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Sample records for laboratory mice rats

  1. 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 anima

  2. The injustice of excluding laboratory rats, mice, and birds from the Animal Welfare Act.

    Science.gov (United States)

    Orlans, F Barbara

    2000-09-01

    A major shortcoming of the Animal Welfare Act is its exclusion of the species most-used in experimentation -- rats, mice, and birds. Considerations of justice dictate that extension of the law to these three species is the morally right thing to do. A brief history of how these species came to be excluded from the laws protecting laboratory animals is also provided, as well as discussion of the implications and significance of expanding the law.

  3. Laboratory domestication changed the expression patterns of oxytocin and vasopressin in brains of rats and mice.

    Science.gov (United States)

    Ruan, Chao; Zhang, Zhibin

    2016-09-01

    The process of domestication is recognized to exert significant effects on the social behaviors of various animal species, including defensive and cognitive behaviors that are closely linked to the expression of oxytocin (OT) and vasopressin (AVP) in selected areas of the brain. However, it is still unclear whether the behavioral changes observed under domestication have resulted in differences in the neurochemical systems that regulate them. In this study, we compared the differences in distribution patterns and regional quantities of OT and/or AVP staining in the forebrains of wild and laboratory strains of rats and mice. Our results indicated that, in the anterior hypothalamus (AH), laboratory strains showed significantly higher densities of OT-ir (immunoreactive) and AVP-ir cells than wild strains, while no significant difference in the densities of those cells in the lateral hypothalamus (LH) was detected between wild and laboratory strains. Laboratory strains showed higher densities of OT-ir and AVP-ir cells than wild strains in the medial preoptic area (MPOA), and differed in almost every MPOA subnucleus. Our results suggest that domestication significantly alters the expression of OT and AVP in related brain areas of laboratory rats and mice, an observation that could explain the identified changes in behavioral patterns.

  4. Testing declarative memory in laboratory rats and mice using the nonconditioned social discrimination procedure.

    Science.gov (United States)

    Engelmann, Mario; Hädicke, Jana; Noack, Julia

    2011-07-14

    Testing declarative memory in laboratory rodents can provide insights into the fundamental mechanisms underlying this type of learning and memory processing, and these insights are likely to be applicable to humans. Here we provide a detailed description of the social discrimination procedure used to investigate recognition memory in rats and mice, as established during the last 20 years in our laboratory. The test is based on the use of olfactory signals for social communication in rodents; this involves a direct encounter between conspecifics, during which the investigatory behavior of the experimental subject serves as an index for learning and memory performance. The procedure is inexpensive, fast and very reliable, but it requires well-trained human observers. We include recent modifications to the procedure that allow memory extinction to be investigated by retroactive and proactive interference, and that enable the dissociated analysis of the central nervous processing of the volatile fraction of an individual's olfactory signature. Depending on the memory retention interval under study (short-term memory, intermediate-term memory, long-term memory or long-lasting memory), the protocol takes ~10 min or up to several days to complete.

  5. Intraperitoneal Injection of Ethanol for the Euthanasia of Laboratory Mice (Mus musculus) and Rats (Rattus norvegicus).

    Science.gov (United States)

    Allen-Worthington, Krystal H; Brice, Angela K; Marx, James O; Hankenson, F Claire

    2015-11-01

    Compassion, professional ethics, and public sensitivity require that animals are euthanized humanely and appropriately under both planned and emergent situations. According to the 2013 AVMA Guidelines for the Euthanasia of Animals, intraperitoneal injection of ethanol is "acceptable with conditions" for use in mice. Because only limited information regarding this technique is available, we sought to evaluate ethanol by using ECG and high-definition video recording. Mice (n = 85) and rats (n = 16) were treated with intraperitoneal ethanol (70% or 100%), a positive-control agent (pentobarbital-phenytoin combination [Pe/Ph]), or a negative-control agent (saline solution). After injection, animals were assessed for behavioral and physiologic responses. Pain-assessment techniques in mice demonstrated that intraperitoneal injection of ethanol was not more painful than was intraperitoneal Pe/Ph. Median time to loss of consciousness for all mice that received ethanol or Pe/Ph was 45 s. Median time to respiratory arrest was 2.75, 2.25, and 2.63 min, and time (mean ± SE) to cardiac arrest was 6.04 ± 1.3, 2.96 ± 0.6, and 4.03 ± 0.5 min for 70% ethanol, 100% ethanol, and Pe/Ph, respectively. No mouse that received ethanol or Pe/Ph regained consciousness. Although successful in mice, intraperitoneal ethanol at the doses tested (9.2 to 20.1 g/kg) was unsuitable for euthanasia of rats (age, 7 to 8 wk) because of the volume needed and prolonged time to respiratory effects. For mice, intraperitoneal injection of 70% or 100% ethanol induced rapid and irreversible loss of consciousness, followed by death, and should be considered as "acceptable with conditions."

  6. AGONISTIC BEHAVIOR OF LABORATORY MICE

    Directory of Open Access Journals (Sweden)

    D. Cinghiţă

    2005-01-01

    Full Text Available In this work we study agonistic behavior of laboratory white mice when they are kept in captivity. For all this experimental work we used direct observation of mice, in small lists, because we need a reduced space to emphasize characteristics of agonistic behavior. Relations between members of the same species that live in organized groups are based in most cases on hierarchical structure. Relations between leader and subservient, decided by fighting, involve a thorough observation between individuals. Each member of a group has its own place on the ierarchical scale depending on resultes of fhights – it can be leader or it can be subsurvient, depending on if it wines or looses the fight. Once hierarchical scale made, every animal will adjust its behavior. After analyzing the obtained data we have enough reasons to believe that after fights the winner, usually, is the massive mouse, but it is also very important the sexual ripeness, so the immature male will be beaten. The leader male had a big exploring area and it checks up all territory.The females can be more aggressive, its fights are more brutal, than male fights are, when they fight for supremacy, but in this case fights are not as frequent as in the case of males. Always the superior female, on hierarchical scale, shows males its own statute, so the strongest genes will be perpetuated.

  7. Magnetocardiogram Measurement of Laboratory Rat

    Energy Technology Data Exchange (ETDEWEB)

    Kim, I. S.; Ahn, San; Kwon, H. C. [Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of); Song, J. H. [Chungnam National University, Daejeon (Korea, Republic of)

    2010-04-15

    We have developed a high-Tc SQUID magnetocardiogram (MCG) system for small laboratory animals. White noise of the measurement system was about 30 fT/ Hz{sup 1/2}when measured in a magnetically shielded room. We optimized the measurement position to obtain clear MCG wave from rat's small heart by using grid measurements. With the optimization, the MCG signal was successfully detected with the peak amplitude of about 30 pT. We could observe well defined P-, QRS-, and T-waves from the rat MCG. The results suggest that the developed system has a strong potential to monitor the progress of the heart disease model by using a laboratory rat.

  8. Nesting materials in environmental enrichment for laboratory rats and mice%筑巢材料在实验大、小鼠环境丰荣中的应用

    Institute of Scientific and Technical Information of China (English)

    张孟蕾; 牛屹东

    2012-01-01

    相对于标准鼠盒,实验大、小鼠更喜好有筑巢材料的“环境丰荣”鼠盒.向标准鼠盒中放入筑巢材料,可以为大、小鼠提供筑巢、躲避、攀爬、休息的环境.因此,在实验大、小鼠饲养过程中,提供筑巢材料,是一个简单有效的丰富实验动物环境,提高实验动物福利的方法.本文就筑巢材料应用背景、近年来在啮齿类实验动物环境丰荣中的应用、对实验动物福利的影响三方面做以综述,并对今后筑巢材料在改善实验动物福利的应用前景作以展望.%Compared with the standard cages, laboratory mice and rats prefer the cages enriched with nesting materials. Nesting materials provided in conventional mouse or rat cages can benefit the rodent's wellbeing, and have been widely used in husbandry and management of laboratory mice and rats for improvement of welfare. Here, we review the background, application, and effect of nesting materials on environmental enrichment and welfare improvement for laboratory mice and rats. This review also provides a clue to improvement of laboratory animal welfare in our routine work.

  9. Epidemiological investigation of Helicobacter in laboratory rats and mice by PCR%应用PCR方法调查实验大小鼠螺杆菌感染情况

    Institute of Scientific and Technical Information of China (English)

    丁聪; 冯洁; 谢建云; 陈庆庆

    2012-01-01

    通过聚合酶链反应(PCR)对上海地区实验大鼠、小鼠的螺杆菌携带情况进行调查,并用5种啮齿动物螺杆菌特异性16S rRNA基因引物对螺杆菌属阳性样品进一步鉴定,为我国实验动物微生物等级及监测标准的制定提供参考依据.结果表明:实验大鼠阳性率为70.3%(71/101),其中清洁级、SPF级分别为69.6%(48/69)和71.9%(23/32);实验小鼠阳性率为35.8%(126/352),其中清洁级、SPF级阳性率分别为51.5%(52/101)和29.5%(74/251).5种啮齿动物螺杆菌特异性16S rRNA基因引物进一步分析,结果显示在携带螺杆菌的107只小鼠及68只大鼠中,主要携带的是H.rodentium、H.hepaticus和H.bilis 3种.上海地区实验大、小鼠皆存在不同程度的螺杆菌感染,PCR法可用于实验大小鼠螺杆菌感染状况的初步调查和流行病学监测.%To provide reference and basis for the establishment of Chinese laboratory animal grades and monitoring standards, the prevalence of rodent Helicobacter infection in laboratory rats and mice were identified by polymerase chain reaction (PCR). The infection types of the rodent Helicobacter in rats and mice were further analyzed by PCR using five kinds of rodent Helicobacter 16S rRNA gene. A total of 352 mice (clean grade of 101,SPF grade of 251) and 101 rats (clean grade of 69,SPF grade of 32) were detected. The positive rate of Helicobacter in rats and mice as follows; the positive rate in rats was 70. 3% (71/101), among them, the positive rate in clean grade and SPF grade were 69. 6% (48/69) and71. 9%(23/32) respectively! the positive rate in mice was 35. 8%(126/352) , among them, the rate in clean grade and SPF grade were 51.5% (52/101)and 29. 5%( 74/251) respectively. H. rodentium, H. hepaticus and H. bilis were the most common Helicobacter species in rats and mice. The results indicated that Helicobacter species infections existed in laboratory rats and mice of the neighborhood of shanghai. PCR is

  10. 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.

  11. Helminth parasites of conventionally mantained laboratory mice

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    Roberto Magalhães Pinto

    1994-03-01

    Full Text Available The spectrum of intestinal parasites present in the SwissWebster, C57B1/6 and DBA/2 mice strains from different animal houses was identified and prevalences compared. Three parasites were observed during the course ofthis study, namely the cestode. Vampirolepis nana (Siebold, 1852 Spasskii, 1954(=Hymenolepis nana and the nematodes Aspiculuris tetraptera (Nitzsch, 1821 Schulz, 1924 and Syphacia obvelata (Rudolphi, 1802 Seurat, 1916. The scope of thisinvestigation has been widened to also include morphometric data on the parasites, to further simplify their identification, since the presence of helminths in laboratory animals is regarded as a restricting factor for the proper attainment of experimental protocols.

  12. Comparison of culture and PCR assays for detection of bacteria in laboratory rats and mice%培养法和 PCR法用于实验大、小鼠细菌检测的比较分析

    Institute of Scientific and Technical Information of China (English)

    冯洁; 谢建云; 冯丽萍; 魏晓锋; 高诚

    2015-01-01

    Objective To compare the efficiency of bacteria culture and PCR assays for detection of Staphylococcus aureus ( S.aureus) , Pseudomonas aeruginosa ( P.aeruginosa) and Klebsiella pneumoniae ( K.pneumoniae) in laboratory rats and mice.Methods Bacteria culture combined with biochemical identification and PCR assay were used to detect 78 SPF rats and 422 SPF mice and the results of the two methods were compared .Results All the 78 rats were negative .Of the 422 mice, the positive rate by culture was 7.11%(30/422), of which, 10 were S.aureus, 22 were P.aeruginosa, and 2 were K.pneumoniae.The positive rate by PCR was 7.58%(32/422), of which, 10 were S.aureus, 25 were P. aeruginosa, and 2 were K.pneumoniae.Conclusions The high sensitivity , rapid procedure and easy to operate of PCR assay makes it valuable for rapid bacteria diagnosis and large-scale screening in laboratory animals .%目的:比较培养法和PCR法对实验大、小鼠的细菌检测效果。方法分别采用传统细菌分离培养结合生化鉴定方法和PCR方法,对78只SPF级大鼠和422只SPF级小鼠进行检测,对两种方法的检测结果进行比较分析。结果78只SPF级大鼠均未检测出阳性。422只SPF级小鼠,培养法检测阳性率7.11%(30/422),其中金黄色葡萄球菌10只,绿脓杆菌22只,肺炎克雷伯杆菌2只。 PCR法检测阳性率7.58%(32/422),其中金黄色葡萄球菌10只,绿脓杆菌25只,肺炎克雷伯杆菌2只。结论 PCR法的敏感性高于培养法,操作简便、快捷,适用于实验动物细菌的快速诊断和大规模的质量筛查。

  13. Zoopharmacognosy in diseased laboratory mice: conflicting evidence.

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    Minesh Kapadia

    Full Text Available Zoopharmacognosy denotes a constellation of learned ingestive responses that promote healing and survival of infected or poisoned animals. A similar self-medication phenomenon was reported in diseased laboratory rodents. In particular, a series of studies revealed that autoimmune MRL/lpr mice readily consume solutions paired or laced with cyclophosphamide (CY, an immunosuppressive drug that prevents inflammatory damage to internal organs. However, due to design limitations, it could not be elucidated whether such a response reflects the learned therapeutic effect of CY, or a deficit in sensory input. We presently assess the behavioural effects of prolonged consumption of CY-laced, 16% sucrose solution in a continuous choice paradigm, with tap water available ad lib. Contrary to overall expectation, MRL/lpr mice did not increase their intake of CY with disease progression. Moreover, they ingested lower doses of CY and preferred less CY-laced sucrose solution than age-matched controls. The results obtained could not confirm zoopharmacognosy in diseased MRL/lpr mice, likely due to impaired responsiveness to palatable stimulation, or attenuated survival mechanisms after prolonged inbreeding in captivity. However, by revealing the effectiveness of unrestricted drinking of drug-laced sucrose solution on behavior and immunity, the current study supports broader use of such an administration route in behavioural studies sensitive to external stressors.

  14. Preferences for nest boxes as environmental enrichment for laboratory mice

    NARCIS (Netherlands)

    Van de Weerd, HA; Van Loo, PLP; Van Zutphen, LFM; Koolhaas, JM; Baumans, [No Value

    1998-01-01

    In nature, mice live in burrows with nest chambers where they breed and may hide from predators. In the laboratory, a shelter or refuge is an easily applicable form of enrichment which may enhance the welfare of laboratory mice by giving them more control over their environment. Six nest boxes made

  15. 两种方法对上海及周边地区实验大小鼠螺杆菌携带情况的调查%An Epidemiological Survey of Helicobacter spp.in Laboratory Mice and Rats in the Area around Shanghai by Two Detection Methods

    Institute of Scientific and Technical Information of China (English)

    丁聪; 冯洁; 谢建云; 高诚; 胡建华

    2011-01-01

    Objective To identity the prevalence of Helicobacter spp. Infection in laboratory mice and laboratory rats in the area around Shanghai, and provide reference and basis for the establishment of Chinese laboratory animals grades and monitoring standards. Methods A total of 352 mice (101 clean grade mice,251 SPF grade mice) and 101 rat (69 clean grade rats, 32 SPF grade rats) obtained from the area around Shanghai were detected by polymerase chain reaction (PCR).88 mice (clean grade mice,62 SPF grade mice) and 165 rats (84 clean grade rats,81 SPF grade rats) were detected by enzyme linked immunosorbent assay (ELISA). Next,the positive rate of the two methods in 88 mice and 101rats were compared. Results PCR detecting percentage in mice and rats were as follows: the average positive rate of mice was 35. 8% (126/352) .among them,the positive rates of clean grade rats and SPF grade mice were 51.5% (52/101)and 29. 5% (74/251 ) .respectively. The average positive rates of rats were 70. 3% (71/101 ) .among them,the positive rate of clean grade and SPF grade were 69. 6% (48/69) and 71. 9% (23/32) .respectively. ELISA detecting percentage in mice and rats as follows;the average positive rate of mice were 15. 9% (14/88) , among them, the positive rates of clean grade and SPF grade mice were 19. 2% (5/26) and 14. 5% (9/62) .respectively. The average positive rate of rats was 52. 7% (87/165), among them, the positive rates of clean grade and SPF grade rats were 53. 6% (45/84) and 51. 9% (42/81), respectively. The positive rates of 88 mice tested by PCR were 72.7% (64/88) and by ELISA 15.9% (14/88). The positive rates of 101 rats detected by PCR were 70.3% (71/101) and by ELISA 49.5% (50/101). Conclusions Helicobacter spp. Infection exists in laboratory mice and laboratory rats in the area around Shanghai. The PCR assay of feces is more sensitive than the examination of the serum antibody against Helicobacter spp.%目的 了解上海及周边地区实验小鼠、大鼠螺杆菌

  16. Preference Testing as Environmental Enrichment Assessment for Laboratory Mice

    National Research Council Canada - National Science Library

    Navakanit Sachanonta; Waridtha Sa-ngeunreung; Somchai Sa-ing-kaew; Raywadee Butraporn

    2013-01-01

      In the field of biomedical research, a wide variety of environmental enrichment items are available for laboratory mice to fulfill its physiological and behavioral needs which influence the outcome...

  17. REVIEW - Thermal Physiology of Laboratory Mice: Defining Thermoneutrality

    Science.gov (United States)

    In terms of total number of publications, the laboratory mouse (Mus musculus) has emerged as the most popular test subject in biomedical research. Mice are used as models to study obesity, diabetes, eNS diseases and variety of other pathologies. Mice are classified as homeotherms...

  18. Differences in ultrasonic vocalizations between wild and laboratory California mice (Peromyscus californicus.

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    Matina C Kalcounis-Rueppell

    Full Text Available BACKGROUND: Ultrasonic vocalizations (USVs emitted by muroid rodents, including laboratory mice and rats, are used as phenotypic markers in behavioral assays and biomedical research. Interpretation of these USVs depends on understanding the significance of USV production by rodents in the wild. However, there has never been a study of muroid rodent ultrasound function in the wild and comparisons of USVs produced by wild and laboratory rodents are lacking to date. Here, we report the first comparison of wild and captive rodent USVs recorded from the same species, Peromyscus californicus. METHODOLOGY AND PRINCIPAL FINDINGS: We used standard ultrasound recording techniques to measure USVs from California mice in the laboratory (Peromyscus Genetic Stock Center, SC, USA and the wild (Hastings Natural History Reserve, CA, USA. To determine which California mouse in the wild was vocalizing, we used a remote sensing method that used a 12-microphone acoustic localization array coupled with automated radio telemetry of all resident Peromyscus californicus in the area of the acoustic localization array. California mice in the laboratory and the wild produced the same types of USV motifs. However, wild California mice produced USVs that were 2-8 kHz higher in median frequency and significantly more variable in frequency than laboratory California mice. SIGNIFICANCE: The similarity in overall form of USVs from wild and laboratory California mice demonstrates that production of USVs by captive Peromyscus is not an artifact of captivity. Our study validates the widespread use of USVs in laboratory rodents as behavioral indicators but highlights that particular characteristics of laboratory USVs may not reflect natural conditions.

  19. The effects of individual housing on mice and rats

    DEFF Research Database (Denmark)

    Krohn, Thomas Cæcius; Sørensen, Dorte Bratbo; Ottesen, Jan Lund

    2006-01-01

    , growth, and behaviour was introduced, rather as a model for psychoneurosis than through any concern for animal welfare. Today, it is often stated as common knowledge in laboratory animal science textbooks that individual housing as well as isolation of rats and mice has an effect on physiology...... these animals individually without negative impact on welfare, eg by providing special housing improvements. A range of studies have shown that individual housing or isolation has effects on corticosterone, the open field behaviour, barbiturate sleeping time and the metabolism of different pharmaceuticals...

  20. Database of Physiological Parameters for Early Life Rats and Mice

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    U.S. Environmental Protection Agency — The Database of Physiological Parameters for Early Life Rats and Mice provides information based on scientific literature about physiological parameters. Modelers...

  1. Mapping Mammary Carcinoma Suppressor Genes in the Laboratory Rat

    Science.gov (United States)

    1997-07-01

    AD GRANT NUMBER DAMDI7-94-J-4040 TITLE: Mapping Mammary Carcinoma Suppressor Genes in the Laboratory Rat PRINCIPAL INVESTIGATOR: Michael Gould, Ph.D...Carcinoma Suppressor Genes in the Laboratory Rat DAMDI7-94-J-4040 6. AUTHOR(S) Michael Gould, Ph.D. Hong Lan, Ph.D. 7. PERFORMING ORGANIZATION NAME(S) AND

  2. The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

    NARCIS (Netherlands)

    Labots, Maaike; Van Lith, Hein A.; Ohl, Frauke; Arndt, Saskia S.

    2015-01-01

    This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure multiple dimensions of unconditioned behavior in small laboratory mammals (e.g., mice, rats, tree shrews and small primates). This paradigm is a valu

  3. Voluntary ingestion of nut paste for administration of buprenorphine in rats and mice.

    Science.gov (United States)

    Abelson, Klas S P; Jacobsen, Kirsten R; Sundbom, Renée; Kalliokoski, Otto; Hau, Jann

    2012-10-01

    An adequate analgesic strategy is important to improve the postoperative recovery and welfare of laboratory rats and mice. It is desirable that the method for administering the drug is non-invasive and stress-free. We have previously validated a method for administering buprenorphine in a nut paste for voluntary ingestion. This method has many advantages over parenteral administration. To use the method in a successful way, however, it is important to prepare and administer the mix correctly. The present paper describes in detail how to implement the method, by means of habituation, presentation, adequate concentrations and amounts of buprenorphine/nut paste, and dosage of buprenorphine to rats and mice.

  4. Intravesical Instillation in Pure Line LEW Rats and Nude Mice

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jie; XIE Shusheng; GUO Xiaoyun; MO Zengnan

    2007-01-01

    In order to study bladder intravesical instillation methods in pure line LEW rats and nude mice, female LEW rats and nude mice aged 2 to 4 weeks were sacrificed. Their urethra and bladder were observed under anatomical microscopy. A trochar was prepared according to the outline and angle of the urethra. Ink was poured into female rats and nude mice bladder though urethra. Filling and staining of bladder were observed and evaluated under anatomical microscopy. Status and urethral injury of rats and mice were observed. The results showed that urethra anatomic structure of rats and nude mice was different from that of human urethra. When bladder was filled with ink and became blue, liquid was not seen to leak out. The success rate of intubation was high (100%). Living activities of animals weren't influenced by intravesical instillation. It was concluded that bladder irrigation might be a kind of valid and utilizable method in pure line rat and nude mouse empirical study. The model may be a more effective tool for study of bladder tumor.

  5. Comparative toxicity of acephate in laboratory mice, white-footed mice, and meadow voles

    Science.gov (United States)

    Rattner, B.A.; Hoffman, D.J.

    1984-01-01

    The LD50 (95% confidence limits) of the organophosphorus insecticide acephate was estimated to be 351, 380, and 321 mg/kg (295?416, 280?516, and 266?388 mg/kg) for CD-1 laboratory mice (Mus musculus), white-footed mice (Peromyscus leucopus noveboracensis), and meadow voles (Microtus pennsylvanicus), respectively. In a second study, these species were provided mash containing 0, 25, 100, and 400 ppm acephate for five days. Brain and plasma cholinesterase activities were reduced in a dose-dependent manner to a similar extent in the three species (inhibition of brain acetyl-cholinesterase averaged for each species ranged from 13 to 22% at 25 ppm, 33 to 42% at 100 ppm, and 56 to 57% at 400 ppm). Mash intake, body or liver weight, plasma enzyme activities (alkaline phosphatase, alanine and aspartate aminotransferase), hepatic enzyme activities (aniline hydroxylase, 7-ethoxycoumarin O-deethylase, and glutathione S-transferase), and cytochrome content (P-450 and b5) were not affected by acephate ingestion, although values differed among species. In a third experiment, mice and voles received 400 ppm acephate for 5 days followed by untreated food for up to 2 weeks. Mean inhibition of brain acetylcholin-esterase for the three species ranged from 47 to 58% on day 5, but by days 12 and 19, activity had recovered to 66 to 76% and 81 to 88% of concurrent control values. These findings indicate that CD-1 laboratory mice, white-footed mice, and meadow voles are equally sensitive to acephate when maintained under uniform laboratory conditions. Several factors (e.g., behavior, food preference, habitat) could affect routes and degree of exposure in the field, thereby rendering some species of wild rodents ecologically more vulnerable to organophosphorus insecticides.

  6. The laboratory rat: Relating its age with human′s

    Directory of Open Access Journals (Sweden)

    Pallav Sengupta

    2013-01-01

    Full Text Available By late 18 th or early 19 th century, albino rats became the most commonly used experimental animals in numerous biomedical researches, as they have been recognized as the preeminent model mammalian system. But, the precise correlation between age of laboratory rats and human is still a subject of debate. A number of studies have tried to detect these correlations in various ways, But, have not successfully provided any proper association. Thus, the current review attempts to compare rat and human age at different phases of their life. The overall findings indicate that rats grow rapidly during their childhood and become sexually mature at about the sixth week, but attain social maturity 5-6 months later. In adulthood, every day of the animal is approximately equivalent to 34.8 human days (i.e., one rat month is comparable to three human years. Numerous researchers performed experimental investigations in albino rats and estimated, in general, while considering their entire life span, that a human month resembles every-day life of a laboratory rat. These differences signify the variations in their anatomy, physiology and developmental processes, which must be taken into consideration while analyzing the results or selecting the dose of any research in rats when age is a crucial factor.

  7. Chronic toxicity study of cyclohexanone in rats and mice.

    Science.gov (United States)

    Lijinsky, W; Kovatch, R M

    1986-10-01

    A 2-year chronic toxicity assay of cyclohexanone (CAS: 108-94-1) was conducted in F344 rats and (C57BL/6 X C3H)F1 mice by administering a solution of cyclohexanone in drinking water. Two concentrations were given to rats, 6,500 and 3,300 ppm (wt/vol). Male mice received 13,000 and 6,500 ppm, while female mice were given three concentrations, 25,000, 13,000, and 6,500 ppm. Each treatment group consisted of 50 or 52 male and 50 or 52 female rats or mice, except 47 male mice treated with the highest dose and 41 female mice treated with the highest dose, and there was a group of untreated controls of each species. Survival and weight gain were similar to those of controls at the lowest cyclohexanone dose in both sexes of both species, but weight gain was depressed at all of the higher doses. Survival was good (greater than 80% at 90 wk) in all groups except in female mice at the 2 highest doses; at 25,000 ppm of cyclohexanone, only 50% of mice lived beyond 1 year. Most of the neoplasms in the treated groups did not differ significantly in number from those in the controls. Male rats receiving 3,300 ppm cyclohexanone had a 13% incidence of adrenal cortex adenomas (7 animals) compared with an incidence of 2% in controls; the incidence of this neoplasm did not increase in the male rats receiving 6,500 ppm or in the female rats given either dose. The mice had a statistically significant increase in incidence of lymphomas-leukemias among the females given 6,500 ppm, but not among the groups given higher doses of cyclohexanone. Male mice given 6,500 ppm cyclohexanone showed an increased incidence of hepatocellular adenomas and carcinomas, 50% versus 32.5% in controls, but the incidence of these neoplasms was only 37% in the male mice given 13,000 ppm cyclohexanone. The incidence of lymphomas in male mice and of hepatocellular neoplasms in female mice given cyclohexanone did not differ from that in the controls. The evidence for carcinogenic activity of cyclohexanone is

  8. Efficient single nucleotide polymorphism discovery in laboratory rat strains using wild rat-derived SNP candidates

    Directory of Open Access Journals (Sweden)

    Hedrich Hans J

    2005-11-01

    Full Text Available Abstract Background The laboratory rat (Rattus norvegicus is an important model for studying many aspects of human health and disease. Detailed knowledge on genetic variation between strains is important from a biomedical, particularly pharmacogenetic point of view and useful for marker selection for genetic cloning and association studies. Results We show that Single Nucleotide Polymorphisms (SNPs in commonly used rat strains are surprisingly well represented in wild rat isolates. Shotgun sequencing of 814 Kbp in one wild rat resulted in the identification of 485 SNPs as compared with the Brown Norway genome sequence. Genotyping 36 commonly used inbred rat strains showed that 84% of these alleles are also polymorphic in a representative set of laboratory rat strains. Conclusion We postulate that shotgun sequencing in a wild rat sample and subsequent genotyping in multiple laboratory or domesticated strains rather than direct shotgun sequencing of multiple strains, could be the most efficient SNP discovery approach. For the rat, laboratory strains still harbor a large portion of the haplotypes present in wild isolates, suggesting a relatively recent common origin and supporting the idea that rat inbred strains, in contrast to mouse inbred strains, originate from a single species, R. norvegicus.

  9. [Spontaneous chromosome aberrations in the oogenesis of laboratory rats].

    Science.gov (United States)

    Dyban, A P; Chebotar', N A

    1975-08-01

    Cytological preparations were made by Tarkovsky's method from 2335 rat oocytes obtained after an induced superodulation. The chromosomes could be counted exactly in 861 oocytes. In 797 oocytes (92.7%) euploidy (metaphase II with 21 chromosomes) and in 64 oocytes (7.5%) aneuploidy was found. 60 oocytes were hypoploid, but only 4 oocytes (0.4%) were hyperploid (with 22 chromosomes). Hypoploidy can often be due to the presence of artefacts. Probably the rate of spontaneous aneuploidy in rat oogenesis is about 0.8%, this being significantly lower than the rate of spontaneous aneuploidy in mice oogenesis.

  10. The effects of individual housing on mice and rats

    DEFF Research Database (Denmark)

    Krohn, Thomas Cæcius; Sørensen, Dorte Bratbo; Ottesen, Jan Lund

    2006-01-01

    and behaviour. It is, however, unclear whether this effect actually impairs animal welfare. The aim of this paper is to analyse studies on individual housing of mice and rats to evaluate whether there is documented proof that individual housing affects welfare, and, alternatively whether it is possible to house...... in the animals. However, this review of 37 studies in rats and 17 studies in mice showed divergence in test results difficult to explain, as many studies lacked basal information about the study, eg information on genetic strains and housing conditions, such as bedding, enrichment and cage sizes. Furthermore...

  11. Inhalation developmental toxicology studies: Gallium arsenide in mice and rats

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Greenspan, B.J.; Dill, J.A.; Stoney, K.H.; Evanoff, J.J.; Rommereim, R.L.

    1990-12-01

    Gallium arsenide is a crystalline compound used extensively in the semiconductor industry. Workers preparing solar cells and gallium arsenide ingots and wafers are potentially at risk from the inhalation of gallium arsenide dust. The potential for gallium arsenide to cause developmental toxicity was assessed in Sprague- Dawley rats and CD-1 (Swiss) mice exposed to 0, 10, 37, or 75 mg/m{sup 3} gallium arsenide, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and {approx}30 positively mated rats or {approx}24 positively mated mice. Mice were exposed on 4--17 days of gestation (dg), and rats on 4--19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Gallium and arsenic concentrations were determined in the maternal blood and uterine contents of the rats (3/group) at 7, 14, and 20 dg. 37 refs., 11 figs., 30 tabs.

  12. Reducing Fear of the Laboratory Rat: A Participant Modeling Approach.

    Science.gov (United States)

    Barber, Nigel

    1994-01-01

    Reports on the use of participant modeling in a study of 56 college-level students to reduce fear of laboratory rats. Discovers that even mild exposure reduced fear significantly. Finds that women were more fearful initially but that their fear reduction was equal to that of men. (CFR)

  13. Efficient single nucleotide polymorphism discovery in laboratory rat strains using wild rat-derived SNP candidates

    OpenAIRE

    Hedrich Hans J; Wedekind Dirk; Zeegers Dimphy; Guryev Victor; Smits Bart MG; Cuppen Edwin

    2005-01-01

    Abstract Background The laboratory rat (Rattus norvegicus) is an important model for studying many aspects of human health and disease. Detailed knowledge on genetic variation between strains is important from a biomedical, particularly pharmacogenetic point of view and useful for marker selection for genetic cloning and association studies. Results We show that Single Nucleotide Polymorphisms (SNPs) in commonly used rat strains are surprisingly well represented in wild rat isolates. Shotgun ...

  14. 9 CFR 355.16 - Control of flies, rats, mice, etc.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Control of flies, rats, mice, etc. 355.16 Section 355.16 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF....16 Control of flies, rats, mice, etc. Flies, rats, mice, and other vermin shall be excluded...

  15. Biologic effects of fenbendazole in rats and mice: a review.

    Science.gov (United States)

    Villar, David; Cray, Carolyn; Zaias, Julia; Altman, Norman H

    2007-11-01

    This review summarizes findings from toxicologic, carcinogenic, immunologic, and metabolic studies on fenbendazole (FBZ). Currently, FBZ is used to treat or prevent pinworm outbreaks in laboratory rodents. Because antiparasitic treatments usually are not part of experimental designs, interactions from the medication on the outcomes of ongoing experiments are a concern. At therapeutic levels, FBZ does not alter the total content of cytochromes P450 but does induce certain hepatic cytochrome P450 isoforms, namely 1A1, 1A2, and 2B1. Although expressed constitutively at low or undetectable levels, these isoforms particularly are known for bioactivating a number of procarcinogens. Lifetime studies in rats have shown that FBZ is not a carcinogen but that it may behave as a tumor promoter when given after certain initiators. Unlike in other animal species, FBZ treatment-associated myelosuppression has not been reported to occur in rodents. The few currently available immunologic studies in mice, including an autoimmune model, have not shown effects on selected immune responses. However, data from other animal species suggest that the ability of B and T lymphocytes to proliferate in the secondary immune response may be suppressed during treatment with FBZ.

  16. Stevia and saccharin preferences in rats and mice.

    Science.gov (United States)

    Sclafani, Anthony; Bahrani, Mahsa; Zukerman, Steven; Ackroff, Karen

    2010-06-01

    Use of natural noncaloric sweeteners in commercial foods and beverages has expanded recently to include compounds from the plant Stevia rebaudiana. Little is known about the responses of rodents, the animal models for many studies of taste systems and food intake, to stevia sweeteners. In the present experiments, preferences of female Sprague-Dawley rats and C57BL/6J mice for different stevia products were compared with those for the artificial sweetener saccharin. The stevia component rebaudioside A has the most sweetness and least off-tastes to human raters. In ascending concentration tests (48-h sweetener vs. water), rats and mice preferred a high-rebaudioside, low-stevioside extract as strongly as saccharin, but the extract stimulated less overdrinking and was much less preferred to saccharin in direct choice tests. Relative to the extract, mice drank more pure rebaudioside A and showed stronger preferences but still less than those for saccharin. Mice also preferred a commercial mixture of rebaudioside A and erythritol (Truvia). Similar tests of sweet receptor T1R3 knockout mice and brief-access licking tests with normal mice suggested that the preferences were based on sweet taste rather than post-oral effects. The preference response of rodents to stevia sweeteners is notable in view of their minimal response to some other noncaloric sweeteners (aspartame and cyclamate).

  17. Stevia and Saccharin Preferences in Rats and Mice

    Science.gov (United States)

    Bahrani, Mahsa; Zukerman, Steven; Ackroff, Karen

    2010-01-01

    Use of natural noncaloric sweeteners in commercial foods and beverages has expanded recently to include compounds from the plant Stevia rebaudiana. Little is known about the responses of rodents, the animal models for many studies of taste systems and food intake, to stevia sweeteners. In the present experiments, preferences of female Sprague–Dawley rats and C57BL/6J mice for different stevia products were compared with those for the artificial sweetener saccharin. The stevia component rebaudioside A has the most sweetness and least off-tastes to human raters. In ascending concentration tests (48-h sweetener vs. water), rats and mice preferred a high-rebaudioside, low-stevioside extract as strongly as saccharin, but the extract stimulated less overdrinking and was much less preferred to saccharin in direct choice tests. Relative to the extract, mice drank more pure rebaudioside A and showed stronger preferences but still less than those for saccharin. Mice also preferred a commercial mixture of rebaudioside A and erythritol (Truvia). Similar tests of sweet receptor T1R3 knockout mice and brief-access licking tests with normal mice suggested that the preferences were based on sweet taste rather than post-oral effects. The preference response of rodents to stevia sweeteners is notable in view of their minimal response to some other noncaloric sweeteners (aspartame and cyclamate). PMID:20413452

  18. Subchronic inhalation toxicity of benzene in rats and mice.

    Science.gov (United States)

    Ward, C O; Kuna, R A; Snyder, N K; Alsaker, R D; Coate, W B; Craig, P H

    1985-01-01

    A subchronic inhalation toxicity study of benzene was conducted in CD-1 mice and Sprague-Dawley rats. Four groups of animals consisting of 150 mice and 50 rats/sex each were exposed to concentrations of 1, 10, 30, and 300 ppm benzene vapor, 6 hours/day, 5 days/week, for 13 weeks. Additional groups of mice and rats, of equal size, were exposed under similar conditions to filtered air and served as control groups. Thirty mice and 10 rats/sex in each group were sacrificed after 7, 14, 28, 56, and 91 days of treatment. Criteria used to evaluate exposure-related effects included behavior, body weights, organ weights, clinical pathology, gross pathology, and histopathology. Fifty animals per sex of each species were exposed concurrently for cytogenetic studies. In addition, blood serum was obtained for immunological assays. The results of these two studies will be reported separately. No consistent exposure-related trends were seen in the clinical observations and body weight data. Exposure-related clinical pathology changes were seen in the high-level (300 ppm) animals of both species. In the mice, these changes included decreases in hematocrit, total hemoglobin, erythrocyte count, leukocyte count, platelet count, myeloid/erythroid ratios, and percentage of lymphocytes. Mean cell volume, mean cell hemoglobin, glycerol lysis time, and the incidence and severity of red cell morphologic changes were increased in the mice. In the rats, decreased lymphocyte counts and a relative increase in neutrophil percentages were the only exposure-related clinical pathology alterations. Histopathologic changes were present in the thymus, bone marrow, lymph nodes, spleen, ovaries, and testes of mice exposed to 300 ppm and in most cases the incidence and severity of the lesions were greater in the males. These changes in the testes and ovaries at 300 ppm were also seen at lower concentrations, but they were of doubtful biological significance. In rats, the only exposure-related lesion

  19. Use of sentinel animals for the microbiological monitoring program in laboratory rats and mice%大鼠、小鼠微生物学质量监测中的哨兵动物设置

    Institute of Scientific and Technical Information of China (English)

    黄小燕; 潘裕; 樊海艇; 张超超; 汤家铭; 蔡贞贞

    2014-01-01

    建立并执行全面的实验动物质量监测,对于确保人员、动物健康和福利,以及实验研究结果的真实性、有效性和可重复性是非常重要的。在实验动物中设置相应的哨兵动物能有效监测实验动物质量。本文对实验动物微生物质量监测中哨兵鼠选择,哨兵鼠与被监测动物接触方式、时间,哨兵鼠放置位置,每笼哨兵鼠代表被监测群体的鼠笼数,以及检测数量、检测频率和项目做一综述。%It is very important to establish and execute the all -sided experimental animal quality monitoring in order to guarantee human health , animal health and welfare as well as the authenticity , validity, and repeatability of the experimental research results.Setting corresponding sentinel animals in the experiment can effectively monitor the quality of experimental animals.This article gives a general review of the selection of sentinel rats in the microbiological quality monitoring of the experiment animals , contact form and time between the sentinel rats and the rats being monitored , the placement of sentinel rats, and the number of rat cages being monitored by each cage of sentinel rats , as well as the test quantity, test frequency and the project.

  20. The Laboratory Rat as an Animal Model for Osteoporosis Research

    OpenAIRE

    Lelovas, Pavlos P; Xanthos, Theodoros T.; Thoma, Sofia E; Lyritis, George P; Dontas, Ismene A

    2008-01-01

    Osteoporosis is an important systemic disorder, affecting mainly Caucasian women, with a diverse and multifactorial etiology. A large variety of animal species, including rodents, rabbits, dogs, and primates, have been used as animal models in osteoporosis research. Among these, the laboratory rat is the preferred animal for most researchers. Its skeleton has been studied extensively, and although there are several limitations to its similarity to the human condition, these can be overcome th...

  1. Normalizing the environment recapitulates adult human immune traits in laboratory mice.

    Science.gov (United States)

    Beura, Lalit K; Hamilton, Sara E; Bi, Kevin; Schenkel, Jason M; Odumade, Oludare A; Casey, Kerry A; Thompson, Emily A; Fraser, Kathryn A; Rosato, Pamela C; Filali-Mouhim, Ali; Sekaly, Rafick P; Jenkins, Marc K; Vezys, Vaiva; Haining, W Nicholas; Jameson, Stephen C; Masopust, David

    2016-04-28

    Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice--like newborn, but not adult, humans--lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.

  2. Voluntary ingestion of nut paste for administration of buprenorphine in rats and mice

    DEFF Research Database (Denmark)

    Abelson, Klas S P; Jacobsen, Kirsten R; Sundbom, Renée

    2012-01-01

    An adequate analgesic strategy is important to improve the postoperative recovery and welfare of laboratory rats and mice. It is desirable that the method for administering the drug is non-invasive and stress-free. We have previously validated a method for administering buprenorphine in a nut paste...... for voluntary ingestion. This method has many advantages over parenteral administration. To use the method in a successful way, however, it is important to prepare and administer the mix correctly. The present paper describes in detail how to implement the method, by means of habituation, presentation, adequate...

  3. [Seromonitoring of laboratory mouse and rat colonies for common murine pathogens (author's transl)].

    Science.gov (United States)

    Fujiwara, K; Tanishima, Y; Tanaka, M

    1979-04-01

    During a period from 1973 to 1978, 392 and 225 lots including 12,232 mouse and 8,044 rat individual sera, respectively, were examined for antibodies to murine hepatitis virus, Sendai virus, Bordetella bronchiseptica, Mycoplasma pulmonis, Tyzzer agents, Salmonella typhimurium and Corynebacterium kutscheri. Of mouse lots 94.5% and 39.3% from breeder and user colonies, respectively, were negative for all antibodies examined as well as 31.6% and 17.2% of rat breeder and user colonies, respectively. Among positive lots from mouse users, high positivity rates were seen with Senai virus (47.6%), M. pulmonis (19.0%), and murine hepatitis virus (JHM : 18.2%, MHV : 31.0%), while the rates were high in rat user lots with Sendai virus (24.4%), B. bronchiseptica (39.3%) M. pulmonis (12.5%), murine coronaviruses (JHM : 19.0%, MHV-2 : 28.0%) and tyzzer agents (MSK : 19.6%, RT : 17.9%). These pathogenes with high positivities should be monitored indispensably as a quality control of laboratory mice and rats.

  4. Preferences for nesting material as environmental enrichment for laboratory mice

    NARCIS (Netherlands)

    VandeWeerd, HA; VanLoo, PLP; VanZutphen, LFM; Koolhaas, JM; Baumans, [No Value; Weerd, H.A. van de; Loo, P.L.P. van; Zutphen, L.F.M. van

    1997-01-01

    Behavioural and psychological needs of laboratory animals generally cannot adequately be met in standard laboratory cages. Environmental enrichment, which provides a more structured environment can enhance the well-being of laboratory animals. They may perform more of their species-specific behaviou

  5. Preferences for nesting material as environmental enrichment for laboratory mice

    NARCIS (Netherlands)

    VandeWeerd, HA; VanLoo, PLP; VanZutphen, LFM; Koolhaas, JM; Baumans, [No Value; Weerd, H.A. van de; Loo, P.L.P. van; Zutphen, L.F.M. van

    Behavioural and psychological needs of laboratory animals generally cannot adequately be met in standard laboratory cages. Environmental enrichment, which provides a more structured environment can enhance the well-being of laboratory animals. They may perform more of their species-specific

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

    Science.gov (United States)

    Sotocinal, Susana G; Sorge, Robert E; Zaloum, Austin; Tuttle, Alexander H; Martin, Loren J; Wieskopf, Jeffrey S; Mapplebeck, Josiane C S; Wei, Peng; Zhan, Shu; Zhang, Shuren; McDougall, Jason J; King, Oliver D; Mogil, Jeffrey S

    2011-07-29

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Glucocorticosteroid injection is a circadian zeitgeber in the laboratory rat

    Energy Technology Data Exchange (ETDEWEB)

    Horseman, N.D.; Ehret, C.F.

    1982-09-01

    Intraperitoneal temperatures were monitored by radiotelemetry to observe the thermoregulatory rhythm of male laboratory rats (Rattus norvegicus albinus). Rats received single injections of dexamethasone (as dexamethasone sodium phosphate) during constant darkness (0.1 lx) with food freely available or no food available. No phase shifts occurred following saline injection or dexamethasone at 1 mg/kg body wt. Depending on the phase of injection relative to the circadian cycle, dexamethasone at 10 mg/kg caused thermoregulatory peaks to be either delayed or advanced on the 4th and 5th days after injection. There was an insensitive interval which corresponded to subjective day. Phase shifts induced by dexamethasone during ad libitum feeding were of less magnitude than those induced during starvation. The determination of phase-shifting parameters (i.e., a phase-response curve) for hormonal substances represents a rigorous and broadly applicable technique for determining endogenous mechanisms for circadian phase control and entrainment.

  9. Efficient single nucleotide polymorphism discovery in laboratory rat strains using wild rat-derived SNP candidates

    NARCIS (Netherlands)

    Smits, B.M.; Guryev, V.; Zeegers, D.; Wedekind, D.; Hedrich, H.J.; Cuppen, E.

    2005-01-01

    BACKGROUND: The laboratory rat (Rattus norvegicus) is an important model for studying many aspects of human health and disease. Detailed knowledge on genetic variation between strains is important from a biomedical, particularly pharmacogenetic point of view and useful for marker selection for genet

  10. Helicobacter Infection Significantly Alters Pregnancy Success in Laboratory Mice.

    Science.gov (United States)

    Bracken, Tara C; Cooper, Caitlin A; Ali, Zil; Truong, Ha; Moore, Julie M

    2017-05-01

    Helicobacter spp. are gram-negative, helically shaped bacteria that cause gastric and enterohepatic infections in mammalian species. Although Helicobacter infection frequently is implicated to interfere with reproductive success, few experimental data support these claims. We therefore retrospectively investigated the effect of Helicobacter infection on murine pregnancy outcome after the identification of endemic Helicobacter infection in an animal research facility. Multiplex conventional PCR analysis was used to characterize Helicobacter infection status in one inbred and 2 transgenic strains of mice in 2 self-contained rooms assigned to the same investigator. Outcomes of timed-mating experiments were compared among Helicobacter spp.-infected and uninfected mice of the same strain; Helicobacter infection was eradicated from the colony through fostering with uninfected dams. Although Helicobacter infection affected fecundity in only one strain of transgenic mouse, the total number of embryos per gravid uterus was significantly reduced in C57BL/6J mice that were infected with a single Helicobacter species, H. typhlonius. Helicobacter infection was also associated with a significant increase in the number of resorbing embryos per uterus and significant decreases in pregnancy-associated weight gain relative to uninfected mice in C57BL6/J mice and one transgenic strain. Helicobacter spp.-infected mice of all tested strains exhibited higher frequency of intrauterine hemorrhaging relative to uninfected mice. These results indicate that naturally-acquired Helicobacter infection not only reduces the productivity of a research animal breeding colony, but also negatively impacts embryo health. Despite these deleterious effects, these data suggest that colonies can be rederived to be Helicobacter-free by Cesarean section and fostering with uninfected dams. This paper provides the first evidence that H. typhlonius infection is sufficient to interfere with reproductive success

  11. Origins of albino and hooded rats: implications from molecular genetic analysis across modern laboratory rat strains.

    Directory of Open Access Journals (Sweden)

    Takashi Kuramoto

    Full Text Available Albino and hooded (or piebald rats are one of the most frequently used laboratory animals for the past 150 years. Despite this fact, the origin of the albino mutation as well as the genetic basis of the hooded phenotype remained unclear. Recently, the albino mutation has been identified as the Arg299His missense mutation in the Tyrosinase gene and the hooded (H locus has been mapped to the ∼460-kb region in which only the Kit gene exists. Here, we surveyed 172 laboratory rat strains for the albino mutation and the hooded (h mutation that we identified by positional cloning approach to investigate possible genetic roots and relationships of albino and hooded rats. All of 117 existing laboratory albino rats shared the same albino missense mutation, indicating they had only one single ancestor. Genetic fine mapping followed by de novo sequencing of BAC inserts covering the H locus revealed that an endogenous retrovirus (ERV element was inserted into the first intron of the Kit gene where the hooded allele maps. A solitary long terminal repeat (LTR was found at the same position to the ERV insertion in another allele of the H locus, which causes the so called Irish (h(i phenotype. The ERV and the solitary LTR insertions were completely associated with the hooded and Irish coat patterns, respectively, across all colored rat strains examined. Interestingly, all 117 albino rat strains shared the ERV insertion without any exception, which strongly suggests that the albino mutation had originally occurred in hooded rats.

  12. A laboratory cage for foster nursing newborn mice

    Directory of Open Access Journals (Sweden)

    S. Marques-de-Araújo

    1999-03-01

    Full Text Available We describe a cage to be used for foster nursing in order to guarantee that original mother's colostrum is not ingested by the newborn mice. A common (30.5 cm x 19.5 cm x 12.0 cm mouse cage was fitted with a wire net tray with a mesh (1 cm x 1 cm, which divides the cage into an upper and a lower compartment. Mice born to females placed in the upper compartment pass through the mesh and fall into the lower compartment, where another lactating female with one or two of its own pups are. Of a total of 28 newborn mice of C3H/He and Swiss strains, 23 were successfully fostered. Important observations are presented to show that this is a valuable alternative for foster studies without great suffering on the part of the female.

  13. Chikungunya virus transmission between Aedes albopictus and laboratory mice.

    Science.gov (United States)

    Hugo, Leon E; Prow, Natalie A; Tang, Bing; Devine, Greg; Suhrbier, Andreas

    2016-10-19

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus associated with epidemics of acute and chronic arthritic disease in humans. Aedes albopictus has emerged as an important new natural vector for CHIKV transmission; however, mouse models for studying transmission have not been developed. Aedes albopictus mosquitoes were infected with CHIKV via membrane feeding and by using infected adult wild-type C57BL/6 mice. Paraffin sections of infected mosquitoes were analysed by immunofluorescent antibody staining using an anti-CHIKV antibody. CHIKV-infected mosquitoes were used to infect adult C57BL/6 and interferon response factor 3 and 7 deficient (IRF3/7(-/-)) mice. Feeding mosquitoes on blood meals with CHIKV titres > 5 log10CCID50/ml, either by membrane feeding or feeding on infected mice, resulted in  ≥ 50 % of mosquitoes becoming infected. However, CHIKV titres in blood meals  ≥ 7 log10CCID50/ml were required before salivary glands showed significant levels of immunofluorescent staining with an anti-CHIKV antibody. Mosquitoes fed on blood meals of 7.5 (but not 5.9) log10CCID50/ml were able efficiently to transmit virus to adult C57BL/6 and IRF3/7(-/-) mice, with the latter mice showing overt signs of arthritis post-infection. The results provide a simple in vivo model for studying transmission of CHIKV from mosquitoes to mammals and also argue against a resistance barrier to CHIKV infection in adult mice.

  14. Assessment of the use of two commercially available environmental enrichments by laboratory mice by preference testing.

    NARCIS (Netherlands)

    Loo, P.L. van; Blom, H.J.; Meijer, M.K.; Baumans, V.

    2005-01-01

    In the field of biomedical research, the demand for standardization of environmental enrichment for laboratory animals is growing. For laboratory mice, a wide variety of environmental enrichment items are commercially available. Most of these comply with the demands for standardization, hygiene and

  15. Antinociceptive effects of voluntarily ingested buprenorphine in the hot-plate test in laboratory rats.

    Science.gov (United States)

    Hestehave, Sara; Munro, Gordon; Pedersen, Tina Brønnum; Abelson, Klas S P

    2016-09-27

    Researchers performing experiments on animals should always strive towards the refinement of experiments, minimization of stress and provision of better animal welfare. An adequate analgesic strategy is important to improve post-operative recovery and welfare in laboratory rats and mice. In addition, it is desirable to provide post-operative analgesia using methods that are minimally invasive and stressful. This study investigated the antinociceptive effects of orally administered buprenorphine ingested in Nutella® in comparison with subcutaneous buprenorphine administration. By exposing the animal to a thermal stimulus using a hot plate, significant antinociceptive effects of voluntarily ingested buprenorphine administered in Nutella® were demonstrated. This was evident at doses of 1.0 mg/kg 60 and 120 min post administration (P Nutella® in a 10-fold higher dose, as well as approximately 60 min earlier, than with the more commonly employed subcutaneous route of administration.

  16. C-peptide responses alter meal challenge in mice transplanted with microencapsulated rat islets

    NARCIS (Netherlands)

    Tatarkiewicz, K; Garcia, M; Omer, A; Weir, GC; De Vos, P

    2001-01-01

    Aims/hypothesis. This study aimed to assess a response of microencapsulated rat islets to a meal challenge after being transplanted intraperitoneally into diabetic mice. Methods. Microencapsulated rat: islets or control naked syngeneic mouse islets were transplanted intraperitoneally into mice with

  17. Two of a Kind or a Full House? Reproductive Suppression and Alloparenting in Laboratory Mice

    Science.gov (United States)

    Garner, Joseph P.; Gaskill, Brianna N.

    2016-01-01

    Alloparenting, a behavior in which individuals other than the actual parents act in a parental role, is seen in many mammals, including house mice. In wild house mice, alloparental care is only seen when familiar sibling females simultaneously immigrate to a male’s territory, so in the laboratory, when a pair of unfamiliar female wild mice are mated with a male, alloparenting does not occur because one female will typically be reproductively suppressed. In contrast, laboratory mice are assumed to alloparent regardless of familiarity or relatedness and are therefore routinely trio bred to increase productivity. Empirical evidence supporting the presence of alloparental care in laboratory mice is lacking. Albino and pigmented inbred mice of the strain C57BL/6NCrl (B6) and outbred mice of the stock Crl:CF1 (CF1) were used to investigate alloparenting in laboratory mice since by mating pigmented and albino females with albino males of the same stock or strain, maternal parentage was easily determined. We housed pairs (M:F) or trios (M:2F) of mice in individually ventilated cages containing nesting material and followed reproductive performance for 16 weeks. Females in trios were tested to determine dominance at the start of the experiment, and again 5 days after the birth of a litter to determine if a female’s dominance shifted with the birth of pups. Results showed a significant and expected difference in number of offspring produced by B6 and CF1 (p infanticide was seen in any cages, so the mechanism of reproductive suppression in trio matings may occur before birth. PMID:27148872

  18. Natural infection of murine norovirus in conventional and specific pathogen-free (SPF laboratory mice

    Directory of Open Access Journals (Sweden)

    Takeo eOhsugi

    2013-01-01

    Full Text Available Noroviruses cause most cases of acute viral gastroenteritis worldwide. The lack of a cell culture infection model for human norovirus necessitates the use of molecular methods and/or viral surrogate models amenable to cell culture to predict norovirus inactivation. Murine norovirus (MNV may be used to construct a small animal model for studying the biology and pathogenesis of noroviruses because MNV is the only norovirus that replicates in cell culture and a small animal model. However, recent studies have shown that natural MNV infection is widespread in laboratory mouse colonies. We investigated MNV infection in both conventional and specific pathogen-free (SPF genetically modified mice from Japan and the US, and commercial mice from several animal breeders in Japan, using serological and molecular techniques. MNV antibodies were detected in 67.3% of conventional mice and 39.1% of SPF mice from Japan and 62.5% of conventional mice from the US. MNV antibodies were also found in 20% of commercial SPF C57BL/6 mice from one of three breeders. Partial gene amplification of fecal isolates from infected animals showed that the isolates were homologous to reported MNV sequences. These results suggest that both conventional and SPF laboratory mice, including commercial mice, are widely infected with MNV, which might require considerable attention as an animal model of human disease.

  19. Environmental enrichment for laboratory mice: preferences and consequences

    NARCIS (Netherlands)

    Weerd, Heleen Ariane van de

    2001-01-01

    Current laboratory housing systems have mainly been developed on the basis of ergonomic and economic factors. These systems provide adequate, basic physiological requirements of animals, but only marginally fulfil other needs, such as the performance of natural behaviour or social interactions. M

  20. Jet fuel kerosene is not immunosuppressive in mice or rats following inhalation for 28 days.

    Science.gov (United States)

    White, Kimber L; DeLorme, Michael P; Beatty, Patrick W; Smith, Matthew J; Peachee, Vanessa L

    2013-01-01

    Previous reports indicated that inhalation of JP-8 aviation turbine fuel is immunosuppressive. However, in some of those studies, the exposure concentrations were underestimated, and percent of test article as vapor or aerosol was not determined. Furthermore, it is unknown whether the observed effects are attributable to the base hydrocarbon fuel (jet fuel kerosene) or to the various fuel additives in jet fuels. The present studies were conducted, in compliance with Good Laboratory Practice (GLP) regulations, to evaluate the effects of jet fuel kerosene on the immune system, in conjunction with an accurate, quantitative characterization of the aerosol and vapor exposure concentrations. Two female rodent species (B6C3F1 mice and Crl:CD rats) were exposed by nose-only inhalation to jet fuel kerosene at targeted concentrations of 0, 500, 1000, or 2000 mg/m(3) for 6 h daily for 28 d. Humoral, cell-mediated, and innate immune functions were subsequently evaluated. No marked effects were observed in either species on body weights, spleen or thymus weights, the T-dependent antibody-forming cell response (plaque assay), or the delayed-type hypersensitivity (DTH) response. With a few exceptions, spleen cell numbers and phenotypes were also unaffected. Natural killer (NK) cell activity in mice was unaffected, while the NK assessment in rats was not usable due to an unusually low response in all groups. These studies demonstrate that inhalation of jet fuel kerosene for 28 d at levels up to 2000 mg/m(3) did not adversely affect the functional immune responses of female mice and rats.

  1. Two of a Kind or a Full House? Reproductive Suppression and Alloparenting in Laboratory Mice.

    Directory of Open Access Journals (Sweden)

    Joseph P Garner

    Full Text Available Alloparenting, a behavior in which individuals other than the actual parents act in a parental role, is seen in many mammals, including house mice. In wild house mice, alloparental care is only seen when familiar sibling females simultaneously immigrate to a male's territory, so in the laboratory, when a pair of unfamiliar female wild mice are mated with a male, alloparenting does not occur because one female will typically be reproductively suppressed. In contrast, laboratory mice are assumed to alloparent regardless of familiarity or relatedness and are therefore routinely trio bred to increase productivity. Empirical evidence supporting the presence of alloparental care in laboratory mice is lacking. Albino and pigmented inbred mice of the strain C57BL/6NCrl (B6 and outbred mice of the stock Crl:CF1 (CF1 were used to investigate alloparenting in laboratory mice since by mating pigmented and albino females with albino males of the same stock or strain, maternal parentage was easily determined. We housed pairs (M:F or trios (M:2F of mice in individually ventilated cages containing nesting material and followed reproductive performance for 16 weeks. Females in trios were tested to determine dominance at the start of the experiment, and again 5 days after the birth of a litter to determine if a female's dominance shifted with the birth of pups. Results showed a significant and expected difference in number of offspring produced by B6 and CF1 (p < 0.0001. Pigmented mice nursed and nested with albino pups and vice-versa, confirming empirical observations from many that group nesting and alloparenting occurs in unrelated laboratory mice. When overall production of both individual mice and cages was examined, reproductive suppression was seen in trio cages. Dominance testing with the tube test did not correlate female reproduction with female dominance in a female-female dyad. Due to the reproductive suppression noted in trios, on a per-mouse basis

  2. Circadian rhythm of outside-nest activity in wild (WWCPS, albino and pigmented laboratory rats.

    Directory of Open Access Journals (Sweden)

    Rafał Stryjek

    Full Text Available The domestication process of the laboratory rat has been going on for several hundred generations in stable environmental conditions, which may have affected their physiological and behavioural functions, including their circadian system. Rats tested in our ethological experiments were laboratory-bred wild Norway rats (WWCPS, two strains of pigmented laboratory rats (Brown Norway and Long Evans, and two strains of albino rats (Sprague-Dawley and Wistar. Rats were placed in purpose-built enclosures and their cycle of activity (time spent actively outside the nest has been studied for one week in standard light conditions and for the next one in round-the-clock darkness. The analysis of circadian pattern of outside-nest activity revealed differences between wild, pigmented laboratory, and albino laboratory strains. During daytime, albino rats showed lower activity than pigmented rats, greater decrease in activity when the light was turned on and greater increase in activity when the light was switched off, than pigmented rats. Moreover albino rats presented higher activity during the night than wild rats. The magnitude of the change in activity between daytime and nighttime was also more pronounced in albino rats. Additionaly, they slept outside the nest more often during the night than during the day. These results can be interpreted in accordance with the proposition that intense light is an aversive stimulus for albino rats, due to lack of pigment in their iris and choroid, which reduces their ability to adapt to light. Pigmented laboratory rats were more active during lights on, not only in comparison to the albino, but also to the wild rats. Since the difference seems to be independent of light intensity, it is likely to be a result of the domestication process. Cosinor analysis revealed a high rhythmicity of circadian cycles in all groups.

  3. A tracking system for laboratory mice to support medical researchers in behavioral analysis.

    Science.gov (United States)

    Macrì, S; Mainetti, L; Patrono, L; Pieretti, S; Secco, A; Sergi, I

    2015-08-01

    The behavioral analysis of laboratory mice plays a key role in several medical and scientific research areas, such as biology, toxicology, pharmacology, and so on. Important information on mice behavior and their reaction to a particular stimulus is deduced from a careful analysis of their movements. Moreover, behavioral analysis of genetically modified mice allows obtaining important information about particular genes, phenotypes or drug effects. The techniques commonly adopted to support such analysis have many limitations, which make the related systems particularly ineffective. Currently, the engineering community is working to explore innovative identification and sensing technologies to develop new tracking systems able to guarantee benefits to animals' behavior analysis. This work presents a tracking solution based on passive Radio Frequency Identification Technology (RFID) in Ultra High Frequency (UHF) band. Much emphasis is given to the software component of the system, based on a Web-oriented solution, able to process the raw tracking data coming from a hardware system, and offer 2D and 3D tracking information as well as reports and dashboards about mice behavior. The system has been widely tested using laboratory mice and compared with an automated video-tracking software (i.e., EthoVision). The obtained results have demonstrated the effectiveness and reliability of the proposed solution, which is able to correctly detect the events occurring in the animals' cage, and to offer a complete and user-friendly tool to support researchers in behavioral analysis of laboratory mice.

  4. Development of animal model for Chandipura virus in laboratory mice

    Institute of Scientific and Technical Information of China (English)

    Raut; CG; Jadi; RS; Chinchwale; AS; Daware; MM

    2005-01-01

    In recent years there was a outbreak of Chandipura virus(CHPV)in Sothern part of India causing encephalitis and acutedeathin children of age group of2.5months to15years withthe mortality rate of55.6%.As this disease is of acutedeath nature in humans no data available on pathogenesis.To understandthe pathogenesis of the disease caused by CHPV,experimental infection in laboratory swiss albino micewas conducted.Animals of age upto one weekfound highlysusceptible to all the routes of inoculation.For further stu...

  5. Trypanosoma (Megatrypanum) lainsoni n. sp. from Mesomys hispidus (Rodentia: Echimyidae) in Brazil: trypomastigotes described from experimentally infected laboratory mice.

    Science.gov (United States)

    Naiff, Roberto Daibes; Barrett, Toby Vincent

    2013-01-01

    We report the detection, isolation and description of Trypanosoma (Megatrypanum) lainsoni n. sp. from a caviomorph rodent, Mesomys hispidus (Rodentia: Echimyidae), obtained in the Rio Negro region of the state of Amazonas, in northern Brazil. Laboratory-bred white mice (Mus musculus) and rats (Rattus rattus) were inoculated with large numbers of culture forms by intraperitoneal route, and trypomastigotes appeared in their blood 3-8 days post-inoculation. One single epimastigote was also found in Mus musculus. Similar attempts to infect Rattus norvegicus, hamsters (Mesocricetus auratus), the opossum Didelphis marsupialis, the anteater Tamandua tetradactyla and triatomine bugs were unsuccessful, following six months of observations and microscopic examinations of blood films and blood cultures. As we have found no previous record of a Trypanosoma (Megatrypanum) species naturally infecting a member of the family Echimyidae, or any other caviomorph rodent, we conclude that this is the first time such an infection has been reported. The new species is unusual in the subgenus for its infectivity to laboratory mice.

  6. Bioavailability of copper bound to dietary fiber in mice and rats

    Energy Technology Data Exchange (ETDEWEB)

    Rockway, S.W.; Brannon, P.M.; Weber, C.W.

    The bioavailability of copper (Cu) was compared in mice or rats fed diets containing wheat bran-bound Cu and adequate Cu (unbound) or deficient Cu with cellulose or wheat bran. Cardiac and hepatic Cu content were comparable in mice fed bran-bound or adequate Cu and greater than mice fed deficient Cu. Cardiac Cu content was comparable in rats fed bran-bound Cu and adequate Cu and greater than rats fed deficient Cu. Hepatic Cu content, however, was less in rats fed bran-bound Cu than adequate Cu and greater in both than deficient Cu. Both rats and mice utilized dietary Cu bound to wheat bran, suggesting that mineral-fiber interactions may not decrease bioavailability when dietary mineral is adequate. Tissue Cu content in Cu-deficiency was lower in animals fed wheat bran compared to cellulose, suggesting that the type of fiber may exacerbate effects of mineral deficiency.

  7. Muscular Basis of Whisker Torsion in Mice and Rats.

    Science.gov (United States)

    Haidarliu, Sebastian; Bagdasarian, Knarik; Shinde, Namrata; Ahissar, Ehud

    2017-09-01

    Whisking mammals move their whiskers in the rostrocaudal and dorsoventral directions with simultaneous rolling about their long axes (torsion). Whereas muscular control of the first two types of whisker movement was already established, the anatomic muscular substrate of the whisker torsion remains unclear. Specifically, it was not clear whether torsion is induced by asymmetrical operation of known muscles or by other largely unknown muscles. Here, we report that mystacial pads of newborn and adult rats and mice contain oblique intrinsic muscles (OMs) that connect diagonally adjacent vibrissa follicles. Each of the OMs is supplied by a cluster of motor end plates. In rows A and B, OMs connect the ventral part of the rostral follicle with the dorsal part of the caudal follicle. In rows C-E, in contrast, OMs connect the dorsal part of the rostral follicle to the ventral part of the caudal follicle. This inverse architecture is consistent with previous behavioral observations [Knutsen et al.: Neuron 59 (2008) 35-42]. In newborn mice, torsion occurred in irregular single twitches. In adult anesthetized rats, microelectrode mediated electrical stimulation of an individual OM that is coupled with two adjacent whiskers was sufficient to induce a unidirectional torsion of both whiskers. Torsional movement was associated with protracting movement, indicating that in the vibrissal system, like in the ocular system, torsional movement is mechanically coupled to horizontal and vertical movements. This study shows that torsional whisker rotation is mediated by specific OMs whose morphology and attachment sites determine rotation direction and mechanical coupling, and motor innervation determines rotation dynamics. Anat Rec, 300:1643-1653, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Identification of an astrovirus commonly infecting laboratory mice in the US and Japan.

    Science.gov (United States)

    Ng, Terry Fei Fan; Kondov, Nikola O; Hayashimoto, Nobuhito; Uchida, Ritsuki; Cha, Yunhee; Beyer, Ashley I; Wong, Walt; Pesavento, Patricia A; Suemizu, Hiroshi; Muench, Marcus O; Delwart, Eric

    2013-01-01

    Mice (Mus musculus) are the most commonly used laboratory animals. Viral metagenomics on tissues of immunodeficient mice revealed sequences of a novel mammalian astrovirus. Using PCR, we screened mice from 4 breeders, 4 pharmaceutical companies, 14 research institutes and 30 universities in the US and Japan. Mice from one US breeder tested positive while none from Japanese breeders were positive for MuAstV. Mice in over half of the universities (19/30), institutes (7/14) and pharmaceutical animal facilities (2/4) investigated revealed the presence of MuAstV. Nine mice strains tested positive including both immunodeficient strains (NSG, NOD-SCID, NSG-3GS, C57BL6-Timp-3 (-/-), and uPA-NOG) and immunocompetent strains (B6J, ICR, Bash2, BALB/c). Our data indicates that MuAstV has a wide geographical, institutional and host strain distribution. Comparison of the MuAstV RdRp sequences showed numerous mutations indicating ongoing viral divergence in different facilities. This study demonstrates the need for metagenomic screening of laboratory animals to identify adventitious infections that may affect experimental outcomes.

  9. Identification of an astrovirus commonly infecting laboratory mice in the US and Japan.

    Directory of Open Access Journals (Sweden)

    Terry Fei Fan Ng

    Full Text Available Mice (Mus musculus are the most commonly used laboratory animals. Viral metagenomics on tissues of immunodeficient mice revealed sequences of a novel mammalian astrovirus. Using PCR, we screened mice from 4 breeders, 4 pharmaceutical companies, 14 research institutes and 30 universities in the US and Japan. Mice from one US breeder tested positive while none from Japanese breeders were positive for MuAstV. Mice in over half of the universities (19/30, institutes (7/14 and pharmaceutical animal facilities (2/4 investigated revealed the presence of MuAstV. Nine mice strains tested positive including both immunodeficient strains (NSG, NOD-SCID, NSG-3GS, C57BL6-Timp-3 (-/-, and uPA-NOG and immunocompetent strains (B6J, ICR, Bash2, BALB/c. Our data indicates that MuAstV has a wide geographical, institutional and host strain distribution. Comparison of the MuAstV RdRp sequences showed numerous mutations indicating ongoing viral divergence in different facilities. This study demonstrates the need for metagenomic screening of laboratory animals to identify adventitious infections that may affect experimental outcomes.

  10. Genetically modified laboratory mice with sebaceous glands abnormalities.

    Science.gov (United States)

    Ehrmann, Carmen; Schneider, Marlon R

    2016-12-01

    Sebaceous glands (SG) are exocrine glands that release their product by holocrine secretion, meaning that the whole cell becomes a secretion following disruption of the membrane. SG may be found in association with a hair follicle, forming the pilosebaceous unit, or as modified SG at different body sites such as the eyelids (Meibomian glands) or the preputial glands. Depending on their location, SG fulfill a number of functions, including protection of the skin and fur, thermoregulation, formation of the tear lipid film, and pheromone-based communication. Accordingly, SG abnormalities are associated with several diseases such as acne, cicatricial alopecia, and dry eye disease. An increasing number of genetically modified laboratory mouse lines develop SG abnormalities, and their study may provide important clues regarding the molecular pathways regulating SG development, physiology, and pathology. Here, we summarize in tabulated form the available mouse lines with SG abnormalities and, focusing on selected examples, discuss the insights they provide into SG biology and pathology. We hope this survey will become a helpful information source for researchers with a primary interest in SG but also as for researchers from unrelated fields that are unexpectedly confronted with a SG phenotype in newly generated mouse lines.

  11. Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories.

    Science.gov (United States)

    Kim, Kyuri; Chini, Naseem; Fairchild, David G; Engle, Steven K; Reagan, William J; Summers, Sandra D; Mirsalis, Jon C

    2016-12-01

    There is a great need for improved diagnostic and prognostic accuracy of potential cardiac toxicity in drug development. This study reports the evaluation of several commercially available biomarker kits by 3 institutions (SRI, Eli Lilly, and Pfizer) for the discrimination between myocardial degeneration/necrosis and cardiac hypertrophy as well as the assessment of the interlaboratory and interplatform variation in results. Serum concentrations of natriuretic peptides (N-terminal pro-atrial natriuretic peptide [NT-proANP] and N-terminal pro-brain natriuretic peptide [NT-proBNP]), cardiac and skeletal troponins (cTnI, cTnT, and sTnI), myosin light chain 3 (Myl3), and fatty acid binding protein 3 (FABP3) were assessed in rats treated with minoxidil (MNX) and isoproterenol (ISO). MNX caused increased heart-to-body weight ratios and prominent elevations in NT-proANP and NT-proBNP concentrations detected at 24-hr postdose without elevation in troponins, Myl3, or FABP3 and with no abnormal histopathological findings. ISO caused ventricular leukocyte infiltration, myocyte fibrosis, and necrosis with increased concentrations of the natriuretic peptides, cardiac troponins, and Myl3. These results reinforce the advantages of a multimarker strategy in elucidating the underlying cause of cardiac insult and detecting myocardial tissue damage at 24-hr posttreatment. The interlaboratory and interplatform comparison analyses also showed that the data obtained from different laboratories and platforms are highly correlated and reproducible, making these biomarkers widely applicable in preclinical studies.

  12. Analysis of Radiation Impact on White Mice through Radiation Dose Mapping in Medical Physics Laboratory

    Science.gov (United States)

    Sutikno, Madnasri; Susilo; Arya Wijayanti, Riza

    2016-08-01

    A study about X-ray radiation impact on the white mice through radiation dose mapping in Medical Physic Laboratory is already done. The purpose of this research is to determine the minimum distance of radiologist to X-ray instrument through treatment on the white mice. The radiation exposure doses are measured on the some points in the distance from radiation source between 30 cm up to 80 with interval of 30 cm. The impact of radiation exposure on the white mice and the effects of radiation measurement in different directions are investigated. It is founded that minimum distance of radiation worker to radiation source is 180 cm and X-ray has decreased leukocyte number and haemoglobin and has increased thrombocyte number in the blood of white mice.

  13. Multisite carcinogenicity and respiratory toxicity of inhaled 1-bromopropane in rats and mice.

    Science.gov (United States)

    Morgan, Daniel L; Nyska, Abraham; Harbo, Sam Jens; Grumbein, Sondra L; Dill, Jeffrey A; Roycroft, Joseph H; Kissling, Grace E; Cesta, Mark F

    2011-10-01

    Two-year 1-bromopropane (1-BP) inhalation studies were conducted because of the potential for widespread exposure, the lack of chronic toxicity and carcinogenicity data, and the known carcinogenicity of structurally related compounds. Male and female F344/N rats and B6C3F1/N mice were exposed by inhalation to 0, 62.5 (mice only), 125, 250, or 500 (rats only) ppm 1-BP for 6 hr/day, 5 days/week for 105 weeks. Exposure of male and female rats to 1-BP resulted in significantly increased incidences of adenomas of the large intestine and skin neoplasms. In male rats, the incidence of malignant mesothelioma of the epididymis was statistically significantly increased at 500 ppm, but the biological significance of this common lesion is unclear. Incidences of pancreatic islet adenoma in male rats were significantly increased at all concentrations relative to concurrent controls but were within the historical control range for inhalation studies. There was no evidence of carcinogenic activity of 1-BP in male B6C3F1 mice; however, significantly increased incidences of alveolar/bronchiolar neoplasms of the lung were present in female mice. Exposure to 1-BP also resulted in increased incidences of nonneoplastic lesions in the nose of rats and mice, the larynx of rats and male mice, the trachea of female rats and male and female mice, and the lungs of mice. Inflammatory lesions with Splendore Hoeppli (S-H) material were present primarily in the nose and skin of exposed male and female rats, indicating that 1-BP caused immunosuppression.

  14. Factors to be considered when defining“SPF” and health monitoring programs in laboratory mice and rats%定义“SPF”级实验大小鼠和制定健康监测方案时需考虑的因素

    Institute of Scientific and Technical Information of China (English)

    周聪颖

    2016-01-01

    The term“specific pathogen free” ( SPF) implies the bioexclusion of a defined list of organisms that can cause disease in a host.Due to many different factors including animal source, vivarium layout, microbiological history, engineering standards, operation practice, and experimental needs, the bioexclusion list tends to be specific for many institutions using live animals in biomedical research.As such, the design and implementation of institution-specific health monitoring program can also vary based on needs.By comparison, laboratory animal producers and users in China are subject to GB regulations which have established a national bioexclusion list based on animal health categories, as well as set detailed engineering standards for vivarium operations based on specific animal health profiles.In addition to summarizing the SPF list of major rodent vendors in North America, the purpose of this article is to bring attention to the different factors animal users should take into consideration when evaluating one ’ s own bioexclusion list and designing institution-specific health monitoring program for laboratory mice and rats, in order to assure animal colony health and scientific integrity.%“无特定病原菌( SPF)”名词意味着排除了对宿主致病的特定的病原菌清单。许多机构在使用活体动物开展生物医学研究时,考虑到许多不同的因素,包括动物来源、设施布局、微生物学背景、工程技术标准、运行实践和试验需要,倾向于制定机构层面的生物排除清单。同样地,机构层面的健康监测方案的设计和实施也根据需要有所不同。相比之下,中国的实验动物生产者和使用者受制于国标,国标中根据动物健康分类建立了国家层面生物排除清单,同时也规定了特定的动物健康等级对应的详细的动物房工程设计标准。此外,本文还汇总了北美主要的啮齿类供应商的SPF

  15. Carcinogenicity of glycidol in F344 rats and B6C3F1 mice.

    Science.gov (United States)

    Irwin, R D; Eustis, S L; Stefanski, S; Haseman, J K

    1996-01-01

    Glycidol, a simple aliphatic epoxide, was administered by gavage in water to groups of male and female F344/N rats and B6C3F1 mice. Rats received 0, 37.5 or 75 mg kg-1 and mice received 0, 25 or 50 mg kg-1 daily, 5 days per week for 2 years. Exposure to glycidol was associated with dose-related increases in the incidences of neoplasms in numerous tissues in both rats and mice. Survival of rats that received glycidol was markedly reduced compared to the control because of the early induction of neoplastic disease. In male rats, mesothelioma arising in the tunica vaginalis and frequently metastasizing to the peritoneum were considered the major cause of early death. Early deaths in female rats were associated with mammary gland neoplasms. Survival of female mice that received 50 mg kg-1 was lower than the control after week 101 due primarily to euthanasia of moribund animals with mammary gland neoplasms. Survival of male mice and female mice that received 25 mg kg-1 was comparable to the control. In mice, exposure to glycidol was associated with increased incidences of neoplasms of the harderian gland in males and females, the forestomach in males and the mammary gland in females.

  16. Chronic toxicity and carcinogenicity study of isomalt in rats and mice.

    Science.gov (United States)

    Smits-Van Prooije, A E; De Groot, A P; Dreef-Van der Meulen, H C; Sinkeldam, E J

    1990-04-01

    The chronic toxicity and possible carcinogenicity of the sugar replacer isomalt was studied in Wistar rats and Swiss mice. Groups of 50 animals of each sex were fed 0, 2.5, 5 or 10% isomalt in the diet for nearly 2.5 yr (rats) or 2 yr (mice). Control groups received either basal diet with 10% maize starch or basal diet with 10% sucrose. Additional groups of ten rats/sex were fed the same diets and were killed after 1 yr. Isomalt and sucrose were included in the diet at the expense of maize starch. Administration of isomalt was started, in rats, in utero, and in mice, at weaning age. Feeding isomalt did not affect the appearance or behaviour of rats or mice, nor did it cause diarrhoea. Mortality rate was unaffected. Body weights of rats and mice fed 10% isomalt were generally slightly lower than those of controls. Periodic examinations of rats for haematological criteria, clinical chemistry of the blood, urine composition and kidney function did not reveal any changes of toxicological significance. Periodic haematological examinations of mice were likewise negative. Caecal enlargement was observed in rats and mice of the high-dose group, but the microscopic structure of the caecal wall was unaffected. An increased number of treated male and female rats showed hyperplasia of the urothelium in the renal pelvis accompanied by mineralization, whereas the number of females showing corticomedullary mineralization was decreased in the treated groups. The incidence, type or location of neoplasia provided no evidence of a carcinogenic potential of isomalt. Feeding 10% sucrose did not induce significant differences compared with the controls fed 10% maize starch, whereas isomalt at levels of up to 10% produced some of the changes that are common to rats fed high levels of poorly digestible carbohydrates.

  17. Hematologic assessment in pet rats, mice, hamsters, and gerbils: blood sample collection and blood cell identification.

    Science.gov (United States)

    Lindstrom, Nicole M; Moore, David M; Zimmerman, Kurt; Smith, Stephen A

    2015-01-01

    Hamsters, gerbils, rats, and mice are presented to veterinary clinics and hospitals for prophylactic care and treatment of clinical signs of disease. Physical examination, history, and husbandry practice information can be supplemented greatly by assessment of hematologic parameters. As a resource for veterinarians and their technicians, this article describes the methods for collection of blood, identification of blood cells, and interpretation of the hemogram in mice, rats, gerbils, and hamsters.

  18. Genome Sequencing Reveals Loci under Artificial Selection that Underlie Disease Phenotypes in the Laboratory Rat

    NARCIS (Netherlands)

    Atanur, Santosh S.; Diaz, Ana Garcia; Maratou, Klio; Sarkis, Allison; Rotival, Maxime; Game, Laurence; Tschannen, Michael R.; Kaisaki, Pamela J.; Otto, Georg W.; Ma, Man Chun John; Keane, Thomas M.; Hummel, Oliver; Saar, Kathrin; Chen, Wei; Guryev, Victor; Gopalakrishnan, Kathirvel; Garrett, Michael R.; Joe, Bina; Citterio, Lorena; Bianchi, Giuseppe; McBride, Martin; Dominiczak, Anna; Adams, David J.; Serikawa, Tadao; Flicek, Paul; Cuppen, Edwin; Hubner, Norbert; Petretto, Enrico; Gauguier, Dominique; Kwitek, Anne; Jacob, Howard; Aitman, Timothy J.

    2013-01-01

    Large numbers of inbred laboratory rat strains have been developed for a range of complex disease phenotypes. To gain insights into the evolutionary pressures underlying selection for these phenotypes, we sequenced the genomes of 27 rat strains, including 11 models of hypertension, diabetes, and ins

  19. Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat

    NARCIS (Netherlands)

    Atanur, S.S.; Diaz, A.G.; Maratou, K.; Sarkis, A.; Rotival, M.; Game, L.; Tschannen, M.R.; Kaisaki, P.J.; Otto, G.W.; Ma, M.C.; Keane, T.M.; Hummel, O.; Saar, K.; Chen, W.; Guryev, V.; Gopalakrishnan, K.; Garrett, M.R.; Joe, B.; Citterio, L.; Bianchi, G.; McBride, M.; Dominiczak, A.; Adams, D.J.; Serikawa, T.; Flicek, P.; Cuppen, E.; Hubner, N.; Petretto, E.; Gauguier, D.; Kwitek, A.; Jacob, H.; Aitman, T.J.

    2013-01-01

    Large numbers of inbred laboratory rat strains have been developed for a range of complex disease phenotypes. To gain insights into the evolutionary pressures underlying selection for these phenotypes, we sequenced the genomes of 27 rat strains, including 11 models of hypertension, diabetes, and ins

  20. Dietary subacute toxicity of ethylene thiourea in the laboratory rat

    Energy Technology Data Exchange (ETDEWEB)

    Freudenthal, R.I.; Kerchner, G.; Persing, R.; Baron, R.L.

    1978-09-01

    Ethylene thiourea (ETU) was fed to groups of rats at 0, 1, 5, 125 or 625 ppM for up to 90 days. Other groups of rats received either propylthiouracil (PTU; 125 ppM) or amitrole (50 ppM) in their diets as positive controls. Only those rats which received ETU at 125 or 625 ppM and those ingesting PTU or amitrole demonstrated a measurable toxic response. This toxicity was reflected as an alteration in thyroid function and a significant change in thyroid morphology. Ingestion of 625 ppM ETU or 125 ppM PTU resulted in very substantial decrease in serum triiodothyronine (T-3) and thyroxine (T-4). Marked increases in serum thyroid stimulating hormone (TSH) levels were found in the 625 and 125 ppM ETU rats, the 125 PTU rats, and the rats receiving amitrole, each time this hormone was measured. Rats which ingested 625 ppM ETU also exhibited a decrease in iodide uptake by the thyroid. While a statistically significant increase in serum T-4 and degree of thyroid hyperplasia was observed for rats ingesting 25 ppM ETU for 60 days, normal thyroid hormone levels and thyroid morphology was found in rats on 25 ppM ETU for either 30 or 90 days. Based on diochemical and microscopic changes examined, the no-effect level for dietary ETU in this 90-day study is considered to be 25 ppM.

  1. Enantioselective metabolism of hydroxychloroquine employing rats and mice hepatic microsomes

    Directory of Open Access Journals (Sweden)

    Carmem Dickow Cardoso

    2009-12-01

    Full Text Available Hydroxychloroquine (HCQ is an important chiral drug used, mainly, in the treatment of rheumatoid arthritis, systemic lupus erythematosus and malaria, and whose pharmacokinetic and pharmacodynamic properties look to be stereoselective. Respecting the pharmacokinetic properties, some previous studies indicate that the stereoselectivity could express itself in the processes of metabolism, distribution and excretion and that the stereoselective metabolism looks to be a function of the studied species. So, the in vitro metabolism of HCQ was investigated using hepatic microsomes of rats and mice. The microsomal fraction of livers of Wistar rats and Balb-C mice was separated by ultracentrifugation and 500 μL were incubated for 180 minutes with 10 μL of racemic HCQ 1000 μg mL-1. Two stereospecific analytical methods, high performance liquid chromatography (HPLC and capillary electrophoresis (CE, were used to separate and quantify the formed metabolites. It was verified that the main formed metabolite is the (--(R-desethyl hydroxychloroquine for both animal species.A hidroxicloroquina (HCQ é um importante fármaco quiral usado, principalmente, no tratamento de artrite reumatóide, lupus eritematoso sistêmico e malária e cujas propriedades farmacocinéticas e farmacodinâmicas parecem ser estereosseletivas. Em relação às propriedades farmacocinéticas, alguns estudos prévios indicam que a estereosseletividade pode se expressar nos processos de metabolismo, distribuição e excreção e que o metabolismo estereosseletivo parece ser função da espécie estudada. Sendo assim, o metabolismo in vitro da HCQ foi investigado usando microssomas de fígado de ratos e de camundongos. A fração microssômica de fígados de ratos Wistar e de camundongos Balb-C foi isolada por ultracentrifugação e 500 μL foram incubados por 180 minutos com 10 μL de HCQ racêmica 1000 μg mL-1. Dois métodos analíticos estereoespecíficos, por cromatografia líquida de

  2. A chronic inhalation toxicity/oncogenicity study of methylethylketoxime in rats and mice.

    Science.gov (United States)

    Newton, P E; Wooding, W L; Bolte, H F; Derelanko, M J; Hardisty, J F; Rinehart, W E

    2001-12-01

    To evaluate the oncogenic potential of methylethylketoxime (MEKO), CD-1 mice (50/sex/group) and F-344 rats (50/sex/group) were coexposed 6 h/day, 5 days/wk for 18 mo (mice) or 26 mo (rats) via whole-body inhalation exposures to target vapor concentrations of 0, 15, 75, and 375 ppm (actual concentrations of 0, 15 +/- 1, 75 +/- 2, or 374 +/- 10 ppm). Satellite groups of rats and mice (10/sex/group/interval) were exposed for 12 mo (mice) and 3, 12, or 18 mo (rats) to evaluate chronic toxicity. Methyl ethyl ketone (MEK), a possible hydrolysis product of MEKO, was present at less than 1%. Treatment-related effects included increased body weight (male rats only), methemoglobin formation, hematology and clinical chemistry changes, increased liver weight, and increased spleen and testes weights (rats only). A high incidence of cataracts and corneal dystrophy occurred in both control and MEKO-exposed rats, with an earlier appearance and slightly higher incidence for these ocular lesions in MEKO-exposed animals compared to controls. Degenerative and reparative changes of the olfactory epithelium in the nasal turbinates, primarily limited to the dorsal meatus, occurred in both rats (75 and 374 ppm) and mice (15, 75, and 374 ppm). In addition, in the mice, liver changes included increased incidences of pigment in reticuloendothelial cells, centilobular hypertrophy, granulomatous inflammation, and a slightly increased incidence of necrosis (75 and 374 ppm). An increase in hepatocellular carcinomas occurred in male mice at 374 ppm. Additional MEKO-related findings in the rat included congestion of the spleen with pigment in reticuloendothelial cells and extramedullary hematopoiesis and a decreased incidence of lymphoreticular mononuclear cell leukemia. Effects observed in the liver of the rats included decreases in the incidence of both peribiliary fibrosis and hyperplasia/proliferation of the biliary duct, an increase of spongiosis hepatis in males, and an increase in the

  3. General parity between trio and pairwise breeding of laboratory mice in static caging.

    Science.gov (United States)

    Kedl, Ross M; Wysocki, Lawrence J; Janssen, William J; Born, Willi K; Rosenbaum, Matthew D; Granowski, Julia; Kench, Jennifer A; Fong, Derek L; Switzer, Lisa A; Cruse, Margaret; Huang, Hua; Jakubzick, Claudia V; Kosmider, Beata; Takeda, Katsuyuki; Stranova, Thomas J; Klumm, Randal C; Delgado, Christine; Tummala, Saigiridhar; De Langhe, Stijn; Cambier, John; Haskins, Katherine; Lenz, Laurel L; Curran-Everett, Douglas

    2014-11-15

    Changes made in the 8th edition of the Guide for the Care and Use of Laboratory Animals included new recommendations for the amount of space for breeding female mice. Adopting the new recommendations required, in essence, the elimination of trio breeding practices for all institutions. Both public opinion and published data did not readily support the new recommendations. In response, the National Jewish Health Institutional Animal Care and Use Committee established a program to directly compare the effects of breeding format on mouse pup survival and growth. Our study showed an overall parity between trio and pairwise breeding formats on the survival and growth of the litters, suggesting that the housing recommendations for breeding female mice as stated in the current Guide for the Care and Use of Laboratory Animals should be reconsidered.

  4. Helicobacter ganmani sp nov., a urease-negative anaerobe isolated from the intestines of laboratory mice

    DEFF Research Database (Denmark)

    Robertson, B.R.; O'Rourke, J.L.; Vandamme, P.

    2001-01-01

    Spiral bacteria were isolated from the intestines of laboratory mice during a study examining the presence of Helicobacter species and other spiral organisms naturally infecting mice maintained at four different animal facilities in Sydney, Australia. One group of 17 isolates, cultured from mice...... from three of the four facilities, were found to be helicobacters but did not fall within any of the 18 currently recognized species. These isolates were unusual in that they only grew anaerobically at 37 degreesC and were incapable of growth under microaerobic conditions. Like Helicobacter rodentium...... and found to be identical to one another. H. rodentium was the most closely related species in terms of 16S rDNA sequence similarity (98.2%). Numerical analysis of whole-cell proteins by SDS-PAGE for nine isolates was carried out with a comparison to all known Helicobacter species, including newly...

  5. Effect of mazindol on dystrophic mice and on growth in young rats.

    Science.gov (United States)

    Coakley, J H; Jackson, M J; Wagenmakers, A J; Ensor, D; Edwards, R H

    1989-01-01

    1. Mazindol, which has been proposed as a therapy for muscular dystrophy because of a suppression of growth hormone release was administered orally (0.1 mg/kg body wt/day) for approximately six weeks to healthy young rats and dystrophic mice. 2. Mazindol had no effect on the dystrophic mice. 3. Mazindol treated rats had reduced wt gain, but this effect was due to appetite suppression not growth hormone inhibition. 4. No effect of mazindol was seen on rat muscle, but there were significant increases in liver, heart and kidney wts compared to controls.

  6. Further evidence of benzene carcinogenicity. Results on Wistar rats and Swiss mice treated by ingestion.

    Science.gov (United States)

    Maltoni, C; Conti, B; Perino, G; Di Maio, V

    1988-01-01

    Wistar rats and Swiss mice were treated by ingestion (stomach tube) with benzene in olive oil at a dose of 500 and 0 mg/kg b.w. once daily, 4-5 days weekly, for 104 weeks (rats) or for 78 weeks (mice). In Wistar rats, benzene caused Zymbal gland carcinomas, carcinomas of the oral cavity, and carcinomas of the nasal cavities, and an increase in the incidence of total malignant tumors. In Swiss mice, benzene produced Zymbal gland carcinomas and dysplasias and an increase in the incidence of mammary carcinomas (in females), lung tumors, and total malignant tumors. These experiments further confirm that benzene is a multipotential carcinogen as was shown before by long-term bioassays performed on Sprague-Dawley rats in the same Experimental Unit.

  7. Carcinogenicity of bisphenol-A in Fischer rats and B6C3F1 mice.

    Science.gov (United States)

    Huff, J

    2001-11-01

    Bisphenol-A (BP-A; 4,4'-isopropylidenediphenol) is a monomer of plastics commonly used in various consumer products, and is used as an intermediate in the manufacture of epoxy, polycarbonate, and polyester-styrene resins. A National Toxicology Program carcinogenesis bioassay of BP-A (>98% pure) was conducted by feeding diets containing 0, 1000, or 2000 ppm BP-A to groups of 50 male and 50 female Fischer (F)344 rats; 0, 1000, or 5000 ppm to groups of 50 male B6C3F1 mice; and 0, 5000, or 10,000 ppm to groups of 50 female B6C3F1 mice for 103 weeks. The mean body weights of the low- and high-dose rats and of female mice and high-dose male mice were lower than those of the controls throughout much of the study. Lower body weight gains in rats were likely caused by reduced food consumption. Survivals were comparable among groups. Regarding neoplasia, leukemias occurred at increased incidences in BP-A-dosed rats of both sexes: male, 13/50 controls vs 12/50 low-dose and 23/50 high-dose (P Toxicology Program concluded that there was no convincing evidence that BP-A was carcinogenic for rats or mice. However, the marginal increases in leukemias in male and female rats, along with increases in the combined incidence of lymphomas and leukemias in male mice, suggest that BP-A may be associated with increased cancers of the hematopoietic system. Increases in interstitial-cell tumors of the testes in rats were also evidence of carcinogenesis, as was the unusual occurrence of mammary gland fibroadenomas in male rats.

  8. Effect of Diet on Metabolism of Laboratory Rats

    Science.gov (United States)

    Harrison, P. C.; Riskowski, G. L.; McKee, J. S.

    1996-01-01

    In previous studies when rats were fed a processed, semipurified, extruded rodent food bar (RFB) developed for space science research, we noted a difference in the appearance of gastrointestinal tissue (GI); therefore the following study evaluated GI characteristics and growth and metabolic rates of rats fed chow (C) or RFB. Two hundred and twenty-four rats (78 g mean body weight) were randomly assigned to 28 cages and provided C or RFB. Each cage was considered the experimental unit and a 95 percent level of significance, indicated by ANOVA, was used for inference. After each 30-, 60-, and 90-day period, eight cages were shifted from the C to RFB diet and housing density was reduced by two rats per cage. The two rats removed from each cage were sacrificed and used for GI evaluation. Metabolic rates of the rats in each cage were determined by indirect calorimetry. No differences in body weight were detected at 0, 30, 60 or 90 days between C and RFB. Heat production (kcal/hr/kg), CO2 production (L/hr/kg) and O2 consumption (L/hr/kg) were different by light:dark and age with no effect of diet. Respiratory quotient was different by age with no effect of light:dark or diet. Rats on the C diet ate less food and drank more water than those on RFB. C rats produced more fecal and waste materials than the RFB. GI lengths increased with age but were less in RFB than C. GI full and empty weights increased with age but weighed less in RFB than C. Gut-associated lymphoid tissue (GALT) numbers increased with age with no effect of diet. No differences in ileum-associated GALT area were detected between C and RFB. Switching C to RFB decreased GI length, GI full and empty weights, with no changes in GALT number or area. We concluded RFB decreased GI mass without affecting metabolic rate or general body growth.

  9. Organization of the main olfactory bulbs of some mammals: musk shrews, moles, hedgehogs, tree shrews, bats, mice, and rats.

    Science.gov (United States)

    Kosaka, Katsuko; Kosaka, Toshio

    2004-04-19

    We immunohistochemically examined the organization of the main olfactory bulbs (MOBs) in seven mammalian species, including moles, hedgehogs, tree shrews, bats, and mice as well as laboratory musk shrews and rats. We focused our investigation on two points: 1) whether nidi, particular spheroidal synaptic regions subjacent to glomeruli, which we previously reported for the laboratory musk shrew MOBs, are also present in other animals and 2) whether the compartmental organization of glomeruli and two types of periglomerular cells we proposed for the rat MOBs are general in other animals. The general laminar pattern was similar among these seven species, but discrete nidi and the nidal layer were recognized only in two insectivores, namely, the mole and laboratory musk shrew. Olfactory marker protein-immunoreactive (OMP-IR) axons extended beyond the limits of the glomerular layer (GL) into the superficial region of the external plexiform layer (EPL) or the nidal layer in the laboratory musk shrew, mole, hedgehog, and tree shrew but not in bat, mouse, and rat. We observed, in nidi and the nidal layer in the mole and laboratory musk shrew MOBs, only a few OMP-IR axons. In the hedgehog, another insectivore, OMP-IR processes extending from the glomeruli were scattered and intermingled with calbindin D28k-IR cells at the border between the GL and the EPL. In the superficial region of the EPL of the tree shrew MOBs, there were a small number of tiny glomerulus-like spheroidal structures where OMP-IR axons protruding from glomeruli were intermingled with dendritic branches of surrounding calbindin D28k-IR cells. Furthermore, we recognized the compartmental organization of glomeruli and two types of periglomerular cells in the MOBs of all of the mammals we examined. These structural features are therefore considered to be common and important organizational principles of the MOBs.

  10. The successive alleys test of anxiety in mice and rats.

    Science.gov (United States)

    Deacon, Robert M J

    2013-06-17

    The plus-maze was derived from the early work of Montgomery. He observed that rats tended to avoid the open arms of a maze, preferring the enclosed ones. Handley, Mithani and File et al. performed the first studies on the plus-maze design we use today, and in 1987 Lister published a design for use with mice. Time spent on, and entries into, the open arms are an index of anxiety; the lower these indices, the more anxious the mouse is. Alternatively, a mouse that spends most of its time in the closed arms is classed as anxious. One of the problems of the plus-maze is that, while time spent on, and entries into, the open arms is a fairly unambiguous measure of anxiety, time in the central area is more difficult to interpret, although time spent here has been classified as "decision making". In many tests central area time is a considerable part of the total test time. Shepherd et al. produced an ingenious design to eliminate the central area, which they called the "zero maze". However, although used by several groups, it has never been as widely adopted as the plus-maze. In the present article I describe a modification of the plus-maze design that not only eliminates the central area but also incorporates elements from other anxiety tests, such as the light-dark box and emergence tests. It is a linear series of four alleys, each having increasing anxiogenic properties. It has given similar results to the plus-maze in general. Although it may not be more sensitive than the plus-maze (more data is needed before a firm conclusion can be reached on this point), it provides a useful confirmation of plus-maze results which would be useful when, for example, only a single example of a mutant mouse was available, as, for example, in ENU-based mutagenesis programs.

  11. Dynamics of testicular germ cell apoptosis in normal mice and transgenic mice overexpressing rat androgen-binding protein

    Directory of Open Access Journals (Sweden)

    Petrusz Peter

    2003-06-01

    Full Text Available Abstract The number and type of testicular germ cells undergoing apoptosis in different age groups of mice (from 7 to 360 days of age was determined and compared in age-matched wild type (WT control and in a transgenic (TG mice homozygous to rat androgen binding protein (ABP using flow cytometry. Flow cytometric quantification revealed that the total number of germ cells undergoing apoptosis did not differ significantly in WT and TG mice up to Day 14. From Day 21 to Day 60, the number of germ cells undergoing apoptosis was consistently higher in TG than in WT mice. Starting from Day 90, the number of germ cells undergoing apoptosis in TG mice was lower than controls until Day 360. In 21–60 days old TG mice, spermatogonia, S-Phase cells, and primary spermatocytes are the cell types undergoing apoptosis at significantly greater numbers than those in WT mice. However, starting from day 60, the total number of spermatids undergoing apoptosis was significantly lower in TG mice than in age-matched WT controls. TdT-mediated dUTP-biotin nick end labeling (TUNEL in testicular sections from TG mice of 21 and 30 days of age confirmed the presence of increased numbers of apoptotic germ cells compared to their age matched controls. These data indicate that the continuous presence of greater than physiological concentrations of ABP in the mouse testis has a biphasic effect on the frequency of apoptosis in germ cells. The initial pre-pubertal increase in testicular germ cell apoptosis may result from direct or indirect actions of ABP and is likely to determine the subsequent life-death balance of germ cell populations in TG mice, whereas the subsequent reduction may result from maturation depletion. A wave of apoptosis during the pre-pubertal period is required for normal spermatogenesis to develop, and our data indicate that this apoptotic wave may be regulated by ABP and/or androgens.

  12. Oxidative Stress Level in the Testes of Mice and Rats during Nickel Intoxication

    Directory of Open Access Journals (Sweden)

    Eugenia Murawska-Ciałowicz

    2012-01-01

    Full Text Available The genotioxic and carcinogenic effect of nickel probably results from its capacity to produce reactive oxygen species (ROS and disturb the redox balance. The aim of the study was to find out if rats lacking spermatic protamine 2 are less susceptible to Ni(II than mice. Consequently, the levels of malondialdehyde + 4 hydroxynonenal (MDA+4HDA − markers of lipid peroxidation, as well as the level of reduced glutathione (GSH were measured within the rat and mouse testes. Our results showed that the levels of lipid peroxidation markers were elevated in testicular homogenates of intoxicated mice without any changes in rats. GSH level was lower in the group of intoxicated mice comparing to the control without statistically significant changes in rats’ homogenates. Moreover, the level of GSH in the testes of intoxicated mice was lower than in rats. On the basis of our results, it appears that Ni(II can initiate oxidative stress in the testes of mice but not of rats and can reduce GSH level. Consequently, the antioxidative defense of the testes is reduced. Ni(II that causes oxidative stress in the testes may also contribute to infertility.

  13. Physiological time structure of the tibialis anterior motor activity during sleep in mice, rats and humans.

    Science.gov (United States)

    Silvani, Alessandro; Lo Martire, Viviana; Salvadè, Agnese; Bastianini, Stefano; Ferri, Raffaele; Berteotti, Chiara; Baracchi, Francesca; Pace, Marta; Bassetti, Claudio L; Zoccoli, Giovanna; Manconi, Mauro

    2015-12-01

    The validation of rodent models for restless legs syndrome (Willis-Ekbom disease) and periodic limb movements during sleep requires knowledge of physiological limb motor activity during sleep in rodents. This study aimed to determine the physiological time structure of tibialis anterior activity during sleep in mice and rats, and compare it with that of healthy humans. Wild-type mice (n = 9) and rats (n = 8) were instrumented with electrodes for recording the electroencephalogram and electromyogram of neck muscles and both tibialis anterior muscles. Healthy human subjects (31 ± 1 years, n = 21) underwent overnight polysomnography. An algorithm for automatic scoring of tibialis anterior electromyogram events of mice and rats during non-rapid eye movement sleep was developed and validated. Visual scoring assisted by this algorithm had inter-rater sensitivity of 92-95% and false-positive rates of 13-19% in mice and rats. The distribution of the time intervals between consecutive tibialis anterior electromyogram events during non-rapid eye movement sleep had a single peak extending up to 10 s in mice, rats and human subjects. The tibialis anterior electromyogram events separated by intervals Willis-Ekbom disease. © 2015 European Sleep Research Society.

  14. Effectiveness of rodenticides for managing invasive roof rats and native deer mice in orchards.

    Science.gov (United States)

    Baldwin, Roger A; Quinn, Niamh; Davis, David H; Engeman, Richard M

    2014-05-01

    Roof rats (Rattus rattus) and deer mice (Peromyscus maniculatus) are occasional pests of nut and tree fruit orchards throughout California and in many other parts of the USA and beyond. In general, the most practical and cost-effective control method for rodents in many agricultural environments is the use of rodenticides (toxic baits), but little or no information exists on the efficacy of current rodenticides in controlling roof rats and deer mice in orchards. Therefore, our goals were to develop an index of rodent activity to monitor efficacy of rodenticides and to subsequently test the efficacy of three California Department of Food and Agriculture rodenticide baits (0.005 % chlorophacinone treated oats, 0.005 % diphacinone treated oats, and 0.005 % diphacinone wax block) to determine their utility for controlling roof rats and deer mice in agricultural orchards. We determined that a general index using the number of roof rat photos taken at a minimum of a 5-min interval was strongly correlated to the minimum number known estimate of roof rats; this approach was used to monitor roof rat and deer mouse populations pre- and post-treatment. Of the baits tested, the 0.005 % diphacinone treated oats was most effective for both species; 0.005 % chlorophacinone grain was completely ineffective against roof rats. Our use of elevated bait stations proved effective at providing bait to target species and should substantially limit access to rodenticides by many non-target species.

  15. Inter-laboratory comparisons of assessment of the allergenic potential of proteins in mice.

    Science.gov (United States)

    Herouet-Guicheney, C; Aldemir, H; Bars, R; de Barbeyrac, D; Kennel, P; Rouquié, D; Stahl, B U; Kimber, I; Dearman, R J

    2009-03-01

    Assessment of the potential allergenicity of novel proteins, including those expressed in genetically modified plants, is an important issue. In previous studies, we have shown that the IgE measurement induced by systemic exposure of BALB/c mice to a range of proteins correlates broadly with what is known of their allergenic potential in humans. The approach used a homologous passive cutaneous anaphylaxis (PCA) assay that reflects IgE-dependent biological activity and is of sufficient sensitivity to detect IgE production in the absence of adjuvant. In previous studies, the immunization phase was conducted independently in two separate facilities, and the subsequent analytical work (PCA) conducted in a single facility. The purpose here was to further evaluate the transferability of this approach. To this end, BALB/c mice were exposed to a range of doses of peanut agglutinin or ovalbumin, allergenic proteins of peanut and hen's egg, respectively, in two independent laboratories. Serial doubling dilutions of serum pooled for each treatment group were analyzed for specific IgE. At higher doses of allergen very similar, or identical, IgE titers were achieved in both laboratories, although at lower doses, responses were somewhat more variable. These data demonstrate that, although technically demanding, the measurement of protein allergen-induced IgE antibody production in mice using PCA is relatively robust and is transferable and reproducible between laboratories. This approach may provide a useful tool for the safety assessment of novel proteins and suggests that continued evaluation of the approach with a wider range of protein allergens and non-sensitising proteins is justified.

  16. Sanitary profile in mice and rat colonies in laboratory animal houses in Minas Gerais: I - Endo and ectoparasites Perfil sanitário de colônias de camundongos e ratos de biotérios de Minas Gerais: I - Endo e ectoparasitos

    Directory of Open Access Journals (Sweden)

    K.A. Bicalho

    2007-12-01

    Full Text Available The sanitary conditions of 13 animal houses in nine public institutions in Minas Gerais, and the presence of endo and ectoparasites of mice and rats colonies kept in these facilities were evaluated. Data about barriers to prevent the transmission of diseases and a program of sanitary monitoring were obtained through a questionnaire and local visit. Parasitological methods were performed for diagnosing mite, lice, helminthes, and protozoa parasites in 344 mice and 111 rats. Data have shown that the majority of the animal houses had neither proper physical environment nor protection barriers to prevent the transmission of infections. Parasitological results have shown that only one animal house (7.7% had parasite free animals, whereas the others have presented infected animals and the prevalences of parasites in the mice colonies were: Myobia musculi (23.1%; Myocoptes musculinus (38.5%; Radfordia affinis (15.4%; Syphacia obvelata (92.3%; Aspiculuris tetraptera (23.1%; Hymenolepis nana (15.4%; Spironucleus muris (46.2%; Giardia muris (46.2%; Tritrichomonas muris (53.8%; Trichomonas minuta (61.5%; Hexamastix muris (7.7%; and Entamoeba muris (84.6%. As for the rat colonies, the prevalences were: Poliplax spinulosa (8.1%; Syphacia muris (46.2%; Trichosomoides crassicauda (28.6%; Spironucleus muris (85.7%; Tritrichomonas muris (85.7%; Trichomonas minuta (85.7%; Hexamastix muris (14.3% and Entamoeba muris (85.7%.Avaliaram-se as condições sanitárias de 13 biotérios de nove instituições públicas do estado de Minas Gerais, bem como a presença de endo e ectoparasitos nos camundongos e ratos criados nesses biotérios. Os dados sobre barreiras contra infecções e sobre o programa de monitoramento sanitário dos animais foram obtidos por meio de um questionário e de visitas aos biotérios. Métodos parasitológicos foram utilizados para o diagnóstico de ácaros, piolhos, helmintos e protozoários em 344 camundongos e 111 ratos. A maioria dos biot

  17. Modelo centinela en colonia de ratones de laboratorio. (Sentinel model in a colony of laboratory mice.

    Directory of Open Access Journals (Sweden)

    García, Itamis C

    2012-06-01

    Full Text Available ResumenEn colonias de ratones de laboratorio es vital preservar la salud de los mismos y el estado microbiológico por el riesgo de infecciones, que pueden ser inaparentes e influyen en los resultados de la experimentación o contaminan los productos biológicos derivados de ellos.AbstractIn laboratory mice colonies is vital to preserve the health of the latter and the microbiological state by infection risk, which can be unapparent and influence in the results of experimentation or contaminate the biological products derived from them.

  18. Basic Microsurgery Training Using the Laboratory Rat (Rattus norvegicus).

    Science.gov (United States)

    2017-03-23

    neurosurgical repair. 12. PROTOCOL OUTCOME SUMMARY: (Please provide, in "ABSTRACT" format, a summary of the protocol objectives, materials and methods, results...techniques required in nerve and vessel reanastamosis. Over a 4 day period, the participant will learn via both didactic and hands-on experience. Using a rat...basic techniques required in nerve and vessel reanastamosis. Methods: Over a 4 day period, the participant will learn via both didactic and hands-on

  19. Baroreflex sensitivity differs among same strain Wistar rats from the same laboratory

    Directory of Open Access Journals (Sweden)

    Celso Ferreira

    2011-09-01

    Full Text Available Previous studies evidenced that a portion of normotensive Sprague–Dawley rats spontaneously exhibit lower baroreflex sensitivity, however, it was no yet investigated in Wistar rats. We aimed to compare baroreflex sensitivity among rats from the same strain and the same laboratory. Male Wistar normotensive rats (300-400g were studied. Cannulas were inserted into the abdominal aortic artery through the right femoral artery to measure mean arterial pressure and heart rate. Baroreflex was calculated as the derivative of the variation of heart rate in function of the mean arterial pressure variation (ΔHR/ΔMAP tested with a depressor dose of sodium nitroprusside (50 μg/kg and with a pressor dose of phenylephrine (8μg/kg in the right femoral venous approach through an inserted cannula. We divided the rats into four groups: i high bradycardic baroreflex, baroreflex gain less than -2 tested with phenylephrine; ii low bradycardic baroreflex, baroreflex gain between -1 and -2 tested with phenylephrine; iii high tachycardic baroreflex, baroreflex gain less than -3 tested with sodium nitroprusside; and iv low tachycardic baroreflex, baroreflex gain between -1 and -3 tested with sodium nitroprusside. Approximately 71% of the rats presented a decrease in bradycardic reflex while around half showed an increase in tachycardic reflex. No significant changes in basal mean arterial pressure and heart rate, tachycardic and bradycardic peak and heart rate range were observed. There was a significant change in baroreflex sensitivity among rats from the same strain and the same laboratory.

  20. Routine habitat change: a source of unrecognized transient alteration of intestinal microbiota in laboratory mice.

    Science.gov (United States)

    Ma, Betty W; Bokulich, Nicholas A; Castillo, Patricia A; Kananurak, Anchasa; Underwood, Mark A; Mills, David A; Bevins, Charles L

    2012-01-01

    The mammalian intestine harbors a vast, complex and dynamic microbial population, which has profound effects on host nutrition, intestinal function and immune response, as well as influence on physiology outside of the alimentary tract. Imbalance in the composition of the dense colonizing bacterial population can increase susceptibility to various acute and chronic diseases. Valuable insights on the association of the microbiota with disease critically depend on investigation of mouse models. Like in humans, the microbial community in the mouse intestine is relatively stable and resilient, yet can be influenced by environmental factors. An often-overlooked variable in research is basic animal husbandry, which can potentially alter mouse physiology and experimental outcomes. This study examined the effects of common husbandry practices, including food and bedding alterations, as well as facility and cage changes, on the gut microbiota over a short time course of five days using three culture-independent techniques, quantitative PCR, terminal restriction fragment length polymorphism (TRFLP) and next generation sequencing (NGS). This study detected a substantial transient alteration in microbiota after the common practice of a short cross-campus facility transfer, but found no comparable alterations in microbiota within 5 days of switches in common laboratory food or bedding, or following an isolated cage change in mice acclimated to their housing facility. Our results highlight the importance of an acclimation period following even simple transfer of mice between campus facilities, and highlights that occult changes in microbiota should be considered when imposing husbandry variables on laboratory animals.

  1. A physiological model for simulation of benzene metabolism by rats and mice.

    Science.gov (United States)

    Medinsky, M A; Sabourin, P J; Lucier, G; Birnbaum, L S; Henderson, R F

    1989-06-15

    Studies conducted by the National Toxicology Program on the chronic toxicity of benzene indicated that B6C3F1 mice are more sensitive to the toxic effects of benzene than are F344 rats. A physiological model was developed to describe the uptake and metabolism of benzene in rats and mice and to determine if the observed differences in toxic effects could be explained by differences in the pathways for metabolism of benzene or by differences in uptake of benzene. Major pathways for elimination of benzene included metabolism to hydroquinone glucuronide or hydroquinone sulfate, phenyl glucuronide or phenyl sulfate, muconic acid, and prephenyl mercapturic acid or phenyl mercapturic acid. Model simulations for total benzene metabolized and for profiles of benzene metabolites were conducted for oral or inhalation exposure and compared to data for urinary excretion of benzene metabolites after exposure of rats and mice to [14C]- or [3H]-benzene by inhalation or gavage. Results for total amount of benzene metabolized, expressed per kilogram body weight, indicated that for inhalation exposure concentrations up to 1000 ppm, mice metabolized at least two to three times as much benzene as did rats. Simulations of oral exposure to benzene resulted in more benzene metabolized per kilogram body weight by rats at oral exposures of greater than 50 mg/kg. Patterns of metabolites formed after either route of exposure were very different for F344/N rats and B6C3F1 mice. Rats primarily formed the detoxification metabolite, phenyl sulfate. Mice formed hydroquinone glucuronide and muconic acid in addition to phenyl sulfate. Hydroquinone and muconic acid are associated with pathways leading to the formation of the putative toxic metabolites of benzene. Metabolic rate parameters, Vmax and Km, were very different for hydroquinone conjugate and muconic acid formation compared to formation of phenyl conjugates and phenyl mercapturic acids. Putative toxication pathways could be characterized as

  2. Carcinogenicity and chronic toxicity of hydrazine monohydrate in rats and mice by two-year drinking water treatment.

    Science.gov (United States)

    Matsumoto, Michiharu; Kano, Hirokazu; Suzuki, Masaaki; Katagiri, Taku; Umeda, Yumi; Fukushima, Shoji

    2016-04-01

    The carcinogenicity and chronic toxicity of hydrazine monohydrate was examined by administrating hydrazine monohydrate in drinking water to groups of 50 F344/DuCrj rats and 50 Crj:BDF1 mice of both sexes for two years. The drinking water concentration of hydrazine monohydrate was 0, 20, 40 or 80 ppm (wt/wt) for male and female rats and male mice; and 0, 40, 80 or 160 ppm for female mice. Survival rates of each group of males and females rats and mice were similar to the respective controls, except female rats administered 80 ppm. Two-year administration of hydrazine monohydrate produced an increase in the incidences of hepatocellular adenomas and carcinomas in rats of both sexes along with hepatic foci. In mice, the incidences of hepatocellular adenomas and carcinomas were increased in females, and significantly increased incidences of hepatocellular adenomas in females administered 160 ppm were observed. Thus, hydrazine monohydrate is carcinogenic in two species, rats and mice. Additionally, non-neoplastic renal lesions in rats and mice and non-neoplastic nasal lesions in mice were observed.

  3. Species and sex differences in propofol glucuronidation in liver microsomes of humans, monkeys, rats and mice.

    Science.gov (United States)

    Mukai, M; Isobe, T; Okada, K; Murata, M; Shigeyama, M; Hanioka, N

    2015-07-01

    Propofol (2,6-diisopropylphenol) is a short-acting anesthetic commonly used in clinical practice, and is rapidly metabolized into glucuronide by UDP-glucuronosyltransferase (UGT). In the present study, propofol glucuronidation was examined in the liver microsomes of male and female humans, monkeys, rats, and mice. The kinetics of propofol glucuronidation by liver microsomes fit the substrate inhibition model for humans and mice, the Hill model for monkeys, and the isoenzyme (biphasic) model for rats. The K(m), V(max), and CL(int) values of human liver microsomes were 50 μM, 5.6 nmol/min/mg protein, and 110 μL/min/mg protein, respectively, for males, and 46 μM, 6.0 nmol/min/mg protein, and 130 μL/min/mg protein, respectively, for females. The rank order of the CL(int) or CL(max) (in vitro clearance) values of liver microsomes was mice humans > monkeys > rats (high-affinity phase) rats (low-affinity phase) in both males and females. Although no significant sex differences were observed in the values of kinetic parameters in any animal species, the in vitro clearance values of liver microsomes were males females in monkeys, rats (high-affinity phase), and mice. These results demonstrated that the kinetic profile of propofol glucuronidation by liver microsomes markedly differed among humans, monkeys, rats, and mice, and suggest that species and sex differences exist in the roles of UGT isoform(s), including UGT1A9, involved in its metabolism.

  4. Validation of the dimensionality emergence assay for the measurement of innate anxiety in laboratory mice.

    Science.gov (United States)

    Jain, Apar; Dvorkin, Anna; Fonio, Ehud; Golani, Ilan; Gross, Cornelius T

    2012-02-01

    The open field test is a common tool to measure innate anxiety in rodents. In the usual configuration of this test the animal is forced to explore the open arena and its behavior includes both anxiety and non-anxiety responses. However, the open arena is generally small and allows only limited expression of exploratory behavior. The recently developed dimensionality emergence assay in which an animal is housed in a home cage with free access to a large circular arena elicits graded exploration and promises to serve as a more ethological test of anxiety. Here we examined the predictive validity of this assay for anxiety-related measures in mice. First, we compared their behavior in the presence or absence of access to the home cage and found that mice with access to the home cage exhibited a gradual build-up in exploration of the arena while those without did not. Then we identified behavioral measures that responded to treatment with the anxiolytic drug diazepam. Diazepam altered several classical measures of innate anxiety, such as distance traveled and thigmotaxis, but also led to a dose-dependent acceleration of the build-up as reflected in a significantly reduced latency to attain several exploratory landmarks. Finally, we tested the utility of the dimensionality emergence assay in assessing alterations in innate anxiety reported in mice carrying a knockout allele for the serotonin 1A receptor (Htr1a). Our findings support the validity of the dimensionality emergence assay as a method to extract an expanded repertoire of behavioral measures for the assessment of anxiety in laboratory mice.

  5. Food neophobia in wild and laboratory rats (multi-strain comparison).

    Science.gov (United States)

    Modlinska, Klaudia; Stryjek, Rafał; Pisula, Wojciech

    2015-04-01

    Although empirical studies comparing neophobia in wild and laboratory rats have been conducted in the past, a few decades have passed since most of them were completed. This is a substantial period of time in the case of fast-breeding animals such as rats. Equally important are the inconsistencies in research findings with respect to comparisons between wild and laboratory rats, and within domesticated strains. As well as having the aim of updating knowledge of neophobia among different types of rats, the present experiment was also an attempt to isolate a specific fear of a new food from a general fear of a novel object. The procedure was that rats accustomed to one type of food served in a specific location and in a familiar container were given a different type of food. Test trials were preceded by food deprivation. The following variables were measured: feeding latency, the pace of eating, the number of approaches to the container, and the number of times food was sampled in each trial. The amount of food consumed in each trial was weighed and also taken into account. Grooming time served as the measure of stress among the rats in the experiment. The results of the experiment did not confirm the assertion of some authors that wild rats avoid eating unfamiliar foods. All groups demonstrated only a temporary decrease in the amount of food consumed, the magnitude of which was similar in all strains. No evidence of particularly low neophobia in albino rats was found. However, the behavioral symptoms indicated higher levels of stress in wild rats compared to the other groups.

  6. Bioavailability of a potato chromium complex to the laboratory rat

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, H.K.

    1985-01-01

    Research objectives were to study the effect of food source, preparation method and chemical form on bioavailability of chromium. Chromium concentration in potatoes was determined and tubers labeled either intrinsically or extrinsically with radioactive chromate. A labeled chromium complexes was isolated from preparations of raw, baked or fried potatoes and chromatographed on gel permeation media. Availability of the potato chromium complex to the rat was examined in three feeding studies. Animals were dosed with radioactive extrinsically or intrinsically labeled potato extract or with chromate. A labeled chromium complex was isolated from gastrointestinal contents of rats and chromatographed. Potato pulp and peel contained 1.63 and 2.70 ..mu..g Cr/g tissue respectively. True and apparent absorption from extrinsically labeled feedings were 33.4 +/- 4.7 and 29.8 +/- 11.2% respectively, and no differences existed between absorption from raw and cooked potatoes. Absorption from the extrinsic labeled potatoes differed significantly from absorption of inorganic chromatium. Apparent absorption of raw (11.1 +/- 7.9%) and cooked (-0.7 +/- 2.8%) intrinsically labeled feedings differed significantly. Absorption of inorganic chromium was 17.8% (true) and 11.5% (apparent). Examination of the chromium complex isolated from gastrointestinal tract contents showed enlargement of the complex in the stomach after consumption.

  7. Remarkable changes in behavior and physiology of laboratory mice after the massive 2011 Tohoku earthquake in Japan.

    Science.gov (United States)

    Yanai, Shuichi; Semba, Yuki; Endo, Shogo

    2012-01-01

    A devastating earthquake and tsunami hit Japan on March 11, 2011, followed by several long and intense aftershocks. Laboratory mice housed in the Tokyo, located approximately 330 km south of this earthquake's epicenter, displayed remarkable changes in a variety of behaviors and physiological measures. Although unusual pre-earthquake behaviors have been previously reported in laboratory animals, little is known about behavioral and physiological changes that occur after a great earthquake. In the present study, the effects of Tohoku earthquake on mice behavior were investigated. "Earthquake-experienced" mice displayed a marked increase in food consumption without gaining body weight in response to the earthquake. They also displayed enhanced anxiety, and in a formal fear memory task, showed significantly greater tone- and context-dependent conditioned freezing. Water maze performance of earthquake-experienced mice showed the quicker acquisition of the task, faster swim speed and longer swim distance than the naive mice. Serum corticosterone levels were elevated compared to the naive mice, indicating that the earthquake and aftershocks were stressful for the mice. These results demonstrate that great earthquakes strongly affect mouse behaviors and physiology. Although the effects of a variety of experimental manipulations on mouse behaviors in disease models or in models of higher cognitive functions have been extensively examined, researchers need to be aware how natural phenomena, such as earthquakes and perhaps other natural environmental factors, influence laboratory animal behaviors and physiology.

  8. Remarkable changes in behavior and physiology of laboratory mice after the massive 2011 Tohoku earthquake in Japan.

    Directory of Open Access Journals (Sweden)

    Shuichi Yanai

    Full Text Available A devastating earthquake and tsunami hit Japan on March 11, 2011, followed by several long and intense aftershocks. Laboratory mice housed in the Tokyo, located approximately 330 km south of this earthquake's epicenter, displayed remarkable changes in a variety of behaviors and physiological measures. Although unusual pre-earthquake behaviors have been previously reported in laboratory animals, little is known about behavioral and physiological changes that occur after a great earthquake. In the present study, the effects of Tohoku earthquake on mice behavior were investigated. "Earthquake-experienced" mice displayed a marked increase in food consumption without gaining body weight in response to the earthquake. They also displayed enhanced anxiety, and in a formal fear memory task, showed significantly greater tone- and context-dependent conditioned freezing. Water maze performance of earthquake-experienced mice showed the quicker acquisition of the task, faster swim speed and longer swim distance than the naive mice. Serum corticosterone levels were elevated compared to the naive mice, indicating that the earthquake and aftershocks were stressful for the mice. These results demonstrate that great earthquakes strongly affect mouse behaviors and physiology. Although the effects of a variety of experimental manipulations on mouse behaviors in disease models or in models of higher cognitive functions have been extensively examined, researchers need to be aware how natural phenomena, such as earthquakes and perhaps other natural environmental factors, influence laboratory animal behaviors and physiology.

  9. Remarkable Changes in Behavior and Physiology of Laboratory Mice after the Massive 2011 Tohoku Earthquake in Japan

    Science.gov (United States)

    Yanai, Shuichi; Semba, Yuki; Endo, Shogo

    2012-01-01

    A devastating earthquake and tsunami hit Japan on March 11, 2011, followed by several long and intense aftershocks. Laboratory mice housed in the Tokyo, located approximately 330 km south of this earthquake’s epicenter, displayed remarkable changes in a variety of behaviors and physiological measures. Although unusual pre-earthquake behaviors have been previously reported in laboratory animals, little is known about behavioral and physiological changes that occur after a great earthquake. In the present study, the effects of Tohoku earthquake on mice behavior were investigated. “Earthquake-experienced” mice displayed a marked increase in food consumption without gaining body weight in response to the earthquake. They also displayed enhanced anxiety, and in a formal fear memory task, showed significantly greater tone- and context-dependent conditioned freezing. Water maze performance of earthquake-experienced mice showed the quicker acquisition of the task, faster swim speed and longer swim distance than the naive mice. Serum corticosterone levels were elevated compared to the naive mice, indicating that the earthquake and aftershocks were stressful for the mice. These results demonstrate that great earthquakes strongly affect mouse behaviors and physiology. Although the effects of a variety of experimental manipulations on mouse behaviors in disease models or in models of higher cognitive functions have been extensively examined, researchers need to be aware how natural phenomena, such as earthquakes and perhaps other natural environmental factors, influence laboratory animal behaviors and physiology. PMID:22957073

  10. Leptospires in field Rats in and around the laboratory animal facilities of Banglore, India

    Directory of Open Access Journals (Sweden)

    G. Vinodkumar

    Full Text Available The present study was undertaken to determine the prevalence of leptospires in field rats in and around laboratory animal facilities in Bangalore. 34 rats were trapped alive in and around the laboratory animal facilities in Bangalore. Urine and serum samples from theses field rats were collected. Serum samples were tested for anti-leptospiral antibodies by microscopic agglutination test, while urine samples were subjected for dark field microscopy and polymerase chain reaction to detect the presence of leptospiral antigens. Serology revealed the presence of antileptospiral antibodies in 19 (61.29 percent field rats and dark field microscopy revealed the presence of leptospiral antigens in 3 (8.82 percent and 6 (17.65 percent of urine samples of these field rats. Among the serovars, Icterohaemorrhagiae was predominant followed by Autumnalis and Pyrogens. Serology dark field microscopy and polymerase chain reaction reveals that field rats are major natural carriers and shedders of leptospires. [Vet. World 2011; 4(9.000: 410-412

  11. Protective Effect of Zizphus Vulgaris Extract, on Liver Toxicity in Laboratory Rats

    OpenAIRE

    S. Ebrahimi; Sadeghi, H.; A Pourmahmoudi; SH Askariyan; Askari, S

    2011-01-01

    Introduction & Objective: Some of natural and synthetic products have antioxidant properties which protect the liver against the destructive factors. This study aimed to investigate the effect of Zizphus Vulgaris extracts on mice liver. Materials & Methods: This experimental study was conducted at Yasouj University of Medical Sciences in 2010 on 30 healthy adult male Wistar rats. Animals were randomly divided into five equal groups: the control group (receiving, olive oil), control group ...

  12. Cytokine and chemokine dynamics differ between rats and mice after collagen implantation

    NARCIS (Netherlands)

    Luttikhuizen, Daniel T.; Harmsen, Martin C.; van Luyn, Marja J. A.

    2007-01-01

    Implanted scaffold materials induce an inflammatory reaction known as the 'foreign body reaction' (FBR). We hypothesized that the observed difference in FBR between rats and mice correlate with different expression dynamics of cytokines and chemokines, which are key orchestrators of the FBR. After i

  13. FLUCONAZOLE-INDUCED HEPATIC CYTOCHROME P450 GENE EXPRESSION AND ENZYMATIC ACTIVITIES IN RATS AND MICE

    Science.gov (United States)

    This study was undertaken to examine the effects of the triazole antifungal agent fluconazole on the expression of hepatic cytochrome P450 (Cyp) genes and the activities of Cyp enzymes in male Sprague-Dawley rats and male CD-1 mice. Alkoxyresorufin O-dealkylation (AROD) methods w...

  14. Inhalation developmental toxicology studies: Teratology study of acetone in mice and rats: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Evanoff, J.J.; Rommereim, R.L.; Stoney, K.H.; Weigel, R.J.; Westerberg, R.B.

    1988-11-01

    Acetone, an aliphatic ketone, is a ubiquitous industrial solvent and chemical intermediate; consequently, the opportunity for human exposure is high. The potential for acetone to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 440, 2200, or 11000 ppm, and in Swiss (CD-1) mice exposed to 0, 440, 2200, and 6600 ppm acetone vapors, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and approx.32 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 46 refs., 6 figs., 27 tabs.

  15. The touchscreen operant platform for testing working memory and pattern separation in rats and mice

    NARCIS (Netherlands)

    Oomen, C.A.; Hvoslef-Eide, M.; Heath, C.J.; Mar, A.C.; Horner, A.E.; Bussey, T.J.; Saksida, L.M.

    2013-01-01

    The automated touchscreen operant chamber for rats and mice allows for the assessment of multiple cognitive domains within the same testing environment. This protocol presents the location discrimination (LD) task and the trial-unique delayed nonmatching-to-location (TUNL) task, which both assess me

  16. The touchscreen operant platform for testing working memory and pattern separation in rats and mice

    NARCIS (Netherlands)

    Oomen, C.A.; Hvoslef-Eide, M.; Heath, C.J.; Mar, A.C.; Horner, A.E.; Bussey, T.J.; Saksida, L.M.

    2013-01-01

    The automated touchscreen operant chamber for rats and mice allows for the assessment of multiple cognitive domains within the same testing environment. This protocol presents the location discrimination (LD) task and the trial-unique delayed nonmatching-to-location (TUNL) task, which both assess me

  17. Inhalation developmental toxicology studies: Teratology study of tetrahydrofuran in mice and rats: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Evanoff, J.J.; Stoney, K.H.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1988-08-01

    Tetrahydrofuran (THF), a four-carbon cyclic ether, is widely used as an industrial solvent. Although it has been used in large quantities for many years, few long-term toxicology studies, and no reproductive or developmental studies, have been conducted on THF. This study addresses the potential for THF to cause developmental toxicity in rodents by exposing Sprague-Dawley rats and Swiss (CD-1) mice to 0, 600, 1800, or 5000 ppm tetrahydrofuran (THF) vapors, 6 h/day, 7 dy/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.33 positively mated rats or mice. Positively mated mice were exposed on days 6--17 of gestation (dg), and rats on 6--19 dg. The day of plug or sperm detection was designated as O dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 27 refs., 6 figs., 23 tabs.

  18. [Evaluation of the carcinogenic effect of ceramic fibers in experiments on rats and mice].

    Science.gov (United States)

    Krajnow, A; Lao, I; Stetkiewicz, J

    1997-01-01

    The carcinogenic effect of Kaowoll raw and thermally used ceramic fibres was assessed in experiments on rats and mice. The fibers were applied intraperitoneally in doses by 25 and 5 mg, and the animals were observed over their life-span. It was found that Kaowoll fibers were carcinogenic and that high temperature did not change these properties.

  19. 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.

  20. Inhalation developmental toxicology studies: Teratology study of isoprene in mice and rats: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Evanoff, J.J.; Stoney, K.H.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1989-01-01

    Isoprene, a reactive, branched diene, is used in large quantities in the manufacture of polyisoprene and as a copolymer in the synthesis of butyl rubber. The potential for isoprene to cause developmental toxicity was assessed in rodents, by exposing four groups each of Sprague-Dawley rats and Swiss (CD-1) mice to 0, 280, 1400, or 7000 ppM isoprene vapors, 6 h/day, 7 day/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.30 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 31 refs., 6 figs., 19 tabs.

  1. Obesity And Laboratory Diets Affects Tissue Malondialdehyde (MDA) Levels In Obese Rats

    Science.gov (United States)

    Chowdhury, Parimal; Scott, Joseph; Holley, Andy; Hakkak, Reza

    2010-04-01

    This study was conducted to investigate the interaction of obesity and laboratory diets on tissue malondialdehyde levels in rats. Female Zucker obese and lean rats were maintained on either regular grain-based diet or purified casein diet for two weeks, orally gavaged at day 50 with 65 mg/kg DMBA and sacrificed 24 hrs later. Malondialdehyde (MDA) levels were measured in blood and harvested tissues. Data were recorded as mean ± SEM and analyzed statistically. Results show that the obese group on purified casein diet had reduction of MDA levels in the brain, duodenum, liver, lung and kidney tissues as compared to lean group, p Obese group on grain-based diet showed significant increase in MDA levels only in the duodenum, p obese rats. It appears that purified casein diets were more effective than grain-based diet in reduction of oxidative stress in obese rats.

  2. Methyl bromide causes DNA methylation in rats and mice but fails to induce somatic mutations in λlacZ transgenic mice

    NARCIS (Netherlands)

    Pletsa, V.; Steenwinkel, M.-J.S.T.; Delft, J.H.M. van; Baan, R.A.; Kyrtopoulos, S.A.

    1998-01-01

    Following single or multiple oral treatments of rats or λlacZ transgenic mice with methyl bromide, methylated DNA adducts (N7- and/or O6-methylguanine) were found at comparable levels in various tissues, including among others the glandular stomach, the forestomach and the liver. Multiple rat treatm

  3. Tissue distribution and excretion of 125I-lidamycin in mice and rats

    Institute of Scientific and Technical Information of China (English)

    You-Ping Liu; Quan-Sheng Li; Yu-Rong Huang; Chang-Xiao Liu

    2005-01-01

    AIM: To investigate the tissue distribution, urinary and fecal excretions of 125I-lidamycin (125I-C-1027) in mice and its biliary excretion in rats.METHODS: The total radioactivity assay (RA method) and the radioactivity assay after precipitation with 200 mL/L trichloroacetic acid (TCA-RA method) were used to dete-rmine the tissue distribution, and the urinary and fecal excretions of 125I-C-1027 in mice and its biliary excretion in rats.RESULTS: Tissue concentrations reached the peak at the fifth minute after administration of 125I-C-1027 to mice. The highest concentration was in kidney, and the lowest in brain at all test-time points. The organs of the concentrations of 125I-C-1027 from high to low were kidney, lung, liver, stomach, spleen, uterus, ovary, intestine, muscle, heart, testis, fat, and brain in mice. The accumulative excretionamounts of 0-24 h, and 0-96 h after administration of125I-C-1027 were 68.36 and 71.64% in urine, and 2.60 and 3.21% in feces of mice, respectively, and the accumulative excretion amount of 0-24 h was 3.57% in bile in rats.CONCLUSION: Our results reflect the characteristics of the tissue distribution, urinary and fecal excretions of 125IC-1027 in mice and the biliary excretion of 125I-C-1027and its metabolites in rats, and indicate that 125I-C-1027and its metabolites are mainly distributed in kidney, and excreted in urine.

  4. Toxicology and carcinogenesis studies of a nondecolorized [corrected] whole leaf extract of Aloe barbadensis Miller (Aloe vera) in F344/N rats and B6C3F1 mice (drinking water study).

    Science.gov (United States)

    Boudreau, M D; Beland, F A; Nichols, J A; Pogribna, M

    2013-08-01

    Extracts from the leaves of the Aloe vera plant (Aloe barbadensis Miller) have long been used as herbal remedies and are also now promoted as a dietary supplement, in liquid tonics, powders or tablets, as a laxative and to prevent a variety of illnesses. We studied the effects of Aloe vera extract on rats and mice to identify potential toxic or cancer-related hazards. We gave solutions of nondecolorized extracts of Aloe vera leaves in the drinking water to groups of rats and mice for 2 years. Groups of 48 rats received solutions containing 0.5%, 1% or 1.5% of Aloe vera extract in the drinking water, and groups of mice received solutions containing 1%, 2%, or 3% of Aloe vera extract. Similar groups of animals were given plain drinking water and served as the control groups. At the end of the study tissues from more than 40 sites were examined for every animal. In all groups of rats and mice receiving the Aloe vera extract, the rates of hyperplasia in the large intestine were markedly increased compared to the control animals. There were also increases in hyperplasia in the small intestine in rats receiving the Aloe vera extract, increases in hyperplasia of the stomach in male and female rats and female mice receiving the Aloe vera extract, and increases in hyperplasia of the mesenteric lymph nodes in male and female rats and male mice receiving the Aloe vera extract. In addition, cancers of the large intestine occurred in male and female rats given the Aloe vera extract, though none had been seen in the control groups of rats for this and other studies at this laboratory. We conclude that nondecolorized Aloe vera caused cancers of the large intestine in male and female rats and also caused hyperplasia of the large intestine, small intestine, stomach, and lymph nodes in male and female rats. Aloe vera extract also caused hyperplasia of the large intestine in male and female mice and hyperplasia of the mesenteric lymph node in male mice and hyperplasia of the stomach

  5. NTP Carcinogenesis Bioassay of Propyl Gallate (CAS No. 121-79-9) in F344/N Rats and B6C3F1 Mice (Feed Study).

    Science.gov (United States)

    1982-12-01

    Propyl gallate is a white to nearly white odorless powder having a slightly bitter taste. Solutions of propyl gallate turn dark in the presence of iron or iron salts. Propyl gallate has been used since 1948 as an antioxidant to stabilize cosmetics, food packaging materials, and foods containing fats. As an additive, it may be found in edible fats, oils, mayonnaise, shortening, baked goods, candy, dried meat, fresh pork sausage, and dried milk, and it is used in hair grooming products, pressure-sensitive adhesives, lubricating oil additives, and transforming oils. A NTP Carcinogenesis bioassay of propyl gallate was conducted by feeding diets containing 6,000 or 12,000 ppm propyl gallate to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. Groups of 50 untreated rats and 50 untreated mice of each sex served as controls. Survival of rats and mice was not adversely affected by propyl gallate, but mean body weights of dosed rats and mice of each sex were lower than those of the controls. At 104 weeks, mean body weights of low-and high-dose rats were 4% and 8% lower than those of the controls for males and 11% and 19% lower than those of the controls for females. Similarly, mean body weights of low-and high-dose mice were 5% and 8% lower than those of the controls for males and 11% (both dose groups) lower than those of the controls for females. Thyroid follicular-cell adenomas or carcinomas (combined) occurred in male rats with a statistically significant (P<0.05) positive trend, but the incidences in the dosed groups were not statistically significant in direct comparisons with the control groups. Moreover, the incidence of high-dose male rats with follicular-cell tumors (3/50, 6%) was not statistically different from the historical control rate (14/584, 2.4%) for the laboratory that conducted this bioassay. Rare tumors (an astrocytoma or a glioma) were found in the brains of two low-dose female rats. The incidence of all brain tumors in the

  6. "Personality" in laboratory mice used for biomedical research: a way of understanding variability?

    Science.gov (United States)

    Lewejohann, Lars; Zipser, Benjamin; Sachser, Norbert

    2011-09-01

    The mouse, including countless lines of transgenic and knockout mice, has become the most prominent model organism in biomedical research. Behavioral characterization is often conducted in batteries of short tests on locomotion, anxiety, learning and memory, etc. In such tests, any individual differences within groups are usually considered to be disturbing variance. In order to reduce variance in experimental animal research enormous efforts of standardization have been made. While a substantial reduction of variability has been reached compared to the earlier years of experimental animal studies a considerable amount of inter-individual differences still seems to escape standardization. This effect is demonstrated and evaluated by re-analyzing data from two experiments conducted in our laboratory with inbred mice. Interestingly, behavioral patterns of individual animals seem to be correlated across context and time. In evolutionary biology, "animal personalities" have been discussed recently to comprise such stable patterns. We argue here, that nonrandom behavioral correlations across contexts and time might underlie the variability commonly found in biomedical mouse studies.

  7. Passive transfer of resistance to mice with sera from rabbits, rats or mice vaccinated with ultraviolet-attenuated cercariae of Schistosoma japonicum.

    Science.gov (United States)

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

    1987-06-01

    All serum transfers from donor rats or rabbits given single or multiple vaccinations of ultraviolet (u.v.)-attenuated Schistosoma japonicum cercariae conferred significant resistance against challenge to mice. Donors given 5 vaccinations, however, produced the most effective sera; rat sera giving up to 88% protection and rabbit sera up to 80%. This protective effect was species-specific and titratable. Sera from vaccinated rabbits and rats were were most effective when transferred to mice 2 h before challenge, but became progressively less effective when transferred with increasing time after challenge. These sera had no efficacy when given 6 days after challenge. Thus, sera from vaccinated rabbits and rats were effective against the early stage of migration, but did not necessarily have to act in the skin as all serum transfers were as effective against intraperitoneal as percutaneous challenge. By contrast, serum from multiply vaccinated mice had little or no protective effect when transferred to mice before challenge, but conferred 62% resistance when transferred 5 days after challenge. Further, there was an additive protective effect when vaccinated rat and mouse sera were given in combination at their optimum transfer times (days 0 and +5, respectively). Thus, there appears to be a stage-specific immune response induced by vaccination depending upon whether the vaccinated hosts are truly permissive or not. Vaccinated rats and rabbits respond to the early phase of migration and vaccinated mice make protective responses against the lung phase of migration.

  8. A neurorobotic platform for locomotor prosthetic development in rats and mice

    Science.gov (United States)

    von Zitzewitz, Joachim; Asboth, Leonie; Fumeaux, Nicolas; Hasse, Alexander; Baud, Laetitia; Vallery, Heike; Courtine, Grégoire

    2016-04-01

    Objectives. We aimed to develop a robotic interface capable of providing finely-tuned, multidirectional trunk assistance adjusted in real-time during unconstrained locomotion in rats and mice. Approach. We interfaced a large-scale robotic structure actuated in four degrees of freedom to exchangeable attachment modules exhibiting selective compliance along distinct directions. This combination allowed high-precision force and torque control in multiple directions over a large workspace. We next designed a neurorobotic platform wherein real-time kinematics and physiological signals directly adjust robotic actuation and prosthetic actions. We tested the performance of this platform in both rats and mice with spinal cord injury. Main Results. Kinematic analyses showed that the robotic interface did not impede locomotor movements of lightweight mice that walked freely along paths with changing directions and height profiles. Personalized trunk assistance instantly enabled coordinated locomotion in mice and rats with severe hindlimb motor deficits. Closed-loop control of robotic actuation based on ongoing movement features enabled real-time control of electromyographic activity in anti-gravity muscles during locomotion. Significance. This neurorobotic platform will support the study of the mechanisms underlying the therapeutic effects of locomotor prosthetics and rehabilitation using high-resolution genetic tools in rodent models.

  9. High-Moisture Diet for Laboratory Rats: Nutrient Analysis, Growth, and Organ Weights

    Science.gov (United States)

    Battles, August H.; Knapka, Joseph T.; Lewis, Laura; Lang, Marie T.; Gruendel, Douglas J.

    1991-01-01

    A diet (KSC-25) to be sterilized by irradiation was formulated to contain 66% moisture and to provide the required nutrients for growing rats. Analyses of the irradiated dry diet provided data to evaluate its nutrient content. The diet was evaluated for its ability to supply all nutrients, including water, required by immature rats. Sixteen Sprague-Dawley rats were fed the high-moisture diet with or without access to a water bottle. Rats (n = 16) fed an irradiated purified diet in a meal form with access to a water bottle were the control animals. Feed efficiency, food and water consumption, and growth rate data were collected during the 28-day study. Organ weights were collected on day 28. The test diet met or exceeded the National Research Council (NRC) estimated nutritional requirements for immature laboratory rats. The 66% moisture KSC-25 diet provided all nutrients, including water, required by weanling male Sprague-Dawley rats for growth equivalent to the established purified diet.

  10. Physiologically based Pharmacokinetic Modeling of 1,4-Dioxane in Rats, Mice, and Humans

    Energy Technology Data Exchange (ETDEWEB)

    Sweeney, Lisa M.; Thrall, Karla D.; Poet, Torka S.; Corley, Rick; Weber, Thomas J.; Locey, B. J.; Clarkson, Jacquelyn; Sager, S.; Gargas, M. L.

    2008-01-01

    ABSTRACT 1,4-Dioxane (CAS No. 123-91-1) is used primarily as a solvent or as a solvent stabilizer. It can cause lung, liver and kidney damage at sufficiently high exposure levels. Two physiologically-based pharmacokinetic (PBPK) models of 1,4-dioxane and its major metabolite, hydroxyethoxyacetic acid (HEAA), were published in 1990. These models have uncertainties and deficiencies that could be addressed and the model strengthened for use in a contemporary cancer risk assessment for 1,4-dioxane. Studies were performed to fill data gaps and reduce uncertainties pertaining to the pharmacokinetics of 1,4-dioxane and HEAA in rats, mice, and humans. Three types of studies were performed:partition coefficient measurements, blood time course in mice, and in vitro pharmacokinetics using rat, mouse, and human hepatocytes. Updated PBPK models were developed based on these new data and previously available data. The optimized rate of metabolism for the mouse was significantly higher than the value previously estimated. The optimized rat kinetic parameters were similar to those in the 1990 models. Only two human studies were identified. Model predictions were consistent with one study, but did not fit the second as well. In addition, a rat nasal exposure was completed. The results confirmed water directly contacts rat nasal tissues during drinking water under bioassays. Consistent with previous PBPK models, nasal tissues were not specifically included in the model. Use of these models will reduce the uncertainty in future 1,4-dioxane risk assessments.

  11. Physiologically based pharmacokinetic modeling of 1,4-Dioxane in rats, mice, and humans.

    Science.gov (United States)

    Sweeney, Lisa M; Thrall, Karla D; Poet, Torka S; Corley, Richard A; Weber, Thomas J; Locey, Betty J; Clarkson, Jacquelyn; Sager, Shawn; Gargas, Michael L

    2008-01-01

    1,4-Dioxane (CAS No. 123-91-1) is used primarily as a solvent or as a solvent stabilizer. It can cause lung, liver, and kidney damage at sufficiently high exposure levels. Two physiologically based pharmacokinetic (PBPK) models of 1,4-dioxane and its major metabolite, hydroxyethoxyacetic acid (HEAA), were published in 1990. These models have uncertainties and deficiencies that could be addressed and the model strengthened for use in a contemporary cancer risk assessment for 1,4-dioxane. Studies were performed to fill data gaps and reduce uncertainties pertaining to the pharmacokinetics of 1,4-dioxane and HEAA in rats, mice, and humans. Three types of studies were performed: partition coefficient measurements, blood time course in mice, and in vitro pharmacokinetics using rat, mouse, and human hepatocytes. Updated PBPK models were developed based on these new data and previously available data. The optimized rate of metabolism for the mouse was significantly higher than the value previously estimated. The optimized rat kinetic parameters were similar to those in the 1990 models. Only two human studies were identified. Model predictions were consistent with one study, but did not fit the second as well. In addition, a rat nasal exposure was completed. The results confirmed water directly contacts rat nasal tissues during drinking water under bioassay conditions. Consistent with previous PBPK models, nasal tissues were not specifically included in the model. Use of these models will reduce the uncertainty in future 1,4-dioxane risk assessments.

  12. Immunohistochemical localization of spermatid nuclear transition protein 2 in the testes of rats and mice.

    Science.gov (United States)

    Alfonso, P J; Kistler, W S

    1993-03-01

    Transition protein 2 (TP2) of the rat was isolated by differential precipitation with trichloroacetic acid, chromatography over Bio-Rex 70, and preparative gel electrophoresis. A polyclonal rabbit antiserum was raised that did not cross-react with unrelated acid-soluble proteins from liver or testes. The antiserum was used to identify TP2-related proteins obtained from testes of mice, hamsters, guinea pigs, rabbits, and boars by Western blotting. Immunohistochemical techniques were used to localize TP2 in paraffin-embedded testis sections from mice and rats. In both species, TP2 was first detected in spermatids that had essentially completed the morphological change from a round to an elongate nucleus and that were undergoing chromosomal condensation (spermatids of step 13 in rat and step 12 in mouse). TP2 was retained in spermatid nuclei until early step 16 in the rat and step 14 in the mouse. Serial sections of rat testis exposed separately to antisera to TP1 and TP2 showed that the great majority of labeled tubules were reactive to both antisera. However, in occasional tubules, TP1 reactivity was retained in relatively late spermatids that were negative for TP2. Thus both TP1 and TP2 appear in the nucleus essentially simultaneously, in association with the beginning of chromatin condensation and at a point well after much of the nuclear shaping has occurred.

  13. Extrapolation modeling of aerosol deposition in human and laboratory rat lungs

    Energy Technology Data Exchange (ETDEWEB)

    Martonen, T.B.; Zhang, Z.; Yang, Y.

    1992-01-01

    Laboratory test animals are often used as surrogates in exposure studies to assess the potential threat to human health following inhalation of airborne contaminants. To aid in the interpretation and extrapolation of data to man, dosimetric considerations need to be addressed. Therefore, a mathematical model describing the behavior and fate of inhaled particulate matter within the respiratory tracts of man and rats has been developed. In the computer simulations, the CO2 concentrations of inhalation exposure chamber atmospheres are controlled to produce desired breathing patterns in the rat which mimic human breathing patterns as functions of physical activity levels. Herein, deposition patterns in human and rat lung airways are specifically examined as functions of respiratory intensities and particle parameters. The model provides a basis for the re-evaluation of data from past experiments, and, perhaps most importantly, permits new inhalation exposure tests to be designed and conducted in a sound scientific manner regarding this endpoint: the extrapolation of results to human conditions.

  14. The diet board: welfare impacts of a novel method of dietary restriction in laboratory rats

    DEFF Research Database (Denmark)

    Kasanen, I H E; Inhilä, K J; Vainio, O M

    2009-01-01

    Laboratory rats are commonly fed ad libitum (AL). Moderate dietary restriction (DR) decreases mortality and morbidity when compared with AL feeding, but there are several obstacles to the implementation of DR. Traditional methods of restricted feeding disrupt normal diurnal eating rhythms...... and are not compatible with group housing. We have designed a novel method, the diet board, to restrict the feeding of group-housed rats. Animals fed from the diet board had 15% lower body weight than the AL-fed animals at the age of 17 weeks. The welfare effects of diet board feeding were assessed by comparing...... to solve the health problems associated with AL feeding, while allowing the rats to be group-housed and to maintain their normal diurnal eating rhythms. The diet board can also be seen as a functional cage furniture item, dividing the cage into compartments and thus increasing the structural complexity...

  15. Food intake in laboratory rats provided standard and fenbendazole-supplemented diets.

    Science.gov (United States)

    Vento, Peter J; Swartz, Megan E; Martin, Lisa Be; Daniels, Derek

    2008-11-01

    The benzimidazole anthelmintic fenbendazole (FBZ) is a common and effective treatment for pinworm infestation in laboratory animal colonies. Although many investigators have examined the potential for deleterious biologic effects of FBZ, more subtle aspects of the treatment remain untested. Accordingly, we evaluated differences in food intake when healthy male Sprague-Dawley rats were provided a standard nonmedicated laboratory rodent chow or the same chow supplemented with FBZ. We also tested for a preference for either food type when subjects were provided a choice of the 2 diets. Data from these experiments showed no differences in food intake or body weight when rats were maintained on either standard or FBZ-supplemented chow. When the rats were given access to both the standard and FBZ-supplemented diets, they showed a clear preference for the standard diet. The preference for the standard diet indicates that the rats can discriminate between the 2 foods and may avoid the FBZ-supplemented chow when possible. Investigators conducting experiments during treatment with FBZ in which differences in food preference are relevant should be aware of these data and plan their studies accordingly.

  16. Susceptibility of Some Wild Rodents Widely Distributed in Egyptian Foci to Schistosoma mansoni Infection under Laboratory Conditions

    Directory of Open Access Journals (Sweden)

    Ismail M. Al-Sharkawi

    2011-01-01

    Full Text Available The most important definitive host of Schistosoma mansoni is the human, however, numerous other mammalian species were found to be infected with this parasite. Among these species, the wild rodents are the most common. In this study, the susceptibility of some wild rodents widely distributed in Egypt to S. mansoni infection was evaluated. Five wild species were tested for the susceptibility of S. mansoni infection in vitro; including Mus musculus (black mice, Acomys cahirinus (Cairo spiny mice, Rattus rattus (house rats, Rattus norvegilcus (Norway rats, Rattus norvegicus (albino rats and Arvicanthis niloticus (Nile rats. Laboratory mice were used as a positive control. Rodents were infected individually with 150 S. mansoni cercariae by tail immersion and housed for 8 week post-infection. The results reported that the Nile rats showed the highest number of worm burden (90 worms, while the Norway rats and the laboratory rats showed the lowest numbers among the tested species. This study also showed that the Nile rats, the house rats and the Norway rats yielded high number of eggs in the liver tissues. In contrast, the Cairo spiny mice, the black mice and albino rats yielded low number of eggs in the liver tissue. As compared to the permissive host albino mice, the Nile rats, the black mice, the Cairo spiny mice and the house rats showed comparable granuloma size. In contrast, albino rats and Norway rats showed a small granuloma size. Alltogether, these data showed that S. mansoni infection to these wild rodents was species dependant.

  17. Differences in Anticipatory Behaviour between Rats (Rattus norvegicus Housed in Standard versus Semi-Naturalistic Laboratory Environments.

    Directory of Open Access Journals (Sweden)

    I Joanna Makowska

    Full Text Available Laboratory rats are usually kept in relatively small cages, but research has shown that they prefer larger and more complex environments. The physiological, neurological and health effects of standard laboratory housing are well established, but fewer studies have addressed the sustained emotional impact of a standard cage environment. One method of assessing affective states in animals is to look at the animals' anticipatory behaviour between the presentation of a cue signalling the arrival of a reward and the arrival of that reward. The primary aim of this study was to use anticipatory behaviour to assess the affective state experienced by female rats a reared and housed long-term in a standard laboratory cage versus a semi-naturalistic environment, and b before and after treatment with an antidepressant or an anxiolytic. A secondary aim was to add to the literature on anticipatory behaviour by describing and comparing the frequency and duration of individual elements of anticipatory behaviour displayed by rats reared in these two systems. In all experiments, total behavioural frequency was higher in standard-housed rats compared to rats from the semi-naturalistic condition, suggesting that standard-housed rats were more sensitive to rewards and experiencing poorer welfare than rats reared in the semi-naturalistic environment. What rats did in anticipation of the reward also differed between housing treatments, with standard-housed rats mostly rearing and rats from the semi-naturalistic condition mostly sitting facing the direction of the upcoming treat. Drug interventions had no effect on the quantity or form of anticipatory behaviour, suggesting that the poorer welfare experienced by standard-housed rats was not analogous to depression or anxiety, or alternatively that the drug interventions were ineffective. This study adds to mounting evidence that standard laboratory housing for rats compromises rat welfare, and provides further

  18. NTP toxicity studies of toxicity studies of 2,4-decadienal (CAS No. 25152-84-5) administered by gavage to F344/N Rats and B6C3F1 mice.

    Science.gov (United States)

    Chan, P C

    2011-01-01

    at doses of 0, 50, 100, 200, 400, or 800 mg 2,4-decadienal/kg 5 days per week for 14 weeks. No chemical-related deaths occurred. Mean body weights of 400 mg/kg male rats and 800 mg/kg male and female rats and male mice were significantly less than those of the vehicle controls. Dosed male and female rats were lethargic after week 7; the severity of the lethargy was dose related. There were changes in the leukon of dosed rats compared to vehicle control rats characterized by decreased leukocyte, lymphocyte, and eosinophil counts and increased neutrophil counts. Spleen weights of 800 mg/kg female rats and thymus weights of 400 and 800 mg/kg female rats were significantly less than those of the vehicle controls. Thymus, spleen, testis, cauda epididymis, and epididymis weights of 800 mg/kg male rats were less than those of the vehicle controls. The incidences of epithelial hyperplasia of the forestomach were significantly greater in 400 and 800 mg/kg male and female rats, 200, 400, and 800 mg/kg male mice, and 800 mg/kg female mice than in the vehicle controls. Incidences of epithelial degeneration of the forestomach were significantly increased in 800 mg/kg rats and the incidence of chronic active inflammation of the forestomach was significantly increased in 800 mg/kg female rats. Incidences of exudate and olfactory epithelial atrophy of the nose were significantly increased in 800 mg/kg male rats, and incidences of olfactory epithelial necrosis occurred in 200 mg/kg or greater mice. Olfactory epithelial hydropic degeneration occurred in a single female mouse from the 100 mg/kg group. 2,4-Decadienal was not mutagenic in any of several strains of S. typhimurium tested with and without liver S9 activation enzymes. Acute bone marrow micronucleus tests in laboratory rodents administered 2,4-decadienal by intraperitoneal injection yielded mixed results. In male rats, a single injection of 2,4-decadienal gave a positive response, but no confirmatory trial was conducted. In

  19. [The development of grooming in the ontogeny of rats and mice].

    Science.gov (United States)

    Sviderskaia, G E; Dmitrieva, L E

    1993-01-01

    Experiments have been made on rats and mice within the first month of postnatal life. Common age dynamics of grooming reactions for these animals was shown which consists of a sharp intensification of grooming movements at the 3rd week, i.e. at the period of "behavioral arousal", as well as of heterochronous onset of different types of movements which results from successive maturation of the brain structures in which rhythmic centres of these movements are located. Quantitative differences in grooming of rats and mice are presumably due to ecological peculiarities of these animals. Periodic pattern of realization of grooming, as well as the parameters of its rhythmic components suggests that stereotype behavioural reactions are governed by mechanisms of autorhythmic excitation which are typical for the early stages of the development of the nervous system.

  20. Ultrastructural Study of Moniliformin Induced Lesions of Myocardium in Rats and Mice

    Institute of Scientific and Technical Information of China (English)

    ZhaoDeyu; FengQl; 等

    1993-01-01

    Effects of moliliformin on the ultrastructure of the myocardium of mice and rats were studies.Mice were given moniliformin orally at a dose of 29.46mg·kg-1 the LD50.One h after dosing,lesions of the mitochondria of the myocardial cells were found which became more severe in 2 and 3 h.Ultrastructrual olesions were also observed in the myofibrils and sarcolemma.Rats were given moniliformin orally at the dosage of 6mg·kg-1 once daily for 56d.Lesions of mitochondria and myofibrils were relatively mild.In the myocardiac specimens taken from the 21d post-toxin administration,lesions of the sarcolemma became more obvious.These moniliformin-induced lesions were simillar to the ultrastructural changes in the myocardium of patients with Keshan disease.Our findings indicate that there may be a close and important relationship between moniliformin intoxication and Keshan disease.

  1. Differential body weight and feeding responses to high-fat diets in rats and mice lacking cholecystokinin 1 receptors.

    Science.gov (United States)

    Bi, Sheng; Chen, Jie; Behles, R Ryan; Hyun, Jayson; Kopin, Alan S; Moran, Timothy H

    2007-07-01

    Prior data demonstrated differential roles for cholecystokinin (CCK)1 receptors in maintaining energy balance in rats and mice. CCK1 receptor deficiency results in hyperphagia and obesity of Otsuka Long-Evans Tokushima Fatty (OLETF) rats but not in mice. To ascertain the role of CCK1 receptors in high-fat-diet (HFD)-induced obesity, we compared alterations in food intake, body weight, fat mass, plasma glucose, and leptin levels, and patterns of hypothalamic gene expression in OLETF rats and mice lacking CCK1 receptors in response to a 10-wk exposure to HFD. Compared with Long-Evans Tokushima Otsuka (LETO) control rats, OLETF rats on HFD had sustained overconsumption over the 10-wk period. High fat feeding resulted in greater increases in body weight and plasma leptin levels in OLETF than in LETO rats. In situ hybridization determinations revealed that, while HFD reduced neuropeptide Y (NPY) mRNA expression in both the arcuate nucleus (Arc) and the dorsomedial hypothalamus (DMH) of LETO rats, HFD resulted in decreased NPY expression in the Arc but not in the DMH of OLETF rats. In contrast to these results in OLETF rats, HFD increased food intake and induced obesity to an equal degree in both wild-type and CCK1 receptor(-/-) mice. NPY gene expression was decreased in the Arc in response to HFD, but was not detectable in the DMH in both wild-type and CCK1 receptor(-/-) mice. Together, these data provide further evidence for differential roles of CCK1 receptors in the controls of food intake and body weight in rats and mice.

  2. Differences in xenobiotic detoxifying activities between bone marrow stromal cells from mice and rats: Implications for benzene-induced hematotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Hong; Li, Yunbo; Trush, M.A. [Johns Hopkins Univ. School of Hygiene and Public Health, Baltimore, MD (United States)

    1995-10-01

    benzene is a human carcinogen; exposure can result in aplastic anemia and leukemia. Data from animal models are frequently used in benzene risk assessment. In rodent studies, mice are more sensitive to benzene-induced hematotoxicity than rats. Bone marrow stromal cells from mice were significantly more susceptible to the cytotoxicity induced by the benzene metabolites hydroquinone (HQ) and benzoquinone (BQ) than cells from rats. Since cellular gluthathione (GSH) and quinone reductase (QR) are known to play critical roles in modulating HQ-induced cytotoxicity, the GSH content and the QR and glutathione S-transferase (GST) activity in stromal cells from both species was measured. In rat cells, the GSH content and the QR specific activity were 2 and 28 times as much as those from mice, respectively. GSH and QR in both mouse and rat stromal cells were inducible by 1,2-dithiole-3-thione (D3T). D3T pretreatment of both mouse and rat stromal cells resulted in a marked protection against HQ-induced toxicity. Pretreatment of both mouse and rat stromal cells with GSH ethyl ester also provided a dramatic protection against HQ-induced toxicity. Conversely, dicoumarol, an inhibitor of QR, enhanced the HQ-induced toxicity in stromal cells from both mice and rats, indicating an important role for QR in modulating HQ-induced stromal toxicity. Buthionine sulfoximine (BSO), which depleted GSH significantly in both species, potentiated the HQ-induced toxicity in mouse but not in rat stromal cells. Surprisingly, incubation of stromal cells with BSO resulted in a significant induction of QR, especially in rats. Overall, this study demonstrates that the differences in stromal cellular GSH content and QR activity between mice and rats contribute to their respective susceptibility to HQ-induced cytotoxicity in vitro, and may be involved in the greater in vivo sensitivity of mice to benzene-induced hematotoxicity. 51 refs., 9 figs., 1 tab.

  3. BACE1 across species: a comparison of the in vivo consequences of BACE1 deletion in mice and rats

    Science.gov (United States)

    Weber, Martin; Wu, Tiffany; Meilandt, William J.; Dominguez, Sara L.; Solanoy, Hilda O.; Maloney, Janice A.; Ngu, Hai; Baca, Miriam; Kung, Chung; Lima, Lisa; Earr, Timothy K.; Fleck, Daniel; Shields, Shannon D.; Forrest, William F.; Foreman, Oded; Warming, Søren; Watts, Ryan J.; Scearce-Levie, Kimberly

    2017-01-01

    Assessing BACE1 (β-site APP cleaving enzyme 1) knockout mice for general health and neurological function may be useful in predicting risks associated with prolonged pharmacological BACE1 inhibition, a treatment approach currently being developed for Alzheimer’s disease. To determine whether BACE1 deletion-associated effects in mice generalize to another species, we developed a novel Bace1−/− rat line using zinc-finger nuclease technology and compared Bace1−/− mice and rats with their Bace1+/+ counterparts. Lack of BACE1 was confirmed in Bace1−/− animals from both species. Removal of BACE1 affected startle magnitude, balance beam performance, pain response, and nerve myelination in both species. While both mice and rats lacking BACE1 have shown increased mortality, the increase was smaller and restricted to early developmental stages for rats. Bace1−/− mice and rats further differed in body weight, spontaneous locomotor activity, and prepulse inhibition of startle. While the effects of species and genetic background on these phenotypes remain difficult to distinguish, our findings suggest that BACE1’s role in myelination and some sensorimotor functions is consistent between mice and rats and may be conserved in other species. Other phenotypes differ between these models, suggesting that some effects of BACE1 inhibition vary with the biological context (e.g. species or background strain). PMID:28281673

  4. BACE1 across species: a comparison of the in vivo consequences of BACE1 deletion in mice and rats.

    Science.gov (United States)

    Weber, Martin; Wu, Tiffany; Meilandt, William J; Dominguez, Sara L; Solanoy, Hilda O; Maloney, Janice A; Ngu, Hai; Baca, Miriam; Kung, Chung; Lima, Lisa; Earr, Timothy K; Fleck, Daniel; Shields, Shannon D; Forrest, William F; Foreman, Oded; Warming, Søren; Watts, Ryan J; Scearce-Levie, Kimberly

    2017-03-10

    Assessing BACE1 (β-site APP cleaving enzyme 1) knockout mice for general health and neurological function may be useful in predicting risks associated with prolonged pharmacological BACE1 inhibition, a treatment approach currently being developed for Alzheimer's disease. To determine whether BACE1 deletion-associated effects in mice generalize to another species, we developed a novel Bace1(-/-) rat line using zinc-finger nuclease technology and compared Bace1(-/-) mice and rats with their Bace1(+/+) counterparts. Lack of BACE1 was confirmed in Bace1(-/-) animals from both species. Removal of BACE1 affected startle magnitude, balance beam performance, pain response, and nerve myelination in both species. While both mice and rats lacking BACE1 have shown increased mortality, the increase was smaller and restricted to early developmental stages for rats. Bace1(-/-) mice and rats further differed in body weight, spontaneous locomotor activity, and prepulse inhibition of startle. While the effects of species and genetic background on these phenotypes remain difficult to distinguish, our findings suggest that BACE1's role in myelination and some sensorimotor functions is consistent between mice and rats and may be conserved in other species. Other phenotypes differ between these models, suggesting that some effects of BACE1 inhibition vary with the biological context (e.g. species or background strain).

  5. Effect of genetic strain and gender on age-related changes in body composition of the laboratory rat.

    Data.gov (United States)

    U.S. Environmental Protection Agency — Body composition data for common laboratory strains of rat as a function of age. This dataset is associated with the following publication: Gordon , C., K. Jarema ,...

  6. Caloric restriction in lean and obese strains of laboratory rat: effects on body composition, metabolism, growth and overall health

    Data.gov (United States)

    U.S. Environmental Protection Agency — Data related to obese and lean strains of rat commonly used in the laboratory that are calorically restricted and its effects on physiologic parameters (Body...

  7. The impact of light, noise, cage cleaning and in-house transport on welfare and stress of laboratory rats

    National Research Council Canada - National Science Library

    Castelhano-Carlos, M J; Baumans, V

    2009-01-01

    ... stressor, the animal's wellbeing is threatened. This review article summarizes several published studies on the impact of environmental factors such as light, noise, cage cleaning and in-house transport on welfare and stress of laboratory rats...

  8. Ovariectomy and 17β-estradiol Replacement in Rats and Mice: A Visual Demonstration

    OpenAIRE

    Jakob O. Ström; Theodorsson, Annette; Ingberg, Edvin; Isaksson, Ida-Maria; Theodorsson, Elvar

    2012-01-01

    Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influen...

  9. [The evaluation of carcinogenic effect in rats and mice after intraperitoneal administration of refractory ceramic fibers].

    Science.gov (United States)

    Krajnow, A; Lao, I; Stetkiewicz, J; Wiecek, E

    1998-01-01

    The carcinogenic effect of Langfaser and Thermowool ceramic fibres was assessed in Wistar rats and BALB/C mice. Fibres were administered into the animal peritoneal cavity in doses of 25 and 5 mg, and the animals were left for survival. Langfaser and Thermowool ceramic fibres were found carcinogenic. The carcinogenic properties of Thermowool ceramic fibre can be compared to those of Krokidoit UICC asbestos.

  10. Different Subsets of Enteric Bacteria Induce and Perpetuate Experimental Colitis in Rats and Mice

    OpenAIRE

    Rath, Heiko C; Schultz, Michael; Freitag, René; Dieleman, Levinus A; Li, Fengling; Linde, Hans-Jörg; Schölmerich, Jürgen; Sartor, R. Balfour

    2001-01-01

    Resident bacteria are incriminated in the pathogenesis of experimental colitis and inflammatory bowel diseases. We investigated the relative roles of various enteric bacteria populations in the induction and perpetuation of experimental colitis. HLA-B27 transgenic rats received antibiotics (ciprofloxacin, metronidazole, or vancomycin-imipenem) in drinking water or water alone in either prevention or treatment protocols. Mice were treated similarly with metronidazole or vancomycin-imipenem bef...

  11. Cystic metacestodes of a rat-adapted Taenia taeniaeformis established in the peritoneal cavity of scid and nude mice.

    Science.gov (United States)

    Ito, A; Ma, L; Sato, Y

    1997-08-01

    In vitro-hatched (but not activated) oncospheres of a rat-adapted strain of Taenia taeniaeformis intraperitoneally inoculated into severe combined immunodeficiency (scid), congenitally athymic (nude) and immunocompetent (normal) female BALB/c mice developed into cystic metacestodes in the peritoneal cavity (but not in the liver) of scid and nude mice exclusively. This suggests that cystic metacestodes of this parasite, usually harboured in the liver only, can establish in scid and nude mice provided that the oncospheres are inoculated into the peritoneal cavity. Immunodeficient mice, especially scid mice, may be a good experimental animal model for the intermediate host of any taeniid species, of human, domestic- or wild-animal origin.

  12. Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F sub 1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Huff, J.E.; Haseman, J.K.; Eustis, S.; Maronpot, R.R. (National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)); DeMarini, D.M. (Environmental Protection Agency, Research Triangle Park, NC (USA)); Peters, A.C.; Persing, R.L. (Battelle Columbus Division, OH (USA)); Chrisp, C.E. (Univ. of Michigan, Ann Arbor (USA)); Jacobs, A.C. (Carltech Associates, Rockville, MD (USA))

    1989-07-01

    Toxicology and carcinogenesis studies of benzene were conducted in groups of 60 F344/N rats and 60 B6C3F{sub 1} mice of each sex for each of three exposure doses and vehicle controls. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations, on clinical pathologic findings and on body weight effects. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten animals in each of the 16 groups were killed at 12 months, and necropsies were performed. Hematologic profiles were performed at 3-month intervals. For the 2-year studies, mean body weights of the top dose groups of male rats and of both sexes of mice were lower than those of the controls. Survivals of the top dose group of rats and mice of each sex were reduced; however, at week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, Harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene in male F344/N rats, female F344/N rats, male B6C3F{sub 1} mice, and female B6C3F{sub 1} mice. Dose-related lymphocytopenia was observed for male and female F344/N rats and male and female B6C3F{sub 1} mice. These unequivocal observations show clearly that benzene is a trans-species, trans-sex, multisite potent carcinogen.

  13. Three distinct subsets of thymic epithelial cells in rats and mice defined by novel antibodies.

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    Yasushi Sawanobori

    Full Text Available AIM: Thymic epithelial cells (TECs are thought to play an essential role in T cell development and have been detected mainly in mice using lectin binding and antibodies to keratins. Our aim in the present study was to create a precise map of rat TECs using antibodies to putative markers and novel monoclonal antibodies (i.e., ED 18/19/21 and anti-CD205 antibodies and compare it with a map from mouse counterparts and that of rat thymic dendritic cells. RESULTS: Rat TECs were subdivided on the basis of phenotype into three subsets; ED18+ED19+/-keratin 5 (K5+K8+CD205+ class II MHC (MHCII+ cortical TECs (cTECs, ED18+ED21-K5-K8+Ulex europaeus lectin 1 (UEA-1+CD205- medullary TECs (mTEC1s, and ED18+ED21+K5+K8dullUEA-1-CD205- medullary TECs (mTEC2s. Thymic nurse cells were defined in cytosmears as an ED18+ED19+/-K5+K8+ subset of cTECs. mTEC1s preferentially expressed MHCII, claudin-3, claudin-4, and autoimmune regulator (AIRE. Use of ED18 and ED21 antibodies revealed three subsets of TECs in mice as well. We also detected two distinct TEC-free areas in the subcapsular cortex and in the medulla. Rat dendritic cells in the cortex were MHCII+CD103+ but negative for TEC markers, including CD205. Those in the medulla were MHCII+CD103+ and CD205+ cells were found only in the TEC-free area. CONCLUSION: Both rats and mice have three TEC subsets with similar phenotypes that can be identified using known markers and new monoclonal antibodies. These findings will facilitate further analysis of TEC subsets and DCs and help to define their roles in thymic selection and in pathological states such as autoimmune disorders.

  14. Manual restraint and common compound administration routes in mice and rats.

    Science.gov (United States)

    Machholz, Elton; Mulder, Guy; Ruiz, Casimira; Corning, Brian F; Pritchett-Corning, Kathleen R

    2012-09-26

    Being able to safely and effectively restrain mice and rats is an important part of conducting research. Working confidently and humanely with mice and rats requires a basic competency in handling and restraint methods. This article will present the basic principles required to safely handle animals. One-handed, two-handed, and restraint with specially designed restraint objects will be illustrated. Often, another part of the research or testing use of animals is the effective administration of compounds to mice and rats. Although there are a large number of possible administration routes (limited only by the size and organs of the animal), most are not used regularly in research. This video will illustrate several of the more common routes, including intravenous, intramuscular, subcutaneous, and oral gavage. The goal of this article is to expose a viewer unfamiliar with these techniques to basic restraint and substance administration routes. This video does not replace required hands-on training at your facility, but is meant to augment and supplement that training.

  15. Comparative analysis of acid sphingomyelinase distribution in the CNS of rats and mice following intracerebroventricular delivery.

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    Christopher M Treleaven

    Full Text Available Niemann-Pick A (NPA disease is a lysosomal storage disorder (LSD caused by a deficiency in acid sphingomyelinase (ASM activity. Previously, we reported that biochemical and functional abnormalities observed in ASM knockout (ASMKO mice could be partially alleviated by intracerebroventricular (ICV infusion of hASM. We now show that this route of delivery also results in widespread enzyme distribution throughout the rat brain and spinal cord. However, enzyme diffusion into CNS parenchyma did not occur in a linear dose-dependent fashion. Moreover, although the levels of hASM detected in the rat CNS were determined to be within the range shown to be therapeutic in ASMKO mice, the absolute amounts represented less than 1% of the total dose administered. Finally, our results also showed that similar levels of enzyme distribution are achieved across rodent species when the dose is normalized to CNS weight as opposed to whole body weight. Collectively, these data suggest that the efficacy observed following ICV delivery of hASM in ASMKO mice could be scaled to CNS of the rat.

  16. Intrahepatic Vascular Anatomy in Rats and Mice--Variations and Surgical Implications.

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    Constanze Sänger

    Full Text Available The intra-hepatic vascular anatomy in rodents, its variations and corresponding supplying and draining territories in respect to the lobar structure of the liver have not been described. We performed a detailed anatomical imaging study in rats and mice to allow for further refinement of experimental surgical approaches.LEWIS-Rats and C57Bl/6N-Mice were subjected to ex-vivo imaging using μCT. The image data were used for semi-automated segmentation to extract the hepatic vascular tree as prerequisite for 3D visualization. The underlying vascular anatomy was reconstructed, analysed and used for determining hepatic vascular territories.The four major liver lobes have their own lobar portal supply and hepatic drainage territories. In contrast, the paracaval liver is supplied by various small branches from right and caudate portal veins and drains directly into the vena cava. Variations in hepatic vascular anatomy were observed in terms of branching pattern and distance of branches to each other. The portal vein anatomy is more variable than the hepatic vein anatomy. Surgically relevant variations were primarily observed in portal venous supply.For the first time the key variations of intrahepatic vascular anatomy in mice and rats and their surgical implications were described. We showed that lobar borders of the liver do not always match vascular territorial borders. These findings are of importance for the design of new surgical procedures and for understanding eventual complications following hepatic surgery.

  17. Opioid microinjection into raphe magnus modulates cardiorespiratory function in mice and rats.

    Science.gov (United States)

    Hellman, Kevin M; Mendelson, Scott J; Mendez-Duarte, Marco A; Russell, James L; Mason, Peggy

    2009-11-01

    The raphe magnus (RM) participates in opioid analgesia and contains pain-modulatory neurons with respiration-related discharge. Here, we asked whether RM contributes to respiratory depression, the most prevalent lethal effect of opioids. To investigate whether opioidergic transmission in RM produces respiratory depression, we microinjected a mu-opioid receptor agonist, DAMGO, or morphine into the RM of awake rodents. In mice, opioid microinjection produced sustained decreases in respiratory rate (170 to 120 breaths/min), as well as heart rate (520 to 400 beats/min). Respiratory sinus arrhythmia, indicative of enhanced parasympathetic activity, was prevalent in mice receiving DAMGO microinjection. We performed similar experiments in rats but observed no changes in breathing rate or heart rate. Both rats and mice experienced significantly more episodes of bradypnea, indicative of impaired respiratory drive, after opioid microinjection. During spontaneous arousals, rats showed less tachycardia after opioid microinjection than before microinjection, suggestive of an attenuated sympathetic tone. Thus, activation of opioidergic signaling within RM produces effects beyond analgesia, including the unwanted destabilization of cardiorespiratory function. These adverse effects on homeostasis consequent to opioid microinjection imply a role for RM in regulating the balance of sympathetic and parasympathetic tone.

  18. Hypoglycemic action of chicken meat extract in type-2 diabetic KKAy mice and GK rats.

    Science.gov (United States)

    Sim, Meng-Kwoon; Wong, Yong-Chiat; Xu, Xiao-Guang; Sim, Sai-Zhen; Tsi, Daniel

    2009-12-01

    This study researched the effects of chicken meat extract on blood glucose and insulin level, membrane glucose transporter-4 (GLUT4), and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in type 2 diabetic KKAy mice and GK rats. Eight-week-old KKAy mice and GK rats and euglycemic control animals, C57BL/6J mice and Wistar rats, were orally administered a liquid commercial chicken meat extract, BRAND'S Essence of Chicken (BEC), for up to 8 weeks. BEC (1.5 ml/kg) had no effect on blood insulin levels, but significantly lessened the hyperglycemia in the diabetic animals. In the BEC-treated diabetic animals, insulin induced a significant increase in plasma membrane GLUT4 and cytosolic tyrosine-phosphorylated IRS-1, indicating that it attenuates insulin resistance. The present findings are the first demonstration of the hypoglycemic action of a dietary protein, and they lend credence to the reported benefits of using chicken meat as a source of protein in the dietary management of diabetic individuals.

  19. Worm burdens in outbred and inbred laboratory rats with morphometric data on Syphacia muris (Yamaguti, 1935 Yamaguti, 1941 (Nematoda, Oxyuroidea

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    Roberto Magalhães Pinto

    2001-01-01

    Full Text Available Syphacia muris worm burdens were evaluated in the rat Rattus norvegicus of the strains Wistar (outbred, Low/M and AM/2/Torr (inbred, maintained conventionally in institutional animal houses in Brazil. Morphometrics and illustration data for S. muris recovered from Brazilian laboratory rats are provided for the first time since its proposition in 1935.

  20. Advantame sweetener preference in C57BL/6J mice and Sprague-Dawley rats.

    Science.gov (United States)

    Sclafani, Anthony; Ackroff, Karen

    2015-03-01

    Advantame is a new ultrahigh-intensity noncaloric sweetener derived from aspartame and approved for human use. Rats and mice are not attracted to the taste of aspartame and this study determined their preference for advantame. In 24-h choice tests with water, C57BL/6J mice and Sprague-Dawley rats were indifferent to advantame at concentrations of 0.01, 0.03, and 0.1mM but significantly preferred 0.3 and 1mM advantame to water. Both species also preferred 1mM advantame to 1mM saccharin in direct choice tests, but preferred 10mM saccharin to 1mM advantame, which is near the solubility limit for this sweetener. Mice also preferred 1mM advantame to 1mM sucralose or acesulfame K, but preferred both sweeteners at 10mM to 1mM advantame. In addition, mice preferred 1mM advantame to 1 and 10mM aspartame. Thus, advantame is a potent sweetener for rodents but, because of limited solubility, is not an effective alternative to saccharin, sucralose, or acesulfame K at higher concentrations.

  1. Metabolism and excretion of the novel bioreductive prodrug PR-104 in mice, rats, dogs, and humans.

    Science.gov (United States)

    Gu, Yongchuan; Atwell, Graham J; Wilson, William R

    2010-03-01

    PR-104 is the phosphate ester of a 3,5-dinitrobenzamide nitrogen mustard (PR-104A) that is reduced to active hydroxylamine and amine metabolites by reductases in tumors. In this study, we evaluate the excretion of [(3)H]PR-104 in mice and determine its metabolite profile in mice, rats, dogs, and humans after a single intravenous dose. Total radioactivity was rapidly and quantitatively excreted in mice, with cumulative excretion of 46% in urine and 50% in feces. The major urinary metabolites in mice were products from oxidative N-dealkylation and/or glutathione conjugation of the nitrogen mustard moiety, including subsequent mercapturic acid pathway metabolites. A similar metabolite profile was seen in mouse bile, mouse plasma, and rat urine and plasma. Dogs and humans also showed extensive thiol conjugation but little evidence of N-dealkylation. Humans, like rodents, showed appreciable reduced metabolites in plasma, but concentrations of the cytotoxic amine metabolite (PR-104M) were higher in mice than humans. The most conspicuous difference in metabolite profile was the much more extensive O-beta-glucuronidation of PR-104A in dogs and humans than in rodents. The structure of the O-beta-glucuronide (PR-104G) was confirmed by independent synthesis. Its urinary excretion was responsible for 13 +/- 2% of total dose in humans but only 0.8 +/- 0.1% in mice. Based on these metabolite profiles, biotransformation of PR-104 in rodents is markedly different from that in humans, suggesting that rodents may not be appropriate for modeling human biotransformation and toxicology of PR-104.

  2. TRIGEMINAL UPTAKE AND CLEARANCE OF INHALED MANGANESECHLORIDE IN RATS AND MICE

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, J; Bench, G; Myers, O; Tinner, B; Staines, W; Barr, E; Divine, K K; Barrington, W; Karlsson, J

    2003-12-09

    Inhaled manganese (Mn) can enter the olfactory bulbs via the olfactory epithelium, and can then be further transported trans-synaptically to deeper brain structures. In addition to olfactory neurons, the nasal cavity is innervated by the maxillary division of the trigeminal nerve that projects to the spinal trigeminal nucleus. Direct uptake and transport of inhaled metal particles in the trigeminal system has not been investigated previously. We studied the uptake, deposition, and clearance of soluble Mn in the trigeminal system following nose-only inhalation of environmentally relevant concentrations. Rats and mice were exposed for 10 days (6 hours/day, 5 days/week) to air or MnCl2 aerosols containing 2.3 {+-} 1.3mg Mn/m{sup 3} with mass median aerodynamic diameter (MMAD) of 3.1 {+-} 1.4 {micro}m for rats and 2.0 {+-} 0.09 mg Mn/m{sup 3} MnCl{sup 2} with MMAD of 1.98 {+-} 0.12 {micro}m for mice. Mn concentrations in the trigeminal ganglia and spinal trigeminal nucleus were measured 2 hours (0 day), 7, 14, or 30 days post-exposure using Proton Induced X-ray Emission (PIXE). Manganese-exposed rats and mice showed statistically elevated levels of Mn in trigeminal ganglia 0, 7 and 14 days after the 10 day exposure period when compared to control animals. The Mn concentration gradually decreased over time with a clearance rate (t{sub 1/2}) of 7-8 days. Rats and mice were similar in both average accumulated Mn levels in trigeminal ganglia and in rates of clearance. We also found a small but significant elevation of Mn in the spinal trigeminal nucleus of mice 7 days post-exposure and in rats 0 and 7 days post-exposure. Our data demonstrate that the trigeminal nerve can serve as a pathway for entry of inhaled Mn to the brain in rodents following nose-only exposure and raise the question of whether entry of toxicants via this pathway may contribute to development of neurodegenerative diseases.

  3. Assessing pharmacokinetics of different doses of fosfomycin in laboratory rats enables adequate exposure for pharmacodynamic models.

    Science.gov (United States)

    Poeppl, Wolfgang; Lingscheid, Tilman; Bernitzky, Dominik; Donath, Oliver; Reznicek, Gottfried; Zeitlinger, Markus; Burgmann, Heinz

    2014-01-01

    Fosfomycin has been the subject of numerous pharmacodynamic in vivo models in recent years. The present study set out to determine fosfomycin pharmacokinetics in laboratory rats to enable adequate dosing regimens in future rodent models. Fosfomycin was given intraperitoneally as single doses of 75, 200 and 500 mg/kg bodyweight to 4 Sprague-Dawley rats per dose group. Blood samples were collected over 8 h and fosfomycin concentrations were determined by HPLC-mass spectrometry. Fosfomycin showed a dose-proportional pharmacokinetic profile indicated by a correlation of 0.99 for maximum concentration and area under the concentration-time curve (AUC). The mean AUC0-8 after intraperitoneal administration of 75, 200 or 500 mg/kg bodyweight fosfomycin were 109.4, 387.0 and 829.1 µg·h/ml, respectively. In conclusion, a dosing regimen of 200-500 mg/kg 3 times daily is appropriate to obtain serum concentrations in laboratory rats, closely mimicking human serum concentrations over time.

  4. Seasonal variations of gonadotropins and prolactin in the laboratory rat. Role of maternal pineal gland.

    Science.gov (United States)

    Vázquez, N; Díaz, E; Fernández, C; Jiménez, V; Esquifino, A; Díaz, B

    2007-01-01

    The laboratory rat, a non-photoperiodic rodent, exhibits seasonal fluctuations of melatonin. Melatonin has been found to be readily transferred from the maternal to the fetal circulation. No data exist on the possible influence of maternal pineal gland upon seasonal variations of the offspring. The aim of the present study was to asses the influence of the maternal melatonin rhythm on the offspring postnatal development of the reproductive hormones LH, FSH and prolactin. Male offspring from control, pinealectomized (PIN-X) and PIN-X + melatonin (PIN-X+MEL) mother Wistar rats were studied at 21, 31, and 60 days of age. Seasonal age-dependent variations were found for all hormones studied in control offspring but PIN-X offspring showed a tendency to have reduced duration or altered seasonal variations. Maternal melatonin treatment to PIN-X mothers partially restored the effect of pinealectomy. The chronological study of LH, FSH, and prolactin in PIN-X offspring also showed an altered pattern as compared to control-offspring. Melatonin treatment to the mothers partially restored the developmental pattern of reproductive hormones. Results of this study indicate that maternal pineal gland of the laboratory rat is involved in the seasonal postnatal development variations of reproductive hormones of the offspring.

  5. Genetic effects of acute spermatogonial x-irradiation of the laboratory rat

    Energy Technology Data Exchange (ETDEWEB)

    Chambers, J.R.; Chapman, A.B.

    1977-02-01

    The genetic effects of one generation of spermatogonial x-irradiation in rats, by a single dose of 600 r in one experiment and by a fractionated dose of 450 r in another, were measured in three generations of their descendants. Estimates of dominant lethal mutation rates, (2 to 3) x 10/sup -4//gamete/r, from litter size differences between irradiated and nonirradiated stock were consistent with previous estimates from rats and mice. Similar consistency was found for estimates of sex-linked recessive mutation rates, (1 to 2) x 10/sup -4/ chromosome/r, from male proportions within strains; however, when measured in crossbreds the proportion of males was higher in the irradiated than in the nonirradiated lines. This inconsistency in results is in keeping with the contradictory results reported for recessive sex-linked lethal mutation rates in mice. The effects used to estimate recessive lethal mutation rates which were unusually high, (2 to 14) x 10/sup -4//gamete/r, were not significant. Other factors that could have contributed to the observed effects are postulated.

  6. Continuous feed medication with nitroscanate for the removal of Hymenolepis nana in naturally infected mice and rats.

    Science.gov (United States)

    Gönenç, B; Sarimehmetoğlu, H O

    2001-10-01

    In this study, the effects of nitroscanate were investigated in naturally acquired Hymenolepis nana infections in rats and mice. The natural infection was determined by centrifugal flotation technique of faeces. The infected rats and mice were divided into two treatment and two control groups (N = 10). Nitroscanate at the dose of 50 mg/kg per day was given in the diet for 4 days. The rats and mice of treatment groups were necropsied on 7th day after the last treatment together with those of control groups. Following necrospsy, in the treatment group a geometric mean of 1.07 Hymenolepis nana were recovered out of ten mice, compared with 8.14 in the control group. In the rat treatment group no Hymenolepis nana were found in ten rats, while the control group showed a geometric mean of 6.23. Nitroscanate was found to be effective 100% and 86.8% at the treatment of H. nana infection in rats and mice respectively.

  7. 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.

  8. Preliminary results of orthotopic en bloc uterus and ovary transplantation in the laboratory rat.

    Science.gov (United States)

    Motoc, A; Jiga, L; Ionac, M; Raica, M; Motoc, M; Chiovschi, S

    2003-01-01

    A new experimental model of whole uterus and ovary transplantation in the laboratory rat was achieved. The main goals of this study were concerned with developing and standardizing the microsurgical technique of uterus transplantation in rats and observing the particular cellular patterns of acute allograft rejection at the level of the transplanted graft. Thirty-five orthotopic uterus transplantations were performed. An additional 20 female rats were used for dissection training sessions. Recipients were euthanasied at 24 hours, 48 hours and 72 hours. Immediate postoperative survival was 100%. Patency of the microsurgical anastomoses, checked at 24 hours, was 100%. At 72 hours thrombosis occurred in all anastomoses. The explanted uterine grafts were fixed in formaline and analyzed under light microscopy and specific imunohistochemical analysis. The acute allograft rejection has a particular cellular reaction pattern, probably due to the unique diversity of the tissues that compose it. Inflammatory cells like LTCD8+, LBCD20+ and mastocytes tend to agglomerate in the vicinity of nervous and vascular structures, showing no signs of lymphoid tissue disposition like in typical acute rejection. Uterus transplantation in rats has proven to be a valid experiment that allows us to express hope that by further research on transplantation of the uterus gynecologists will be able to introduce an adapted technique in the treatment of specific cases of human female infertility.

  9. Electroacupuncture at ST37 Enhances Jejunal Motility via Excitation of the Parasympathetic System in Rats and Mice

    Science.gov (United States)

    Yuan, Mengqian; Li, Yuqin; Wang, Yidan; Zhang, Na; Hu, XuanMing; Yin, Yin; Zhu, Bing

    2016-01-01

    Background. The roles of the sympathetic and parasympathetic systems in mediating the effect of electroacupuncture (EA) at ST37 on jejunal motility have yet to be demonstrated. Aim. We used rats and mice to investigate the effect and mechanism of action of EA at ST37 on jejunal motility. Methods. Jejunal motility was recorded by a balloon placed in the jejunum and connected to a biological signal collection system through a transducer. The effects of EA (3 mA) at ST37 were evaluated in Sprague-Dawley rats without drugs and with the administration of clenbuterol, propranolol, acetylcholine, and atropine. Further, the efficacy of EA at different intensities (1/2/4/6/8 mA) was measured in wild-type mice and β1β2−/− mice and M2M3−/− mice. Results. In Sprague-Dawley rats, the excitatory effect of EA at ST37 on jejunal motility disappeared in the presence of the muscarinic receptor antagonist atropine. EA at ST37 was less effective in M2M3−/− mice than in wild-type mice. Furthermore, to a certain extent, there existed “intensity-response” relationship between jejunal motility and EA. Conclusions. EA at ST37 can enhance jejunal motility in rats and mice mainly via excitation of the parasympathetic pathway. There is an “intensity-response” relationship between EA and effect on jejunal motility.

  10. Metabolism and excretion of canagliflozin in mice, rats, dogs, and humans.

    Science.gov (United States)

    Mamidi, Rao N V S; Cuyckens, Filip; Chen, Jie; Scheers, Ellen; Kalamaridis, Dennis; Lin, Ronghui; Silva, Jose; Sha, Sue; Evans, David C; Kelley, Michael F; Devineni, Damayanthi; Johnson, Mark D; Lim, Heng Keang

    2014-05-01

    Canagliflozin is an oral antihyperglycemic agent used for the treatment of type 2 diabetes mellitus. It blocks the reabsorption of glucose in the proximal renal tubule by inhibiting the sodium-glucose cotransporter 2. This article describes the in vivo biotransformation and disposition of canagliflozin after a single oral dose of [(14)C]canagliflozin to intact and bile duct-cannulated (BDC) mice and rats and to intact dogs and humans. Fecal excretion was the primary route of elimination of drug-derived radioactivity in both animals and humans. In BDC mice and rats, most radioactivity was excreted in bile. The extent of radioactivity excreted in urine as a percentage of the administered [(14)C]canagliflozin dose was 1.2%-7.6% in animals and approximately 33% in humans. The primary pathways contributing to the metabolic clearance of canagliflozin were oxidation in animals and direct glucuronidation of canagliflozin in humans. Unchanged canagliflozin was the major component in systemic circulation in all species. In human plasma, two pharmacologically inactive O-glucuronide conjugates of canagliflozin, M5 and M7, represented 19% and 14% of total drug-related exposure and were considered major human metabolites. Plasma concentrations of M5 and M7 in mice and rats from repeated dose safety studies were lower than those in humans given canagliflozin at the maximum recommended dose of 300 mg. However, biliary metabolite profiling in rodents indicated that mouse and rat livers had significant exposure to M5 and M7. Pharmacologic inactivity and high water solubility of M5 and M7 support glucuronidation of canagliflozin as a safe detoxification pathway.

  11. Comparative pulmonary toxicity of inhaled metalworking fluids in rats and mice.

    Science.gov (United States)

    Ryan, Kristen R; Cesta, Mark F; Herbert, Ronald; Brix, Amy; Cora, Michelle; Witt, Kristine; Kissling, Grace; Morgan, Daniel L

    2017-05-01

    Metalworking fluids (MWFs) are complex formulations designed for effective lubricating, cooling, and cleaning tools and parts during machining operations. Adverse health effects such as respiratory symptoms, dermatitis, and cancer have been reported in workers exposed to MWFs. Several constituents of MWFs have been implicated in toxicity and have been removed from the formulations over the years. However, animal studies with newer MWFs demonstrate that they continue to pose a health risk. This investigation examines the hypothesis that unrecognized health hazards exist in currently marketed MWF formulations that are presumed to be safe based on hazard assessments of individual ingredients. In vivo 13-week inhalation studies were designed to characterize and compare the potential toxicity of four MWFs: Trim VX, Cimstar 3800, Trim SC210, and Syntilo 1023. Male and female Wistar Han rats or Fischer 344N/Tac rats and B6C3F1/N mice were exposed to MWFs via whole-body inhalation at concentrations of 0, 25, 50, 100, 200, or 400 mg/m(3) for 13 weeks, after which, survival, body and organ weights, hematology and clinical chemistry, histopathology, and genotoxicity were assessed following exposure. Although high concentrations were used, survival was not affected and toxicity was primarily within the respiratory tract of male and female rats and mice. Minor variances in toxicity were attributed to differences among species as well as in the chemical components of each MWF. Pulmonary fibrosis was present only in rats and mice exposed to Trim VX. These data confirm that newer MWFs have the potential to cause respiratory toxicity in workers who are repeatedly exposed via inhalation.

  12. Inhibition of the Prostaglandin Transporter PGT Lowers Blood Pressure in Hypertensive Rats and Mice.

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    Yuling Chi

    Full Text Available Inhibiting the synthesis of endogenous prostaglandins with nonsteroidal anti-inflammatory drugs exacerbates arterial hypertension. We hypothesized that the converse, i.e., raising the level of endogenous prostaglandins, might have anti-hypertensive effects. To accomplish this, we focused on inhibiting the prostaglandin transporter PGT (SLCO2A1, which is the obligatory first step in the inactivation of several common PGs. We first examined the role of PGT in controlling arterial blood pressure blood pressure using anesthetized rats. The high-affinity PGT inhibitor T26A sensitized the ability of exogenous PGE2 to lower blood pressure, confirming both inhibition of PGT by T26A and the vasodepressor action of PGE2 T26A administered alone to anesthetized rats dose-dependently lowered blood pressure, and did so to a greater degree in spontaneously hypertensive rats than in Wistar-Kyoto control rats. In mice, T26A added chronically to the drinking water increased the urinary excretion and plasma concentration of PGE2 over several days, confirming that T26A is orally active in antagonizing PGT. T26A given orally to hypertensive mice normalized blood pressure. T26A increased urinary sodium excretion in mice and, when added to the medium bathing isolated mouse aortas, T26A increased the net release of PGE2 induced by arachidonic acid, inhibited serotonin-induced vasoconstriction, and potentiated vasodilation induced by exogenous PGE2. We conclude that pharmacologically inhibiting PGT-mediated prostaglandin metabolism lowers blood pressure, probably by prostaglandin-induced natriuresis and vasodilation. PGT is a novel therapeutic target for treating hypertension.

  13. Comparison of hepatotoxicity and metabolism of butyltin compounds in the liver of mice, rats and guinea pigs

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, Shunji; Kashimoto, Takashige; Susa, Nobuyuki; Ishii, Masamitsu; Chiba, Toshikazu [Laboratory of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23-35-1, 034-8628, Towada-shi, Aomori (Japan); Mutoh, Ken-ichiro [Laboratory of Veterinary Anatomy, School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23-35-1, 034-8628, Towada-shi, Aomori (Japan); School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23-35-1, 034-8628, Towada-shi, Aomori (Japan); Hoshi, Fumio [Laboratory of Veterinary Anatomy, School of Veterinary Medicine and Animal Sciences, Kitasato University, Higashi 23-35-1, 034-8628, Towada-shi, Aomori (Japan); Suzuki, Takashi [Laboratory of Environmental Health and Toxicology, Kyoto Prefectural University, Hangi-cho, Shimogamo, Sakyo-ku, 606-5822, Kyoto (Japan); Sugiyama, Masayasu [Sugiyama Pharmacy, 1335-1 Shimotama, Tamagawa-cho, 759-3112, Yamaguchi (Japan)

    2003-03-01

    The hepatotoxicity of tributyltin chloride (TBTC) and dibutyltin dichloride (DBTC) was compared among mice, rats and guinea pigs in vivo. Further, the metabolism of these butyltin compounds in the liver was also investigated in these species. The oral administration of TBTC and DBTC to mice induced obvious liver injury, as demonstrated by both serodiagnosis and histopathological diagnosis. The concentrations of TBTC and DBTC that induced hepatotoxicity in mice at 24 h after oral administration were 180 and 60 {mu}mol/kg, respectively. In the case of rats, the liver injury induced by TBTC and DBTC was detected at 24 h by the serodiagnosis, but not by histopathological diagnosis. On the other hand, in guinea pigs, TBTC and DBTC administration did not produce any clear liver injury at 24 h, as evaluated by these two diagnostic methods. Thus, the following ranking was obtained with regard to increasing order of sensitivity to liver injury caused by TBTC and DBTC: mice, rats and guinea pigs. The total butyltin contents in the liver of mice were equivalent at 3 h and 24 h after the administration of TBTC or DBTC; however, the contents in the liver of rats and guinea pigs were relatively lower at 3 h and higher at 24 h than those of mice, although there were no differences between rats and guinea pigs in the total liver butyltin content. Concerning the liver metabolism of these butyltin compounds, the main form of butyltin compounds in these animals treated with TBTC was DBTC within 3 h after oral administration, while the main metabolites at 24 h were different in each species, indicating that the liver metabolism of TBTC might vary by animal type. When the animals were treated with DBTC orally, DBTC was hardly metabolized in the livers of these animals even at 24 h, and the liver levels of DBTC were two times greater in mice and guinea pigs than in rats at 3 h and were lower in mice at 24 h than in rats and guinea pigs. The analysis of cellular distributions of DBTC in

  14. Chemistry of clitoral gland secretions of the laboratory rat: Assessment of behavioural response to identified compounds

    Indian Academy of Sciences (India)

    S Kannan; G Archunan

    2001-06-01

    The present investigations were carried out to find out the chemical nature of clitoral gland extracts and their involvement in reproductive and social behaviour. Homogenates of clitoral glands of mature estrous female rats were extracted with -hexane and dichloromethane (1 : 1 ratio v/v) and analysed by gas chromatography linked mass spectrometry (GC-MS). Three peaks were found to be in higher concentration, which were identified as 6,11-dihydro-dibenz-b,e-oxepin-11-one (I); 2,6,10-dodecatrien-1-ol-3,7,11-trimethyl(Z) (II); and 1,2-benzene-dicarboxylic acid butyl(2-ethylpropyl) ester (III).Odour preference tests demonstrated that the first compound attracted conspecifics of the opposite sex. By contrast, the second and third compounds were found to attract both sexes. The results conclude that the clitoral gland of laboratory rat contains three major chemical compounds which have a unique function in maintaining social and reproductive status.

  15. Mathematical modeling of convective air drying of quinoa-supplemented feed for laboratory rats

    Directory of Open Access Journals (Sweden)

    Antonio Vega-Gálvez

    2011-02-01

    Full Text Available Drying kinetics of quinoa-supplemented feed for laboratory rats during processing at 50, 60, 70, 80 and 90ºC was studied and modeled in this work. Desorption isotherm was obtained at 60ºC giving a monolayer moisture content of 0.04 g water/g d.m. The experimental drying curves showed that drying process took place only in the falling rate period. Several thin-layer drying equations available in the literature were evaluated based on determination coefficient (r², sum squared errors (SSE and Chi-square (χ2 statisticals. In comparison to the experimental moisture values, the values estimated with the Logarithmic model gave the best fit quality (r² >0.994, SSE < 0.00015 and χ2 < 0.00018, showing this equation could predict very accurately the drying time of rat feed under the operative conditions applied.

  16. Illumination of murine gammaherpesvirus-68 cycle reveals a sexual transmission route from females to males in laboratory mice.

    Directory of Open Access Journals (Sweden)

    Sylvie François

    Full Text Available Transmission is a matter of life or death for pathogen lineages and can therefore be considered as the main motor of their evolution. Gammaherpesviruses are archetypal pathogenic persistent viruses which have evolved to be transmitted in presence of specific immune response. Identifying their mode of transmission and their mechanisms of immune evasion is therefore essential to develop prophylactic and therapeutic strategies against these infections. As the known human gammaherpesviruses, Epstein-Barr virus and Kaposi's Sarcoma-associated Herpesvirus are host-specific and lack a convenient in vivo infection model; related animal gammaherpesviruses, such as murine gammaherpesvirus-68 (MHV-68, are commonly used as general models of gammaherpesvirus infections in vivo. To date, it has however never been possible to monitor viral excretion or virus transmission of MHV-68 in laboratory mice population. In this study, we have used MHV-68 associated with global luciferase imaging to investigate potential excretion sites of this virus in laboratory mice. This allowed us to identify a genital excretion site of MHV-68 following intranasal infection and latency establishment in female mice. This excretion occurred at the external border of the vagina and was dependent on the presence of estrogens. However, MHV-68 vaginal excretion was not associated with vertical transmission to the litter or with horizontal transmission to female mice. In contrast, we observed efficient virus transmission to naïve males after sexual contact. In vivo imaging allowed us to show that MHV-68 firstly replicated in penis epithelium and corpus cavernosum before spreading to draining lymph nodes and spleen. All together, those results revealed the first experimental transmission model for MHV-68 in laboratory mice. In the future, this model could help us to better understand the biology of gammaherpesviruses and could also allow the development of strategies that could prevent

  17. Helicobacter sp. MIT 01-6451 infection during fetal and neonatal life in laboratory mice.

    Science.gov (United States)

    Yamanaka, Hitoki; Nakanishi, Tai; Takagi, Toshikazu; Ohsawa, Makiko; Kubo, Noriaki; Yamamoto, Naoto; Takemoto, Takahira; Ohsawa, Kazutaka

    2015-01-01

    Helicobacter sp. MIT 01-6451 has been detected in SPF mice kept in Japan. To characterize strain MIT 01-6451, its infection route during fetal and neonatal life and effects on pregnancy were investigated using immunocompetent and immunodeficient mouse strains (BALB/c, C57BL/6, and SCID). MIT 01-6451 was detected in the uterus, vagina, and mammary glands of 50% of infected SCID mice, whereas these tissues were all negative in immunocompetent mice. No fetal infections with MIT 01-6451 were detected at 16-18 days after pregnancy in any mouse strain. In newborn mice, MIT 01-6451 was detected in intestinal tissue of C57BL/6 and SCID mice at 9-11 days after birth, but not in BALB/c mice. The IgA and IgG titers to MIT 01-6451 in sera of C57BL/6 female mice were significantly lower than those of BALB/c mice. Although no significant differences in the number of newborns per litter were observed between MIT 01-6451-infected and MIT 01-6451-free dams, the birth rate was lower in infected SCID mice than in control SCID mice. The present results indicated that MIT 01-6451 infects newborn mice after birth rather than by vertical transmission to the fetus via the placenta and that MIT 01-6451 infection shows opportunistically negative effects on the birth rate. In addition, the maternal immune response may affect infection of newborn mice with MIT 01-6451 through breast milk.

  18. CM 40907: a structurally novel anticonvulsant in mice, rats and baboons

    Energy Technology Data Exchange (ETDEWEB)

    Chambon, J.P.; Brochard, J.; Hallot, A.; Heaulme, M.; Brodin, R.; Roncucci, R.; Biziere, K.

    1985-06-01

    CM 40907 (3-(4-hydroxypiperidyl)-6-(2'-chlorophenyl)-pyridazine) is a chemically original compound which possesses the pharmacological properties of a potent, p.o. active anticonvulsant. The anticonvulsant activity of CM 40907 was examined in mice, rats and photosensitive Papio-papio baboons and compared to that of phenobarbital, diphenylhydantoin, carbamazepine, sodium valproate and ethosuximide. In mice, CM 40907 antagonized electroconvulsive shock and chemically induced seizures with an overall potency comparable to that of carbamazepine and a therapeutic ratio (ED50 rotorod/ED50 electroshock) superior to that of ethosuximide, sodium valproate, phenobarbital and carbamazepine. In the rat CM 40907 suppressed completed kindled amygdaloid seizures and was approximately as active as phenobarbital. In naturally photosensitive Senegalese Papio-papio baboons CM 40907 antagonized myoclonus and cortical paroxysmal discharges. In this model CM 40907 was approximately one-fourth as potent as phenobarbital, twice as potent as carbamazepine and 6 times more potent than sodium valproate. In mice CM 40907, at anticonvulsant doses, increased the affinity of (/sup 3/H)flunitrazepam for its central receptor site. Based on these results it is postulated that CM 40907 is a potent and relatively nonsedative anticonvulsant and may be of therapeutic benefit in epileptic disorders.

  19. Butylbenzyl phthalate hydrolysis in liver microsomes of humans, monkeys, dogs, rats and mice.

    Science.gov (United States)

    Takahara, Yuka; Kinashi, Yu; Takahara, Yuusuke; Hichiya, Hiroyuki; Okada, Kenji; Murata, Mikio; Shigeyama, Masato; Hanioka, Nobumitsu

    2014-01-01

    Butylbenzyl phthalate (BBzP) is used as a plasticizer to import flexibility to polyvinylchloride plastics. In this study, hydrolysis of BBzP to monobutyl phthalate (MBP) and monobenzyl phthalate (MBzP) in liver microsomes of humans, monkeys, dogs, rats and mice was examined. The kinetics for MBP formation by human, dog and mouse liver microsomes followed the Michaelis-Menten model, whereas the kinetics by monkey and rat liver microsomes fitted the Hill model. The kinetics for MBzP formation fitted the Hill model for all liver microsomes. The Vmax and in vitro clearance (CLint or CLmax) ratios of MBP/MBzP formation varied among animal species, although the Km for MBP and MBzP formation in each liver microsomes were generally comparable. The hydrolysis of BBzP to monoester phthalates in mammalian liver microsomes could be classified into two types: MBzP>MBP type for humans and dogs, and MBP>MBzP type for monkeys, rats and mice. These findings suggest that the formation profile of MBzP and MBP from BBzP by liver microsomes differs extensively among animal species.

  20. Sensory dynamics of intense microwave irradiation: A comparative study of aversive behaviors by mice and rats

    Energy Technology Data Exchange (ETDEWEB)

    Justesen, D.R.

    1981-10-01

    The results of two experiments are reported, the first on 24 mice and 14 rats, all experimentally naive, that were observed for evidence of adventitious escape from faradic shock or from a potentially lethal, 2450-MHz microwave field in a multi-mode cavity. All of ten rats irradiated at a whole-body-averaged dose rate of 60 mW/g convulsed and expired, presumably from radiation-induced hyperpyrexia. Eight of ten mice irradiated at 60 mW/g survived the four sessions of irradiation, but reliable evidence of escape learning was not observed. The data of the second experiment, which was a pilot study of four rats with an extensive history of exposure to intense but intermittently applied microwave fields, revealed that the animals learned to thermoregulate behaviorally by locomoting in and out of the safe-area circle. A strong relation between dose rate (30, 60, and 120 mW/g) and proportion of time spent in the safe area was observed (r = .97). Post-exposure means of colonic temperature during three sets of sessions under the different rates of energy dosing were highly stable and averaged 39.6 deg C.

  1. Accumulation of polychlorinated dibenzo-p-dioxins and dibenzofurans in liver of control laboratory rats.

    Science.gov (United States)

    Vanden Heuvel, J P; Clark, G C; Tritscher, A m; Lucier, G W

    1994-10-01

    Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls belong to a class of compounds, the polyhalogenated aromatic hydrocarbons (PHAHs), which are ubiquitous environmental contaminants. Due to the existence of a common mechanism of action, i.e., binding to the Ah receptor, the activity of members of this class of compounds is generally expressed relative to the prototypical 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as toxic equivalency factors (TEFs). In the present studies we examined the presence of liver of untreated PCDFs in standard laboratory feed and in the liver of untreated rats at three different ages (60, 140, and 200 days) in terms of concentration and in toxic equivalents (TEQs, TEF x concentration). Feed was shown to contain trace amounts of PCDDs and PCDFs and control rat liver was shown to contain several PCDD and PCDF congeners in terms of concentration of congener and concentration of TEQs contributed by that congener. The total concentration of TEQs increased with increasing age in rat liver, going from 20 ppt TEQ at 60 days to 78 ppt TEQ at 200 days of age. This accumulation in dioxin-like activity was due primarily to PCDFs. In particular the congener 2,3,4,7,8-pentachlorodibenzofuran accrued in untreated rat liver accounting for approximately 80% of the total TEQ at 200 days of age. These studies affirm the pervasive presence of PHAHs and suggest prudence in evaluating chronic rat studies in which interference from background levels of PCDDs and PCDFs may be a factor.

  2. Laser speckle-imaging of blood microcirculation in the brain cortex of laboratory rats in stress

    Energy Technology Data Exchange (ETDEWEB)

    Vilensky, M A; Semyachkina-Glushkovskaya, Oxana V; Timoshina, P A; Kuznetsova, Jana V; Semyachkin-Glushkovskii, I A; Agafonov, Dmitry N; Tuchin, Valerii V

    2012-06-30

    The results of experimental approbation of the method of laser full-field speckle-imaging for monitoring the changes in blood microcirculation state of the brain cortex of laboratory rats under the conditions of developing stroke and administration of vasodilating and vasoconstrictive agents are presented. The studies aimed at the choice of the optimal conditions of speckle-image formation and recording were performed and the software implementing an adaptive algorithm for processing the data of measurements was created. The transfer of laser radiation to the probed region of the biotissue was implemented by means of a silica-polymer optical fibre. The problems and prospects of speckle-imaging of cerebral microcirculation of blood in laboratory and clinical conditions are discussed.

  3. Metabolism and disposition of 1-bromopropane in rats and mice following inhalation or intravenous administration.

    Science.gov (United States)

    Garner, C E; Sumner, S C J; Davis, J G; Burgess, J P; Yueh, Y; Demeter, J; Zhan, Q; Valentine, J; Jeffcoat, A R; Burka, L T; Mathews, J M

    2006-08-15

    Workplace exposure to 1-bromopropane (1-BrP) can potentially occur during its use in spray adhesives, fats, waxes, and resins. 1-BrP may be used to replace ozone depleting solvents, resulting in an increase in its annual production in the US, which currently exceeds 1 million pounds. The potential for human exposure to 1-BrP and the reports of adverse effects associated with potential occupational exposure to high levels of 1-BrP have increased the need for the development of biomarkers of exposure and an improved understanding of 1-BrP metabolism and disposition. In this study, the factors influencing the disposition and biotransformation of 1-BrP were examined in male F344 rats and B6C3F1 mice following inhalation exposure (800 ppm) or intravenous administration (5, 20, and 100 mg/kg). [1,2,3-(13)C]1-BrP and [1-(14)C]1-BrP were administered to enable characterization of urinary metabolites using NMR spectroscopy, LC-MS/MS, and HPLC coupled radiochromatography. Exhaled breath volatile organic chemicals (VOC), exhaled CO(2), urine, feces, and tissues were collected for up to 48 h post-administration for determination of radioactivity distribution. Rats and mice exhaled a majority of the administered dose as either VOC (40-72%) or (14)CO(2) (10-30%). For rats, but not mice, the percentage of the dose exhaled as VOC increased between the mid ( approximately 50%) and high ( approximately 71%) dose groups; while the percentage of the dose exhaled as (14)CO(2) decreased (19 to 10%). The molar ratio of exhaled (14)CO(2) to total released bromide, which decreased as dose increased, demonstrated that the proportion of 1-BrP metabolized via oxidation relative to pathways dependent on glutathione conjugation is inversely proportional to dose in the rat. [(14)C]1-BrP equivalents were recovered in urine (13-17%, rats; 14-23% mice), feces (1-bromopropane to 1-bromo-2-propanol and bromoacetone and following subsequent glutathione conjugation with either of these compounds. Rats

  4. Opposite lipemic response of Wistar rats and C57BL/6 mice to dietary glucose or fructose supplementation.

    Science.gov (United States)

    Barbosa, C R; Albuquerque, E M V; Faria, E C; Oliveira, H C F; Castilho, L N

    2007-03-01

    The metabolic effects of carbohydrate supplementation in mice have not been extensively studied. In rats, glucose- and fructose-rich diets induce hypertriacylglycerolemia. In the present study, we compared the metabolic responses to two monosaccharide supplementations in two murine models. Adult male Wistar rats (N = 80) and C57BL/6 mice (N = 60), after 3 weeks on a standardized diet, were submitted to dietary supplementation by gavage with glucose (G) or fructose (F) solutions (500 g/L), 8 g/kg body weight for 21 days. Glycemia was significantly higher in rats after fructose treatment (F: 7.9 vs 9.3 mM) and in mice (G: 6.5 vs 10 and F: 6.6 vs 8.9 mM) after both carbohydrate treatments. Triacylglycerolemia increased significantly 1.5 times in rats after G or F supplementation. Total cholesterol did not change with G treatment in rats, but did decrease after F supplementation (1.5 vs 1.4 mM, P vs 1.4 and F: 1.9 vs 1.4 mM, P vs 2.5 mM, P glucose and fructose supplementation regarding serum triacylglycerol, free fatty acids, and insulin levels after monosaccharide treatment. Thus, while Wistar rats developed features of plurimetabolic syndrome, C57BL/6 mice presented changes in serum biochemical profile considered to be healthier for the cardiovascular system.

  5. 基于RFID的实验鼠种群溯源的数据结构与算法设计%DATA STRUCTURE AND ALGORITHM DESIGN OF POPULATIONS TRACEABILITY OF LABORATORY RATS BASED ON RFID

    Institute of Scientific and Technical Information of China (English)

    王劲松; 黄钢; 胡建华; 魏晓锋

    2013-01-01

    According to the biological characteristics of laboratory rats and the demand characteristics of data collection,we design the data structures and algorithms adapting to population traceability of laboratory rats,including the identity traceability of mice species,the source query of laboratory rats and the identity information queries such as the genetic background,etc.On the basis of “GB/T 20563-2006 RadioFrequency Identification of Animals-Code Structure”,in this article we complement the structure of recognition code to enable it to store more data,so as to meet the application of laboratory rats recognition and population traceability,etc.%根据实验鼠的生物学特性和数据采集需求特性,设计适用于实验鼠种群溯源的数据结构和算法,包括:鼠种身份追溯,实验鼠来源查询和遗传背景等身份信息查询.在《GB/T 20563-2006动物射频识别代码结构》的基础上,对识别代码结构进行补充,使得代码结构能存储更多的信息,以满足实验鼠的识别和种群溯源等应用.

  6. Stressful presentations: mild cold stress in laboratory mice influences phenotype of dendritic cells in naïve and tumor-bearing mice.

    Science.gov (United States)

    Kokolus, Kathleen M; Spangler, Haley M; Povinelli, Benjamin J; Farren, Matthew R; Lee, Kelvin P; Repasky, Elizabeth A

    2014-01-01

    The ability of dendritic cells (DCs) to stimulate and regulate T cells is critical to effective anti-tumor immunity. Therefore, it is important to fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily to model immune responses. The goals of this report are to 1) briefly summarize previous work revealing how DCs respond to various forms of physiological stress and 2) to present new data highlighting the potential for chronic mild cold stress inherent to mice housed at the required standard ambient temperatures to influence baseline DCs properties in naïve and tumor-bearing mice. As recent data from our group shows that CD8(+) T cell function is significantly altered by chronic mild cold stress and since DC function is crucial for CD8(+) T cell activation, we wondered whether housing temperature may also be influencing DC function. Here we report that there are several significant phenotypical and functional differences among DC subsets in naïve and tumor-bearing mice housed at either standard housing temperature or at a thermoneutral ambient temperature, which significantly reduces the extent of cold stress. The new data presented here strongly suggests that, by itself, the housing temperature of mice can affect fundamental properties and functions of DCs. Therefore differences in basal levels of stress due to housing should be taken into consideration when interpreting experiments designed to evaluate the impact of additional variables, including other stressors on DC function.

  7. Distribution of chiral PCBs in selected tissues in the laboratory rat

    Energy Technology Data Exchange (ETDEWEB)

    Lehmler, H.J.; Kania-Korwel, I.; Robertson, L.W. [Iowa Univ., Iowa City, IA (United States). Dept. of Occupational and Environmental Health; Avants, J.K.; Garrison, W.A. [U.S. Environmental Protection Agency, National Exposure Research Laboratory, Athens, GA (United States); Hornbuckle, K.C. [Iowa Univ., Iowa City, IA (United States). Dept. of Civil and Environmental Engineering; Sulkowski, W.W. [Silesian Univ., Katowice (Poland). Dept. of Environmental Chemistry and Technology

    2004-09-15

    Polychlorinated biphenyls (PCBs) were manufactured for a large number of technical applications including for use in transformers and capacitors. The widespread commercial utilization of PCBs and their persistence in the environment have resulted in their worldwide distribution. Physicochemical characteristics, such as lipophilicity and stability towards biological and thermal degradation, have resulted in their accumulation in the food chain, raising concerns about human health effects. Animal and epidemiological studies have implicated PCBs in a number of human disease processes, such as carcinogenesis and atherosclerosis. However, mechanisms of PCB toxicity are still poorly understood, partly because technical PCB products contain a complex mixture of the possible 209 PCB derivatives or congeners. One of the most intriguing, but frequently overlooked, aspects of PCB toxicity is related to the existence of chiral PCB congeners, possessing at least three ortho (to the biphenyl bridge) chlorine atoms. Racemic PCBs in this group have been implicated in developmental and neurotoxic effects. Two studies with individual congeners have shown that the (+)-enantiomer of PCB 844 and 1395 are selectively enriched in tissues, e.g. the liver, of laboratory animals. However, nothing is currently known about the distribution and enrichment of chiral PCBs after administration of a complex PCB mixture to laboratory animals such as the rat. The present study investigates the enantiomeric fraction of PCBs 91, 95 and 149 in male rats after administration of (a) Aroclor 1254 and (b) an environmental mixture obtained from soil contaminated with Chlorofen, a Polish PCB mixture.

  8. Capacitive Sensing for Non-Invasive Breathing and Heart Monitoring in Non-Restrained, Non-Sedated Laboratory Mice

    Directory of Open Access Journals (Sweden)

    Carlos González-Sánchez

    2016-07-01

    Full Text Available Animal testing plays a vital role in biomedical research. Stress reduction is important for improving research results and increasing the welfare and the quality of life of laboratory animals. To estimate stress we believe it is of great importance to develop non-invasive techniques for monitoring physiological signals during the transport of laboratory animals, thereby allowing the gathering of information on the transport conditions, and, eventually, the improvement of these conditions. Here, we study the suitability of commercially available electric potential integrated circuit (EPIC sensors, using both contact and contactless techniques, for monitoring the heart rate and breathing rate of non-restrained, non-sedated laboratory mice. The design has been tested under different scenarios with the aim of checking the plausibility of performing contactless capture of mouse heart activity (ideally with an electrocardiogram. First experimental results are shown.

  9. Hymenolepis nana: worm recovery from congenitally athymic nude and phenotypically normal rats and mice.

    Science.gov (United States)

    Ito, A; Kamiyama, T

    1984-10-01

    When eggs or mouse-derived cysticercoids of Hymenolepis nana were inoculated into previously uninfected congenitally athymic nude (rnu/rnu) rats of an outbred Rowett strain, they failed to mature in the intestinal lumen. They also failed to mature in phenotypically normal (rnu/+) littermates, except when these hosts were treated with cortisone acetate from the beginning of the lumen phase. The Rowett rat, either thymus-deficient or not, was susceptible to tissue cysticercoids but resistant to luminal adults. It is therefore considered to be an unnatural host, at least for mouse-derived H. nana. There was little or no difference in susceptibility to initial tissue cysticercoids between these nude rats and phenotypically normal ones. The normal rats became completely resistant to reinfection with eggs and no secondary cysticercoids developed in their intestinal tissue, whereas the nude rats showed unaltered susceptibility to secondary tissue cysticercoids. Thus, acquired resistance to egg challenge, assessed by the failure of tissue cysticercoid recovery, was thymus-dependent. However, innate resistance to both a primary egg dose, assessed by the low recovery rates of tissue cysticercoids, and to a primary cysticercoid dose, assessed by the failure of luminal adult recovery, were thymus-independent. The effect of cortisone acetate to initiate maturation of H. nana appeared to be unrelated to thymus function. In contrast, all mice, either thymus-deficient or not, were highly susceptible to both phases. The number of worms recovered was more than 10 times greater than that of cysticercoids established in the rat's intestinal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Toxicological and teratological studies of a rapeseed protein diet in rats and mice.

    Science.gov (United States)

    Sharpe, G L; Larsson, K S; Liedén, S A

    1975-01-01

    Pregnant Sprague-Dawley rats, a fed a rapeseed protein diet (containing 0.2 mg glucosinolates/g protein concentrate) from day 0, showed no teratological effects on the 18th day. However, rats which were permitted to deliver, developed anorexia and weight loss after day 18. A reddish discharge, not blood, from the nose stained the fur of most animals fed rapeseed protein. A similar discharge developed in dams fed on lab chow but fasted after day 18. At delivery, dams would neglect the newborn during the first 24 h but would then resume their diet and litter care. Surviving litters of rapeseed-fed animals were comparable to controls in weight after 3 weeks. Vitamin supplementation did not prevent these effects. Force feeding the diet by gavage aggravated these toxic effects and prolonged the gestation period. No toxic effects were seen until day 18 of gestation when the rapeseed protein diet was fed to rats 3--6 weeks before mating. Control rats given glucosinolates by gavage did not show any adverse effects. The rapeseed protein diet had no effect on NMRI mice during pregnancy and on litter care up to 3 weeks.

  11. Laxative and anti-diarrheal activity of polycarbophil in mice and rats.

    Science.gov (United States)

    Saito, Takaharu; Mizutani, Fujie; Iwanaga, Yuji; Morikawa, Kouji; Kato, Hideo

    2002-06-01

    We investigated the laxative and anti-diarrheal activity of polycarbophil, an insoluble hydrophilic polymer, in comparison with other agents used for treating functional bowel disorder (FBD). In naive rats, polycarbophil (500 mg/kg) increased fecal weight and water contents without producing diarrhea. Carboxymethylcellulose (CMC) did not produce evident changes in bowel movement. Picosulfate markedly produced diarrhea. Loperamide, trimebutine and granisetron decreased stool output dose-dependently. Constipation, indicated by decrease in fecal weight, was produced by loperamide and clonidine in rats. Polycarbophil (500 mg/kg) and CMC increased fecal weight without diarrhea. Conversely trimebutine further decreased fecal weight in constipated rats. Polycarbophil (500 mg/kg) suppressed diarrhea induced by castor oil, and at 250-500 mg/kg, it produced shaped stools in animals with stools loosened by prostaglandin E2, serotonin or carbachol in mice. Polycarbophil (500 mg/kg) also reduced stools in rats with stool output increased by wrap restraint stress (WRS). CMC had no effect in the diarrhea models, except for carbachol-induced diarrhea, and WRS-induced evacuation. Loperamide, trimebutine and granisetron inhibited diarrhea production and WRS-induced evacuation, except for carbachol-induced diarrhea. The results show that polycarbophil prevents constipation and diarrhea without inducing diarrhea or constipation, which is different from the other agents. Hydrophilic polymers such as polycarbophil will be promising agents for the treatment of FBD.

  12. Macrophage micro-RNA-155 promotes lipopolysaccharide-induced acute lung injury in mice and rats.

    Science.gov (United States)

    Wang, Wen; Liu, Zhi; Su, Jie; Chen, Wen-Sheng; Wang, Xiao-Wu; Bai, San-Xing; Zhang, Jin-Zhou; Yu, Shi-Qiang

    2016-08-01

    Micro-RNA (miR)-155 is a novel gene regulator with important roles in inflammation. Herein, our study aimed to explore the role of miR-155 in LPS-induced acute lung injury(ALI). ALI in mice was induced by intratracheally delivered LPS. Loss-of-function experiments performed on miR-155 knockout mice showed that miR-155 gene inactivation protected mice from LPS-induced ALI, as manifested by preserved lung permeability and reduced lung inflammation compared with wild-type controls. Bone marrow transplantation experiments identified leukocytes, but not lung parenchymal-derived miR-155-promoted acute lung inflammation. Real-time PCR analysis showed that the expression of miR-155 in lung tissue was greatly elevated in wild-type mice after LPS stimulation. In situ hybridization showed that miR-155 was mainly expressed in alveolar macrophages. In vitro experiments performed in isolated alveolar macrophages and polarized bone marrow-derived macrophages confirmed that miR-155 expression in macrophages was increased in response to LPS stimulation. Conversely, miR-155 gain-of-function in alveolar macrophages remarkably exaggerated LPS-induced acute lung injury. Molecular studies identified the inflammation repressor suppressor of cytokine signaling (SOCS-1) as the downstream target of miR-155. By binding to the 3'-UTR of the SOCS-1 mRNA, miR-155 downregulated SOCS-1 expression, thus, permitting the inflammatory response during lung injury. Finally, we generated a novel miR-155 knockout rat strain and showed that the proinflammatory role of miR-155 was conserved in rats. Our study identified miR-155 as a proinflammatory factor after LPS stimulation, and alveolar macrophages-derived miR-155 has an important role in LPS-induced ALI. Copyright © 2016 the American Physiological Society.

  13. Respiratory tract changes in guinea pigs, rats, and mice following a single six-hour exposure to methyl isocyanate vapor.

    OpenAIRE

    Fowler, E H; Dodd, D E

    1987-01-01

    Groups of male and female Fischer 344 rats, B6C3F1 mice, and Hartley guinea pigs were exposed once for 6 hr to mean concentrations of 10.5, 5.4, 2.4, 1.0, or 0 (control) ppm of methyl isocyanate (MIC) vapor. Rats and mice were also exposed to 20.4 ppm of MIC. The majority of deaths occurred during postexposure days 1 through 3. The 6-hr LC50 values (with 95% confidence limits) were 6.1 (4.6 to 8.2) ppm for rats, 12.2 (8.4 to 17.5) ppm for mice, and 5.4 (4.4 to 6.7) ppm for guinea pigs. Notabl...

  14. Effect of long-term geomagnetic field deprivation on the concentration of some elements in the hair of laboratory rats.

    Science.gov (United States)

    Tombarkiewicz, Barbara

    2008-07-01

    The aim of the study was to determine the effect of long-term geomagnetic field (GMF) deprivation on the concentration of selected elements in the hair of laboratory rats. A total of 32 Wistar laboratory rats were divided into four equal groups (males and females) kept under hypomagnetic conditions (GMF vertical component below 20nT) and two control groups (males and females) kept free of field disturbances (GMF vertical component approx. 38000nT). At the beginning and at 7 months of the experiment, hair was taken from the dorsal part of all rats and analysed using atomic emission spectrometry for the concentration of selected magnetic elements (Fe, Ni, Co, Cr, Mn and Cu). Long-term GMF deprivation was found to affect the concentration of Fe, Mn, Cu and Cr, but had no significant effect on the concentration of Co or Ni in the hair of the analysed rats.

  15. Genotype-dependent participation of coat color gene loci in the behavioral traits of laboratory mice.

    Science.gov (United States)

    Yamamuro, Yutaka; Shiraishi, Aya

    2011-10-01

    To evaluate if loci responsible for coat color phenotypes contribute to behavioral characteristics, we specified novel gene loci associated with social exploratory behavior and examined the effects of the frequency of each allele at distinct loci on behavioral expression. We used the F2 generation, which arose from the mating of F1 mice obtained by interbreeding DBA/2 and ICR mice. Phenotypic analysis indicated that the agouti and albino loci affect behavioral traits. A genotype-based analysis revealed that novel exploratory activity was suppressed in a manner dependent on the frequency of the dominant wild-type allele at the agouti, but not albino, locus. The allele-dependent suppression was restricted to colored mice and was not seen in albino mice. The present results suggest that the agouti locus contributes to a particular behavioral trait in the presence of a wild-type allele at the albino locus, which encodes a structural gene for tyrosinase.

  16. Impact of Seasonal Variant Temperatures and Laboratory Room Ambient Temperature on Mortality of Rats with Ischemic Brain Injury

    Science.gov (United States)

    Gopalakrishanan, Sivakumar; Babu, Mg. Ramesh; Thangarajan, Rajesh; Punja, Dhiren; Jaganath, Vidyadhara Devarunda; Kanth, Akriti B.; Rao, Mohandas

    2016-01-01

    Introduction A popular rat model for hypoperfusion ischemic brain injury is bilateral common carotid artery occlusion (BCCAO). BCCAO surgery when performed in varying geographical locations and during different seasons of the year is reported to have variable mortality rates. Studies have also documented the diminishing influence of Ketamine-Xylazine (KT-XY) on thermoregulatory functions in rodents. Aim To explore the impact of seasonal variant temperatures and laboratory room ambient temperatures on mortality of rats following BCCAO surgery. Materials and Methods The study has two parts: 1 The first part is an analysis of a three year retrospective data to explore the association between the geographical season (hot summer and cold winter) induced laboratory room ambient temperature variations and the mortality rate in KT-XY anaesthetized BCCAO rats. 2. The second part investigated the effect of conditioned laboratory room ambient temperature (CAT) (23-250C) in KT-XY anaesthetized BCCAO group of rats. Rats were divided into 4 groups(n =8/group) as-Normal control, BCCAO and Sham BCCAO where they were all exposed to unconditioned ambient temperature (UCAT) during their surgery and postoperative care. And finally fourth group rats exposed to CAT during the BCCAO surgery and postoperative care. Results Pearson’s chi-square test indicates a significantly high association (p<0.006) between post-BCCAO mortality and hot season of the year. CAT during the hot season reduced the mortality rate (24% less) in post- BCCAO rats compared to the rats of UCAT. Conclusion Despite seasonal variations in temperature, conditioning the laboratory room ambient temperatures to 23–250C, induces hypothermia in KT-XY anaesthetized ischemic brain injured rodents and improves their survival rate. PMID:27190796

  17. Multiplex polymerase chain reaction assay for the detection of minute virus of mice and mouse parvovirus infections in laboratory mice.

    Science.gov (United States)

    Wang, K W; Chueh, L L; Wang, M H; Huang, Y T; Fang, B H; Chang, C Y; Fang, M C; Chou, J Y; Hsieh, S C; Wan, C H

    2013-04-01

    Mouse parvoviruses are among the most prevalent infectious pathogens in contemporary mouse colonies. To improve the efficiency of routine screening for mouse parvovirus infections, a multiplex polymerase chain reaction (PCR) assay targeting the VP gene was developed. The assay detected minute virus of mice (MVM), mouse parvovirus (MPV) and a mouse housekeeping gene (α-actin) and was able to specifically detect MVM and MPV at levels as low as 50 copies. Co-infection with the two viruses with up to 200-fold differences in viral concentrations can easily be detected. The multiplex PCR assay developed here could be a useful tool for monitoring mouse health and the viral contamination of biological materials.

  18. Toxic responses in F344 rats and B6C3F1 mice given roxarsone in their diets for up to 13 weeks.

    Science.gov (United States)

    Abdo, K M; Elwell, M R; Montgomery, C A; Thompson, M B; Thompson, R B; Prejean, J D

    1989-01-01

    Thirteen-week toxicity studies were conducted in groups of 10 F344 rats and B6C3F1 mice of each sex fed roxarsone at 0, 50, 100, 200, 400, or 800 ppm in the diet. Arsenic levels in blood, urine, kidneys, and liver of rats were measured in additional animals of each sex dosed with 100 or 400 ppm roxarsone. Compound-related mortality occurred in both sexes of rats at 800 ppm and mice at 800 and 400 ppm. Significant body weight gain depression occurred in both sexes of rats at 200, 400, and 800 ppm and mice at 800 ppm. Clinical signs of toxicity (trembling, ataxia, and pale skin) were seen primarily in rats and mice at 800 ppm. Lesions associated with roxarsone administration were noted only in the kidney of rats and were characterized by tubular necrosis and mineralization at the corticomedullary junction. Arsenic levels in urine, blood, liver, and kidneys increased over time and were directly proportional to the level of roxarsone in feed. These levels were greater than 6 times higher in rats than in mice and were about 2 time higher in males than in females. The no-observable-effect level for roxarsone toxicity was estimated at 100 ppm for rats and 200 ppm for mice. No hematology or clinical chemistry effects were found in rats or mice of either sex.

  19. A rapid method for the infection of laboratory mice with Schistosoma japonicum.

    Science.gov (United States)

    Moloney, N A; Webbe, G

    1982-01-01

    Known numbers of medium-suspended cercariae of Schistosoma japonicum were injected either intraperitoneally, subcutaneously, intramuscularly or intravenously into mice and were compared for infectivity with S. japonicum cercariae that had been administered percutaneously. The injected cercariae appeared to be no less infective or fecund even after their maintenance in vitro for up to six hours. The intraperitoneal route of inoculation was preferred as it facilitated the rapid infection of mice and furthermore was much safer than conventional percutaneous application of cercariae.

  20. High-Moisture Diet for Laboratory Rats: Complete Blood Counts, Serum Biochemical Values, and Intestinal Enzyme Activity

    Science.gov (United States)

    Battles, August H.; Knapka, Joseph T.; Stevens, Bruce R.; Lewis, Laura; Lang, Marie T.; Gruendel, Douglas J.

    1991-01-01

    Rats were fed an irradiated high-moisture diet (KSC-25) with or without access to a water bottle. Physiologic values were compared between these two groups and a group of rats fed a purified diet. Hematologic and serum biochemical values, urine specific gravity, and intestinal enzyme activities were determined from samples collected from the three groups of rats. Sprague Dawley rats (n=32) fed the irradiated high-moisture diet with or without a water bottle were the test animals. Rats (n=16) fed an irradiated purified diet and water provided via a water bottle were the control group. The purified diet formulation, modified AIN-76A, is a commonly used purified diet for laboratory rodents. All rats remained alert and healthy throughout the study. A comparison of the physiologic values of rats in this study with reported normal values indicated that all of the rats in the study were in good health. Significant differences (P less than 0.05) of the physiologic values from each rat group are reported.

  1. High-Moisture Diet for Laboratory Rats: Complete Blood Counts, Serum Biochemical Values, and Intestinal Enzyme Activity

    Science.gov (United States)

    Battles, August H.; Knapka, Joseph T.; Stevens, Bruce R.; Lewis, Laura; Lang, Marie T.; Gruendel, Douglas J.

    1991-01-01

    Rats were fed an irradiated high-moisture diet (KSC-25) with or without access to a water bottle. Physiologic values were compared between these two groups and a group of rats fed a purified diet. Hematologic and serum biochemical values, urine specific gravity, and intestinal enzyme activities were determined from samples collected from the three groups of rats. Sprague Dawley rats (n=32) fed the irradiated high-moisture diet with or without a water bottle were the test animals. Rats (n=16) fed an irradiated purified diet and water provided via a water bottle were the control group. The purified diet formulation, modified AIN-76A, is a commonly used purified diet for laboratory rodents. All rats remained alert and healthy throughout the study. A comparison of the physiologic values of rats in this study with reported normal values indicated that all of the rats in the study were in good health. Significant differences (P less than 0.05) of the physiologic values from each rat group are reported.

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

    Energy Technology Data Exchange (ETDEWEB)

    McGill, Mitchell R.; Williams, C. David; Xie, Yuchao; Ramachandran, Anup; Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu

    2012-11-01

    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

  3. Ovariectomy and 17β-estradiol replacement in rats and mice: a visual demonstration.

    Science.gov (United States)

    Ström, Jakob O; Theodorsson, Annette; Ingberg, Edvin; Isaksson, Ida-Maria; Theodorsson, Elvar

    2012-06-07

    Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures.

  4. Antidepressant effect of bioactive compounds from Paecilomyces tenuipes in mice and rats

    Institute of Scientific and Technical Information of China (English)

    Hongwei Kan; Liang Ming; Chunru Li; Hongxing Kan; Bei Sun; Yan Liang

    2010-01-01

    A bioactive compound from Paecilomyces tenuipes(BCPT)has an inhibitory effect on monoamine oxidase A(MAO-A)in vitro.Researchers have thought that BCPT may be a potential antidepressant.The MAO-A suppressor moclobemide served as a control,and this study investigated the mechanisms of BCPT as an antidepressant.Results demonstrated that BCPT induced significantly increased sucrose intake in chronic unpredictable stressed rats,shortened immobility time in forced swimming mice,improved the scores of blepharoptosis and akinesia in reserpine-treated mice,increased the number of 5-hydroxy tryptophan-induced head-twitches,remarkably enhanced the expression of hippocampus mineralcorticoid receptor and glucocorticoid receptor mRNA,decreased the ratio of mineralcorticoid receptor to glucocorticoid receptor and raised the levels of dopamine,norepinephrine and 5-hydroxytryptamine,while decreasing hydroxyindole acetic acid levels or dihydroxy-phenyl acetic acid in chronic unpredictable stressed rats.Behavioral test results suggested that BCPT potentially had antidepressant-like activity.Meanwhile,BCPT increased the levels of neurotransmitters,and mineralcorticoid receptor and glucocorticoid receptor mRNA in the hippocampus,which may be an important mechanism of its antidepressant effect.

  5. Pre- and post-conditioning hormesis in elderly mice, rats, and humans: its loss and restoration.

    Science.gov (United States)

    Calabrese, Edward J

    2016-08-01

    This paper assessed differences and similarities in the capacity for preconditioning (PC) and post-conditioning (PostC) to prevent ischemic reperfusion (IR) damage to the heart in the old/elderly as compared to young adult mice, rats, and humans. While PC reliably reduces myocardial ischemia-induced heart damage by about 30-60 % in young adult (2-3 months old) mice and rats, such protection begins to diminish in middle age (1 year old) and is fully lost in the old and elderly (≥18 months). Common rearing practices (i.e., no exercise; ad libitum feeding) are strongly associated with the loss of PC to prevent IR damage to the heart in old/elderly rodents. Substantial restoration of lost PC in old/elderly animal models is affected via various types of exercise and exercise protocols, several types of dietary interventions and pharmacological means. Evidence of PC-mediated cardioprotection in old/elderly humans via epidemiological investigations has been reported using multiple research protocols. These findings suggest the need for animal studies to better reflect human dietary, exercise and lifestyle patterns to enhance their extrapolative relevance.

  6. OB protein binds specifically to the choroid plexus of mice and rats.

    Science.gov (United States)

    Devos, R; Richards, J G; Campfield, L A; Tartaglia, L A; Guisez, Y; van der Heyden, J; Travernier, J; Plaetinck, G; Burn, P

    1996-05-28

    Binding studies were conducted to identify the anatomical location of brain target sites for OB protein, the ob gene product. 125I-labeled recombinant mouse OB protein or alkaline phosphatase-OB fusion proteins were used for in vitro and in vivo binding studies. Coronal brain sections or fresh tissue from lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats were probed to identify potential central OB protein-binding sites. We report here that recombinant OB protein binds specifically to the choroid plexus. The binding of OB protein (either radiolabeled or the alkaline phosphatase-OB fusion protein) and its displacement by unlabeled OB protein was similar in lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats. These findings suggest that OB protein binds with high affinity to a specific receptor in the choroid plexus. After binding to the choroid plexus receptor, OB protein may then be transported across the blood-brain barrier into the cerebrospinal fluid. Alternatively, binding of OB protein to a specific receptor in the choroid plexus may activate afferent neural inputs to the neural network that regulates feeding behavior and energy balance or may result in the clearance or degradation of OB protein. The identification of the choroid plexus as a brain binding site for OB protein will provide the basis for the construction of expression libraries and facilitate the rapid cloning of the choroid plexus OB receptor.

  7. Comparative anticonvulsant activity and neurotoxicity of clobazam, diazepam, phenobarbital, and valproate in mice and rats.

    Science.gov (United States)

    Shenoy, A K; Miyahara, J T; Swinyard, E A; Kupferberg, H J

    1982-08-01

    The 1.5-benzodiazepine (clobazam), the 1,4-benzodiazepine (diazepam), and two nonbenzodiazepine antiepileptic drugs (phenobarbital and valproate) were evaluated in mice and rats with a battery of well-standardized anticonvulsant test procedures. The results obtained indicate that clobazam and valproate exhibit a wider range of experimental anticonvulsant activity than either diazepam or phenobarbital. Except for clobazam by the maximal electroshock seizure (MES) test in rats, clobazam and valproate are effective in nontoxic doses against MES and all four chemically induced seizures (Metrazol, bicuculline, picrotoxin, and strychnine). Clobazam is effective by the MES test in rats only in doses that exceed the median minimal toxic dose. Phenobarbital is effective against all of the above tests, but minimal toxic doses must be employed to prevent strychnine seizures. Diazepam, on the other hand, is effective in nontoxic doses against seizures induced by Metrazol, bicuculline, and picrotoxin, but protects animals from maximal electroshock and strychnine seizures only when given in toxic doses. When compared on the basis of protective indices (PI = TD50/ED50) calculated from intraperitoneal data, the PIs for clobazam were 1.6 to 13 times higher than those for diazepam. Overall, except for the MES test in rats, the PIs for clobazam were from 1.5 to 44 times higher than those for any of the other three substances. With respect to the MES test in rats, the PI for clobazam was 10.8 times higher than that for diazepam; however, the PIs for phenobarbital and valproate were 3.5 and 4.4 times higher, respectively, than that for clobazam. These data suggest that the spectrum of anticonvulsant activity for the 1,5-benzodiazepine (clobazam) is superior to that for the 1,4-benzodiazepine (diazepam). Also, the broad experimental profile of anticonvulsant activity of clobazam agrees well with its reported broad clinical efficacy.

  8. Light catalytically cracked naphtha: subchronic toxicity of vapors in rats and mice and developmental toxicity screen in rats.

    Science.gov (United States)

    Dalbey, W E; Feuston, M H; Yang, J J; Kommineni, C V; Roy, T A

    1996-01-01

    Both a subchronic inhalation study and a developmental toxicity screen were performed with vapors of light catalytically cracked naphtha (LCCN). In the subchronic study, four groups of mice and rats (10 animals per sex per species) were exposed for approximately 13 wk (6 h/d, 5 d/wk) to concentrations of LCCN vapors of 0, 530, 2060, or 7690 mg/m3. An untreated control group was also included. Animals were observed daily and body weights were taken weekly. No significant treatment-related changes were found in clinical signs, body weight, serum chemistry, hematology, histopathology of 24 tissues, or weights of 12 organs. A marginal decrease was noted in the number of sperm per gram of epididymis. In the developmental toxicity screen, presumed-pregnant Sprague-Dawley rats were exposed to 0, 2150, or 7660 mg/m3 of LCCN vapors, 6 h/d on d 0-19 of gestation. Females were sacrificed on d 20; dams and fetuses were examined grossly and fetuses were later evaluated for skeletal and visceral effects. The number of resorptions was increased by approximately 140% in the group receiving 7660 mg/m3; no other definite treatment-related changes were observed. Overall, the effects of exposure to partially vaporized LCCN were minimal.

  9. Physiological and Pathological Impact of Blood Sampling by Retro-Bulbar Sinus Puncture and Facial Vein Phlebotomy in Laboratory Mice

    DEFF Research Database (Denmark)

    Teilmann, Anne Charlotte; Nygaard Madsen, Andreas; Holst, Birgitte

    2014-01-01

    Retro-bulbar sinus puncture and facial vein phlebotomy are two widely used methods for blood sampling in laboratory mice. However, the animal welfare implications associated with these techniques are currently debated, and the possible physiological and pathological implications of blood sampling...... using these methods have been sparsely investigated. Therefore, this study was conducted to assess and compare the impacts of blood sampling by retro-bulbar sinus puncture and facial vein phlebotomy. Blood was obtained from either the retro-bulbar sinus or the facial vein from male C57BL/6J mice at two...... time points, and the samples were analyzed for plasma corticosterone. Body weights were measured at the day of blood sampling and the day after blood sampling, and the food consumption was recorded automatically during the 24 hours post-procedure. At the end of study, cheeks and orbital regions were...

  10. Quantitative effects of diet on fecal corticosterone metabolites in two strains of laboratory mice.

    Science.gov (United States)

    Kalliokoski, Otto; Jacobsen, Kirsten R; Teilmann, Anne Charlotte; Hau, Jann; Abelson, Klas S P

    2012-01-01

    The analysis of glucocorticoids excreted in feces is becoming a widespread technique for determining animal wellbeing in a wide variety of settings. In the present study an extraction protocol and an ELISA assay for quantifying fecal corticosterone metabolites (FCM) in BALB/c and C57bl/6 mice were validated. Lower ratios of solvent (ethanol) to mass of fecal sample were found to be sufficient in extracting FCM compared to what has been reported previously. Feeding mice a high energy diet, high in fat content (60% of calories from fat), significantly lowered the FCM excretion, approximately halving the FCM output. This diet also reduced the fecal mass voided to approximately a third of that of the regular diet. The two reductions were not correlated. A difference in defecation pattern was seen between the two strains, with the BALB/c mice having a more pronounced diurnal rhythm compared to the C57bl/6 mice. Furthermore, throughout the experiment, the C57bl/6 mice excreted significantly higher levels of FCM compared to the BALB/c mice. The mice were also challenged with synthetic adrenocorticotropic hormone (ACTH) and dexamethasone (DEX). The effect of the challenges could readily be detected, but had a considerably lesser impact on data than did the difference in diet. The study demonstrates some problematic consequences of expressing FCM excretion as a measure of fecal dry mass. The study also serves to emphasize the caution that must be exercised when interpreting FCM excretion in conjunction with an uncontrolled or varied diet, or perturbations of gastro-intestinal functioning.

  11. Cadmium accelerates bone loss in ovariectomized mice and fetal rat limb bones in culture

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharyya, M.H.; Whelton, B.D.; Stern, P.H.; Peterson, D.P. (Argonne National Lab., IL (USA))

    1988-11-01

    Loss of bone mineral after ovariectomy was studied in mice exposed to dietary cadmium at 0.25, 5, or 50 ppm. Results show that dietary cadmium at 50 ppm increased bone mineral loss to a significantly greater extent in ovariectomized mice than in sham-operated controls. These results were obtained from two studies, one in which skeletal calcium content was determined 6 months after ovariectomy and a second in which {sup 45}Ca release from {sup 45}Ca-prelabeled bones was measured immediately after the start of dietary cadmium exposure. Furthermore, experiments with {sup 45}Ca-prelabeled fetal rat limb bones in culture demonstrated that Cd at 10 nM in the medium, a concentration estimated to be in the plasma of mice exposed to 50 ppm dietary Cd, strikingly increased bone resorption. These in vitro results indicate that cadmium may enhance bone mineral loss by a direct action on bone. Results of the in vivo studies are consistent with a significant role of cadmium in the etiology of Itai-Itai disease among postmenopausal women in Japan and may in part explain the increased risk of postmenopausal osteoporosis among women who smoke.

  12. Quantitative effects of diet on fecal corticosterone metabolites in two strains of laboratory mice

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Jacobsen, Kirsten Rosenmaj; Teilmann, Anne Charlotte

    2012-01-01

    The analysis of glucocorticoids excreted in feces is becoming a widespread technique for determining animal wellbeing in a wide variety of settings. In the present study an extraction protocol and an ELISA assay for quantifying fecal corticosterone metabolites (FCM) in BALB/c and C57bl/6 mice were...... validated. Lower ratios of solvent (ethanol) to mass of fecal sample were found to be sufficient in extracting FCM compared to what has been reported previously. Feeding mice a high energy diet, high in fat content (60% of calories from fat), significantly lowered the FCM excretion, approximately halving...... the FCM output. This diet also reduced the fecal mass voided to approximately a third of that of the regular diet. The two reductions were not correlated. A difference in defecation pattern was seen between the two strains, with the BALB/c mice having a more pronounced diurnal rhythm compared to the C57bl...

  13. Subchronic toxicity of triethylenetetramine dihydrochloride in B6C3F1 mice and F344 rats.

    Science.gov (United States)

    Greenman, D L; Morrissey, R L; Blakemore, W; Crowell, J; Siitonen, P; Felton, P; Allen, R; Cronin, G

    1996-02-01

    Triethylenetetramine dihydrochloride (trien-2HCl; CAS No. 38260-01-04), a chelating agent used to treat Wilson's disease patients who are intolerant of the drug of choice, was tested for subchronic toxicity in B6C3F1 mice and F344 rats. Mice and rats received trien-2HCl in the drinking water at concentrations of 0, 120, 600, or 3000 ppm for up to 92 days. Twenty mice and 18 rats of each sex were assigned to each dose group fed either a cereal-based (NIH-31) or a purified (AIN-76A) diet, both containing nutritionally adequate levels of copper. An additional control group of rats and mice received a Cu-deficient AIN-76A diet. This low copper diet resulted in Cu-deficiency symptoms, such as anemia, liver periportal cytomegaly, pancreatic atrophy and multifocal necrosis, spleen hematopoietic cell proliferation, and increased heart weight, together with undetectable levels of plasma copper in rats but not in mice. Trien-2HCl lowered plasma copper levels some-what (at 600 and 3000 ppm) in rats fed the AIN-76A diet, but did not induce the usual signs of copper deficiency. Trien-2HCl caused an increased frequency of uterine dilatation at 3000 ppm in rats fed AIN-76A diet that was not noted in females fed the Cu-deficient diet. Trien-2HCl toxicity occurred only in mice in the highest dose group fed an AIN-76A diet. Increased frequencies of inflammation of the lung interstitium and liver periportal fatty infiltration were seen in both sexes, and hematopoietic cell proliferation was seen in the spleen of males. Kidney and body weights were reduced in males as was the incidence of renal cytoplasmic vacuolization. There were no signs of copper deficiency in mice exposed to trien-2HCl. The only effect of trien-2HCl in animals fed the NIH-31 diet was a reduced liver copper level in both rat sexes, noted at 3000 ppm.

  14. Pharmacological effects of ethanol extract of Egyptian Artemisia herba-alba in rats and mice

    Institute of Scientific and Technical Information of China (English)

    Heba Mohammed Ibrahim Abdallah; Nawal E.L. Sayed Gomaa

    2016-01-01

    Objective: To investigate some pharmacological effects including gastroprotective, anti-inflammatory, analgesic, antipyretic and in vitro antioxidant effects of Artemisia herba-alba extract in different experimental models. Methods: Inflammation was induced in rat paw by subcutaneous injection of 1% (v/v) carrageenan solution. Writhes was induced in mice by intraperitoneal injection of 0.6%(v/v) acetic acid solution. Pyrexia was induced using Brewer's yeast suspension. Gastric lesion was induced in rats by oral administration of 99% ethanol. The anti-inflammatory, analgesic, antipyretic and gastroprotective activities of Artemisia herba-alba extract were investigated respectively. In vitro antioxidant effect was investigated using DPPH free radical. Results: The plant extract showed anti-inflammatory effect in carrageenan-induced paw edema in rats, analgesic effect against acetic acid-induced writhing, and antipyretic ac-tivity in Brewer's yeast model of pyrexia. Besides, it was shown to be a gastroprotective agent against ethanol-induced gastric ulcers. The plant also exhibited a free radical scavenging potential in an in vitro antioxidant study using DPPH. Conclusions: The results validate the use of the investigated plant in traditional medicine for different ailments.

  15. Developmental sex differences in nicotinic currents of prefrontal layer VI neurons in mice and rats.

    Directory of Open Access Journals (Sweden)

    Nyresa C Alves

    Full Text Available BACKGROUND: There is a large sex difference in the prevalence of attention deficit disorder; yet, relatively little is known about sex differences in the development of prefrontal attention circuitry. In male rats, nicotinic acetylcholine receptors excite corticothalamic neurons in layer VI, which are thought to play an important role in attention by gating the sensitivity of thalamic neurons to incoming stimuli. These nicotinic currents in male rats are significantly larger during the first postnatal month when prefrontal circuitry is maturing. The present study was undertaken to investigate whether there are sex differences in the nicotinic currents in prefrontal layer VI neurons during development. METHODOLOGY/PRINCIPAL FINDINGS: Using whole cell recording in prefrontal brain slice, we examined the inward currents elicited by nicotinic stimulation in male and female rats and two strains of mice. We found a prominent sex difference in the currents during the first postnatal month when males had significantly greater nicotinic currents in layer VI neurons compared to females. These differences were apparent with three agonists: acetylcholine, carbachol, and nicotine. Furthermore, the developmental sex difference in nicotinic currents occurred despite male and female rodents displaying a similar pattern and proportion of layer VI neurons possessing a key nicotinic receptor subunit. CONCLUSIONS/SIGNIFICANCE: This is the first illustration at a cellular level that prefrontal attention circuitry is differently affected by nicotinic receptor stimulation in males and females during development. This transient sex difference may help to define the cellular and circuit mechanisms that underlie vulnerability to attention deficit disorder.

  16. Role of Endothelial Differentiated Adipose-derived Stem Cells in Repairing Calvarial Critical Size Defects in the Laboratory Rat (Rattus norvegicus)

    Science.gov (United States)

    2014-07-16

    Differentiated Adipose-derived Stem Cells in Repairing Calvarial Critical Size Defects in the Laboratory Rat (Rattus norvegicus) PRINCIPAL INVESTIGATOR...SUBTITLE FDG20110033A "Role of Endothelial Differentiated Adipose-derived Stem Cells in Repairing Calvarial Critical Size Defects in the Laboratory Rat (Rattus

  17. Acute Lethality of Inhaled Hydrogen Cyanide in the Laboratory Rat: Impact of Concentration x Time Profile and Evaluation of the Predictivity of Toxic Load Models

    Science.gov (United States)

    2013-05-03

    Naval Medical Research Unit Dayton Acute Lethality of Inhaled Hydrogen Cyanide in the Laboratory Rat : Impact of Concentration × Time Profile and...Cyanide in the Laboratory Rat : Impact of Concentration x Time Profile and Evaluation of the Predictivity of “Toxic Load” Models. 5a. Contract

  18. Using Castration Surgery in Male Rats to Demonstrate the Physiological Effects of Testosterone on Seminal Vesicle Anatomy in an Undergraduate Laboratory Setting

    Science.gov (United States)

    Belanger, Rachelle M.; Conant, Stephanie B.; Grabowski, Gregory M.

    2013-01-01

    Rats can be used as a model organism to teach physiological concepts in a laboratory setting. This article describes a two-part laboratory that introduces students to hypothesis testing, experimental design, the appropriate use of controls and surgical techniques. Students perform both a castration and sham-control surgery on male rats and test…

  19. The applicability of a gel delivery system for self-administration of buprenorphine to laboratory mice

    DEFF Research Database (Denmark)

    Hovard, A. M. B.; Teilmann, A. C.; Hau, J.

    2015-01-01

    have previously demonstrated sticky nut and chocolate paste to be well-liked by mice and readily ingested in most cases. However, a disadvantage with nut and chocolate paste is its high content of fat and sugar, which may have undesirable effects in some experimental models. Alternatively, a delivery...

  20. Exposure of Laboratory Mice to Domestic Cooking Gas: - Implications for Toxicity

    Directory of Open Access Journals (Sweden)

    Madu D. Ibegbu

    2008-09-01

    Full Text Available The ability of domestic cooking gas to induce hepatotoxicity and clastogenicity in mice was studied. The mice were exposed to domestic gas for twenty-one days at doses of 100 mg/kg, 200 mg/kg and 300 mg/kg respectively. The positive control group of mice were given sodium arsenite intraperitoneously at a dose of 2.5mg/kg body weight. While the negative control group had only distilled water, sodium arsenite significantly (p < 0.05 induced the formation of micronucleated polychromatic erythrocytes (mPCEs, serum and liver gamma glutamyl transferase (γGT and alkaline phosphatase (AP activities respectively as compared with the observations made in the negative control group. Similarly, the domestic gas significantly (p<0.05 induced mPCEs formation, serum and liver, γGT and AP activities. The degree of induction was in the order of 100 mg/kg < 200 mg/kg < 300 mg/kg. However, when compared with the positive control group, the domestic cooking gas at the tested doses was not as potent as sodium arsenite in its ability to induce enzyme activity and mPCEs formation. Limited histopathological analysis of liver samples from treated and untreated mice showed distended blood vessels, necrosis and hepatocellular degeneration in the groups treated with high doses of domestic gas or sodium arsenite as compared with the untreated group. Our findings suggest that the domestic cooking gas has some degree of clastogenic and hepatotoxic activities in mice. Health risks may therefore be associated with long-term occupational and / or domestic exposure in humans.

  1. Comparative phamacokinetics of perfluorobutyrate (PFBA) in rats, mice, monkeys and humans and relevance to human exposure via drinking water

    Science.gov (United States)

    Perfluorobutyrate (PFBA) has been detected in precipitation, surface waters, water treatment effluent, and in public and private wells in Minnesota at up to low mug/L concentrations. We evaluated the pharmacokinetics of PFBA in rats, mice, monkeys, and humans to provide a rationa...

  2. Comparative Pharmacokinetics of Perfluorobutyrate in Rats, Mice,Monkeys, and Humans and Relevance to Human Exposurevia Drinking Water

    Science.gov (United States)

    Perfluorobutyrate (PFBA) has been detected in precipitation, surface waters, water treatment effluent, and in public and private wells in Minnesota at up to low mg/l concentrations. We evaluated the pharmacokinetics of PFBA in rats, mice, monkeys, and humans to provide a rati...

  3. Dynamics of glucagon secretion in mice and rats revealed using a validated sandwich ELISA for small sample volumes

    DEFF Research Database (Denmark)

    Albrechtsen, Nicolai Jacob Wewer; Kuhre, Rune Ehrenreich; Windeløv, Johanne Agerlin

    2016-01-01

    secretion in response to intravenous glucose and arginine in anesthetized mice (isoflurane) and rats (Hypnorm/midazolam). Glucose caused a long-lasting suppression to very low values (1–2 pmol/l) within 2 min in both species. Arginine stimulated secretion 8- to 10-fold in both species, peaking at 1–2 min...

  4. What the laboratory rat has taught us about social play behavior: role in behavioral development and neural mechanisms

    NARCIS (Netherlands)

    Vanderschuren, L.J.M.J.; Trezza, V.

    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 briefl

  5. Knockout of the aryl hydrocarbon receptor results in distinct hepatic and renal phenotypes in rats and mice

    Energy Technology Data Exchange (ETDEWEB)

    Harrill, Joshua A. [The Hamner Institute for Health Sciences, Institute for Chemical Safety Sciences, RTP, NC 27709 (United States); Hukkanen, Renee R.; Lawson, Marie; Martin, Greg [The Dow Chemical Company, Midland, MI 48640 (United States); Gilger, Brian [North Carolina State University, College of Veterinary Medicine, Raleigh, NC 27606 (United States); Soldatow, Valerie [University of North Carolina, Department of Environmental Sciences and Engineering, Chapel Hill, NC 27599 (United States); LeCluyse, Edward L. [The Hamner Institute for Health Sciences, Institute for Chemical Safety Sciences, RTP, NC 27709 (United States); Budinsky, Robert A.; Rowlands, J. Craig [The Dow Chemical Company, Midland, MI 48640 (United States); Thomas, Russell S., E-mail: RThomas@thehamner.org [The Hamner Institute for Health Sciences, Institute for Chemical Safety Sciences, RTP, NC 27709 (United States)

    2013-10-15

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor which plays a role in the development of multiple tissues and is activated by a large number of ligands, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to examine the roles of the AHR in both normal biological development and response to environmental chemicals, an AHR knockout (AHR-KO) rat model was created and compared with an existing AHR-KO mouse. AHR-KO rats harboring either 2-bp or 29-bp deletion mutation in exon 2 of the AHR were created on the Sprague–Dawley genetic background using zinc-finger nuclease (ZFN) technology. Rats harboring either mutation type lacked expression of AHR protein in the liver. AHR-KO rats were also insensitive to thymic involution, increased hepatic weight and the induction of AHR-responsive genes (Cyp1a1, Cyp1a2, Cyp1b1, Ahrr) following acute exposure to 25 μg/kg TCDD. AHR-KO rats had lower basal expression of transcripts for these genes and also accumulated ∼ 30–45-fold less TCDD in the liver at 7 days post-exposure. In untreated animals, AHR-KO mice, but not AHR-KO rats, had alterations in serum analytes indicative of compromised hepatic function, patent ductus venosus of the liver and persistent hyaloid arteries in the eye. AHR-KO rats, but not AHR-KO mice, displayed pathological alterations to the urinary tract: bilateral renal dilation (hydronephrosis), secondary medullary tubular and uroepithelial degenerative changes and bilateral ureter dilation (hydroureter). The present data indicate that the AHR may play significantly different roles in tissue development and homeostasis and toxicity across rodent species. - Highlights: • An AHR knockout rat was generated on a Sprague–Dawley outbred background. • AHR-KO rats lack expression of AHR protein. • AHR-KO rats are insensitive to TCDD-mediated effects. • Data suggests difference in the role of AHR in tissue development of rats and mice. • Abnormalities in vascular

  6. Antibody is responsible for the passive transfer of immunity to mice from rabbits, rats or mice vaccinated with attenuated Schistosoma japonicum cercariae.

    Science.gov (United States)

    Moloney, N A; Webbe, G

    1990-04-01

    Sera from rabbits, rats and mice multiply-vaccinated with attenuated cercariae of Schistosoma japonicum conferred high levels of resistance against challenge to naive recipient mice (up to 97, 64 and 60% respectively). Vaccinated rabbit and rat sera were given before challenge and vaccinated mouse serum 5 days after challenge. To show that the protective factors in these sera were antibodies, vaccinated rabbit and mouse sera were fractionated by protein A-Sepharose and the fractions precipitated by 50% ammonium sulphate. The protein A-Sepharose binding or non-binding fractions in vaccinated rabbit serum transferred approximately equal levels of significant resistance to mice, suggesting that both the IgG and non-IgG components of vaccinated rabbit serum are protective. The major part of the protective activity in vaccinated mouse serum was transferred to recipients by the protein A-Sepharose binding fraction, i.e. the IgG antibodies. Heat inactivation of sera at 56 degrees C for 3 h affected the protective capacity of vaccinated rat sera, but not that of vaccinated rabbit or mouse sera.

  7. Ethylene oxide in blood of ethylene-exposed B6C3F1 mice, Fischer 344 rats, and humans.

    Science.gov (United States)

    Filser, Johannes Georg; Kessler, Winfried; Artati, Anna; Erbach, Eva; Faller, Thomas; Kreuzer, Paul Erich; Li, Qiang; Lichtmannegger, Josef; Numtip, Wanwiwa; Klein, Dominik; Pütz, Christian; Semder, Brigitte; Csanády, György András

    2013-12-01

    The gaseous olefin ethylene (ET) is metabolized in mammals to the carcinogenic epoxide ethylene oxide (EO). Although ET is the largest volume organic chemical worldwide, the EO burden in ET-exposed humans is still uncertain, and only limited data are available on the EO burden in ET-exposed rodents. Therefore, EO was quantified in blood of mice, rats, or 4 volunteers that were exposed once to constant atmospheric ET concentrations of between 1 and 10 000 ppm (rodents) or 5 and 50 ppm (humans). Both the compounds were determined by gas chromatography. At ET concentrations of between 1 and 10 000 ppm, areas under the concentration-time curves of EO in blood (µmol × h/l) ranged from 0.039 to 3.62 in mice and from 0.086 to 11.6 in rats. At ET concentrations ≤ 30 ppm, EO concentrations in blood were 8.7-fold higher in rats and 3.9-fold higher in mice than that in the volunteer with the highest EO burdens. Based on measured EO concentrations, levels of EO adducts to hemoglobin and lymphocyte DNA were calculated for diverse ET concentrations and compared with published adduct levels. For given ET exposure concentrations, there were good agreements between calculated and measured levels of adducts to hemoglobin in rats and humans and to DNA in rats and mice. Reported hemoglobin adduct levels in mice were higher than calculated ones. Furthermore, information is given on species-specific background adduct levels. In summary, the study provides most relevant data for an improved assessment of the human health risk from exposure to ET.

  8. Short-term treatment with nitrate is not sufficient to induce in vivo antithrombotic effects in rats and mice.

    Science.gov (United States)

    Kramkowski, K; Leszczynska, A; Przyborowski, K; Proniewski, B; Marcinczyk, N; Rykaczewska, U; Jarmoc, D; Chabielska, E; Chlopicki, S

    2017-01-01

    In humans, short-term supplementation with nitrate is hypotensive and inhibits platelet aggregation via an nitric oxide (NO)-dependent mechanism. In the present work, we analyzed whether short-term treatment with nitrate induces antithrombotic effects in rats and mice. Arterial thrombosis was evoked electrically in a rat model in which renovascular hypertension was induced by partial ligation of the left renal artery. In mice expressing green fluorescent protein, laser-induced thrombosis was analyzed intravitally by using confocal microscope. Sodium nitrate (NaNO3) or sodium nitrite (NaNO2) was administered orally at a dose of 0.17 mmol/kg, twice per day for 3 days. Short-term nitrate treatment did not modify thrombus formation in either rats or mice, while nitrite administration led to pronounced antithrombotic activity. In hypertensive rats, nitrite treatment resulted in a significant decrease in thrombus weight (0.50 ± 0.08 mg vs. VEH 0.96 ± 0.09 mg; p nitrate did not affect ex vivo platelet aggregation or prothrombin time and led to only slightly elevated nitrite plasma concentration. In mice, nitrate was also ineffective, while nitrite led to decreased platelet accumulation in the area of laser-induced endothelial injury. In conclusion, although nitrite induced profound NO-dependent antithrombotic effects in vivo, conversion of nitrates to nitrite in rats and mice over short-term 3-day treatment was not sufficient to elicit NO-dependent antiplatelet or antithrombotic effects.

  9. Quantitative effects of diet on fecal corticosterone metabolites in two strains of laboratory mice

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Jacobsen, Kirsten Rosenmaj; Teilmann, Anne Charlotte;

    2012-01-01

    The analysis of glucocorticoids excreted in feces is becoming a widespread technique for determining animal wellbeing in a wide variety of settings. In the present study an extraction protocol and an ELISA assay for quantifying fecal corticosterone metabolites (FCM) in BALB/c and C57bl/6 mice were...... validated. Lower ratios of solvent (ethanol) to mass of fecal sample were found to be sufficient in extracting FCM compared to what has been reported previously. Feeding mice a high energy diet, high in fat content (60% of calories from fat), significantly lowered the FCM excretion, approximately halving......, but had a considerably lesser impact on data than did the difference in diet. The study demonstrates some problematic consequences of expressing FCM excretion as a measure of fecal dry mass. The study also serves to emphasize the caution that must be exercised when interpreting FCM excretion...

  10. PCO(2) in the large intestine of mice, rats, guinea pigs, and dogs and effects of the dietary substrate.

    Science.gov (United States)

    Rasmussen, Henrik; Mirtaheri, Peyman; Dirven, Hubert; Johnsen, Helge; Kvarstein, Gunnvald; Tønnessen, Tor Inge; Midtvedt, Tore

    2002-01-01

    PCO(2) in the lumen and serosa of cecum and colon was measured in rats, guinea pigs, and dogs to examine the relationship between serosal PCO(2) and the incidence of intestinal necrotic lesions after administration of gas-carrier contrast agents in rodents. The effects of the dietary substrate were tested in a group of mice maintained on a diet based on glucose as the only carbohydrate source. The anesthetic used was a fentanyl-fluanison-midazolam mixture (rodents) and pentobarbital (dogs). PCO(2) was measured in vivo and postmortem, and the kinetics of the postmortem serosal PCO(2) [transmural CO(2) flux (J(CO(2)))] was calculated. PCO(2) in the cecal serosa and lumen, respectively, was 64 +/- 4 and 392 +/- 18 Torr in rats, 67 +/- 3 and 276 +/- 17 Torr in guinea pigs, and 73 +/- 6 and 137 +/- 7 Torr in mice on glucose-based diet. In the colon serosa and lumen of dogs, PCO(2) was 30 +/- 6 and 523 +/- 67 Torr, respectively. Serosal PCO(2) increased rapidly after death in rats and slower in guinea pigs and mice, and the slowest change was observed in dogs. Compared with dogs, serosal PCO(2) and J(CO(2)) of rats and guinea pigs were significantly higher. Serosal PCO(2) of guinea pigs was similar to that of rats, whereas the J(CO(2)) of guinea pigs was significantly lower. These data suggest a causal relationship between the ability of the cecal and colonic wall to act as a barrier to CO(2) diffusion and the presence of characteristic gas-carrier contrast agent-induced intestinal lesions in mice and rats and their absence in guinea pigs, dogs, and other species.

  11. T-2 Toxin-induced Toxicity in Pregnant Mice and Rats

    Directory of Open Access Journals (Sweden)

    Shinya Sehata

    2008-11-01

    Full Text Available T-2 toxin is a cytotoxic secondary fungal metabolite that belongs to the trichothecene mycotoxin family. This mycotoxin is a well known inhibitor of protein synthesis through its high binding affinity to peptidyl transferase, which is an integral part of the ribosomal 60s subunit, and it also inhibits the synthesis of DNA and RNA, probably secondary to the inhibition of protein synthesis. In addition, T-2 toxin is said to induce apoptosis in many types of cells bearing high proliferating activity. T-2 toxin readily passes the placenta and is distributed to embryo/fetal tissues, which include many component cells bearing high proliferating activity. This paper reviews the reported data related to T-2 toxin-induced maternal and fetal toxicities in pregnant mice and rats. The mechanisms of T-2 toxin-induced apoptosis in maternal and fetal tissues are also discussed in this paper.

  12. Toxicology and immunology of Ganoderma lucidum polysaccharides in Kunming mice and Wistar rats.

    Science.gov (United States)

    Zhang, Jianjun; Gao, Xia; Pan, Yaogang; Xu, Nuo; Jia, Le

    2016-04-01

    In the present work, the toxicology and immunology of polysaccharides from fruiting body of Ganoderma lucidum (GPs) were investigated. No abnormal clinical-symptoms or deaths and no significant difference in body weight and food in-taking rate were found in Wistar rats during the 30-day feeding administration. No significant differences were found in each hematology value, clinical chemistry value and organ/body weight ratio, either. It had no mutagenicity due to the negative experimental results of Ames test, micronucleus test of polychromatic erythrocyte, sperm abnormality test, and chromosome aberration test in Kunming mice, respectively. The immune experiments indicated that high-dose GPs had immune effects in increasing the degree of toe swelling and enhancing the primary immune response to SRBC (P<0.01). But no-significant influence of GPs on the phagocytic function of mononuclear macrophages (MΦ) could be obtained.

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

    Science.gov (United States)

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

    2012-11-01

    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.

  14. Effects of laboratory housing on exploratory behaviour, novelty discrimination and spatial reference memory in a subterranean, solitary rodent, the Cape mole-rat (Georychus capensis)

    OpenAIRE

    Oosthuizen, Maria Kathleen; Scheibler, Anne-Gita; Bennett, Nigel Charles; Amrein, Irmgard

    2013-01-01

    A large number of laboratory and field based studies are being carried out on mole-rats, both in our research group and others. Several studies have highlighted the development of adverse behaviours in laboratory animals and have emphasised the importance of enrichment for captive animals. Hence we were interested in evaluating how laboratory housing would affect behavioural performance in mole-rats. We investigated exploratory behaviour, the ability to discriminate between novel and familiar...

  15. Toxicology and carcinogenesis studies of acrylamide (CASRN 79-06-1) in F344/N rats and B6C3F1 mice (feed and drinking water studies).

    Science.gov (United States)

    2012-07-01

    Acrylamide, a water-soluble α,β-unsaturated amide, is a contaminant in baked and fried starchy foods, including french fries, potato chips, and bread, as a result of Maillard reactions involving asparagine and reducing sugars. Additional sources of acrylamide exposure include cigarettes, laboratory procedures involving polyacrylamide gels, and various occupations (e.g, monomer production and polymerization processes). Acrylamide is carcinogenic in experimental animals. To obtain data for developing quantitative risk assessments for dietary exposures to acrylamide, the Food and Drug Administration nominated acrylamide for an in-depth toxicological evaluation by the National Toxicology Program. As part of this evaluation, male and female B6C3F1/Nctr (C57BL/6N x C3H/HeN MTV-) mice and male and female F344/N Nctr rats were exposed to acrylamide (at least 99.4% pure) in drinking water for 2 years. 2-WEEK STUDY IN RATS: Groups of four male and four female F344/N rats were administered 0, 0.14, 0.35, 0.70, 1.41, 3.52, or 7.03 mM acrylamide in the drinking water (0, 10, 25, 50, 100, 250, or 500 ppm acrylamide) or 0.0, 7.4, 18.5, 37, 74, 185, or 370 mg acrylamide per kg diet for 14 days. One male rat administered 7.03 mM acrylamide in the drinking water died on day 14. Male and female rats receiving 7.03 mM acrylamide weighed 56% and 64% of controls, respectively. Male and female rats fed 370 mg acrylamide per kg diet weighed 74% and 83% of controls, respectively. Female rats receiving 3.52 mM acrylamide in drinking water and male rats fed 185 mg acrylamide per kg diet weighed 85% and 89% of controls, respectively. Rats receiving 7.03 mM acrylamide in drinking water or 370 mg acrylamide per kg diet exhibited hind-leg paralysis on day 14. Mild to moderate dilatation of the urinary bladder was observed in all rats given 370 mg acrylamide per kg diet, and in three of four male rats and all four female rats given 7.03 mM acrylamide in drinking water, and in one of four male

  16. In utero recombinant adeno-associated virus gene transfer in mice, rats, and primates

    Directory of Open Access Journals (Sweden)

    Marrero Luis

    2003-09-01

    Full Text Available Abstract Background Gene transfer into the amniotic fluid using recombinant adenovirus vectors was shown previously to result in high efficiency transfer of transgenes into the lungs and intestines. Adenovirus mediated in utero gene therapy, however, resulted in expression of the transgene for less than 30 days. Recombinant adenovirus associated viruses (rAAV have the advantage of maintaining the viral genome in daughter cells thus providing for long-term expression of transgenes. Methods Recombinant AAV2 carrying green fluorescent protein (GFP was introduced into the amniotic sac of fetal rodents and nonhuman primates. Transgene maintenance and expression was monitor. Results Gene transfer resulted in rapid uptake and long-term gene expression in mice, rats, and non-human primates. Expression and secretion of the reporter gene, GFP, was readily demonstrated within 72 hours post-therapy. In long-term studies in rats and nonhuman primates, maintenance of GFP DNA, protein expression, and reporter gene secretion was documented for over one year. Conclusions Because only multipotential stem cells are present at the time of therapy, these data demonstrated that in utero gene transfer with AAV2 into stem cells resulted in long-term systemic expression of active transgene roducts. Thus, in utero gene transfer via the amniotic fluid may be useful in treatment of gene disorders.

  17. Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir [Pharmacology and Toxicology, Rutgers University-Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Richardson, Jason R. [Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ (United States); Heck, Diane E. [Environmental Science, School of Health Sciences and Practice, New York Medical College, Valhalla, NY (United States); Laskin, Debra L. [Pharmacology and Toxicology, Rutgers University-Ernest Mario School of Pharmacy, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Environmental and Occupational Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway, NJ (United States)

    2014-08-15

    The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractions from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.

  18. Metabolic disposition of casopitant, a potent neurokinin-1 receptor antagonist, in mice, rats, and dogs.

    Science.gov (United States)

    Miraglia, Lidia; Pagliarusco, Sabrina; Bordini, Ellenia; Martinucci, Silvia; Pellegatti, Mario

    2010-10-01

    Casopitant [1-piperidinecarboxamide,4-(4-acetyl-1-piperazinyl)-N-((1R)-1-(3,5-bis(trifluoromethyl)phenyl)-ethyl)-2-(4-fluoro-2-methylphenyl)-N-methyl-(2R,4S)] is a potent and selective antagonist of the neurokinin-1 (NK1) receptor, developed for the prevention of chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting. Absorption, distribution, metabolism, and elimination of [(14)C]casopitant have been investigated in the mouse, rat, and dog after single oral administration and compared with those in humans. [(14)C]Casopitant was rapidly absorbed in all three species: the maximum plasma concentration of radioactivity was generally observed 0.5 to 2 h after a single oral dose. In dog and female rat, as observed for humans, the principal circulating radiolabeled components were unchanged casopitant and its hydroxylated derivative M13. In rats, there was an evident sex-related difference in the rate of elimination of drug-related material with elimination being more rapid in males than in females. In dogs and mice, no notable sex differences were observed in the pattern of excretion. The elimination of drug-related radioactivity was largely by metabolism, with metabolites excreted primarily in the feces. The predominant route of metabolism was the oxidation of the parent molecule, observed together with loss of the N-acetyl group, N-demethylation, and modification of piperazine with consequent opening and cleavage of the ring, giving a complex pattern of metabolites. Conjugation of some of those oxidized products with glucuronic acid was observed. Urinary excretion in all three species was a minor route of elimination, accounting for between 2 and 7% of the dose, with unchanged parent drug never quantifiable.

  19. Herbex-Kid Inhibits Immediate Hypersensitivity Reactions in Mice and Rats

    Directory of Open Access Journals (Sweden)

    Anil Kumar

    2008-01-01

    Full Text Available Herbex-kid (HK, a polyherbal formulation was evaluated in various experimental allergic models of Type I hypersensitivity reactions. Compound 48/80 (C 48/80 has been shown to induce rat mesentery mast cell degranulation and HK (1.07, 10.75 and 107.5 mg ml−1 inhibited the mast cell degranulation in a dose dependent manner. HK (1.07, 10.75 and 107.5 mg kg−1; p.o. showed dose-dependent protection against C 48/80 induced systemic anaphylaxis in male Balb/C mice. In active anaphylaxis model, male Wistar rats orally administered with 10.75 and 107.5 mg kg−1 of HK showed significant (P < 0.01 protection against mast cell degranulation, while in passive anaphylaxis model, only at 107.5 mg kg−1 showed significant (P < 0.01 reduction in mast cell degranulation. HK at all dose levels was able to significantly decrease the time spent in nasal rubbing in Wistar rats sensitized to ovalbumin, while only at 107.5 mg kg−1 it showed significant (P < 0.01 reduction in number of sneezes. In C 48/80-induced skin itch model, all dose levels of HK significantly (P < 0.001 decreased the time spent in itching and the number of itches. HK did not produce any significant inhibition in histamine induced contraction in guinea pig ileum. From the above findings we conclude that the HK possesses antiallergic activity mediated by reducing of the release mediators from mast cells and also by 5-HT antagonism without the involvement of histamine (H1 receptors.

  20. Murine gammaherpesvirus-68 (MHV-68) is not horizontally transmitted amongst laboratory mice by cage contact.

    Science.gov (United States)

    Aligo, Jason; Brosnan, Kerry; Walker, Mindi; Emmell, Eva; Mikkelsen, S Rochelle; Burleson, Gary R; Burleson, Florence G; Volk, Amy; Weinstock, Daniel

    2015-01-01

    Murine gammaherpesvirus-68 (MHV-68), a natural pathogen of mice, is being evaluated as a model of Epstein Barr Virus (EBV) infection for use in investigation of the effects of immunomodulatory therapy on herpesvirus pathogenesis in humans. Immunosuppressive agents are used for treatment of a variety of autoimmune diseases as well as for prevention of tissue rejection after organ transplantation and can result in recrudescence of latent herpesvirus infections. Prior to examination of MHV-68 as a suitable model for EBV, better characterization of the MHV-68 model was desirable. Characterization of the MHV-68 model involved development of assays for detecting virus and for demonstration of safety when present in murine colonies. Limited information is available in the literature regarding MHV-68 transmission, although recent reports indicate the virus is not horizontally spread in research facilities. To further determine transmission potential, immunocompetent and immunodeficient mice were infected with MHV-68 and co-habitated with naïve animals. Molecular pathology assays were developed to characterize the MHV-68 model and to determine viral transmission. Horizontal transmission of virus was not observed from infected animals to naïve cagemates after fluorescence microscopy assays and quantitative PCR (qPCR). Serologic analysis complemented these studies and was used as a method of monitoring infection amongst murine colonies. Overall, these findings demonstrate that MHV-68 infection can be controlled and monitored in murine research facilities, and the potential for unintentional infection is low.

  1. Comparison of white-footed mice and rice rats as biomonitors of polychlorinated biphenyl and metal contamination.

    Science.gov (United States)

    Smith, Philip N; Cobb, George P; Harper, Frances M; Adair, Blakely M; McMurry, Scott T

    2002-01-01

    A study was conducted to assess differences in contaminant assimilation among co-occurring white-footed mice (Peromyscus leucopus) and rice rats (Oryomys palustris) captured at a contaminated site. Rodents were collected from five areas at the Paducah Gaseous Diffusion Plant (PGDP), a uranium enrichment facility. Relatively few white-footed mice (8.7%) had quantifiable concentrations of PCBs compared to 42% of rice rats (chi2 = 6.49, d.f. = 1, P < 0.025), and seven of the 11 rice rats (64%) over 50 g body mass had quantifiable concentrations of PCBs in their livers. White-footed mice had higher mean concentrations of barium (P < 0.0001), chromium (P = 0.0010), copper (P = 0.0011), lead (P = 0.0335), and aluminum (P = 0.0006) than rice rats at all five sampling areas. Species-specific differences in accumulation of PCBs and metals were observed and attributed to differences in habitat use and foraging strategies.

  2. Improving reproducibility and external validity. The role of standardization and data reporting of laboratory rat husbandry and housing.

    Science.gov (United States)

    Fontoura-Andrade, José Luiz; Amorim, Rivadávio Fernandes Batista de; Sousa, João Batista de

    2017-03-01

    To identify the most relevant flaws in standardization in husbandry practices and lack of transparency to report them. This review proposes some measures in order to improve transparency, reproducibility and eventually external validity in experimental surgery experiments with rat model. We performed a search of scientific articles in PUBMED data base. The survey was conducted from august 2016 to January 2017. The keywords used were "reproducibility", "external validity", "rat model", "rat husbandry", "rat housing", and the time frame was up to January 2017. Articles discarded were the ones which the abstract or the key words did not imply that the authors would discuss any relationship of husbandry and housing with the reproducibility and transparency of reporting animal experiment. Reviews and papers that discussed specifically reproducibility and data reporting transparency were laboriously explored, including references for other articles that could fulfil the inclusion criteria. A total of 246 articles were initially found but only 44 were selected. Lack of transparency is the rule and not the exception when reporting results with rat model. This results in poor reproducibility and low external validity with the consequence of considerable loss of time and financial resources. There are still much to be done to improve compliance and adherence of researchers, editors and reviewers to adopt guidelines to mitigate some of the challenges that can impair reproducibility and external validity. Authors and reviewers should avoid pitfalls of absent, insufficient or inaccurate description of relevant information the rat model used. This information should be correctly published or reported on another source easily available for readers. Environmental conditions are well known by laboratory animal personnel and are well controlled in housing facilities, but usually neglected in experimental laboratories when the rat model is a novelty for the researcher.

  3. Differences in the pathways for metabolism of benzene in rats and mice simulated by a physiological model.

    Science.gov (United States)

    Medinsky, M A; Sabourin, P J; Henderson, R F; Lucier, G; Birnbaum, L S

    1989-07-01

    Studies conducted by the National Toxicology Program on the chronic toxicity of benzene indicated that B6C3F1 mice were more sensitive to the carcinogenic effects of benzene than were F344 rats. A physiological model was developed to describe the uptake and metabolism of benzene in rats and mice. Our objective was to determine if differences in toxic effects could be explained by differences in pathways for benzene metabolism or by differences in total uptake of benzene. Compartments incorporated into the model included liver, fat, a poorly perfused tissue group, a richly perfused tissue group, an alveolar or lung compartment and blood. Metabolism of benzene was assumed to take place only in the liver and to proceed by four major competing pathways. These included formation of hydroquinone conjugates (HQC), formation of phenyl conjugates (PHC), ring-breakage and formation of muconic acid (MUC), and conjugation with glutathione with subsequent mercapturic acid (PMA) formation. Values for parameters such as alveolar ventilation, cardiac output, organ volumes, blood flow, partition coefficients, and metabolic rate constants were taken from the literature. Model simulations confirmed that during and after 6-hr inhalation exposures mice metabolized more benzene on a mumole per kilogram body weight basis than did rats. After oral exposure, rats metabolized more benzene than mice at doses above 50 mg/kg because of the more rapid absorption and exhalation of benzene by mice. Model simulations for PHC and PMA, generally considered to be detoxification metabolites, were similar in shape and dose-response to those for total metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Differences in the pathways for metabolism of benzene in rats and mice simulated by a physiological model.

    Science.gov (United States)

    Medinsky, M A; Sabourin, P J; Henderson, R F; Lucier, G; Birnbaum, L S

    1989-01-01

    Studies conducted by the National Toxicology Program on the chronic toxicity of benzene indicated that B6C3F1 mice were more sensitive to the carcinogenic effects of benzene than were F344 rats. A physiological model was developed to describe the uptake and metabolism of benzene in rats and mice. Our objective was to determine if differences in toxic effects could be explained by differences in pathways for benzene metabolism or by differences in total uptake of benzene. Compartments incorporated into the model included liver, fat, a poorly perfused tissue group, a richly perfused tissue group, an alveolar or lung compartment and blood. Metabolism of benzene was assumed to take place only in the liver and to proceed by four major competing pathways. These included formation of hydroquinone conjugates (HQC), formation of phenyl conjugates (PHC), ring-breakage and formation of muconic acid (MUC), and conjugation with glutathione with subsequent mercapturic acid (PMA) formation. Values for parameters such as alveolar ventilation, cardiac output, organ volumes, blood flow, partition coefficients, and metabolic rate constants were taken from the literature. Model simulations confirmed that during and after 6-hr inhalation exposures mice metabolized more benzene on a mumole per kilogram body weight basis than did rats. After oral exposure, rats metabolized more benzene than mice at doses above 50 mg/kg because of the more rapid absorption and exhalation of benzene by mice. Model simulations for PHC and PMA, generally considered to be detoxification metabolites, were similar in shape and dose-response to those for total metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2792050

  5. Protective Effect of Zizphus Vulgaris Extract, on Liver Toxicity in Laboratory Rats

    Directory of Open Access Journals (Sweden)

    S Ebrahimi

    2011-06-01

    Full Text Available Introduction & Objective: Some of natural and synthetic products have antioxidant properties which protect the liver against the destructive factors. This study aimed to investigate the effect of Zizphus Vulgaris extracts on mice liver. Materials & Methods: This experimental study was conducted at Yasouj University of Medical Sciences in 2010 on 30 healthy adult male Wistar rats. Animals were randomly divided into five equal groups: the control group (receiving, olive oil, control group (receiving olive oil and carbon tetrachloride and three intervention groups (receiving different dose of carbon tetrachloride and olive oil groups. The intervention group was given daily doses of 200, 400 and 600 mg per Kg of Zizphus Vulgaris extract by gavage respectively. After 45 days, the amount of liver enzymes, total protein, albumin and bilirubin in animal’s sera were measured. Data were analyzed by the SPSS software, using ANOVA and t-test. Results: The concentration of total protein, albumin, AST, ALT, ALP in test groups I, II and III receiving Z.Vulgaris extract (200, 400 and 600 mg/kg weight compared with control group were statistically not significant. Consumption of Z.Vulgaris reduced the bilirubin concentration in test groups I and II but this decrease was significant only in the test group I Increasing of Z.Vulgaris dose in the test group III (600 mg Z.Vulgaris per kg body weight showed increase in the level of serum bilirubin. Increase in the ratio of liver weight to body weight of rats in groups I and III in comparison with control groups was noticed although this difference was not statistically significant. Findings of this study revealed that dosage of 600 mg/kg extract of Z.Vulgaris caused significant improvements in CCl4 induced liver necrosis (P <0.01 and reduced portal cells inflammation (P <0.01. Dose of 400 mg/kg of Z.Vulgaris induced some destruction and necrosis of liver cells in animals but significant reduction of portal cells

  6. Comparative characterization of microRNAs in Schistosoma japonicum schistosomula from Wistar rats and BALB/c mice.

    Science.gov (United States)

    Han, Hongxiao; Peng, Jinbiao; Hong, Yang; Fu, Zhiqiang; Lu, Ke; Li, Hao; Zhu, Chuangang; Zhao, Qiuhua; Lin, Jiaojiao

    2015-07-01

    More than 40 kinds of mammals in China are known to be naturally infected with Schistosoma japonicum (S. japonicum) (Peng et al. Parasitol Res 106:967-76, 2010). Compared with permissive BALB/c mice, rats are less susceptible to S. japonicum infection and are considered to provide an unsuitable microenvironment for parasite growth and development. MicroRNAs (miRNAs), via the regulation of gene expression at the transcriptional and post-transcriptional levels, may be responsible for developmental differences between schistosomula in these two rodent hosts. Solexa deep-sequencing technology was used to identify differentially expressed miRNAs from schistosomula isolated from Wistar rats and BALB/c mice 10 days post-infection. The deep-sequencing analysis revealed that nearly 40 % of raw reads (10.37 and 10.84 million reads in schistosomula isolated from Wistar rats and BALB/c mice, respectively) can be mapped to selected mirs in miRBase or in species-specific genomes. Further analysis revealed that several miRNAs were differentially expressed in schistosomula isolated from these two rodents; 18 were downregulated (by 2-fold) (expression levels in rats compare with those in mice). Additionally, three novel miRNAs were primarily predicted and identified. Among the 41 differentially expressed miRNAs, 4 miRNAs had been identified with specific functions in schistosome development or host-parasite interaction, such as sexual maturation (sja-miR-1, sja-miR-7-5p), embryo development (sja-miR-36-3p) in schistosome, and pathogenesis of schistosomiasis (sja-bantam). Then, the target genes were mapped, filtered, and correlated with a set of genes that were differentially expressed genes in schistosomula isolated from mice and rats, which we identified in a S. japonicum oligonucleotide microarray analysis in a previous study. Gene Ontology (GO) analysis of the predicted target genes of 13 differentially expressed miRNAs revealed that they were involved in some important

  7. The distribution of Tap2 alleles among laboratory rat RT1 haplotypes.

    Science.gov (United States)

    Joly, E; Deverson, E V; Coadwell, J W; Günther, E; Howard, J C; Butcher, G W

    1994-01-01

    We are reporting the cDNA sequences of Tap2 from two cima and two cimb rat strains. Comparison of the cDNA sequences shows that these alleles fall into two groups, which we refer to as Tap2-A and Tap2-B. We found that alleles from the Tap2-B group are more closely related to the mouse homologue than are Tap2-A alleles, and among the 48 nucleotides which differ between the Tap2-A and Tap2-B cDNAs, three affect restriction sites. We defined pairs of oligonucleotides which allow amplification of the regions bearing these restriction sites from genomic DNA or cDNA, and this technique has been successful for the genotyping of all of the 56 laboratory strains of Rattus norvegicus tested and for five cell lines tested so far. All 14 known RT1 standard haplotypes were tested, and 7 found to belong to the Tap2-B group, and 7 to Tap2-A. We also found that intron sizes among the alleles of the Tap2-B group fall into two subgroups, providing further insight into the phylogeny of these various haplotypes.

  8. Low energy scatter due to in-situ irradiation of solid tumors in laboratory rats

    Energy Technology Data Exchange (ETDEWEB)

    Ritenour, E.R. Jr.

    1980-01-01

    A study of the pattern of scattered radiation in laboratory rat cadavers during irradiation of solid tumors on the animals' flanks was performed. The animals were wrapped in a lead shield having a circular cutout through which the tumor protruded. Irradiations were performed with a 250 kVp 15ma X-ray machine with a measured half value layer of 1.39 mmCu. Lead shielding was of sufficient thickness to attenuate essentially all of the beam. The absorbed dose measured in the animal was then due to internal scatter from the tumor. Arrays of thermoluminescent dosimeters (TLDs) were placed beneath the skin of 17 animals bearing a solid tumor (hepatoma H-4-II-E). Absorbed dose was seen to vary isotropically, decreasing as the inverse distance squared from the tumor. Analysis of experimental error played a major role in this study. A pilot study resulted in standard errors that were 35% of the mean absorbed dose measurements. A careful reassessment of methods of manipulating the animals and the dosimetry system resulted in a reduction in standard error to 14% of the mean for small groups (less than 10 animals).

  9. [The combined effect of lead and zinc on the embryonic development of laboratory rats].

    Science.gov (United States)

    Bezetskaia, E N; Onul, N M

    2014-01-01

    In the article there are presented the results of the study of the impact of inorganic lead and zinc compounds, as well as their organic forms produced with the use of nanotechnoloy, on the embryonic development of laboratory rats. Metals were orally administered daily during 19 days of gestation at the doses of 0.05 mg/kg of lead, and 1.5 mg/kg of zinc. The impact of the test substances was evaluated by integral and specific indices with the use of physiological, morphological and quantitative methods of analysis. Lead in a dose of 0.05 mg/kg was established to disturb the antenatal development of the offspring of experimental animals, which is pronounced in the increased embryo lethality rate, deterioration of somatometric indices of male fetuses in the litter as compared with the control group, and compared with females. In permits to suggest the greater sensitivity of male fetuses to exposure to lead. The isolated impact of zinc in the dose of 1.5 mg/kg body weight does not influence on the levels of embrio mortality rate, as well as somatometric indices of fetuses. However, the combined administration of the compounds of zinc and lead weakens the embryotoxic effect of the latter in terms of embrio lethality and the amount of live fetuses in the litter with more effective bioprotection for zinc in the nanoaquachelate form.

  10. Assessment of post-laparotomy pain in laboratory mice by telemetric recording of heart rate and heart rate variability

    Directory of Open Access Journals (Sweden)

    Kasermann Hans P

    2007-08-01

    Full Text Available Abstract Background Pain of mild to moderate grade is difficult to detect in laboratory mice because mice are prey animals that attempt to elude predators or man by hiding signs of weakness, injury or pain. In this study, we investigated the use of telemetry to identify indicators of mild-to-moderate post-laparotomy pain. Results Adult mice were subjected to laparotomy, either combined with pain treatment (carprofen or flunixin, 5 mg/kg s/c bid, for 1 day or without pain relief. Controls received anesthesia and analgesics or vehicle only. Telemetrically measured locomotor activity was undisturbed in all animals, thus confirming that any pain experienced was of the intended mild level. No symptoms of pain were registered in any of the groups by scoring the animals' outer appearance or spontaneous and provoked behavior. In contrast, the group receiving no analgesic treatment after laparotomy demonstrated significant changes in telemetry electrocardiogram recordings: increased heart rate and decreased heart rate variability parameters pointed to sympathetic activation and pain lasting for 24 hours. In addition, core body temperature was elevated. Body weight and food intake were reduced for 3 and 2 days, respectively. Moreover, unstructured cage territory and destroyed nests appeared for 1–2 days in an increased number of animals in this group only. In controls these parameters were not affected. Conclusion In conclusion, real-time telemetric recordings of heart rate and heart rate variability were indicative of mild-to-moderate post-laparotomy pain and could define its duration in our mouse model. This level of pain cannot easily be detected by direct observation.

  11. Regionalization of epididymal duct and epithelium in rats and mice by automatic computer-aided morphometric analysis

    Institute of Scientific and Technical Information of China (English)

    C. Soler; J. J. de Monserrat; M. Nú(n)ez; R. Gutiérrez; J. Nú(n)ez; M. Sancho; T. G. Cooper

    2005-01-01

    Aim: To establish a rat and mouse epididymal map based on the use of the Epiquatre automatic software for histologic image analysis. Methods: Epididymides from five adult rats and five adult mice were fixed in alcoholic Bouin's fixative and embedded in paraffin. Serial longitudinal sections through the medial aspect of the organ were cut at 10 μm and stained with hematoxylin and eosin. As determined from major connective tissue septa, nine subdivisions of the rat epididymis and seven for the mouse were determined, consisting of five sub-regions in the caput (rat and mouse), one (mouse) or three (rat) in the corpus and one in the cauda (rat and mouse). Using the Epiquatre software,several tubular, luminal and epithelial morphometric parameters were evaluated. Results: Statistical comparison of the quantitative parameters revealed regional differences (2-5 in the rat, 3-6 in the mouse, dependent on parameters)with caput regions 1 and 2 being largely distinguishable from the similar remaining caput and corpus, which were in turn recognizable from the cauda regions in both species. Conclusion: The use of the Epiquatre software allowed us to establish regression curves for different morphometric parameters that can permit the detection of changes in their values under different pathological or experimental conditions.

  12. Laboratory Mice Are Frequently Colonized with Staphylococcus aureus and Mount a Systemic Immune Response-Note of Caution for In vivo Infection Experiments.

    Science.gov (United States)

    Schulz, Daniel; Grumann, Dorothee; Trübe, Patricia; Pritchett-Corning, Kathleen; Johnson, Sarah; Reppschläger, Kevin; Gumz, Janine; Sundaramoorthy, Nandakumar; Michalik, Stephan; Berg, Sabine; van den Brandt, Jens; Fister, Richard; Monecke, Stefan; Uy, Benedict; Schmidt, Frank; Bröker, Barbara M; Wiles, Siouxsie; Holtfreter, Silva

    2017-01-01

    Whether mice are an appropriate model for S. aureus infection and vaccination studies is a matter of debate, because they are not considered as natural hosts of S. aureus. We previously identified a mouse-adapted S. aureus strain, which caused infections in laboratory mice. This raised the question whether laboratory mice are commonly colonized with S. aureus and whether this might impact on infection experiments. Publicly available health reports from commercial vendors revealed that S. aureus colonization is rather frequent, with rates as high as 21% among specific-pathogen-free mice. In animal facilities, S. aureus was readily transmitted from parents to offspring, which became persistently colonized. Among 99 murine S. aureus isolates from Charles River Laboratories half belonged to the lineage CC88 (54.5%), followed by CC15, CC5, CC188, and CC8. A comparison of human and murine S. aureus isolates revealed features of host adaptation. In detail, murine strains lacked hlb-converting phages and superantigen-encoding mobile genetic elements, and were frequently ampicillin-sensitive. Moreover, murine CC88 isolates coagulated mouse plasma faster than human CC88 isolates. Importantly, S. aureus colonization clearly primed the murine immune system, inducing a systemic IgG response specific for numerous S. aureus proteins, including several vaccine candidates. Phospholipase C emerged as a promising test antigen for monitoring S. aureus colonization in laboratory mice. In conclusion, laboratory mice are natural hosts of S. aureus and therefore, could provide better infection models than previously assumed. Pre-exposure to the bacteria is a possible confounder in S. aureus infection and vaccination studies and should be monitored.

  13. Impaired immune function in seals and laboratory rats exposed to dioxin-like compounds from Baltic herring

    Energy Technology Data Exchange (ETDEWEB)

    Ross, P.S. [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands); Swart, R.L. de [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[Erasmus Univ., Rotterdam (Netherlands); Timmerman, H.H.; Loveren, H. van [National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands); Osterhaus, A.D.M.E. [Seal Rehabilitation and Research Centre, Pieterburen (Netherlands)]|[National Inst. of Public Health and Environmental Protection, Bilthoven (Netherlands)]|[Erasmus Univ., Rotterdam (Netherlands)

    1995-12-31

    Complex mixtures of lipophilic contaminants have been shown to affect certain top predators in the aquatic food chain, including seals. A recent demonstration that harbor seals (Phoca vitulina) fed Baltic Sea herring displayed impaired natural killer cell activity and T-lymphocyte function represented the first demonstration of immunotoxicity induced by ambient levels of contaminants in the environment. While these animals had a lower ability to respond to immunizations with inactivated vaccines, specific antibody responses, and in vitro antigen-specific lymphoproliferative responses, obvious constraints limited the ability to extend these results with host resistance tests or an evaluation of thymus and other lymphoid organs. The authors therefore set up a parallel study by exposing pregnant laboratory rats to the same Baltic herring contaminant mixture as received the seals. They then examined immune function parameters and host resistance to virus infection. As in the seals, rat pups of the Baltic group had impaired T-lymphocyte function. In addition, thymus cells and/or their precursors appeared to be targeted, as their numbers and function were reduced in the rats. Following challenge with rat cytomegalovirus in a host resistance study, rat pups in the Baltic group had impaired natural killer cell responses to the virus infection, and lower specific CD8 + (cytotoxic T-lymphocyte) responses following in vitro stimulation. By extrapolation, these results suggest that the impaired immune responses observed in the Baltic group of seals may lead to a less effective defense against virus infections in marine mammals inhabiting polluted coastal waters. Toxicological profiles and results of both the captive seal and laboratory rat experiments tend to implicate the 2,3,7,8-TCDD-like PCB, dioxin and furan congeners in the immunosuppression, and point to a major role for the PCBs.

  14. Enhanced elimination of theophylline, phenobarbital and strychnine from the bodies of rats and mice by squalane treatment.

    Science.gov (United States)

    Kamimura, H; Koga, N; Oguri, K; Yoshimura, H

    1992-05-01

    Our previous study suggested that squalane would be a good candidate for an antidote to reduce the toxicity of drug ingested accidentally at a high dose by enhancing the drug elimination from the body. In the present study, we investigated whether squalane given orally could enhance the elimination of theophylline, phenobarbital and strychnine which were administered parenterally to rats or mice. Squalane increased the fecal excretion of theophylline and reduced the serum level of the drug in rats. Squalane accelerated the fecal excretion of strychnine in mice. These results suggest that squalane may stimulate more the elimination of neutral (theophylline) or basic (strychnine) drugs which should be present in unionized form in intestinal lumen, than that of acidic drugs.

  15. Effects of spirulina, a blue-green alga, on bone metabolism in ovariectomized rats and hindlimb-unloaded mice.

    Science.gov (United States)

    Ishimi, Yoshiko; Sugiyama, Fumie; Ezaki, Junko; Fujioka, Maiko; Wu, Jian

    2006-02-01

    The safety and effectiveness were examined of the spirulina alga on bone metabolism in ovariectomized estrogen-deficient rats and hindlimb-unloaded mice. The dosage range was from an amount equal to that recommended in so-called health foods for humans (0.08 g/kg BW/day) to a 100-fold higher dose. The bone mineral density (BMD) of the whole femur and tibia of ovariectomized rats in the any spirulina-treated groups was not significantly different from that of the ovariectomized group, although BMD of the distal femur and proximal tibia was significantly lower in the spirulina-treated groups than in the ovariectomized group after a 6 week-experimental period. BMD of the femur and tibia was not affected by treatment with any dose of spirulina in hindlimb-unloaded mice. These results suggest that the intake of spirulina decreased BMD in the trabecular bone of rodents under estrogen-deficient conditions.

  16. Patterns of infection with the nematodes Syphacia obvelata and Aspiculuris tetraptera in conventionally maintained laboratory mice

    Directory of Open Access Journals (Sweden)

    Telma Bazzano

    2002-09-01

    Full Text Available Data on the frequency, distribution and mean intensity of the helminth fauna recovered from outbred and inbred mice conventionally maintained in Brazilian animal houses, are reported. The oxyurid nematodes Syphacia obvelata and Aspiculuris tetraptera presented overall frequencies of 91.5% and 8.5%, respectively. The frequency of S. obvelata in animals of three groups out of the four investigated ranged from 9% to 74% and A. tetraptera from 17% to 83%, since animals of one of the groups were negative for helminths. Infections due to a single species were observed in 62% of the animals, compared to 16% related to associations. The frequency of single infections in each group varied from 58.6% to 100% whereas associations varied from 24.1% to 41.4%. The analysis of specific mean intensities showed that S. obvelata was represented by 13.35 to 66.58 specimens/host and A. tetraptera by 5.85 to 16.75 specimens/host.

  17. A comparison of the efficacy of pyridostigmine alone and the combination of pyridostigmine with anticholinergic drugs as pharmacological pretreatment of tabun-poisoned rats and mice.

    Science.gov (United States)

    Kassa, Jirí; Vachek, J

    2002-08-15

    The ability of two types of pharmacological pretreatment (pyridostigmine alone or pyridostigmine in combination with two anticholinergic drugs) to increase the resistance of rats and mice against tabun and to increase the therapeutic efficacy of common antidotal treatment of tabun-poisoned rats and mice was compared. A significant decrease in the LD50 values of tabun was observed when mice as well as rats were pretreated with the prophylactic antidotal mixture consisting of pyridostigmine, benactyzine and trihexyphenidyle, designated PANPAL. Pyridostigmine-pretreated rats were also more resistant against acute lethal effects of tabun but pyridostigmine-induced resistance of rats was not so high as PANPAL-induced resistance. In addition, the pharmacological pretreatment with pyridostigmine alone was not able to protect mice against tabun-induced acute toxicity. The pharmacological pretreatment with pyridostigmine alone was able to increase the efficacy of currently used antidotal treatment (obidoxime in combination with atropine and diazepam) of tabun-induced poisoning, but PANPAL-induced increase in the efficacy of the same antidotal treatment was significantly higher than an increase induced by pyridostigmine alone. PANPAL-induced increase in the efficacy of antidotal treatment of tabun poisoning was also observed in mice. These findings confirm that PANPAL pretreatment of tabun-poisoned rats and mice seems to be much more suitable than currently used pyridostigmine alone.

  18. Reevaluation and Classification of Duodenal Lesions in B6C3F1 Mice and F344 Rats from 4 Studies of Hexavalent Chromium in Drinking Water.

    Science.gov (United States)

    Cullen, John M; Ward, Jerrold M; Thompson, Chad M

    2016-02-01

    Thirteen-week and 2-year drinking water studies conducted by the National Toxicology Program (NTP) reported that hexavalent chromium (Cr(VI)) induced diffuse epithelial hyperplasia in the duodenum of B6C3F1 mice but not F344 rats. In the 2-year study, Cr(VI) exposure was additionally associated with duodenal adenomas and carcinomas in mice only. Subsequent 13-week Cr(VI) studies conducted by another group demonstrated non-neoplastic duodenal lesions in B6C3F1 mice similar to those of the NTP study as well as mild duodenal hyperplasia in F344 rats. Because intestinal lesions in mice are the basis for proposed safety standards for Cr(VI), and the histopathology data are relevant to the mode of action, consistency (an important Hill criterion for causality) was assessed across the aforementioned studies. Two veterinary pathologists applied uniform diagnostic criteria to the duodenal lesions in rats and mice from the 4 repeated-dose studies. Comparable non-neoplastic intestinal lesions were evident in mice and rats from all 4 studies; however, the incidence and severity of intestinal lesions were greater in mice than rats. These findings demonstrate consistency across studies and species and highlight the importance of standardized nomenclature for intestinal pathology. The differences in the severity of non-neoplastic lesions also likely contribute to the differential tumor response.

  19. Respiratory tract changes in guinea pigs, rats, and mice following a single six-hour exposure to methyl isocyanate vapor

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, E.H.; Dodd, D.E.

    1987-06-01

    Groups of male and female Fischer 344 rats, B6C3F1 mice, and Hartley guinea pigs were exposed once for 6 hr to mean concentrations of 10.5, 5.4, 2.4, 1.0, or 0 (control) ppm of methyl isocyanate (MIC) vapor. Rats and mice were also exposed to 20.4 ppm of MIC. The majority of deaths occurred during postexposure days 1 through 3. The 6-hr LC/sub 50/ values were 6.1 ppm for rats, 12.2 ppm for mice, and 5.4 ppm for guinea pigs. Notable clinical observations during and immediately following MIC exposure were lacrimation, perinasal/perioral wetness, respiratory difficulty (e.g., mouth breathing), decreased activity, ataxia, and hypothermia. Body weight losses were common in all species following MIC exposures of 2.4 ppm or greater. Microscopic lesions included acute necrosis of the epithelial lining throughout the respiratory tract in animals that died shortly after exposure, coupled with congestion, edema, and inflammation. A microscopic lesion that appeared unique to guinea pigs was bronchiolitis obliterans. Additional microscopic lesions observed in some animals that died or were sacrificed at the end of the study (postexposure day 14) consisted of squamous metaplasia of respiratory epithelium in the nasal cavity, which extended into the larynx, trachea, and in some cases, the bronchi. In addition, epithelial regeneration throughout the tract and submucosal fibroplasia in the trachea, bronchi, and bronchioles were observed, the latter lesion being primarily confined to rodents. Only in guinea pigs were there lesions in the 1.0 ppm group attributed to MIC exposure. In conclusion, guinea pigs were more sensitive to the MIC vapor than were rats, which were in turn more sensitive than mice.

  20. Antinociceptive and anti-inflammatory activities of crude extracts of Ipomoea involucrata leaves in mice and rats

    Institute of Scientific and Technical Information of China (English)

    Uche Fidelia Ijeoma; Shorinwa Olusayo Aderonke; Okorie Ogbonna; Mgbahurike Amaka Augustina; Chijioke-Nwauche Ifeyinwa

    2011-01-01

    Objective: To investigate antinociceptive and anti-inflammatory activities of crude extract from Ipomoea involucrata leaves (Convolvulaceae) in mice and rats.Methods:The antinociceptive activity was tested using acetic acid-induced abdominal writhing test in mice. The anti-inflammatory activity was evaluated using egg albumin–induced oedema of rat paw.Results:Phytochemical screening showed the presence of alkaloids, flavonoids, saponins, terpenoids and tannin. At the doses of 25-100 mg/kg,Ipomoea involucrata exhibited dose-dependent and significant increase in pain threshold in acetic acid–induced writhing test of mice (P<0.05, student t-test) The administration ofIpomoea involucrata leaf extract (25-100 mg/kg) showed dose-dependent decreases in paw volume of egg albumin induced oedema in rats and a significant higher anti-inflammatory activity compared to the standard control (Aspirin). Conclusions: These results support the claims on the traditional use of the ofIpomoea involucrata leaves in the treatment of toothache, rheumatic pains and other inflammatory conditions. Studies on the isolation and structural elucidation of the active principle are still needed being carried out.

  1. Mutant laboratory mice with abnormalities in hair follicle morphogenesis, cycling, and/or structure: an update.

    Science.gov (United States)

    Nakamura, Motonobu; Schneider, Marlon R; Schmidt-Ullrich, Ruth; Paus, Ralf

    2013-01-01

    Human hair disorders comprise a number of different types of alopecia, atrichia, hypotrichosis, distinct hair shaft disorders as well as hirsutism and hypertrichosis. Their causes vary from genodermatoses (e.g. hypotrichoses) via immunological disorders (e.g. alopecia areata, autoimmune cicatrical alopecias) to hormone-dependent abnormalities (e.g. androgenetic alopecia). A large number of spontaneous mouse mutants and genetically engineered mice develop abnormalities in hair follicle morphogenesis, cycling, and/or hair shaft formation, whose analysis has proven invaluable to define the molecular regulation of hair growth, ranging from hair follicle development, and cycling to hair shaft formation and stem cell biology. Also, the accumulating reports on hair phenotypes of mouse strains provide important pointers to better understand the molecular mechanisms underlying human hair growth disorders. Since numerous new mouse mutants with a hair phenotype have been reported since the publication of our earlier review on this matter a decade ago, we present here an updated, tabulated mini-review. The updated annotated tables list a wide selection of mouse mutants with hair growth abnormalities, classified into four categories: Mutations that affect hair follicle (1) morphogenesis, (2) cycling, (3) structure, and (4) mutations that induce extrafollicular events (for example immune system defects) resulting in secondary hair growth abnormalities. This synthesis is intended to provide a useful source of reference when studying the molecular controls of hair follicle growth and differentiation, and whenever the hair phenotypes of a newly generated mouse mutant need to be compared with existing ones. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Effects of Dietary Proteins of Proso, Japanese and Korean Foxtail Millets on Lipid Metabolism and Type-2 Diabetes in Rats and Mice

    Institute of Scientific and Technical Information of China (English)

    Naoyuki Nishizawa; M-R Choi; Y-Y. Choi; Y. Miyakoshi; D. Sato; T. Togawa; T. Nagasawa; Y. Ito; M Watanabe; M. Sato

    2005-01-01

    @@ Summary We examined the effects of dietary Japanese millet protein (JMP) and Korean foxtail millet protein (KFMP) on lipid metabolism and type 2 diabetes in rats and mice. When type 2 diabetic rats were fed with JMP for 20 days, plasma glucose levels lowered, whereas those of HDL-cholesterol and adiponectin rose significantly compared to the control group.

  3. Disposition and metabolism of cumene in F344 rats and B6C3F1 mice.

    Science.gov (United States)

    Chen, Ling-Jen; Wegerski, Christopher J; Kramer, Daniel J; Thomas, Leslie A; McDonald, Jacob D; Dix, Kelly J; Sanders, J Michael

    2011-03-01

    Cumene is a high-production volume chemical that has been shown to be a central nervous system depressant and has been implicated as a long-term exposure carcinogen in experimental animals. The absorption, distribution, metabolism, and excretion of [(14)C]cumene (isopropylbenzene) was studied in male rats and mice of both sexes after oral or intravenous administration. In both species and sexes, urine accounted for the majority of the excretion (typically ≥ 70%) by oral and intravenous administration. Enterohepatic circulation of cumene and/or its metabolites was indicated because 37% of the total dose was excreted in bile in bile duct-cannulated rats with little excreted in normal rats. The highest tissue (14)C levels in rats were observed in adipose tissue, liver, and kidney with no accumulation observed after repeat dosing up to 7 days. In contrast, mice contained the highest concentrations of (14)C at 24 h after dosing in the liver, kidney, and lung, with repeat dosing accumulation of (14)C observed in these tissues as well as in the blood, brain, heart, muscle, and spleen. The metabolites in the expired air, urine, bile, and microsomes were characterized with 16 metabolites identified. The volatile organics in the expired air comprised mainly cumene and up to 4% α-methylstyrene. The major urinary and biliary metabolite was 2-phenyl-2-propanol glucuronide, which corresponded with the main microsomal metabolite being 2-phenyl-2-propanol.

  4. Sustained release of BMP-2 in bioprinted alginate for osteogenicity in mice and rats.

    Directory of Open Access Journals (Sweden)

    Michelle T Poldervaart

    Full Text Available The design of bioactive three-dimensional (3D scaffolds is a major focus in bone tissue engineering. Incorporation of growth factors into bioprinted scaffolds offers many new possibilities regarding both biological and architectural properties of the scaffolds. This study investigates whether the sustained release of bone morphogenetic protein 2 (BMP-2 influences osteogenicity of tissue engineered bioprinted constructs. BMP-2 loaded on gelatin microparticles (GMPs was used as a sustained release system, which was dispersed in hydrogel-based constructs and compared to direct inclusion of BMP-2 in alginate or control GMPs. The constructs were supplemented with goat multipotent stromal cells (gMSCs and biphasic calcium phosphate to study osteogenic differentiation and bone formation respectively. BMP-2 release kinetics and bioactivity showed continuous release for three weeks coinciding with osteogenicity. Osteogenic differentiation and bone formation of bioprinted GMP containing constructs were investigated after subcutaneous implantation in mice or rats. BMP-2 significantly increased bone formation, which was not influenced by the release timing. We showed that 3D printing of controlled release particles is feasible and that the released BMP-2 directs osteogenic differentiation in vitro and in vivo.

  5. Ketogenic Diet Prevents Epileptogenesis and Disease Progression in Adult Mice and Rats

    Science.gov (United States)

    Lusardi, Theresa A.; Akula, Kiran K.; Coffman, Shayla Q.; Ruskin, David; Masino, Susan A.; Boison, Detlev

    2015-01-01

    Epilepsy is a highly prevalent seizure disorder which tends to progress in severity and become refractory to treatment. Yet no therapy is proven to halt disease progression or to prevent the development of epilepsy. Because a high fat low carbohydrate ketogenic diet (KD) augments adenosine signaling in the brain and because adenosine not only suppresses seizures but also affects epileptogenesis, we hypothesized that a ketogenic diet might prevent epileptogenesis through similar mechanisms. Here, we tested this hypothesis in two independent rodent models of epileptogenesis. Using a pentylenetetrazole kindling paradigm in mice, we first show that a KD, but not a conventional antiepileptic drug (valproic acid), suppressed kindling-epileptogenesis. Importantly, after treatment reversal, increased seizure thresholds were maintained in those animals kindled in the presence of a KD, but not in those kindled in the presence of valproic acid. Next, we tested whether a KD can halt disease progression in a clinically relevant model of progressive epilepsy. Epileptic rats that developed spontaneous recurrent seizures after a pilocarpine-induced status epilepticus were treated with a KD or control diet (CD). Whereas seizures progressed in severity and frequency in the CD-fed animals, KD-fed animals showed a prolonged reduction of seizures, which persisted after diet reversal. KD-treatment was associated with increased adenosine and decreased DNA methylation, the latter being maintained after diet discontinuation. Our findings demonstrate that a KD prevented disease progression in two mechanistically different models of epilepsy, and suggest an epigenetic mechanism underlying the therapeutic effects. PMID:26256422

  6. Preliminary toxicity study of dichloromethane extract of Kielmeyera coriacea stems in mice and rats.

    Science.gov (United States)

    Obici, Simoni; Otobone, Fernanda Jacques; da Silva Sela, Vânia Ramos; Ishida, Kelly; da Silva, José Carlos; Nakamura, Celso Vataru; Garcia Cortez, Diógenes Aparício; Audi, Elisabeth Aparecida

    2008-01-01

    Kielmeyera coriacea Mart. (Clusiaceae), known as "Pau Santo" or "Saco de Boi" in the central Brazilian plateau region, is used to treat several tropical diseases. The present study evaluated the toxic effects of dichloromethane (DcM) extract of Kielmeyera coriacea stems, administered to rodents. In the acute toxicity tests, mice receiving doses of this extract by the oral and intraperitoneal routes, showed reversible effects, with LD50 values of 1503.0 and 538.8 mg/kg, respectively. In the repeated-dose oral (90 days) toxicity tests, male and female Wistar rats were treated by gavage with different doses of DcM extract (5, 25 or 125 mg/kg). In biochemical and haematological evaluations, the results varied widely in respect to dose and sex, with no linear profile, and did not show clinical correlations. In the histopathological examinations, the groups exhibited some changes, but there were no significant differences between the groups compared to the controls. In conclusion, these investigations appeared to indicate the safety of acute and repeated oral administration of the DcM extract of Kielmeyera coriacea stems, which can therefore be continuously used with safety.

  7. Ketogenic diet prevents epileptogenesis and disease progression in adult mice and rats.

    Science.gov (United States)

    Lusardi, Theresa A; Akula, Kiran K; Coffman, Shayla Q; Ruskin, David N; Masino, Susan A; Boison, Detlev

    2015-12-01

    Epilepsy is a highly prevalent seizure disorder which tends to progress in severity and become refractory to treatment. Yet no therapy is proven to halt disease progression or to prevent the development of epilepsy. Because a high fat low carbohydrate ketogenic diet (KD) augments adenosine signaling in the brain and because adenosine not only suppresses seizures but also affects epileptogenesis, we hypothesized that a ketogenic diet might prevent epileptogenesis through similar mechanisms. Here, we tested this hypothesis in two independent rodent models of epileptogenesis. Using a pentylenetetrazole kindling paradigm in mice, we first show that a KD, but not a conventional antiepileptic drug (valproic acid), suppressed kindling-epileptogenesis. Importantly, after treatment reversal, increased seizure thresholds were maintained in those animals kindled in the presence of a KD, but not in those kindled in the presence of valproic acid. Next, we tested whether a KD can halt disease progression in a clinically relevant model of progressive epilepsy. Epileptic rats that developed spontaneous recurrent seizures after a pilocarpine-induced status epilepticus were treated with a KD or control diet (CD). Whereas seizures progressed in severity and frequency in the CD-fed animals, KD-fed animals showed a prolonged reduction of seizures, which persisted after diet reversal. KD-treatment was associated with increased adenosine and decreased DNA methylation, the latter being maintained after diet discontinuation. Our findings demonstrate that a KD prevented disease progression in two mechanistically different models of epilepsy, and suggest an epigenetic mechanism underlying the therapeutic effects.

  8. Comparative Immunogenicity of the Tetanus Toxoid and Recombinant Tetanus Vaccines in Mice, Rats, and Cynomolgus Monkeys.

    Science.gov (United States)

    Yu, Rui; Fang, Ting; Liu, Shuling; Song, Xiaohong; Yu, Changming; Li, Jianmin; Fu, Ling; Hou, Lihua; Xu, Junjie; Chen, Wei

    2016-06-25

    Tetanus is caused by the tetanus neurotoxin (TeNT) and is one of the most dreaded diseases especially in the developing countries. The current vaccine against tetanus is based on an inactivated tetanus toxin, which is effective but has many drawbacks. In our previous study, we developed a recombinant tetanus vaccine based on protein TeNT-Hc, with clear advantages over the toxoid vaccine in terms of production, characterization, and homogeneity. In this study, the titers, growth extinction, and persistence of specific antibodies induced by the two types of vaccine in mice, rats, and cynomolgus monkeys were compared. The booster vaccination efficacy of the two types of vaccines at different time points and protection mechanism in animals were also compared. The recombinant tetanus vaccine induced persistent and better antibody titers and strengthened the immunity compared with the commercially available toxoid vaccine in animals. Our results provide a theoretical basis for the development of a safe and effective recombinant tetanus vaccine to enhance the immunity of adolescents and adults as a substitute for the current toxoid vaccine.

  9. Comparison of apoptosis between adult worms of Schistosoma japonicum from susceptible (BALB/c mice) and less-susceptible (Wistar rats) hosts.

    Science.gov (United States)

    Wang, Tao; Guo, Xiaoyong; Hong, Yang; Han, Hongxiao; Cao, Xiaodan; Han, Yanhui; Zhang, Min; Wu, Miaoli; Fu, Zhiqiang; Lu, Ke; Li, Hao; Zhao, Zhixin; Lin, Jiaojiao

    2016-10-30

    Schistosomiasis remains a serious public health concern in China. BALB/c mice are susceptible to Schistosoma japonicum infection, whereas the Wistar rats are less susceptible. Apoptosis phenomenon was observed in 42d adult worms of S. japonicum from both rats and mice at the morphologic, DNA, cellular, and gene levels by transmission electron microscopy (TEM), fluorometric terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) analysis, fluorescein isothiocyanate-annexin-V/propidium iodide staining flow cytometry (FCM) analysis, and real-time PCR. The results showed that the apoptotic state in worms from two different susceptible hosts was diverse. Several classical hallmarks of apoptosis, including cell shrinkage, chromatin condensation and lunate marginalization, splitting of the nucleoli, nuclear shrinkage and apoptotic body formation were observed by TEM. TUNEL analysis showed that there were much more apoptosis spots in adult worms from rats than those from mice. Statistical analysis revealed that the degree of apoptosis and percentage of necrotic cells in adult worms from Wistar rats were significantly greater (Pworms from Wistar rats, as compared to those from BALB/c mice. The results obtained in this study collectively demonstrated that differential development of adult S. japonicum in less-susceptible rats and susceptible mice was significantly associated with apoptosis in the worm, and provided valuable information to guide further investigations of the mechanisms governing apoptosis and host interactions in schistosome infection.

  10. Accelerated Maturation of Human Stem Cell-Derived Pancreatic Progenitor Cells into Insulin-Secreting Cells in Immunodeficient Rats Relative to Mice

    Directory of Open Access Journals (Sweden)

    Jennifer E. Bruin

    2015-12-01

    Full Text Available Pluripotent human embryonic stem cells (hESCs are a potential source of transplantable cells for treating patients with diabetes. To investigate the impact of the host recipient on hESC-derived pancreatic progenitor cell maturation, cells were transplanted into immunodeficient SCID-beige mice or nude rats. Following the transplant, basal human C-peptide levels were consistently higher in mice compared with rats, but only rats showed robust meal- and glucose-responsive human C-peptide secretion by 19–21 weeks. Grafts from rats contained a higher proportion of insulin:glucagon immunoreactivity, fewer exocrine cells, and improved expression of mature β cell markers compared with mice. Moreover, ECM-related genes were enriched, the collagen network was denser, and blood vessels were more intricately integrated into the engrafted endocrine tissue in rats relative to mice. Overall, hESC-derived pancreatic progenitor cells matured faster in nude rats compared with SCID-beige mice, indicating that the host recipient can greatly influence the fate of immature pancreatic progenitor cells post-transplantation.

  11. Investigation and identification of etiologies involved in the development of acquired hydronephrosis in aged laboratory mice with the use of high-frequency ultrasound imaging

    Directory of Open Access Journals (Sweden)

    Danielle A. Springer

    2014-08-01

    Full Text Available Laboratory mice develop naturally occurring lesions that affect biomedical research. Hydronephrosis is a recognized pathologic abnormality of the mouse kidney. Acquired hydronephrosis can affect any mouse, as it is caused by any naturally occurring disease that impairs free urine flow. Many etiologies leading to this condition are of particular significance to aging mice. Non-invasive ultrasound imaging detects renal pelvic dilation, renal enlargement, and parenchymal loss for pre-mortem identification of this condition. High-frequency ultrasound transducers produce high-resolution images of small structures, ideal for detecting organ pathology in mice. Using a 40 MHz linear array transducer, we obtained high-resolution images of a diversity of pathologic lesions occurring within the abdomen of seven geriatric mice with acquired hydronephrosis that enabled a determination of the underlying etiology. Etiologies diagnosed from the imaging results include pyelonephritis, neoplasia, urolithiasis, mouse urologic syndrome, and spontaneous hydronephrosis, and were confirmed at necropsy. A retrospective review of abdominal scans from an additional 149 aging mice shows that the most common etiologies associated with acquired hydronephrosis are mouse urologic syndrome and abdominal neoplasia. This report highlights the utility of high-frequency ultrasound for surveying research mice for age-related pathology, and is the first comprehensive report of multiple cases of acquired hydronephrosis in mice.

  12. [Comparative sensitivity of several laboratory animals to infection by nasal instillation of the saprophytic phase of Emmonsia crescens Emmons & Jellison, 1960: frequency and intensity of parasitism, histological reactions].

    Science.gov (United States)

    Boisseau-Lebreuil, M T

    1975-11-21

    Comparative observations were made on the development of Emmonsia crescens in the lungs of laboratory rats and mice, golden hamsters and guinea pigs after a nasal instillation of a heavy suspension of the saprophytic phase of the fungus. 95% of 80 experimental rats were found to be parasited against 80% of 200 inoculated mice, while only 30% of 70 hamsters and all of 4 guinea pigs showed an infection. The lungs of the mice, rats and guinea pigs were frequently more heavily infected than those of the hamsters. In addition, the adiaspores obtained from the mice and rats had, on average, a diameter double those from the hamsters and their walls were thicker. Thus, the laboratory mice and rats were shown to be better hosts of E. crescens than were golden hamsters.

  13. Effect of multilevel laboratory rat caging system on the well-being of the singly-housed Sprague Dawley rat.

    Science.gov (United States)

    Wheeler, R R; Swan, M P; Hickman, D L

    2015-01-01

    Current regulations emphasize that good husbandry practices allow animals to engage in species appropriate postural adjustments without touching the enclosure walls. This study evaluated the well-being of rats housed in a commercially available multilevel rat caging system, with or without access to the upper level of the caging. The evaluation methodologies included assessment of behavioral observations in the home cage, physiological assessment of metabolism and immune function, and determination of the affective state using a spatial cognitive bias assay. The study determined that rats that were provided access to the full multilevel cage during testing after initial restriction to the lower level of the cage demonstrated behavioral changes consistent with a positive affective state, while those with no changes to their housing situation had no significant differences in their affective states. Rats that were consistently housed with access restricted to the lower level of the cage exhibited a tendency to increased neutrophil:lymphocyte ratios as compared with those provided with access to all levels of the multilevel cage. There were no differences in body weight demonstrated between the experimental groups. Overall use of the cage space, as documented through analysis of behavioral observations in the home cage, demonstrated no significant differences in preferred location in the cage during the light or dark cycles, though rats with access to both levels of the cage were significantly more active during the light cycle. The results of this study suggest that the use of a multilevel caging system may improve the well-being of rats used in research.

  14. Effect of dietary fructose on portal and systemic serum fructose levels in rats and in KHK-/- and GLUT5-/- mice.

    Science.gov (United States)

    Patel, Chirag; Sugimoto, Keiichiro; Douard, Veronique; Shah, Ami; Inui, Hiroshi; Yamanouchi, Toshikazu; Ferraris, Ronaldo P

    2015-11-01

    Elevated blood fructose concentrations constitute the basis for organ dysfunction in fructose-induced metabolic syndrome. We hypothesized that diet-induced changes in blood fructose concentrations are regulated by ketohexokinase (KHK) and the fructose transporter GLUT5. Portal and systemic fructose concentrations determined by HPLC in wild-type mice fed for 7 days 0% free fructose were 1 mM) with reversed portal to systemic gradients. Systemic fructose in wild-type and KHK(-/-) mice changed by 0.34 and 1.8 mM, respectively, for every millimolar increase in portal fructose concentration. Systemic glucose varied strongly with systemic, but not portal, fructose levels in wild-type, and was independent of systemic and portal fructose in KHK(-/-), mice. With ad libitum feeding for 12 wk, fructose-induced hyperglycemia in wild-type, but not hyperfructosemia in KHK(-/-) mice, increased HbA1c concentrations. Increasing dietary fructose to 40% intensified the hyperfructosemia of KHK(-/-) and the fructose-induced hyperglycemia of wild-type mice. Fructose perfusion or feeding in rats also caused duration- and dose-dependent hyperfructosemia and hyperglycemia. Significant levels of blood fructose are maintained independent of dietary fructose, KHK, and GLUT5, probably by endogenous synthesis of fructose. KHK prevents hyperfructosemia and fructose-induced hyperglycemia that would markedly increase HbA1c levels. These findings explain the hyperfructosemia of human hereditary fructosuria as well as the hyperglycemia of fructose-induced metabolic syndrome. Copyright © 2015 the American Physiological Society.

  15. Identification and sequencing of a novel rodent gammaherpesvirus that establishes acute and latent infection in laboratory mice.

    Science.gov (United States)

    Loh, Joy; Zhao, Guoyan; Nelson, Christopher A; Coder, Penny; Droit, Lindsay; Handley, Scott A; Johnson, L Steven; Vachharajani, Punit; Guzman, Hilda; Tesh, Robert B; Wang, David; Fremont, Daved H; Virgin, Herbert W

    2011-03-01

    Gammaherpesviruses encode numerous immunomodulatory molecules that contribute to their ability to evade the host immune response and establish persistent, lifelong infections. As the human gammaherpesviruses are strictly species specific, small animal models of gammaherpesvirus infection, such as murine gammaherpesvirus 68 (γHV68) infection, are important for studying the roles of gammaherpesvirus immune evasion genes in in vivo infection and pathogenesis. We report here the genome sequence and characterization of a novel rodent gammaherpesvirus, designated rodent herpesvirus Peru (RHVP), that shares conserved genes and genome organization with γHV68 and the primate gammaherpesviruses but is phylogenetically distinct from γHV68. RHVP establishes acute and latent infection in laboratory mice. Additionally, RHVP contains multiple open reading frames (ORFs) not present in γHV68 that have sequence similarity to primate gammaherpesvirus immunomodulatory genes or cellular genes. These include ORFs with similarity to major histocompatibility complex class I (MHC-I), C-type lectins, and the mouse mammary tumor virus and herpesvirus saimiri superantigens. As these ORFs may function as immunomodulatory or virulence factors, RHVP presents new opportunities for the study of mechanisms of immune evasion by gammaherpesviruses.

  16. Effect of Erythropoietin, Iron Deficiency and Iron Overload on Liver Matriptase-2 (TMPRSS6) Protein Content in Mice and Rats.

    Science.gov (United States)

    Frýdlová, Jana; Přikryl, Petr; Truksa, Jaroslav; Falke, Lucas L; Du, Xin; Gurieva, Iuliia; Vokurka, Martin; Krijt, Jan

    2016-01-01

    Matriptase-2 (TMPRSS6) is an important negative regulator of hepcidin expression; however, the effects of iron overload or accelerated erythropoiesis on liver TMPRSS6 protein content in vivo are largely unknown. We determined TMPRSS6 protein content in plasma membrane-enriched fractions of liver homogenates by immunoblotting, using a commercial antibody raised against the catalytic domain of TMPRSS6. Plasma membrane-enriched fractions were obtained by centrifugation at 3000 g and washing. TMPRSS6 was detected in the 3000 g fraction as a 120 kDa full-length protein in both mice and rats. Feeding of iron-deficient diet as well as erythropoietin treatment increased TMPRSS6 protein content in rats and mice by a posttranscriptional mechanism; the increase in TMPRSS6 protein by erythropoietin was also observed in Bmp6-mutant mice. Administration of high doses of iron to mice (200, 350 and 700 mg/kg) decreased TMPRSS6 protein content. Hemojuvelin was detected in the plasma membrane-enriched fractions of control animals as a full length protein of approximately 52 kDa; in iron deficient animals, the full length protein was partially cleaved at the N-terminus, resulting in an additional weak band of approximately 47 kDa. In livers from hemojuvelin-mutant mice, TMPRSS6 protein content was strongly decreased, suggesting that intact hemojuvelin is necessary for stable TMPRSS6 expression in the membrane. Overall, the results demonstrate posttranscriptional regulation of liver TMPRSS6 protein by iron status and erythropoietin administration, and provide support for the interaction of TMPRSS6 and hemojuvelin proteins in vivo.

  17. Estimation of the novel antipyretic, anti-inflammatory, antinociceptive and antihyperlipidemic effects of silymarin in Albino rats and mice

    Institute of Scientific and Technical Information of China (English)

    Mohamed; Mahmoud; Amin; Mahmoud; Soliman; Arbid

    2015-01-01

    Objective: To evaluate the other pharmacological actions of silymarin in Albino rats and mice such as antipyretic, anti-inflammatory, antinociceptive and antihyperlipidemic effects. Methods: Rats were injected intramuscularly with pyrogenic dose of brewer’s yeast for the antipyretic test of silymarin. Another group of rats injected with 0.1 mL of 1% carrageenan solution in saline at the subplanter area of the right hind paw for the anti-inflammatory test of silymarin. Another group of mice tested by hot plate method for determination of antinociceptive effect of silymarin. Hyperlipidemia was induced using high fat diet for 2 months to estimate the antihyperlipidemic activity of silymarin. Results: Silymarin showed a significant antipyretic effect of both doses(50 and 100 mg/kg) compared with control untreated group. Moreover, silymarin elucidated a significant anti-inflammatory effect of both doses reflected on the decrease of the rat paw edema every hour interval for 4 h after administration in comparison with control positive group. By the same taken, both doses of silymarine revealed a significant antinociceptive action in hot plate method at 30 and 60 min post administration. Besides, it lowered significantly the serum levels of prostaglandin E2, tumor necrosis factor alpha and interleukin 1 beta after 2 h of silymarin administration in carrageenan induced rat paw edema besides the significant decrease of total cholesterol, triglycerides, low density lipoprotein and significantly elevated high density lipoprotein after 2 weeks of silymarin administration. Conclusions: These outcomes delivered a new vision into the possible pharmacological mechanisms by which silymarin advances antipyretic, anti-inflammatory, antinociceptive and antihyperlipidemic effects.

  18. Method for determining the lung burden of talc in rats and mice after inhalation exposure to talc aerosols.

    Science.gov (United States)

    Hanson, R L; Benson, J M; Henderson, T R; Carpenter, R L; Pickrell, J A; Brown, S C

    1985-10-01

    A method has been developed to quantitate talc lung burdens in rats and mice after inhalation exposure to talc aerosols. The method is based on acid-insoluble magnesium (Mg) determination by flame atomic absorption. Precipitating protein from homogenates of lungs of unexposed rodents with 5% perchloric acid and washing with 5% trichloroacetic acid removed the soluble and naturally occurring Mg. This resulted in residual Mg content averaging 0.43 micrograms Mg per g lung in rats and less than 0.1 microgram Mg per g lung in mice for young rodents less than 12 weeks old. Rodents 12-18 months old had residual mean (+/- SD) Mg contents of 3.4 +/- 2.0 micrograms Mg per g rat lung (n = 17) and 6.5 +/- 2.9 micrograms Mg per g mouse lung (n = 12). Thus, the background residual acid-insoluble Mg content in rodent lungs appears to increase with age. Negligible quantities of Mg were extracted directly from the talc treated by these procedures. Adding 50-2000 micrograms talc to lungs from unexposed rodents, followed by the sample treatment, gave mean (+/- SD) Mg recoveries of 89 +/- 12% (n = 19) for rat lungs and 96 +/- 26% (n = 15) for mouse lungs. The lung burden of talc in rodents exposed to talc aerosols for 6 h per day, 5 days per week for 4 weeks was determined. Mean lung burdens in rats were 77, 187, and 806 micrograms talc per g lung (n = 10) for exposures at 2.3, 4.3, and 17 mg talc m-3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep.

    Science.gov (United States)

    Härtig, Wolfgang; Mages, Bianca; Aleithe, Susanne; Nitzsche, Björn; Altmann, Stephan; Barthel, Henryk; Krueger, Martin; Michalski, Dominik

    2017-01-01

    As part of the extracellular matrix (ECM), perineuronal nets (PNs) are polyanionic, chondroitin sulfate proteoglycan (CSPG)-rich coatings of certain neurons, known to be affected in various neural diseases. Although these structures are considered as important parts of the neurovascular unit (NVU), their role during evolution of acute ischemic stroke and subsequent tissue damage is poorly understood and only a few preclinical studies analyzed PNs after acute ischemic stroke. By employing three models of experimental focal cerebral ischemia, this study was focused on histopathological alterations of PNs and concomitant vascular, glial and neuronal changes according to the NVU concept. We analyzed brain tissues obtained 1 day after ischemia onset from: (a) mice after filament-based permanent middle cerebral artery occlusion (pMCAO); (b) rats subjected to thromboembolic MACO; and (c) sheep at 14 days after electrosurgically induced focal cerebral ischemia. Multiple fluorescence labeling was applied to explore simultaneous alterations of NVU and ECM. Serial mouse sections labeled with the net marker Wisteria floribunda agglutinin (WFA) displayed largely decomposed and nearly erased PNs in infarcted neocortical areas that were demarcated by up-regulated immunoreactivity for vascular collagen IV (Coll IV). Subsequent semi-quantitative analyses in mice confirmed significantly decreased WFA-staining along the ischemic border zone and a relative decrease in the directly ischemia-affected neocortex. Triple fluorescence labeling throughout the three animal models revealed up-regulated Coll IV and decomposed PNs accompanied by activated astroglia and altered immunoreactivity for parvalbumin, a calcium-binding protein in fast-firing GABAergic neurons which are predominantly surrounded by neocortical PNs. Furthermore, ischemic neocortical areas in rodents simultaneously displayed less intense staining of WFA, aggrecan, the net components neurocan, versican and the cartilage link

  20. Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep

    Directory of Open Access Journals (Sweden)

    Wolfgang Härtig

    2017-08-01

    Full Text Available As part of the extracellular matrix (ECM, perineuronal nets (PNs are polyanionic, chondroitin sulfate proteoglycan (CSPG-rich coatings of certain neurons, known to be affected in various neural diseases. Although these structures are considered as important parts of the neurovascular unit (NVU, their role during evolution of acute ischemic stroke and subsequent tissue damage is poorly understood and only a few preclinical studies analyzed PNs after acute ischemic stroke. By employing three models of experimental focal cerebral ischemia, this study was focused on histopathological alterations of PNs and concomitant vascular, glial and neuronal changes according to the NVU concept. We analyzed brain tissues obtained 1 day after ischemia onset from: (a mice after filament-based permanent middle cerebral artery occlusion (pMCAO; (b rats subjected to thromboembolic MACO; and (c sheep at 14 days after electrosurgically induced focal cerebral ischemia. Multiple fluorescence labeling was applied to explore simultaneous alterations of NVU and ECM. Serial mouse sections labeled with the net marker Wisteria floribunda agglutinin (WFA displayed largely decomposed and nearly erased PNs in infarcted neocortical areas that were demarcated by up-regulated immunoreactivity for vascular collagen IV (Coll IV. Subsequent semi-quantitative analyses in mice confirmed significantly decreased WFA-staining along the ischemic border zone and a relative decrease in the directly ischemia-affected neocortex. Triple fluorescence labeling throughout the three animal models revealed up-regulated Coll IV and decomposed PNs accompanied by activated astroglia and altered immunoreactivity for parvalbumin, a calcium-binding protein in fast-firing GABAergic neurons which are predominantly surrounded by neocortical PNs. Furthermore, ischemic neocortical areas in rodents simultaneously displayed less intense staining of WFA, aggrecan, the net components neurocan, versican and the

  1. Chronic psychosocial stressors in adulthood: Studies in mice, rats and tree shrews

    Directory of Open Access Journals (Sweden)

    Christopher R. Pryce

    2017-02-01

    Full Text Available Human psychological stress is the major environmental risk factor for major depression and certain of the anxiety disorders. Psychological stressors often occur in the context of the adult social environment, and they or the memory formed of them impact on the individual across an extended period, thereby constituting chronic psychosocial stress (CPS. Psychosocial stressors often involve loss to the individual, such as the ending of a social relationship or the onset of interpersonal conflict leading to loss of social control and predictability. Given the difficulty in studying the etio-pathophysiological processes mediating between CPS and brain and behavior pathologies in human, considerable effort has been undertaken to study manipulations of the social environment that constitute adulthood chronic psychosocial stressors in other mammals. The majority of such research has been conducted in rodents; the focus for a considerable time period was on rats and more recently both rats and mice have been investigated, the latter species in particular providing the opportunity for essential gene x chronic psychosocial stressor interaction studies. Key studies in the tree shrew demonstrate that this approach should not be limited to rodents, however. The animal adult CPS paradigms are based on resident-intruder confrontations. These are typified by the intruder-subject's brief proximate interactions with and attacks by, and otherwise continuous distal exposure to, the resident stressor. In contrast to humans where cognitive capacities are such that the stressor pertains in its physical absence, the periods of continuous distal exposure are apparently essential in these species. Whilst the focus of this review is on the stressor rather than the stress response, we also describe some of the depression- and anxiety disorder-relevant effects on behavior, physiology and brain structure-function of chronic psychosocial stressors, as well as evidence for the

  2. Chronic psychosocial stressors in adulthood: Studies in mice, rats and tree shrews.

    Science.gov (United States)

    Pryce, Christopher R; Fuchs, Eberhard

    2017-02-01

    Human psychological stress is the major environmental risk factor for major depression and certain of the anxiety disorders. Psychological stressors often occur in the context of the adult social environment, and they or the memory formed of them impact on the individual across an extended period, thereby constituting chronic psychosocial stress (CPS). Psychosocial stressors often involve loss to the individual, such as the ending of a social relationship or the onset of interpersonal conflict leading to loss of social control and predictability. Given the difficulty in studying the etio-pathophysiological processes mediating between CPS and brain and behavior pathologies in human, considerable effort has been undertaken to study manipulations of the social environment that constitute adulthood chronic psychosocial stressors in other mammals. The majority of such research has been conducted in rodents; the focus for a considerable time period was on rats and more recently both rats and mice have been investigated, the latter species in particular providing the opportunity for essential gene x chronic psychosocial stressor interaction studies. Key studies in the tree shrew demonstrate that this approach should not be limited to rodents, however. The animal adult CPS paradigms are based on resident-intruder confrontations. These are typified by the intruder-subject's brief proximate interactions with and attacks by, and otherwise continuous distal exposure to, the resident stressor. In contrast to humans where cognitive capacities are such that the stressor pertains in its physical absence, the periods of continuous distal exposure are apparently essential in these species. Whilst the focus of this review is on the stressor rather than the stress response, we also describe some of the depression- and anxiety disorder-relevant effects on behavior, physiology and brain structure-function of chronic psychosocial stressors, as well as evidence for the predictive validity

  3. Effects of fasting and/or oxidizing and reducing agents on absorption of neptunium from the gastrointestinal tract of mice and adult or neonatal rats.

    Science.gov (United States)

    Sullivan, M F; Ruemmler, P S; Ryan, J L

    1984-12-01

    Neptunium-237(V) nitrate was administered by gavage to groups of fed or fasted adult and 5-day-old rats. Some groups also received the oxidants quinhydrone or ferric iron, and others received the reducing agent ferrous iron. Adult mice received ferric or ferrous iron and 235Np. When the adult rats were killed at 7 days after gavage, measurements showed that, compared with rats that were fed, a 24-hr fast caused a fivefold increase in 237Np absorption and retention. Both quinhydrone and ferric iron caused an even greater increase in absorption in both fed and fasted rats. Ferrous iron, on the other hand, decreased absorption in fasted rats to values lower than those obtained in fed rats. Similar results were obtained in mice treated with 235Np and either ferric or ferrous iron. The highest absorption obtained after gavage of ferric iron to fasted rats and mice was about two orders of magnitude higher than the value obtained in animals that were fed before gavage. The effects of ferric and ferrous iron on neptunium absorption by neonatal rats were similar to their effects on adult animals but of lesser magnitude. These results are consistent with the hypothesis that Np(V), when given in small mass quantities to fed animals, is reduced in the gastrointestinal tract to Np(IV), which is less well absorbed than Np(V).

  4. Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats.

    Science.gov (United States)

    Ojewole, John A O

    2006-09-01

    The present study was undertaken to investigate the analgesic, antiinflammatory and hypoglycaemic effects of Zingiber officinale dried rhizomes ethanol extract (ZOE) in mice and rats. The analgesic effect of ZOE was evaluated by 'hot-plate' and 'acetic acid' analgesic test methods in mice; while the antiinflammatory and hypoglycaemic effects of the plant extract were investigated in rats, using fresh egg albumin-induced pedal oedema, and streptozotocin (STZ)-induced diabetes mellitus models. Morphine (MPN, 10 mg/kg), diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used as reference drugs for comparison. ZOE (50-800 mg/kg i.p.) produced dose-dependent, significant (p diabetic rats. The findings of this experimental animal study indicate that Zingiber officinale rhizomes ethanol extract possesses analgesic, antiinflammatory and hypoglycaemic properties; and thus lend pharmacological support to folkloric, ethnomedical uses of ginger in the treatment and/or management of painful, arthritic inflammatory conditions, as well as in the management and/or control of type 2 diabetes mellitus in some rural Africa communities.

  5. Evaluation of DNA damage by alkaline elution technique after inhalation exposure of rats and mice to 1,3-butadiene.

    Science.gov (United States)

    Vangala, R R; Laib, R J; Bolt, H M

    1993-01-01

    The alkaline filter elution technique was used to evaluate single strand breaks (SSB), DNA-DNA (DDCL) and DNA-protein cross-links (DPCL) in liver and lung of male rats (Sprague-Dawley) and male mice (B6C3F1) after exposure to 2000 ppm 1,3-butadiene (BD) for 7 days (7 h/day and/or to 100, 250, 500, 1000) 2000 ppm BD for 7 h. SSB were detected in liver DNA of both species at 2000 ppm. Cross-links are more pronounced in mouse lung than in mouse liver. Elution rates of lung DNA from mice exposed for 7 h to different concentrations of BD revealed an increase in cross-links between 250 and 500 ppm, and a further increase in cross-links up to 2000 ppm. No such signs of genotoxicity could be observed for the lung of rats. Our data support the involvement of reactive metabolites (epoxybutene and especially diepoxybutane) in butadiene-induced carcinogenesis in the mouse but not to that extent in the rat.

  6. Synthesis of lipid mediators during UVB-induced inflammatory hyperalgesia in rats and mice.

    Directory of Open Access Journals (Sweden)

    Marco Sisignano

    Full Text Available Peripheral sensitization during inflammatory pain is mediated by a variety of endogenous proalgesic mediators including a number of oxidized lipids, some of which serve endogenous modulators of sensory TRP-channels. These lipids are eicosanoids of the arachidonic acid and linoleic acid pathway, as well as lysophophatidic acids (LPAs. However, their regulation pattern during inflammatory pain and their contribution to peripheral sensitization is still unclear. Here, we used the UVB-model for inflammatory pain to investigate alterations of lipid concentrations at the site of inflammation, the dorsal root ganglia (DRGs as well as the spinal dorsal horn and quantified 21 lipid species from five different lipid families at the peak of inflammation 48 hours post irradiation. We found that known proinflammatory lipids as well as lipids with unknown roles in inflammatory pain to be strongly increased in the skin, whereas surprisingly little changes of lipid levels were seen in DRGs or the dorsal horn. Importantly, although there are profound differences between the number of cytochrome (CYP genes between mice and rats, CYP-derived lipids were regulated similarly in both species. Since TRPV1 agonists such as LPA 18∶1, 9- and 13-HODE, 5- and 12-HETE were elevated in the skin, they may contribute to thermal hyperalgesia and mechanical allodynia during UVB-induced inflammatory pain. These results may explain why some studies show relatively weak analgesic effects of cyclooxygenase inhibitors in UVB-induced skin inflammation, as they do not inhibit synthesis of other proalgesic lipids such as LPA 18∶1, 9-and 13-HODE and HETEs.

  7. Incomplete segregation of endorgan-specific vestibular ganglion cells in mice and rats

    Science.gov (United States)

    Maklad, A.; Fritzsch, B.

    1999-01-01

    The endorgan-specific distribution of vestibular ganglion cells was studied in neonatal and postnatal rats and mice using indocarbocyanine dye (DiI) and dextran amines for retrograde and anterograde labeling. Retrograde DiI tracing from the anterior vertical canal labeled neurons scattered throughout the whole superior vestibular ganglion, with denser labeling at the dorsal and central regions. Horizontal canal neurons were scattered along the dorsoventral axis with more clustering toward the dorsal and ventral poles of this axis. Utricular ganglion cells occupied predominantly the central region of the superior vestibular ganglion. This utricular population overlapped with both the anterior vertical and horizontal canals' ganglion cells. Posterior vertical canal neurons were clustered in the posterior part of the inferior vestibular ganglion. The saccular neurons were distributed in the two parts of the vestibular ganglion, the superior and inferior ganglia. Within the inferior ganglion, the saccular neurons were clustered in the anterior part. In the superior ganglion, the saccular neurons were widely scattered throughout the whole ganglion with more numerous neurons at the posterior half. Small and large neurons were labeled from all endorgans. Examination of the fiber trajectory within the superior division of the vestibular nerve showed no clear lamination of the fibers innervating the different endorgans. These results demonstrate an overlapping pattern between the different populations within the superior ganglion, while in the inferior ganglion, the posterior canal and saccular neurons show tighter clustering but incomplete segregation. This distribution implies that the ganglion cells are assigned for their target during development in a stochastic rather than topographical fashion.

  8. The impact of different blood sampling methods on laboratory rats under different types of anaesthesia

    DEFF Research Database (Denmark)

    Toft, Martin Fitzner; Petersen, Mikke Haxø; Dragsted, Nils

    2006-01-01

    for rats sampled from the tail vein, which showed fluctuations in body temperature in excess of 30 h after sampling. Increases in heart rate and blood pressure within the first hours after sampling indicated that periorbital puncture was the method that had the largest acute impact on the rats......Rats with implanted telemetry transponders were blood sampled by jugular puncture, periorbital puncture or tail vein puncture, or sampled by jugular puncture in carbon dioxide (CO?), isoflurane or without anaesthesia in a crossover design. Heart rate, blood pressure and body temperature were...... registered for three days after sampling. Initially blood pressure increased, but shortly after sampling it decreased, which led to increased heart rate. Sampling induced rapid fluctuations in body temperature, and an increase in body temperature. Generally, rats recovered from sampling within 2-3 h, except...

  9. Effects of laboratory housing on exploratory behaviour, novelty discrimination and spatial reference memory in a subterranean, solitary rodent, the Cape mole-rat (Georychus capensis).

    Science.gov (United States)

    Oosthuizen, Maria Kathleen; Scheibler, Anne-Gita; Bennett, Nigel Charles; Amrein, Irmgard

    2013-01-01

    A large number of laboratory and field based studies are being carried out on mole-rats, both in our research group and others. Several studies have highlighted the development of adverse behaviours in laboratory animals and have emphasised the importance of enrichment for captive animals. Hence we were interested in evaluating how laboratory housing would affect behavioural performance in mole-rats. We investigated exploratory behaviour, the ability to discriminate between novel and familiar environments and reference memory in the solitary Cape mole-rat (Georychus capensis). Our data showed that both wild and captive animals readily explore open spaces and tunnels. Wild animals were however more active than their captive counterparts. In the Y maze two trial discrimination task, wild animals failed to discriminate between novel and familiar environments, while laboratory housed mole-rats showed preferential spatial discrimination in terms of the length of time spent in the novel arm. The performance of the laboratory and wild animals were similar when tested for reference memory in the Y maze, both groups showed a significant improvement compared to the first day, from the 3rd day onwards. Wild animals made more mistakes whereas laboratory animals were slower in completing the task. The difference in performance between wild and laboratory animals in the Y-maze may be as a result of the lower activity of the laboratory animals. Laboratory maintained Cape mole-rats show classic behaviours resulting from a lack of stimulation such as reduced activity and increased aggression. However, they do display an improved novelty discrimination compared to the wild animals. Slower locomotion rate of the laboratory animals may increase the integration time of stimuli, hence result in a more thorough inspection of the surroundings. Unlike the captive animals, wild animals show flexibility in their responses to unpredictable events, which is an important requirement under

  10. Surgical Anatomy of the Gastrointestinal Tract and Its Vasculature in the Laboratory Rat

    OpenAIRE

    Katarína Vdoviaková; Eva Petrovová; Marcela Maloveská; Lenka Krešáková; Jana Teleky; Mario Zefanias Joao Elias; Darina Petrášová

    2015-01-01

    The aim of this study was to describe and illustrate the morphology of the stomach, liver, intestine, and their vasculature to support the planning of surgical therapeutic methods in abdominal cavity. On adult Wistar rats corrosion casts were prepared from the arterial system and Duracryl Dental and PUR SP were used as a casting medium and was performed macroscopic anatomical dissection of the stomach, liver, and intestine was performed. The rat stomach was a large, semilunar shaped sac with ...

  11. Occurrence and identification of hemotropic mycoplasmas (Hemoplasmas) in free ranging and laboratory rats (Rattus norvegicus) from two Brazilian zoos.

    Science.gov (United States)

    Conrado, Francisco de Oliveira; do Nascimento, Naíla Cannes; dos Santos, Andrea Pires; Zimpel, Cristina Kraemer; Messick, Joanne Belle; Biondo, Alexander Welker

    2015-11-23

    Hemotropic mycoplasmas (hemoplasmas), bacteria belonging to the class Mollicutes, are obligatory red blood cell pathogens of a variety of animal species. They may cause acute anemia that is life-threatening or chronic disease that is clinically silent, but may interfere with results of experimental studies when using infected animals. Since these bacteria cannot be cultivated, molecular techniques are the gold standard for diagnosing an infection, investigating its prevalence, and describing new species. Mycoplasma coccoides and M. haemomuris are the most commonly recognized hemoplasmas in the blood of wild and laboratory rodents. Neither the epidemiology nor clinical and molecular characterization of hemoplasma infection in free-ranging rodents in Brazil has been previously reported. The aims of this study were to investigate the occurrence of hemoplasmas in free-ranging rats (Rattus norvegicus) captured in the Passeio Público and Curitiba Zoo and compare hematologic parameters of infected and non-infected animals. Anti-coagulated blood samples collected from 43 free-ranging and 20 nursery rats were included in the study. Overall 63.5% were positive using SYBR® Green quantitative PCR (qPCR) of the 16S rRNA gene to screen for hemoplasma infection (72% among free-ranging rats; 45% among laboratory-raised rats). Sequencing of the qPCR products showed that all but one sample had >98% identity to M. haemomuris. Phylogenetic analysis based on a fragment of approximately 1300 bp of the 16S rRNA gene showed 99% identity to a new hemoplasma from European rats and 98% identity to a hemotropic mycoplasma described infecting a European harvest mouse (Micromys minutus). No statistically significant changes in hematologic parameters between infected and non-infected rats were found, confirming the low pathogenicity and/or silent characteristics of the infection. Our findings suggest that hemoplasmas are likely endemic in rodent species in this region. The epidemiology

  12. 信息动态%Therapeutic Effect of Kangtai Capsule on Rats Models with Irritable Bowel Syndrome and on Mice Models with Diarrhea

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Objective To observe the effect of Kangtai Capsule on rats irritable bowel syndrome (IBS) induced by neonatal maternal separation, and to explore its anti-diarrhea on diarrhea mice. Methods The rat models of IBS were induced by neonatal maternal separation method. The threshold of abdominal rebound reflex (ARR) and the amount of defecation induced by water immersion in rats were adopted as observation indexes to evaluate the therapeutic effect. The anti-diarrhea effect of Kangtai Capsule was observed in mice models of diarrhea induced by Folium Sennae. Results Kangtai Capsule increased the threshold of visceral sensitivity pressure and reduced visceral sensitivity in IBS rat models (P <0. 05 or P <0. 01 ). The rat defecation amount was reduced in Kangtai Capsule groups, and the effect was the best in high-dose Kangtai Capsule group ( P < 0. 05 ). The accumulative frequency of defecation within 4 and 6 hours in mice was significantly reduced (P <0. 05 or P <0. 01 ) in middleand high-dose Kangtai Capsule groups. Conclusion Kangtai Capsule has certain therapeutic effect for rat IBS induced by neonatal maternal separation, and has anti-diarrhea effect in mice.

  13. NTP Toxicology and Carcinogenesis Studies of Glycidol (CAS No. 556-52-5) In F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1990-03-01

    Glycidol is a viscous liquid that is used as a stabilizer in the manufacture of vinyl polymers, as an additive for oil and synthetic hydraulic fluids, and as a diluent in some epoxy resins. NTP Toxicology and Carcinogenesis studies were conducted by administering glycidol (94% pure, containing 1.2% 3-methoxy-1,2-propanediol, 0.4% 3-chloro-1,2-propanediol, 2.8% diglycidyl ether, and 1.1% 2,6-dimethanol-1,4-dioxane) in water by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Chinese hamster ovary (CHO) cells, Drosophila melanogaster, and the bone marrow of male B6C3F1 mice. Sixteen-Day Studies: Glycidol doses for groups of five rats or five mice of each sex ranged from 37.5 to 600 mg/kg; vehicle controls received distilled water. All rats that received 600 mg/kg died between days 3 and 13. Edema and degeneration of the epididymal stroma, atrophy of the testis, and granulomatous inflammation of the epididymis occurred in males that received 300 mg/kg. All mice that received 600 mg/kg and two males and two females that received 300 mg/kg died by day 4 of the studies. Focal demyelination in the medulla and thalamus of the brain occurred in all female mice that received 300 mg/kg. Thirteen-Week Studies: Doses for groups of 10 rats ranged from 25 to 400 mg/kg, and doses for groups of 10 mice ranged from 19 to 300 mg/kg; vehicle controls received distilled water. All rats that received 400 mg/kg died by week 2; three males and one female that received 200 mg/kg died during weeks 11-12. Final mean body weights of male rats that received 50, 100, or 200 mg/kg were 96%-85% that of vehicle controls; final mean body weights of female rats receiving the same doses were 95%-89% that of vehicle controls. Sperm count and sperm motility were reduced in male rats that received 100 or 200 mg/kg. Necrosis of the cerebellum, demyelineation in the medulla of the brain

  14. Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and dogs.

    Science.gov (United States)

    Turowska, Agnieszka; Librizzi, Damiano; Baumgartl, Nadja; Kuhlmann, Jens; Dicke, Tanja; Merkel, Olivia; Homburg, Ursula; Höffken, Helmut; Renz, Harald; Garn, Holger

    2013-10-15

    The DNAzyme hgd40 was shown to effectively reduce expression of the transcription factor GATA-3 RNA which plays an important role in the regulation of Th2-mediated immune mechanisms such as in allergic bronchial asthma. However, uptake, biodistribution and pharmacokinetics of hgd40 have not been investigated yet. We examined local and systemic distribution of hgd40 in naive mice and mice suffering from experimental asthma. Furthermore, we evaluated the pharmacokinetics as a function of dose following single and repeated administration in rats and dogs. Using intranasal administration of fluorescently labeled hgd40 we demonstrated that the DNAzyme was evenly distributed in inflamed asthmatic mouse lungs within minutes after single dose application. Systemic distribution was investigated in mice using radioactive labeled hgd40. After intratracheal application, highest amounts of hgd40 were detected in the lungs. High amounts were also detected in the bladder indicating urinary excretion as a major elimination pathway. In serum, low systemic hgd40 levels were detected already at 5 min post application (p.a.), subsequently decreasing over time to non-detectable levels at 2h p.a. As revealed by Single Photon Emission Computed Tomography, trace amounts of hgd40 were detectable in lungs up to 7 days p.a. Also in the toxicologically relevant rats and dogs, hgd40 was detectable in blood only shortly after inhalative application. The plasma pharmacokinetic profile was dose and time dependent. Repeated administration did not lead to drug accumulation in plasma of dogs and rats. These pharmacokinetic of hgd40 provide guidance for clinical development, and support an infrequent and convenient dose administration regimen.

  15. Developmental expression of the Ca2+-binding proteins calretinin and parvalbumin at the calyx of Held of rats and mice.

    Science.gov (United States)

    Felmy, Felix; Schneggenburger, Ralf

    2004-09-01

    Ca(2+)-binding proteins of the EF-hand family are widely expressed in the CNS, and contribute to intracellular Ca(2+) buffering in neurons. In nerve terminals, Ca(2+)-binding proteins are likely to regulate transmitter release probability and synaptic short-term-plasticity. Here, we investigated the developmental expression pattern of calretinin and parvalbumin at a large excitatory synapse, the calyx of Held in the medial nucleus of the trapezoid body (MNTB) of rats and mice. We used two-colour immunofluorescence imaging with primary antibodies detecting one of the Ca(2+)-binding proteins, and a presynaptic marker protein, Rab-3A. Calretinin was found in nerve terminals of the calyx of Held, but not in postsynaptic principal cells. The presynaptic density of Calretinin staining, and the degree of colocalization with Rab-3A increased during postnatal development (P6-P31). Surprisingly, not all calyces of Held expressed calretinin. In rats, calretinin-containing calyces were irregularly interspersed with calretinin-negative calyces, whereas in mice, calretinin-positive calyces were preferentially located in the lateral portion of the MNTB. The percentage of calretinin-positive calyces increased during development, to about 75% and 20% at P30 in rats and in mice, respectively. Parvalbumin was present in the presynaptic calyces of Held and in the nerve fibres entering the MNTB, as well as in the somata of the MNTB principal neurons. An up-regulation of calretinin and parvalbumin in calyces of Held probably increases the presynaptic Ca(2+) buffering strength during postnatal development, but the unexpected heterogeneity of calretinin expression might cause differences in Ca(2+) signalling and transmitter release probability between calyces of Held.

  16. Syphacia obvelata (Nematode, Oxyuridae) infecting laboratory mice Mus musculus (Rodentia, Muridae): phylogeny and host-parasite relationship.

    Science.gov (United States)

    Abdel-Gaber, Rewaida

    2016-03-01

    Syphacia obvelata is a pinworm nematode parasite infecting man and laboratory animals in high abundance. This parasitological study was carried out during the period of March 2014-February 2015 to investigate the helminth parasites infecting the laboratory mice Mus musculus in the Animal House at Cairo University, Egypt. The prevalence of S. obvelata in M. musculus was 75.0 %. The extent of infection with S. obvelata is analyzed according to the sex of the host mice. It was shown that the prevalence of male infection was greater than female worms. Morphological characterization revealed that the present Oxyurid species possesses a rounded cephalic end with less developed lips, esophagus divided into cylindrical corpus, and globular bulb supported internally with valvular apparatus; three mamelons are located at the ventral surface with a single chitinized spicule and a gubernaculum provided with an accessory hook in males, and ovijector apparatus opens ventrally by the vulva surrounded by protruded lips in female worms. Body of the male was 0.623-1.130 (0.830 ± 0.11) mm long and 0.092-0.130 (0.110 ± 0.01) mm wide; the esophagus was 0.164-0.280 (0.210 ± 0.01) mm long; the nerve ring and excretory pore are located at 0.035-0.132 (0.073 ± 0.01) and 0.087-0.191 (0.145 ± 0.01) mm from the anterior end, respectively, while the female measured 2.930-4.650 (3.540 ± 0.1) mm long and 0.120-0.232 (0.156 ± 0.001) mm wide; the esophagus was 0.213-0.410 (0.342 ± 0.01) mm long; the nerve ring, excretory pore, and vulval opening are located at 0.026-0.157 (0.121 ± 0.01), 0.134-0.243 (0.195 ± 0.01), and 0.323-0.632 (0.546 ± 0.11) mm from the anterior end, respectively; eggs measured 0.120-0.139 (0.129 ± 0.001) mm long and 0.030-0.052 (0.045 ± 0.001) mm wide. It compared morphometrically with other Syphacia species described previously and showed little differences in

  17. 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

    Kiss1 mRNA and its corresponding peptide products, kisspeptins, are expressed in two restricted brain areas of rodents, the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC). The concentration of mature kisspeptins may not directly correlate with Kiss1 mRNA levels, because...... mRNA translation and/or posttranslational modification, degradation, transportation and release of kisspeptins could be regulated independently of gene expression, and there may thus be differences in kisspeptin expression even in species with similar Kiss1 mRNA profiles. We measured and compared...... kisspeptin-immunoreactivity in both nuclei and both sexes of rats and mice and quantified kisspeptin-immunoreactive nerve fibers. We also determined Kiss1 mRNA levels and measured kisspeptin-immunoreactivity in colchicine pretreated rats. Overall, we find higher levels of kisspeptin...

  18. Characterization of the toxicity, mutagenicity, and carcinogenicity of methacrylonitrile in F344 Rats and B6C3F1 mice.

    Science.gov (United States)

    Nyska, Abraham; Ghanayem, Burhan I

    2003-04-01

    Methacrylonitrile is an unsaturated aliphatic nitrile. It is widely used in the preparation of homopolymers and copolymers, elastomers, and plastics, and as a chemical intermediate in the preparation of acids, amides, amines, esters, and other nitriles. Methacrylonitrile was nominated for study by the National Cancer Institute (USA) because of the potential for human exposure, structural similarity to the known carcinogen acrylonitrile, and a lack of toxicity and carcinogenicity data. Doses selected for the 2-year study were based on the results of the 13-week gavage studies. Groups of 50 male and 50 female animals were exposed by gavage to 0, 3, 10, or 30 mg/kg in F344 rats, and 0, 1.5, 3 or 6 mg/kg in B6C3F1 mice, 5 days per week for 2 years. Urinary excretion of N-acetyl- S-(2-cyanopropyl)- l-cysteine (NACPC) and N-acetyl- S-(2-hydroxypropyl)- l-cysteine (NAHPC) were measured as markers of exposure at various time points after methacrylonitrile administration, and demonstrated that exposure of animals to methacrylonitrile occurred as intended. Urinary excretion of NACPC and NAHPC increased in rats and mice in a dose-dependent manner. In contrast to observations in rats, the ratios of NACPC/creatinine were generally higher in female than in male mice. Further, the ratios of NAHPC/creatinine in rats were significantly greater at all time points and all doses than the corresponding ratios of NACPC/creatinine in male and female mice. In both rats and mice, survival was not affected by treatment. In rats, mean body weights of the 30 mg/kg groups were less than those of the vehicle controls after weeks 21 and 37 for males and females, respectively. No treatment-related effect on body weight was seen in mice. There were no neoplasms (in either species) or non-neoplastic lesions (mice only) that were attributed to methacrylonitrile administration. In rats, the incidences of olfactory epithelial atrophy and metaplasia of the nose were significantly greater in 30 mg

  19. Surgical Anatomy of the Gastrointestinal Tract and Its Vasculature in the Laboratory Rat

    Directory of Open Access Journals (Sweden)

    Katarína Vdoviaková

    2016-01-01

    Full Text Available The aim of this study was to describe and illustrate the morphology of the stomach, liver, intestine, and their vasculature to support the planning of surgical therapeutic methods in abdominal cavity. On adult Wistar rats corrosion casts were prepared from the arterial system and Duracryl Dental and PUR SP were used as a casting medium and was performed macroscopic anatomical dissection of the stomach, liver, and intestine was performed. The rat stomach was a large, semilunar shaped sac with composite lining. On the stomach was very marked fundus, which formed a blind sac (saccus cecus. The rat liver was divided into six lobes, but without gall bladder. Intestine of the rat was simple, but cecum had a shape as a stomach. The following variations were observed in the origin of the cranial mesenteric artery. On the corrosion cast specimens we noticed the presence of the anastomosis between middle colic artery (a. colica media and left colic artery (a. colica sinistra. We investigated the second anastomosis between middle colic artery and left colic artery. The results of this study reveal that the functional anatomical relationship between the rat stomach, liver and intestine is important for the development of surgical research in human and veterinary medicine.

  20. Surgical Anatomy of the Gastrointestinal Tract and Its Vasculature in the Laboratory Rat

    Science.gov (United States)

    Vdoviaková, Katarína; Petrovová, Eva; Maloveská, Marcela; Krešáková, Lenka; Teleky, Jana; Elias, Mario Zefanias Joao; Petrášová, Darina

    2016-01-01

    The aim of this study was to describe and illustrate the morphology of the stomach, liver, intestine, and their vasculature to support the planning of surgical therapeutic methods in abdominal cavity. On adult Wistar rats corrosion casts were prepared from the arterial system and Duracryl Dental and PUR SP were used as a casting medium and was performed macroscopic anatomical dissection of the stomach, liver, and intestine was performed. The rat stomach was a large, semilunar shaped sac with composite lining. On the stomach was very marked fundus, which formed a blind sac (saccus cecus). The rat liver was divided into six lobes, but without gall bladder. Intestine of the rat was simple, but cecum had a shape as a stomach. The following variations were observed in the origin of the cranial mesenteric artery. On the corrosion cast specimens we noticed the presence of the anastomosis between middle colic artery (a. colica media) and left colic artery (a. colica sinistra). We investigated the second anastomosis between middle colic artery and left colic artery. The results of this study reveal that the functional anatomical relationship between the rat stomach, liver and intestine is important for the development of surgical research in human and veterinary medicine. PMID:26819602

  1. A specific polymerase chain reaction based on the gyrB gene sequence and subsequent restriction fragment length polymorphism analysis of Pasteurella pneumotropica isolates from laboratory mice.

    Science.gov (United States)

    Hayashimoto, Nobuhito; Ueno, Masami; Takakura, Akira; Itoh, Toshio

    2007-03-01

    For a molecular identification and typing tool, we developed a specific polymerase chain reaction (PCR) based on the gyrB gene sequence and a subsequent restriction fragment length polymorphism (RFLP) analysis using the products amplified from the specific PCR to facilitate discrimination of biotypes of Pasteurella pneumotropica from laboratory mice. Appropriate PCR products, a 1039-basepair fragment for biotype Jawetz and a 1033-basepair fragment for biotype Heyl, were amplified by use of the primers CZO-1 and NJO-2 from all 105 P. pneumotropica isolates tested and the 2 reference strains but not from other bacterial species tested. MspI digestion of PCR-generated products showed 3 RFLP patterns among the 105 isolates, and these patterns correlated with the biotype of the isolate (RFLP pattern 1, biotype Jawetz; RFLP pattern 2, biotype Heyl; and RFLP pattern 3, biotype Jawetz with Beta-hemolytic activity). Our procedure identifies and biotypes isolates of P. pneumotropica from laboratory mice, using simple PCR and enzymatic restriction techniques. Therefore, this procedure is useful as a rapid identification and biotyping tool for isolates of P. pneumotropica from laboratory mice.

  2. The Bacteria and Mycoplasma Monitoring in the Laboratory Animal Facility by Using Sentinel Mice%实验动物设施内哨兵鼠对病原菌监控的研究

    Institute of Scientific and Technical Information of China (English)

    马元元; 孔申申; 陶迎红; 杨国生; 李雪迎

    2012-01-01

    目的 通过使用哨兵鼠的监控探讨我院实验动物屏障环境中病原菌的产生途径.方法 选择27只ICR小鼠、27只Nu/+裸鼠和27只SD大鼠作为哨兵鼠,分为实验组(手术组、非手术组)和正常对照组,实验组通过更换“脏垫料”进行饲养,对照组按正常饲养方式饲养,每隔3个月送检27只哨兵鼠进行检测,共送检3次.结果 正常对照组3次均未检测到病原菌,实验组在冬季月份未检测到病原菌感染,春、夏二季检测到病原菌感染,三个季节的病原菌感染率有显著性差异,P=0.012,其中春季较冬/夏季感染率有显著性差异,P=0.004,另两个季节之间差异不显著;病原菌感染率随着动物饲养量的增减而升高或降低;实验组中手术组病原菌感染率较非手术组略高;大鼠的病原菌感染率略高于小鼠.结论 屏障环境内实验鼠群的病原菌感染可能与季节、饲养量、频繁实验操作、动物种类等有直接关系.%To investigate the spread of bacteria and mycoplasma in the laboratory animal' s barrier environment in our hospital by using sentinel mice. Method A total 27 ICR mice, 27 Nu/ + nude mice and 27 SD rats were observed as "sentinel mice", divided into experimental groups (surgical group and non-surgical group) and normal control group. The animals in experimental groups were housed by different "dirty bedding" exposure. Those in the normal control group were housed with the normal breeding procedure. 27 sentinel mice were examined every three months, three times in all. Results Bacteria and mycoplasma infection was not detected in normal control group at all, compared with the higher infection rates in experimental groups. The infections occurred more frequently during spring, then summer, but were not able to be detected during winter season. The infection rates in three seasons showed statistical difference (P =0.012) , especially during spring, showed significant statistical difference

  3. The effect of repetitive intraperitoneal anesthesia by application of fentanyl-medetomidine and midazolam in laboratory rats.

    Science.gov (United States)

    Rahmanian-Schwarz, Afshin; Held, Manuel; Knoeller, Tabea; Amr, Amro; Schaller, Hans-Eberhard; Jaminet, Patrick

    2012-04-01

    Literature reviews show numerous options for anesthesia in the small laboratory animals. Many methods are associated with complications, such as high technical effort, difficult monitoring, respiratory and cardiovascular depression, and prolonged sedation. In the present study, we report first time results after repeated use of an intraperitoneal combined anesthesia with a high tolerability. Three hundred and seventy-four anesthesias were performed on 38 adult male Lewis rats (280-460 g). Each animal was anesthetized repeatedly over a period of three months, using an intraperitoneal combination of Fentanyl-Medetomidine and Midazolam (FMM). The time required for the animals to lose ear pinch response and the ability to perform a righting and pedal withdrawal reflex was measured. For evaluation of the clinical state, a four-point vitality scale was developed. The anesthesia was antagonized with Naloxone, Flumazenil, and Atipamezole (s.c.). The animals lost all three reflex responses within 5 (± 2.4) min of injection. Without antagonism of anesthesia, the ear pinch response returned on average within 125 (± 21.5) min. After antagonism of anesthesia, the rats needed 5 (± 2.9) min to regain all three reflex responses. No significant differences of vitality-index were measured after repeated use of FMM during the investigation period. A repeatable and secure anesthesia is indispensable for any experimental studies that require multiple anesthesia of a single animal. Intraperitoneal combination of FMM provides an adequate procedure to induce a well tolerable, repeatable state of anesthesia, which conforms to all the necessary requirements for laboratory rats.

  4. Chemical form of technetium in corn (Zea mays) and the gastrointestinal absorption of plant-incorporated Tc by laboratory rats

    Energy Technology Data Exchange (ETDEWEB)

    Garten, C.T. Jr.; Myttenaere, C.; Vandecasteele, C.M.; Kirchmann, R.; Van Bruwaene, R.

    1984-01-01

    The food chain availability of technetium incorporated into plant tissue, its chemical form in corn leaves, and the potential for gastrointestinal absorption of plant-incorporated technetium was investigated. Technetium-95m was incorporated into corn leaves via root uptake. Chemical fractionation of the /sup 95m/Tc in leaves showed that 60% was extractable with boiling ethanol and weak mineral acids. The remainder was associated with cell walls and was extractable by harsh chemical treatment. Gel permeation chromatography of the cytosol, indicated that 50% of the /sup 95m/Tc co-chromatographed with anionic pertechnetate; however, it was impossible to distinguish if this pure pertechnetate or technetium complexed with organic molecules. Technetium-95m was administered to laboratory rats in a single dose as: (1) intravenous injection of pertechnetate, (2) pertechnetate mixed with standard laboratory food, and (3) a meal containing /sup 95m/Tc biologically incorporated into corn leaves. High concentrations of /sup 95m/Tc were found in the thyroids, hair, kidneys, and liver of rats. Technetium rapidly disappeared from the liver, kidneys, and other tissues, but remained in the thyroids and hair. Urinary excretion of technetium decreased, and fecal excretion increased when technetium was fed to rats as a /sup 95m/Tc incorporated into corn leaves. The percent of the administered dose absorbed into thyroid gland and the kidneys was less when technetium was biologically incorporated into corn leaves than when pertechnetate was mixed with food. Biological incorporation of technetium into plants appears to reduce its potential for food chain transfer by decreasing its availability for gastrointestinal absorption. 5 references, 4 figures, 3 tables.

  5. Preclinical Development of an anti-5T4 Antibody-Drug Conjugate: Pharmacokinetics in Mice, Rats, and NHP and Tumor/Tissue Distribution in Mice.

    Science.gov (United States)

    Leal, Mauricio; Wentland, JoAnn; Han, Xiaogang; Zhang, Yanhua; Rago, Brian; Duriga, Nicole; Spriggs, Franklin; Kadar, Eugene; Song, Wei; McNally, James; Shakey, Quazi; Lorello, Leslie; Lucas, Judy; Sapra, Puja

    2015-11-18

    The pharmacokinetics of an antibody (huA1)-drug (auristatin microtubule disrupting MMAF) conjugate, targeting 5T4-expressing cells, were characterized during the discovery and development phases in female nu/nu mice and cynomolgus monkeys after a single dose and in S-D rats and cynomolgus monkeys from multidose toxicity studies. Plasma/serum samples were analyzed using an ELISA-based method for antibody and conjugate (ADC) as well as for the released payload using an LC-MS/MS method. In addition, the distribution of the Ab, ADC, and released payload (cys-mcMMAF) was determined in a number of tissues (tumor, lung, liver, kidney, and heart) in two tumor mouse models (H1975 and MDA-MB-361-DYT2 models) using similar LBA and LC-MS/MS methods. Tissue distribution studies revealed preferential tumor distribution of cys-mcMMAF and its relative specificity to the 5T4 target containing tissue (tumor). Single dose studies suggests lower CL values at the higher doses in mice, although a linear relationship was seen in cynomolgus monkeys at doses from 0.3 to 10 mg/kg with no evidence of TMDD. Evaluation of DAR (drug-antibody ratio) in cynomolgus monkeys (at 3 mg/kg) indicated that at least half of the payload was still on the ADC 1 to 2 weeks after IV dosing. After multiple doses, the huA1 and conjugate data in rats and monkeys indicate that exposure (AUC) increases with increasing dose in a linear fashion. Systemic exposure (as assessed by Cmax and AUC) of the released payload increased with increasing dose, although exposure was very low and its pharmacokinetics appeared to be formation rate limited. The incidence of ADA was generally low in rats and monkeys. We will discuss cross species comparison, relationships between the Ab, ADC, and released payload exposure after multiple dosing, and insights into the distribution of this ADC with a focus on experimental design as a way to address or bypass apparent obstacles and its integration into predictive models.

  6. Impacts of Persian Gulf blackfin stonefish crude venom on the haematological factors and serum enzymes levels of laboratory rat

    Directory of Open Access Journals (Sweden)

    Amir Vazirizadeh

    2014-10-01

    Full Text Available Background: One of the venomous fishes of Persian Gulf is a type of stonefish called blackfin stonefish (Pseudosynanceia melanostigma that is very poorly-known. This fish lives on the muddy bottoms of marine shallow waters and have venomous spines on its stone like body. The envenomation usually is happened by unwanted contact of human body to its body and the proteinic venom is injected into the skin. Upon the venom entrance to the body various symptoms and signs will occur that their intensity depends on the venom amount.The aim of study is the understanding of some pharmacological impacts of blackfin stonefish for future studies. Material and Methods: A total of 18 male laboratory rats were divided into three groups of control, second and third and envenomed by sub lethal doses (1/3 LD50 and ½ LD50 intravenously and the serum enzymes namely Creatine Phosphokinase, Lactate Dehydrogenase, Glutamate-Oxaloacetate Transaminase, Gamma-Glutamyl Transpeptidase , Alkaline Phosphatase and Amylase, serum electrolytes namely Sodium. Potassium and Calcium and also complete blood cells of control and experimental rats were measured. Results: The serum enzymes levels, potassium and calcium levels and withe blood cells count in envenomed rats by blackfin stonefish crude venom in compare with control rats had significant increase while the haemoglobin level, red blood cells count and also serum sodium level had significant decrease (p<0.001. Conclusion: The increase in hepatomascular enzyme levels, and the decrease in haemoglobin level can be a probable marker of the presence of rhabdomyolysis, haemolysis and also hepatotoxicity activities in the blackfin stonefish venom and that needs to the histopathologic studies in these systems.

  7. Drug-induced chimerism and prevention of graft-versus-host disease in lethally irradiated mice transplanted with rat bone marrow. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Pierpaoli, W.; Maestroni, G.J.M.

    1978-12-01

    L-5-hydroxytryptophan, haloperidol, and phentolamine were administered subcutaneously to groups of mice. Some groups were inoculated i.p. or i.v. with bone marrow cells. The mice were given a dose of 900 rad of whole-body gamma radiation. Observations were made on survival rate, reconstitution with rat hematopoietic tissue, and capacity to reject or accept skin grafts. Results indicate that the combination of drug-induced tolerance and a newly established preconditioning regimen that eliminated postradiation damage and mortality results in reduction in incidence or delay in onset of GVHD, successful bone marrow grafting, and induction of persistent rat chimerism. (HLW)

  8. Visualization of small lesions in rat cartilage by means of laboratory-based x-ray phase contrast imaging

    Science.gov (United States)

    Marenzana, Massimo; Hagen, Charlotte K.; Das Neves Borges, Patricia; Endrizzi, Marco; Szafraniec, Magdalena B.; Ignatyev, Konstantin; Olivo, Alessandro

    2012-12-01

    Being able to quantitatively assess articular cartilage in three-dimensions (3D) in small rodent animal models, with a simple laboratory set-up, would prove extremely important for the development of pre-clinical research focusing on cartilage pathologies such as osteoarthritis (OA). These models are becoming essential tools for the development of new drugs for OA, a disease affecting up to 1/3 of the population older than 50 years for which there is no cure except prosthetic surgery. However, due to limitations in imaging technology, high-throughput 3D structural imaging has not been achievable in small rodent models, thereby limiting their translational potential and their efficiency as research tools. We show that a simple laboratory system based on coded-aperture x-ray phase contrast imaging (CAXPCi) can correctly visualize the cartilage layer in slices of an excised rat tibia imaged both in air and in saline solution. Moreover, we show that small, surgically induced lesions are also correctly detected by the CAXPCi system, and we support this finding with histopathology examination. Following these successful proof-of-concept results in rat cartilage, we expect that an upgrade of the system to higher resolutions (currently underway) will enable extending the method to the imaging of mouse cartilage as well. From a technological standpoint, by showing the capability of the system to detect cartilage also in water, we demonstrate phase sensitivity comparable to other lab-based phase methods (e.g. grating interferometry). In conclusion, CAXPCi holds a strong potential for being adopted as a routine laboratory tool for non-destructive, high throughput assessment of 3D structural changes in murine articular cartilage, with a possible impact in the field similar to the revolution that conventional microCT brought into bone research.

  9. NTP Toxicology and Carcinogenesis Studies of Roxarsone (CAS No. 121-19-7) in F344/N Rats and B6C3F1 Mice (Feed Studies).

    Science.gov (United States)

    1989-03-01

    Roxarsone is a veterinary drug used as a growth promoter and as an anticoccidial agent and for treatment of swine dysentery. Toxicology and carcinogenesis studies were conducted by administering roxarsone (greater than 99.4% pure) in feed to groups of F344/N rats and B6C3F1 mice of each sex for 14 days, 13 weeks, or 2 years. Fourteen-Day and Thirteen-Week Studies: In the 14-day studies, the diets fed to rats contained 0 or 100-1,600 ppm roxarsone, and those fed to mice contained 0 or 60-1,000 ppm. Deaths occurred in rats and mice that received the highest doses. Rats that received 800 or 1,600 ppm lost weight. Male mice that received 1,000 ppm and female mice that received 500 ppm lost weight. In the first 13-week studies, roxarsone was fed to rats and mice at dietary concentrations of 0 or 50-800 ppm. Decreases (more than 10%) in final mean body weights of dosed rats relative to those of controls were observed for males that received 200, 400, or 800 ppm and for females that received 400 or 800 ppm. Deaths occurred in groups that received 800 ppm. Clinical signs of toxicity (trembling, ataxia, and pale skin) were seen primarily in rats that received 800 ppm. Kidney lesions were observed in rats that received 800 ppm. These lesions were characterized by tubular necrosis and mineralization in the rats that died during the studies and by tubular dilatation and casts, interstitial inflammation, and tubular epithelial cell regeneration in the rats that lived to the end of the studies. Additional 13-week studies were conducted in rats at dietary concentrations of 0, 100, or 400 ppm to demonstrate the absorption of roxarsone from the gastrointestinal tract; to determine its distribution in liver, kidney, and blood; and to study its effects on various hematologic and clinical chemical values. No deaths occurred. Renal lesions of minimal severity observed in male rats that received 400 ppm were characterized by tubular epithelial cell degeneration and regeneration, tubular

  10. The use of rats and mice as animal models in ex vivo bone growth and development studies

    Science.gov (United States)

    Abubakar, A. A.; Noordin, M. M.; Azmi, T. I.; Kaka, U.

    2016-01-01

    In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of rats and mice for ex vivo bone studies, nutritional requirements in ex vivo bone growth and emerging developments and technologies. This compilation of information could assist researchers in the field of regenerative medicine and bone tissue engineering towards a better understanding of skeletal growth and development for application in general clinical medicine. Cite this article: A. A. Abubakar, M. M. Noordin, T. I. Azmi, U. Kaka, M. Y. Loqman. The use of rats and mice as animal models in ex vivo bone growth and development studies. Bone Joint Res 2016;5:610–618. DOI: 10.1302/2046-3758.512.BJR-2016-0102.R2. PMID:27965220

  11. In vitro hepatic conversion of the anticancer agent nemorubicin to its active metabolite PNU-159682 in mice, rats and dogs: a comparison with human liver microsomes.

    Science.gov (United States)

    Quintieri, Luigi; Fantin, Marianna; Palatini, Pietro; De Martin, Sara; Rosato, Antonio; Caruso, Michele; Geroni, Cristina; Floreani, Maura

    2008-09-15

    We recently demonstrated that nemorubicin (MMDX), an investigational antitumor drug, is converted to an active metabolite, PNU-159682, by human liver cytochrome P450 (CYP) 3A4. The objectives of this study were: (1) to investigate MMDX metabolism by liver microsomes from laboratory animals (mice, rats, and dogs of both sexes) to ascertain whether PNU-159682 is also produced in these species, and to identify the CYP form(s) responsible for its formation; (2) to compare the animal metabolism of MMDX with that by human liver microsomes (HLMs), in order to determine which animal species is closest to human beings; (3) to explore whether differences in PNU-159682 formation are responsible for previously reported species- and sex-related differences in MMDX host toxicity. The animal metabolism of MMDX proved to be qualitatively similar to that observed with HLMs since, in all tested species, MMDX was mainly converted to PNU-159682 by a single CYP3A form. However, there were marked quantitative inter- and intra-species differences in kinetic parameters. The mouse and the male rat exhibited V(max) and intrinsic metabolic clearance (CL(int)) values closest to those of human beings, suggesting that these species are the most suitable animal models to investigate MMDX biotransformation. A close inverse correlation was found between MMDX CL(int) and previously reported values of MMDX LD(50) for animals of the species, sex and strain tested here, indicating that differences in the in vivo toxicity of MMDX are most probably due to sex- and species-related differences in the extent of PNU-159682 formation.

  12. Effect of chronic melatonin administration on several physiological parameters from old Wistar rats and SAMP8 mice.

    Science.gov (United States)

    Tresguerres, Jesus A F; Kireev, Roman; Forman, Katherine; Cuesta, Sara; Tresguerres, Ana F; Vara, Elena

    2012-12-01

    The effect of melatonin administration on age-induced alterations in hepatocytes, central nervous system, immune system, and skin are reviewed. Twenty-two-month-old Wistar rats and SAMP8 (senescence prone) mice of 10 months of age were used as experimental models. Wistar rats were analyzed untreated or after the chronic administration of melatonin at a dose of 1 mg/kg/day in the drinking water for 10 weeks. At the end of the treatment period, the various parameters were investigated. Results were compared with those of 2-month-old controls. In hepatocytes, aging induced a significant increase in oxidative stress, inflammation, and apoptosis when compared to young animals. Melatonin administration significantly ameliorated all these age-related changes. The impairment of the cardiovascular system with aging appears to contribute to the increased morbidity and mortality of the aged subjects. The process was investigated in SAMP8 mice of 10 months of age. Melatonin was provided for 30 days at two different dosages (1 mg/kg/day and 10 mg/kg/day), also in the drinking water. After treatment, the expression of inflammatory mediators (tumor necrosis factor-α, interleukin 1 and 10, NFκBp50 and NFκBp52), apoptosis markers (BAD, BAX, and Bcl2), and parameters related to oxidative stress (heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases) were determined in the heart. Inflammation as well as oxidative stress and apoptosis markers were increased in old SAMP8 males, as compared to young controls. After treatment with melatonin, these age-altered parameters were partially reversed. The results suggest that oxidative stress and inflammation increase with aging and that chronic treatment with melatonin is able to reduce these parameters. In the skin, a reduction of epidermal thickness together with a marked increase of the hypodermis with great fat accumulation was observed in old rats, together with an increase in caspase 3, 8 of nucleosomes and LPO and

  13. Laboratory and histological similarities between Wilson's disease and rats with copper toxicity.

    Directory of Open Access Journals (Sweden)

    Narasaki,Mikio

    1980-04-01

    Full Text Available Rats were injected intraperitoneally with copper-lactate daily for over 160 days (total dose of 30 mg copper in each animal. At 120 to 160 days of copper administration, animals developed symptoms similar to those of Wilson's disease, i.e., kidney functional disturbances, proteinuria, aminoaciduria, decreased blood ceruloplasmin oxidase activity and increased urinary copper excretion. Cirrhosis was found in some animals. Tubular necrosis of the kidneys, liver fibrosis and tigrolysis of thalamic nerve cells were also found. Copper depositions were observed in liver parenchymal cells, renal tubular epithels, thalamus glia cells and on the Descemet's membrane of the cornea. The similarities between induced copper- intoxication in rats and Wilson's disease are discussed.

  14. Haematological changes in the laboratory rat Rattus norvegicus infected with Echinostoma caproni (Trematoda: Echinostomatidae).

    Science.gov (United States)

    Muñoz-Antoli, C; Cortés, A; Torres, D; Esteban, J G; Toledo, R

    2015-09-01

    To study possible indirect effects of the infection with intestinal helminths, 12 Rattus norvegicus (Wistar) were each experimentally exposed to 100 metacercariae of Echinostoma caproni, and blood samples were taken weekly up to 4 weeks post-exposure for comparison with control rats. Values of haematocrit (HCT), red blood cells (RBC), platelets (PLT), white blood cells (WBC), haemoglobin (HGB) and haematimatrix indices, and mean corpuscular haemoglobin concentrations (MCHC) were determined. In addition, leucocyte counts, including lymphocytes, neutrophils, monocytes, eosinophils and basophils were analysed. These parameters, including the leucocyte counts, showed no significant differences, except for MCHC at 4 weeks post-exposure. The present results indicate that in rats infected with E. caproni, although eosinophilia did not significantly increase, a significant reduction in MCHC was associated with an increase in the number of RBC.

  15. Brain-derived neurotrophic factor signaling does not stimulate subventricular zone neurogenesis in adult mice and rats.

    Science.gov (United States)

    Galvão, Rui P; Garcia-Verdugo, José Manuel; Alvarez-Buylla, Arturo

    2008-12-10

    In rodents, the adult subventricular zone (SVZ) generates neuroblasts which migrate to the olfactory bulb (OB) and differentiate into interneurons. Recent work suggests that the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) can enhance adult SVZ neurogenesis, but the mechanism by which it acts is unknown. Here, we analyzed the role of BDNF and its receptor TrkB in adult SVZ neurogenesis. We found that TrkB is the most prominent neurotrophin receptor in the mouse SVZ, but only the truncated, kinase-negative isoform (TrkB-TR) was detected. TrkB-TR is expressed in SVZ astrocytes and ependymal cells, but not in neuroblasts. TrkB mutants have reduced SVZ proliferation and survival and fewer new OB neurons. To test whether this effect is cell-autonomous, we grafted SVZ cells from TrkB knock-out mice (TrkB-KO) into the SVZ of wild-type mice (WT). Grafted progenitors generated neuroblasts that migrated to the OB in the absence of TrkB. The survival and differentiation of granular interneurons and Calbindin(+) periglomerular interneurons seemed unaffected by the loss of TrkB, whereas dopaminergic periglomerular neurons were reduced. Intra-ventricular infusion of BDNF yielded different results depending on the animal species, having no effect on neuron production from mouse SVZ, while decreasing it in rats. Interestingly, mice and rats also differ in their expression of the neurotrophin receptor p75. Our results indicate that TrkB is not essential for adult SVZ neurogenesis and do not support the current view that delivering BDNF to the SVZ can enhance adult neurogenesis.

  16. Laboratory rats (Rattus norvegicus) do not use binaural phase differences to localize sound.

    Science.gov (United States)

    Wesolek, Christina M; Koay, Gimseong; Heffner, Rickye S; Heffner, Henry E

    2010-06-14

    The ability of Norway rats to use binaural time- and intensity-difference cues to localize sound was investigated by determining their ability to localize pure tones from 500 Hz to 32 kHz. In addition, their ability to use the binaural time cues present in the envelope of a signal was determined by presenting them with a 1-kHz tone that was amplitude modulated at either 250 or 500 Hz. Although the animals were easily able to localize tones above 2 kHz, indicating that they could use the binaural intensity-difference cue, they were virtually unable to localize the lower-frequency stimuli, indicating that they could not use the binaural phase (time) cue. Although some animals showed a residual ability to localize low-frequency tones, control tests indicated that they were using the transient interaural intensity difference in the onset of a sound that exists after it reaches the near ear but before it reaches the far ear. Thus, in contrast to earlier studies, we conclude that the Norway rat is unable to use the ongoing time cues available in low-frequency tones to localize sound, raising the possibility that the rat may not use interaural time differences to localize sound. 2010 Elsevier B.V. All rights reserved.

  17. Anti-nociceptive and anti-inflammatory activities of ethanolic flower extract of Newbouldia laevis in mice and rats

    Directory of Open Access Journals (Sweden)

    Y Tanko

    2008-09-01

    Full Text Available Summary: The ethanolic flower extract of Newbouldia laevis was investigated for possible anti-nociceptive and anti-inflammatory effects in rodents. Acetic acid induced writhing (in mice and formalin tests (in rats were used to study. The extract caused a significant decrease (P< 0.05, which was not dose a dependent inhibition on acetic acid-induced writhing and the neurogenic pain induced by formalin. The extract at the doses (25, 50 and 100mg/kg tested showed 59, 71 and 47% inhibition of abdominal constriction in mice respectively. The highest activity resides more at the lowest dose of 50mg/kg on the acetic acid induced abdominal constrictions. The intraperitoneal LD50 value of the extract was found to be 1264.9mg/kg body weight in mice. Preliminary phytochemical screening reveals the presence of alkaloids, saponins, tannins and flavonoids. The results suggest the extract contains pharmacologically active principles, and are in agreement with the local application of the plant in painful and inflammatory conditions.   Industrial relevance: Plant sources have provided inspiration in the development of an impressive number of synthetic drugs. These resources provide a host of novel chemical compounds, which have been optimized on the basis of their biological activities. This study will be helpful for the industry to produce herbal formulation more potent with less side effect and less costly than the present synthetic drugs used as analgesic and anti-inflammatory drugs that is devoid of more seriously adverse effects

  18. Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis.

    Science.gov (United States)

    Everaerts, Wouter; Zhen, Xiaoguang; Ghosh, Debapriya; Vriens, Joris; Gevaert, Thomas; Gilbert, James P; Hayward, Neil J; McNamara, Colleen R; Xue, Fenqin; Moran, Magdalene M; Strassmaier, Timothy; Uykal, Eda; Owsianik, Grzegorz; Vennekens, Rudi; De Ridder, Dirk; Nilius, Bernd; Fanger, Christopher M; Voets, Thomas

    2010-11-02

    Reduced functional bladder capacity and concomitant increased micturition frequency (pollakisuria) are common lower urinary tract symptoms associated with conditions such as cystitis, prostatic hyperplasia, neurological disease, and overactive bladder syndrome. These symptoms can profoundly affect the quality of life of afflicted individuals, but available pharmacological treatments are often unsatisfactory. Recent work has demonstrated that the cation channel TRPV4 is highly expressed in urothelial cells and plays a role in sensing the normal filling state of the bladder. In this article, we show that the development of cystitis-induced bladder dysfunction is strongly impaired in Trpv4(-/-) mice. Moreover, we describe HC-067047, a previously uncharacterized, potent, and selective TRPV4 antagonist that increases functional bladder capacity and reduces micturition frequency in WT mice and rats with cystitis. HC-067047 did not affect bladder function in Trpv4(-/-) mice, demonstrating that its in vivo effects are on target. These results indicate that TRPV4 antagonists may provide a promising means of treating bladder dysfunction.

  19. Novel Helicobacter species H.japonicum isolated from laboratory mice from Japan induces typhlocolitis and lower bowel carcinoma in C57BL/129 IL10-/- mice.

    Science.gov (United States)

    Shen, Zeli; Feng, Yan; Muthupalani, Sureshkumar; Sheh, Alexander; Cheaney, Lenzie E; Kaufman, Christian A; Gong, Guanyu; Paster, Bruce J; Fox, James G

    2016-12-01

    A novel Helicobacter species Helicobacter japonicum was isolated from the stomach and intestines of clinically normal mice received from three institutes from Japan. The novel Helicobacter sp. was microaerobic, grew at 37°C and 42°C, was catalase and oxidase positive, but urease negative. It is most closely related to the 16S rRNA gene of H.muridarum (98.6%); to the 23S rRNA gene of H.hepaticus (97.9%); to the hsp60 gene of H.typhlonius (87%). The novel Helicobacter sp. has in vitro cytolethal distending toxin (CDT) activity; its cdtB gene sequence has 83.8% identity with that of H.hepaticus The whole genome sequence of H.japonicum MIT 01-6451 has a 2.06-Mb genome length with a 37.5% G + C content. When the organism was inoculated into C57BL/129 IL10(-/-) mice, it was cultured from the stomach, colon and cecum of infected mice at 6 and 10 weeks post-infection. The cecum had the highest H.japonicum colonization levels by quantitative PCR. The histopathology of the lower bowel was characterized by moderate to severe inflammation, mild edema, epithelial defects, mild to severe hyperplasia, dysplasia and carcinoma. Inflammatory cytokines IFNγ, TNFα and IL17a, as well as iNOS were significantly upregulated in the cecal tissue of infected mice. These results demonstrate that the novel H.japonicum can induce inflammatory bowel disease and carcinoma in IL10(-/-) mice and highlights the importance of identifying novel Helicobacter spp. especially when they are introduced from outside mouse colonies from different geographic locations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Comparison of dosimetric mapping of radiation induced skin ulcer animal model in Nud mice and Wistar rat

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Nelson M.; Mosca, Rodrigo C.; Ferreira, Danilo C.; Somessari, Elizabeth S.R.; Silveira, Carlos Gaia da; Dornelles, Leonardo D.P.; Bueno, Carmem C.; Mathor, Monica B., E-mail: nelsonnininho@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Skin ulcer (SU) is the damage caused to the skin by ionizing radiation, becoming evident at the end or after the conclusion of radiotherapeutic treatments. Technological advances have enabled dose increases in radiotherapy protocols, augmenting SU cases. In order to investigate potential therapies for the SU, an animal model (AM) was devised for Wistar rats, based upon the AM of the Nud mice. The AM dose rate (DR) was measured with silicium diode in the gamma irradiator and lead blocks. Three animals were positioned into immobilizers with their dorsal region skin pinched and held up by a suture point fixed in the immobilizer and exposed to 85 Gy. The DR variation in the immobilizer tangential point with the source median plane was non-significant, thus establishing an average DR. Such shielding reduced the DR in the rat in more than 93%. The difference in the immobilizer's dimensions impaired the comparison between the DRs; nevertheless, the DR comparison in the immobilizer tangential point with the source median plane became the reference point for AM comparison. The appearance of SU symptoms and their maximum extensions were similar, notwithstanding the difference regarding their healing periods. The specified dose induced the SU emerging. Mass variation exerted no influence onto the healing, despite having age affected it. The animals, throughout and after the experiment, showed normal health with just the SU symptoms. This work granted us the AM for the Wistar rats, which shall reinforce the investigation of new therapies for SU treatment. (author)

  1. NTP Toxicology and Carcinogenesis Studies of Xylenes (Mixed) (60% m-Xylene, 14% p-Xylene, 9% o-Xylene, and 17% Ethylbenzene) (CAS No. 1330-20-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1986-12-01

    The technical grade of xylenes (mixed) (hereafter termed xylenes) contains the three isomeric forms and ethylbenzene (percentage composition shown above). The annual production for 1985 was approximately 7.4 x 108 gallons. Xylenes is used as a solvent and a cleaning agent and as a degreaser and is a constituent of aviation and automobile fuels. Xylenes is also used in the production of benzoic acid, phthalate anhydride, and isophthalic and terephthalic acids as well as their dimethyl esters. Toxicology and carcinogenesis studies of xylenes were conducted in laboratory animals because a large number of workers are exposed and because the long- term effects of exposure to xylenes were not known. Exposure for the present studies was by gavage in corn oil. In single-administration studies, groups of five F344/N rats and B6C3F1 mice of each sex received 500, 1,000, 2,000, 4,000, or 6,000 mg/kg. Administration of xylenes caused deaths at 6,000 mg/kg in rats and mice of each sex and at 4,000 mg/kg in male rats. In rats, clinical signs observed within 24 hours of dosing at 4,000 mg/kg included prostration, muscular incoordination, and loss of hind limb movement; these effects continued through the second week of observation. Tremors, prone position, and slowed breathing were recorded for mice on day 3, but all mice appeared normal by the end of the 2- week observation period. In 14- day studies, groups of five rats of each sex were administered 0, 125, 250, 500, 1,000, or 2,000 mg/kg, and groups of five mice of each sex received 0, 250, 500, 1,000, 2,000, or 4,000 mg/kg. Chemical- related mortality occurred only at 2,000 mg/kg in rats and at 4,000 mg/kg in mice. Rats and mice exhibited shallow breathing and prostration within 48 hours following dosing at 2,000 mg/kg. These signs persisted until day 12 for rats, but no clinical signs were noted during the second week for mice. In 13- week studies, groups of 10 rats of each sex received 0, 62.5, 125, 250, 500, or 1,000 mg

  2. Implantation of radiotelemetry transmitters yielding data on ECG, heart rate, core body temperature and activity in free-moving laboratory mice.

    Science.gov (United States)

    Cesarovic, Nikola; Jirkof, Paulin; Rettich, Andreas; Arras, Margarete

    2011-11-21

    The laboratory mouse is the animal species of choice for most biomedical research, in both the academic sphere and the pharmaceutical industry. Mice are a manageable size and relatively easy to house. These factors, together with the availability of a wealth of spontaneous and experimentally induced mutants, make laboratory mice ideally suited to a wide variety of research areas. In cardiovascular, pharmacological and toxicological research, accurate measurement of parameters relating to the circulatory system of laboratory animals is often required. Determination of heart rate, heart rate variability, and duration of PQ and QT intervals are based on electrocardiogram (ECG) recordings. However, obtaining reliable ECG curves as well as physiological data such as core body temperature in mice can be difficult using conventional measurement techniques, which require connecting sensors and lead wires to a restrained, tethered, or even anaesthetized animal. Data obtained in this fashion must be interpreted with caution, as it is well known that restraining and anesthesia can have a major artifactual influence on physiological parameters. Radiotelemetry enables data to be collected from conscious and untethered animals. Measurements can be conducted even in freely moving animals, and without requiring the investigator to be in the proximity of the animal. Thus, known sources of artifacts are avoided, and accurate and reliable measurements are assured. This methodology also reduces interanimal variability, thus reducing the number of animals used, rendering this technology the most humane method of monitoring physiological parameters in laboratory animals. Constant advancements in data acquisition technology and implant miniaturization mean that it is now possible to record physiological parameters and locomotor activity continuously and in realtime over longer periods such as hours, days or even weeks. Here, we describe a surgical technique for implantation of a

  3. Generation of Rag1-knockout immunodeficient rats and mice using engineered meganucleases.

    Science.gov (United States)

    Ménoret, Séverine; Fontanière, Sandra; Jantz, Derek; Tesson, Laurent; Thinard, Reynald; Rémy, Séverine; Usal, Claire; Ouisse, Laure-Hélène; Fraichard, Alexandre; Anegon, Ignacio

    2013-02-01

    Despite the recent availability of gene-specific nucleases, such as zinc-finger nucleases (ZFNs) and transcription activator-like nucleases (TALENs), there is still a need for new tools to modify the genome of different species in an efficient, rapid, and less costly manner. One aim of this study was to apply, for the first time, engineered meganucleases to mutate an endogenous gene in animal zygotes. The second aim was to target the mouse and rat recombination activating gene 1 (Rag1) to describe, for the first time, Rag1 knockout immunodeficient rats. We microinjected a plasmid encoding a meganuclease for Rag1 into the pronucleus of mouse and rat zygotes. Mutant animals were detected by PCR sequencing of the targeted sequence. A homozygous RAG1-deficient rat line was generated and immunophenotyped. Meganucleases were efficient, because 3.4 and 0.6% of mouse and rat microinjected zygotes, respectively, generated mutated animals. RAG1-deficient rats showed significantly decreased proportions and numbers of immature and mature T and B lymphocytes and normal NK cells vs. littermate wild-type controls. In summary, we describe the use of engineered meganucleases to inactivate an endogenous gene with efficiencies comparable to those of ZFNs and TALENs. Moreover, we generated an immunodeficient rat line useful for studies in which there is a need for biological parameters to be analyzed in the absence of immune responses.

  4. NTP Toxicology and Carcinogenesis Studies of Isobutene (CAS No. 115-11-7) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1998-12-01

    Isobutene is produced during the fractionation of refinery gases or through the catalytic cracking of methyl-t-butyl ether. Isobutene is primarily used to produce diisobutylene, trimers, butyl rubber, and other polymers. In addition, it is used in the production of isooctane, high-octane aviation gasoline, methyl-t-butyl ether, and copolymer resins with butadiene and acrylonitrile. Isobutene was selected for evaluation because of the potential for human exposure due to its large production volume and the lack of adequate data on its carcinogenic potential. The toxicity and carcinogenicity of isobutene were determined in male and female F344/N rats and B6C3F1 mice exposed to isobutene (greater than 98% pure) by inhalation for 14 weeks or 2 years. The mutagenicity of isobutene was assessed in Salmonella typhimurium, and the frequency of micronuclei was determined in the peripheral blood of mice exposed by inhalation for 14 weeks. 14-WEEK STUDIES: Groups of 10 male and 10 female F344/N rats and B6C3F1 mice were exposed to isobutene at concentrations of 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm 6 hours per day, 5 days per week, for 14 weeks. Concentrations greater than 8,000 ppm isobutene were not used because of the danger of explosion. All rats and mice survived to the end of the study. The final mean body weights and body weight gains of all exposed groups were similar to those of the chamber controls. No exposure-related gross lesions were observed in male or female rats or mice at necropsy. Microscopically, minimal hypertrophy of goblet cells lining the nasopharyngeal duct in the most caudal nose section was observed in some rats in each exposed group of males and females. 2-YEAR STUDIES: Based on the lack of significant exposure-related toxicologic effects in the 14-week rat and mouse studies, 8,000 ppm was selected as the highest exposure concentration in the 2-year studies. Concentrations of 0, 500, 2,000, and 8,000 ppm were selected for rats and mice with the

  5. Quantification of DNA adducts formed in liver, lungs, and isolated lung cells of rats and mice exposed to (14)C-styrene by nose-only inhalation.

    Science.gov (United States)

    Boogaard, P J; de Kloe, K P; Wong, B A; Sumner, S C; Watson, W P; van Sittert, N J

    2000-10-01

    Bronchiolo-alveolar tumors were observed in mice exposed chronically to 160 ppm styrene, whereas no tumors were seen in rats up to concentrations of 1000 ppm. Clara cells, which are predominant in the bronchiolo-alveolar region in mouse lungs but less numerous in rat and human lung, contain various cytochrome P450s, which may oxidize styrene to the rodent carcinogen styrene-7,8-oxide (SO) and other reactive metabolites. Reactive metabolites may form specific DNA adducts and induce the tumors observed in mice. To determine DNA adducts in specific tissues and cell types, rats and mice were exposed to 160 ppm [ring-U-(14)C]styrene by nose-only inhalation for 6 h in a recirculating exposure system. Liver and lungs were isolated 0 and 42 h after exposure. Fractions enriched in Type II cells and Clara cells were isolated from rat and mouse lung, respectively. DNA adduct profiles differed quantitatively and qualitatively in liver, total lung, and enriched lung cell fractions. At 0 and 42 h after exposure, the two isomeric N:7-guanine adducts of SO (measured together, HPEG) were present in liver at 3.0 +/- 0.2 and 1.9 +/- 0.3 (rat) and 1.2 +/- 0.2 and 3.2 +/- 0.5 (mouse) per 10(8) bases. Several other, unidentified adducts were present at two to three times higher concentrations in mouse, but not in rat liver. In both rat and mouse lung, HPEG was the major adduct at approximately 1 per 10(8) bases at 0 h, and these levels halved at 42 h. In both rat Type II and non-Type II cells, HPEG was the major adduct and was about three times higher in Type II cells than in total lung. For mice, DNA adduct levels in Clara cells and non-Clara cells were similar to total lung. The hepatic covalent binding index (CBI) at 0 and 42 h was 0.19 +/- 0.06 and 0.14 +/- 0.03 (rat) and 0. 25 +/- 0.11 and 0.44 +/- 0.23 (mouse), respectively. The pulmonary CBIs, based on tissues combined for 0 and 42 h, were 0.17 +/- 0.04 (rat) and 0.24 +/- 0.04 (mouse). Compared with CBIs for other genotoxicants

  6. Chemical Concentrations in Field Mice from Open-Detonation Firing Sites TA-36 Minie and TA-39 Point 6 at Los Alamos National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Fresquez, Philip R. [Los Alamos National Laboratory

    2011-01-01

    Field mice (mostly Peromyscus spp.) were collected at two open-detonation (high explosive) firing sites - Minie at Technical Area (TA) 36 and Point 6 at TA-39 - at Los Alamos National Laboratory in August of 2010 and in February of 2011 for chemical analysis. Samples of whole body field mice from both sites were analyzed for target analyte list elements (mostly metals), dioxin/furans, polychlorinated biphenyl congeners, high explosives, and perchlorate. In addition, uranium isotopes were analyzed in a composite sample collected from TA-36 Minie. In general, all constituents, with the exception of lead at TA-39 Point 6, in whole body field mice samples collected from these two open-detonation firing sites were either not detected or they were detected below regional statistical reference levels (99% confidence level), biota dose screening levels, and/or soil ecological chemical screening levels. The amount of lead in field mice tissue collected from TA-39 Point 6 was higher than regional background, and some lead levels in the soil were higher than the ecological screening level for the field mouse; however, these levels are not expected to affect the viability of the populations over the site as a whole.

  7. Arcuate nucleus homeostatic systems are not altered immediately prior to the scheduled consumption of large, binge-type meals of palatable solid or liquid diet in rats and Mice.

    Science.gov (United States)

    Bake, T; Duncan, J S; Morgan, D G A; Mercer, J G

    2013-04-01

    Meal feeding is a critical issue in the over-consumption of calories leading to human obesity. To investigate the mechanisms involved in the regulation of meal feeding in rodents, we studied a scheduled feeding regime that induces substantial food intake over short periods of time. Male Sprague-Dawley rats and C57BL6 mice were fed one of four palatable diets [45% fat pellet, 60% fat pellet or standard pellet supplemented with Ensure (EN; Abbott Laboratories, Maidenhead, UK) or 12.5% sucrose (SUC)] either ad lib. or with daily 2-h scheduled access and standard pellet available for 22 h. Energy balance gene expression in the hypothalamic arcuate nucleus (ARC) and nucleus accumbens (NAcc) reward gene expression were assessed by in situ hybridisation. Rats fed ad lib. on 45% or 60% fat diet were heavier and fatter than controls, and had reduced neuropeptide Y (NPY) gene expression in the ARC. Mice fed ad lib. on any of the palatable diets were heavier, fatter and had higher blood leptin than controls, and had reduced NPY and increased cocaine- and-amphetamine-regulated transcript mRNA in the ARC. Schedule-fed rats and mice quickly adapted their feeding behaviour to 2-h access on palatable food. Three schedule-fed groups binged: the percentage of daily calories consumed in 2 h on 45% fat diet, 60% fat diet or EN, respectively, was 55%, 63% and 49% in rats, and 86%, 86% and 45% in mice. However, changed feeding behaviour was not reflected in an induction of orexigenic neuropeptide or suppression of anorexigenic neuropeptide gene expression in the ARC, in the 2-h period prior to scheduled feeding. The mechanisms underlying large meal/binge-type eating may be regulated by nonhomeostatic processes involving other genes in the hypothalamus or other brain areas. However, assessment of opioid and dopamine receptor gene expression in the NAcc did not reveal evidence of the involvement of these genes in driving large meals, at least at the investigated time point.

  8. Mitochondrial superoxide mediates labile iron level: evidence from Mn-SOD-transgenic mice and heterozygous knockout mice and isolated rat liver mitochondria.

    Science.gov (United States)

    Ibrahim, Wissam H; Habib, Hosam M; Kamal, Hina; St Clair, Daret K; Chow, Ching K

    2013-12-01

    Superoxide is the main reactive oxygen species (ROS) generated by aerobic cells primarily in mitochondria. It is also capable of producing other ROS and reactive nitrogen species (RNS). Moreover, superoxide has the potential to release iron from its protein complexes. Unbound or loosely bound cellular iron, known as labile iron, can catalyze the formation of the highly reactive hydroxyl radical. ROS/RNS can cause mitochondrial dysfunction and damage. Manganese superoxide dismutase (Mn-SOD) is the chief ROS-scavenging enzyme and thereby the primary antioxidant involved in protecting mitochondria from oxidative damage. To investigate whether mitochondrial superoxide mediates labile iron in vivo, the levels of labile iron were determined in the tissues of mice overexpressing Mn-SOD and heterozygous Mn-SOD-knockout mice. Furthermore, the effect of increased mitochondrial superoxide generation on labile iron levels was determined in isolated rat liver mitochondria exposed to various electron transport inhibitors. The results clearly showed that increased expression of Mn-SOD significantly lowered the levels of labile iron in heart, liver, kidney, and skeletal muscle, whereas decreased expression of Mn-SOD significantly increased the levels of labile iron in the same organs. In addition, the data showed that peroxidative damage to membrane lipids closely correlated with the levels of labile iron in various tissues and that altering the status of Mn-SOD did not alter the status of other antioxidant systems. Results also showed that increased ROS production in isolated liver mitochondria significantly increased the levels of mitochondrial labile iron. These findings constitute the first evidence suggesting that mitochondrial superoxide is capable of releasing iron from its protein complexes in vivo and that it could also release iron from protein complexes contained within the organelle.

  9. Pharmacokinetics of rh-IFNalpha-2a-NGR, a tumor targeted-therapy candidate, following intramuscular administration to mice, rats and monkeys.

    Science.gov (United States)

    Lu, L I; Wang, Xuexi; Wang, Li; Zhang, Baolai; Yan, Shuai; Zhao, Xin; Li, Wan; Cui, MingXia; Gao, MingTang; Zhang, YingQi; Wu, YongJie

    2011-09-01

    The compound rh-IFNalpha-2a-NGR can inhibit tumor angiogenesis and could be used for targeted therapy. In the present study, double antibody sandwich ELISA analysis was used to determine the concentration of rh-IFNalpha-2a-NGR in serum after intramuscular administration of various dosages to mice, rats and monkeys. The results showed that the pharmacokinetic properties of rh-IFNalpha2a-NGR after i.m. administration to mice, rats and monkeys were consistent with a one-compartment open model. The main pharmacokinetic parameters in mice (9.36 microg/kg), rats (4.68 microg/kg) and monkeys (2.34 microg/kg) after i.m. rh-IFNalpha2a-NGR were as follows: T(peak) was 0.49, 1.65 and 3.60h, C(max) was 3030.20, 654.49 and 268.13 ng/L, t1/2 was 0.39, 4.52 and 2.70 h, and AUC(0-infinity)) was 4197.65, 5784.58 and 2622.06 ng/L x h, respectively. Also, mice, rats and monkeys had their own distinct metabolic characteristics. These data would provide references for further clinical pharmacokinetic study of rh-IFNalpha2a-NGR.

  10. Effects of Saiko-ka-ryukotsu-borei-to, a Japanese Kampo medicine, on tachycardia and central nervous system stimulation induced by theophylline in rats and mice.

    Science.gov (United States)

    Sanae, F; Hayashi, H; Chisaki, K; Komatsu, Y

    1999-03-01

    Effects of Saiko-ka-ryukotsu-borei-to (SRBT) on theophylline-induced tachycardia in anesthetized rats and theophylline-induced locomotion and convulsions in mice were examined. An intraduodenal administration of SRBT (1 g/kg) prevented theophylline (5 mg/kg, i.v.)-induced tachycardia in rats. SRBT also attenuated an increase in arterial blood pressure with a slow reduction in heart rate of rats treated with theophylline, with no influence on the plasma level of theophylline. However, SRBT did not change the beating rate of right atrium isolated from rats in the absence or presence of theophylline or isoproterenol. The locomotor activity of theophylline in mice was reduced by the treatment with SRBT. Furthermore, the latency of convulsions in mice induced by administration of theophylline at a higher dose (240 mg/kg, i.p.) was prolonged by treatment with SRBT (1 g/kg, p.o.) and seven out of fifteen mice were saved from death due to convulsions. These results suggest that theophylline-induced tachycardia and central nervous stimulation are suppressed by SRBT and that SRBT may reduce the undesirable actions of theophylline on the cardiovascular and central nervous systems.

  11. Perfluoroalkyl substances in the blood of wild rats and mice from 47 prefectures in Japan: use of samples from nationwide specimen bank.

    Science.gov (United States)

    Taniyasu, Sachi; Senthilkumar, Kurunthachalam; Yamazaki, Eriko; Yeung, Leo W Y; Guruge, Keerthi S; Kannan, Kurunthachalam; Yamashita, Nobuyoshi

    2013-07-01

    Numerous studies have reported on the global distribution, persistence, fate, and toxicity of perfluoroalkyl and polyfluoroalkyl substances (PFASs). However, studies on PFASs in terrestrial mammals are scarce. Rats can be good sentinels of human exposure to toxicants because of their habitat, which is in close proximity to humans. Furthermore, exposure data measured for rats can be directly applied for risk assessment because many toxicological studies use rodent models. In this study, a nationwide survey of PFASs in the blood of wild rats as well as surface water samples collected from rats' habitats from 47 prefectures in Japan was conducted. In addition to known PFASs, combustion ion chromatography technique was used for analysis of total fluorine concentrations in the blood of rats. In total, 216 blood samples representing three species of wild rats (house rat, Norway rats, and field mice) were analyzed for 23 PFASs. Perfluorooctanesulfonate (PFOS; concentration range 80 % of the blood samples. Concentrations of several PFASs in rat blood were similar to those reported for humans. PFSAs (mainly PFOS) accounted for 45 % of total PFASs, whereas perfluoroalkyl carboxylates (PFCAs), especially PFUnDA and PFNA, accounted for 20 and 10 % of total PFASs, respectively. In water samples, PFCAs were the predominant compounds with PFOA and PFNA found in >90 % of the samples. There were strong correlations (p blood.

  12. Thermal latency studies in opiate-treated mice

    OpenAIRE

    Noam Schildhaus; Eliana Trink; Chirs Polson; Louis DeTolla; Tyler, Betty M.; Jallo, George I.; Sino Tok; Michael Guarnieri

    2014-01-01

    Background: The change in the reaction time of a tail or paw exposed to a thermal stimulus is a measure of nociceptive activity in laboratory animals. Tail-flick and plantar thermal sensitivity (Hargreaves) tests are non-invasive, minimize stress, and can be used to screen animals for phenotype and drug activity. Objective: Hargreaves testing has been widely used in rats. We investigated its use to measure the activity of opiate analgesia in mice. Methods: Mice were used in thermal stimulus s...

  13. Anti-nociceptive and anti-inflammatory activities of ethanol extract of syzygium aromaticum flower bud in Wistar rats and mice.

    Science.gov (United States)

    Tanko, Y; Mohammed, A; Okasha, M A; Umar, A H; Magaji, R A

    2008-01-22

    The ethanol extracts of Syzygium aromaticum flower bud were tested for anti-nociceptive and anti-inflammatory effects in mice and Wistar rats which were carried out using acetic acid-induced abdominal contractions in mice and formalin-induced hind paw edema in Wistar rats. Three doses of the ethanol extract (50, 100, and 200 mg/kg body weight i.p.) were used for both studies. The extract had an LD(50) of 565.7 mg/kg body weight intraperitoneally in mice. The extracts produced significant effect (P<0.05) at all the three doses. Similarly, the anti-nociceptive activity produced significant effects (P<0.05) at all the three doses of the extract. The result supports the local use of the plant in painful and inflammatory conditions.

  14. The tissue distribution of diazinon and the inhibition of blood cholinesterase activities in rats and mice receiving a single intraperitoneal dose of diazinon.

    Science.gov (United States)

    Tomokuni, K; Hasegawa, T; Hirai, Y; Koga, N

    1985-10-01

    The tissue distribution of diazinon and the inhibition of cholinesterase (ChE) activities in plasma, erythrocyte and brain were investigated using male rats and mice which received a single intraperitoneal (i.p.) dose of diazinon (20 or 100 mg/kg body wt) in olive oil. The blood diazinon level was estimated to reach a maximum at 1-2 h after the i.p. administration. It was demonstrated that the diazinon residue levels are the highest in the kidney, when comparing the distribution of diazinon among liver, kidney and brain in the animals after dosing. It was indicated that the ChE inhibition by diazinon exposure is greater in the plasma than in the erythrocytes for male mice, while its inhibition is greater in the erythrocytes for male rats. Brain ChE activity was also inhibited markedly in the mice after dosing.

  15. Pharmacokinetics, tissue distribution, and metabolites of a polyvinylpyrrolidone-coated norcantharidin chitosan nanoparticle formulation in rats and mice, using LC-MS/MS

    Directory of Open Access Journals (Sweden)

    Ding XY

    2012-04-01

    Full Text Available Xin-Yuan Ding1, Cheng-Jiao Hong2, Yang Liu1, Zong-Lin Gu1, Kong-Lang Xing1, Ai-Jun Zhu1, Wei-Liang Chen1, Lin-Seng Shi1, Xue-Nong Zhang1, Qiang Zhang31Department of Pharmaceutics, College of Pharmaceutical science, Soochow University, Suzhou, 2Jiang Su Provincial Key Laboratory of Radiation Medicine and Protection, Suzhou, 3Department of Pharmaceutics, School of Pharmaceutical Science, Peking University, Beijing, People’s Republic of ChinaAbstract: A novel formulation containing polyvinylpyrrolidone (PVP K30-coated norcantharidin (NCTD chitosan nanoparticles (PVP–NCTD–NPs was prepared by ionic gelation between chitosan and sodium tripolyphosphate. The average particle size of the PVP–NCTD–NPs produced was 140.03 ± 6.23 nm; entrapment efficiency was 56.33% ± 1.41%; and drug-loading efficiency was 8.38% ± 0.56%. The surface morphology of NCTD nanoparticles (NPs coated with PVP K30 was characterized using various analytical techniques, including X-ray diffraction and atomic force microscopy. NCTD and its metabolites were analyzed using a sensitive and specific liquid chromatography-tandem mass spectrometry method with samples from mice and rats. The results indicated the importance of the PVP coating in controlling the shape and improving the entrapment efficiency of the NPs. Pharmacokinetic profiles of the NCTD group and PVP–NCTD–NP group, after oral and intravenous administration in rats, revealed that relative bioavailabilities were 173.3% and 325.5%, respectively. The elimination half-life increased, and there was an obvious decrease in clearance. The tissue distribution of NCTD in mice after the intravenous administration of both formulations was investigated. The drug was not quantifiable at 6 hours in all tissues except for the liver and kidneys. The distribution of the drug in the liver and bile was notably improved in the PVP–NCTD–NP group. The metabolites and excretion properties of NCTD were investigated by analyzing

  16. Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development

    OpenAIRE

    Beauchemin, Kyle J.; Julie M. Wells; Kho, Alvin T.; Philip, Vivek M.; Kamir, Daniela; Kohane, Isaac S; Graber, Joel H.; Bult, Carol J.

    2016-01-01

    To characterize temporal patterns of transcriptional activity during normal lung development, we generated genome wide gene expression data for 26 pre- and post-natal time points in three common inbred strains of laboratory mice (C57BL/6J, A/J, and C3H/HeJ). Using Principal Component Analysis and least squares regression modeling, we identified both strain-independent and strain-dependent patterns of gene expression. The 4,683 genes contributing to the strain-independent expression patterns w...

  17. Rat embryonic stem cells create new era in development of genetically manipulated rat models

    Institute of Scientific and Technical Information of China (English)

    Kazushi; Kawaharada; Masaki; Kawamata; Takahiro; Ochiya

    2015-01-01

    Embryonic stem(ES) cells are isolated from theinner cell mass of a blastocyst, and are used for the generation of gene-modified animals. In mice, the transplantation of gene-modified ES cells into recipient blastocysts leads to the creation of gene-targeted mice such as knock-in and knock-out mice; these gene-targeted mice contribute greatly to scientific development. Although the rat is considered a useful laboratory animal alongside the mouse, fewer genemodified rats have been produced due to the lack of robust establishment methods for rat ES cells. A new method for establishing rat ES cells using signaling inhibitors was reported in 2008. By considering the characteristics of rat ES cells, recent research has made progress in improving conditions for the stable culture of rat ES cells in order to generate gene-modified rats efficiently. In this review, we summarize several advanced methods to maintain rat ES cells and generate gene-targeted rats.

  18. Conversion of Suspected Food Carcinogen 5-Hydroxymethylfurfural by Sulfotransferases and Aldehyde Dehydrogenases in Postmitochondrial Tissue Preparations of Humans, Mice, and Rats.

    Science.gov (United States)

    Sachse, Benjamin; Meinl, Walter; Glatt, Hansruedi; Monien, Bernhard H

    2016-01-01

    The food contaminant 5-hydroxymethylfurfural (HMF) is formed by heat- and acid-catalyzed reactions from carbohydrates. More than 80% of HMF is metabolized by oxidation of the aldehyde group in mice and rats. Sulfo conjugation yields mutagenic 5-sulfoxymethylfurfural, the probable cause for the neoplastic effects observed in HMF-treated rodents. Considerable metabolic differences between species hinder assessing the tumorigenic risk associated with human dietary HMF uptake. Here, we assayed HMF turnover catalyzed by sulfotransferases or by aldehyde dehydrogenases (ALDHs) in postmitochondrial preparations from liver, kidney, colon, and lung of humans, mice, and rats. The tissues-specific clearance capacities of HMF sulfo conjugation (CL(SC)) and ALDH-catalyzed oxidation (CL(OX)) were concentrated to the liver. The hepatic clearance CL(SC) in mice (males: 487 µl/min/kg bw, females: 2520 µl/min/kg bw) and rats (males: 430 µl/min/kg bw, females: 198 µl/min/kg bw) were considerably higher than those in humans (males: 21.2 µl/min/kg bw, females: 32.2 µl/min/kg bw). The ALDH-related clearance rates CLOX in mice (males: 3400 ml/min/kg bw, females: 1410 ml/min/kg bw) were higher than those of humans (males: 436 ml/min/kg bw, females: 646 ml/min/kg bw) and rats (males: 627 ml/min/kg bw, females: 679 ml/min/kg bw). The ratio of CL(OX) to CL(SC) was lowest in female mice. This finding indicated that HMF sulfo conjugation was most substantial in the liver of female mice, a target tissue for HMF-induced neoplastic effects, and that humans may be less sensitive regarding HMF sulfo conjugation compared with the rodent models.

  19. AVE8134, a novel potent PPARα agonist, improves lipid profile and glucose metabolism in dyslipidemic mice and type 2 diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Hans Ludwig SCH(A)FER; Wolfgang LINZ; Eugen FALK; Maike GLIEN; Heiner GLOMBIK; Mlarcus KORN; Wolfgang WEN-DLER; Andreas W HERLING; Hartmut R(U)TTEN

    2012-01-01

    AVE8134 is a structurally novel potent PPARα agonist.The aim of this study is to investigate the efficacy of AVE8134 on lipid profile and glucose metabolism in dyslipidemic mice and type 2 diabetic rats.Methods:A cell based PPAR Gal4 transactivation assay was constructed for testing the activities of AVE8134 at 3 different PPAR isoforms in vitro.Transgenic human Apo A1 (hApo A1) mice and insulin-resistant ZDF rats were used to evaluate the effects of AVE8134 in vivo.Results:AVE8134 was a full PPARα dominated PPAR agonist (the values of EC5o for human and rodent PPARα receptor were 0.01 and 0.3 μmol/L,respectively).AVE8134 was not active at PPARδ receptor.In female hApo A1 mice,AVE8134 (1-30 mg·kg-1-d-1,po for 12 d)dose-dependently lowered the plasma triglycerides,and increased the serum HDL-cholesterol,hApo A1 and mouse Apo E levels.In female ZDF rats,AVE8134 (3-30 mg·kg-1-d-1 for 2 weeks) improved insulin-sensitivity index.In pre-diabetic male ZDF rats (at the age of 7 weeks),AVE8134 (10 mg·kg-1-d-1 for 8 weeks) produced an anti-diabetic action comparable to rosiglitazone,without the PPARy mediated adverse effects on body weight and heart weight.In male ZDF rats (at the age of 6 weeks),AVE8134 (20 mg·kg-1-d-1 for 12 weeks) increased mRNA levels of the target genes LPL and PDK4 about 20 fold in the liver,and there was no relevant effect with rosiglitazone.Conclusion:AVE8134 improves lipid profile and glucose metabolism in dyslipidemic mice and type 2 diabetic rats.

  20. Helminth Parasites of Conventionally Maintained Laboratory Mice: II- Inbred Strains with an Adaptation of the Anal Swab Technique

    Directory of Open Access Journals (Sweden)

    Lucineide Gonçalves

    1998-01-01

    Full Text Available Worm burdens recovered from inbred mice strains, namely C57Bl/6, C57Bl/10, CBA, BALB/c, DBA/2 and C3H/He, conventionally maintained in two institutional animal houses in the State of Rio de Janeiro, RJ, Brazil, were analyzed and compared, regarding their prevalences and mean intensities.Three parasite species were observed: the nematodes Aspiculuris tetraptera, Syphacia obvelata and the cestode Vampirolepis nana. A modification of the anal swab technique is also proposed for the first time as an auxiliary tool for the detection of oxyurid eggs in mice

  1. Phage displaying peptides mimic schistosoma antigenic epitopes selected by rat natural antibodies and protective immunity induced by their immunization in mice

    Institute of Scientific and Technical Information of China (English)

    Min Wang; Xin-Yuan Yi; Xian-Ping Li; Dong-Ming Zhou; McReynolds Larry; Xian-Fang Zeng

    2005-01-01

    AIM: To obtain the short peptides mimic antigenic epitopes selected by rat natural antibodies to schistosomes, and to explore their immunoprotection against schistosomiasis in mice.METHODS: Adults worm antigens (AWA) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and enzyme-linked transferred immunoblotting methods with normal SD rat sera (NRS). The killing effects on schistosomula with fresh and heat-inactivated sera from SD rats were observed. Then the purified IgG from sera of SD rats was used to biopan a phage random peptide library and 20 randomly selected positive clones were detected by ELISA and 2 of them were sequenced.Sixty female mice were immunized thrice with positive phage clones (0, 2nd, 4th wk). Each mouse was challenged with 40 cercariae, and all mice were killed 42 d after challenge. The worms and the liver eggs were counted. RESULTS: NRS could specifically react to the molecules of 75 000, 47 000, 34 500 and 23 000 of AWA. Sera from SD rats showed that the mortality rate of schistosomula was 76.2%, and when the sera were heat-inactivated in vitro, the mortality rate was decreased to 41.0% after being cultured for 48 h. The specific phages bound to IgG were enriched about 300-folds after three rounds of biopanning. Twenty clones were detected by ELISA, 19 of them bound to the specific IgG of rat sera. Immunization with these epitopes was carried out in mice. Compared with the control groups, the mixture of two mimic peptides could induce 34.9% (P = 0.000) worm reduction and 67.6% (P = 0.000) total liver egg reduction in mice. Two different mimic peptides could respectively induce 31.0% (P = 0.001), 14.5% (P = 0.074) worm reduction and 61.2% (P = 0.000), 35.7% (P = 0.000) total liver egg reduction. The specific antibody could be induced by immunization of the mimic peptides, and the antibody titer in immunized mice reached more than 1:6 400 as detected by ELISA.CONCLUSION: Specific peptides mimic antigenic

  2. Application of metallomic and metabolomic approaches in exposure experiments on laboratory mice for environmental metal toxicity assessment.

    Science.gov (United States)

    García-Sevillano, M A; García-Barrera, T; Gómez-Ariza, J L

    2014-02-01

    Metals have a central role in biological systems, regulating numerous cellular processes, and in other cases having toxic or deleterious effects on the metabolism. Hence, the study of metal-induced changes in cellular metabolic pathways is crucial to understanding the biological response associated with environmental issues. In this context, the finding of biomarkers has great interest, representing -omics techniques, such as metallomics and metabolomics, powerful tools for this purpose. The present work evaluates the exposure of mice Mus musculus to toxic metals (As, Cd and Hg), considering the changes induced in both the metallome and metabolome as a consequence of the high genetic homology between Mus musculus/Mus spretus mice, which allows the use of the database from M. musculus to identify the proteins and metabolites expressed by M. spretus. For this purpose a metallomic approach based on size exclusion chromatography (SEC) in combination with other complementary orthogonal separation techniques and heteroelement monitoring by ICP-ORS-qMS was performed, followed by identification of metallobiomolecules by organic mass spectrometry. In addition, simultaneous speciation of selenoproteins and selenometabolites in mouse plasma was accomplished by tandem (double) SEC-(dual) affinity chromatography (AF)-HPLC and online isotope dilution analysis (IDA)-ICP-ORS-qMS. Finally, the simultaneous changes in metabolic expression in mice caused by metal exposure (metabolome) were considered, using direct infusion mass spectrometry (DI-ESI-QqQ-TOF-MS) of extracts from mice plasma. Subsequently altered metabolites were identified using MS/MS experiments. The results obtained under controlled conditions were extrapolated to homologous free-living mice captured in Doñana National Park (DNP) and surroundings (southwest Spain) affected by As, Cd and Hg pollution. In summary, such studies are needed to understand the effect of heavy metal exposure and cope with heavy metal

  3. Capacitive Sensing for Non-Invasive Breathing and Heart Monitoring in Non-Restrained, Non-Sedated Laboratory Mice

    OpenAIRE

    Carlos González-Sánchez; Juan-Carlos Fraile; Javier Pérez-Turiel; Ellen Damm; Schneider, Jochen G; Heiko Zimmermann; Daniel Schmitt; Ihmig, Frank R.

    2016-01-01

    Animal testing plays a vital role in biomedical research. Stress reduction is important for improving research results and increasing the welfare and the quality of life of laboratory animals. To estimate stress we believe it is of great importance to develop non-invasive techniques for monitoring physiological signals during the transport of laboratory animals, thereby allowing the gathering of information on the transport conditions, and, eventually, the improvement of these conditions. Her...

  4. DNA barcoding reveals the coral "laboratory-rat", Stylophora pistillata encompasses multiple identities.

    Science.gov (United States)

    Keshavmurthy, Shashank; Yang, Sung-Yin; Alamaru, Ada; Chuang, Yao-Yang; Pichon, Michel; Obura, David; Fontana, Silvia; De Palmas, Stephane; Stefani, Fabrizio; Benzoni, Francesca; MacDonald, Angus; Noreen, Annika M E; Chen, Chienshun; Wallace, Carden C; Pillay, Ruby Moothein; Denis, Vianney; Amri, Affendi Yang; Reimer, James D; Mezaki, Takuma; Sheppard, Charles; Loya, Yossi; Abelson, Avidor; Mohammed, Mohammed Suleiman; Baker, Andrew C; Mostafavi, Pargol Ghavam; Suharsono, Budiyanto A; Chen, Chaolun Allen

    2013-01-01

    Stylophora pistillata is a widely used coral "lab-rat" species with highly variable morphology and a broad biogeographic range (Red Sea to western central Pacific). Here we show, by analysing Cytochorme Oxidase I sequences, from 241 samples across this range, that this taxon in fact comprises four deeply divergent clades corresponding to the Pacific-Western Australia, Chagos-Madagascar-South Africa, Gulf of Aden-Zanzibar-Madagascar, and Red Sea-Persian/Arabian Gulf-Kenya. On the basis of the fossil record of Stylophora, these four clades diverged from one another 51.5-29.6 Mya, i.e., long before the closure of the Tethyan connection between the tropical Indo-West Pacific and Atlantic in the early Miocene (16-24 Mya) and should be recognised as four distinct species. These findings have implications for comparative ecological and/or physiological studies carried out using Stylophora pistillata as a model species, and highlight the fact that phenotypic plasticity, thought to be common in scleractinian corals, can mask significant genetic variation.

  5. Differences in microglia activation between rats-derived cell and mice-derived cell after stimulating by soluble antigen of IV larva from Angiostrongylus cantonensis in vitro.

    Science.gov (United States)

    Wei, Jie; Wu, Feng; Sun, Xi; Zeng, Xin; Liang, Jin-Yi; Zheng, Huan-Qin; Yu, Xin-Bing; Zhang, Kou-Xing; Wu, Zhong-Dao

    2013-01-01

    Angiostrongylus cantonensis is a rodent nematode. Adult worms of A. cantonensis live in the pulmonary arteries of rats. Humans and mice are accidental hosts or named nonpermissive hosts. The larva cannot develop into an adult worm and only causes serious eosinophilic meningitis or meningoencephalitis if humans or mice eat food containing larva of A. cantonensis in the third stage. The differing consequences largely depend on differing immune responses of the host to parasite during A. cantonensis invasion and development. Microglia is considered to be the key immune cell in the central nervous system like macrophage. To further understand the reasons for why mice and rats attain different outcomes in A. cantonensis infection, we set up the method to isolate and culture newborn rats' primary microglia and observe the activation of the microglia cells, comparing with mice microglia cell line N9. We treated cells with soluble antigen of the fourth larva of A. cantonensis (L4 larva) and measured mRNA levels of IL-1β, IL-5, IL-6, IL-13, eotaxin, iNOS, and TNF-α by real-time PCR. The results showed that N9 expressed high mRNA level of IL-6, IL-1β, TNF-α, iNOS, IL-5, IL-13, and eotaxin, but primary microglia only had IL-5, IL-13, and eotaxin mRNA level. It implies that microglia from rats and mice had different reaction to soluble antigen of A. cantonensis. Therefore, we supposed that microglia may play an immune modulation role during the brain inflammation induced by A. cantonensis.

  6. NTP Toxicology and Carcinogenesis Studies of Salicylazosulfapyridine (CAS No. 599-79-1) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1997-05-01

    Salicylazosulfapyridine is widely used for the treatment of ulcerative colitis and Crohn's disease. It has been beneficial in the treatment of psoriasis and rheumatoid arthritis, and it has been used in veterinary medicine for the treatment of granulomatous colitis. Salicylazosulfapyridine was nominated for toxicity and carcinogenicity testing by the National Cancer Institute on the basis of its widespread use in humans and because it is a representative chemical from a class of aryl sulfonamides. Salicylazosulfapyridine is a suspect carcinogen because reductive cleavage of the azo linkage yields a p-amino aryl sulfonamide (sulfapyridine), and a related p-amino aryl sulfonamide (sulfamethoxazole) has been shown to produce thyroid neoplasms in rats. Toxicology and carcinogenicity studies were conducted in F344/N rats and B6C3F1 mice. Rats and mice were administered salicylazosulfapyridine (96% to 98% pure) in corn oil by gavage for 16 days, 13 weeks, or 2 years. The gavage route of administration was selected for these studies because it approximates the typical route of human exposure to the chemical. Genetic toxicology studies were conducted in vitro in Salmonella typhimurium and cultured Chinese hamster ovary cells and in vivo in rat and mouse bone marrow and mouse peripheral blood cells. 16-DAY STUDY IN RATS: Groups of five male and five female rats were administered 0, 675, 1,350, or 2,700 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for 16 days excluding weekends. All rats survived to the end of the study. With the exception of the 675 mg/kg male group, the final mean body weights of all dosed groups of males and females were significantly lower than those of controls. Mean body weight gains of all dosed groups were less than those of controls. Clinical findings included ruffled fur and distended abdomens in male and female rats receiving 2,700 mg/kg. Hypothyroidism, evidenced by decreased serum triiodothyronine and thyroxine concentrations

  7. NTP Toxicology and Carcinogenesis Studies of Propylene (CAS No. 115-07-1) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1985-11-01

    Propylene is used as a starting material in the production of polypropylene plastics and various other chemicals, including acrylonitrile, isopropyl alcohol, propylene oxide, butyraldehyde, cumene, dodecane, nonene, and allyl chloride. The major derivatives are polypropylene (25%), acrylonitrile (15%), isopropyl alcohol (10%), and propylene oxide (10%). It is also a valuable feed-stock chemical for the production of gasoline. Other miscellaneous applications include use as a starting material for polymerization reactions to form vinyl chloride copolymers and low-molecular-weight homopolymers that are used as additives in lubricating oils and in the manufacture of hydroquinone. The chemical is also used as an aerosol propellant or component. The major end uses of propylene are in the production of fabricated plastics (50%) and fibers (15%). Toxicology and carcinogenesis studies of propylene (greater than 99% pure) were conducted by exposing groups of 50 F344/N rats and 49 or 50 B6C3F1 mice of each sex to propylene in air by inhalation at concentrations of 5,000 or 10,000 ppm, 6 hours per day, 5 days per week, for 103 weeks. Other groups of 50 rats and 50 mice of each sex in chambers received air only on the same schedule and served as chamber controls. The highest concentration of propylene that was considered safe for these studies was 10,000 ppm because of the risk of explosion that can occur at higher concentrations. The survival of exposed and control rats and mice was comparable. Throughout most of the studies, mean body weights of exposed male and female rats were slightly lower (0%-5%) than those of the controls, but the decrements were not concentration related. After week 59 of the study, mean body weights of 10,000-ppm male mice were usually slightly lower (5%) than those of the controls, whereas those in other exposed groups of male and female mice were generally comparable with those of the controls. No compound-related adverse clinical signs were

  8. 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

  9. 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.

  10. Comparative effects of hypoxia on behavioral thermoregulation in rats, hamsters, and mice.

    Science.gov (United States)

    Gordon, C J; Fogelson, L

    1991-01-01

    Recent studies using reptiles and other ectothermic species have shown that hypoxia lowers the set point for the control of body temperature. This is characterized by a preference for cooler ambient (Ta) and deep body temperatures (Tb) when placed in a temperature gradient. To elucidate the presence of this effect in mammals, the selected Ta and Tb of three rodent species (mouse, hamster, and rat) were measured while subjected to graded hypoxia in a temperature gradient. Individual animals were placed in the gradient for 30 min. Oxygen content of air entering the gradient was then reduced to a constant level for a period of 60 min by dilution with nitrogen. Tb was significantly reduced in all species at %O2 levels of 5.5-10%. Selected Ta was significantly reduced in the mouse at %O2 levels of 5.5 and 7.3%. Selected Ta of the hamster and rat were reduced slightly at %O2 levels of 5.8 and 7.4%, respectively; however, the effect was not statistically significant. To clarify the effects of hypoxia in these two species, the sample size of rat and hamster was increased to strengthen statistical analysis, and the animals were exposed for 60 min to %O2 levels of 7.4 and 6.7%, respectively. Both species exhibited a significant reduction in selected Ta during hypoxia concomitant with hypothermia. These data support the hypothesis that hypoxia lowers the set point for the control of body temperature in rodents.

  11. Effect of paraquat on microsomal lipid peroxidation in vitro and in vivo. [Rats, rabbits, man, mice

    Energy Technology Data Exchange (ETDEWEB)

    Kornbrust, D.J.; Mavis, R.D.

    1980-01-01

    Rat lung and liver microsomes did not undergo lipid peroxidation in the absence of iron when incubated with NADPH and concentrations of paraquat ranging from 10/sup -7/ to 10/sup -2/ M. Paraquat also did not stimulate rat liver and lung microsomal peroxidation induced by added iron and NADPH, and was inhibitory at concentrations above 10 ..mu..M. Similarly, no stimulation of peroxidation was produced by paraquat in rabbit or human lung microsomes; however, under similar conditions, paraquat enhanced NADPH/iron-dependent peroxidation in mouse lung and liver microsomes obtained from rats sacrificed at 12, 18, and 24 hr following a lethal dose of paraquat (50 mg/kg, ip), there was no loss of vitamin E or increase in susceptibility to in vitro peroxidation which would be expected if lipid peroxidation had occurred in vivo although extensive lung damage developed during this time period. These results indicate that paraquat does not cause pulmonary toxicity by initiating peroxidation of lung lipids, and the decrease of palmitate in paraquat-damaged lungs is consistent with inhibition of fatty acid synthesis as an early event in the pathogenesis of paraquat toxicity.

  12. The effective dose and pattern of soybean extract administration to regulate body weight of laboratory rats

    Directory of Open Access Journals (Sweden)

    Meilinah Hidayat

    2016-07-01

    the intake of protein and suppress appetite for short-term. Detam 1 variety is a high-quality soybean according to the Minister of Agriculture of Indonesia. Soybean protein extract Detam 1 by Deak method contains high levels of β conglycinin. The purpose of this study was to determine the effective dose of protein extract Detam 1 soybean Deak Method (PEDSDM in reducing food intake, regulate body weight, and plasma CCK level for 14 and 28 days at various dosage and pattern of treatment on male Wistar rats. Methods: There were eleven groups of treatment (n = 3, administrated with extracts at 5 mg/1x/day, 10 mg/1x/day, 20 mg/1x/day, 2.5 mg/2x/day, 5 mg/2x/day, 10 mg/2x/day and 1.7mg/3x/day, 3.4mg/3x/day, 6.7 mg/3x/day, negative control group (distilled water and positive control group (Sibutramine. Food intake (g, weight loss (g and measurement of plasma Cholecystokinin levels by ELISA (ng /ml Results: The results showed that the highest percentage decrease in food intake is: group 3.4mg /3x/ day (p <0.05, inhibition weight gain for 14 days: group 10 mg /1x/ day, for 28 days: group 1.7 mg/3x/day (p <0.05, increased plasma Cholecystokinin levels: group 20 mg /1x/day (p <0.05. Conclusions: The effective dose and pattern administrating the rats for 14 days is extract of 10 mg once a day in the morning, for 28 days is 1.7 mg three times a day. (Health Science Journal of Indonesia 2016;7:17-26 Keywords: Soybean var Detam 1 -effective dose - body weight - Cholecystokinin 

  13. An enzyme-linked immunosorbent assay for the detection of mouse polyomavirus-specific antibodies in laboratory mice.

    NARCIS (Netherlands)

    H.W.J. Broeders; J. Groen (Jan); A.D.M.E. Osterhaus (Albert); G. van Steenis (Bert)

    1994-01-01

    textabstractAn enzyme-linked immunosorbent assay (ELISA) was developed for the detection and quantification of IgM and IgG serum antibodies to mouse polyomavirus (MPV). To evaluate the potential of this ELISA for the screening of laboratory rodents, serum samples from specific pathogen free (SPF) BA

  14. Differences in Butadiene Adduct Formation between Rats and Mice Not Due to Selective Inhibition of CYP2E1 by Butadiene Metabolites

    Science.gov (United States)

    Pianalto, Kaila M.; Hartman, Jessica H.; Boysen, Gunnar; Miller, Grover P.

    2013-01-01

    CYP2E1 metabolizes 1,3-butadiene (BD) into genotoxic and possibly carcinogenic 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB), and 1,2-epoxy-3,4-butanediol (EB-diol). The dose response of DNA and protein adducts derived from BD metabolites increase linearly at low BD exposures and then saturate at higher exposures in rats, but not mice. It was hypothesized that differences in adduct formation between rodents reflect more efficient BD oxidation in mice than rats. Herein, we assessed whether BD-derived metabolites selectively inhibit rat but not mouse CYP2E1 activity using B6C3F1 mouse and Fisher 344 rat liver microsomes. Basal CYP2E1 activities toward 4-nitrophenol were similar between rodents. Through IC50 studies, EB was the strongest inhibitor (IC50 54 μM, mouse; 98 μM, rat), BD-diol considerably weaker (IC50 1200 μM, mouse; 1000 μM, rat), and DEB inhibition nonexistent (IC50 >25 mM). Kinetic studies showed that in both species EB and BD-diol inhibited 4-nitrophenol oxidation through two-site mechanisms in which inhibition constants reflected trends observed in IC50 studies. None of the reactive epoxide metabolites inactivated CYP2E1 irreversibly. Thus, there was no selective inhibition or inactivation of rat CYP2E1 by BD metabolites relative to mouse Cyp2e1, and it can be inferred that CYP2E1 activity toward BD between rodent species would similarly not be impacted by the presence of BD metabolites. Inhibition of CYP2E1 by BD metabolites is then not responsible for the reported species difference in BD metabolism, formation of BD-derived DNA and protein adducts, mutagenicity and tumorigenesis. PMID:24021170

  15. Acute and subacute pulmonary toxicity and mortality in mice after intratracheal instillation of ZnO nanoparticles in three laboratories

    DEFF Research Database (Denmark)

    Jacobsen, Nicklas Raun; Stoeger, Tobias; van den Brule, Sybille

    2015-01-01

    Inhalation is the main pathway of ZnO exposure in the occupational environment but only few studies have addressed toxic effects after pulmonary exposure to ZnO nanoparticles (NP). Here we present results from three studies of pulmonary exposure and toxicity of ZnO NP in mice. The studies were...... prematurely terminated because interim results unexpectedly showed severe pulmonary toxicity. High bolus doses of ZnO NP (25 up to 100μg; ≥1.4mg/kg) were clearly associated with a dose dependent mortality in the mice. Lower doses (≥6μg; ≥0.3mg/kg) elicited acute toxicity in terms of reduced weight gain......, desquamation of epithelial cells with concomitantly increased barrier permeability of the alveolar/blood as well as DNA damage. Oxidative stress was shown via a strong increase in lipid peroxidation and reduced glutathione in the pulmonary tissue. Two months post-exposure revealed no obvious toxicity for 12...

  16. Family relationship of female breeders reduce the systematic inter-individual variation in the gut microbiota of inbred laboratory mice

    DEFF Research Database (Denmark)

    Hufeldt, Majbritt Ravn; Nielsen, Dennis Sandris; Vogensen, Finn Kvist

    2010-01-01

    The gut microbiota (GM) may influence disease expression in several animal models for inflammatory diseases. It may therefore seem reasonable to pursue reduction in the number of animals used for individual studies by reducing the variation in the GM. Previous studies have shown that the composit......The gut microbiota (GM) may influence disease expression in several animal models for inflammatory diseases. It may therefore seem reasonable to pursue reduction in the number of animals used for individual studies by reducing the variation in the GM. Previous studies have shown...... that the composition of the GM is related to genetics to a certain extent. We hypothesized that the GM similarity in a group of mice born by mothers not being sisters would be lower than that in a group born by mothers being sisters. The lower similarity could lead to clustering of the GM of mice born by non......-sisters according to their mothers, while such clustering would not be visible if the mothers were sisters. We used 16S rRNA gene (V3 region) polymerase chain reaction-derived amplicon profiling by denaturing gradient gel electrophoresis (DGGE) to study the GM composition in caecum samples of 33 eight-week-old C57...

  17. Family relationship of female breeders reduce the systematic inter-individual variation in the gut microbiota of inbred laboratory mice

    DEFF Research Database (Denmark)

    Hufeldt, Majbritt Ravn; Nielsen, Dennis Sandris; Vogensen, Finn Kvist

    2010-01-01

    The gut microbiota (GM) may influence disease expression in several animal models for inflammatory diseases. It may therefore seem reasonable to pursue reduction in the number of animals used for individual studies by reducing the variation in the GM. Previous studies have shown that the composit......The gut microbiota (GM) may influence disease expression in several animal models for inflammatory diseases. It may therefore seem reasonable to pursue reduction in the number of animals used for individual studies by reducing the variation in the GM. Previous studies have shown...... that the composition of the GM is related to genetics to a certain extent. We hypothesized that the GM similarity in a group of mice born by mothers not being sisters would be lower than that in a group born by mothers being sisters. The lower similarity could lead to clustering of the GM of mice born by non......-sisters according to their mothers, while such clustering would not be visible if the mothers were sisters. We used 16S rRNA gene (V3 region) polymerase chain reaction-derived amplicon profiling by denaturing gradient gel electrophoresis (DGGE) to study the GM composition in caecum samples of 33 eight-week-old C57...

  18. Effects of different types of bedding materials on behavioral development in laboratory CD1 mice (Mus musculus).

    Science.gov (United States)

    Tanaka, Toyohito; Ogata, Akio; Inomata, Akiko; Nakae, Dai

    2014-10-01

    Male and female mice were housed in cages, containing different types of bedding materials (wood flakes or pulp chips), from 4 weeks of age in the F0 generation to 11 weeks of age in the F1 generation; selected reproductive and neurobehavioral parameters were measured in the F1 generation. There were no adverse effects of bedding materials on litter size, litter weight, or sex ratios at the time of birth. With regard to behavioral development parameters, bedding materials did not influence any variables (p > 0.05) in both sexes. Regarding exploratory behavior in the F1 generation, number of defecations significantly varied (p = 0.0203) with bedding materials in males at 3 weeks of age. The number of horizontal activities also significantly varied (p = 0.0342) with bedding materials in males at 8 weeks of age. Multiple-T water maze performance data indicated that the time required was significantly shortened across trials in pulp chips group than wood flakes group in males (p = 0.0211). Moreover, all spontaneous behavior variables in males significantly varied with bedding materials, particularly the average time of movement was significantly different (p = 0.0037) in distance between parallel lines of types of bedding materials in the F1 generation. The present study shows that bedding materials influence the neurobehavioral development in mice.

  19. Differential genotoxicity of acrylamide in the micronucleus and Pig-a gene mutation assays in F344 rats and B6C3F1 mice.

    Science.gov (United States)

    Hobbs, Cheryl A; Davis, Jeffrey; Shepard, Kim; Chepelev, Nikolai; Friedman, Marvin; Marroni, Dennis; Recio, Leslie

    2016-11-01

    Acrylamide is used in many industrial processes and is present in a variety of fried and baked foods. In rodent carcinogenicity assays, acrylamide exposure leads to tumour formation at doses lower than those demonstrated to induce genotoxic damage. We evaluated the potential of acrylamide to induce structural DNA damage and gene mutations in rodents using highly sensitive flow cytometric analysis of micronucleus and Pig-a mutant frequencies, respectively. Male F344 rats and B6C3F1 mice were administered acrylamide in drinking water for 30 days at doses spanning and exceeding the range of acrylamide exposure tested in cancer bioassays-top dose of 12.0 and 24.0mg/kg/day in mice and in rats, respectively. A positive control, N-ethyl-N-nitrosourea, was administered at the beginning and end of the study to meet the expression time for the two DNA damage phenotypes. The results of the micronucleus and Pig-a assays were negative and equivocal, respectively, for male rats exposed to acrylamide at the concentrations tested. In contrast, acrylamide induced a dose-dependent increase in micronucleus formation but tested negative in the Pig-a assay in mice. Higher plasma concentrations of glycidamide in mice than rats are hypothesized to explain, at least in part, the differences in the response. Benchmark dose modelling indicates that structural DNA damage as opposed to point mutations is most relevant to the genotoxic mode of action of acrylamide-induced carcinogenicity. Moreover, the lack of genotoxicity detected at acrylamide-induced carcinogenicity in rodents. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Hyperplasia of the lymphoepithelium of NALT in rats but not in mice upon 28-day exposure to 15 ppm formaldehyde vapor

    OpenAIRE

    Frieke Kuper, C.; Van Oostrum, Lidy; Ma-Hock, Lan; Durrer, Stefan; Woutersen, Ruud A.

    2010-01-01

    Abstract To investigate if local lymphoid tissues are a target of FA, nasopharynx-associated lymphoid tissues (NALT) and upper-respiratory tract-draining lymph nodes were examined in a 28-day inhalation study with FA vapor in Fischer-344 rats and B6C3F1 mice. Paraffin-embedded tissues were sectioned and stained with H&E or stained immunohistochemically for cell proliferation (BrdU incorporation). Light microscopy revealed simple hyperplasia of NALT lymphoepith...

  1. Anti-Inflammatory Activity Of Polyherbal Formulation By Using Cotton Pellet Granuloma In Rat And Xylene Induced Mice Ear Edema Model

    OpenAIRE

    Bhanu, Nafiza; N K Mishra; Panda, J. R.; Patra, S.

    2014-01-01

    Andrographis paniculata, Alpinia galanga, Boswellia serrata, Curcuma longa and Withania somnifera are the ethno medicinal plants widely used traditionally for the treatment of many inflammatory diseases because of plenty of source of flavonoid, saponin, steroids and terpenes. The present study has been focused to assess the anti-inflammatory activity of Poly herbal mixture in syrup base by using cotton pellet granuloma in rat and xylene induced mice ear edema model for the better therapeutic ...

  2. Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Gribble, Fiona M; Hartmann, Bolette

    2014-01-01

    glucose potently stimulated GIP release, fructose was without effect. Similar patterns were found in the mouse and rat, with both fructose and glucose stimulating GLP-1 secretion, whereas only glucose caused GIP secretion. In GLUTag cells, a murine cell line used as model for L cells, fructose...... was metabolized and stimulated GLP-1 secretion dose-dependently (EC50 = 0.155 mM) by ATP-sensitive potassium channel closure and cell depolarization. Because fructose elicits GLP-1 secretion without simultaneous release of glucagonotropic GIP, the pathways underlying fructose-stimulated GLP-1 release might...... be useful targets for type 2 diabetes mellitus and obesity drug development....

  3. HISTOPATHOLOGICAL DETECTION OF THE LARVAL STAGE OF TAENIA TAENIAEFORMIS (STROBILOCERCI AND ITS ASSOCIATED LESIONS IN LIVER OF LABORATORY RATS: CASE REPORT

    Directory of Open Access Journals (Sweden)

    Remigius Ibe Onoja

    2017-06-01

    Full Text Available Histopathological examination of liver tissues of rats maintained in laboratory condition showed the presence of strobilocerci of Taenia taeniaformis. Infiltration of mononuclear cells such as plasma cells, lymphocytes, macrophages and occasional eosinophils were seen. Active fibroplasia was found in the surrounding tissues. The finding is having importance in zoonatic effects and also for possibility of alteration of result of biomedical research works.

  4. Effect of currently approved carriers and adjuvants on the pre-clinical efficacy of a conjugate vaccine against oxycodone in mice and rats.

    Directory of Open Access Journals (Sweden)

    Marco Pravetoni

    Full Text Available Vaccination against the highly abused prescription opioid oxycodone has shown pre-clinical efficacy for blocking oxycodone effects. The current study further evaluated a candidate vaccine composed of oxycodone derivatized at the C6 position (6OXY conjugated to the native keyhole limpet hemocyanin (nKLH carrier protein. To provide an oxycodone vaccine formulation suitable for human studies, we studied the effect of alternative carriers and adjuvants on the generation of oxycodone-specific serum antibody and B cell responses, and the effect of immunization on oxycodone distribution and oxycodone-induced antinociception in mice and rats. 6OXY conjugated to tetanus toxoid (TT or a GMP grade KLH dimer (dKLH was as effective as 6OXY conjugated to the nKLH decamer in mice and rats, while the 6OXY hapten conjugated to a TT-derived peptide was not effective in preventing oxycodone-induced antinociception in mice. Immunization with 6OXY-TT s.c. absorbed on alum adjuvant provided similar protection to 6OXY-TT administered i.p. with Freund's adjuvant in rats. The toll-like receptor 4 (TLR4 agonist monophosphoryl lipid A (MPLA adjuvant, alone or in combination with alum, offered no advantage over alum alone for generating oxycodone-specific serum antibodies or 6OXY-specific antibody secreting B cells in mice vaccinated with 6OXY-nKLH or 6OXY-TT. The immunogenicity of oxycodone vaccines may be modulated by TLR4 signaling since responses to 6OXY-nKLH in alum were decreased in TLR4-deficient mice. These data suggest that TT, nKLH and dKLH carriers provide consistent 6OXY conjugate vaccine immunogenicity across species, strains and via different routes of administration, while adjuvant formulations may need to be tailored to individual immunogens or patient populations.

  5. Divergent effects of estradiol and the estrogen receptor-alpha agonist PPT on eating and activation of PVN CRH neurons in ovariectomized rats and mice.

    Science.gov (United States)

    Thammacharoen, Sumpun; Geary, Nori; Lutz, Thomas A; Ogawa, Sonoko; Asarian, Lori

    2009-05-01

    Eating is modulated by estradiol in females of many species and in women. To further investigate the estrogen receptor mechanism mediating this effect, ovariectomized rats and mice were treated with estradiol benzoate or the estrogen receptor-alpha (ER-alpha)-selective agonist PPT. PPT inhibited eating in rats much more rapidly than estradiol (approximately 2-6 h versus >24 h). In contrast, the latencies to vaginal estrus after PPT and estradiol were similar (>24 h). PPT also inhibited eating within a few hours in wild-type mice, but failed to inhibit eating in transgenic mice deficient in ER-alpha (ERalphaKO mice). PPT, but not estradiol, induced the expression of c-Fos in corticotrophin-releasing hormone (CRH)-expressing cells of the paraventricular nucleus (PVN) of the hypothalamus within 90-180 min in rats. Both PPT and estradiol reduced c-Fos expression in an ER-alpha-containing area of the nucleus of the solitary tract. The anomalously rapid eating-inhibitory effect of PPT suggests that PPT's neuropharmacological effect differs from estradiol's, perhaps because PPT differentially activates membrane versus nuclear ER-alpha or because PPT activates non-ER-alpha membrane estrogen receptors in addition to ER-alpha. The failure of PPT to inhibit eating in ERalphaKO mice, however, indicates that ER-alpha is necessary for PPT's eating-inhibitory action and that any PPT-induced activation of non-ER-alpha estrogen receptors is not sufficient to inhibit eating. Finally, the rapid induction of c-Fos in CRH-expressing cells in the PVN by PPT suggests that PPT elicits a neural response that is similar to that elicited by stress or aversive emotional stimuli.

  6. Administration of bleomycin via the oropharyngeal aspiration route leads to sustained lung fibrosis in mice and rats as quantified by UTE-MRI and histology.

    Directory of Open Access Journals (Sweden)

    Christine Egger

    Full Text Available Pulmonary fibrosis can be experimentally induced in small rodents by bleomycin. The antibiotic is usually administered via the intratracheal or intranasal routes. In the present study, we investigated the oropharyngeal aspiration of bleomycin as an alternative route for the induction of lung fibrosis in rats and mice. The development of lung injury was followed in vivo by ultrashort echo time magnetic resonance imaging (UTE-MRI and by post-mortem analyses (histology of collagen, hydroxyproline determination, and qRT-PCR. In C57BL/6 mice, oropharyngeal aspiration of bleomycin led to more prominent lung fibrosis as compared to intranasal administration. Consequently, the oropharyngeal aspiration route allowed a dose reduction of bleomycin and, therewith, a model refinement. Moreover, the distribution of collagen after oropharyngeal aspiration of bleomycin was more homogenous than after intranasal administration: for the oropharyngeal aspiration route, fibrotic areas appeared all over the lung lobes, while for the intranasal route fibrotic lesions appeared mainly around the largest superior airways. Thus, oropharyngeal aspiration of bleomycin induced morphological changes that were more comparable to the human disease than the intranasal administration route did. Oropharyngeal aspiration of bleomycin led to a homogeneous fibrotic injury also in rat lungs. The present data suggest oropharyngeal aspiration of bleomycin as a less invasive means to induce homogeneous and sustained fibrosis in the lungs of mice and rats.

  7. A comparison of the reactivating and therapeutic efficacy of chosen combinations of oximes with individual oximes against VX in rats and mice.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana Zdarova; Sepsova, Vendula; Caisberger, Filip; Bajgar, Jiri

    2011-10-01

    The ability of 2 combinations of oximes (HI-6 + trimedoxime and HI-6 + K203) to reactivate VX-inhibited acetylcholinesterase and reduce acute toxicity of VX was compared with the reactivating and therapeutic efficacy of antidotal treatment involving a single oxime (HI-6, trimedoxime, K203) in rats and mice. Our results showed that the reactivating efficacy of both combinations of oximes studied in rats is significantly higher than the reactivating efficacy of all individual oximes in diaphragm and roughly corresponds to the most effective individual oxime in blood and brain. Both combinations of oximes were found to be more effective in the reduction of acute lethal toxicity of VX in mice than the antidotal treatment involving the most efficacious individual oxime although the difference is not significant. Based on the obtained data, we can conclude that the antidotal treatment involving the chosen combinations of oximes brings benefit for the reactivation of VX-inhibited acetylcholinesterase in rats and for the antidotal treatment of VX-induced acute poisoning in mice.

  8. Health aspects of power transmission. [Effects of 60 Hz electric field on biochemical, morphological, and physiological parameters in mice and rats

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, R. D.

    1979-03-01

    Exposure of rats and mice to 60-Hz electric fields at 100 kV/m for up to 120 days had no statistically significant, reproducible effects on a number of measures of metabolic status and growth, bone growth and structure, reproduction, hematology and serum chemistry, endocrinology, cardiovascular function, nerve function, or organ and tissue morphology. An effect on cell-mediated immunity was detected and is being evaluated further in additional experiments. Exposure of rats in utero (day 0 of gestation to 8 days of age) had a transient effect at 14 days of age on motile behavior and development of the righting reflex. Significant effects were observed in synaptic transmission and behavior. Exposure to 60-Hz electric fields may increase the excitability of the nervous system of rats. Experiments are in progress to obtain a better understanding of these effects and their potential consequences.

  9. Multiple organ parenchymal cell apoptosis and its induction early after ischemia-reperfusion in rats and mice

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To determine the evolutionary pattern of parenchymal cell apoptosis in multiple organs early after intestinal ischemia-reperfusion(I/R) and its induction mechanisms and the role of apoptosis in triggering SIRS/MODS. METHODS: An I/R model was reproduced by clipping and releasing the superior mesenteric artery in rats and mice. Flow cytometry, electron microscope, DNA agarose gel electrophoresis, TUNEL method, fluorescent and Gomori's silver-HE staining were used to detect apoptosis. Distribution features of apoptotic parenchymal cells in multiple organs were observed. Immunohistochemical staining of HSP 70 and Bcl-2 were performd to study the induction mechanisms of apoptosis.RESULTS and CONCLUSION: 1. Damage of the liver, lung, gut and kidney was appeared in early phase of I/R. The percentages of apoptosis in parenchyma organs increased progressively. The percentages of cell necrosis increased with the prolonged I/R duration. 2. Percentages of apoptosis were much higher near the central veins of liver lobules, in the outer medulla of the kidney, and the antimescenteric border of intestinal mucosal epithelium because of ischemia. 3. The expression of HSP 70 increased and Bcl-2 reduced in the areas mentioned above because of hypoperfusion. 4. Apoptosis of I/R hepatocytes, splenocytes and thymocytes was obviously increased after Kupffer cell blockage with GdCl3, showing the functional state of Kupffer cells may play an important role in SIRS/MODS.

  10. A survey on helminthic infection in mice (Mus musculus and rats (Rattus norvegicus and Rattus rattus in Kermanshah, Iran

    Directory of Open Access Journals (Sweden)

    Norollah Pakdel

    2013-06-01

    Full Text Available Parasitic infections of rodents can compromise scientific research as well as the health of the animals and humans. Based on previous studies, infection rate of parasitic helminths is different in various regions of Iran. The current survey was aimed to determine endoparasitic helminths infection in 138 trapped rodents of Kermanshah county, Iran. Mice and rats were trapped using metal snares from January to October 2011 and euthanized. Rodents included 110 Mus musculus (79.00%, 23 Rattus norvegicus (17.00%, and five Rattus rattus (4.00%. The gastrointestinal and respiratory tracts were removed and examined to identify parasitic helminths. The results indicated that 42.02% of examined rodents were infected with eight helminths species, i.e. Trichuris muris (14.49%, Syphacia obvelata (13.76%, Syphacia muris (2.89%, Aspicularis tetrapetra (5.07%, Heterakis spumosa (5.07%, Capillaria hepatica eggs (3.62%, Hyminolepis diminuta (12.30%, and Cystisercus fasciolaris, the larva of Taenia teanieformis (4.34%. Given the results of this study, we concluded that examined rodents were more infected with nematodes than other helminths. As rodents are usually infected with a number of zoonotic parasites, hence control of these animals has an important role in safeguarding public health.

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

    Science.gov (United States)

    Nault, Rance; Kim, Suntae; Zacharewski, Timothy R

    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 20μg/kg TCDD for 1, 3 and 5days, while female C57BL/6 ovariectomized mice were examined 1, 3 and 7days after a single oral gavage of 30μg/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.

  12. Negligible Colon Cancer Risk from Food-Borne Acrylamide Exposure in Male F344 Rats and Nude (nu/nu) Mice-Bearing Human Colon Tumor Xenografts

    Science.gov (United States)

    Raju, Jayadev; Roberts, Jennifer; Sondagar, Chandni; Kapal, Kamla; Aziz, Syed A.; Caldwell, Don; Mehta, Rekha

    2013-01-01

    Acrylamide, a possible human carcinogen, is formed in certain carbohydrate-rich foods processed at high temperature. We evaluated if dietary acrylamide, at doses (0.5, 1.0 or 2.0 mg/kg diet) reflecting upper levels found in human foods, modulated colon tumorigenesis in two rodent models. Male F344 rats were randomized to receive diets without (control) or with acrylamide. 2-weeks later, rats in each group received two weekly subcutaneous injections of either azoxymethane (AOM) or saline, and were killed 20 weeks post-injections; colons were assessed for tumors. Male athymic nude (nu/nu) mice bearing HT-29 human colon adenocarcinoma cells-derived tumor xenografts received diets without (control) or with acrylamide; tumor growth was monitored and mice were killed 4 weeks later. In the F344 rat study, no tumors were found in the colons of the saline-injected rats. However, the colon tumor incidence was 54.2% and 66.7% in the control and the 2 mg/kg acrylamide-treated AOM-injected groups, respectively. While tumor multiplicity was similar across all diet groups, tumor size and burden were higher in the 2 mg/kg acrylamide group compared to the AOM control. These results suggest that acrylamide by itself is not a “complete carcinogen”, but acts as a “co-carcinogen” by exacerbating the effects of AOM. The nude mouse study indicated no differences in the growth of human colon tumor xenografts between acrylamide-treated and control mice, suggesting that acrylamide does not aid in the progression of established tumors. Hence, food-borne acrylamide at levels comparable to those found in human foods is neither an independent carcinogen nor a tumor promoter in the colon. However, our results characterize a potential hazard of acrylamide as a colon co-carcinogen in association with known and possibly other environmental tumor initiators/promoters. PMID:24040114

  13. DETERMINATION OF AGE AND GENDER DIFFERENCES IN BIOCHEMICAL PROCESSES AFFECTING THE DISPOSITION OF 2-BUTOXYETHANOL AND ITS METABOLITES IN MICE AND RATS TO IMPROVE PBPK MODELING

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Rick A.; Grant, Donna M.; Farris, Elizabeth; Weitz, Karl K.; Soelberg, Jolen J.; Thrall, K D.; Poet, Torka S.

    2005-03-28

    2-Butoxyethanol (BE) is the most widely used glycol ether solvent. BE's major metabolite, butoxyacetic acid (BAA), causes hemolysis with significant species differences in sensitivity. Several PBPK models have been developed over the past two decades to describe the disposition of BE and BAA in male rats and humans to refine health risk assessments. More recent efforts by Lee et al. (1998) to describe the kinetics of BE and BAA in the National Toxicology Program (NTP) chronic inhalation studies required the use of several assumptions to extrapolate model parameters from earlier PBPK models developed for young male rats to include female F344 and both sexes of B6C3F1 mice and the effects of aging. To replace these assumptions, studies were conducted to determine the impact of age, gender and species on the metabolism of BE, and the tissue partitioning, renal acid transport and plasma protein binding of BAA. In the current study, the Lee et al. PBPK model was updated and expanded to include the further metabolism of BAA and the salivary excretion of BE and BAA which may contribute to the forestomach irritation observed in mice in the NTP study. The revised model predicted that peak blood concentrations of BAA achieved following 6-hr inhalation exposures are greatest in young adult female rats at concentrations up to 300 ppm. This is not the case predicted for old (>18 months) animals, where peak blood concentrations of BAA in male and female mice were similar to or greater than female rats. The revised model serves as a quantitative tool for integrating an extensive pharmacokinetic and mechanistic database into a format that can readily be used to compare internal dosimetry across dose, route of exposure and species.

  14. Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice.

    Science.gov (United States)

    Castagné, Vincent; Moser, Paul; Roux, Sylvain; Porsolt, Roger D

    2011-04-01

    The development of antidepressants requires simple rodent behavioral tests for initial screening before undertaking more complex preclinical tests and clinical evaluation. Presented in the unit are two widely used screening tests used for antidepressants, the forced swim (also termed behavioral despair) test in the rat and mouse, and the tail suspension test in the mouse. These tests have good predictive validity and allow rapid and economical detection of substances with potential antidepressant-like activity. The behavioral despair and the tail suspension tests are based on the same principle: measurement of the duration of immobility when rodents are exposed to an inescapable situation. The majority of clinically used antidepressants decrease the duration of immobility. Antidepressants also increase the latency to immobility, and this additional measure can increase the sensitivity of the behavioral despair test in the mouse for certain classes of antidepressant. Testing of new substances in the behavioral despair and tail suspension tests allows a simple assessment of their potential antidepressant activity by the measurement of their effect on immobility.

  15. Antidiarrheal Activity of 19-Deoxyicetexone Isolated from Salvia ballotiflora Benth in Mice and Rats

    Directory of Open Access Journals (Sweden)

    Ernesto Sánchez-Mendoza

    2013-07-01

    Full Text Available The antidiarrheal properties of 19-deoxyicetexone, a diterpenoid isolated from Salvia ballotiflora were evaluated on castor oil-, arachidonic acid (AA- and prostaglandin (PGE2-induced diarrhea in rodent models. The structure of 19-deoxyicetexone was determined by X-ray crystallography, mass spectrometry (EI-MS, as well as ultraviolet (UV-Vis, infrared (FT-IR and nuclear magnetic resonance (NMR spectroscopies. This compound significantly and dose-dependently reduced frequency of stooling in castor oil-induced diarrhea, and at dose of 25 mg/kg it also inhibited diarrhea induced with AA, while it had no effect on PGE2-induced diarrhea. This compound at doses of 25 mg/kg also diminished castor oil-induced enteropooling and intestinal motility, and inhibited the contraction of the rats’ ileum induced by carbachol chloride at a concentration of 100 µg/mL. 19-Deoxyicetexone did not present acute toxicity at doses of 625 mg/kg. Its antidiarrheal activity may be due to increased reabsorption of NaCl and water and inhibition of the release of prostaglandins, gastrointestinal motility and fluid accumulation in the intestinal tracts of rats. These findings suggest that 19-deoxyicetexone may be used in the treatment of diarrhea, although more studies must be carried out to confirm this.

  16. NTP Toxicology and Carcinogenesis Studies of Diethanolamine (CAS No. 111-42-2) in F344/N Rats and B6C3F1 Mice (Dermal Studies).

    Science.gov (United States)

    1999-07-01

    Diethanolamine is widely used in the preparation of diethanolamides and diethanolamine salts of long-chain fatty acids that are formulated into soaps and surfactants used in liquid laundry and dishwashing detergents, cosmetics, shampoos, and hair conditioners. Diethanolamine is also used in textile processing, in industrial gas purification to remove acid gases, as an anticorrosion agent in metalworking fluids, and in preparations of agricultural chemicals. Aqueous diethanolamine solutions are used as solvents for numerous drugs that are administered intravenously. Diethanolamine was selected for evaluation because its large-scale production and pattern of use indicate the potential for widespread human exposure. Male and female F344/N rats and B6C3F1 mice received dermal applications of diethanolamine in 95% ethanol for 2 years. Genetic toxicology studies were performed in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, and B6C3F1 mouse peripheral blood erythrocytes. RATS: Groups of 50 male rats were administered 0, 16, 32, or 64 mg diethanolamine/kg body weight in ethanol dermally for 2 years. Groups of 50 female rats were administered 0, 8, 16, or 32 mg/kg in ethanol dermally for 2 years. Survival, Body Weights, and Clinical Findings Survival of vehicle control and dosed male and female rats was similar. Mean body weights of 64 mg/kg males were less than those of the vehicle controls beginning week 8, and mean body weights of females were generally similar to those of the vehicle control group. The only clinical finding attributed to diethanolamine administration was irritation of the skin at the site of application. Pathology Findings: Minimal to mild nonneoplastic lesions occurred at the site of application in the epidermis of dosed male and female rats. The incidence of acanthosis in 64 mg/kg males, the incidences of hyperkeratosis in 32 and 64 mg/kg males and in all dosed female groups, and the incidences of exudate

  17. Generation of gene knockouts and mutant models in the laboratory rat by ENU-driven target-selected mutagenesis

    NARCIS (Netherlands)

    Smits, Bart M G; Mudde, Josine B; van de Belt, Jose; Verheul, Mark; Olivier, Jocelien; Homberg, Judith; Guryev, Victor; Cools, Alexander R; Ellenbroek, Bart A; Plasterk, Ronald H A; Cuppen, Edwin

    2006-01-01

    OBJECTIVE: The rat is one of the most important model organisms for biomedical and pharmacological research. However, the generation of novel models for studying specific aspects of human diseases largely depends on selection for specific traits using existing rat strains, thereby solely depending o

  18. Caloric Restriction in Lean and Obese Strains of Laboratory Rat: Effects on Body Composition, Metabolism, Growth, and Overall Health

    Science.gov (United States)

    NEW FINDINGS: What is the central question of this study? How do lean and obese rats respond physiologically to caloric restriction? What is the main finding and its importance? Obese rats show marked benefits compared with lean animals. Reduced body fat is associated with improv...

  19. Generation of gene knockouts and mutant models in the laboratory rat by ENU-driven target-selected mutagenesis.

    NARCIS (Netherlands)

    Smits, B.M.; Mudde, J.B.; Belt, J. van de; Verheul, M.; Olivier, J.; Homberg, J.R.; Guryev, V.; Cools, A.R.; Ellenbroek, B.A.; Plasterk, R.H.; Cuppen, E.

    2006-01-01

    OBJECTIVE: The rat is one of the most important model organisms for biomedical and pharmacological research. However, the generation of novel models for studying specific aspects of human diseases largely depends on selection for specific traits using existing rat strains, thereby solely depending o

  20. Analysis of toxicity produced by inhalation of trichloroethylene within rat and mice`s respiratory epithelium; Comparazione del danno indotto dall`inalazione di tricloroetilene nell`epitelio nasale e tracheobronchiale del ratto e del topo

    Energy Technology Data Exchange (ETDEWEB)

    Mancuso, M.T.; Fravolini, M.E.; Parasacchi, P.; Lombardi, C.C.; Giovanetti, A. [ENEA, Casaccia (Italy). Area Energia Ambiente e Salute

    1994-05-01

    The aim of this study was to define the sites of cytotoxicity within the respiratory tract (nasal cavity and tracheobronchial tree) after acute inhalation of trichloroethylene (TCE), an organic solvent requiring metabolic activation by cytochrome P-450 enzymatic system to exert its toxic effects. Two animals species, rats and mice, were exposed to 3500 and 7000 ppm of TCE for 30 minutes. The morphological analysis of the respiratory epithelium has underlined a species-specific difference in the cellular sensitivity after treatment with TCE. This work is a part of ENEA (Italian Agency for New Technologies, Energy and the Environment) INTO program, environmental department, sector of effects on man and ecosystem.

  1. Ethylene glycol monomethyl ether (EGME) and propylene glycol monomethyl ether (PGME): inhalation fertility and teratogenicity studies in rats, mice and rabbits.

    Science.gov (United States)

    Hanley, T R; Young, J T; John, J A; Rao, K S

    1984-08-01

    A combined dominant lethal-fertility study was conducted in which male and female Sprague-Dawley (CD) rats were exposed to 0, 30, 100 or 300 ppm of ethylene glycol monomethyl ether (EGME) vapor for 6 hr/day, 5 days/week for 13 weeks and then mated to untreated counterparts. Among males, fertility was completely suppressed after exposure to 300 ppm. A partial restoration of reproductive function was evident following 13 weeks of recovery. No treatment-related reproductive effects were observed among males exposed subchronically to 100 ppm, or among females exposed to 300 ppm or below of EGME. Studies to assess the effects of inhaled EGME on embryonal and fetal development were also conducted in Fischer 344 rats, CF-1 mice, and New Zealand White rabbits. Rats and rabbits were exposed to concentrations of 0, 3, 10 or 50 ppm for 6 hr/day on days 6-15 or 6-18 of gestation, respectively. Exposure of rabbits to 50 ppm resulted in significant teratologic effects, an increased resorption rate, and decreased fetal body weight. Slight fetotoxicity in the form of skeletal variations were observed among rats exposed to 50 ppm. Exposure of pregnant mice to 0, 10, or 50 ppm for 6 hr/day on days 6-15 of gestation resulted in slight fetotoxicity at 50 ppm. No significant treatment-related effects were observed at 10 ppm of EGME or below in any of the species tested. Separate groups of pregnant rats and rabbits were exposed to 0, 500, 1500 or 3000 ppm of propylene glycol monomethyl ether (PGME) during organogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Neuronal death and synapse elimination in the olivocerebellar system. II. Cell counts in the inferior olive of adult x-irradiated rats and weaver and reeler mutant mice

    Energy Technology Data Exchange (ETDEWEB)

    Shojaeian, H.; Delhaye-Bouchaud, N.; Mariani, J.

    1985-02-15

    Cell death in the developing rat inferior olive precedes the regression of the polyneuronal innervation of Purkinje cells by olivary axons (i.e., climbing fibers), suggesting that the involution of the redundant olivocerebellar contacts is caused by a withdrawal of supernumerary axonal collaterals rather than by degeneration of the parent cell. However, a subsequent apparent increase of the olivary population occurs, which could eventually mask a residual presynaptic cell death taking place at the same time. Therefore, cell counts were performed in the inferior olive of adult rodents in which the multiple innervation of Purkinje cells by olivary axons is maintained, with the idea that if cell death plays a role in the regression of supernumerary climbing fibers, the number of olivary cells should be higher in these animals than in their controls. The results show that the size of the cell population in the inferior olive of weaver and reeler mutant mice and rats degranulated by early postnatal x-irradiation does not differ significantly from that of their controls. Similarly, the distribution of the cells in the four main olivary subnuclei is not modified in weaver mice and x-irradiated rats. The present data further support the assumption that the regression of the polyneuronal innervation of Purkinje cells occurs independently of cell death in the presynaptic population.

  3. Lack of in vitro and in vitro effects of fenbendazole on phase I and phase II biotransformation enzymes in rats, mice and chickens.

    Science.gov (United States)

    Dalvi, R R; Gawai, K R; Dalvi, P S

    1991-12-01

    Intraperitoneal administration of 10 mg fenbendazole/kg bw daily for 5 d caused no significant alterations in the activities of hepatic microsomal drug-metabolizing enzymes viz aminopyrine N-demethylase, aniline hydroxylase and cytosolic glutathione S-transferase in rats, mice and chickens. Similarly no significant difference in the amount of microsomal cytochrome P-450 and NADPH-cytochrome c reductase was found between control and treated animals. In vitro incubation of fenbendazole with rat, mouse and chicken microsomes suggests that the drug neither binds to microsomal protein cytochrome P-450 nor inhibits the activities of aminopyrine N-demethylase and aniline hydroxylase. Similarly in vitro addition of fenbendazole to cytosolic glutathione S-transferase from the above species did not alter the activity of this enzyme. The results indicate that fenbendazole does not alter the activity of hepatic microsomal monooxygenase system significantly in rats, mice and chickens at a dosage level of 10 mg/kg body weight. In vitro studies also indicate that fenbendazole does not interact with the hepatic microsomal monooxygenase system, indicating it is not a substrate for cytochrome P-450-dependent monooxygenase system.

  4. Polarization properties of single layers in the posterior eyes of mice and rats investigated using high resolution polarization sensitive optical coherence tomography.

    Science.gov (United States)

    Fialová, Stanislava; Augustin, Marco; Glösmann, Martin; Himmel, Tanja; Rauscher, Sabine; Gröger, Marion; Pircher, Michael; Hitzenberger, Christoph K; Baumann, Bernhard

    2016-04-01

    We present a high resolution polarization sensitive optical coherence tomography (PS-OCT) system for ocular imaging in rodents. The system operates at 840 nm and uses a broadband superluminescent diode providing an axial resolution of 5.1 µm in air. PS-OCT data was acquired at 83 kHz A-scan rate by two identical custom-made spectrometers for orthogonal polarization states. Pigmented (Brown Norway, Long Evans) and non-pigmented (Sprague Dawley) rats as well as pigmented mice (C57BL/6) were imaged. Melanin pigment related depolarization was analyzed in the retinal pigment epithelium (RPE) and choroid of these animals using the degree of polarization uniformity (DOPU). For all rat strains, significant differences between RPE and choroidal depolarization were observed. In contrast, DOPU characteristics of RPE and choroid were similar for C57BL/6 mice. Moreover, the depolarization within the same tissue type varied significantly between different rodent strains. Retinal nerve fiber layer thickness, phase retardation, and birefringence were mapped and quantitatively measured in Long Evans rats in vivo for the first time. In a circumpapillary annulus, retinal nerve fiber layer birefringence amounted to 0.16°/µm ± 0.02°/µm and 0.17°/µm ± 0.01°/µm for the left and right eyes, respectively.

  5. Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and β-thujone mixture in male and female F344/N rats and B6C3F1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Waidyanatha, Suramya, E-mail: waidyanathas@niehs.nih.gov [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Johnson, Jerry D.; Hong, S. Peter [Battelle Memorial Institute, Columbus, OH 43201 (United States); Robinson, Veronica Godfrey [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Gibbs, Seth; Graves, Steven W. [Battelle Memorial Institute, Columbus, OH 43201 (United States); Hooth, Michelle J.; Smith, Cynthia S. [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States)

    2013-09-01

    Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and β-thujone (which will be referred to as α,β-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,β-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. C{sub max} and AUC{sub ∞} increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,β-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC{sub ∞} for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,β-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,β-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration. - Highlights: • Absorption of α-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to α-thujone than mice. • α-Thujone brain

  6. NTP technical report on the toxicity studies of Castor Oil (CAS No. 8001-79-4) in F344/N Rats and B6C3F1 Mice (Dosed Feed Studies).

    Science.gov (United States)

    Irwin, R

    1992-03-01

    Castor oil is a natural oil derived from the seeds of the castor bean, Ricinus communis. It is comprised largely of triglycerides with a high ricinolin content. Toxicity studies with castor oil were performed by incorporating the material at concentrations as high as 10% in diets given to F344/N rats and B6C3F1 mice of both sexes for 13 weeks. Genetic toxicity studies also were performed and were negative for mutation induction in Salmonella typhimurium, for induction of sister chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells, and for induction of micronuclei in the peripheral blood erythrocytes of mice evaluated at the end of the 13-week studies. Exposure to castor oil at dietary concentrations as high as 10% in 13-week studies did not affect survival or body weight gains of rats or mice (10 per sex and dose). There were no biologically significant effects noted in hematologic analyses in rats. Mild increases in total bile acids and in serum alkaline phosphatase were noted at various times during the studies in rats receiving the higher dietary concentrations of castor oil. Liver weights were increased in male rats receiving the 10% dietary concentration and in male and female mice receiving diets containing 5% or 10% castor oil. However, there were no histopathologic lesions associated with these liver changes, nor were there any compound-related morphologic changes in any organ in rats or mice. No significant changes were noted in a screening for male reproductive endpoints, including sperm count and motility, and no changes were observed in the length of estrous cycles of rats or mice given diets containing castor oil. Thus, no significant adverse effects of castor oil administration were noted in these studies. Synonyms: Ricinus Oil, oil of Palma Christi, tangantangan oil, phorboyl, Neoloid.

  7. On-line analysis of middle latency auditory evoked potentials (MLAEP) for monitoring depth of anaesthesia in laboratory rats

    DEFF Research Database (Denmark)

    Jensen, E W; Nygaard, M; Henneberg, S W

    1998-01-01

    using neuromuscular blocking agents (NMBA). A number of studies suggest that the Middle Latency Auditory Evoked Potentials (MLAEP) contain information about the state of consciousness in humans. The purpose of this study was to examine whether the AEP could serve as an indicator of depth of anaesthesia...... and decreasing gradually to a level between 50 and 20 as the rat was anaesthetised. Nine rats were anaesthetised and included in the study. Four doses of Hypnorm vet. and Dormicum were given as a total, each with 5 minutes interval. Clinical signs of the level of anaesthesia were observed simultaneously...... with the AEP. The results showed that in four rats DAI decreased to a level below 30 while anaesthetised. In the remaining five rats the AEP was only decreased to a level below 45. The results indicated that a simple dosing regimen based on weight was unable to give the same depth of anaesthesia in individual...

  8. Detection of bacterial antigens and Alzheimer’s disease-like pathology in the central nervous system of BALB/c mice following intranasal infection with a laboratory isolate of Chlamydia pneumoniae

    Directory of Open Access Journals (Sweden)

    Christopher Scott Little

    2014-12-01

    Full Text Available Pathology consistent with that observed in Alzheimer’s disease (AD has previously been documented following intranasal infection of normal wild-type mice with Chlamydia pneumoniae (Cpn isolated from an AD brain (96-41. In the current study, BALB/c mice were intranasally infected with a laboratory strain of Cpn, AR-39, and brain and olfactory bulbs were obtained at 1-4 months post-infection (pi. Immunohistochemistry for amyloid beta or Cpn antigens was performed on sections from brains of infected or mock-infected mice. Chlamydia-specific immunolabeling was identified in olfactory bulb tissues and in cerebrum of AR-39 infected mice. The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months. Viable Cpn was recovered from olfactory bulbs of 3 of 3 experimentally infected mice at 1 and 3 months pi, and in 2 of 3 mice at 4 months pi. In contrast, in cortical tissues of infected mice at 1 and 4 months pi no viable organism was obtained. At 3 months pi, only 1 of 3 mice had a measurable burden of viable Cpn from the cortical tissues. Mock-infected mice (0 of 3 had no detectable Cpn in either olfactory bulbs or cortical tissues. These data indicate that the AR-39 isolate of Cpn establishes a limited infection predominantly in the olfactory bulbs of BALB/c mice. Although infection with the laboratory strain of Cpn promotes deposition of amyloid beta, this appears to resolve following reduction of the Cpn antigen burden over time. Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41. These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology.

  9. Detection of bacterial antigens and Alzheimer's disease-like pathology in the central nervous system of BALB/c mice following intranasal infection with a laboratory isolate of Chlamydia pneumoniae.

    Science.gov (United States)

    Little, Christopher S; Joyce, Timothy A; Hammond, Christine J; Matta, Hazem; Cahn, David; Appelt, Denah M; Balin, Brian J

    2014-01-01

    Pathology consistent with that observed in Alzheimer's disease (AD) has previously been documented following intranasal infection of normal wild-type mice with Chlamydia pneumoniae (Cpn) isolated from an AD brain (96-41). In the current study, BALB/c mice were intranasally infected with a laboratory strain of Cpn, AR-39, and brain and olfactory bulbs were obtained at 1-4 months post-infection (pi). Immunohistochemistry for amyloid beta or Cpn antigens was performed on sections from brains of infected or mock-infected mice. Chlamydia-specific immunolabeling was identified in olfactory bulb tissues and in cerebrum of AR-39 infected mice. The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months. Viable Cpn was recovered from olfactory bulbs of 3 of 3 experimentally infected mice at 1 and 3 months pi, and in 2 of 3 mice at 4 months pi. In contrast, in cortical tissues of infected mice at 1 and 4 months pi no viable organism was obtained. At 3 months pi, only 1 of 3 mice had a measurable burden of viable Cpn from the cortical tissues. Mock-infected mice (0 of 3) had no detectable Cpn in either olfactory bulbs or cortical tissues. These data indicate that the AR-39 isolate of Cpn establishes a limited infection predominantly in the olfactory bulbs of BALB/c mice. Although infection with the laboratory strain of Cpn promotes deposition of amyloid beta, this appears to resolve following reduction of the Cpn antigen burden over time. Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41. These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology.

  10. Effect of conjugated linoleic acid (CLA) on lipid profile and liver histology in laboratory rats fed high-fructose diet.

    Science.gov (United States)

    Kostogrys, Renata B; Pisulewski, Paweł M

    2010-11-01

    The objective of the study was to assess the effect of CLA on serum lipid profile, plasma malondialdehyde and liver histology in Wistar rats fed high-fructose diet. Eighteen rats were randomly assigned to three experimental groups and fed for the next 21 days. The experimental diets were: I, Control; II, Fructose (63.2% of fructose); and III, CLA+Fructose (1% CLA and 63.2% of fructose). The experimental treatments had no effect on body weight of the rats. The LDL+VLDL cholesterol, TG and liver weight were significantly increased in animals fed Fructose. MDA concentrations were significantly increased in rats fed Fructose diet but CLA+Fructose diet had no effect on this marker. In the same line, the histological examination of the livers showed a series of morphological alterations, notably hepatic steatosis in animals fed high-fructose diet. No signs of the steatosis in rats fed CLA+Fructose diet were observed. In conclusion, CLA in high-fructose diet, decreases serum LDL+VLDL and TG and plasma MDA concentrations as well as liver weight and liver cholesterol, thus opposing the effects of high-fructose diet and showing a potential antiatherogenic effect. Similarly, dietary CLA fed at 1% level (w/w) in high-fructose diet, prevented steatosis observed histologically in livers of rats fed high-fructose diets.

  11. Isolation of Trichophyton mentogrophytes var mentogrophytes from naturally infected laboratory albino rats: experimental infection and treatment in rabbits

    Directory of Open Access Journals (Sweden)

    N. A. Issa

    2009-01-01

    Full Text Available The present study demonstrated for the first time the occurrence of dermatophytosis in naturally infected rats and from asymptomatic and from breeding boxes of white rats kept in animal housing of college of Veterinary Medicine, University of Dohuk, Iraq. The prevalence rate of infection was (28%, clinically infected rats characterized by appearance of scaly ovoid type lesions with crusty edge and patch of hair loss mostly seen on the back, neck and face of the infected rats, itching was reported in some rats. Only one species of the trichophyton, T. mentogrophytes var mentogrophytes was isolated with growth rate (85.71% of samples collected from clinically infected rats, and (28.57% from asymptomatic and from breeding cages, the growth was observed within the 21 days at 25ºC on Sabouraud's Dextrose Agar. Lacto phenol cotton blue staining slides of T. mentogrophytes var mentogrophytes revealed both microconidia and macroconidia. Microconidia found in numerous numbers often in dense cluster which were hyaline, smooth walled and predominantly spherical to sub spherical in shape, varying numbers of chlamydoconidia. Spiral hyphae and smooth, thin walled clavate shaped multicelled macroconidia were also present. The study also dealt with experimental infection in rabbits with T. mentogrophytes var mentogrophytes and treated by two drugs, natural herbal preparation of acidic pomegranate (Punica granatum fruit and synthetic nystatine ointment. The complete recovery of lesions was recorded after 14 days and 21 days of topical application of a pomegranate and nystatine ointment for 5 successive days respectively.

  12. Dose-independent pharmacokinetics of a new peroxisome proliferator-activated receptor-γ agonist, KR-62980, in Sprague-Dawley rats and ICR mice.

    Science.gov (United States)

    Park, Jong-Shik; Kim, Min-Sun; Song, Jin Sook; Choi, Sung Heum; Lee, Byung Hoi; Woo, Jaechun; Ahn, Jin Hee; Bae, Myung Ae; Ahn, Sung-Hoon

    2011-12-01

    The pharmacokinetics of a novel peroxisome proliferator-activated receptor-γ agonist, KR-62980, were characterized in vitro with respect to liver metabolic stability, cell permeability, and plasma protein binding and in vivo using Sprague-Dawley rats and ICR mice. The metabolic half-life of 0.1-10 μM KR-62980 was 11.5-15.2 min in rat liver microsomes and 25.8-28.8 min in human liver microsomes. KR-62980 showed high permeability across MDCK cell monolayers, with apparent permeability coefficients of 20.4 × 10(-6) to 30.8 × 10(-6) cm/sec. The plasma protein binding rate of KR-62980 was 89.4%, and most was bound to serum albumin. After intravenous administration of KR-62980 (2 mg/kg), the systemic clearance was 2.50 L/h/kg, and the volume of distribution at steady-state was 9.16 L/kg. The bioavailability after oral administration was approximately 60.9%. The dose-normalized AUC values were 0.50 ± 0.09, 0.41 ± 0.20, and 0.62 ± 0.08 h · μg/mL after oral administration of 2, 5, and 10 mg/kg KR-62980, respectively, showing no dose-dependency. The in vivo pharmacokinetic parameters in ICR mice were also dose independent. These data suggest that KR-62980 is not significantly dose dependent in rats or mice, although it may disappear rapidly from the systemic circulation via metabolism in the liver.

  13. o-p′-DDT-mediated uterotrophy and gene expression in immature C57BL/6 mice and Sprague–Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Kwekel, Joshua C.; Forgacs, Agnes L. [Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI (United States); Center for Integrative Toxicology, Michigan State University, East Lansing, MI (United States); Williams, Kurt J. [Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI (United States); Zacharewski, Timothy R., E-mail: tzachare@msu.edu [Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI (United States); Center for Integrative Toxicology, Michigan State University, East Lansing, MI (United States)

    2013-12-15

    1,1,1-Trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p′-DDT) is an organochlorine pesticide and endocrine disruptor known to activate the estrogen receptor. Comprehensive ligand- and species-comparative dose- and time-dependent studies were conducted to systematically assess the uterine physiological, morphological and gene expression responses elicited by o,p′-DDT and ethynyl estradiol (EE) in immature ovariectomized C57BL/6 mice and Sprague–Dawley rats. Custom cDNA microarrays were used to identify conserved and divergent differential gene expression responses. A total of 1256 genes were differentially expressed by both ligands in both species, 559 of which exhibited similar temporal expression profiles suggesting that o,p′-DDT elicits estrogenic effects at high doses when compared to EE. However, 51 genes exhibited species-specific uterine expression elicited by o,p′-DDT. For example, carbonic anhydrase 2 exhibited species- and ligand-divergent expression as confirmed by quantitative real-time PCR. The identification of comparable temporal phenotypic responses linked to gene expression demonstrates that systematic comparative gene expression assessments are valuable for elucidating conserved and divergent estrogen signaling mechanisms in rodent uterotrophy. - Highlights: • o,p′-DDT and enthynyl estradiol (EE) both elicit uterotrophy in mice and rats. • o,p′-DDT and EE have different kinetics in uterine wet weight induction. • o,p′-DDT elicited stromal hypertrophy in rats but myometrial hypertrophy in mice. • 1256 genes were differentially expressed by both ligands in both species. • Only 51 genes had species-specific uterine expression.

  14. Effects of (+) SKF 10,047, a sigma-1 receptor agonist, on anxiety,tested in two laboratory models in mice.

    Science.gov (United States)

    Navarro, José Francisco; Beltrán, David; Cavas, María

    2012-01-01

    Recently, sigma-1 receptor modulators have been considered drugs with an interesting therapeutic potential for the treatment of anxiety. However, there is no clear information in preclinical studies about the possible effects of sigma-1 ligands on anxiety in experimental animal models. Therefore, the present study examined the effects of (+)SKF 10,047 (2-8 mg/kg, ip), a sigma-1 agonist, on anxiety, tested in two classical laboratory models (social interaction test and elevated plus maze). (+)SKF 10,047 (8 mg/kg) produced a significant decrease of social investigation in the "social interaction test", whereas in the "elevated plus maze", the drug (4 and 8 mg/kg) provoked a significant reduction in the number of entries into open arms, as well as in the time spent in this area, as compared with the control group, without affecting motor activity. Overall, these findings indicate that (+)SKF 10,047 exhibits an anxiogenic-like profile in mice. It is suggested that anxiogenic effects of this sigma-1 ligand could be related to its potent ability to modulate diverse neurotransmitter systems involved in anxiety regulation.

  15. In vivo mutagenicity studies in rats mice and Chinese hamsters fed irradiated foodstuffs - chicken, fish, dates, pulses, mangoes and cocoa beans

    Energy Technology Data Exchange (ETDEWEB)

    Renner, H.W.

    1982-11-01

    Three in vivo genetic toxicity tests were performed in rats, mice and Chinese hamsters to detect possible mutagenic effects of irradiated chicken, dried dates, fish, cocoa beans, pulses and mangoes. The tests employed were the micronucleus test and sister-chromatid exchange (SCE) test for irradiated and unirradiated samples of all foodstuffs listed, and the spermatogonia test, (including SCE technique) in mice for irradiated and unirradiated chicken, fish and dates only. In the case of cocoa beans, the mutagenicity tests were performed on an additional test group fed beans fumigated with ethylene oxide. The different mammalian species used for the various experiments are given below. None of the tests provided any evidence of mutagenicity induced by irradiation in any of the foodstuffs studied. Moreover, these tests are currently considered to be the most sensitive in vivo mutagenicity tests in mammals.

  16. Ethylene glycol monomethyl ether (EGME) and propylene glycol monomethyl ether (PGME): inhalation fertility and teratogenicity studies in rats, mice and rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Hanley, T.R. Jr.; Young, J.T.; John, J.A.; Rao, K.S.

    1984-08-01

    A combined dominant lethal-fertility study was conducted in which male and female Sprague-Dawley (CD) rats were exposed to 0, 30, 100, or 300 ppm of ethylene glycol monomethyl ether (EGME) vapor for 6 hr/day, 5 days/week for 13 weeks and then mated to untreated counterparts. Among males, fertility was completely suppressed after exposure to 300 ppm. A partial restoration of reproductive function was evident following 13 weeks of recovery. No treatment-related reproductive effects were observed among males exposed subchronically to 100 ppm, or among females exposed to 300 ppm or below of EGME. Studies to assess the effects of inhaled EGME on embryonal and fetal development were also conducted in Fischer 344 rats. CF-1 mice, and New Zealand White rabbits. Rats and rabbits were exposed to concentrations of 0, 3, 10, or 50 ppm for 6 hr/day on days 6-15 or 6-18 of gestation, respectively. Exposure of rabbits to 50 ppm resulted in significant teratologic effects, an increased resorption rate, and decreased fetal body weight. Slight fetotoxicity in the form of skeletal variations were observed among rats exposed to 50 ppm. Separate groups of pregnant rats and rabbits were exposed to 0, 500, 1500, or 3000 ppm of propylene glycol monomethyl ether (PGME) during organogenesis. Mild CNS depression was observed among rats and rabbits exposed to 3000 ppm of PGME. Fetal examination revealed no embryotoxic or teratogenic effects among either species. Thus, it was concluded that PGME was not teratogenic at exposure levels up to 3000 ppm.

  17. Carboxyl ester lipase overexpression in rat hepatoma cells and CEL deficiency in mice have no impact on hepatic uptake or metabolism of chylomicron-retinyl ester.

    Science.gov (United States)

    van Bennekum, A M; Li, L; Piantedosi, R; Shamir, R; Vogel, S; Fisher, E A; Blaner, W S; Harrison, E H

    1999-03-30

    To study the role of carboxyl ester lipase (CEL) in hepatic retinoid (vitamin A) metabolism, we investigated uptake and hydrolysis of chylomicron (CM)-retinyl esters (RE) by rat hepatoma (McArdle-RH7777) cells stably transfected with a rat CEL cDNA. We also studied tissue uptake of CM-RE in CEL-deficient mice generated by targeted disruption of the CEL gene. CEL-transfected cells secreted active enzyme into the medium. However, both control and CEL-transfected cells accumulated exogenously added CM-RE or CM remnant (CMR)-derived RE in equal amounts. Serum clearance of intravenously injected CM-RE and cholesteryl ester were not different between wild-type and CEL-deficient mice. Also, the uptake of the two compounds by the liver and other tissues did not differ. These data indicate that the lack of CEL expression does not affect the uptake of dietary CM-RE by the liver or other tissues. Moreover, the percentage of retinol formed in the liver after CM-RE uptake, the levels of retinol and retinol-binding protein in serum, and retinoid levels in various tissues did not differ, indicating that CEL deficiency does not affect hepatic retinoid metabolism and retinoid distribution throughout the body. Surprisingly, in both pancreas and liver of wild-type, heterozygous, and homozygous CEL-deficient mice, the levels of bile salt-dependent retinyl ester hydrolase (REH) activity were similar. This indicates that in the mouse pancreas and liver an REH enzyme activity, active in the presence of bile salt and distinct from CEL, is present, compatible with the results from our accompanying paper that the intestinal processing and absorption of RE were unimpaired in CEL-deficient mice.

  18. Biological effects of high-strength electric fields on small laboratory animals. Interim report, March 1, 1978-September 30, 1979

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, R.D.; Anderson, L.E.; Kaune, W.T.

    1979-12-01

    Progress is described on a project assessing the biological effects of 60-Hz electric fields on small laboratory animals (rats and mice). The report includes sections on hematology and seram chemistry, immunology, pathology, metabolism, bone growth, endocrinology, cardiovascular function, neurophysiology, growth and development, and animal behavior. (ACR)

  19. Induction of an antigen specific gut inflammatory reaction in mice and rats: a model for human Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Gerlinde Agate Platais Brasil Teixeira

    2009-06-01

    Full Text Available Food allergy is an adverse reaction that occurs in susceptible people when they eat sensitizing foods and is one of the causes of Inflammatory Bowel Disease (IBD. The effort to understand the induction process of these diseases is important as IBD is increasing worldwide, including in Brazil. The aim of this study was to develop an experimental antigen specific inflammatory process of the gut of mice and rats, using peanut seeds. Animals were immunized with peanut protein extract before their exposure to the in natura peanut seeds. Results showed that systemic immunization with peanut protein extracts rendered significantly higher antibody titers than control groups and that immunized animals submitted to a challenge diet containing peanuts presented time dependent alterations of the gut similar to celiac disease. In conclusion, results suggested that this experimental model was a convenient tool to study the evolution of alterations in chronic antigen specific gut inflammatory process.A alergia alimentar consiste em uma reação adversa que ocorre em pessoas susceptíveis quando ingerem alimentos sensibilizantes, sendo uma das causas das Doenças Inflamatórias Intestinais (IBD. O objetivo deste estudo foi desenvolver um protocolo experimental de indução de um processo inflamatório intestinal antígeno-específico em camundongos e ratos. Foi escolhida para a indução deste processo a semente de amendoim. Os animais foram imunizados com o extrato protéico previamente à exposição com a semente in natura. Nossos resultados mostram que a imunização sistêmica com extratos protéicos de amendoim ocasiona títulos significativamente maiores de anticorpos quando comparado ao grupo controle e que os animais imunizados submetidos ao desafio com a dieta contendo exclusivamente amendoim apresentam alterações intestinais tempo-dependente similares àquelas observadas na doença celíaca. Os resultados obtidos sugerem que este modelo

  20. NTP technical report on the toxicity studies of Cupric Sulfate (CAS No. 7758-99-8) Administered in Drinking Water and Feed to F344/N Rats and B6C3F1 Mice.

    Science.gov (United States)

    Hebert, Charles

    1993-07-01

    Cupric sulfate is an inorganic salt which is widely used in industry, agriculture, and veterinary medicine. Its applications include use as an algicide in potable waters and as a feed additive and therapeutic agent in swine, sheep, and cattle. Because copper salts are found in human water supplies, toxicity studies of cupric sulfate pentahydrate were conducted in male and female F344/N rats and B6C3F1 mice by the drinking water (2-week studies only) and dosed feed routes (2-week and 13-week studies). Animals were evaluated for hematology, clinical chemistry, urinalysis, reproductive toxicity, tissue metal accumulation, and histopathology. In the 2-week drinking water studies, groups of five rats and five mice per sex received cupric sulfate at concentrations of 300 to 30,000 ppm for 15 days. One female rat, one male mouse, and three female mice in the 3000 ppm groups and all rats and mice in the 10,000 and 30,000 ppm groups died before the end of the studies. The remaining mice and rats in the 3000 ppm groups gained little or lost weight. Water consumption in the three highest dose groups of both species was reduced by more than 65%. Clinical signs observed in these groups were typical of those seen in moribund animals and were attributed to dehydration. The only gross or microscopic change specifically related to cupric sulfate toxicity was an increase in the size and number of cytoplasmic protein droplets in the epithelium of the renal proximal convoluted tubule in male rats from the 300 and 1000-ppm groups. In the 2-week feed studies, groups of five rats and five mice per sex were fed diets containing 1000 to 16,000 ppm cupric sulfate. No chemical-related deaths occurred in any dose group. Compared to the controls, rats and mice in the two highest dose groups had reduced body weight gains which were attributed to decreased feed consumption. Hyperplasia with hyperkeratosis of the squamous epithelium on the limiting ridge of the forestomach was seen in rats and

  1. Effect of dietary fructose on portal and systemic serum fructose levels in rats and in KHK−/− and GLUT5−/− mice

    Science.gov (United States)

    Patel, Chirag; Sugimoto, Keiichiro; Douard, Veronique; Shah, Ami; Inui, Hiroshi; Yamanouchi, Toshikazu

    2015-01-01

    Elevated blood fructose concentrations constitute the basis for organ dysfunction in fructose-induced metabolic syndrome. We hypothesized that diet-induced changes in blood fructose concentrations are regulated by ketohexokinase (KHK) and the fructose transporter GLUT5. Portal and systemic fructose concentrations determined by HPLC in wild-type mice fed for 7 days 0% free fructose were fructose levels, however, increased markedly in those fed isocaloric 20% fructose, causing significant hyperglycemia. Deletion of KHK prevented fructose-induced hyperglycemia, but caused dramatic hyperfructosemia (>1 mM) with reversed portal to systemic gradients. Systemic fructose in wild-type and KHK−/− mice changed by 0.34 and 1.8 mM, respectively, for every millimolar increase in portal fructose concentration. Systemic glucose varied strongly with systemic, but not portal, fructose levels in wild-type, and was independent of systemic and portal fructose in KHK−/−, mice. With ad libitum feeding for 12 wk, fructose-induced hyperglycemia in wild-type, but not hyperfructosemia in KHK−/− mice, increased HbA1c concentrations. Increasing dietary fructose to 40% intensified the hyperfructosemia of KHK−/− and the fructose-induced hyperglycemia of wild-type mice. Fructose perfusion or feeding in rats also caused duration- and dose-dependent hyperfructosemia and hyperglycemia. Significant levels of blood fructose are maintained independent of dietary fructose, KHK, and GLUT5, probably by endogenous synthesis of fructose. KHK prevents hyperfructosemia and fructose-induced hyperglycemia that would markedly increase HbA1c levels. These findings explain the hyperfructosemia of human hereditary fructosuria as well as the hyperglycemia of fructose-induced metabolic syndrome. PMID:26316589

  2. The influence of combinations of oximes on the reactivating and therapeutic efficacy of antidotal treatment of tabun poisoning in rats and mice.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana Zdarova; Pavlikova, Ruzena; Misik, Jan; Caisberger, Filip; Bajgar, Jiri

    2010-03-01

    The influence of the combination of oximes on the reactivating and therapeutic efficacy of antidotal treament of acute tabun poisoning was evaluated. The ability of two combinations of oximes (HI-6 + obidoxime and HI-6 + K203) to reactivate tabun-inhibited acetylcholinesterase and reduce acute toxicity of tabun was compared with the reactivating and therapeutic efficacy of antidotal treatment involving single oxime (HI-6, obidoxime, K203) using in vivo methods. Studies determining percentage of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in poisoned rats showed that the reactivating efficacy of both combinations of oximes is higher than the reactivating efficacy of the most effective individual oxime in blood and diaphragm and comparable with the reactivating effects of the most effective individual oxime in brain. Moreover, both combinations of oximes were found to be slightly more efficacious in the reduction of acute lethal toxic effects in tabun-poisoned mice than the antidotal treatment involving individual oxime. A comparison of reactivating and therapeutic efficacy of individual oximes showed that the newly developed oxime K203 is slightly more effective than commonly used obidoxime and both of them are markedly more effective than the oxime HI-6. Based on the obtained data, we can conclude that the antidotal treatment involving chosen combinations of oximes brings beneficial effects for the potency of antidotal treatment to reactivate tabun-inhibited acetylcholinesterase in rats and to reduce acute toxicity of tabun in mice.

  3. Cross-Sectional Study of Leptospira Seroprevalence in Humans, Rats, Mice, and Dogs in a Main Tropical Sea-Port City

    Science.gov (United States)

    Romero-Vivas, Claudia M. E.; Cuello-Pérez, Margarett; Agudelo-Flórez, Piedad; Thiry, Dorothy; Levett, Paul N.; Falconar, Andrew K. I.

    2013-01-01

    Samples were collected from 128 symptomatic humans, 83 dogs, 49 mice, and 20 rats (Rattus rattus: 16; Rattus norvegicus: 4) in neighborhoods where human leptospirosis have been reported within the principal sea-port city of Colombia. Seroprevalences were assessed against 19 pathogenic, 1 intermediate pathogenic, and 1 saprophytic Leptospira serogroups. Pathogenic Leptospira were confirmed using conventional Leptospira-specific polymerase chain-reaction and pulsed-field gel electrophoresis analysis was used for serovar identification. Seroprevalences of 20.4%, 12.5%, 25.0%, 22.9%, and 12.4% were obtained against one to seven different serogroups in mice, R. rattus, R. norvegicus, dogs, and humans, respectively. The DNA was confirmed to be from pathogenic Leptospira by detecting the lipL32 gene in 12.5%, 3.7%, and 0.03% of the R. rattus, dog, and human samples, respectively. The first genetically typed Colombian isolate was obtained from a rat and identified as Leptospira interrogans serovar Icterohaemorrhagiae/Copenhageni. PMID:23149584

  4. Increased Radioresistance to Lethal Doses of Gamma Rays in Mice and Rats after Exposure to Microwave Radiation Emitted by a GSM Mobile Phone Simulator.

    Science.gov (United States)

    Mortazavi, Smj; Mosleh-Shirazi, Ma; Tavassoli, Ar; Taheri, M; Mehdizadeh, Ar; Namazi, Sas; Jamali, A; Ghalandari, R; Bonyadi, S; Haghani, M; Shafie, M

    2013-01-01

    The aim of this study was to investigate the effect of pre-irradiation with microwaves on the induction of radioadaptive response. In the 1(st) phase of the study, 110 male mice were divided into 8 groups. The animals in these groups were exposed/sham-exposed to microwave, low dose rate gamma or both for 5 days. On day six, the animals were exposed to a lethal dose (LD). In the 2(nd) phase, 30 male rats were divided into 2 groups of 15 animals. The 1(st) group received microwave exposure. The 2(nd) group (controls) received the same LD but there was no treatment before the LD. On day 5, all animals were whole-body irradiated with the LD. Statistically significant differences between the survival rate of the mice only exposed to lethal dose of gamma radiation before irradiation with a lethal dose of gamma radiation with those of the animals pre-exposed to either microwave (p=0.02), low dose rate gamma (p=0.001) or both of these physical adapting doses (p=0.003) were observed. Likewise, a statistically significant difference between survival rates of the rats in control and test groups was observed. Altogether, these experiments showed that exposure to microwave radiation may induce a significant survival adaptive response.

  5. Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice.

    Science.gov (United States)

    Detrait, Eric R; Carr, Greg V; Weinberger, Daniel R; Lamberty, Yves

    2016-08-01

    The critical involvement of dopamine in cognitive processes has been well established, suggesting that therapies targeting dopamine metabolism may alleviate cognitive dysfunction. Catechol-O-methyl transferase (COMT) is a catecholamine-degrading enzyme, the substrates of which include dopamine, epinephrine, and norepinephrine. The present work illustrates the potential therapeutic efficacy of COMT inhibition in alleviating cognitive impairment. A brain-penetrant COMT inhibitor, tolcapone, was tested in normal and phencyclidine-treated rats and COMT-Val transgenic mice. In a novel object recognition procedure, tolcapone counteracted a 24-h-dependent forgetting of a familiar object as well as phencyclidine-induced recognition deficits in the rats at doses ranging from 7.5 to 30 mg/kg. In contrast, entacapone, a COMT inhibitor that does not readily cross the blood-brain barrier, failed to show efficacy at doses up to 30 mg/kg. Tolcapone at a dose of 30 mg/kg also improved novel object recognition performance in transgenic mice, which showed clear recognition deficits. Complementing earlier studies, our results indicate that central inhibition of COMT positively impacts recognition memory processes and might constitute an appealing treatment for cognitive dysfunction related to neuropsychiatric disorders.

  6. Tissues and hair residues and histopathology in wild rats (Rattus rattus L.) and Algerian mice (Mus spretus Lataste) from an abandoned mine area (Southeast Portugal)

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, R. [Departamento de Biologia da Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal) and Instituto Piaget, Campus Academico de Viseu, Estrada do Alto do Gaio, Lordosa, 3515-776 Viseu (Portugal)]. E-mail: ruthp@bio.ua.pt; Pereira, M.L. [Departamento de Biologia da Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Ribeiro, R. [Instituto do Ambiente e Vida, Departamento de Zoologia da Universidade de Coimbra, Largo Marques de Pombal, 3004-517 Coimbra (Portugal); Goncalves, F. [Departamento de Biologia da Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal)

    2006-02-15

    Data gathered in this study suggested the exposure of rats and Algerian mice, living in an abandoned mining area, to a mixture of heavy metals. Although similar histopathological features were recorded in the liver and spleen of both species, the Algerian mouse has proved to be the strongest bioaccumulator species. Hair was considered to be a good biological material to monitor environmental contamination of Cr in rats. Significant positive associations were found between the levels of this element in hair/kidney (r = 0.826, n = 9, p < 0.01) and hair/liver (r = 0.697, n = 9, p = 0.037). Although no association was found between the levels of As recorded in the hair and in the organs, the levels of this element recorded in the hair, of both species, were significantly higher in animals captured in the mining area, which met the data from the organs analysed. Nevertheless, more studies will be needed to reduce uncertainty about cause-effect relationships. - The bioaccumulation of As and Cd and signs of renal histopathological injury proved the value of Algerian mice as a bioindicator species in the risk assessment of contaminated sites.

  7. Continuous inhibition of 11β-hydroxysteroid dehydrogenase type I in adipose tissue leads to tachyphylaxis in humans and rats but not in mice.

    Science.gov (United States)

    Morentin Gutierrez, P; Gyte, A; deSchoolmeester, J; Ceuppens, P; Swales, J; Stacey, C; Eriksson, J W; Sjöstrand, M; Nilsson, C; Leighton, B

    2015-10-01

    11β-hydroxysteroid dehydrogenase type I (11β-HSD1), a target for Type 2 diabetes mellitus, converts inactive glucocorticoids into bioactive forms, increasing tissue concentrations. We have compared the pharmacokinetic-pharmacodynamic (PK/PD) relationship of target inhibition after acute and repeat administration of inhibitors of 11β-HSD1 activity in human, rat and mouse adipose tissue (AT). Studies included abdominally obese human volunteers, rats and mice. Two specific 11β-HSD1 inhibitors (AZD8329 and COMPOUND-20) were administered as single oral doses or repeat daily doses for 7-9 days. 11β-HSD1 activity in AT was measured ex vivo by conversion of (3) H-cortisone to (3) H-cortisol. In human and rat AT, inhibition of 11β-HSD1 activity was lost after repeat dosing of AZD8329, compared with acute administration. Similarly, in rat AT, there was loss of inhibition of 11β-HSD1 activity after repeat dosing with COMPOUND-20 with continuous drug cover, but effects were substantially reduced if a 'drug holiday' period was maintained daily. Inhibition of 11β-HSD1 activity was not lost in mouse AT after continuous cover with COMPOUND-20 for 7 days. Human and rat AT, but not mouse AT, exhibited tachyphylaxis for inhibition of 11β-HSD1 activity after repeat dosing. Translation of observed efficacy in murine disease models to human for 11β-HSD1 inhibitors may be misleading. Investigators of the effects of 11β-HSD1 inhibitors should confirm that desired levels of enzyme inhibition in AT can be maintained over time after repeat dosing and not rely on results following a single dose. © 2015 The British Pharmacological Society.

  8. Gene targeting technologies in rats: zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats.

    OpenAIRE

    Mashimo, Tomoji

    2013-01-01

    The laboratory rat has been widely used as an animal model in biomedical science for more than 150 years. Applying zinc-finger nucleases or transcription activator-like effector nucleases to rat embryos via microinjection is an efficient genome editing tool for generating targeted knockout rats. Recently, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated endonucleases have been used as an effective tool for precise and multiplex genome editing in mice and ra...

  9. Fecal dehydroepiandrosterone (DHEA) immunoreactivity as a noninvasive index of circulating DHEA activity in young male laboratory rats.

    Science.gov (United States)

    Bardi, Massimo; Hampton, Joseph E; Lambert, Kelly G

    2010-12-01

    Evidence suggests that dehydroepiandrosterone (DHEA) plays a key role in stress and coping responses. Fecal sampling permits assessment of hormone-behavior interactions reliably and effectively, but no previous study has compared circadian- or stress-dependent alterations between serum DHEA and its fecal metabolites. In the current study, young (28 d of age) male rats were assigned to either an experimental (n = 6) or control (n = 6) group. Rats in the experimental group were exposed to a forced swim test to assess their behavioral and physiologic response to an environmental stressor; blood samples were drawn before the test (baseline), immediately after the test, and at 2 later time points. Only fecal samples were collected from control animals. Fecal DHEA and corticosterone metabolites were monitored in all animals for 24 h. DHEA metabolites in control rats exhibited significant diurnal variation, showing a similar temporal pattern as that of corticosterone metabolites. In addition, fecal and serum DHEA levels were highly correlated. Significant peaks in both DHEA and corticosterone metabolite levels were detected. These data suggest that measures of fecal DHEA can provide a complementary, noninvasive method of assessing adrenal gland function in rats.

  10. Acute and sub-chronic toxicity studies of the aqueous extract from leaves of Cistus ladaniferus L. in mice and rats.

    Science.gov (United States)

    El Kabbaoui, Mohamed; Chda, Alae; El-Akhal, Jamila; Azdad, Ouarda; Mejrhit, Najlae; Aarab, Lotfi; Bencheikh, Rachid; Tazi, Abdelali

    2017-09-14

    Cistus ladaniferus L. (C.ladaniferus) (Cistaceae) is an aromatic shrub native to the Mediterranean region. The leaves are widely used in traditional medicine throughout Morocco for the treatment of various diseases including, diabetes, diarrhea, inflammation, and skin ailments. However, to the best of our knowledge, no systematic study concerning its toxicity profile has been reported. The study carried out evaluates the potential toxicity of the aqueous extract from leaves of the C.ladaniferus (CL extract) shrub, through the method of acute and sub-chronic oral administration in mice and rats. During the acute toxicity study, male and female mice were orally administrated with CL aqueous extract at single doses of 500, 1000, 2000, 3000 and 5000mg/kg (n = 5/group/sex). Abnormal behavior, toxic symptoms, weight, and death were observed for 14 consecutive days to assess the acute toxicity. During the sub-chronic toxicity study, the aqueous extract was administered orally at doses of 500, 700 and 1000mg/kg (n = 6/group) daily to Wistar rats of both sexes for 90 days. The general behavior of the rats was observed daily, and their body weight was recorded weekly. A urinalysis, biochemical analysis, hematological analysis, macroscopic examination and histopathological examination of several organs were conducted at the end of the treatment period. During the acute toxicity test, when mice were administered doses of 3000 and 5000mg/kg, the CL extract produced a 10-30% mortality rate, respectively, and induced signs of toxicity. However, no mortality or adverse effect was noted at the doses of 1000 and 2000mg/kg. The median lethal dose (LD50) of the extract was estimated to be more than 5000mg/kg. In the subchronic study, the CL extract induced no mortality or treatment-related adverse effects with regard to body weight, general behavior, relative organ weights, urine, hematological, and biochemical parameters. Histopathological examination of vital organs showed normal

  11. Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice

    DEFF Research Database (Denmark)

    Hartmann, B; Thulesen, J; Kissow, Hannelouise;

    2000-01-01

    s.c. injection of GLP-2 with or without the specific DPP-IV inhibitor, valine-pyrrolidide (VP). Rats were injected s.c. with 40 microg GLP-2 or 40 microg GLP-2+15 mg VP. Plasma was collected at different time points and analyzed, by RIA, for intact GLP-2. Rats were treated for 14 days with: saline...

  12. Internal organs morphology and tumors in laboratory rats with transplanted liver cancer PC-1 by oral intoduction containing extract of Gratiola (Gratiola Officinalis L.) and Anthocyan Maize (Zea Mays L.)

    OpenAIRE

    2013-01-01

    The purpose of the work is to study antitumor activity of flavonoid-containing extracts of anthocyan maize and gratiola in experiments in vivo and to estimate their effects on the internal organs, tumors and blood of rats with transplanted liver cancer PC-1. Materials and methods: Effect of extracts of anthocyan maize and gratiola has been studied in experiments in vivo in 30 laboratory rats with transplanted liver cancer PC-1 using morphological and biochemical methods. Results: It has been ...

  13. About Rats and Mice

    Science.gov (United States)

    Some rodent species are pests. Others are helpful. Pests can damage habitats, food supplies, and spread disease through bites or contamination. Prevent or reduce infestations by eliminating conditions that provide access to food, water, and shelter.

  14. Calculation of a First-In-Man Dose of 7-O-Succinyl Macrolactin A Based on Allometric Scaling of Data from Mice, Rats, and Dogs.

    Science.gov (United States)

    Noh, Keumhan; Kang, Wonku

    2017-03-10

    7-O-succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anticancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.

  15. Comparison of the effects of hexavalent chromium in the alimentary canal of F344 rats and B6C3F1 mice following exposure in drinking water: implications for carcinogenic modes of action.

    Science.gov (United States)

    Thompson, Chad M; Proctor, Deborah M; Suh, Mina; Haws, Laurie C; Hébert, Charles D; Mann, Jill F; Shertzer, Howard G; Hixon, J Gregory; Harris, Mark A

    2012-01-01

    Exposure to high concentrations of hexavalent chromium (Cr[VI]) in drinking water is reported to induce oral mucosa tumors in F344 rats and intestinal tumors in B6C3F1 mice. To investigate the modes of action underlying these tumors, 90-day drinking water studies (with interim necropsy at day 8) were conducted with concentrations of 0.1-182 mg/l Cr(VI), administered as 0.3-520 mg/l sodium dichromate dihydrate. Blood and tissue samples were analyzed for chromium content, oxidative stress, iron levels, and gross and microscopic lesions. Results for the F344 rats are described herein and compared with results from B6C3F1 mice published previously. After 90 days of exposure, total chromium concentrations in the rat and mouse oral mucosae were comparable, yet significant dose-dependent decreases in the reduced-to-oxidized glutathione ratio (GSH/GSSG) were observed only in rats. In the duodenum, changes in GSH/GSSG were only observed in mice. Levels of 8-hydroxydeoxyguanosine were not increased in the oral or duodenal mucosae of either species. Glutathione levels were increased in the duodenum but decreased in the jejunum of both species, indicating potential differential responses in the intestinal segments. Histiocytic infiltration was observed in the duodenum of both species, yet duodenal cytokines were repressed in mice but increased in rats. Serum and bone marrow iron levels were more decreased in rats than mice. Collectively, these data suggest that Cr(VI)-induced carcinogenesis in the rodent alimentary canal involves oxidative stress; however, differences in histopathology, cytokines, and iron status suggest potential contributions from other factors as well.

  16. Evaluation of Nutritional Quality of Dried Cashew Nut Testa Using Laboratory Rat as a Model for Pigs

    OpenAIRE

    Armstrong Donkoh; Victoria Attoh-Kotoku; Reginald Osei Kwame; Richard Gascar

    2012-01-01

    Dried cashew nut testa (DCNT) was characterized with respect to proximate, mineral, and energy profile. The crude protein, crude fibre, and fat and ash contents were, in g kg−1 DM, 190.0, 103.0, 20.1, and 20.2, respectively, with metabolizable energy of 7.12 MJ kg−1 DM. In a feeding trial, isoproteic diets containing DCNT (O, 50, 100, and 150 g kg−1) were fed ad libitum to 4 groups of Sprague-Dawley male rats (110 g body weight, = 2 0 ) for a period of 4 weeks. The rats, used as model for p...

  17. Toxicology and carcinogenesis studies of 1-bromopropane (CAS No. 106-94-5) in F344/N rats and B6C3F1 mice (inhalation studies).

    Science.gov (United States)

    2011-08-01

    In the early to mid 1990s, 1-bromopropane was used primarily as an intermediate in the production of pesticides, quaternary ammonium compounds, flavors and fragrances, pharmaceuticals, and other chemicals in well-controlled, closed processes. In the mid to late 1990s, it was introduced as a less toxic replacement for methylene chloride in emissive applications such as vapor and immersion degreasing operations and critical cleaning of electronics and metals. 1-Bromopropane was also introduced as a nonflammable, nontoxic, fast-drying, and inexpensive solvent for adhesive resins, and has been marketed as a replacement for ozone depleting refrigerants. 1-Bromopropane was nominated for study by the Occupational Safety and Health Administration based on the potential for widespread occupational and environmental exposure and a lack of toxicity and carcinogenicity data. Male and female F344/N rats and B6C3F1 mice were exposed to 1-bromopropane (99% or greater pure) by inhalation for 2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Escherichia coli and mouse peripheral blood. 2-WEEK STUDY IN RATS: Groups of five male and five female rats were exposed to 1-bromopropane vapor at concentrations of 0, 125, 250, 500, 1,000, or 2,000 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 16 days. All rats survived to the end of the study except one 500 ppm male. Mean body weights of 2,000 ppm rats were significantly less than those of the chamber controls. The absolute kidney weight of 1,000 ppm males, relative kidney weights of all exposed groups of males, and absolute and relative kidney weights of all exposed groups of females were significantly increased. The absolute and relative liver weights of 1,000 ppm males, relative liver weights of 500 and 2,000 ppm males, and absolute and relative liver weights of 500 ppm or greater females were significantly increased. Nasal lesions included suppurative inflammation in

  18. Exposure-response of 1,2:3,4-diepoxybutane-specific N-terminal valine adducts in mice and rats after inhalation exposure to 1,3-butadiene.

    Science.gov (United States)

    Georgieva, Nadia I; Boysen, Gunnar; Bordeerat, Narisa; Walker, Vernon E; Swenberg, James A

    2010-06-01

    1,3-Butadiene (BD) is a known rodent and human carcinogen that is metabolized mainly by P450 2E1 to three epoxides, 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB), and 1,2-epoxy-3,4-butanediol. The individual epoxides vary up to 200-fold in their mutagenic potency, with DEB being the most mutagenic metabolite. It is important to understand the internal formation of the individual epoxides to assign the relative risk for each metabolite and to understand the molecular mechanisms responsible for extensive species differences in carcinogenicity. This study presents a comprehensive exposure-response for the formation of the DEB-specific N,N-(2,3-dihydroxy-1,4-butadiyl)valine (pyr-Val) in mice and rats. Using nano-ultra high pressure liquid chromatography-tandem-mass spectrometry allowed analysis of pyr-Val in mice and rats exposed to BD as low as 0.1 and 0.5 ppm BD, respectively, and demonstrated significant differences in the amounts and exposure-response of pyr-Val formation. Mice formed 10- to 60-fold more pyr-Val compared to rats at similar exposures. The formation of pyr-Val increased with exposures, and the formation was most efficient with regard to formation per parts per million BD at low exposures. While formation at higher exposures appeared linear in mice, in rats formation saturated at exposures > or = 200 ppm for 10 days. In rats, amounts of pyr-Val were lower after 20 days than after 10 days of exposure, suggesting that the lifespan of rat erythrocytes may be shortened following exposure to BD. This research supports the hypothesis that the lower susceptibility of rats to BD-induced carcinogenesis results from greatly reduced formation of DEB following exposure to BD.

  19. Construction and characterization of a 10-genome equivalent yeast artificial chromosome library for the laboratory rat, Rattus norvegicus

    Energy Technology Data Exchange (ETDEWEB)

    Cai, L.; Zee, R.Y.L. [Harvard Medical School, Boston, MA (United States); Schalkwyk, L.C. [Max Planck Institute for Molecular Genetics, Berlin (Germany)] [and others

    1997-02-01

    Increasing attention has been focused in recent years on the rat as a model organism for genetic studies, in particular for the investigation of complex traits, but progress has been limited by the lack of availability of large-insert genomic libraries. Here, we report the construction and characterization of an arrayed yeast artificial chromosome (YAC) library for the rat genome containing approximately 40,000 clones in the AB1380 host using the pCGS966 vector. An average size of 736 kb was estimated from 166 randomly chosen clones; thus the library provides 10-fold coverage of the genome, with a 99.99% probability of containing a unique sequence. Eight of 39 YACs analyzed by fluorescence in situ hybridization were found to be chimeric, indicating a proportion of about 20-30% of chimeric clones. The library was spotted on high-density filters to allow the identification of YAC clones by hybridization and was pooled using a 3-dimensional scheme for screening by PCR. Among 48 probes used to screen the library, an average of 9.3 positive clones were found, consistent with the calculated 10-fold genomic coverage of the library. This YAC library represents the first large-insert genomic library for the rat. It will be made available to the research community at large as an important new resource for complex genome analysis in this species. 35 refs., 4 figs.

  20. NTP Toxicology and Carcinogenesis Studies of Pentaerythritol Tetranitrate (CAS No. 78-11-5) with 80% D-Lactose Monohydrate (PETN, NF) in F344/N Rats and B6C3F1 Mice (Feed Studies).

    Science.gov (United States)

    1989-08-01

    Pentaerythritol tetranitrate (PETN, NF) is a drug used to prevent angina pectoris. PETN without a lactose stabilizer is used as an explosive. NTP Toxicology and Carcinogenesis studies were conducted by administering PETN, NF, to groups of F344/N rats and B6C3F1 mice of each sex once by gavage or in feed for 14 days, 13 or 14 weeks, or 2 years. The PETN component was greater than 99% pure. Genetic toxicology studies were conducted with Salmonella typhimurium and Chinese hamster ovary (CHO) cells. Fourteen-Day and Thirteen-Week Studies: All rats and mice lived to the end of the 14-day studies (dietary concentrations up to 50,000 ppm). Final mean body weights of dosed and control rats were comparable. The final mean body weight of female mice that received 50,000 ppm was 13% lower than that of controls. No clinical signs or toxic lesions were attributed to PETN, NF, administration. All rats and mice lived to the end of the 13-week (mice) and 14-week (rats) studies (dietary concentrations up to 50,000 ppm). Final mean body weights of dosed and control rats and mice were similar, although weight gains of female rats at 25,000 and 50,000 ppm were less than that of controls. The nitrite level in urine of rats and methemoglobin levels in whole blood of rats and mice were not affected by administration of PETN, NF. An adenoma of the Zymbal gland was seen in a female rat that received 50,000 ppm. A hepatocellular adenoma was seen in a female mouse that received 50,000 ppm. Based on these results and the NTP convention of limiting concentrations in 2-year feed studies to 5% of the diet, the 2-year studies were conducted by administering 0, 25,000 or 50,000 ppm PETN, NF, in feed for 104 weeks to groups of 50 male rats and for 103 weeks to groups of 49 or 50 mice of each sex. Groups of 50 female rats were given feed containing 0, 6,200, or 12,500 ppm PETN, NF, for 104 weeks. Body Weight and Survival in the Two-Year Studies: Mean body weights of high dose male rats were 2

  1. Effects of acute chemotherapy-induced mucositis on spontaneous behaviour and the grimace scale in laboratory rats.

    Science.gov (United States)

    Whittaker, A L; Leach, M C; Preston, F L; Lymn, K A; Howarth, G S

    2016-04-01

    Intestinal mucositis is a frequent side-effect of chemotherapy treatment. Many oncological research programs aim to identify novel treatments for this distressing condition, and these programs frequently use rat models. Little is known about the presence and progression of pain in these models and how this can best be treated by analgesic therapy. We used a number of behaviour-based methods of pain assessment to determine which tools were best suited for pain identification. Baseline measures for behavioural assessment, rat grimace score and sociability were determined through analysis of continuously recorded video data and an applied social interaction test (n = 16). Mucositis was then induced by intraperitoneal injection of 5-fluorouracil (150 mg/kg) and further behavioural analyses undertaken. An assessment of enrichment interaction was also made by determining the mass of a plastic chew toy gnawed both pre- and post-chemotherapy injection. Behavioural scoring was performed 1, 6, 12, 24 and 48 h after injection, with facial expression being scored at the 12, 24 and 48 h time-points. Sociability testing was performed once during the post-injection period. No significant differences were found in grimace scores between baseline and later daily measures. Behaviours similar to those previously reported post-laparotomy were observed. Writhing, twitching and back-arching behaviours were most evident in rats affected by mucositis and were increased in frequency (respective P values: 0.002, 0.004 and 0.008) 48 h after chemotherapy injection compared with baseline, implying that pain onset occurred around this time-point. Social investigatory behaviour was also increased (P = 0.002) following disease onset. Each day, rats post-5FU injection gnawed a greater percentage of their Nylabone enrichment by weight than the saline-injected control rats (P = 0.046). These data suggest that, of the tools tested, behavioural assessment scoring may find greatest

  2. Infecção via oral por Trypanosoma evansi em animais de laboratório Oral infection by Trypanosoma evansi in rats and mice

    Directory of Open Access Journals (Sweden)

    Aleksandro Schafer da Silva

    2007-06-01

    Full Text Available Testou-se a infecção de Trypanosoma evansi pela via oral em ratos e camundongos, através de sangue contaminado de ambas as espécies. Dez ratos e dez camundongos foram alocados em quatro grupos iguais A e B (ratos, C e D (camundongos. Os grupos A e C receberam sangue contaminado de um rato e o grupo B e D de um camundongo, através de uma sonda. O volume de sangue administrado foi de 0,2ml, o qual apresentava uma concentração de 10(7 tripanossomas ml-1. Os animais foram mantidos em temperatura e umidade constantes (25°C e 80% UR, sendo realizados esfregaços sanguíneos diários para identificar o período pré-patente e a evolução do parasita na circulação. Nos grupos A e B, o período pré-patente variou de 19 a 25 dias, e o período entre a detecção dos parasitas e a morte dos animais foi em média de 12,7 dias. Os camundongos do grupo C e D não apresentaram infecção pelo parasita, sendo estes avaliados por 60 dias. Os ratos foram susceptíveis a infecção por T. evansi pela via oral; entretanto, os camundongos não se contaminaram com o protozoário por via digestiva.In this research, Trypanosoma evansi infection was tested in rats and mice by oral ingestion of contaminated blood. Groups of ten rats and ten mice were disposed in four experimental groups: A and B (rats, C and D (mice. The groups A and C were contaminated by rat-contaminated blood; B and C groups by mouse-contaminated blood. The blood was given using a probe filled with 0.2ml of contaminated blood with 10(7 trypanosomes ml-1. These animals were maintained at constant temperature and humidity (25°C and 80% UR. Dairy blood smear were done to identify the prepatent period and evolution of parasite in the circulation. In the A and B groups, the pre latency period varied from 19 to 25 days and the period of parasite detection and animals death was an average of 12.7 days. The C and D groups did not present infection by the parasite even when evaluated for 60 days

  3. Ntp technical report on toxicity, reproductive, and developmental studies of 60-Hz magnetic fields, administered by whole body exposure to F344/N rats, Sprague-Dawley rats, and B6C3F1 mice. Toxicity report series

    Energy Technology Data Exchange (ETDEWEB)

    Boorman, G.A.

    1996-09-01

    Electric and magnetic fields are associated with the production, transmission, and use of electricity; thus the potential for human exposure is high. These electric and magnetic fields are predominantly of low frequency (60 Hz) and generally of low intensity. The prevailing view among physicists is that exposure to these low-frequency, low-intensity fields does not pose a health hazard. However, this view has been challenged by reports linking magnetic field exposure to the development of leukemia and other cancers. Because multiple epidemiologic studies suggested a potential for increased cancer rates with increasing exposure, and because of public concern, the effects of 60-Hz magnetic field exposure were examined in F344/N rats and B6C3F1 mice in 8-week full-body-exposure studies. Animals were evaluated for hematology and clinical chemistry (rats only) parameters, pineal gland hormone concentrations, and histopathology. Additional studies were performed in Sprague-Dawley rats to examine teratologic and reproductive effects of magnetic field exposure.

  4. Gene targeting technologies in rats: zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats.

    Science.gov (United States)

    Mashimo, Tomoji

    2014-01-01

    The laboratory rat has been widely used as an animal model in biomedical science for more than 150 years. Applying zinc-finger nucleases or transcription activator-like effector nucleases to rat embryos via microinjection is an efficient genome editing tool for generating targeted knockout rats. Recently, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated endonucleases have been used as an effective tool for precise and multiplex genome editing in mice and rats. In this review, the advantages and disadvantages of these site-specific nuclease technologies for genetic analysis and manipulation in rats are discussed.

  5. Pavlovian influences on learning differ between rats and mice in a counter-balanced Go/NoGo judgement bias task.

    Science.gov (United States)

    Jones, Samantha; Paul, Elizabeth S; Dayan, Peter; Robinson, Emma S J; Mendl, Michael

    2017-07-28

    Judgement bias tests of animal affect and hence welfare assume that the animal's responses to ambiguous stimuli, which may herald positive or negative outcomes, are under instrumental control and reflect 'optimism' or 'pessimism' about what will happen. However, Pavlovian control favours responses (e.g. approach or withdrawal) according to the valence associated with a stimulus, rather than the anticipated response outcomes. Typically, positive contexts promote action and approach whilst negative contexts promote inhibition or withdrawal. The prevalence of Go-for-reward (Go-pos) and NoGo-to-avoid-punishment (NoGo-neg) judgement bias tasks reflects this Pavlovian influence. A Pavlovian increase or decrease in activity or vigour has also been argued to accompany positive or negative affective states, and this may interfere with instrumental Go or NoGo decisions under ambiguity based on anticipated decision outcomes. One approach to these issues is to develop counter-balanced Go-pos/NoGo-neg and Go-neg/NoGo-pos tasks. Here we implement such tasks in Sprague Dawley rats and C57BL/6J mice using food and air-puff as decision outcomes. We find striking species/strain differences with rats achieving criterion performance on the Go-pos/NoGo-neg task but failing to learn the Go-neg/NoGo-pos task, in line with predictions, whilst mice do exactly the opposite. Pavlovian predispositions may thus differ between species, for example reflecting foraging and predation ecology and/or baseline activity rates. Learning failures are restricted to cues predicting a negative outcome; use of a more powerful air-puff stimulus may thus allow implementation of a fully counter-balanced task. Rats and mice achieve criterion faster than in comparable automated tasks and also show the expected generalisation of responses across ambiguous tones. A fully counter-balanced task thus offers a potentially rapidly implemented and automated method for assessing animal welfare, identifying welfare

  6. An ectopic study of tissue-engineered bone with Nell-1 gene modified rat bone marrow stromal cells in nude mice

    Institute of Scientific and Technical Information of China (English)

    HU Jing-zhou; ZHANG Zhi-yuan; ZHAO Jun; ZHANG Xiu-li; LIU Gen-tao; JIANG Xin-quan

    2009-01-01

    Background Tissue engineering techniques combined with gene therapy have been recently used to improve osteogenesis. NEL-like molecule-1 (Nell-1), a novel growth factor, has been reported to have specificity for osteochondral lineage. The study assessed the osteogenic differentiation of rat bone marrow stromal cells (bMSCs) after Nell-1 gene modification and examined its ectopic bone formation ability in a nude mice model with tissue engineering technique.Methods bMSCs obtained from Fischer 344 rats were transduced with either AdNell-1 (Nell-1 group) or Ad-β-galactosidase (AdLacZ, LacZ group) or left untransduced (untransduced group). The expression of Nell-1 protein was determined by Western blotting and transfer efficiency was assessed, mRNA expressions of osteopontin (OP), bone sialoprotein (BSP) and osteocalcin (OC) were assessed by real-time PCR 0, 3, 7, 14, and 21 days after gene transfer. Alkaline phosphatase (ALP) activity was measured and von Kossa test was also conducted. Finally, with a tissue engineering technique, gene transduced bMSCs, combining with β-tricalcium phosphate (β-TCP) at a concentration of 2×107 cells/ml, were implanted at subcutaneous sites on the back of nude mice. Four weeks after surgery, the implants were evaluated with histological staining and computerized analysis of new bone formation.Results Under current transduction conditions, gene transfer efficiency reached (57.9±6.8)%. Nell-1 protein was detected in Nell-1 group but not in untransduced group and LacZ group. Induced by Nell-1, BSPand OPexpression were increased at intermediate stage and OC expression was increased at later stage. ALP activity and the number of calcium nodules were highest in Nell-1 group. Four weeks after implanted into nude mice subcutaneously, the percentage of new bone area in Nell-1 group was (18.1±5.0)%, significantly higher than those of untransduced group (11.3±3.2)% and LacZ group (12.3±3.1)% (P<0.05).Conclusions This study has demonstrated

  7. GC–MS-Based Metabonomic Profiling Displayed Differing Effects of Borna Disease Virus Natural Strain Hu-H1 and Laboratory Strain V Infection in Rat Cortical Neurons

    Directory of Open Access Journals (Sweden)

    Siwen Liu

    2015-08-01

    Full Text Available Borna disease virus (BDV persists in the central nervous systems of a wide variety of vertebrates and causes behavioral disorders. Previous studies have revealed that metabolic perturbations are associated with BDV infection. However, the pathophysiological effects of different viral strains remain largely unknown. Rat cortical neurons infected with human strain BDV Hu-H1, laboratory BDV Strain V, and non-infected control (CON cells were cultured in vitro. At day 12 post-infection, a gas chromatography coupled with mass spectrometry (GC–MS metabonomic approach was used to differentiate the metabonomic profiles of 35 independent intracellular samples from Hu-H1-infected cells (n = 12, Strain V-infected cells (n = 12, and CON cells (n = 11. Partial least squares discriminant analysis (PLS-DA was performed to demonstrate discrimination between the three groups. Further statistical testing determined which individual metabolites displayed significant differences between groups. PLS-DA demonstrated that the whole metabolic pattern enabled statistical discrimination between groups. We identified 31 differential metabolites in the Hu-H1 and CON groups (21 decreased and 10 increased in Hu-H1 relative to CON, 35 differential metabolites in the Strain V and CON groups (30 decreased and 5 increased in Strain V relative to CON, and 21 differential metabolites in the Hu-H1 and Strain V groups (8 decreased and 13 increased in Hu-H1 relative to Strain V. Comparative metabonomic profiling revealed divergent perturbations in key energy and amino acid metabolites between natural strain Hu-H1 and laboratory Strain V of BDV. The two BDV strains differentially alter metabolic pathways of rat cortical neurons in vitro. Their systematic classification provides a valuable template for improved BDV strain definition in future studies.

  8. 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.

  9. On-line analysis of middle latency auditory evoked potentials (MLAEP) for monitoring depth of anaesthesia in laboratory rats

    DEFF Research Database (Denmark)

    Jensen, E W; Nygaard, M; Henneberg, S W

    1998-01-01

    using neuromuscular blocking agents (NMBA). A number of studies suggest that the Middle Latency Auditory Evoked Potentials (MLAEP) contain information about the state of consciousness in humans. The purpose of this study was to examine whether the AEP could serve as an indicator of depth of anaesthesia...... in rats. The AEP was elicited with a click stimulus and monitored in an 80 ms window synchronised to the stimulus. The AEP was extracted applying an Auto Regressive Model with Exogenous Input (ARX-model) from which a Depth of Anaesthesia Index (DAI) was calculated. DAI was normalised to 100 while awake...

  10. Different importance of the volatile and non-volatile fractions of an olfactory signature for individual social recognition in rats versus mice and short-term versus long-term memory.

    Science.gov (United States)

    Noack, Julia; Richter, Karin; Laube, Gregor; Haghgoo, Hojjat Allah; Veh, Rüdiger W; Engelmann, Mario

    2010-11-01

    When tested in the olfactory cued social recognition/discrimination test, rats and mice differ in their retention of a recognition memory for a previously encountered conspecific juvenile: Rats are able to recognize a given juvenile for approximately 45 min only whereas mice show not only short-term, but also long-term recognition memory (≥ 24 h). Here we modified the social recognition/social discrimination procedure to investigate the neurobiological mechanism(s) underlying the species differences. We presented a conspecific juvenile repeatedly to the experimental subjects and monitored the investigation duration as a measure for recognition. Presentation of only the volatile fraction of the juvenile olfactory signature was sufficient for both short- and long-term recognition in mice but not rats. Applying additional volatile, mono-molecular odours to the "to be recognized" juveniles failed to affect short-term memory in both species, but interfered with long-term recognition in mice. Finally immunocytochemical analysis of c-Fos as a marker for cellular activation, revealed that juvenile exposure stimulated areas involved in the processing of olfactory signals in both the main and the accessory olfactory bulb in mice. In rats, we measured an increased c-Fos synthesis almost exclusively in cells of the accessory olfactory bulb. Our data suggest that the species difference in the retention of social recognition memory is based on differences in the processing of the volatile versus non-volatile fraction of the individuals' olfactory signature. The non-volatile fraction is sufficient for retaining a short-term social memory only. Long-term social memory - as observed in mice - requires a processing of both the volatile and non-volatile fractions of the olfactory signature. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Evaluation of the effect of time on the distribution of zinc oxide nanoparticles in tissues of rats and mice: a systematic review.

    Science.gov (United States)

    Chen, Aijie; Feng, Xiaoli; Sun, Ting; Zhang, Yanli; An, Shengli; Shao, Longquan

    2016-06-01

    To evaluate the time effect on the distribution of zinc oxide nanoparticles (ZnO NPs) in tissues from rats and mice, a search on the PubMed, Embase, SpringerLink, Scopus, Science Direct, Cochrane, CNKI, Wanfang, and vip databases up to September 2014 was performed, followed by screening, data extraction, and quality assessment. Thirteen studies were included. At 24 h, Zn content was mainly distributed in the liver, kidney, and lung. At ≥7 days, Zn content was mainly distributed in the liver, kidney, lung, and brain. ZnO NPs are readily deposited in tissues. Furthermore, as time increases, Zn content decreases in the liver and kidney, but increases in the brain.

  12. GLP-1 Amidation Efficiency Along the Length of the Intestine in Mice, Rats and Pigs and in GLP-1 Secreting Cell Lines

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Albrechtsen, Nicolai Jacob Wewer; Windeløv, Johanne Agerlin

    2014-01-01

    XXX: Measurements of plasma concentrations of the incretin hormone GLP-1 are complex because of extensive molecular heterogeneity. This is partly due to a varying and incompletely known degree of C-terminal amidation. Given that virtually all GLP-1 assays rely on a C-terminal antibody, it is esse......XXX: Measurements of plasma concentrations of the incretin hormone GLP-1 are complex because of extensive molecular heterogeneity. This is partly due to a varying and incompletely known degree of C-terminal amidation. Given that virtually all GLP-1 assays rely on a C-terminal antibody......, it is essential to know whether or not the molecule one wants to measure is amidated. We performed a detailed analysis of extractable GLP-1 from duodenum, proximal jejunum, distal ileum, caecum, proximal colon and distal colon of mice (n=9), rats (n=9) and pigs (n=8) and determined the degree of amidation...

  13. A comparison of the therapeutic and reactivating efficacy of newly developed bispyridinium compounds (K206, K269) with currently available oximes against tabun in rats and mice.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana; Bajgar, Jiri; Kuca, Kamil; Musilek, Kamil

    2008-12-01

    The potency of newly developed bispyridinium compounds (K206, K269) in reactivating tabun-inhibited acetylcholinesterase and eliminating tabun-induced lethal toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies which determined percentage of reactivation of tabun-inhibited blood and tissue AChE in poisoned rats showed that the reactivating efficacy of both newly developed oximes is comparable with obidoxime and trimedoxime in blood but lower than the reactivating potency of trimedoxime and obidoxime in the diaphragm and brain. Nevertheless, the differences in reactivating efficacy of obidoxime, trimedoxime and K206 was not significant while the potency of K269 to reactivate tabun-inhibited acetylcholinesterase was significantly lower. Both newly developed oximes were also found to be relatively efficacious in elimination of the lethal toxic effects in tabun-poisoned mice. Their therapeutic efficacy corresponds to the therapeutic potency of obidoxime. The oxime HI-6, relatively efficacious against soman, did not seem to be an adequately effective oxime in reactivation of tabun-inhibited AChE and to counteract lethal effects of tabun. Both newly developed oximes (K206, K269) are significantly more efficacious in reactivating tabun-inhibited AChE in rats and to eliminate lethal toxic effects of tabun in mice than the oxime HI-6 but their reactivating and therapeutic potency does not prevail over the effectiveness of currently available obidoxime and trimedoxime and, therefore, they are not suitable for their replacement of commonly used oximes for the treatment of acute tabun poisoning.

  14. Evaluation of nutritional quality of dried cashew nut testa using laboratory rat as a model for pigs.

    Science.gov (United States)

    Donkoh, Armstrong; Attoh-Kotoku, Victoria; Osei Kwame, Reginald; Gascar, Richard

    2012-01-01

    Dried cashew nut testa (DCNT) was characterized with respect to proximate, mineral, and energy profile. The crude protein, crude fibre, and fat and ash contents were, in g kg(-1)DM, 190.0, 103.0, 20.1, and 20.2, respectively, with metabolizable energy of 7.12 MJ kg(-1) DM. In a feeding trial, isoproteic diets containing DCNT (O, 50, 100, and 150 g kg(-1)) were fed ad libitum to 4 groups of Sprague-Dawley male rats (110 g body weight, n = 20) for a period of 4 weeks. The rats, used as model for pigs, had free access to water. As the dietary DCNT content was increased from 0 to 150 g kg(-1), there was a significant (P feed intake (r = -0.99), water intake (r = -0.87), and a reduction in body weight gain (r = -0.93) and efficiency of feed utilization (r = 0.78). However, no deaths or health-related problems were recorded during the study. Dietary treatments had no impact on liver, heart, lungs, kidneys, and intestinal weights. Cost per gram feed and feed cost per gram live weight gain were reduced when DCNT was used. The experimental diet containing 50 g DCNT kg(-1) supported the best growth performance with the lowest feed cost per gram live weight gain of GH¢0.18. Seasonal increases in the prices of conventional feedstuffs like maize and fishmeal would make the use of agroindustrial by-products such as DCNT in pig diets even more attractive.

  15. Evaluation of Nutritional Quality of Dried Cashew Nut Testa Using Laboratory Rat as a Model for Pigs

    Directory of Open Access Journals (Sweden)

    Armstrong Donkoh

    2012-01-01

    Full Text Available Dried cashew nut testa (DCNT was characterized with respect to proximate, mineral, and energy profile. The crude protein, crude fibre, and fat and ash contents were, in g kg−1 DM, 190.0, 103.0, 20.1, and 20.2, respectively, with metabolizable energy of 7.12 MJ kg−1 DM. In a feeding trial, isoproteic diets containing DCNT (O, 50, 100, and 150 g kg−1 were fed ad libitum to 4 groups of Sprague-Dawley male rats (110 g body weight, =20 for a period of 4 weeks. The rats, used as model for pigs, had free access to water. As the dietary DCNT content was increased from 0 to 150 g kg−1, there was a significant (<0.01 decrease in feed intake (=−0.99, water intake (=−0.87, and a reduction in body weight gain (=−0.93 and efficiency of feed utilization (=0.78. However, no deaths or health-related problems were recorded during the study. Dietary treatments had no impact on liver, heart, lungs, kidneys, and intestinal weights. Cost per gram feed and feed cost per gram live weight gain were reduced when DCNT was used. The experimental diet containing 50 g DCNT kg−1 supported the best growth performance with the lowest feed cost per gram live weight gain of GHȼ0.18. Seasonal increases in the prices of conventional feedstuffs like maize and fishmeal would make the use of agroindustrial by-products such as DCNT in pig diets even more attractive.

  16. NTP Toxicology and Carcinogenesis Studies of d-Limonene (CAS No. 5989-27-5) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1990-01-01

    Toxicology and carcinogenesis studies of d-limonene, a naturally occurring monoterpene found in many volatile oils, especially in citrus oils, were conducted because of its widespread use as a flavor and fragrance additive for food and household cleaning products and its increasing use as an industrial solvent. The d-limonene used in these studies was more than 99% pure and was administered in corn oil by gavage. Short-term studies were conducted in F344/N rats and B6C3F1 mice to identify toxic effects and affected sites and to help establish doses for the 2-year studies. Genetic toxicology studies were conducted in Salmonella typhimurium, mouse L5178Y cells, and Chinese hamster ovary (CHO) cells. The doses selected for the 16-day studies ranged from 413 to 6,600 mg/kg for both rats and mice; deaths and reduction in body weight gain occurred at the two highest doses. No compound-related clinical signs or histopathologic lesions were observed in any of the surviving dose groups. In the 13-week studies, doses of d-limonene ranged from 150 to 2,400 mg/kg for rats and from 125 to 2,000 mg/kg for mice. Deaths occurred in the high dose group of each species and sex. Greater than 10% reductions in body weight gain were observed in the two highest dose groups of male rats and male mice and the high dose female rats. Rough hair coats and decreased activity were observed at the two highest doses in both rats and mice. There were no chemical-related histopathologic lesions in female rats or in mice of either sex. A compound-related increased severity of nephropathy was observed in the kidney of male rats. This lesion was characterized by degeneration of epithelial cells in the convoluted tubules, granular casts in the outer stripe of the outer medulla, and epithelial regeneration. These lesions have been described as reasonably characteristic of the hyaline droplet nephropathy that is associated with an accumulation of liver-generated a2u-globulin in the cytoplasm of tubular

  17. Evaluation of the antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities of ethanolic extract of Ammi majus seeds in albino rats and mice.

    Science.gov (United States)

    Koriem, Khaled M M; Asaad, Gihan F; Megahed, Hoda A; Zahran, Hanan; Arbid, Mahmoud S

    2012-06-01

    Pharmacological and biochemical studies on the Ammi majus seeds L. (family Umbelliferae) grown in Egypt are limited. Furocoumarins are the major constituents in the plant seeds. In the present study, the evaluation of the antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities on albino rats and mice was done. After 2 months of administration, both the doses (50 and 100 mg/kg body weight [bwt], respectively) of the alcoholic extract of the A. majus seed result in a significant decrease in the concentrations of cholesterol, triglycerides, and low-density lipoprotein and increase in the concentration of high-density lipoprotein. The extract was found to inhibit the rat paw edema at both the doses, which means that it exerts a significant anti-inflammatory activity compared with control-untreated groups at the intervals of 30 and 60 minutes posttreatment. The antipyretic effect of the extract was quite obvious; it showed that 100 mg/kg bwt was more potent in lowering body temperature starting after 1 hour of treatment than the lower dose (50 mg/kg bwt). It is worth to mention that the A. majus extract with its coumarin contents as well as the tested biological activities of the plant was investigated for the first time in the current study. In conclusion, ethanolic extract of the A. majus seeds had antihyperlipidemic, anti-inflammatory, analgesic, and antipyretic activities that are dose dependant.

  18. 大、小鼠吸收和代谢双酚A的差异%The differences in absorption and metabolism of bisphenol A between rats and mice

    Institute of Scientific and Technical Information of China (English)

    黄春妍; 姚陈娟; 鞠晶昀; 潘少聪; 任飞林; 陈刚

    2010-01-01

    ,差异有统计学意义(F=21.215,P=0.001).结论 大、小鼠经口给予300 mg/kg BPA染毒后,由于小鼠肠吸收BPA的能力高于大鼠,而大鼠代谢及排出BPA能力高于小鼠,引起小鼠血清中BPA的浓度明显高于大鼠.%Objective To investigate the mechanism of the different levels of serum bisphenol A(BPA) between rat and mouse after oral administration. Methods A total of 18 specific pathogen free(SPF) male rats and 18 mice were treated with 300 mg/kg BPA by oral administration,blood samples were taken from rats and mice after BPA administration at 0.5,1.0,12.0 h time points(n =6 at each point).Serum BPA levels were quantified using fluorescence-high performance liquid chromatography (FL-HPLC)analysis. The rats and mice (n = 6, respectively ) were perfused with 100 ml of 0.1 mmol/L BPA by intestinal absorption in situ,then the BPA levels of perfusion fluid at 0.5,1.0,2.0 h time points and serum at 2.0 h after BPA perfusion were determined by FL-HPLC analysis. The levels of UDP-glucuronosyltransferase 2B1 ( UGT2B1 ) mRNA expression in the liver of rats and mice were analyzed by semi-quantitative RT-PCR and UGT2B1 enzymatic activity was determined by FL-HPLC method. The rats and mice (n = 6,respectively) were treated with 300 mg/kg BPA by omal administration after fasting 24 h,the feces were collected during 24 h and the levels of BPA in feces were determined by FL-HPLC analysis. Results At 0.5,1.0,12.0 h after oral administration at 300 mg/kg BPA, the levels of serum BPA in mice ( (66.57 ± 14.95 ), ( 51.16 ± 16.06 ), ( 22.73 ± 5.00 ) μg/ml, respectively) were significantly higher than in rats ( ( 15.63 ± 5.65 ), ( 18.34 ± 5.02 ), (7.65 ± 2.58 ) μg/ml, respectively) (F values were 50.660,17.957,8.420,respectively,P < 0.05) ,the rates of absorption in mice small intestine during 0 h -,0.5 h- ,1.0-2.0 h ((10.20 ±4.20),(1.49 ±0.67),(1.31 ±0.55) μg · cm-2 · min-1 ,respectively)were higher than that in rats ((1.87 ±0.69),(0.47 ± 0.13),(0.36 ±0.08) μg · cm

  19. Species- and tissue-specific relationships between mitochondrial permeability transition and generation of ROS in brain and liver mitochondria of rats and mice.

    Science.gov (United States)

    Panov, Alexander; Dikalov, Sergey; Shalbuyeva, Natalia; Hemendinger, Richelle; Greenamyre, John T; Rosenfeld, Jeffrey

    2007-02-01

    In animal models of neurodegenerative diseases pathological changes vary with the type of organ and species of the animals. We studied differences in the mitochondrial permeability transition (mPT) and reactive oxygen species (ROS) generation in the liver (LM) and brain (BM) of Sprague-Dawley rats and C57Bl mice. In the presence of ADP mouse LM and rat LM required three times less Ca(2+) to initiate mPT than the corresponding BM. Mouse LM and BM sequestered 70% and 50% more Ca(2+) phosphate than the rat LM and BM. MBM generated 50% more ROS with glutamate than the RBM, but not with succinate. With the NAD substrates, generation of ROS do not depend on the energy state of the BM. Organization of the respiratory complexes into the respirasome is a possible mechanism to prevent ROS generation in the BM. With BM oxidizing succinate, 80% of ROS generation was energy dependent. Induction of mPT does not affect ROS generation with NAD substrates and inhibit with succinate as a substrate. The relative insensitivity of the liver to systemic insults is associated with its high regenerative capacity. Neuronal cells with low regenerative capacity and a long life span protect themselves by minimizing ROS generation and by the ability to withstand very large Ca(2+) insults. We suggest that additional factors, such as oxidative stress, are required to initiate neurodegeneration. Thus the observed differences in the Ca(2+)-induced mPT and ROS generation may underlie both the organ-specific and species-specific variability in the animal models of neurodegenerative diseases.

  20. GLP-1 amidation efficiency along the length of the intestine in mice, rats and pigs and in GLP-1 secreting cell lines.

    Science.gov (United States)

    Kuhre, Rune Ehrenreich; Albrechtsen, Nicolai Wewer; Windeløv, Johanne Agerlin; Svendsen, Berit; Hartmann, Bolette; Holst, Jens Juul

    2014-05-01

    XXX: Measurements of plasma concentrations of the incretin hormone GLP-1 are complex because of extensive molecular heterogeneity. This is partly due to a varying and incompletely known degree of C-terminal amidation. Given that virtually all GLP-1 assays rely on a C-terminal antibody, it is essential to know whether or not the molecule one wants to measure is amidated. We performed a detailed analysis of extractable GLP-1 from duodenum, proximal jejunum, distal ileum, caecum, proximal colon and distal colon of mice (n=9), rats (n=9) and pigs (n=8) and determined the degree of amidation and whether this varied with the six different locations. We also analyzed the amidation in 3 GLP-1 secreting cell lines (GLUTag, NCI-H716 and STC-1). To our surprise there were marked differences between the 3 species with respect to the concentration of GLP-1 in gut. In the mouse, concentrations increased continuously along the intestine all the way to the rectum, but were highest in the distal ileum and proximal colon of the rat. In the pig, very little or no GLP-1 was present before the distal ileum with similar levels from ileum to distal colon. In the mouse, GLP-1 was extensively amidated at all sampling sites, whereas rats and pigs on average had around 2.5 and 4 times higher levels of amidated compared to non-amidated GLP-1, although the ratio varied depending upon the location. GLUTag, NCI-H716 and STC-1 cells all exhibited partial amidation with 2-4 times higher levels of amidated compared to non-amidated GLP-1.

  1. Molecular characterization of pneumococcal isolates from pets and laboratory animals.

    Directory of Open Access Journals (Sweden)

    Mark van der Linden

    Full Text Available BACKGROUND: Between 1986 and 2008 Streptococcus pneumoniae was isolated from 41 pets/zoo animals (guinea pigs (n = 17, cats (n = 12, horses (n = 4, dogs (n = 3, dolphins (n = 2, rat (n = 2, gorilla (n = 1 treated in medical veterinary laboratories and zoos, and 44 laboratory animals (mastomys (multimammate mice; n = 32, mice (n = 6, rats (n = 4, guinea pigs (n = 2 during routine health monitoring in an animal facility. S. pneumoniae was isolated from nose, lung and respiratory tract, eye, ear and other sites. METHODOLOGY/PRINCIPAL FINDINGS: Carriage of the same isolate of S. pneumoniae over a period of up to 22 weeks was shown for four mastomys. Forty-one animals showed disease symptoms. Pneumococcal isolates were characterized by optochin sensitivity, bile solubility, DNA hybridization, pneumolysin PCR, serotyping and multilocus sequence typing. Eighteen of the 32 mastomys isolates (56% were optochin resistant, all other isolates were optochin susceptible. All mastomys isolates were serotype 14, all guinea pig isolates serotype 19F, all horse isolates serotype 3. Rats had serotypes 14 or 19A, mice 33A or 33F. Dolphins had serotype 23F, the gorilla serotype 14. Cats and dogs had many different serotypes. Four isolates were resistant to macrolides, three isolates also to clindamycin and tetracycline. Mastomys isolates were sequence type (ST 15 (serotype 14, an ST/serotype combination commonly found in human isolates. Cats, dogs, pet rats, gorilla and dolphins showed various human ST/serotype combinations. Lab rats and lab mice showed single locus variants (SLV of human STs, in human ST/serotype combinations. All guinea pig isolates showed the same completely new combination of known alleles. The horse isolates showed an unknown allele combination and three new alleles. CONCLUSIONS/SIGNIFICANCE: The isolates found in mastomys, mice, rats, cats, dogs, gorilla and dolphins are most likely identical to human pneumococcal isolates. Isolates from

  2. Slow oxidation of acetoxime and methylethyl ketoxime to the corresponding nitronates and hydroxy nitronates by liver microsomes from rats, mice, and humans.

    Science.gov (United States)

    Völkel, W; Wolf, N; Derelanko, M; Dekant, W

    1999-02-01

    Acetoxime and methylethyl ketoxime (MEKO) are tumorigenic in rodents, inducing liver tumors in male animals. The mechanisms of tumorigenicity for these compounds are not well defined. Oxidation of the oximes to nitronates of secondary-nitroalkanes, which are mutagenic and tumorigenic in rodents, has been postulated to play a role in the bioactivation of ketoximes. In these experiments, we have compared the oxidation of acetoxime and methylethyl ketoxime to corresponding nitronates in liver microsomes from different species. The oximes were incubated with liver microsomes from mice, rats, and several human liver samples. After tautomeric equilibration and extraction with n-hexane, 2-nitropropane and 2-nitrobutane were quantitated by GC/MS-NCI (limit of detection of 250 fmol/injection volume). In liver microsomes, nitronate formation from MEKO and acetoxime was dependent on time, enzymatically active proteins, and the presence of NADPH. Nitronate formation was increased in liver microsomes of rats pretreated with inducers of cytochrome P450 and reduced in the presence of inhibitors (n-octylamine and diethyldithiocarbamate). Rates of oxidation of MEKO (Vmax) were 1.1 nmol/min/mg (mice), 0.5 nmol/min/mg (humans), and 0.1 nmol/min/mg (rats). In addition to nitronates, several minor metabolites were also enzymatically formed (two diastereoisomers of 3-nitro-2-butanol, 2-hydroxy-3-butanone oxime and 2-nitro-1-butanol). Acetoxime was also metabolized to the corresponding nitronate at rates approximately 50% of those observed with MEKO oxidation in the three species examined. 2-Nitro-1-propanol was identified as a minor product formed from acetoxime. No sex differences in the capacity to oxidize acetoxime and MEKO were observed in the species examined. The observed results show that formation of sec-nitronates from ketoximes occurs slowly, but is not the only pathway involved in the oxidative biotransformation of these compounds. Due to the lack of sex-specific oxidative

  3. Guidelines for the care and use of laboratory animals in biomedical research.

    Science.gov (United States)

    Jones-Bolin, Susan

    2012-12-01

    This unit provides a general overview on topics related to the practical care and use of laboratory animals in biomedical research. These topics are briefly described and provide Web sites and/or research articles that can be accessed for more detailed information. While the primary focus is on the care and use of rats and mice bred for biomedical research, many of the Web sites listed provide information on other species used for this purpose.

  4. VDTs: Field levels, epidemiology, and laboratory studies

    Energy Technology Data Exchange (ETDEWEB)

    Kavet, R.; Tell, R.A. (Richard Tell Associates, Inc., Las Vegas, NV (USA))

    1991-07-01

    As the use of video display terminals (VDTs) has expanded, questions have been raised as to whether working at a VDT affects the risk of adverse pregnancy outcome. A particular focus for these questions has been the very low frequency (VLF) magnetic field produced by a VDT's horizontal deflection coil. VDTs also produce VLF electric fields, extremely low frequency (ELF) electric and magnetic fields, and static electric fields, Ten studies of pregnancy outcome in VDT operators have been conducted in six countries, and with one exception, none has concluded that magnetic fields from VDTs may predispose pregnant operators to spontaneous abortion or congenital malformation. The epidemiologic studies conducted thus far do not provide a basis for concluding that VDT work and adverse pregnancy outcome are associated. Studies of fetal resorptions and malformations in rodents exposed to VLF magnetic fields have produced inconsistent findings. Two laboratories in Sweden that studied mice have reported positive results, one laboratory showing field-related malformations (but not resorptions) and the other showing field-related resorptions (but not malformations). Two Canadian laboratories have reported negative results in rats and mice. Studies of avian embryos have also yielded inconsistent results, but lacking a maternal-fetal placental interface, avian embryos are a questionable model for evaluating human reproductive risks. Finally, VLF electric and magnetic fields measured at the operator position are in compliance with field strength standards and guidelines that have been established around the world. 55 refs.

  5. 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.

  6. High resolution 3D laboratory x-ray tomography data of femora from young, 1–14 day old C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Emely L. Bortel

    2015-09-01

    Full Text Available This data article contains high resolution (1.2 µm effective pixel size lab-based micro-computed tomography (µCT reconstructed volume data of the femoral mid-shafts from young C57BL/6 mice. This data formed the basis for the analyses of bone structural development in healthy mice, including closed and open porosity as reported in Bortel et al. [1]. The data reveals changes seen in bone material and porosity distribution observed when mouse bones transform from porous scaffolds into solid structures during normal organogenesis.

  7. Hepatic and intestinal glucuronidation of mono(2-ethylhexyl) phthalate, an active metabolite of di(2-ethylhexyl) phthalate, in humans, dogs, rats, and mice: an in vitro analysis using microsomal fractions.

    Science.gov (United States)

    Hanioka, Nobumitsu; Isobe, Takashi; Kinashi, Yu; Tanaka-Kagawa, Toshiko; Jinno, Hideto

    2016-07-01

    Mono(2-ethylhexyl) phthalate (MEHP) is an active metabolite of di(2-ethylhexyl) phthalate (DEHP) and has endocrine-disrupting effects. MEHP is metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in mammals. In the present study, the hepatic and intestinal glucuronidation of MEHP in humans, dogs, rats, and mice was examined in an in vitro system using microsomal fractions. The kinetics of MEHP glucuronidation by liver microsomes followed the Michaelis-Menten model for humans and dogs, and the biphasic model for rats and mice. The K m and V max values of human liver microsomes were 110 µM and 5.8 nmol/min/mg protein, respectively. The kinetics of intestinal microsomes followed the biphasic model for humans, dogs, and mice, and the Michaelis-Menten model for rats. The K m and V max values of human intestinal microsomes were 5.6 µM and 0.40 nmol/min/mg protein, respectively, for the high-affinity phase, and 430 µM and 0.70 nmol/min/mg protein, respectively, for the low-affinity phase. The relative levels of V max estimated by Eadie-Hofstee plots were dogs (2.0) > mice (1.4) > rats (1.0) ≈ humans (1.0) for liver microsomes, and mice (8.5) > dogs (4.1) > rats (3.1) > humans (1.0) for intestinal microsomes. The percentages of the V max values of intestinal microsomes to liver microsomes were mice (120 %) > rats (57 %) > dogs (39 %) > humans (19 %). These results suggest that the metabolic abilities of UGT enzymes expressed in the liver and intestine toward MEHP markedly differed among species, and imply that these species differences are strongly associated with the toxicity of DEHP.

  8. Susceptibility of laboratory rodents to Trichinella papuae.

    Science.gov (United States)

    Sadaow, Lakkhana; Intapan, Pewpan M; Boonmars, Thidarut; Morakote, Nimit; Maleewong, Wanchai

    2013-12-01

    Members of the genus Trichinella are small nematodes that can infect a wide range of animal hosts. However, their infectivity varies depending on the parasite and host species combination. In this study, we examined the susceptibility of 4 species of laboratory rodents, i.e., mice, rats, hamsters, and gerbils to Trichinella papuae, an emerging non-encapsulated Trichinella species. Trichinella spiralis and Trichinella pseudospiralis were also included in this study for comparison. Fifteen animals of each rodent species were infected orally with 100 muscle larvae of each Trichinella species. Intestinal worm burden was determined at day 6 and 10 post-inoculation (PI). The numbers of muscle larvae were examined at day 45 PI. The reproductive capacity index (RCI) of the 3 Trichinella species in different rodent hosts was determined. By day 6 PI, 33.2-69.6% of the inoculated larvae of the 3 Trichinella species became adult worms in the small intestines of the host animals. However, in rats, more than 96% of adult worms of all 3 Trichinella species were expelled from the gut by day 10 PI. In gerbils, only 4.8-18.1% of adult worms were expelled by day 10 PI. In accordance with the intestinal worm burden and the persistence of adults, the RCI was the highest in gerbils with values of 241.5±41.0 for T. papuae, 432.6±48 for T. pseudospiralis, and 528.6±20.6 for T. spiralis. Hamsters ranked second and mice ranked third in susceptibility in terms of the RCI, Rats yielded the lowest parasite RCI for all 3 Trichinella species. Gerbils may be an alternative laboratory animal for isolation and maintenance of Trichinella spp.

  9. Beneficial Effect of HHI-Ⅰ(活血化瘀注射液Ⅰ号)on Cerebral Microcirculation,Blood-Brain Barrier in Rats and Anti-hypoxic Activity in Mice

    Institute of Scientific and Technical Information of China (English)

    赵连根; 吴咸中; 伍孝先

    2009-01-01

    Objective:To investigate the effect of HHI-Ⅰ(活血化瘀注射液Ⅰ号) on the cerebral microcirculation,the blood-brain barrier permeability in rats and anti-hypoxic activity in mice.Methods:(1) The blood microcirculation of the brain in rats was investigated by laser Doppler flowmetry with the probes laid on the cerebral pia mater or inserted into the brain parenchyma.(2) The protective action of HHI-Ⅰagainst the brain microcirculation disturbance induced by intravenous injection of high-molecular dextran(10%,9 mL/kg)...

  10. Unilateral and bilateral cryptorchidism and its effect on the testicular morphology, histology, accessory sex organs, and sperm count in laboratory mice

    Directory of Open Access Journals (Sweden)

    Soumita Dutta

    2013-01-01

    Full Text Available Background: Experimental unilateral cryptorchidism (ULC and bilateral cryptorchidism (BLC are excellent methods to study undescended testis in relation to spermatogenesis against a temperature gradient. Objectives: In case of ULC, it is possible to compare the testicular functions between normal condition and cryptorchidism in the same animal, whereas BLC shows the necessity of testicular androgens for proper maintenance of reproductive structures and functions. Materials and Methods: In the present study, experimental ULC and BLC was done on same-aged adult mature male mice and kept for 15 days and 30 days, respectively, to observe the changes due to the induced cryptorchidism on the different reproductive organs, viz., the testis and accessory sex organs along with epididymal sperm count. Reproductive tissues were collected from individual animals and histopathological studies of testis were done to investigate different cytological changes. Results: The size of the testes and accessory sex organs were found to be significantly reduced in BLC mice, whereas only testicular weight reduction was observed in ULC mice. Histopathological studies showed degenerative changes throughout the seminiferous tubules. Conclusion: Thus, the present investigation showed compensatory androgen production in ULC mice, whereas absence of androgen mediated reproductive functions in BLC animals.

  11. 肠道菌群变化对实验小鼠肠黏膜免疫的影响%Impact of intestinal flora changes on the intestinal mucosal immunity in laboratory mice

    Institute of Scientific and Technical Information of China (English)

    高倩; 王友明; 吴旧生

    2012-01-01

    目的 探讨肠道菌群变化对肠黏膜相关淋巴组织的影响.方法 通过变性梯度凝胶电泳( Denaturing gradient gel electrophoresis,DGGE)法研究了三种不同级别实验小鼠即清洁级小鼠、SPF小鼠和普通小鼠肠道菌群的组成,并用免疫组织化学( immunohistochemistry,IHC)方法研究了此三种不同级别的实验小鼠肠黏膜相关淋巴组织sIgA阳性细胞分布情况.结果 普通小鼠肠道细菌种类最多,其sIgA阳性细胞分布最多,肠道不同部位之间sIgA分布情况差异有显著性(P<0.05),小肠和大肠之间的阳性细胞分布差异极显著(P<0.01);其次是清洁级小鼠,其肠道不同部位之间菌种组成差异无显著性,小肠和大肠