exist in two internally similar classes. The satellite DNAs from three other rodents were characterized (densities listed are in neutral CsCl). The pocket gopher, Thomomys bottae, contains Th-..cap alpha.. (1.713 g/ml) and Th-..beta.. (1.703 g/ml). The guinea pig (Cavia porcellus) contains Ca-..cap alpha.., Ca-..beta.., and Ca-..gamma.. at densities of 1.706 g/ml, 1.704 g/ml, and 1.704 g/ml, respectively. The antelope ground squirrel (Ammospermophilus harrisi) contains Am-..cap alpha.., 1.708 g/ml, Am-..beta.., 1.717 g/ml, and Am-..gamma.., 1.707 g/ml. The physical and chemical properties of the alpha-satellites from the above four rodents representing four different families in two suborders of Rodentia were compared. They show nearly identical Tm, nucleoside composition of single strands, and single strand densities in alkaline CsCl. Similar comparisons on the second or third satellite DNAs from these rodents also indicate a close relationship to each other. Thus the high degree of similarity of satellite sequences found in such a diverse group of rodents suggests a cellular function that is subject to natural selection, and implies that these sequences have been conserved over a considerable span of evolutionary time since the divergence of these rodents about 50 million years ago.

  3. Similarity of satellite DNA properties in the order Rodentia

    Energy Technology Data Exchange (ETDEWEB)

    Mazrimas, J A; Hatch, F T

    1977-09-01

    Satellite DNAs from 9 species of kangaroo rat (Dipodomys) have been characterized and have shown that the HS-..cap alpha.. and HS-..beta.. satellites, where present, are nearly identical in all species as to melting transition midpoint (Tm), and density in neutral CsCl, alkaline CsCl, and Cs/sub 2/SO/sub 4/-Ag/sup +/ gradients. However, the MS satellites exist in two internally similar classes. The satellite DNAs from three other rodents were characterized (densities listed are in neutral CsCl). The pocket gopher, Thomomys bottae, contains Th-..cap alpha.. (1.713 g/ml) and Th..beta.. (1.703 g/ml). The guinea pig (Cavia porcellus) contains Ca-..cap alpha.., Ca-..beta.. and Ca-..gamma.. at densities of 1.706 g/ml, 1.704 g/ml and 1.704 g/ml, respectively. The antelope ground squirrel (Ammospermophilus harrisi) contains Am-..cap alpha.., 1.708 g/ml, Am-..beta.., 1.717 g/ml, and Am-..gamma.., 1.707 g/ml. The physical and chemical properties of the alpha-satellites from the above four rodents representing four different families in two suborders of Rodentia were compared. They show nearly identical Tm, nucleoside composition of single strands, and single strand densities in alkaline CsCl. Similar comparisons on the second or third satellite DNAs from these rodents also indicate a close relationship to each other. Thus the high degree of similarity of satellite sequences found in such a diverse group of rodents suggests a cellular function that is subject to natural selection, and implies that these sequences have been conserved over a considerable span of evolutionary time since the divergence of these rodents about 50 million years ago.

  4. Wildfires alter rodent community structure across four vegetation types in southern California, USA

    Science.gov (United States)

    Brehme, Cheryl S.; Clark, Denise R.; Rochester, Carlton J.; Fisher, Robert N.

    2011-01-01

    We surveyed burned and unburned plots across four habitat reserves in San Diego County, California, USA, in 2005 and 2006, to assess the effects of the 2003 wildfires on the community structure and relative abundance of rodent species. The reserves each contained multiple vegetation types (coastal sage scrub, chaparral, woodland, and grassland) and spanned from 250 m to 1078 m in elevation. Multivariate analyses revealed a more simplified rodent community structure in all burned habitats in comparison to unburned habitats. Reduction in shrub and tree cover was highly predictive of changes in post-fire rodent community structure in the burned coastal sage scrub and chaparral habitats. Reduction in cover was not predictive for the less substantially burned woodlands and grasslands, for which we hypothesized that interspecific competition played a greater role in post-fire community structure. Across vegetation types, generalists and open habitat specialists typically increased in relative abundance, whereas closed habitat specialists decreased. We documented significant increases in relative abundance of the deer mouse (Peromyscus maniculatus Wagner) and Dulzura kangaroo rat (Dipodomys simulans Merriam). In contrast, we found significant decreases in relative abundance for the California mouse (Peromyscus californicus Gambel), San Diego pocket mouse (Chaetodipus fallax Merriam), desert woodrat (Neotoma lepida Thomas), and brush mouse (Peromyscus boylii Baird). Currently, our research program involves assessment of whether habitat conservation plans (HCPs) in southern California provide long-term protection to HCP covered species, as well as preserve ecosystem function. The scenario of increased wildfires needs to be incorporated into this assessment. We discuss our results in relation to management and conservation planning under a future scenario of larger and more frequent wildfires in southern California.

  5. High molecular weight hyaluronan mediates the cancer resistance of the naked mole-rat

    OpenAIRE

    Tian, Xiao; Azpurua, Jorge; Hine, Christopher; Vaidya, Amita; Myakishev-Rempel, Max; Ablaeva, Julia; Mao, Zhiyong; Nevo, Eviatar; Gorbunova, Vera; Seluanov, Andrei

    2013-01-01

    The naked mole-rat displays exceptional longevity, with a maximum lifespan exceeding 30 years 1–3 . This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole-rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years 4,5 . In addition to their longevity, naked mole-rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single inci...

  6. Local extinction of the Asian tiger mosquito (Aedes albopictus) following rat eradication on Palmyra Atol

    Science.gov (United States)

    Lafferty, Kevin D.; McLaughlin, John P.; Gruner, Daniel S.; Bogar, Taylor A.; Bui, An; Childress, Jasmine N.; Espinoza, Magaly; Forbes, Elizabeth S.; Johnston, Cora A.; Klope, Maggie; Kuile, Ana Miller-ter; Lee, Michelle; Plummer, Katherine A.; Weber, David A.; Young, Ronald T.; Young, Hillary S.

    2018-01-01

    The Asian tiger mosquito, Aedes albopictus, appears to have been extirpated from Palmyra Atoll following rat eradication. Anecdotal biting reports, collection records, and regular captures in black-light traps showed the species was present before rat eradication. Since then, there have been no biting reports and no captures over 2 years of extensive trapping (black-light and scent traps). By contrast, the southern house mosquito, Culex quinquefasciatus, was abundant before and after rat eradication. We hypothesize that mammals were a substantial and preferred blood meal for Aedes, whereas Culex feeds mostly on seabirds. Therefore, after rat eradication, humans and seabirds alone could not support positive population growth or maintenance of Aedes. This seems to be the first documented accidental secondary extinction of a mosquito. Furthermore, it suggests that preferred host abundance can limit mosquito populations, opening new directions for controlling important disease vectors that depend on introduced species like rats.

  7. Comparison of Mitochondrial Reactive Oxygen Species Production of Ectothermic and Endothermic Fish Muscle

    Directory of Open Access Journals (Sweden)

    Lilian Wiens

    2017-09-01

    Full Text Available Recently we demonstrated that the capacity of isolated muscle mitochondria to produce reactive oxygen species, measured as H2O2 efflux, is temperature-sensitive in isolated muscle mitochondria of ectothermic fish and the rat, a representative endothermic mammal. However, at physiological temperatures (15° and 37°C for the fish and rat, respectively, the fraction of total mitochondrial electron flux that generated H2O2, the fractional electron leak (FEL, was far lower in the rat than in fish. Those results suggested that the elevated body temperatures associated with endothermy may lead to a compensatory decrease in mitochondrial ROS production relative to respiratory capacity. To test this hypothesis we compare slow twitch (red muscle mitochondria from the endothermic Pacific bluefin tuna (Thunnus orientalis with mitochondria from three ectothermic fishes [rainbow trout (Oncorhynchus mykiss, common carp (Cyprinus carpio, and the lake sturgeon (Acipenser fulvescens] and the rat. At a common assay temperature (25°C rates of mitochondrial respiration and H2O2 efflux were similar in tuna and the other fishes. The thermal sensitivity of fish mitochondria was similar irrespective of ectothermy or endothermy. Comparing tuna to the rat at a common temperature, respiration rates were similar, or lower depending on mitochondrial substrates. FEL was not different across fish species at a common assay temperature (25°C but was markedly higher in fishes than in rat. Overall, endothermy and warming of Pacific Bluefin tuna red muscle may increase the potential for ROS production by muscle mitochondria but the evolution of endothermy in this species is not necessarily associated with a compensatory reduction of ROS production relative to the respiratory capacity of mitochondria.

  8. Acetaminophen-induced liver injury in rats and mice: Comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity

    International Nuclear Information System (INIS)

    McGill, Mitchell R.; Williams, C. David; Xie, Yuchao; Ramachandran, Anup; Jaeschke, Hartmut

    2012-01-01

    Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the West. In mice, APAP hepatotoxicity can be rapidly induced with a single dose. Because it is both clinically relevant and experimentally convenient, APAP intoxication has become a popular model of liver injury. Early data demonstrated that rats are resistant to APAP toxicity. As a result, mice are the preferred species for mechanistic studies. Furthermore, recent work has shown that the mechanisms of APAP toxicity in humans are similar to mice. Nevertheless, some investigators still use rats. New mechanistic information from the last forty years invites a reevaluation of the differences between these species. Comparison may provide interesting insights and confirm or exclude the rat as an option for APAP studies. To this end, we treated rats and mice with APAP and measured parameters of liver injury, APAP metabolism, oxidative stress, and activation of the c-Jun N-terminal kinase (JNK). Consistent with earlier data, we found that rats were highly resistant to APAP toxicity. Although overall APAP metabolism was similar in both species, mitochondrial protein adducts were significantly lower in rats. Accordingly, rats also had less oxidative stress. Finally, while mice showed extensive activation and mitochondrial translocation of JNK, this could not be detected in rat livers. These data support the hypothesis that mitochondrial dysfunction is critical for the development of necrosis after APAP treatment. Because mitochondrial damage also occurs in humans, rats are not a clinically relevant species for studies of APAP hepatotoxicity. Highlights: ► Acetaminophen overdose causes severe liver injury only in mice but not in rats. ► APAP causes hepatic GSH depletion and protein adduct formation in rats and mice. ► Less protein adducts were measured in rat liver mitochondria compared to mouse. ► No oxidant stress, peroxynitrite formation or JNK activation was present in rats. ► The

  9. Different Astrocytic Activation between Adult Gekko japonicus and Rats during Wound Healing In Vitro.

    Directory of Open Access Journals (Sweden)

    Yun Gu

    Full Text Available Glial scar formation is a major obstacle to regeneration after spinal cord injury. Moreover, it has been shown that the astrocytic response to injury differs between species. Gekko japonicas is a type of reptile and it shows differential glial activation compared to that of rats. The purpose of the present study was to compare the proliferation and migration of astrocytes in the spinal cords of geckos and rats after injury in vitro. Spinal cord homogenate stimulation and scratch wound models were used to induce astrocytic activation in adult and embryonic rats, as well as in adult geckos. Our results indicated that astrocytes from the adult rat were likely activated by mechanical stimulation, even though they showed lower proliferation abilities than the astrocytes from the gecko under normal conditions. Furthermore, a transcriptome analysis revealed that the differentially expressed genes in astrocytes from adult rats and those from geckos were enriched in pathways involved in proliferation and the response to stimuli. This implies that intrinsic discrepancies in gene expression patterns might contribute to the differential activation of astrocytes between species.

  10. Metabolite analysis of [11C]Ro15-4513 in mice, rats, monkeys and humans

    International Nuclear Information System (INIS)

    Kida, T.; Noguchi, J.; Zhang, M.-R.; Suhara, T.; Suzuki, K.

    2003-01-01

    We performed in vitro and in vivo assays of the metabolism of [ 11 C]Ro15-4513 over time in the plasma of mice, rats, monkeys and humans, using a radio-HPLC equipped with a sensitive positron detector, in order to compare the metabolic rates of the radiopharmaceutical agent among the different animal species and to establish a highly sensitive analytical method for the radiotracer agent. We also examined the metabolism of [ 11 C]Ro15-4513 in the brain tissue of mice and rats. The analytical method used in this study permitted detection of even extremely low levels of radioactivity (approximately 5,000 dpm). In vitro experiments revealed that [ 11 C]Ro15-4513 in the blood was metabolized to hydrolysate [ 11 C]A. The species were classified in descending order of the metabolic rate of the radiotracer in vitro as follows; mice, rats, and monkeys/humans. In the in vitro experiment, the percentage of the unchanged drug in the plasma at 60 minutes postdose was 9% in mice, 70% in rats, 97% in monkeys, and 98% in humans. In vivo metabolite analysis in the blood showed the presence of two radioactive metabolites, consisting of one hydrolysate [ 11 C]A and another unidentified substance. The species were classified in descending order of the metabolic rate of the radiotracer in vivo as follows; mice, rats/humans, and monkeys. The percentage of the unchanged drug in the plasma was 6% in mice, 21% in rats, 26% in humans, and 40% in monkeys. Furthermore, the in vitro and in vivo experiments conducted to analyze the metabolism of [ 11 C]Ro15-4513 in the brain tissue of mice and rats revealed that the radiotracer was metabolized to some extent in the brain tissue of these animals. In the in vivo experiment, the percentage of the unchanged drug at 60 min postdose was 86% in the brain tissue of mice and 88% in the brain tissue of rats, while in the in vitro experiment, the corresponding percentage was 93% in mice, and 91% in rats

  11. Regulation of Taurine transporter activity in cultured rat retinal ganglion cells and rat retinal Muller Cells

    International Nuclear Information System (INIS)

    Eissa, Laila A.; Smith, Sylvia B.; El-sherbeny, Amira A.

    2006-01-01

    Diabetic retinopathy is one of the most common complications of diabetes. The amino acid taurine is believed to play an antioxidant protective role in diabetic retinopathy through the scavenging of the reactive species. It is not well established whether taurine uptake is altered in retina cells during diabetic conditions. Thus, the present study was designed to investigate the changes in taurine transport in cultures of rat retinal Muller cells and rat retinal ganglion cells under conditions associated with diabetes. Taurine was abundantly taken up by retinal Muller cells and rat retinal ganglion cells under normal glycemic condition. Taurine was actively transported to rat Muller cells and rat retinal ganglion cells in a Na and Cl dependant manner. Taurine uptake further significantly elevated in both type of cells after the incubation with high glucose concentration. This effect could be attributed to the increase in osmolarity. Because Nitric Oxide (NO) is a molecule implicated in the pathogenesis of diabetes, we also determined the activity of taurine transporter in cultured rat retinal Muller cells and rat retinal ganglion cells in the presence of the NO donors, SIN-1 and SNAP. Taurine uptake was elevated above control value after 24-h incubation with low concentration of NO donors. We finally investigated the ability of neurotoxic glutamate to change taurine transporter activity in both types of cells. Uptake of taurine was significantly increased in rat retinal ganglion cells when only incubated with high concentration of glutamate. Our data provide evidence that taurine transporter is present in cultured rat retinal ganglion and Muller cells and is regulated by hyperosmolarity. The data are relevant to disease such as diabetes and neuronal degeneration where retinal cell volume may dramatically change. (author)

  12. Aspergillus Species and Their Associated Mycotoxins.

    Science.gov (United States)

    Perrone, Giancarlo; Gallo, Antonia

    2017-01-01

    The genus Aspergillus is among the most abundant and widely distributed organism on earth, and at the moment comprises 339 known species. It is one of the most important economically fungal genus and the biotechnological use of Aspergillus species is related to production of soy sauce, of different hydrolytic enzymes (amylases, lipases) and organic acid (citric acid, gluconic acid), as well as biologically active metabolites such as lovastatin. Although they are not considered to be major cause of plant diseases, Aspergillus species are responsible for several disorders in various plants and plant products, especially as opportunistic storage moulds. The notable consequence of their presence is contamination of foods and feeds by mycotoxins, among which the most important are aflatoxins, ochratoxin A, and, at a less extent, fumonisins. Aflatoxins B 1 , B 2 , G 1 , G 2 are the most toxic and carcinogenic mycotoxins, due to their extreme hepatocarcinogenicity; ochratoxin A is a potent nephrotoxin, it is also carcinogenic, teratogenic, and immunotoxic in rats and possibly in humans; fumonisins are hepatotoxic and nephrotoxic with potential carcinogenic effects on rat and mice. In this chapter we summarize the main aspects of morphology, ecology, epidemiology, and toxigenicity of Aspergillus foodborne pathogens which belong to sections Flavi, Circumdati, and Nigri, occurring in several agricultural products and responsible of aflatoxin, ochratoxin A, and fumonisins contamination of food and feed.

  13. Man is not a big rat: concerns with traditional human risk assessment of phthalates based on their anti-androgenic effects observed in the rat foetus.

    Science.gov (United States)

    Habert, René; Livera, Gabriel; Rouiller-Fabre, Virginie

    2014-01-01

    Phthalates provide one of the most documented example evidencing how much we must be cautious when using the traditional paradigm based on extrapolation of experimental data from rodent studies for human health risk assessment of endocrine disruptors (EDs). Since foetal testis is known as one of the most sensitive targets of EDs, phthalate risk assessment is routinely based on the capacity of such compounds to decrease testosterone production by the testis or to impair masculinization in the rat during foetal life. In this paper, the well-established inhibiting effects of phthalates of the foetal Leydig cells function in the rat are briefly reviewed. Then, data obtained in humans and other species are carefully analysed. Already in January 2009, using the organotypic culture system named Fetal Testis Assay (FeTA) that we developed, we reported that phthalates might not affect testosterone production in human foetal testes. Several recent experimental studies using xenografts confirm the absence of detectable anti-androgenic effect of phthalates in the human foetal testes. Epidemiological studies led to contradictory results. Altogether, these findings suggest that phthalates effects on foetal Leydig cells are largely species-specific. Consequently, the phthalate threshold doses that disturb foetal steroidogenesis in rat testes and that are presently used to define the acceptable daily intake levels for human health protection must be questioned. This does not mean that phthalates are safe because these compounds have many deleterious effects upon germ cell development that may be common to the different studied species including human. More generally, the identification of common molecular, cellular or/and phenotypic targets in rat and human testes should precede the choice of the toxicological endpoint in rat to accurately assess the safety threshold of any ED in humans.

  14. Species-specific pharmacology of antiestrogens: role of metabolism

    International Nuclear Information System (INIS)

    Jordan, V.C.; Robinson, S.P.

    1987-01-01

    The nonsteroidal antiestrogen tamoxifen exhibits a paradoxial space species pharmacology. The drug is a full estrogen in the mouse, a partial estrogen/antiestrogen in humans and the rat, and an antiestrogen in the chick oviduct. Inasmuch as tamoxifen has antiestrogenic effects in vitro, differential metabolism of tamoxifen to estrogens might occur in the species in which it has antiestrogen pharmacology. Tamoxifen or its metabolite 4-hydroxytamoxifen could lose the alkylaminoethane side chain to form the estrogenic compound metabolite E of bisphenol. Sensitive metabolic studies with [ 3 H]tamoxifen in chicks, rats, and mice identified 4-hydroxytamoxifen as the major metabolite. Athymic mice with transplanted human breast tumors can be used to study the ability of tamoxifen to stimulate tissue or tumor growth. Estradiol caused the growth of transplanted breast cancer cells into solid tumors and a uterotrophic response. However, tamoxifen does not support tumor growth when administered alone, although it stimulates uterines growth. Since a similar profile of metabolites is sequestered in human mouse tissues, these studies strongly support the concept that the drug can selectively stimulate or inhibit events in the target tissues of different species without hometabolic intervention

  15. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat.

    Science.gov (United States)

    Tian, Xiao; Azpurua, Jorge; Hine, Christopher; Vaidya, Amita; Myakishev-Rempel, Max; Ablaeva, Julia; Mao, Zhiyong; Nevo, Eviatar; Gorbunova, Vera; Seluanov, Andrei

    2013-07-18

    The naked mole rat (Heterocephalus glaber) displays exceptional longevity, with a maximum lifespan exceeding 30 years. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years. In addition to their longevity, naked mole rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer. Here we identify a mechanism responsible for the naked mole rat's cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high-molecular-mass hyaluronan (HA), which is over five times larger than human or mouse HA. This high-molecular-mass HA accumulates abundantly in naked mole-rat tissues owing to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signalling, as they have a higher affinity to HA compared with mouse or human cells. Perturbation of the signalling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high-molecular-mass HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, HYAL2, naked mole-rat cells become susceptible to malignant transformation and readily form tumours in mice. We speculate that naked mole rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species.

  16. High molecular weight hyaluronan mediates the cancer resistance of the naked mole-rat

    Science.gov (United States)

    Tian, Xiao; Azpurua, Jorge; Hine, Christopher; Vaidya, Amita; Myakishev-Rempel, Max; Ablaeva, Julia; Mao, Zhiyong; Nevo, Eviatar; Gorbunova, Vera; Seluanov, Andrei

    2013-01-01

    The naked mole-rat displays exceptional longevity, with a maximum lifespan exceeding 30 years1–3. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole-rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years4,5. In addition to their longevity, naked mole-rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer2,6. Here we identify a mechanism responsible for the naked mole-rat’s cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high molecular weight hyaluronan (HA), which is over five times larger than human or mouse HA. This high molecular weight HA accumulates abundantly in naked mole rat tissues due to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signaling, as the naked mole rat cells have a higher affinity to HA than the mouse or human cells. Perturbation of the signaling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high molecular weight HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, Hyal2, naked mole-rat cells become susceptible to malignant transformation and readily form tumors in mice. We speculate that naked mole-rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species. PMID:23783513

  17. Genome Stability Maintenance in Naked Mole-Rat.

    Science.gov (United States)

    Petruseva, I O; Evdokimov, A N; Lavrik, O I

    2017-01-01

    The naked mole-rat ( Heterocephalus glaber ) is one of the most promising models used to study genome maintenance systems, including the effective repair of damage to DNA. The naked mole-rat is the longest lived rodent species, which is extraordinarily resistant to cancer and has a number of other unique phenotypic traits. For at least 80% of its lifespan, this animal shows no signs of aging or any increased likelihood of death and retains the ability to reproduce. The naked mole-rat draws the heightened attention of researchers who study the molecular basis of lengthy lifespan and cancer resistance. Despite the fact that the naked mole-rat lives under genotoxic stress conditions (oxidative, etc.), the main characteristics of its genome and proteome are a high stability and effective functioning. Replicative senescence in the somatic cells of naked mole-rats is missing, while an additional p53/pRb-dependent mechanism of early contact inhibition has been revealed in its fibroblasts, which controls cell proliferation and its mechanism of arf- dependent aging. The unique traits of phenotypic and molecular adaptations found in the naked mole-rat speak to a high stability and effective functioning of the molecular machinery that counteract damage accumulation in its genome. This review analyzes existing results in the study of the molecular basis of longevity and high cancer resistance in naked mole-rats.

  18. Verbascum kurdistanicum (Scrophulariaceae, a new species from Hakkâri, Turkey

    Directory of Open Access Journals (Sweden)

    Mehmet Fırat

    2015-07-01

    Full Text Available Verbascum kurdistanicum Fırat (Scrophulariaceae, is described and illustrated as a new species that is located in Hakkâri, Turkey. In this study, diagnostic morphological characters of this and closely related species (V. oreophilum K.Koch and V. pyramidatum M. Bieb are discussed. Furthermore, distribution maps for the three taxa are provided.

  19. Quantitation of species differences in albumin–ligand interactions for bovine, human and rat serum albumins using fluorescence spectroscopy: A test case with some Sudlow's site I ligands

    Energy Technology Data Exchange (ETDEWEB)

    Poór, Miklós [Institute of Laboratory Medicine, University of Pécs, Ifjúság u. 13, Pécs H-7624 (Hungary); Li, Yin; Matisz, Gergely [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); János Szentágothai Research Center, Pécs H-7624 (Hungary); Kiss, László [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); Kunsági-Máté, Sándor [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); János Szentágothai Research Center, Pécs H-7624 (Hungary); Kőszegi, Tamás, E-mail: koszegit@freemail.hu [Institute of Laboratory Medicine, University of Pécs, Ifjúság u. 13, Pécs H-7624 (Hungary)

    2014-01-15

    Albumin, the most abundant plasma protein is an approximately 67 kDa sized water-soluble macromolecule. Since several drugs and xenobiotics circulate in the blood at least partially in albumin-bound form, albumin plays a key role in the pharmacokinetics/toxicokinetics of these chemicals. Most of the drugs and xenobiotics are Sudlow's site I ligands. In numerous studies, bovine serum albumin (BSA) is used for modeling albumin–ligand interactions and the results are extrapolated to human serum albumin (HSA). Furthermore, only limited information is available related to albumin–ligand interactions of different albumin species. Therefore, in our study, we have focused on the quantification of differences between bovine, human and rat serum albumin (RSA) using four Sudlow's site I ligands (luteolin, ochratoxin A, phenylbutazone and warfarin). Interactions were analyzed by fluorescence spectroscopy. Stability constants as well as competing capacities of the ligands were determined, and thermodynamic study was also performed. Our results highlight that there could be major differences between BSA, HSA and RSA in their ligand binding properties. Based on our observations we emphasize that in molecular aspects BSA behaves considerably differently from HSA or from albumins of other species therefore, it is strongly recommended to apply at least some confirmatory measurements when data obtained from other species are attempted to be extrapolated to HSA. -- Highlights: • Albumin–ligand interactions of human, bovine and rat albumins were studied. • Four Sudlow's site I ligands were tested by fluorescence spectroscopy. • Substantial differences were found in stability constants among albumin complexes. • Competing capacity of ligands showed major differences in the studied species. • Data obtained for BSA cannot be directly extrapolated to human albumin.

  20. Reversed-phase high-performance liquid chromatographic analyses of insulin biosynthesis in isolated rat and mouse islets

    DEFF Research Database (Denmark)

    Linde, S; Hansen, Bruno A.; Welinder, B S

    1989-01-01

    deletion compared to rat C-peptide I. A marked species difference in the ratio between insulin I and II was observed, i.e., 2:1 in the rat and 1:2 in the mouse. Pulse-chase experiments in rat islets have demonstrated that the ratio between insulin I and II in newly synthesized insulin is higher than...

  1. Modeling the distribution of Norway rats (Rattus norvegicus on offshore islands in the Falkland Islands

    Directory of Open Access Journals (Sweden)

    Michael A. Tabak

    2015-01-01

    Full Text Available Non-native rats (Rattus spp. threaten native island species worldwide. Efforts to eradicate them from islands have increased in frequency and become more ambitious in recent years. However, the long-term success of some eradication efforts has been compromised by the ability of rats, particularly Norway rats (Rattus norvegicus which are good swimmers, to recolonize islands following eradications. In the Falkland Islands, an archipelago in the South Atlantic Ocean, the distance of 250 m between islands (once suggested as the minimum separation distance for an effective barrier to recolonization has shown to be insufficient. Norway rats are present on about half of the 503 islands in the Falklands. Bird diversity is lower on islands with rats and two vulnerable passerine species, Troglodytes cobbi (the only endemic Falkland Islands passerine and Cinclodes antarcticus, have greatly reduced abundances and/or are absent on islands with rats. We used logistic regression models to investigate the potential factors that may determine the presence of Norway rats on 158 islands in the Falkland Islands. Our models included island area, distance to the nearest rat-infested island, island location, and the history of island use by humans as driving variables. Models best supported by data included only distance to the nearest potential source of rats and island area, but the relative magnitude of the effect of distance and area on the presence of rats varied depending on whether islands were in the eastern or western sector of the archipelago. The human use of an island was not a significant parameter in any models. A very large fraction (72% of islands within 500 m of the nearest potential rat source had rats, but 97% of islands farther than 1,000 m away from potential rat sources were free of rats.

  2. Heterogeneity of rat tropoelastin mRNA revealed by cDNA cloning

    International Nuclear Information System (INIS)

    Pierce, R.A.; Deak, S.B.; Stolle, C.A.; Boyd, C.D.

    1990-01-01

    A λgt11 library constructed from poly(A+) RNA isolated from aortic tissue of neonatal rats was screened for rat tropoelastin cDNAs. The first, screen, utilizing a human tropoelastin cDNA clone, provided rat tropoelastin cDNAs spanning 2.3 kb of carboxy-terminal coding sequence and extended into the 3'-untranslated region. A subsequent screen using a 5' rat tropoelastin cDNA clone yielded clones extending into the amino-terminal signal sequence coding region. Sequence analysis of these clones has provided the complete derived amino acid sequence of rat tropoelastin and allowed alignment and comparison with published bovine cDNA sequence. While the overall structure of rat tropoelastin is similar to bovine sequence, numerous substitutions, deletions, and insertions demonstrated considerable heterogeneity between species. In particular, the pentapeptide repeat VPGVG, characteristic of all tropoelastins analyzed to date, is replaced in rat tropoelastin by a repeating pentapeptide, IPGVG. The hexapeptide repeat VGVAPG, the bovine elastin receptor binding peptide, is not encoded by rat tropoelastin cDNAs. Variations in coding sequence between rat tropoelastin CDNA clones were also found which may represent mRNA heterogeneity produced by alternative splicing of the rat tropoelastin pre-mRNA

  3. Species differences in biliary excretion of benzo[a]pyrene

    International Nuclear Information System (INIS)

    Weyand, E.H.; Bevan, D.R.

    1986-01-01

    Biliary excretion of benzo[a]pyrene (B[a]P) was investigated in rats, hamsters, and guinea pigs following intratracheal administration. [ 3 H]-B[a]P, in amounts of approximately 150 ng or 350 μg, was instilled into lungs and amounts of radioactivity excreted in bile were monitored for six hrs following administration. Differences in biliary excretion of [ 3 H]-B[a]P and/or metabolites among species were observed at low doses but not at high doses. Six hours after instillation of a low dose of B[a]P, 70, 54, and 62% of the dose was excreted in bile of rats, hamsters, and guinea pigs, respectively. Upon administration of the higher dose of B[a]P, approximately 50% of the dose was excreted in bile in six hrs by all species. Thus, rats and guinea pigs exhibit differences in biliary excretion of low and high doses of B[a]P whereas hamsters do not. Profiles of phase II metabolites in rats and hamsters were similar at both low and high doses, with the majority of metabolites being glucuronides and thioether conjugates. However, differences in relative amounts of these conjugates were observed between the two doses, with a shift towards a greater proportion of glucuronides at the higher dose. Metabolites in bile from guinea pigs were primarily thioether conjugates, which accounted for 88% of metabolites at the low dose and 95% at the high dose

  4. Qualitative and quantitative differences between taste buds of the rat and mouse

    Directory of Open Access Journals (Sweden)

    Ma Huazhi

    2007-01-01

    Full Text Available Abstract Background Numerous electrophysiological, ultrastructural, and immunocytochemical studies on rodent taste buds have been carried out on rat taste buds. In recent years, however, the mouse has become the species of choice for molecular and other studies on sensory transduction in taste buds. Do rat and mouse taste buds have the same cell types, sensory transduction markers and synaptic proteins? In the present study we have used antisera directed against PLCβ2, α-gustducin, serotonin (5-HT, PGP 9.5 and synaptobrevin-2 to determine the percentages of taste cells expressing these markers in taste buds in both rodent species. We also determined the numbers of taste cells in the taste buds as well as taste bud volume. Results There are significant differences (p 3 is smaller than a rat taste bud (64,200 μm3. The numerical density of taste cells in mouse circumvallate taste buds (2.1 cells/1000 μm3 is significantly higher than that in the rat (1.2 cells/1000 μm3. Conclusion These results suggest that rats and mice differ significantly in the percentages of taste cells expressing signaling molecules. We speculate that these observed dissimilarities may reflect differences in their gustatory processing.

  5. Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber).

    Science.gov (United States)

    Park, Thomas J; Lu, Ying; Jüttner, René; Smith, Ewan St J; Hu, Jing; Brand, Antje; Wetzel, Christiane; Milenkovic, Nevena; Erdmann, Bettina; Heppenstall, Paul A; Laurito, Charles E; Wilson, Steven P; Lewin, Gary R

    2008-01-01

    In all mammals, tissue inflammation leads to pain and behavioral sensitization to thermal and mechanical stimuli called hyperalgesia. We studied pain mechanisms in the African naked mole-rat, an unusual rodent species that lacks pain-related neuropeptides (e.g., substance P) in cutaneous sensory fibers. Naked mole-rats show a unique and remarkable lack of pain-related behaviors to two potent algogens, acid and capsaicin. Furthermore, when exposed to inflammatory insults or known mediators, naked mole-rats do not display thermal hyperalgesia. In contrast, naked mole-rats do display nocifensive behaviors in the formalin test and show mechanical hyperalgesia after inflammation. Using electrophysiology, we showed that primary afferent nociceptors in naked mole-rats are insensitive to acid stimuli, consistent with the animal's lack of acid-induced behavior. Acid transduction by sensory neurons is observed in birds, amphibians, and fish, which suggests that this tranduction mechanism has been selectively disabled in the naked mole-rat in the course of its evolution. In contrast, nociceptors do respond vigorously to capsaicin, and we also show that sensory neurons express a transient receptor potential vanilloid channel-1 ion channel that is capsaicin sensitive. Nevertheless, the activation of capsaicin-sensitive sensory neurons in naked mole-rats does not produce pain-related behavior. We show that capsaicin-sensitive nociceptors in the naked mole-rat are functionally connected to superficial dorsal horn neurons as in mice. However, the same nociceptors are also functionally connected to deep dorsal horn neurons, a connectivity that is rare in mice. The pain biology of the naked mole-rat is unique among mammals, thus the study of pain mechanisms in this unusual species can provide major insights into what constitutes "normal" mammalian nociception.

  6. Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber.

    Directory of Open Access Journals (Sweden)

    Thomas J Park

    2008-01-01

    Full Text Available In all mammals, tissue inflammation leads to pain and behavioral sensitization to thermal and mechanical stimuli called hyperalgesia. We studied pain mechanisms in the African naked mole-rat, an unusual rodent species that lacks pain-related neuropeptides (e.g., substance P in cutaneous sensory fibers. Naked mole-rats show a unique and remarkable lack of pain-related behaviors to two potent algogens, acid and capsaicin. Furthermore, when exposed to inflammatory insults or known mediators, naked mole-rats do not display thermal hyperalgesia. In contrast, naked mole-rats do display nocifensive behaviors in the formalin test and show mechanical hyperalgesia after inflammation. Using electrophysiology, we showed that primary afferent nociceptors in naked mole-rats are insensitive to acid stimuli, consistent with the animal's lack of acid-induced behavior. Acid transduction by sensory neurons is observed in birds, amphibians, and fish, which suggests that this tranduction mechanism has been selectively disabled in the naked mole-rat in the course of its evolution. In contrast, nociceptors do respond vigorously to capsaicin, and we also show that sensory neurons express a transient receptor potential vanilloid channel-1 ion channel that is capsaicin sensitive. Nevertheless, the activation of capsaicin-sensitive sensory neurons in naked mole-rats does not produce pain-related behavior. We show that capsaicin-sensitive nociceptors in the naked mole-rat are functionally connected to superficial dorsal horn neurons as in mice. However, the same nociceptors are also functionally connected to deep dorsal horn neurons, a connectivity that is rare in mice. The pain biology of the naked mole-rat is unique among mammals, thus the study of pain mechanisms in this unusual species can provide major insights into what constitutes "normal" mammalian nociception.

  7. Low prevalence of human enteropathogenic Yersinia spp. in brown rats (Rattus norvegicus in Flanders.

    Directory of Open Access Journals (Sweden)

    Lieze Oscar Rouffaer

    Full Text Available Brown rats (Rattus norvegicus have been identified as potential carriers of Yersinia enterocolitica and Y. pseudotuberculosis, the etiological agents of yersiniosis, the third most reported bacterial zoonosis in Europe. Enteropathogenic Yersinia spp. are most often isolated from rats during yersiniosis cases in animals and humans, and from rats inhabiting farms and slaughterhouses. Information is however lacking regarding the extent to which rats act as carriers of these Yersinia spp.. In 2013, 1088 brown rats across Flanders, Belgium, were tested for the presence of Yersinia species by isolation method. Identification was performed using MALDI-TOF MS, PCR on chromosomal- and plasmid-borne virulence genes, biotyping and serotyping. Yersinia spp. were isolated from 38.4% of the rats. Of these, 53.4% were designated Y. enterocolitica, 0.7% Y. pseudotuberculosis and 49.0% other Yersinia species. Two Y. enterocolitica possessing the virF-, ail- and ystA-gene were isolated. Additionally, the ystB-gene was identified in 94.1% of the other Y. enterocolitica isolates, suggestive for biotype 1A. Three of these latter isolates simultaneously possessed the ail-virulence gene. Significantly more Y. enterocolitica were isolated during winter and spring compared to summer. Based on our findings we can conclude that brown rats are frequent carriers for various Yersinia spp., including Y. pseudotuberculosis and (human pathogenic Y. enterocolitica which are more often isolated during winter and spring.

  8. Quantitative comparison of luteal histology in the rat and rabbit: changes from mid- to late gestation.

    Science.gov (United States)

    Dharmarajan, A M; Bruce, N W; Meyer, G T

    1989-01-01

    Progesterone secretion by the corpora lutea (CL) of rats and rabbits declines from a peak, at about Day 16 of gestation, to near term (Day 22 rats and 28 rabbits). However there are major differences between the two species in CL growth and blood flow over this period. In the present work quantitative histological measurements were made of CL at these stages to examine the accompanying structural changes. Eight rats and five rabbits were examined at each stage: standard morphometric techniques were used. There was gross discrepancy between the two species in the histology of their CL at peak secretory activity. Although the proportions of the major tissue components were similar, the rabbit luteal cell (52 pl) was five times larger than that in the rat (9 pl). There was substantially less vascular and interstitial space in the rabbit, all characteristics which might affect transport processes between luteal cell cytoplasm and blood. Over the period examined, there was no change in CL volume in the rat but a 37% reduction in the rabbit due to loss of luteal cells. The vascular space in the rat, however, was reduced, whereas that in the rabbit declined only in proportion to the overall decrease in CL volume. These results show that structurally there is a substantial difference in patterns of early regression between the two species which reflect different mechanisms involved. Images Fig. 1 Fig. 2 PMID:2621138

  9. High Autophagy in the Naked Mole Rat may Play a Significant Role in Maintaining Good Health

    Directory of Open Access Journals (Sweden)

    Shanmin Zhao

    2014-02-01

    Full Text Available Background/Aims: The maximum lifespan of the naked mole rat is over 28.3 years, which exceeds that of any other rodent species, suggesting that age-related changes in its body composition and functionality are either attenuated or delayed in this extraordinarily long-lived species. However, the mechanisms underlying the aging process in this species are poorly understood. In this study, we investigated whether long-lived naked mole rats display more autophagic activity than short-lived mice. Methods: Hepatic stellate cells isolated from naked mole rats were treated with 50 nM rapamycin or 20 mM 3-methyladenine (3-MA for 12 or 24 h. Expression of the autophagy marker proteins LC3-II and beclin 1 was measured with western blotting and immunohistochemistry. The induction of apoptosis was analyzed by flow cytometry. Results: Our results demonstrate that one-day-old naked mole rats have higher levels of autophagy than one-day-old short-lived C57BL/6 mice, and that both adult naked mole rats (eight months old and adult C57BL/6 mice (eight weeks old have high basal levels of autophagy, which may be an important mechanism inhibiting aging and reducing the risk of age-related diseases. Conclusion: Here, we report that autophagy facilitated the survival of hepatic stellate cells from the naked mole rat, and that treatment with 3-MA or rapamycin increased the ratio of apoptotic cells to normal hepatic stellate cells.

  10. Comparative analysis of TCDD-induced AhR-mediated gene expression in human, mouse and rat primary B cells

    Energy Technology Data Exchange (ETDEWEB)

    Kovalova, Natalia, E-mail: kovalova@msu.edu [Department of Pharmacology and Toxicology, Michigan State University, Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Nault, Rance, E-mail: naultran@msu.edu [Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Crawford, Robert, E-mail: crawfo28@msu.edu [Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Zacharewski, Timothy R., E-mail: tzachare@msu.edu [Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States); Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824 (United States); Kaminski, Norbert E., E-mail: kamins11@msu.edu [Department of Pharmacology and Toxicology, Michigan State University, Lansing, MI 48824 (United States); Institute for Integrative Toxicology, Michigan State University, Lansing, MI 48824 (United States)

    2017-02-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant that activates the aryl hydrocarbon receptor (AhR) resulting in altered gene expression. In vivo, in vitro, and ex vivo studies have demonstrated that B cells are directly impaired by TCDD, and are a sensitive target as evidenced by suppression of antibody responses. The window of sensitivity to TCDD-induced suppression of IgM secretion among mouse, rat and human B cells is similar. Specifically, TCDD must be present within the initial 12 h post B cell stimulation, indicating that TCDD disrupts early signaling network(s) necessary for B lymphocyte activation and differentiation. Therefore, we hypothesized that TCDD treatment across three different species (mouse, rat and human) triggers a conserved, B cell-specific mechanism that is involved in TCDD-induced immunosuppression. RNA sequencing (RNA-Seq) was used to identify B cell-specific orthologous genes that are differentially expressed in response to TCDD in primary mouse, rat and human B cells. Time course studies identified TCDD-elicited differential expression of 515 human, 2371 mouse and 712 rat orthologous genes over the 24-h period. 28 orthologs were differentially expressed in response to TCDD in all three species. Overrepresented pathways enriched in all three species included cytokine-cytokine receptor interaction, ECM-receptor interaction, focal adhesion, regulation of actin cytoskeleton and pathways in cancer. Differentially expressed genes functionally associated with cell-cell signaling in humans, immune response in mice, and oxidation reduction in rats. Overall, these results suggest that despite the conservation of the AhR and its signaling mechanism, TCDD elicits species-specific gene expression changes. - Highlights: • Kovalova TAAP Highlights Nov. 2016 • RNA-Seq identified TCDD-induced gene expression in PWM-activated primary B cells. • TCDD elicited differential expression of 515 human, 2371 mouse and 712

  11. The molecular basis of acid insensitivity in the African naked mole-rat.

    Science.gov (United States)

    Smith, Ewan St John; Omerbašić, Damir; Lechner, Stefan G; Anirudhan, Gireesh; Lapatsina, Liudmila; Lewin, Gary R

    2011-12-16

    Acid evokes pain by exciting nociceptors; the acid sensors are proton-gated ion channels that depolarize neurons. The naked mole-rat (Heterocephalus glaber) is exceptional in its acid insensitivity, but acid sensors (acid-sensing ion channels and the transient receptor potential vanilloid-1 ion channel) in naked mole-rat nociceptors are similar to those in other vertebrates. Acid inhibition of voltage-gated sodium currents is more profound in naked mole-rat nociceptors than in mouse nociceptors, however, which effectively prevents acid-induced action potential initiation. We describe a species-specific variant of the nociceptor sodium channel Na(V)1.7, which is potently blocked by protons and can account for acid insensitivity in this species. Thus, evolutionary pressure has selected for an Na(V)1.7 gene variant that tips the balance from proton-induced excitation to inhibition of action potential initiation to abolish acid nociception.

  12. A defect in the inflammation-primed macrophage-activation cascade in osteopetrotic rats.

    Science.gov (United States)

    Yamamoto, N; Lindsay, D D; Naraparaju, V R; Ireland, R A; Popoff, S N

    1994-05-15

    Macrophages were activated by administration of lysophosphatidylcholine (lyso-Pc) or dodecylglycerol (DDG) to wild-type rats but not in osteopetrotic (op) mutant rats. In vitro treatment of wild-type rat peritoneal cells with lyso-Pc or DDG efficiently activated macrophages whereas treatment of op mutant rat peritoneal cells with lyso-Pc or DDG did not activate macrophages. The inflammation-primed macrophage activation cascade in rats requires participation of B lymphocytes and vitamin D binding protein (DBP). Lyso-Pc-inducible beta-galactosidase of wild-type rat B lymphocytes can convert DBP to the macrophage-activating factor (MAF), whereas B lymphocytes of the op mutant rats were shown to be deficient in lyso-Pc-inducible beta-galactosidase. DBP is conserved among mammalian species. Treatment of human DBP (Gc1 protein) with commercial glycosidases yields an extremely high titrated MAF as assayed on mouse and rat macrophages. Because the enzymatically generated MAF (GcMAF) bypasses the role of lymphocytes in macrophage activation, the op mutant rat macrophages were efficiently activated by administration of a small quantity (100 pg/rat) of GcMAF. Likewise, in vitro treatment of op rat peritoneal cells with as little as 40 pg GcMAF/ml activated macrophages.

  13. The rat closely mimics oxidative stress and inflammation in humans after exercise but not after exercise combined with vitamin C administration.

    Science.gov (United States)

    Veskoukis, Aristidis S; Goutianos, Georgios; Paschalis, Vassilis; Margaritelis, Nikos V; Tzioura, Aikaterini; Dipla, Konstantina; Zafeiridis, Andreas; Vrabas, Ioannis S; Kyparos, Antonios; Nikolaidis, Michalis G

    2016-04-01

    The purpose of the present study was to directly compare oxidative stress and inflammation responses between rats and humans. We contrasted rat and human oxidative stress and inflammatory responses to exercise (pro-oxidant stimulus) and/or vitamin C (anti-oxidant stimulus) administration. Vitamin C was administered orally in both species (16 mg kg(-1) of body weight). Twelve redox biomarkers and seven inflammatory biomarkers were determined in plasma and erythrocytes pre- and post-exercise or pre- and post-exercise combined with vitamin C administration. Exercise increased oxidative stress and induced an inflammatory state in rats and humans. There were only 1/19 significant species × exercise interactions (catalase), indicating similar responses to exercise between rats and humans in redox and inflammatory biomarkers. Vitamin C decreased oxidative stress and increased antioxidant capacity only in humans and did not affect the redox state of rats. In contrast, vitamin C induced an anti-inflammatory state only in rats and did not affect the inflammatory state of humans. There were 10/19 significant species × vitamin C interactions, indicating that rats poorly mimic human oxidative stress and inflammatory responses to vitamin C administration. Exercise after acute vitamin C administration altered redox state only in humans and did not affect the redox state of rats. On the contrary, inflammation biomarkers changed similarly after exercise combined with vitamin C in both rats and humans. The rat adequately mimics human responses to exercise in basic blood redox/inflammatory profile, yet this is not the case after exercise combined with vitamin C administration.

  14. Species differences in blood-brain barrier transport of three positron emission tomography radioligands with emphasis on P-glycoprotein transport

    DEFF Research Database (Denmark)

    Syvanen, S.; Lindhe, O.; Palner, M.

    2009-01-01

    preclinical data to humans. Compounds found to be P-gp substrates in rodents are likely to also be substrates in higher species, but sufficient blood-brain barrier permeability may be retained in humans to allow the compound to act at intracerebral targets Udgivelsesdato: 2009/3......Species differences occur in the brain concentrations of drugs, but the reasons for these differences are not yet apparent. This study was designed to compare brain uptake of three radiolabeled P-glycoprotein (P-gp) substrates across species using positron emission tomography. Brain concentrations...... and brain-to-plasma ratios were compared; [(11)C]verapamil in rats, guinea pigs, and monkeys; [(11)C](S)-(2-methoxy-5-(5-trifluoromethyltetrazol-1-yl)-phenylmethylamino )-2(S)-phenylpiperidine (GR205171) in rats, guinea pigs, monkeys, and humans; and [(18)F]altanserin in rats, minipigs, and humans...

  15. Breath ethane as a marker of reactive oxygen species during manipulation of diet and oxygen tension in rats.

    Science.gov (United States)

    Risby, T H; Jiang, L; Stoll, S; Ingram, D; Spangler, E; Heim, J; Cutler, R; Roth, G S; Rifkind, J M

    1999-02-01

    Breath ethane, O2 consumption, and CO2 production were analyzed in 24-mo-old female Fischer 344 rats that had been fed continuously ad libitum (AL) or restricted 30% of AL level (DR) diets since 6 wk of age. Rats were placed in a glass chamber that was first flushed with air, then with a gas mixture containing 12% O2. After equilibration, a sample of the outflow was collected in gas sampling bags for subsequent analyses of ethane and CO2. The O2 and CO2 levels were also directly monitored in the outflow of the chamber. O2 consumption and CO2 production increased for DR rats. Hypoxia decreased O2 consumption and CO2 production for the AL-fed and DR rats. These changes reflect changes in metabolic rate due to diet and PO2. A significant decrease in ethane generation was found in DR rats compared with AL-fed rats. Under normoxic conditions, breath ethane decreased from 2.20 to 1.61 pmol ethane/ml CO2. During hypoxia the levels of ethane generation increased, resulting in a DR-associated decrease in ethane from 2.60 to 1.90 pmol ethane/ml CO2. These results support the hypothesis that DR reduces the level of oxidative stress.

  16. Modulatory effect of curcumin on ketamine-induced toxicity in rat thymocytes: Involvement of reactive oxygen species (ROS and the phosphoinositide 3-kinase (PI3K/protein kinase B (Akt pathway

    Directory of Open Access Journals (Sweden)

    Svetlana Pavlovic

    2018-03-01

    Full Text Available Ketamine is a widely used anesthetic in pediatric clinical practice. Previous studies have demonstrated that ketamine induces neurotoxicity and has a modulatory effect on the cells of the immune system. Here, we evaluated the potential protective effect and underlying mechanisms of natural phenolic compound curcumin against ketamine-induced toxicity in rat thymocytes. Rat thymocytes were exposed to 100 µM ketamine alone or combined with increasing concentrations of curcumin (0.3, 1, and 3 μM for 24 hours. Cell viability was analyzed with CCK-8 assay kit. Apoptosis was analyzed using flow cytometry and propidium iodide as well as Z-VAD-FMK and Z-LEHD-FMK inhibitors. Reactive oxygen species (ROS production and mitochondrial membrane potential [MMP] were measured by flow cytometry. Colorimetric assay with DEVD-pNA substrate was used for assessing caspase-3 activity. Involvement of phosphoinositide 3-kinase (PI3K/protein kinase B (Akt signaling pathway was tested with Wortmannin inhibitor. Ketamine induced toxicity in cells, increased the number of hypodiploid cells, caspase-3 activity and ROS production, and inhibited the MMP. Co-incubation of higher concentrations of curcumin (1 and 3 μM with ketamine markedly decreased cytotoxicity, apoptosis rate, caspase-3 activity, and ROS production in rat thymocytes, and increased the MMP. Application of Z-VAD-FMK (a pan caspase inhibitor or Z-LEHD-FMK (caspase-9 inhibitor with ketamine effectively attenuated the ketamine-induced apoptosis in rat thymocytes. Administration of Wortmannin (a PI3K inhibitor with curcumin and ketamine significantly decreased the protective effect of curcumin on rat thymocytes. Our results indicate that ketamine-induced toxicity in rat thymocytes mainly occurs through the mitochondria-mediated apoptotic pathway and that the PI3K/Akt signaling pathway is involved in the anti-apoptotic effect of curcumin.

  17. Barriers to seed and seedling survival of once-common Hawaiian palms: the role of invasive rats and ungulates.

    Science.gov (United States)

    Shiels, Aaron B; Drake, Donald R

    2015-05-27

    Mammalian herbivores can limit plant recruitment and affect forest composition. Loulu palms (Pritchardia spp.) once dominated many lowland ecosystems in Hawai'i, and non-native rats (Rattus spp.), ungulates (e.g. pigs Sus scrofa, goats Capra hircus) and humans have been proposed as major causes of their decline. In lowland wet forest, we experimentally determined the vulnerability of seeds and seedlings of two species of Pritchardia, P. maideniana and P. hillebrandii, by measuring their removal by introduced vertebrates; we also used motion-sensing cameras to identify the animals responsible for Pritchardia removal. We assessed potential seed dispersal of P. maideniana by spool-and-line tracking, and conducted captive-feeding trials with R. rattus and seeds and seedlings of both Pritchardia species. Seed removal from the forest floor occurred rapidly for both species: >50 % of Pritchardia seeds were removed from the vertebrate-accessible stations within 6 days and >80 % were removed within 22 days. Although rats and pigs were both common to the study area, motion-sensing cameras detected only rats (probably R. rattus) removing Pritchardia seeds from the forest floor. Captive-feeding trials and spool-and-line tracking revealed that vertebrate seed dispersal is rare; rats moved seeds up to 8 m upon collection and subsequently destroyed them (100 % mortality in 24-48 h in captivity). Surprisingly, seedlings did not suffer vertebrate damage in field trials, and although rats damaged seedlings in captivity, they rarely consumed them. Our findings are consistent with the hypothesis generated from palaeoecological studies, indicating that introduced rats may have assisted in the demise of native insular palm forests. These findings also imply that the seed stage of species in this Pacific genus is particularly vulnerable to rats; therefore, future conservation efforts involving Pritchardia should prioritize the reduction of rat predation on the plant recruitment stages

  18. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been...... no studies directly comparing blood BDNF levels to brain BDNF levels in different species. We examined blood, serum, plasma and brain-tissue BDNF levels in three different mammalian species: rat, pig, and mouse, using an ELISA method. As a control, we included an analysis of blood and brain tissue from...... conditional BDNF knockout mice and their wild-type littermates. Whereas BDNF could readily be measured in rat blood, plasma and brain tissue, it was undetectable in mouse blood. In pigs, whole-blood levels of BDNF could not be measured with a commercially available ELISA kit, but pig plasma BDNF levels (mean...

  19. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A

    2011-01-01

    no studies directly comparing blood BDNF levels to brain BDNF levels in different species. We examined blood, serum, plasma and brain-tissue BDNF levels in three different mammalian species: rat, pig, and mouse, using an ELISA method. As a control, we included an analysis of blood and brain tissue from......Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been...... conditional BDNF knockout mice and their wild-type littermates. Whereas BDNF could readily be measured in rat blood, plasma and brain tissue, it was undetectable in mouse blood. In pigs, whole-blood levels of BDNF could not be measured with a commercially available ELISA kit, but pig plasma BDNF levels (mean...

  20. Inhibition of rat, mouse, and human glutathione S-transferase by eugenol and its oxidation products

    NARCIS (Netherlands)

    Rompelberg, C.J.M.; Ploemen, J.H.T.M.; Jespersen, S.; Greef, J. van der; Verhagen, H.; Bladeren, P.J. van

    1996-01-01

    The irreversible and reversible inhibition of glutathione S-transferases (GSTs) by eugenol was studied in rat, mouse and man. Using liver cytosol of human, rat and mouse, species differences were found in the rate of irreversible inhibition of GSTs by eugenol in the presence of the enzyme

  1. Changes in gut microbiota in rats fed a high fat diet correlate with obesity-associated metabolic parameters.

    Science.gov (United States)

    Lecomte, Virginie; Kaakoush, Nadeem O; Maloney, Christopher A; Raipuria, Mukesh; Huinao, Karina D; Mitchell, Hazel M; Morris, Margaret J

    2015-01-01

    The gut microbiota is emerging as a new factor in the development of obesity. Many studies have described changes in microbiota composition in response to obesity and high fat diet (HFD) at the phylum level. In this study we used 16s RNA high throughput sequencing on faecal samples from rats chronically fed HFD or control chow (n = 10 per group, 16 weeks) to investigate changes in gut microbiota composition at the species level. 53.17% dissimilarity between groups was observed at the species level. Lactobacillus intestinalis dominated the microbiota in rats under the chow diet. However this species was considerably less abundant in rats fed HFD (Pdevelopment of the obese phenotype, we correlated their abundance with metabolic parameters associated with obesity. Of the taxa contributing the most to dissimilarity between groups, 10 presented significant correlations with at least one of the tested parameters, three of them correlated positively with all metabolic parameters: Phascolarctobacterium, Proteus mirabilis and Veillonellaceae, all propionate/acetate producers. Lactobacillus intestinalis was the only species whose abundance was negatively correlated with change in body weight and fat mass. This species decreased drastically in response to HFD, favouring propionate/acetate producing bacterial species whose abundance was strongly correlated with adiposity and deterioration of metabolic factors. Our observations suggest that these species may play a key role in the development of obesity in response to a HFD.

  2. Comparison of febrile responsiveness of rats and rabbits to endogenous pyrogen.

    Science.gov (United States)

    Stitt, J T; Shimada, S G; Bernheim, H A

    1985-12-01

    The fever responses of rats and rabbits were compared in detail using a single common source of semipurified endogenous pyrogen prepared from human monocytes. The characteristics and dynamics of the fever-response curves for each species were examined and their dose-response curves were determined and compared. The fevers displayed by rats were qualitatively similar to those of rabbits, but, typically, they developed and terminated more rapidly than those of rabbits. Rabbits were much more sensitive to the endogenous pyrogen than rats. The threshold dose of pyrogen required to elicit a fever was 5 times lower in the rabbit, and the slope of the rabbit's dose-response curve was 1.5 times steeper than that of the rat. The maximum fevers attainable in rabbits were approximately twice those attainable in rats. It was also shown that the more rapid febrile responses of the rat were not due to the 10-fold smaller mass of the rat; instead, we proposed that this difference was more likely due to a closer diffusional proximity of the pyrogen receptor sites to the circulation in rats. The lower sensitivity of the rat to endogenous pyrogen was attributed to a relative insensitivity of the pyrogen receptor sites in rats in the translation of the endogenous pyrogen stimulus into fever.

  3. RatMap--rat genome tools and data.

    Science.gov (United States)

    Petersen, Greta; Johnson, Per; Andersson, Lars; Klinga-Levan, Karin; Gómez-Fabre, Pedro M; Ståhl, Fredrik

    2005-01-01

    The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB-Genetics at Goteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided.

  4. RatMap—rat genome tools and data

    Science.gov (United States)

    Petersen, Greta; Johnson, Per; Andersson, Lars; Klinga-Levan, Karin; Gómez-Fabre, Pedro M.; Ståhl, Fredrik

    2005-01-01

    The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB–Genetics at Göteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided. PMID:15608244

  5. The Pathophysiological Effects of Acrylamide in Albino Wister Rats

    Directory of Open Access Journals (Sweden)

    Shler Akram Faqe Mahmood

    2016-07-01

    Full Text Available Studies of the pathophysiological effects of suspected compounds are conducted in rodent species, especially rats and mice, to determine the potential toxic effects of a particular compound. In the assessment of acrylamide (ACR which is available as a dietary compound in daily food stuffs, the potential toxicity was determined following the method described earlier. In this study, Albino Wister rats were used and were observed for clinical abnormalities, changes in food consumption, a n d s y m p t o m s o f toxicity over a period of two months following the oral administration of ACR. Among the parameters used to assess the effect of ACR were include ovarian histopathology, blood sugar, haemogram and lipid profile. The most notable clinical abnormalities observed in a few rats were a rough coat and decreased activity. None of the rats died or howedbehavioural change resulting from treatment with ACR. The concentration of serum biochemical parameters and haemogram showed significant differences between normal and treated rats. Histological examination of the ovaries of the treated rats showed great abnormalities as well. In fact, oral ACR doses are practically toxic with regard to rats after exposure for two months at a dose rate of 30 mg/kg, suggesting the compound is quite non-innocuous.

  6. Neuronal damage in chick and rat embryos following X-irradiation

    International Nuclear Information System (INIS)

    Schneider, B.F.; Norton, S.

    1980-01-01

    Exposure of rat and chick embryos to X-irradiation at the time of development of neurons at the telencephalic-diencephalic border results in prolonged damage to neurons in this area as measured by neuronal nuclear size. A dose of 100 rads to the seven-day-old chick embryo has about the same effect as 125 rads to the 15-day-old rat fetus. The nuclear volume of large, multipolar neurons in the chick paleostriatum primitivum and the rat lateral preoptic area are reduced from 10 to 15%. Larger doses of X-irradiation to the chick (150 and 200 rads) cause progressively greater reductions in nuclear size. The large neurons which were measured in the rat and chick are morphologically similar in the two species. Both contain cytoplasmic acetylcholinesterase and have several branched, spiny dendritic processes. The similarity of response of chick and rat neurons to X-irradiation diminishes the significance of maternal factors as the cause of the effects of fetal irradiation in these experiments

  7. Aerial-broadcast application of diphacinone bait for rodent control in Hawai`i: Efficacy and non-target species risk assessment

    Science.gov (United States)

    Foote, David; Spurr, Eric B.; Lindsey, Gerald D.; Forbes Perry, Charlotte

    2015-01-01

    Introduced rats (Rattus rattus, R. exulans, and R. norvegicus) have been implicated in the decline or extinction of numerous species of plants and animals in Hawai‘i. This study investigated the efficacy of aerial-broadcast application of Ramik® Green baits containing 50 ppm (0.005%) diphacinone in reducing rat and mouse populations and the risk to non-target species. The study was undertaken in paired 45.56-ha treatment and non-treatment plots in Hawai‘i Volcanoes National Park. All 21 radio-collared rats in the treatment plot died within nine days of bait application, whereas none of the 18 radio-collared rats in the non-treatment plot died. There was a 99% drop in both the rat capture rate and percentage of non-toxic census bait blocks gnawed by rats in the treatment plot relative to the non-treatment plot three weeks after bait application. The only rat captured in the treatment plot three weeks after bait application was not ear-tagged (i.e., it was not a recapture), whereas 44% of the 52 rats captured in the non-treatment plot were ear-tagged. Most of the bait had disappeared from the forest floor within about one month of application. No birds likely to have eaten bait were found dead, although residues of diphacinone were found in the livers of three species of introduced seed-eating/omnivorous birds captured alive after bait application. No predatory birds were found dead one month or three months after bait application. The remains of a Hawaiian hawk (Buteo solitarius) were found six months after bait application, but it was not possible to determine the cause of death. This study demonstrated the efficacy of aerially broadcast diphacinone bait for control of rats and mice in Hawaiian montane forests, and was part of the dataset submitted to the U.S. Environmental Protection Agency for the national registration of a diphacinone bait for the control of rat populations in conservation areas.

  8. 1200 nt rat liver mRNA identified by differential hybridization exhibits coordinate regulation with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase

    International Nuclear Information System (INIS)

    Tanaka, R.D.; Clarke, C.F.; Fogelman, A.M.; Edwards, P.A.

    1986-01-01

    Differential hybridization has been used to identify genes in rat liver that encode transcripts which are increased by the drugs cholestyramine and mevinolin and are decreased by dietary cholesterol. This approach should prove useful in isolating and identifying coordinately regulated genes involved in the isoprene biosynthetic pathway. Rat liver poly (A) + RNA was isolated from animals fed diets supplemented with either cholestyramine and mevinolin or with cholesterol. Radiolabeled cDNAs generated from these two RNA preparations were used to screen a rat cDNAs library. A preliminary screen of 10,000 recombinants has led to the identification of a clone with an insert of 1200 bp that hybridizes to a mRNA species of about 1200 nt. The level of this RNA species in rat liver is elevated by the drugs cholestyramine and mevinolin and is decreased by cholesterol feeding. This RNA species is also decreased by mevalonate administration to rats. The regulation of this 1200 nt mRNA species mirrors that of HMG CoA reductase and HMG CoA synthase. It seems very likely that this 1200 nt mRNA encodes a polypeptide which is involved in the isoprene biosynthetic pathway

  9. Studies of (±)-3,4-methylenedioxymethamphetamine (MDMA) metabolism and disposition in rats and mice: relationship to neuroprotection and neurotoxicity profile.

    Science.gov (United States)

    Mueller, Melanie; Maldonado-Adrian, Concepcion; Yuan, Jie; McCann, Una D; Ricaurte, George A

    2013-02-01

    The neurotoxicity of (±)-3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") is influenced by temperature and varies according to species. The mechanisms underlying these two features of MDMA neurotoxicity are unknown, but differences in MDMA metabolism have recently been implicated in both. The present study was designed to 1) assess the effect of hypothermia on MDMA metabolism, 2) determine whether the neuroprotective effect of hypothermia is related to inhibition of MDMA metabolism, and 3) determine if different neurotoxicity profiles in mice and rats are related to differences in MDMA metabolism and/or disposition in the two species. Rats and mice received single neurotoxic oral doses of MDMA at 25°C and 4°C, and body temperature, pharmacokinetic parameters, and serotonergic and dopaminergic neuronal markers were measured. Hypothermia did not alter MDMA metabolism in rats and only modestly inhibited MDMA metabolism in mice; however, it afforded complete neuroprotection in both species. Rats and mice metabolized MDMA in a similar pattern, with 3,4-methylenedioxyamphetamine being the major metabolite, followed by 4-hydroxy-3-methoxymethamphetamine and 3,4-dihydroxymethamphetamine, respectively. Differences between MDMA pharmacokinetics in rats and mice, including faster elimination in mice, did not account for the different profile of MDMA neurotoxicity in the two species. Taken together, the results of these studies indicate that inhibition of MDMA metabolism is not responsible for the neuroprotective effect of hypothermia in rodents, and that different neurotoxicity profiles in rats and mice are not readily explained by differences in MDMA metabolism or disposition.

  10. Extrapolation of plasma clearance to understand species differences in toxicokinetics of bisphenol A.

    Science.gov (United States)

    Poet, Torka; Hays, Sean

    2017-10-13

    1. Understanding species differences in the toxicokinetics of bisphenol A (BPA) is central to setting acceptable exposure limits for human exposures to BPA. BPA toxicokinetics have been well studied, with controlled oral dosing studies in several species and across a wide dose range. 2. We analyzed the available toxicokinetic data for BPA following oral dosing to assess potential species differences and dose dependencies. BPA is rapidly conjugated and detoxified in all species. The toxicokinetics of BPA can be well described using non-compartmental analyses. 3. Several studies measured free (unconjugated) BPA in blood and reported area under the curve (AUC) of free BPA in blood of mice, rats, monkeys, chimpanzees and humans following controlled oral doses. Extrinsic clearance was calculated and analyzed across species and dose using allometric scaling. 4. The results indicate free BPA clearance is well described using allometric scaling with high correlation coefficients across all species and doses up to 10 mg/kg. The results indicate a human equivalent dose factor (HEDf) of 0.9 is appropriate for extrapolating a point of departure from mice and rats to a human equivalent dose (HED), thereby replacing default uncertainty factors for animal to human toxicokinetics.

  11. Evaluation of developmental toxicity of coniine to rats and rabbits.

    Science.gov (United States)

    Forsyth, C S; Frank, A A

    1993-07-01

    Conium maculatum (poison hemlock, CM) is teratogenic in several domestic species, presumably due to its piperidine alkaloids, including coniine, which has been verified to be teratogenic in cattle. Coniine/CM teratogenicity culminates in production of arthrogryposis. The purpose of this study was to evaluate coniine-induced teratogenicity in two laboratory animal species, Sprague-Dawley rats and New Zealand white rabbits. Pregnant rats were given coniine (25 mg/kg body weight) by oral gavage at 8-hour intervals on gestation days 16-18. Pregnant rabbits were given coniine (40 mg/kg body weight) by oral gavage at 8-hour intervals on gestation days 20-24. Rats were killed on day 19 and rabbits on day 29. Fetuses were immediately removed, weighed, and examined for external abnormalities. Alternate fetuses were either stained for skeletal examinations with alizarin red-S or fixed in Bouin's solution for visceral examination. Symptoms of maternal intoxication due to coniine administration were observed in both the rat and the rabbit, and higher doses were uniformly lethal. Rabbits treated with coniine appeared to lose more weight and eat less than controls, but there was no statistically significant difference between groups. Fetal weights were significantly lower in coniine-exposed rat and rabbit fetuses indicating fetotoxicity. The only statistically significant treatment-related visceral or skeletal malformation was a reduction of cranial ossification of rabbit fetuses, probably related to maternal toxicity. Coniine-exposed rabbit litters tended to be affected by arthrogryposis (no bony deformities noted on skeletal exam) more than controls (2/6 vs. 0/9).

  12. Hypocholesterolemic Effects of Probiotic Mixture on Diet-Induced Hypercholesterolemic Rats

    Directory of Open Access Journals (Sweden)

    Shang-Jin Kim

    2017-03-01

    Full Text Available Growing evidence has indicated that supplementation with probiotics improves lipid metabolism. We aimed to investigate the beneficial effects of a probiotics mixture (PM of three strains belonging to the species Bifidobacterium (B. longum, B. lactis, and B. breve and two strains belonging to the species Lactobacillus (L. reuteri and L. plantarum on cholesterol-lowering efficacy in hypercholesterolemic rats. A hypercholesterolemic rat model was established by feeding a high-cholesterol diet for eight weeks. To test the effects of PM on hypercholesterolemia, hypercholesterolemic rats were assigned to four groups, which were treated daily with low (1.65 × 109 cfu/kg, medium (5.5 × 109 cfu/kg, or high (1.65 × 1010 cfu/kg doses of probiotic mixture or simvastatin for eight weeks. Significant reductions of serum total cholesterol (TC, triacylglycerol (TG, and low-density lipoprotein (LDL-cholesterol levels, but increases of high-density lipoprotein (HDL-cholesterol were observed after supplementation of PM in hypercholesterolemic rats. In PM-supplemented hypercholesterolemic rats, hepatic tissue contents of TC and TG also significantly decreased. Notably, the histological evaluation of liver tissues demonstrated that PM dramatically decreased lipid accumulation. For their underlying mechanisms, we demonstrated that PM reduced expressions of cholesterol synthesis-related proteins such as sterol regulatory element-binding protein 1 (SREBP1, fatty acid synthase (FAS, and acetyl-CoA carboxylase (ACC in the liver. Taken together, these findings suggest that PM has beneficial effects against hypercholesterolemia. Accordingly, our PM might be utilized as a novel therapeutic agent for the management of hypercholesterolemia.

  13. Changes in gut microbiota in rats fed a high fat diet correlate with obesity-associated metabolic parameters.

    Directory of Open Access Journals (Sweden)

    Virginie Lecomte

    Full Text Available The gut microbiota is emerging as a new factor in the development of obesity. Many studies have described changes in microbiota composition in response to obesity and high fat diet (HFD at the phylum level. In this study we used 16s RNA high throughput sequencing on faecal samples from rats chronically fed HFD or control chow (n = 10 per group, 16 weeks to investigate changes in gut microbiota composition at the species level. 53.17% dissimilarity between groups was observed at the species level. Lactobacillus intestinalis dominated the microbiota in rats under the chow diet. However this species was considerably less abundant in rats fed HFD (P<0.0001, this being compensated by an increase in abundance of propionate/acetate producing species. To further understand the influence of these species on the development of the obese phenotype, we correlated their abundance with metabolic parameters associated with obesity. Of the taxa contributing the most to dissimilarity between groups, 10 presented significant correlations with at least one of the tested parameters, three of them correlated positively with all metabolic parameters: Phascolarctobacterium, Proteus mirabilis and Veillonellaceae, all propionate/acetate producers. Lactobacillus intestinalis was the only species whose abundance was negatively correlated with change in body weight and fat mass. This species decreased drastically in response to HFD, favouring propionate/acetate producing bacterial species whose abundance was strongly correlated with adiposity and deterioration of metabolic factors. Our observations suggest that these species may play a key role in the development of obesity in response to a HFD.

  14. The human immunodeficiency virus-1 protein Tat and its discrete fragments evoke selective release of acetylcholine from human and rat cerebrocortical terminals through species-specific mechanisms.

    Science.gov (United States)

    Feligioni, Marco; Raiteri, Luca; Pattarini, Roberto; Grilli, Massimo; Bruzzone, Santina; Cavazzani, Paolo; Raiteri, Maurizio; Pittaluga, Anna

    2003-07-30

    The effect of the human immunodeficiency virus-1 protein Tat was investigated on neurotransmitter release from human and rat cortical nerve endings. Tat failed to affect the release of several neurotransmitters, such as glutamate, GABA, norepinephrine, and others, but it evoked the release of [3H]ACh via increase of cytosolic [Ca2+]. In human nerve terminals, the Tat effect partly depends on Ca2+ entry through voltage-sensitive Ca2+ channels, because Cd2+ halved the Tat-evoked release. Activation of group I metabotropic glutamate receptors (mGluR) and mobilization of Ca2+ from IP3-sensitive intraterminal stores are also involved, because the Tat effect was prevented by mGluR antagonists 2-methyl-6-(phenylethynyl)pyridine hydrochloride and 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester and by the IP3 receptor antagonists heparin and xestospongin C. Furthermore, the group I selective mGlu agonist (RS)-3,5-dihydroxyphenylglycine enhanced [3H]ACh release. In rat nerve terminals, the Tat-evoked release neither depends on external Ca2+ ions entry nor on IP3-mediated mechanisms. Tat seems to cause mobilization of Ca2+ from ryanodine-sensitive internal stores because its effect was prevented by both 8-bromo-cyclic adenosine diphosphate-ribose and dantrolene. The Tat-evoked release from human synaptosomes was mimicked by the peptide sequences Tat 32-62, Tat 49-86, and Tat 41-60. In contrast, the Tat 49-86 and Tat 61-80 fragments, but not the Tat 32-62 fragment, were active in rat synaptosomes. In conclusion, Tat elicits Ca2+-dependent [3H]ACh release by species-specific intraterminal mechanisms by binding via discrete amino acid sequences to different receptive sites on human and rat cholinergic terminals.

  15. Diet choice patterns in rodents depend on novelty of the diet, exercise, species, and sex.

    Science.gov (United States)

    Yang, Tiffany; Xu, Wei-Jie; York, Haley; Liang, Nu-Chu

    2017-07-01

    Prolonged consumption of a palatable, high fat (HF) diet paired with a lack of physical activity can exacerbate the development of obesity. Exercise can facilitate the maintenance of a healthy body weight, possibly though mediating changes in diet preference. Using a two-diet choice and wheel running (WR) paradigm, our laboratory previously demonstrated that WR induces HF diet avoidance with different persistency in male and female rats when HF diet and WR are introduced simultaneously. The aims of this study were to examine whether this behavior is species dependent and to what extent the novelty of the diet affects WR induced HF diet avoidance. Experiment 1 utilized male C57BL6 mice in a two-diet choice and WR paradigm. Results show that all mice preferred HF to chow diet regardless of exercise and the order in which exercise and HF diet were presented. Experiment 2A (diet novelty) utilized Sprague-Dawley rats that were first habituated to a 45% HF diet prior to the simultaneous introduction of WR and a novel high-carbohydrate, low-fat (DK) diet. All rats avoided the novel high-carbohydrate diet and neither male nor female wheel running rats exhibited reduction in HF diet intake or HF diet avoidance. After all rats were returned to a sedentary condition, female rats consumed significantly more of the DK diet than the male rats. In Experiment 2B (diet familiarity), rats remained sedentary and were re-habituated to the DK diet until intake stabilized. Subsequently, a 60% HF diet was introduced for all rats and for running rats, access to the running wheels were provided simultaneously. Consistent with our previous findings, HF diet intake and preference was significantly reduced in all wheel running rats. These data suggest that exercise induced HF diet avoidance is affected by species and the novelty of the diet. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Neuropeptide Y-enhanced diuresis and natriuresis in anaesthetized rats is independent of renal blood flow reduction

    NARCIS (Netherlands)

    Bischoff, A.; Erdbrügger, W.; Smits, J.; Michel, M. C.

    1996-01-01

    1. Neuropeptide Y (NPY) has been reported to enhance diuresis and natriuresis in anaesthetized rats although it is a potent renal vasoconstrictor in vitro in vivo in several species. Therefore, we have investigated anaesthetized rats to see whether reduction in renal blood flow (RBF) and enhancement

  17. Lipid synthesis in the aorta of chick and other species

    International Nuclear Information System (INIS)

    Rao, A.R.

    1976-01-01

    The relative rate of fatty acid biosynthesis from labelled acetate in the adipose tissue of chicken is much lower than that in the rat (O'Hea and Leveille, 1968). To determine similar species differences in lipid synthesis in the aortas of cock, rat, rabbit and monkey, thoracic and abdominal segments of fresh aortas were incubated in vitro with (1- 14 C)-acetate for 3 h. Total lipids and their fractions (free and total cholesterol, free fatty acids, triglycerides and phospholipids) were counted for radioactivity. Incorporation of radioactivity into total as well as all classes of lipids was several times greater in chicken than in other species. Significant and consistent incorporation into cholesterol occurred only in chicks. Synthesis into total lipids and triglycerides was greater in the thoracic segment of chicks. These findings (Rao and Rao, 1968) are consistent with the ready susceptibility of chicken to atherosclerosis. (author)

  18. Comparative analysis of kisspeptin-immunoreactivity reveals genuine differences in the hypothalamic Kiss1 systems between rats and mice

    DEFF Research Database (Denmark)

    Overgaard, Agnete; Tena-Sempere, Manuel; Franceschini, Isabelle

    2013-01-01

    cells, only after axonal transport inhibition. Interestingly, the density of kisspeptin innervation in the anterior periventricular area was higher in female compared to male in both species. Species differences in the ARC were evident, with the mouse ARC containing dense fibers, while the rat ARC......-immunoreactivity in the mouse compared to the rat, independently of brain region and gender. In the female mouse AVPV high numbers of kisspeptin-immunoreactive neurons were present, while in the rat, the female AVPV displays a similar number of kisspeptin-immunoreactive neurons compared to the level of Kiss1 mRNA expressing...... contains clearly discernable cells. In addition, we show a marked sex difference in the ARC, with higher kisspeptin levels in females. These findings show that the translation of Kiss1 mRNA and/or the degradation/transportation/release of kisspeptins are different in mice and rats....

  19. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  20. Differences in TCDD-elicited gene expression profiles in human HepG2, mouse Hepa1c1c7 and rat H4IIE hepatoma cells

    Directory of Open Access Journals (Sweden)

    Burgoon Lyle D

    2011-04-01

    Full Text Available Abstract Background 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD is an environmental contaminant that elicits a broad spectrum of toxic effects in a species-specific manner. Current risk assessment practices routinely extrapolate results from in vivo and in vitro rodent models to assess human risk. In order to further investigate the species-specific responses elicited by TCDD, temporal gene expression responses in human HepG2, mouse Hepa1c1c7 and rat H4IIE cells were compared. Results Microarray analysis identified a core set of conserved gene expression responses across species consistent with the role of AhR in mediating adaptive metabolic responses. However, significant species-specific as well as species-divergent responses were identified. Computational analysis of the regulatory regions of species-specific and -divergent responses suggests that dioxin response elements (DREs are involved. These results are consistent with in vivo rat vs. mouse species-specific differential gene expression, and more comprehensive comparative DRE searches. Conclusions Comparative analysis of human HepG2, mouse Hepa1c1c7 and rat H4IIE TCDD-elicited gene expression responses is consistent with in vivo rat-mouse comparative gene expression studies, and more comprehensive comparative DRE searches, suggesting that AhR-mediated gene expression is species-specific.

  1. Interactions of xylazine and detomidine with alpha2-adrenoceptors in brain tissue from cattle, swine and rats.

    Science.gov (United States)

    Törneke, K; Bergström, U; Neil, A

    2003-06-01

    Xylazine is an alpha2-adrenoceptor agonist sedative with a much higher interspecies variability in effect than detomidine, another alpha2-agonist used in veterinary practice. In the present study, we have used radioligand binding in brain tissue to investigate if the high species variation in sensitivity to xylazine could be explained in terms of receptor interactions. Species known to be more (cattle) or less (swine and rats) sensitive to xylazine were used. There was no variation in the density or the subtype pattern of the alpha2-adrenoceptors that could explain the species variation recorded in vivo, as a homogenous population of the alpha2A/D-subtype (200-300 fmol/mg protein) was found in all species. The species differences in the affinities of xylazine and detomidine were minor and similar for the two drugs. The only parameter investigated where a significant species difference was found for xylazine but not for detomidine was the slope of the inhibition binding curve when the G-protein coupling was diminished. For xylazine this slope was considerably lower than unity (i.e. 0.77 +/- 0.075) using cattle preparations compared with 0.92 +/- 0.037 (mean +/- SE) and 0.90 +/- 0.028, respectively for swine and rats, while for detomidine this parameter was close to unity in all species (cattle, swine, rat). This finding indicates that the species variation in effect for xylazine could be due to differences at the G-protein level or further down-stream in the effect cascade.

  2. Decorporation of 241Am and 252Cf by Ca-DTPA from rat, Syrian and Chinese hamster

    International Nuclear Information System (INIS)

    Seidel, A.

    1977-01-01

    Retention and mobilization by Ca-DTPA of 241 Am and 252 Cf from rats, Syrian and Chinese hamsters are compared. Previous observations of a much longer residence time of actinides in hamsters liver than in rat liver are confirmed. Identical dose-effect functions were obtained for skeleton of rats and Syrian hamsters whereas 252 Cf removal from Chinese hamster skeleton was lower. The mobilization of 241 Am was lower than that of 252 Cf. With regard to species differences, qualitatively similar results were obtained for 241 Am as for 252 Cf. The results will be discussed with regard to the reduction by DTPA treatment of radiation risk in animal species with different biological half times of actinides in their livers. In this connection, attention will be paid to the usefulness of long-term DTPA treatment

  3. Unraveling the message: insights into comparative genomics of the naked mole-rat.

    Science.gov (United States)

    Lewis, Kaitlyn N; Soifer, Ilya; Melamud, Eugene; Roy, Margaret; McIsaac, R Scott; Hibbs, Matthew; Buffenstein, Rochelle

    2016-08-01

    Animals have evolved to survive, and even thrive, in different environments. Genetic adaptations may have indirectly created phenotypes that also resulted in a longer lifespan. One example of this phenomenon is the preternaturally long-lived naked mole-rat. This strictly subterranean rodent tolerates hypoxia, hypercapnia, and soil-based toxins. Naked mole-rats also exhibit pronounced resistance to cancer and an attenuated decline of many physiological characteristics that often decline as mammals age. Elucidating mechanisms that give rise to their unique phenotypes will lead to better understanding of subterranean ecophysiology and biology of aging. Comparative genomics could be a useful tool in this regard. Since the publication of a naked mole-rat genome assembly in 2011, analyses of genomic and transcriptomic data have enabled a clearer understanding of mole-rat evolutionary history and suggested molecular pathways (e.g., NRF2-signaling activation and DNA damage repair mechanisms) that may explain the extraordinarily longevity and unique health traits of this species. However, careful scrutiny and re-analysis suggest that some identified features result from incorrect or imprecise annotation and assembly of the naked mole-rat genome: in addition, some of these conclusions (e.g., genes involved in cancer resistance and hairlessness) are rejected when the analysis includes additional, more closely related species. We describe how the combination of better study design, improved genomic sequencing techniques, and new bioinformatic and data analytical tools will improve comparative genomics and ultimately bridge the gap between traditional model and nonmodel organisms.

  4. Comparison of TCDD-elicited genome-wide hepatic gene expression in Sprague–Dawley rats and C57BL/6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Nault, Rance; Kim, Suntae; Zacharewski, Timothy R., E-mail: tzachare@msu.edu

    2013-03-01

    Although the structure and function of the AhR are conserved, emerging evidence suggests that downstream effects are species-specific. In this study, rat hepatic gene expression data from the DrugMatrix database (National Toxicology Program) were compared to mouse hepatic whole-genome gene expression data following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For the DrugMatrix study, male Sprague–Dawley rats were gavaged daily with 20 μg/kg TCDD for 1, 3 and 5 days, while female C57BL/6 ovariectomized mice were examined 1, 3 and 7 days after a single oral gavage of 30 μg/kg TCDD. A total of 649 rat and 1386 mouse genes (|fold change| ≥ 1.5, P1(t) ≥ 0.99) were differentially expressed following treatment. HomoloGene identified 11,708 orthologs represented across the rat Affymetrix 230 2.0 GeneChip (12,310 total orthologs), and the mouse 4 × 44K v.1 Agilent oligonucleotide array (17,578 total orthologs). Comparative analysis found 563 and 922 orthologs differentially expressed in response to TCDD in the rat and mouse, respectively, with 70 responses associated with immune function and lipid metabolism in common to both. Moreover, QRTPCR analysis of Ceacam1, showed divergent expression (induced in rat; repressed in mouse) functionally consistent with TCDD-elicited hepatic steatosis in the mouse but not the rat. Functional analysis identified orthologs involved in nucleotide binding and acetyltransferase activity in rat, while mouse-specific responses were associated with steroid, phospholipid, fatty acid, and carbohydrate metabolism. These results provide further evidence that TCDD elicits species-specific regulation of distinct gene networks, and outlines considerations for future comparisons of publicly available microarray datasets. - Highlights: ► We performed a whole-genome comparison of TCDD-regulated genes in mice and rats. ► Previous species comparisons were extended using data from the DrugMatrix database. ► Less than 15% of TCDD

  5. Mites (acari) infesting commensal rats in Suez Canal zone, Egypt.

    Science.gov (United States)

    el Kady, G A; Shoukry, A; Ragheb, D A; el Said, A M; Habib, K S; Morsy, T A

    1995-08-01

    Mites are arthropods distinguished from ticks by usually being microscopical in size and have a hypostome unarmed with tooth-like anchoring processes. They are group in a number of suborders, each with super-families and families including many genera of medical and economic importance. In this paper, commensal rodents (Rattus norvegicus, R. r. alexandrinus and R. r. frugivorous) were surveyed in the Suez Canal Zone for their acari ectoparasites. Four species of mites were recovered. In a descending order of mite indices, they were Eulaelaps stabularis (4.83 on 6 rats), Laelaps nuttalli (3.11 on 27 rats), Ornithonyssus bacoti (1.66 on 9 rats) and Dermanyssus gallinae (0.66 on 24 rats). The overall mite indices in the three governorates were 3.66 in Suez, 2.82 in Ismailia and zero in Port Said. The medical and economic importance of the mites were discussed.

  6. Intestinal helminths infection of rats (Ratus norvegicus) in the Belgrade area (Serbia): the effect of sex, age and habitat.

    Science.gov (United States)

    Kataranovski, M; Mirkov, I; Belij, S; Popov, A; Petrovic, Z; Gaci, Z; Kataranovski, D

    2011-05-01

    Gastrointestinal helminths of Norway rat (Rattus norvegicus) from the Belgrade area were studied as a part of a wider ecological research of rats in Serbia (data on the distribution, population ecology, economic and epizoothiological-epidemiological importance, and density control). Rats were captured from May 2005 to July 2009 at both urban and suburban-rural sites. Of a total of 302 trapped rats 48% were males and 52% females, with 36.5% and 38.8% of juvenile-subadult individuals, per sex respectively. Intestinal helminth infection was noted in 68.5% of rats, with a higher prevalence in male hosts and in adult individuals. Higher numbers of infected juveniles-subadults were noted in suburban-rural habitats, while an opposite tendency was noted in adult rats. Seven helminth species were recovered, of which five were nematode (Heterakis spumosa, Nippostrongylus brasiliensis, Capillaria sp., Trichuris muns and Syphacia muris) and two cestode species (Hymenolepis diminuta and Rodentolepis fraterna). The most prevalent parasites were Heterakis spumosa (36.7%) and Hymenolepis diminuta (30.5 %). Sex and habitat-related differences were noted in the prevalence of infection with Capillaria sp. and Trichuris muris, while there were no age-related differences in the prevalence of infection with any individual helminth species. Significantly higher prevalence of infection was noted in summer as compared to spring or winter, with a tendency to be higher in autumn as compared to spring. The only significant difference in the prevalence of infection between habitat-related was noted during spring. H. spumosa was most prevalent in summer, while H. diminuta and N. brasiliensis in autumn. The mean intensity of infection with H. spumosa, R. fraterna, S. muris and T muris was higher in autumn than in the other seasons, while N. brasiliensis and Capillaria sp. occured in winter. No more than four helminth species were found in one host.

  7. Protective effects of agmatine on doxorubicin-induced chronic cardiotoxicity in rat.

    Science.gov (United States)

    Yarmohmmadi, Fatemeh; Rahimi, Nastaran; Faghir-Ghanesefat, Hedyeh; Javadian, Nina; Abdollahi, Alireza; Pasalar, Parvin; Jazayeri, Farahnaz; Ejtemaeemehr, Shahram; Dehpour, Ahmad Reza

    2017-02-05

    The detrimental cardio-toxic effect of doxorubicin, an effective chemotherapeutic agent, limited its clinical use. It has been claimed that doxorubicin cardio-toxicity occurs through calcium ions (Ca 2+ ) overload and reactive oxygen species production. Agmatine, an endogenous imidazoline receptor agonist, induce uptake of cytosolic Ca 2+ and cause an increase in activity of calcium pumps, including Ca 2+ -ATPase. Also it shows self-scavenging effect against reactive oxygen species production. Therefore, present study was designed to investigate the effects of agmatine against chronic cardio-toxicity of doxorubicin in rats. Male wistar rats were intraperitoneally injected with doxorubicin and agmatine four times a week for a month. Agmatine significantly alleviate the adverse effect of doxorubicin on left ventricular papillary muscle stimulation threshold and contractibility. Chronic co-administration of agmatine with doxorubicin blocked electrocardiographic changes induced by doxorubicin. In addition, agmatine improved body weight and decreased the mortality rate of animals by doxorubicin. Moreover, reversing the doxorubicin induced myocardial lesions was observed in animals treated by agmatine. A significant rise in the total antioxidant capacity of rat plasma was achieved in agmatine-treated animals in comparison to doxorubicin. To conclude, agmatine may improve therapeutic outcomes of doxorubicin since it exerts protective effects against doxorubicin-induced chronic cardiotoxicity in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Effects of Social Housing on Hippocampal Dendrites and Behavior in Ovariectomized Rats

    OpenAIRE

    Leedy, Gail M.; Burrows, Lorraine F.; Clark, Suzanne

    2012-01-01

    Social stress is both species and gender specific. For female rats, individual housing and social instability housing conditions are associated with behavioral indicators of stress and depression. The present study directly compared the effects of six weeks of individual housing, social instability and mixed sex, semi-crowded housing in a visible burrow system (VBS) on ovariectomized female rats. Paired, stable housing was used as the control. Behavioral tests were conducted two, four and six...

  9. Qualitative and quantitative differences between taste buds of the rat and mouse

    OpenAIRE

    Ma Huazhi; Yang Ruibiao; Thomas Stacey M; Kinnamon John C

    2007-01-01

    Abstract Background Numerous electrophysiological, ultrastructural, and immunocytochemical studies on rodent taste buds have been carried out on rat taste buds. In recent years, however, the mouse has become the species of choice for molecular and other studies on sensory transduction in taste buds. Do rat and mouse taste buds have the same cell types, sensory transduction markers and synaptic proteins? In the present study we have used antisera directed against PLCβ2, α-gustducin, serotonin ...

  10. Clinical Procedures Training for Veterinary Technicians and Investigators using Common Laboratory Animal Species, including: Mice (Mus musculus), Rats (Rattus norvegicus), Hamsters (Mesocricetus auratus), Guinea Pigs (Gavia porcellus), Rabbits (Otyctolagus cuniculus), Ferrets (Mustela putorius furo), Pigs (Sus scrofa), Sheep (Ovis aries), and Goats (Capra hircus)

    Science.gov (United States)

    2016-08-30

    60th Medical Group (AMC), Travis AFB, CA INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) FINAL REPORT SUMMARY (Please !ml all information. Use...Technicians and Investigators using Common Laboratory Animal Species, including: Mice (Mus muscu/us), Rats (Rattus norvegicus), Hamsters (Mesocricetus auratus...DATE: 14 November 2016 FUNDING SOURCE: SG O&M funds LAST TRIENNIAL REVISION DATE: 15 October 2015 1. RECORD OF ANIMAL USAGE: Animal Species: Total

  11. Liver dysfunction following whole-body Co-60 irradiation in gerbil (Meriones hurrianae Jerdon) and house rat (Rattus rattus rufescens)

    International Nuclear Information System (INIS)

    Dixit, V.P.; Agrawal, M.; Gupta, C.

    1976-01-01

    Liver dysfunction following whole-body Co-60 irradiation has been studied in domestic and desert rat species. A significant elevation in the serum transaminases activity was noticed both in gerbil and house rat. Alkaline phosphatase and plasma cholesterol levels were also increased indicating an early radiation impairment of the liver tissue, which was later confirmed by histological studies. A steady fall in liver glycogen in irradiated gerbils was strikingly in contrast to an increase in irradiated house rat. Drastic depletion in liver glycogen, changes in the serum enzyme levels and the severity of the hepatic necrosis in gerbils point out that desert mammalian species are much more sensitive to radiation hazard as compared with domestic ones. (orig.) [de

  12. Social modulation of risky decision-making in rats (Rattus norvegicus) and tufted capuchin monkeys (Sapajus spp.).

    Science.gov (United States)

    Zoratto, F; Oddi, G; Gori, E; Micucci, A; De Petrillo, F; Paglieri, F; Adriani, W; Laviola, G; Addessi, E

    2018-02-24

    Both human and non-human animals frequently deal with risky decisions in a social environment. Nevertheless, the influence of the social context on decision-making has been scarcely investigated. Here, we evaluated for the first time whether the presence of a conspecific influences risk preferences in rats and in tufted capuchin monkeys. Subjects received a series of choices between a constant, safe option and a variable, risky option, both alone (Alone condition) and when paired with a conspecific (Paired condition). The average payoff of the risky option was always lower than that of the safe option. Overall, the two species differed in their attitude towards risk: whereas rats were indifferent between options, capuchins exhibited a preference for the safe option. In both species, risk preferences changed in the Paired condition compared to the Alone condition, although in an opposite way. Whereas rats increased their risk preferences over time when paired with a conspecific, capuchins chose the risky option less in the Paired condition than in the Alone condition. Moreover, whereas anxiety-like behaviours decreased across sessions in rats, these behaviours where more represented in the Paired condition than in the Alone condition in capuchins. Thus, our findings extends to two distantly-related non-human species the evidence, so far available for human beings, that a decrease in anxiety corresponds to an increase in risk preferences, and vice versa. This suggests that the modulation of risk preferences by social influences observed in rats and capuchin monkeys may rely on a common, evolutionarily ancient, mechanism. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. 76 FR 24047 - Palmyra Atoll National Wildlife Refuge, U.S. Pacific Island Territory; Nonnative Rat Eradication...

    Science.gov (United States)

    2011-04-29

    ...). The comments we received covered topics such as threats to nontarget species, our proposed selection... eradication, threats to nontarget species, our proposed selection of the rodenticide brodifacoum over... directional manner to all potential rat territories within a short operational period. Special measures to...

  14. A comparative immunohistochemical study on amylase localization in the rat and human exocrine pancreas

    International Nuclear Information System (INIS)

    Aughsteen, Adib A.

    2001-01-01

    Objective was to localize amylase enzyme immunohistochemically in the pancreatic acinar cells of rats and humans using polyclonal sheep anti-human amylase antibody, and to compare between the intensities of their amylase-immunostaining. Indirect immunofluorescence method was applied on formaldehyde-fixed, and paraffin-embedded pancreatic sections obtained from adult male Wistar rats and autopsied human samples. Primary incubation was performed using sheep anti-amylase antibody followed by secondary incubation with fluorescein isothiocyanate-labeled rabbit anti-sheep IgG serum. Control tests of amylase immunospecificity were also undertaken either by incubation with primary antibodies previously pre-adsorbed with an excess of human pancreatic amylase, or only with secondary antibodies. The amylase immunofluorescence was positively and homogenously detected in all acinar cells of both rat and human pancreatic stained sections. The immunostaining was clearly demonstrated in the cell apices and peri-nuclear areas, but it was consistently brighter and more intense in the human acinar cells compared with that of the rat pancreas. Control tests of amylase immunofluorescence revealed the specificity of the antibodies applied for amylase localization in rat and human pancreas. Although many previous immunohisto- and cytochemical reports have successfully localized amylase in the pancreas of different mammalian species, but all of them have used locally prepared anti-amylase antibodies. The present report successfully illustrates immuno-localization of amylase in the pancreatic acinar cells of rats and humans using commercial polyclonal sheep anti-human pancreatic amylase antibodies, and also suggests their useful application in the immunochemical studies on various mammalian species. Additionally, the results indicate a structural similarity between the human and rat pancreatic amylases, a concept required further exploration. (author)

  15. Neurally mediated airway constriction in human and other species: a comparative study using precision-cut lung slices (PCLS.

    Directory of Open Access Journals (Sweden)

    Marco Schlepütz

    Full Text Available The peripheral airway innervation of the lower respiratory tract of mammals is not completely functionally characterized. Recently, we have shown in rats that precision-cut lung slices (PCLS respond to electric field stimulation (EFS and provide a useful model to study neural airway responses in distal airways. Since airway responses are known to exhibit considerable species differences, here we examined the neural responses of PCLS prepared from mice, rats, guinea pigs, sheep, marmosets and humans. Peripheral neurons were activated either by EFS or by capsaicin. Bronchoconstriction in response to identical EFS conditions varied between species in magnitude. Frequency response curves did reveal further species-dependent differences of nerve activation in PCLS. Atropine antagonized the EFS-induced bronchoconstriction in human, guinea pig, sheep, rat and marmoset PCLS, showing cholinergic responses. Capsaicin (10 µM caused bronchoconstriction in human (4 from 7 and guinea pig lungs only, indicating excitatory non-adrenergic non-cholinergic responses (eNANC. However, this effect was notably smaller in human responder (30 ± 7.1% than in guinea pig (79 ± 5.1% PCLS. The transient receptor potential (TRP channel blockers SKF96365 and ruthenium red antagonized airway contractions after exposure to EFS or capsaicin in guinea pigs. In conclusion, the different species show distinct patterns of nerve-mediated bronchoconstriction. In the most common experimental animals, i.e. in mice and rats, these responses differ considerably from those in humans. On the other hand, guinea pig and marmoset monkey mimic human responses well and may thus serve as clinically relevant models to study neural airway responses.

  16. Levels of human and rat hypothalamic growth hormone-releasing factor as determined by specific radioimmunoassay systems

    International Nuclear Information System (INIS)

    Audhya, T.; Manzione, M.M.; Nakane, T.; Kanie, N.; Passarelli, J.; Russo, M.; Hollander, C.S.

    1985-01-01

    Polyclonal antibodies to synthetic human pancreatic growth hormone-releasing factor [hpGRF(1-44)NH 2 ] and rat hypothalamic growth hormone-releasing factor [rhGRF(1-43)OH] were produced in rabbits. A subsequent booster injection by the conventional intramuscular route resulted in high-titer antibodies, which at a 1:20,000 dilution were used to develop highly sensitive and specific radioimmunoassays for these peptides. The antibody to hpGRF(1-44)NH 2 is directed against the COOH-terminal region of the molecule, as shown by its cross reactivity with various hpGRF analogues. Serial dilutions of human and rat hypothalamic extracts demonstrated parallelism with the corresponding species-specific standard and 125 I-labeled tracer. There was no cross reactivity with other neuropeptides, gastrointestinal peptides, or hypothalamic extracts of other species. Age-related changes in hypothalamic GRF content were present in rats, with a gradual increase from 2 to 16 weeks and a correlation between increasing body weight and GRF content. These radioimmunoassays will serve as important tools for understanding the regulation of growth hormone secretion in both human and rat

  17. Differential strain vulnerability to binge eating behaviors in rats.

    Science.gov (United States)

    Hildebrandt, Britny A; Klump, Kelly L; Racine, Sarah E; Sisk, Cheryl L

    2014-03-29

    Binge eating is a significantly heritable phenotype, but efforts to detect specific risk genes have fallen short. Identification of animal strain differences in risk for binge eating could highlight genetic differences across individuals of the same species that can be exploited in future animal and molecular genetic research. The current study aimed to explore strain differences in risk for binge eating in Sprague-Dawley versus Wistar female rats using the Binge Eating Resistant/Binge Eating Prone model. A sample of male Sprague-Dawley rats, a known low-risk group for binge eating, was included as a comparison group. A total of 83 rats (23 Wistar females, 30 Sprague-Dawley females, 30 Sprague-Dawley males) completed a protocol of intermittently administered, palatable food. Binge eating prone (BEP) and binge eating resistant (BER) rats were identified using a tertile approach. Sprague-Dawley female rats consumed the highest amount of palatable food and were more likely to be classified as BEP compared to Wistar female and Sprague-Dawley male rats. Wistar female rats were not significantly different from Sprague-Dawley male rats in their palatable food intake and tendency to be classified as BER rather than BEP. Sprague-Dawley female rats appear to be a particularly vulnerable genotype for binge eating. Comparisons between this group and others could help identify specific genetic/biological factors that differentiate it from lower risk groups. The reward system, linked to binge eating in humans, is a possible candidate to explore. Strain differences in the reward system could help increase understanding of individual differences in risk for binge eating in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Ebselen protects against behavioral and biochemical toxicities induced by 3-nitropropionic acid in rats: correlations between motor coordination, reactive species levels, and succinate dehydrogenase activity.

    Science.gov (United States)

    Wilhelm, Ethel A; Bortolatto, Cristiani F; Jesse, Cristiano R; Luchese, Cristiane

    2014-12-01

    The protective effect of ebselen was investigated against 3-nitropropionic acid (3-NP)-induced behavioral and biochemical toxicities in rats. Ebselen (10 or 25 mg/kg, intragastrically) was administered to rats 30 min before 3-NP (20 mg/kg, intraperitoneally) once a day for a period of 4 days. Locomotor activity, motor coordination, and body weight gain were determined. The striatal content of reactive oxygen species (ROS), reduced glutathione (GSH), ascorbic acid (AA), and protein carbonyl as well as catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST) activities was determined 24 h after the last dose of 3-NP. Na(+)/ K(+)-ATPase, succinate dehydrogenase (SDH), and δ-aminolevulinic dehydratase (δ-ALA-D) activities were also determined. The results demonstrated that ebselen at a dose of 25 mg/kg, but not at 10 mg/kg, protected against (1) a decrease in locomotor activity, motor coordination impairment, and body weight loss; (2) striatal oxidative damage, which was characterized by an increase in ROS levels, protein carbonyl content, and GR activity, an inhibition of CAT and GPx activities, and a decrease in GSH levels; and (3) an inhibition of SDH and Na(+)/K(+)-ATPase activities, induced by 3-NP. GST activity and AA levels were not modified by ebselen or 3-NP. Ebselen was not effective against the inhibition of δ-ALA-D activity induced by 3-NP. The results revealed a significant correlation between SDH activity and ROS levels, and SDH activity and latency to fall (rotarod test). The present study highlighted the protective effect of ebselen against 3-NP-induced toxicity in rats.

  19. Endogenous retroviruses function as species-specific enhancer elements in the placenta.

    Science.gov (United States)

    Chuong, Edward B; Rumi, M A Karim; Soares, Michael J; Baker, Julie C

    2013-03-01

    The mammalian placenta is remarkably distinct between species, suggesting a history of rapid evolutionary diversification. To gain insight into the molecular drivers of placental evolution, we compared biochemically predicted enhancers in mouse and rat trophoblast stem cells (TSCs) and found that species-specific enhancers are highly enriched for endogenous retroviruses (ERVs) on a genome-wide level. One of these ERV families, RLTR13D5, contributes hundreds of mouse-specific histone H3 lysine 4 monomethylation (H3K4me1)- and histone H3 lysine 27 acetylation (H3K27ac)-defined enhancers that functionally bind Cdx2, Eomes and Elf5-core factors that define the TSC regulatory network. Furthermore, we show that RLTR13D5 is capable of driving gene expression in rat placental cells. Analysis in other tissues shows that species-specific ERV enhancer activity is generally restricted to hypomethylated tissues, suggesting that tissues permissive for ERV activity gain access to an otherwise silenced source of regulatory variation. Overall, our results implicate ERV enhancer co-option as a mechanism underlying the extensive evolutionary diversification of placental development.

  20. Trichloroethylene-Induced DNA Methylation Changes in Male F344 Rat Liver.

    Science.gov (United States)

    Jiang, Yan; Chen, Jiahong; Yue, Cong; Zhang, Hang; Chen, Tao

    2016-10-17

    Trichloroethylene (TCE), a common environmental contaminant, causes hepatocellular carcinoma in mice but not in rats. To understand the mechanisms of the species-specific hepatocarcinogenecity of TCE, we examined the methylation status of DNA in the liver of rats exposed to TCE at 0 or 1000 mg/kg b.w. for 5 days using MeDIP-chip, bisulfite sequencing, COBRA, and LC-MS/MS. The related mRNA expression levels were measured by qPCR. Although no global DNA methylation change was detected, 806 genes were hypermethylated and 186 genes were hypomethylated. The genes with hypermethylated DNA were enriched in endocytosis, MAPK, and cAMP signaling pathways. We further confirmed the hypermethylation of Uhrf2 DNA and the hypomethylation of Hadhb DNA, which were negatively correlated with their mRNA expression levels. The transcriptional levels of Jun, Ihh, and Tet2 were significantly downregulated, whereas Cdkn1a was overexpressed. No mRNA expression change was found for Mki67, Myc, Uhrf1, and Dnmt1. In conclusion, TCE-induced DNA methylation changes in rats appear to suppress instead of promote hepatocarcinogenesis, which might play a role in the species-specific hepatocarcinogenecity of TCE.

  1. Swimming exercise enhances the hippocampal antioxidant status of female Wistar rats.

    Science.gov (United States)

    Stone, Vinícius; Kudo, Karen Yurika; Marcelino, Thiago Beltram; August, Pauline Maciel; Matté, Cristiane

    2015-05-01

    Moderate exercise is known to have health benefits, while both sedentarism and strenuous exercise have pro-oxidant effects. In this study, we assessed the effect of moderate exercise on the antioxidant homeostasis of rats' hippocampi. Female Wistar rats were submitted to a 30-minute swimming protocol on 5 days a week, for 4 weeks. Control rats were immersed in water and carefully dried. Production of hippocampal reactive species, activity of antioxidant enzymes, and glutathione levels in these animals were determined up to 30 days after completion of the 4-week protocol. Production of reactive species and hippocampal glutathione levels were increased 1 day after completion of the 4-week protocol, and returned to control levels after 7 days. Antioxidant enzyme activities were increased both 1 day (catalase) and 7 days (superoxide dismutase and glutathione peroxidase) after completion of the protocol. Thirty days after completion of the protocol, none of the antioxidant parameters evaluated differed from those of controls. Our results reinforce the benefits of aerobic exercise, which include positive modulation of antioxidant homeostasis in the hippocampi. The effects of exercise are not permanent; rather, an exercise regimen must be continued in order to maintain the neurometabolic adaptations.

  2. Species Differences in the Binding of Sodium 4-Phenylbutyrate to Serum Albumin.

    Science.gov (United States)

    Yamasaki, Keishi; Enokida, Taisuke; Taguchi, Kazuaki; Miyamura, Shigeyuki; Kawai, Akito; Miyamoto, Shuichi; Maruyama, Toru; Seo, Hakaru; Otagiri, Masaki

    2017-09-01

    Sodium 4-phenylbutyrate (PB) is clinically used as a drug for treating urea cycle disorders. Recent research has shown that PB also has other pharmacologic activities, suggesting that it has the potential for use as a drug for treating other disorders. In the process of drug development, preclinical testing using experimental animals is necessary to verify the efficacy and safety of PB. Although the binding of PB to human albumin has been studied, our knowledge of its binding to albumin from the other animal species is extremely limited. To address this issue, we characterized the binding of PB to albumin from several species (human, bovine, rabbit, and rat). The results indicated that PB interacts with 1 high-affinity site of albumin from these species, which corresponds to site II of human albumin. The affinities of PB to human and bovine albumins were higher than those to rabbit and rat albumin, and that to rabbit albumin was the lowest. Binding and molecular docking studies using structurally related compounds of PB suggested that species differences in the affinity are attributed to differences in the structural feature of the PB-binding sites on albumins (e.g., charge distribution, hydrophobicity, shape, or size). Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  3. Quantitative autoradiographic localization of cholecystokinin receptors in rat and guinea pig brain using 125I-Bolton-Hunter-CCK8

    International Nuclear Information System (INIS)

    Niehoff, D.L.

    1989-01-01

    The autoradiographic localization of receptors for the brain-gut peptide cholecystokinin (CCK) has shown differences in receptor distribution between rat and guinea pig brain. However the full anatomical extent of the differences has not been determined quantitatively. In the present study, 125 I-Bolton-Hunter-CCK8 ( 125 I-BH-CCK8) was employed in a comparative quantitative autoradiographic analysis of the distribution of CCK receptors in these two species. The pharmacological profile of 125 I-BH-CCK8 binding in guinea pig forebrain sections was comparable to those previously reported for rat and human. Statistically significant differences in receptor binding between rat and guinea pig occurred in olfactory bulb, caudate-putamen, amygdala, several cortical areas, ventromedial hypothalamus, cerebellum, and a number of midbrain and brainstem nuclei. The results of this study confirm the presence of extensive species-specific variation in the distribution of CCK receptors, suggesting possible differences in the physiological roles of this peptide in different mammalian species

  4. Acute rejection after kidney transplantation promotes graft fibrosis with elevated adenosine level in rat.

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    Mingliang Li

    Full Text Available Chronic allograft nephropathy is a worldwide issue with the major feature of progressive allograft fibrosis, eventually ending with graft loss. Adenosine has been demonstrated to play an important role in process of fibrosis. Our study aimed to investigate the relationship between adenosine and fibrosis in renal allograft acute rejection in rat.Wistar rats and SD rats were selected as experimental animals. Our study designed two groups. In the allograft transplantation group, kidneys of Wistar rats were orthotopically transplanted into SD rat recipients, the same species but not genetically identical, to induce acute rejection. Kidney transplantations of SD rats to SD rats which were genetically identical were served as the control. We established rat models and detected a series of indicators. All data were analyzed statistically. P<0.05 was considered statistically significant.Compared with the control group, levels of adenosine increased significantly in the allograft transplantation group, in which acute rejection was induced (P<0.05. Progressive allograft fibrosis as well as collagen deposition were observed.These findings suggested that level of adenosine was upregulated in acute rejection after kidney allograft transplantation in rat. Acute rejection may promote renal allograft fibrosis via the adenosine signaling pathways.

  5. Inflammasome sensor NLRP1 controls rat macrophage susceptibility to Toxoplasma gondii.

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    Kimberly M Cirelli

    2014-03-01

    Full Text Available Toxoplasma gondii is an intracellular parasite that infects a wide range of warm-blooded species. Rats vary in their susceptibility to this parasite. The Toxo1 locus conferring Toxoplasma resistance in rats was previously mapped to a region of chromosome 10 containing Nlrp1. This gene encodes an inflammasome sensor controlling macrophage sensitivity to anthrax lethal toxin (LT induced rapid cell death (pyroptosis. We show here that rat strain differences in Toxoplasma infected macrophage sensitivity to pyroptosis, IL-1β/IL-18 processing, and inhibition of parasite proliferation are perfectly correlated with NLRP1 sequence, while inversely correlated with sensitivity to anthrax LT-induced cell death. Using recombinant inbred rats, SNP analyses and whole transcriptome gene expression studies, we narrowed the candidate genes for control of Toxoplasma-mediated rat macrophage pyroptosis to four genes, one of which was Nlrp1. Knockdown of Nlrp1 in pyroptosis-sensitive macrophages resulted in higher parasite replication and protection from cell death. Reciprocally, overexpression of the NLRP1 variant from Toxoplasma-sensitive macrophages in pyroptosis-resistant cells led to sensitization of these resistant macrophages. Our findings reveal Toxoplasma as a novel activator of the NLRP1 inflammasome in rat macrophages.

  6. Consideration of the Development of the Gastrointestinal Tract in the Choice of Species for Regulatory Juvenile Studies.

    Science.gov (United States)

    Downes, Noel John

    2018-01-15

    Although the rat is close to being the automatic choice for regulatory juvenile toxicity studies, there are several shortcomings in this model. Choosing a species should take into serious consideration the importance of gastrointestinal tract development in the period before weaning as this may have a major effect on exposure. A comparison of the anatomical changes in the stomach and small intestine of mini-pig and rat show that the mini-pig is a far closer model for man than is the rat, although there are a few unusual aspects of small intestinal development in the mini-pig. Considerations of the development of the gastrointestinal tract and choice of species have the potential to affect safety assessment and should be a prime consideration when planning an investigation. Birth Defects Research 110:56-62, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Species-dependent adaptation of the cardiac Na+/K+ pump kinetics to the intracellular Na+ concentration.

    Science.gov (United States)

    Lewalle, Alexandre; Niederer, Steven A; Smith, Nicolas P

    2014-12-15

    The Na(+)/K(+) ATPase (NKA) plays a critical role in maintaining ionic homeostasis and dynamic function in cardiac myocytes, within both the in vivo cell and in silico models. Physiological conditions differ significantly between mammalian species. However, most existing formulations of NKA used to simulate cardiac function in computational models are derived from a broad range of experimental sources spanning many animal species. The resultant inability of these models to discern species-specific features is a significant obstacle to achieving a detailed quantitative and comparative understanding of physiological behaviour in different biological contexts. Here we present a framework for characterising the steady-state NKA current using a biophysical mechanistic model specifically designed to provide a mechanistic explanation of the NKA flux supported by self-consistent species-specific data. We thus compared NKA kinetics specific to guinea- pig and rat ventricular myocytes. We observe that the apparent binding affinity for sodium in the rat is significantly lower, whereas the overall pump cycle rate is doubled, in comparison to the guinea pig. This sensitivity of NKA to its regulatory substrates compensates for the differences in Na(+) concentrations between the cell types. NKA is thereby maintained within its dynamic range over a wide range of pacing frequencies in these two species, despite significant disparities in sodium concentration. Hence, by replacing a conventional generic NKA model with our rat-specific NKA formula into a whole-cell simulation, we have, for the first time, been able to accurately reproduce the action potential duration and the steady-state sodium concentration as functions of pacing frequency. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  8. The Rat Grimace Scale: A partially automated method for quantifying pain in the laboratory rat via facial expressions

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    Zhan Shu

    2011-07-01

    Full Text Available Abstract We recently demonstrated the utility of quantifying spontaneous pain in mice via the blinded coding of facial expressions. As the majority of preclinical pain research is in fact performed in the laboratory rat, we attempted to modify the scale for use in this species. We present herein the Rat Grimace Scale, and show its reliability, accuracy, and ability to quantify the time course of spontaneous pain in the intraplantar complete Freund's adjuvant, intraarticular kaolin-carrageenan, and laparotomy (post-operative pain assays. The scale's ability to demonstrate the dose-dependent analgesic efficacy of morphine is also shown. In addition, we have developed software, Rodent Face Finder®, which successfully automates the most labor-intensive step in the process. Given the known mechanistic dissociations between spontaneous and evoked pain, and the primacy of the former as a clinical problem, we believe that widespread adoption of spontaneous pain measures such as the Rat Grimace Scale might lead to more successful translation of basic science findings into clinical application.

  9. Morphological divergence of breeders and helpers in wild Damaraland mole-rat societies.

    Science.gov (United States)

    Young, Andrew J; Bennett, Nigel C

    2010-11-01

    The specialization of body shape to an individual's role within society represents a pinnacle of social evolution. Although commonplace among social insects, divergence in the body shapes of breeders and helpers has to date been documented in just one social vertebrate, the naked mole-rat, Heterocephalus glaber; an extraordinary species in which large colony size and frequent inbreeding may have favored the evolution of such specialization. Here, we present new evidence of morphological divergence between breeders and helpers in the Damaraland mole-rat, Fukomys damarensis; a much less socially extreme species that reflects an independent evolutionary origin of sociality. Using longitudinal data from wild populations, we show that dominant female Damaraland mole-rats, like many social insect queens, have a significantly more elongate body shape than subordinates. This difference arises not from a pre-existing difference in the body shapes of subordinates that do, and those that do not, become dominant, but from a modification to the growth trajectory of subordinates on dominance acquisition. Our findings reveal a wider role for morphological divergence within vertebrate societies and, as Damaraland mole-rats neither live in unusually large groups nor inbreed, suggest that circumstances favoring the evolution of such specializations may be more widespread among vertebrates than previously supposed. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

  10. Challenging the inbreeding hypothesis in a eusocial mammal: population genetics of the naked mole-rat, Heterocephalus glaber.

    Science.gov (United States)

    Ingram, Colleen M; Troendle, Nicholas J; Gill, Clare A; Braude, Stanton; Honeycutt, Rodney L

    2015-10-01

    The role of genetic relatedness in the evolution of eusociality has been the topic of much debate, especially when contrasting eusocial insects with vertebrates displaying reproductive altruism. The naked mole-rat, Heterocephalus glaber, was the first described eusocial mammal. Although this discovery was based on an ecological constraints model of eusocial evolution, early genetic studies reported high levels of relatedness in naked mole-rats, providing a compelling argument that low dispersal rates and consanguineous mating (inbreeding as a mating system) are the driving forces for the evolution of this eusocial species. One caveat to accepting this long-held view is that the original genetic studies were based on limited sampling from the species' geographic distribution. A growing body of evidence supports a contrary view, with the original samples not representative of the species-rather reflecting a single founder event, establishing a small population south of the Athi River. Our study is the first to address these competing hypotheses by examining patterns of molecular variation in colonies sampled from north and south of the Athi and Tana rivers, which based on our results, serve to isolate genetically distinct populations of naked mole-rats. Although colonies south of the Athi River share a single mtDNA haplotype and are fixed at most microsatellite loci, populations north of the Athi River are considerably more variable. Our findings support the position that the low variation observed in naked mole-rat populations south of the Athi River reflects a founder event, rather than a consequence of this species' unusual mating system. © 2015 John Wiley & Sons Ltd.

  11. Genomic instability in rat: Breakpoints induced by ionising radiation and interstitial telomeric-like sequences

    International Nuclear Information System (INIS)

    Camats, Nuria; Ruiz-Herrera, Aurora; Parrilla, Juan Jose; Acien, Maribel; Paya, Pilar; Giulotto, Elena; Egozcue, Josep; Garcia, Francisca; Garcia, Montserrat

    2006-01-01

    The Norwegian rat (Rattus norvegicus) is the most widely studied experimental species in biomedical research although little is known about its chromosomal structure. The characterisation of possible unstable regions of the karyotype of this species would contribute to the better understanding of its genomic architecture. The cytogenetic effects of ionising radiation have been widely used for the study of genomic instability, and the importance of interstitial telomeric-like sequences (ITSs) in instability of the genome has also been reported in previous studies in vertebrates. In order to describe the unstable chromosomal regions of R. norvegicus, the distribution of breakpoints induced by X-irradiation and ITSs in its karyotype were analysed in this work. For the X-irradiation analysis, 52 foetuses (from 14 irradiated rats) were studied, 4803 metaphases were analysed, and a total of 456 breakpoints induced by X-rays were detected, located in 114 chromosomal bands, with 25 of them significantly affected by X-irradiation (hot spots). For the analysis of ITSs, three foetuses (from three rats) were studied, 305 metaphases were analysed and 121 ITSs were detected, widely distributed in the karyotype of this species. Seventy-six percent of all hot spots analysed in this study were co-localised with ITSs

  12. Genomic instability in rat: Breakpoints induced by ionising radiation and interstitial telomeric-like sequences

    Energy Technology Data Exchange (ETDEWEB)

    Camats, Nuria [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Ruiz-Herrera, Aurora [Departament de Biologia Cel.lular, Fisiologia i Immunologia Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, Juan Jose [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, Ctra, Madrid-Cartagena, s/n, El Palmar, 30120 Murcia (Spain); Acien, Maribel [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, Ctra, Madrid-Cartagena, s/n, El Palmar, 30120 Murcia (Spain); Paya, Pilar [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, Ctra, Madrid-Cartagena, s/n, El Palmar, 30120 Murcia (Spain); Giulotto, Elena [Dipartimento di Genetica e Microbiologia Adriano Buzzati Traverso, Universita degli Studi di Pavia, 27100 Pavia (Italy); Egozcue, Josep [Departament de Biologia Cel.lular, Fisiologia i Immunologia Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Francisca [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Montserrat [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain) and Departament de Biologia Cellular, Fisiologia i Immunologia Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)]. E-mail: Montserrat.Garcia.Caldes@uab.es

    2006-03-20

    The Norwegian rat (Rattus norvegicus) is the most widely studied experimental species in biomedical research although little is known about its chromosomal structure. The characterisation of possible unstable regions of the karyotype of this species would contribute to the better understanding of its genomic architecture. The cytogenetic effects of ionising radiation have been widely used for the study of genomic instability, and the importance of interstitial telomeric-like sequences (ITSs) in instability of the genome has also been reported in previous studies in vertebrates. In order to describe the unstable chromosomal regions of R. norvegicus, the distribution of breakpoints induced by X-irradiation and ITSs in its karyotype were analysed in this work. For the X-irradiation analysis, 52 foetuses (from 14 irradiated rats) were studied, 4803 metaphases were analysed, and a total of 456 breakpoints induced by X-rays were detected, located in 114 chromosomal bands, with 25 of them significantly affected by X-irradiation (hot spots). For the analysis of ITSs, three foetuses (from three rats) were studied, 305 metaphases were analysed and 121 ITSs were detected, widely distributed in the karyotype of this species. Seventy-six percent of all hot spots analysed in this study were co-localised with ITSs.

  13. The effect of dietary fat on the molecular species of lecithin from rat liver

    NARCIS (Netherlands)

    Golde, L.M.G. van; Deenen, L.L.M. van

    1966-01-01

    1. 1. Lecithins from the liver of rats maintained on diets devoid of essential fatty acids or supplemented with coconut oil or corn oil revealed significant differences in fatty acid composition, whilst monomolecular films of these lecithin samples exhibited only limited differences in force-area

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

    Science.gov (United States)

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

    2016-07-01

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

  15. The Presence Of Rat And House Sanitation Associated With Leptospira sp. Bacterial Infection In Rats (A Cross Sectional Study In Semarang, Central Java Province, Indonesia

    Directory of Open Access Journals (Sweden)

    Setiyani Endang

    2018-01-01

    Full Text Available The Gajah Mungkur sub-district in Semarang, Indonesia had highest leptospirosis cases (reported in human with seven infected and one dead in 2015. The purpose of this study was to analyze the association between house sanitation and density of rats with Leptospira sp. infection in rats. The study design was cross sectional observational analytic. The number of 308 trapswere placed in study sites over three consecutive nights afterwards. Every houses were placed with four traps, inside and outside. Trapped rats were anesthetized with atropine dose from 0.02 to 0.05 mg/kg body weight of rats continued with Ketamine HCL dose of 50-100 mg/kg body weight of rats by injecting in the thick thigh muscle of it. After that, identification of rats by species and gender then continues with surgery in which a kidney sample was taken to confirm the presence of bacteria Leptospirasp using PCR techniques. The trap installed in 77 houses which later had further observation on house sanitation which includes the existence of a pile of used goods, food storage, garbage can, and the presence of the ceiling, windows and other ventilation.Data was analyzed using distribution frequency and bivariate chi-square test. We had 100 rats captured with live traps as the samples.The proportion of Rattusnorvegicuswas 27% (14.8% positive Leptospira sp.infection and Rattustanezumi 73% (11%positive Leptospira sp.infection. The proportion of male and female rats were almost equal. The statistic test result was significant between the density of rats (p = 0.0001, OR 12.833, 95%CI: 1.565-105.261 and sex of rats (p = 0.019, OR 0.095, 95%CI: 0.012–0.769 with Leptospira sp. infection in rats. The number of rats may increase the infection of Leptospirasp., especially female rats and poor condition of house sanitation. It is recommended to improve house sanitation and regularly trapping rats.

  16. The Presence Of Rat And House Sanitation Associated With Leptospira sp. Bacterial Infection In Rats (A Cross Sectional Study In Semarang, Central Java Province, Indonesia)

    Science.gov (United States)

    Setiyani, Endang; Martini, Martini; Saraswati, Lintang Dian

    2018-02-01

    The Gajah Mungkur sub-district in Semarang, Indonesia had highest leptospirosis cases (reported in human with seven infected and one dead) in 2015. The purpose of this study was to analyze the association between house sanitation and density of rats with Leptospira sp. infection in rats. The study design was cross sectional observational analytic. The number of 308 trapswere placed in study sites over three consecutive nights afterwards. Every houses were placed with four traps, inside and outside. Trapped rats were anesthetized with atropine dose from 0.02 to 0.05 mg/kg body weight of rats continued with Ketamine HCL dose of 50-100 mg/kg body weight of rats by injecting in the thick thigh muscle of it. After that, identification of rats by species and gender then continues with surgery in which a kidney sample was taken to confirm the presence of bacteria Leptospirasp using PCR techniques. The trap installed in 77 houses which later had further observation on house sanitation which includes the existence of a pile of used goods, food storage, garbage can, and the presence of the ceiling, windows and other ventilation.Data was analyzed using distribution frequency and bivariate chi-square test. We had 100 rats captured with live traps as the samples.The proportion of Rattusnorvegicuswas 27% (14.8% positive Leptospira sp.infection) and Rattustanezumi 73% (11%positive Leptospira sp.infection). The proportion of male and female rats were almost equal. The statistic test result was significant between the density of rats (p = 0.0001, OR 12.833, 95%CI: 1.565-105.261) and sex of rats (p = 0.019, OR 0.095, 95%CI: 0.012-0.769) with Leptospira sp. infection in rats. The number of rats may increase the infection of Leptospirasp., especially female rats and poor condition of house sanitation. It is recommended to improve house sanitation and regularly trapping rats.

  17. Spatial modeling of rat bites and prediction of rat infestation in Peshawar valley using binomial kriging with logistic regression.

    Science.gov (United States)

    Ali, Asad; Zaidi, Farrah; Fatima, Syeda Hira; Adnan, Muhammad; Ullah, Saleem

    2018-03-24

    In this study, we propose to develop a geostatistical computational framework to model the distribution of rat bite infestation of epidemic proportion in Peshawar valley, Pakistan. Two species Rattus norvegicus and Rattus rattus are suspected to spread the infestation. The framework combines strengths of maximum entropy algorithm and binomial kriging with logistic regression to spatially model the distribution of infestation and to determine the individual role of environmental predictors in modeling the distribution trends. Our results demonstrate the significance of a number of social and environmental factors in rat infestations such as (I) high human population density; (II) greater dispersal ability of rodents due to the availability of better connectivity routes such as roads, and (III) temperature and precipitation influencing rodent fecundity and life cycle.

  18. Revisiting the taxonomy of the Rattini tribe: a phylogeny-based delimitation of species boundaries

    Directory of Open Access Journals (Sweden)

    Waengsothorn Surachit

    2010-06-01

    Full Text Available Abstract Background Rodents are recognized as hosts for at least 60 zoonotic diseases and may represent a serious threat for human health. In the context of global environmental changes and increasing mobility of humans and animals, contacts between pathogens and potential animal hosts and vectors are modified, amplifying the risk of disease emergence. An accurate identification of each rodent at a specific level is needed in order to understand their implications in the transmission of diseases. Among the Muridae, the Rattini tribe encompasses 167 species inhabiting South East Asia, a hotspot of both biodiversity and emerging and re-emerging diseases. The region faces growing economical development that affects habitats, biodiversity and health. Rat species have been demonstrated as significant hosts of pathogens but are still difficult to recognize at a specific level using morphological criteria. DNA-barcoding methods appear as accurate tools for rat species identification but their use is hampered by the need of reliable identification of reference specimens. In this study, we explore and highlight the limits of the current taxonomy of the Rattini tribe. Results We used the DNA sequence information itself as the primary information source to establish group membership and estimate putative species boundaries. We sequenced two mitochondrial and one nuclear genes from 122 rat samples to perform phylogenetic reconstructions. The method of Pons and colleagues (2006 that determines, with no prior expectations, the locations of ancestral nodes defining putative species was then applied to our dataset. To give an appropriate name to each cluster recognized as a putative species, we reviewed information from the literature and obtained sequences from a museum holotype specimen following the ancient DNA criteria. Conclusions Using a recently developed methodology, this study succeeds in refining the taxonomy of one of the most difficult groups of

  19. Long term lung clearance and cellular retention of cadmium in rats and monkeys

    International Nuclear Information System (INIS)

    Oberdorster, G.; Cox, C.; Baggs, R.

    1987-01-01

    The paper describes experiments to determine the long term lung clearance and cellular retention of cadmium in rats and monkeys. The rats and monkeys were exposed to 109 Cd Cl 2 aerosols, and one monkey was exposed to 115 CdO particles. The thoracic activity of the respective Cd isotopes was measured with time after exposure, for both species. Accumulation of 109 Cd in the kidneys of the monkeys exposed to 109 Cd Cl 2 was also examined, and autoradiographs of lung sections of these monkeys were also prepared. The results showed that the cadmium accumulated differently in the lungs of the rats and primates. (U.K.)

  20. The sub-chronic toxicity of regular White Spirit in rats.

    Science.gov (United States)

    Carrillo, Juan-Carlos; Adenuga, M David; Mckee, Richard H

    2014-10-01

    Hydrocarbon solvents are mostly complex substances (UVCB) with carbon numbers in the range of approximately C5-C20. One of the most common types is a C9-C14 aliphatic solvent containing approximately 20% aromatics and commonly known as White Spirit in Europe and mineral spirits in the US. In previous repeated inhalation toxicity studies, White Spirit was reported to cause minimal systemic effects in most animal species with few effects other than male rat-specific kidney changes at levels up to approximately 2000mg/m(3). In the present study male and female rats were exposed to White Spirit vapors, 6h/day, 5days/week for 13weeks at levels of approximately 2000, 4000, or 8000mg/m(3) to assess the potential for effects at higher exposure levels. All of the rats survived the treatment period. In life observations were largely restricted to acute central nervous system (CNS) effects in the high exposure group. Terminal body weights of high exposure groups animals were significantly below control values. Statistically significant differences in the clinical and hematological observations were small and within normal physiological limits. Weights of some organs including liver, spleen and kidneys were elevated, but microscopic examination indicated that the only pathological effects were changes in the kidneys of the male rats, consistent with an α2u-globulin-mediated process, which is gender and species-specific and not relevant to humans. The overall no observed adverse effect level (NOAEC) was 4000mg/m(3). Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Immunoreactivity for thymosin beta 4 and thymosin beta 10 in the adult rat oro-gastro-intestinal tract

    Directory of Open Access Journals (Sweden)

    S. Nemolato

    2013-05-01

    Full Text Available Thymosin beta 4 (Tβ4 and thymosin beta 10 (Tβ10 are two members of the β-thymosin family, involved in multiple cellular activities in different organs in multiple animal species. Here we report the expression pattern of Tβ4 and Tβ10 in rat tissues, in the gut and in annexed glands. The two peptide were differently expressed: Tβ4 was absent in salivary glands whereas Tβ10 was expressed in parotid and in submandibular glands. Tβ4 was mildly expressed in the tongue and in the oesophagus, where Tβ10 was absent. A similar expression was found in the stomach, ileum and colon mucosa. In pancreas Tβ4 reactivity was restricted to the Langerhans islet cells; Tβ4 was also detected in the exocrine cells. Both peptide were not expressed in liver cells. When the rat expression pattern in rat organs was compared to reactivity for Tβ4 and Tβ10 in humans, marked differences were found. Our data clearly indicate a species-specific expression of Tβ4 and Tβ10, characterized by the actual unpredictability of the expression of these peptides in different cells and tissues. The common high expression of Tβ4 in mast cells, both in humans and in rats, represents one of the few similarities between these two species.

  2. Quantitative autoradiographic localization of cholecystokinin receptors in rat and guinea pig brain using sup 125 I-Bolton-Hunter-CCK8

    Energy Technology Data Exchange (ETDEWEB)

    Niehoff, D.L. (Abbott Laboratories, Abbott Park, IL (USA))

    1989-03-01

    The autoradiographic localization of receptors for the brain-gut peptide cholecystokinin (CCK) has shown differences in receptor distribution between rat and guinea pig brain. However the full anatomical extent of the differences has not been determined quantitatively. In the present study, {sup 125}I-Bolton-Hunter-CCK8 ({sup 125}I-BH-CCK8) was employed in a comparative quantitative autoradiographic analysis of the distribution of CCK receptors in these two species. The pharmacological profile of {sup 125}I-BH-CCK8 binding in guinea pig forebrain sections was comparable to those previously reported for rat and human. Statistically significant differences in receptor binding between rat and guinea pig occurred in olfactory bulb, caudate-putamen, amygdala, several cortical areas, ventromedial hypothalamus, cerebellum, and a number of midbrain and brainstem nuclei. The results of this study confirm the presence of extensive species-specific variation in the distribution of CCK receptors, suggesting possible differences in the physiological roles of this peptide in different mammalian species.

  3. Effect of mass of neptunium V in intestinal absorption in the monkey and the rat

    International Nuclear Information System (INIS)

    Metivier, H.; Masse, R.; Lafuma, J.

    1983-01-01

    The coefficient of gastrointestinal transfer of neptunium as pentavalent neptunyl nitrate was studied in rats and monkeys as a function of the ingested mass. In both species, the transfer coefficient ranged between 1.10 - 3 - 1.10 - 2 when the administered mass varied from 0.3 ng to 2 mg per kg. At low concentrations, the values obtained in the monkey are about twice as low as thoses obtained in the rat. Considering the strong urinary excretion, the amounts retained at the organ levels represent about 0.1% in the rat and 0.04% in the monkey for low concentrations. The values obtained are usually in good agreement with the few data published on the rat [fr

  4. Myocardial kinetics of hexakis (trimethylphosphite) technetium-99m (I) chloride (Tc-TMP) in rats, rabbits, dogs, cats and pigs

    International Nuclear Information System (INIS)

    Robbins, M.S.; Adams, M.D.

    1984-01-01

    Tc-TMP is readily taken up by the myocardium following intravenous administration to rats and dogs. In order to assess its potential as a myocardial perfusion imaging agent, the biodistribution and pharmacokinetics of Tc-TMP were evaluated following intravenous administration to rats, rabbits, dogs, cats and miniature pigs. Rats and rabbits were killed at several time points within a 24 hr period after treatment and tissue samples were assayed for radioactivity. In rats, estimated heart, liver and lung half-lives were 14.4 hr, 24 min and 40 min, respectively. In rabbits, 0.6% dose/g was observed in the heart at 30 min. Corresponding heart/blood, heart/liver and heart/lung ratios were 39.1, 10.7 and 5.1. Gamma camera imaging experiments were conducted in rabbits, dogs, cats and pigs over a 1-2 hr period following administration of Tc-TMP. All species exhibited myocardial uptake resulting in sustained visualization, although myocardial image intensity was less pronounced in the pig compared to the other species. Regions of interest were selected over the heart, liver and background, and time-activity curves were generated. Minimal myocardial clearance was observed in all species during the imaging time course. Hepatic activity was rapidly cleared in rabbits and pigs (t1/2 < 1.0 hr) resulting in improved heart/liver ratios at later time intervals. The myocardial accumulation and retention of Tc-TMP, demonstrated in five species, supports clinical evaluation as a myocardial imaging agent

  5. Central visual system of the naked mole-rat (Heterocephalus glaber).

    Science.gov (United States)

    Crish, Samuel D; Dengler-Crish, Christine M; Catania, Kenneth C

    2006-02-01

    Naked mole-rats are fossorial rodents native to eastern Africa that spend their lives in extensive subterranean burrows where visual cues are poor. Not surprisingly, they have a degenerated eye and optic nerve, suggesting they have poor visual abilities. However, little is known about their central visual system. To investigate the organization of their central visual system, we injected a neuronal tracer into the eyes of naked mole-rats and mice to compare the neural structures mediating vision. We found that the superior colliculus and lateral geniculate nucleus were severely atrophied in the naked mole-rat. The olivary pretectal nucleus was reduced but still retained its characteristic morphology, possibly indicating a role in light detection. In addition, the suprachiasmatic nucleus is well innervated and resembles the same structure in other rodents. The naked mole-rat appears to have selectively lost structures that mediate form vision while retaining structures needed for minimal entrainment of circadian rhythms. Similar results have been reported for other mole-rat species. Taken together, these data suggest that light detection may still play an important role in the lives of these "blind" animals: most likely for circadian entrainment or setting seasonal rhythms.

  6. Glucuronidation of deoxynivalenol (DON) by different animal species: identification of iso-DON glucuronides and iso-deepoxy-DON glucuronides as novel DON metabolites in pigs, rats, mice, and cows.

    Science.gov (United States)

    Schwartz-Zimmermann, Heidi E; Hametner, Christian; Nagl, Veronika; Fiby, Iris; Macheiner, Lukas; Winkler, Janine; Dänicke, Sven; Clark, Erica; Pestka, James J; Berthiller, Franz

    2017-12-01

    The Fusarium mycotoxin deoxynivalenol (DON) is a frequent contaminant of cereal-based food and feed. Mammals metabolize DON by conjugation to glucuronic acid (GlcAc), the extent and regioselectivity of which is species-dependent. So far, only DON-3-glucuronide (DON-3-GlcAc) and DON-15-GlcAc have been unequivocally identified as mammalian DON glucuronides, and DON-7-GlcAc has been proposed as further DON metabolite. In the present work, qualitative HPLC-MS/MS analysis of urine samples of animals treated with DON (rats: 2 mg/kg bw, single bolus, gavage; mice: 1 mg/kg bw, single i.p. injection; pigs: 74 µg/kg bw, single bolus, gavage; cows: 5.2 mg DON/kg dry mass, oral for 13 weeks) revealed additional DON and deepoxy-DON (DOM) glucuronides. To elucidate their structures, DON and DOM were incubated with human (HLM) and rat liver microsomes (RLM). Besides the expected DON/DOM-3- and 15-GlcAc, minor amounts of four DON- and four DOM glucuronides were formed. Isolation and enzymatic hydrolysis of four of these compounds yielded iso-DON and iso-DOM, the identities of which were eventually confirmed by NMR. Incubation of iso-DON and iso-DOM with RLM and HLM yielded two main glucuronides for each parent compound, which were isolated and identified as iso-DON/DOM-3-GlcAc and iso-DON/DOM-8-GlcAc by NMR. Iso-DON-3-GlcAc, most likely misidentified as DON-7-GlcAc in the literature, proved to be a major DON metabolite in rats and a minor metabolite in pigs. In addition, iso-DON-8-GlcAc turned out to be one of the major DON metabolites in mice. DOM-3-GlcAc was the dominant DON metabolite in urine of cows and an important DON metabolite in rat urine. Iso-DOM-3-GlcAc was detected in urine of DON-treated rats and cows. Finally, DON-8,15-hemiketal-8-glucuronide, a previously described by-product of DON-3-GlcAc production by RLM, was identified in urine of DON-exposed mice and rats. The discovery of several novel DON-derived glucuronides in animal urine requires adaptation of

  7. Radiation-induced PKC signaling system in cultured rat hepatocytes

    International Nuclear Information System (INIS)

    Nakajima, Tetsuo; Yukawa, Osami

    1998-01-01

    Radiation effects on living organisms are mainly caused through reactive oxygen species (ROS) on living cells. It is known that ROS damages various membranes and the bio membranes play an important role in cellular signal transduction pathways. The effects of radiation on cellular signal transduction pathways in cultured rat hepatocytes have been studied

  8. Immunological evaluation of Aeromonas infection in albino rats | El ...

    African Journals Online (AJOL)

    Aeromonas hydrophila is the most common bacterial species causing an acute self limiting diarrheal illness in mammals. Albino rats were categorized into treated and control groups. Treated groups were injected daily intraperitoneally with 0.2ml of bacterial suspension containing 6x106 cells/ml of 0.9% NaCl, while the ...

  9. The Effect of Size and Species on Lens Intracellular Hydrostatic Pressure

    Science.gov (United States)

    Gao, Junyuan; Sun, Xiurong; Moore, Leon C.; Brink, Peter R.; White, Thomas W.; Mathias, Richard T.

    2013-01-01

    Purpose. Previous experiments showed that mouse lenses have an intracellular hydrostatic pressure that varied from 335 mm Hg in central fibers to 0 mm Hg in surface cells. Model calculations predicted that in larger lenses, all else equal, pressure should increase as the lens radius squared. To test this prediction, lenses of different radii from different species were studied. Methods. All studies were done in intact lenses. Intracellular hydrostatic pressures were measured with a microelectrode-manometer–based system. Membrane conductances were measured by frequency domain impedance analysis. Intracellular Na+ concentrations were measured by injecting the Na+-sensitive dye sodium-binding benzofuran isophthalate. Results. Intracellular hydrostatic pressures were measured in lenses from mice, rats, rabbits, and dogs with radii (cm) 0.11, 0.22, 0.49, and 0.57, respectively. In each species, pressure varied from 335 ± 6 mm Hg in central fiber cells to 0 mm Hg in surface cells. Further characterization of transport in lenses from mice and rats showed that the density of fiber cell gap junction channels was approximately the same, intracellular Na+ concentrations varied from 17 mM in central fiber cells to 7 mM in surface cells, and intracellular voltages varied from −45 mV in central fiber cells to −60 mV in surface cells. Fiber cell membrane conductance was a factor of 2.7 times larger in mouse than in rat lenses. Conclusions. Intracellular hydrostatic pressure is an important physiological parameter that is regulated in lenses from these different species. The most likely mechanism of regulation is to reduce the density of open Na+-leak channels in fiber cells of larger lenses. PMID:23211824

  10. Plasticity and constraints on social evolution in African mole-rats: ultimate and proximate factors.

    Science.gov (United States)

    Faulkes, Chris G; Bennett, Nigel C

    2013-05-19

    Here, we review comparative studies of African mole-rats (family Bathyergidae) to explain how constraints acting at the ultimate (environmental) and proximate (organismal) levels have led to convergent gains and losses of sociality within this extensive adaptive radiation of subterranean rodents endemic to sub-Saharan Africa. At the ultimate level, living in environments that range from mesic through to arid has led to both variation and flexibility in social organization among species, culminating in the pinnacle of social evolution in the eusocial naked and Damaraland mole-rats (Heterocephalus glaber and Fukomys damarensis). The common mole-rat (Cryptomys hottentotus) provides a model example of how plasticity in social traits exists within a single species inhabiting areas with different ecological constraint. At the proximate level, reproductive strategies and cooperative breeding may be constrained by the correlated evolution of a suite of traits including physiological suppression of reproduction, the development of physiological and morphological castes, and the mode of ovulatory control and seasonality in breeding. Furthermore, recent neurobiological advances indicate that differential patterns of neurotransmitter expression within the forebrain may underpin (and limit) either a solitary or group living/cooperative lifestyle not only in mole-rats, but also more widely among disparate mammalian taxa.

  11. Species dependence of [64Cu]Cu-Bis(thiosemicarbazone) radiopharmaceutical binding to serum albumins

    International Nuclear Information System (INIS)

    Basken, Nathan E.; Mathias, Carla J.; Lipka, Alexander E.; Green, Mark A.

    2008-01-01

    Introduction: Interactions of three copper(II) bis(thiosemicarbazone) positron emission tomography radiopharmaceuticals with human serum albumin, and the serum albumins of four additional mammalian species, were evaluated. Methods: 64 Cu-labeled diacetyl bis(N 4 -methylthiosemicarbazonato)copper(II) (Cu-ATSM), pyruvaldehyde bis(N 4 -methylthiosemicarbazonato)copper(II) (Cu-PTSM) and ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) were synthesized and their binding to human, canine, rat, baboon and porcine serum albumins quantified by ultrafiltration. Protein binding was also measured for each tracer in human, porcine, rat and mouse serum. Results: The interaction of these neutral, lipophilic copper chelates with serum albumin is highly compound- and species-dependent. Cu-PTSM and Cu-ATSM exhibit particularly high affinity for human serum albumin (HSA), while the albumin binding of Cu-ETS is relatively insensitive to species. At HSA concentrations of 40 mg/ml, '% free' (non-albumin-bound) levels of radiopharmaceutical were 4.0±0.1%, 5.3±0.2% and 38.6±0.8% for Cu-PTSM, Cu-ATSM and Cu-ETS, respectively. Conclusions: Species-dependent variations in radiopharmaceutical binding to serum albumin may need to be considered when using animal models to predict the distribution and kinetics of these compounds in humans

  12. The Naked Mole Rat Genome Resource: facilitating analyses of cancer and longevity-related adaptations.

    Science.gov (United States)

    Keane, Michael; Craig, Thomas; Alföldi, Jessica; Berlin, Aaron M; Johnson, Jeremy; Seluanov, Andrei; Gorbunova, Vera; Di Palma, Federica; Lindblad-Toh, Kerstin; Church, George M; de Magalhães, João Pedro

    2014-12-15

    The naked mole rat (Heterocephalus glaber) is an exceptionally long-lived and cancer-resistant rodent native to East Africa. Although its genome was previously sequenced, here we report a new assembly sequenced by us with substantially higher N50 values for scaffolds and contigs. We analyzed the annotation of this new improved assembly and identified candidate genomic adaptations which may have contributed to the evolution of the naked mole rat's extraordinary traits, including in regions of p53, and the hyaluronan receptors CD44 and HMMR (RHAMM). Furthermore, we developed a freely available web portal, the Naked Mole Rat Genome Resource (http://www.naked-mole-rat.org), featuring the data and results of our analysis, to assist researchers interested in the genome and genes of the naked mole rat, and also to facilitate further studies on this fascinating species. © The Author 2014. Published by Oxford University Press.

  13. Andrographis paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats.

    Directory of Open Access Journals (Sweden)

    Daleya Abdulaziz Bardi

    Full Text Available This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg or ELAP (250 or 500 mg/kg. Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson's Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed

  14. Andrographis paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats.

    Science.gov (United States)

    Abdulaziz Bardi, Daleya; Halabi, Mohammed Farouq; Hassandarvish, Pouya; Rouhollahi, Elham; Paydar, Mohammadjavad; Moghadamtousi, Soheil Zorofchian; Al-Wajeeh, Nahla Saeed; Ablat, Abdulwali; Abdullah, Nor Azizan; Abdulla, Mahmood Ameen

    2014-01-01

    This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP) on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control) or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis) three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg) or ELAP (250 or 500 mg/kg). Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson's Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed to result from

  15. Comments on the rat lung as a human surrogate in inhalation studies

    International Nuclear Information System (INIS)

    Koblinger, L.

    1988-01-01

    The laboratory rat is often used as a surrogate to estimate the hazard to human health following inhalation exposure to ambient aerosols. Extrapolation of rat deposition data to humans depends, however, on the similarities and differences between the morphometric structures of the two airway systems. The main structural difference between the lungs of the two species, aside from dimensions per se, is their respective airway branching pattern : while the human lung is a rather symmetrically, dichotomously dividing system, the rat network is a more monopodial branching structure. In our stochastic modelling approach to defining suitable morphologies for human and rat lung, we utilise measured morphometric dimensions as the data base upon which a rigorous statistical analysis is performed, instead of forcing them into a formalised, average pathway scheme. This stochastic approach allows us, therefore, to account for structural irregularities, such as asymmetric branching, monopodial structure, and inter and intra-subject variability

  16. Texas Red transport across rat and dogfish shark (Squalus acanthias) choroid plexus.

    Science.gov (United States)

    Reichel, Valeska; Miller, David S; Fricker, Gert

    2008-10-01

    Confocal microscopy and image analysis were used to compare driving forces, specificity, and regulation of transport of the fluorescent organic anion, Texas Red (sulforhodamine 101 free acid; TR), in lateral choroid plexus (CP) isolated from rat and an evolutionarily ancient vertebrate, dogfish shark (Squalus acanthias). CP from both species exhibited concentrative, specific, and metabolism-dependent TR transport from bath to subepithelial/vascular space; at steady state, TR accumulation in vascular/subepithelial space was substantially higher than in epithelial cells. In rat CP, steady-state TR accumulation in subepithelial/vascular spaces was reduced by Na(+)-replacement, but was not affected by a 10-fold increase in buffer K(+). In shark CP, Na(+)-replacement did not alter TR accumulation in either tissue compartment; subepithelial/vascular space levels of TR were reduced in high-K(+) medium. In both species, steady-state TR accumulation was not affected by p-aminohippurate or leukotriene C4, suggesting that neither organic anion transporters (SLC22A family) nor multidrug resistance-associated proteins (ABCC family) contributed. In rat CP, digoxin was without effect, indicating that organic anion transporting polypeptide isoform 2 was not involved. Several organic anions reduced cellular and subepithelial/vascular space TR accumulation in both tissues, including estrone sulfate, taurocholate, and the Mrp1 inhibitor MK571. In rat CP, TR accumulation in subepithelial/vascular spaces increased with PKA activation (forskolin), but was not affected by PKC activation (phorbol ester). In shark, neither PKA nor PKC activation specifically affected TR transport. Thus, rat and dogfish shark CP transport TR but do so using different basic mechanisms that respond to different regulatory signals.

  17. Optimizing hyaluronidase dose and plasmid DNA delivery greatly improves gene electrotransfer efficiency in rat skeletal muscle

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Vedel, Kenneth; Needham Andersen, Josefine

    2015-01-01

    Transfection of rat skeletal muscle in vivo is a widely used research model. However, gene electrotransfer protocols have been developed for mice and yield variable results in rats. We investigated whether changes in hyaluronidase pre-treatment and plasmid DNA delivery can improve transfection...... with a homogenous distribution. We also show that transfection was stable over five weeks of regular exercise or inactivity. Our findings show that species-specific plasmid DNA delivery and hyaluronidase pre-treatment greatly improves transfection efficiency in rat skeletal muscle....... efficiency in rat skeletal muscle. We found that pre-treating the muscle with a hyaluronidase dose suitable for rats (0.56. U/g b.w.) prior to plasmid DNA injection increased transfection efficiency by >200% whereas timing of the pre-treatment did not affect efficiency. Uniformly distributing plasmid DNA...

  18. A cytosolic protein factor from the naked mole-rat activates proteasomes of other species and protects these from inhibition

    Science.gov (United States)

    Rodriguez, Karl A.; Osmulski, Pawel A.; Pierce, Anson; Weintraub, Susan T.; Gaczynska, Maria; Buffenstein, Rochelle

    2015-01-01

    The naked mole-rat maintains robust proteostasis and high levels of proteasome-mediated proteolysis for most of its exceptional (~31y) life span. Here, we report that the highly active proteasome from the naked mole-rat liver resists attenuation by a diverse suite of proteasome-specific small molecule inhibitors. Moreover, mouse, human, and yeast proteasomes exposed to the proteasome-depleted, naked mole-rat cytosolic fractions, recapitulate the observed inhibition resistance, and mammalian proteasomes also show increased activity. Gel filtration coupled with mass spectrometry and atomic force microscopy indicates that these traits are supported by a protein factor that resides in the cytosol. This factor interacts with the proteasome and modulates its activity. Although HSP72 and HSP40 (Hdj1) are among the constituents of this factor, the observed phenomenon, such as increasing peptidase activity and protecting against inhibition cannot be reconciled with any known chaperone functions. This novel function may contribute to the exceptional protein homeostasis in the naked mole-rat and allow it to successfully defy aging. PMID:25018089

  19. Assessment of naked mole-rat distribution and threats in Eastern Ethiopia

    Directory of Open Access Journals (Sweden)

    Mengistu Wale

    2016-08-01

    Full Text Available Objective: To identify the distribution, threats and community attitudes towards naked molerat in Eastern Ethiopia. Methods: Data were collected through direct observation and interview and Chi-square at 95% confidence interval was used for significance test. Results: Naked mole-rat was identified in Fafan, City/Shinele, Eastern Hararghe Zone and Dire Dawa Administrative. The main threats of naked mole-rat identified were agricultural expansion, human killing and lack of awareness. From a total of 100 respondents, 92% of them considered naked mole-rat as pest as a result that 46% of them participated in direct killing. Literacy rate significantly affects the willingness to participate in the conservation of naked mole-rat (χ2 = 7.478, df = 1, P < 0.05. From a total of 26% respondents who did not show the willingness to participate in the conservation, 80.8% of them were illiterate. Conclusions: Naked mole-rat is fairly common in many of the study sites. However, rapid shift from nomadic life style to cultivation of crops and lacks of awareness were the main threats of naked mole-rat. Therefore, since there is no conservation action currently, further comprehensive study is required to design conservation plan for this species.

  20. RNA sequencing reveals differential expression of mitochondrial and oxidation reduction genes in the long-lived naked mole-rat when compared to mice.

    Science.gov (United States)

    Yu, Chuanfei; Li, Yang; Holmes, Andrew; Szafranski, Karol; Faulkes, Chris G; Coen, Clive W; Buffenstein, Rochelle; Platzer, Matthias; de Magalhães, João Pedro; Church, George M

    2011-01-01

    The naked mole-rat (Heterocephalus glaber) is a long-lived, cancer resistant rodent and there is a great interest in identifying the adaptations responsible for these and other of its unique traits. We employed RNA sequencing to compare liver gene expression profiles between naked mole-rats and wild-derived mice. Our results indicate that genes associated with oxidoreduction and mitochondria were expressed at higher relative levels in naked mole-rats. The largest effect is nearly 300-fold higher expression of epithelial cell adhesion molecule (Epcam), a tumour-associated protein. Also of interest are the protease inhibitor, alpha2-macroglobulin (A2m), and the mitochondrial complex II subunit Sdhc, both ageing-related genes found strongly over-expressed in the naked mole-rat. These results hint at possible candidates for specifying species differences in ageing and cancer, and in particular suggest complex alterations in mitochondrial and oxidation reduction pathways in the naked mole-rat. Our differential gene expression analysis obviated the need for a reference naked mole-rat genome by employing a combination of Illumina/Solexa and 454 platforms for transcriptome sequencing and assembling transcriptome contigs of the non-sequenced species. Overall, our work provides new research foci and methods for studying the naked mole-rat's fascinating characteristics.

  1. RNA sequencing reveals differential expression of mitochondrial and oxidation reduction genes in the long-lived naked mole-rat when compared to mice.

    Directory of Open Access Journals (Sweden)

    Chuanfei Yu

    Full Text Available The naked mole-rat (Heterocephalus glaber is a long-lived, cancer resistant rodent and there is a great interest in identifying the adaptations responsible for these and other of its unique traits. We employed RNA sequencing to compare liver gene expression profiles between naked mole-rats and wild-derived mice. Our results indicate that genes associated with oxidoreduction and mitochondria were expressed at higher relative levels in naked mole-rats. The largest effect is nearly 300-fold higher expression of epithelial cell adhesion molecule (Epcam, a tumour-associated protein. Also of interest are the protease inhibitor, alpha2-macroglobulin (A2m, and the mitochondrial complex II subunit Sdhc, both ageing-related genes found strongly over-expressed in the naked mole-rat. These results hint at possible candidates for specifying species differences in ageing and cancer, and in particular suggest complex alterations in mitochondrial and oxidation reduction pathways in the naked mole-rat. Our differential gene expression analysis obviated the need for a reference naked mole-rat genome by employing a combination of Illumina/Solexa and 454 platforms for transcriptome sequencing and assembling transcriptome contigs of the non-sequenced species. Overall, our work provides new research foci and methods for studying the naked mole-rat's fascinating characteristics.

  2. Protective effect of caffeine and a selective A2A receptor antagonist on impairment of memory and oxidative stress of aged rats.

    Science.gov (United States)

    Leite, Marlon Régis; Wilhelm, Ethel A; Jesse, Cristiano R; Brandão, Ricardo; Nogueira, Cristina Wayne

    2011-04-01

    In this study, the effects of caffeine (CAF) and SCH58261, a selective A(2A) receptor antagonist, on memory impairment and oxidative stress generated by aging in rats were investigated. Young and aged rats were treated daily per 10 days with CAF (30 mg/kg p.o.) or SCH58261 (0.5mg/kg, p.o.) or vehicle (1 ml/kg p.o.). Rats were trained and tested in a novel object recognition task. After the behavioral test, ascorbic acid and oxygen and nitrogen reactive species levels as well as Na(+)K(+) ATPase activity were determined in rat brain. The results demonstrated that the age-related memory deficit was reversed by treatment with CAF or SCH58261. Treatment with CAF or SCH58261 significantly normalized oxygen and nitrogen reactive species levels increased in brains of aged rats. Na(+)K(+) ATPase activity inhibited in brains of aged rats was also normalized by CAF or SCH58261 treatment. A decrease in basal ascorbic acid levels in brains of aged rats was not changed by CAF or SCH58261. These results demonstrated that CAF and SCH58261, modulators of adenosinergic receptors, were able to reverse age-associated memory impairment and to partially reduce oxidative stress. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Determination of human and Sprague-Dawley rat trimethylseleonium ion and total selenium urine concentrations from endogenous body selenium pool by neutron activation analysis

    International Nuclear Information System (INIS)

    Blotcky, A.J.; Claassen, J.P.; Rack, E.P.

    1992-01-01

    This study determined trimethylselenonium ion [TMSe,(CH 3 ) 3 Se + ] and total organic selenium cationic species urinary excretion values for healthy human subjects and Sprague-Dawley rats fed regular diets. The only source of TMSe was from the endogenous selenium body pool. Total selenium concentration in urine was determined by instrumental neutron activation analysis. TMSe and total selenium cationic species concentrations and percent of total selenium urine excretion were determined by chemical neutron activation analysis and coupled anion-cation exchange chromatography and anion-exchange chromatography, respectively. Within experimental error, mean values for TMSe and cationic species as percent selenium were comparable for both human subjects and Sprague-Dawley rats. This study suggested that TMSe excreated in urine by healthy human subjects and Sprague-Dawley rats fed a normal diet is not a minor but a general metabolite of selenium ingested in a normal diet. (author) 27 refs.; 1 fig.; 2 tabs

  4. Inhaled 239PuO2 and/or total-body gamma radiation: Early mortality and morbidity in rats and dogs

    International Nuclear Information System (INIS)

    Filipy, R.E.; Decker, J.R.; Lai, Y.L.

    1988-08-01

    Rats and beagle dogs were given doses of 60 Co gamma radiation and/or body burdens of 239 PuO 2 within lethal ranges in an experiment to determine and compare morbidity and mortality responses of both species within 1 year after exposure. Radiation-induced morbidity was assessed by measuring changes in body weights, hematologic parameters, and pulmonary-function parameters. Gamma radiation caused transient morbidity, reflected by immediately depressed blood cell concentrations and by long-term loss of body weight and diminished pulmonary function in animals of both species that survived the acute gamma radiation syndrome. Inhaled plutonium caused a loss of body weight and diminished pulmonary function in both species, but its only effect on blood cell concentrations was lymphocytopenia in dogs. Combined gamma irradiation and plutonium lung burdens were synergistic, in that animals receiving both radiation insults had higher morbidity and mortality rates than would be predicted based on the effect of either kind of radiation alone. Plutonium lung burdens enhanced the effect of gamma radiation in rats within the first 30 days of exposure, and gamma radiation enhanced the long-term effect of plutonium lung burdens in both species. Rats were less sensitive to both kinds of radiation, whether administered alone or in combination. 71 refs., 105 figs., 48 tabs

  5. Hepatoprotective potential of three sargassum species from Karachi coast against carbon tetrachloride and acetaminophen intoxication

    Directory of Open Access Journals (Sweden)

    Khan Hira

    2016-01-01

    Full Text Available Objective: To assess the hepatoprotective effect of ethanol extracts of Sargassum variegatum (S. variegatum, Sargassum tenerrimum (S. tenerrimum and Sargassum binderi occurring at Karachi coast against carbon tetrachloride (CCl4 and acetaminophen intoxication in rats. Methods: Sargassum species were collected at low tide from Buleji beach at Karachi coast. Effect of ethanol extracts of Sargassum spp., on lipid parameter, serum glucose and kidney function was examined. Liver damage in rats was induced by CCl4 or acetaminophen. Rats were administered with ethanol extracts of S. tenerrimum, S. variegatum and Sargassum binderi at 200 mg/kg body weight daily for 14 days separately. Hepatotoxicity was determined in terms of cardiac and liver enzymes and other biochemical parameters. Results: S. variegatum showed highest activity by reducing the elevated level of hepatic enzymes, bilirubin, serum glucose, triglyceride with restoration of cholesterol. Urea and creatinine concentrations were also significantly (P < 0.05 reduced as compared to acetaminophen intoxicated rats. S. tenerrimum and S. variegatum showed moderate activity against CCl4 hepatic toxicity. Conclusions: The protective role of S. variegatum against acetaminophen liver damage and its positive impact on disturbed lipid, glucose metabolism, kidney dysfunction and S. tenerrimum against CCl4 liver toxicity suggest that Sargassum species offer a non-chemical means for the treatment of toxicity mediated liver damage.

  6. Efficacy of maslinic acid and fenbendazole on muscle larvae of Trichinella zimbabwensis in laboratory rats.

    Science.gov (United States)

    Mukaratirwa, S; Gcanga, L; Kamau, J

    2016-01-01

    Trichinellosis is a zoonotic disease caused by nematode species of the genus Trichinella. Anthelmintics targeting the intestinal adults and muscle-dwelling larvae of Trichinella spp. have been tested, with limited success. This study was aimed at determining the efficacy of maslinic acid and fenbendazole on muscle larvae of Trichinella zimbabwensis in laboratory rats. Forty-two Sprague-Dawley rats, with an average weight of 270 g and 180 g for males and females respectively, were infected with T. zimbabwensis larvae. Infected rats were randomly assigned to three groups which were subjected to single treatments with each of maslinic acid, fenbendazole and a combination of both on day 25 post-infection (pi), and three groups which were subjected to double treatments with each of these drugs and a combination on days 25 and 32 pi. The untreated control group received a placebo. In single-treatment groups, the efficacy of each treatment, measured by rate of reduction in muscle larvae, was significant (P0.05). We conclude that the efficacy of maslinic acid against larval stages of T. zimbabwensis in rats was comparable to that of fenbendazole, with no side-effects observed, making maslinic acid a promising anthelmintic against larval stages of Trichinella species.

  7. Metabolism, Distribution, and Elimination of Mequindox in Pigs, Chickens, and Rats.

    Science.gov (United States)

    Huang, Lingli; Yin, Fujun; Pan, Yuanhu; Chen, Dongmei; Li, Juan; Wan, Dan; Liu, Zhenli; Yuan, Zonghui

    2015-11-11

    Mequindox (MEQ), a quinoxaline-N,N-dioxide antibacterial agent used to control bacterial enteritis in various food-producing animals, is a potential violative residue in food animal-derived products. The disposition and elimination of MEQ in rats, pigs, and chickens was comprehensively investigated to identify the marker residue and target tissue of MEQ in food animals for residue monitoring. Following a single oral administration, 62-71% of MEQ was rapidly excreted via urine and feces in all species within 24 h. Urinary excretion of radioactivity was 84 and 83.5% of the administered dose in rats and pigs, respectively. More than 92% of the administered dose was excreted in all species within 15 days. Radioactivity was found in nearly all tissues at the first 6 h after dosing, with the majority of radioactivity cleared within 4-6 days. The highest radioactivity and longest persisting time were found to be in the liver and kidney. Totals of 11, 12, and 7 metabolites were identified in rats, chickens, and pigs, respectively. No parent drug could be detected in any of the tissues of pigs and chickens. 3-Methyl-2-acetyl quinoxaline (M1), 3-methyl-2-(1-hydroxyethyl) quinoxaline-N4-monoxide (M4), and 3-methyl-2-(1-hydroxyethyl) quinoxaline-1,4-dioxide (M6) were the common and major metabolites of MEQ in all three species. Additionally, 3-methyl-2-(1-hydroxyethyl) quinoxaline (M5), 3-hydroxymethyl-2-ethanol quinoxaline-1,4-dioxide (M7), and 3-methyl-2-(1-hydroxyethyl) quinoxaline-N1-monoxide (M8) were the major metabolites of MEQ in rats, pigs, and chickens, respectively. M1 was designated to be the marker residue of MEQ in pigs and chickens. These results provide scientific data for the determination of marker residues and withdrawal time of MEQ in food animals and improve the understanding of the toxicity and disposition of MEQ in animals.

  8. Consideration of species differences in developing novel molecules as cognition enhancers.

    Science.gov (United States)

    Young, Jared W; Jentsch, J David; Bussey, Timothy J; Wallace, Tanya L; Hutcheson, Daniel M

    2013-11-01

    The NIH-funded CNTRICS initiative has coordinated efforts to promote the vertical translation of novel procognitive molecules from testing in mice, rats and non-human primates, to clinical efficacy in patients with schizophrenia. CNTRICS highlighted improving construct validation of tasks across species to increase the likelihood that the translation of a candidate molecule to humans will be successful. Other aspects of cross-species behaviors remain important however. This review describes cognitive tasks utilized across species, providing examples of differences and similarities of innate behavior between species, as well as convergent construct and predictive validity. Tests of attention, olfactory discrimination, reversal learning, and paired associate learning are discussed. Moreover, information on the practical implication of species differences in drug development research is also provided. The issues covered here will aid in task development and utilization across species as well as reinforcing the positive role preclinical research can have in developing procognitive treatments for psychiatric disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Worsening of memory deficit induced by energy-dense diet in a rat model of early-Alzheimer's disease is associated to neurotoxic Aβ species and independent of neuroinflammation.

    Science.gov (United States)

    Martino Adami, Pamela V; Galeano, Pablo; Wallinger, Marina L; Quijano, Celia; Rabossi, Alejandro; Pagano, Eleonora S; Olivar, Natividad; Reyes Toso, Carlos; Cardinali, Daniel; Brusco, Luis I; Do Carmo, Sonia; Radi, Rafael; Gevorkian, Goar; Castaño, Eduardo M; Cuello, A Claudio; Morelli, Laura

    2017-03-01

    Diet is a modifiable risk factor for Alzheimer's disease (AD), but the mechanisms linking alterations in peripheral metabolism and cognition remain unclear. Since it is especially difficult to study long-term effects of high-energy diet in individuals at risk for AD, we addressed this question by using the McGill-R-Thy1-APP transgenic rat model (Tg(+/-)) that mimics presymptomatic AD. Wild-type and Tg(+/-) rats were exposed during 6months to a standard diet or a Western diet (WD), high in saturated fat and sugar. Results from peripheral and hippocampal biochemical analysis and in situ respirometry showed that WD induced a metabolic syndrome and decreased presynaptic bioenergetic parameters without alterations in hippocampal insulin signaling or lipid composition. Cognitive tests, ELISA multiplex, Western blot, immunohistochemistry and RT-qPCR indicated that WD worsened cognition in Tg(+/-) rats, increased hippocampal levels of monomeric Aβ isoforms and oligomeric species, promoted deposits of N-Terminal pyroglutamate-Aβ (AβN3(pE)) in CA1 pyramidal neurons and interneurons, decreased transcript levels of genes involved in neuroprotective pathways such as Sirtuin-1 and increased nitrated proteins. Our results support the concept that in the presence of early Aβ pathology, diet-induced metabolic dysfunctions may contribute as a "second hit" to impair cognition. Noteworthy, such effect is not mediated by higher microglia activation or disruption of blood brain barrier. However, it may be attributed to increased amyloidogenic processing of amyloid precursor protein, generation of AβN3(pE) and dysregulation of pathways governed by Sirtuin-1. This evidence reinforces the implementation of prophylactic interventions in individuals at risk for AD. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. In vitro phagocytosis of several Candida berkhout species by murine leukocytes.

    Science.gov (United States)

    Fontenla de Petrino, S E; Bibas Bonet de Jorrat, M E; Sirena, A

    1985-03-01

    In vitro phagocytosis of thirteen Candida berkhout species by rat leukocytes was studied to assess a possible correlation between pathogenicity and phagocytosis Yeast-leukocyte suspensions were mixed up for 3 h and phagocytic index, germ-tube formation and leukocyte candidacidal activity were evaluated. Highest values for phagocytosis were reached in all cases at the end of the first hour. Leukocyte candidacidal activity was absent. Only C. albicans produced germ-tubes. The various phagocytosis indices were determined depending on the Candida species assayed. Under these conditions, the more pathogenic species presented the lower indices of phagocytosis. It is determined that the in vitro phagocytic index may bear a close relationship with the pathogenicity of the Candida berkhout.

  11. Left hemispheric dominance of vestibular processing indicates lateralization of cortical functions in rats.

    Science.gov (United States)

    Best, Christoph; Lange, Elena; Buchholz, Hans-Georg; Schreckenberger, Mathias; Reuss, Stefan; Dieterich, Marianne

    2014-11-01

    Lateralization of cortical functions such as speech dominance, handedness and processing of vestibular information are present not only in humans but also in ontogenetic older species, e.g. rats. In human functional imaging studies, the processing of vestibular information was found to be correlated with the hemispherical dominance as determined by the handedness. It is located mainly within the right hemisphere in right handers and within the left hemisphere in left handers. Since dominance of vestibular processing is unknown in animals, our aim was to study the lateralization of cortical processing in a functional imaging study applying small-animal positron emission tomography (microPET) and galvanic vestibular stimulation in an in vivo rat model. The cortical and subcortical network processing vestibular information could be demonstrated and correlated with data from other animal studies. By calculating a lateralization index as well as flipped region of interest analyses, we found that the vestibular processing in rats follows a strong left hemispheric dominance independent from the "handedness" of the animals. These findings support the idea of an early hemispheric specialization of vestibular cortical functions in ontogenetic older species.

  12. Membrane phospholipid composition may contribute to exceptional longevity of the naked mole-rat (Heterocephalus glaber): a comparative study using shotgun lipidomics.

    Science.gov (United States)

    Mitchell, Todd W; Buffenstein, Rochelle; Hulbert, A J

    2007-11-01

    Phospholipids containing highly polyunsaturated fatty acids are particularly prone to peroxidation and membrane composition may therefore influence longevity. Phospholipid molecules, in particular those containing docosahexaenoic acid (DHA), from the skeletal muscle, heart, liver and liver mitochondria were identified and quantified using mass-spectrometry shotgun lipidomics in two similar-sized rodents that show an approximately 9-fold difference in maximum lifespan. The naked mole rat is the longest-living rodent known with a maximum lifespan of >28 years. Total phospholipid distribution is similar in tissues of both species; DHA is only found in phosphatidylcholines (PC), phosphatidylethanolamines (PE) and phosphatidylserines (PS), and DHA is relatively more concentrated in PE than PC. Naked mole-rats have fewer molecular species of both PC and PE than do mice. DHA-containing phospholipids represent 27-57% of all phospholipids in mice but only 2-6% in naked mole-rats. Furthermore, while mice have small amounts of di-polyunsaturated PC and PE, these are lacking in naked mole-rats. Vinyl ether-linked phospholipids (plasmalogens) are higher in naked mole-rat tissues than in mice. The lower level of DHA-containing phospholipids suggests a lower susceptibility to peroxidative damage in membranes of naked mole-rats compared to mice. Whereas the high level of plasmalogens might enhance membrane antioxidant protection in naked mole-rats compared to mice. Both characteristics possibly contribute to the exceptional longevity of naked mole-rats and may indicate a special role for peroxisomes in this extended longevity.

  13. The influence of very low doses of N-nitrosodimethylamine (NDMA) on the apoptosis of rat neutrophils in vivo. The role of reactive oxygen species.

    Science.gov (United States)

    Jablonski, J; Jablonska, E; Chojnowski, M

    2001-08-13

    N-nitrosodimethylamine (NDMA) causes the apoptosis of neutrophils in vitro experiments. This compound also has the ability to stimulate neutrophils for the production of reactive oxygen species. It has been decided to examine more closely whether the apoptosis of neutrophils by NDMA is caused by the influence of the radicals produced by these cells and whether the stimulation to undergo apoptosis of neutrophils is caused by NDMA in either the original form or by its metabolites. The experiment was conducted on rats. The animals were administered a one-time dose of NDMA intragastrically, 1.5 mg/kg. The research was conducted 1,2,4,12 h consecutively following NDMA administration. The concentration of NDMA in blood was evaluated by means of the gas chromatography method. The neutrophils were isolated from blood by means of differential centrifugation. Respiratory burst was assessed in cells, by means of the cytochrome c reduction method. The percentage of cells revealing morphological properties of apoptosis was determined under the fluorescent microscope. It has been observed that the activation of the respiratory burst is caused mainly by non-metabolised NDMA. Probably the non-metabolised molecules of this compound also have a decisive role in the initiation of apoptosis of neutrophils. It can be assumed that the main factor responsible for the apoptosis of neutrophil rats following a one-time NDMA administration is the induction of respiratory burst in neutrophils by this compound.

  14. Species dependence of [{sup 64}Cu]Cu-Bis(thiosemicarbazone) radiopharmaceutical binding to serum albumins

    Energy Technology Data Exchange (ETDEWEB)

    Basken, Nathan E. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States)], E-mail: nbasken@purdue.edu; Mathias, Carla J. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States); Lipka, Alexander E. [Department of Statistics, Purdue University, West Lafayette, IN 47907 (United States); Green, Mark A. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States)], E-mail: magreen@purdue.edu

    2008-04-15

    Introduction: Interactions of three copper(II) bis(thiosemicarbazone) positron emission tomography radiopharmaceuticals with human serum albumin, and the serum albumins of four additional mammalian species, were evaluated. Methods: {sup 64}Cu-labeled diacetyl bis(N{sup 4}-methylthiosemicarbazonato)copper(II) (Cu-ATSM), pyruvaldehyde bis(N{sup 4}-methylthiosemicarbazonato)copper(II) (Cu-PTSM) and ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) were synthesized and their binding to human, canine, rat, baboon and porcine serum albumins quantified by ultrafiltration. Protein binding was also measured for each tracer in human, porcine, rat and mouse serum. Results: The interaction of these neutral, lipophilic copper chelates with serum albumin is highly compound- and species-dependent. Cu-PTSM and Cu-ATSM exhibit particularly high affinity for human serum albumin (HSA), while the albumin binding of Cu-ETS is relatively insensitive to species. At HSA concentrations of 40 mg/ml, '% free' (non-albumin-bound) levels of radiopharmaceutical were 4.0{+-}0.1%, 5.3{+-}0.2% and 38.6{+-}0.8% for Cu-PTSM, Cu-ATSM and Cu-ETS, respectively. Conclusions: Species-dependent variations in radiopharmaceutical binding to serum albumin may need to be considered when using animal models to predict the distribution and kinetics of these compounds in humans.

  15. Characterization of the nociceptin receptor (ORL-1) agonist, Ro64-6198, in tests of anxiety across multiple species.

    Science.gov (United States)

    Varty, G B; Hyde, L A; Hodgson, R A; Lu, S X; McCool, M F; Kazdoba, T M; Del Vecchio, R A; Guthrie, D H; Pond, A J; Grzelak, M E; Xu, X; Korfmacher, W A; Tulshian, D; Parker, E M; Higgins, G A

    2005-10-01

    Previous studies have demonstrated behaviors indicative of anxiolysis in rats pretreated with the nociceptin receptor (opioid receptor like-1, ORL-1) agonist, Ro64-6198. The aim of this study was to examine the effects of Ro64-6198 in anxiety models across three species: rat, guinea pig, and mouse. In addition, the receptor specificity of Ro64-6198 was studied, using the ORL-1 receptor antagonist, J-113397, and ORL-1 receptor knockout (KO) mice. Finally, neurological studies examined potential side effects of Ro64-6198 in the rat and mouse. Ro64-6198 (3-10 mg/kg) increased punished responding in a rat conditioned lick suppression test similarly to chlordiazepoxide (6 mg/kg). This effect of Ro64-6198 was attenuated by J-113397 (10 mg/kg), but not the mu opioid antagonist, naltrexone (3 mg/kg). In addition, Ro64-6198 (1-3 mg/kg) reduced isolation-induced vocalizations in rat and guinea pig pups. Ro64-6198 (3 mg/kg) increased the proportion of punished responding in a mouse Geller-Seifter test in wild-type (WT) but not ORL-1 KO mice, whereas diazepam (1-5.6 mg/kg) was effective in both genotypes. In rats, Ro64-6198 reduced locomotor activity (LMA) and body temperature and impaired rotarod, beam walking, and fixed-ratio (FR) performance at doses of 10-30 mg/kg, i.e., three to ten times higher than an anxiolytic dose. In WT mice, Ro64-6198 (3-10 mg/kg) reduced LMA and rotarod performance, body temperature, and FR responding, but these same measures were unaffected in ORL-1 KO mice. Haloperidol (0.3-3 mg/kg) reduced these measures to a similar extent in both genotypes. These studies confirm the potent, ORL-1 receptor-mediated, anxiolytic-like effects of Ro64-6198, extending the findings across three species. Ro64-6198 has target-based side effects, although the magnitude of these effects varies across species.

  16. IDENTIFICATION OF RATS AND SHREW IN ARGASOKA AND KUTABANJAR VILLAGE BANJARNEGARA SUB DISTRICT BANJARNEGARA DISTRICT 2014

    Directory of Open Access Journals (Sweden)

    Hendri Anggi Widayani

    2014-08-01

    Full Text Available ABSTRAKTikus (Ordo Rodentia merupakan hewan yang mempunyai peranan penting dalam kehidupan manusia baik bersifatmenguntungkan maupun merugikan. Spesies tikus mempunyai habitat masing-masing untuk berkembangbiak. Pemukimanmerupakan habitat tikus untuk memperoleh makanan. Tujuan penelitian untuk menggambarkan keberhasilan penangkapantikus dan mengidentifikasi tikus yang tertangkap di Kelurahan Argasoka dan Kutabanjarnegara. Metode penelitianmenggunakan survei dengan pendekatan cross sectional. Populasi adalah tikus yang berada di Kelurahan Argasoka danKelurahan Kutabanjarnegara. Sampel adalah tikus yang tertangkap menggunakan perangkap sebanyak 100 perangkapyang dipasang di lokasi penelitian selama 2 malam,dengan menggunakan umpan kelapa bakar dan ikan asin. Analisis datasecara deskriptif disajikan dalam bentuk narasi dan tabel distribusi frekuensi. Hasil penelitian menunjukkan keberhasilanpenangkapan tikus di Kelurahan Argasoka sebesar 10,5% dan di Kelurahan Kutabanjarnegara sebesar 6%. Tikus yangtertangkap 25 ekor Rattus tanezumi (75,76%, 1ekor R. tiomanicus (3,03%, dan 7 ekor Suncus murinus (21,21%. Tikus dancecurut berjenis kelamin jantan lebih banyak ditemukan (54,54 % daripada betina (45,45 %.Kata kunci: tikus, keberhasilan penangkapan, identifikasiABSTRACTRat is an animal that have important role to human being, even its profitable or adverse. This species have their own habitatto each depression. The community settlement is one of rat habitat to get food. The research purpose is to measure the trapsuccess of rat and to identify rat species in Argasoka and Kutabanjar Village, Banjarnegara. The research used surveymethod with cross sectional approach. Population were rats those lived in Argasoka and Kutabanjar Village. The samplewere rats those caught using single live traps in Argasoka and Kutabanjar Village, Banjarnegara. Rat trapping wasconducted for 2 nights using 100 single live traps with the roasted coconut and salted fish. Technical

  17. Protective effect of melatonin in the diabetic rat retina.

    Science.gov (United States)

    Mehrzadi, Saeed; Motevalian, Manijeh; Rezaei Kanavi, Mozhgan; Fatemi, Iman; Ghaznavi, Habib; Shahriari, Mansoor

    2018-03-01

    Diabetic retinopathy (DR) is one of the most common and serious microvascular complications of diabetes. The aim of this study was to evaluate the effects of melatonin (MEL) on retinal injury in diabetic rats. In this study, 21 rats were randomly divided into three groups: control, diabetic, and diabetic + MEL. Streptozotocin was used to induce diabetes at a dose of 50 mg/kg, i.p., and blood glucose was measured to choose the diabetic rats for the study. MEL (20 mg/kg) was given orally for 7 weeks in diabetic rats starting 1 week after induction of diabetes. After 8 weeks, the groups were compared in terms of mean scores of fluorescein leakage, using fluorescein angiography. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels were estimated in retina using commercially available assays. Structural changes in retinas were evaluated by light microscopy. Results showed that diabetes significantly increased the mean scores of fluorescein leakage, and MDA and ROS levels compared to control group. Treatment of the diabetic rats with MEL for 7 weeks prevented the alterations induced by diabetes in comparison with the diabetic control group.Based on these findings, it can be concluded that MEL might have beneficial effects in prevention of DR. © 2018 Société Française de Pharmacologie et de Thérapeutique.

  18. 239Pu and 241Am contamination of small vertebrates in NAEG study areas of NTS and TTR

    International Nuclear Information System (INIS)

    Moor, K.S.; Naele, S.R.; Bradley, W.G.

    1977-01-01

    Ecological studies of small vertebrates in three plutonium (Pu) contaminated study areas of Nevada Test Site began in Spring, 1972, and were expanded to include four areas of Tonopah Test Range in Fall, 1973. This report consists primarily of presentation and analysis of radioanalytical data on rodents and lizards from Area 11-C, Nevada Test Site. In addition, methodology and preliminary results of initial hematologic studies are presented. Dipodomys microps is a dominant rodent species in all study areas. Concentrations of 239 Pu and 241 Am in pelt, GI tract, and carcass of 74 resident D. microps from five study areas were determined. The only consistent trend evident was that carcass burdens were lower than pelt or GI tract burdens by a factor of 10 2 . Mean ratios of Pu/Am in tissue aliquots were variable, and many were significantly different than ratios in soil or vegetation samples

  19. Allopurinol does not decrease blood pressure or prevent the development of hypertension in the deoxycorticosterone acetate-salt rat model.

    Science.gov (United States)

    Szasz, Theodora; Linder, A Elizabeth; Davis, Robert P; Burnett, Robert; Fink, Gregory D; Watts, Stephanie W

    2010-12-01

    Reactive oxygen species play an important role in the pathogenesis of hypertension, disease in which reactive oxygen species levels and markers of oxidative stress are increased. Xanthine oxidase (XO) is a reactive oxygen species-producing enzyme the activity of which may increase during hypertension. Studies on XO inhibition effects on blood pressure have yielded controversial results. We hypothesized that XO inhibition would decrease blood pressure or attenuate the development of deoxycorticosterone acetate (DOCA)-salt hypertension. We administered the XO inhibitor, allopurinol (50 mg/kg per day, orally) or its vehicle to rats during the established or development stages of DOCA-salt hypertension. We validated XO inhibition by high-performance liquid chromatography measurements of XO metabolites in urine, serum, and tissues demonstrating a decrease in products, increase in substrates, and detection of the active metabolite of allopurinol, oxypurinol. We monitored blood pressure continuously through radiotelemetry and performed gross evaluations of target organs of hypertension. Allopurinol treatment did not impact the course of DOCA-salt hypertension regardless of the timing of administration. Aside from a significant decrease in pulse pressure in allopurinol-treated rats, no positive differences were observed between the allopurinol and the vehicle-treated rats. We conclude that XO does not play an important role in the development or maintenance of hypertension in the rat DOCA-salt hypertension model.

  20. Cyanidin-3-glucoside inhibits glutamate-induced Zn2+ signaling and neuronal cell death in cultured rat hippocampal neurons by inhibiting Ca2+-induced mitochondrial depolarization and formation of reactive oxygen species.

    Science.gov (United States)

    Yang, Ji Seon; Perveen, Shazia; Ha, Tae Joung; Kim, Seong Yun; Yoon, Shin Hee

    2015-05-05

    Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is a potent natural antioxidant. However, effects of C3G on glutamate-induced [Zn(2+)]i increase and neuronal cell death remain unknown. We studied the effects of C3G on glutamate-induced [Zn(2+)]i increase and cell death in cultured rat hippocampal neurons from embryonic day 17 maternal Sprague-Dawley rats using digital imaging methods for Zn(2+), Ca(2+), reactive oxygen species (ROS), mitochondrial membrane potential and a MTT assay for cell survival. Treatment with glutamate (100 µM) for 7 min induces reproducible [Zn(2+)]i increase at 35 min interval in cultured rat hippocampal neurons. The intracellular Zn(2+)-chelator TPEN markedly blocked glutamate-induced [Zn(2+)]i increase, but the extracellular Zn(2+) chelator CaEDTA did not affect glutamate-induced [Zn(2+)]i increase. C3G inhibited the glutamate-induced [Zn(2+)]i response in a concentration-dependent manner (IC50 of 14.1 ± 1.1 µg/ml). C3G also significantly inhibited glutamate-induced [Ca(2+)]i increase. Two antioxidants such as Trolox and DTT significantly inhibited the glutamate-induced [Zn(2+)]i response, but they did not affect the [Ca(2+)]i responses. C3G blocked glutamate-induced formation of ROS. Trolox and DTT also inhibited the formation of ROS. C3G significantly inhibited glutamate-induced mitochondrial depolarization. However, TPEN, Trolox and DTT did not affect the mitochondrial depolarization. C3G, Trolox and DTT attenuated glutamate-induced neuronal cell death in cultured rat hippocampal neurons, respectively. Taken together, all these results suggest that cyanidin-3-glucoside inhibits glutamate-induced [Zn(2+)]i increase through a release of Zn(2+) from intracellular sources in cultured rat hippocampal neurons by inhibiting Ca(2+)-induced mitochondrial depolarization and formation of ROS, which is involved in neuroprotection against glutamate-induced cell death. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Punica granatum L. Fruit Aqueous Extract Suppresses Reactive Oxygen Species-Mediated p53/p65/miR-145 Expressions followed by Elevated Levels of irs-1 in Alloxan-Diabetic Rats.

    Science.gov (United States)

    Gharib, Ehsan; Montasser Kouhsari, Shideh; Izad, Maryam

    2018-01-01

    Reactive oxygen species (ROS) is an apoptosis inducer in pancreatic β-cells that stimulates p53/p65 mediated microRNA (miR)-145 expression. Punica granatum L. (pomegranate) is an antioxidant fruit that attenuates ROS generation. This study examines the effects of pomegranate fruit aqueous extract (PGE) on the levels of ROS, p53, p65, miR-145, and its target insulin receptor substrate 1 (irs-1) mRNA in Alloxan-diabetic male Wistar rats. In this experimental study, diabetic rats received different doses of PGE. The effects of the PGE polyphenols were examined through a long-term PGE treatment period model, followed by an evaluation of the plasma and tissue contents of free fatty acids (FFAs), triglycerides (TG), and glycogen compared with diabetic controls (DC) and normal controls (NC). We used real-time polymerase chain reaction (PCR) to investigate the modulation of p53, p65, miR-145, and irs-1 expression levels. There was a noticeable reduction in fasting blood glucose (FBG) and ROS generation compared to DC. We observed marked decreases in p53, p65, miR-145 expression levels followed by an elevated level of irs-1, which contributed to improvement in insulin sensitivity. PGE administration downregulated miR-145 levels in Alloxan-diabetic Wistar rats by suppression of ROS-mediated p53 and p65 overexpression. Copyright© by Royan Institute. All rights reserved.

  2. Comparison of stem-spermatogonial renewal and mitotic activity in the #betta#-irratiated mouse and rat

    International Nuclear Information System (INIS)

    Erickson, B.H.; Hall, G.G.

    1983-01-01

    The Sprague-Dawley rat exceeds the CRF 1 mouse in number of isolated or purported stem cells per unit area of seminiferous tubule by a factor of 2.1, yet the mouse exceeds the rat in number of first-generation spermatogonia (A 1 ) per unit of tubule by a factor of 1.8. This difference could lead to an interspecies difference in irradiation response and help clarify the identity of spermatogonial stem cell. To test this thesis, mice and rats were irradiated with 600 R of 60 Co #betta#-radiation and killed at postirradiation intervals of 1-16 weeks. Both tubular whole mounts and cross sections were evaluated. The species did not differ in percent survival of isolated spermatogonia, but the mouse exceeded the rat in survival and/or production of A 1 or clonal spermatogonia by a factor of 5. By week 16 after irradiation, the mouse restis had regained 67% of its preirradiation weight, in contrast to the rat's 52%. Clonal renewal was in progress by the end of the 2 (mouse) and 3 (rat) weeks and was substantially complete by the 8 week. In both species the isolated population, however, diminished throughout the first 8 weeks and was renewed between 8 and 16 weeks. Clonal renewal was not accompanied by an increase in the number of isolated spermatogonial mitoses, but was accompanied by increases in the mitotis of pairs and clones and the apparent splitting of existing clones to form additional clones. Thus, the mouse's superiority in the rate and completeness of spermatogonial renewal was apparently due to the attributes of the undifferentiated A 1 spermatogonial clone. (orig.)

  3. A Physiologically Based Pharmacokinetic (PB/PK) Model for Multiple Exposure Routes of Soman in Multiple Species

    National Research Council Canada - National Science Library

    Sweeney, Richard E; Langenberg, Jan P; Maxwell, Donald M

    2006-01-01

    ...) levels of soman challenge in three species (rat, guinea pig, marmoset). Allometric formulae were used to compute the compartment volumes, blood flow rates, tidal volume and respiratory rate based upon total animal weight...

  4. Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats.

    Science.gov (United States)

    Vilaseca, Marina; García-Calderó, Héctor; Lafoz, Erica; Ruart, Maria; López-Sanjurjo, Cristina Isabel; Murphy, Michael P; Deulofeu, Ramon; Bosch, Jaume; Hernández-Gea, Virginia; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

    2017-07-01

    In cirrhosis, activated hepatic stellate cells (HSC) play a major role in increasing intrahepatic vascular resistance and developing portal hypertension. We have shown that cirrhotic livers have increased reactive oxygen species (ROS), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these ROS, our aim was to assess the effects of the oral mitochondria-targeted antioxidant mitoquinone on hepatic oxidative stress, HSC phenotype, liver fibrosis and portal hypertension. Ex vivo: Hepatic stellate cells phenotype was analysed in human precision-cut liver slices in response to mitoquinone or vehicle. In vitro: Mitochondrial oxidative stress was analysed in different cell type of livers from control and cirrhotic rats. HSC phenotype, proliferation and viability were assessed in LX2, and in primary human and rat HSC treated with mitoquinone or vehicle. In vivo: CCl 4 - and thioacetamide-cirrhotic rats were treated with mitoquinone (5 mg/kg/day) or the vehicle compound, DecylTPP, for 2 weeks, followed by measurement of oxidative stress, systemic and hepatic haemodynamic, liver fibrosis, HSC phenotype and liver inflammation. Mitoquinone deactivated human and rat HSC, decreased their proliferation but with no effects on viability. In CCl 4 -cirrhotic rats, mitoquinone decreased hepatic oxidative stress, improved HSC phenotype, reduced intrahepatic vascular resistance and diminished liver fibrosis. These effects were associated with a significant reduction in portal pressure without changes in arterial pressure. These results were further confirmed in the thioacetamide-cirrhotic model. We propose mitochondria-targeted antioxidants as a novel treatment approach against portal hypertension and cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Influence of fenofibrate treatment on triacylglycerides, diacylglycerides and fatty acids in fructose fed rats.

    Science.gov (United States)

    Kopf, Thomas; Schaefer, Hans-Ludwig; Troetzmueller, Martin; Koefeler, Harald; Broenstrup, Mark; Konovalova, Tatiana; Schmitz, Gerd

    2014-01-01

    Fenofibrate (FF) lowers plasma triglycerides via PPARα activation. Here, we analyzed lipidomic changes upon FF treatment of fructose fed rats. Three groups with 6 animals each were defined as control, fructose-fed and fructose-fed/FF treated. Male Wistar Unilever Rats were subjected to 10% fructose-feeding for 20 days. On day 14, fenofibrate treatment (100 mg/kg p.o.) was initiated and maintained for 7 days. Lipid species in serum were analyzed using mass spectrometry (ESI-MS/MS; LC-FT-MS, GC-MS) on days 0, 14 and 20 in all three groups. In addition, lipid levels in liver and intestine were determined. Short-chain TAGs increased in serum and liver upon fructose-feeding, while almost all TAG-species decreased under FF treatment. Long-chain unsaturated DAG-levels (36:1, 36:2, 36:4, 38:3, 38:4, 38:5) increased upon FF treatment in rat liver and decreased in rat serum. FAs, especially short-chain FAs (12:0, 14:0, 16:0) increased during fructose-challenge. VLDL secretion increased upon fructose-feeding and together with FA-levels decreased to control levels during FF treatment. Fructose challenge of de novo fatty acid synthesis through fatty acid synthase (FAS) may enhance the release of FAs ≤ 16:0 chain length, a process reversed by FF-mediated PPARα-activation.

  6. Influence of fenofibrate treatment on triacylglycerides, diacylglycerides and fatty acids in fructose fed rats.

    Directory of Open Access Journals (Sweden)

    Thomas Kopf

    Full Text Available Fenofibrate (FF lowers plasma triglycerides via PPARα activation. Here, we analyzed lipidomic changes upon FF treatment of fructose fed rats. Three groups with 6 animals each were defined as control, fructose-fed and fructose-fed/FF treated. Male Wistar Unilever Rats were subjected to 10% fructose-feeding for 20 days. On day 14, fenofibrate treatment (100 mg/kg p.o. was initiated and maintained for 7 days. Lipid species in serum were analyzed using mass spectrometry (ESI-MS/MS; LC-FT-MS, GC-MS on days 0, 14 and 20 in all three groups. In addition, lipid levels in liver and intestine were determined. Short-chain TAGs increased in serum and liver upon fructose-feeding, while almost all TAG-species decreased under FF treatment. Long-chain unsaturated DAG-levels (36:1, 36:2, 36:4, 38:3, 38:4, 38:5 increased upon FF treatment in rat liver and decreased in rat serum. FAs, especially short-chain FAs (12:0, 14:0, 16:0 increased during fructose-challenge. VLDL secretion increased upon fructose-feeding and together with FA-levels decreased to control levels during FF treatment. Fructose challenge of de novo fatty acid synthesis through fatty acid synthase (FAS may enhance the release of FAs ≤ 16:0 chain length, a process reversed by FF-mediated PPARα-activation.

  7. Cloning and expression of a rat brain α2B-adrenergic receptor

    International Nuclear Information System (INIS)

    Flordellis, C.S.; Handy, D.E.; Bresnahan, M.R.; Zannis, V.I.; Gavras, H.

    1991-01-01

    The authors isolated a cDNA clone (RBα 2B ) and its homologous gene (GRα 2B ) encoding an α 2B -adrenergic receptor subtype by screening a rat brain cDNA and a rat genomic library. Nucleotide sequence analysis showed that both clones code for a protein of 458 amino acids, which is 87% homologous to the human kidney glycosylated adrenergic receptor (α 2 -C4) and divergent from the rat kidney nonglycosylated α 2B subtype (RNGα 2 ). Transient expression of RBα 2B in COS-7 cells resulted in high-affinity saturable binding for [ 3 H]rauwolscine and a high receptor number in the membranes of transfected COS-7 cells. Pharmacological analysis demonstrated that the expressed receptor bound adrenergic ligands with the following order of potency: rauwolscine > yohimbine > prazosin > oxymetazoline, with a prazosin-to-oxymetazoline K i ratio of 0.34. This profile is characteristic of the α 2B -adrenergic receptor subtype. Blotting analysis of rat brain mRNA gave one major and two minor mRNA species, and hybridization with strand-specific probes showed that both DNA strands of GRα 2B may be transcriptionally active. These findings show that rat brain expresses an α 2B -adrenergic receptor subtype that is structurally different from the rat kidney nonglycosylated α 2B subtype. Thus the rat expresses at least two divergent α 2B -adrenergic receptors

  8. Toxicity of aerosol propellants in the respiratory and circulatory systems. VI. Influence of cardiac and pulmonary vascular lesions in the rat.

    Science.gov (United States)

    Doherty, R E; Aviado, D M

    1975-01-01

    Three propellants were selected for investigation in rats because of their non-uniform effect in mice and monkeys. Trichlorofluoromethane (FC 11) provoked arrhythmia in all three animal species, dichlorodifluoromethane (FC 12) in monkeys and rats but not in mice, and difluoroethane (FC 152a) only in rats. In rats the alterations in heart rate and electrocardiographic pattern during inhalation of these propellants are largely brought about by release of catecholamines from the adrenal gland, because adrenalectomy or prior injection of beta-adrenergic blocking drugs decreased the incidence of cardiac effects. Rats that have pulmonary vascular thrombosis or cardiac necrosis become more sensitive to proarrhythmic activity of these propellants.

  9. Establishment of a rat and guinea pig aortic interposition graft model reveals model-specific patterns of intimal hyperplasia.

    Science.gov (United States)

    Gregory, Elaine K; Vercammen, Janet M; Flynn, Megan E; Kibbe, Melina R

    2016-12-01

    Although the aortic interposition bypass model has been widely used to evaluate biomaterials for bypass grafting, there is no comprehensive description of the procedure or of the distribution of intimal hyperplasia that results. The objectives of this study were to (1) review and summarize approaches of aortic interposition grafting in animal models, (2) determine the pertinent anatomy for this procedure, (3) validate this model in the rat and guinea pig, and (4) compare the distribution of intimal hyperplasia that develops in each species. A literature search was performed in PubMed from 1980 to the present to analyze the use of anesthesia, anticoagulation, antiplatelet agents, graft material, suture, and anastomotic techniques. Using 10-week-old male Sprague-Dawley rats and Hartley guinea pigs, we established pertinent aortic anatomy, developed comparable models, and assessed complications for each model. At 30 days, the graft and associated aorta were explanted, intimal formation was assessed morphometrically, and cellularity was assessed via nuclear counting. We reviewed 30 articles and summarized the pertinent procedural findings. Upon establishing both animal models, key anatomic differences between the species that affect this model were noted. Guinea pigs have a much larger cecum, increased retroperitoneal fat, and lack the iliolumbar vessels compared with the rat. Surgical outcomes for the rat model included a 53% technical success rate and a 32% technical error rate. Surgical outcomes for the guinea pig model included a 69% technical success rate and a 31% technical error rate. These two species demonstrated unique distribution of intimal hyperplasia at 30 days. Intimal hyperplasia in the rat model was greatest at two areas, the proximal graft (5400 μm 2 ; P guinea pig model developed similar intimal hyperplasia throughout the graft (4500-5100 μm 2 ; P guinea pig, and describe a unique distribution of intimal formation that results in both species

  10. Subchronic toxicity studies of t-butyl alcohol in rats and mice.

    Science.gov (United States)

    Lindamood, C; Farnell, D R; Giles, H D; Prejean, J D; Collins, J J; Takahashi, K; Maronpot, R R

    1992-07-01

    The purpose of this study was to evaluate the toxicity of t-butyl alcohol, an important commodity chemical, an additive to unleaded gasoline, and a contaminant of drinking water. Ninety-day toxicity studies were conducted in B6C3F1 mice and Fischer 344 (F344) rats of both sexes using dosed water. Dose levels of t-butyl alcohol were 0, 0.25, 0.5, 1, 2, and 4% (w/v). Lethality was observed at the 4% level of both sexes and species. Weight-gain depression was present in all dose levels of male rats; 4% female rats; 1, 2, and 4% male mice; and 2 and 4% female mice. Water consumption was increased at lower dose levels in male rats and decreased in the higher dose levels of both sexes of rats and female mice. Clinical signs in rats were ataxia in both sexes and hypoactivity in males. Clinical signs in mice were ataxia, abnormal posture, and hypoactivity. In rats, urine volumes were reduced, in association with crystalluria. Gross lesions at necropsy were urinary tract calculi, renal pelvic and ureteral dilatation, and thickening of the urinary bladder mucosa. Microscopic lesions were hyperplasia of transitional epithelia and inflammation of the urinary bladder. In male rats treated with t-butyl alcohol, microscopic renal changes were suggestive of alpha-2 mu-globulin nephropathy. No-effect levels for the urinary tract lesions were 1% in male rats and mice (803.7 mg/kg/day for the male rats and 1565.8 mg/kg/day for the male mice) and 2% in female rats and mice (1451.5 mg/kg/day for the female rats and 4362.9 mg/kg/day for the female mice). The results indicate that in rodents the urinary tract is the target organ for t-butyl alcohol toxicity, and males are more sensitive to t-butyl alcohol toxicity than females.

  11. Kinetics of adenylate metabolism in human and rat myocardium

    OpenAIRE

    Tavenier, M.; Skladanowski, A.C.; Abreu, R.A. de; Jong, J.W. de

    1995-01-01

    textabstractPathways producing and converting adenosine have hardly been investigated in human heart, contrasting work in other species. We compared the kinetics of enzymes associated with purine degradation and salvage in human and rat heart cytoplasm assaying for adenosine deaminase, nucleoside phosphorylase, xanthine oxidoreductase, AMP deaminase, AMP- and IMP-specific 5′-nucleotidases, adenosine kinase and hypoxanthine guanine phosphoribosyltransferase (HGPRT). Xanthine oxidoreductase was...

  12. Non-invasive assessment of glucocorticoid and androgen metabolite levels in cooperatively breeding Damaraland mole-rats (Fukomys damarensis).

    Science.gov (United States)

    Medger, Katarina; Bennett, Nigel C; Lutermann, Heike; Ganswindt, Andre

    2018-05-18

    Dominant females of cooperative breeding species often use aggression to suppress reproduction of subordinate females, resulting in subordinates experiencing stress-related increases in glucocorticoid levels, which may cause reproductive down-regulation. This would suggest a general pattern with higher glucocorticoid levels in subordinate compared to dominant individuals; however, the opposite was found in a number of cooperatively breeding species. Furthermore, breeding females of the cooperatively breeding Damaraland mole-rats (Fukomys damarensis) exhibit very high androgen concentrations during the wet season, presumably to support their breeding monopoly. Hormone analysis in Damaraland mole-rats have typically been measured using plasma and urine, but faecal analysis offers additional advantages especially for field studies on this species. The present study examines the suitability of Damaraland mole-rat faecal samples for determining glucocorticoid metabolite (fGCM) and androgen metabolite (fAM) concentrations using enzyme immunoassays. Using these assays, we further evaluated the effects of breeding status on fGCM and fAM concentrations in wild-caught and captive Damaraland mole-rats. Wild-caught breeding and non-breeding males and females exhibited no differences in fAM concentrations. Immunoreactive fGCM concentrations were only high in male breeders and comparatively low in non-breeders and breeding females. Concentrations of fAMs and fGCMs were similar in captive males and females, but fAM concentrations were elevated in captive compared to wild-caught individuals, which may be related to a higher reproductive activity due to removal from the breeding female. The relatively uniform fAM and fGCM concentrations found in wild-caught mole-rats may be explained by a stable colony structure during the dry season during which this study was conducted. Limited dispersal opportunities result in lower aggression and stress levels within a colony and as a result

  13. The pharmacokinetics of a new benzamide drug clebopride, in the rat and the dog.

    Science.gov (United States)

    Segura, J; García, I; Borja, L; Tarrús, E; Bakke, O M

    1981-04-01

    After intravenous, intramuscular and oral administration of clebopride in the rat and the dog its apparent volume of distribution is high (1.6-3.2 1 kg-1) and it has a longer biological half-life than metoclopramide in both species. High clearance values and concentrations of metabolites in plasma after oral administration indicate that the drug is subjected to an extensive first pass metabolism in the rat. Thus, clebopride administered orally gives relatively low concentrations in the systemic circulation in rats even though it is rapidly absorbed. The metabolic processes appear to become saturated at high doses which is reflected in dose-dependent kinetics. Linear kinetics were observed in the dog, although enterohepatic recycling could occur.

  14. Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain

    Directory of Open Access Journals (Sweden)

    Haider Raza

    2015-02-01

    Full Text Available Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS production in the ZDF rat brain compared to the liver, while nitric oxide (NO production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-a confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.

  15. Dose-response and histopathological study, with special attention to the hypophysis, of the differential effects of domoic acid on rats and mice.

    Science.gov (United States)

    Vieira, Andrés Crespo; Martínez, J Manuel Cifuentes; Pose, Roberto Bermúdez; Queijo, Álvaro Antelo; Posadas, Nuria Alemañ; López, Luis M Botana

    2015-05-01

    The effects of the neurotoxin domoic acid (DA) in the central nervous system of rodents (essentially rats and mice) after intraperitoneal administration have been profusely studied in the past. These observations have shown that the toxin induces similar symptoms and pathology in both species, but the lethality varies greatly. This article addresses the common and specific histopathological effects in rats and mice and the difference in sensitivity of these species to DA. Various sublethal and lethal doses were employed in mice (from 3 mg/kg to 8 mg/kg) to observe their neurotoxicity by using different histological techniques, and these results were compared with the pathological effects after the administration of LD50 in rats (2.5 mg/kg). Additionally we also detected the presence of this toxin in various tissues by means of immunohistochemistry. Our results showed that rats are more vulnerable than mice to the neurotoxic effects of DA after intraperitoneal inoculation: lethality was extremely high in rats and the toxin produced hippocampal damage in rats surviving the intoxication, while lesions were not observed in DA-inoculated mice. As for similarities between rats and mice, both displayed similar clinical signs and in both the toxin was detected in the hypophysis by immunohistochemistry, a brain region not reported to date as target of the toxin. © 2015 Wiley Periodicals, Inc.

  16. Differential effects of centrally-active antihypertensives on 5-HT1A receptors in rat dorso-lateral septum, rat hippocampus and guinea-pig hippocampus.

    Science.gov (United States)

    Leishman, D J; Boeijinga, P H; Galvan, M

    1994-01-01

    1. The electrophysiological responses elicited by 5-hydroxytryptamine1A-(5-HT1A) receptor agonists in rat and guinea-pig CA1 pyramidal neurones and rat dorso-lateral septal neurones were compared in vitro by use of conventional intracellular recording techniques. 2. In the presence of 1 microM tetrodotoxin (TTX), to prevent indirect effects, 5-HT, N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT) and 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT) hyperpolarized the neurones from rat and guinea-pig brain. 3. The hypotensive drug flesinoxan, a selective 5-HT1A receptor agonist, hyperpolarized neurones in all three areas tested; however, another hypotensive agent with high affinity at 5-HT1A-receptors, 5-methyl-urapidil, hyperpolarized only the neurones in rat hippocampus and septum. 4. In guinea-pig hippocampal neurones, 5-methyl-urapidil behaved as a 5-HT1A-receptor antagonist. 5. The relative efficacies (5-HT = 1) of DP-5-CT, 8-OH-DPAT, flesinoxan and 5-methyl-urapidil at the three sites were: rat hippocampus, 1.09, 0.7, 0.5 and 0.24; rat septum, 0.88, 0.69, 0.82 and 0.7; guinea-pig hippocampus, 1.0, 0.69, 0.89 and 0, respectively. 6. It is concluded that the hypotensive agents flesinoxan and 5-methyl-urapidil appear to have different efficacies at 5-HT1A receptors located in different regions of the rodent brain. Whether these regional and species differences arise from receptor plurality or variability in intracellular transduction mechanisms remains to be elucidated.

  17. PhyloChip microarray analysis reveals altered gastrointestinal microbial communities in a rat model of colonic hypersensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, T.A.; Holmes, S.; Alekseyenko, A.V.; Shenoy, M.; DeSantis, T.; Wu, C.H.; Andersen, G.L.; Winston, J.; Sonnenburg, J.; Pasricha, P.J.; Spormann, A.

    2010-12-01

    Irritable bowel syndrome (IBS) is a chronic, episodic gastrointestinal disorder that is prevalent in a significant fraction of western human populations; and changes in the microbiota of the large bowel have been implicated in the pathology of the disease. Using a novel comprehensive, high-density DNA microarray (PhyloChip) we performed a phylogenetic analysis of the microbial community of the large bowel in a rat model in which intracolonic acetic acid in neonates was used to induce long lasting colonic hypersensitivity and decreased stool water content and frequency, representing the equivalent of human constipation-predominant IBS. Our results revealed a significantly increased compositional difference in the microbial communities in rats with neonatal irritation as compared with controls. Even more striking was the dramatic change in the ratio of Firmicutes relative to Bacteroidetes, where neonatally irritated rats were enriched more with Bacteroidetes and also contained a different composition of species within this phylum. Our study also revealed differences at the level of bacterial families and species. The PhyloChip is a useful and convenient method to study enteric microflora. Further, this rat model system may be a useful experimental platform to study the causes and consequences of changes in microbial community composition associated with IBS.

  18. Determination of Leptospira borgpetersenii serovar Javanica and Leptospira interrogans serovar Bataviae as the persistent Leptospira serovars circulating in the urban rat populations in Peninsular Malaysia.

    Science.gov (United States)

    Benacer, Douadi; Mohd Zain, Siti Nursheena; Sim, Shin Zhu; Mohd Khalid, Mohd Khairul Nizam; Galloway, Renee L; Souris, Marc; Thong, Kwai Lin

    2016-03-01

    Leptospirosis is an emerging infectious disease of global significance, and is endemic in tropical countries, including Malaysia. Over the last decade, a dramatic increase of human cases was reported; however, information on the primary vector, the rat, and the Leptospira serovars circulating among the rat population is limited. Therefore, the present study was undertaken to isolate Leptospira and characterise the serovars circulating in the urban rat populations from selected main cities in Peninsular Malaysia. Rat trappings were carried out between October 2011 to February 2014 in five urban cities which were chosen as study sites to represent different geographical locations in Peninsular Malaysia. Microscopic agglutination test (MAT) and PCR were carried out to identify the Leptospiral serogroup and determine the pathogenic status of the isolates, respectively while pulsed-field gel electrophoresis (PFGE) and random amplified polymorphic DNA (RAPD)-PCR were used to characterize the isolates. Three rat species were identified from the three hundred and fifty seven rats captured with Rattus rattus, being the dominant rat species (285, 80 %) followed by Rattus norgevicus (53, 15 %) and Rattus exulans (19, 5 %). Only 39 samples (11.0 %) were positive by culture and further confirmed as pathogenic Leptospira by PCR. Significant associations were shown between host infection with locality, season, host-age and species. Based on MAT, two serogroups were identified in the population namely; L. borgpetersenii serogroup Javanica (n = 16) and L. interrogans serogroup Bataviae (n = 23). Pulsed-field gel electrophoresis (PFGE) distinguished the two serovars in the urban rat populations: L. borgpetersenii serovar Javanica (41 %), and L. interrogans serovar Bataviae (59 %). RAPD-PCR yielded 14 distinct patterns and was found to be more discriminative than PFGE. This study confirms two Leptospira serovars circulating among the urban rats population in Peninsular

  19. Altered composition of liver proteasome assemblies contributes to enhanced proteasome activity in the exceptionally long-lived naked mole-rat.

    Science.gov (United States)

    Rodriguez, Karl A; Edrey, Yael H; Osmulski, Pawel; Gaczynska, Maria; Buffenstein, Rochelle

    2012-01-01

    The longest-lived rodent, the naked mole-rat (Bathyergidae; Heterocephalus glaber), maintains robust health for at least 75% of its 32 year lifespan, suggesting that the decline in genomic integrity or protein homeostasis routinely observed during aging, is either attenuated or delayed in this extraordinarily long-lived species. The ubiquitin proteasome system (UPS) plays an integral role in protein homeostasis by degrading oxidatively-damaged and misfolded proteins. In this study, we examined proteasome activity in naked mole-rats and mice in whole liver lysates as well as three subcellular fractions to probe the mechanisms behind the apparently enhanced effectiveness of UPS. We found that when compared with mouse samples, naked mole-rats had significantly higher chymotrypsin-like (ChT-L) activity and a two-fold increase in trypsin-like (T-L) in both whole lysates as well as cytosolic fractions. Native gel electrophoresis of the whole tissue lysates showed that the 20S proteasome was more active in the longer-lived species and that 26S proteasome was both more active and more populous. Western blot analyses revealed that both 19S subunits and immunoproteasome catalytic subunits are present in greater amounts in the naked mole-rat suggesting that the observed higher specific activity may be due to the greater proportion of immunoproteasomes in livers of healthy young adults. It thus appears that proteasomes in this species are primed for the efficient removal of stress-damaged proteins. Further characterization of the naked mole-rat proteasome and its regulation could lead to important insights on how the cells in these animals handle increased stress and protein damage to maintain a longer health in their tissues and ultimately a longer life.

  20. A gene-environment study of cytoglobin in the human and rat hippocampus

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Elfving, Betina; Müller, Heidi Kaastrup

    2013-01-01

    Cytoglobin (Cygb) was discovered a decade ago as the fourth vertebrate heme-globin. The function of Cygb is still unknown, but accumulating evidence from in vitro studies point to a putative role in scavenging of reactive oxygen species and nitric oxide metabolism and in vivo studies have shown C......NOS) in the rat hippocampus; 3) The effect of chronic restraint stress (CRS) on Cygb and nNOS expression.......Cytoglobin (Cygb) was discovered a decade ago as the fourth vertebrate heme-globin. The function of Cygb is still unknown, but accumulating evidence from in vitro studies point to a putative role in scavenging of reactive oxygen species and nitric oxide metabolism and in vivo studies have shown...... Cygb to be up regulated by hypoxic stress. This study addresses three main questions related to Cygb expression in the hippocampus: 1) Is the rat hippocampus a valid neuroanatomical model for the human hippocampus; 2) What is the degree of co-expression of Cygb and neuronal nitric oxide synthase (n...

  1. Mechanism (s) of Gamma Radiation-Induced Synthesis of Metalothioneins in Rat Liver

    International Nuclear Information System (INIS)

    Soliman, M.S.; El-Shamy, EL.

    2004-01-01

    The mechanism (s) of metallothioneins (MT) induction by irradiation are still unknown. The present study was undertaken to investigate mechanism (s) of radiation induction of MT whether directly through mediation of radiation-induced reactive oxygen species, indirectly through mediation of a variety of agents or mediators (lipid peroxidation, metal accumulation and cytokines) or both directly and indirectly through mediation of reactive oxygen species in conjunction with these mediators. Seventy-two albino rats were divided into two groups each of 36 animals: Control group and irradiated group. Animals in each group were sacrificed 1,6,12,18,24 and 48 hours after irradiation, 6 rats at each time point. Samples of liver tissues were subjected to the following investigations: measurement of zinc (Zn), metallothioneins (MT), lipid peroxidation(MDA), Interleukin-6 (IL-6) and Tumor Necrosis Factor alpha (TNF-alpha). Post-irradiation, at 1 hr, the MT levels started to increase with mean value of up to 9.9 times of the control level at 48 hr

  2. Audiovisual Temporal Processing and Synchrony Perception in the Rat.

    Science.gov (United States)

    Schormans, Ashley L; Scott, Kaela E; Vo, Albert M Q; Tyker, Anna; Typlt, Marei; Stolzberg, Daniel; Allman, Brian L

    2016-01-01

    that our behavioral and electrophysiological results were consistent with studies conducted on human participants and previous recordings made in multisensory brain regions of different species, we suggest that the rat represents an effective model for studying audiovisual temporal synchrony at both the neuronal and perceptual level.

  3. Soft-food diet induces oxidative stress in the rat brain.

    Science.gov (United States)

    Yoshino, Fumihiko; Yoshida, Ayaka; Hori, Norio; Ono, Yumie; Kimoto, Katsuhiko; Onozuka, Minoru; Lee, Masaichi Chang-il

    2012-02-02

    Decreased dopamine (DA) release in the hippocampus may be caused by dysfunctional mastication, although the mechanisms involved remain unclear. The present study examined the effects of soft- and hard-food diets on oxidative stress in the brain, and the relationship between these effects and hippocampal DA levels. The present study showed that DA release in the hippocampus was decreased in rats fed a soft-food diet. Electron spin resonance studies using the nitroxyl spin probe 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl directly demonstrated a high level of oxidative stress in the rat brain due to soft-food diet feeding. In addition, we confirmed that DA directly react with reactive oxygen species such as hydroxyl radical and superoxide. These observations suggest that soft-food diet feeding enhances oxidative stress, which leads to oxidation and a decrease in the release of DA in the hippocampus of rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. Low sulfide levels and a high degree of cystathionine β-synthase (CBS activation by S-adenosylmethionine (SAM in the long-lived naked mole-rat

    Directory of Open Access Journals (Sweden)

    Maja Dziegelewska

    2016-08-01

    Full Text Available Hydrogen sulfide (H2S is a gaseous signalling molecule involved in many physiological and pathological processes. There is increasing evidence that H2S is implicated in aging and lifespan control in the diet-induced longevity models. However, blood sulfide concentration of naturally long-lived species is not known. Here we measured blood sulfide in the long-lived naked mole-rat and five other mammalian species considerably differing in lifespan and found a negative correlation between blood sulfide and maximum longevity residual. In addition, we show that the naked mole-rat cystathionine β-synthase (CBS, an enzyme whose activity in the liver significantly contributes to systemic sulfide levels, has lower activity in the liver and is activated to a higher degree by S-adenosylmethionine compared to other species. These results add complexity to the understanding of the role of H2S in aging and call for detailed research on naked mole-rat transsulfuration.

  5. Application of ovine luteinizing hormone (LH) radioimmunoassay in the quantitation of LH in different mammalian species

    International Nuclear Information System (INIS)

    Millar, R.P.; Aehnelt, C.

    1977-01-01

    A sensitive double antibody radioimmunoassay has been developed for measuring luteinizing hormone (LH) in various African mammalian species, using rabbit anti-ovine LH serum (GDN 15) and radioiodinated rat LH or ovine LH. Serum and pituitary homogenates from some African mammals (hyrax, reedbuck, sable, impala, tsessebe, thar, spring-hare, ground squirrel and cheetah, as well as the domestic sheep, cow and horse and laboratory rat and hamster) produced displacement curves parallel to that of the ovine LH standards. The specificity of the assay was examined in detail for one species, the rock hyrax. Radioimmunoassay and bioassay estimates of LH in hyrax pituitaries containing widely differing quantities of pituitary hormones were similar. In sexually active male hyrax mean plasma LH was 12.1 ng/ml and pituitary LH 194 μg/gland, but in sexually quiescent hyrax mean plasma LH was 2.4 ng/ml and mean pituitary LH 76 μg/gland. Intravenous injection of 10 μg of luteinizing hormone releasing hormone increased mean LH levels in hyrax from 0.9 ng/ml to 23.2 ng/ml by 30 min. Conversely, im injection of 250 μg testosterone induced a fall in LH levels in male hyrax from 1.7 ng/ml to 0.7 ng/ml 6 h after administration. Although the specificity of the assay for quantitating plasma LH in other species was not categorically established, there was a good correlation between plasma LH concentration and reproductive state in the bontebok, impala, spring-hare, thar, cheetah, domestic horse and laboratory rat, suggesting the potential use of the antiserum in quantitating LH in a variety of mammalian species

  6. Enhancement of intestinal growth in neonatal rats by epidermal growth factor in milk

    International Nuclear Information System (INIS)

    Berseth, C.L.

    1987-01-01

    Breast milk has been shown to enhance neonatal intestinal growth. Because epidermal growth factor (EGF) is present in the milk of various mammalian species, the hypothesis was tested that EGF in rodent milk mediates, in part, the breast milk-enhanced intestinal growth in neonatal rat. Fifty-eight rat pups fed artificial formal that contained 1.2, 3.0, and 6.0 μg/ml EGF for 39 h had greater incorporation of [ 3 H]thymidine into DNA and DNA content of intestine than 29 pups fed unsupplemented formula. Pups fed EGF for 5 days had significantly greater body weight, intestinal weight, length, and DNA content than control pups. Conversely, pups fed pooled rat milk containing rabbit-derived antibody to EGF for 39 h had intestines of lower weight that contained less DNA than animals fed rat milk containing normal rabbit serum. EGF appears to mediate, in part, breast milk-enhanced neonatal intestinal growth

  7. Contribution of reactive oxygen species to the pathogenesis of pulmonary arterial hypertension

    Science.gov (United States)

    Naik, Jay S.; Weise-Cross, Laura; Detweiler, Neil D.; Herbert, Lindsay M.; Yellowhair, Tracylyn R.; Resta, Thomas C.

    2017-01-01

    Pulmonary arterial hypertension is associated with a decreased antioxidant capacity. However, neither the contribution of reactive oxygen species to pulmonary vasoconstrictor sensitivity, nor the therapeutic efficacy of antioxidant strategies in this setting are known. We hypothesized that reactive oxygen species play a central role in mediating both vasoconstrictor and arterial remodeling components of severe pulmonary arterial hypertension. We examined the effect of the chemical antioxidant, TEMPOL, on right ventricular systolic pressure, vascular remodeling, and enhanced vasoconstrictor reactivity in both chronic hypoxia and hypoxia/SU5416 rat models of pulmonary hypertension. SU5416 is a vascular endothelial growth factor receptor antagonist and the combination of chronic hypoxia/SU5416 produces a model of severe pulmonary arterial hypertension with vascular plexiform lesions/fibrosis that is not present with chronic hypoxia alone. The major findings from this study are: 1) compared to hypoxia alone, hypoxia/SU5416 exposure caused more severe pulmonary hypertension, right ventricular hypertrophy, adventitial lesion formation, and greater vasoconstrictor sensitivity through a superoxide and Rho kinase-dependent Ca2+ sensitization mechanism. 2) Chronic hypoxia increased medial muscularization and superoxide levels, however there was no effect of SU5416 to augment these responses. 3) Treatment with TEMPOL decreased right ventricular systolic pressure in both hypoxia and hypoxia/SU5416 groups. 4) This effect of TEMPOL was associated with normalization of vasoconstrictor responses, but not arterial remodeling. Rather, medial hypertrophy and adventitial fibrotic lesion formation were more pronounced following chronic TEMPOL treatment in hypoxia/SU5416 rats. Our findings support a major role for reactive oxygen species in mediating enhanced vasoconstrictor reactivity and pulmonary hypertension in both chronic hypoxia and hypoxia/SU5416 rat models, despite a

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  9. Evaluation of treadmill exercise effect on muscular lipid profiles of diabetic fatty rats by nanoflow liquid chromatography-tandem mass spectrometry

    Science.gov (United States)

    Lee, Jong Cheol; Kim, Il Yong; Son, Yeri; Byeon, Seul Kee; Yoon, Dong Hyun; Son, Jun Seok; Song, Han Sol; Song, Wook; Seong, Je Kyung; Moon, Myeong Hee

    2016-07-01

    We compare comprehensive quantitative profiling of lipids at the molecular level from skeletal muscle tissues (gastrocnemius and soleus) of Zucker diabetic fatty rats and Zucker lean control rats during treadmill exercise by nanoflow liquid chromatography-tandem mass spectrometry. Because type II diabetes is caused by decreased insulin sensitivity due to excess lipids accumulated in skeletal muscle tissue, lipidomic analysis of muscle tissues under treadmill exercise can help unveil the mechanism of lipid-associated insulin resistance. In total, 314 lipid species, including phospholipids, sphingolipids, ceramides, diacylglycerols (DAGs), and triacylglycerols (TAGs), were analyzed to examine diabetes-related lipid species and responses to treadmill exercise. Most lysophospholipid levels increased with diabetes. While DAG levels (10 from the gastrocnemius and 13 from the soleus) were >3-fold higher in diabetic rats, levels of most of these decreased after exercise in soleus but not in gastrocnemius. Levels of 5 highly abundant TAGs (52:1 and 54:3 in the gastrocnemius and 48:2, 50:2, and 52:4 in the soleus) displaying 2-fold increases in diabetic rats decreased after exercise in the soleus but not in the gastrocnemius in most cases. Thus, aerobic exercise has a stronger influence on lipid levels in the soleus than in the gastrocnemius in type 2 diabetic rats.

  10. Functional characteristics of the naked mole rat μ-opioid receptor.

    Directory of Open Access Journals (Sweden)

    Melanie Busch-Dienstfertig

    Full Text Available While humans and most animals respond to µ-opioid receptor (MOR agonists with analgesia and decreased aggression, in the naked mole rat (NMR opioids induce hyperalgesia and severe aggression. Single nucleotide polymorphisms in the human mu-opioid receptor gene (OPRM1 can underlie altered behavioral responses to opioids. Therefore, we hypothesized that the primary structure of the NMR MOR may differ from other species. Sequencing of the NMR oprm1 revealed strong homology to other mammals, but exposed three unique amino acids that might affect receptor-ligand interactions. The NMR and rat oprm1 sequences were cloned into mammalian expression vectors and transfected into HEK293 cells. Radioligand binding and 3'-5'-cyclic adenosine monophosphate (cAMP enzyme immunoassays were used to compare opioid binding and opioid-mediated cAMP inhibition. At normalized opioid receptor protein levels we detected significantly lower [3H]DAMGO binding to NMR compared to rat MOR, but no significant difference in DAMGO-induced cAMP inhibition. Strong DAMGO-induced MOR internalization was detectable using radioligand binding and confocal imaging in HEK293 cells expressing rat or NMR receptor, while morphine showed weak or no effects. In summary, we found minor functional differences between rat and NMR MOR suggesting that other differences e.g. in anatomical distribution of MOR underlie the NMR's extreme reaction to opioids.

  11. Comparative toxicokinetics of MMB4 DMS in rats, rabbits, dogs, and monkeys following single and repeated intramuscular administration.

    Science.gov (United States)

    Hong, S Peter; Gibbs, Seth T; Kobs, Dean J; Hawk, Michael A; Croutch, Claire R; Osheroff, Merrill R; Johnson, Jerry D; Burback, Brian L

    2013-01-01

    1,1'-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] (MMB4) dimethanesulfonate (DMS) is a bisquaternary pyridinium aldoxime that reactivates acetylcholinesterase inhibited by organophosphorus nerve agent. Time courses of MMB4 concentrations in plasma were characterized following 7-day repeated intramuscular (IM) administrations of MMB4 DMS to male and female Sprague-Dawley rats, New Zealand White rabbits, beagle dogs (single dose only), and rhesus monkeys at drug dose levels used in earlier toxicology studies. In general, there were no significant differences in MMB4 toxicokinetic (TK) parameters between males and females for all the species tested in these studies. After a single IM administration to rats, rabbits, dogs, and monkeys, MMB4 DMS was rapidly absorbed, resulting in average T max values ranging from 5 to 30 minutes. Although C max values did not increase dose proportionally, the overall exposure to MMB4 in these preclinical species, as indicated by area under the curve (AUC) extrapolated to the infinity (AUC∞) values, increased in an approximately dose-proportional manner. The MMB4 DMS was extensively absorbed into the systemic circulation after IM administration as demonstrated by greater than 80% absolute bioavailability values for rats, rabbits, and dogs. Repeated administrations of MMB4 DMS for 7 days did not overtly alter TK parameters for MMB4 in rats, rabbits, and monkeys (150 and 300 mg/kg/d dose groups only). However, C max and AUC values decreased in monkeys given 450 and 600 mg/kg IM doses of MMB4 DMS following repeated administrations for 7 days. Based on the TK results obtained from the current study and published investigations, it was found that the apparent volume of distribution and clearance values were similar among various preclinical species, except for the rat.

  12. Shiitake Culinary-Medicinal Mushroom, Lentinus edodes (Agaricomycetes): A Species with Antioxidant, Immunomodulatory, and Hepatoprotective Activities in Hypercholesterolemic Rats.

    Science.gov (United States)

    Nisar, Jaweria; Mustafa, Imtiaz; Anwar, Haseeb; Sohail, Muhammad Umar; Hussain, Ghulam; Ullah, Muhammad Irfan; Faisal, Muhammad Naeem; Bukhari, Shazia Anwer; Basit, Abdul

    2017-01-01

    Lentinus edodes is a culinary-medicinal mushroom that has an established history of use in Asian therapies. The mushroom offers well-documented beneficial health effects such as antihypercholesterolemic, antitumor, and antibacterial activities. In this study, dried powder of L. edodes fruiting bodies was used to evaluate immunomodulatory, hepatoprotective, and antioxidant effects in hypercholesterolemic rats. Albino rats (n = 24) were divided into 3 groups: the control (CON) group, the hypercholesterolemia-only group (HCG), and the L. edodes group (LEG). Hypercholesterolemia was induced in rats in the HCG and LEG by feeding cholesterol and cholic acid in a chow maintenance diet (CMD) for 24 days. The CON group was fed the CMD throughout the experiment. The HCG continued on the high-cholesterol diet without any L. edodes supplement. The LEG was fed the high-cholesterol diet supplemented with L. edodes for an additional 42 days. Various biological health biomarkers, such as total antioxidant capacity, total oxidant status, arylesterase, paraoxonase activity, and liver enzymes in serum were studied to evaluate antioxidant and hepatoprotective responses. Cell-mediated immunity was evaluated in each group through a delayed type of hypersensitivity reaction. The total oxidant status decreased significantly (P ≤ 0.05) after administration of L. edodes in the diet. The cell-mediated immune response significantly increased (P ≤ 0.05) in the LEG. The significant decrease in liver enzymes supports the hepatoprotective effect of L. edodes. In conclusion, the results show the immunomodulatory, hepatoprotective, and antioxidant activities of L. edodes supplementation in hypercholesterolemic rats.

  13. Distribution of /sup 14/C-labelled acrylamide and betaine in foetuses of rats, rabbits, beagle dogs and miniature pigs

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, G.J.; Miller, E.; Sapienza, P.P.; Michel, T.C.; King, M.T.; Turner, V.A.; Blumenthal, H.; Jackson, W.E.; Levin, S.

    1983-02-01

    (/sup 14/C)Acrylamide and (/sup 14/C)betaine hydrochloride were administered in a single iv dose to pregnant rats, rabbits, beagle dogs and miniature pigs late in gestation (1-2 days before expected parturition). Dosages used were 10 mg/kg for rats and 5 mg/kg for the other species. The compounds were allowed to equilibrate in the animal (for 1 hr in rats and for 2 hr in the other species); the dam was then killed and the foetuses were removed by caesarean section. Each foetus was weighed and analysed for radioactivity, either by homogenization of the whole foetus (rat and rabbit) or by determining separately the radioactivity in individual organs and tissues (dog and pig). Foetal uptake of the polar compound betaine hydrochloride was much lower than that of the more lipophilic acrylamide. The sex of the foetus did not appear to affect uptake of either compound. There were no significant differences in total uptake of isotope attributable to the position of the foetus within the uterus in any of the four species given either acrylamide or betaine. Similarly, uterine position did not affect the uptake of acrylamide or betaine by individual tissues of foetal dogs or pigs. Since the distributions of /sup 14/C-labelled acrylamide and betaine hydrochloride were essentially uniform throughout a litter, it would not be necessary to sample all of the members of a litter to obtain a representative picture of foetal distribution.

  14. Role of some selected Bifidobacterium strains in modulating immunosenescence of aged albino rats

    Directory of Open Access Journals (Sweden)

    Hanan A. El-Bakry

    2013-10-01

    Full Text Available Probiotic administration has been associated with enhanced immune function in elderly subjects. However, approaches for selection of an “ideal” strain of bifidobacteria are still difficult. The aim of the present study is to investigate the possible modulatory effects of three strains of Bifidobacterium species (Bifidobacterium adolescentis ATCC 15704, Bifidobacterium breve ATCC 15700 and Bifidobacterium longum ATCC 15707 on haematological and immunological parameters of aged albino rats corresponding to normal adult ones. The animals were divided into six groups; three groups of aged rats were fed yoghurt inoculated with one of the Bifidobacterium strains; one group of aged rats was fed yoghurt alone (control aged; two groups of adult and aged rats were provided with normal diet and assigned as normal groups. The total leucocyte count was significantly increased in the three bifidobacteria-treated aged groups as compared with both normal and control aged rats. Serum IgA level was considerably increased in all treated rats. On the contrary, serum IgE level was significantly decreased in rats supplemented with yoghurt inoculated with B. adolescentis or B. breve. Both B. adolescentis and B. breve groups showed significant enhanced production of TNF-α. Furthermore, the production of cytokine IL-8 was significantly increased in the B. adolescentis group. Interestingly, it was apparent that only B. adolescentis had the most pronounced effect on aged rats to regain nearly normal values as measured in normal adult rats. Conclusively, the present work indicates that dietary consumption of selected bifidobacteria strains may have a particular application in the elderly especially in terms of immunomodulation.

  15. Vertebrate species introductions in the United States and its territories

    Science.gov (United States)

    Witmer, Gary W.; Fuller, Pam L.

    2011-01-01

    At least 1,065 introduced vertebrate species have been introduced in the United States and its territories, including at least 86 mammalian, 127 avian, 179 reptilian/amphibian, and 673 fish species. Examples in each major taxonomic group include domestic cat, small Indian mongoose, red fox, goat, pig, rabbit, rats, house mouse, gray squirrel, nutria, starling, Indian common myna, red-vented bulbul, brown treesnake, red-eared slider, brown trout, tilapia, and grass carp. We briefly review some of these species and the types of damage they cause. We then review the basic types of methods used for control or eradication of each taxonomic group, including physical, chemical, biological, and cultural methods. We discuss some of the challenges in managing these species, including issues with the use of toxicants, land access, public attitudes, and monitoring difficulties. Finally, we list some ongoing research and future research needs, including improved detection methods, improved attractants, improved barriers, improved capture methods, fertility control, and risk assessment methods.

  16. Influence of sex hormones on relative quantities of multiple species of cytochrome P-450 in rat liver microsomes

    International Nuclear Information System (INIS)

    Fujita, S.; Peisach, J.; Chevion, M.; Hebrew Univ., Jerusalem

    1981-01-01

    EPR spectra of rat liver microsomes from male, female and hormonally-treated castrated hepatectomized rats were studied. The spectra, especially in the region of gsub(max) suggested a heterogeneity of local environments of the low spin ferric heme indicative of multiple structures for cytochrome P-450. Certain features in the spectrum correlated with sexual differences. It is suggested that the changes in the relative amplitudes of the EPR features represent differences in the relative abundance of the individual proteins in the mixture that, in turn, are related to the sexual differences of metabolic patterns for reactions catalyzed by cytochrome P-450. (author)

  17. MINIMAL ROLE FOR REACTIVE OXYGEN SPECIES IN DICHLOROACETIC ACID-INDUCED DYSMORPHOLOGY IN MOUSE WHOLE EMBRYO CULTURE.

    Science.gov (United States)

    Administration of dichloroacetate (DCA) to pregnant rats produces craniofacial, heart and other defects in their offspring. Exposure of zebrafish to DCA induces malformations and increases superoxide and nitric oxide production suggesting that reactive oxygen species (ROS) are as...

  18. Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils

    Directory of Open Access Journals (Sweden)

    Paino I.M.M.

    2005-01-01

    Full Text Available The release of reactive oxygen specie (ROS by activated neutrophil is involved in both the antimicrobial and deleterious effects in chronic inflammation. The objective of the present investigation was to determine the effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs (NSAIDs on the production of ROS by stimulated rat neutrophils. Diclofenac (3.6 µM, indomethacin (12 µM, naproxen (160 µM, piroxicam (13 µM, and tenoxicam (30 µM were incubated at 37ºC in PBS (10 mM, pH 7.4, for 30 min with rat neutrophils (1 x 10(6 cells/ml stimulated by phorbol-12-myristate-13-acetate (100 nM. The ROS production was measured by luminol and lucigenin-dependent chemiluminescence. Except for naproxen, NSAIDs reduced ROS production: 58 ± 2% diclofenac, 90 ± 2% indomethacin, 33 ± 3% piroxicam, and 45 ± 6% tenoxicam (N = 6. For the lucigenin assay, naproxen, piroxicam and tenoxicam were ineffective. For indomethacin the inhibition was 52 ± 5% and diclofenac showed amplification in the light emission of 181 ± 60% (N = 6. Using the myeloperoxidase (MPO/H2O2/luminol system, the effects of NSAIDs on MPO activity were also screened. We found that NSAIDs inhibited both the peroxidation and chlorinating activity of MPO as follows: diclofenac (36 ± 10, 45 ± 3%, indomethacin (97 ± 2, 100 ± 1%, naproxen (56 ± 8, 76 ± 3%, piroxicam (77 ± 5, 99 ± 1%, and tenoxicam (90 ± 2, 100 ± 1%, respectively (N = 3. These results show that therapeutic levels of NSAIDs are able to suppress the oxygen-dependent antimicrobial or oxidative functions of neutrophils by inhibiting the generation of hypochlorous acid.

  19. Metabolism of ginger component [6]-shogaol in liver microsomes from mouse, rat, dog, monkey, and human.

    Science.gov (United States)

    Chen, Huadong; Soroka, Dominique; Zhu, Yingdong; Sang, Shengmin

    2013-05-01

    There are limited data on the metabolism of [6]-shogaol (6S), a major bioactive component of ginger. This study demonstrates metabolism of 6S in liver microsomes from mouse, rat, dog, monkey, and human. The in vitro metabolism of 6S was compared among five species using liver microsomes from mouse, rat, dog, monkey, and human. Following incubations with 6S, three major reductive metabolites 1-(4'-hydroxy-3'-methoxyphenyl)-4-decen-3-ol (M6), 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol (M9), and 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M11), as well as two new oxidative metabolites (1E,4E)-1-(4'-hydroxy-3'-methoxyphenyl)-deca-1,4-dien-3-one (M14) and (E)-1-(4'-hydroxy-3'-methoxyphenyl)-dec-1-en-3-one (M15) were found in all species. The kinetic parameters of M6 in liver microsomes from each respective species were quantified using Michaelis-Menten theory. A broad CYP-450 inhibitor, 1-aminobenzotriazole, precluded the formation of oxidative metabolites, M14 and M15, and 18β-glycyrrhetinic acid, an aldo-keto reductase inhibitor, eradicated the formation of the reductive metabolites M6, M9, and M11 in all species. Metabolites M14 and M15 were tested for cancer cell growth inhibition and induction of apoptosis and both showed substantial activity, with M14 displaying greater potency than 6S. We conclude that 6S is metabolized extensively in mammalian species mouse, rat, dog, monkey, and human, and that there are significant interspecies differences to consider when planning preclinical trials toward 6S chemoprevention. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Comparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine.

    Science.gov (United States)

    Balestrini, Jenna L; Gard, Ashley L; Gerhold, Kristin A; Wilcox, Elise C; Liu, Angela; Schwan, Jonas; Le, Andrew V; Baevova, Pavlina; Dimitrievska, Sashka; Zhao, Liping; Sundaram, Sumati; Sun, Huanxing; Rittié, Laure; Dyal, Rachel; Broekelmann, Tom J; Mecham, Robert P; Schwartz, Martin A; Niklason, Laura E; White, Eric S

    2016-09-01

    Lung engineering is a promising technology, relying on re-seeding of either human or xenographic decellularized matrices with patient-derived pulmonary cells. Little is known about the species-specificity of decellularization in various models of lung regeneration, or if species dependent cell-matrix interactions exist within these systems. Therefore decellularized scaffolds were produced from rat, pig, primate and human lungs, and assessed by measuring residual DNA, mechanical properties, and key matrix proteins (collagen, elastin, glycosaminoglycans). To study intrinsic matrix biologic cues, human endothelial cells were seeded onto acellular slices and analyzed for markers of cell health and inflammation. Despite similar levels of collagen after decellularization, human and primate lungs were stiffer, contained more elastin, and retained fewer glycosaminoglycans than pig or rat lung scaffolds. Human endothelial cells seeded onto human and primate lung tissue demonstrated less expression of vascular cell adhesion molecule and activation of nuclear factor-κB compared to those seeded onto rodent or porcine tissue. Adhesion of endothelial cells was markedly enhanced on human and primate tissues. Our work suggests that species-dependent biologic cues intrinsic to lung extracellular matrix could have profound effects on attempts at lung regeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Renal uptake and retention of radiolabeled somatostatin, bombesin, neurotensin, minigastrin and CCK analogues: species and gender differences

    Energy Technology Data Exchange (ETDEWEB)

    Melis, Marleen [Department of Nuclear Medicine, Erasmus MC Rotterdam, 3015 CE Rotterdam (Netherlands)], E-mail: m.melis@erasmusmc.nl; Krenning, Eric P.; Bernard, Bert F.; Visser, Monique de; Rolleman, Edgar; Jong, Marion de [Department of Nuclear Medicine, Erasmus MC Rotterdam, 3015 CE Rotterdam (Netherlands)

    2007-08-15

    Introduction: During therapy with radiolabeled peptides, the kidney is most often the critical organ. Newly developed peptides are evaluated preclinically in different animal models before their application in humans. In this study, the renal retention of several radiolabeled peptides was compared in male and female rats and mice. Methods: After intravenous injection of radiolabeled peptides [somatostatin, cholecystokinin (CCK), minigastrin, bombesin and neurotensin analogues], renal uptake was determined in both male and female Lewis rats and C57Bl mice. In addition, ex vivo autoradiography of renal sections was performed to localize accumulated radioactivity. Results: An equal distribution pattern of renal radioactivity was found for all peptides: high accumulation in the cortex, lower accumulation in the outer medulla and no radioactivity in the inner medulla of the kidneys. In both male rats and mice, an increasing renal uptake was found: [{sup 111}In-DTPA]CCK8<[{sup 111}In-DTPA-Pro{sup 1},Tyr{sup 4}]bombesin{approx}[{sup 111}In-DTPA] neurotensin<[{sup 111}In-DTPA]octreotide<<[{sup 111}In-DTPA]MG0. Renal uptake of [{sup 111}In-DTPA]octreotide in rats showed no gender difference, and renal radioactivity was about constant over time. In mice, however, renal uptake in females was significantly higher than that in males and decreased rapidly over time in both genders. Moreover, renal radioactivity in female mice injected with [{sup 111}In-DTPA]octreotide showed a different localization pattern. Conclusions: Regarding the renal uptake of different radiolabeled peptides, both species showed the same ranking order. Similar to findings in patients, rats showed comparable and constant renal retention of radioactivity in both genders, in contrast to mice. Therefore, rats appear to be the more favorable species for the study of the renal retention of radioactivity.

  2. Renal uptake and retention of radiolabeled somatostatin, bombesin, neurotensin, minigastrin and CCK analogues: species and gender differences

    International Nuclear Information System (INIS)

    Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Visser, Monique de; Rolleman, Edgar; Jong, Marion de

    2007-01-01

    Introduction: During therapy with radiolabeled peptides, the kidney is most often the critical organ. Newly developed peptides are evaluated preclinically in different animal models before their application in humans. In this study, the renal retention of several radiolabeled peptides was compared in male and female rats and mice. Methods: After intravenous injection of radiolabeled peptides [somatostatin, cholecystokinin (CCK), minigastrin, bombesin and neurotensin analogues], renal uptake was determined in both male and female Lewis rats and C57Bl mice. In addition, ex vivo autoradiography of renal sections was performed to localize accumulated radioactivity. Results: An equal distribution pattern of renal radioactivity was found for all peptides: high accumulation in the cortex, lower accumulation in the outer medulla and no radioactivity in the inner medulla of the kidneys. In both male rats and mice, an increasing renal uptake was found: [ 111 In-DTPA]CCK8 111 In-DTPA-Pro 1 ,Tyr 4 ]bombesin∼[ 111 In-DTPA] neurotensin 111 In-DTPA]octreotide 111 In-DTPA]MG0. Renal uptake of [ 111 In-DTPA]octreotide in rats showed no gender difference, and renal radioactivity was about constant over time. In mice, however, renal uptake in females was significantly higher than that in males and decreased rapidly over time in both genders. Moreover, renal radioactivity in female mice injected with [ 111 In-DTPA]octreotide showed a different localization pattern. Conclusions: Regarding the renal uptake of different radiolabeled peptides, both species showed the same ranking order. Similar to findings in patients, rats showed comparable and constant renal retention of radioactivity in both genders, in contrast to mice. Therefore, rats appear to be the more favorable species for the study of the renal retention of radioactivity

  3. Regional brain glucose use in unstressed rats after two days of starvation

    International Nuclear Information System (INIS)

    Mans, A.M.; Davis, D.W.; Hawkins, R.A.

    1987-01-01

    Regional brain glucose use was measured in conscious, unrestrained, fed rats and after 2 days of starvation, using quantitative autoradiography and [6- 14 C]glucose. Plasma glucose, lactate, and ketone body concentrations and brain glucose and lactate content were measured in separate groups of rats. Glucose concentrations were lower in starved rats in both plasma and brain; plasma ketone body concentrations were elevated. Glucose use was found to be lower throughout the brain by about 12%. While some areas seemed to be affected more than others, statistical analysis showed that none were exceptionally different. The results could not be explained by increased loss of 14 C as lactate or pyruvate during the experimental period, because the arteriovenous differences of these species were insignificant. The calculated contribution by ketone bodies to the total energy consumption was between 3 and 9% for the brain as a whole in the starved rats and could, therefore, partially account for the depression seen in glucose use. It was concluded that glucose oxidation is slightly depressed throughout the brain after 2 days of starvation

  4. Ontogenetic changes of lipofuscin-like pigments in the rat heart

    Czech Academy of Sciences Publication Activity Database

    Wilhelm, Jiří; Ošťádalová, Ivana

    2012-01-01

    Roč. 61, Suppl.1 (2012), S173-S179 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP303/11/0298 Institutional research plan: CEZ:AV0Z50110509 Keywords : rat heart * ontogenetic development * lipofuscin-like pigments (LFP) * reactive oxygen species (ROS) * gender difference * right/left ventricle ratio Subject RIV: ED - Physiology Impact factor: 1.531, year: 2012

  5. The reproductive biology of the giant Zambian mole-rat, Cryptomys ...

    African Journals Online (AJOL)

    1994-09-29

    Sep 29, 1994 ... gala (12° 27'S, 2T51'E) in the Copperbelt of northern Zam- hia. ... mole-rat, a pair of animals and a group comprising one male and three females .... Figure 1 Changes In bouy mass of a captive female Cr.vptom.vs mechowi ... The sex distribution was .... 'Ine social Cryptomys species are chmacteril,ed hy.

  6. Blunted neuronal calcium response to hypoxia in naked mole-rat hippocampus.

    Directory of Open Access Journals (Sweden)

    Bethany L Peterson

    Full Text Available Naked mole-rats are highly social and strictly subterranean rodents that live in large communal colonies in sealed and chronically oxygen-depleted burrows. Brain slices from naked mole-rats show extreme tolerance to hypoxia compared to slices from other mammals, as indicated by maintenance of synaptic transmission under more hypoxic conditions and three fold longer latency to anoxic depolarization. A key factor in determining whether or not the cellular response to hypoxia is reversible or leads to cell death may be the elevation of intracellular calcium concentration. In the present study, we used fluorescent imaging techniques to measure relative intracellular calcium changes in CA1 pyramidal cells of hippocampal slices during hypoxia. We found that calcium accumulation during hypoxia was significantly and substantially attenuated in slices from naked mole-rats compared to slices from laboratory mice. This was the case for both neonatal (postnatal day 6 and older (postnatal day 20 age groups. Furthermore, while both species demonstrated more calcium accumulation at older ages, the older naked mole-rats showed a smaller calcium accumulation response than even the younger mice. A blunted intracellular calcium response to hypoxia may contribute to the extreme hypoxia tolerance of naked mole-rat neurons. The results are discussed in terms of a general hypothesis that a very prolonged or arrested developmental process may allow adult naked mole-rat brain to retain the hypoxia tolerance normally only seen in neonatal mammals.

  7. Blunted neuronal calcium response to hypoxia in naked mole-rat hippocampus.

    Science.gov (United States)

    Peterson, Bethany L; Larson, John; Buffenstein, Rochelle; Park, Thomas J; Fall, Christopher P

    2012-01-01

    Naked mole-rats are highly social and strictly subterranean rodents that live in large communal colonies in sealed and chronically oxygen-depleted burrows. Brain slices from naked mole-rats show extreme tolerance to hypoxia compared to slices from other mammals, as indicated by maintenance of synaptic transmission under more hypoxic conditions and three fold longer latency to anoxic depolarization. A key factor in determining whether or not the cellular response to hypoxia is reversible or leads to cell death may be the elevation of intracellular calcium concentration. In the present study, we used fluorescent imaging techniques to measure relative intracellular calcium changes in CA1 pyramidal cells of hippocampal slices during hypoxia. We found that calcium accumulation during hypoxia was significantly and substantially attenuated in slices from naked mole-rats compared to slices from laboratory mice. This was the case for both neonatal (postnatal day 6) and older (postnatal day 20) age groups. Furthermore, while both species demonstrated more calcium accumulation at older ages, the older naked mole-rats showed a smaller calcium accumulation response than even the younger mice. A blunted intracellular calcium response to hypoxia may contribute to the extreme hypoxia tolerance of naked mole-rat neurons. The results are discussed in terms of a general hypothesis that a very prolonged or arrested developmental process may allow adult naked mole-rat brain to retain the hypoxia tolerance normally only seen in neonatal mammals.

  8. Deposition and retention patterns for 3-, 9-, and 15-micron latex microspheres inhaled by rats and guinea pigs

    International Nuclear Information System (INIS)

    Snipes, M.B.; Olson, T.R.; Yeh, H.C.

    1988-01-01

    This study was designed to determine the deposition patterns and fate of large particles inhaled by two species of small laboratory animals during nose breathing. Rats and guinea pigs inhaled 3-, 9-, or 15 micron polystyrene latex microspheres labeled with 46 Sc. Approximately 1.4% and 0.55% of the initial internally deposited body burden of 3-micron microspheres was in the alveolar region of the respiratory tract of rats and guinea pigs, respectively. None of the 9- or 15-micron microspheres were detected in the alveolar regions of the rats or guinea pigs. Ninety-five to 99% of the deposited microspheres cleared from these animals with biological half-times of 0.5-1.0 day. Most of the cleared radioactivity was in the feces. Approximations for long-term biological half-times for alveolar retention of the 3-micron microspheres were 63 days for rats and 83 days for guinea pigs. About 1% of the initial lung burden of 3-micron microspheres was translocated from lung to lung-associated lymph nodes in both species; none of the 9- or 15-micron microspheres were detected in those lymph nodes. Small fractions of the microspheres initially deposited in the airways of the head were retained with biological clearance half-times ranging from 9 to 350 days. Results from this study do not allow projections for deposition and retention patterns for similar particles inhaled by humans. Such projections must come from studies with humans, or from studies with animal species having deposition patterns for inhaled materials more comparable to those of humans

  9. Cellular location of rat muscle ferritins and their preferential loss during cell isolation.

    Science.gov (United States)

    Linder, M C; Roboz, M; McKown, M J; Pardridge, W M; Zak, R

    1984-04-10

    Heart and other muscles of the rat contain two forms of ferritin separable in polyacrylamide gel electrophoresis. The cellular location of the fast- and slow-migrating ferritins was investigated using primary cultures of hindlimb skeletal muscle, and isolated myocardial cell populations. Muscle and non-muscle cells were isolated in good yield from hearts of adult rats pretreated with large doses of iron to increase their ferritin content. In virtually all cases, the isolated muscle cells contained traces only of the fast-migrating species and the non-muscle cells contained small amounts of the slow-migrating ferritin. During cell isolation, 90-100% of both ferritins was lost and could be recovered in the perfusates and solutions employed, while one third of the total tissue protein, and a larger percentage of creatine phosphokinase, was recovered in the isolated cells. Primary cultures of thigh muscle from adult rats which had differentiated into multi-nucleated myotubes, were incubated for 1-3 days with chelated iron. These cells contained substantial amounts of the electrophoretically fast migrating ferritin, with its characteristic larger Stokes' radius (determined by quantitative polyacrylamide gel electrophoresis). None of the slow-migrating ferritin species was detected, although hindlimb muscle from iron-treated rats contained both forms. It is concluded that the fast-migrating ferritin of muscle, which is much larger and more asymmetric than other ferritins, is confined to the muscle cell population, while the other form is predominantly or exclusively in the non-muscle cells. Both ferritins are lost preferentially over other proteins during procedures which injure muscle tissue.

  10. Gender differences in the metabolism of 1,3-butadiene to butadiene diepoxide in Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Thornton-Manning, J.R.; Dahl, A.R.; Bechtold, W.E. [and others

    1995-12-01

    1,3-Butadiene (BD), a gaseous compound used in the production of rubber, is a potent carcinogen in mice and a weak carcinogen in rats. The mechanism of BD-induced carcinogenicity is thought to involve genotoxic effects of its reactive epoxide metabolites butadiene monoepoxide (BDO) and butadiene diepoxide (BDO{sub 2}). Studies in our laboratory have shown that levels of the epoxides, particularly BDO{sub 2}, are greater in mice-the more sensitive species-than rats. While both epoxides are genotoxic in a number of assays, BDO{sub 2} is mutagenic in TK6 human lymphoblastoid cells at concentrations approximately 100-fold lower than BDO. Species differences in carcinogenicity of BD have posed a dilemma to investigators deciding which animal model is most appropriate for BD risk assessment.

  11. Molecular cloning of cDNA for rat brain metallothionein-2 and regulation of its gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Saijoh, Kiyofumi; Sumino, Kimiaki [Department of Public Health, Kobe University School of Medicine (Japan); Kuno, Takayoshi; Shuntoh, Hisato; Tanaka, Chikako [Department of Pharmacology, Kobe University of Medicine (Japan)

    1989-01-01

    A rat brain metallothionein-II (MT-II) complementary DNA (cDNA) clone was isolated from a cDNA plasmid library, which was prepared from non-treated rat brain mRNA, by a colony screening procedure using /sup 32/P-labeled synthetic oligonucleotide probes. It is deduced that the clone encodes for a protein of 61 amino acids comprising 20 cysteines, which is highly homologous to MT-IIs in other species. Northern blot analysis demonstrated major mRNA species in the brain, liver and kidneys (approximately 350 b in size), which is induced in response to dexamethasone, zinc, cadmium and mercury but not to methyl mercury. These findings confirm that MT-II genes are expressed and regulated both by steroid and heavy metals in the brain as well as in peripheral organs. (author).

  12. Molecular cloning of cDNA for rat brain metallothionein-2 and regulation of its gene expression

    International Nuclear Information System (INIS)

    Saijoh, Kiyofumi; Sumino, Kimiaki; Kuno, Takayoshi; Shuntoh, Hisato; Tanaka, Chikako

    1989-01-01

    A rat brain metallothionein-II (MT-II) complementary DNA (cDNA) clone was isolated from a cDNA plasmid library, which was prepared from non-treated rat brain mRNA, by a colony screening procedure using 32 P-labeled synthetic oligonucleotide probes. It is deduced that the clone encodes for a protein of 61 amino acids comprising 20 cysteines, which is highly homologous to MT-IIs in other species. Northern blot analysis demonstrated major mRNA species in the brain, liver and kidneys (approximately 350 b in size), which is induced in response to dexamethasone, zinc, cadmium and mercury but not to methyl mercury. These findings confirm that MT-II genes are expressed and regulated both by steroid and heavy metals in the brain as well as in peripheral organs. (author)

  13. Effects of thyroid state on respiration of perfused rat and guinea pig hearts

    International Nuclear Information System (INIS)

    Read, L.C.; Wallace, P.G.; Berry, M.N.

    1987-01-01

    The effects of thyroid state on the respiration of the isolated heart were investigated using retrograde perfused rat and guinea pig hearts. In both species, hypothyroidism caused a marked depression in circulating thyroid hormone concentrations and in the respiration of the isolated, retrograde perfused heart. Hypothyroidism was caused by injecting animals with Na 131 I. The effects on myocardial respiration could be attributed to changes in the contraction frequency and in the oxygen consumption per beat, with little contribution from basal respiration. Treatment of animals with thyroxine elevated plasma thyroid hormones to a similar extent in rats and guinea pigs. In the latter, thyroxine treatment was associated with substantial increases in the contraction frequency and the oxygen consumption per beat of the isolated heart. In contrast, only small changes were apparent in the retrograde perfused rat heart, observations that were confirmed in rat hearts perfused at near physiological work loads. It was concluded that rat hearts isolated from normal animals function at near maximal thyroid state, in contrast to the guinea pig heart, which requires higher circulating concentrations of thyroid hormones to attain maximal responses

  14. Recovery of Pavlovian sign-tracking (autoshaping) following the discontinuation of inter-trial interval food in rats.

    Science.gov (United States)

    Kearns, David N; Weiss, Stanley J

    2007-07-01

    In pigeons, Pavlovian autoshaped keypecking produced by keylight-food pairings has been eliminated by introducing food during periods between CS presentations (i.e., during the inter-trial intervals). Keypecking eliminated in this manner reappears when the inter-trial USs are discontinued even though the CS is no longer paired with US. The present experiment investigated whether this recovery of responding produced by discontinuing unpaired inter-trial US presentations could be extended to another species, rats, within a Pavlovian sign-tracking paradigm. Rats were initially trained on a procedure where insertion of one retractable lever (CS(+)) was followed, response independently, with food, while insertion of another lever (CS(-)) was not paired with food. Rats quickly came to contact the CS(+) lever at high rates, but contacted the CS(-) lever infrequently. In the next phase, CS(+) was no longer followed by food. Explicitly unpaired food was presented only during the inter-trial intervals when both levers were absent. This treatment essentially eliminated the sign-tracking response. In the final phase, the unpaired inter-trial food presentations were discontinued while both CSs continued to be presented without food. This produced a significant recovery of the sign-tracking elicited by the CS(+) lever, extending the species generality of the Pavlovian resurgence phenomenon that has previously only been reported in pigeons, to rats.

  15. Altered composition of liver proteasome assemblies contributes to enhanced proteasome activity in the exceptionally long-lived naked mole-rat.

    Directory of Open Access Journals (Sweden)

    Karl A Rodriguez

    Full Text Available The longest-lived rodent, the naked mole-rat (Bathyergidae; Heterocephalus glaber, maintains robust health for at least 75% of its 32 year lifespan, suggesting that the decline in genomic integrity or protein homeostasis routinely observed during aging, is either attenuated or delayed in this extraordinarily long-lived species. The ubiquitin proteasome system (UPS plays an integral role in protein homeostasis by degrading oxidatively-damaged and misfolded proteins. In this study, we examined proteasome activity in naked mole-rats and mice in whole liver lysates as well as three subcellular fractions to probe the mechanisms behind the apparently enhanced effectiveness of UPS. We found that when compared with mouse samples, naked mole-rats had significantly higher chymotrypsin-like (ChT-L activity and a two-fold increase in trypsin-like (T-L in both whole lysates as well as cytosolic fractions. Native gel electrophoresis of the whole tissue lysates showed that the 20S proteasome was more active in the longer-lived species and that 26S proteasome was both more active and more populous. Western blot analyses revealed that both 19S subunits and immunoproteasome catalytic subunits are present in greater amounts in the naked mole-rat suggesting that the observed higher specific activity may be due to the greater proportion of immunoproteasomes in livers of healthy young adults. It thus appears that proteasomes in this species are primed for the efficient removal of stress-damaged proteins. Further characterization of the naked mole-rat proteasome and its regulation could lead to important insights on how the cells in these animals handle increased stress and protein damage to maintain a longer health in their tissues and ultimately a longer life.

  16. Multiplex PCR assay discriminates rabbit, rat and squirrel meat in food chain.

    Science.gov (United States)

    Ahamad, Mohammad Nasir Uddin; Ali, Md Eaqub; Hossain, M A Motalib; Asing, Asing; Sultana, Sharmin; Jahurul, M H A

    2017-12-01

    Rabbit meat is receiving increasing attention because it contains a high level of proteins with relatively little fat. On the other hand, squirrel meat is served in upper-class meals in certain countries, so is sold at higher prices. The other side of the coin is rat meat, which has family ties with rabbit and squirrel but poses substantial threats to public health because it is a potential carrier of several zoonotic organisms. Recently, rat meat was mislabelled and sold as lamb after chemical modification. Thus, the chances of rabbit and squirrel meat substitution by rat meat cannot be ruled out. For the first time, a multiplex PCR assay was developed in Malaysia for the discriminatory identification of rat, rabbit and squirrel in the food chain. Rabbit (123 bp), rat (108 bp) and squirrel (243 bp) targets were amplified from ATP6 and cytb genes, along with a eukaryotic internal control (141bp). The products were sequenced and cross-tested against 22 species. A total of 81 reference samples and 72 meatball specimens were screened to validate the assay. Analyte stability was evaluated through boiling, autoclaving and micro-oven cooking. The tested lower limits of detection were 0.01 ng DNA for pure meat and 0.1% for meatballs.

  17. Peripheral administration of oxytocin increases social affiliation in the naked mole-rat (Heterocephalus glaber).

    Science.gov (United States)

    Mooney, Skyler J; Douglas, Natasha R; Holmes, Melissa M

    2014-04-01

    The neuropeptide oxytocin regulates a wide variety of social behaviors across diverse species. However, the types of behaviors that are influenced by this hormone are constrained by the species in question and the social organization that a particular species exhibits. Therefore, the present experiments investigated behaviors regulated by oxytocin in a eusocial mammalian species by using the naked mole-rat (Heterocephalus glaber). In Experiment 1, adult non-breeding mole-rats were given intraperitoneal injections of either oxytocin (1mg/kg or 10mg/kg) or saline on alternate days. Animals were then returned to their colony and behavior was recorded for minutes 15-30 post-injection. Both doses of oxytocin increased huddling behavior during this time period. In Experiment 2, animals received intraperitoneal injections of either oxytocin (1mg/kg), an oxytocin-receptor antagonist (0.1mg/kg), a cocktail of oxytocin and the antagonist, or saline across 4 testing days in a counterbalanced design. Animals were placed in either a 2-chamber arena with a familiar conspecific or in a small chamber with 1week old pups from their home colony and behaviors were recorded for minutes 15-30 post-injection. Oxytocin increased investigation of, and time spent in close proximity to, a familiar conspecific; these effects were blocked by the oxytocin antagonist. No effects were seen on pup-directed behavior. These data suggest that oxytocin is capable of modulating affiliative-like behavior in this eusocial species. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Multiplex PCR assay for the detection of five meat species forbidden in Islamic foods.

    Science.gov (United States)

    Ali, Md Eaqub; Razzak, Md Abdur; Hamid, Sharifah Bee Abd; Rahman, Md Mahfujur; Amin, Md Al; Rashid, Nur Raifana Abd; Asing

    2015-06-15

    Food falsification has direct impact on public health, religious faith, fair-trades and wildlife. For the first time, here we described a multiplex polymerase chain reaction assay for the accurate identification of five meat species forbidden in Islamic foods in a single assay platform. Five pairs of species-specific primers were designed targeting mitochondrial ND5, ATPase 6, and cytochrome b genes to amplify 172, 163, 141, 129 and 108 bp DNA fragments from cat, dog, pig, monkey and rat meats, respectively. All PCR products were identified in gel-images and electrochromatograms obtained from Experion Bioanalyzer. Species-specificity checking against 15 important meat and fish and 5 plant species detected no cross-species amplification. Screening of target species in model and commercial meatballs reflected its application to detect target species in process foods. The assay was tested to detect 0.01-0.02 ng DNA under raw states and 1% suspected meats in meatball formulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Subcellular distribution of Pu-239 in the liver of rat, mouse, Syrian and Chinese hamster

    International Nuclear Information System (INIS)

    Winter, R.; Seidel, A.

    1980-01-01

    The aim of our studies was to elucidate the biochemical mechanisms responsible for the differences in the biological half life of actinides in the liver of different mammalian species. Rats and mice were chosen as models for rapid elimination, and Syrian and Chinese hamsters as models for slow elimination. To distinguish between fixation in lysosomes and mitochondria, the lysosomes were isolated following injection of Triton WR1339 6 days after 239 Pu administration. The animals were sacrificed 4 days later. In order to study the possible association with ferritin, 59 Fe was also injected. Liver homogenates were subjected to differential and isopycnic centrifugation in a sucrose density gradient. The typical shift in the density of the lysosomal marker acid phosphatase from rho approximately 1.2 to rho approximately 1.1 following Triton WR1339 injection was observed in all species. It was possible therefore to separate lysosomes from other cell organelles, especially mitochondria. It was concluded that: 1) Mitochondria can virtually be excluded as binding sites in all four species; 2) Lysosomes are one important storage site in rats, mice and Syrian hamsters; 3) If 239 Pu is bound to another cell constituent in addition to lysosomes in the hamster species (which is not yet proven) its density should be approximately 1.17. (H.K.)

  20. Modeling the systemic retention of beryllium in rat. Extrapolation to human

    International Nuclear Information System (INIS)

    Montero Prieto, M.; Vidania Munoz, R. de

    1994-01-01

    In this work, we analyzed different approaches, assayed in order to numerically describe the systemic behaviour of Beryllium. The experimental results used in this work, were previously obtained by Furchner et al. (1973), using Sprague-Dawley rats, and others animal species. Furchner's work includes the obtained model for whole body retention in rats, but not for each target organ. In this work we present the results obtained by modeling the kinetic behaviour of Beryllium in several target organs. The results of this kind of models were used in order to establish correlations among the estimated kinetic constants. The parameters of the model were extrapolated to humans and, finally, compared with others previously published. (Author) 12 refs

  1. Modeling of systematic retention of beryllium in rats. Extrapolation to humans

    International Nuclear Information System (INIS)

    Montero Prieto, M.; Vidania Munoz, R. de.

    1994-01-01

    In this work, we analyzed different approaches, assayed in order to numerically describe the systemic behaviour of Beryllium. The experimental results used in this work, were previously obtained by Furchner et al. (1973), using Sprague-Dawley rats, and other animal species. Furchner's work includes the obtained model for whole body retention in rats but not for each target organ. In this work we present the results obtained by modeling the kinetic behaviour of Beryllium in several target organs. The results of this kind of models were used in order to establish correlations among the estimated kinetic constants. The parameters of the model were extrapolated to humans and, finally, compared with other previously published

  2. Investigation of the Blood Glucose Lowering Potential of the Jamaican Momordica charantia (Cerasee) Fruit in Sprague-Dawley Rats

    Science.gov (United States)

    Burnett, A; McKoy, M-L; Singh, P

    2015-01-01

    ABSTRACT The Momordica charantia (MC) fruit has been documented to possess antidiabetic properties. However, these studies were not without controversy surrounding the blood glucose-lowering ability and the mechanism of action in diabetes therapy. In an effort to evaluate such claims in the Jamaican MC species known as cerasee, aqueous extracts of the unripe fruit were studied in normal and diabetic rats. Normal male Sprague-Dawley rats were divided into groups (n = 6) orally administered distilled water, 10% dimethyl sulfoxide (DMSO) solution, the aqueous extract (400 mg/kg body weight) and glibenclamide (15 mg/kg body weight), respectively prior to assessment of fasting blood glucose (FBG) concentration. The oral glucose tolerance test (OGTT) was conducted in normoglycaemic rats orally administered distilled water, 10% DMSO solution, glibenclamide (15 mg/kg body weight) or aqueous extracts of the fruit (200 and 400 mg/kg body weight). Blood glucose concentration was also monitored in streptozotocin-induced diabetic rats administered the aqueous extract (250 mg/kg body weight) or water vehicle after an overnight fast. The aqueous extracts showed no hypoglycaemic or antidiabetic activity. However, the administration of the aqueous extracts (200 and 400 mg/kg body weight) resulted in significant improvement in glucose tolerance of glucose-primed normoglycaemic rats during the OGTT. These data suggest that the glucose-lowering mechanism of the Jamaican MC fruit species likely involves altered glucose absorption across the gastrointestinal tract. PMID:26624580

  3. Species and Sex Differences in the Morphogenic Response of Primary Rodent Neurons to 3,3'-Dichlorobiphenyl (PCB 11).

    Science.gov (United States)

    Sethi, Sunjay; Keil, Kimberly P; Lein, Pamela J

    2017-12-23

    PCB 11 is an emerging global pollutant that we recently showed promotes axonal and dendritic growth in primary rat neuronal cell cultures. Here, we address the influence of sex and species on neuronal responses to PCB 11. Neuronal morphology was quantified in sex-specific primary hippocampal and cortical neuron-glia co-cultures derived from neonatal C57BL/6J mice and Sprague Dawley rats exposed for 48 h to vehicle (0.1% DMSO) or PCB 11 at concentrations ranging from 1 fM to 1 nM. Total axonal length was quantified in tau-1 immunoreactive neurons at day in vitro (DIV) 2; dendritic arborization was assessed by Sholl analysis at DIV 9 in neurons transfected with MAP2B-FusRed. In mouse cultures, PCB 11 enhanced dendritic arborization in female, but not male, hippocampal neurons and male, but not female, cortical neurons. In rat cultures, PCB 11 promoted dendritic arborization in male and female hippocampal and cortical neurons. PCB 11 also increased axonal growth in mouse and rat neurons of both sexes and neuronal cell types. These data demonstrate that PCB 11 exerts sex-specific effects on neuronal morphogenesis that vary depending on species, neurite type, and neuronal cell type. These findings have significant implications for risk assessment of this emerging developmental neurotoxicant.

  4. Edaravone injection reverses learning and memory deficits in a rat model of vascular dementia.

    Science.gov (United States)

    Li, Xu; Lu, Fen; Li, Wei; Qin, Lingzhi; Yao, Yong; Ge, Xuerong; Yu, Qingkai; Liang, Xinliang; Zhao, Dongmei; Li, Xiaohong; Zhang, Jiewen

    2017-01-01

    Edaravone is a novel free radical scavenger that exerts neuroprotective effects by inhibiting endothelial injury and by ameliorating neuronal damage in brain ischemia. Recently, it was reported that edaravone could alleviate the pathology and cognitive deficits of Alzheimer's disease patients. However, its relevance to vascular dementia (VaD) is not clear. In this study, we partially occluded the bilateral carotid arteries of rats surgically to induce chronic cerebral hypoperfusion (CCH), a well-known rat model of VaD. Water maze and step-down inhibitory test were used to evaluate the memory deficit. The activities of superoxide dismutase (SOD) and lactate dehydrogenase (LDH), the content of malondialdehyde (MDA) and total reactive oxygen species were measured to evaluate the oxidative stress level. Western blot analysis was used to evaluate the synaptic protein expression. It was found that treatment with edaravone for a 5-week period was able to reverse both spatial and fear-memory deficits in rats with CCH. Edaravone significantly reduced the level of oxidative stress in the brains of rats with CCH by increasing SOD activity and decreasing the content of MDA, LDH, and total reactive oxygen species. Furthermore, edaravone treatment also restored the levels of multiple synaptic proteins in the hippocampi of rats with CCH. Our data provide direct evidence supporting the neuroprotective effects of edaravone in VaD. We propose that the alleviation of oxidative stress and restoration of synaptic proteins play important roles in neuroprotection. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Notes on the impact of the black rat (Rattus rattus L.) on the flora and fauna of Fungus Rock (Gozo, Maltese Islands)

    OpenAIRE

    Sciberras, Arnold; Lalov, Sdravko Vesselinov

    2007-01-01

    Recently the presence of the black rat Rattus rattus was reported from the island of Fungus Rock which houses a remarkable flora and fauna and has been a protected site for over 250 years. A preliminary account of the rat's impact on some Fungus Rock species is given and threats to the island's ecosystem are discussed.

  6. Do rats have orgasms?

    Science.gov (United States)

    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

  7. Do rats have orgasms?

    Directory of Open Access Journals (Sweden)

    James G. Pfaus

    2016-10-01

    Full Text Available 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.

  8. The influence of starvation upon hepatic drug metabolism in rats, mice, and guinea pigs.

    Science.gov (United States)

    Furner, R. L.; Feller, D. D.

    1971-01-01

    Male rats, mice, and guinea pigs were starved for 1, 2, or 3 days, and the metabolism of ethylmorphine, p-nitroanisole, and aniline was studied. Results suggest that the oxidative enzyme systems studied are not interdependent, and the pathways studied appear to be species dependent.

  9. Inhaled /sup 239/PuO/sub 2/ and/or total-body gamma radiation: Early mortality and morbidity in rats and dogs

    Energy Technology Data Exchange (ETDEWEB)

    Filipy, R.E.; Decker, J.R.; Lai, Y.L.; Lauhala, K.E.; Buschbom, R.L.; Hiastala, M.P.; McGee, D.R.; Park, J.F.; Kuffel, E.G.; Ragan, H.A.; Cannon, W.C.; Yaniv, S.S.; Scott, B.R.

    1988-08-01

    Rats and beagle dogs were given doses of /sup 60/Co gamma radiation and/or body burdens of /sup 239/PuO/sub 2/ within lethal ranges in an experiment to determine and compare morbidity and mortality responses of both species within 1 year after exposure. Radiation-induced morbidity was assessed by measuring changes in body weights, hematologic parameters, and pulmonary-function parameters. Gamma radiation caused transient morbidity, reflected by immediately depressed blood cell concentrations and by long-term loss of body weight and diminished pulmonary function in animals of both species that survived the acute gamma radiation syndrome. Inhaled plutonium caused a loss of body weight and diminished pulmonary function in both species, but its only effect on blood cell concentrations was lymphocytopenia in dogs. Combined gamma irradiation and plutonium lung burdens were synergistic, in that animals receiving both radiation insults had higher morbidity and mortality rates than would be predicted based on the effect of either kind of radiation alone. Plutonium lung burdens enhanced the effect of gamma radiation in rats within the first 30 days of exposure, and gamma radiation enhanced the long-term effect of plutonium lung burdens in both species. Rats were less sensitive to both kinds of radiation, whether administered alone or in combination. 71 refs., 105 figs., 48 tabs.

  10. Exercise training prevents the attenuation of anesthetic pre-conditioning-mediated cardioprotection in diet-induced obese rats.

    Science.gov (United States)

    Li, L; Meng, F; Li, N; Zhang, L; Wang, J; Wang, H; Li, D; Zhang, X; Dong, P; Chen, Y

    2015-01-01

    Obesity abolishes anesthetic pre-conditioning-induced cardioprotection due to impaired reactive oxygen species (ROS)-mediated adenosine monophosphate-activated protein kinase (AMPK) pathway, a consequence of increased basal myocardial oxidative stress. Exercise training has been shown to attenuate obesity-related oxidative stress. This study tests whether exercise training could normalize ROS-mediated AMPK pathway and prevent the attenuation of anesthetic pre-conditioning-induced cardioprotection in obesity. Male Sprague-Dawley rats were divided into lean rats fed with control diet and obese rats fed with high-fat diet. After 4 weeks of feeding, lean and obese rats were assigned to sedentary conditions or treadmill exercise for 8 weeks. There was no difference in infarct size between lean sedentary and obese sedentary rats after 25 min of myocardial ischemia followed by 120 min reperfusion. In lean rats, sevoflurane equally reduced infarct size in lean sedentary and lean exercise-trained rats. Molecular studies revealed that AMPK activity, endothelial nitric oxide synthase, and superoxide production measured at the end of ischemia in lean rats were increased in response to sevoflurane. In obese rats, sevoflurane increased the above molecular parameters and reduced infarct size in obese exercise-trained rats but not in obese sedentary rats. Additional study showed that obese exercise-trained rats had decreased basal oxidative stress than obese sedentary rats. The results indicate that exercise training can prevent the attenuation of anesthetic cardioprotection in obesity. Preventing the attenuation of this strategy may be associated with reduced basal oxidative stress and normalized ROS-mediated AMPK pathway, but the causal relationship remains to be determined. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  11. Blunted behavioral and c Fos responses to acidic fumes in the African naked mole-rat.

    Science.gov (United States)

    LaVinka, Pamela Colleen; Park, Thomas J

    2012-01-01

    Acidosis in the skin triggers activation of pain pathways and behaviors indicative of pain in vertebrates. The exception is the naked mole-rat, the only known vertebrate to show physiological and behavioral insensitivity to acid pain in the skin. The goal of the present study was to determine behavioral and physiological responses of this species to airborne acidic fumes, which would be expected to affect the trigeminal pain pathway in other species. Behaviorally, naked mole-rats did not avoid fumes from moderately high concentrations of acetic acid (10 and 20%), and c Fos labeling showed no increase in activity in the trigeminal nuclei and nucleus tractus solitarius. In contrast, these concentrations triggered behavioral aversion and increased Fos activity in other laboratory rodents. For a very high concentration of acetic acid (50%), naked mole-rats showed significant avoidance behavior and increased Fos labeling in the nucleus tractus solitarius caudal region, which receives vagal chemosensory information. However, there was no increase in trigeminal labeling, and in fact, activity significantly decreased. This pattern is opposite of that associated with another irritant, ammonia fumes, which elicited an increase in trigeminal but not nucleus tractus solitarius Fos labeling, and no behavioral avoidance. Behavioral avoidance of acidic fumes, but no increased labeling in the trigeminal pain nucleus is consistent with the notion of adaptations to blunt acid pain, which would be advantageous for naked mole-rats as they normally live under chronically high levels of acidosis-inducing CO(2).

  12. Blunted behavioral and c Fos responses to acidic fumes in the African naked mole-rat.

    Directory of Open Access Journals (Sweden)

    Pamela Colleen LaVinka

    Full Text Available Acidosis in the skin triggers activation of pain pathways and behaviors indicative of pain in vertebrates. The exception is the naked mole-rat, the only known vertebrate to show physiological and behavioral insensitivity to acid pain in the skin. The goal of the present study was to determine behavioral and physiological responses of this species to airborne acidic fumes, which would be expected to affect the trigeminal pain pathway in other species. Behaviorally, naked mole-rats did not avoid fumes from moderately high concentrations of acetic acid (10 and 20%, and c Fos labeling showed no increase in activity in the trigeminal nuclei and nucleus tractus solitarius. In contrast, these concentrations triggered behavioral aversion and increased Fos activity in other laboratory rodents. For a very high concentration of acetic acid (50%, naked mole-rats showed significant avoidance behavior and increased Fos labeling in the nucleus tractus solitarius caudal region, which receives vagal chemosensory information. However, there was no increase in trigeminal labeling, and in fact, activity significantly decreased. This pattern is opposite of that associated with another irritant, ammonia fumes, which elicited an increase in trigeminal but not nucleus tractus solitarius Fos labeling, and no behavioral avoidance. Behavioral avoidance of acidic fumes, but no increased labeling in the trigeminal pain nucleus is consistent with the notion of adaptations to blunt acid pain, which would be advantageous for naked mole-rats as they normally live under chronically high levels of acidosis-inducing CO(2.

  13. Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

    International Nuclear Information System (INIS)

    Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

    2009-01-01

    Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

  14. IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function.

    Science.gov (United States)

    Pardo, Joaquín; Abba, Martin C; Lacunza, Ezequiel; Ogundele, Olalekan M; Paiva, Isabel; Morel, Gustavo R; Outeiro, Tiago F; Goya, Rodolfo G

    2018-03-14

    In rats, learning and memory performance decline during normal aging, which makes this rodent species a suitable model to evaluate therapeutic strategies. In aging rats, insulin-like growth factor-I (IGF-I), is known to significantly improve spatial memory accuracy as compared to control counterparts. A constellation of gene expression changes underlie the hippocampal phenotype of aging but no studies on the effects of IGF-I on the hippocampal transcriptome of old rodents have been documented. Here, we assessed the effects of IGF-I gene therapy on spatial memory performance in old female rats and compared them with changes in the hippocampal transcriptome. In the Barnes maze test, experimental rats showed a significantly higher exploratory frequency of the goal hole than controls. Hippocampal RNA-sequencing showed that 219 genes are differentially expressed in 28-month-old rats intracerebroventricularly injected with an adenovector expressing rat IGF-I as compared with placebo adenovector-injected counterparts. From the differentially expressed genes, 81 were down and 138 upregulated. From those genes, a list of functionally relevant genes, concerning hippocampal IGF-I expression, synaptic plasticity as well as neuronal function was identified. Our results provide an initial glimpse at the molecular mechanisms underlying the neuroprotective actions of IGF-I in the aging brain.

  15. Ameliorative effect of the sea cucumber Holothuria arenicola extract against gastric ulcer in rats

    Directory of Open Access Journals (Sweden)

    Sohair R. Fahmy

    2015-10-01

    Full Text Available Holothuria arenicola is the most important and abundant sea cucumber species in the Mediterranean Sea on the Egyptian coast. This work aimed to investigate the prophylactic and the curative effects of H. arenicola extract HaE (200 mg/kg on gastric mucosal damage following indomethacin and cold stress in healthy rats. Sixty-four rats were randomly divided into four main groups. Rats of the first group (8 rats/group were administered distilled water orally (control group, rats of the second group (8 rats/group were administered single oral dose of indomethacin (150 mg/kg and exposed to cold stress (4 ± 1 °C for 30 min to induce gastric ulcer (GU model (ulcer group, rats of the third group, prophylactic group (24 rats/group were treated with HaE and/or ranitidine (RAN and then exposed to GU and rats of the fourth group, curative group (24 rats/group were exposed firstly to GU and then treated with HaE and/or RAN. The results clearly indicate that pre-treatment with HaE and/or ranitidine significantly decreases the ulcer index, showing 72.50%, 53.11% and 80.56% ulceration inhibition, respectively. However, post-treatment with HaE and/or ranitidine significantly decreases the ulcer index, showing 51.66%, 62.41% and 67.78% ulceration inhibition, respectively. The results also showed that pre and post-treatment with HaE and/or RAN significantly decreased gastric malondialdehyde (MDA level and enhanced reduced glutathione (GSH, catalase (CAT, glutathione-S-transferase (GST and superoxide dismutase (SOD levels. The results clearly indicate that pre-treatment with HaE is preferable.

  16. Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats.

    Science.gov (United States)

    Valladares, Ricardo; Sankar, Dhyana; Li, Nan; Williams, Emily; Lai, Kin-Kwan; Abdelgeliel, Asmaa Sayed; Gonzalez, Claudio F; Wasserfall, Clive H; Larkin, Joseph; Schatz, Desmond; Atkinson, Mark A; Triplett, Eric W; Neu, Josef; Lorca, Graciela L

    2010-05-06

    The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development. Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat). In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNgamma were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin. It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in BioBreeding diabetes prone rats. Taken collectively, these data

  17. Plasma cholinesterase activity of rats, western grey kangaroos, alpacas, sheep, cattle, and horses.

    Science.gov (United States)

    Mayberry, Chris; Mawson, Peter; Maloney, Shane K

    2015-01-01

    Plasma cholinesterase activity levels of various species may be of interest to toxicologists or pathologists working with chemicals that interfere with the activity of plasma cholinesterase. We used a pH titration method to measure the plasma cholinesterase activity of six mammalian species. Plasma cholinesterase activity varied up to 50-fold between species: sheep (88 ± 45 nM acetylcholine degraded per ml of test plasma per minute), cattle (94 ± 35), western grey kangaroos (126 ± 92), alpaca (364 ± 70), rats (390 ± 118) and horses (4539 ± 721). We present a simple, effective technique for the assay of plasma cholinesterase activity levels from a range of species. Although labour-intensive, it requires only basic laboratory equipment. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Comparative Metabolism Study of Five Protoberberine Alkaloids in Liver Microsomes from Rat, Rhesus Monkey, and Human.

    Science.gov (United States)

    Li, Yan; Zhou, Yanyan; Si, Nan; Han, Lingyu; Ren, Wei; Xin, Shaokun; Wang, Hongjie; Zuo, Ran; Wei, Xiaolu; Yang, Jian; Zhao, Haiyu; Bian, Baolin

    2017-11-01

    Protoberberine alkaloids including berberine, palmatine, jatrorrhizine, coptisine, and epiberberine are major components in many medicinal plants. They have been widely used for the treatment of cancer, inflammation, diabetes, depression, hypertension, and various infectious areas. However, the metabolism of five protoberberine alkaloids among different species has not been clarified previously. In order to elaborate on the in vitro metabolism of them, a comparative analysis of their metabolic profile in rat, rhesus monkey, and human liver microsomes was carried out using ultrahigh-performance liquid chromatography coupled with a high-resolution linear trap quadrupole-Orbitrap mass spectrometer (UHPLC-electrospray ionization-Orbitrap MS) for the first time. Each metabolite was identified and semiquantified by its accurate mass data and peak area. Fifteen metabolites were characterized based on accurate MS/MS spectra and the proposed MS/MS fragmentation pathways including demethylation, hydroxylation, and methyl reduction. Among them, the content of berberine metabolites in human liver microsomes was similar with those in rhesus monkey liver microsomes, whereas berberine in rat liver microsomes showed no demethylation metabolites and the content of metabolites showed significant differences with that in human liver microsomes. On the contrary, the metabolism of palmatine in rat liver microsomes resembled that in human liver microsomes. The content of jatrorrhizine metabolites presented obvious differences in all species. The HR-ESI-MS/MS fragmentation behavior of protoberberine alkaloids and their metabolic profile in rat, rhesus monkey, and human liver microsomes were investigated for the first time. The results demonstrated that the biotransformation characteristics of protoberberine alkaloids among different species had similarities as well differences that would be beneficial for us to better understand the pharmacological activities of protoberberine alkaloids

  19. Oxidative Stress in the Developing Rat Brain due to Production of Reactive Oxygen and Nitrogen Species

    Czech Academy of Sciences Publication Activity Database

    Wilhelm, Jiří; Vytášek, Richard; Uhlík, Jiří; Vajner, Luděk

    2016-01-01

    Roč. 2016, č. 2016 (2016), č. článku 5057610. ISSN 1942-0900 R&D Projects: GA ČR(CZ) GAP303/11/0298 Institutional support: RVO:67985823 Keywords : oxidative stress * developing rat brain * lipid peroxidation Subject RIV: ED - Physiology Impact factor: 4.593, year: 2016

  20. Lignans from Opuntia ficus-indica seeds protect rat primary hepatocytes and HepG2 cells against ethanol-induced oxidative stress.

    Science.gov (United States)

    Kim, Jung Wha; Yang, Heejung; Kim, Hyeon Woo; Kim, Hong Pyo; Sung, Sang Hyun

    2017-01-01

    Bioactivity-guided isolation of Opuntia ficus-indica (Cactaceae) seeds against ethanol-treated primary rat hepatocytes yielded six lignan compounds. Among the isolates, furofuran lignans 4-6, significantly protected rat hepatocytes against ethanol-induced oxidative stress by reducing intracellular reactive oxygen species levels, preserving antioxidative defense enzyme activities, and maintaining the glutathione content. Moreover, 4 dose-dependently induced the heme oxygenase-1 expression in HepG2 cells.

  1. Natural β-carotene and whole body irradiation in rats

    International Nuclear Information System (INIS)

    Ben-Amotz, A.; Rachmilevich, B.; Greenberg, S.; Sela, M.; Weshler, Z.

    1996-01-01

    β-Carotene and other carotenoids are reported to be potent free radical quenchers, singlet oxygen scavengers, and lipid antioxidants. Whole-body irradiation is known to cause an immunosuppression effect in mammals through the possible initiation and production of reactive oxygen species. We decided to test the possible antioxidative effect against whole-body irradiation of a natural β-carotene, composed of equal amounts of the all-trans and 9-cis isomers, obtained from the unicellular alga Dunaliella bardawil. Rats were fed on ground commercial food enriched with natural β-carotene (50 mg/kg diet). On completion of 1 week with β-carotene, the rats were exposed to a single dose of 4 Gy whole-body irradiation, after which their livers and blood were removed for β-carotene and retinol analysis in comparison with control livers of animals irradiated or not, or supplemented with β-carotene after irradiation. A normal increase in body weight with no ill effects was noted in the groups of rats whose diet was supplemented by β-carotene before and after irradiation, compared with the reduction in the specific growth rate in the group of rats irradiated without β-carotene. Liver β-carotene and retinol decreased significantly after irradiation compared with the rats which were not irradiated. This decrease was not shown in rats fed β-carotene prior to irradiation, and the effect of irradiation was partially cured by supplementation with β-carotene after irradiation. High-pressure liquid chromatography (HPLC) analysis of the irradiated animals showed a selective decline in 9-cis β-carotene and in retinol over all-trans β-carotene and retinyl esters. These results suggest that 9-cis β-carotene and retinol protect in vivo against the cellular damage by free radicals induced after whole-body irradiation. (orig.). With 1 fig., 2 tabs

  2. From ratites to rats: the size of fleshy fruits shapes species' distributions and continental rainforest assembly.

    Science.gov (United States)

    Rossetto, Maurizio; Kooyman, Robert; Yap, Jia-Yee S; Laffan, Shawn W

    2015-12-07

    Seed dispersal is a key process in plant spatial dynamics. However, consistently applicable generalizations about dispersal across scales are mostly absent because of the constraints on measuring propagule dispersal distances for many species. Here, we focus on fleshy-fruited taxa, specifically taxa with large fleshy fruits and their dispersers across an entire continental rainforest biome. We compare species-level results of whole-chloroplast DNA analyses in sister taxa with large and small fruits, to regional plot-based samples (310 plots), and whole-continent patterns for the distribution of woody species with either large (more than 30 mm) or smaller fleshy fruits (1093 taxa). The pairwise genomic comparison found higher genetic distances between populations and between regions in the large-fruited species (Endiandra globosa), but higher overall diversity within the small-fruited species (Endiandra discolor). Floristic comparisons among plots confirmed lower numbers of large-fruited species in areas where more extreme rainforest contraction occurred, and re-colonization by small-fruited species readily dispersed by the available fauna. Species' distribution patterns showed that larger-fruited species had smaller geographical ranges than smaller-fruited species and locations with stable refugia (and high endemism) aligned with concentrations of large fleshy-fruited taxa, making them a potentially valuable conservation-planning indicator. © 2015 The Author(s).

  3. The effects of oxotremorine, epibatidine, atropine, mecamylamine and naloxone in the tail-flick, hot-plate, and formalin tests in the naked mole-rat (Heterocephalus glaber)

    DEFF Research Database (Denmark)

    Dulu, Thomas D; Kanui, Titus I; Towett, Philemon K

    2014-01-01

    The naked mole-rat (Heterocephalus glaber) is a promising animal model for the study of pain mechanisms, therefore a thorough characterization of this species is essential. The aim of the present study was to establish the naked mole-rat as a model for studying the cholinergic receptor system in ...

  4. Low sulfide levels and a high degree of cystathionine β-synthase (CBS) activation by S-adenosylmethionine (SAM) in the long-lived naked mole-rat.

    Science.gov (United States)

    Dziegelewska, Maja; Holtze, Susanne; Vole, Christiane; Wachter, Ulrich; Menzel, Uwe; Morhart, Michaela; Groth, Marco; Szafranski, Karol; Sahm, Arne; Sponholz, Christoph; Dammann, Philip; Huse, Klaus; Hildebrandt, Thomas; Platzer, Matthias

    2016-08-01

    Hydrogen sulfide (H2S) is a gaseous signalling molecule involved in many physiological and pathological processes. There is increasing evidence that H2S is implicated in aging and lifespan control in the diet-induced longevity models. However, blood sulfide concentration of naturally long-lived species is not known. Here we measured blood sulfide in the long-lived naked mole-rat and five other mammalian species considerably differing in lifespan and found a negative correlation between blood sulfide and maximum longevity residual. In addition, we show that the naked mole-rat cystathionine β-synthase (CBS), an enzyme whose activity in the liver significantly contributes to systemic sulfide levels, has lower activity in the liver and is activated to a higher degree by S-adenosylmethionine compared to other species. These results add complexity to the understanding of the role of H2S in aging and call for detailed research on naked mole-rat transsulfuration. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Conserved repertoire of orthologous vomeronasal type 1 receptor genes in ruminant species

    Directory of Open Access Journals (Sweden)

    Okamura Hiroaki

    2009-09-01

    Full Text Available Abstract Background In mammals, pheromones play an important role in social and innate reproductive behavior within species. In rodents, vomeronasal receptor type 1 (V1R, which is specifically expressed in the vomeronasal organ, is thought to detect pheromones. The V1R gene repertoire differs dramatically between mammalian species, and the presence of species-specific V1R subfamilies in mouse and rat suggests that V1R plays a profound role in species-specific recognition of pheromones. In ruminants, however, the molecular mechanism(s for pheromone perception is not well understood. Interestingly, goat male pheromone, which can induce out-of-season ovulation in anestrous females, causes the same pheromone response in sheep, and vice versa, suggesting that there may be mechanisms for detecting "inter-species" pheromones among ruminant species. Results We isolated 23 goat and 21 sheep intact V1R genes based on sequence similarity with 32 cow V1R genes in the cow genome database. We found that all of the goat and sheep V1R genes have orthologs in their cross-species counterparts among these three ruminant species and that the sequence identity of V1R orthologous pairs among these ruminants is much higher than that of mouse-rat V1R orthologous pairs. Furthermore, all goat V1Rs examined thus far are expressed not only in the vomeronasal organ but also in the main olfactory epithelium. Conclusion Our results suggest that, compared with rodents, the repertoire of orthologous V1R genes is remarkably conserved among the ruminants cow, sheep and goat. We predict that these orthologous V1Rs can detect the same or closely related chemical compound(s within each orthologous set/pair. Furthermore, all identified goat V1Rs are expressed in the vomeronasal organ and the main olfactory epithelium, suggesting that V1R-mediated ligand information can be detected and processed by both the main and accessory olfactory systems. The fact that ruminant and rodent V1Rs

  6. What the laboratory rat has taught us about social play behavior: role in behavioral development and neural mechanisms.

    Science.gov (United States)

    Vanderschuren, Louk J M J; Trezza, Viviana

    2014-01-01

    Social play behavior is the most vigorous and characteristic form of social interaction displayed by developing mammals. The laboratory rat is an ideal species to study this behavior, since it shows ample social play that can be easily recognized and quantified. In this chapter, we will first briefly describe the structure of social play behavior in rats. Next, we will discuss studies that used social isolation rearing during the period in life when social play is most abundant to investigate the developmental functions of social play behavior in rats, focusing on the consequences of play deprivation on social, cognitive, emotional, and sensorimotor development. Last, we will discuss the neural substrates of social play behavior in rats, with emphasis on the limbic corticostriatal circuits that underlie emotions and their influence on behavior.

  7. Comprehensive identification of age-related lipidome changes in rat amygdala during normal aging.

    Directory of Open Access Journals (Sweden)

    Roman Šmidák

    Full Text Available Brain lipids are integral components of brain structure and function. However, only recent advancements of chromatographic techniques together with mass spectrometry allow comprehensive identification of lipid species in complex brain tissue. Lipid composition varies between the individual areas and the majority of previous reports was focusing on individual lipids rather than a lipidome. Herein, a mass spectrometry-based approach was used to evaluate age-related changes in the lipidome of the rat amygdala obtained from young (3 months and old (20 months males of the Sprague-Dawley rat strain. A total number of 70 lipid species with significantly changed levels between the two animal groups were identified spanning four main lipid classes, i.e. glycerolipids, glycerophospholipids, sphingolipids and sterol lipids. These included phospholipids with pleiotropic brain function, such as derivatives of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine. The analysis also revealed significant level changes of phosphatidic acid, diacylglycerol, sphingomyelin and ceramide that directly represent lipid signaling and affect amygdala neuronal activity. The amygdala is a crucial brain region for cognitive functions and former studies on rats and humans showed that this region changes its activity during normal aging. As the information on amygdala lipidome is very limited the results obtained in the present study represent a significant novelty and may contribute to further studies on the role of lipid molecules in age-associated changes of amygdala function.

  8. Species-Specific Expression of Full-Length and Alternatively Spliced Variant Forms of CDK5RAP2.

    Directory of Open Access Journals (Sweden)

    John S Y Park

    Full Text Available CDK5RAP2 is one of the primary microcephaly genes that are associated with reduced brain size and mental retardation. We have previously shown that human CDK5RAP2 exists as a full-length form (hCDK5RAP2 or an alternatively spliced variant form (hCDK5RAP2-V1 that is lacking exon 32. The equivalent of hCDK5RAP2-V1 has been reported in rat and mouse but the presence of full-length equivalent hCDK5RAP2 in rat and mouse has not been examined. Here, we demonstrate that rat expresses both a full length and an alternatively spliced variant form of CDK5RAP2 that are equivalent to our previously reported hCDK5RAP2 and hCDK5RAP2-V1, repectively. However, mouse expresses only one form of CDK5RAP2 that is equivalent to the human and rat alternatively spliced variant forms. Knowledge of this expression of different forms of CDK5RAP2 in human, rat and mouse is essential in selecting the appropriate model for studies of CDK5RAP2 and primary microcephaly but our findings further indicate the evolutionary divergence of mouse from the human and rat species.

  9. Characterization of xenogeneic mouse-to-rat bone marrow chimeras. I. Examination of hematologic and immunologic function

    International Nuclear Information System (INIS)

    Wade, A.C.; Luckert, P.H.; Tazume, S.; Niedbalski, J.L.; Pollard, M.

    1987-01-01

    Eighteen xenogeneic chimeric rats (survival: greater than 100 days) were established by transplanting bone marrow cells from femurs of 10 gnotobiotic CFW mice into each germfree Sprague-Dawley or Wistar rat. The erythrocytes circulating in the rats were of mouse origin as determined by hemagglutination. Hemoglobin electrophoresis, radial immunodiffusion for IgG, and assay of granulocytic neutrophils for leukocyte alkaline phosphatase verified that true chimerism was achieved. The extent of hematological and immunological reconstitution varied. In general, hematocrit levels were low to normal, white blood cell counts and differentials were within normal limits, and serum protein levels were normal. Levels of circulating IgG of each species were comparable to those of germfree rat and mouse controls. Natural killer (NK) activity was depressed, a phenomenon that may be attributable to the radiation treatment of recipients, or to failure to transfer NK cells or precursors. Mitogenic stimulation reactions were varied, but most chimeric rats demonstrated moderately depressed responses. Reactions as a whole suggested that gnotobiotic rats with xenogeneic bone marrow are incompletely reconstituted, both hematologically and immunologically. No acute graft-versus-host reaction was seen

  10. Clear Evidence of Carcinogenic Activity by a Whole-Leaf Extract of Aloe barbadensis Miller (Aloe vera) in F344/N Rats

    Science.gov (United States)

    Boudreau, Mary D.

    2013-01-01

    Aloe barbadensis Miller (Aloe vera) is an herbal remedy promoted to treat a variety of illnesses; however, only limited data are available on the safety of this dietary supplement. Drinking water exposure of F344/N rats and B6C3F1 mice to an Aloe vera whole-leaf extract (1, 2, and 3%) for 13 weeks resulted in goblet cell hyperplasia of the large intestine in both species. Based upon this observation, 2-year drinking water studies were conducted to assess the carcinogenic potential of an Aloe vera whole-leaf extract when administered to F344/N rats (48 per sex per group) at 0.5, 1, and 1.5%, and B6C3F1 mice (48 per sex per group) at 1, 2, and 3%. Compared with controls, survival was decreased in the 1.5% dose group of female rats. Treatment-related neoplasms and nonneoplastic lesions in both species were confined primarily to the large intestine. Incidences of adenomas and/or carcinomas of the ileo-cecal and cecal-colic junction, cecum, and ascending and transverse colon were significantly higher than controls in male and female rats in the 1 and 1.5% dose groups. There were no neoplasms of the large intestine in mice or in the 0 or 0.5% dose groups of rats. Increased incidences of mucosa hyperplasia of the large intestine were observed in F344/N rats, and increased incidences of goblet cell hyperplasia of the large intestine occurred in B6C3F1 mice. These results indicate that Aloe vera whole-leaf extract is an intestinal irritant in F344/N rats and B6C3F1 mice and a carcinogen of the large intestine in F344/N rats. PMID:22968693

  11. Disparate patterns of age-related changes in lipid peroxidation in long-lived naked mole-rats and shorter-lived mice.

    Science.gov (United States)

    Andziak, Blazej; Buffenstein, Rochelle

    2006-12-01

    A key tenet of the oxidative stress theory of aging is that levels of accrued oxidative damage increase with age. Differences in damage generation and accumulation therefore may underlie the natural variation in species longevity. We compared age-related profiles of whole-organism lipid peroxidation (urinary isoprostanes) and liver lipid damage (malondialdehyde) in long living naked mole-rats [maximum lifespan (MLS) > 28.3 years] and shorter-living CB6F1 hybrid mice (MLS approximately 3.5 years). In addition, we compared age-associated changes in liver non-heme iron to assess how intracellular conditions, which may modulate oxidative processes, are affected by aging. Surprisingly, even at a young age, concentrations of both markers of lipid peroxidation, as well as of iron, were at least twofold (P naked mole tats than in mice. This refutes the hypothesis that prolonged naked mole-rat longevity is due to superior protection against oxidative stress. The age-related profiles of all three parameters were distinctly species specific. Rates of lipid damage generation in mice were maintained throughout adulthood, while accrued damage in old animals was twice that of young mice. In naked mole-rats, urinary isoprostane excretion declined by half with age (P naked mole-rats is independent of oxidative stress parameters.

  12. Repeated dose intramuscular injection of the CIMAvax-EGF vaccine in Sprague Dawley rats induces local and systemic toxicity.

    Science.gov (United States)

    Mancebo, A; Casacó, A; González, B; Ledón, N; Sorlozabal, J; León, A; Gómez, D; González, Y; Bada, A M; González, C; Arteaga, M E; Ramírez, H; Fuentes, D

    2012-05-09

    CIMAvax-EGF consists of a human recombinant epidermal growth factor (EGF), coupled to P64k, a recombinant carrier protein from N. meningitis, and Montanide ISA 51 as adjuvant. The vaccine immunization induces a specific antibody production, inhibiting the EGF/EGF-R interaction through EGF deprivation. The objective of this study was to assess the CIMAvax-EGF toxicity in Sprague Dawley rats after intramuscular administration of repeated doses (6 months) and at the same time to determine if rat is a relevant species for studying CIMAvax-EGF vaccine. Rats were randomly distributed into four groups: control, Montanide ISA 51, treated with 1× and 15× of human total dose of the antigen. Animals were immunized weekly during 9 weeks, plus 9 immunizations every 14 days. Rats were inspected daily for clinical signs. Body weight, food consumption, and rectal temperature were measured during the administration of doses. Blood samples were collected for hematological, serum biochemical determinations and EGF titles at the beginning, three months and at the end of experimentation. Gross necropsy and histological examination of tissues were performed on animals at the end of the assay. Vaccine provoked the apparition of antibodies against EGF in the rats, demonstrating rat species relevance in these studies. Body weight gain, food and water consumption were not affected. CIMAvax-EGF and Montanide ISA 51 produced local damage at the administration site, showing multiple cysts and granulomas. Both vaccine-treated groups showed neutrophil elevation, besides an AST increase probably related to the damage at the administration site. Rectal temperature was found to be significantly higher in 15× treated group after immunizations, probably induced by the inflammatory process at the injection site. In summary, the clinical pathology findings together with the body temperature results, appear to be caused by the inflammatory reaction at the administration site of the vaccine, mainly

  13. Vertebrate species introductions in the United States and its territories

    Directory of Open Access Journals (Sweden)

    Gary W. WITMER, Pam L. FULLER

    2011-10-01

    Full Text Available At least 1,065 introduced vertebrate species have been introduced in the United States and its territories, including at least 86 mammalian, 127 avian, 179 reptilian/amphibian, and 673 fish species. Examples in each major taxonomic group include domestic cat, small Indian mongoose, red fox, goat, pig, rabbit, rats, house mouse, gray squirrel, nutria, starling, Indian common myna, red-vented bulbul, brown treesnake, red-eared slider, brown trout, tilapia, and grass carp. We briefly review some of these species and the types of damage they cause. We then review the basic types of methods used for control or eradication of each taxonomic group, including physical, chemical, biological, and cultural methods. We discuss some of the challenges in managing these species, including issues with the use of toxicants, land access, public attitudes, and monitoring difficulties. Finally, we list some ongoing research and future research needs, including improved detection methods, improved attractants, improved barriers, improved capture methods, fertility control, and risk assessment methods [Current Zoology 57 (5: 559–567, 2011].

  14. Na(+)/Ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart.

    Science.gov (United States)

    Farkas, A S; Acsai, K; Nagy, N; Tóth, A; Fülöp, F; Seprényi, G; Birinyi, P; Nánási, P P; Forster, T; Csanády, M; Papp, J G; Varró, A; Farkas, A

    2008-05-01

    The Na(+)/Ca(2+) exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na(+) concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 microM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na(+) concentrations in rabbit and rat hearts. The concentration-dependent effects of SEA0400 on I(Na/Ca) were studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff-perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry. SEA0400 inhibited I(Na/Ca) with similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration-dependent manner, for example, 1.0 microM SEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities. NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na(+) concentration may play an important role in the contractility response to NCX inhibition.

  15. Proteomic profiling of the rat hypothalamus

    Directory of Open Access Journals (Sweden)

    Pedroso Amanda P

    2012-04-01

    Full Text Available Abstract Background The hypothalamus plays a pivotal role in numerous mechanisms highly relevant to the maintenance of body homeostasis, such as the control of food intake and energy expenditure. Impairment of these mechanisms has been associated with the metabolic disturbances involved in the pathogenesis of obesity. Since rodent species constitute important models for metabolism studies and the rat hypothalamus is poorly characterized by proteomic strategies, we performed experiments aimed at constructing a two-dimensional gel electrophoresis (2-DE profile of rat hypothalamus proteins. Results As a first step, we established the best conditions for tissue collection and protein extraction, quantification and separation. The extraction buffer composition selected for proteome characterization of rat hypothalamus was urea 7 M, thiourea 2 M, CHAPS 4%, Triton X-100 0.5%, followed by a precipitation step with chloroform/methanol. Two-dimensional (2-D gels of hypothalamic extracts from four-month-old rats were analyzed; the protein spots were digested and identified by using tandem mass spectrometry and database query using the protein search engine MASCOT. Eighty-six hypothalamic proteins were identified, the majority of which were classified as participating in metabolic processes, consistent with the finding of a large number of proteins with catalytic activity. Genes encoding proteins identified in this study have been related to obesity development. Conclusion The present results indicate that the 2-DE technique will be useful for nutritional studies focusing on hypothalamic proteins. The data presented herein will serve as a reference database for studies testing the effects of dietary manipulations on hypothalamic proteome. We trust that these experiments will lead to important knowledge on protein targets of nutritional variables potentially able to affect the complex central nervous system control of energy homeostasis.

  16. Putative anticancer potential of novel 4-thiazolidinone derivatives: cytotoxicity toward rat C6 glioma in vitro and correlation of general toxicity with the balance of free radical oxidation in rats.

    Science.gov (United States)

    Коbylinska, Lesya I; Boiko, Nataliya M; Panchuk, Rostyslav R; Grytsyna, Iryna I; Klyuchivska, Olga Yu; Biletska, Liliya P; Lesyk, Roman B; Zіmenkovsky, Borys S; Stoika, Rostyslav S

    2016-04-23

    To evaluate the cytotoxic action of 4-thiazolidinone derivatives (ID 3288, ID 3882, and ID 3833) toward rat glioma C6 cells and to compare the effects of these compounds and doxorubicin on the balance of free radical oxidation (FRO) and antioxidant activity (AOA) in the serum of rats. Glioma cells were treated with ID 3882, ID 3288, ID 3833, and doxorubicin, and their cytotoxicity was studied using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and Trypan blue exclusion test, light and fluorescent microscopy, and flow cytometric study of cell cycling and apoptosis, including measuring of Annexin V-positive cells. The contents of superoxide radical, hydrogen peroxide, hydroxyl radical, malonic dialdehyde, and hydrogen sulfide were measured in the serum of rats. Enzymatic activity of superoxide dismutase (SOD), catalase (Cat), and glutathione peroxydase (GPO) was determined. Among novel 4-thiazolidinone derivatives, ID 3288 was most toxic toward rat glioma C6 cells, even compared with doxorubicin. All applied derivatives were less active than doxorubicin in inducing reactive oxygen species-related indicators in the serum of rats. A similar effect was observed when enzymatic indicators of AOA processes were measured. While doxorubicin inhibited the activity of SOD, GPO, and Cat, the effects of 4-thiazolidinone derivatives were less prominent. Novel 4-thiazolidinone derivatives differ in their antineoplastic action toward rat glioma C6 cells, and ID 3288 possesses the highest activity compared to doxorubicin. Measurement of indicators of FRO and AOA in the serum of rats treated with these compounds showed their lower general toxicity compared with doxorubicin's toxicity.

  17. A Comparative Analysis of Perinatal Development of Barrel Cortex in Rat, Mouse and Guinea Pig Using Acetylcholinesterase Histochemistry

    OpenAIRE

    ŞENDEMİR, Erdoğan

    2014-01-01

    The role of acetylcholinesterase (AChE) in the developing neocortex was reexamined by comparing its expression in rats, mice and guinea pigs, following the protocol for acetylcholinesterase histochemistry (described in Sendemir et al., 1996) in order to determine the suitability of the breeding colony at UludaÛ University for use as an animal model. A total of 103 pups as well as two adult animals of each species were used. In the rat pups, acetylcholinesterase-rich patches were d...

  18. Species differences in the biotransformation of an alpha 4 beta 2 nicotinic acetylcholine receptor partial agonist: the effects of distinct glucuronide metabolites on overall compound disposition.

    Science.gov (United States)

    Shaffer, Christopher L; Gunduz, Mithat; Ryder, Tim F; O'Connell, Thomas N

    2010-02-01

    The metabolism and disposition of (1R,5S)-2,3,4,5-tetrahydro-7-(trifluoromethyl)-1,5-methano-1H-3-benzazepine (1), an alpha(4)beta(2) nicotinic acetylcholine receptor partial agonist, was investigated in Sprague-Dawley rats and cynomolgus monkeys receiving (1R,5S)-2,3,4,5-tetrahydro-7-(trifluoromethyl)-1,5-methano-1H-4[(14)C]-3- benzazepine hydrochloride ([(14)C]1) orally. Although both species chiefly (>or=62%) cleared 1 metabolically, species-specific dispositional profiles were observed for both 1 and total radioactivity. Radioactivity was excreted equally in the urine and feces of intact rats but largely (72%) in bile in bile duct-cannulated animals. In monkeys, radioactivity recoveries were 50-fold greater in urine than feces and minimal (<5%) in bile. Both species metabolized 1 similarly: four-electron oxidation to one of four amino acids or two lactams (minor) and glucuronide formation (major). In rats, the latter pathway predominantly formed an N-carbamoyl glucuronide (M6), exclusively present in bile (69% of dose), whereas in monkeys it afforded an N-O-glucuronide (M5), a minor biliary component (4%) but the major plasma (62%) and urinary (42%) entity. In rats, first-pass hepatic conversion of 1 to M6, which was confirmed in rat hepatocytes, and its biliary secretion resulted in the indirect enterohepatic cycling of 1 via M6 and manifested in double-humped plasma concentration-time curves and long t(1/2) for both 1 and total radioactivity. In monkeys, in which only M5 was formed, double-humped plasma concentration-time curves were absent, and moderate t(1/2) for both 1 and total radioactivity were observed. A seemingly subtle, yet critical, difference in the chemical structures of these two glucuronide metabolites considerably affected the overall disposition of 1 in rats versus monkeys.

  19. C-Psilocin tissue distribution in pregnant rats after intravenous administration

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    Francis C.P. Law

    2014-06-01

    Full Text Available Background: Many species of hallucinogenic mushrooms have been found in the genus Psilocybe. The main psychoactive chemicals of Psilocybe mushrooms are psilocin and its phosphoryloxy derivative, psilocybin. In addition to its psychedelic effects, psilocybin is an effective agent to lift the mood of depressed patients with terminal cancers. Objective: To study the dispositional kinetics of 14C-psilocin in pregnant rats after intravenous injection, to calculate tissue dose surrogates i.e., tissue 14C concentration and area under the concentration-time curve using the experimental data, to quantify trans-placental passage of psilocin and/or its metabolites, and to identify new psilocin metabolite(s in rat urine. Methods: A group of 15 pregnant Wistar rats weighing between 0.30-0.36 kg was used in the study. Each rat was given a single dose of 7.5 mg/kg 14C-psilocin i.v. Three rats were randomly selected and sacrificed at 0.5, 1.0, 2.0, 4.0, and 8.0 hr post-dosing. The maternal and fetal tissues were quickly removed and the radioactivity in these tissues determined by liquid scintillation counting. In a separate study, urine samples were collected from 6 male Wistar rats after administering 15 mg/kg of unlabeled psilocin i.p. The urine samples were collected and extracted by chloroform-methanol (9:1 v/v and analyzed using a gas chromatograph/mass spectrometer. Results: 14C-Psilocin crossed the placental barrier of pregnant rats readily after i.v. administration; maternal tissue 14C concentrations were found to be much higher than those in fetal tissues. The areas under the curve for maternal tissues also were much higher than the fetal tissues. In general, maternal tissues could be divided into the fast eliminating organ group, which included the brain (elimination half-life 13 hr. A new psilocin metabolite tentatively identified as dihydroxyindoleacetic acid was found in the urine. Conclusion: Our study showed that psilocin readily crossed the

  20. Effect of TheraCyte-encapsulated parathyroid cells on lumbar fusion in a rat model.

    Science.gov (United States)

    Chen, Sung-Hsiung; Huang, Shun-Chen; Lui, Chun-Chung; Lin, Tzu-Ping; Chou, Fong-Fu; Ko, Jih-Yang

    2012-09-01

    Implantation of TheraCyte 4 × 10(6) live parathyroid cells can increase the bone marrow density of the spine of ovariectomized rats. There has been no published study examining the effect of such implantation on spinal fusion outcomes. The purpose of this study was to examine the effect of TheraCyte-encapsulated parathyroid cells on posterolateral lumbar fusions in a rat model. Forty Sprague-Dawley rats underwent single-level, intertransverse process spinal fusions using iliac crest autograft. The rats were randomly assigned to two groups: Group 1 rats received sham operations on their necks (control; N = 20); Group 2 rats were implanted with TheraCyte-encapsulated 4 × 10(6) live parathyroid cells into the subcutis of their necks (TheraCyte; N = 20). Six weeks after surgery the rats were killed. Fusion was assessed by inspection, manual palpation, radiography, and histology. Blood was drawn to measure the serum levels of calcium, phosphorus, and intact parathyroid hormone (iPTH). Based on manual palpation, the control group had a fusion rate of 33 % (6/18) and the TheraCyte group had a fusion rate of 72 % (13/18) (P = 0.044). Histology confirmed the manual palpation results. Serum iPTH levels were significantly higher in the TheraCyte group compared with the control group (P TheraCyte-encapsulated 4 × 10(6) live parathyroid cells than in control rats without significant change in serum calcium or phosphorus concentrations. As with any animal study, the results may not extrapolate to a higher species. Further studies are needed to determine if these effects are clinically significant.

  1. Structural and numerical chromosome aberration inducers in liver micronucleus test in rats with partial hepatectomy.

    Science.gov (United States)

    Itoh, Satoru; Hattori, Chiharu; Nagata, Mayumi; Sanbuissho, Atsushi

    2012-08-30

    The liver micronucleus test is an important method to detect pro-mutagens such as active metabolites not reaching bone marrow due to their short lifespan. We have already reported that dosing of the test compound after partial hepatectomy (PH) is essential to detect genotoxicity of numerical chromosome aberration inducers in mice [Mutat. Res. 632 (2007) 89-98]. In naive animals, the proportion of binucleated cells in rats is less than half of that in mice, which suggests a species difference in the response to chromosome aberration inducers. In the present study, we investigated the responses to structural and numerical chromosome aberration inducers in the rat liver micronucleus test. Two structural chromosome aberretion inducers (diethylnitrosamine and 1,2-dimethylhydrazine) and two numerical chromosome aberration inducers (colchicine and carbendazim) were used in the present study. PH was performed a day before or after the dosing of the test compound in 8-week old male F344 rats and hepatocytes were isolated 4 days after the PH. As a result, diethylnitrosamine and 1,2-dimethylhydrazine, structural chromosome aberration inducers, exhibited significant increase in the incidence of micronucleated hepatocyte (MNH) when given either before and after PH. Colchicine and carbendazim, numerical chromosome aberration inducers, did not result in any toxicologically significant increase in MNH frequency when given before PH, while they exhibited MNH induction when given after PH. It is confirmed that dosing after PH is essential in order to detect genotoxicity of numerical chromosome aberration inducers in rats as well as in mice. Regarding the species difference, a different temporal response to colchicine was identified. Colchicine increased the incidence of MNH 4 days after PH in rats, although such induction in mice was observed 8-10 days after PH. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Comparative study of the organisation and phenotypes of bladder interstitial cells in human, mouse and rat.

    Science.gov (United States)

    Gevaert, Thomas; Neuhaus, Jochen; Vanstreels, Els; Daelemans, Dirk; Everaerts, Wouter; Der Aa, Frank Van; Timmermans, Jean-Pierre; Roskams, Tania; Steiner, Clara; Pintelon, Isabel; De Ridder, Dirk

    2017-12-01

    With most research on interstitial cells (IC) in the bladder being conducted on animal models, it remains unclear whether all structural and functional data on IC from animal models can be translated to the human context. This prompted us to compare the structural and immunohistochemical properties of IC in bladders from mouse, rat and human. Tissue samples were obtained from the bladder dome and subsequently processed for immunohistochemistry and electron microscopy. The ultrastructural properties of IC were compared by means of electron microscopy and IC were additionally characterized with single/double immunohistochemistry/immunofluorescence. Our results reveal a similar organization of the IC network in the upper lamina propria (ULP), the deep lamina propria (DLP) and the detrusor muscle in human, rat and mouse bladders. Furthermore, despite several similarities in IC phenotypes, we also found several obvious inter-species differences in IC, especially in the ULP. Most remarkably in this respect, ULP IC in human bladder predominantly displayed a myoid phenotype with abundant presence of contractile micro-filaments, while those in rat and mouse bladders showed a fibroblast phenotype. In conclusion, the organization of ULP IC, DLP IC and detrusor IC is comparable in human, rat and mouse bladders, although several obvious inter-species differences in IC phenotypes were found. The present data show that translating research data on IC in laboratory animals to the human setting should be carried out with caution.

  3. Inbred rats as a model to study persistent renal colonization and associated cellular immune responsiveness

    Science.gov (United States)

    Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Rats are regarded as one of the most significant reservoir hosts of infection for human disease, and in the absence of clinical signs of infection...

  4. Plasma disappearance, urine excretion, and tissue distribution of ribavirin in rats and rhesus monkeys

    International Nuclear Information System (INIS)

    Ferrara, E.A.; Oishi, J.S.; Wannemacher, R.W. Jr.; Stephen, E.L.

    1981-01-01

    Ribavirin has been shown to have broad-spectrum antiviral. To study its tissue distribution and disappearance rate, a single dose of 10 mg/kg which contained 10 microCi of [14C]ribavirin was injected intravenously into rhesus monkeys and intramuscularly into monkeys and rats. Except for peak plasma concentrations and the initial phases of the plasma disappearance and urine excretion curves, no significant difference was observed between plasma, tissue, or urine values for intramuscularly or intravenously injected monkeys. Plasma disappearance curves were triphasic; plasma concentrations of ribavirin were similar for both monkeys and rats. Rats excreted ribavirin in the urine more rapidly and to a greater extent (82% excreted in 24 h) than did monkeys (60% excreted in 72 h). In the rat, only 3% of the injected [14C]ribavirin was detected in expired CO2. Therefore, for both species, urine was the major route for the elimination of labeled ribavirin and its metabolites from the body. In monkeys, the amount of parent drug in blood cells increased through 48 h and remained stable for 72 h, whereas in rats, ribavirin decreased at a rate similar to the plasma disappearance curve. Concentrations of ribavirin at 8 h were consistently higher in monkeys than in rats for all tissues except the brain. Thus, these differences in blood cellular components and organ content and in urine excretion suggested that there was greater tissue retention of ribavirin in monkeys than in rats

  5. Comparison of rats and dogs exposed to 239PuO2

    International Nuclear Information System (INIS)

    Mahaffey, J.A.; Sanders, C.L.; Park, J.F.; Dagle, G.E.

    1979-01-01

    Rats and dogs inhaled aerosols of 239 PuO 2 at comparable ages relative to their lifespan. Both received a single exposure. The estimated lung doses at death in dogs were between 1100 and 11,000 rad. From two inhalation experiments, rats receiving doses in this range were chosen from the high-level exposed animals for comparison. Based on this data base, several comparisons were investigated. Metabolism of the material was compared for all animals and for animals which developed lung tumors. The differences in histopathology and tumor incidence in the lung were also reviewed. Although there were several differences between species, there were also many similarities. On-going research in dogs should produce data which will allow clarification of these relationships

  6. Antioxidant activity of citrullus colocynthis pulp extract in the RBC's of alloxan-induced diabetic rats

    International Nuclear Information System (INIS)

    Dallak, M.; Jaliah, B.I.

    2010-01-01

    Previous studies in our laboratory showed that Citrullus colocynthis pulp seedless extract have antihyperglycemic and insulinotropic effects in alloxan induced diabetes. Reactive oxygen species have been implicated in the mechanism of damage of red blood cells and anaemia in diabetic patients. So the current study was carried out to investigate the protective role of citrullus colocynthis against oxidative stress in the RBC's of alloxan induced diabetic rats. Methods: Rats were divided into four groups each of ten rats, the first group was normal non diabetic rats given normal saline orally and was named control group, the second group was diabetic rats given normal saline orally and were named normal saline treated-diabetic rats, the third and fourth group were diabetic rats treated with the pulp extract or glibenclamide (a positive control) orally. Evaluations were made for haematological parameters in the blood and for lipid peroxidation and oxidative stress enzymes activities in the RBC's of all experimental rats. Results: The diabetic rats had a significant decrease (p<0.05) in total erythrocytes count and Packed Cell Volume (PCV) and a normal Haemoglobin (Hb) value in the blood. They also showed decreased levels of Thiobarbituric Acid Reactive Substances (TBARS) and decreased activities of Superoxide Dismutase (SOD) and Catalase (CAT) in the RBC's hemolysate. On other hand, oral administration of citrullus colocynthis or glibenclamide alleviated these altered parameters in the treated rats, they resulted in a significant increase (p<0.05) in the in total erythrocytes count and PCV (Haematocrit) values in the blood and caused a significant decreased levels of TBARS and increased activities of SOD and CAT in the RBC's of those diabetic treated rats when compared to diabetic rats given normal saline. The effect was more profound in citrullus colocynthis treated diabetic rats. Conclusion: Citrullus colocynthis pulp extract possesses a potent antioxidant property

  7. Incidence of Nocardia species in raw milk collected from different localities of Assiut City of Egypt

    Directory of Open Access Journals (Sweden)

    Nahed Mohamad Wahba

    2011-10-01

    Full Text Available This study aimed to isolate and enumerate Nocardiae from the examined raw milk samples. 240 random milk samples were collected from cows, buffaloes, sheep and goats from different localities in Assiut city- Egypt. The incidences of Nocardia spp. were 47.8, 43.3, 53.3 and 66.7% with average counts of 3.8 x104, 4.5x104, 1.4x104 and 7.6x103/CFUmL of the examined samples, respectively. Pathogenicity of the isolates was also studied. N. otitidiscavarium and N. brasiliensis caused sudden death of rats while, N. farcinica and N. carnea strains were non pathogenic. Other species caused several lesions. It was concluded from the study that, Nocardia species are existed in retailed and fresh milk of different farm animals. Most of the isolated strains were highly pathogenic to rats. Consequently, preventive measures should be taken to protect consumers from being infected. [Vet. World 2011; 4(5.000: 201-204

  8. SIRT3 Expression Decreases with Reactive Oxygen Species Generation in Rat Cortical Neurons during Early Brain Injury Induced by Experimental Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Wei Huang

    2016-01-01

    Full Text Available Sirtuin3 (SIRT3 is an important protein deacetylase which predominantly presents in mitochondria and exhibits broad bioactivities including regulating energy metabolism and counteracting inflammatory effect. Since inflammatory cascade was proved to be critical for pathological damage following subarachnoid hemorrhage (SAH, we investigated the overall expression and cell-specific distribution of SIRT3 in the cerebral cortex of Sprague-Dawley rats with experimental SAH induced by internal carotid perforation. Results suggested that SIRT3 was expressed abundantly in neurons and endothelia but rarely in gliocytes in normal cerebral cortex. After experimental SAH, mRNA and protein expressions of SIRT3 decreased significantly as early as 8 hours and dropped to the minimum value at 24 h after SAH. By contrast, SOD2 expression increased slowly as early as 12 hours after experimental SAH, rose up sharply at the following 12 hours, and then was maintained at a higher level. In conclusion, attenuated SIRT3 expression in cortical neurons was associated closely with enhanced reactive oxygen species generation and cellular apoptosis, implying that SIRT3 might play an important neuroprotective role during early brain injury following SAH.

  9. Docosahexaenoic Acid Helps to Lessen Extinction Memory in Rats

    Directory of Open Access Journals (Sweden)

    Michio Hashimoto

    2018-02-01

    Full Text Available Abstract: Memory extinction is referred to as a learning process in which a conditioned response (CR progressively reduces over time as an animal learns to uncouple a response from a stimulus. Extinction occurs when the rat is placed into a context without shock after training. Docosahexaenoic acid (DHA, C22:6, n-3 is implicated in memory formation in mammalian brains. In a two-way active shuttle-avoidance apparatus, we examined whether DHA affects the extinction memory and the expression of brain cognition-related proteins, including gastrin-releasing peptide receptor (GRPR, brain-derived neurotrophic factor receptor (BDNFR tyrosine kinase receptor B (TrKB, and N-methyl-d-aspartate receptor (NMDAR subunits NR2A and NR2B. Also, the protein levels of GRP, BDNF, postsynaptic density protein-95 (PSD-95, and vesicular acetylcholine transporter (VAChT, and the antioxidative potentials, in terms of lipid peroxide (LPO and reactive oxygen species (ROS, were examined in the hippocampus. During the acquisition phase, the rats received a conditioned stimulus (CS-tone paired with an unconditioned stimulus (UCS foot shock for three consecutive days (Sessions S1, S2, and S3, each consisting of 30-trials after 12 weeks of oral administration of DHA. After a three-day interval, the rats were re-subjected to two extinction sessions (S4, S5, each comprising 30 trials of CS alone. During the acquisition training in S1, the shock-related avoidance frequency (acquisition memory was significantly higher in the DHA-administered rats compared with the control rats. The avoidance frequency, however, decreased with successive acquisition trainings in sessions S2 and S3. When the rats were subjected to the extinction sessions after a break for consolidation, the conditioned response (CR was also significantly higher in the DHA-administered rats. Interestingly, the freezing responses (frequency and time also significantly decreased in the DHA-administered rats, thus

  10. Live attenuated Francisella novicida vaccine protects against Francisella tularensis pulmonary challenge in rats and non-human primates.

    Directory of Open Access Journals (Sweden)

    Ping Chu

    2014-10-01

    Full Text Available Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt, leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP. The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform.

  11. Protective effect of Zingiber officinale extract on rat testis after cyclophosphamide treatment.

    Science.gov (United States)

    Mohammadi, F; Nikzad, H; Taghizadeh, M; Taherian, A; Azami-Tameh, A; Hosseini, S M; Moravveji, A

    2014-08-01

    Decreasing the side effects of chemotherapy in testis has been the subjects of many studies. In this study, the protective effects of Zingiber officinale extract on rat testis were investigated after chemotherapy with cyclophosphamide. Histological and biochemical parameters were compared in cyclophosphamide-treated rats with or without ginger extract intake. Wistar male rats were randomly divided into four groups each 10. The control group received a single injection of 1 ml isotonic saline intraperitoneally. The Cyclophosphamide (CP) group received a single dose of cyclophosphamide (100 mg kg(-1) BW) intraperitoneally. CP + 300 and CP + 600 groups received orally 300 or 600 mg of ginger extract, respectively, for a period of 6 weeks after cyclophosphamide injection. The morphologic and histological structure of the testis was compared in different groups of the rats. Also, factors like malondialdehyde, reactive oxygen species, total antioxidant capacity and testosterone level were assessed in blood serum as well. Our results showed that although ginger extract could not change testis weight, malondialdehyde (MDA) and ROS, but antioxidant and testosterone levels in serum were increased significantly. Also, an obvious improved histological change was seen in CP + 300 and CP + 600 groups in comparison with CP group. These protective effects of ginger on rat testis after cyclophosphamide treatment could be attributed to the higher serum level of antioxidants. © 2013 Blackwell Verlag GmbH.

  12. Impaired Mitochondrial Respiratory Functions and Oxidative Stress in Streptozotocin-Induced Diabetic Rats

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    Subbuswamy K. Prabu

    2011-05-01

    Full Text Available We have previously shown a tissue-specific increase in oxidative stress in the early stages of streptozotocin (STZ-induced diabetic rats. In this study, we investigated oxidative stress-related long-term complications and mitochondrial dysfunctions in the different tissues of STZ-induced diabetic rats (>15 mM blood glucose for 8 weeks. These animals showed a persistent increase in reactive oxygen and nitrogen species (ROS and RNS, respectively production. Oxidative protein carbonylation was also increased with the maximum effect observed in the pancreas of diabetic rats. The activities of mitochondrial respiratory enzymes ubiquinol: cytochrome c oxidoreductase (Complex III and cytochrome c oxidase (Complex IV were significantly decreased while that of NADH:ubiquinone oxidoreductase (Complex I and succinate:ubiquinone oxidoreductase (Complex II were moderately increased in diabetic rats, which was confirmed by the increased expression of the 70 kDa Complex II sub-unit. Mitochondrial matrix aconitase, a ROS sensitive enzyme, was markedly inhibited in the diabetic rat tissues. Increased expression of oxidative stress marker proteins Hsp-70 and HO-1 was also observed along with increased expression of nitric oxide synthase. These results suggest that mitochondrial respiratory complexes may play a critical role in ROS/RNS homeostasis and oxidative stress related changes in type 1 diabetes and may have implications in the etiology of diabetes and its complications.

  13. Renoprotective effect of lansoprazole in streptozotocin-induced diabetic nephropathy in wistar rats.

    Science.gov (United States)

    Kaur, Rupinder; Sodhi, Rupinder Kaur; Aggarwal, Neha; Kaur, Jaspreet; Jain, Upendra K

    2016-01-01

    Proton pump inhibitors (PPIs) have exhibited glucose lowering action in animal models of diabetes; however, their potential in diabetes-related complications has not yet been evaluated. Hence, the present study has been undertaken to investigate the renoprotective potential of lansoprazole in streptozotocin-induced diabetic nephropathy in wistar rats. Diabetic nephropathy was induced with a single injection of streptozotocin (STZ, 45 mg/kg, i.p.). Lansoprazole (40 mg/kg; 80 mg/kg, p.o.; 4 weeks) was administered to diabetic rats after 4 weeks of STZ treatment. A battery of biochemical tests such as serum glucose, glycated hemoglobin, blood urea nitrogen (BUN), serum creatinine, albumin, and kidney weight/body weight (%) ratio were performed to evaluate the renal functions. Oxidative stress was determined by estimating renal thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH) levels. Lipid profile was assessed by determining serum cholesterol (TC), triglyceride (TG), and high-density lipoprotein (HDL). The STZ-treated rats demonstrated deleterious alterations in kidney functions, enhanced oxidative stress, and disturbed lipid profile. Administration of lansoprazole to diabetic rats significantly reduced serum glucose, glycated hemoglobin, BUN, creatinine, albumin levels, and oxidative stress. Serum lipids like TC and TG were decreased, and HDL was enhanced in lansoprazole-treated STZ rats. The findings of our study indicate that renoprotective effects of lansoprazole may be attributed to its glucose-lowering, lipid-lowering, and antioxidative potential.

  14. Biobreeding rat islets exhibit reduced antioxidative defense and N-acetyl cysteine treatment delays type 1 diabetes

    Science.gov (United States)

    Bogdani, Marika; Henschel, Angela M.; Kansra, Sanjay; Fuller, Jessica M.; Geoffrey, Rhonda; Jia, Shuang; Kaldunski, Mary L.; Pavletich, Scott; Prosser, Simon; Chen, Yi-Guang; Lernmark, Åke; Hessner, Martin J.

    2014-01-01

    Islet-level oxidative stress has been proposed as a trigger for type 1 diabetes (T1D), and release of cytokines by infiltrating immune cells further elevates reactive oxygen species (ROS), exacerbating β cell duress. To identify genes/mechanisms involved with diabeto-genesis at the β cell level, gene expression profiling and targeted follow-up studies were used to investigate islet activity in the biobreeding (BB) rat. Forty-day-old spontaneously diabetic lymphopenic BB DRlyp/lyp rats (before T cell insulitis) as well as nondiabetic BB DR+/+ rats, nondiabetic but lymphopenic F344lyp/lyp rats, and healthy Fischer (F344) rats were examined. Gene expression profiles of BB rat islets were highly distinct from F344 islets and under-expressed numerous genes involved in ROS metabolism, including glutathione S-transferase (GST) family members (Gstm2, Gstm4, Gstm7, Gstt1, Gstp1, and Gstk1), superoxide dismutases (Sod2 and Sod3), peroxidases, and peroxiredoxins. This pattern of under-expression was not observed in brain, liver, or muscle. Compared with F344 rats, BB rat pancreata exhibited lower GST protein levels, while plasma GST activity was found significantly lower in BB rats. Systemic administration of the antioxidant N-acetyl cysteine to DRlyp/lyp rats altered abundances of peripheral eosinophils, reduced severity of insulitis, and significantly delayed but did not prevent diabetes onset. We find evidence of β cell dysfunction in BB rats independent of T1D progression, which includes lower expression of genes related to antioxidative defense mechanisms during the pre-onset period that may contribute to overall T1D susceptibility. PMID:23111281

  15. Structure of the vitreoretinal border region in spontaneously hypertensive rats (SHR rats)

    DEFF Research Database (Denmark)

    Heegaard, Steffen

    1993-01-01

    Øjenpatologi, vitreoretinal border region, inner limiting membrane of the retina, spontaneously hypertensive rats, SHR rats, ultrastructure......Øjenpatologi, vitreoretinal border region, inner limiting membrane of the retina, spontaneously hypertensive rats, SHR rats, ultrastructure...

  16. Comparison of Species and Cell-Type Differences in Fraction Unbound of Liver Tissues, Hepatocytes, and Cell Lines.

    Science.gov (United States)

    Riccardi, Keith; Ryu, Sangwoo; Lin, Jian; Yates, Phillip; Tess, David; Li, Rui; Singh, Dhirender; Holder, Brian R; Kapinos, Brendon; Chang, George; Di, Li

    2018-04-01

    Fraction unbound ( f u ) of liver tissue, hepatocytes, and other cell types is an essential parameter used to estimate unbound liver drug concentration and intracellular free drug concentration. f u,liver and f u,cell are frequently measured in multiple species and cell types in drug discovery and development for various applications. A comparison study of 12 matrices for f u,liver and f u,cell of hepatocytes in five different species (mouse, rat, dog, monkey, and human), as well as f u,cell of Huh7 and human embryonic kidney 293 cell lines, was conducted for 22 structurally diverse compounds with the equilibrium dialysis method. Using an average bioequivalence approach, our results show that the average difference in binding to liver tissue, hepatocytes, or different cell types was within 2-fold of that of the rat f u,liver Therefore, we recommend using rat f u,liver as a surrogate for liver binding in other species and cell types in drug discovery. This strategy offers the potential to simplify binding studies and reduce cost, thereby enabling a more effective and practical determination of f u for liver tissues, hepatocytes, and other cell types. In addition, f u under hepatocyte stability incubation conditions should not be confused with f u,cell , as one is a diluted f u and the other is an undiluted f u Cell density also plays a critical role in the accurate measurement of f u,cell . Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  17. Cordycepin Increases Nonrapid Eye Movement Sleep via Adenosine Receptors in Rats.

    Science.gov (United States)

    Hu, Zhenzhen; Lee, Chung-Il; Shah, Vikash Kumar; Oh, Eun-Hye; Han, Jin-Yi; Bae, Jae-Ryong; Lee, Kinam; Chong, Myong-Soo; Hong, Jin Tae; Oh, Ki-Wan

    2013-01-01

    Cordycepin (3'-deoxyadenosine) is a naturally occurring adenosine analogue and one of the bioactive constituents isolated from Cordyceps militaris/Cordyceps sinensis, species of the fungal genus Cordyceps. It has traditionally been a prized Chinese folk medicine for the human well-being. Because of similarity of chemical structure of adenosine, cordycepin has been focused on the diverse effects of the central nervous systems (CNSs), like sleep regulation. Therefore, this study was undertaken to know whether cordycepin increases the natural sleep in rats, and its effect is mediated by adenosine receptors (ARs). Sleep was recorded using electroencephalogram (EEG) for 4 hours after oral administration of cordycepin in rats. Sleep architecture and EEG power spectra were analyzed. Cordycepin reduced sleep-wake cycles and increased nonrapid eye movement (NREM) sleep. Interestingly, cordycepin increased θ (theta) waves power density during NREM sleep. In addition, the protein levels of AR subtypes (A1, A2A, and A2B) were increased after the administration of cordycepin, especially in the rat hypothalamus which plays an important role in sleep regulation. Therefore, we suggest that cordycepin increases theta waves power density during NREM sleep via nonspecific AR in rats. In addition, this experiment can provide basic evidence that cordycepin may be helpful for sleep-disturbed subjects.

  18. Cordycepin Increases Nonrapid Eye Movement Sleep via Adenosine Receptors in Rats

    Directory of Open Access Journals (Sweden)

    Zhenzhen Hu

    2013-01-01

    Full Text Available Cordycepin (3′-deoxyadenosine is a naturally occurring adenosine analogue and one of the bioactive constituents isolated from Cordyceps militaris/Cordyceps sinensis, species of the fungal genus Cordyceps. It has traditionally been a prized Chinese folk medicine for the human well-being. Because of similarity of chemical structure of adenosine, cordycepin has been focused on the diverse effects of the central nervous systems (CNSs, like sleep regulation. Therefore, this study was undertaken to know whether cordycepin increases the natural sleep in rats, and its effect is mediated by adenosine receptors (ARs. Sleep was recorded using electroencephalogram (EEG for 4 hours after oral administration of cordycepin in rats. Sleep architecture and EEG power spectra were analyzed. Cordycepin reduced sleep-wake cycles and increased nonrapid eye movement (NREM sleep. Interestingly, cordycepin increased θ (theta waves power density during NREM sleep. In addition, the protein levels of AR subtypes (A1, A2A, and A2B were increased after the administration of cordycepin, especially in the rat hypothalamus which plays an important role in sleep regulation. Therefore, we suggest that cordycepin increases theta waves power density during NREM sleep via nonspecific AR in rats. In addition, this experiment can provide basic evidence that cordycepin may be helpful for sleep-disturbed subjects.

  19. Genetic signatures for enhanced olfaction in the African mole-rats.

    Directory of Open Access Journals (Sweden)

    Sofia Stathopoulos

    Full Text Available The Olfactory Receptor (OR superfamily, the largest in the vertebrate genome, is responsible for vertebrate olfaction and is traditionally subdivided into 17 OR families. Recent studies characterising whole-OR subgenomes revealed a 'birth and death' model of evolution for a range of species, however little is known about fine-scale evolutionary dynamics within single-OR families. This study reports the first assessment of fine-scale OR evolution and variation in African mole-rats (Bathyergidae, a family of subterranean rodents endemic to sub-Saharan Africa. Because of the selective pressures of life underground, enhanced olfaction is proposed to be fundamental to the evolutionary success of the Bathyergidae, resulting in a highly diversified OR gene-repertoire. Using a PCR-sequencing approach, we analysed variation in the OR7 family across 14 extant bathyergid species, which revealed enhanced levels of functional polymorphisms concentrated across the receptors' ligand-binding region. We propose that mole-rats are able to recognise a broad range of odorants and that this diversity is reflected throughout their OR7 gene repertoire. Using both classic tests and tree-based methods to test for signals of selection, we investigate evolutionary forces across the mole-rat OR7 gene tree. Four well-supported clades emerged in the OR phylogeny, with varying signals of selection; from neutrality to positive and purifying selection. Bathyergid life-history traits and environmental niche-specialisation are explored as possible drivers of adaptive OR evolution, emerging as non-exclusive contributors to the positive selection observed at OR7 genes. Our results reveal unexpected complexity of evolutionary mechanisms acting within a single OR family, providing insightful perspectives into OR evolutionary dynamics.

  20. Normobaric, intermittent hypoxia conditioning is cardio- and vasoprotective in rats.

    Science.gov (United States)

    Manukhina, Eugenia B; Belkina, Ludmila M; Terekhina, Olga L; Abramochkin, Denis V; Smirnova, Elena A; Budanova, Olga P; Mallet, Robert T; Downey, H Fred

    2013-12-01

    Favorable versus detrimental cardiovascular responses to intermittent hypoxia conditioning (IHC) are heavily dependent on experimental or pathological conditions, including the duration, frequency and intensity of the hypoxia exposures. Recently, we demonstrated that a program of moderate, normobaric IHC (FIO2 9.5-10% for 5-10 min/cycle, with intervening 4 min normoxia, 5-8 cycles/day for 20 days) in dogs afforded robust cardioprotection against infarction and arrhythmias induced by coronary artery occlusion-reperfusion, but this protection has not been verified in other species. Accordingly, in this investigation cardio- as well as vasoprotection were examined in male Wistar rats completing the normobaric IHC program or a sham program in which the rats continuously breathed atmospheric air. Myocardial ischemia and reperfusion (IR) was imposed by occlusion and reperfusion of the left anterior descending coronary artery in in situ experiments and by subjecting isolated, perfused hearts to global ischemia-reperfusion. Cardiac arrhythmias and myocardial infarct size were quantified in in situ experiments. Endothelial function was evaluated from the relaxation to acetylcholine of norepinephrine-precontracted aortic rings taken from in situ IR experiments, and from the increase in coronary flow produced by acetylcholine in isolated hearts. IHC sharply reduced cardiac arrhythmias during ischemia and decreased infarct size by 43% following IR. Endothelial dysfunction in aorta was marked after IR in sham rats, but not significant in IHC rats. Similar findings were found for the coronary circulations of isolated hearts. These findings support the hypothesis that moderate, normobaric IHC is cardio- and vasoprotective in a rat model of IR.

  1. Food Neophobia in Wild Rats (Rattus norvegicus Inhabiting a Changeable Environment-A Field Study.

    Directory of Open Access Journals (Sweden)

    Klaudia Modlinska

    Full Text Available Food neophobia is a reaction to novel food observed in many animal species, particularly omnivores, including Rattus norvegicus. A neophobic reaction is typically characterised by avoidance of novel food and the necessity to assess both its potential value and toxicity by the animal. It has been hypothesised that this reaction is not observed in rats inhabiting a changeable environment with a high level of variability with regard to food and food sources. This study was conducted in such changeable conditions and it aims to demonstrate the behaviour of wild rats R. norvegicus in their natural habitat. The rats were studied in a farm setting, and the experimental arena was demarcated by a specially constructed pen which was freely accessible to the rats. At regular intervals, the rats were given new flavour- and smell-altered foods, while their behaviour was video-recorded. The results obtained in the study seem to confirm the hypothesis that rats inhabiting a highly changeable environment do not exhibit food neophobia. The observed reaction to novel food may be connected with a reaction to a novel object to a larger extent than to food neophobia. The value of the results obtained lies primarily in the fact that the study was conducted in the animals' natural habitat, and that it investigated their spontaneous behaviours.

  2. Effects of insulin combined with idebenone on blood-brain barrier permeability in diabetic rats.

    Science.gov (United States)

    Sun, Yan-Na; Liu, Li-Bo; Xue, Yi-Xue; Wang, Ping

    2015-04-01

    This study investigates the effect of insulin combined with idebenone on blood-brain barrier (BBB) permeability in experimental streptozotocin-induced diabetic rats as well as the underlying mechanisms. With a diabetic rat model, we show that insulin and idebenone normalize body weight and water intake and restore BBB permeability and that their combination displays a synergistic effect. The results from transmission electron microscopy show that the combination of insulin and idebenone significantly closed the tight junction (TJ) in diabetic rats. The results from Western blotting in diabetic rats show that the upregulation of TJ-associated proteins occludin, and zonula occludens (ZO)-1 caused by the combination of insulin and idebenone is more remarkable than that with either agent alone. In addition, the activations of reactive oxygen species (ROS) and advanced glycation end products (AGEs) and the expression levels of receptors for advanced glycation end-products (RAGE) and nuclear factor-κB (NF-κB) were significantly decreased after treatment with insulin and idebenone in diabetic rats. These results suggest that the combination of insulin and idebenone could decrease the BBB permeability in diabetic rats by upregulating the expression of occludin, claudin-5, and ZO-1 and that the ROS/AGE/RAGE/NF-κB signal pathway might be involved in the process. © 2014 Wiley Periodicals, Inc.

  3. In vivo metabolism of clebopride in three animal species and in man.

    Science.gov (United States)

    Segura, J; Bakke, O M; Huizing, G; Beckett, A H

    1980-01-01

    Clebopride is extensively metabolized in the rat, rabbit, dog, and man. By use of chromatographic methods, up to 25 metabolites in hydrolyzed and nonhydrolyzed urine have been detected. All four species produced the same main metabolites, as indicated by thin-layer chromatography. These, isolated from urine of the three animal species, were identified as N-(4'-piperidyl)-2-methoxy-4-amino-5-chlorobenzamide, N-(4'-piperidyl-2'-one)-2-methoxy-4-amino-5-chlorobenzamide, and N-(1'-alpha-hydroxybenzyl-4'-piperidyl)-2-methoxy-4-amino-5-chlorobenzamide (tentative structure of a carbinolamine more stable than expected). In the dog, 2-methoxy-4-amino-5-chlorobenzoic acid was also detected. N4-glucuronidation of clebopride and some of its metabolites has been shown to occur in the three animal species. The rabbit produced large amounts of these conjugates. Clebopride N4-sulfonate was not present in the urine of any of the species investigated.

  4. Protective effect of agmatine in acute chlorpromazine hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Bratislav Dejanovic

    2014-01-01

    Full Text Available The present study focused on potentially beneficial effects of agmatine on oxidative stress development in the liver during chlorpromazine treatment in rats. We wanted to examine the role of reactive oxygen species and efficiency of antioxidant protection through the determination of malondylaldehyde and total glutathione concentrations in rat liver homogenate, as well as plasma concentrations of malonylaldehyde and sulfhydryl groups after the treatment. Also, liver tissue sections were examined to follow histological changes. Chlorpromazine was applied intraperitoneally at a single dose of 38.7 mg/kg b.w. The second group was treated with both chlorpromazine (at a single dose of 38.7 mg/kg b.w. and agmatine (at a single dose of 75 mg/kg b.w.. Agmatine was applied immediately after the chlorpromazine. The control group was treated with 0.9% saline solution in the same manner. Rats were sacrificed by decapitation 24 h after the treatment and biochemical and immunohistochemical examinations were performed. Analysis of data showed that treatment with agmatine significantly attenuated the oxidative stress indicators as evidenced by lowering malonylaldehyde concentrations in the liver and in plasma while not affecting liver concentrations of total glutathione and plasma concentration of sulfhydryl groups. Additionally, histological evaluation revealed the improvement of liver damage in this respect. The presented data indicated that intraperitoneally administered agmatine protects against chlorpromazine-induced liver disease in rats.

  5. Inhibition of serum cholesterol oxidation by dietary vitamin C and selenium intake in high fat fed rats.

    Science.gov (United States)

    Menéndez-Carreño, M; Ansorena, D; Milagro, F I; Campión, J; Martínez, J A; Astiasarán, I

    2008-04-01

    Cholesterol oxidation products (COPs) have been considered as specific in vivo markers of oxidative stress. In this study, an increased oxidative status was induced in Wistar rats by feeding them a high-fat diet (cafeteria diet). Another group of animals received the same diet supplemented with a combination of two different antioxidants, ascorbic acid (100 mg/kg rat/day) and sodium selenite (200 microg/kg rat/day) and a third group fed on a control diet. Total and individual COPs analysis of the different diets showed no differences among them. At the end of the experimental trial, rats were sacrificed and serum cholesterol, triglycerides and COPs were measured. None of the diets induced changes in rats body weight, total cholesterol and triglycerides levels. Serum total COPs in rats fed on the high-fat diet were 1.01 microg/ml, two times the amount of the control rats (0.47 microg/ml). When dietary antioxidant supplementation was given, serum total COPs concentration (0.44 microg/ml) showed the same levels than those of the rats on control diet. 7beta-hydroxycholesterol, formed non-enzymatically via cholesterol peroxidation in the presence of reactive oxygen species, showed slightly lower values in the antioxidant-supplemented animals compared to the control ones. This study confirms the importance of dietary antioxidants as protective factors against the formation of oxysterols.

  6. Orally administered nicotine induces urothelial hyperplasia in rats and mice

    International Nuclear Information System (INIS)

    Dodmane, Puttappa R.; Arnold, Lora L.; Pennington, Karen L.; Cohen, Samuel M.

    2014-01-01

    Highlights: • Rats and mice orally administered with nicotine tartrate for total of 4 weeks. • No treatment-related death or whole body toxicity observed in any of the groups. • Urothelium showed simple hyperplasia in treated rats and mice. • No significant change in BrdU labeling index or SEM classification of urothelium. - Abstract: Tobacco smoking is a major risk factor for multiple human cancers including urinary bladder carcinoma. Tobacco smoke is a complex mixture containing chemicals that are known carcinogens in humans and/or animals. Aromatic amines a major class of DNA-reactive carcinogens in cigarette smoke, are not present at sufficiently high levels to fully explain the incidence of bladder cancer in cigarette smokers. Other agents in tobacco smoke could be excreted in urine and enhance the carcinogenic process by increasing urothelial cell proliferation. Nicotine is one such major component, as it has been shown to induce cell proliferation in multiple cell types in vitro. However, in vivo evidence specifically for the urothelium is lacking. We previously showed that cigarette smoke induces increased urothelial cell proliferation in mice. In the present study, urothelial proliferative and cytotoxic effects were examined after nicotine treatment in mice and rats. Nicotine hydrogen tartrate was administered in drinking water to rats (52 ppm nicotine) and mice (514 ppm nicotine) for 4 weeks and urothelial changes were evaluated. Histopathologically, 7/10 rats and 4/10 mice showed simple hyperplasia following nicotine treatment compared to none in the controls. Rats had an increased mean BrdU labeling index compared to controls, although it was not statistically significantly elevated in either species. Scanning electron microscopic visualization of the urothelium did not reveal significant cytotoxicity. These findings suggest that oral nicotine administration induced urothelial hyperplasia (increased cell proliferation), possibly due to a

  7. Comparative Study of the Liver Anatomy in the Rat, Rabbit, Guinea Pig and Chinchilla

    Directory of Open Access Journals (Sweden)

    Florin Gheorghe STAN

    2018-05-01

    Based on detailed study of the macroscopic anatomy of rat, rabbit, guinea pig and chinchilla a proper experimental model in liver research, could be assessed. In this regard, the vascular anatomy of the liver in the mentioned species is of a great importance and it is subject of another report.

  8. Comparative histology of mouse, rat, and human pelvic ligaments.

    Science.gov (United States)

    Iwanaga, Ritsuko; Orlicky, David J; Arnett, Jameson; Guess, Marsha K; Hurt, K Joseph; Connell, Kathleen A

    2016-11-01

    The uterosacral (USL) and cardinal ligaments (CL) provide support to the uterus and pelvic organs, and the round ligaments (RL) maintain their position in the pelvis. In women with pelvic organ prolapse (POP), the connective tissue, smooth muscle, vasculature, and innervation of the pelvic support structures are altered. Rodents are commonly used animal models for POP research. However, the pelvic ligaments have not been defined in these animals. In this study, we hypothesized that the gross anatomy and histological composition of pelvic ligaments in rodents and humans are similar. We performed an extensive literature search for anatomical and histological descriptions of the pelvic support ligaments in rodents. We also performed anatomical dissections of the pelvis to define anatomical landmarks in relation to the ligaments. In addition, we identified the histological components of the pelvic ligaments and performed quantitative analysis of the smooth muscle bundles and connective tissue of the USL and RL. The anatomy of the USL, CL, and RL and their anatomical landmarks are similar in mice, rats, and humans. All species contain the same cellular components and have similar histological architecture. However, the cervical portion of the mouse USL and RL contain more smooth muscle and less connective tissue compared with rat and human ligaments. The pelvic support structures of rats and mice are anatomically and histologically similar to those of humans. We propose that both mice and rats are appropriate, cost-effective models for directed studies in POP research.

  9. Molecular analyses of two bacterial sampling methods in ligature-induced periodontitis in rats.

    Science.gov (United States)

    Fontana, Carla Raquel; Grecco, Clovis; Bagnato, Vanderlei Salvador; de Freitas, Laura Marise; Boussios, Constantinos I; Soukos, Nikolaos S

    2018-02-01

    The prevalence profile of periodontal pathogens in dental plaque can vary as a function of the detection method; however, the sampling technique may also play a role in determining dental plaque microbial profiles. We sought to determine the bacterial composition comparing two sampling methods, one well stablished and a new one proposed here. In this study, a ligature-induced periodontitis model was used in 30 rats. Twenty-seven days later, ligatures were removed and microbiological samples were obtained directly from the ligatures as well as from the periodontal pockets using absorbent paper points. Microbial analysis was performed using DNA probes to a panel of 40 periodontal species in the checkerboard assay. The bacterial composition patterns were similar for both sampling methods. However, detection levels for all species were markedly higher for ligatures compared with paper points. Ligature samples provided more bacterial counts than paper points, suggesting that the technique for induction of periodontitis could also be applied for sampling in rats. Our findings may be helpful in designing studies of induced periodontal disease-associated microbiota.

  10. Arctigenin Increases Hemeoxygenase-1 Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat Primary Astrocytes

    OpenAIRE

    Jeong, Yeon-Hui; Park, Jin-Sun; Kim, Dong-Hyun; Kim, Hee-Sun

    2014-01-01

    In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-J...

  11. Spatial midsession reversal learning in rats: Effects of egocentric Cue use and memory.

    Science.gov (United States)

    Rayburn-Reeves, Rebecca M; Moore, Mary K; Smith, Thea E; Crafton, Daniel A; Marden, Kelly L

    2018-07-01

    The midsession reversal task has been used to investigate behavioral flexibility and cue use in non-human animals, with results indicating differences in the degree of control by environmental cues across species. For example, time-based control has been found in rats only when tested in a T-maze apparatus and under specific conditions in which position and orientation (i.e., egocentric) cues during the intertrial interval could not be used to aid performance. Other research in an operant setting has shown that rats often produce minimal errors around the reversal location, demonstrating response patterns similar to patterns exhibited by humans and primates in this task. The current study aimed to reduce, but not eliminate, the ability for rats to utilize egocentric cues by placing the response levers on the opposite wall of the chamber in relation to the pellet dispenser. Results showed that rats made minimal errors prior to the reversal, suggesting time-based cues were not controlling responses, and that they switched to the second correct stimulus within a few trials after the reversal event. Video recordings also revealed highly structured patterns of behavior by the majority of rats, which often differed depending on which response was reinforced. We interpret these findings as evidence that rats are adept at utilizing their own egocentric cues and that these cues, along with memory for the recent response-reinforcement contingencies, aid in maximizing reinforcement over the session. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. EFFECT OF ETHANOL ON HEPATOBILIARY TRANSPORT OF CATIONIC DRUGS - A STUDY IN THE ISOLATED-PERFUSED RAT-LIVER, RAT HEPATOCYTES AND RAT MITOCHONDRIA

    NARCIS (Netherlands)

    STEEN, H; MEIJER, DKF; Merema, M.T.

    The effect of ethanol on the hepatic uptake of various cationic drugs was studied in isolated perfused rat livers, isolated rat hepatocytes and isolated rat liver mitochondria. In isolated rat hepatocytes and in isolated perfused rat livers, the uptake of the model organic cation

  13. Human and rat gut microbiome composition is maintained following sleep restriction.

    Science.gov (United States)

    Zhang, Shirley L; Bai, Lei; Goel, Namni; Bailey, Aubrey; Jang, Christopher J; Bushman, Frederic D; Meerlo, Peter; Dinges, David F; Sehgal, Amita

    2017-02-21

    Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is associated with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurological and cognitive impairments. Shifts in gut microbiome composition have also been associated with the same pathologies; therefore, we hypothesized that sleep restriction may perturb the gut microbiome to contribute to a disease state. In this study, we examined the fecal microbiome by using a cross-species approach in both rat and human studies of sleep restriction. We used DNA from hypervariable regions (V1-V2) of 16S bacteria rRNA to define operational taxonomic units (OTUs) of the microbiome. Although the OTU richness of the microbiome is decreased by sleep restriction in rats, major microbial populations are not altered. Only a single OTU, TM7-3a, was found to increase with sleep restriction of rats. In the human microbiome, we find no overt changes in the richness or composition induced by sleep restriction. Together, these results suggest that the microbiome is largely resistant to changes during sleep restriction.

  14. A comparison of reactive oxygen species metabolism in the rat aorta and vena cava: focus on xanthine oxidase.

    Science.gov (United States)

    Szasz, Theodora; Thompson, Janice M; Watts, Stephanie W

    2008-09-01

    Reactive oxygen species (ROS) are important mediators in vascular biology. Venous function, although relevant to cardiovascular disease, is still understudied. We compared aspects of ROS metabolism between a major artery (the aorta) and a major vein (the vena cava, VC) of the rat, with the hypothesis that venous ROS metabolism would be overall increased compared with its arterial counterpart. Superoxide and hydrogen peroxide (H2O2) release in basal conditions was higher in VC compared with aorta. The antioxidant capacity for H2O2 was also higher in VC than in aorta. Exogenous superoxide induced a higher contraction in VC compared with aorta. Protein expression of three major ROS metabolizing enzymes, xanthine oxidase (XO), CuZn-SOD, and catalase, was higher in VC compared with aorta. Because XO seemed a likely source of the higher VC ROS levels, we examined it further and found higher mRNA expression and activity of XO in VC compared with aorta. We also investigated the impact of XO inhibition by allopurinol on aorta and VC functional responses to norepinephrine, ANG II, ET-1, and ACh. Maximal ET-1-mediated contraction was decreased by allopurinol in VC but not in the aorta. Our results suggest that there are overall differences in ROS metabolism between aorta and VC, with the latter operating normally at a higher set point, releasing but also being able to handle, higher ROS levels. We propose XO to be an important source for these differences. The result of this particular comparison may be reflective of a general arteriovenous contrast.

  15. Multiple geographic origins of commensalism and complex dispersal history of Black Rats.

    Science.gov (United States)

    Aplin, Ken P; Suzuki, Hitoshi; Chinen, Alejandro A; Chesser, R Terry; Ten Have, José; Donnellan, Stephen C; Austin, Jeremy; Frost, Angela; Gonzalez, Jean Paul; Herbreteau, Vincent; Catzeflis, Francois; Soubrier, Julien; Fang, Yin-Ping; Robins, Judith; Matisoo-Smith, Elizabeth; Bastos, Amanda D S; Maryanto, Ibnu; Sinaga, Martua H; Denys, Christiane; Van Den Bussche, Ronald A; Conroy, Chris; Rowe, Kevin; Cooper, Alan

    2011-01-01

    The Black Rat (Rattus rattus) spread out of Asia to become one of the world's worst agricultural and urban pests, and a reservoir or vector of numerous zoonotic diseases, including the devastating plague. Despite the global scale and inestimable cost of their impacts on both human livelihoods and natural ecosystems, little is known of the global genetic diversity of Black Rats, the timing and directions of their historical dispersals, and the risks associated with contemporary movements. We surveyed mitochondrial DNA of Black Rats collected across their global range as a first step towards obtaining an historical genetic perspective on this socioeconomically important group of rodents. We found a strong phylogeographic pattern with well-differentiated lineages of Black Rats native to South Asia, the Himalayan region, southern Indochina, and northern Indochina to East Asia, and a diversification that probably commenced in the early Middle Pleistocene. We also identified two other currently recognised species of Rattus as potential derivatives of a paraphyletic R. rattus. Three of the four phylogenetic lineage units within R. rattus show clear genetic signatures of major population expansion in prehistoric times, and the distribution of particular haplogroups mirrors archaeologically and historically documented patterns of human dispersal and trade. Commensalism clearly arose multiple times in R. rattus and in widely separated geographic regions, and this may account for apparent regionalism in their associated pathogens. Our findings represent an important step towards deeper understanding the complex and influential relationship that has developed between Black Rats and humans, and invite a thorough re-examination of host-pathogen associations among Black Rats.

  16. Oxidative stress is reduced in Wistar rats exposed to smoke from tobacco and treated with specific broad-band pulse electromagnetic fields

    Directory of Open Access Journals (Sweden)

    Bajić V.

    2009-01-01

    Full Text Available There have been a number of attempts to reduce the oxidative radical burden of tobacco. A recently patented technology, pulse electromagnetic technology, has been shown to induce differential action of treated tobacco products versus untreated products on the production of reactive oxygen species (ROS in vivo. In a 90-day respiratory toxicity study, Wistar rats were exposed to cigarette smoke from processed and unprocessed tobacco and biomarkers of oxidative stress were compared with pathohistological analysis of rat lungs. Superoxide dismutase (SOD activity was decreased in a dose-dependent manner to 81% in rats exposed to smoke from normal cigarettes compared to rats exposed to treated smoke or the control group. These results correspond to pathohistological analysis of rat lungs, in which those rats exposed to untreated smoke developed initial signs of emphysema, while rats exposed to treated smoke showed no pathology, as in the control group. The promise of inducing an improved health status in humans exposed to smoke from treated cigarettes merits further investigation.

  17. Divergent brain changes in two audiogenic rat strains: A voxel-based morphometry and diffusion tensor imaging comparison of the genetically epilepsy prone rat (GEPR-3) and the Wistar Audiogenic Rat (WAR).

    Science.gov (United States)

    Lee, Yichien; Rodriguez, Olga C; Albanese, Chris; Santos, Victor Rodrigues; Cortes de Oliveira, José Antônio; Donatti, Ana Luiza Ferreira; Fernandes, Artur; Garcia-Cairasco, Norberto; N'Gouemo, Prosper; Forcelli, Patrick A

    2018-03-01

    Acoustically evoked seizures (e.g., audiogenic seizures or AGS) are common in models of inherited epilepsy and occur in a variety of species including rat, mouse, and hamster. Two models that have been particularly well studied are the genetically epilepsy prone rat (GEPR-3) and the Wistar Audiogenic Rat (WAR) strains. Acute and repeated AGS, as well as comorbid conditions, displays a close phenotypic overlap in these models. Whether these similarities arise from convergent or divergent structural changes in the brain remains unknown. Here, we examined the brain structure of Sprague Dawley (SD) and Wistar (WIS) rats, and quantified changes in the GEPR-3 and WAR, respectively. Brains from adult, male rats of each strain (n=8-10 per group) were collected, fixed, and embedded in agar and imaged using a 7 tesla Bruker MRI. Post-acquisition analysis included voxel-based morphometry (VBM), diffusion tensor imaging (DTI), and manual volumetric tracing. In the VBM analysis, GEPR-3 displayed volumetric changes in brainstem structures known to be engaged by AGS (e.g., superior and inferior colliculus, periaqueductal grey) and in forebrain structures (e.g., striatum, septum, nucleus accumbens). WAR displayed volumetric changes in superior colliculus, and a broader set of limbic regions (e.g., hippocampus, amygdala/piriform cortex). The only area of significant overlap in the two strains was the midline cerebellum: both GEPR-3 and WAR showed decreased volume compared to their control strains. In the DTI analysis, GEPR-3 displayed decreased fractional anisotropy (FA) in the corpus callosum, posterior commissure and commissure of the inferior colliculus (IC). WAR displayed increased FA only in the commissure of IC. These data provide a biological basis for further comparative and mechanistic studies in the GEPR-3 and WAR models, as well as provide additional insight into commonalities in the pathways underlying AGS susceptibility and behavioral comorbidity. Copyright © 2017

  18. Radiation response of skin in young and old rats

    Energy Technology Data Exchange (ETDEWEB)

    Hamlet, R.; Hopewell, J.W. (Churchill Hospital, Oxford (UK))

    1982-11-01

    The results of this investigation clearly demonstrate the different radiation skin response in rats of differing ages. The reasons for these differences cannot be clarified until cell kinetic studies have been completed. These results obtained for rodent skin would appear to be in disagreement with the available data for human skin (Rubin and Casarett 1968) where no marked age-related changes were reported. Also, in pig skin studies (Hopewell and Young 1982) there was no evidence of an age effect in the dermal vascular response in 3-12-month-old animals. This may be related to the different tissue being investigated or it may reflect important species differences. Whatever the reasons behind these observations, the different skin response to radiation in rats of 7, 14 and 52 weeks of age has clearly been demonstrated and should be borne in mind when extrapolating data with rodent skin to the clinical situation.

  19. Differences in both glycosylation and binding properties between rat and mouse liver prolactin receptors.

    Science.gov (United States)

    Lascols, O; Cherqui, G; Munier, A; Picard, J; Capeau, J

    1994-05-01

    To investigate whether glycanic chains of prolactin receptors (PRL-R) play a role in hormone binding activity, comparison was made of rat and mouse liver solubilized receptors with respect to both their affinity for the hormone and their glycosylation properties. As compared with rat receptors, mouse receptors exhibited a 2-fold higher affinity for human growth hormone (hGH), the hormone being bound by both tissues with a lactogenic specificity. Along with this increased affinity, mouse receptors had a 2 lower M(r) relative to rat receptors (62 kDa versus 64 kDa as measured on hGH cross-linked receptors). These differences could be ascribed to different glycosylation properties of the receptors from the two species, as supported by the followings. 1) After treatment with endoglycosidase F (endo F), rat and mouse PRL-R no longer exhibited any difference in their M(r) (54 kDa for both cross-linked receptors). 2) Neuraminidase treatment increased by 37% the binding of hGH to mouse receptors, but was ineffective on the hormone-binding to rat receptors. Conversely, wheat germ agglutinin (WGA), another sialic acid specific probe, decreased hGH binding to rat receptors by 25%, but had no effect on this process for mouse ones. 3) Marked differences were observed in the recoveries of rat and mouse hormone-receptor (HR) complexes from ricin-1- (RCA1-), concanavalin A- (ConA-) and WGA-immobilized lectins. These differences were reduced (RCA1 and ConA) or abolished (WGA) after rat and mouse receptor desialylation by neuraminidase, a treatment which decreased the M(r) of both receptors by 2 kDa. Taken together, these results strongly suggest that the PRL-R from rat and mouse liver contain biantennary N-linked oligosaccharidic chains with distinct type of sialylation, which may account for their differential hormone-binding affinities.

  20. The Effect of Exercise on the Skeletal Muscle Phospholipidome of Rats Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Jong Sam Lee

    2010-10-01

    Full Text Available The aim of this study was to examine the effect of endurance training on skeletal muscle phospholipid molecular species from high-fat fed rats. Twelve female Sprague-Dawley rats were fed a high-fat diet (78.1% energy. The rats were randomly divided into two groups, a sedentary control group and a trained group (125 min of treadmill running at 8 m/min, 4 days/wk for 4 weeks. Forty-eight hours after their last training bout phospholipids were extracted from the red and white vastus lateralis and analyzed by electrospray-ionization mass spectrometry. Exercise training was associated with significant alterations in the relative abundance of a number of phospholipid molecular species. These changes were more prominent in red vastus lateralis than white vastus lateralis. The largest observed change was an increase of ~30% in the abundance of 1-palmitoyl-2-linoleoyl phosphatidylcholine ions in oxidative fibers. Reductions in the relative abundance of a number of phospholipids containing long-chain n-3 polyunsaturated fatty acids were also observed. These data suggest a possible reduction in phospholipid remodeling in the trained animals. This results in a decrease in the phospholipid n-3 to n-6 ratio that may in turn influence endurance capacity.

  1. Biodistribution of 99MTc-antimony trisulphide colloid in a species of squamate versus rats

    International Nuclear Information System (INIS)

    Lai, C.; Cooter, R.D.; Tsopelas, C.; Chatterton, B.E.; Munns, S.; Daniels, C.B.

    2003-01-01

    Full text: We were interested in visualising the lymphatic system of dragon lizards, as a prelude to a study investigating regenerating lymphatics in other squamate models. Subcutaneous injection of 99m Tc-antimony trisulphide colloid (AC) intradermally of the tail resulted in rapid migration to the pelvic plexus, with subsequent visualisation of the blood pool and intraabdominal organs. Thirty minutes after intravenous administration of 99m Tc-AC in dragon lizards, there was high blood activity of 7.50% dose/g, liver uptake of 0.27% dose/g, spleen uptake of 0.33% dose/g and femur uptake of 0.03% dose/g. In comparison to a mammalian model of similar size, intravenous injection of this tracer in rats resulted in far lower blood activity of 0.46% dose/g, and substantially higher liver uptake of 9.70% dose/g, spleen uptake of 22.30% dose/g and femur uptake of 1.72% dose/g. These results agree with the British Pharmacopoeial test limits set for the distribution of 99m Tc-AC in mice. In summary, results show the cold blooded lizards to have rapidly migrating lymph in the tail, appearing to enter the circulation near the pelvic plexus. A low metabolic rate of the squamate retained 99m Tc-AC in slowly circulating blood, gradually depositing this colloid in liver and spleen. In contrast, rats have much faster yet typical colloidal uptake by the reticuloendothelial system. Copyright (2003) The Australian and New Zealand Society of Nuclear Medicine Inc

  2. Standardisation of environmental enrichment for laboratory mice and rats: Utilisation, practicality and variation in experimental results

    NARCIS (Netherlands)

    Baumans, V.; Loo, P.L.P. van; Pham, T.M.

    2010-01-01

    Rats and mice are the most commonly used species as laboratory animal models of diseases in biomedical research. Environmental factors such as cage size, number of cage mates and cage structure such as environmental enrichment can affect the physiology and behavioural development of laboratory

  3. Activation and odor conditioning of suckling behavior in 3-day-old albino rats.

    Science.gov (United States)

    Pedersen, P E; Williams, C L; Blass, E M

    1982-10-01

    The circumstances under which a novel odor could elicit nipple attachment behavior in 3-day-old albino rats were investigated. In Experiment 1, rats suckled washed nipples scented with citral (a lemon odor) only if they either had received tactile stimulation (by stroking with a soft artist's brush) or had been administered amphetamine in the presence of citral prior to the suckling test. Pups stimulated in citral's absence or simply exposed to citral without stimulation failed to suckle such nipples. In Experiment 2, rats stimulated in a benzaldehyde (an almond odor) ambience suckled washed nipples scented with benzaldehyde but not those with citral scent. The opposite held for rats stimulated in a citral-rich environment. The stimulus conditions that support this conditioning were investigated in Experiment 3. Simultaneously increasing citral concentration and raising ambient temperature markedly attenuated the phenomenon. Experiment 4 demonstrated that not all classes of stimulation produced conditioning. Caffeine, in a wide range of doses, did not allow citral to elicit suckling on washed nipples. These findings are discussed within a framework of higher order conditioning. They may provide a mechanism by which naturally occurring stimuli come to elicit the species- and age-typical behavior of suckling.

  4. Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats.

    Directory of Open Access Journals (Sweden)

    Ricardo Valladares

    Full Text Available BACKGROUND: The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development. METHODOLOGY/PRINCIPAL: Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat. In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNgamma were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin. CONCLUSIONS: It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in Bio

  5. Protective effect of polyphenols on presbycusis via oxidative/nitrosative stress suppression in rats.

    Science.gov (United States)

    Sánchez-Rodríguez, Carolina; Martín-Sanz, Eduardo; Cuadrado, Esperanza; Granizo, Juan José; Sanz-Fernández, Ricardo

    2016-10-01

    Age-related hearing loss (AHL) -presbycusis- is the number one neurodegenerative disorder and top communication deficit of our aged population. Experimental evidence suggests that mitochondrial dysfunction associated with reactive oxygen species (ROS) plays a central role in the aging process of cochlear cells. Dietary antioxidants, in particular polyphenols, have been found to be beneficial in protecting against the generation of ROS in various diseases associated with oxidative stress, such as cancer, neurodegenerative diseases and aging. This study was designed to investigate the effects of polyphenols on AHL and to determine whether oxidative stress plays a role in the pathophysiology of AHL. Sprague-Dawley rats (n=100) were divided into five groups according to their age (3, 6, 12, 18 and 24months old) and treated with 100mg/kg/day body weight of polyphenols dissolved in tap water for half of the life of the animal. Auditory steady-state responses (ASSR) threshold shifts were measured before sacrificing the rats. Then, cochleae were harvested to measure total superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, reactive oxidative and nitrogen species levels, superoxide anions and nitrotyrosine levels. Increased levels of ROS and RNS in cochlea observed with age decreases with polyphenol treatment. In addition, the activity of SOD and GPx enzymes in older rats recovered after the administration of polyphenols. The reduction in oxidative and nitrosative stress in the presence of polyphenols correlates with significant improvements in ASSR threshold shifts. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Variation in nocturnality and circadian activity rhythms between photoresponsive F344 and nonphotoresponsive Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Johnson Cynthia E

    2008-09-01

    Full Text Available Abstract Background Variation in circadian rhythms and nocturnality may, hypothetically, be related to or independent of genetic variation in photoperiodic mediation of seasonal changes in physiology and behavior. We hypothesized that strain variation in photoperiodism between photoperiodic F344 rats and nonphotoperiodic Harlan Sprague Dawley (HSD rats might be caused by underlying variation in clock function. We predicted that HSD rats would have more activity during the day or subjective day, longer free-running rhythms, poor entrainment to short day length, and shorter duration of activity, traits that have been associated with nonphotoperiodism in other laboratory rodent species, relative to F344 rats. An alternative hypothesis, that differences are due to variation in melatonin secretion or responses to melatonin, predicts either no such differences or inconsistent combinations of differences. Methods We tested these predictions by examining activity rhythms of young male F344 and HSD rats given access to running wheels in constant dark (DD, short day length (L8:D16; SD, and long day length (L16:D8; LD. We compared nocturnality (the proportion of activity during night or subjective night, duration of activity (alpha, activity onset and offset, phase angle of entrainment, and free running rhythms (tau of F344 and HSD rats. Results HSD rats had significantly greater activity during the day, were sometimes arrhythmic in DD, and had significantly longer tau than F344 rats, consistent with predictions. However, HSD rats had significantly longer alpha than F344 rats and both strains entrained to SD, inconsistent with predictions. Conclusion The ability of HSD rats to entrain to SD, combined with longer alpha than F344 rats, suggests that the circadian system of HSD rats responds correctly to SD. These data offer best support for the alternative hypothesis, that differences in photoresponsiveness between F344 and HSD rats are caused by non

  7. Will Climate Change, Genetic and Demographic Variation or Rat Predation Pose the Greatest Risk for Persistence of an Altitudinally Distributed Island Endemic?

    Directory of Open Access Journals (Sweden)

    Alison Shapcott

    2012-11-01

    Full Text Available Species endemic to mountains on oceanic islands are subject to a number of existing threats (in particular, invasive species along with the impacts of a rapidly changing climate. The Lord Howe Island endemic palm Hedyscepe canterburyana is restricted to two mountains above 300 m altitude. Predation by the introduced Black Rat (Rattus rattus is known to significantly reduce seedling recruitment. We examined the variation in Hedyscepe in terms of genetic variation, morphology, reproductive output and demographic structure, across an altitudinal gradient. We used demographic data to model population persistence under climate change predictions of upward range contraction incorporating long-term climatic records for Lord Howe Island. We also accounted for alternative levels of rat predation into the model to reflect management options for control. We found that Lord Howe Island is getting warmer and drier and quantified the degree of temperature change with altitude (0.9 °C per 100 m. For H. canterburyana, differences in development rates, population structure, reproductive output and population growth rate were identified between altitudes. In contrast, genetic variation was high and did not vary with altitude. There is no evidence of an upward range contraction as was predicted and recruitment was greatest at lower altitudes. Our models predicted slow population decline in the species and that the highest altitude populations are under greatest threat of extinction. Removal of rat predation would significantly enhance future persistence of this species.

  8. A novel lens epithelium gene, LEP503, is highly conserved in different vertebrate species and is developmentally regulated in postnatal rat lens.

    Science.gov (United States)

    Wen, Y; Sachs, G; Athmann, C

    2000-02-01

    The development of the lens is dependent on the proliferation of lens epithelial cells and their differentiation into fiber cells near the lens bow/equator. Identification of genes specifically expressed in the lens epithelial cells and their functions may provide insight into molecular events that regulate the processes of lens epithelial cell differentiation. In this study, a novel lens epithelium gene product, LEP503, identified from rat by a subtractive cDNA cloning strategy was investigated in the genome organization, mRNA expression and protein localization. The genomic sequences for LEP503 isolated from rat, mouse and human span 1754 bp, 1694 bp and 1895 bp regions encompassing the 5'-flanking region, two exons, one intron and 3'-flanking region. All exon-intron junction sequences conform to the GT/AG rule. Both mouse and human LEP503 genes show very high identity (93% for mouse and 79% for human) to rat LEP503 gene in the exon 1 that contains an open reading frame coding for a protein of 61 amino acid residues with a leucine-rich domain. The deduced protein sequences also show high identity (91% between mouse and rat and 77% between human and rat). Western blot shows that LEP503 is present as a specific approximately 6.9 kDa band in the water-insoluble-urea-soluble fraction of lens cortex where lens epithelium is included. Immuno-staining shows that LEP503 is localized in the epithelial cells along the entire anterior surface of rat lens. Developmentally, LEP503 is expressed at a low level at newborn, and then the expression level increases by about ten-fold around postnatal day 14 and remains at this high level for about 25 days before it drops back to the low level by postnatal day 84. These data suggest that the LEP503 may be an important lens epithelial cell gene involving the processes of epithelial cell differentiation. Copyright 2000 Academic Press.

  9. Chronic organic manganese administration in the rat does not damage dopaminergic nigrostriatal neurons.

    Science.gov (United States)

    Yong, V W; Perry, T L; Godolphin, W J; Jones, K A; Clavier, R M; Ito, M; Foulks, J G

    1986-01-01

    In an attempt to produce an animal model of Parkinson's disease, we injected rats repeatedly with high doses of methylcyclopentadienyl manganese tricarbonyl (MMT), a compound which has been reported to lower striatal dopamine content in mice. Chronic MMT administration for up to 5 months, even though it produced a substantial elevation in brain manganese content during the period of exposure, did not destroy dopaminergic nigrostriatal neurons. This was assessed by measurements of tyrosine hydroxylase activity and contents of dopamine and its metabolites in the striatum, and by histological examination of the substantia nigra. Our results differ from those of others who administered manganese chloride in drinking water to rats. This discrepancy is unlikely to be a consequence of differences in duration of exposure or route of administration. It could be due to our having used an organic rather than an inorganic manganese compound, or to a species difference in vulnerability to organic manganese between rats and mice.

  10. Environmental Factors and Zoonotic Pathogen Ecology in Urban Exploiter Species.

    Science.gov (United States)

    Rothenburger, Jamie L; Himsworth, Chelsea H; Nemeth, Nicole M; Pearl, David L; Jardine, Claire M

    2017-09-01

    Knowledge of pathogen ecology, including the impacts of environmental factors on pathogen and host dynamics, is essential for determining the risk that zoonotic pathogens pose to people. This review synthesizes the scientific literature on environmental factors that influence the ecology and epidemiology of zoonotic microparasites (bacteria, viruses and protozoa) in globally invasive urban exploiter wildlife species (i.e., rock doves [Columba livia domestica], European starlings [Sturnus vulgaris], house sparrows [Passer domesticus], Norway rats [Rattus norvegicus], black rats [R. rattus] and house mice [Mus musculus]). Pathogen ecology, including prevalence and pathogen characteristics, is influenced by geographical location, habitat, season and weather. The prevalence of zoonotic pathogens in mice and rats varies markedly over short geographical distances, but tends to be highest in ports, disadvantaged (e.g., low income) and residential areas. Future research should use epidemiological approaches, including random sampling and robust statistical analyses, to evaluate a range of biotic and abiotic environmental factors at spatial scales suitable for host home range sizes. Moving beyond descriptive studies to uncover the causal factors contributing to uneven pathogen distribution among wildlife hosts in urban environments may lead to targeted surveillance and intervention strategies. Application of this knowledge to urban maintenance and planning may reduce the potential impacts of urban wildlife-associated zoonotic diseases on people.

  11. Effects of proteins on absorption by the rat of iron from polymeric and low-molecular-weight iron species

    International Nuclear Information System (INIS)

    Berner, L.; Miller, D.

    1986-01-01

    To examine effects of proteins on Fe absorption from polymeric ferric hydroxides (polys) or low-molecular-weight complexes (LMW Fe), 2 studies were conducted. First, anemic rats were given 59 Fe-labeled polys or LMW Fe in the presence and absence of pepsin-digested soy protein isolate, casein, and BSA. The doses were introduced into ligated duodenal segments for 1 hr. Uptake into the carcass of 59 Fe from polys was doubled in the presence of BSA (7.8 vs 16.1%, p 59 Fe from LMW Fe was 7X greater than from polys; BSA and casein had no effect but soy depressed Fe uptake by almost 50% (57.4 vs 35.5%, p < .05). The second experiment repeated the first except that the proteins were not pepsin-digested and the doses were given by gastric intubation. All Fe, whether from polys or LMW Fe, was highly available (although in vitro digestions reveal that polys are not depolymerized to a large degree under simulated stomach conditions). Soy depressed Fe uptake from both sources (92.9 vs. 81.6%, LMW Fe and 85.4 vs 73.7%, polys) while casein and BSA had no effect. These results show: (1) BSA can depolymerize polys in the rat duodenum, thus enhancing absorption; (2) soy isolate generally depressed Fe uptake; and (3) the rat stomach appears to have an exceptional capacity for equalizing Fe sources

  12. Effect of naturally mouldy wheat or fungi administration on metallothioneins level in brain tissues of rats.

    Science.gov (United States)

    Vasatkova, Anna; Krizova, Sarka; Krystofova, Olga; Adam, Vojtech; Zeman, Ladislav; Beklova, Miroslava; Kizek, Rene

    2009-01-01

    The aim of this study is to determine level of metallothioneins (MTs) in brain tissues of rats administered by feed mixtures with different content of mouldy wheat or fungi. Selected male laboratory rats of Wistar albino at age of 28 days were used in our experiments. The rats were administered by feed mixtures with different content of vitamins, naturally mouldy wheat or fungi for 28 days. At the very end of the experiment, the animals were put to death and brains were sampled. MT level was determined by differential pulse voltammetry Brdicka reaction. We found that MTs' level in brain tissues from rats administered by standard feed mixtures was significantly higher compared to the level of MTs in rats supplemented by vitamins. Further we studied the effect of supplementation of naturally mouldy wheat on MTs level in rats. In mouldy wheat we detected the presence of following fungi species: Mucor spp., Absidia spp., Penicillium spp., Aspergillus spp. and Fusarium spp. Moreover we also identified and quantified following mycotoxins - deoxynivalenol, zearalenone, T2-toxin and aflatoxins. Level of MTs determined in rats treated with 33 or 66% of mouldy wheat was significantly lower compared to control ones. On the other hand rats treated with 100% of mouldy wheat had less MTs but not significantly. Supplementation of vitamins to rats fed by mouldy wheat had adverse effect on MTs level compared to rats with no other supplementation by vitamins. Moreover vitamins supplementation has no effect on MTs level in brain tissues of rats treated or non-treated with Ganoderma lucidum L. Both mycotoxins and vitamins have considerable effect on level of MTs in brain tissues. It can be assumed that the administered substances markedly influence redox metabolism, which could negatively influence numerous biochemical pathways including those closely related with MTs.

  13. Phencyclidine Disrupts the Auditory Steady State Response in Rats.

    Directory of Open Access Journals (Sweden)

    Emma Leishman

    Full Text Available The Auditory Steady-State Response (ASSR in the electroencephalogram (EEG is usually reduced in schizophrenia (SZ, particularly to 40 Hz stimulation. The gamma frequency ASSR deficit has been attributed to N-methyl-D-aspartate receptor (NMDAR hypofunction. We tested whether the NMDAR antagonist, phencyclidine (PCP, produced similar ASSR deficits in rats. EEG was recorded from awake rats via intracranial electrodes overlaying the auditory cortex and at the vertex of the skull. ASSRs to click trains were recorded at 10, 20, 30, 40, 50, and 55 Hz and measured by ASSR Mean Power (MP and Phase Locking Factor (PLF. In Experiment 1, the effect of different subcutaneous doses of PCP (1.0, 2.5 and 4.0 mg/kg on the ASSR in 12 rats was assessed. In Experiment 2, ASSRs were compared in PCP treated rats and control rats at baseline, after acute injection (5 mg/kg, following two weeks of subchronic, continuous administration (5 mg/kg/day, and one week after drug cessation. Acute administration of PCP increased PLF and MP at frequencies of stimulation below 50 Hz, and decreased responses at higher frequencies at the auditory cortex site. Acute administration had a less pronounced effect at the vertex site, with a reduction of either PLF or MP observed at frequencies above 20 Hz. Acute effects increased in magnitude with higher doses of PCP. Consistent effects were not observed after subchronic PCP administration. These data indicate that acute administration of PCP, a NMDAR antagonist, produces an increase in ASSR synchrony and power at low frequencies of stimulation and a reduction of high frequency (> 40 Hz ASSR activity in rats. Subchronic, continuous administration of PCP, on the other hand, has little impact on ASSRs. Thus, while ASSRs are highly sensitive to NMDAR antagonists, their translational utility as a cross-species biomarker for NMDAR hypofunction in SZ and other disorders may be dependent on dose and schedule.

  14. Age dependent in vitro metabolism of bifenthrin in rat and human hepatic microsomes.

    Science.gov (United States)

    Nallani, Gopinath C; Chandrasekaran, Appavu; Kassahun, Kelem; Shen, Li; ElNaggar, Shaaban F; Liu, Zhiwei

    2018-01-01

    Bifenthrin, a pyrethroid insecticide, undergoes oxidative metabolism leading to the formation of 4'-hydroxy-bifenthrin (4'-OH-BIF) and hydrolysis leading to the formation of TFP acid in rat and human hepatic microsomes. In this study, age-dependent metabolism of bifenthrin in rats and humans were determined via the rates of formation of 4'-OH-BIF and TFP acid following incubation of bifenthrin in juvenile and adult rat (PND 15 and PND 90) and human (18years) liver microsomes. Furthermore, in vitro hepatic intrinsic clearance (CL int ) of bifenthrin was determined by substrate consumption method in a separate experiment. The mean V max (±SD) for the formation of 4'-OH-BIF in juvenile rat hepatic microsomes was 25.0±1.5pmol/min/mg which was significantly lower (pbifenthrin occurs primarily via oxidative pathway with relatively lesser contribution (~30%) from hydrolytic pathway in both rat and human liver microsomes. The CL int values for bifenthrin, determined by monitoring the consumption of substrate, in juvenile and adult rat liver microsomes fortified with NADPH were 42.0±7.2 and 166.7±20.5μl/min/mg, respectively, and the corresponding values for human liver microsomes were 76.0±4.0 and 21.3±1.2μl/min/mg, respectively. The data suggest a major species difference in the age dependent metabolism of bifenthrin. In human liver microsomes, bifenthrin is metabolized at a much higher rate in juveniles than in adults, while the opposite appears to be true in rat liver microsomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. 76 FR 10621 - Palmyra Atoll National Wildlife Refuge, U.S. Pacific Island Territory; Nonnative Rat Eradication...

    Science.gov (United States)

    2011-02-25

    ... any of the following methods. For information on viewing or obtaining the documents, see ``Public... species in their natural setting on the Atoll. The Pacific Remote Islands Marine National Monument... eliminate black rats from Palmyra Atoll. Public Availability of the DEIS The DEIS is available for viewing...

  16. Upper respiratory tract nociceptor stimulation and stress response following acute and repeated Cyfluthrin inhalation in normal and pregnant rats: Physiological rat-specific adaptions can easily be misunderstood as adversities.

    Science.gov (United States)

    Pauluhn, Juergen

    2018-01-05

    This paper reviews the results from past regulatory and mechanistic inhalation studies in rats with the type II pyrethroid Cyfluthrin. Apart from many chemical irritants, Cyfluthrin was shown to be a neuroexcitatory agent without any inherent tissue-destructive or irritant property. Thus, any Cyfluthrin-induced neuroexcitatory afferent sensory stimulus from peripheral nociceptors in the upper respiratory tract is likely to be perceived as a transient stimulus triggering annoyance and/or avoidance by both rats and humans. However, while thermolabile rats respond to such stresses reflexively, homeothermic humans appear to respond psychologically. With this focus in mind, past inhalation studies in rats and human volunteers were reevaluated and assessed to identify common denominators to such neuroexcitatory stimuli upon inhalation exposure. This analysis supports the conclusion that the adaptive physiological response occurring in rats secondary to such chemosensory stimuli requires inhalation exposures above the chemosensory threshold. Rats, a species known to undergo adaptively a hibernation-like physiological state upon environmental stresses, experienced reflexively-induced bradypnea, bradycardia, hypothermia, and changes in acid-base status during inhalation exposure. After cessation of the sensory stimulus, rapid recovery occurred. Physiological data of male and female rats from a 4-week repeated inhalation study (exposure 6-h/day, 5-times/week) were used to select concentration for a 10-day developmental inhalation toxicity study in pregnant rats. Maternal hypothermia and hypoventilation were identified as likely cause of fetal and placental growth retardations because of a maternal adaptation-driven reduced feto-placental transfer of oxygen. In summary, maternal reflex-hypothermia, reduced cardiac output and placental perfusion, and disruption of the gestation-related hyperventilation are believed to be the maternally mediated causes for developmental

  17. Branched-Chain Amino Acid Supplementation Reduces Oxidative Stress and Prolongs Survival in Rats with Advanced Liver Cirrhosis

    Science.gov (United States)

    Mifuji-Moroka, Rumi; Hara, Nagisa; Miyachi, Hirohide; Sugimoto, Ryosuke; Tanaka, Hideaki; Fujita, Naoki; Gabazza, Esteban C.; Takei, Yoshiyuki

    2013-01-01

    Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (PBCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver. PMID:23936183

  18. Spread of the Rat Lungworm (Angiostrongylus cantonensis) in Giant African Land Snails (Lissachatina fulica) in Florida, USA.

    Science.gov (United States)

    Iwanowicz, Deborah D; Sanders, Lakyn R; Schill, W Bane; Xayavong, Maniphet V; da Silva, Alexandre J; Qvarnstrom, Yvonne; Smith, Trevor

    2015-07-01

    The rat lungworm (Angiostrongylus cantonensis) is a parasitic nematode that causes rat lungworm disease. It is the leading cause of eosinophilic meningitis and is a zoonotic health risk. We confirmed the presence of A. cantonensis using species-specific, quantitative PCR in 18 of 50 (36%) giant African land snails (Lissachatina fulica) collected from Miami, Florida, US in May 2013. These snails were collected from seven of 21 core areas that the Florida Department of Agriculture and Consumer Services monitor weekly. Rat lungworms have not previously been identified in these areas. Duplicate DNA extractions of foot muscle tissue from each snail were tested. Of the seven core areas we examined, six were positive for A. cantonensis and prevalence of infection ranged from 27% to 100%. Of the 18 positive snails, only five were positive in both extractions. Our results confirm an increase in the range and prevalence of rat lungworm infection in Miami. We also emphasize the importance of extracting sufficient host tissue to minimize false negatives.

  19. Expression of Sirtuins in the Retinal Neurons of Mice, Rats, and Humans

    Directory of Open Access Journals (Sweden)

    Hongdou Luo

    2017-11-01

    Full Text Available Sirtuins are a class of histone deacetylases (HDACs that have been shown to regulate a range of pathophysiological processes such as cellular aging, inflammation, metabolism, and cell proliferation. There are seven mammalian Sirtuins (SIRT1-7 that play important roles in stress response, aging, and neurodegenerative diseases. However, the location and function of Sirtuins in neurons are not well defined. This study assessed the retinal expression of Sirtuins in mice, rats, and humans and measured the expression of Sirtuins in aged and injured retinas. Expression of all 7 Sirtuins was confirmed by Western blot and Real-Time PCR analysis in all three species. SIRT1 is highly expressed in mouse, rat, and human retinas, whereas SIRT2-7 expression was relatively lower in human retinas. Immunofluorescence was also used to examine the expression and localization of Sirtuins in rat retinal neurons. Importantly, we demonstrate a marked reduction of SIRT1 expression in aged retinal neurons as well as retinas injured by acute ischemia-reperfusion. On the other hand, none of the other Sirtuins exhibit any significant age-related changes in expression except for SIRT5, which was significantly higher in the retinas of adults compared to both young and aged rats. Our work presents the first composite analysis of Sirtuins in the retinal neurons of mice, rats, and humans, and suggests that increasing the expression and activity of SIRT1 may be beneficial for the treatment of glaucoma and other age-related eye dysfunction.

  20. Characterization of TTN Novex Splicing Variants across Species and the Role of RBM20 in Novex-Specific Exon Splicing

    Directory of Open Access Journals (Sweden)

    Zhilong Chen

    2018-02-01

    Full Text Available Titin (TTN is a major disease-causing gene in cardiac muscle. Titin (TTN contains 363 exons in human encoding various sizes of TTN protein due to alternative splicing regulated mainly by RNA binding motif 20 (RBM20. Three isoforms of TTN protein are produced by mutually exclusive exons 45 (Novex 1, 46 (Novex 2, and 48 (Novex 3. Alternatively splicing in Novex isoforms across species and whether Novex isoforms are associated with heart disease remains completely unknown. Cross-species exon comparison with the mVISTA online tool revealed that exon 45 is more highly conserved across all species than exons 46 and 48. Importantly, a conserved region between exons 47 and 48 across species was revealed for the first time. Reverse transcript polymerase chain reaction (RT-PCR and DNA sequencing confirmed a new exon named as 48′ in Novex 3. In addition, with primer pairs for Novex 1, a new truncated form preserving introns 44 and 45 was discovered. We discovered that Novex 2 is not expressed in the pig, mouse, and rat with Novex 2 primer pairs. Unexpectedly, three truncated forms were identified. One TTN variant with intron 46 retention is mainly expressed in the human and frog heart, another variant with co-expression of exons 45 and 46 exists predominantly in chicken and frog heart, and a third with retention of introns 45 and 46 is mainly expressed in pig, mouse, rat, and chicken. Using Rbm20 knockout rat heart, we revealed that RBM20 is not a splicing regulator of Novex variants. Furthermore, the expression levels of Novex variants in human hearts with cardiomyopathies suggested that Novexes 2 and 3 could be associated with dilated cardiomyopathy (DCM and/or arrhythmogenic right ventricular cardiomyopathy (ARVC. Taken together, our study reveals that splicing diversity of Novex exons across species and Novex variants might play a role in cardiomyopathy.

  1. Autoradiographic localization of substance P receptors in the rat and bovine spinal cord and the rat and cat spinal trigeminal nucleus pars caudalis and the effects of neonatal capsaicin

    Energy Technology Data Exchange (ETDEWEB)

    Mantyh, P.W.; Hunt, S.P. (Medical Research Council Centre, Cambridge (UK). Medical School, MRC Neurochemical Pharmacology Unit)

    1985-04-22

    Substance P (SP) is a putative neurotransmitter in the central nervous system. In the present report the authors have used autoradiographic receptor binding techniques to investigate the distribution of SP receptor binding sites in the rat and bovine spinal cord and in the rat and cat spinal trigeminal nucleus pars caudalis. Although some quantitative differences were evident, all species appeared to have a similar distribution of SP receptor binding sites in both the spinal cord and in the spinal trigeminal nucleus pars caudalis. In the spinal cord the heaviest concentration of SP receptors is located in lamina X, while moderate to heavy concentrations were found in laminae I, II and V-IX. Very low concentrations of SP receptors were present in laminae III and IV. Examination of the cat and rat spinal trigeminal nucleus pars caudalis revealed a moderate density of SP receptor binding sites in laminae I and II, very low concentrations in laminae III and IV, and low to moderate concentrations in lamina V. Rats treated neonatally with capsaicin showed a small (11%) but significant (P < 0.02) increase in the levels of SP receptor binding sites in laminae I and II of the cervical and lumbar spinal cord while in all other laminae the levels remained unchanged.

  2. DNA fingerprinting, biological and chemical investigation of certain Yucca species.

    Science.gov (United States)

    El Hawary, Seham; El Sayed, Abeer; Helmy, Maged W; El Naggar, El Moataz Bellah; Marzouk, Hanan S; Bassam, Samar M

    2018-01-05

    Yucca aloifolia, Y. aloifolia variegata, Y. elephantipes and Y. filamentosa were investigated. DNA sequencing was performed for the four plants and a genomic DNA fingerprint was obtained and provided. The cytotoxic activities against four human cancer cell lines were investigated. The ethanolic extracts of leaves of Y. aloifolia variegata prevailed, especially against liver cancer HepG-2 and breast cancer MCF-7. In vivo assessment of hepatoprotective activity in rats also revealed the hepatoprotective potential of the ethanolic extracts of the four plants against CCl 4 - induced rats' liver damage. Qualitative and quantitative analysis of the flavonoid and phenolic content of the promising species was performed using HPLC. The analysis identified and quantified 18 flavonoids and 19 phenolic acids in the different fractions of Y. aloifolia variegata, among which the major flavonoids were hesperidin and kaemp-3-(2-p-coumaroyl) glucose and the major phenolic acids were gallic acid and protocatechuic acid.

  3. SUBCHRONIC PULMONARY PATHOLOGY, IRON-OVERLOAD AND TRANSCRIPTIONAL ACTIVITY AFTER LIBBY AMPHIBOLE EXPOSURE IN RAT MODELS OF CARDIOVASCULAR DISEASE

    Science.gov (United States)

    Background: Surface-available iron (Fe) is proposed to contribute to asbestos-induced toxicity through the production of reactive oxygen species.Objective: Our goal was to evaluate the hypothesis that rat models of cardiovascular disease with coexistent Fe overload would be incre...

  4. Differential effects of chronic fluoxetine on the behavior of dominant and subordinate naked mole-rats.

    Science.gov (United States)

    Mongillo, Daniel L; Kosyachkova, Ekaterina A; Nguyen, Tam M; Holmes, Melissa M

    2014-01-01

    Naked mole-rats are eusocial rodents that live in large subterranean colonies with a strict reproductive and social hierarchy. The breeding female (referred to as the queen) and 1 to 3 breeding males are the only reproductive members of the colony. Breeders are socially dominant and all other colony members are non-reproductive subordinates. The effects of manipulating the serotonergic neurotransmitter system on aggression and dominance behaviors are well studied in many species, but not in eusocial rodents like the naked mole-rat. The current study investigated how the serotonergic system influences aggressive/dominant behaviors in this species. To do this, two separate but related experiments were conducted: the effects of fluoxetine hydrochloride (FLX) on status-specific behaviors of subordinates (Experiment 1) and dominant queens (Experiment 2) were evaluated both in-colony and in a social-pairing paradigm. In accordance with our main hypothesis, chronic treatment of FLX attenuated the frequency and duration of aggression in queens, but not subordinates, when paired with an unfamiliar conspecific. Further exploration of pharmacological manipulation on status-specific behaviors of this eusocial species may elucidate the neurobiological mechanisms underlying their unique and rigid social hierarchy. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Application of ovine luteinizing hormone (LH) radioimmunoassay in the quantitation of LH in different mammalian species. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Millar, R.P.; Aehnelt, C.

    1977-09-01

    A sensitive double antibody radioimmunoassay has been developed for measuring luteinizing hormone (LH) in various African mammalian species, using rabbit anti-ovine LH serum (GDN 15) and radioiodinated rat LH or ovine LH. Serum and pituitary homogenates from some African mammals (hyrax, reedbuck, sable, impala, tsessebe, thar, spring-hare, ground squirrel and cheetah, as well as the domestic sheep, cow and horse and laboratory rat and hamster) produced displacement curves parallel to that of the ovine LH standards. The specificity of the assay was examined in detail for one species, the rock hyrax. Radioimmunoassay and bioassay estimates of LH in hyrax pituitaries containing widely differing quantities of pituitary hormones were similar. In sexually active male hyrax mean plasma LH was 12.1 ng/ml and pituitary LH 194 ..mu..g/gland, but in sexually quiescent hyrax mean plasma LH was 2.4 ng/ml and mean pituitary LH 76 ..mu..g/gland. Intravenous injection of 10 ..mu..g of luteinizing hormone releasing hormone increased mean LH levels in hyrax from 0.9 ng/ml to 23.2 ng/ml by 30 min. Conversely, im injection of 250 ..mu..g testosterone induced a fall in LH levels in male hyrax from 1.7 ng/ml to 0.7 ng/ml 6 h after administration. Although the specificity of the assay for quantitating plasma LH in other species was not categorically established, there was a good correlation between plasma LH concentration and reproductive state in the bontebok, impala, spring-hare, thar, cheetah, domestic horse and laboratory rat, suggesting the potential use of the antiserum in quantitating LH in a variety of mammalian species.

  6. Valerian inhibits rat hepatocarcinogenesis by activating GABA(A receptor-mediated signaling.

    Directory of Open Access Journals (Sweden)

    Anna Kakehashi

    Full Text Available Valerian is widely used as a traditional medicine to improve the quality of sleep due to interaction of several active components with the γ-aminobutyric acid (GABA A receptor (GABA(AR system. Recently, activation of GABA signaling in stem cells has been reported to suppress cell cycle progression in vivo. Furthermore, possible inhibitory effects of GABA(AR agonists on hepatocarcinogenesis have been reported. The present study was performed to investigate modulating effects of Valerian on hepatocarcinogenesis using a medium-term rat liver bioassay. Male F344 rats were treated with one of the most powerful Valerian species (Valeriana sitchensis at doses of 0, 50, 500 and 5000 ppm in their drinking water after initiation of hepatocarcinogenesis with diethylnitrosamine (DEN. Formation of glutathione S-transferase placental form positive (GST-P(+ foci was significantly inhibited by Valerian at all applied doses compared with DEN initiation control rats. Generation of 8-hydroxy-2'-deoxyguanosine in the rat liver was significantly suppressed by all doses of Valerian, likely due to suppression of Nrf2, CYP7A1 and induction of catalase expression. Cell proliferation was significantly inhibited, while apoptosis was induced in areas of GST-P(+ foci of Valerian groups associated with suppression of c-myc, Mafb, cyclin D1 and induction of p21(Waf1/Cip1, p53 and Bax mRNA expression. Interestingly, expression of the GABA(AR alpha 1 subunit was observed in GST-P(+ foci of DEN control rats, with significant elevation associated with Valerian treatment. These results indicate that Valerian exhibits inhibitory effects on rat hepatocarcinogenesis by inhibiting oxidative DNA damage, suppressing cell proliferation and inducing apoptosis in GST-P(+ foci by activating GABA(AR-mediated signaling.

  7. Localization of plutonium retention in the small intestine of the neonatal rat, guinea pig, baboon and macaca after Pu-citrate ingestion

    International Nuclear Information System (INIS)

    Fritsch, P.; Lataillade, G.; Beauvallet, M.; L'Hullier, I.; Lepage, M.; Metivier, H.; Masse, R.; Moutairou, K.; avi, 526, Republique Populaire du Benin)

    1988-01-01

    The retention of Pu-citrate in the gastrointestinal wall was compared at similar post ingestion times after ingestion at 2 days of age by rats and guinea pigs and at 1 to 34 days by neonatal primates. The small intestine was the main site of the Pu retention in all species. In rats and primates, most of the Pu was retained in the distal ileum, whereas in guinea pigs it was more homogeneously distributed. In the rats, Pu was retained in the epithelial cells on villi, but in the guinea pigs and primates it was confined to the macrophages under the epithelial cells in the lacteal region. (author)

  8. Expression of acid-sensing ion channels and selection of reference genes in mouse and naked mole rat.

    Science.gov (United States)

    Schuhmacher, Laura-Nadine; Smith, Ewan St John

    2016-12-13

    Acid-sensing ion channels (ASICs) are a family of ion channels comprised of six subunits encoded by four genes and they are expressed throughout the peripheral and central nervous systems. ASICs have been implicated in a wide range of physiological and pathophysiological processes: pain, breathing, synaptic plasticity and excitotoxicity. Unlike mice and humans, naked mole-rats do not perceive acid as a noxious stimulus, even though their sensory neurons express functional ASICs, likely an adaptation to living in a hypercapnic subterranean environment. Previous studies of ASIC expression in the mammalian nervous system have often not examined all subunits, or have failed to adequately quantify expression between tissues; to date there has been no attempt to determine ASIC expression in the central nervous system of the naked mole-rat. Here we perform a geNorm study to identify reliable housekeeping genes in both mouse and naked mole-rat and then use quantitative real-time PCR to estimate the relative amounts of ASIC transcripts in different tissues of both species. We identify RPL13A (ribosomal protein L13A) and CANX (calnexin), and β-ACTIN and EIF4A (eukaryotic initiation factor 4a) as being the most stably expressed housekeeping genes in mouse and naked mole-rat, respectively. In both species, ASIC3 was most highly expressed in dorsal root ganglia (DRG), and ASIC1a, ASIC2b and ASIC3 were more highly expressed across all brain regions compared to the other subunits. We also show that ASIC4, a proton-insensitive subunit of relatively unknown function, was highly expressed in all mouse tissues apart from DRG and hippocampus, but was by contrast the lowliest expressed ASIC in all naked mole-rat tissues.

  9. Repeated-Dose and Reproductive/Developmental Toxicity of NTO (3-Nitro-1,2,4-Triazol-5-One) in the Rat

    Science.gov (United States)

    2014-03-21

    strength, and stereotypes or changes in behavior (e.g., self- mutilation). Pregnant females approaching gestation day 21 were observed more frequently...and stereotypes or abnormal behavior (e.g., self mutilation , walking backwards). All data related to the observation of rats will be detailed and...are the recommended species due to an historical and extensive database. V.3.3. Laboratory animals V.3.3.1. Genus and Species: Rattus norvegicus V

  10. A window into extreme longevity; the circulating metabolomic signature of the naked mole-rat, a mammal that shows negligible senescence.

    Science.gov (United States)

    Lewis, Kaitlyn N; Rubinstein, Nimrod D; Buffenstein, Rochelle

    2018-04-20

    Mouse-sized naked mole-rats (Heterocephalus glaber), unlike other mammals, do not conform to Gompertzian laws of age-related mortality; adults show no age-related change in mortality risk. Moreover, we observe negligible hallmarks of aging with well-maintained physiological and molecular functions, commonly altered with age in other species. We questioned whether naked mole-rats, living an order of magnitude longer than laboratory mice, exhibit different plasma metabolite profiles, which could then highlight novel mechanisms or targets involved in disease and longevity. Using a comprehensive, unbiased metabolomics screen, we observe striking inter-species differences in amino acid, peptide, and lipid metabolites. Low circulating levels of specific amino acids, particularly those linked to the methionine pathway, resemble those observed during the fasting period at late torpor in hibernating ground squirrels and those seen in longer-lived methionine-restricted rats. These data also concur with metabolome reports on long-lived mutant mice, including the Ames dwarf mice and calorically restricted mice, as well as fruit flies, and even show similarities to circulating metabolite differences observed in young human adults when compared to older humans. During evolution, some of these beneficial nutrient/stress response pathways may have been positively selected in the naked mole-rat. These observations suggest that interventions that modify the aging metabolomic profile to a more youthful one may enable people to lead healthier and longer lives.

  11. Photo-oxidative damage to isolated rat liver mitochondria induced by phenothiazines

    Directory of Open Access Journals (Sweden)

    T. RODRIGUES

    2009-01-01

    Full Text Available

    Photosensitization is a well-known side-effect of phenothiazines that could involve photochemically promoted oxidative damage to mitochondria, leading to the impairment of metabolic functions and apoptosis. In this work, for the first time, we investigated the effects of photoexcited thioridazine (TR, trifluoperazine (TFP and fluphenazine (FP on isolated rat liver mitochondria. Under UV irradiation, the presence of these phenothiazines led to a dose-dependent lack of the respiratory control ratio. These effects were not accompanied by significant swelling and oxidation of protein thiol groups but were accompanied by lipid peroxidation. Lycopene and sorbate, well-known quenchers of singlet oxygen and triplet species, respectively, were ineffective at protecting mitochondrial lipids against the damage promoted by the excited phenothiazines, suggesting that photochemically-produced cation radicals were the prooxidant species. Corroborating this proposal, butylated hydroxytoluene (BHT completely inhibited the lipid peroxidation induced by UV irradiation in the presence of phenothiazines. These novel results make a significant contribution to the understanding of the photochemical properties of phenothiazines in biological systems. Keywords: Trifluoperazine, thioridazine, fluphenazine, rat liver mitochondria, oxidative stress, photochemistry, photodamage, respiratory chain.

  12. Temporal microbiota changes of high-protein diet intake in a rat model.

    Science.gov (United States)

    Mu, Chunlong; Yang, Yuxiang; Luo, Zhen; Zhu, Weiyun

    2017-10-01

    Alterations of specific microbes serve as important indicators that link gut health with specific diet intake. Although a six-week high-protein diet (45% protein) upregulates the pro-inflammatory response and oxidative stress in colon of rats, the dynamic alteration of gut microbiota remains unclear. To dissect temporal changes of microbiota, dynamic analyses of fecal microbiota were conducted using a rat model. Adult rats were fed a normal-protein diet or an HPD for 6 weeks, and feces collected at different weeks were used for microbiota and metabolite analysis. The structural alteration of fecal microbiota was observed after 4 weeks, especially for the decreased appearance of bands related to Akkermansia species. HPD increased numbers of Escherichia coli while decreased Akkermansia muciniphila, Bifidobacterium, Prevotella, Ruminococcus bromii, and Roseburia/Eubacterium rectale (P protein diet. HPD also decreased the copies of genes encoding butyryl-CoA:acetate CoA-transferase and Prevotella-associated methylmalonyl-CoA decarboxylase α-subunit (P high-protein diet. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-01-20

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

  15. Release from proactive interference in rat spatial working memory.

    Science.gov (United States)

    Roberts, William A; MacDonald, Hayden; Brown, Lyn; Macpherson, Krista

    2017-09-01

    A three-phase procedure was used to produce proactive interference (PI) in one trial on an eight-arm radial maze. Rats were forced to enter four arms for reward on an initial interference phase, to then enter the four remaining arms on a target phase, and to then choose among all eight arms on a retention test, with only the arms not visited in the target phase containing reward. Control trials involved only the target phase and the retention test. Lower accuracy was found on PI trials than on control trials, but performance on PI trials significantly exceeded chance, showing some retention of target memories. Changes in temporal and reward variables between the interference, target, and retention test phases showed release from PI, but changes in context and pattern of arm entry did not. It is suggested that the release from PI paradigm can be used to understand spatial memory encoding in rats and other species.

  16. The Regulatory Role of Nuclear Factor Kappa B in the Heart of Hereditary Hypertriglyceridemic Rat

    Czech Academy of Sciences Publication Activity Database

    Vranková, S.; Barta, A.; Klimentová, J.; Dovinová, I.; Líšková, Silvia; Dobešová, Zdenka; Pecháňová, O.; Kuneš, Jaroslav; Zicha, Josef

    2016-01-01

    Roč. 2016, č. 2016 (2016), s. 9814038 ISSN 1942-0900 R&D Projects: GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : nuclear factor-kB * nitric oxide * reactive oxygen species * heart * hereditary hypertriglyceridemic rats Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.593, year: 2016

  17. Fresh onion juice enhanced copulatory behavior in male rats with and without paroxetine-induced sexual dysfunction.

    Science.gov (United States)

    Allouh, Mohammed Z; Daradka, Haytham M; Al Barbarawi, Mohammed M; Mustafa, Ayman G

    2014-02-01

    Onion (Allium cepa) is one of the most commonly cultivated species of the family Liliaceae, and has long been used in dietary and therapeutic applications. Treatment with fresh onion juice has been reported to promote testosterone production in male rats. Testosterone is the male sex hormone responsible for enhancing sexual libido and potency. This study aimed to investigate the effects of onion juice on copulatory behavior of sexually potent male rats and in male rats with paroxetine-induced sexual dysfunction. Sexually experienced male rats were divided into seven groups: a control group, three onion juice-treated groups, a paroxetine-treated group, and two groups treated with paroxetine plus different doses of onion juice. At the end of the treatments, sexual behavior parameters and testosterone levels were measured and compared among the groups. Administration of onion juice significantly reduced mount frequency and latency and increased the copulatory efficacy of potent male rats. In addition, administration of onion juice attenuated the prolonged ejaculatory latency period induced by paroxetine and increased the percentage of ejaculating rats. Serum testosterone levels increased significantly by onion juice administration. However, a significant reduction in testosterone because of paroxetine therapy was observed. This reduction was restored to normal levels by administration of onion juice. This study conclusively demonstrates that fresh onion juice improves copulatory behavior in sexually potent male rats and in those with paroxetine-induced sexual dysfunction by increasing serum testosterone levels.

  18. Establishment of rat embryonic stem-like cells from the morula using a combination of feeder layers.

    Science.gov (United States)

    Sano, Chiaki; Matsumoto, Asako; Sato, Eimei; Fukui, Emiko; Yoshizawa, Midori; Matsumoto, Hiromichi

    2009-08-01

    Embryonic stem (ES) cells are characterized by pluripotency, in particular the ability to form a germline on injection into blastocysts. Despite numerous attempts, ES cell lines derived from rat embryos have not yet been established. The reason for this is unclear, although certain intrinsic biological differences among species and/or strains have been reported. Herein, using Wistar-Imamichi rats, specific characteristics of preimplantation embryos are described. At the blastocyst stage, Oct4 (also called Pou5f1) was expressed in both the inner cell mass (ICM) and the trophectoderm (TE), whereas expression of Cdx2 was localized to the TE. In contrast, at an earlier stage, expression of Oct4 was detected in all the nuclei in the morula. These stages were examined using a combination of feeder layers (rat embryonic fibroblast [REF] for primary outgrowth and SIM mouse embryo-derived thioguanine- and ouabain-resistant [STO] cells for passaging) to establish rat ES-like cell lines. The rat ES-like cell lines obtained from the morula maintained expression of Oct4 over long-term culture, whereas cell lines derived from blastocysts lost pluripotency during early passage. The morula-derived ES-like cell lines showed Oct4 expression in a long-term culture, even after cryogenic preservation, thawing and EGFP transfection. These results indicate that rat ES-like cell lines with long-term Oct4 expression can be established from the morula of Wistar-Imamichi rats using a combination of feeder layers.

  19. Modulatory role of allopurinol on xanthine oxidoreductase system and antioxidant status in irradiated rats

    International Nuclear Information System (INIS)

    Zahran, A.M.; Azab, Kh.Sh.; Abbady, M.I.

    2006-01-01

    Allopurinol is a xanthine oxidase (XO) inhibitor, used for management of hyperuricaema. It acts on purine catabolism without disrupting the biosynthesis of purine. The present work was conducted to examine the role of xanthine oxidase inhibitor (allopurinol) in minimizing radiation injuries in male albino rats. Allopurinol was given to rats via intraperitoneal (i.p) injection at a dose of 30 mg/kg body wt/day for 7 successive days before starting irradiation and 14 successive days during and in between exposure to gamma radiation. Rats were exposed to whole body gamma radiation, delivered as 1 Gy every other day up to total dose 8 Gy. Results demonstrate that treatment with allopurinol by the regime assumed in the present study minimized significantly the amount of thiobarbituric acid reactive substances (TBARS), product of lipid peroxidation, in liver, intestine and plasma. This effect was associated with significant amelioration in xanthine oxidoreductase (XOR) system as observed on the 1st and 7th days post last radiation fraction. The severity of changes in antioxidant parameters namely: superoxide dismutase (SOD), Catalase (CAT) and reduced glutathione (GSH) were less manifested in liver, intestine and blood as compared to irradiated rats. The levels of nitric oxide (NO) were significantly improved in plasma and the two investigated tissues as compared to irradiated rats. A significant decrease in plasma uric acid concentration was recorded on the 1st and 7th days post last allopurinol dose. However, significant amelioration was recorded in the plasma uric acid of rats treated with allopurinol before and during radiation exposure as compared to irradiated rats. Accordingly, it could be concluded that XO inhibitor (allopurinol) play a significant role in minimizing the tissue damages upon exposure to ionizing radiation via preventing the over production of reactive oxygen species (ROS) in irradiated cells through the XOR system of irradiation rats

  20. Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat.

    Science.gov (United States)

    Seluanov, Andrei; Hine, Christopher; Azpurua, Jorge; Feigenson, Marina; Bozzella, Michael; Mao, Zhiyong; Catania, Kenneth C; Gorbunova, Vera

    2009-11-17

    The naked mole-rat is the longest living rodent with a maximum lifespan exceeding 28 years. In addition to its longevity, naked mole-rats have an extraordinary resistance to cancer as tumors have never been observed in these rodents. Furthermore, we show that a combination of activated Ras and SV40 LT fails to induce robust anchorage-independent growth in naked mole-rat cells, while it readily transforms mouse fibroblasts. The mechanisms responsible for the cancer resistance of naked mole-rats were unknown. Here we show that naked mole-rat fibroblasts display hypersensitivity to contact inhibition, a phenomenon we termed "early contact inhibition." Contact inhibition is a key anticancer mechanism that arrests cell division when cells reach a high density. In cell culture, naked mole-rat fibroblasts arrest at a much lower density than those from a mouse. We demonstrate that early contact inhibition requires the activity of p53 and pRb tumor suppressor pathways. Inactivation of both p53 and pRb attenuates early contact inhibition. Contact inhibition in human and mouse is triggered by the induction of p27(Kip1). In contrast, early contact inhibition in naked mole-rat is associated with the induction of p16(Ink4a). Furthermore, we show that the roles of p16(Ink4a) and p27(Kip1) in the control of contact inhibition became temporally separated in this species: the early contact inhibition is controlled by p16(Ink4a), and regular contact inhibition is controlled by p27(Kip1). We propose that the additional layer of protection conferred by two-tiered contact inhibition contributes to the remarkable tumor resistance of the naked mole-rat.

  1. Acute effects of low-level laser therapy (660 nm) on oxidative stress levels in diabetic rats with skin wounds.

    Science.gov (United States)

    Denadai, Amanda Silveira; Aydos, Ricardo Dutra; Silva, Iandara Schettert; Olmedo, Larissa; de Senna Cardoso, Bruno Mendonça; da Silva, Baldomero Antonio Kato; de Carvalho, Paulo de Tarso Camillo

    2017-09-01

    Laser therapy influences oxidative stress parameters such as the activity of antioxidant enzymes and the production of reactive oxygen species. To analyze the effects of low-level laser therapy on oxidative stress in diabetics rats with skin wounds. Thirty-six animals were divided into 4 groups: NDNI: non-diabetic rats with cutaneous wounds that not received laser therapy; NDI: non-diabetic rats with cutaneous wounds that received laser therapy; DNI: diabetic rats with skin wounds who did not undergo laser therapy; DI: rats with diabetes insipidus and cutaneous wounds and received laser therapy. The animals were treated with LLLT (660 nm, 100 mW, 6 J/cm, spot size 0.028 cm). On the day of killing the animals, tissue-wrapped cutaneous wounds were collected and immediately frozen, centrifuged, and stored to analyze malondialdehyde (MDA) levels. Significant difference was observed within the groups of MDA levels (ANOVA, p = 0.0001). Tukey's post-hoc test showed significantly lower values of MDA in irradiated tissues, both in diabetic and non-diabetic rats. ANOVA of the diabetic group revealed a significant difference (p < 0.01) when all groups, except NDI and DI, were compared. LLLT was effective in decreasing MDA levels in acute surgical wounds in diabetic rats.

  2. Benfotiamine enhances antioxidant defenses and protects against cisplatin-induced DNA damage in nephrotoxic rats.

    Science.gov (United States)

    Harisa, Gamaleldin I

    2013-08-01

    The objective of the present study was to assess superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), paraoxonase (PON1), glutathione reductase (GR), and catalase (CAT) activities ratio and their relationship with DNA oxidative damage in rats treated with cisplatin (3 mg/kg bwt/day) in the presence and absence of benfotiamine (100 mg/kg/day) for 25 days. Cisplatin-induced renal damage was evidenced by renal dysfunction and elevated oxidative stress markers. SOD activity and levels of nitric oxide, protein carbonyl, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine were significantly increased by cisplatin treatment. Moreover, the ratios of GPx/GR, SOD/GPx, SOD/CAT, and SOD/PON1 were significantly increased compared to control. In contrast, glutathione levels were significantly decreased by cisplatin treatment. Simultaneous treatment of rats with cisplatin and benfotiamine ameliorate these variables to values near to those of control rats. This study suggests that benfotiamine can prevent cisplatin-induced nephrotoxicity by inhibiting formation reactive species of oxygen and nitrogen. © 2013 Wiley Periodicals, Inc.

  3. role of conjugated linoleic acid in the prevention of radiation hazard in male rats

    International Nuclear Information System (INIS)

    Hussien, E.M.; Osman, N.N.; Haggag, A.M.

    2009-01-01

    the objective of the present study was to examine the effect of conjugated linoleic acid (CLA) as a natural product in minimizing the radiation hazards. male rats were assigned to six groups each of 7 animals throughout six weeks, fed 1% CLA (wt/wt)added to commercial diet in the form of milk powder 182 g/kg diet. rats exposed to 6 Gy whole body gamma irradiation showed significant increase in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C).triglycerides (TG), atherosclerosis index, total lipid (TL), phospholipids (ph-lipids), malondialdehyde (MDA), urea,creatinine, uric acid, calcium (Ca) and phosphorous levels associated with decrease in high density lipoprotein-cholesterol (HDL-C), activity of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant status, body weight, testes weight and testosterone both irradiated and non-irradiated milk powder administrated to irradiated rat groups minimized the radiation damage in the assayed parameters indicating its beneficial role as a promising antioxidant in scavenging free radicals and reactive oxygen species

  4. Population Structure of Rat-Derived Pneumocystis carinii in Danish Wild Rats

    DEFF Research Database (Denmark)

    Palmer, Robert J.; Settnes, Osvald P.; Lodal, Jens

    2000-01-01

    The rat model of Pneumocystis carinii pneumonia is frequently used to study human P. carinii infection, but there are many differences between the rat and human infections. We studied naturally acquired P. carinii in wild rats to examine the relevance of the rat model for human infection. P. cari...

  5. Role of reactive oxygen species and poly-ADP-ribose polymerase in the development of AZT-induced cardiomyopathy in rat.

    Science.gov (United States)

    Szabados, E; Fischer, G M; Toth, K; Csete, B; Nemeti, B; Trombitas, K; Habon, T; Endrei, D; Sumegi, B

    1999-02-01

    The short term cardiac side-effects of AZT (3'-azido-3'-deoxythymidine, zidovudine) was studied in rats to understand the biochemical events contributing to the development of AZT-induced cardiomyopathy. Developing rats were treated with AZT (50 mg/kg/day) for 2 wk and the structural and functional changes were monitored in the cardiac muscle. AZT treatment provoked a surprisingly fast appearance of cardiac malfunctions in developing animals characterized by prolonged RR, PR and QT intervals and J point depression. Electron microscopy showed abnormal mitochondrial structure but the cardiomyocyte had normal myofibers. The AZT treatment of rats significantly increased ROS and peroxynitrite formation in heart tissues as determined by the oxidation of nonfluorescent dihydrorhodamine123 and dichlorodihydro-fluorescein diacetate (H2DCFDA) to fluorescent dyes, and induced single-strand DNA breaks. Lipid peroxidation and oxidation of cellular proteins determined from protein carbonyl content were increased as a consequence of AZT treatment. Activation of the nuclear poly-ADP-ribose polymerase and the accelerated NAD+ catabolism were also observed in AZT-treated animals. Western blot analysis showed that mono-ADP-ribosylation of glucose regulated protein (GRP78/BIP) was enhanced by AZT treatment, that process inactivates GRP78. In this way moderate decrease in the activity of respiratory complexes was detected in the heart of AZT-treated animals indicating a damaged mitochondrial energy production. There was a significant decrease in creatine phosphate concentration resulting in a decrease in creatine phosphate/creatine ratio from 2.08 to 0.58. ATP level remained close to normal but the total extractable ADP increased with 45%. The calculated free ATP/ADP ratio decreased from 340 to 94 in the heart of AZT-treated rats as a consequence of increased free ADP concentration. It was assumed that the increased free ADP in AZT-treated cardiomyocyte may help cells to compensate the

  6. The naked mole-rat exhibits an unusual cardiac myofilament protein profile providing new insights into heart function of this naturally subterranean rodent.

    Science.gov (United States)

    Grimes, Kelly M; Barefield, David Y; Kumar, Mohit; McNamara, James W; Weintraub, Susan T; de Tombe, Pieter P; Sadayappan, Sakthivel; Buffenstein, Rochelle

    2017-12-01

    The long-lived, hypoxic-tolerant naked mole-rat well-maintains cardiac function over its three-decade-long lifespan and exhibits many cardiac features atypical of similar-sized laboratory rodents. For example, they exhibit low heart rates and resting cardiac contractility, yet have a large cardiac reserve. These traits are considered ecophysiological adaptations to their dank subterranean atmosphere of low oxygen and high carbon dioxide levels and may also contribute to negligible declines in cardiac function during aging. We asked if naked mole-rats had a different myofilament protein signature to that of similar-sized mice that commonly show both high heart rates and high basal cardiac contractility. Adult mouse ventricles predominantly expressed α-myosin heavy chain (97.9 ± 0.4%). In contrast, and more in keeping with humans, β myosin heavy chain was the dominant isoform (79.0 ± 2.0%) in naked mole-rat ventricles. Naked mole-rat ventricles diverged from those of both humans and mice, as they expressed both cardiac and slow skeletal isoforms of troponin I. This myofilament protein profile is more commonly observed in mice in utero and during cardiomyopathies. There were no species differences in phosphorylation of cardiac myosin binding protein-C or troponin I. Phosphorylation of both ventricular myosin light chain 2 and cardiac troponin T in naked mole-rats was approximately half that observed in mice. Myofilament function was also compared between the two species using permeabilized cardiomyocytes. Together, these data suggest a cardiac myofilament protein signature that may contribute to the naked mole-rat's suite of adaptations to its natural subterranean habitat.

  7. The radiation response of skin in young and old rats

    International Nuclear Information System (INIS)

    Hamlet, R.; Hopewell, J.W.

    1982-01-01

    The results of this investigation clearly demonstrate the different radiation skin response in rats of differing ages. The reasons for these differences cannot be clarified until cell kinetic studies have been completed. These results obtained for rodent skin would appear to be in disagreement with the available data for human skin (Rubin and Casarett 1968) where no marked age-related changes were reported. Also, in pig skin studies (Hopewell and Young 1982) there was no evidence of an age effect in the dermal vascular response in 3-12-month-old animals. This may be related to the different tissue being investigated or it may reflect important species differences. Whatever the reasons behind these observations, the different skin response to radiation in rats of 7, 14 and 52 weeks of age has clearly been demonstrated and should be borne in mind when extrapolating data with rodent skin to the clinical situation. (author)

  8. The biochemical mechanisms responsible for differences in the half-life of monomeric 239Pu in rat and Syrian hamster liver

    International Nuclear Information System (INIS)

    Seidel, A.; Winter, R.; Jentzsch, C.; Gruner, R.; Heumann, H.G.; Hanke, S.

    1979-01-01

    The subcellular distribution of 239 Pu citrate in rat and Syrian hamster liver was studied with the help of the non-ionic detergent Triton WR1339, used as method for separating lysosomes from other cell organelles. Triton WR1339 was injected six days after 239 Pu and the animals were sacrificed after Day 10. Liver homogenates were subjected to differential and isopycnic centrifugation in sucrose gradients. In both animal species 90% of 239 Pu of the post-nuclear supernatant was found in the fraction containing mitochondria, lysosomes, endoplasmatic reticulum and ferritin. Triton WR1339 injection caused a concomitant shift of the lysosomal marker acid phosphatase and of 239 Pu from high densities to rho approximately 1.10 in both animal species. According to our results, binding of 239 Pu to mitochondria and peroxisomes can be excluded, and association to endoplasmatic reticulum and plasma membranes is not very probable. We must consider the possibility that a part of the radioactivity occurring at rho approximately 1.10 can also be bound to ferritin. According to these findings, lysosomes could be one of the main storage sites for 239 Pu in both species. From studies on the pharmacokinetics of 3 H-labelled Triton WR1339 and on the behaviour of Triton-filled rat liver lysosomes, which are also presented in the paper, it is tentatively concluded that the rapid excretion of 239 Pu from rat liver is due to the normally rapid elimination of lysosomal material from hepatocytes into the bile in this species. In Syrian hamsters the fate of lysosomal material in liver may be different or redistribution of 239 Pu occurs at a later time. (author)

  9. The relationship between impulsive choice and impulsive action: a cross-species translational study.

    Directory of Open Access Journals (Sweden)

    Nienke Broos

    Full Text Available Maladaptive impulsivity is a core symptom in various psychiatric disorders. However, there is only limited evidence available on whether different measures of impulsivity represent largely unrelated aspects or a unitary construct. In a cross-species translational study, thirty rats were trained in impulsive choice (delayed reward task and impulsive action (five-choice serial reaction time task paradigms. The correlation between those measures was assessed during baseline performance and after pharmacological manipulations with the psychostimulant amphetamine and the norepinephrine reuptake inhibitor atomoxetine. In parallel, to validate the animal data, 101 human subjects performed analogous measures of impulsive choice (delay discounting task, DDT and impulsive action (immediate and delayed memory task, IMT/DMT. Moreover, all subjects completed the Stop Signal Task (SST, as an additional measure of impulsive action and filled out the Barratt impulsiveness scale (BIS-11. Correlations between DDT and IMT/DMT were determined and a principal component analysis was performed on all human measures of impulsivity. In both rats and humans measures of impulsive choice and impulsive action did not correlate. In rats the within-subject pharmacological effects of amphetamine and atomoxetine did not correlate between tasks, suggesting distinct underlying neural correlates. Furthermore, in humans, principal component analysis identified three independent factors: (1 self-reported impulsivity (BIS-11; (2 impulsive action (IMT/DMT and SST; (3 impulsive choice (DDT. This is the first study directly comparing aspects of impulsivity using a cross-species translational approach. The present data reveal the non-unitary nature of impulsivity on a behavioral and pharmacological level. Collectively, this warrants a stronger focus on the relative contribution of distinct forms of impulsivity in psychopathology.

  10. Anti-inflammatory effects of royal jelly on ethylene glycol induced renal inflammation in rats

    Directory of Open Access Journals (Sweden)

    Zeyneb Aslan

    2015-10-01

    Full Text Available ABSTRACT Objective: In this study, anti-inflammatory effects of Royal Jelly were investigated by inducing renal inflammation in rats with the use of ethylene glycol. For this purpose, the calcium oxalate urolithiasis model was obtained by feeding rats with ethylene glycol in drinking water. Materials and Methods: The rats were divided in five study groups. The 1st group was determined as the control group. The rats in the 2nd group received ethylene glycol (1% in drinking water. The rats in the 3rd group were daily fed with Royal Jelly by using oral gavage. The 4th group was determined as the preventive group and the rats were fed with ethylene glycol (1% in drinking water while receiving Royal Jelly via oral gavage. The 5th group was determined as the therapeutic group and received ethylene glycol in drinking water during the first 2 weeks of the study and Royal Jelly via oral gavage during the last 2 weeks of the study. Results: At the end of the study, proinflammatory/anti-inflammatory cytokines, TNF-α, IL-1β and IL-18 levels in blood and renal tissue samples from the rats used in the application were measured. Conclusion: The results have shown that ethylene glycol does induce inflammation and renal damage. This can cause the formation of reactive oxygen species. Royal Jelly is also considered to have anti-inflammatory effects due to its possible antiradical and antioxidative effects. It can have positive effects on both the prevention of urolithiasis and possible inflammation during the existing urolithiasis and support the medical treatment.

  11. Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

    International Nuclear Information System (INIS)

    Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing; He, Xiaoyun; Huang, Kunlun; Luo, Yunbo; Xu, Wentao

    2014-01-01

    Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation

  12. Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); He, Xiaoyun; Huang, Kunlun; Luo, Yunbo [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentao@cau.edu.cn [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

    2014-11-01

    Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation.

  13. Rats and seabirds: effects of egg size on predation risk and the potential of conditioned taste aversion as a mitigation method.

    Science.gov (United States)

    Latorre, Lucía; Larrinaga, Asier R; Santamaría, Luis

    2013-01-01

    Seabirds nesting on islands are threatened by invasive rodents, such as mice and rats, which may attack eggs, chicks and even adults. The low feasibility of rat eradications on many islands makes the development of alternate control plans necessary. We used a combination of field experiments on a Mediterranean island invaded by black rats (Rattusrattus) to evaluate (1) the predation risk posed to different-sized seabird eggs and (2), the potential of two deterrent methods (electronic and chemical) to reduce its impact. Rats were able to consume eggs of all sizes (12 to 68 g), but survival increased 13 times from the smallest to the largest eggs (which also had more resistant eggshells). Extrapolation to seabird eggs suggests that the smallest species (Hydrobatespelagicus) suffer the most severe predation risk, but even the largest (Larusmichahellis) could suffer >60% mortality. Nest attack was not reduced by the deterrents. However, chemical deterrence (conditioned taste aversion by lithium chloride) slowed the increase in predation rate over time, which resulted in a three-fold increase in egg survival to predation as compared to both control and electronic deterrence. At the end of the experimental period, this effect was confirmed by a treatment swap, which showed that conferred protection remains at least 15 days after cessation of the treatment. Results indicate that small seabird species are likely to suffer severe rates of nest predation by rats and that conditioned taste aversion, but not electronic repellents, may represent a suitable method to protect colonies when eradication or control is not feasible or cost-effective.

  14. Pharmacokinetic interaction of enrofloxacin/trimethoprim combination following single-dose intraperitoneal and oral administration in rats.

    Science.gov (United States)

    Choi, Myung-Jin; Yohannes, Sileshi Belew; Lee, Seung-Jin; Damte, Dereje; Kim, Jong-Choon; Suh, Joo-Won; Park, Seung-Chun

    2014-03-01

    The pharmacokinetic interaction of enrofloxacin and trimethoprim was evaluated after single-dose intraperitoneal or oral co-administration in rats. Plasma concentrations of the two drugs were determined by high-performance liquid chromatography. Following intraperitoneal combination, a significant (P trimethoprim, respectively. There was a significant (P trimethoprim. Further study is recommended in other species of animals.

  15. Centrally-administered oxytocin promotes preference for familiar objects at a short delay in ovariectomized female rats.

    Science.gov (United States)

    Madularu, Dan; Athanassiou, Maria; Yee, Jason R; Mumby, Dave G

    2014-11-01

    Oxytocin has been previously associated with social attachment behaviors in various species, however, most studies focused on partner preference in the socially-monogamous prairie vole. In these, oxytocin treatment was shown to promote partner preference, such that females receiving either central or pulsatile peripheral administration would spend more time with a familiar male. This behavioral outcome was blocked by oxytocin receptor antagonist treatment. The aim of the current study was to further explore the preference-inducing properties of oxytocin by examining its effects on object preference on ovariectomized female rats. In other words, we assessed whether these effects would apply to objects and if they would be persistent across species. Eight rats were infused with oxytocin into the left ventricle and object preference was assessed at two delays: 30min and 4h. At the 30min delay, oxytocin-treated animals showed preference for the familiar object, whereas saline-treated controls exhibited preference for the novel object. At the 4h delay, both groups showed novel-object preference. Our findings show that oxytocin modulates object preference in the female rat at a shorter delay, similar to the findings from partner-preference studies in the prairie vole, suggesting that the mechanisms driving object preference might be in part similar to those responsible for partner preference. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Taurine Alleviates the Progression of Diabetic Nephropathy in Type 2 Diabetic Rat Model

    Directory of Open Access Journals (Sweden)

    Jang Hyun Koh

    2014-01-01

    Full Text Available The overexpression of vascular endothelial growth factor (VEGF is known to be involved in the pathogenesis of diabetic nephropathy. In this study, the protective effects of taurine on diabetic nephropathy along with its underlying mechanism were investigated. Experimental animals were divided into three groups: LETO rats as normal group (n=10, OLETF rats as diabetic control group (n=10, and OLETF rats treated with taurine group (n=10. We treated taurine (200 mg/kg/day for 20 weeks and treated high glucose (HG, 30 mM with or without taurine (30 mM in mouse cultured podocyte. After taurine treatment, blood glucose level was decreased and insulin secretion was increased. Taurine significantly reduced albuminuria and ACR. Also it decreased glomerular volume, GBM thickness and increased open slit pore density through decreased VEGF and increased nephrin mRNA expressions in renal cortex. The antioxidant effects of taurine were confirmed by the reduction of urine MDA in taurine treated diabetic group. Also reactive oxygen species (ROS levels were decreased in HG condition with taurine treated podocytes compared to without taurine. These results indicate that taurine lowers glucose level via increased insulin secretion and ameliorates the progression of diabetic nephropathy through antifibrotic and antioxidant effects in type 2 diabetes rat model.

  17. A comparison of two methods of labelling autologous platelets with 111In-oxine in five different species

    International Nuclear Information System (INIS)

    Christenson, J.T.; Arvidsson, D.; Thoerne, J.; Norgren, L.; Olsson, P.I.; Strand, S.E.

    1983-01-01

    Several different methods for labelling autologous platelets with 111 In-oxine have been described. However, no comparative study has been reported. In the present investigation two different labelling methods were compared in terms of labelling efficiency and platelet function in five species: human, dog, pig, rabbit and rat. One of the labelling methods, utilising among other things a serum albumin gradient separation fo platelets and incubation of 111 In-oxine in a water bath at 37 0 C, was superior in all species with significantly higher labelling efficiency and unchanged platelet function. (orig.)

  18. The effect of Urtica dioica extract on the number of astrocytes in the dentate gyrus of diabetic rats.

    Science.gov (United States)

    Jahanshahi, M; Golalipour, M J; Afshar, M

    2009-05-01

    Diabetes mellitus is associated with cerebral alterations in both human and animal models of the disease. These alterations include abnormal expression of hypothalamic neuropeptides and hippocampal astrogliosis. Urtica dioica (Nettle) is among several species listed for their use against diabetes in folk medicine. The aim of this study was the evaluation of the astrocyte number in the dentate gyrus of diabetic rats after treatment with nettle. A total of 21 male albino Wistar rats were used in the present study. The animals were divided into three groups: control, nettle-untreated diabetic, and nettle treated diabetic. Hyperglycaemia was induced by streptozotocin (80 mg/kg) in the animals of the diabetic and treatment groups. One week after injection of the streptozotocin, the animals in the treatment group received a hydroalcoholic extract of Urtica dioica (100 mg/kg/day) for 4 weeks intraperitoneally. After a 5-week survival period, all the rats were sacrificed and coronal sections were taken from the dorsal hippocampal formation of the right cerebral hemispheres. The area densities of the astrocytes were measured and compared between the three groups (p < 0.05). The number of astrocytes increased in the diabetic rats (24.06 +/- 9.57) compared with the controls (17.52 +/- 6.66). The densities in the treated rats (19.50 +/- 6.16) were lower than in the diabetic rats. Furthermore, the control and treated rats showed similar densities. We concluded that U. dioica extract helped compensate for astrocytes in the treatment rats dentate gyrus in comparison with diabetic rats.

  19. Absorption, distribution, metabolism, and excretion of 14C-MMB4 DMS administered intramuscularly to Sprague-Dawley rats and New Zealand White rabbits.

    Science.gov (United States)

    Lusiak, Bozena D; Kobs, Dean J; Hong, S Peter; Burback, Brian L; Johnson, Jerry D

    2013-01-01

    1,1'-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate (MMB4 DMS) is currently under development for the treatment of chemical warfare organophosphorus nerve agent poisoning. The present study evaluates the absorption, distribution, metabolism, and excretion of (14)C-MMB4 DMS administered intramuscularly to rats and rabbits. The formulated mixture of radiolabeled and nonradiolabeled MMB4 DMS was administered as a single or 7-day repeated dose. Rat doses were 55 or 220 mg/kg (100 µCi/kg), and rabbit doses were 25 or 100 mg/kg (31.25 and 62.5 µCi/kg, respectively). Urine, bile (rats only), feces, blood, and tissues were collected for up to 72 hours. Metabolic profiling using high-performance liquid chromatography with radiodetection was performed on selected urine samples. For both animal species, the majority of the total radioactivity was excreted in the urine (74%-94%) by 72 hours after dosing with greater than 90% of the radioactivity measured in the urine within 8 to 12 hours after dosing. There were no apparent species or dose differences in the urine excretion pattern. The distribution of (14)C-MMB4 DMS-derived radioactivity was rapid and generally reached the highest concentration by the first collection time point (0.25 hours). The tissue-blood concentration ratios were highest at the injection sites and in the kidneys and gastrointestinal tract contents for both the species. Two metabolites of MMB4 DMS were detected in rat and rabbit urine; their structure was confirmed by liquid chromatography with tandem mass spectrometry as 4-pyridine aldoxime and isonicotinic acid (pyridine-4-carboxylic acid).

  20. Retinal ganglion cell survival and axon regeneration after optic nerve injury in naked mole-rats.

    Science.gov (United States)

    Park, Kevin K; Luo, Xueting; Mooney, Skyler J; Yungher, Benjamin J; Belin, Stephane; Wang, Chen; Holmes, Melissa M; He, Zhigang

    2017-02-01

    In the adult mammalian central nervous system (CNS), axonal damage often triggers neuronal cell death and glial activation, with very limited spontaneous axon regeneration. In this study, we performed optic nerve injury in adult naked mole-rats, the longest living rodent, with a maximum life span exceeding 30 years, and found that injury responses in this species are quite distinct from those in other mammalian species. In contrast to what is seen in other mammals, the majority of injured retinal ganglion cells (RGCs) survive with relatively high spontaneous axon regeneration. Furthermore, injured RGCs display activated signal transducer and activator of transcription-3 (STAT3), whereas astrocytes in the optic nerve robustly occupy and fill the lesion area days after injury. These neuron-intrinsic and -extrinsic injury responses are reminiscent of those in "cold-blooded" animals, such as fish and amphibians, suggesting that the naked mole-rat is a powerful model for exploring the mechanisms of neuronal injury responses and axon regeneration in mammals. J. Comp. Neurol. 525:380-388, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Establishment of a novel dwarf rat strain: cartilage calcification insufficient (CCI) rats.

    Science.gov (United States)

    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.

  2. Establishment of a novel dwarf rat strain: cartilage calcification insufficient (CCI) rats

    Science.gov (United States)

    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

    2014-01-01

    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. PMID:25736479

  3. Hydroxyl radicals' production and ECG parameters during ischemia and reperfusion in rat, guinea pig and rabbit isolated heart.

    Science.gov (United States)

    Paulova, Hana; Stracina, Tibor; Jarkovsky, Jiri; Novakova, Marie; Taborska, Eva

    2013-06-01

    Ischemic and reperfusion injury is a serious condition related to numerous biochemical and electrical abnormalities of the myocardium. It has been repeatedly studied in various animal models. In this study, the production of hydroxyl radicals and electrophysiological parameters were compared in three species. Rat, guinea pig and rabbit isolated hearts were perfused according to Langendorff under strictly identical conditions. The heart rate and arrhythmia were monitored during ischemia and reperfusion periods at defined time intervals; the production of hydroxyl radical was determined by HPLC as 2.5-dihydroxybenzoic acid (2.5-DHBA) formed by salicylic acid hydroxylation. Relationship between arrhythmias and production of 2.5-DHBA was studied. The inter-species differences were observed in timing of arrhythmias onset and their severity, and in the production of 2.5-DHBA in both ischemia and reperfusion. The most considerable changes were observed in rats, where arrhythmias appeared early and with highest severity during ischemia on one side and the regular rhythm was restored early and completely during reperfusion. The corresponding changes in the production of 2.5-DHBA were observed. It can be concluded that rat isolated heart is the most suitable model for evaluation of ischemia/reperfusion injury under given experimental conditions.

  4. Metabolism of 210Po in rats: Volatile 210Po from faeces

    International Nuclear Information System (INIS)

    Sadi, B. B.; Li, C.; Wyatt, H.; Bugden, M.; Wilkinson, D.; Kramer, G.

    2011-01-01

    The metabolic formation of volatile 210 Po species in a rat that was intravenously administered with 210 Po-citrate was investigated in this study. A slurry of the faecal sample was prepared in water and was bubbled with nitrogen gas in a closed system. The discharged gas was passed through a trapping device filled with liquid scintillation cocktail in order to capture any volatile 210 Po species. The amount of 210 Po trapped in the scintillation cocktail was measured by a liquid scintillation analyser that provided evidence of the presence of volatile 210 Po species in the faeces. The presence of volatile 210 Po in the faeces indicates that the metabolic formation of volatile 210 Po is likely to occur in the gut due to bacterial activity. The amount of volatile 210 Po species was compared with the daily faecal excretion of 210 Po. After 2 h of bubbling, the volatile 210 Po collected from the faeces sample was found to be between 1.0 and 1.7 % of the daily faecal excretion for the 4 d following 210 Po-citrate administration. (authors)

  5. An interspecies comparison of the phagocytosis and dissolution of 241AmO2 particles by rat, dog and monkey alveolar macrophages in vitro

    International Nuclear Information System (INIS)

    Taya, A.; Carmack, D.B.; Muggenburg, B.A.; Mewhinney, J.A.

    1992-01-01

    Experiments were conducted to study the phagocytosis and dissolution of 241 AmO 2 particles by rat, dog and monkey alveolar macrophages (PAM) in vitro. The phagocytosis and dissolution of 241 AmO 2 particles were followed up to 20 and 72 h, respectively. Dog and monkey PAM took up 241 AmO 2 particles at similar rates, whereas rat PAM phagocytosed only 60% of the amount phagocytosed by dog and monkey PAM at 20h. The PAM of the three species dissolved 241 AmO 2 particles at similar rates; 8-10% was dissolved by 72h. The results of the 241 AmO 2 uptake in vitro may reflect in vivo situations, where the differences in uptake seen in vitro would probably diminish at later times after exposure. The dissolution results imply that the dissolution of 241 AmO 2 particles by alveolar macrophages of the three species might be species-independent. (author)

  6. The effects of response cost and species-typical behaviors on a daily time-place learning task.

    Science.gov (United States)

    Deibel, Scott H; Thorpe, Christina M

    2013-03-01

    Two theories that have been hypothesized to mediate acquisition in daily time-place learning (TPL) tasks were investigated in a free operant daily TPL task: the response cost hypothesis and the species-typical behavior hypothesis. One lever at the end of one of the choice arms of a T-maze provided food in the morning, and 6 h later, a lever in the other choice arm provided food. Four groups were used to assess the effect of two possible sources of response cost: physical effort of the task and costs associated with foraging ecology. One group was used to assess the effect of explicitly allowing for species-typical behaviors. If only first arm choice data were considered, there was little evidence of learning. However, both first press and percentage of presses on the correct lever prior to the first reinforcement revealed evidence of TPL in most rats tested. Unexpectedly, the high response cost groups for both of the proposed sources did not perform better than the low response cost groups. The groups that allowed animals to display species-typical behaviors performed the worst. Skip session probe trials confirmed that the majority of the rats that acquired the task were using a circadian timing strategy. The results from the present study suggest that learning in free operant daily TPL tasks might not be dependent on response cost.

  7. Distribution of vasopressin in the brain of the eusocial naked mole-rat.

    Science.gov (United States)

    Rosen, Greta J; De Vries, Geert J; Goldman, Sharry L; Goldman, Bruce D; Forger, Nancy G

    2007-02-20

    Naked mole-rats are eusocial rodents that live in large subterranean colonies in which one queen breeds with one to three males. All other animals are nonbreeding subordinates. The external features of male and female subordinates, including their genitalia, are remarkably monomorphic, as is their behavior. Because vasopressin (VP) is associated with social behaviors and sex differences in other species, its distribution in naked mole-rats was of interest. We used immunohistochemistry to examine VP in the brains of subordinate and breeding naked mole-rats of both sexes. As in other mammals, VP-immunoreactive (-ir) somata were found in the paraventricular (PVN) and supraoptic nuclei (SON) and VP-ir projections from these nuclei ran through the internal and external zone of the median eminence. However, naked mole-rats had very few VP-ir cells in the bed nucleus of the stria terminalis (BST) and none in the suprachiasmatic nucleus (SCN); the extensive network of fine-caliber VP-ir fibers usually seen in projection sites of the BST and SCN were also absent. Equally unexpected was the abundance of large-caliber VP-ir fibers in the dorsomedial septum. VP immunoreactivity was generally similar in all groups, with the exception of VP-ir cell number in the dorsomedial hypothalamus (DMH). Breeders had a population of labeled cells in the DMH that was absent, or nearly absent, in subordinates. Future studies on the function of VP in these areas are needed to determine how the atypical distribution of VP immunoreactivity relates to eusociality and the unusual physiology of naked mole-rats.

  8. Hepatoprotective, Antihyperlipidemic, and Anti-inflammatory Activity of Moringa oleifera in Diabetic-induced Damage in Male Wistar Rats

    Science.gov (United States)

    Omodanisi, Elizabeth I.; Aboua, Yapo G.; Chegou, Novel N.; Oguntibeju, Oluwafemi O.

    2017-01-01

    Background: The number of individuals with diabetes is increasing daily, and diabetes is presently estimated to affect about 422 million adults worldwide. Conventional drugs used to treat diabetes are not without severe side effects, accessibility, and affordability. This study elucidates the potential effects of Moringa oleifera (MO) leaves extract to manage and treat diabetes induced in male Wistar rats. Materials and Methods: Adult male Wistar rats were randomly divided into four groups (n = 12/group): NC – nondiabetic rats (positive control), MO – nondiabetic-treated rats, DM – diabetic rats (negative control), DM + MO – diabetic-treated rats. Hepatic enzymes and biochemical parameters as well as antioxidant capacity and inflammatory cytokine levels were assessed. Levels of low-density lipoprotein, high-density lipoprotein, and total cholesterol were evaluated. Results: Oral administration of methanolic extract of MO (250 mg/kg) to diabetic rats for 42 days showed a significant reduction in hepatic enzyme markers and normalized lipid profile parameters in the serum compared to normal control group. Treatment also increased the level of antioxidant capacity and alleviated inflammatory biomarkers of the liver. Histology sections of the liver tissue showed protective effect of MO in treated rats. Conclusions: MO showed hepatoprotective, anti-inflammatory, and lipid-lowering effects against streptozotocin-induced hepatotoxicity. Histological section demonstrated specific alterations in the liver of the diabetic and nondiabetic male Wistar rats while MO treatment revealed improvement in liver alterations. Abbreviations Used: IL 1: Interleukin 1, IL 6: Interleukin 16, MCP-1: Monocyte chemotactic protein, TNF-α: Tumor Necrotic factor alpha, ROS: Reactive oxygen species, MO: Moringa oleifera, STZ: Streptozotocin, SRC: Standard rat chow, ALP: Alkaline phosphatase, AST: Aspartate aminotransferase, ALT: Alanine aminotransferase, ORAC: Oxygen radical absorbance

  9. Bile Salt Homeostasis in Normal and Bsep Gene Knockout Rats with Single and Repeated Doses of Troglitazone.

    Science.gov (United States)

    Cheng, Yaofeng; Chen, Shenjue; Freeden, Chris; Chen, Weiqi; Zhang, Yueping; Abraham, Pamela; Nelson, David M; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

    2017-09-01

    The interference of bile acid secretion through bile salt export pump (BSEP) inhibition is one of the mechanisms for troglitazone (TGZ)-induced hepatotoxicity. Here, we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep knockout (KO) rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on day 1 and day 7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7.6- and 9.3-fold lower than in WT on day 1 and day 7, respectively, due to increased TS biliary excretion. With Bsep KO, the mRNA levels of multidrug resistance-associated protein 2 (Mrp2), Mrp3, Mrp4, Mdr1, breast cancer resistance protein (Bcrp), sodium taurocholate cotransporting polypeptide, small heterodimer partner, and Sult2A1 were significantly altered in KO rats. Following seven daily TGZ treatments, Cyp7A1 was significantly increased in both WT and KO rats. In the vehicle groups, plasma exposures of individual bile acids demonstrated variable changes in KO rats as compared with WT. WT rats dosed with TGZ showed an increase of many bile acid species in plasma on day 1, suggesting the inhibition of Bsep. Conversely, these changes returned to base levels on day 7. In KO rats, alterations of most bile acids were observed after seven doses of TGZ. Collectively, bile acid homeostasis in rats was regulated through bile acid synthesis and transport in response to Bsep deficiency and TGZ inhibition. Additionally, our study is the first to demonstrate that repeated TGZ doses can upregulate Cyp7A1 in rats. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  10. 4S RNA is transported axonally in normal and regenerating axons of the sciatic nerves of rats

    Energy Technology Data Exchange (ETDEWEB)

    Lindquist, T D; Ingoglia, N A; Gould, R M [Departments of Physiology and Neuroscience, New Jersey Medical School, Newark, NJ, USA

    1982-12-28

    Experiments were designed to determine if following injection of (/sup 3/H)uridine into the lumbar spinal cord of the rat, (/sup 3/H)RNA could be demonstrated within axons of the sciatic nerve, and if 4S RNA is the predominant predominant RNA species present in these axons.

  11. Activation of adenosine A(1) receptors alters behavioral and biochemical parameters in hyperthyroid rats.

    Science.gov (United States)

    Bruno, Alessandra Nejar; Fontella, Fernanda Urruth; Bonan, Carla Denise; Barreto-Chaves, Maria Luiza M; Dalmaz, Carla; Sarkis, João José Freitas

    2006-02-28

    Adenosine acting on A(1) receptors has been related with neuroprotective and neuromodulatory actions, protection against oxidative stress and decrease of anxiety and nociceptive signaling. Previous studies demonstrated an inhibition of the enzymes that hydrolyze ATP to adenosine in the rat central nervous system after hyperthyroidism induction. Manifestations of hyperthyroidism include increased anxiety, nervousness, high O(2) consumption and physical hyperactivity. Here, we investigated the effects of administration of a specific agonist of adenosine A(1) receptor (N(6)-cyclopentyladenosine; CPA) on nociception, anxiety, exploratory response, locomotion and brain oxidative stress of hyperthyroid rats. Hyperthyroidism was induced by daily intraperitoneal injections of l-thyroxine (T4) for 14 days. Nociception was assessed with a tail-flick apparatus and exploratory behavior, locomotion and anxiety were analyzed by open-field and plus-maze tests. We verified the total antioxidant reactivity (TAR), lipid peroxide levels by the thiobarbituric acid reactive species (TBARS) reaction and the free radicals content by the DCF test. Our results demonstrated that CPA reverted the hyperalgesia induced by hyperthyroidism and decreased the exploratory behavior, locomotion and anxiety in hyperthyroid rats. Furthermore, CPA decreased lipid peroxidation in hippocampus and cerebral cortex of control rats and in cerebral cortex of hyperthyroid rats. CPA also increased the total antioxidant reactivity in hippocampus and cerebral cortex of control and hyperthyroid rats, but the production of free radicals verified by the DCF test was changed only in cerebral cortex. These results suggest that some of the hyperthyroidism effects are subjected to regulation by adenosine A(1) receptor, demonstrating the involvement of the adenosinergic system in this pathology.

  12. Cardiac retention of PET neuronal imaging agent LMI1195 in different species: Impact of norepinephrine uptake-1 and -2 transporters

    International Nuclear Information System (INIS)

    Yu, Ming; Bozek, Jody; Kagan, Mikhail; Guaraldi, Mary; Silva, Paula; Azure, Michael; Onthank, David; Robinson, Simon P.

    2013-01-01

    Introduction: Released sympathetic neurotransmitter norepinephrine (NE) in the heart is cleared by neuronal uptake-1 and extraneuronal uptake-2 transporters. Cardiac uptake-1 and -2 expression varies among species, but the uptake-1 is the primary transporter in humans. LMI1195 is an NE analog labeled with 18 F for PET evaluation of cardiac neuronal function. This study investigated the impact of cardiac neuronal uptake-1 associated with different species on LMI1195 heart uptake. Methods: Cardiac uptake-1 was blocked by desipramine, a selective uptake-1 inhibitor, and sympathetic neuronal denervation was induced by 6-hydroxydopamine, a neurotoxin, in rats, rabbits and nonhuman primates (NHP). Tissue biodistribution and cardiac imaging of LMI1195 and 123 I-metaiodobenzylguanidine (MIBG) were performed. Results: In rats, uptake-1 blockade did not alter LMI1195 heart uptake compared to the control at 60-min post injection [1.41 ± 0.07 vs. 1.47 ± 0.23 % injected dose per gram tissue (%ID/g)]. In contrast, LMI1195 heart uptake was reduced by 80% in uptake-1 blocked rabbits. In sympathetically denervated rats, LMI1195 heart uptake was similar to the control (2.18 ± 0.40 vs. 2.58 ± 0.76 %ID/g). However, the uptake decreased by 79% in denervated rabbits. Similar results were found in MIBG heart uptake in rats and rabbits with uptake-1 blockade. Consistently, LMI1195 cardiac imaging showed comparable myocardial activity in uptake-1 blocked or sympathetically denervated rats to the control, but marked activity reduction in uptake-1 blocked or denervated rabbits and NHPs. Conclusions: LMI1195 is retained in the heart of rabbits and NHPs primarily via the neuronal uptake-1 with high selectivity and can be used for evaluation of cardiac sympathetic denervation. Similar to the human, the neuronal uptake-1 is the dominant transporter for cardiac retention of NE analogs in rabbits and NHPs, but not in rats

  13. The three-kidney rat

    International Nuclear Information System (INIS)

    Provoost, A.P.; Van Aken, M.

    1984-01-01

    In contrast to the numerous research into the adaption of renal function when nephons are lost, much less attention has been paid to the effects of an extra kidney. Through the availability of inbred rat strains, techniques to transplant rat kidneys, and methods to measure total and individual kidney function repeatedly in the same animal, it became possible to study the renal function in rats with three kidneys. Adult male rats of a highly inbred Wistar strain were used. Nine recipients of a third kidney (3-K) were compared with 5 sham operated control (2-K) rats. The total GFR, as measured by the plasma clearance of Cr-5l EDTA, was taken 1,3,6,9, and 15 weeks after operation. The contribution of each kidney to the total renal function was determined by a Tc-99m DTPA scan performed at weeks 10 and 16. After transplantation the total GFR of 3-K rats was, in general, not different from the value before transplantation or from that of 2-K rats. The lack of increase of the GFR of 3-K rats was not the result of a non-functioning graft

  14. The effects of tungstate on skin lesions caused by PPD in rats.

    Science.gov (United States)

    Lee, Sang-Hee; Cho, Hyun-Gug; Lee, Sang-Il

    2008-04-01

    P-phenylenediamine (PPD) has been used as one of the ingredients in hair dye. The purpose of this study is to investigate the skin toxicity of PPD application in a tungstate-induced xanthine oxidase (XO) deficient animal model. PPD (2.5% PPD in 2% NH4OH) was applied to rat skin (25 mg/16.5 cm2) five times every other day in rats fed a standard diet (SD) or a tungstate supplemented diet (TD). The skin structure in the SD and the TD group was intact, whereas XO activity was not detected in the TD group during experimental periods. Furthermore, there were no differences between the SD and the TD group in dermal reactive oxygen species (ROS) scavenging enzymes. In these experimental conditions, although XO activity was not detected in the applied PPD rats fed a tungstate supplemented diet (PTD) group, it showed more severe tissue damage compared with the applied PPD rats fed a standard diet (PSD) group. In addition, the PTD group showed higher increased rates of ROS scavenging enzyme activity and lipid peroxide (LPO) content, and decreased glutathione (GSH) content than in the PSD group. In conclusion, the increase of PPD dermal toxicity in tungstate-induced XO deficient animals may be due to excessive ROS via ROS imbalance during PPD skin application.

  15. Adeno-associated viral vector serotype 5 poorly transduces liver in rat models.

    Directory of Open Access Journals (Sweden)

    Paula S Montenegro-Miranda

    Full Text Available Preclinical studies in mice and non-human primates showed that AAV serotype 5 provides efficient liver transduction and as such seems a promising vector for liver directed gene therapy. An advantage of AAV5 compared to serotype 8 already shown to provide efficient correction in a phase 1 trial in patients suffering from hemophilia B, is its lower seroprevalence in the general population. Our goal is liver directed gene therapy for Crigler-Najjar syndrome type I, inherited severe unconjugated hyperbilirubinemia caused by UGT1A1 deficiency. In a relevant animal model, the Gunn rat, we compared the efficacy of AAV 5 and 8 to that of AAV1 previously shown to be effective. Ferrying a construct driving hepatocyte specific expression of UGT1A1, both AAV8 and AAV1 provided an efficient correction of hyperbilirubinemia. In contrast to these two and to other animal models AAV5 failed to provide any correction. To clarify whether this unexpected finding was due to the rat model used or due to a problem with AAV5, the efficacy of this serotype was compared in a mouse and two additional rat strains. Administration of an AAV5 vector expressing luciferase under the control of a liver specific promoter confirmed that this serotype poorly performed in rat liver, rendering it not suitable for proof of concept studies in this species.

  16. Oxidative and antioxidative status in the testes of rats with acute epididymitis.

    Science.gov (United States)

    Kaya, Mete; Boleken, Mehmet Emin; Zeyrek, Fadile; Ozardali, Ilyas; Kanmaz, Turan; Erel, Ozcan; Yücesan, Selçuk

    2006-01-01

    Epididymitis is an inflammation or infection of the epididymis, a convoluted duct that lies on the posterior surface of the testicle. Oxidative stress due to excessive production of reactive oxygen species in epididymitis, impaired antioxidant defense mechanisms, or both, precipitates a range of pathologies that are currently believed to negatively affect the male reproductive function. How oxidative stress affects the testes is still unknown. We aimed to investigate the oxidative and antioxidative status of testes of rats with unilateral acute Escherichia coli epididymitis. The study included 36 male Wistar albino rats which were divided into three groups. In the epididymitis group (n = 12), an E. coli suspension was injected into the right ductus deferens of rats, and the same amount of saline was injected in the saline groups (n = 12). No surgery was performed in the control group (n = 12) for baseline values. Rats were sacrificed after 24 h and the epididymis and testes removed. The infection was confirmed by histopathologic evaluation and microbiological tests. The oxidative status of testes was evaluated by measuring myeloperoxidase (MPO) activity, and antioxidative status was evaluated by measuring total antioxidant response (TAR) and total antioxidant capacity levels (TAC). MPO activity in both the ipsilateral and contralateral testes of the epididymitis group was significantly higher than those of the saline and control groups (p antioxidants. 2006 S. Karger AG, Basel.

  17. Comparison of the subcellular distribution of monomeric 239Pu and 59Fe in the liver of rat, mouse, and Syrian and Chinese hamsters

    International Nuclear Information System (INIS)

    Winter, R.; Seidel, A.

    1982-01-01

    The subcellular distribution of 239 Pu and 59 Fe 10 days after intravenous injection as a citrate complex was investigated by sucrose density gradient centrifugation in the liver of rat, mouse, and Syrian and Chinese hamsters. Lysosomes were separated from other cell constituents by injection of the nonionic detergent Triton WR 1339 4 days before sacrifice. The Triton-induced decrease in the density of the lysosomes was very similar in all four animal species and was followed closely by a corresponding decrease of the median density of the 239 Pu profiles in rat, mouse, and, to a smaller extent, Syrian hamster. However, in Chinese hamster a clear correspondence between lysosomes and 239 Pu was not found 10 days after nuclide injection. It was concluded that lysosomes are the main storage organelles fo 239 Pu in the liver of rat and mouse and that in all four animal species mitochondria and endoplasmic reticulum do not play any significant role in binding the radionuclide. The relevance of pericellular membranes has to be checked. The distribution patterns of 59 Fe and 239 Pu were quite different

  18. Resistance to experimental tumorigenesis in cells of a long-lived mammal, the naked mole-rat (Heterocephalus glaber).

    Science.gov (United States)

    Liang, Sitai; Mele, James; Wu, Yuehong; Buffenstein, Rochelle; Hornsby, Peter J

    2010-08-01

    The naked mole-rat (NMR, Heterocephalus glaber) is a long-lived mammal in which spontaneous cancer has not been observed. To investigate possible mechanisms for cancer resistance in this species, we studied the properties of skin fibroblasts from the NMR following transduction with oncogenes that cause cells of other mammalian species to form malignant tumors. Naked mole-rat fibroblasts were transduced with a retrovirus encoding SV40 large T antigen and oncogenic Ras(G12V). Following transplantation of transduced cells into immunodeficient mice, cells rapidly entered crisis, as evidenced by the presence of anaphase bridges, giant cells with enlarged nuclei, multinucleated cells, and cells with large number of chromosomes or abnormal chromatin material. In contrast, similarly transduced mouse and rat fibroblasts formed tumors that grew rapidly without crisis. Crisis was also observed after > 40 population doublings in SV40 TAg/Ras-expressing NMR cells in culture. Crisis in culture was prevented by additional infection of the cells with a retrovirus encoding hTERT (telomerase reverse transcriptase). SV40 TAg/Ras/hTERT-expressing NMR cells formed tumors that grew rapidly in immunodeficient mice without evidence of crisis. Crisis could also be induced in SV40 TAg/Ras-expressing NMR cells by loss of anchorage, but after hTERT transduction, cells were able to proliferate normally following loss of anchorage. Thus, rapid crisis is a response of oncogene-expressing NMR cells to growth in an in vivo environment, which requires anchorage independence, and hTERT permits cells to avoid crisis and to achieve malignant tumor growth. The unique reaction of NMR cells to oncogene expression may form part of the cancer resistance of this species.

  19. Specific paucity of unmyelinated C-fibers in cutaneous peripheral nerves of the African naked-mole rat: comparative analysis using six species of Bathyergidae.

    Science.gov (United States)

    St John Smith, Ewan; Purfürst, Bettina; Grigoryan, Tamara; Park, Thomas J; Bennett, Nigel C; Lewin, Gary R

    2012-08-15

    In mammalian peripheral nerves, unmyelinated C-fibers usually outnumber myelinated A-fibers. By using transmission electron microscopy, we recently showed that the saphenous nerve of the naked mole-rat (Heterocephalus glaber) has a C-fiber deficit manifested as a substantially lower C:A-fiber ratio compared with other mammals. Here we determined the uniqueness of this C-fiber deficit by performing a quantitative anatomical analysis of several peripheral nerves in five further members of the Bathyergidae mole-rat family: silvery (Heliophobius argenteocinereus), giant (Fukomys mechowii), Damaraland (Fukomys damarensis), Mashona (Fukomys darlingi), and Natal (Cryptomys hottentotus natalensis) mole-rats. In the largely cutaneous saphenous and sural nerves, the naked mole-rat had the lowest C:A-fiber ratio (∼1.5:1 compared with ∼3:1), whereas, in nerves innervating both skin and muscle (common peroneal and tibial) or just muscle (lateral/medial gastrocnemius), this pattern was mostly absent. We asked whether lack of hair follicles alone accounts for the C-fiber paucity by using as a model a mouse that loses virtually all its hair as a consequence of conditional deletion of the β-catenin gene in the skin. These β-catenin loss-of function mice (β-cat LOF mice) displayed only a mild decrease in C:A-fiber ratio compared with wild-type mice (4.42 compared with 3.81). We suggest that the selective cutaneous C-fiber deficit in the cutaneous nerves of naked mole-rats is unlikely to be due primarily to lack of skin hair follicles. Possible mechanisms contributing to this unique peripheral nerve anatomy are discussed. Copyright © 2012 Wiley Periodicals, Inc.

  20. Digital dissection of the masticatory muscles of the naked mole-rat, Heterocephalus glaber (Mammalia, Rodentia

    Directory of Open Access Journals (Sweden)

    Philip G. Cox

    2014-06-01

    Full Text Available The naked mole-rat, Heterocephalus glaber, of the family Bathyergidae is a subterranean rodent that feeds on underground roots and tubers and digs extensive tunnel systems with its incisors. It is a highly unusual mammal with regard to its social structure, longevity, pain insensitivity and cancer resistance, all of which have made it the subject of a great deal of research in recent years. Yet, much of the basic anatomy of this species remains undocumented. In this paper, we describe the morphology of the jaw-closing musculature of the naked mole-rat, as revealed by contrast-enhanced micro-computed tomography. This technique uses an iodine stain to enable the imaging of soft tissues with microCT. The iodine-enhanced scans were used to create 3D reconstructions of the naked mole-rat masticatory muscles from which muscle masses were calculated. The jaw-closing musculature of Heterocephalus glaber is relatively very large compared to other rodents and is dominated by the superficial masseter, the deep masseter and the temporalis. The temporalis in particular is large for a rodent, covering the entirety of the braincase and much of the rear part of the orbit. The morphology of the masseter complex described here differs from two other published descriptions of bathyergid masticatory muscles, but is more similar to the arrangement seen in other rodent families. The zygomaticomandibularis (ZM muscle does not protrude through the infraorbital foramen on to the rostrum and thus the naked mole-rat should be considered protrogomorphous rather than hystricomorphous, and the morphology is consistent with secondarily lost hystricomorphy as has been previously suggested for Bathyergidae. Overall, the morphology of the masticatory musculature indicates a species with a high bite force and a wide gape–both important adaptations for a life dominated by digging with the incisors.