Effects of thyroid state on respiration of perfused rat and guinea pig hearts

International Nuclear Information System (INIS)

Read, L.C.; Wallace, P.G.; Berry, M.N.

1987-01-01

The effects of thyroid state on the respiration of the isolated heart were investigated using retrograde perfused rat and guinea pig hearts. In both species, hypothyroidism caused a marked depression in circulating thyroid hormone concentrations and in the respiration of the isolated, retrograde perfused heart. Hypothyroidism was caused by injecting animals with Na 131 I. The effects on myocardial respiration could be attributed to changes in the contraction frequency and in the oxygen consumption per beat, with little contribution from basal respiration. Treatment of animals with thyroxine elevated plasma thyroid hormones to a similar extent in rats and guinea pigs. In the latter, thyroxine treatment was associated with substantial increases in the contraction frequency and the oxygen consumption per beat of the isolated heart. In contrast, only small changes were apparent in the retrograde perfused rat heart, observations that were confirmed in rat hearts perfused at near physiological work loads. It was concluded that rat hearts isolated from normal animals function at near maximal thyroid state, in contrast to the guinea pig heart, which requires higher circulating concentrations of thyroid hormones to attain maximal responses

Non-terminal blood sampling techniques in Guinea pigs

DEFF Research Database (Denmark)

Birck, Malene Muusfeldt; Tveden-Nyborg, Pernille; Lindblad, Maiken Marie

2014-01-01

Guinea pigs possess several biological similarities to humans and are validated experimental animal models(1-3). However, the use of guinea pigs currently represents a relatively narrow area of research and descriptive data on specific methodology is correspondingly scarce. The anatomical features...... of guinea pigs are slightly different from other rodent models, hence modulation of sampling techniques to accommodate for species-specific differences, e.g., compared to mice and rats, are necessary to obtain sufficient and high quality samples. As both long and short term in vivo studies often require...... repeated blood sampling the choice of technique should be well considered in order to reduce stress and discomfort in the animals but also to ensure survival as well as compliance with requirements of sample size and accessibility. Venous blood samples can be obtained at a number of sites in guinea pigs e...

Streptomycin action to the mammalian inner ear vestibular organs: comparison between pigmented guinea pigs and rats.

Science.gov (United States)

Meza, Graciela; Aguilar-Maldonado, Beatriz

2007-01-01

Streptomycin is the antibiotic of choice to treat tuberculosis and other infectious diseases but it causes vestibular malfunction and hipoacusia. Rodents are usually employed as models of drug action to the inner ear and results are extrapolated to what happens in humans. In rats, streptomycin destroys macular sensory cells and does not affect cochlear ones, whereas in guinea pigs the contrary is true. Action on the vestibular cristae cells involved in vestibulo-ocular reflex integrity is less clear. Thus, we compared this response in both pigmented guinea pigs (Cavia cobaya) and rats (Rattus norvegicus) after parallel streptomycin chronic treatment. In guinea pigs, the reflex was obliterated along treatment time; in rats this behavior was not observed, suggesting that the end organ target was diverse. In recent studies, streptidine, a streptomycin derivative found in the blood of humans and rats treated with streptomycin, was the actual ototoxic agent. The putative streptomycin vestibular organ target observed in humans corresponds with the guinea pig observations. Results observed in rats are controversial: streptidine did not cause any damage either to vestibular cristae nor auditory cells. We hypothesize differential drug metabolism and distribution and conclude that results in laboratory animals may not always be applicable in the human situation.

Changes of the kallikrein-kinin system in the course of the postirradiation syndrome in rats and guinea pigs

International Nuclear Information System (INIS)

Pouckova, P.; Pospisil, J.; Dienstbier, Z.

1978-01-01

Within the study of the postirradiation distortion of the hemocoagulation and hemostasis changes were investigated of the level of prekallikrein, kininogens, and kininases in the blood serum and plasma of the whole-body irradiated animals. The rats and guinea pigs were exposed to 800 R (206.4 mC.kg -1 ) and 300 R (77.4 mC.kg -1 ), respectively, of 60 Co gamma rays which represented the LD 50/30 for the two species. In the observed postirradiation time intervals i.e. 10, 30, 60, 120 min, 6, 12 and 24 hrs the changes of the level of prekallikrein were idential with those of the level of prekallikrein in the blood serum whole-body irradiated guinea pigs. At 2, 4, 7, 10, 12 and 14 days after irradiation the course of the level of the prekallikrein in the blood serum of the rats and guinea pigs showed mutual mirror symmetry. Changes were observed of the level of kininogens in the blood plasma of the rats and guinea pigs after the exposures to 800 and 300 R, respectively. In this case, the level of kininogens in the rats and guinea pigs had changed similarly, in the guinea pigs, however, the changes of the level of kininogens varied within the range of control values. The level of kininases in the blood plasma of irradiated rats reached its maximum value on the 4th day after total irradiation, and later decreased. In the blood plasma of irradiated guinea pigs the course of the level of kininases was characterized by mirror symmetry, always with maximum and minimum values on the 7th day after total exposure. (author)

Short-term toxicity studies with triphenyltin compounds in rats and guinea-pigs

NARCIS (Netherlands)

Verschuuren, H.G.; Kroes, R.; Vink, H.H.; Esch, G.J. van

1966-01-01

Short-term toxicity studies have been carried out in rats and guinea-pigs fed diets containing triphenyltin acetate (TPTA), triphenyltin hydroxide (TPTH) or triethyltin hydroxide (TETH) for 90 days at levels ranging from 0 to 50 ppm. The lowest dietary levels found to retard growth in rats and

Absorption of transuranic nitrates by rats, guinea pigs, and dogs

International Nuclear Information System (INIS)

Sullivan, M.F.

1978-01-01

Absorption of 238 Pu and 241 Am from the gstrointestinal tract was found to be quite similar for rats, guinea pigs, and dogs. Different oxidation state mixtures of 238 Pu nitrate (95% versus 65% Pu IV) were absorbed to about the same extent

Characteristics and function of bone marrow stromal adherent cells in normal and irradiated mice and guinea pigs

Energy Technology Data Exchange (ETDEWEB)

Changyu, Zheng; Ji, Liu; Xiaoying, Bi

1986-04-01

It has been shown from cytochemical and other characteristic studies of bone marrow stromal cells in CFU-F that there are seven types of stromal cells in the stromal adherent cell layer of normal and irradiated C/sub 57/ mice whereas there are only six types in guinea pigs. On the other hand, a radioresistant cell subtype appears in adherent layer after irradiation of both C/sub 57/ mice and guinea pig since the supernatant of cultured CFU-F of the normal and irradiated C/sub 57/ mice can stimulate production of CFU-Gm. It is justifiable that the bone marrow stromal adherent cells of the C/sub 57/ mice could produce CSF.

Effect of venlafaxine hydrochloride in different preparations of isolated guinea-pig and rat organ tissues.

Science.gov (United States)

Velasco, A; Arruza, A; Maroto, M; Carvajal, A; Fernández del Busto, E; García del Pozo, J

1999-04-01

A study was undertaken to know better the effects of venlafaxine hydrochloride on the responses of isolated rat vas deferens to noradrenaline and dopamine, those of isolated rat uterus to serotonin and histamine, and those of isolated guinea-pig ileum to acetylcholine and histamine. Venlafaxine hydrochloride increased the response of rat vas deferens to noradrenaline but not to dopamine. Venlafaxine did not alter the response of rat isolated uterus to serotonin. In rat uterus, venlafaxine did not modify the response to histamine but was able to increase it in guinea-pig ileum. An anticholinergic effect was observed with the lowest concentration tested. Although venlafaxine is a selective serotonine reuptake inhibitor in the central nervous system, serotonin uptake was not seen in the rat uterus. The anticholinergic effects observed in the present study might be consistent with some of the side-effects associated with venlafaxine.

Hepatic metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the rat and guinea pig

International Nuclear Information System (INIS)

Wroblewski, V.J.; Olson, J.R.

1985-01-01

Marked interspecies variability exists in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with the rat having an LD 50 about 25-fold greater than the guinea pig. The metabolism of TCDD was examined by incubating hepatocytes isolated from these animals with purified [ 14 C]TCDD (2.2 microM) for 8 hr. Over the 8-hr incubation, cytochrome P-450 content and ethoxyresorufin O-deethylase and benzphetamine N-demethylase activities were well maintained, indicating the functional viability of the hepatocytes. Quantitative differences were observed in the rate of [ 14 C]TCDD metabolism, with hepatocytes from control rats metabolizing TCDD at a rate 2.8-fold greater than hepatocytes from control guinea pigs. The role of the hepatic cytochrome P-450-448-dependent monooxygenase system in the metabolism of TCDD was examined through the use of hepatocytes isolated from animals pretreated with either TCDD or phenobarbital. The rate of [ 14 C]TCDD metabolite formation in hepatocytes from TCDD pretreated guinea pigs (0.26 +/- 0.14 pmol mg cell protein-1 hr-1) was unchanged from the control rate, while the rate in hepatocytes from TCDD pretreated rats was 3.2-fold greater than control and nine times greater than in hepatocytes from TCDD-pretreated guinea pigs. On the other hand, phenobarbital pretreatment produced little change in the rate of [ 14 C]TCDD metabolism in rat hepatocytes. These results suggest that TCDD may be metabolized by a TCDD inducible form of cytochrome P-448 which is expressed in the rat but not in the guinea pig

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

Science.gov (United States)

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

1994-01-01

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

Differential susceptibility of rats and guinea pigs to the ototoxic effects of ethyl benzene

NARCIS (Netherlands)

Cappaert, N.L.M.; Klis, S.F.L.; Muijser, H.; Kulig, B.M.; Ravensberg, L.C.; Smoorenburg, G.F.

2002-01-01

The present study was designed to compare the ototoxic effects of volatile ethyl benzene in guinea pigs and rats. Rats showed deteriorated auditory thresholds in the mid-frequency range, based on electrocochleography, after 550-ppm ethyl benzene (8 h/day, 5 days). Outer hair cell (OHC) loss was

Localization of plutonium retention in the small intestine of the neonatal rat, guinea pig, baboon and macaca after Pu-citrate ingestion

International Nuclear Information System (INIS)

Fritsch, P.; Lataillade, G.; Beauvallet, M.; L'Hullier, I.; Lepage, M.; Metivier, H.; Masse, R.; Moutairou, K.; avi, 526, Republique Populaire du Benin)

1988-01-01

The retention of Pu-citrate in the gastrointestinal wall was compared at similar post ingestion times after ingestion at 2 days of age by rats and guinea pigs and at 1 to 34 days by neonatal primates. The small intestine was the main site of the Pu retention in all species. In rats and primates, most of the Pu was retained in the distal ileum, whereas in guinea pigs it was more homogeneously distributed. In the rats, Pu was retained in the epithelial cells on villi, but in the guinea pigs and primates it was confined to the macrophages under the epithelial cells in the lacteal region. (author)

Protective immunity induced by 67 K outer membrane protein of phase I Coxiella burnetii in mice and guinea pigs

International Nuclear Information System (INIS)

Zhang, Y.X.; Zhi, N.; Yu, S.R.; Li, Q.J.; Yu, G.Q.; Zhang, X.

1994-01-01

A 67 K outer membrane protein (OMP) isolated from phase I Coxiella burnetii QiYi strain was purified with monoclonal antibodies (MoAb) coupled to CNBr-Sepharose 4B. Chemical analyses of the 67 K protein showed that it contained seventeen kids of amino acids and no lipopolysaccharides. The immunogenicity and protectivity of the 67 K protein against C. burnetii was evaluated in mice and guinea pigs bi in vitro lymphocyte proliferation assay, delayed-type skin test, antibody conversion rate, and immunization and challenge tests. Intraperitoneal injection of the 67 K protein resulted in antibody production against phase I and II whole cell antigens. The anti-67 K antibody conversion rate was found to be 100% in mice and guinea pigs as well. Lymphocytes were responses in vitro to specific antigen. In addition, delayed-type hypersensitivity appeared two weeks after immunization with the 67 K protein. Moreover, 199% of mice and guinea pigs inoculated with the 67 K protein were protected against a challenge with 10 3 ID 50 virulent C. burnetii. In conclusion, these results demonstrate that the 67 K OMP elicits in vivo and in vitro both B cell-mediated and T cell-mediated immunity in mice and guinea pigs. Thus the 67 K protein is a candidate for an effective subunit vaccine against Q fever. (author)

The Guinea Pig as a Model for Sporadic Alzheimer’s Disease (AD): The Impact of Cholesterol Intake on Expression of AD-Related Genes

Science.gov (United States)

Ong, Daniel; Wijaya, Linda; Laws, Simon M.; Taddei, Kevin; Newman, Morgan; Lardelli, Michael; Martins, Ralph N.; Verdile, Giuseppe

2013-01-01

We investigated the guinea pig, Cavia porcellus, as a model for Alzheimer’s disease (AD), both in terms of the conservation of genes involved in AD and the regulatory responses of these to a known AD risk factor - high cholesterol intake. Unlike rats and mice, guinea pigs possess an Aβ peptide sequence identical to human Aβ. Consistent with the commonality between cardiovascular and AD risk factors in humans, we saw that a high cholesterol diet leads to up-regulation of BACE1 (β-secretase) transcription and down-regulation of ADAM10 (α-secretase) transcription which should increase release of Aβ from APP. Significantly, guinea pigs possess isoforms of AD-related genes found in humans but not present in mice or rats. For example, we discovered that the truncated PS2V isoform of human PSEN2, that is found at raised levels in AD brains and that increases γ-secretase activity and Aβ synthesis, is not uniquely human or aberrant as previously believed. We show that PS2V formation is up-regulated by hypoxia and a high-cholesterol diet while, consistent with observations in humans, Aβ concentrations are raised in some brain regions but not others. Also like humans, but unlike mice, the guinea pig gene encoding tau, MAPT, encodes isoforms with both three and four microtubule binding domains, and cholesterol alters the ratio of these isoforms. We conclude that AD-related genes are highly conserved and more similar to human than the rat or mouse. Guinea pigs represent a superior rodent model for analysis of the impact of dietary factors such as cholesterol on the regulation of AD-related genes. PMID:23805206

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

Science.gov (United States)

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

2016-12-01

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

Gastrointestinal abosrption of radionuclides by the neonatal rat, guinea pig and swine

International Nuclear Information System (INIS)

Sullivan, M.F.

1977-01-01

Ruthenium-106 administered to newborn rats and swine was incorporated into the epithelium of the lower small intestine and retained there for a few weeks after gavage; the stomach and small bowel of guinea pigs incorporated 106 Ru but did not retain it

Mechanoelectric feedback does not contribute to the Frank-Starling relation in the rat and guinea pig heart

Directory of Open Access Journals (Sweden)

D Kelly

2014-12-01

Full Text Available Mechanoelectric feedback (MEF is the process by which mechanical forces on the myocardium can alter its electrical properties. The effect can be large enough to induce ectopic beats or fibrillation. However, the role of MEF at physiological levels of mechanical stress is not clear. We have investigated alteration in action potential morphology in rat and guinea pig ventricle and in rat atrial tissue at levels of stretch near the plateau of the Frank-Starling curve. Stretch of >100 mm.Hg End Diastolic Left Ventricular Pressure (EDLVP or rapidly applied stretch (EDLVP increased by 25 mm.Hg within 100 ms often triggered ectopic beats in isolated rat and guinea-pig hearts. However, ventricular epicardial monophasic action potentials (MAPs recorded during stretch to EDLVP up to 30 mm. Hg showed no consistent changes in action potential duration (at APD20, APD50 or APD80 in either species. MAP recording detected APD prolongation with very small concentrations of 4-AP (10 μM, confirming the discrimination of the recording technique. In isolated rat atrial strips, no changes in intracellular action potential morphology or membrane potential were seen when stretched to levels producing an optimum increase in contractility. We conclude that alteration in action potential morphology with stretch does not contribute to the Frank-Starling relation in ventricle of rat or guinea-pig isolated heart, or in rat atrial tissue.

Placental transfer of ruthenium in rat and guinea-pig

International Nuclear Information System (INIS)

Levack, V.M.; Pottinger, H.; Harrison, J.D.

1994-01-01

Ruthenium-106 in citrate solution was administered intravenously to rat at different stages of pregnancy and to guinea-pig either before conception or in late pregnancy. The results for rat showed that retention in the embryo/foetus measured at 3-5 days after administration increased from about 0.0002% of injected activity per embryo/foetus on day 12 of gestation to about 0.05% at birth. The relative concentrations of 106 Ru in embryo/foetus and mother (C f /C m ratio) were about 0.1 in each case. Concentrations in the yolk sac on day 12 were about 1% g -1 compared with 0.01% g -1 kin the foetus/ Retention in the guinea-pig foetus in late gestation at 7 days after administration (days 50-57) was about 0.2% injected activity per foetus, corresponding to a C f /C m = 0.2. Retention in each foetoplacental unit was 2% of injected 106 Ru with 50% in the yolk sac, 35% in the placenta and 10% in the foetus. For administration 4 weeks prior to conception, the level of 106 Ru retained in the foetus on day 57 of gestation was two orders of magnitude lower than after short-term administration, with a C f /C m about 0.004. (author)

Opioid binding sites in the guinea pig and rat kidney: Radioligand homogenate binding and autoradiography

Energy Technology Data Exchange (ETDEWEB)

Dissanayake, V.U.; Hughes, J.; Hunter, J.C. (Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge (England))

1991-07-01

The specific binding of the selective {mu}-, {delta}-, and {kappa}-opioid ligands (3H)(D-Ala2,MePhe4,Gly-ol5)enkephalin ((3H) DAGOL), (3H)(D-Pen2,D-Pen5)enkephalin ((3H)DPDPE), and (3H)U69593, respectively, to crude membranes of the guinea pig and rat whole kidney, kidney cortex, and kidney medulla was investigated. In addition, the distribution of specific 3H-opioid binding sites in the guinea pig and rat kidney was visualized by autoradiography. Homogenate binding and autoradiography demonstrated the absence of {mu}- and {kappa}-opioid binding sites in the guinea pig kidney. No opioid binding sites were demonstrable in the rat kidney. In the guinea pig whole kidney, cortex, and medulla, saturation studies demonstrated that (3H)DPDPE bound with high affinity (KD = 2.6-3.5 nM) to an apparently homogeneous population of binding sites (Bmax = 8.4-30 fmol/mg of protein). Competition studies using several opioid compounds confirmed the nature of the {delta}-opioid binding site. Autoradiography experiments demonstrated that specific (3H)DPDPE binding sites were distributed radially in regions of the inner and outer medulla and at the corticomedullary junction of the guinea pig kidney. Computer-assisted image analysis of saturation data yielded KD values (4.5-5.0 nM) that were in good agreement with those obtained from the homogenate binding studies. Further investigation of the {delta}-opioid binding site in medulla homogenates, using agonist ((3H)DPDPE) and antagonist ((3H)diprenorphine) binding in the presence of Na+, Mg2+, and nucleotides, suggested that the {delta}-opioid site is linked to a second messenger system via a GTP-binding protein. Further studies are required to establish the precise localization of the {delta} binding site in the guinea pig kidney and to determine the nature of the second messenger linked to the GTP-binding protein in the medulla.

COMPARATIVE GENOTOXIC RESPONSES TO ARSENITE IN GUINEA PIG, MOUSE, RAT AND HUMAN LYMPHOCYTES

Science.gov (United States)

Comparative genotoxic responses to arsenite in guinea pig, mouse, rat and human lymphocytes.Inorganic arsenic is a known human carcinogen causing skin, lung, and bladder cancer following chronic exposures. Yet, long-term laboratory animal carcinogenicity studies have ...

Gastrointestinal absorption and retention of polonium in adult and newborn rats and guinea pigs

International Nuclear Information System (INIS)

Haines, J.W.; Naylor, G.P.L.; Pottinger, H.; Harrison, J.D.

1993-01-01

The gastrointestinal absorption of 210 Po was determined by comparing tissue retention after oral and systemic administration. The results indicate an increase in absorption in adult rats for 210 Po administered in liver compared with 210 Po nitrate with estimated absorption of 5 and 13%, respectively. For 210 Po citrate, values of about 7% were obtained in 1-day-old neonate and adult rats while absorption in guinea pigs was estimated to be about 23% in 1-day-old neonates, 17% in 5-day-old neonates, and 9% in adults. Gut retention of ingested 210 Po in neonates was high in rats but not guinea pigs. In adult animals, but not neonates, the liver accounted for a greater proportion of 210 Po reaching the bloodstream after ingestion than after systemic injection. The significance of these results is discussed in relation to current assumptions made in the calculation of doses from 210 Po. (author)

Arginine-esterase activity of kallikrein in the sera of whole-body irradiated rats and guinea-pigs

Energy Technology Data Exchange (ETDEWEB)

Pouckova, P; Pospisil, J; Dienstbier, Z [Karlova Univ., Prague (Czechoslovakia). Biofyzikalni Ustav

1977-09-01

In whole-body irradiated rats (800 R=LDsub(50/30)) and guinea pigs (300 R=LDsub(50/30)) changes were investigated in the arginine esterase activity of kallikrein in native serum as well as in serum exposed to contact with a clay suspension. From the values obtained the activity of prekallikrein was calculated. While in the rat serum significant changes in the arginine esterase activity of kallikrein were found, in the guinea pig serum the kallikrein activity did not change markedly. The activity of prekallikrein immediately after irradiation assumes a similar course in both types of laboratory animals while during later intervals a reverse pattern was observed.

Nasal cavity dimensions in guinea pig and rat measured by acoustic rhinometry and fluid-displacement method

DEFF Research Database (Denmark)

Straszek, Sune; Pedersen, O.F.

2004-01-01

The purpose of the study was to measure nasal passageway dimensions in guinea pigs and rats by use of acoustic rhinometry (AR) and by a previously described fluid-displacement method (FDM) (Straszek SP, Taagehoej F, Graff S, and Pedersen OF. J Appl Physiol 95: 635-642, 2003) to investigate...... the potential of AR in pharmacological research with these animals. We measured the area-distance relationships by AR of nasal cavities postmortem in five guinea pigs (Duncan Hartley, 400 g) and five rats (Wistar, 250 g) by using custom-made equipment scaled for the purpose. Nosepieces were made from plastic...... pipette tips and either inserted into or glued onto the nostrils. We used liquid perfluorocarbon in the fluid-displacement study, and it was carried out subsequent to the acoustic measurements. We found for guinea pigs that AR measured a mean volume of 98 mm(3) (95-100 mm(3)) (mean and 95% confidence...

Absorption of cadmium in the newborn and juvenile guinea pig

International Nuclear Information System (INIS)

Sasser, L.B.; Jarboe, G.E.

1978-01-01

The accepted premise that absorption is enhanced in the newborn animal is based primarily on studies using the rat, which has a relatively immature gastrointestinal system at birth. This study was conducted to determine if enhanced absorption of cadmium also occurs in the guinea pig, a species that is more precocious at birth than the rat. Newborn guinea pigs were administered a single oral dose of 5 μCi of /sup 115m/Cd (0.25 mCi of /sup 115m/Cd per milligram of cadmium) between 8 and 24 hr of age and killed at intervals between 1 and 14 days after the dosing. Juvenile guinea pigs were similarly dosed with 20 μCi of /sup 115m/Cd and killed 1 to 5 days later. Guinea pigs dosed on the day of birth absorbed approximately 6% of the dose by 1 day after the dosing and nearly 25% of the dose by 11 days. This is a cumulative absorption five times that found in rats dosed at 24 hr and two times that of rats dosed at 2 hr. The residence time of cadmium in the gastrointestinal tract was longer in newborn guinea pigs than in juvenile guinea pigs but was still significantly less than that in the newborn rat. We concluded that the absorption of cadmium from the gastrointestinal tract was greater in newborn guinea pigs than in rats, even though the residence time of cadmium in the intestinal tract was less in guinea pigs than in rats and the maturity at birth of the guinea pig is greater than that of the rat. The bases of these differences were not readily apparent

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

International Nuclear Information System (INIS)

Niehoff, D.L.

1989-01-01

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

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.

Malignant transformation of guinea pig cells after exposure to ultraviolet-irradiated guinea pig cytomegalovirus

International Nuclear Information System (INIS)

Isom, H.C.; Mummaw, J.; Kreider, J.W.

1983-01-01

Guinea pig cells were malignantly transformed in vitro by ultraviolet (uv)-irradiated guinea pig cytomegalovirus (GPCMV). When guinea pig hepatocyte monolayers were infected with uv-irradiated GPCMV, three continuous epithelioid cell lines which grew in soft agarose were established. Two independently derived GPCMV-transformed liver cells and a cell line derived from a soft agarose clone of one of these lines induced invasive tumors when inoculated subcutaneously or intraperitoneally into nude mice. The tumors were sarcomas possibly derived from hepatic stroma or sinusoid. Transformed cell lines were also established after infection of guinea pig hepatocyte monolayers with human cytomegalovirus (HCMV) or simian virus 40 (SV40). These cell lines also formed colonies in soft agarose and induced sarcomas in nude mice. It is concluded that (i) GPCMV can malignantly transform guinea pig cells; (ii) cloning of GPCMV-transformed cells in soft agarose produced cells that induced tumors with a shorter latency period but with no alteration in growth rate or final tumor size; and (iii) the tumors produced by GPCMV-and HCMV-transformed guinea pig cells were more similar to each other in growth rate than to those induced by SV40-transformed guinea pig cells

Effect of compensating filters on the isodose charts of rat and guinea-pig phantoms irradiated with ''fission-neutrons''

Energy Technology Data Exchange (ETDEWEB)

Zar' and, P

1976-01-01

Isodose charts were calculated for rat and guinea-pig phantoms exposed to a modified fission spectrum with a most probable energy of 1.3 MeV. Infinite tissue equivalent cylinders (r = 2.5 and 3.3 cm) and a plane source emitting neutrons according to a cosine distribution were assumed and an albedo code was used. Combined effect of (tissue-equivalent or polyethylene) compensating filters (or simply filters) and a bilateral irradiation or rotation was studied. Bilateral irradiation and the use of a filter resulted in a uniform irradiation of a rat phantom (Dmax/Dmin less than 1.15), while a uniform irradiation of a guinea-pig phantom could be obtained by the combined use of filters and rotation. If rotation is possible a Dmax/Dmin less than 1.05 ratio can be achieved. Filters + rotation should be used in all circumstances when geometrical restrictions do not prevent the installation of a rotation equipment. In this case bilateral irradiation + compensating filters are advisable. Unilateral irradiation of small laboratory animals (mouse, rat, guinea-pig) should be avoided.

A critical examination of the occurrence of FMRFamide immunoreactivity in the brain of guinea pig and rat

DEFF Research Database (Denmark)

Triepel, J; Grimmelikhuijzen, C J

1984-01-01

Several reports (cf. Weber et al. (1981) Science 214:1248-1251) have described the extensive occurrence, in rat brain, of material immunologically related to the molluscan neuropeptide FMRFamide. We have reexamined these data in guinea pig and rat, using six different antisera to FMRFamide...

Sulfide silver architectonics of rat, cat, and guinea pig spinal cord. A light microscopic study with Timm's method for demonstration of heavy metals

DEFF Research Database (Denmark)

Schroder, H D

1977-01-01

The distribution of heavy metals in the spinal cord of the cat, rat, and guinea pig has been studied histochemically with Timm's sulfide silver method. There was considerable variation in the degree of staining of the neuropil. The dorsal horn showed a laminar staining pattern corresponding...... to the cytoarchitectonic lamination. Lamina I in the cat and guinea pig was light. Lamina II in all three species was heavily stained. In the rat and guinea pig it could be subdivided in a ventral and a dorsal layer, and moreover in the rat a darkly staining borderzone abutting on lamina III was present. Lamina III......, characterized by heterogeneous staining, also appeared dark, although less obvious in the guinea pig. In the ventral horn the coarser stained particles in lamina IX contrasted with the surrounding lamina. Cell staining varied between different cell groups, and within single cell populations. In the cat thoracic...

CHARACTERIZATION OF MUSCARINIC RECEPTORS IN GUINEA-PIG UTERUS

NARCIS (Netherlands)

DOODS, HN; WILLIM, KD; BODDEKE, HWGM; ENTZEROTH, M

1993-01-01

To characterize the muscarinic receptor present in guinea-pig uterus smooth muscle the affinities of a series of 27 muscarinic receptor antagonists for M1 (rat cortex), M2 (rat heart), M3 (rat submandibular gland), m4 (transfected in CHO cells) and muscarinic binding sites in guinea-pig uterus

Deposition and retention patterns for 3-, 9-, and 15-micron latex microspheres inhaled by rats and guinea pigs

International Nuclear Information System (INIS)

Snipes, M.B.; Olson, T.R.; Yeh, H.C.

1988-01-01

This study was designed to determine the deposition patterns and fate of large particles inhaled by two species of small laboratory animals during nose breathing. Rats and guinea pigs inhaled 3-, 9-, or 15 micron polystyrene latex microspheres labeled with 46 Sc. Approximately 1.4% and 0.55% of the initial internally deposited body burden of 3-micron microspheres was in the alveolar region of the respiratory tract of rats and guinea pigs, respectively. None of the 9- or 15-micron microspheres were detected in the alveolar regions of the rats or guinea pigs. Ninety-five to 99% of the deposited microspheres cleared from these animals with biological half-times of 0.5-1.0 day. Most of the cleared radioactivity was in the feces. Approximations for long-term biological half-times for alveolar retention of the 3-micron microspheres were 63 days for rats and 83 days for guinea pigs. About 1% of the initial lung burden of 3-micron microspheres was translocated from lung to lung-associated lymph nodes in both species; none of the 9- or 15-micron microspheres were detected in those lymph nodes. Small fractions of the microspheres initially deposited in the airways of the head were retained with biological clearance half-times ranging from 9 to 350 days. Results from this study do not allow projections for deposition and retention patterns for similar particles inhaled by humans. Such projections must come from studies with humans, or from studies with animal species having deposition patterns for inhaled materials more comparable to those of humans

Non-terminal blood sampling techniques in guinea pigs.

Science.gov (United States)

Birck, Malene M; Tveden-Nyborg, Pernille; Lindblad, Maiken M; Lykkesfeldt, Jens

2014-10-11

Guinea pigs possess several biological similarities to humans and are validated experimental animal models(1-3). However, the use of guinea pigs currently represents a relatively narrow area of research and descriptive data on specific methodology is correspondingly scarce. The anatomical features of guinea pigs are slightly different from other rodent models, hence modulation of sampling techniques to accommodate for species-specific differences, e.g., compared to mice and rats, are necessary to obtain sufficient and high quality samples. As both long and short term in vivo studies often require repeated blood sampling the choice of technique should be well considered in order to reduce stress and discomfort in the animals but also to ensure survival as well as compliance with requirements of sample size and accessibility. Venous blood samples can be obtained at a number of sites in guinea pigs e.g., the saphenous and jugular veins, each technique containing both advantages and disadvantages(4,5). Here, we present four different blood sampling techniques for either conscious or anaesthetized guinea pigs. The procedures are all non-terminal procedures provided that sample volumes and number of samples do not exceed guidelines for blood collection in laboratory animals(6). All the described methods have been thoroughly tested and applied for repeated in vivo blood sampling in studies within our research facility.

Studies on the percutaneous absorption of /sup 14/C-labelled Flurbiprofen, 3. Whole body autoradiography of rats and guinea-pigs

Energy Technology Data Exchange (ETDEWEB)

Nagao, Soshichi; Sakai, Takeo; Hayakawa, Toru (Nihon Univ., Tokyo. Coll. of Agriculture and Veterinary Medicine)

1983-03-01

Whole body autoradiography was carried out to clarify and compare the distribution of /sup 14/C-labelled Flurbiprofen which was applied to the skin as an ointment in rats and guinea-pigs. Both in rats and guinea-pigs almost the same autoradiogram was gained. The radioactivity was strongest at the skin area inspite of the time elapse, showing that the drug was fixed in the site of skin applied. In other parts of the body, however, it was small except the kidney and intestine. It seemed that the absorption of the drug was a little although the migration of the drug into the blood circulation is fast at the beginning as was shown in pigs previously. A stronger radioactivity in the kidney and intestine might indicate that a main pathway of excretion of this drug was through those two organs. Absorption, distribution and excretion of the drug were not different between rats and guinea-pigs, similar to those observed in pigs.

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

Energy Technology Data Exchange (ETDEWEB)

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

1989-03-01

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

Molecular cloning and expression of the calmodulin gene from guinea pig hearts.

Science.gov (United States)

Feng, Rui; Liu, Yan; Sun, Xuefei; Wang, Yan; Hu, Huiyuan; Guo, Feng; Zhao, Jinsheng; Hao, Liying

2015-06-01

The aim of the present study was to isolate and characterize a complementary DNA (cDNA) clone encoding the calmodulin (CaM; GenBank accession no. FJ012165) gene from guinea pig hearts. The CaM gene was amplified from cDNA collected from guinea pig hearts and inserted into a pGEM®-T Easy vector. Subsequently, CaM nucleotide and protein sequence similarity analysis was conducted between guinea pigs and other species. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to investigate the CaM 3 expression patterns in different guinea pig tissues. Sequence analysis revealed that the CaM gene isolated from the guinea pig heart had ∼90% sequence identity with the CaM 3 genes in humans, mice and rats. Furthermore, the deduced peptide sequences of CaM 3 in the guinea pig showed 100% homology to the CaM proteins from other species. In addition, the RT-PCR results indicated that CaM 3 was widely and differentially expressed in guinea pigs. In conclusion, the current study provided valuable information with regard to the cloning and expression of CaM 3 in guinea pig hearts. These findings may be helpful for understanding the function of CaM3 and the possible role of CaM3 in cardiovascular diseases.

Functional analysis of guinea pig β1-adrenoceptor.

Science.gov (United States)

Tanaka, Yoshio; Takahashi, Hiromi; Shibata, Sayuri; Namiki, Kana; Kimura, Sadao; Koike, Katsuo; Kasuya, Yoshitoshi

2011-12-01

Although similarity of pharmacological responses to certain stimuli between guinea pigs and humans has been reported, this has been poorly defined by a molecular biological approach. In this study, we cloned the gene of guinea pig ?1-adrenoceptor (ADRB1). The deduced amino acid sequence of guinea pig ADRB1 (467-aa) showed 91% and 92% identity with the human and rat ADRB1 sequences, respectively. Using HEK293T cells expressing guinea pig, human and rat ADRB1s independently, we elucidated the functional characteristics of each ADRB1. The ligand-binding profiles and the concentration-response relationships for isoprenaline-induced cyclic adenosine monophosphate (cAMP) production were similar among the three ADRB1s. Isoprenaline also induced phosphorylation of extracellular-signal related kinases (ERK) through ADRB1s in a concentration-dependent manner. The minimum effective concentration of isoprenaline for phosphorylation of ERK, through guinea pig ADRB1 was the same as through human ADRB1, but markedly lower than that of through rat ADRB1. ERK phosphorylation through guinea pig ADRB1 was sensitive to pertussis toxin, a dominant-negative ras and PD98059, indicating that a G(i)-mediated pathway is involved in the ADRB1/ERK signaling loop. These results suggest that the G(i)-coupling efficacy of guinea pig and human ADRB1s may be higher than that of rat ADRB1.

Listeria monocytogenes strains encoding premature stop codons in inlA invade mice and guinea pig fetuses in orally dosed dams

DEFF Research Database (Denmark)

Holch, Anne; Ingmer, Hanne; Licht, Tine Rask

2013-01-01

potential of a group of food-processing persistent L. monocytogenes strains encoding a premature stop codon in inlA (encoding internalin A) by using two orally dosed models, pregnant mice and pregnant guinea pigs. A food-processing persistent strain of L. monocytogenes invaded placentas (n = 58; 10...... % positive) and fetuses (3 % positive) of pregnant mice (n = 9 animals per strain), similar to a genetically manipulated murinized strain, EGD-e InlAm* (n = 61; 3 and 2 %, respectively). In pregnant guinea pigs (n = 9 animals per bacterial strain), a maternofetal strain (from a human fetal clinical fatal...... case) was isolated from 34 % of placenta samples (n = 50), whereas both food-processing persistent strains were found in 5 % of placenta samples (n = 36 or 37). One of the food-processing persistent strains, N53-1, was found in up to 8 % of guinea pig fetal liver and brain samples, whereas...

Intestinal absorption and retention of cadmium in neonatal pigs compared to rats and guinea pigs

International Nuclear Information System (INIS)

Sasser, L.B.; Jarboe, G.E.

1980-01-01

The purpose of this study was to measure intestinal absorption and retention of cadmium in the newborn pig and to compare data from the pig, rat and guinea pig, three species that differ greatly in their ability to absorb macromolecules at birth. Newborn pigs were administered a single oral dose of 50 μCi of /sup 115m/Cd 24 hours after birth and killed at intervals between 1 and 14 days after dosing. Cd absorption and gastrointestinal retention were then determined; these data were compared with similar data from the rat and guinea pig. Cd absorption in the neonate appears to be a two-step process; mucosal uptake of Cd from the lumen, probably by pinocytosis, followed by transfer of a portion of this Cd into the body. This transfer process is similar, but does not entirely coincide with changes associated with protein absorption in the neonate

Comparative Study of the Liver Anatomy in the Rat, Rabbit, Guinea Pig and Chinchilla

Directory of Open Access Journals (Sweden)

Florin Gheorghe STAN

2018-05-01

Based on detailed study of the macroscopic anatomy of rat, rabbit, guinea pig and chinchilla a proper experimental model in liver research, could be assessed. In this regard, the vascular anatomy of the liver in the mentioned species is of a great importance and it is subject of another report.

Evaluation of Ebola Virus Countermeasures in Guinea Pigs.

Science.gov (United States)

Marzi, Andrea

2017-01-01

Ebola virus (EBOV) pathology in humans remains incompletely understood; therefore, a number of rodent and nonhuman primate (NHP) models have been established to study the disease caused by this virus. While the macaque model most accurately recapitulates human disease, rodent models, which display only certain aspects of human disease but are more cost-effective, are widely used for initial screens during EBOV countermeasure development. In particular, mice and guinea pigs were among the first species used for the efficacy testing of EBOV vaccines and therapeutics. While mice have low predictive value, guinea pigs have proven to be a more reliable predictor for the evaluation of countermeasures in NHPs. In addition, guinea pigs are larger in size compared to mice, allowing for more frequent collection of blood samples at larger volumes. However, guinea pigs have the disadvantage that there is only a limited pool of immunological tools available to characterize host responses to vaccination, treatment and infection. In this chapter, the efficacy testing of an EBOV vaccine and a therapeutic in the guinea pig model are described.

Testing the hypothesis that vitamin C deficiency is a risk factor for clozapine-induced agranulocytosis using guinea pigs and ODS rats.

Science.gov (United States)

Ip, Julia; Wilson, John X; Uetrecht, Jack P

2008-04-01

The use of clozapine is limited by a relatively high incidence of drug-induced agranulocytosis. Clozapine is oxidized by bone marrow cells to a reactive nitrenium ion. Although many idiosyncratic drug reactions are immune-mediated, the fact that patients with a history of clozapine-induced agranulocytosis do not immediately develop agranulocytosis on rechallenge suggests that some other factor may be responsible for the idiosyncratic nature of this reaction. The reactive nitrenium ion is very rapidly reduced back to clozapine by vitamin C, and many schizophrenic patients are vitamin C deficient. We set out to test the hypothesis that vitamin C deficiency is a major risk factor for clozapine-induced agranulocytosis using a vitamin C deficient guinea pig model. Although the vitamin C deficient guinea pigs did not develop agranulocytosis, the amount of clozapine covalent binding in these animals was less than we had previously observed in samples from rats and humans. Therefore, we studied ODS rats that also cannot synthesize vitamin C. Vitamin C deficient ODS rats also did not develop agranulocytosis, and furthermore, although covalent binding in the bone marrow was greater than that in the guinea pig, it was not increased in the vitamin C deficient ODS rats relative to ODS rats that had adequate vitamin C in their diet. Therefore, it is very unlikely that vitamin C deficiency is a major risk factor for clozapine-induced agranulocytosis.

The actions of isoprenaline and mirabegron in the isolated whole rat and guinea pig bladder.

Science.gov (United States)

Persyn, Sara; De Wachter, Stefan; Wyndaele, Jean-Jacques; Eastham, Jane; Gillespie, James

2016-07-01

β3-adrenoceptor agonists influence overactive bladder in humans and animal models. However, data is emerging that the mode of action of these drugs is complex. The present study explored the actions of the β3-adrenergic agonist mirabegron and the non-selective agonist isoprenaline on the contractile systems in the rat and guinea pig bladder. Intravesical pressure was measured in isolated whole bladders from female adult animals. In both species spontaneous contractile activity was observed. The muscarinic agonist arecaidine produced complex responses consisting of an initial transient pressure rise followed by complex phasic activity. Three contractile elements were identified: intrinsic micro-contractile activity, initial transient response and steady state phasic activity. The intrinsic and steady state activity could be further divided into a baseline pressure with superimposed phasic activity. The effects of isoprenaline and mirabegron were investigated on these elements. In the rat, the micro-contractile activity could be completely inhibited by isoprenaline (full agonist). The arecaidine-induced initial and steady state baseline pressures were partially reduced, while the phasic activity was little affected. In the guinea pig, both the arecaidine-induced baseline pressure and the phasic activity were affected by isoprenaline. Mirabegron didn't produce significant inhibitory effects in any of the contractile elements in either species. These results show that complex contractile systems operate in the rat and guinea pig bladder that can be modulated by β1/β2-adrenoceptor mechanisms. No evidence was obtained for any β3-dependent regulation of contraction. These data support similar data in humans. Therefore the primary site of therapeutic action of β3-adrenergic agonists remains unknown. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of endorphins on different parts of the gastrointestinal tract of rat and guinea-pig in vitro.

Science.gov (United States)

Nijkamp, F P; Van Ree, J M

1980-04-01

1 The spasmogenic and spasmolytic effects of beta-lipotropin (LPH) fragments and one analogue were investigated on different parts of the gastro-intestinal tract of guinea-pig and rat in vitro.2 Changes in muscle tone were observed in colon and rectum and to a lesser extent in jejunum and ileum of both species. Rat colon and rectum contracted to the peptides. Guinea-pig colon and rectum relaxed after an initial short-lasting contraction.3 On the rat rectum (D-ala(2))met-enkephalin, leu-enkephalin, gamma-endorphin, alpha-endorphin and beta-LPH 80-91 caused dose-dependent contractions, their ED(50) values being 0.96 x 10(-12) mol, 1.05 x 10(-11) mol, 1.22 x 10(-11) mol, 1.08 x 10(-10) mol, 2.65 x 10(-10) mol and 6.5 x 10(-9) mol, respectively.4 Naloxone dose-dependently shifted the dose-response curve of met-enkephalin to the right. Atropine, hexamethonium, burimamide, mepyramine, propranolol and indomethacin did not influence the response to met-enkephalin.5 In the presence of tetrodotoxin, the ED(50) for met-enkephalin and the maximal contractor response induced by met-enkephalin, appeared to be increased.6 The 5-hydroxytryptamine (5-HT) antagonists, methysergide and cyproheptadine, reduced the contractor response in a non-competitive manner. The alpha-adrenoceptor antagonist phentolamine, in contrast, caused an increase of the maximal response to met-enkephalin of up to 200%. Noradrenergic and tryptaminergic systems, therefore, might be involved in the changes in muscle tone induced by met-enkephalin.7 These results demonstrate that rectum and colon of guinea-pig and rat are very sensitive to opioid-like peptides.

Absorption and retention of inorganic and organically incorporated technetium-95 by rats and guinea pigs

International Nuclear Information System (INIS)

Sullivan, M.F.; Graham, T.M.; Cataldo, D.A.; Schreckhise, R.G.

1978-01-01

Transport of /sup 95m/Tc, administered in both an inorganic and organically incorporated form, was measured across the gastrointestinal tracts of rats and guinea pigs. Absorption of Tc incorporated in animal tissue was about half that of inorganic pertechnitate administered by gavage. The form in which it was administered did not alter elimination rates. When Tc was administered to newborn rats by gavage, 50% remained in carcasses at 1 wk, mostly associated with the pelt, whereas only about 10% was retained by adults

Effect of low dose x irradiation on the succinate dehydrogenase activity of guinea pig, rat and mouse tissues

Energy Technology Data Exchange (ETDEWEB)

Shah, V C; Bhatavdekar, J M; Aravinda Babu, K [Gujarat Univ., Ahmedabad (India). Dept. of Zoology

1976-07-01

The histochemical changes in succinate dehydrogenase (SDH) were investigated in pectoralis major muscle of guinea pig, rat and mouse after level X-irradiation (72 R and 240 R) and compared with control animals. Biochemical studies were carried out on liver, kidney, muscle (pectoralis major), adrenal and spleen of these animals after low dose local X-irradiation and compared with control animals. Changes in SDH activity were studied up to 72-h post-irradiation, which shows that low dose local X-irradiation leads to increased enzymic activity. The increase in enzymic activity was remarkable in mouse tissues as compared with guinea pig and rat. Adrenals of all the three animals showed significant activation after all the doses of radiation studied. The significance of these results, with special reference to oxidative metabolism, has been discussed.

The guinea pig as an animal model for developmental and reproductive toxicology studies.

Science.gov (United States)

Rocca, Meredith S; Wehner, Nancy G

2009-04-01

Regulatory guidelines for developmental and reproductive toxicology (DART) studies require selection of "relevant" animal models as determined by kinetic, pharmacological, and toxicological data. Traditionally, rats, mice, and rabbits are the preferred animal models for these studies. However, for test articles that are pharmacologically inactive in the traditional animal models, the guinea pig may be a viable option. This choice should not be made lightly, as guinea pigs have many disadvantages compared to the traditional species, including limited historical control data, variability in pregnancy rates, small and variable litter size, long gestation, relative maturity at birth, and difficulty in dosing and breeding. This report describes methods for using guinea pigs in DART studies and provides results of positive and negative controls. Standard study designs and animal husbandry methods were modified to allow mating on the postpartum estrus in fertility studies and were used for producing cohorts of pregnant females for developmental studies. A positive control study with the pregnancy-disrupting agent mifepristone resulted in the anticipated failure of embryo implantation and supported the use of the guinea pig model. Control data for reproductive endpoints collected from 5 studies are presented. In cases where the traditional animal models are not relevant, the guinea pig can be used successfully for DART studies. (c) 2009 Wiley-Liss, Inc.

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

Science.gov (United States)

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

1992-07-01

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

Correlation between oxytocin neuronal sensitivity and oxytocin receptor binding: An electrophysiological and autoradiographical study comparing rat and guinea pig hippocampus

International Nuclear Information System (INIS)

Raggenbass, M.; Tribollet, E.; Dubois-Dauphin, M.; Dreifuss, J.J.

1989-01-01

In transverse hippocampal slices from rat and guinea pig brains, the authors obtained unitary extracellular recordings from nonpyramidal neurones located in or near the stratum pyramidale in the CA1 field and in the transition region between the CA1 and the subiculum. In rats, these neurones responded to oxytocin at 50-1,000 nM by a reversible increase in firing rate. The oxytocin-induced excitation was suppressed by a synthetic structural analogue that acts as a potent, selective antioxytocic on peripheral receptors. Nonpyramidal neurones were also excited by carbachol at 0.5-10 μM. The effect of this compound was postsynaptic and was blocked by the muscarinic antagonist atropine. In guinea pigs, by contrast, nonpyramidal neurones were unaffected by oxytocin, although they were excited by carbachol. Light microscopic autoradiography, carried out using a radioiodinated selective antioxytocic as a ligand, revealed labeling in the subiculum and in the CA1 area of the hippocampus of rats, whereas no oxytocin-binding sites were detected in the hippocampus of guinea pigs. The results indicate (i) that a hippocampal action of oxytocin is species-dependent and (ii) that a positive correlation exists between neuronal responsiveness to oxytocin and the presence in the hippocampus of high-affinity binding sites for this peptide

Cardiac actions of phencyclidine in isolated guinea pig and rat heart: possible involvement of slow channels

International Nuclear Information System (INIS)

Temma, K.; Akera, T.; Ng, Y.C.

1985-01-01

The mechanisms responsible for the positive inotropic effect of phencyclidine were studied in isolated preparations of guinea pig and rat heart. In electrically paced left atrial muscle preparations, phencyclidine increased the force of contraction; rat heart muscle preparations were more sensitive than guinea pig heart muscle preparations. The positive inotropic effect of phencyclidine was not significantly reduced by a combination of phentolamine and nadolol; however, the effect was competitively blocked by verapamil in the presence of phentolamine and nadolol. Inhibition of the outward K+ current by tetraethylammonium chloride also produced a positive inotropic effect; however, the effect of tetraethylammonium was reduced by phentolamine and nadolol, and was almost insensitive to verapamil. The inotropic effect of phencyclidine was associated with a marked prolongation of the action potential duration and a decrease in maximal upstroke velocity of the action potential, with no change in the resting membrane potential. The specific [ 3 H]phencyclidine binding observed with membrane preparations from guinea pig ventricular muscle was saturable with a single class of high-affinity binding site. This binding was inhibited by verapamil, diltiazem, or nitrendipine, but not by ryanodine or tetrodotoxin. These results suggest that the positive inotropic effect of phencyclidine results from enhanced Ca 2+ influx via slow channels, either by stimulation of the channels or secondary to inhibition of outward K + currents

Calibration and validation of a physiologically based model for soman intoxication in the rat, marmoset, guinea pig and pig.

Science.gov (United States)

Chen, Kaizhen; Seng, Kok-Yong

2012-09-01

A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model has been developed for low, medium and high levels of soman intoxication in the rat, marmoset, guinea pig and pig. The primary objective of this model was to describe the pharmacokinetics of soman after intravenous, intramuscular and subcutaneous administration in the rat, marmoset, guinea pig, and pig as well as its subsequent pharmacodynamic effects on blood acetylcholinesterase (AChE) levels, relating dosimetry to physiological response. The reactions modelled in each physiologically realistic compartment are: (1) partitioning of C(±)P(±) soman from the blood into the tissue; (2) inhibition of AChE and carboxylesterase (CaE) by soman; (3) elimination of soman by enzymatic hydrolysis; (4) de novo synthesis and degradation of AChE and CaE; and (5) aging of AChE-soman and CaE-soman complexes. The model was first calibrated for the rat, then extrapolated for validation in the marmoset, guinea pig and pig. Adequate fits to experimental data on the time course of soman pharmacokinetics and AChE inhibition were achieved in the mammalian models. In conclusion, the present model adequately predicts the dose-response relationship resulting from soman intoxication and can potentially be applied to predict soman pharmacokinetics and pharmacodynamics in other species, including human. Copyright © 2011 John Wiley & Sons, Ltd.

Seasonal superoxide overproduction and endothelial activation in guinea-pig heart; seasonal oxidative stress in rats and humans.

Science.gov (United States)

Konior, Anna; Klemenska, Emilia; Brudek, Magdalena; Podolecka, Ewa; Czarnowska, Elżbieta; Beręsewicz, Andrzej

2011-04-01

Seasonality in endothelial dysfunction and oxidative stress was noted in humans and rats, suggesting it is a common phenomenon of a potential clinical relevance. We aimed at studying (i) seasonal variations in cardiac superoxide (O(2)(-)) production in rodents and in 8-isoprostane urinary excretion in humans, (ii) the mechanism of cardiac O(2)(-) overproduction occurring in late spring/summer months in rodents, (iii) whether this seasonal O(2)(-)-overproduction is associated with a pro-inflammatory endothelial activation, and (iv) how the summer-associated changes compare to those caused by diabetes, a classical cardiovascular risk factor. Langendorff-perfused guinea-pig and rat hearts generated ~100% more O(2)(-), and human subjects excreted 65% more 8-isoprostane in the summer vs. other seasons. Inhibitors of NADPH oxidase, xanthine oxidase, and NO synthase inhibited the seasonal O(2)(-)-overproduction. In the summer vs. other seasons, cardiac NADPH oxidase and xanthine oxidase activity, and protein expression were increased, the endothelial NO synthase and superoxide dismutases were downregulated, and, in guinea-pig hearts, adhesion molecules upregulation and the endothelial glycocalyx destruction associated these changes. In guinea-pig hearts, the summer and a streptozotocin-induced diabetes mediated similar changes, yet, more severe endothelial activation associated the diabetes. These findings suggest that the seasonal oxidative stress is a common phenomenon, associated, at least in guinea-pigs, with the endothelial activation. Nonetheless, its biological meaning (regulatory vs. deleterious) remains unclear. Upregulated NADPH oxidase and xanthine oxidase and uncoupled NO synthase are the sources of the seasonal O(2)(-)-overproduction. Copyright © 2010 Elsevier Ltd. All rights reserved.

Evaluation of the biodisposition of diisopropylfluorophosphate (DFP) in mice and guinea pigs after inhalation

International Nuclear Information System (INIS)

Scimeca, J.A.

1987-01-01

The disposition of 3 H-DFP and its metabolites was determined in the major tissues of the mouse and guinea pig from 5 min to 24 hr after treatment. 3 H-DFP rapidly penetrated all tissues in both species and was quickly hydrolyzed to 3 H-diisopropylphosphoric acid (free 3 H-DIP), or was covalently bound to tissue (bound 3 H-DIP). By 1 hr, the greater portion of the radioactivity in the tissues of the mouse was in the form of bound 3 H-DIP, with similar results found in the guinea pig at 4 hr. Studies were also performed to determine the effect of acute DFP exposure on 3 H-(+/-)-nicotine binding to mouse brain homogenate. The nicotinic binding sites in brain homogenate from DFP-treated mice that were sacrificed 20 min or 10 hr after exposure did not exhibit significant alterations from control. However, brain homogenate from treated mice that were sacrificed 24 hr after exposure resulted in statistically significant differences in the low-affinity KD and Bmax values from controls. Since no alterations were found in the high-affinity binding parameters and DFP had only a minimal effect on the low-affinity site at 24 hr, it was concluded that nicotinic receptor down regulation does not appear to be a compensating mechanism for DFP-induced cholinesterase inhibition

A comparative study of voiding in rat and guinea pig: simultaneous measurement of flow rate and pressure

NARCIS (Netherlands)

E. van Asselt (Els); J.M. Groen (Jan); R. van Mastrigt (Ron)

1995-01-01

textabstractIn this study, the voiding phase of the micturition cycle in the anesthetized rat and guinea pig is analyzed. In both animals, voiding is characterized by an increase in intravesical pressure and then a decrease, which is accompanied by flow through the urethra and emission of urine. An

Cardiac and renal upregulation of Nox2 and NF-κB and repression of Nox4 and Nrf2 in season- and diabetes-mediated models of vascular oxidative stress in guinea-pig and rat.

Science.gov (United States)

Gajos-Draus, Anna; Duda, Monika; Beręsewicz, Andrzej

2017-11-01

The superoxide-forming NADPH oxidase homologues, Nox1, Nox2, and Nox5, seem to mediate the pro-atherosclerotic vascular phenotype. The hydrogen peroxide-forming Nox4 afforded vascular protection, likely via NF-E2-related factor-2 (Nrf2) activation and/or Nox2 downregulation in transgenic mice. We hypothesized that oxidative stress in the intact vasculature involves, aside from the upregulation of the superoxide-forming Noxs, the downregulation of the Nox4/Nrf2 pathway. Guinea-pigs and rats were studied either in winter or in summer, and the streptozotocin diabetic rats in winter. Plasma nitrite, and superoxide production by isolated hearts were measured, while frozen tissues served in biochemical analyses. Summer in both species and diabetes in rats downregulated myocardial Nox4 while reciprocally upregulating Nox2 and Nox5 in guinea-pigs, and Nox2 in rats. Simultaneously, myocardial Nrf2 activity and the expression of the Nrf2-directed heme oxygenase-1 and endothelial NO synthase were reduced while activity of the nuclear factor κ B (NF- κ B) and the expression of NF- κ B-directed inducible NO synthase and the vascular cell adhesion molecule-1 were increased. Cardiac superoxide production was increased while plasma nitrite was decreased reciprocally. Analogous disregulation of Noxs, Nrf2, and NF- κ B, occurred in diabetic rat kidneys. Given the diversity of the experimental settings and the uniform pattern of the responses, we speculate that: (1) chronic vascular oxidative stress is a nonspecific (model-, species-, organ-independent) response involving the induction of Nox2 (and Nox5 in guinea-pigs) and the NF- κ B pathway, and the repression of Nox4 and the Nrf2 pathway; and (2) the systems Nox2-NF- κ B and Nox4-Nrf2 regulate each other negatively. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Brain biochemistry of infant mice and rats exposed to lead

Energy Technology Data Exchange (ETDEWEB)

Berber, G.B.; Maes, J.; Gilliavod, N.; Casale, G.

1978-05-01

Brains of rats and mice exposed to lead from birth receive biochemical examinations. Mice are given drinking water with lead and are studied until they are 17 days old. Rats ae given lead in the diet and followed for more than a year. In mice a retardation in body growth and development in brain DNA is found. In rats, cathepsin is enhanced at almost all times. An important role of proteolytic processes and biogenic animes is suggested in lead encephalopathy. (33 references, 7 tables)

Synthesis of N-benzoyl-[α-14C]-N'-phenyl-2,6-diaminobenzoic acid and N-benzoyl-N'-phenyl-[3'-3H]-2,6-diaminobenzoic acid, and their absorption, excretion, and distribution in rats and guinea pigs

International Nuclear Information System (INIS)

Baba, Shigeo; Kuroki, Michitake; Kasuya, Yasuji; Suzuki, Kenji.

1975-01-01

N-benzoyl-N'-phenyl-2, 6-diaminobenzoic acid (F-1) is a new anti-inflammatory agent. Two isotopically labeled compounds of F-1 ( 3 H-F-1 and 14 C-F-1) were synthesized and their absorption and distribution were investigated in rats and guinea pigs. When 3 H-F-1 was orally administered to rats and guinea pigs, about 20% of the administered radioactivity was excreted in the urine and approximately 70% of it was excreted in the feces during 7 days after 3 H-F-1 administration. A higher concentration of 3 H-F-1 in the blood was observed in rats than in guinea pigs. The maximum blood concentration of 3 H-activity appeared one hour after the oral administration of 3 H-F-1 to rats, while in guinea pigs in appeared three hours later. These facts are in good agreement with the difference in the anti-inflammatory effect between rats and guinea pigs. The highest concentration of 3 H-activity in various organs, such as liver, adrenal, kidney, and lung, was found three hours after the oral administration of 3 H-F-1. (auth.)

Efficacy of a parainfluenza virus 5 (PIV5-based H7N9 vaccine in mice and guinea pigs: antibody titer towards HA was not a good indicator for protection.

Directory of Open Access Journals (Sweden)

Zhuo Li

Full Text Available H7N9 has caused fatal infections in humans. A safe and effective vaccine is the best way to prevent large-scale outbreaks in the human population. Parainfluenza virus 5 (PIV5, an avirulent paramyxovirus, is a promising vaccine vector. In this work, we generated a recombinant PIV5 expressing the HA gene of H7N9 (PIV5-H7 and tested its efficacy against infection with influenza virus A/Anhui/1/2013 (H7N9 in mice and guinea pigs. PIV5-H7 protected the mice against lethal H7N9 challenge. Interestingly, the protection did not require antibody since PIV5-H7 protected JhD mice that do not produce antibody against lethal H7N9 challenge. Furthermore, transfer of anti-H7 serum did not protect mice against H7N9 challenge. PIV5-H7 generated high HAI titers in guinea pigs, however it did not protect against H7N9 infection or transmission. Intriguingly, immunization of guinea pigs with PIV5-H7 and PIV5 expressing NP of influenza A virus H5N1 (PIV5-NP conferred protection against H7N9 infection and transmission. Thus, we have obtained a H7N9 vaccine that protected both mice and guinea pigs against lethal H7N9 challenge and infection respectively.

Guinea Pig Oxygen-Sensing and Carotid Body Functional Properties

Science.gov (United States)

Gonzalez-Obeso, Elvira; Docio, Inmaculada; Olea, Elena; Cogolludo, Angel; Obeso, Ana; Rocher, Asuncion; Gomez-Niño, Angela

2017-01-01

Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the carotid body (CB) chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated carotid body chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K+ currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca2+ levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied. PMID:28533756

Guinea Pig Oxygen-Sensing and Carotid Body Functional Properties.

Science.gov (United States)

Gonzalez-Obeso, Elvira; Docio, Inmaculada; Olea, Elena; Cogolludo, Angel; Obeso, Ana; Rocher, Asuncion; Gomez-Niño, Angela

2017-01-01

Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the carotid body (CB) chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO 2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated carotid body chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K + currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca 2+ levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied.

Strontium-85 in the fetuses of pregnant rats and mice

International Nuclear Information System (INIS)

Onyskowova, Z.; Josifko, M.

1985-01-01

Pregnant SPF Wistar rats and ICR/Swiss albino mice were injected in the tail vein with 85 SrCl 2 with 0.05mM inactive carrier (SrCl 2 ) given in volumes of 0.1 ml. The activity in the injected volume.was about 14 MBq per kg of rat and 13 MBq per kg of mouse. The animals were injected on day 3 or 13 of gestation. Activity retained by the fetuses was quantitatively determined at three stages of the fetal intrauterine development: in rats on days 14, 16 and 21 of gestation, in mice on days 14, 16 and 20 of gestation. The activity of fetuses and/or placentas with fetal membranes was measured using a TESLA automatic gamma counter. The results indicate that the fetuses of mice retained a significantly (P<0.01) greater proportion of strontium activity than the fetuses of rats. The highest specific activities (the percentage of total activity retained per gram of fetal tissue) were found in the late pregnancy period on (day 21 of gestation in rats and on day 20 of gestation in mice) in animals that were injected with the radionuclide on day 13 of gestation. (author)

Effect of cholesterol feeding on tissue lipid perioxidation, glutathione peroxidase activity and liver microsomal functions in rats and guinea pigs

NARCIS (Netherlands)

TSAI, A. C.; THIE, G. M.; Lin, C. R.

1977-01-01

The effect of cholesterol feeding on liver and aortic nonenzymatic lipid peroxidation and glutathione peroxidase activities, and on liver microsomal NADPH-dependent lipid peroxidation, codeine hydroxylation and cytochrome P-450 levels was examined in rats and guinea pigs. One percent cholesterol was

Orally administered nicotine induces urothelial hyperplasia in rats and mice

International Nuclear Information System (INIS)

Dodmane, Puttappa R.; Arnold, Lora L.; Pennington, Karen L.; Cohen, Samuel M.

2014-01-01

Highlights: • Rats and mice orally administered with nicotine tartrate for total of 4 weeks. • No treatment-related death or whole body toxicity observed in any of the groups. • Urothelium showed simple hyperplasia in treated rats and mice. • No significant change in BrdU labeling index or SEM classification of urothelium. - Abstract: Tobacco smoking is a major risk factor for multiple human cancers including urinary bladder carcinoma. Tobacco smoke is a complex mixture containing chemicals that are known carcinogens in humans and/or animals. Aromatic amines a major class of DNA-reactive carcinogens in cigarette smoke, are not present at sufficiently high levels to fully explain the incidence of bladder cancer in cigarette smokers. Other agents in tobacco smoke could be excreted in urine and enhance the carcinogenic process by increasing urothelial cell proliferation. Nicotine is one such major component, as it has been shown to induce cell proliferation in multiple cell types in vitro. However, in vivo evidence specifically for the urothelium is lacking. We previously showed that cigarette smoke induces increased urothelial cell proliferation in mice. In the present study, urothelial proliferative and cytotoxic effects were examined after nicotine treatment in mice and rats. Nicotine hydrogen tartrate was administered in drinking water to rats (52 ppm nicotine) and mice (514 ppm nicotine) for 4 weeks and urothelial changes were evaluated. Histopathologically, 7/10 rats and 4/10 mice showed simple hyperplasia following nicotine treatment compared to none in the controls. Rats had an increased mean BrdU labeling index compared to controls, although it was not statistically significantly elevated in either species. Scanning electron microscopic visualization of the urothelium did not reveal significant cytotoxicity. These findings suggest that oral nicotine administration induced urothelial hyperplasia (increased cell proliferation), possibly due to a

Characterization of gonadotrophin-releasing hormone precursor cDNA in the Old World mole-rat Cryptomys hottentotus pretoriae: high degree of identity with the New World guinea pig sequence.

Science.gov (United States)

Kalamatianos, T; du Toit, L; Hrabovszky, E; Kalló, I; Marsh, P J; Bennett, N C; Coen, C W

2005-05-01

Regulation of pituitary gonadotrophins by the decapeptide gonadotrophin-releasing hormone 1 (GnRH1) is crucial for the development and maintenance of reproductive functions. A common amino acid sequence for this decapeptide, designated as 'mammalian' GnRH, has been identified in all mammals thus far investigated with the exception of the guinea pig, in which there are two amino acid substitutions. Among hystricognath rodents, the members of the family Bathyergidae regulate reproduction in response to diverse cues. Thus, highveld mole-rats (Cryptomys hottentotus pretoriae) are social bathyergids in which breeding is restricted to a particular season in the dominant female, but continuously suppressed in subordinate colony members. Elucidation of reproductive control in these animals will be facilitated by characterization of their GnRH1 gene. A partial sequence of GnRH1 precursor cDNA was isolated and characterized. Comparative analysis revealed the highest degree of identity (86%) to guinea pig GnRH1 precursor mRNA. Nevertheless, the deduced amino acid sequence of the mole-rat decapeptide is identical to the 'mammalian' sequence rather than that of guinea pigs. Successful detection of GnRH1-synthesizing neurones using either a guinea pig GnRH1 riboprobe or an antibody against the 'mammalian' decapeptide is consistent with the guinea pig-like sequence for the precursor and the classic 'mammalian' form for the decapeptide. The high degree of identity in the GnRH1 precursor sequence between this Old World mole-rat and the New World guinea pig is consistent with the theory that caviomorphs and phiomorphs originated from a common ancestral line in the Palaeocene to mid Eocene, some 63-45 million years ago.

Kinetic analysis of interactions of paraoxon and oximes with human, Rhesus monkey, swine, rabbit, rat and guinea pig acetylcholinesterase.

Science.gov (United States)

Worek, Franz; Aurbek, Nadine; Wille, Timo; Eyer, Peter; Thiermann, Horst

2011-01-15

Previous in vitro studies showed marked species differences in the reactivating efficiency of oximes between human and animal acetylcholinesterase (AChE) inhibited by organophosphorus (OP) nerve agents. These findings provoked the present in vitro study which was designed to determine the inhibition, aging, spontaneous and oxime-induced reactivation kinetics of the pesticide paraoxon, serving as a model compound for diethyl-OP, and the oximes obidoxime, pralidoxime, HI 6 and MMB-4 with human, Rhesus monkey, swine, rabbit, rat and guinea pig erythrocyte AChE. Comparable results were obtained with human and monkey AChE. Differences between human, swine, rabbit, rat and guinea pig AChE were determined for the inhibition and reactivation kinetics. A six-fold difference of the inhibitory potency of paraoxon with human and guinea pig AChE was recorded while only moderate differences of the reactivation constants between human and animal AChE were determined. Obidoxime was by far the most effective reactivator with all tested species. Only minor species differences were found for the aging and spontaneous reactivation kinetics. The results of the present study underline the necessity to determine the inhibition, aging and reactivation kinetics in vitro as a basis for the development of meaningful therapeutic animal models, for the proper assessment of in vivo animal data and for the extrapolation of animal data to humans. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

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.

NK3 Receptors mediate an increase in firing rate of midbrain dopamine neurons of the rat and the guinea pig

NARCIS (Netherlands)

Werkman, T.R.; McCreary, A.C.; Kruse, C.G.; Wadman, W.J.

2011-01-01

This in vitro study investigates and compares the effects of NK3 receptor ligands on the firing rate of rat and guinea pig midbrain dopamine neurons. The findings are discussed in the light of choosing suitable animal models for investigating pharmacological properties of NK3 receptor antagonists,

Schistosoma mansoni: analysis of the humoral and cellular basis of resistance in guinea-pigs vaccinated with radiation-attenuated cercariae

International Nuclear Information System (INIS)

McLaren, D.J.; Delgado, V.S.; Gordon, J.R.; Rogers, M.V.

1990-01-01

This study addresses the humoral and cellular basis of specific acquired immunity in the guinea-pig irradiated vaccine model of schistosomiasis mansoni. Rodents vaccinated with 500 gamma-irradiated cercariae and then splenectomized 4. 5 weeks later showed a 33% reduction in resistance to challenge as compared to vaccinated animals or vaccinated/sham splenectomized controls. Serum harvested from once vaccinated individuals conferred modest levels of resistance upon naive recipients in some experiments, but transfer was not achieved consistently. Serum from vaccinated and thrice boosted rodents (Vbbb) routinely transferred about 45% immunity, however, provided it was given in 4 ml aliquots on day 9 post-challenge; Vbbb serum thus transferred 50% of donor immunity. Interestingly, multiple doses of this protective serum given on and either side of day 9 did not enhance the protection achieved with a single 4 ml aliquot. Neither peripheral lymph node cells nor splenocytes from the polyvaccinated serum donors were able to transfer resistance to recipient guinea-pigs and they failed to augment the protection achieved with Vbbb serum. Foot-pad testing revealed no correlation between delayed hypersensitivity responses and immunity to challenge in vaccinated guinea-pigs. Polyvaccine guinea-pig serum failed to protect mice and guinea-pigs could not be protected with polyvaccine rat serum. (author)

Toxicology and carcinogenesis studies of dipropylene glycol in rats and mice.

Science.gov (United States)

Hooth, Michelle J; Herbert, Ronald A; Haseman, Joseph K; Orzech, Denise P; Johnson, Jerry D; Bucher, John R

2004-11-15

Dipropylene glycol (DPG) is a component of many commercial products such as antifreeze, air fresheners, cosmetic products, solvents, and plastics. Male and female F344/N rats and B6C3F1 mice were exposed to DPG in the drinking water for 2 weeks, 3 months, or 2 years. In the 2-week and 3-month studies, rats and mice were exposed to 0, 5000, 10,000, 20,000, 40,000, or 80,000 ppm DPG. There was no mortality in the 2-week studies. In the 3-month rat study, all animals survived to the end of the study. Liver weights of rats exposed to 10,000 ppm or greater and kidney weights of rats exposed to 40,000 and 80,000 ppm were greater than those of the controls. The incidences of liver and kidney lesions were significantly increased in males exposed to 20,000 ppm or greater and females exposed to 80,000 ppm. Focal olfactory epithelial degeneration was present in all rats exposed to 80,000 ppm. In males, the incidences of testicular atrophy, epididymal hypospermia, and preputial gland atrophy were significantly increased in the 80,000 ppm group. In the 3-month mouse study, three males and one female exposed to 80,000 ppm died. Liver weights were increased, as was the incidence of centrilobular hypertrophy in males exposed to 40,000 ppm and males and females exposed to 80,000 ppm. In the 2-year studies, exposure groups were 0, 2500 (rats only), 10,000, 20,000 (mice only) or 40,000 ppm DPG. Survival of male rats exposed to 40,000 ppm and mean body weights of males and females exposed to 40,000 ppm were significantly less than controls. In male rats, exposure to DPG resulted in increased incidences and severities of nephropathy and secondary lesions in the parathyroid and forestomach. Increased incidences of focal histiocytic and focal granulomatous inflammation of the liver were also observed. In male and female rats, there were increased incidences of bile duct hyperplasia and changes in the olfactory epithelium of the nose. In mice, survival of males and females was similar to

Characterization of cutaneous vascular permeability induced by platelet-activating factor in guinea pigs and rats and its inhibition by a platelet-activating factor receptor antagonist

International Nuclear Information System (INIS)

Hwang, S.B.; Li, C.L.; Lam, M.H.; Shen, T.Y.

1985-01-01

Mechanisms of platelet-activating factor (PAF)-induced increases of cutaneous vascular permeability in guinea pigs and in rats were further explored. PAF so far is the most potent vasoactive mediator, being more than 1000-fold more potent than histamine and bradykinin in both species. In guinea pigs, there is a time delay of 5 to 10 minutes before PAF action, whereas, in the rat, the increased vasopermeability occurs immediately following the intradermal PAF injection. Relative vasoactive potencies of PAF and several structure-related analogues in both species correlate very well with their relative inhibition of the binding of 3 H-PAF to specific receptor sites on isolated rabbit platelet plasma membranes and their aggregatory abilities of rabbit platelets. Furthermore, the PAF-induced cutaneous vascular permeability is inhibitable by a competitive specific PAF receptor antagonist, kadsurenone, suggesting that binding of PAF to its specific receptor site is the first step to initiate its action of increased cutaneous vascular permeability. Several pure cyclooxygenase inhibitors, including indomethacin, diflunisal, and flurbiprofen, and the dual cyclooxygenase/lipoxygenase inhibitor, BW755C, but not the histamine antagonists, inhibit the PAF-induced vasopermeability in guinea pigs. The inhibition by indomethacin or BW755C can be fully reversed by coinjection intradermally with PAF and prostaglandin E1 but not leukotriene B4. Also, prostaglandin E1 but not leukotriene B4 enhances the guinea pig in vivo response to PAF in this model. However, in rats, none of the cyclooxygenase inhibitors, histamine antagonists, or BW755C inhibit the PAF effect of cutaneous phenomena

Effects of single dose X-irradiation on the guinea-pig spinal cord

Energy Technology Data Exchange (ETDEWEB)

Knowles, J F [Medical Research Council, Harwell (UK). Radiobiological Research Unit

1981-09-01

Lumbar or cervical regions of the guinea-pig spinal cord were irradiated with a single dose of 250 kV X-rays. The latency for paralysis, whether of hind- or fore-limbs, and the histopathology of the radiation-induced cord lesions depended critically on the radiation dose. There were definite but only minor differences between the reactions of lumbar and cervical cord to the same radiation dose. After 30 or 40 Gy there was white matter necrosis but after 20 Gy widespread demyelination associated with vacuolar spaces occurred. After irradiation of the lumbar cord with 30-40 Gy, the lesions in the guinea-pig differed from those reported in the rat. White-matter necrosis in the guinea-pig cord was only occasionally associated with spinal nerve root necrosis, whereas in the rat, nerve-root necrosis with sparing of the white matter was the main lesion. After 20 Gy to the cervical or lumbar cord the guinea-pig showed widespread demyelination and vacuolation whereas in rats vascular lesions were the main result.

Effect of undecylenic acid as a topical microbicide against genital herpes infection in mice and guinea pigs.

Science.gov (United States)

Bourne, N; Ireland, J; Stanberry, L R; Bernstein, D I

1999-01-01

There is increasing interest in the use of topical microbicides to help prevent the spread of sexually transmitted diseases (STD). Undecylenic acid (UA), a monosaturated fatty acid, is the active ingredient in a number of over-the-counter (OTC) antifungal spray powders, that also exhibits in vitro antibacterial and antiviral activity, including herpes simplex virus (HSV) activity. We, therefore, evaluated UA as a topical microbicide against genital HSV infection using the murine and guinea pig models of genital herpes. Mice were administered a 20% solution of UA in polyethylene glycol (PEG) vehicle, vehicle alone or phosphate buffered saline (PBS) intravaginally immediately prior to vaginal challenge with HSV-2. Pre-treatment with UA decreased the number of mice that became infected (P < 0.001 vs. PBS or vehicle control), developed symptoms (P <0.001) or died (P <0.001). However, when treatment was extended to either 5 min prior to or after viral inoculation, protection was lost. Similar findings were found using the guinea pig model, where UA treatment completely prevented HSV-2 vaginal infection when given immediately prior to HSV-2 inoculation (P<0.001 vs. PBS or vehicle control). Thus, UA, an approved OTC medication, provided significant protection against HSV disease and infection only when applied immediately before viral inoculation, indicating that better formulations were needed to extend the duration of protection.

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

International Nuclear Information System (INIS)

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

2003-01-01

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

Ca(2+)-dependent nonspecific permeability of the inner membrane of liver mitochondria in the guinea fowl (Numida meleagris).

Science.gov (United States)

Vedernikov, Aleksander A; Dubinin, Mikhail V; Zabiakin, Vladimir A; Samartsev, Victor N

2015-06-01

This comparative study presents the results of the induction of Ca(2+)-dependent nonspecific permeability of the inner membrane (pore opening) of rat and guinea fowl liver mitochondria by mechanisms that are both sensitive and insensitive to cyclosporin A (CsA). It was established that energized rat and guinea fowl liver mitochondria incubated with 1 mM of inorganic phosphate (Pi) are capable of swelling upon addition of at least 125 and 875 nmol of CaCl2 per 1 mg protein, respectively. Under these conditions, the Ca(2+) release from the mitochondria of these animals and a drop in Δψ are observed. All of these processes are inhibited by 1 μM of CsA. FCCP, causing organelle de-energization, induces pore opening in rat and guinea fowl liver mitochondria upon addition of 45 и 625 nmol of CaCl2 per 1 mg protein, respectively. These results suggest the existence of a CsA-sensitive mechanism for the induction of Ca(2+)-dependent pores in guinea fowl liver mitochondria, which has been reported in rat liver mitochondria. However, guinea fowl liver mitochondria have a significantly greater resistance to Ca(2+) as a pore inducer compared to rat liver mitochondria. It was found that the addition of α,ω-hexadecanedioic acid (HDA) to rat and guinea fowl liver mitochondria incubated with CsA and loaded with Ca(2+) causes organelle swelling and Ca(2+) release from the matrix. It is assumed that in contrast to the CsA-sensitive pore, the CsA-insensitive pore induced by HDA in the inner membrane of guinea fowl liver mitochondria, as well as in rat liver mitochondria, is lipid in nature.

Distribution of sulfhydryl boranes in mice and rats

International Nuclear Information System (INIS)

Slatkin, D.N.; Micca, P.L.; Laster, B.H.; Fairchild, R.G.

1986-01-01

The distribution of boron in mice bearing transplanted Harding-Passey melanomas after rapid and slow administration of monomer were studied. Thin layer chromatographic analysis of the corresponding infusion solution revealed a slow-moving principal band that was later shown to correspond to Na 4 B 24 H 22 S 2 , the dimer of Na 2 B 12 H 11 SH. It was found that while monomer and chemically synthesized dimer yielded similar boron concentrations when they were given rapidly intraperitoneally to mice, the dimer yielded higher boron concentrations in mouse melanoma and higher melanoma-blood boron concentration when each was infused slowly intraperitoneally for 8 to 9 days. Studies have been started on the uptake of dimer into an intracerebrally implanted rat glioma. Boron levels in the rat glioma and in the mouse melanoma from slow intraperitoneal infusion of proportionately comparable amounts of dimer, are similar. However, after these slow infusions boron levels in rat blood are about as high as boron levels in rat brain tumor. 6 refs., 1 fig., 4 tabs

Comparative disposition and metabolism of 1,2,3-trichloropropane in rats and mice.

Science.gov (United States)

Mahmood, N A; Overstreet, D; Burka, L T

1991-01-01

1,2,3-Trichloropropane (TCP) has been used as a solvent and degreasing agent and as an intermediate in pesticide manufacture. TCP is currently the subject of a National Toxicology Program chronic toxicity study. The present study is part of a larger effort to characterize the toxicity of TCP. Following acute oral exposure of male and female F344 rats (30 mg/kg) and male B6C3F1 mice (30 and 60 mg/kg), TCP was rapidly absorbed, metabolized, and excreted. The major route of excretion of TCP was in the urine. By 60 hr postdosing, rats had excreted 50% and mice 65% of the administered dose by this route. Exhalation as 14CO2 and excretion in the feces each accounted for 20% of the total dose in 60 hr rats and 20 and 15%, respectively, in mice. No apparent sex-related differences were observed in the ability of the rats to excrete TCP-derived radioactivity. At 60 hr, TCP-derived radioactivity was most concentrated in the liver, kidney, and forestomach in both rats and male mice. Male mice eliminated TCP-derived radioactivity more rapidly than rats and lower concentrations of radioactivity were found in tissues 60 hr after dosing in mice. Two urinary metabolites were isolated and identified by NMR, mass spectroscopy, and comparison with synthetic standards, as N-acetyl- and S-(3-chloro-2-hydroxypropyl)cysteine. Analyses of the early urine (0-6 hr) showed this mercapturic acid to be the major metabolite in rat urine and was only a minor component in mouse urine. 2-(S-Glutathionyl)malonic acid was identified by NMR and mass spectrometry and by chemical synthesis as the major biliary metabolite in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Systemic gene delivery transduces the enteric nervous system of guinea pigs and cynomolgus macaques.

Science.gov (United States)

Gombash, S E; Cowley, C J; Fitzgerald, J A; Lepak, C A; Neides, M G; Hook, K; Todd, L J; Wang, G-D; Mueller, C; Kaspar, B K; Bielefeld, E C; Fischer, A J; Wood, J D; Foust, K D

2017-10-01

Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or phosphate-buffered saline. Piglets were euthanized three weeks post injection and tissues were harvested for immunofluorescent analysis. GFP expression was detected in myenteric and submucosal neurons along the length of the gastrointestinal tract in AAV8 injected guinea pigs. GFP-positive neurons were found in dorsal motor nucleus of the vagus and dorsal root ganglia. Less transduction occurred in AAV9-treated tissues. Gastrointestinal tissues were analyzed from young cynomolgus macaques that received systemic injection of AAV9 GFP. GFP expression was detected in myenteric neurons of the stomach, small and large intestine. These data demonstrate that ENS gene delivery translates to larger species. This work develops tools for the field of neurogastroenterology to explore gut physiology and anatomy using emerging technologies such as optogenetics and gene editing. It also provides a basis to develop novel therapies for chronic gut disorders.

1,2,3-Trichloropropane: a multisite carcinogen in rats and mice.

Science.gov (United States)

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

1995-05-01

1,2,3-Trichloropropane was evaluated in 2-year toxicology and carcinogenesis studies by the National Toxicology Program. The selection of this chemical for study was based on the potential for human exposure, its positive in vitro genotoxicity, and the carcinogenicity of structurally related chemicals. During the 2-year study 1,2,3-trichloropropane was administered in corn oil by gavage 5 days per week; groups of 60 F344/N rats received 0, 3, 10, or 30 mg/kg, while groups of 60 B6C3F1 mice received 0,6,20, or 60 mg/kg. Because of reduced survival associated with the development of chemical-related neoplasms, rats that received 30 mg/kg were terminated at 65 weeks (females) or 76 weeks (males). Similarly, mice that received 60 mg/kg were terminated at 73 weeks (females) or 79 weeks (males), while groups of mice that received 20 mg/kg were terminated at 88 weeks. 1,2,3-Trichloropropane induced benign and/or malignant neoplasms at multiple sites in both rats and mice; this included increased incidences of benign and malignant neoplasms of the squamous epithelium of the oral mucosa and forestomach of male and female rats, benign neoplasms of the kidney and pancreas and benign or malignant neoplasms of the preputial gland in male rats, malignant neoplasms of the mammary gland, and benign or malignant neoplasms of the clitoral gland in female rats. In mice, 1,2,3-trichloropropane induced a low incidence of malignant neoplasms of the oral mucosa in females, high incidences of benign and malignant neoplasms of the forestomach in males and females, benign neoplasms of the liver and harderian gland of males and females, and uterine neoplasms in females.

Structural determination, distribution, and physiological actions of ghrelin in the guinea pig.

Science.gov (United States)

Okuhara, Yuji; Kaiya, Hiroyuki; Teraoka, Hiroki; Kitazawa, Takio

2018-01-01

We identified guinea pig ghrelin (gp-ghrelin), and examined its distribution and physiological actions in the guinea-pig. Gp-ghrelin is a 28-amino acid peptide (GASFR SPEHH SAQQR KESRK LPAKI QPR); seven amino acids are different from that of rat ghrelin at positions 2, 5, 10, 11, 19, 21, and 25, which include the conserved region known in mammals. The third serine residue is mainly modified by n-decanoyl acid. Both gp-ghrelin and rat ghrelin increased intracellular Ca 2+ concentration of HEK293 cells expressing guinea pig growth hormone secretagogue receptor 1a (GHS-R1a), and the affinity of gp-ghrelin was slightly higher than that of rat ghrelin. In addition, gp-ghrelin was also effective in CHO cells expressing rat GHS-R1a with similar affinity to that of rat ghrelin. Gp-ghrelin mRNA was predominantly expressed in the stomach, whereas the expression levels in other organs was low. High levels of GHS-R1a mRNA expression were observed in the pituitary, medulla oblongata, and kidney, while medium levels were noted in the thalamus, pons, olfactory bulb, and heart. Immunohistochemistry identified gp-ghrelin-immunopositive cells in the gastric mucosa and pancreas. Intraperitoneal injection of gp-ghrelin increased food intake in the guinea pig. Gp-ghrelin did not cause any mechanical responses in isolated gastrointestinal smooth muscles in vitro, similar to rat ghrelin. In conclusion, the N-terminal structures that are conserved in mammals were different in gp-ghrelin. Moreover, the functional characteristics of gp-ghrelin, other than its distribution, were dissimilar from those in other Rodentia. Copyright © 2017 Elsevier Inc. All rights reserved.

Experimental treatment of diabetic mice with microencapsulated rat islet cells transplantation

International Nuclear Information System (INIS)

Luo Yun; Xue Yilong; Li Yanling; Li Xinjian

2006-01-01

To observe treatment effects of diabetic mice with microcapsulated and non-microcapsulated rat islet cell transplantation, pancreas of SD rat was perfused with collagenase through cloledchus, and then the pancreatic tissues were isolated and digested. Histopaque-1077 was used to purify the digested pancreas. Islet cells were collected and implanted into the peritoneal cavity of diabetic mice. The isolated islets had a response upon glucose stimulation. When the microcapsulated islets and non- microcapsulated islets were transplanted into diabetic mices the high blood glucose level could be decreased to normal. The normal blood glucose level in the diabetic mice transpanted with microcapsulated islets could be maintained for over 30 days,but it could be mainlained only for 2-3 days in the diabetic mice transplanted with non-microcapsulated islets. Thus it is believed that microcapsulated islet cell transplantation exerts good effect on diabetic mice and the microcapsules possessed good immunoisolating function. (authors)

Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes

NARCIS (Netherlands)

van der Geld, Ymke M.; Hellmark, Thomas; Selga, Daina; Heeringa, Peter; Huitema, Minke G.; Limburg, Pieter C.; Kallenberg, Cees G. M.

2007-01-01

Aim: In this study, we employed chimeric human/ mouse Proteinase 3 ( PR3) proteins as tools to induce an autoantibody response to PR3 in rats and mice. Method: Rats and mice were immunised with recombinant human PR3 ( HPR3), recombinant murine PR3 ( mPR3), single chimeric human/ mouse PR3 ( HHm,

Toluene-induced hearing loss in the guinea pig.

Science.gov (United States)

Waniusiow, Delphine; Campo, Pierre; Venet, Thomas; Cossec, Benoît; Cosnier, Frédéric; Beydon, Dominique; Rieger, Benoît; Burgart, Manuella; Ferrari, Luc; Parietti-Winkler, Cécile

2009-10-01

Toluene is a high-production industrial solvent, which can disrupt the auditory system in rats. However, toluene-induced hearing loss is species dependent. For instance, despite long-lasting exposures to high concentrations of aromatic solvent, no study has yet succeeded in causing convincing hearing loss in the guinea pig. This latter species can be characterized by two metabolic particularities: a high amount of hepatic cytochrome P-450s (P-450s) and a high concentration of glutathione in the cochlea. It is therefore likely that the efficiency of both the hepatic and cochlear metabolisms plays a key role in the innocuousness of the hearing of guinea pigs to exposure to solvent. The present study was carried out to test the auditory resistance to toluene in glutathione-depleted guinea pigs whose the P-450 activity was partly inhibited. To this end, animals on a low-protein diet received a general P-450 inhibitor, namely SKF525-A. Meanwhile, they were exposed to 1750 ppm toluene for 4 weeks, 5 days/week, 6 h/day. Auditory function was tested by electrocochleography and completed by histological analyses. For the first time, a significant toluene-induced hearing loss was provoked in the P-450-inhibited guinea pigs. However, the ototoxic process caused by the solvent exposure was different from that observed in the rat. Only the stria vascularis and the spiral fibers were disrupted in the apical coil of the cochlea. The protective mechanisms developed by guinea pigs are discussed in the present publication.

High lenticular tolerance to ultraviolet radiation-B by pigmented guinea-pig; application of a safety limit strategy for UVR-induced cataract.

Science.gov (United States)

Mody, Vino C; Kakar, Manoj; Söderberg, Per G; Löfgren, Stefan

2012-05-01

The purpose of this study was to determine a threshold measure, maximum tolerable dose (MTD), for avoidance of UVR-B-induced cataract in the pigmented guinea-pig. Thirty pupil-dilated anesthetized young female guinea-pigs, divided into five equal groups, received between 0 and 84.9 kJ/m(2) unilateral UVR-B. Lens extraction and in vitro lens photography occurred 24 hr after exposure. Measurement of intensity of lens light scattering served as quantifying tool for the degree of cataract. Data analysis included regression, using a second order polynomial model. The applied MTD concept was based on the UVR-B dose-response curve obtained for the pigmented guinea-pig. A smaller number of pigmented guinea-pigs, pigmented rats and albino rats underwent morphometric analysis of the anterior segment geometry. All eyes exposed to UVR-B developed cataract in the anterior subcapsular region. MTD for avoidance of UVR-B-induced cataract was 69.0 kJ/m(2) in the pigmented guinea-pig. Iris was considerably thicker in the guinea-pig than in the rats. Lens blockage by the dilated iris was lowest in the guinea-pig. Maximum tolerable dose for avoidance of UVR-B-induced cataract in the pigmented guinea-pig was 69.0 kJ/m(2), over 10-fold higher than the threshold 5 kJ/m(2) obtained by Pitts et al. in the pigmented rabbit. Maximum tolerable dose is an appropriate method for estimation of toxicity for UVR-B-induced cataract in the guinea-pig. The pigmented guinea-pig is significantly less sensitive to UVR-B exposure than the pigmented rabbit and pigmented rat. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

Porcine parvovirus capsid protein expressed in Escherichia coli self-assembles into virus-like particles with high immunogenicity in mice and guinea pigs.

Science.gov (United States)

Ji, Pengchao; Liu, Yunchao; Chen, Yumei; Wang, Aiping; Jiang, Dawei; Zhao, Baolei; Wang, Jvcai; Chai, Shujun; Zhou, Enmin; Zhang, Gaiping

2017-03-01

Porcine parvovirus (PPV) is a causative agent of reproductive failure in pregnant sows. Classical inactivated vaccine is extensively used to control PPV infection, but problems concerning safety, such as incomplete inactivation may occur. In this study, a novel subunit vaccine against PPV based on virus-like particles (VLPs) formed from the complete PPV VP2 protein expressed in a prokaryotic system with co-expressed chaperones is reported. The VLPs have a similar size, shape, and hemagglutination property to the PPV. Immunization with these VLPs stimulated the neutralization antibody and hemagglutination inhibition (HI) antibody responses in mice and guinea pigs. The lymphocyte proliferation response and cytokine secretion was also induced in immunized guinea pigs comparable to those immunized with PPV inactivated vaccine. In addition, immunization with VLPs also significantly reduced the PPV content in the spleen of guinea pigs 14 days after the challenge with intact virus. These studies suggest that PPV VLPs created as described here could be a potential candidate for vaccine development. Copyright © 2017 Elsevier B.V. All rights reserved.

Distribution of sulfhydryl boranes in mice and rats

International Nuclear Information System (INIS)

Slatkin, D.N.; Micca, P.L.; Laster, B.H.; Fairchild, R.G.

1986-01-01

The results of experiments on the distribution of boranes in rat and mice tissues and melanomas are reported. Comparisons are made between the behavior of borane monomers and dimers under different dose rates and cummulative doses

Identification of Metabolism and Excretion Differences of Procymidone between Rats and Humans Using Chimeric Mice: Implications for Differential Developmental Toxicity.

Science.gov (United States)

Abe, Jun; Tomigahara, Yoshitaka; Tarui, Hirokazu; Omori, Rie; Kawamura, Satoshi

2018-02-28

A metabolite of procymidone, hydroxylated-PCM, causes rat-specific developmental toxicity due to higher exposure to it in rats than in rabbits or monkeys. When procymidone was administered to chimeric mice with rat or human hepatocytes, the plasma level of hydroxylated-PCM was higher than that of procymidone in rat chimeric mice, and the metabolic profile of procymidone in intact rats was well reproduced in rat chimeric mice. In human chimeric mice, the plasma level of hydroxylated-PCM was less, resulting in a much lower exposure. The main excretion route of hydroxylated-PCM-glucuronide was bile (the point that hydroxylated-PCM enters the enterohepatic circulation) in rat chimeric mice, and urine in human chimeric mice. These data suggest that humans, in contrast to rats, extensively form the glucuronide and excrete it in urine, as do rabbits and monkeys. Overall, procymidone's potential for causing teratogenicity in humans must be low compared to that in rats.

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.

Health surveillance of specific pathogen-free and conventionally-housed mice and rats in Korea.

Science.gov (United States)

Seok, Seunghyeok; Park, Jonghwan; Cho, Suna; Baek, Minwon; Lee, Huiyoung; Kim, Dongjae; Yang, Kihwa; Jang, Dongdeuk; Han, Beomseok; Nam, Kitaek; Park, Jaehak

2005-01-01

The present study contains information about proper microbiological monitoring of laboratory animals' health and the standardization of microbiological monitoring methods in Korea. Microbiological quality control for laboratory animals, composed of biosecurity and health surveillance, is essential to guard against research complications and public health dangers that have been associated with adventitious infections. In this study, one hundred and twenty-two mice and ninety rats from laboratory animal breeding companies and one animal facility of the national universities in Korea were monitored in 2000-2003. Histopathologically, thickening of the alveolar walls and lymphocytic infiltration around the bronchioles were observed in mice and rats from microbiologically contaminated facilities. Cryptosporidial oocysts were observed in the gastric pits of only conventionally-housed mice and rats. Helicobacter spp. infection was also detected in 1 of 24 feces DNA samples in mice and 9 of 40 feces DNA samples in rats by PCR in 2003, but they were not Helicobacter hepaticus. This paper describes bacteriological, parasitological, and virological examinations of the animals.

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.

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.

Use of a Guinea pig-specific transcriptome array for evaluation of protective immunity against genital chlamydial infection following intranasal vaccination in Guinea pigs.

Science.gov (United States)

Wali, Shradha; Gupta, Rishein; Veselenak, Ronald L; Li, Yansong; Yu, Jieh-Juen; Murthy, Ashlesh K; Cap, Andrew P; Guentzel, M Neal; Chambers, James P; Zhong, Guangming; Rank, Roger G; Pyles, Richard B; Arulanandam, Bernard P

2014-01-01

Guinea pigs have been used as a second animal model to validate putative anti-chlamydial vaccine candidates tested in mice. However, the lack of guinea pig-specific reagents has limited the utility of this animal model in Chlamydia sp. vaccine studies. Using a novel guinea pig-specific transcriptome array, we determined correlates of protection in guinea pigs vaccinated with Chlamydia caviae (C. caviae) via the intranasal route, previously reported by us and others to provide robust antigen specific immunity against subsequent intravaginal challenge. C. caviae vaccinated guinea pigs resolved genital infection by day 3 post challenge. In contrast, mock vaccinated animals continued to shed viable Chlamydia up to day 18 post challenge. Importantly, at day 80 post challenge, vaccinated guinea pigs experienced significantly reduced genital pathology - a sequelae of genital chlamydial infections, in comparison to mock vaccinated guinea pigs. Sera from vaccinated guinea pigs displayed antigen specific IgG responses and increased IgG1 and IgG2 titers capable of neutralizing GPIC in vitro. Th1-cellular/inflammatory immune genes and Th2-humoral associated genes were also found to be elevated in vaccinated guinea pigs at day 3 post-challenge and correlated with early clearance of the bacterium. Overall, this study provides the first evidence of guinea pig-specific genes involved in anti-chlamydial vaccination and illustrates the enhancement of the utility of this animal model in chlamydial pathogenesis.

Genetic structure and inter-generic relationship of closed colony of laboratory rodents based on RAPD markers.

Science.gov (United States)

Kumar, Mahadeo; Kumar, Sharad

2014-11-01

Molecular genetic analysis was performed using random amplified polymorphic DNA (RAPD) on three commonly used laboratory bred rodent genera viz. mouse (Mus musculus), rat (Rattus norvegicus) and guinea pig (Cavia porcellus) as sampled from the breeding colony maintained at the Animal Facility, CSIR-Indian Institute of Toxicology Research, Lucknow. In this study, 60 samples, 20 from each genus, were analyzed for evaluation of genetic structure of rodent stocks based on polymorphic bands using RAPD markers. Thirty five random primers were assessed for RAPD analysis. Out of 35, only 20 primers generated a total of 56.88% polymorphic bands among mice, rats and guinea pigs. The results revealed significantly variant and distinct fingerprint patterns specific to each of the genus. Within-genera analysis, the highest (89.0%) amount of genetic homogeneity was observed in mice samples and the least (79.3%) were observed in guinea pig samples. The amount of genetic homogeneity was observed very high within all genera. The average genetic diversity index observed was low (0.045) for mice and high (0.094) for guinea pigs. The inter-generic distances were maximum (0.8775) between mice and guinea pigs; and the minimum (0.5143) between rats and mice. The study proved that the RAPD markers are useful as genetic markers for assessment of genetic structure as well as inter-generic variability assessments.

Guinea Pig Prion Protein Supports Rapid Propagation of Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease Prions.

Science.gov (United States)

Watts, Joel C; Giles, Kurt; Saltzberg, Daniel J; Dugger, Brittany N; Patel, Smita; Oehler, Abby; Bhardwaj, Sumita; Sali, Andrej; Prusiner, Stanley B

2016-11-01

The biochemical and neuropathological properties of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) prions are faithfully maintained upon transmission to guinea pigs. However, primary and secondary transmissions of BSE and vCJD in guinea pigs result in long incubation periods of ∼450 and ∼350 days, respectively. To determine if the incubation periods of BSE and vCJD prions could be shortened, we generated transgenic (Tg) mice expressing guinea pig prion protein (GPPrP). Inoculation of Tg(GPPrP) mice with BSE and vCJD prions resulted in mean incubation periods of 210 and 199 days, respectively, which shortened to 137 and 122 days upon serial transmission. In contrast, three different isolates of sporadic CJD prions failed to transmit disease to Tg(GPPrP) mice. Many of the strain-specified biochemical and neuropathological properties of BSE and vCJD prions, including the presence of type 2 protease-resistant PrP Sc , were preserved upon propagation in Tg(GPPrP) mice. Structural modeling revealed that two residues near the N-terminal region of α-helix 1 in GPPrP might mediate its susceptibility to BSE and vCJD prions. Our results demonstrate that expression of GPPrP in Tg mice supports the rapid propagation of BSE and vCJD prions and suggest that Tg(GPPrP) mice may serve as a useful paradigm for bioassaying these prion isolates. Variant Creutzfeldt-Jakob disease (vCJD) and bovine spongiform encephalopathy (BSE) prions are two of the prion strains most relevant to human health. However, propagating these strains in mice expressing human or bovine prion protein has been difficult because of prolonged incubation periods or inefficient transmission. Here, we show that transgenic mice expressing guinea pig prion protein are fully susceptible to vCJD and BSE prions but not to sporadic CJD prions. Our results suggest that the guinea pig prion protein is a better, more rapid substrate than either bovine or human prion protein for

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.

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

International Nuclear Information System (INIS)

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

1990-01-01

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

Database of Physiological Parameters for Early Life Rats and Mice

Data.gov (United States)

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...

In vitro and in silico derived relative effect potencies of ah-receptor-mediated effects by PCDD/Fs and PCBs in rat, mouse, and guinea pig CALUX cell lines.

Science.gov (United States)

Ghorbanzadeh, Mehdi; van Ede, Karin I; Larsson, Malin; van Duursen, Majorie B M; Poellinger, Lorenz; Lücke-Johansson, Sandra; Machala, Miroslav; Pěnčíková, Kateřina; Vondráček, Jan; van den Berg, Martin; Denison, Michael S; Ringsted, Tine; Andersson, Patrik L

2014-07-21

For a better understanding of species-specific relative effect potencies (REPs), responses of dioxin-like compounds (DLCs) were assessed. REPs were calculated using chemical-activated luciferase gene expression assays (CALUX) derived from guinea pig, rat, and mouse cell lines. Almost all 20 congeners tested in the rodent cell lines were partial agonists and less efficacious than 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For this reason, REPs were calculated for each congener using concentrations at which 20% of the maximal TCDD response was reached (REP20TCDD). REP20TCDD values obtained for PCDD/Fs were comparable with their toxic equivalency factors assigned by the World Health Organization (WHO-TEF), while those for PCBs were in general lower than the WHO-TEF values. Moreover, the guinea pig cell line was the most sensitive as indicated by the 20% effect concentrations of TCDD of 1.5, 5.6, and 11.0 pM for guinea pig, rat, and mouse cells, respectively. A similar response pattern was observed using multivariate statistical analysis between the three CALUX assays and the WHO-TEFs. The mouse assay showed minor deviation due to higher relative induction potential for 2,3,7,8-tetrachlorodibenzofuran and 2,3,4,6,7,8-hexachlorodibenzofuran and lower for 1,2,3,4,6,7,8-heptachlorodibenzofuran and 3,3',4,4',5-pentachlorobiphenyl (PCB126). 2,3,7,8-Tetrachlorodibenzofuran was more than two times more potent in the mouse assay as compared with that of rat and guinea pig cells, while measured REP20TCDD for PCB126 was lower in mouse cells (0.05) as compared with that of the guinea pig (0.2) and rat (0.07). In order to provide REP20TCDD values for all WHO-TEF assigned compounds, quantitative structure-activity relationship (QSAR) models were developed. The QSAR models showed that specific electronic properties and molecular surface characteristics play important roles in the AhR-mediated response. In silico derived REP20TCDD values were generally consistent with the WHO

Comparison of immunogenicity and protective efficacy of genital herpes vaccine candidates herpes simplex virus 2 dl5-29 and dl5-29-41L in mice and guinea pigs.

Science.gov (United States)

Hoshino, Yo; Pesnicak, Lesley; Dowdell, Kennichi C; Lacayo, Juan; Dudek, Timothy; Knipe, David M; Straus, Stephen E; Cohen, Jeffrey I

2008-07-29

A replication-defective herpes simplex virus (HSV)-2 vaccine, dl5-29, which is deleted for two essential early genes, UL5 and UL29, is highly immunogenic and protective in mice and guinea pigs. In a prior study, a derivative of HSV-2 dl5-29 termed dl5-29-41L, which has an additional deletion in UL41 (that encodes the virion-host shut-off protein), was more immunogenic and protective against challenge with wild-type HSV-2 in mice when compared with dl5-29. To determine if deletion of UL41 improves the efficacy of dl5-29 in protecting guinea pigs from HSV-2, animals were immunized with dl5-29, dl5-29-41L, or PBS. The geometric mean neutralizing antibody titers from the dl5-29 and dl5-29-41L recipients were comparable (10(1.97) and 10(2.19), respectively, p=0.15). After intravaginal challenge with wild-type HSV-2, the dl5-29-41L and dl5-29 recipients shed similar titers of HSV-2 from the vagina. Mean acute disease severity scores, numbers of recurrences during 3 months after infection, and latent viral loads in sacral ganglia were similar for dl5-29 and dl5-29-41L (all p values >0.05). dl5-29 and dl5-29-41L completely protected mice from lethal challenge with HSV-2 and induced virus-specific CD8(+) T cells in the spleens of the animals. Thus, dl5-29 was as immunogenic and protective as dl5-29-41L under these conditions. dl5-29 was at least 250,000-fold less virulent than parental virus by intracranial inoculation in healthy mice, and caused no disease in SCID mice. Both dl5-29-41L and dl5-29 are equally effective and immunogenic in guinea pigs, and dl5-29 is very safe in immunocompromised animals.

Comparison of predictability for human pharmacokinetics parameters among monkeys, rats, and chimeric mice with humanised liver.

Science.gov (United States)

Miyamoto, Maki; Iwasaki, Shinji; Chisaki, Ikumi; Nakagawa, Sayaka; Amano, Nobuyuki; Hirabayashi, Hideki

2017-12-01

1. The aim of the present study was to evaluate the usefulness of chimeric mice with humanised liver (PXB mice) for the prediction of clearance (CL t ) and volume of distribution at steady state (Vd ss ), in comparison with monkeys, which have been reported as a reliable model for human pharmacokinetics (PK) prediction, and with rats, as a conventional PK model. 2. CL t and Vd ss values in PXB mice, monkeys and rats were determined following intravenous administration of 30 compounds known to be mainly eliminated in humans via the hepatic metabolism by various drug-metabolising enzymes. Using single-species allometric scaling, human CL t and Vd ss values were predicted from the three animal models. 3. Predicted CL t values from PXB mice exhibited the highest predictability: 25 for PXB mice, 21 for monkeys and 14 for rats were predicted within a three-fold range of actual values among 30 compounds. For predicted human Vd ss values, the number of compounds falling within a three-fold range was 23 for PXB mice, 24 for monkeys, and 16 for rats among 29 compounds. PXB mice indicated a higher predictability for CL t and Vd ss values than the other animal models. 4. These results demonstrate the utility of PXB mice in predicting human PK parameters.

Fluid mechanical consequences of pendular activity, segmentation and pyloric outflow in the proximal duodenum of the rat and the guinea pig

Science.gov (United States)

de Loubens, Clément; Lentle, Roger G.; Love, Richard J.; Hulls, Corrin; Janssen, Patrick W. M.

2013-01-01

We conducted numerical experiments to study the influence of non-propagating longitudinal and circular contractions, i.e. pendular activity and segmentation, respectively, on flow and mixing in the proximal duodenum. A lattice-Boltzmann numerical method was developed to simulate the fluid mechanical consequences for each of 22 randomly selected sequences of high-definition video of real longitudinal and radial contractile activity in the isolated proximal duodenum of the rat and guinea pig. During pendular activity in the rat duodenum, the flow was characterized by regions of high shear rate. Mixing was so governed by shearing deformation of the fluid that increased the interface between adjacent domains and accelerated their inter-diffusion (for diffusion coefficients approx. less than 10−8 m² s−1). When pendular activity was associated with a slow gastric outflow characteristic of post-prandial period, the dispersion was also improved, especially near the walls. Mixing was not promoted by isolated segmentative contractions in the guinea pig duodenum and not notably influenced by pylorus outflow. We concluded that pendular activity generates mixing of viscous fluids ‘in situ’ and accelerates the diffusive mass transfer, whereas segmentation may be more important in mixing particulate suspensions with high solid volume ratios. PMID:23536539

Fluid mechanical consequences of pendular activity, segmentation and pyloric outflow in the proximal duodenum of the rat and the guinea pig.

Science.gov (United States)

de Loubens, Clément; Lentle, Roger G; Love, Richard J; Hulls, Corrin; Janssen, Patrick W M

2013-06-06

We conducted numerical experiments to study the influence of non-propagating longitudinal and circular contractions, i.e. pendular activity and segmentation, respectively, on flow and mixing in the proximal duodenum. A lattice-Boltzmann numerical method was developed to simulate the fluid mechanical consequences for each of 22 randomly selected sequences of high-definition video of real longitudinal and radial contractile activity in the isolated proximal duodenum of the rat and guinea pig. During pendular activity in the rat duodenum, the flow was characterized by regions of high shear rate. Mixing was so governed by shearing deformation of the fluid that increased the interface between adjacent domains and accelerated their inter-diffusion (for diffusion coefficients approx. less than 10(-8) m² s(-1)). When pendular activity was associated with a slow gastric outflow characteristic of post-prandial period, the dispersion was also improved, especially near the walls. Mixing was not promoted by isolated segmentative contractions in the guinea pig duodenum and not notably influenced by pylorus outflow. We concluded that pendular activity generates mixing of viscous fluids 'in situ' and accelerates the diffusive mass transfer, whereas segmentation may be more important in mixing particulate suspensions with high solid volume ratios.

Mystacial Whisker Layout and Musculature in the Guinea Pig (Cavia porcellus): A Social, Diurnal Mammal.

Science.gov (United States)

Grant, Robyn A; Delaunay, Mariane G; Haidarliu, Sebastian

2017-03-01

All mammals (apart from apes and humans) have whiskers that make use of a similar muscle arrangement. Whisker specialists, such as rats and mice, tend to be nocturnal and arboreal, relying on their whisker sense of touch to guide exploration around tree canopies at night. As such, nocturnal arboreal rodents have many whiskers that are organised into a grid-like pattern, and moved using a complex array of muscles. Indeed, most arboreal, nocturnal mammals tend to have specialised whiskers that are longer and arranged in a dense, regular grid, compared with terrestrial, diurnal mammals. The guinea pig diverged early from murid rodents (around 75 million years ago), and are ground-dwelling, diurnal animals. It would be predicted that, as a terrestrial mammal, they may have less whiskers and a reduced muscle architecture compared to arboreal, nocturnal rodents. We examined the mystacial whisker layout, musculature and movement capacity of Guinea pig (Cavia porcellus) whiskers and found that they did indeed have a disorganized whisker layout, with a fortification around the eye area. In addition, there was a reduction in musculature, especially in the intrinsic muscles. Despite guinea pigs not cyclically moving their whiskers, the mystacial musculature was still very similar to that of murid rodents. We suggest that the conserved presence of whisker layout and musculature, even in visual mammals such as primates and guinea pigs, may indicate that whiskers still play an important role in these animals, including protecting the eyes and being involved in tactile social behaviors. Anat Rec, 300:527-536, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Development of Protective Immunity against Inactivated Iranian Isolate of Foot-and-Mouth Disease Virus Type O/IRN/2007 Using Gamma Ray-Irradiated Vaccine on BALB/c Mice and Guinea Pigs.

Science.gov (United States)

Motamedi-Sedeh, Farahnaz; Soleimanjahi, Hoorieh; Jalilian, Amir Reza; Mahravani, Homayoon; Shafaee, Kamalodin; Sotoodeh, Masood; Taherkarami, Hamdolah; Jairani, Faramarz

2015-01-01

Foot-and-mouth disease virus (FMDV) causes a highly contagious disease in cloven-hoofed animals and is the most damaging disease of livestock worldwide, leading to great economic losses. The aim of this research was the inactivation of FMDV type O/IRN/1/2007 to produce a gamma ray-irradiated (GRI) vaccine in order to immunize mice and guinea pigs. In this research, the Iranian isolated FMDV type O/IRN/1/2007 was irradiated by gamma ray to prepare an inactivated whole virus antigen and formulated as a GRI vaccine with unaltered antigenic characteristics. Immune responses against this vaccine were evaluated on mice and guinea pigs. The comparison of the immune responses between the GRI vaccine and conventional vaccine did not show any significant difference in neutralizing antibody titer, memory spleen T lymphocytes or IFN-γ, IL-4, IL-2 and IL-10 concentrations (p > 0.05). In contrast, there were significant differences in all of the evaluated immune factors between the two vaccinated groups of mice and negative control mice (p GRI vaccines obtained were 6.28 and 7.07, respectively, which indicated the high potency of both vaccines. GRI vaccine is suitable for both routine vaccination and control of FMDV in emergency outbreaks.

Trypanosoma cruzi: partial prevention of the natural infection of guinea pigs with a killed parasite vaccine.

Science.gov (United States)

Basombrio, M A

1990-07-01

Guinea pigs are natural reservoirs of Chagas' disease. Domestic breeding and local trade of these animals are common practices among andean communities in South America. Infection by Trypanosoma cruzi occurs when the animals live in triatomine-infested houses or yards. The preventive effect of a vaccine consisting of cultured T. cruzi killed by freezing and thawing plus saponin was tested both in mice and in the guinea pig ecosystem. Resistance against T. cruzi challenge in mice was improved by increasing the trypomastigote/epimastigote ratio in live attenuated vaccines but not in killed parasite vaccines. Although the killing of attenuated parasites sharply reduced their immunogenicity for mice, a protective effect against natural T. cruzi infection was detected in guinea pigs. A total of 88 guinea pigs were vaccinated in four intradermal sites on three occasions. Eighty controls received similar inoculations of culture medium plus saponin. All animals were kept in a triatomine-infested yard. Parasitemia was studied with the capillary microhematocrit method. After an exposure time averaging 4 months, natural T. cruzi infection occurred in 55% (44/80) of the controls and in 33% (29/88) of the vaccinated group (P less than 0.01). The number of highly parasitemic guinea pigs was also significantly decreased (6/80 vs 0/88, P less than 0.01). Thus, immunizing protocols which are only partially protective against artificial callenge with T. cruzi may nevertheless constrain the exchange of parasites between natural hosts and vectors.

Dose dependent transfer of 203lead to milk and tissue uptake in suckling offspring studied in rats and mice

International Nuclear Information System (INIS)

Palminger Hallen, I.; Oskarsson, A.

1993-01-01

The dose-dependent transfer of 203 Pb to milk and uptake in suckling rats and mice during a three-day nursing period was studied. On day 14 of lactation, the dams were administered a single intravenous dose of lead, labelled with 203 Pb, in four or five doses from 0.0005 to 2.0 mg Pb/kg b.wt. There was a linear relationship between Pb levels in plasma and milk of both species. The Pb milk: plasma ratios at 24 hr after administration were 119 and 89 in mice and rats, respectively. At 72 hr the Pb milk: plasma ratio had decreased to 72 in mice and 35 in rats. The tissue levels of lead in the suckling rats and mice were also linearly correlated with lead concentration in milk at 72 hr, showing that milk could be used as an indicator of lead exposure to the suckling offspring. It is concluded that lead is transported into rat and mouse milk to a very high extent and the excretion into milk is more efficient in mice than in rats. On the other hand, rat pups had higher lead levels in tissues than mice pups, which might be due to a higher bioavailability and/or a lower excretion of lead in rat pups. Thus, lead in breast milk could be used as a biological indicator of lead exposure in the mother as well as in the suckling offspring. (au) (38 refs.)

High blood pressure in transgenic mice carrying the rat angiotensinogen gene.

Science.gov (United States)

Kimura, S; Mullins, J J; Bunnemann, B; Metzger, R; Hilgenfeldt, U; Zimmermann, F; Jacob, H; Fuxe, K; Ganten, D; Kaling, M

1992-01-01

Transgenic mice were generated by injecting the entire rat angiotensinogen gene into the germline of NMRI mice. The resulting transgenic animals were characterized with respect to hemodynamics, parameters of the renin angiotension system, and expression of the transgene. The transgenic line TGM(rAOGEN)123 developed hypertension with a mean arterial blood pressure of 158 mmHg in males and 132 mmHg in females. In contrast, the transgenic line TGM(rAOGEN)92 was not hypertensive. Rat angiotensinogen was detectable only in plasma of animals of line 123. Total plasma angiotensinogen and plasma angiotensin II concentrations were about three times as high as those of negative control mice. In TGM(rAOGEN)123 the transgene was highly expressed in liver and brain. Transcripts were also detected in heart, kidney and testis. In TGM(rAOGEN)92 the brain was the main expressing organ. In situ hybridization revealed an mRNA distribution in the brain of TGM(rAOGEN)123 similar to the one in rat. In TGM(rAOGEN)92 the expression pattern in the brain was aberrant. These data indicate that overexpression of the angiotensinogen gene in liver and brain leads to the development of hypertension in transgenic mice. The TGM(rAOGEN)123 constitutes a high angiotensin II type of hypertension and may provide a new experimental animal model to study the kinetics and function of the renin angiotensin system. Images PMID:1547785

(/sup 3/H)diprenorphine binding to kappa-sites in guinea-pig and rat brain: Evidence for apparent heterogeneity

Energy Technology Data Exchange (ETDEWEB)

Wood, M.S.; Traynor, J.R.

1989-07-01

The binding of the unselective opioid antagonist (/sup 3/H)diprenorphine to homogenates prepared from rat brain and from guinea-pig brain and cerebellum has been studied in HEPES buffer containing 10 mM Mg2+ ions. Sequential displacement of bound (/sup 3/H)diprenorphine by ligands with selectivity for mu-, delta-, and kappa-opioid receptors uncovers the multiple components of binding. In the presence of cold ligands that occupy all mu-, delta-, and kappa-sites, opioid binding still remains. This binding represents 20% of total specific sites and is displaced by naloxone. The nature of these undefined opioid binding sites is discussed.

Conhecimento da anatomia da orelha de cobaias e ratos e sua aplicação na pesquisa otológica básica Understanding the anatomy of ears from guinea pigs and rats and its use in basic otologic research

Directory of Open Access Journals (Sweden)

Agnes Afrodite Sumarelli Albuquerque

2009-02-01

Full Text Available O uso de mostras animais é importante na pesquisa otológica e o conhecimento da anatomia de sua orelha permite sua utilização adequada. OBJETIVO: Estudar a anatomia da orelha da cobaia e do rato por microscopia óptica de luz (MOL e microscopia eletrônica de varredura (MEV e suas vantagens anatômicas na pesquisa otológica básica. MATERIAL E MÉTODO: Os ossos temporais, as bulas timpânicas e cócleas de três cobaias e ratos albinos foram fotografados e analisados ao MOL e MEV. RESULTADOS: O rato não é tão simples de manipular como a cobaia, e freqüentemente apresenta otite média. O rato apresenta uma junção frágil da bula timpânica, duas e meia espiras na cóclea e a membrana timpânica não veda todo o conduto auditivo externo. A cobaia possui uma bula inteiriça, martelo e bigorna fundidos e três e meia espiras na cóclea. Pela MEV a cobaia e o rato possuem Membrana Tectória, Membrana de Raissner e o Órgão de Corti. As Células de Hensen estão presentes somente na cobaia. CONCLUSÃO: A cobaia foi considerada de fácil manipulação para a microdissecção, pelo tamanho e rigidez do osso temporal, e para experimentos cirúrgicos envolvendo o estribo, janela oval e a membrana timpânica. Pela MEV nota-se semelhança entre cobaia e rato, podendo ambos serem utilizados em estudos da orelha interna.The use of animal samples is important in otologic research and understanding the anatomy of their ears help make proper use of them in research projects. AIM: to study guinea pig's and rat's ears under light microscopy(LM and scanning electron microscopy(SEM and understand their anatomical advantages in basic otologic research. MATERIALS AND METHODS: The temporal bones, tympanic bullas and cochleas from three albino guinea pigs and rats were photographed and analyzed under LM and SEM. RESULTS: Rats aren't as simple to handle as guinea pigs, and often present with otitis media. Rats have a fragile junction of the tympanic bulla

Effect of fenspiride on pulmonary function in the rat and guinea pig.

Science.gov (United States)

Bee, D; Laude, E A; Emery, C J; Howard, P

1995-03-01

1. Fenspiride is an anti-inflammatory agent that may have a role in reversible obstructive airways disease. Small, but significant, improvements have been seen in airways function and arterial oxygen tension in patients with mild chronic obstructive pulmonary disease. These changes have been attributed to the anti-inflammatory properties of the drug. However, airways function can be improved by other means, e.g. improved ventilation/perfusion ratio or reduced airways resistance. The possibility that fenspiride may have actions other than anti-inflammatory was investigated in two animal species. 2. In the rat, actions on the pulmonary circulation were investigated in the isolated perfused lung, but fenspiride proved to be a poor pulmonary vasodilator, showing only a small reversal of the raised pulmonary artery pressure induced by hypoxia. 3. Ventilation was measured in the anaesthetized rat using whole-body plethysmography. Fenspiride caused no increase in ventilation or changes in arterial blood gases. However, a profound hypotensive action was observed with high doses. 4. The possibility that a decrease in airways resistance (R(aw)) might occur with fenspiride was investigated in anaesthetized guinea pigs. Capsaicin (30 mumol/l) was used to increase baseline R(aw) through bronchoconstriction. Fenspiride gave a dose-dependent partial reversal of the raised R(aw), and its administration by aerosol proved as efficacious as the intravenous route. In addition, the hypotensive side-effect found with intravenous injection was alleviated by aerosolized fenspiride.(ABSTRACT TRUNCATED AT 250 WORDS)

Vaccination with Trypanosoma rangeli induces resistance of guinea pigs to virulent Trypanosoma cruzi.

Science.gov (United States)

Basso, B; Moretti, E; Fretes, R

2014-01-15

Chagas' disease, endemic in Latin America, is spread in natural environments through animal reservoirs, including marsupials, mice and guinea pigs. Farms breeding guinea pigs for food are located in some Latin-American countries with consequent risk of digestive infection. The aim of this work was to study the effect of vaccination with Trypanosoma rangeli in guinea pigs challenged with Trypanosoma cruzi. Animals were vaccinated with fixated epimastigotes of T. rangeli, emulsified with saponin. Controls received only PBS. Before being challenged with T. cruzi, parasitemia, survival rates and histological studies were performed. The vaccinated guinea pigs revealed significantly lower parasitemia than controls (pguinea pigs and dogs. The development of vaccines for use in animals, like domestic dogs and guinea pigs in captivity, opens up new opportunities for preventive tools, and could reduce the risk of infection with T. cruzi in the community. Copyright © 2013 Elsevier B.V. All rights reserved.

Sensitivity of perianal tape impressions to diagnose pinworm (Syphacia spp.) infections in rats (Rattus norvegicus) and mice (Mus musculus).

Science.gov (United States)

Hill, William Allen; Randolph, Mildred M; Mandrell, Timothy D

2009-07-01

We determined the sensitivity of perianal tape impressions to detect Syphacia spp. in rats and mice. We evaluated 300 rat and 200 mouse perianal impressions over 9 wk. Pinworm-positive perianal tape impressions from animals with worm burdens at necropsy were considered as true positives. Conversely, pinworm-negative perianal tape impressions from animals with worm burdens were considered false negatives. The sensitivity of perianal tape impressions for detecting Syphacia muris infections in rats was 100%, and for detecting Syphacia obvelata in mice was 85.5%. Intermittent shedding of Syphacia obvelata ova is the most probable explanation for the decreased sensitivity rate we observed in mice. We urge caution in use of perianal tape impressions alone for Syphacia spp. screening in sentinel mice and rats.

CA V is present in rat kidney mitochondria

International Nuclear Information System (INIS)

Dodgson, S.J.; Contino, L.C.

1987-01-01

Guinea pig liver mitochondria contain the unique carbonic anhydrase isozyme, CA V. Prior to sacrifice, 15 rats and 15 guinea pigs were either fed normal lab chow (group 1), starved 48 hours (group 2) or fed normal lab chow and given to drink only water with added HCl, pH 2.5 (group 3). Mitochondria were prepared from excised livers and kidneys. CA V activity of disrupted mitochondria was measured by 18 O-mass spectrometric technique at pH 7.4, 37 0 C, 25 mM NaHCO 3 . Mass spectrometric CA assays with intact kidney mitochondria localize CA V activity to the matrix, as was found for liver mitochondria. It has been shown in hepatocytes prepared from starved guinea pigs and rats that inhibition of CA V results in decreased rate of gluconeogenesis from pyruvate. These present results are in line with the published observation that rat kidneys are much more gluconeogenic than guinea pig, and that this is increased by starvation and acidosis

Sex peculiarities of radiosensitivity. Communication 4. Action of ionizing radiation on the sexual cycles of mouse and guinea pig females

International Nuclear Information System (INIS)

Alekseeva, L.V.; Kudryavtseva, A.A.

1975-01-01

Animals (mice, guinea pigs) were irradiated with doses of 500, 700 and 750 r, while a control group was subjected to mock radiation. In all cases after mock and real irradiation, the sexual cycles of the female mice and guinea pigs were disturbed after 1-3 hours (after mock irradiation slightly, and after irradiation doses of 500 and 700 r to a greater extent). The restoration of the cycles of some animals after mock irradiation took place after 2 - 3 days, and of others after 10 - 14 days. After irradiation with doses of 500 - 700 r restoration of the cycles did not occur for two months and longer. Despite the considerable individual differences in the duration of the reaction, the delay was observed in all mice principally in the phase after heat, and in the guinea pigs during the inactive phase. (author)

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

Directory of Open Access Journals (Sweden)

C.R. Barbosa

2007-03-01

Full Text Available 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 < 0.05. Both supplementations in rats induced insulin resistance, as suggested by the higher Homeostasis Model Assessment Index. In contrast, mice showed significant decreases in triacylglycerol (G: 1.8 vs 1.4 and F: 1.9 vs 1.4 mM, P < 0.01 and total cholesterol levels (G and F: 2.7 vs 2.5 mM, P < 0.05 after both monosaccharide supplementations. Wistar rats and C57BL/6 mice, although belonging to the same family (Muridae, presented opposite responses to 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.

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.

Autoradiographic visualization of A 1-adenosine receptors in brain and peripheral tissues of rat and guinea pig using 125I-HPIA

International Nuclear Information System (INIS)

Weber, R.G.; Lohse, M.J.; Jones, C.R.; Palacios, J.M.

1988-01-01

A 1 -adenosine receptors were identified in sections of rat brain and guinea pig kidney with the radioiodinated agonist 1 25I-N 6 -p-hydroxyphenylisopropyladenosine ( 1 25I-HPIA) using in vitro autoradiography. The affinities of adenosine receptor ligands in competing with 1 25I-HPIA binding to tissue sections were in good agreement with those found in membranes and indicate that the binding site represents an A 1 pattern of [ 3 H]N 6 -cyclohexyladenosine ([ 3 H]CHA) binding sites determined previously, with highest densities in the hippocampus and dentate gyrus, the cerebellar cortex, some thalamic nuclei and certain layers of the cerebral cortex. In the guinea pig kidney 1 25I-HPIA labelled longitudinal structures in the medulla. This study demonstrates that 1 25I-HPIA allows the autoradiographic detection of A-1 adenosine receptors in the brain and peripheral organs and has the advantage of short exposure times (author)

Studies on the fate of poisonous metals in experimental animal. VIII. Species difference on biological half life of cadmium

Energy Technology Data Exchange (ETDEWEB)

Urakubo, G; Hasegawa, A; Ikebuchi, H; Onoda, K; Nakaura, S [National Inst. of Hygienic Sciences, Tokyo (Japan)

1978-04-01

About 30 -- 60 ..mu..Ci/0.15 mg Cd/kg of cadmium chloride solution containing sup(115m)Cd was injected intraperitoneally to mice, rats, guinea pigs, rabbits and quails, and thereafter the whole body retention of Cd was measured continuously for 60 -- 92 days in order to find the biological half lives of the metal in these animals. The whole body retention was determined by whole body counting of radioactivity in mice, rats, guinea pigs and quails, but in the case of rabbit it was determined by counting rates of excreta. The biological half lives thus obtained in mouse, rat, guinea pig, rabbit and quail were 220, 150 and 181, 334, 299 and 367 days, respectively. Namely, an apparent species difference was observed even under the same conditions such as sex of animal, dose of metal per kg and dosing route.

Some factors influencing liver metallothionein levels in rats and mice

International Nuclear Information System (INIS)

Jang, T.; Lee, M.

1981-01-01

Liver metallothionein (MT) was measured by the 203-mercury binding method of Piotrowski in the livers of rats and mice subjected to bilateral adrenalectomy or to sham adrenalectomy. Sham operation was followed by an increase in the level of MT at 24 hours; this immediately began to decrease, reaching control levels by 7 days. Adrenalectomy was also followed by an increase in MT, but the levels remained elevated for several days before beginning to decline. Mice which were adrenalectomized and allowed to recover for 28 days showed an increase in MT when subjected to sham operation. Ether anaesthesia without an incision did not increase the level of MT. Hypophysectomized mice had higher levels of MT than did controls, and these levels were further increased by sham adrenalectomy. Sprague-Dawley rats showed a similar response to adrenalectomy and to sham operation. It is concluded that the sham operation-induced increase in MT is probably not a result of a stress-induced release of adrenal hormones, but that adrenal hormones may play some role in the degradation or turnover of MT. The pituitary may also have some role in MT turnover

Sex peculiarities of radiosensitivity. Communication IV. Action of ionizing radiation on the sexual cycles of mouse and guinea pig females

Energy Technology Data Exchange (ETDEWEB)

Alekseeva, L V; Kudryavtseva, A A [AN SSSR, Pushchino-na-Oke. Inst. Biologicheskoj Fiziki

1975-01-01

Animals (mice, guinea pigs) were irradiated with doses of 500, 700 and 750 R, while a control group was subjected to mock radiation. In all cases after mock and real irradiation, the sexual cycles of the female mice and guinea pigs were disturbed after 1 to 3 hours (after mock irradiation slightly, and after irradiation doses of 500 and 700 R to a greater extent). The restoration of the cycles of some animals after mock irradiation took place after 2 to 3 days, and of others after 10 to 14 days. After irradiation with doses of 500 to 700 R restoration of the cycles did not occur for two months and longer. Despite the considerable individual differences in the duration of the reaction, the delay was observed in all mice principally in the phase after heat, and in the guinea pigs during the inactive phase.

Restoration of radiation injury by ginseng, 3

International Nuclear Information System (INIS)

Takeda, Atsuhiko; Katoh, Norio; Yonezawa, Morio

1982-01-01

Radiation protection by post-irradiation injection of a thermostable fraction of the ginseng extract in mice, rats and guinea pigs was studied. The thermostable fraction lost ''by-effects'' of decrease in body weight and splenic hyperplasia which were caused in injected mice by the original ginseng extract. The fraction protected mice (male) irradiated with 720 R of X-rays and rats (male) irradiated with 825 R with the dose about 6 mg per 100 g of body weight. The fraction also protected guinea pigs, both female and male, irradiated with 325 R with the dose about 80 mg per 300 g of body weight. The thermostable fraction stimulated recovery of thrombocyte and erythrocyte counts, but not leukocyte counts, in 550-R irradiated mice. Recovery of all the three blood cell counts was stimulated by the fraction in rats irradiated with 630 R and guinea pigs irradiated with 200 R. Comparison of stimulated recovery by the thermostable fraction of the ginseng extract among the three blood cell counts showed that restoring action was the most marked on thrombocyte counts, commonly in the three species of the animals. (author)

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

Glucagon-like peptide-2 (GLP-2) induces intestinal growth in mice; but in normal rats, it seems less potent, possibly because of degradation of GLP-2 by the enzyme dipeptidyl peptidase IV (DPP-IV). The purpose of this study was to investigate the survival and effect of GLP-2 in rats and mice afte...

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Vaccination with a HSV-2 UL24 mutant induces a protective immune response in murine and guinea pig vaginal infection models.

Science.gov (United States)

Visalli, Robert J; Natuk, Robert J; Kowalski, Jacek; Guo, Min; Blakeney, Susan; Gangolli, Seema; Cooper, David

2014-03-10

The rational design and development of genetically attenuated HSV-2 mutant viruses represent an attractive approach for developing both prophylactic and therapeutic vaccines for genital herpes. Previously, HSV-2 UL24 was shown to be a virulence determinant in both murine and guinea pig vaginal infection models. An UL24-βgluc insertion mutant produced syncytial plaques and replicated to nearly wild type levels in tissue culture, but induced little or no pathological effects in recipient mice or guinea pigs following vaginal infection. Here we report that immunization of mice or guinea pigs with high or low doses of UL24-βgluc elicited a highly protective immune response. UL24-βgluc immunization via the vaginal or intramuscular routes was demonstrated to protect mice from a lethal vaginal challenge with wild type HSV-2. Moreover, antigen re-stimulated splenic lymphocytes harvested from immunized mice exhibited both HSV-2 specific CTL activity and IFN-γ expression. Humoral anti-HSV-2 responses in serum were Th1-polarized (IgG2a>IgG1) and contained high-titer anti-HSV-2 neutralizing activity. Guinea pigs vaccinated subcutaneously with UL24-βgluc or the more virulent parental strain (186) were challenged with a heterologous HSV-2 strain (MS). Acute disease scores were nearly indistinguishable in guinea pigs immunized with either virus. Recurrent disease scores were reduced in UL24-βgluc immunized animals but not to the same extent as those immunized with strain 186. In addition, challenge virus was not detected in 75% of guinea pigs subcutaneously immunized with UL24-βgluc. In conclusion, disruption of the UL24 gene is a prime target for the development of a genetically attenuated live HSV-2 vaccine. Copyright © 2014 Elsevier Ltd. All rights reserved.

Montmorillonite ameliorates hyperthyroidism of rats and mice attributed to its adsorptive effect.

Science.gov (United States)

Cai, Yan; Meng, Xin-fang; Cao, Yong-xiao; Lu, Hua; Zhu, Shao-fei; Zhou, Liang-zhen

2006-12-03

The present study aims to evaluate the adsorbing effect of montmorillonite on thyroid hormone in the entero-hepatic circulation. The concentration of thyroid hormone in the serum of hyperthyroidism model rats and in solution was measured by radioimmunoassay and ultraviolet spectrometry, respectively. The body weight, temperature, and consumption of food and water were observed in hyperthyroidism model rats. Furthermore, hypoxia tolerance, sodium-pentobarbital-induced sleep time, spontaneous activities were measured on hyperthyroidism model mice after being treated with montmorillonite. Results showed that montmorillonite adsorbed thyroxin (T(4)) and triiodothyronine (T(3)) in vitro. Montmorillonite at dosage of 1.0 g/kg and 0.3 g/kg decreased thyroid hormone levels on hyperthyroidism model rats; Montmorillonite (2.0 g/kg and 0.6 g/kg) prolonged the sleep time, improved the hypoxia tolerant capacity and reduced the spontaneous activities of the hyperthyroidism model mice. These results suggest montmorillonite has anti-hyperthyroidism effect attributed to its adsorptive effect.

Developmental toxicity evaluation of inhaled tertiary amyl methyl ether in mice and rats.

Science.gov (United States)

Welsch, Frank; Elswick, Barbara; James, R Arden; Marr, Melissa C; Myers, Christina B; Tyl, Rochelle W

2003-01-01

This evaluation was part of a much more comprehensive testing program to characterize the mammalian toxicity potential of the gasoline oxygenator additive tertiary amyl methyl ether (TAME), and was initiated upon a regulatory agency mandate. A developmental toxicity hazard identification study was conducted by TAME vapor inhalation exposure in two pregnant rodent species. Timed-pregnant CD(Sprague-Dawley) rats and CD-1 mice, 25 animals per group, inhaled TAME vapors containing 0, 250, 1500 or 3500 ppm for 6 h a day on gestational days 6-16 (mice) or 6-19 (rats). The developmental toxicity hazard potential was evaluated following the study design draft guidelines and end points proposed by the United States Environmental Protection Agency. Based on maternal body weight changes during pregnancy, the no-observable-adverse-effect level (NOAEL) was 250 ppm for maternal toxicity in rats and 1500 ppm for developmental toxicity in rats using the criterion of near-term fetal body weights. In mice, more profound developmental toxicity was present than in rats, at both 1500 and 3500 ppm. At the highest concentration, mouse litters revealed more late fetal deaths, significantly reduced fetal body weights per litter and increased incidences of cleft palate (classified as an external malformation), as well as enlarged lateral ventricles of the cerebrum (a visceral variation). At 1500 ppm, mouse fetuses also exhibited an increased incidence of cleft palate and the dam body weights were reduced. Therefore, the NOAEL for the mouse maternal and developmental toxicity was 250 ppm under the conditions of this study. Copyright 2003 John Wiley & Sons, Ltd.

Immunoglobulin Genomics in the Guinea Pig (Cavia porcellus)

Science.gov (United States)

Guo, Yongchen; Bao, Yonghua; Meng, Qingwen; Hu, Xiaoxiang; Meng, Qingyong; Ren, Liming; Li, Ning; Zhao, Yaofeng

2012-01-01

In science, the guinea pig is known as one of the gold standards for modeling human disease. It is especially important as a molecular and cellular biology model for studying the human immune system, as its immunological genes are more similar to human genes than are those of mice. The utility of the guinea pig as a model organism can be further enhanced by further characterization of the genes encoding components of the immune system. Here, we report the genomic organization of the guinea pig immunoglobulin (Ig) heavy and light chain genes. The guinea pig IgH locus is located in genomic scaffolds 54 and 75, and spans approximately 6,480 kb. 507 VH segments (94 potentially functional genes and 413 pseudogenes), 41 DH segments, six JH segments, four constant region genes (μ, γ, ε, and α), and one reverse δ remnant fragment were identified within the two scaffolds. Many VH pseudogenes were found within the guinea pig, and likely constituted a potential donor pool for gene conversion during evolution. The Igκ locus mapped to a 4,029 kb region of scaffold 37 and 24 is composed of 349 Vκ (111 potentially functional genes and 238 pseudogenes), three Jκ and one Cκ genes. The Igλ locus spans 1,642 kb in scaffold 4 and consists of 142 Vλ (58 potentially functional genes and 84 pseudogenes) and 11 Jλ -Cλ clusters. Phylogenetic analysis suggested the guinea pig’s large germline VH gene segments appear to form limited gene families. Therefore, this species may generate antibody diversity via a gene conversion-like mechanism associated with its pseudogene reserves. PMID:22761756

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

Science.gov (United States)

2010-01-01

... INSPECTION AND CERTIFICATION CERTIFIED PRODUCTS FOR DOGS, CATS, AND OTHER CARNIVORA; INSPECTION... 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...

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

Science.gov (United States)

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

2013-02-01

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

A simple method for accurate endotracheal placement of an intubation tube in Guinea pigs to assess lung injury following chemical exposure.

Science.gov (United States)

Nambiar, M P; Gordon, R K; Moran, T S; Richards, S M; Sciuto, A M

2007-01-01

ABSTRACT Guinea pigs are considered as the animal model of choice for toxicology and medical countermeasure studies against chemical warfare agents (CWAs) and toxic organophosphate pesticides because of the low levels of carboxylesterase compared to rats and mice. However, it is difficult to intubate guinea pigs without damaging the larynx to perform CWA inhalation experiments. We describe an easy technique of intubation of guinea pigs for accurate endotracheal placement of the intubation tube. The technique involves a speculum made by cutting the medium-size ear speculum in the midline leaving behind the intact circular connector to the otoscope. Guinea pigs were anesthetized with Telazol/meditomidine, the tongue was pulled using blunt forceps, and an otoscope attached with the specially prepared speculum was inserted gently. Insertion of the speculum raises the epiglottis and restrains the movements of vocal cord, which allows smooth insertion of the metal stylet-reinforced intubation tube. Accurate endotracheal placement of the intubation tube was achieved by measuring the length from the tracheal bifurcation to vocal cord and vocal cord to the upper front teeth. The average length of the trachea in guinea pigs (275 +/- 25 g) was 5.5 +/- 0.2 cm and the distance from the vocal cord to the front teeth was typically 3 cm. Coinciding an intubation tube marked at 6 cm with the upper front teeth accurately places the intubation tube 2.5 cm above the tracheal bifurcation. This simple method of intubation does not disturb the natural flora of the mouth and causes minimum laryngeal damage. It is rapid and reliable, and will be very valuable in inhalation exposure to chemical/biological warfare agents or toxic chemicals to assess respiratory toxicity and develop medical countermeasures.

Hydroxyl radicals' production and ECG parameters during ischemia and reperfusion in rat, guinea pig and rabbit isolated heart.

Science.gov (United States)

Paulova, Hana; Stracina, Tibor; Jarkovsky, Jiri; Novakova, Marie; Taborska, Eva

2013-06-01

Ischemic and reperfusion injury is a serious condition related to numerous biochemical and electrical abnormalities of the myocardium. It has been repeatedly studied in various animal models. In this study, the production of hydroxyl radicals and electrophysiological parameters were compared in three species. Rat, guinea pig and rabbit isolated hearts were perfused according to Langendorff under strictly identical conditions. The heart rate and arrhythmia were monitored during ischemia and reperfusion periods at defined time intervals; the production of hydroxyl radical was determined by HPLC as 2.5-dihydroxybenzoic acid (2.5-DHBA) formed by salicylic acid hydroxylation. Relationship between arrhythmias and production of 2.5-DHBA was studied. The inter-species differences were observed in timing of arrhythmias onset and their severity, and in the production of 2.5-DHBA in both ischemia and reperfusion. The most considerable changes were observed in rats, where arrhythmias appeared early and with highest severity during ischemia on one side and the regular rhythm was restored early and completely during reperfusion. The corresponding changes in the production of 2.5-DHBA were observed. It can be concluded that rat isolated heart is the most suitable model for evaluation of ischemia/reperfusion injury under given experimental conditions.

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

Science.gov (United States)

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

2015-05-01

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

Effects of a thirteen-week inhalation exposure to ethyl tertiary butyl ether on fischer-344 rats and CD-1 mice.

Science.gov (United States)

Medinsky, M A; Wolf, D C; Cattley, R C; Wong, B; Janszen, D B; Farris, G M; Wright, G A; Bond, J A

1999-09-01

The 1990 Clean Air Act Amendments require that oxygenates be added to automotive fuels to reduce emissions of carbon monoxide and hydrocarbons. One potential oxygenate is the aliphatic ether ethyl tertiary butyl ether (ETBE). Our objective was to provide data on the potential toxic effects of ETBE. Male and female Fisher 344 rats and CD-1 mice were exposed to 0 (control), 500, 1750, or 5000 ppm of ETBE for 6 h/day and 5 days/wk over a 13-week period. ETBE exposure had no effect on mortality and body weight with the exception of an increase in body weights of the female rats in the 5000-ppm group. No major changes in clinical pathology parameters were noted for either rats or mice exposed to ETBE for 6 (rats only) or 13 weeks. Liver weights increased with increasing ETBE-exposure concentration for both sexes of rats and mice. Increases in kidney, adrenal, and heart (females only) weights were noted in rats. Degenerative changes in testicular seminiferous tubules were observed in male rats exposed to 1750 and 5000 ppm but were not seen in mice. This testicular lesion has not been reported previously for aliphatic ethers. Increases in the incidence of regenerative foci, rates of renal cell proliferation, and alpha2u-globulin containing protein droplets were noted in the kidneys of all treated male rats. These lesions are associated with the male rat-specific syndrome of alpha2u-globulin nephropathy. Increases in the incidence of centrilobular hepatocyte hypertrophy and rates of hepatocyte cell proliferation were seen in the livers of male and female mice in the 5000-ppm group, consistent with a mitogenic response to ETBE. These two target organs for ETBE toxicity, mouse liver and male rat kidney, have also been reported for methyl tertiary butyl ether and unleaded gasoline.

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

International Nuclear Information System (INIS)

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

1985-01-01

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 [ 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

Diadenosine pentaphosphate affects electrical activity in guinea pig atrium via activation of potassium acetylcholine-dependent inward rectifier.

Science.gov (United States)

Abramochkin, Denis V; Karimova, Viktoria M; Filatova, Tatiana S; Kamkin, Andre

2017-07-01

Diadenosine pentaphosphate (Ap5A) belongs to the family of diadenosine polyphosphates, endogenously produced compounds that affect vascular tone and cardiac performance when released from platelets. The previous findings indicate that Ap5A shortens action potentials (APs) in rat myocardium via activation of purine P2 receptors. The present study demonstrates alternative mechanism of Ap5A electrophysiological effects found in guinea pig myocardium. Ap5A (10 -4  M) shortens APs in guinea pig working atrial myocardium and slows down pacemaker activity in the sinoatrial node. P1 receptors antagonist DPCPX (10 -7  M) or selective GIRK channels blocker tertiapin (10 -6  M) completely abolished all Ap5A effects, while P2 blocker PPADS (10 -4  M) was ineffective. Patch-clamp experiments revealed potassium inward rectifier current activated by Ap5A in guinea pig atrial myocytes. The current was abolished by DPCPX or tertiapin and therefore was considered as potassium acetylcholine-dependent inward rectifier (I KACh ). Thus, unlike rat, in guinea pig atrium Ap5A produces activation of P1 receptors and subsequent opening of KACh channels leading to negative effects on cardiac electrical activity.

Comparison of mouse, guinea pig and rabbit models for evaluation of plague subunit vaccine F1+rV270.

Science.gov (United States)

Qi, Zhizhen; Zhou, Lei; Zhang, Qingwen; Ren, Lingling; Dai, Ruixia; Wu, Benchuan; Wang, Tang; Zhu, Ziwen; Yang, Yonghai; Cui, Baizhong; Wang, Zuyun; Wang, Hu; Qiu, Yefeng; Guo, Zhaobiao; Yang, Ruifu; Wang, Xiaoyi

2010-02-10

In this study, a new subunit vaccine that comprised native F1 and recombinant rV270 was evaluated for protective efficacy using mouse, guinea pig and rabbit models in comparison with the live attenuated vaccine EV76. Complete protection against challenging with 10(6) colony-forming units (CFU) of virulent Yersinia pestis strain 141 was observed for mice immunized with the subunit vaccines and EV76 vaccine. In contrast, the subunit vaccine recipes VII (F1-20 microg+rV270-10 microg) and IX (F1-40 microg+rV270-20 microg) and EV76 vaccine provided 86%, 79% and 93% protection against the same level of challenge in guinea pigs and 100%, 83% and 100% protection in rabbits, respectively. The immunized mice with the vaccines had significantly higher IgG titres than the guinea pigs and rabbits, and the immunized guinea pigs developed significantly higher IgG titres than the rabbits, but the anti-F1 response in guinea pigs was more variable than in the mice and rabbits, indicating that guinea pig is not an ideal model for evaluating protective efficacy of plague subunit vaccine, instead the rabbits could be used as an alternative model. All the immunized animals with EV76 developed a negligible IgG titre to rV270 antigen. Furthermore, analysis of IgG subclasses in the immunized animals showed a strong response for IgG1, whereas those receiving EV76 immunization demonstrated predominant production of IgG1 and IgG2a isotypes. The subunit vaccine and EV76 vaccine are able to provide protection for animals against Y. pestis challenge, but the subunit vaccines have obvious advantages over EV76 in terms of safety of use. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

A comparison of various methods of blood sampling in mice and rats: Effects on animal welfare

DEFF Research Database (Denmark)

Harikrishnan, Vs; Hansen, Axel K; Abelson, Klas Sp

2018-01-01

-puncture activity and anxiety levels of rats and mice were measured using an elevated plus maze test and an open field test. Stress levels 24 h post-puncture were assessed by analysing faecal corticosteroid metabolites. Sucrose intake and faecal corticosteroid levels were not affected by the blood sampling...... procedures. Rats showed reduced activity in the open field test and an increased level of anxiety in the elevated plus maze test following retrobulbar plexus puncture and isoflurane anaesthesia. In mice, nest building activity was affected in all the groups compared with the control group, except for animals...... subjected to facial vein puncture. Retrobulbar sinus puncture, tail vein puncture and sublingual puncture in mice resulted in reduced activity and increased anxiety. We conclude that, of the tested methods, puncture of the tail vein and the sublingual vein have the least adverse effects in rats, whereas...

Myocardial structural, contractile and electrophysiological changes in the guinea-pig heart failure model induced by chronic sympathetic activation

DEFF Research Database (Denmark)

Soltysinska, Ewa; Osadchiy, Oleg; Olesen, Søren-Peter

2011-01-01

Widely used murine models of adrenergic-induced cardiomyopathy offer little insight into electrical derangements seen in human heart failure owing to profound differences in the characteristics of ventricular repolarization in mice and rats compared with humans. We therefore sought to determine...... whether sustained adrenergic activation may produce a clinically relevant heart failure phenotype in the guinea-pig, an animal species whose ventricular action potential shape and restitution properties resemble those determined in humans. Isoprenaline (ISO), a ß-adrenoceptor agonist, was infused...... at variable dosage and duration using either subcutaneously implanted osmotic minipumps or daily injections, in an attempt to establish the relevant treatment protocol. We found that 3 months of daily ISO injections (final dose of 1 mg kg(-1), i.p.) promote heart failure evidenced by cardiac hypertrophy...

Repeated low-dose exposures to sarin, soman, or VX affect acoustic startle in guinea pigs.

Science.gov (United States)

Smith, C D; Lee, R B; Moran, A V; Sipos, M L

2016-01-01

Chemical warfare nerve agents (CWNAs) are known to cause behavioral abnormalities in cases of human exposures and in animal models. The behavioral consequences of single exposures to CWNAs that cause observable toxic signs are particularly well characterized in animals; however, less is known regarding repeated smaller exposures that may or may not cause observable toxic signs. In the current study, guinea pigs were exposed to fractions (0.1, 0.2, or 0.4) of a medial lethal dose (LD50) of sarin, soman, or VX for two weeks. On each exposure day, and for a post-exposure period, acoustic startle response (ASR) was measured in each animal. Although relatively few studies use guinea pigs to measure behavior, this species is ideal for CWNA-related experiments because their levels of carboxylesterases closely mimic those of humans, unlike rats or mice. Results showed that the 0.4 LD50 doses of soman and VX transiently increased peak startle amplitude by the second week of injections, with amplitude returning to baseline by the second week post-exposure. Sarin also increased peak startle amplitude independent of week. Latencies to peak startle and PPI were affected by agent exposure but not consistently among the three agents. Most of the changes in startle responses returned to baseline following the cessation of exposures. These data suggest that doses of CWNAs not known to produce observable toxic signs in guinea pigs can affect behavior in the ASR paradigm. Further, these deficits are transient and usually return to baseline shortly after the end of a two-week exposure period. Published by Elsevier Inc.

Microscopic distribution patterns of microspheres deposited by inhalation in lungs of rats, guinea pigs, and dogs

Energy Technology Data Exchange (ETDEWEB)

Snipes, M.B.; Guilmette, R.A.; Nikula, K.J.

1995-12-01

Acute inhalation exposures of mammalian species to small amounts of poorly soluble particles result in deposition of the particles in the head airways, tracheobronchial region, and pulmonary region of the respiratory tract. Most of the particles that deposit in the head airways and tracheobronchial region are believed to clear rapidly, but some as yet undefined fraction of the particles is retained in the airway epithelium or subepithelial interstitium for extended times. This long-term retention has important implications for the new respiratory tract dosimetry model of the International Commission on Radiological Protection because particles retained within the region can result in long-term exposure of airway epithelial cells. Preliminary results from this study demonstrate that a substantial fraction of the PSL microspheres inhaled by these rats, guinea pigs, and dogs was incorporated into the epithelium and interstitium of the tracheobronchial region.

Microscopic distribution patterns of microspheres deposited by inhalation in lungs of rats, guinea pigs, and dogs

International Nuclear Information System (INIS)

Snipes, M.B.; Guilmette, R.A.; Nikula, K.J.

1995-01-01

Acute inhalation exposures of mammalian species to small amounts of poorly soluble particles result in deposition of the particles in the head airways, tracheobronchial region, and pulmonary region of the respiratory tract. Most of the particles that deposit in the head airways and tracheobronchial region are believed to clear rapidly, but some as yet undefined fraction of the particles is retained in the airway epithelium or subepithelial interstitium for extended times. This long-term retention has important implications for the new respiratory tract dosimetry model of the International Commission on Radiological Protection because particles retained within the region can result in long-term exposure of airway epithelial cells. Preliminary results from this study demonstrate that a substantial fraction of the PSL microspheres inhaled by these rats, guinea pigs, and dogs was incorporated into the epithelium and interstitium of the tracheobronchial region

Comparative Study of Experimentally Induced Cancer of the Kidney in Mice and Rats with X-Rays

Energy Technology Data Exchange (ETDEWEB)

Maldague, P. [Cancer Institute, University of Louvain (Belgium)

1969-11-15

Local irradiation of a kidney in rats and mice results in the development of radiation- induced cancers in the irradiated kidney. The production of these cancers is considerably greater in rats than in mice, and their frequency depends on: (1) The X-ray dose absorbed by the kidney; (2) The latency period which is longer for carcinomas than for sarcomas; and (3) The degree and extent of renal radiation- induced lesions. A study of the relationship between dose and carcinogenic effect has enabled us to define three types of X-ray dose: (a) An ineffective dose of 570 rads at which the inducement of cancer is zero; (b) An optimum dose of 1700 rads at which the frequency of renal tumours is maximal (85%); and (c) Excessive doses between 7000 and 14 000 rads after which the frequency of radiation-induced cancers of the kidney approaches zero. Studies of the latent period have shown that radiation-induced cancers of the kidney in mice do not appear until 790 days after irradiation, whereas in rats the first cancers appear after 280 days. As regards the mechanism of the inducement of renal cancer by radiation, we have been able to establish that cancers of the kidney only develop from visible renal lesions. Radiation-induced cancers have not been observed in rats or mice whose kidneys were morphologically and functionally normal. (author)

Guinea pig-adapted foot-and-mouth disease virus with altered receptor recognition can productively infect a natural host.

Science.gov (United States)

Núñez, José I; Molina, Nicolas; Baranowski, Eric; Domingo, Esteban; Clark, Stuart; Burman, Alison; Berryman, Stephen; Jackson, Terry; Sobrino, Francisco

2007-08-01

We report that adaptation to infect the guinea pig did not modify the capacity of foot-and-mouth disease virus (FMDV) to kill suckling mice and to cause an acute and transmissible disease in the pig, an important natural host for this pathogen. Adaptive amino acid replacements (I(248)-->T in 2C, Q(44)-->R in 3A, and L(147)-->P in VP1), selected upon serial passages of a type C FMDV isolated from swine (biological clone C-S8c1) in the guinea pig, were maintained after virus multiplication in swine and suckling mice. However, the adaptive replacement L(147)-->P, next to the integrin-binding RGD motif at the GH loop in VP1, abolished growth of the virus in different established cell lines and modified its antigenicity. In contrast, primary bovine thyroid cell cultures could be productively infected by viruses with replacement L(147)-->P, and this infection was inhibited by antibodies to alphavbeta6 and by an FMDV-derived RGD-containing peptide, suggesting that integrin alphavbeta6 may be used as a receptor for these mutants in the animal (porcine, guinea pig, and suckling mice) host. Substitution T(248)-->N in 2C was not detectable in C-S8c1 but was present in a low proportion of the guinea pig-adapted virus. This substitution became rapidly dominant in the viral population after the reintroduction of the guinea pig-adapted virus into pigs. These observations illustrate how the appearance of minority variant viruses in an unnatural host can result in the dominance of these viruses on reinfection of the original host species.

Expression of Sirtuins in the Retinal Neurons of Mice, Rats, and Humans

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Hongdou Luo

2017-11-01

Full Text Available Sirtuins are a class of histone deacetylases (HDACs that have been shown to regulate a range of pathophysiological processes such as cellular aging, inflammation, metabolism, and cell proliferation. There are seven mammalian Sirtuins (SIRT1-7 that play important roles in stress response, aging, and neurodegenerative diseases. However, the location and function of Sirtuins in neurons are not well defined. This study assessed the retinal expression of Sirtuins in mice, rats, and humans and measured the expression of Sirtuins in aged and injured retinas. Expression of all 7 Sirtuins was confirmed by Western blot and Real-Time PCR analysis in all three species. SIRT1 is highly expressed in mouse, rat, and human retinas, whereas SIRT2-7 expression was relatively lower in human retinas. Immunofluorescence was also used to examine the expression and localization of Sirtuins in rat retinal neurons. Importantly, we demonstrate a marked reduction of SIRT1 expression in aged retinal neurons as well as retinas injured by acute ischemia-reperfusion. On the other hand, none of the other Sirtuins exhibit any significant age-related changes in expression except for SIRT5, which was significantly higher in the retinas of adults compared to both young and aged rats. Our work presents the first composite analysis of Sirtuins in the retinal neurons of mice, rats, and humans, and suggests that increasing the expression and activity of SIRT1 may be beneficial for the treatment of glaucoma and other age-related eye dysfunction.

Eosinophilic spleen colonies are produced in rat-marrow-transplanted but not in murine-marrow-transplanted mice

International Nuclear Information System (INIS)

Szabo, L.G.; Kelemen, E.

1988-01-01

Differential counts of about 5000 splenic clusters and colonies developing in whole-body-irradiated mice and rats were made, using semi-serial histological sections prepared 9 to 12 d after transplantation with bone marrow haemopoietic cells. The investigated mouse and rat spleens were from syngeneically, allogeneically, or xenogeneically transplanted recipients. Splenic eosinophil clusters were always found when rat eosinophil-producing progenitors were present in the inoculum, whereas murine inocula failed to produce splenic eosinophilic clusters even in the syngeneic mouse. The limiting factor in the production pf splenic eosinophilic clusters was the appropriate donor progenitor/committed stem cell itself. Changes in the percentages of eosinophil clusters with the number of injected cells and with increased doses of irradiation, as well as formation of rat eosinophil colonies in mice, as against mainly clusters in rats, themselves show that regulatory mechanisms of the recipients also play a role. These regulatory mechanisms cannot be attributed to the splenic microenvironment. (author)

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

; 15 mg VP; 40 microg GLP-2, 40 microg GLP-2+15 mg VP; 40 microg GLP-2 (3-33). Mice were treated for 10 days with: saline; 5 microg GLP-2; 5 microg GLP-2+1.5 mg VP; 25 microg GLP-2; 25 microg GLP-2 (3-33). In both cases, body weight, intestinal weight, length, and morphometric data were measured. After...... (4.68 +/- 0.11%, relative to body weight), compared with the two control groups, [3.01 +/- 0.06% (VP) and 2.94 +/- 0.07% (NaCl)] and GLP-2 alone (3.52 +/- 0.10%). In mice, the growth effect of 5 microg GLP-2+VP was comparable with that of 25 microg GLP-2. GLP-2 (3-33) had no effect in rats......, but it had a weak effect on intestinal growth in mice. The extensive GLP-2 degradation in rats can be reduced by VP, and DPP-IV inhibition markedly enhances the intestinotrophic effect of GLP-2 in both rats and mice. We propose that DPP-IV inhibition may be considered to enhance the efficacy of GLP-2...

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

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Marco Schlepütz

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

Guinea pigs as an animal model for sciatic nerve injury

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Malik Abu Rafee

2017-01-01

Full Text Available The overwhelming use of rat models in nerve regeneration studies is likely to induce skewness in treatment outcomes. To address the problem, this study was conducted in 8 adult guinea pigs of either sex to investigate the suitability of guinea pig as an alternative model for nerve regeneration studies. A crush injury was inflicted to the sciatic nerve of the left limb, which led to significant decrease in the pain perception and neurorecovery up to the 4th weak. Lengthening of foot print and shortening of toe spread were observed in the paw after nerve injury. A 3.49 ± 0.35 fold increase in expression of neuropilin 1 (NRP1 gene and 2.09 ± 0.51 fold increase in neuropilin 2 (NRP2 gene were recorded 1 week after nerve injury as compared to the normal nerve. Ratios of gastrocnemius muscle weight and volume of the experimental limb to control limb showed more than 50% decrease on the 30th day. Histopathologically, vacuolated appearance of the nerve was observed with presence of degenerated myelin debris in digestion chambers. Gastrocnemius muscle also showed degenerative changes. Scanning electron microscopy revealed loose and rough arrangement of connective tissue fibrils and presence of large spherical globules in crushed sciatic nerve. The findings suggest that guinea pigs could be used as an alternative animal model for nerve regeneration studies and might be preferred over rats due to their cooperative nature while recording different parameters.

FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units.

Science.gov (United States)

Mähler Convenor, M; Berard, M; Feinstein, R; Gallagher, A; Illgen-Wilcke, B; Pritchett-Corning, K; Raspa, M

2014-07-01

The microbiological quality of experimental animals can critically influence animal welfare and the validity and reproducibility of research data. It is therefore important for breeding and experimental facilities to establish a laboratory animal health monitoring (HM) programme as an integrated part of any quality assurance system. FELASA has published recommendations for the HM of rodent and rabbit colonies in breeding and experimental units (Nicklas et al. Laboratory Animals, 2002), with the intention of harmonizing HM programmes. As stated in the preamble, these recommendations need to be adapted periodically to meet current developments in laboratory animal medicine. Accordingly, previous recommendations have been revised and shall be replaced by the present recommendations. These recommendations are aimed at all breeders and users of laboratory mice, rats, Syrian hamsters, guinea pigs and rabbits as well as diagnostic laboratories. They describe essential aspects of HM, such as the choice of agents, selection of animals and tissues for testing, frequency of sampling, commonly used test methods, interpretation of results and HM reporting. Compared with previous recommendations, more emphasis is put on the role of a person with sufficient understanding of the principles of HM, opportunistic agents, the use of sentinel animals (particularly under conditions of cage-level containment) and the interpretation and reporting of HM results. Relevant agents, testing frequencies and literature references are updated. Supplementary information on specific agents and the number of animals to be monitored and an example of a HM programme description is provided in the appendices. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Experimental Inoculation in Rats and Mice by the Giant Marseillevirus Leads to Long-Term Detection of Virus

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Sarah Aherfi

2018-03-01

Full Text Available The presence of the giant virus of amoeba Marseillevirus has been identified at many different sites on the human body, including in the bloodstream of asymptomatic subjects, in the lymph nodes of a child with adenitis, in one adult with Hodgkin's disease, and in the pharynx of an adult. A high seroprevalence of the Marseillevirus has been recorded in the general population. Whether Marseillevirus can disseminate and persist within a mammal after entry remains unproven. We aimed to assess the ability of the virus to disseminate and persist into healthy organisms, especially in the lymphoid organs. Parenteral inoculations were performed by intraperitoneal injection (in rats and mice or intravenous injection (in rats. Airway inoculation was performed by aerosolization (in mice. Dissemination and persistence were assessed by using PCR and amebal co-culture. Serologies were performed by immunofluorescent assay. Pathological examination was conducted after standard and immunohistochemistry staining. After intraperitoneal inoculation in mice and rats, Marseillevirus was detected in the bloodstream during the first 24 h. Persistence was noted until the end of the experiment, i.e., at 14 days in rats. After intravenous inoculation in rats, the virus was first detected in the blood until 48 h and then in deep organs with infectious virus detected until 14 and 21 days in the liver and the spleen, respectively. Its DNA was detected for up to 30 days in the liver and the spleen. After aerosolization in mice, infectious Marseillevirus was present in the lungs and nasal associated lymphoid tissue until 30 days post inoculation but less frequently and at a lower viral load in the lung than in the nasal associated lymphoid tissue. No other site of dissemination was found after aerosol exposure. Despite no evidence of disease being observed, the 30-day long persistence of Marseillevirus in rats and mice, regardless of the route of inoculation, supports the

Experimental study of neuropharmacological profile of Euphorbia pulcherrima in mice and rats

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Kundan Kr Singh

2012-01-01

Full Text Available Context: Euphorbia pulcherrima (EP belongs to the family: Euphorbiaceae and Genus: Euphorbia. Many species of Euphorbia have been reported as having beneficial properties like anticonvulsive effect, central analgesic properties, antipyretic action, central depressant action and strong sedative effect. However, little study has been done and published on EP. Aims: To observe and evaluate various neuropharmacological effects like antinociceptive effect, anticonvulsant effect, motor in-coordination, pentobarbital induced sleeping time and behavioral responses of EP in mice and rats. Setting and Design: Quantitative experimental study in mice and rats by various experimental models. Materials and Methods: Different experimental models were used to assess the antinociceptive effect (hotplate, tail flick and acetic acid induced writhing test, anticonvulsant effect (Maximal Electroshock Seizure test [MES] and Pentylenetetrazole induced seizures [PTZ], motor in-coordination effect (Rota rod test, pentobarbital induced sleeping time and behavioral responses of EP in mice and rats after oral administration of EP crude dried extracts in three different doses (250, 500 and 1000 mg/kg. Statistical Analysis Used: The significance of difference with respect to control was evaluated using the Mann-Whitney U test. A probability (P-value level less than 0.05 was considered as significant. Results: In MES test model, duration of tonic hind limb extension in mice treated with EP was significantly less as compared to vehicle treated group. EP was most effective in a dose of 1000 mg/kg. There was also significant increase in the latency and decrease in the incidence of convulsions with the use of EP in three different doses in PTZ induced seizure model. Conclusions: This study showed EP (crude dried extracts to possess anticonvulsant properties but no effect on motor co-ordination and anxiety.

Disposition and metabolism of the bisphenol analogue, bisphenol S, in Harlan Sprague Dawley rats and B6C3F1/N mice and in vitro in hepatocytes from rats, mice, and humans.

Science.gov (United States)

Waidyanatha, Suramya; Black, Sherry R; Snyder, Rodney W; Yueh, Yun Lan; Sutherland, Vicki; Patel, Purvi R; Watson, Scott L; Fennell, Timothy R

2018-05-10

With the removal of bisphenol A (BPA) from many consumer products, the potential use of alternatives such as bisphenol S (BPS) and its derivatives is causing some concerns. These studies investigated the comparative in vitro hepatic clearance and metabolism of BPS and derivatives and the disposition and metabolism of BPS in rats and mice following gavage and intravenous administration. The clearance of BPS and its derivatives was slower in human hepatocytes than in rodents. In male rats following gavage administration of 50, 150, and 500 mg/kg [ 14 C]BPS the main route of excretion was via urine; the urinary excretion decreased (72 to 48%) and the fecal excretion increased (16 to 30%) with increasing dose. The disposition was similar in female rats and male and female mice following gavage administration. Radioactivity remaining in tissues at 72 h in both species and sexes was ≤2.4%. In bile duct cannulated rats 53% of a gavage dose was secreted in bile suggesting extensive enterohepatic recirculation of [ 14 C]BPS. Following an intravenous dose in rats and mice, the pattern of excretion was similar to gavage. These data suggest that the dose excreted in feces folowing gavage administration is likely the absorbed dose. Urinary metabolites included the glucuronide and sulfate conjugates with a moderate amount of parent. The pattern of in vitro hepatic metabolsim was similar to in vivo with some difference among derivatives. These data suggest that similar to other bisphenol analogues, BPS was well absorbed following oral expsosure and extensively excreted with minimal tissue retention. Copyright © 2017. Published by Elsevier Inc.

Chromium and vanadium effects on glucose and lipid metabolism of guinea pigs and obese and diabetic mice

International Nuclear Information System (INIS)

Li, Y.C.

1987-01-01

Severe chromium deficiency in experimental animals may contribute to insulin resistance, impaired glucose tolerance and elevated serum cholesterol concentration. Vanadium also has been reported to be a nutritionally important element for both chicks and rats, but its function and even its essentiality are still in question. Chromium absorption even from supplemented diets is poor, thus efforts were made to study the site of absorption of 51 Cr from CrCl 3 . 51 Cr was found to move very rapidly through the GI tract and appears to flow with dietary and secreted water. It was not absorbed from the stomach. In a study with guinea pigs, vanadate supplementation appeared to affect cholesterol fraction. Chromium supplementation lowered serum triacylglycerol concentrations at the end of an 18-week study. Since the previous study and others have indicated a role for chromium and vanadium in lipid carbohydrate metabolism, experiments were designed to compare effects of chromium and vanadium supplements on related parameters

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.

Guinea-Bissau.

Science.gov (United States)

1985-04-01

This discussion of Guinea-Bissau focuses on the following: the people; geography; history; government and political conditions; the economy; foreign relations; and relations between the US and Guinea-Bissau. In 1983 the population was estimated at 827,000 with an annual estimated growth rate of 2.2%. 87% of the population was rural, with 13% living in urban areas. The infant mortality rate is 200/1000 with a life expectancy of 42 years. The population comprises several diverse tribal groups, each with its own language, customs, and social organization. Most people are farmers and follow the traditional religious beliefs of their forebears. Most of the nonindigenous population consists of a significant Cape Verdian ethnic community, a small Portuguese community engaged primarily in commerce and civil service, and a few foreign technical consultants. Guinea-Bissau is a small enclave on the west coast of Africa, bounded by Senegal and on the south and east by Guinea (Conakry). Portugal claimed Portuguese Guinea in 1446 when the fleet of Nuno Tristao arrived on the west coast of Africa. In 1956 the African Party for the Independence of Guinea and Cape Verde (PAIGC) was organized clandestinely by the Amilcar Cabral and Raphael Barbosa. The PAIGC moved its headquarters to Conakry in 1960 and began an armed rebellion in 1961. Despite the presence of more than 30,000 Portuguese troops, the PAIGC exercised influence over much of the country by 1972. It established civilian rule in the territory that it controlled and elections took place for a National Assembly. The National Assembly of the PAIGC declared the independence of Guinea-Bissau on September 24, 1973. Portugal granted "de jure" independence on September 10, 1974, when the US recognized the new nation. Guinea-Bissau is a 1-party state. Until May 1984, power was held by a provisional government responsible to a Revolutionary Council. In May 1984 the Revolutionary Council was dissolved, and the 150-member National

Development and characterization of a guinea pig model for Marburg virus

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Gary Wong

2018-01-01

Full Text Available The Angolan strain of Marburg virus (MARV/Ang can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice (MARV/Ang-MA, with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate (NHP model. In this study, we serially passaged the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs until a variant emerged that causes 100% lethality in guinea pigs (MARV/Ang-GA. Animals infected with MARV/Ang-GA showed signs of filovirus infection including lymphocytopenia, thrombocytopenia, and high viremia leading to spread to major organs, including the liver, spleen, lungs, and kidneys. The MARV/Ang-GA guinea pigs died between 7–9 days after infection, and the LD50 was calculated to be 1.1×10–1 TCID50 (median tissue culture infective dose. Mutations in MARV/Ang-GA were identified and compared to sequences of known rodent-adapted MARV/Ang variants, which may benefit future studies characterizing important host adaptation sites in the MARV/Ang viral genome.

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

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

International Nuclear Information System (INIS)

Harrill, Joshua A.; Hukkanen, Renee R.; Lawson, Marie; Martin, Greg; Gilger, Brian; Soldatow, Valerie; LeCluyse, Edward L.; Budinsky, Robert A.; Rowlands, J. Craig; Thomas, Russell S.

2013-01-01

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

Disparate patterns of age-related changes in lipid peroxidation in long-lived naked mole-rats and shorter-lived mice.

Science.gov (United States)

Andziak, Blazej; Buffenstein, Rochelle

2006-12-01

A key tenet of the oxidative stress theory of aging is that levels of accrued oxidative damage increase with age. Differences in damage generation and accumulation therefore may underlie the natural variation in species longevity. We compared age-related profiles of whole-organism lipid peroxidation (urinary isoprostanes) and liver lipid damage (malondialdehyde) in long living naked mole-rats [maximum lifespan (MLS) > 28.3 years] and shorter-living CB6F1 hybrid mice (MLS approximately 3.5 years). In addition, we compared age-associated changes in liver non-heme iron to assess how intracellular conditions, which may modulate oxidative processes, are affected by aging. Surprisingly, even at a young age, concentrations of both markers of lipid peroxidation, as well as of iron, were at least twofold (P naked mole tats than in mice. This refutes the hypothesis that prolonged naked mole-rat longevity is due to superior protection against oxidative stress. The age-related profiles of all three parameters were distinctly species specific. Rates of lipid damage generation in mice were maintained throughout adulthood, while accrued damage in old animals was twice that of young mice. In naked mole-rats, urinary isoprostane excretion declined by half with age (P naked mole-rats is independent of oxidative stress parameters.

Experimental aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs.

Science.gov (United States)

Twenhafel, N A; Shaia, C I; Bunton, T E; Shamblin, J D; Wollen, S E; Pitt, L M; Sizemore, D R; Ogg, M M; Johnston, S C

2015-01-01

Eight guinea pigs were aerosolized with guinea pig-adapted Zaire ebolavirus (variant: Mayinga) and developed lethal interstitial pneumonia that was distinct from lesions described in guinea pigs challenged subcutaneously, nonhuman primates challenged by the aerosol route, and natural infection in humans. Guinea pigs succumbed with significant pathologic changes primarily restricted to the lungs. Intracytoplasmic inclusion bodies were observed in many alveolar macrophages. Perivasculitis was noted within the lungs. These changes are unlike those of documented subcutaneously challenged guinea pigs and aerosolized filoviral infections in nonhuman primates and human cases. Similar to findings in subcutaneously challenged guinea pigs, there were only mild lesions in the liver and spleen. To our knowledge, this is the first report of aerosol challenge of guinea pigs with guinea pig-adapted Zaire ebolavirus (variant: Mayinga). Before choosing this model for use in aerosolized ebolavirus studies, scientists and pathologists should be aware that aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs. © The Author(s) 2014.

An Adjuvanted Herpes Simplex Virus 2 Subunit Vaccine Elicits a T Cell Response in Mice and Is an Effective Therapeutic Vaccine in Guinea Pigs

Science.gov (United States)

Skoberne, Mojca; Cardin, Rhonda; Lee, Alexander; Kazimirova, Ana; Zielinski, Veronica; Garvie, Danielle; Lundberg, Amy; Larson, Shane; Bravo, Fernando J.; Bernstein, David I.; Flechtner, Jessica B.

2013-01-01

Immunotherapeutic herpes simplex virus 2 (HSV-2) vaccine efficacy depends upon the promotion of antigen-specific immune responses that inhibit reactivation or reactivated virus, thus controlling both recurrent lesions and viral shedding. In the present study, a candidate subunit vaccine, GEN-003/MM-2, was evaluated for its ability to induce a broad-spectrum immune response in mice and therapeutic efficacy in HSV-2-infected guinea pigs. GEN-003 is comprised of HSV-2 glycoprotein D2 (gD2ΔTMR340-363) and a truncated form of infected cell polypeptide 4 (ICP4383-766), formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM-2). In addition to eliciting humoral immune responses, CD4+ and CD8+ T cells characterized by the secretion of multiple cytokines and cytolytic antigen-specific T cell responses that were able to be recalled at least 44 days after the last immunization were induced in immunized mice. Furthermore, vaccination with either GEN-003 or GEN-003/MM-2 led to significant reductions in both the prevalence and severity of lesions in HSV-2-infected guinea pigs compared to those of phosphate-buffered saline (PBS) control-vaccinated animals. While vaccination with MM-2 adjuvant alone decreased recurrent disease symptoms compared to the PBS control group, the difference was not statistically significant. Importantly, the frequency of recurrent viral shedding was considerably reduced in GEN-003/MM-2-vaccinated animals but not in GEN-003- or MM-2-vaccinated animals. These findings suggest a possible role for immunotherapeutic GEN-003/MM-2 vaccination as a viable alternative to chronic antiviral drugs in the treatment and control of genital herpes disease. PMID:23365421

Form-deprivation myopia induces decreased expression of bone morphogenetic protein-2, 5 in guinea pig sclera

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Qing Wang

2015-02-01

Full Text Available AIM: To identify the presence of various bone morphogenetic proteins (BMPs and their receptors in normal sclera of human, rat and guinea pigs, and to determine whether their expression changed with form-deprivation myopia (FDM in guinea pig sclera. METHODS: The expression of BMPs and BMP receptors were detected using reverse transcription polymerase chain reaction (RT-PCR and immunofluorescence. Two-week-old guinea pigs were monocularly form-deprived with a translucent lens. After fourteen days induction of FDM, total RNA was isolated and subjected to RT-PCR to examine the changes of BMPs and BMP receptors in tissues from the posterior sclera. Western blotting analysis was used to investigate their changes in protein levels. RESULTS: Human sclera expressed mRNAs for BMP-2, -4, -5, -7, -RIA, -RIB and BMP-RII. Conversely, rat sclera only expressed mRNA for BMP-7 and BMP-RIB, while the expression of BMPs and BMP receptors in guinea pigs were similar to that of humans. Human sclera also expresses BMP-2, -4, -5,-7 in protein level. Fourteen days after the induction of myopia, significant decreased expressions for BMP-2 and BMP-5 in the posterior sclera of FDM-affected eyes (PCONCLUSION: Various BMPs were expressed in human and guinea pig sclera. In the posterior sclera, expressions of BMP-2 and BMP-5 significantly decreased in FDM eyes. This finding indicates that various BMPs as components of the scleral cytokines regulating tissue homeostasis and provide evidence that alterations in the expression of BMP-2 and BMP-5 are associated with sclera remodeling during myopia induction.

Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs

Science.gov (United States)

Kim, Hwan Keun; Falugi, Fabiana; Thomer, Lena; Missiakas, Dominique M.

2015-01-01

ABSTRACT   Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links VH3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High VH3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host B cell responses. Immunization with SpAKKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity. Importance  Staphylococcus aureus is the leading cause of soft tissue and bloodstream infections; however, a vaccine with clinical efficacy is not available. Using mice to model staphylococcal infection, earlier work identified protective antigens; however, corresponding human clinical trials did not reach their endpoints. We show that B cell receptor (IgM) cross-linking by protein A is an important immune evasion strategy of S. aureus that can be monitored in a guinea pig model of bloodstream infection. Further, immunization with nontoxigenic protein A enables infected guinea pigs to elicit antibody responses that are protective against S. aureus. Thus, the guinea pig model may support preclinical development of staphylococcal vaccines. PMID:25564466

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

Glucagon is a metabolically important hormone, but many aspects of its physiology remain obscure, because glucagon secretion is difficult to measure in mice and rats due to methodological inadequacies. Here, we introduce and validate a low-volume, enzyme-linked immunosorbent glucagon assay...... according to current analytical guidelines, including tests of sensitivity, specificity, and accuracy, and compare it, using the Bland-Altman algorithm and size-exclusion chromatography, with three other widely cited assays. After demonstrating adequate performance of the assay, we measured glucagon...... and returning to basal levels at 6 min (mice) and 12 min (rats). d-Mannitol (osmotic control) was without effect. Ketamine/xylazine anesthesia in mice strongly attenuated (P assay. In conclusion, dynamic analysis...

Comparison between narcotic 'receptors' in the guinea-pig ileum and the rat brain

Energy Technology Data Exchange (ETDEWEB)

Terenius, L [Uppsala Univ. (Sweden)

1975-01-01

The receptors, i.e., specific binding molecules, for narcotic analgesics in the guinea-pig ileum and rat brain have been compared. The relative affinities of a number of narcotics for the two receptors were very similar and discrimination between stereoisomeric agents was identical. The dissociation constants for dihydromorphine binding were 0.78 nM for the ileum and 1.4 nM for the brain receptor, respectively. There was a good correspondance between receptor affinities on the ileum preparation and the literature data on biologic activity on the isolated ileum. Codeine, diphenoxylate, difenoxine and loperamide, which are used clinically for the treatment of diarrhoea showed no selectivity against the ileum receptor. The two latter drugs had a very high receptor affinity and their lack of narcotic activity after oral administration is probably attributable to lack of penetration of the CNS. Receptor binding in both ileum and brain preparations was inhibited by N-ethylmaleimide, Triton X-100, trypsin and phospholipase C. There were small quantitative differences in sensitivity to these agents but it is difficult to assess whether this is because of real differences between the receptor molecules or attributable to secondary effects. As previously described for the brain receptor, the ileum receptor appeared to be present in a fraction enriched in plasma membranes.

Use of a Guinea Pig-Specific Transcriptome Array for Evaluation of Protective Immunity against Genital Chlamydial Infection following Intranasal Vaccination in Guinea Pigs.

Science.gov (United States)

2014-12-11

modulation in several innate immunity markers particularly associated with NK cells and Th1/Th2 specific cytokines and chemokines in immunized guinea pigs...reduced antigen-specific activation (IL-12 and IFN-c production) of CD4+ T cells isolated from lymphoid tissues and genital tract, and an associated...CD4+ T cells [12, 13]. However, due to differences in immunological responses [23, 24, 25, 26], and chlamydial strain susceptibilities between mice

Gastroprotective activity of ferruginol in mice and rats: effects on gastric secretion, endogenous prostaglandins and non-protein sulfhydryls.

Science.gov (United States)

Areche, Carlos; Theoduloz, Cristina; Yáñez, Tania; Souza-Brito, Alba R M; Barbastefano, Víctor; de Paula, Débora; Ferreira, Anderson L; Schmeda-Hirschmann, Guillermo; Rodríguez, Jaime A

2008-02-01

The gastroprotective mechanism of the natural diterpene ferruginol was assessed in mice and rats. The involvement of gastric prostaglandins (PGE(2)), reduced glutathione, nitric oxide or capsaicin receptors was evaluated in mice either treated or untreated with indometacin, N-ethylmaleimide (NEM), N-nitro-L-arginine methyl ester (L-NAME) or ruthenium red, respectively, and then orally treated with ferruginol or vehicle. Gastric lesions were induced by oral administration of ethanol. The effects of ferruginol on the parameters of gastric secretion were assessed in pylorus-ligated rats. Gastric PGE(2) content was determined in rats treated with ferruginol and/or indometacin. The reduction of gastric glutathione (GSH) content was determined in rats treated with ethanol after oral administration of ferruginol, lansoprazole or vehicle. Finally, the acute oral toxicity was assessed in mice. Indometacin reversed the gastroprotective effect of ferruginol (25 mg kg(-1)) but not NEM, ruthenium red or L-NAME. The diterpene (25 mg kg(-1)) increased the gastric juice volume and its pH value, and reduced the titrable acidity but was devoid of effect on the gastric mucus content. Ferruginol (25, 50 mg kg(-1)) increased gastric PGE(2) content in a dose-dependent manner and prevented the reduction in GSH observed due to ethanol-induced gastric lesions in rats. Single oral doses up to 3 g kg(-1) ferruginol did not elicit mortality or acute toxic effects in mice. Our results showed that ferruginol acted as a gastroprotective agent stimulating the gastric PGE(2) synthesis, reducing the gastric acid output and improving the antioxidant capacity of the gastric mucosa by maintaining the GSH levels.

Review of CO₂ as a Euthanasia Agent for Laboratory Rats and Mice.

Science.gov (United States)

Boivin, Gregory P; Hickman, Debra L; Creamer-Hente, Michelle A; Pritchett-Corning, Kathleen R; Bratcher, Natalie A

2017-09-01

Selecting an appropriate, effective euthanasia agent is controversial. Several recent publications provide clarity on the use of CO2 in laboratory rats and mice. This review examines previous studies on CO2 euthanasia and presents the current body of knowledge on the subject. Potential areas for further investigation and recommendations are provided.

Molecular cloning, sequence identification and expression profile of domestic guinea pig (Cavia porcellus UGT1A1 gene

Directory of Open Access Journals (Sweden)

Yang Deming

2016-01-01

Full Text Available Domestic guinea pig is a model animal for human disease research. Uridine diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1 is an important human disease-related gene. In this study, the complete coding sequence of domestic guinea pig gene UGT1A1 was amplified by reverse transcription-polymerase chain reaction. The open reading frame of the domestic guinea pig UGT1A1 gene is 1602 bp in length and was found to encode a protein of 533 amino acids. Sequence analysis revealed that the UGT1A1 protein of domestic guinea pig shared high homology with the UGT1A1 proteins of degu (84%, damara mole-rat (84%, human (80%, northern white-cheeked gibbon (80%, Colobus angolensis palliatus (80% and golden snub-nosed monkey (79%. This gene contains five exons and four introns, as revealed by the computer-assisted analysis. The results also showed that the domestic guinea pig UGT1A1 gene had a close genetic relationship with the UGT1A1 gene of degu. The prediction of transmembrane helices showed that domestic guinea pig UGT1A1 might be a transmembrane protein. Expression profile analysis indicated that the domestic guinea pig UGT1A1 gene was differentially expressed in detected domestic guinea pig tissues. Our experiment laid a primary foundation for using the domestic guinea pig as a model animal to study the UGT1A1-related human diseases.

Modeling the Disease Course of Zaire ebolavirus Infection in the Outbred Guinea Pig.

Science.gov (United States)

Cross, Robert W; Fenton, Karla A; Geisbert, Joan B; Mire, Chad E; Geisbert, Thomas W

2015-10-01

Rodent models that accurately reflect human filovirus infection are needed as early screens for medical countermeasures. Prior work in rodents with the Zaire species of Ebola virus (ZEBOV) primarily used inbred mice and guinea pigs to model disease. However, these inbred species do not show some of the important features of primate ZEBOV infection, most notably, coagulation abnormalities. Thirty-six outbred guinea pigs were infected with guinea pig-adapted ZEBOV and examined sequentially over an 8-day period to investigate the pathologic events that lead to death. Features of disease in ZEBOV-infected outbred guinea pigs were largely consistent with disease in humans and nonhuman primates and included early infection of macrophages and dendritiform cells, apoptosis of bystander lymphocytes, and increases in levels of proinflammatory cytokines. Most importantly, dysregulation of circulating levels of fibrinogen, protein C activity, and antifibrinolytic proteins and deposition of fibrin in tissues demonstrated both biochemical and microscopic evidence of disseminated intravascular coagulation. These findings suggest that the outbred guinea pig model recapitulates ZEBOV infection of primates better than inbred rodent models, is useful for dissecting key events in the pathogenesis of ZEBOV, and is useful for evaluating candidate interventions prior to assessment in primates. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

76 FR 69642 - Flutriafol; Pesticide Tolerances

Science.gov (United States)

2011-11-09

... tested in guinea pigs. Short-term, subchronic, and chronic toxicity studies in rats, mice, and dogs...: Crop production (NAICS code 111). Animal production (NAICS code 112). Food manufacturing (NAICS code...

77 FR 47296 - Flutriafol; Pesticide Tolerances

Science.gov (United States)

2012-08-08

... guinea pigs. Short-term, subchronic, and chronic toxicity studies in rats, mice, and dogs identified the... those engaged in the following activities: Crop production (NAICS code 111). Animal production (NAICS...

Distribution of 18F-5-fluorouracil in tumor-bearing mice and rats

International Nuclear Information System (INIS)

Shani, J.; Wolf, W.; Schlesinger, T.

1978-01-01

Extensive distribution studies of 18 F-5-fluorouracil ( 18 F-5-FU) in control and tumor-bearing mice (seven lines) and rats (eight lines) that have been shown or suspected to be responsive to 5-FU treatment were investigated with 18 F-5-FU. Studies were performed as a function of time, loading dose of 5-FU, and after a pretreatment regimen of 5-FU. Following the parenteral administration of 18 F-5-FU to tumor-bearing mice and rats there was slight preferential uptake by some of the tumor types, particularly subcutaneous leukemic tumors and breast adenocarcinomas. The degree of concentration in tumor tissue in comparison with surrounding tissues (blood, Muscle) was not such as to consider the radiopharmaceutical suitable for tumor localization. However, sufficient amounts of radioactivity localized in some tumors so that it might be possible to determine if a correlation exists between tumor uptake and anti-tumor effect of 5-fluorouracil. Another possible area of use might be in regulating the method of administration of the chemotherapeutic agent. (author)

Pathogenesis of a Chinese strain of bovine adenovirus type 3 infection in albino guinea pigs.

Science.gov (United States)

Shi, Hong-Fei; Zhu, Yuan-Mao; Yan, Hao; Ma, Lei; Wang, Xue-Zhi; Xue, Fei

2014-12-01

Bovine adenovirus type 3 (BAV-3) is considered one of the most important respiratory tract agents of cattle and is widespread among cattle around the world. A BAV-3 strain was isolated from a bovine nasal swab for the first time in China in 2009 and named HLJ0955. Subsequently, BAV-3 has frequently been isolated from calves with respiratory diseases in China. To date, only limited study on the pathogenesis of BAV-3 infection in cotton rats has been conducted, and the pathogenesis of BAV-3 infection in guinea pigs has not been reported. Therefore, sixteen albino guinea pigs were inoculated intranasally with HLJ0955. All of the infected guinea pigs had apparently elevated rectal temperatures (39.2 °C-39.9 °C) at 2-7 days post-inoculation (PI). Consolidation and petechial hemorrhage were also observed in guinea pigs experimentally infected with HLJ0955. Viral replication was detectable by virus isolation and titration and by immunohistochemistry in the lungs of guinea pigs as early as 24 h PI. Viral DNA was detectable in the lungs of infected guinea pigs during 11 days of observation by real-time PCR. Virus-neutralizing antibodies against BAV-3 were detectable from 11 days PI and reached a peak titer at 15 days PI. Histopathological changes mainly occurred in the lungs of infected guinea pigs and were characterized by thickening of alveolar septa, mononuclear cell infiltration, hemorrhage and alveolar epithelial necrosis. These results indicate that HLJ0955 can replicate in the lungs of guinea pigs and cause fever and gross and histological lesions. The guinea pig infection model of BAV-3 would serve as a useful system for monitoring the infection process and pathogenesis of the Chinese BAV-3 strain HLJ0955, as well as immune responses to BAV-3 vaccines.

Disposition and metabolism of aniline in Fischer 344 rats and C57BL/6 X C3H F1 mice

International Nuclear Information System (INIS)

McCarthy, D.J.; Waud, W.R.; Struck, R.F.; Hill, D.L.

1985-01-01

We examined the metabolism and disposition of aniline, which induces spleen hemangiosarcomas in rats but no tumors in mice, in normal and predosed Fischer 344 rats, and C57BL/6 X C3H F1 mice administered low (50 and 100 mg/kg, respectively) or high (250 and 500 mg/kg, respectively) doses. Of 11 tissues examined, the highest levels of binding of [ 14 C]aniline to DNA were in the kidney, large intestine, and spleen of high-dose rats that had received prior dosing; these tissues had covalent binding indices of 14.2, 4.3, and 3.7 mumol/mol nucleotides/dose, respectively. Protein and RNA were the major macromolecular targets for binding of radioactivity from [ 14 C]aniline. Relative to controls, most tissues from predosed mice (low dose and high dose) showed less binding to protein and RNA; but for most tissues from predosed rats administered 50-mg/kg doses of [ 14 C]aniline, there was more extensive binding. Also relative to controls, binding of radioactivity in the spleen of predosed rats given [ 14 C]aniline (50 mg/kg) was 148% greater for protein and 302% greater for RNA. For rats administered 250 mg of [ 14 C]aniline per kg, however, there were no outstanding differences in binding to RNA and protein between normal and predosed animals. The profiles of urinary metabolites produced by rats and mice were not appreciably different in animals predosed with aniline. For rats, however, the profiles were different for the low and high doses, suggesting that the main metabolic pathway was saturated at the higher dose. p-Acetamidophenyl sulfate represented over 70% of the total radioactivity recovered from the urine of rats dosed with 50 mg of aniline per kg but only 30% in the urine of those dosed with 250 mg/kg. The urine of the high-dose rats contained greater percentages of p-aminophenyl sulfate, p-acetamidophenyl glucuronide, and unconjugated metabolites

Threshold dose to developing central nerve system of rats and mice from prenatal exposure to tritiated water

International Nuclear Information System (INIS)

Zhou Xiangyan; Wang Bing; Gao Weimin; Lu Huimin

1999-01-01

Objective: To study the threshold dose to the developing central nerve system of rats and mice from prenatal exposure to tritiated water. methods: Pregnant adult C 57 BL/6J strain mice and Wistar strain rats were irradiated with beta-rays from HTO by a single intraperitoneal injection on the 12.5 th and 13 th days of gestation. The activities of HTO were 24.09, 48.18 and 144.54 ( x 10 4 Bq/g bw), respectively. Fifty-six parameters including postnatal growth, neutro-behavior, pathology of brain, neuropeptide contents, changes of hippocampal neurons, Ca 2+ conductance of hippocampal neurons etc were used to test the teratogenic threshold dose the lowest dose was different from that of the control). Results: Of the observed 56 parameters of rats and mice 80.4% indicated that the threshold doses for prenatal HTO exposure ranged from 0.030 Gy to 0.092 Gy, and the other 19.6% showed the threshold doses from 0.093 to 0.300 Gy. Conclusions: There exists threshold dose from the low level tritiated water irradiation of the developing central nerve system

THE EFFECT OF ROUTE OF ADMINISTRATION OF POLYCYCLIC AROMATIC HYDROCARBONS ON DNA ADDUCTION AND CYTOGENETIC DAMAGE IN PERIPHERAL BLOOD LYMPHOCYTES OF MICE AND RATS

Science.gov (United States)

Experiments were designed to investigate how the route of exposure to polycyclic aromatic hydrocarbons (PAHs) in mice and rats affects the induction of cytogenetic endpoints and DNA adduction. Both mice and rats were exposed to 100 mg/kg of benz[a]anthracene (B[a]A), benzo[b]fl...

Relation of type-C RNA virus infectivity and leukemogenesis in rats and mice

International Nuclear Information System (INIS)

Nagao, Kenji; Ito, Takaaki; Yokoro, Kenjiro

1976-01-01

Observation was made as to movement of type-C RNA virus infectivity in the process of leukemogensis induced by Gross virus, N-nitrosoethylurea (NEU), or, x-ray. Total dose of 680 R in 4 times was given to the whole body or parts of the body at intervals of 5 days. Thymic leukemia occurred in 100% or rats which were inoculated with type-C RNA virus at the period of newborn 64 days after, on the average. Infectious titer of virus rose only in thymus toward leukemogenesis. Thymic leukemia was induced 100% in mice by NEU 122 days after, but its incidence was 9% of mice of which thymus was extracted. Leukemia virus was not detected in non-extracted thymus of mice, and pattern of virus infectivity in other organs did not show any difference with that of mice of which thymus was extracted. Virus showed high infectious titer in uterus of mice of both groups. Leukemia occurred 87% in the whole body irradiated mice, 15% in partially irradiated mice, and 39% in mice of which thymus was extracted and the whole body was irradiated. Virus did not show any homeostatic infectious titer in three kinds of leukemia, but it showed high infectious titer in uterus. (Kanao, N.)

Equatorial Guinea.

Science.gov (United States)

1989-03-01

Equatorial Guinea is situated on the Gulf of Guinea along the west African coast between Cameroon and Gabon. The people are predominantly of Bantu origin. The country's ties with Spain are significant; in 1959, it became the Spanish Equatorial region ruled by Spain's commissioner general. Recent political developments in Equatorial Guinea include the formation of the Democratic Party for Equatorial Guinea in July of 1987 and the formation of a 60-member unicameral Chamber of Representatives of the People in 1983. Concerning the population, 83% of the people are Catholic and the official language is Spanish. Poverty and serious health, education and sanitary problems exist. There is no adequate hospital and few trained physicians, no dentists, and no opticians. Malaria is endemic and immunization for yellow fever is required for entrance into the country. The water is not potable and many visitors to the country bring bottled water. The tropical climate of Equatorial Guinea provides the climate for the country's largest exports and source of economy; cacao, wood and coffee. Although the country, as a whole, has progressed towards developing a participatory political system, there are still problems of governmental corruption in the face of grave health and welfare conditions. In recent years, the country has received assistance from the World Bank and the United States to aid in its development.

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

Comparison of the virulence of three H3N2 canine influenza virus isolates from Korea and China in mouse and Guinea pig models.

Science.gov (United States)

Xie, Xing; Na, Woonsung; Kang, Aram; Yeom, Minjoo; Yuk, Heejun; Moon, Hyoungjoon; Kim, Sung-Jae; Kim, Hyun-Woo; Kim, Jeong-Ki; Pang, Maoda; Wang, Yongshan; Liu, Yongjie; Song, Daesub

2018-05-02

Avian-origin H3N2 canine influenza virus (CIV) has been the most common subtype in Korea and China since 2007. Here, we compared the pathogenicity and transmissibility of three H3N2 CIV strains [Chinese CIV (JS/10), Korean CIV (KR/07), and Korean recombinant CIV between the classic H3N2 CIV and the pandemic H1N1 virus (MV/12)] in BALB/c mouse and guinea pig models. The pandemic H1N1 (CA/09) strain served as the control. BALB/c mice infected with H1N1 had high mortality and obvious body weight loss, whereas no overt disease symptoms were observed in mice inoculated with H3N2 CIV strains. The viral titers were higher in the group MV/12 than those in groups JS/10 and KR/07, while the mice infected with JS/10 showed higher viral titers in all tissues (except for the lung) than the mice infected with KR/07. The data obtained in guinea pigs also demonstrated that group MV/12 presented the highest loads in most of the tissues, followed by group JS/10 and KR/07. Also, direct contact transmissions of all the three CIV strains could be observed in guinea pigs, and for the inoculated and the contact groups, the viral titer of group MV/12 and KR/07 was higher than that of group JS/10 in nasal swabs. These findings indicated that the matrix (M) gene obtained from the pandemic H1N1 may enhance viral replication of classic H3N2 CIV; JS/10 has stronger viral replication ability in tissues as compared to KR/07, whereas KR/07 infected guinea pigs have more viral shedding than JS/10 infected guinea pigs. There exists a discrepancy in pathobiology among CIV isolates. Reverse genetics regarding the genomes of CIV isolates will be helpful to further explain the virus characteristics.

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

Directory of Open Access Journals (Sweden)

Yasushi Sawanobori

Full Text Available 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.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.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.

NTP Toxicology and Carcinogenesis Studies of Benzene (CAS No. 71-43-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

Science.gov (United States)

1986-04-01

Benzene ranks 16th in production volume for chemicals produced in the United States, with approximately 9.9 billion pounds being produced in 1984, 9.1 billion pounds in 1983, and 7.8 billion pounds in 1982. This simplest aromatic chemical in used in the synthesis of styrene (polystyrene plastics and synthetic rubber), phenol (phenolic resins), cyclohexane (nylon), aniline, maleic anhydride (polyester resins), alkylbenzenes (detergents), chlorobenzenes, and other products used in the production of drugs, dyes, insecticides, and plastics. Benzene, along with other light, high-octane aromatic hydrocarbons, such as toluene and xylenes, is a component of motor gasoline. Benzene is also used as a solvent, but for most applications, it has been replaced by less hazardous solvents. During the 17-week studies, groups of 10 or 15 male and female F344/N rats and B6C3F1 mice were gavaged 5 days per week with benzene in corn oil (5 ml/kg) at doses of 0 to 600 mg/kg. No benzene-related deaths occurred; in rats that received benzene, final mean body weights were 14%-22% lower compared with vehicle controls and in mice, slight dose-related reductions were observed (less than 10% differences). Doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Two-year toxicology and carcinogenesis studies of benzene (greater than 99.7% pure) were conducted in groups of 50 F344/N rats and 50 B6C3F1 mice of each sex and for each dose. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil (5 ml/kg) 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 additional animals in each of the 16 groups were killed at 12 months and necropsies were performed. Hematologic

D701N mutation in the PB2 protein contributes to the pathogenicity of H5N1 avian influenza viruses but not transmissibility in guinea pigs

Directory of Open Access Journals (Sweden)

Peirong eJiao

2014-11-01

Full Text Available H5N1 highly pathogenic avian influenza virus (HPAIV of clade 2.3.2 has been circulating in waterfowl in Southern China since 2003. Our previous studies showed that certain H5N1 HPAIV isolates within clade 2.3.2 from Southern China had high pathogenicity in different birds. Guinea pigs have been successfully used as models to evaluate the transmissibility of AIVs and other species of influenza viruses in mammalian hosts. However, few studies have reported pathogenicity and transmissibility of H5N1 HPAIVs of this clade in guinea pigs. In this study, we selected an H5N1 HPAIV isolate, A/duck/Guangdong/357/2008, to investigate the pathogenicity and transmissibility of the virus in guinea pigs. The virus had high pathogenicity in mice; additionally, it only replicated in some tissues of the guinea pigs without production of clinical signs, but was transmissible among guinea pigs. Interestingly, virus isolates from co-caged guinea pigs had the D701N mutation in the PB2 protein. These mutant viruses showed higher pathogenicity in mice and higher replication capability in guinea pigs but did not demonstrate enhanced the transmissibility among guinea pigs. These findings indicate the transmission of the H5N1 virus between mammals could induce virus mutations, and the mutant viruses might have higher pathogenicity in mammals without higher transmissibility. Therefore, the continued evaluation of the pathogenicity and transmissibility of avian influenza virus (AIVs in mammals is critical to the understanding of the evolutionary characteristics of AIVs and the emergence of potential pandemic strains.

A wireless multi-channel recording system for freely behaving mice and rats.

Science.gov (United States)

Fan, David; Rich, Dylan; Holtzman, Tahl; Ruther, Patrick; Dalley, Jeffrey W; Lopez, Alberto; Rossi, Mark A; Barter, Joseph W; Salas-Meza, Daniel; Herwik, Stanislav; Holzhammer, Tobias; Morizio, James; Yin, Henry H

2011-01-01

To understand the neural basis of behavior, it is necessary to record brain activity in freely moving animals. Advances in implantable multi-electrode array technology have enabled researchers to record the activity of neuronal ensembles from multiple brain regions. The full potential of this approach is currently limited by reliance on cable tethers, with bundles of wires connecting the implanted electrodes to the data acquisition system while impeding the natural behavior of the animal. To overcome these limitations, here we introduce a multi-channel wireless headstage system designed for small animals such as rats and mice. A variety of single unit and local field potential signals were recorded from the dorsal striatum and substantia nigra in mice and the ventral striatum and prefrontal cortex simultaneously in rats. This wireless system could be interfaced with commercially available data acquisition systems, and the signals obtained were comparable in quality to those acquired using cable tethers. On account of its small size, light weight, and rechargeable battery, this wireless headstage system is suitable for studying the neural basis of natural behavior, eliminating the need for wires, commutators, and other limitations associated with traditional tethered recording systems.

A wireless multi-channel recording system for freely behaving mice and rats.

Directory of Open Access Journals (Sweden)

David Fan

Full Text Available To understand the neural basis of behavior, it is necessary to record brain activity in freely moving animals. Advances in implantable multi-electrode array technology have enabled researchers to record the activity of neuronal ensembles from multiple brain regions. The full potential of this approach is currently limited by reliance on cable tethers, with bundles of wires connecting the implanted electrodes to the data acquisition system while impeding the natural behavior of the animal. To overcome these limitations, here we introduce a multi-channel wireless headstage system designed for small animals such as rats and mice. A variety of single unit and local field potential signals were recorded from the dorsal striatum and substantia nigra in mice and the ventral striatum and prefrontal cortex simultaneously in rats. This wireless system could be interfaced with commercially available data acquisition systems, and the signals obtained were comparable in quality to those acquired using cable tethers. On account of its small size, light weight, and rechargeable battery, this wireless headstage system is suitable for studying the neural basis of natural behavior, eliminating the need for wires, commutators, and other limitations associated with traditional tethered recording systems.

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.

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

Review of CO2 as a Euthanasia Agent for Laboratory Rats and Mice

Science.gov (United States)

Boivin, Gregory P; Hickman, Debra L; Creamer-Hente, Michelle A; Pritchett-Corning, Kathleen R; Bratcher, Natalie A

2017-01-01

Selecting an appropriate, effective euthanasia agent is controversial. Several recent publications provide clarity on the use of CO2 in laboratory rats and mice. This review examines previous studies on CO2 euthanasia and presents the current body of knowledge on the subject. Potential areas for further investigation and recommendations are provided. PMID:28903819

The multidrug resistance 1 gene Abcb1 in brain and placenta: comparative analysis in human and guinea pig.

Science.gov (United States)

Pappas, Jane J; Petropoulos, Sophie; Suderman, Matthew; Iqbal, Majid; Moisiadis, Vasilis; Turecki, Gustavo; Matthews, Stephen G; Szyf, Moshe

2014-01-01

The Multidrug Resistance 1 (MDR1; alternatively ABCB1) gene product P-glycoprotein (P-gp), an ATP binding cassette transporter, extrudes multiple endogenous and exogenous substrates from the cell, playing an important role in normal physiology and xenobiotic distribution and bioavailability. To date, the predominant animal models used to investigate the role of P-gp have been the mouse and rat, which have two distinct genes, Abcb1a and Abcb1b. In contrast, the human has a single gene, ABCB1, for which only a single isoform has been validated. We and others have previously shown important differences between Abcb1a and Abcb1b, limiting the extrapolation from rodent findings to the human. Since the guinea pig has a relatively long gestation, hemomonochorial placentation and neuroanatomically mature offspring, it is more similar to the human, and may provide a more comparable model for investigating the regulation of P-gp in the brain and placenta, however, to date, the Abcb1 gene in the guinea pig remains to be characterized. The placenta and fetal brain are barrier sites that express P-gp and that play a critical role of protection of the fetus and the fetal brain from maternally administered drugs and other xenobiotics. Using RNA sequencing (RNA-seq), reverse transcription-polymerase chain reaction (RT-PCR) and quantitative PCR (QPCR) to sequence the expressed isoforms of guinea pig Abcb1, we demonstrate that like the human, the guinea pig genome contains one gene for Abcb1 but that it is expressed as at least three different isoforms via alternative splicing and alternate exon usage. Further, we demonstrate that these isoforms are more closely related to human than to rat or mouse isoforms. This striking, overall similarity and evolutionary relatedness between guinea pig Abcb1 and human ABCB1 indicate that the guinea pig represents a relevant animal model for investigating the function and regulation of P-gp in the placenta and brain.

Effect of IgG subclasses on in vivo bioavailability and metabolic fate of immune-complexed insulin in Lewis rats

International Nuclear Information System (INIS)

Arquilla, E.R.; Stenger, D.; McDougall, B.; Ulich, T.R.

1987-01-01

The bioavailability, distribution, and metabolic fate of 125 I-labeled insulin complexed to antibodies in guinea pig antiserum, purified guinea pig IgG1, IgG2, a mixture of IgG1 and IgG2, and homologous Lou/m rat antiserum were studied in inbred Lewis rats. 125 I-insulin complexed to purified guinea pig IgG2 antibodies was rapidly cleared from the blood and sequestered in increasing amounts with time in the liver. Large amounts of the 125 I-insulin complexed to guinea pig IgG1 antibodies remained in the blood for at least 30 min. The bioavailability of 125 I-insulin bound to IgG1 and IgG2 antibodies was inhibited for at least 30 min because significantly less was available for rapid binding to insulin receptors on hepatocytes and renal tubular cells and its subsequent rapid degradation. The bioavailability of 125 I-insulin was further decreased when bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies compared with the 125 I-insulin complexed to either purified IgG1 or IgG2 antibodies alone. The 125 I-insulin bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies was distributed in vivo in a manner reflecting the relative concentrations of the IgG1 and IgG2 antibodies present. The bioavailability, distribution, and metabolic fate of 125 I-insulin in immune complexes prepared with homologous Lou/m rat insulin antiserum was qualitatively similar to that observed with immune complexes prepared with guinea pig insulin antiserum. It appears that the Lewis rat can be used as an in vivo model to study the bioavailability,distribution,and metabolic fate of insulin bound to xenogenic or homologous insulin antibodies

NTP toxicity studies of dimethylaminopropyl chloride, hydrochloride (CAS No. 5407-04-5) administered by Gavage to F344/N rats and B6C3F1 mice.

Science.gov (United States)

Abdo, Km

2007-07-01

Dimethylaminopropyl chloride, hydrochloride is used primarily as an industrial and research organic chemical intermediate acting as an alkylating reagent in Grignard and other types of reactions. It is also used as a pharmaceutical intermediate for the synthesis of many types of drugs, as an agricultural chemical intermediate, as a photographic chemical intermediate, and as a biochemical reagent for enzyme and other studies. Human occupational or other accidental exposure can occur by inhalation, ingestion, or skin absorption. Male and female F344/N rats and B6C3F1 mice received dimethylaminopropyl chloride, hydrochloride (greater than 99% pure) in water by gavage for 2 weeks or 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. In the 2-week toxicity studies, groups of five male and five female F344/N rats and B6C3F1 mice were administered doses of 0, 6.25, 12.5, 25, 50, or 100 mg dimethylaminopropyl chloride, hydrochloride/kg body weight in deionized water by gavage, 5 days per week for 16 days. All dosed male and female rats and mice survived until the end of the 2-week study; one vehicle control female mouse died early. Mean body weights of all dosed groups of rats and mice were similar to those of the vehicle control groups. No gross or microscopic lesions were considered related to dimethylaminopropyl chloride, hydrochloride administration. In the 3-month toxicity studies, groups of 10 male and 10 female F344/N rats and B6C3F1 mice were administered doses of 0, 6.25, 12.5, 25, 50, or 100 mg/kg in deionized water by gavage, 5 days per week for 3 months. One male rat in the 50 mg/kg group died during week 12 of the study, and one female mouse in the 100 mg/kg group died during week 9 and another during week 13. The final mean body weights of 50 mg/kg male rats and 50 mg/kg female mice were significantly less than those of the vehicle controls. Possible chemical-related clinical findings in rats

Response properties of the pharyngeal branch of the glossopharyngeal nerve for umami taste in mice and rats.

Science.gov (United States)

Kitagawa, Junichi; Takahashi, Yoshihiro; Matsumoto, Shigeji; Shingai, Tomio

2007-04-24

Many studies have reported the mechanism underlying umami taste. However, there are no investigations of responses to umami stimuli taste originating from chemoreceptors in the pharyngeal region. The pharyngeal branch of the glossopharyngeal nerve (GPN-ph) innervating the pharynx has unique responses to taste stimulation that differs from responses of the chorda tympani nerve and lingual branch of the glossopharyngeal nerve. Water evokes robust response, but NaCl solutions at physiological concentrations do not elicit responses. The present study was designed to examine umami taste (chemosensory) responses in the GPN-ph. Response characteristics to umami taste were compared between mice and rats. In mice, stimulation with compounds eliciting umami taste (0.1M monosodium L-glutamate (MSG), 0.01M inosine monophosphate (IMP) and the mixture of 0.1M MSG+0.01M IMP) evoked higher responses than application of distilled water (DW). However, synergistic response of a mixture of 0.1M MSG+0.01M IMP was not observed. In rats, there is no significant difference between the responses to umami taste (0.1M MSG, 0.01M IMP and the mixture of 0.1M MSG+0.01M IMP) and DW. Monopotassium glutamate (MPG) was used in rats to examine the contribution of the sodium component of MSG on the response. Stimulation with 0.1M MPG evoked a higher response when compared with responses to DW. The present results suggest that umami taste compounds are effective stimuli of the chemoreceptors in the pharynx of both mice and rats.

29 CFR 780.120 - Raising of “livestock.”

Science.gov (United States)

2010-07-01

..., mules, donkeys, and goats. It does not include such animals as albino and other rats, mice, guinea pigs... F. 2d 1), but employees employed in propagating or farming of fish may qualify for exemption under...

Case Report of a Satin Guinea Pig with Fibrous Osteodystrophy That Resembles Human Pseudohypoparathyroidism

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Miguel Gallego

2017-01-01

Full Text Available A case report of a 2-year-old female satin guinea pig with a history of dental overgrowth and lameness and radiological lesions of fibrous osteodystrophy is presented. The most relevant clinical findings were bone demineralization, high level of parathyroid hormone (PTH, normophosphatemia, normal ionized calcium, and low total thyroxine (tT4 with a normal renal function. Long-term treatment was based on teeth coronal reduction and maintaining a balanced diet. PTH measurement was performed with a kit suitable for rats to test 4 different paired samples of guinea pigs and resulted in similar results for each pair of measurements. Two kits routinely employed in dogs and cats failed in measuring PTH in guinea pig serum samples. The ionized calcium, PTH, and tT4 values, not previously reported in similar cases, were obtained. The determination of tT4 could be useful in the diagnosis of fibrous osteodystrophy in guinea pigs. The observed findings show similarity with human pseudohypoparathyroidism type Ia, a disease caused by an inactivating heterozygous mutation of the stimulatory G protein α subunit from the maternal genome that induces multiple hormone resistance and that courses with a syndrome called Albright hereditary osteodystrophy. Naturally occurring pseudohypoparathyroidism in animals has been reported previously only in a ferret.

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.

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.

Characterization of urinary volatiles in Swiss male mice (Mus ...

Indian Academy of Sciences (India)

Unknown

Information about diet is also available in guinea pigs. (Beauchamp ... change in diet can alter urine odours. Urinary ... adult male mice, which are dependent upon high levels of ... a protein or protein related substance (Marchlewska-Koj. 1977 ...

The induction by X-rays of chromosome aberrations in male guinea-pigs, golden hamsters and rabbits

International Nuclear Information System (INIS)

Cox, B.D.; Lyon, M.F.

1975-01-01

Translocations induced by X-rays in post-meiotic germ cells of male guinea-pigs, golden hamsters and rabbits were studied cytologically in the F 1 sons of the irradiated males. The percentage of spermatocytes displaying multivalent configurations varied with the translocation, but the average percentage appeared to depend on the species: fewer quadrivalents were observed in hamster than in guinea-pig heterozygotes and most were recorded for rabbit heterozygotes. Chain quadrivalents were more abundant than ring quadrivalents at meiosis for the guinea-pig and hamster in contrast to the mouse. Too few translocation heterozygotes were examined to determine which meiotic configuration was the more prevalent in the rabbit. In all three species, as in the mouse, translocations were found which caused male sterility, due to partial or complete failure of spermatogenesis, although most translocations caused semi-sterility. For these semi-sterile males both the frequency and time of embryonic death in the progeny appeared to be the same as in the mouse. It is concluded that similar types of chromosome aberrations are induced by X-rays in post-meiotic germ cells of male guinea-pigs, rabbits, golden hamsters and mice

NTP Toxicology and Carcinogenesis Studies of Dimethyl Methylphosphonate (CAS No. 756-79-6) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

Science.gov (United States)

1987-11-01

Dimethyl methylphosphonate (98% pure) is one of four chemicals nominated by the U.S. Army for toxicology and carcinogenesis studies because it was being considered for use to simulate the physical and spectroscopic (but not the biologic) properties of anticholinesterase (nerve) agents. Dimethyl methylphosphonate is also used as a flame retardant, a preignition additive for gasoline, an antifoam agent, a plasticizer and stabilizer, a textile conditioner and antistatic agent, and an additive for solvents and low-temperature hydraulic fluids. The United States produces 0.2-2 million pounds (91,000-910,000 kg) of per year. Gavage was chosen as the route of administration for all four candidate "simulants" to mimic potential exposure. Experimental Design: Dimethyl methylphosphonate was administered in corn oil by gavage to male and female F344/N rats and B6C3F1 mice in single-administration, 15-day, and 13-week studies to obtain toxicity data, to establish dose levels for the 2-year studies, and to identify target tissues. Additional studies were also performed to determine toxicity to the reproductive system of male F344/N rats and B6C3F1 mice and to study the potential for genetic damage in bacteria, mammalian cells, and Drosophila. Single-Administration Studies: In the single-administration studies, dimethyl methylphosphonate was given to rats and mice at doses up to 6,810 mg/kg body weight. No compound-related deaths were seen in male or female rats or male mice; two high dose female mice died. Rats exhibited inactivity, unsteady gait, and prostration after dosing; mice were inactive after dosing. Fifteen-Day Studies: Rats and mice received doses of 0, 1,250, 2,500, 5,000, 10,000, or 15,000 mg/kg dimethyl methylphosphonate per day. Compound-related deaths occurred in the three highest dose groups of rats and the two highest dose groups of mice. Rats receiving doses of 2,500 mg/kg or higher were inactive and at 5,000 or 10,000 mg/kg had an unsteady gait after dosing

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."

The impact of mouse passaging of Mycobacterium tuberculosis strains prior to virulence testing in the mouse and guinea pig aerosol models.

Directory of Open Access Journals (Sweden)

Paul J Converse

2010-04-01

Full Text Available It has been hypothesized that the virulence of lab-passaged Mycobacterium tuberculosis and recombinant M. tuberculosis mutants might be reduced due to multiple in vitro passages, and that virulence might be augmented by passage of these strains through mice before quantitative virulence testing in the mouse or guinea pig aerosol models.By testing three M. tuberculosis H37Rv samples, one deletion mutant, and one recent clinical isolate for survival by the quantitative organ CFU counting method in mouse or guinea pig aerosol or intravenous infection models, we could discern no increase in bacterial fitness as a result of passaging of M. tuberculosis strains in mice prior to quantitative virulence testing in two animal models. Surface lipid expression as assessed by neutral red staining and thin-layer chromatography for PDIM analysis also failed to identify virulence correlates.These results indicate that animal passaging of M. tuberculosis strains prior to quantitative virulence testing in mouse or guinea pig models does not enhance or restore potency to strains that may have lost virulence due to in vitro passaging. It is critical to verify virulence of parental strains before genetic manipulations are undertaken and comparisons are made.

Transoral tracheal intubation of rodents using a fiberoptic laryngoscope.

Science.gov (United States)

Costa, D L; Lehmann, J R; Harold, W M; Drew, R T

1986-06-01

A fiberoptic laryngoscope which allows direct visualization of the deep pharynx and epiglottis has been developed for transoral tracheal intubation of small laboratory mammals. The device has been employed in the intubation and instillation of a variety of substances into the lungs of rats, and with minor modification, has had similar application in mice, hamsters, and guinea pigs. The simplicity and ease of handling of the laryngoscope permits one person to intubate large numbers of enflurane anesthetized animals either on an open counter top or in a glove-box, as may be required for administration of carcinogenic materials. Instillation of 7Be-labeled carbon particles into the lungs of mice, hamsters, rats, and guinea pigs resulted in reasonably consistent interlobal distribution of particles for each test animal species with minimal tracheal deposition. However, actual lung tissue doses of carbon exhibited some species dependence.

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.

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

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

Differential Postnatal Expression of Neuronal Maturation Markers in the Dentate Gyrus of Mice and Rats

Directory of Open Access Journals (Sweden)

Tijana Radic

2017-11-01

Full Text Available The dentate gyrus (DG is a unique structure of the hippocampus that is distinguished by ongoing neurogenesis throughout the lifetime of an organism. The development of the DG, which begins during late gestation and continues during the postnatal period, comprises the structural formation of the DG as well as the establishment of the adult neurogenic niche in the subgranular zone (SGZ. We investigated the time course of postnatal maturation of the DG in male C57BL/6J mice and male Sprague-Dawley rats based on the distribution patterns of the immature neuronal marker doublecortin (DCX and a marker for mature neurons, calbindin (CB. Our findings demonstrate that the postnatal DG is marked by a substantial maturation with a high number of DCX-positive granule cells (GCs during the first two postnatal weeks followed by a progression toward more mature patterns and increasing numbers of CB-positive GCs within the subsequent 2 weeks. The most substantial shift in maturation of the GC population took place between P7 and P14 in both mice and rats, when young, immature DCX-positive GCs became confined to the innermost part of the GC layer (GCL, indicative of the formation of the SGZ. These results suggest that the first month of postnatal development represents an important transition phase during which DG neurogenesis and the maturation course of the GC population becomes analogous to the process of adult neurogenesis. Therefore, the postnatal DG could serve as an attractive model for studying a growing and functionally maturing neural network. Direct comparisons between mice and rats revealed that the transition from immature DCX-positive to mature CB-positive GCs occurs more rapidly in the rat by approximately 4–6 days. The remarkable species difference in the speed of maturation on the GC population level may have important implications for developmental and neurogenesis research in different rodent species and strains.

Differences in the metabolism and disposition of inhaled [3H]benzene by F344/N rats and B6C3F1 mice

International Nuclear Information System (INIS)

Sabourin, P.J.; Bechtold, W.E.; Birnbaum, L.S.; Lucier, G.; Henderson, R.F.

1988-01-01

Benzene is a potent hematotoxin and has been shown to cause leukemia in man. Chronic toxicity studies indicate that B6C3F1 mice are more susceptible than F334/N rats to benzene toxicity. The purpose of the studies presented in this paper was to determine if there were metabolic differences between F344/N rats and B6C3F1 mice which might be responsible for this increased susceptibility. Metabolites of benzene in blood, liver, lung, and bone marrow were measured during and following a 6-hr 50 ppm exposure to benzene vapor. Hydroquinone glucuronide, hydroquinone, and muconic acid, which reflect pathways leading to potential toxic metabolites of benzene, were present in much greater concentrations in the mouse than in rat tissues. Phenylsulfate, a detoxified metabolite, and an unknown water-soluble metabolite were present in approximately equal concentrations in these two species. These results indicate that the proportion of benzene metabolized via pathways leading to the formation of potentially toxic metabolites as opposed to detoxification pathways was much higher in B6C3F1 mice than in F344 rats, which may explain the higher susceptibility of mice to benzene-induced hematotoxicity and carcinogenicity

Metabolic Characterization of Acutely Isolated Hippocampal and Cerebral Cortical Slices Using [U-(13)C]Glucose and [1,2-(13)C]Acetate as Substrates

DEFF Research Database (Denmark)

McNair, Laura F; Kornfelt, Rasmus; Walls, Anne B

2017-01-01

Brain slice preparations from rats, mice and guinea pigs have served as important tools for studies of neurotransmission and metabolism. While hippocampal slices routinely have been used for electrophysiology studies, metabolic processes have mostly been studied in cerebral cortical slices. Few...

Exploring the Pregnant Guinea Pig as a Model for Group B Streptococcus Intrauterine Infection.

Science.gov (United States)

Harrell, Maria I; Burnside, Kellie; Whidbey, Christopher; Vornhagen, Jay; Adams Waldorf, Kristina M; Rajagopal, Lakshmi

2017-09-01

Infection of the amniotic cavity remains a major cause of preterm birth, stillbirth, fetal injury and early onset, fulminant infections in newborns. Currently, there are no effective therapies to prevent in utero infection and consequent co-morbidities. This is in part due to the lack of feasible and appropriate animal models to understand mechanisms that lead to in utero infections. Use of mouse and rat models do not fully recapitulate human pregnancy, while pregnant nonhuman primate models are limited by ethical considerations, technical constraints, and cost. Given these limitations, the guinea pig is an attractive animal model for studying pregnancy infections, particularly as the placental structure is quite similar to the human placenta. Here, we describe our studies that explored the pregnant guinea pig as a model to study in utero Group B Streptococci (GBS) infections. We observed that intrauterine inoculation of wild type GBS in pregnant guinea pigs resulted in bacterial invasion and dissemination to the placenta, amniotic fluid and fetal organs. Also, hyperhemolytic GBS such as those lacking the hemolysin repressor CovR/S showed increased dissemination into the amniotic fluid and fetal organs such as the fetal lung and brain. These results are similar to those observed in mouse and non-human primate models of in utero infection, and support use of the guinea pig as a model for studying GBS infections in pregnancy.

Interaction of chelating agents with cadmium in mice and rats.

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Eybl, V; Sýkora, J; Koutenský, J; Caisová, D; Schwartz, A; Mertl, F

1984-01-01

The influence of several chelating agents (CaDTPA, ZnDTPA, CaEDTA, ZnEDTA, DMSA, D-penicillamine and DMPS, DMP and DDC) on the acute toxicity of CdCl2 and on the whole body retention and tissue distribution of cadmium after the IV application of 115mCdCl2 was compared in mice. The chelating agents were applied immediately after the application of cadmium. CaDTPA, ZnDTPA and DMSA appeared to be the most effective antidotes. However, DMSA increased the amount of cadmium retained in kidneys. The treatment of cadmium-poisoned mice with the combination of DMSA (IP) and ZnDTPA (SC) (all the compounds were injected in equimolar dose) decreased the toxicity of cadmium more than treatment with one chelating agents (given in a 2:1 dose). However, by studying the effect of these chelating agents and their combination of the retention and distribution of Cd in mice, it was demonstrated that the combined application of the antidotes showed little or no improvement over the results obtained with the most effective of the individual components. In the urine of rats injected with CdCl2 and treated with the chelating agents (CaDTPA, ZnDTPA, DMSA), the presence of cadmium complexes was demonstrated. The formation of mixed ligand chelates in vivo was not proved. Experiments in mice given a single injection of 115mCd-labeled Cd complexes of DMPS, DMSA and DTPA showed a high retention of cadmium in the organisms after the IV application of CdDMPS and CdDMSA complexes. PMID:6734561

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

Pharmacological characterization and autoradiographic localization of substance P receptors in guinea pig brain

International Nuclear Information System (INIS)

Dam, T.V.; Quirion, R.

1986-01-01

[ 3 H]Substance P ([ 3 H]SP) was used to characterize substance P (SP) receptor binding sites in guinea pig brain using membrane preparations and in vitro receptor autoradiography. Curvilinear Scatchard analysis shows that [ 3 H]SP binds to a high affinity site (Kd = 0.5 nM) with a Bmax of 16.4 fmol/mg protein and a low affinity site (Kd = 29.6 nM) with a Bmax of 189.1 fmol/mg protein. Monovalent cations generally inhibit [ 3 H]SP binding while divalent cations substantially increased it. The ligand selectivity pattern is generally similar to the one observed in rat brain membrane preparation with SP being more potent than SP fragments and other tachykinins. However, the potency of various nucleotides is different with GMP-PNP greater than GDP greater than GTP. The autoradiographic distribution of [ 3 H]SP binding sites shows that high amounts of sites are present in the hippocampus, striatum, olfactory bulb, central nucleus of the amygdala, certain thalamic nuclei and superior colliculus. The cortex is moderately enriched in [ 3 H]SP binding sites while the substantia nigra contains only very low amounts of sites. Thus, the autoradiographic distribution of SP binding sites is fairly similar in both rat and guinea pig brain

Prevalence and risk factors of Lassa seropositivity in inhabitants of the forest region of Guinea: a cross-sectional study.

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Solen Kernéis

Full Text Available BACKGROUND: Lassa fever is a viral hemorrhagic fever endemic in West Africa. The reservoir host of the virus is a multimammate rat, Mastomys natalensis. Prevalence estimates of Lassa virus antibodies in humans vary greatly between studies, and the main modes of transmission of the virus from rodents to humans remain unclear. We aimed to (i estimate the prevalence of Lassa virus-specific IgG antibodies (LV IgG in the human population of a rural area of Guinea, and (ii identify risk factors for positive LV IgG. METHODS AND FINDINGS: A population-based cross-sectional study design was used. In April 2000, all individuals one year of age and older living in three prefectures located in the tropical secondary forest area of Guinea (Gueckedou, Lola and Yomou were sampled using two-stage cluster sampling. For each individual identified by the sampling procedure and who agreed to participate, a standardized questionnaire was completed to collect data on personal exposure to potential risk factors for Lassa fever (mainly contact with rodents, and a blood sample was tested for LV IgG. A multiple logistic regression model was used to determine risk factors for positive LV IgG. A total of 1424 subjects were interviewed and 977 sera were tested. Prevalence of positive LV Ig was of 12.9% [10.8%-15.0%] and 10.0% [8.1%-11.9%] in rural and urban areas, respectively. Two risk factors of positive LV IgG were identified: to have, in the past twelve months, undergone an injection (odds ratio [OR] = 1.8 [1.1-3.1], or lived with someone displaying a haemorrhage (OR = 1.7 [1.1-2.9]. No factors related to contacts with rats and/or mice remained statistically significant in the multivariate analysis. CONCLUSIONS: Our study underlines the potential importance of person-to-person transmission of Lassa fever, via close contact in the same household or nosocomial exposure.

Methymazole (MMI) effects on seric levels of thyroid hormones in rats and mices; Influencia do metimazol (MMI) sob os niveis sericos dos hormonios da tireoide em rato e camundongos

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Lima Filho, G.L.; Carvalho, E.B.; Lima, G.M.S.; Neves, S.R.S.; Catanho, M.T.J.A. [Pernambuco Univ., Recife, PE (Brazil). Dept. de Biofisica e Radiobiologia; Lima, G.M.T. [Pernambuco Univ., Recife, PE (Brazil). DMC

1997-12-01

The thyroid gland secretes the metabolic hormones thyroxine (T4) and triiodothyronine (T3) which regulate the oxygen consumption of the majority of cells in the body. Their synthesis and release are controlled by the anterior pituitary hormone and also for drugs that mediated the serum concentration of T4 and T3 in the thyroid gland or in the peripheral tissues. The present study evaluates the sinergic effect on the basal secretion of the T4 and T3 after administration of throidal and nonthyroidal drugs in rats and mice. The study achievements with the oral administration of methymazole (MMI) in rats and mice. The study achievements with the oral administration of Methymazole (MMI) in rats and mice resulted in the reduction of the T4 and T3 serum levels, obtained through kinertic treatment. there was a significant reduction in T4 serum values among treated rats and mice for up to 14 days of MMI. Moreover, increased T3 serum concentration was found in rats treated with MMI, after 7 days of treatment, when compared to the serum level of treated mice. The serie levels of T3 and T4 were determined by radioimmunoassay. (author). 11 refs., 2 figs.

Acute toxicity of the hydrolysis products of uranium hexafluoride (UF6) when inhaled by the rat and guinea pig. Final report

International Nuclear Information System (INIS)

Leach, L.J.; Gelein, R.M.; Panner, B.J.; Yulie, C.L.; Cox, C.C.; Balys, M.M.; Rolchigo, P.M.

1984-04-01

This report presents the experimental animal data base from which human health consequences may be predicted from exposures mimicing accidental discharges of uranium hexafluoride (UF 6 ) in the uranium industry. Rats or guinea pigs were exposed for two, five, or ten minutes duration to air having 0.44 g U/m 3 + 0.16 g HF/m 3 to 276.67 g U/m 3 + 94.07 g HF/m 3 . Survivors of each exposure were observed for 14 days for signs of U or HF intoxication. Selected animals were necropsied and samples of major organs were studied histopathologically. When enriched UF 6 (94 percent 235 U) was used, the urine and feces from each animal were measured daily for U content. Selected samples of urine were bioassayed in order to trace the course of renal injury during the two week postexposure period. 28 references, 51 figures, 23 tables

Spasmolytic effect of traditional herbal formulation on guinea pig ileum

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Dushyant Kumar

2015-01-01

Full Text Available Background: The herbal formulation consisting of Andrographis paniculata Nees., Cassia fistula L., Foeniculum vulgare Mill. and Cuminum cyminum L. is widely used by the local traditional practitioners in rural Northern Karnataka for spasmodic abdominal pain. Objective: The present study was undertaken to evaluate safety and spasmolytic effect of poly-herbal formulation. Materials and Methods: Acute toxicity studies were carried out in Swiss mice, as per the Organization for Economic Co-operation and Development (OECD guidelines. The spasmolytic activity of the formulation was studied in isolated guinea pig ileum model using histamine and acetylcholine as agonists. The data were analyzed by one-way ANOVA, followed by Dunnetts post-hoc test and P ≤ 0.05 was considered as significant. Results: The formulation did not show any adverse toxic effects and found to be safe. It also showed significant (P < 0.05 relaxation in different agonist like histamine and acetylcholine-induced contractions in guinea pig ileum. Conclusions: Antispasmodic activity of the herbal formulation can be attributed to its atropine-like activity. The present findings, therefore, support its utility in spasmodic abdominal pain.

NTP toxicology and carcinogensis studies of dipropylene glycol (CAS No. 25265-71-8) in F344/N rats and B6C3F1 mice (drinking water studies).

Science.gov (United States)

2004-06-01

Dipropylene glycol is found in antifreeze, air fresheners, cosmetic products, solvents, and plastics. We studied the effects of dipropylene glycol on male and female rats and mice to identify potential or cancer-related hazards to humans. We gave groups of 50 male and female mice drinking water containing dipropylene glycol at concentrations of 10,000, 20,000, or 40,000 parts per million (corresponding to 1%, 2%, or 4%) for two years. Male and female rats received concentrations of 2,500, 10,000, or 40,000 parts per million. Other groups received untreated water and were the control group. Tissues from more than 40 sites were examined for every animal. The groups of animals receiving 40,000 ppm dipropylene glycol weighed less than the control animals. All the make rats receiving 40,000 ppm dipropylene glycol died before the end of the study, mainly because of kidney disease. All the other animal group survived as well as the controls. No increase in tumor rates were seen in any of the groups of rats or mice. We conclude that dipropylene glycol did not cause cancer in male or female rats or mice. Exposure to dipropylene glycol did increase the rate and severity of kidney nephropathy and inflammation of the liver and salivary gland in male rats and some atrophy of the epithelial tissue of the nose in male and female rats.

Identification and characterization of metabolites of ASP015K, a novel oral Janus kinase inhibitor, in rats, chimeric mice with humanized liver, and humans.

Science.gov (United States)

Nakada, Naoyuki; Oda, Kazuo

2015-01-01

1. Here, we elucidated the structure of metabolites of novel oral Janus kinase inhibitor ASP015K in rats and humans and evaluated the predictability of human metabolites using chimeric mice with humanized liver (PXB mice). 2. Rat biological samples collected after oral dosing of (14)C-labelled ASP015K were examined using a liquid chromatography-radiometric detector and mass spectrometer (LC-RAD/MS). The molecular weight of metabolites in human and the liver chimeric mouse biological samples collected after oral dosing of non-labelled ASP015K was also investigated via LC-MS. Metabolites were also isolated from rat bile samples and analyzed using nuclear magnetic resonance. 3. Metabolic pathways of ASP015K in rats and humans were found to be glucuronide conjugation, methyl conjugation, sulfate conjugation, glutathione conjugation, hydroxylation of the adamantane ring and N-oxidation of the 1H-pyrrolo[2,3-b]pyridine ring. The main metabolite of ASP015K in rats was the glucuronide conjugate, while the main metabolite in humans was the sulfate conjugate. Given that human metabolites were produced by human hepatocytes in chimeric mice with humanized liver, this human model mouse was believed to be useful in predicting the human metabolic profile of various drug candidates.

English and Tok Pisin (New Guinea Pidgin English) in Papua New Guinea.

Science.gov (United States)

Romaine, Suzanne

1989-01-01

Tok Pisin, New Guinea Pidgin English, is becoming increasingly important as a "lingua franca" in Papua New Guinea, even though English is the country's official language. Urban versus rural and spoken versus written varieties of the pidgin are examined, and the influence of English on Tok Pisin is investigated. 73 references. (Author/CB)

Identification of 5HT2-receptors on longitudinal muscle of the guinea pig ileum

International Nuclear Information System (INIS)

Engel, G.; Hoyer, D.; Kalkman, H.O.; Wick, M.B.

1984-01-01

In binding experiments with the radioligands [ 3 H]Ketanserin (HKet) and [ 125 I]LSD (ILSD) 21 compounds were investigated using rat brain cortex membranes. The pK/sub D/-values of the compounds were virtually independent of the radioligand used and their rank order was consistent with classification of the binding sites as being of the 5-HT 2 -type. In contrast, in the longitudinal muscle of the guinea pig ileum in the presence of 0.3 microM cinanserin, ILSD labelled sites which were quite different to those in the cortex. In a functional test antagonism of the 5HT induced contraction of the guinea-pig ileum was measured in the presence of 1 microM atropine. The pharmacological inhibition constants (IC 50 -values) of 8 compounds correlated well with the dissociation constants for HKet binding in the cortex and did not correlate with the data from ILSD binding in the guinea pig ileum. It is concluded that the ileum contains postjunctional 5HT 2 -receptors which mediate contraction. The nature of the ILSD binding sites in the ileum remains to be elucidated

Prolactin family of the guinea pig, Cavia porcellus.

Science.gov (United States)

Alam, S M Khorshed; Konno, Toshihiro; Rumi, M A Karim; Dong, Yafeng; Weiner, Carl P; Soares, Michael J

2010-08-01

Prolactin (PRL) is a multifunctional hormone with prominent roles in regulating growth and reproduction. The guinea pig (Cavia porcellus) has been extensively used in endocrine and reproduction research. Thus far, the PRL cDNA and protein have not been isolated from the guinea pig. In the present study, we used information derived from the public guinea pig genome database as a tool for identifying guinea pig PRL and PRL-related proteins. Guinea pig PRL exhibits prominent nucleotide and amino acid sequence differences when compared with PRLs of other eutherian mammals. In contrast, guinea pig GH is highly conserved. Expression of PRL and GH in the guinea pig is prominent in the anterior pituitary, similar to known expression patterns of PRL and GH for other species. Two additional guinea pig cDNAs were identified and termed PRL-related proteins (PRLRP1, PRLRP2). They exhibited a more distant relationship to PRL and their expression was restricted to the placenta. Recombinant guinea pig PRL protein was generated and shown to be biologically active in the PRL-responsive Nb2 lymphoma cell bioassay. In contrast, recombinant guinea pig PRLRP1 protein did not exhibit PRL-like bioactivity. In summary, we have developed a new set of research tools for investigating the biology of the PRL family in an important animal model, the guinea pig.

Endocrine tumours in the guinea pig.

Science.gov (United States)

Künzel, Frank; Mayer, Jörg

2015-12-01

Functional endocrine tumours have long been thought to be rare in guinea pigs, although conditions such as hyperthyroidism and hyperadrenocorticism have been documented with increasing frequency so the prevalence of hormonal disorders may have been underestimated. Both the clinical signs and diagnosis of hyperthyroidism in guinea pigs appear to be very similar to those described in feline hyperthyroidism, and methimazole has been proven to be a practical therapy option. Hyperadrenocorticism has been confirmed in several guinea pigs with an adrenocorticotropic hormone stimulation test using saliva as a non-invasive sample matrix; trilostane has been successfully used to treat a guinea pig with hyperadrenocorticism. Insulinomas have only rarely been documented in guinea pigs and one animal was effectively treated with diazoxide. Copyright © 2015 Elsevier Ltd. All rights reserved.

NTP Toxicology and Carcinogenesis Studies of Molybdenum Trioxide (CAS No. 1313-27-5) in F344 Rats and B6C3F1 Mice (Inhalation Studies).

Science.gov (United States)

1997-04-01

Molybdenum is an essential element for the function of nitrogenase in plants and as a cofactor for enzymes including xanthine oxidoreductase, aldehyde oxidase, and sulfide oxidase in animals. Molybdenum trioxide is used primarily as an additive to steel and corrosion-resistant alloys. It is also used as a chemical intermediate for molybdenum products; an industrial catalyst; a pigment; a crop nutrient; components of glass, ceramics, and enamels; a flame retardant for polyester and polyvinyl chloride resins; and a reagent in chemical analyses. Molybdenum trioxide was nominated by the NCI for toxicity and carcinogenicity studies as a representative inorganic molybdenum compound. The production of molybdenum trioxide is the largest of all the molybdenum compounds examined. Male and female F344/N rats and B6C3F1 mice were exposed to molybdenum trioxide (approximately 99% pure) by inhalation for 14 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and cultured Chinese hamster ovary cells. 14-DAY STUDY IN RATS: Groups of five male and five female F344/N rats were exposed to 0, 3, 10, 30, 100, or 300 mg molybdenum trioxide/m(3). Rats were exposed for 6 hours per day, 5 days per week, for a total of 10 exposure days during a 14-day period. All rats survived to the end of the study. The final mean body weights of male rats exposed to 100 mg/m(3) and male and female rats exposed to 300 mg/m(3) were significantly lower than those of the control groups. Male rats exposed to 300 mg/m(3) lost weight during the study. There were no clinical findings related to exposure to molybdenum trioxide. No chemical-related lesions were observed. 14-DAY STUDY IN MICE: Groups of five male and five female B6C3F1 mice were exposed to 0, 3, 10, 30, 100, or 300 mg molybdenum trioxide/m(3). Mice were exposed 6 hours per day, 5 days per week, for a total of 10 exposure days during a 14-day period. All mice survived to the end of the study. Final mean

Studies on distribution and excretion of 14C-glycerol in rats, rabbits and mice

International Nuclear Information System (INIS)

Takanashi, Shigeru; Kamiyama, Hiroshi; Suzuki, Hidetaka; Tohira, Yasuo; Ogawa, Machiko

1978-01-01

Tissue distribution and excretion of uniformly labeled 14 C-glycerol were investigated using rats, rabbits and mice. Blood disappearance half life of 14 W/V% 14 C-glycerol in mice (1 ml/head), rats (1 ml/head) and rabbits (2 ml/head) given intravenously was 0.4, 1.8 and 2.4 hours, respectively. When 14 W/V% 14 C-glycerol was injected in rats (1 ml/head) and rabbits (2 ml/head), 65% of administered radioactivity was excreted in to expired air within 48 hrs. This suggests that glycerol is mostly metabolised via the Embden-Meyehof pathway and the TCA cycle, and finally converted to CO 2 and H 2 O. At a low dose, the conversion ratio to CO 2 was greater than the case of a high dose, and a inverse relationship was observed between the CO 2 -conversion ratio and the dose. At levels above 1 ml of 56 W/V% glycerol, an approximately constant portion of the administered dose appeared to be oxidized. The results of the whole body autoradiogram showed the distribution of the radioactivity throughout the body. Disappearance of radioactivity from liver and blood was rapid, but transport to brain, excretion to the salivary gland, and secretion to Harder's gland were slow. The distribution in tissues showed that the highest distribution of 14 C-glycerol was found in the carcass; liver showed the next highest distribution; high distribution was also found initially in the kidneys; brain, heart, lung and spleen showed low distribution, but they decreased with time elapsed. Disappearance of radioactivity from the brain was relatively slower than the liver. Besides, another result indicated that in pregnant mice 14 C-glycerol did not cross the placenta very quickly. The fact that the apparent disappearance rate from the foetuses does not seem to parallel that of the placenta is suggestive of selective accumulation in foetal tissues. (auth.)

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

International Nuclear Information System (INIS)

Waidyanatha, Suramya; Johnson, Jerry D.; Hong, S. Peter; Robinson, Veronica Godfrey; Gibbs, Seth; Graves, Steven W.; Hooth, Michelle J.; Smith, Cynthia S.

2013-01-01

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 max and AUC ∞ 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 ∞ 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:plasma ratios

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

Dermatophytes in pet Guinea pigs and rabbits.

Science.gov (United States)

Kraemer, A; Mueller, R S; Werckenthin, C; Straubinger, R K; Hein, J

2012-05-25

The frequency of dermatophytes in pet Guinea pigs and rabbits. To determine the frequency and types of dermatophytes in pet Guinea pigs and rabbits. First, 2153 samples collected from pet Guinea pigs (n=1132) and rabbits (n=1021) with suspected dermatophytosis and submitted to three different laboratories for fungal culture were analysed. Subsequently, healthy Guinea pigs and rabbits, animals with skin lesions and with noncutaneous diseases were examined prospectively for dermatophytes. Trichophyton (T.) mentagrophytes was the most common fungal species isolated (91.6% and 72.3% of positive cultures from Guinea pigs (n=431) and rabbits (n=83), respectively). Animals with positive fungal culture did not show any gender predisposition, but affected animals were younger than those with negative fungal culture (PGuinea pigs and 0/140 healthy rabbits. In addition, fungal cultures of Guinea pigs with skin lesions (n=26) and other diseases (n=25) were positive in 7.7% and 8.0% respectively. Samples collected from 17 rabbits with skin lesions and 32 rabbits with noncutaneous disease were all negative in culture. T. mentagrophytes is the most common dermatophyte in pet Guinea pigs and rabbits, asymptomatic carriers are regularly seen in Guinea pigs, but not in rabbits. Copyright © 2011 Elsevier B.V. All rights reserved.

Interaction of chelating agents with cadmium in mice and rats

International Nuclear Information System (INIS)

Eybl, V.; Sykora, J.; Koutensky, J.; Caisova, D.; Schwartz, A.; Mertl, F.

1984-01-01

The influence of several chelating agents (CaDTPA, ZnDTPA, CaEDTA, ZnEDTA, DMSA, D-penicillamine and DMPS, DMP and DDC) on the acute toxicity of CdCl 2 and on the whole body retention and tissue distribution of cadmium after the IV application of /sup 115mCdCl 2 was compared in mice. The chelating agents were applied immediately after the application of cadmium. CaDTPA, ZnDTPA and DMSA appeared to be the most effective antidotes. However, DMSA increased the amount of cadmium retained in kidneys. The treatement of cadmium-poisoned mice with the combination of DMSA (IP) and ZnDTPA (SC) (all the compounds were injected in equimolar dose) decreased the toxicity of cadmium more than treatment with one chelating agents (given in a 2:1 dose). However, by studying the effect of these chelating agents and their combination application of the antidotes showed little or no improvement over the results obtained with the most effective of the individual components. In the urine of rats injected with CdCl 2 and treated with the chelating agents (CaDTPA, ZnDTPA, DMSA), the presence of cadmium complexes was demonstrated. The formation of mixed ligand chelates in vivo was not proved. Experiments in mice given a single injection of /sup 115m/Cd-labeled Cd complexes of DMPS, DMSA and DTPA showed a high retention of cadmium in the organisms after the IV application of CdDMPS and CdDMSA complexes

Dimethylarsinic acid: Results of chronic toxicity/oncogenicity studies in F344 rats and in B6C3F1 mice

International Nuclear Information System (INIS)

Arnold, Lora L.; Eldan, Michal; Nyska, Abraham; Gemert, Marcia van; Cohen, Samuel M.

2006-01-01

Dimethylarsinic acid (DMA V , cacodylic acid), a foliar herbicide, was administered in the diet to B6C3F1 mice (at dose levels of 0, 8, 40, 200, and 500 ppm) and to F344 rats (at dose levels of 0, 2, 10, 40, and 100 ppm) for 2 years, according to US EPA guidelines. In mice, there were no treatment-related tumors observed at any site. Treatment-related progressive glomerulonephropathy and nephrocalcinosis were observed in the kidneys in both sexes. The incidence of vacuolation of the epithelium in the urinary bladder was increased in both sexes, but was not associated with cytotoxicity, necrosis or hyperplasia. Based on non-neoplastic lesions found in the urinary bladder, the NOEL for mice was assessed to be 40 ppm in males and 8 ppm in females. In rats, treatment-related mortality occurred early in the study in five males in the 100 ppm group and in one male in the 40 ppm group. Papillomas and carcinomas with degeneration of the urothelium, necrosis and urothelial cell hyperplasia, were found in the urinary bladders of both sexes. In male rats, one papilloma was found in each of the 10 and 40 ppm groups; one urothelial cell carcinoma was found in the 2 ppm group and two in the 100 ppm group. Four papillomas and six urothelial cell carcinomas were found in the female 100 ppm group. Non-neoplastic treatment-related kidney lesions were confined to the 40 and 100 ppm levels and included necrosis, pyelonephritis, medullary nephrocalcinosis and tubular cystic dilation, hyperplasia of the epithelial lining of the papilla, and pelvic urothelial cell hyperplasia. All of these kidney changes appear to be related to an increase in the aging nephropathy of the rat. Dose-related increases in the height of the thyroid follicular epithelium were also noted in males and females, however, such changes reflect an adaptive response of the thyroid to decreased levels of circulating thyroid hormone, rather than an adverse effect. Based on the kidney and bladder lesions, the NOEL for

Studies on the localization of Trypanosoma brucei in the female reproductive tract of bka mice and hooded lister rats

International Nuclear Information System (INIS)

Chipepa, J.A.S.; Brown, H.; Holmes, P.

1991-01-01

A study was conducted to establish whether Trypanosoma brucei migrated preferentially to the reproductive tracts of female BKA mice, or Hooded Lister rats and lodged there as the site of choice compared to other organs. Blood flow to the reproductive tracts, the liver and spleen was measured using red blood cells labelled with chromium- 51. The distribution of trypanosomes labelled with 75 Se-methionine. The average percentage of the blood flow to the reproductive tract was 0.21Plus or minus0.08 in mice, while the mean concentration of trypanosomes there was 0.30% in both mice and rats. Blood flow to the liver was lower than the percentage distribution of Se-labelled T.Brucei(5.17Plus or minus1.34 versus 8.1Plus or Minus1.2). There were, on the contrary, less labelled trypanosomes as compared to the mean blood flow to the spleen (0.54% plus or minus0.18 versus 2.10%pPlus or minus0.88). After 24 hours there were adequate numbers of T. brucei in the reproductive tract to cause parasitaemia in recipient mice. From these preliminary data it was concluded that T. brucei did not lodge in the reproductive organ system a site of choice. (author). 9 refs., 3 tabs

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.

9 CFR 113.38 - Guinea pig safety test.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals...

Intermediate rough Brucella abortus S19Δper mutant is DIVA enable, safe to pregnant guinea pigs and confers protection to mice.

Science.gov (United States)

Lalsiamthara, Jonathan; Gogia, Neha; Goswami, Tapas K; Singh, R K; Chaudhuri, Pallab

2015-05-21

Brucella abortus S19 is a smooth strain used as live vaccine against bovine brucellosis. Smooth lipopolysaccharide (LPS) is responsible for its residual virulence and serological interference. Rough mutants defective of LPS are more attenuated but confers lower level of protection. We describe a modified B. abortus S19 strain, named as S19Δper, which exhibits intermediate rough phenotype with residual O-polysaccharide (OPS). Deletion of perosamine synthetase gene resulted in substantial attenuation of S19Δper mutant without affecting immunogenic properties. It mounted strong immune response in Swiss albino mice and conferred protection similar to S19 vaccine. Immunized mice produced higher levels of IFN-γ, IgG2a and thus has immune response inclined towards Th1 cell mediated immunity. Sera from immunized animals did not show agglutination reaction with RBPT antigen and thus could serve as DIVA (Differentiating Infected from Vaccinated Animals) vaccine. S19Δper mutant displayed more susceptibility to serum complement mediated killing and sensitivity to polymyxin B. Pregnant guinea pigs injected with S19Δper mutant completed full term of pregnancy and did not cause abortion, still birth or birth of weak offspring. S19Δper mutant with intermediate rough phenotype displayed remarkable resemblance to S19 vaccine strain with improved properties of safety, immunogenicity and DIVA capability for control of bovine brucellosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Cuscuta reflexa stem and Calotropis procera leaf extracts on glucose tolerance in glucose-induced hyperglycemic rats and mice.

Science.gov (United States)

Rahmatullah, Mohammed; Sultan, Shamsuddin; Toma, Tanzila Taher; Lucky, Sayeda-A-Safa; Chowdhury, Majeedul H; Haque, Wahid Mozammel; Annay, Eashmat Ara; Jahan, Rownak

2009-12-30

Cuscuta reflexa (whole plant) and Calotropis procera (leaves) are used in folk medicine of Bangladesh to control blood sugar in patients suffering from diabetes mellitus. The hypoglycemic effects of methanol and chloroform extracts of whole plants of Cuscuta reflexa, and methanol extract of leaves of Calotropis procera were investigated in oral glucose tolerance tests in Long Evans rats and Swiss albino mice, respectively. Both methanol and chloroform extracts of Cuscuta reflexa whole plant demonstrated significant oral hypoglycemic activity in glucose-loaded rats at doses of 50, 100 and 200 mg/kg body weight. The methanol extract of leaves of Calotropis procera, when tested at doses of 100 and 250 mg/kg body weight did not demonstrate any oral hypoglycemic effect when tested in glucose-loaded mice.

Density profile and cholesterol concentration of serum lipoproteins in experimental animals and human subjects on hypercholesterolaemic diets

NARCIS (Netherlands)

Beynen, A.C.; Terpstra, A.H.M.

1984-01-01

1. 1. The density profile of Sudan black stained serum lipoproteins was studied in human subjects and various animal species on diets supplemented with cholesterol. 2. 2. In the animals studied (rabbits, calves, mice, chickens, rats and guinea-pigs), the feeding of cholesterol resulted in an

Animal Models for Testing the DOHaD Hypothesis

Science.gov (United States)

Since the seminal work in human populations by David Barker and colleagues, several species of animals have been used in the laboratory to test the Developmental Origins of Health and Disease (DOHaD) hypothesis. Rats, mice, guinea pigs, sheep, pigs and non-human primates have bee...

Gastrointestinal absorption of plutonium in mice, rats, and dogs: application to establishing values of f1 for soluble plutonium

International Nuclear Information System (INIS)

Bhattacharyya, M.H.; Larsen, R.P.; Oldham, R.D.; Moretti, E.S.; Spaletto, M.I.

1985-04-01

The gastrointestinal (GI) absorption of plutonium was measured in mice, rats, and dogs under conditions relevant to setting drinking water standards. The fractional GI absorption of Pu(VI) in adult mice was 2 x 10 -4 (0.02%) in fed mice and 2 x 10 -3 (0.2%) in fasted mice. The GI absorption of plutonium was independent of plutonium oxidation state, administration medium, and plutonium concentration; absorption was dependent upon animal species, state of animal fasting, state of Pu(IV) hydrolysis, and age of the animal. Fractional GI absorption values ranged from 3 x 10 -5 (0.003%) for hydrolyzed Pu(IV) administered to fed adult mice to 7 x 10 -3 (0.7%) for Pu(VI) administered to fed neonatal rats. From analysis of our data, we suggested values of f 1 (the fraction transferred from gut to blood in humans) for use in establishment of oral limits of exposure to plutonium. For an acute exposure in the occupational setting, we proposed one value of f 1 for fed (2 x 10 -4 ) and one for fasted (2 x 10 -3 ) individuals. For the environmental setting, we developed two approaches to obtaining values of f 1 ; suggested values were 6 x 10 -4 and 4 x 10 -3 , respectively. Both approaches took into account effects of animal age and fasting. We discussed uncertainties in proposed values of f 1 and made recommendations for further research. 41 refs., 8 figs., 24 tabs

[Observation of antiarrhythmic effects of Cinnamomum migao H. W. Li on experimental arrhythmia].

Science.gov (United States)

Sui, Y; Qiu, D; Xie, C; Chen, K

1998-08-01

To investigate the effects of Cinnamomum migao on experimental arrhythmia. Arrhythmic models of mice, rabbits, guinea pigs and rats were built using chloroform(Chl), adrenalin(Adr), strophanthin-K (Spt-K) and barium chloride (BaCl2). The affected animals were divided randomly into three groups: control group, Cinnamomum migao (CV-3) group and mexiletine (MXL) group, so as to observe and compare the antiarrhythmic effects. CV-3 could reduce the incidence of ventricular fibrillation caused by ch1 in mice and the ventricular tachycardia induced by Adr in rabbits, delay the onset time of this arrhythmia, increase the arrhythmic doses of Spt-K in guinea pigs, reduce the incidence of some arrhythmia caused by BaCl2 in rats and slow down their heart rate. CV-3 has obvious antiarrhythmic effects on experimental arrhythmia. The mechanism of these effects is probably related to the arrest of the intraflow of Na+, Ca2+ in the cardiac cells and the depression of their cardiac autoarrhythmicity and conductivity.

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

International Nuclear Information System (INIS)

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

2013-01-01

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 2 h 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. - Highlights: • Local and systemic distribution of GATA-3-specific DNAzyme hgd40 was investigated. • Pharmacokinetics of hgd40 was tested in rats and dogs. • hgd40 dissolved in PBS was easily taken up into the lungs after local application. • No

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

Energy Technology Data Exchange (ETDEWEB)

Turowska, Agnieszka [sterna biologicals GmbH and Co. KG, Marburg (Germany); Librizzi, Damiano [Department of Nuclear Medicine, University Hospital Giessen and Marburg GmbH, Baldingerstrasse, 35043 Marburg (Germany); Baumgartl, Nadja [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany); Kuhlmann, Jens; Dicke, Tanja [sterna biologicals GmbH and Co. KG, Marburg (Germany); Merkel, Olivia [Department of Pharmaceutical Sciences, Wayne State University, Detroit (United States); Homburg, Ursula [sterna biologicals GmbH and Co. KG, Marburg (Germany); Höffken, Helmut [Department of Nuclear Medicine, University Hospital Giessen and Marburg GmbH, Baldingerstrasse, 35043 Marburg (Germany); Renz, Harald [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany); Garn, Holger, E-mail: garn@staff.uni-marburg.de [Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps University of Marburg (Germany)

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 2 h 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. - Highlights: • Local and systemic distribution of GATA-3-specific DNAzyme hgd40 was investigated. • Pharmacokinetics of hgd40 was tested in rats and dogs. • hgd40 dissolved in PBS was easily taken up into the lungs after local application. • No

Quantitative studies of the fate of epidermal Langerhans cells after X-irradiation of guinea-pig and mouse footpad skin

Energy Technology Data Exchange (ETDEWEB)

Cole, S.; Fairweather, J.M.; Townsend, K.M.S.

1987-01-01

Langerhans cell numbers, morphology and distribution were observed in cross sections of footpad epidermis from 1 to 28 days after exposure of the hind feed of CBA/H mice or albino guinea-pigs to a single absorbed dose of 20 Gy of X-rays. In mice, the number of Langerhans cells reactive with anti-macrophage F4/80 monoclonal antibody steadily declined by approximately 85% within 10 days after irradiation. Remaining Langerhans cells were exceptionally dendritic. Very few Birbeck granule-containing cells were found in murine popliteal lymph nodes before or after irradiation but damaged cells were present in superficial strata of irradiated epidermis. The morphology and number of epidermal F4/80-positive cells approached normal by 15 days after irradiation. In guinea-pigs, gradual suprabasal movement and loss of rounded, ATPase-positive Langerhans cells from the epidermis were detectable from 5 to 20 days after irradiation but the magnitude of the cell loss and redistribution was partially obscured by the simultaneous appearance of clusters of replacement Langerhans cells in the basal layer and by keratinocyte hyperplasia.

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.

Ventilatory function assessment in safety pharmacology: Optimization of rodent studies using normocapnic or hypercapnic conditions

International Nuclear Information System (INIS)

Goineau, Sonia; Rompion, Sonia; Guillaume, Philippe; Picard, Sandra

2010-01-01

Although the whole body plethysmography for unrestrained animals is the most widely used method to assess the respiratory risk of new drugs in safety pharmacology, non-appropriate experimental conditions may mask deleterious side effects of some substances. If stimulant or bronchodilatory effects can be easily evidenced in rodents under standard experimental conditions, i.e. normal air breathing and diurnal phase, drug-induced respiratory depression remains more difficult to detect. This study was aimed at comparing the responsiveness of Wistar rats, Duncan Hartley guinea-pigs or BALB/c mice to the respiratory properties of theophylline (50 or 100 mg/kg p.o.) or morphine (30 mg/kg i.p.) under varying conditions (100% air versus 5% CO 2 -enriched air, light versus dark day phase), in order to select the most appropriate experimental conditions to each species for safety airway investigations. Our results showed that under normocapnia the ventilatory depressant effects of morphine can be easily evidenced in mice, slightly observed in guinea-pigs and not detected in rats in any day phase. Slight hypercapnic conditions enhanced the responsiveness of rats to morphine but not that of guinea-pigs and importantly they did not blunt the airway responsiveness of rats to the stimulation and bronchodilation evoked by theophylline, the most widely used reference agent in safety pharmacology studies. In conclusion, hypercapnic conditions associated with the non-invasive whole body plethysmography should be considered for optimizing the assessment of both the ventilatory depressant potential of morphine-like substances or the respiratory stimulant effects of new drugs in the rat, the most extensively used species in rodent safety and toxicological investigations.

Studies in iodine metabolism. Progress report, April 1975 -- March 1976. [Rats, mice, cattle, /sup 125/I, /sup 131/I

Energy Technology Data Exchange (ETDEWEB)

Van Middlesworth, L.

1976-01-01

Investigations during the past twelve months have included the following subjects: factors which influence release of radioiodine from thyroid glands; contamination of commercially available low-iodine diets; effects of hypoxia on release of iodine from thyroid glands of rats and mice; development of practical tests for available iodine in low-iodine diets; reproduction and abnormal thyroglobulin of rats maintained on low-iodine diets; observations on radioactivity in animal thyroids; collaboration with other laboratories regarding radium in bovine thyroids.

Blood pharmacokinetics of tertiary amyl methyl ether in male and female F344 rats and CD-1 mice after nose-only inhalation exposure.

Science.gov (United States)

Sumner, Susan C J; Janszen, Derek B; Asgharian, Bahman; Moore, Timothy A; Bobbitt, Carol M; Fennell, Timothy R

2003-01-01

Interest in understanding the biological behavior of aliphatic ethers has increased owing to their use as gasoline additives. The purpose of this study was to investigate the blood pharmacokinetics of the oxygenate tertiary amyl methyl ether (TAME), its major metabolite tertiary amyl alcohol (TAA) and acetone in rats and mice following inhalation exposure to TAME. Species differences in the area under the curve (AUC) for TAME were significant at each exposure concentration. For rats, the blood TAME AUC increased in proportion with an increase in exposure concentration. For mice, an increase in exposure concentration (100-500 ppm) resulted in a disproportional increase in the TAME AUC. Mice had greater (two- to threefold) blood concentrations of TAA compared with rats following exposure to 2500 or 500 ppm TAME. Mice had a disproportional increase in the TAA AUC with an increase in exposure concentration (100-500 ppm). This difference could result from saturation of a process (e.g. oxidation, glucuronide conjugation) that is involved in the further metabolism of TAA. For each species, gender and exposure concentration, acetone increased during exposure and returned to control values by 16 h following exposure. The source of acetone could be both as a metabolite of TAA or an effect on endogenous metabolism produced by exposure to TAME. Copyright 2003 John Wiley & Sons, Ltd.

Adenocarcinoma of the gallbladder in guinea pigs

International Nuclear Information System (INIS)

Hoch-Ligeti, C.; Congdon, C.C.; Deringer, M.K.; Stewart, H.L.

1979-01-01

Adenocarcinoma of the gallbladder developed in 17 of 68 untreated and in 26 of 83 irradiated guinea pigs of inbred strains 2 and 13. The carcinomas spread widely by direct extension and through lymphatic and blood vessels to lymph nodes, mesenteries, omenta, abdominal wall, liver, lungs, bones, and spleen. Whole-body exposure to gamma or x radiation increased both the number of tumors and metastases in male inbred guinea pigs but not in females. Significantly fewer (9 of 98) noninbred than inbred guinea pigs developed gallbladder carcinomas after irradiation. In 9 untreated noninbred guinea pigs gallbladder carcinomas were not found. Inasmuch as the effect of irradiation was not dose-dependent, an indirect systemic effect of irradiation was postulated. This is the first report on the occurrence of spontaneous gallbladder adenocarcinomas in guinea pigs

Metallochaperone for Cu,Zn-superoxide dismutase (CCS) protein but not mRNA is higher in organs from copper-deficient mice and rats.

Science.gov (United States)

Prohaska, Joseph R; Broderius, Margaret; Brokate, Bruce

2003-09-15

Cu,Zn-superoxide dismutase (SOD1) is an abundant metalloenzyme important in scavenging superoxide ions. Cu-deficient rats and mice have lower SOD1 activity and protein, possibly because apo-SOD1 is degraded faster than holo-SOD1. SOD1 interacts with and requires its metallochaperone CCS for donating copper. We produced dietary Cu deficiency in rodents to determine if the reduction in SOD1 was related to the level of its specific metallochaperone CCS. CCS levels determined by immunoblot were 2- to 3-fold higher in liver, heart, kidney, and brain from male Cu-deficient rats and mice under a variety of conditions. CCS was also higher in livers of Cu-deficient dams. Interestingly, CCS levels in brain of Cu-deficient mice were also higher even though SOD1 activity and protein were not altered, suggesting that the rise in CCS is correlated with altered Cu status rather than a direct result of lower SOD1. A DNA probe specific for rat CCS detected a single transcript by Northern blot hybridization with liver RNA. CCS mRNA levels in mouse and rat liver were not altered by dietary treatment. These results suggest a posttranscriptional mechanism for higher CCS protein when Cu is limiting in the cell, perhaps due to slower protein turnover. Elevation in CCS level is one of the most dramatic alterations in Cu binding proteins accompanying Cu deficiency and may be useful to assess Cu status.

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

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...... 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......, test and control groups most frequently differed in cage sizes and stocking densities, and behavioural tests differed in ways which may very well explain the differences in results. Overall, there seemed to be an effect of individual housing, although it may be small, and it seems reasonable to assume...

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

DEFF Research Database (Denmark)

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

2013-01-01

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

Toxicology and carcinogenesis studies of tetralin (CAS No. 119-64-2) in F344/N rats and B6C3F1 mice (inhalation studies).

Science.gov (United States)

2011-04-01

Tetralin is used as an industrial solvent primarily for naphthalene, fats, resins, oils, and waxes; as a solvent and stabilizer for shoe polishes and floor waxes; as a solvent for pesticides, rubber, asphalt, and aromatic hydrocarbons (e.g., anthracene); as a dye solvent carrier in the textile industry; as a substitute for turpentine in lacquers, paints, and varnishes; in paint thinners and as a paint remover; in alkali-resistant lacquers for cleaning printing ink from rollers and type; as a constituent of motor fuels and lubricants; for the removal of naphthalene in gas distribution systems; and as an insecticide for clothes moths. Tetralin was nominated by the National Cancer Institute for carcinogenicity and disposition studies because of its structure, high production volume, and high potential for worker and consumer exposure. Male and female F344/N rats and B6C3F1 mice were exposed to tetralin (at least 97% pure) by inhalation for 2 weeks, 3 months, or 2 years; male NCI Black Reiter (NBR) rats were exposed to tetralin by inhalation for 2 weeks. Male NBR rats do not produce 2u-globulin; the NBR rats were included to study the relationship of 2u-globulin and renal lesion induction. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male (F344/N and NBR) and five female (F344/N) rats were exposed to tetralin at air concentrations of 0, 7.5, 15, 30, 60, or 120 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 12 exposures. All rats survived to the end of the studies. The final mean body weight of female rats exposed to 120 ppm and mean body weight gains of female rats exposed to 30 ppm or greater were significantly less than those of the chamber controls. Final mean body weights of exposed groups of male NBR rats and mean body weight gains of all exposed groups of male rats were significantly less than those of the chamber controls. Dark

The oil boom in Equatorial Guinea

International Nuclear Information System (INIS)

Frynas, J.G.

2004-01-01

In less than a decade, Equatorial Guinea has transformed itself from an African backwater into one of the world's fastest growing economies and a sought-after political partner in the Gulf of Guinea. The sole reason for this transformation has been the discovery of oil and gas. This article outlines the rise of Equatorial Guinea as one of Africa's leading oil-producing countries and investigates the political, economic and social effects of becoming a petro-state. The article is based on the author's field research in Equatorial Guinea in the autumn of 2003 and interviews with senior oil company staff, government officials and staff of international organizations as well as secondary sources. This research demonstrates how reliance on oil and gas exports can lead to profound changes in a country's political economy. (author)

Effects of casoxin 4 on morphine inhibition of small animal intestinal contractility and gut transit in the mouse

Directory of Open Access Journals (Sweden)

Glen S Patten

2011-02-01

Full Text Available Glen S Patten1,2, Richard J Head1, Mahinda Y Abeywardena1,21CSIRO Preventative Health National Research Flagship, Adelaide, Australia; 2CSIRO Food and Nutritional Sciences, Adelaide, AustraliaBackground and aims: Chronic opioid analgesia has the debilitating side-effect of constipation in human patients. The major aims of this study were to: 1 characterize the opioid-specific antagonism of morphine-induced inhibition of electrically driven contraction of the small intestine of mice, rats, and guinea pigs; and 2 test if the oral delivery of small milk-derived opioid antagonist peptides could block morphine-induced inhibition of intestinal transit in mice.Methods: Mouse, rat, and guinea pig intact ileal sections were electrically stimulated to contract and inhibited with morphine in vitro. Morphine inhibition was then blocked by opioid subtype antagonists in the mouse and guinea pig. Using a polymeric dye, Poly R-478, the opioid antagonists casoxin 4 and lactoferroxin A were tested orally for blocking activity of morphine inhibition of gut transit in vivo by single or double gavage techniques.Results: The guinea pig tissue was more sensitive to morphine inhibition compared with the mouse or the rat (IC50 [half maximal inhibitory concentration] values as nmol/L ± SEM were 34 ± 3, 230 ± 13, and 310 ± 14 respectively (P < 0.01. The inhibitory influence of opioid agonists (IC50 in electrically driven ileal mouse preparations were DADLE ([D-Ala2, D-Leu5]-enkephalin ≥ met-enkephalin ≥ dynorphin A ≥ DAMGO ([D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin > morphine > morphiceptin as nmol/L 13.9, 17.3, 19.5, 23.3, 230, and 403 respectively. The mouse demonstrated predominantly Κ- and δ-opioid receptor activity with a smaller µ-opioid receptor component. Both mouse and guinea pig tissue were sensitive to casoxin 4 antagonism of morphine inhibition of contraction. In contrast to naloxone, relatively high oral doses of the µ-opioid receptor antagonists

Experimental animal models for COPD: a methodological review

Directory of Open Access Journals (Sweden)

Vahideh Ghorani

2017-05-01

The present review provides various methods used for induction of animal models of COPD, different animals used (mainly mice, guinea pigs and rats and measured parameters. The information provided in this review is valuable for choosing appropriate animal, method of induction and selecting parameters to be measured in studies concerning COPD.

Muscle Moment Arms and Sensitivity Analysis of a Mouse Hindlimb Musculoskeletal Model

Science.gov (United States)

2016-05-12

musculature in squirrels, rats, and guinea pigs with con- trast-enhanced microCT. Anat Rec (Hoboken) 294, 915–928. Deisseroth K (2011) Optogenetics. Nat...downhill running in mdx mice. Muscle Nerve 43, 878–886. Medler S (2002) Comparative trends in shortening velocity and force production in skeletal muscles

Dracunculiasis (guinea worm disease).

Science.gov (United States)

Greenaway, Chris

2004-02-17

Dracunculiasis (guinea worm disease) is a parasitic disease that is limited to remote, rural villages in 13 sub-Saharan African countries that do not have access to safe drinking water. It is one the next diseases targeted for eradication by the World Health Organization. Guinea worm disease is transmitted by drinking water containing copepods (water fleas) that are infected with Dracunculiasis medinensis larvae. One year after human ingestion of infected water a female adult worm emerges, typically from a lower extremity, producing painful ulcers that can impair mobility for up to several weeks. This disease occurs annually when agricultural activities are at their peak. Large proportions of economically productive individuals of a village are usually affected simultaneously, resulting in decreased agricultural productivity and economic hardship. Eradication of guinea worm disease depends on prevention, as there is no effective treatment or vaccine. Since 1986, there has been a 98% reduction in guinea worm disease worldwide, achieved primarily through community-based programs. These programs have educated local populations on how to filter drinking water to remove the parasite and how to prevent those with ulcers from infecting drinking-water sources. Complete eradication will require sustained high-level political, financial and community support.

Unilateral flank ovariohysterectomy in guinea pigs (Cavia porcellus).

Science.gov (United States)

Rozanska, D; Rozanski, P; Orzelski, M; Chlebicka, N; Putowska, K

2016-11-01

To describe a simple, minimally invasive method of ovariohysterectomy via a unilateral flank approach in guinea pigs, for use in routine desexing of healthy female guinea pigs or treatment of ovarian cysts. The subjects of this retrospective study were 41 client-owned guinea pigs submitted for routine desexing or treatment of ovarian cysts. They included 16 healthy female guinea pigs aged 8-12 months (Group 1), and 15 females aged from 9 months to 3 years (Group 2), and 10 females aged from 3 to 7 years (Group 3) with different-sized ovarian cysts. Prior to surgery, the animals received clinical examination, blood testing (complete blood count and serum biochemistry profile) and examination of the abdomen using ultrasonography, to assess the condition of the reproductive tract and ensure the guinea pigs were fit for surgery. Ovariohysterectomy was performed via a unilateral flank incision made close to the erector spinae muscle starting approximately 1 cm caudal to the last rib. Both ovaries, uterine horns, and the uterine cervix were localised, ligated, and dissected through this unilateral retroperitoneal incision. Ovariohysterectomy was successfully completed via a single flank incision in 38/41 (93%) guinea pigs. Three guinea pigs with ovarian cysts from Group 3, which were >6 years old died during surgery due to circulatory and respiratory failure under anaesthesia. In the remaining 38 cases, surgery proceeded without complications. A further two guinea pigs from Group 3 were reluctant to move or eat for the first 3 days after surgery but recovered after provision of supportive care. All 38 animals fully recovered and wound healing was normal. This is the first report of ovariohysterectomy via a unilateral flank incision in guinea pigs. This approach is a simple, minimally invasive and safe alternative to the midline or bilateral flank approaches currently used for surgery of the reproductive tract in guinea pigs.

Analgesic and Anti-Inflammatory Activities of Resveratrol through Classic Models in Mice and Rats

Directory of Open Access Journals (Sweden)

Guangxi Wang

2017-01-01

Full Text Available Background. Inflammation and pain are closely related to humans’ and animals’ health. Resveratrol (RSV is a natural compound with various biological activities. The current study is aimed to evaluate the analgesic and anti-inflammatory activities of RSV in vivo. Materials and Methods. The analgesic effects were assessed by the acetic acid-induced writhing and hot plate tests. The anti-inflammatory effects were determined using the xylene-induced mouse ear oedema, the acetic acid-induced rat pleurisy, and carrageenan-induced rat synovitis tests, respectively. Results. The analgesic results showed that RSV could significantly inhibit the number of writhes and improve the time and pain threshold of mice standing on hot plate. The anti-inflammatory results showed that RSV could inhibit the ear oedema of mice. In acetic acid-induced pleurisy test, RSV could significantly inhibit the WBC and pleurisy exudates, could decrease the production of NO, and elevate the activity of SOD in serum. In carrageenan-induced synovitis test, RSV could reduce the content of MDA and elevate the T-SOD activity in serum; RSV could inhibit the expressions of TP, PGE2, NO, and MDA. Conclusion. Shortly, these results indicated that RSV had potent analgesic and anti-inflammatory activities and could be a potential new drug candidate for the treatment of inflammation and pain.

Toxicology and carcinogenesis studies of nitrofurantoin (CAS No. 67-20-9) in F344/n rats and B6C3F1 mice (feed studies). Technical report

Energy Technology Data Exchange (ETDEWEB)

French, J.E.

1989-09-01

Two-year toxicology and carcinogenesis studies were conducted by administering diets containing 0, 600, or 1,300 ppm nitrofurantoin to groups of 50 female rats for 103 weeks. Groups of 50 male rats and 50 mice of each sex were fed diets containing 0, 1,300 or 2,500 ppm for 103 weeks. Under the conditions of these 2-year feed studies, there was some evidence of carcinogenic activity of nitrofurantoin for male F344/N rats as shown by increased incidences of uncommon kidney tubular cell neoplasms. Uncommon osteosarcomas of the bone and neoplasms of the subcutaneous tissue were observed in dosed male rats. Incidences of interstitial cell adenomas of the testis and neoplasms of the preputial gland were decreased in the 2,500-ppm group of male rats. There was no evidence of carcinogenic activity of nitrofurantoin for female F344/N rats fed diets containing 600 ppm or 1,300 ppm for 2 years. Female rats may have been able to tolerate higher doses. There was no evidence of carcinogenic activity of nitrofurantoin for male B6C3F(1) mice fed diets containing 1,300 ppm or 2,500 ppm for 2 years. There was clear evidence of carcinogenic activity of nitrofurantoin for female B6C3F(1) mice as shown by increased incidences of tubular adenomas, benign mixed tumors, and granulosa cell tumors of the ovary.

Cadmium in milk and mammary gland in rats and mice

International Nuclear Information System (INIS)

Petersson Grawe, K.; Oskarsson, A.

2000-01-01

The purpose of the present investigation was to study the uptake of cadmium in mammary tissue, effects on milk secretion and composition, and lactational transport of cadmium to the sucklings. Cadmium exposure during lactation resulted in retention of cadmium in the mammary tissue in mice and rats. The uptake of cadmium in the mammary tissue was rapid, as shown in lactating mice by whole-body autoradiography 4 h after an intravenous injection of a tracer dose of 109 CdCl 2 . Retention of cadmium in kidneys of suckling pups was observed in the autoradiograms at 7 days after exposure of the dams. Lactating rats were intravenously infused with 109 CdCl 2 in 0.9% saline via osmotic minipumps from day 3 to day 16 after parturition. The cadmium dose given was 0, 8.8, 62 and 300 μg Cd/kg body wt. per day. Plasma and milk were collected at day 10 and 16 after parturition. Plasma cadmium levels in dams increased from day 10 to day 16. Cadmium levels were higher in milk than in plasma, with milk/plasma ratios varying from 2 to 6. Zinc levels in milk were positively correlated to cadmium levels in milk (r 2 =0.26; P=0.03). In milk, 109 Cd was distributed in fat (46-52%), casein fraction (40-46%), and whey fraction (6-8%). There was a high correlation between cadmium concentrations in pups' kidney and cadmium concentrations in dam's milk (r 2 =0.98; P 109 Cd was bound to metallothionein in mammary tissue. The fraction of radiolabelled cadmium bound to metallothionein increased in a dose-dependent manner in both the liver (88-98%) and mammary tissue (57-80%). The present results indicate a low transfer of cadmium to the suckling pup, which might be due to binding of cadmium to metallothionein in the mammary tissue. However, during the susceptible developmental period even a low cadmium exposure may be of concern. (orig.)

The guinea-pig

DEFF Research Database (Denmark)

Andersen, Klaus Ejner; Maibach, H I; Anjo, M D

1980-01-01

14C ring-labelled hydrocortisone, testosterone and benzoic acid dissolved in acetone were applied to the backs of guinea-pigs (4 microgram/cm2). Percutaneous absorption was quantified by following the excretion of tracer in urine and faeces for 5 days. Absorption of hydrocortisone and benzoic acid...... was 2.4% (s.d. = 0.5; n = 3) and 31.4% (s.d. = 9.1; n = 3) of the applied dose respectively, similar to published human absorption data. Testosterone was absorbed to a greater extent in guinea-pigs (34.9% +/- 5.4; n = 5) than man. A thioglycollate based depilatory cream significantly increased the skin...

Model for deposition and long-term disposition of 134Cs-labeled fused aluminosilicate particles inhaled by guinea pigs

International Nuclear Information System (INIS)

Snipes, M.B.; McClellan, R.O.

1986-01-01

When considering which laboratory animal species to use in inhalation studies, it is important to evaluate the similarities and differences in deposition and fate of the inhaled materials in various laboratory animals compared with humans. Beagle dogs have deposition and clearance patterns of inhaled particles similar to humans. However, some studies require smaller laboratory animals to be cost effective or to allow an adequate number of animals to address the scientific questions. This study evaluated the deposition and clearance of a relatively insoluble aerosol inhaled by guinea pigs. The test aerosol was monodisperse 134 Cs-labeled fused aluminosilicate particles inhaled during 75 minute inhalation exposure. The guinea pigs had deposition similar to rats but respiratory tract retention and clearance patterns were similar to dogs and humans. 5 references, 2 figures, 1 table

An experimental analysis of the specificity of actively acquired tolerance in mice

Energy Technology Data Exchange (ETDEWEB)

Doria, G.

1963-08-15

Tolerance to CBA skin was induced in C3H mice by neonatal injection of CBA spleen cells. When two months old, the C3H recipients were grafted with CBA skin. These skin grafts showed no signs of rejection during the observation time of three months, whereas CBA skins grafted onto C3H mice non injected at birth showed complete necrosis in 11.7 days. Normal C3H and C3H mice tolerant to CBA skin were injected with rat RBC and sacrificed 12 days later for serum titration of anti-rat RBC agglutinins. The agglutinin titer was the same in both groups. This indicates that the unresponsiveness of C3H mice to CBA skin was specific, for the tolerant mice were able to respond with normal vigor to antigens (rat RBC) unrelated to C3H and CBA. Whether this response was due to the host immune system or to the CBA spleen cells which may have colonized the C3H newborns was subsequently investigated. Spleen cells from tolerant C3H mice sensitized to rat RBC were injected into two groups of lethally irradiated recipients: C3H mice preimmunized against CBA and CBA mice preimmunized against C3H. Both groups were given rat RBC immediately after the spleen cell transfer from the tolerant mice and sacrified a week later for serum titration of anti-rat RBC agglutinins. These agglutinins, due to the secondary response of the transferred spleen cells, could be detected only in the group of C3H recipients preimmunized against CBA. This shows that anti-rat RBC agglutinins in tolerant mice were produced y the immune system of the C3H host. The theoretical implications of this finding are discussed. (auth)

Development of a Guinea Pig Lung Deposition Model

Science.gov (United States)

2016-01-01

Development of a Guinea Pig Lung Deposition Model Distribution Statement A. Approved for public release; distribution is unlimited. January...4 Figure 2. Particle deposition in the lung of the guinea pig via endotracheal breathing...Particle deposition in the lungs of guinea pigs via nasal breathing. ......................................... 12 v PREFACE The research work

Leptopirosis in animal of animal house of Biologic Science Center of Londrina State University / Leptospirose em animais do biotério central do Centro de Ciências Biológicas da Universidade Estadual de Londrina

Directory of Open Access Journals (Sweden)

Ernst Eckehardt Muller

2000-12-01

Full Text Available Leptospirosis has been described in laboratory animal house of several countries happening among mice. albino rats. guinea pigs, dogs, rabbits, monkeys and man. The laboratory animal house of Biologic Science Center of Londrina State University maintains and breeds several species of animals and stray dogs trapped in citíes of Paraná State. In this paper w e r e utilized for leptospirosis research, 325 wistar rats. 323 albino mice. 289 dogs, 135 rabbits. 119 guinea pigs, and 57 black rats trapped around of animal house. The microscopic agglutination test with 22 cultures of Leptospira interrogans showed positive results in 110 dogs and o n e guinea pig, having been found antibodies against serovars canicola (62, 7%, pyrogenes (51,8%, castellonis (30.9% and icterobaemorrhagiae (23,6%. The dark field microscopy examination of 574 urine samples (282 albino mice, 224 wistar rats, 29 black rats, 24 dogs, 13 rabbits and two guinea pigs showed positive resuíts in six dogs. The seven attempts of urine and kidneys isolation were negatives.A leptospirose tem sido descrita em biotérios de vários países, acometendo camundongos, ratos albinos, cobaios, cães, coelhos e macacos além do manipuladores. O Biotério Centrai do Centro de Ciências Biológicas da Universidade Estadual de Londrina mantém e cria várias espécies de animais além de receber cães de rua, capturados em municípios do Estado do Paraná. Neste trabalho foram utilizados para a pesquisa de leptospirose, soros de 325 ratos wistar, 323 camundongos albinos. 289 cães de rua, 135 coelhos, 119 cobaios, além de 57 ratos pretos capturados nas proximidades do biotério. A prova de somaglutinação microscópica com 22 soroiipos de Lepiospira interrogans mostrou resultados positivos em 110 cães e um cobaio, sendo encontrado anticorpos principalmente contra os soroiipos canicola (62. 7%. pyrogenes (51.8%. castellonis (30,9% e icterohaemorrhagiae (23.6%. A pesquisa direta de leptospira em

Lack of effect of ivermectin on prepatent guinea-worm

DEFF Research Database (Denmark)

Issaka-Tinorgah, A.; Magnussen, P.; Bloch, P.

1994-01-01

The effect of ivermectin on prepatent guinea-worm was tested in a single-blind placebo-controlled trial; 400 adults were randomly allocated to a single dose of ivermectin (150 µg/kg) or placebo. Fifty-four of the 385 participants who were followed for 15 months developed a total of 69 emergent...... guinea-worms. There was no significant differencein the proportion of persons with emergent guinea-worms between the 2 treatment groups; 58% appeared in males. 80% of emergent guinea-worms were located below the knee. Migration of guinea-worms in the tissues was not affected. It is concluded...

Toxicology and Carcinogenesis Studies of Furfuryl Alcohol (CAS No. 98-00-0) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

Science.gov (United States)

1999-02-01

Furfuryl alcohol-based resins are used as binding agents in foundry sand and as corrosion inhibitors in mortar, grout, and cement. Because of their heat resistance, furan resins are used in the manufacture of fiberglass-reinforced plastic equipment. Furfuryl alcohol was selected for evaluation because of the absence of data on its carcinogenic potential and its large production volume, widespread use in manufacturing, and ubiquitous presence in consumer goods. Male and female F344/N rats and B6C3F1 mice were exposed to furfuryl alcohol (greater than 98% pure) by inhalation for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse bone marrow cells. 16-DAY STUDY IN RATS: Groups of five male and five female rats were exposed to concentrations of 0, 16, 31, 63, 125, or 250 ppm furfuryl alcohol by inhalation, 6 hours per day, 5 days per week for 16 days. All male and female rats exposed to 250 ppm died by day 2 of the study, and one male rat exposed to 125 ppm died on day 5. Final mean body weights of male and female rats exposed to 125 ppm were significantly less than those of the chamber control groups. Male rats exposed to 31, 63, or 125 ppm and female rats exposed to 125 ppm gained less weight than the chamber control groups. Clinical findings included dyspnea, hypoactivity, and nasal and ocular discharge in males and females exposed to 63, 125, or 250 ppm. All exposed animals developed lesions in the nasal respiratory epithelium and olfactory epithelium, and the severities of these lesions generally increased with increasing exposure concentration. 16-DAY STUDY IN MICE: Groups of five male and five female mice were exposed to concentrations of 0, 16, 31, 63, 125, or 250 ppm furfuryl alcohol by inhalation, 6 hours per day, 5 days per week for 16 days. All male and female mice exposed to 250 ppm died by day 4 of the study, and one female mouse exposed to 125 ppm died on day

Long-term exposure to hypoxia inhibits tumor progression of lung cancer in rats and mice

International Nuclear Information System (INIS)

Yu, Lunyin; Hales, Charles A

2011-01-01

Hypoxia has been identified as a major negative factor for tumor progression in clinical observations and in animal studies. However, the precise role of hypoxia in tumor progression has not been fully explained. In this study, we extensively investigated the effect of long-term exposure to hypoxia on tumor progression in vivo. Rats bearing transplanted tumors consisting of A549 human lung cancer cells (lung cancer tumor) were exposed to hypoxia for different durations and different levels of oxygen. The tumor growth and metastasis were evaluated. We also treated A549 lung cancer cells (A549 cells) with chronic hypoxia and then implanted the hypoxia-pretreated cancer cells into mice. The effect of exposure to hypoxia on metastasis of Lewis lung carcinoma in mice was also investigated. We found that long-term exposure to hypoxia a) significantly inhibited lung cancer tumor growth in xenograft and orthotopic models in rats, b) significantly reduced lymphatic metastasis of the lung cancer in rats and decreased lung metastasis of Lewis lung carcinoma in mice, c) reduced lung cancer cell proliferation and cell cycle progression in vitro, d) decreased growth of the tumors from hypoxia-pretreated A549 cells, e) decreased Na + -K + ATPase α1 expression in hypoxic lung cancer tumors, and f) increased expression of hypoxia inducible factors (HIF1α and HIF2α) but decreased microvessel density in the lung cancer tumors. In contrast to lung cancer, the growth of tumor from HCT116 human colon cancer cells (colon cancer tumor) was a) significantly enhanced in the same hypoxia conditions, accompanied by b) no significant change in expression of Na + -K + ATPase α1, c) increased HIF1α expression (no HIF2α was detected) and d) increased microvessel density in the tumor tissues. This study demonstrated that long-term exposure to hypoxia repressed tumor progression of the lung cancer from A549 cells and that decreased expression of Na + -K + ATPase was involved in hypoxic

Papua New Guinea.

Science.gov (United States)

1986-10-01

The situation of the island archipelago nation of Papua New Guinea is reviewed in terms of its geography, people, history, government, politics economy and foreign relations. Papua New Guinea consists of the eastern half of the main island of New Guinea (the western portion is Indonesia), and several island groups, all located northeast of Australia. The island has extreme geographical variations, ranging from precipitous mountains to extensive swamps and river valleys, all in a monsoon cimate. As a result, there are hundreds of small groups each with unique cultures and languages; over 650 languages, many unrelated to each other. The population is estimated at 3.5 million, growing at about 2.5% per year. Historically, the region has been occupied by Germany, Britain, Japan, and the U.S. The country came under the international trusteeship system in 1949, and now has a vigorous parliamentary government. The economy is based on subsistence agriculture, but is buttressed by resources such as gold, copper, and other metals, oil, timber, tropical agricultural products, fish. The only indusry is local production, since the minimum wage is too high to compete with Asian labor.

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.

Mechanism of the negative force-frequency relationship in physiologically intact rat ventricular myocardium. Studies by intracellular Ca2+ monitor with iodo-1 and by 31P-nuclear magnetic resonance spectroscopy

International Nuclear Information System (INIS)

Morii, Isao; Kihara, Yasuki; Sasayama, Shigetake; Konishi, Takashi; Inubushi, Toshiro.

1996-01-01

We studied the subcellular mechanisms of the negative force-frequency relationship in rat myocardium by measuring intracellular Ca 2+ transients by indo-1 fluorometry and intracellular pH (pH i ) and phosphate compounds with 31 P-nuclear magnetic resonance (NMR). The data were compared with those from guinea pig hearts, which show a positive force-frequency relationship. By increasing the pacing rate from 3 Hz to 5 Hz, the peak positive first derivative of left ventricular pressure (LVdP/dt) in rat heart decreased by 10±1% (n=6). In contrast to this negative inotropic response, simultaneously measured peak Ca 2+ transients increased by 6±1%. Guinea pig heart (n=6) showed an increase in peak positive LVdP/dt (33±1%) which was associated with an increase in peak Ca 2+ transients (8±1%). Under equivalent experimental conditions in an NMR spectrometer, this increase in the pacing rate did not affect intracellular levels of phosphate compounds in either rat (n=6) or guinea pig heart (n=6). In contrast, pH i showed a decrease of 0.031±0.006 pH units in rat heart, while no changes were observed in guinea pig heart. These results suggest that in physiological rat myocardium, pH i is susceptible to changes in the stimulus frequency and may affect the Ca 2+ -responsiveness of contractile proteins, which results in the negative force-frequency relationship. (author)

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

International Nuclear Information System (INIS)

Bhattacharyya, M.H.; Whelton, B.D.; Stern, P.H.; Peterson, D.P.

1988-01-01

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 45 Ca release from 45 Ca-prelabeled bones was measured immediately after the start of dietary cadmium exposure. Furthermore, experiments with 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

Assessment of immunotoxicity in female Fischer 344/N and Sprague Dawley rats and female B6C3F1 mice exposed to hexavalent chromium via the drinking water.

Science.gov (United States)

Shipkowski, Kelly A; Sheth, Christopher M; Smith, Matthew J; Hooth, Michelle J; White, Kimber L; Germolec, Dori R

2017-12-01

Sodium dichromate dihydrate (SDD), an inorganic compound containing hexavalent chromium (Cr(VI)), is a common environmental contaminant of groundwater sources due to widespread industrial use. There are indications in the literature that Cr(VI) may induce immunotoxic effects following dermal exposure, including acting as both an irritant and a sensitizer; however, the potential immunomodulatory effects of Cr(VI) following oral exposure are relatively unknown. Following the detection of Cr(VI) in drinking water sources, the National Toxicology Program (NTP) conducted extensive evaluations of the toxicity and carcinogenicity of SDD following drinking water exposure, including studies to assess the potential for Cr(VI) to modulate immune function. For the immunotoxicity assessments, female Fischer 344/N (F344/N) and Sprague Dawley (SD) rats and female B 6 C 3 F 1 mice were exposed to SDD in drinking water for 28 consecutive days and evaluated for alterations in cellular and humoral immune function as well as innate immunity. Rats were exposed to concentrations of 0, 14.3, 57.3, 172, or 516 ppm SDD while mice were exposed to concentrations of 0, 15.6, 31.3, 62.5, 125, or 250 ppm SDD. Final mean body weight and body weight gain were decreased relative to controls in 250 ppm B 6 C 3 F 1 mice and 516 ppm SD rats. Water consumption was significantly decreased in F344/N and SD rats exposed to 172 and 516 ppm SDD; this was attributed to poor palatability of the SDD drinking water solutions. Several red blood cell-specific parameters were significantly (5-7%) decreased in 250 ppm mice; however, these parameters were unaffected in rats. Sporadic increases in the spleen IgM antibody response to sheep red blood cells (SRBC) were observed, however, these increases were not dose-dependent and were not reproducible. No significant effects were observed in the other immunological parameters evaluated. Overall, exposure to Cr(VI) in drinking water had limited effects on

Effect of serum from rats with destructed nuclei of the posterior hypothalamus on the formation of hemopoietic colonies in the spleen of lethally irradiated mice after bone marrow cell transplantation

International Nuclear Information System (INIS)

Fedorov, N.A.; Likhovetskaya, Z.M.; Kurbanova, G.N.; Prigozhina, T.A.; L'vovich, A.I.

1982-01-01

Colony formation capability of serum from animals with destructed nuclei of the posterior hypothalamus was studied in lethally irradiated mice. Male-rats of Wistar line and hybrid mice (CBA x C57 BL) were used in the experiments. The serum from rats with destructed nuclei of the posterior hypothalamus was injected simultaneously with bone marrow transplantation into lethally irradiated mice. The number of macrocolonies in the spleen was counted on the 9th day. It was ascertained that the serum from rats with destructed nuclei of the posterior hypothalamus caused an increase of the number of macroscopically visible colonies in the spleen of lethally irradiated mice. The determination of hemopoetic types of colonies showed that the effect of the serum from those animals caused an increase of the number of granulocytic-type colonies. The initiation of colony stimulating and leukopoetic activity in the blood of animals after the destruction of mammillary body nuclei and posterior hypothalamic nucleus attested, according to the authors point of view, that humoral mediators (humoral mediator) could participated in the mechanism of hypothalamus effect on leulopoiesis

Desensitization by progressive up-titration prevents first-dose effects on the heart: guinea pig study with ponesimod, a selective S1P1 receptor modulator.

Directory of Open Access Journals (Sweden)

Markus Rey

Full Text Available Ponesimod, a selective S1P1 receptor modulator, reduces the blood lymphocyte count in all tested species by preventing egress of T and B cells from thymus and peripheral lymphoid organs. In addition, ponesimod transiently affects heart rate and atrioventricular (AV conduction in humans, effects not observed in mice, rats, and dogs with selective S1P1 receptor modulators, suggesting that the regulation of heart rate and rhythm is species dependent. In the present study, we used conscious guinea pigs implanted with a telemetry device to investigate the effects of single and multiple oral doses of ponesimod on ECG variables, heart rate, and blood pressure. Oral administration of ponesimod did not affect the sinus rate (P rate but dose-dependently induced AV block type I to III. A single oral dose of 0.1 mg/kg had no effect on ECG variables, while a dose of 3 mg/kg induced AV block type III in all treated guinea pigs. Repeated oral dosing of 1 or 3 mg/kg ponesimod resulted in rapid desensitization, so that the second dose had no or a clearly reduced effect on ECG variables as compared with the first dose. Resensitization of the S1P1 receptor in the heart was concentration dependent. After desensitization had been induced by the first dose of ponesimod, the cardiac system remained desensitized as long as the plasma concentration was ≥75 ng/ml. By using a progressive up-titration regimen, the first-dose effect of ponesimod on heart rate and AV conduction was significantly reduced due to desensitization of the S1P1 receptor. In summary, conscious guinea pigs implanted with a telemetry device represent a useful model to study first-dose effects of S1P1 receptor modulators on heart rate and rhythm. This knowledge was translated to a dosing regimen of ponesimod to be tested in humans to avoid or significantly reduce the first-dose effects.

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

Science.gov (United States)

2016-08-30

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

Toxicity and carcinogenicity of methyl isobutyl ketone in F344N rats and B6C3F1 mice following 2-year inhalation exposure

International Nuclear Information System (INIS)

Stout, Matthew D.; Herbert, Ronald A.; Kissling, Grace E.; Suarez, Fernando; Roycroft, Joseph H.; Chhabra, Rajendra S.; Bucher, John R.

2008-01-01

Methyl isobutyl ketone (MIBK) is primarily used as a denaturant for rubbing alcohol, as a solvent and in the manufacture of methyl amyl alcohol. Inhalation of vapors is the most likely route of exposure in the work place. In order to evaluate the potential of MIBK to induce toxic and carcinogenic effects following chronic exposure, groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to MIBK at concentrations of 0, 450, 900, or 1800 ppm by inhalation, 6 h/day, 5 days per week for 2 years. Survival was decreased in male rats at 1800 ppm. Body weight gains were decreased in male rats at 900 and 1800 ppm and in female mice at 1800 ppm. The primary targets of MIBK toxicity and carcinogenicity were the kidney in rats and the liver in mice. In male rats, there was increased mineralization of the renal papilla at all exposure concentrations. The incidence of chronic progressive nephropathy (CPN) was increased at 1800 ppm and the severity was increased in all exposed groups. There were also increases in renal tubule hyperplasia at all exposure concentrations, and in adenoma and adenoma or carcinoma (combined) at 1800 ppm; these lesions are thought to represent a continuum in the progression of proliferative lesions in renal tubule epithelium. These increases may have resulted from the increased severity of CPN, either through α2μ-globulin-dependent or -independent mechanisms. An increase in mononuclear cell leukemia at 1800 ppm was an uncertain finding. Adrenal medulla hyperplasia was increased at 1800 ppm, and there was a positive trend for increases in benign or malignant pheochromocytomas (combined). In female rats, there were increases in the incidence of CPN in all exposure concentrations and in the severity at 1800 ppm, indicating that CPN was increased by mechanisms in addition to those related to α2μ-globulin. There were renal mesenchymal tumors, which have not been observed in historical control animals, in two female rats at 1800 ppm. The

Complex adenovirus-vectored vaccine protects guinea pigs from three strains of Marburg virus challenges

International Nuclear Information System (INIS)

Wang Danher; Hevey, Michael; Juompan, Laure Y.; Trubey, Charles M.; Raja, Nicholas U.; Deitz, Stephen B.; Woraratanadharm, Jan; Luo Min; Yu Hong; Swain, Benjamin M.; Moore, Kevin M.; Dong, John Y.

2006-01-01

The Marburg virus (MARV), an African filovirus closely related to the Ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of MARV infections. In order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cAdVax) to overexpress a MARV glycoprotein (GP) fusion protein derived from the Musoke and Ci67 strains of MARV. Vaccination with the cAdVaxM(fus) vaccine led to efficient production of MARV-specific antibodies in both mice and guinea pigs. Significantly, guinea pigs vaccinated with at least 5 x 10 7 pfu of cAdVaxM(fus) vaccine were 100% protected against lethal challenges by the Musoke, Ci67 and Ravn strains of MARV, making it a vaccine with trivalent protective efficacy. Therefore, the cAdVaxM(fus) vaccine serves as a promising vaccine candidate to prevent and contain multi-strain infections by MARV

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

Science.gov (United States)

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

2005-10-01

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

African Journals Online: Papua New Guinea

African Journals Online (AJOL)

African Journals Online: Papua New Guinea. Home > African Journals Online: Papua New Guinea. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Browse By Category · Browse Alphabetically · Browse By Country · List All Titles · Free to read Titles This Journal is ...

A new species of Rhododendron from New Guinea (Ericaceae)

NARCIS (Netherlands)

Kores, Paul

1978-01-01

The Star Mountains of New Guinea are situated at the geographic center of the Island of New Guinea extending on both sides of the Indonesian-Papua New Guinea border. Access to these mountains from either side of the border which divides the island is relatively difficult and as a result few

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.

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

Acute oral toxicity of 3-MCPD mono- and di-palmitic esters in Swiss mice and their cytotoxicity in NRK-52E rat kidney cells.

Science.gov (United States)

Liu, Man; Gao, Bo-Yan; Qin, Fang; Wu, Ping-Ping; Shi, Hai-Ming; Luo, Wei; Ma, Ai-Niu; Jiang, Yuan-Rong; Xu, Xue-Bing; Yu, Liang-Li Lucy

2012-10-01

The acute oral toxicity of 1-palmitoyl-3-chloropropanediol (3-MCPD 1-monopalmitate) and 1,2-bis-palmitoyl-3-chloropropanediol (3-MCPD dipalmitate) in Swiss mice were examined, along with their cytotoxicity in NRK-52E rat kidney cells. LD50 (median lethal dose) value of 3-MCPD 1-monopalmitate was determined 2676.81 mg/kg body weight (BW). The results showed that 3-MCPD 1-monopalmitate dose-dependently decreased the mean body weight, and caused significant increase of serum urea nitrogen and creatinine in dead mice compared to the control and survived mice. Major histopathological changes in mice fed 3-MCPD 1-monopalmitate were renal tubular necrosis, protein casts and spermatids decrease in the seminiferous tubules. According to the limit test for 3-MCPD dipalmitate, LD50 value of 3-MCPD dipalmitate was presumed to be greater than 5000 mg/kg BW. Obvious changes were not observed on mean body weight, absolute and relative organ weight or serum urea nitrogen and creatinine levels in mice fed 3-MCPD dipalmitate. However, renal tubular necrosis, protein casts and spermatids decrease were also observed in the dead mice. In addition, MTT and LDH assay results only showed the cytotoxicity of 3-MCPD 1-monopalmitate in NRK-52E rat kidney cells in a dose-dependent manner. Together, the results indicated a greater toxicity of 3-MCPD 1-monopalmitate compared to 3-MCPD dipalmitate. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Vaginal Microbiota of Guinea Pigs

OpenAIRE

Hafner, L. M.; Rush, C. M.; Timms, P.

2011-01-01

The vaginae of four guinea pigs were swabbed and samples cultured aerobically on horse blood agar, in 5 per cent carbon dioxide on MRS agar or anaerobically on anaerobic horse blood agar. Vaginal microbiota consisted almost exclusively of gram-positive bacteria including Corynebacterium, Streptococcus, Enterococcus, Staphylococcus and Lactobacillus species.Keywords: guinea pigs, vaginal microbiota, vaginal vaccines.

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

Heterogeneous infectiousness in guinea pigs experimentally infected with Trypanosoma cruzi.

Science.gov (United States)

Castillo-Neyra, Ricardo; Borrini Mayorí, Katty; Salazar Sánchez, Renzo; Ancca Suarez, Jenny; Xie, Sherrie; Náquira Velarde, Cesar; Levy, Michael Z

2016-02-01

Guinea pigs are important reservoirs of Trypanosoma cruzi, the causative parasite of Chagas disease, and in the Southern Cone of South America, transmission is mediated mainly by the vector Triatoma infestans. Interestingly, colonies of Triatoma infestans captured from guinea pig corrals sporadically have infection prevalence rates above 80%. Such high values are not consistent with the relatively short 7-8 week parasitemic period that has been reported for guinea pigs in the literature. We experimentally measured the infectious periods of a group of T. cruzi-infected guinea pigs by performing xenodiagnosis and direct microscopy each week for one year. Another group of infected guinea pigs received only direct microscopy to control for the effect that inoculation by triatomine saliva may have on parasitemia in the host. We observed infectious periods longer than those previously reported in a number of guinea pigs from both the xenodiagnosis and control groups. While some guinea pigs were infectious for a short time, other "super-shedders" were parasitemic up to 22 weeks after infection, and/or positive by xenodiagnosis for a year after infection. This heterogeneity in infectiousness has strong implications for T. cruzi transmission dynamics and control, as super-shedder guinea pigs may play a disproportionate role in pathogen spread. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Mitochondrial DNA4568 deletions in guinea-pig associated with presbycusis].

Science.gov (United States)

Wei, Xue-mei; Yang, Yuan; Liang, Chuang-yu; Zheng, Zhong

2006-12-01

To determine weather or not the mtDNA(4568) deletions in guinea-pig contribute to the development of presbycusis. Forty-four guinea-pigs were divided into 2 groups: group A (young control group, normal hearing, 22 guineas) and group B (aged group). The group B was subdivided into group B(1) (old normal hearing, 6 guineas) and group B(2) (old hearing loss, 16 guineas). First the guineas were tested by auditory brainstem response (ABR), and then the Cortis's tissues, auditory nerve tissues, brain and blood were harvested and the total DNA was extracted. The mtDNA(4568) deletion was analyzed by PCR. Hearing loss was occurred with age. The mtDNA(4568) deletion incidence of aged group in all tissues was significant higher than that of young control group (Ppresbycusis (B(2) group) were significant higher than that of aged normal hearing group (B(1) group) (Ppresbycusis and aged normal hearing group (P> 0.05). mtDNA(4568) deletion of guinea-pig possibly contributes to aging and mtDNA(4568) deletion in Cortis's and auditory nerve tissues of guinea-pig may be associated with presbycusis. There is no enough evidence to prove that the mtDNA(4568) deletions in brain and blood are related with presbycusis.

TISCON, a BASIC computer program for the calculation of the biodistribution of radionuclide-labelled drugs in rats and mice

International Nuclear Information System (INIS)

Maddalena, D.J.

1983-09-01

Animal biodistribution studies on radionuclide-labelled drugs are labour-intensive and time-consuming. A method for rapidly carrying out these studies on rats and mice is presented. An interactive computer program, written in BASIC, is used to calculate parameters of interest, such as per cent injected dose (%ID),%ID per gram and target to non-target ratios

Guinea pig ID-like families of SINEs.

Science.gov (United States)

Kass, David H; Schaetz, Brian A; Beitler, Lindsey; Bonney, Kevin M; Jamison, Nicole; Wiesner, Cathy

2009-05-01

Previous studies have indicated a paucity of SINEs within the genomes of the guinea pig and nutria, representatives of the Hystricognathi suborder of rodents. More recent work has shown that the guinea pig genome contains a large number of B1 elements, expanding to various levels among different rodents. In this work we utilized A-B PCR and screened GenBank with sequences from isolated clones to identify potentially uncharacterized SINEs within the guinea pig genome, and identified numerous sequences with a high degree of similarity (>92%) specific to the guinea pig. The presence of A-tails and flanking direct repeats associated with these sequences supported the identification of a full-length SINE, with a consensus sequence notably distinct from other rodent SINEs. Although most similar to the ID SINE, it clearly was not derived from the known ID master gene (BC1), hence we refer to this element as guinea pig ID-like (GPIDL). Using the consensus to screen the guinea pig genomic database (Assembly CavPor2) with Ensembl BlastView, we estimated at least 100,000 copies, which contrasts markedly to just over 100 copies of ID elements. Additionally we provided evidence of recent integrations of GPIDL as two of seven analyzed conserved GPIDL-containing loci demonstrated presence/absence variants in Cavia porcellus and C. aperea. Using intra-IDL PCR and sequence analyses we also provide evidence that GPIDL is derived from a hystricognath-specific SINE family. These results demonstrate that this SINE family continues to contribute to the dynamics of genomes of hystricognath rodents.

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

Science.gov (United States)

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

2008-01-01

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

Analyzing Protein Changes in Guinea Pig Tissue Lysates Using Non-guinea Pig Specific Antibodies: Procedures for Western Blotting and Examples Using 16 Individual Antibodies for Common CNS Proteins

Science.gov (United States)

2006-05-01

guinea pig model does present a significant problem...trying to correlate behavioral and protein changes due to the absence of guinea pig -specific antibodies. We...have developed a procedure to determine the specificity of commercially available, non- guinea pig -specific antibodies in guinea pig lysates.

Gastric volvulus in guinea pigs: comparison with other species.

Science.gov (United States)

Dudley, Emily S; Boivin, Gregory P

2011-07-01

Gastric volvulus has been documented in several species of animals and is associated with high morbidity and mortality. We report 2 cases of gastric volvulus in guinea pigs that died without detection of prior clinical signs. Both guinea pigs were adult female guinea pigs in a breeding colony and had given birth to multiple litters; one was pregnant at the time of death. Gastric rotations of 540° and 360° were identified at necropsy examination. These cases include the first known report of gastric rotation greater than 360° in any species. Although gastric volvulus has been reported to occur in guinea pigs, little is known about its risk factors, etiology, and pathogenesis. We conducted a literature review to compare gastric volvulus between guinea pigs and other species. Copyright 2011 by the American Association for Laboratory Animal Science

Guinea Pigs: Versatile Animals for the Classroom

Science.gov (United States)

Barman, Charles R.

1977-01-01

Guinea pigs are presented as versatile classroom animals. Suggestions for animal behavior and genetics studies are given. Also included is information concerning sex determination and the breeding of guinea pigs, and hints on keeping these animals in the classroom. References and illustrations complete the article. (MA)

Toxicological Evaluation of the Methanol Extract of Gmelina arborea Roxb. Bark in Mice and Rats

OpenAIRE

Kulkarni, Y. A.; Veeranjaneyulu, A.

2012-01-01

Objective: The present study was designed to evaluate acute and repeated dose toxicity of the methanol extract (ME) of the Gmelina arborea stem bark. Materials and Methods: For the acute toxicity study, ME of G. arborea was orally administered to Swiss albino mice at a dose range of 300–5000 mg/kg. For the repeated dose toxicity study, the Wistar rats of either sex were orally administered with ME of G. arborea at the doses of 300, 1000, and 2000 mg/kg/day for a period of 28 days. The effects...

[Spontaneous neoplasms in guinea pigs].

Science.gov (United States)

Khar'kovskaia, N A; Khrustalev, S A; Vasil'eva, N N

1977-01-01

The authors present an analysis of the data of foreign literature and the results of their personal studies of spontaneous neoplasms in 40 guinea pigs of national breeding observed during observed during a 5-year period. In 4 of them malignant tumors were diagnosed-lympholeucosis (2 cases), dermoid ovarian cysts and also cancer and adenoma of the adrenal cortex (in one animal). The neoplasms described developed in guinea pigs, aged over 4 years, and they are referred to as mostly common tumors in this species of animals.

Effect of crude methanol leaf extract of Combretum racemosum on histamine-stimulated gastric secretion in rats

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Chukwugozie Nwachukwu Okwuosa

2017-02-01

Full Text Available Objective: To investigate the effect of crude methanolic extract of Combretum racemosum (C. racemosum leaves on histamine-stimulated gastric secretion in rats. Methods: Phytochemical and acute toxicity tests were performed. Anti-secretory activity of C. racemosum extract was investigated in pyloric ligated rats administered histamine. Gastric juice was collected from all the animals and the volume, titratable acidity, pH and mucus content were measured. The effect of C. racemosum extract on calcium chloride induced contractions of the guinea-pig ileum suspended in high potassium, calcium-deficient depolarizing solution was investigated. The H2 receptor antagonistic potency was also evaluated using the isolated non-gravid rat uterus. Results: Phytochemistry revealed the presence of abundant amounts of saponins and moderate amounts of glycosides, terpenoids, proteins, reducing sugar, resins, alkaloids, flavonoids and carbohydrates. The oral LD50 of the extract was greater than 8 000 mg/kg body weight in mice. Pretreatment of pyloric ligated rats with C. racemosum prior to histamine administration significantly reduced (P < 0.001 the volume of gastric juice and titratable acidity, and significantly increased (P < 0.001 gastric pH and gastric mucus when compared to the negative control. Both doses of C. racemosum protected rats significantly (P < 0.001 from histamine-induced ulceration. C. racemosum potently inhibited contractions evoked by calcium chloride in a dose-dependent and reversible manner with an IC50 of 1 132 µg/mL. It also antagonized the relaxant effect of histamine on the isolated rat uterus in a manner comparable to cimetidine. Conclusions: The leaves of C. racemosum possess gastric anti-secretory and anti-ulcer effects and justify its use in traditional medicine in South-East Nigeria for the treatment of peptic ulcer disease.

Metabolism and disposition of 2-ethylhexyl-p-methoxycinnamate following oral gavage and dermal exposure in Harlan Sprague Dawley rats and B6C3F1/N mice and in hepatocytes in vitro.

Science.gov (United States)

Fennell, Timothy R; Mathews, James M; Snyder, Rodney W; Hong, Yan; Watson, Scott L; Black, Sherry R; McIntyre, Barry S; Waidyanatha, Suramya

2017-11-23

1. 2-Ethylhexyl-p-methoxycinnamate (EHMC) is commonly used as an ingredient in sunscreens, resulting in potential oral and dermal exposure in humans. 2. Clearance and metabolism of EHMC in hepatocytes and disposition and metabolism of EHMC in rodents following oral (8-800 mg/kg) intravenous (IV) (8 mg/kg) or dermal (0.8-80 mg/kg representing 0.1-10% formulation concentration) exposure to [ 14 C]EHMC were investigated in rats and mice. 3. EHMC was rapidly cleared from rat and mouse hepatocytes (half-life ≤3.16 min) and less rapidly (half-life ≤48 min) from human hepatocytes. 4. [ 14 C]EHMC was extensively absorbed and excreted primarily in urine by 72 h after oral administration to rats (65-80%) and mice (63-72%). Oral doses to rats were excreted to a lesser extent (3-8%) in feces and as CO 2 (1-4%). Radioactive residues in tissues were <1% of the dose. There were no sex or species differences in disposition in rats. 5. Following dermal application, 34-42% of an 8-mg/kg dose was absorbed in rats, and 54-62% in mice in 72-h. 6. Among numerous urinary metabolites associated with hydrolysis of the ester, two potential reproductive and developmental toxicants, 2-ethylhexanol and 2-ethylhexanoic acid were produced by metabolism of EHMC.

An annotated ornithological bibliography of Guinea-Bissau

NARCIS (Netherlands)

Hazevoet, C.J.

1995-01-01

Guinea-Bissau, a former Portuguese colony, is a small country (36,125 km²) in West Africa bordered by Senegal in the north and Guinea (Conakry) in the east and south. Little is known about the country’s ornithology and comparatively few papers on its birds have been published. The following is an

Cell structure and function and response to chemotherapy in tumors heterotransplanted into the subrenal capsule of mice and rats.

Science.gov (United States)

Stenbäck, F; Kangas, L; Wasenius, V M

1985-12-01

Specimens from 16 freshly biopsied human tumors, two mammary adenocarcinomas, ten ovarian adenocarcinomas, two squamous cell carcinomas, one malignant histiocytoma and one chondrosarcoma of the bone, two human ovarian adenocarcinomas established by transplantation into nude mice and two adenocarcinomas induced in rat mammary gland were transplanted under the renal capsule of 510 normal immunocompetent mice and 180 rats and the effects of chemotherapy were evaluated. The results showed successful transplantation of all types of tumors in both animal species. Morphological analysis revealed preserved glandular structures with surface microvilli, mucin and CEA production and partially preserved basement membranes. Treatment with cyclophosphamide, vinblastine, adriamycin and cisplatin caused cell shrinkage, degradation and partial or total disappearance of the tumor cells. Vascularization was distinct in all specimens. A cellular infiltrate was found frequently but not consistently. A common end stage was a fibrotic scar with no cellular activity, occasionally giving a misleading impression of a growing tumor on gross observation. The results were obtained rapidly and suggest that the subrenal capsule assay would be useful for evaluating the sensitivity of human tumors to therapeutic manipulation, but needs supplementary histological examination.

Effects of methimepip and JNJ-5207852 in Wistar rats exposed to an open-field with and without object and in Balb/c mice exposed to a radial-arm maze.

Science.gov (United States)

Abuhamdah, Rushdie M A; van Rensburg, Ruan; Lethbridge, Natasha L; Ennaceur, Abdel; Chazot, Paul L

2012-01-01

The role of the histamine H(3) receptor (H(3)R) in anxiety is controversial, due to limitations in drug selectivity and limited validity of behavioral tests used in previous studies. In the present report, we describe two experiments. In the first one, Wistar rats were treated with an H(3)R agonist (methimepip), and exposed to an open-field. In the second one, Balb/c mice were treated with H(3)R agonist (methimepip) or antagonist (JNJ-5207852), and exposed to an open space 3D maze which is a modified version of the radial-arm maze. C57BL/6J saline treated mice were included for comparisons. When exposed to an empty open field, Wistar rats spent more time in the outer area and made very low number of brief crossings in the central area. However, when an object occupied the central area, rats crossed frequently into and spent a long time in the central area. Administration of a range of different doses of methimepip (selective H(3)R agonist) reduced the entries into the central area with a novel object, indicating enhanced avoidance response. In the 3D maze, both Balb/c and C57BL/6J saline-treated mice crossed frequently onto the bridges that radiate from the central platform but only C57BL/6J mice crossed onto the arms which extend the bridges. This suggests that Balb/c mice are more anxious than C57BL/6J mice. Neither methimepip nor JNJ-5207852 (selective H(3)R antagonist/inverse agonist) induced entry into the arms of the maze, indicative of lack of anxiolytic effects.

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

Briti eliit üritas kukutada Ekvatoriaal-Guinea valitsust

Index Scriptorium Estoniae

2004-01-01

Ekvatoriaal-Guineas ja Zimbabwes on vahistatud kümneid inimesi, keda süüdistatakse riigipöördekatses Ekvatoriaal-Guineas. Suurbritannia endise peaministri Margaret Thatcher'i poega Mark Thatcher'it süüdistatakse riigipöördekatse rahastamisele kaasaaitamises

Differences in social interaction- vs. cocaine reward in mouse vs. rat.

Science.gov (United States)

Kummer, Kai K; Hofhansel, Lena; Barwitz, Constanze M; Schardl, Aurelia; Prast, Janine M; Salti, Ahmad; El Rawas, Rana; Zernig, Gerald

2014-01-01

We previously developed rat experimental models based on the conditioned place preference (CPP) paradigm in which only four 15-min episodes of dyadic social interaction with a sex- and weight-matched male Sprague Dawley (SD) rat (1) reversed CPP from cocaine to social interaction despite continuing cocaine training, and (2) prevented the reacquisition/re-expression of cocaine CPP. In a concurrent conditioning schedule, pairing one compartment with social interaction and the other compartment with 15 mg/kg cocaine injections, rats spent the same amount of time in both compartments and the most rewarding sensory component of the composite stimulus social interaction was touch (taction). In the present study, we validated our experimental paradigm in C57BL/6 mice to investigate if our experimental paradigm may be useful for the considerable number of genetically modified mouse models. Only 71% of the tested mice developed place preference for social interaction, whereas 85% of the rats did. Accordingly, 29% of the mice developed conditioned place aversion (CPA) to social interaction, whereas this was true for only 15% of the rats. In support of the lesser likelihood of mice to develop a preference for social interaction, the average amount of time spent in direct contact was 17% for mice vs. 79% for rats. In animals that were concurrently conditioned for social interaction vs. cocaine, the relative reward strength for cocaine was 300-fold higher in mice than in rats. Considering that human addicts regularly prefer drugs of abuse to drug-free social interaction, the present findings suggest that our experimental paradigm of concurrent CPP for cocaine vs. social interaction is of even greater translational power if performed in C57BL/6 mice, the genetic background for most transgenic rodent models, than in rats.

Differences in social interaction- vs cocaine reward in rat vs mouse

Directory of Open Access Journals (Sweden)

Kai K Kummer

2014-10-01

Full Text Available We previously developed rat experimental models based on the conditioned place preference (CPP paradigm in which only four 15-min episodes of dyadic social interaction with a sex- and weight-matched male Sprague Dawley rat (1 reversed CPP from cocaine to social interaction despite continuing cocaine training, and (2 prevented the reacquisition/re-expression of cocaine CPP. In a concurrent conditioning schedule, pairing one compartment with social interaction and the other compartment with 15 mg/kg cocaine injections, rats spent the same amount of time in both compartments and the most rewarding sensory component of the composite stimulus social interaction was touch (taction. In the present study, we validated our experimental paradigm in C57BL/6 mice to investigate if our experimental paradigm may be useful for the considerable number of genetically modified mouse models. Only 71% of the tested mice developed place preference for social interaction, whereas 85% of the rats did. Accordingly, 29% of the mice developed conditioned place aversion to social interaction, whereas this was true for only 15% of the rats. In support of the lesser likelihood of mice to develop a preference for social interaction, the average amount of time spent in direct contact was 17% for mice vs 79% for rats. In animals that were concurrently conditioned for social interaction vs cocaine, the relative reward strength for cocaine was 300-fold higher in mice than in rats.Considering that human addicts regularly prefer drugs of abuse to drug-free social interaction, the present findings suggest that our experimental paradigm of concurrent CPP for cocaine vs social interaction is of even greater translational power if performed in C57BL/6 mice, the genetic background for most transgenic rodent models, than in rats.

Light-enhanced inhibition of ouabain binding to digitalis receptor in rat brain and guinea pig heart by the food dye erythrosine

International Nuclear Information System (INIS)

Hnatowich, M.; LaBella, F.S.

1982-01-01

Erythrosine (ERY) (FD and C red no. 3) inhibited specific binding of [ 3 H]ouabain to rat brain homogenates with an IC50 of 23 mM in the dark and 1 mM in ordinary fluorescent light. Competition studies demonstrated the presence of two components, only one of which was affected by light. Lineweaver-Burk analysis indicated that ERY preferentially antagonizes [ 3 H]ouabain binding at a high-affinity site in the light, whereas in the dark the dye inhibits binding in a manner qualitatively similar to inhibition by ouabain. Light enhancement of ERY potency occurred only when dye and tissue were present together in the incubation medium, pointing to participation of transient molecular species. However, neither superoxide dismutase nor catalase altered the effects of ERY in the light or dark, suggesting the absence of oxygen free radicals. In contrast to brain, membranes from guinea pig heart showed only one binding site for [ 3 H]ouabain, and antagonism by ERY at this site was markedly enhanced by light. Structural differences between classes of ouabain binding regions probably accounts for the discrimination exhibited by ERY in the presence of light and oxygen. Our findings also caution that metabolic transformation of this common food dye, light decomposition, or photoreaction with foodstuff may yield more toxic derivatives

Hyperplasia of the lymphoepithelium of NALT in rats but not in mice upon 28-day exposure to 15ppm formaldehyde vapor

NARCIS (Netherlands)

Kuper, C. F.; Oostrum, L. van; Ma-Hock, L.; Durrer, S.; Woutersen, R.A.

2011-01-01

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

Hyperplasia of the lymphoepithelium of NALT in rats but not in mice upon 28-day exposure to 15 ppm formaldehyde vapor

NARCIS (Netherlands)

Kuper, C.F.; Oostrum, van L.; Ma-Hock, I.; Durrer, S.; Woutersen, R.A.

2011-01-01

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

[Arbovirus circulation in the Republic of Guinea].

Science.gov (United States)

Butenko, A M

1996-01-01

In 1978-1991 the USSR-Guinea Virological and Microbiological Laboratory functioned in Kindia, the Republic of Guinea. Arbovirus activity in this country was studied by a number of virologists and other specialists. Their personal contribution and achievements in this collaboration are reflected in the present paper. About 74,000 mosquitoes, 100,000 Ixodidae ticks, 1,500 wild birds, 2,700 bats, 106 monkeys, and 308 other mammals, 927 blood samples collected from febrile patients were examined in 1978-1989, using inoculation of new-born white mice. As a result of this work 127 strains of the following arboviruses were isolated: Chikungunia (1 strain), Dengue 2 (4), Saboya (7), Wesselsbron (1), Bunyamwera (4), M'Poko (5), Rift Valley Fever (6), CHF-Congo (9), Dugbe (22), Bhanja (6), Forecariah (2), Jos (26), Abadina (15), Kindia (2), Ark 6956 (1), Fomede (2), Bluetongue (9), Mossuril (2), AnK 6009 (1), and Kolente (2). Dengue 2, Wesselsbron, Bunyamwera, M'Poko, Kindia, Mossuril viruses were isolated from mosquitoes. Ixodidae ticks were sources for isolation of Chikungunia, Saboya, CCHF, Dugbe, Bhanja, Forecaciah, Jos, Abadina, Kindia, Ark 6956, Fomede, Bluetongue, and Kolente viruses. Saboya, RVF, Fomede, Kolente, AnK 6909 were isolated from bats (Chiroptera); Saboya, Abadina, and Bluetongue viruses from birds. One strain of Dugbe virus was originated from the brain of Cercopithecus patas. Bunyamwera and Abadina viruses were isolated from the blood of two febrile patients. Serological identification of many strains was kindly conducted at the Pasteur Institute, Dakar (J. P.Digoutte) and some at the YARU, USA (R. Shope). Kindia and Ark 6956 (Reovirus, gr. Palyam), Fomede (gr. Chobar Gorge), Forecariah (Bunyavirus, gr. Bhanja), Kolente (Rhabdovirus) were identified as an original type of Lagos bat virus. The results of seroepidemiological surveys are also presented.

In vivo efficacy of SM-8668 (Sch 39304), a new oral triazole antifungal agent.

Science.gov (United States)

Tanio, T; Ichise, K; Nakajima, T; Okuda, T

1990-06-01

SM-8668 (Sch 39304) is a new oral antifungal agent which we evaluated in comparison with fluconazole in various fungal infection models. The prophylactic effect of SM-8668 was excellent against systemic candidiasis, aspergillosis, and cryptococcosis in mice. The 50% effective dose for SM-8668 was assessed at 10 days after infection and was 0.18, 3.7, and 5.9 mg/kg (body weight), respectively, for the above-mentioned fungal diseases. Fluconazole was about four times less effective than SM-8668 against systemic candidiasis and was only slightly effective at doses of 80 and 25 mg/kg against systemic aspergilosis and cryptococcosis, respectively. SM-8668 was also about four to eight times more active than fluconazole against vaginal candidiasis in rats and against dermatophytic infection in guinea pigs. In addition, topical SM-8668 was as effective as topical miconazole or tioconazole against skin mycosis in guinea pigs. After oral administration, SM-8668 showed a maximum concentration in serum similar to that of fluconazole in both mice and rats, but the elimination half-life and area under the serum concentration-time curve for SM-8668 were twice those for fluconazole.

Transmission pattern of parainfluenza 3 virus in guinea pig breeding herds.

Science.gov (United States)

Blomqvist, Gunilla A M; Martin, Krister; Morein, Bror

2002-07-01

In searching for the cause of experimental variations in respiratory research data, serology revealed the prevalence of antibodies against parainfluenza virus type 3 (PIV 3) in guinea pigs. The aim of the present study was to explore the transmission rate, course, and kinetics of enzootic PIV 3 infection in guinea pig breeding units. In the first part of the study, blood samples to be analyzed for PIV 3 antibodies were collected from guinea pigs of a PIV 3-positive breeding colony at different times after birth. In the same breeding unit, 6 of 12 2-week-old guinea pigs were relocated and separately housed. The PIV 3 serum antibody titers of the two groups were compared at various times from birth to 13 weeks after birth. In the second part of the study, the spread of infectious virus and virus persistence were explored by housing seronegative sentinel animals together with 2- to 3-week-old guinea pigs from three different PIV 3-positive breeding units. The guinea pigs remaining in the breeding colony as well as those removed and housed separately showed declining serum antibody titers for about 1 month after birth, thereafter the titers were stable until about 8 weeks after birth. Five weeks later, the mean antibody titer of the guinea pigs remaining in the breeding colony had increased to a markedly higher level than that of the relocated, separately housed guinea pigs. Seroconversion was demonstrated in 7 of the 14 sentinels housed with the 2- to 3-week-old guinea pigs from PIV 3-positive breeding units. Sentinels housed together with PIV 3-positive guinea pigs 24 weeks after the start of the experiment did not seroconvert. We conclude that young guinea pigs born to PIV 3-positive mothers were protected by maternal immunity against infection with PIV 3 during their first 14 days of life. The guinea pig offspring became infected during the period from about 2 weeks until 8 weeks after birth, as demonstrated by seroconversion of sentinel animals and an increasing

Negligible colon cancer risk from food-borne acrylamide exposure in male F344 rats and nude (nu/nu mice-bearing human colon tumor xenografts.

Directory of Open Access Journals (Sweden)

Jayadev Raju

Full Text Available 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.

Analyzing Protein Changes in Guinea Pig Tissue Lysates Using Non-guinea Pig Specific Antibodies: Procedures for Western Blotting and Examples Using 16 Individual Antibodies for Common CNS Proteins

National Research Council Canada - National Science Library

Johnson, Erik A; Daugherty, Kelly S

2006-01-01

... behavioral and protein changes due to the absence of guinea pig-specific antibodies. We have developed a procedure to determine the specificity of commercially available, non-guinea pig-specific antibodies in guinea pig lysates...

Effects of ultraviolet irradiation on skin of guinea pig

International Nuclear Information System (INIS)

Zhang Wenwen; Chen Qiang; Li Peng; Ling Ling; Lin Xiaochen; Ren Shuping; Liu Yajuan; Li Yun

2008-01-01

Objective: To explore the adverse effects of ultraviolet B (UV-B) on the skin of guinea pig. Methods: Guinea pig skin was irradiated with UV-B, the skin changes in external appearance, pathology, and the contents of OH and O 2 - produced in the skin were determined to study the adverse effects of UV-B on the guinea pig skin. Results: UV-B caused red swelling and desquamation of skin, with the increasing of the UV-B irradiation, the cells in stratum spinosum began to proliferate vigorously, the MDA and ROS contents in UVB radiation group were significantly higher than those in control group (P<0.05). Conclusion: UV-B can cause injury to guinea pig skin and has the potential to produce skin cancer. (authors)

Blood profiles in unanesthetized and anesthetized guinea pigs (Cavia porcellus).

Science.gov (United States)

Williams, Wendy R; Johnston, Matthew S; Higgins, Sarah; Izzo, Angelo A; Kendall, Lon V

2016-01-01

The guinea pig is a common animal model that is used in biomedical research to study a variety of systems, including hormonal and immunological responses, pulmonary physiology, corticosteroid response and others. However, because guinea pigs are evolutionarily a prey species, they do not readily show behavioral signs of disease, which can make it difficult to detect illness in a laboratory setting. Minimally invasive blood tests, such as complete blood counts and plasma biochemistry assays, are useful in both human and veterinary medicine as an initial diagnostic technique to rule in or rule out systemic illness. In guinea pigs, phlebotomy for such tests often requires that the animals be anesthetized first. The authors evaluated hematological and plasma biochemical effects of two anesthetic agents that are commonly used with guinea pigs in a research setting: isoflurane and a combination of ketamine and xylazine. Hematological and plasma biochemical parameters were significantly different when guinea pigs were under either anesthetic, compared to when they were unanesthetized. Plasma proteins, liver enzymes, white blood cells and red blood cells appeared to be significantly altered by both anesthetics, and hematological and plasma biochemical differences were greater when guinea pigs were anesthetized with the combination of ketamine and xylazine than when they were anesthetized with isoflurane. Overall these results indicate that both anesthetics can significantly influence hematological and plasma biochemical parameters in guinea pigs.

Operant ethanol self-administration in ethanol dependent mice.

Science.gov (United States)

Lopez, Marcelo F; Becker, Howard C

2014-05-01

While rats have been predominantly used to study operant ethanol self-administration behavior in the context of dependence, several studies have employed operant conditioning procedures to examine changes in ethanol self-administration behavior as a function of chronic ethanol exposure and withdrawal experience in mice. This review highlights some of the advantages of using operant conditioning procedures for examining the motivational effects of ethanol in animals with a history of dependence. As reported in rats, studies using various operant conditioning procedures in mice have demonstrated significant escalation of ethanol self-administration behavior in mice rendered dependent via forced chronic ethanol exposure in comparison to nondependent mice. This paper also presents a summary of these findings, as well as suggestions for future studies. Copyright © 2014 Elsevier Inc. All rights reserved.

A 2-D guinea pig lung proteome map

Science.gov (United States)

Guinea pigs represent an important model for a number of infectious and non-infectious pulmonary diseases. The guinea pig genome has recently been sequenced to full coverage, opening up new research avenues using genomics, transcriptomics and proteomics techniques in this species. In order to furth...

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

OpenAIRE

Y Tanko; B Kamba; MI Saleh; K Y Musa; A Mohammed

2008-01-01

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...

Hypervitaminosis D in Guinea Pigs with α-Mannosidosis

Science.gov (United States)

Jensen, JanLee A; Brice, Angela K; Bagel, Jessica H; Mexas, Angela M; Yoon, Sea Young; Wolfe, John H

2013-01-01

A colony of guinea pigs (n = 9) with α-mannosidosis was fed a pelleted commercial laboratory guinea pig diet. Over 2 mo, all 9 guinea pigs unexpectedly showed anorexia and weight loss (11.7% to 30.0% of baseline weight), and 3 animals demonstrated transient polyuria and polydipsia. Blood chemistry panels in these 3 guinea pigs revealed high-normal total calcium, high-normal phosphate, and high ALP. Urine specific gravity was dilute (1.003, 1.009, 1.013) in the 3 animals tested. Postmortem examination of 7 animals that were euthanized after failing to respond to supportive care revealed renal interstitial fibrosis with tubular mineralization, soft tissue mineralization in multiple organs, hepatic lipidosis, and pneumonia. Analysis of the pelleted diet revealed that it had been formulated with a vitamin D3 content of more than 150 times the normal concentration. Ionized calcium and 25-hydroxyvitamin D values were both high in serum saved from 2 euthanized animals, confirming the diagnosis of hypervitaminosis D. This report discusses the clinical signs, blood chemistry results, and gross and histologic findings of hypervitaminosis D in a colony of guinea pigs. When unexpected signs occur colony-wide, dietary differentials should be investigated at an early time point. PMID:23582422

Radiation protection by botanical extract from Araliaceae family

International Nuclear Information System (INIS)

Yonezawa, M.; Katoh, N.; Takeda, A.

1988-01-01

A single post-irradiation injection of a ginseng extract increased the 30-day survival ratios of X-ray irradiated mice, rats and guinea pigs. The injection accelerated the recovery of hemogram (erythrocyte, leukocyte and thrombocyte couts), particularly strongly that of thrombocyte count, commonly in the three species of the experimental animals. The extract increased the 30-day survival ratio, but stimulated recovery of only thrombocyte count in splenectomized mice. We consider that recovery of thrombocyte count is one of the most important factors for the decrease in bone marrow death after acute ionizing irradiation

Toxicology and carcinogenesis studies of p,p'-dichlorophenyl sulfone (CAS No. 80-07-9) in F344/N rats and B6C3F1 mice (feed studies).

Science.gov (United States)

2001-09-01

p,pN-Dichlorodiphenyl sulfone is used as a starting material in the production of polysulfones and polyethersulfones and as a component in reactive dyes in the textile industry; it is also a by-product of pesticide production. p,pN-Dichlorodiphenyl sulfone was nominated for study by the National Cancer Institute because of its history of high production and use, the prospect of increased production and use, and the absence of adequate toxicity testing. Male and female F344/N rats and B6C3F1 mice were exposed top,pN-dichlorodiphenyl sulfone (greater than 99% pure)in feed for 14 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium,cultured Chinese hamster ovary cells, and mouse bone marrow. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were fed diets containing 0, 30, 100, 300, 1,000, or 3,000 ppm p,pN-dichlorodiphenyl sulfone (equivalent to average daily doses of approximately 2, 6, 19, 65, or 200 mgp,pN-dichlorodiphenyl sulfone/kg body weight) for 14 weeks. All rats survived until the end of the study. Mean body weights of groups exposed to 300 ppm or greater were significantly less than those of the controls. Liver weights of groups exposed to 100 ppm or greater and kidney weights of 1,000 and 3,000 ppm male rats were significantly greater than those of the controls. Centrilobular hepatocyte hypertrophy of the liver was observed in most male rats exposed to 100 ppm or greater and in all female rats exposed to 300 ppm or greater, and the severities were increased in 300 ppm males and 1,000 and 3,000 ppm males and females. The incidences of nephropathy in 1,000 and 3,000 ppm female rats were significantly increased. Dose-related increases in severity of nephropathy were observed in male rats. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were fed diets containing 0, 30, 100, 300, 1,000, or 3,000 ppm p,pN-dichlorodiphenyl sulfone (equivalent to average daily doses of approximately 3.5, 15, 50

Polysaccharide prodigiosan therapy of irradiated guinea pigs

International Nuclear Information System (INIS)

Chertkov, K.S.; Mosina, Z.M.; Khramchenkova, S.P.

1976-01-01

In the experiments with irradiated guinea-pigs, a therapeutic action of prodigiosan has been detected. A parenteral administration of the preparation (125 to 500 μg/kg) within the interval from 15 min to 6 hours after a short-term exposure increased the survival of animals to 50%. Prodigiosan administered to guinea-pigs given prolonged irradiation failed to affect the survival rate

Inferences from the collaboration in the field of pharmaco-chemical protection and treatment of radiation injury according to the 'Intercosmos' program

International Nuclear Information System (INIS)

Rogozkin, V.D.

1976-01-01

Thiamine pyrophosphate protection against radiation was considered in the case of both individual and combined administration with tryptophan or gamma-amino butyric acid. Experiments were done in mice, rats, guinea-pigs, and dogs, using acute or protracted gamma-rays, and scoring animal survival, incidence of bone-marrow cells bearing chromosome aberrations, and proportion of nucleated cells in spleen and bone-marrow hemopoietic centers. (A.B.)

Ebola Virus Imported from Guinea to Senegal, 2014.

Science.gov (United States)

Ka, Daye; Fall, Gamou; Diallo, Viviane Cissé; Faye, Ousmane; Fortes, Louise Deguenonvo; Faye, Oumar; Bah, Elhadji Ibrahim; Diallo, Kadia Mbaye; Balique, Fanny; Ndour, Cheikh Tidiane; Seydi, Moussa; Sall, Amadou Alpha

2017-06-01

In March 2014, the World Health Organization declared an outbreak of Ebola virus disease in Guinea. In August 2014, a case caused by virus imported from Guinea occurred in Senegal, most likely resulting from nonsecure funerals and travel. Preparedness and surveillance in Senegal probably prevented secondary cases.

Piper (Piperaceae) in New Guinea: the climbing species

NARCIS (Netherlands)

Gardner, R.O.

2012-01-01

Sixteen climbing Piper species are accepted for New Guinea. The three endemics, P. arfakianum, P. subcanirameum and P. versteegii, are fully described. Eight taxa of unclear circumscription are noted. A new variety of P. macropiper, endemic to Morobe Province of Papua New Guinea, is described. The

ECG telemetry in conscious guinea pigs.

Science.gov (United States)

Ruppert, Sabine; Vormberge, Thomas; Igl, Bernd-Wolfgang; Hoffmann, Michael

2016-01-01

During preclinical drug development, monitoring of the electrocardiogram (ECG) is an important part of cardiac safety assessment. To detect potential pro-arrhythmic liabilities of a drug candidate and for internal decision-making during early stage drug development an in vivo model in small animals with translatability to human cardiac function is required. Over the last years, modifications/improvements regarding animal housing, ECG electrode placement, and data evaluation have been introduced into an established model for ECG recordings using telemetry in conscious, freely moving guinea pigs. Pharmacological validation using selected reference compounds affecting different mechanisms relevant for cardiac electrophysiology (quinidine, flecainide, atenolol, dl-sotalol, dofetilide, nifedipine, moxifloxacin) was conducted and findings were compared with results obtained in telemetered Beagle dogs. Under standardized conditions, reliable ECG data with low variability allowing largely automated evaluation were obtained from the telemetered guinea pig model. The model is sensitive to compounds blocking cardiac sodium channels, hERG K(+) channels and calcium channels, and appears to be even more sensitive to β-blockers as observed in dogs at rest. QT interval correction according to Bazett and Sarma appears to be appropriate methods in conscious guinea pigs. Overall, the telemetered guinea pig is a suitable model for the conduct of early stage preclinical ECG assessment. Copyright © 2016 Elsevier Inc. All rights reserved.

Petroleum service projects in the Gulf of Guinea

Science.gov (United States)

Ken-Worgu, Kenneth Chukwumeka

2011-07-01

The goal of this record of study is to examine the major facets involved in managing several petroleum service projects located in three different countries in the Gulf of Guinea simultaneously, while effectively engaging in business development activities for the Oil and Industrial Services Group (OIS). This work also furnishes adequate background on related subject matters to enable understanding of the projects presented. The petroleum services sector is the back bone of the oil and gas industry. Services companies are vital to the success of all petroleum and energy producers in the USA, the Gulf of Guinea and the world. There is a need and demand for these service companies because they play various roles such as logistics, drilling, construction, dredging, pipe laying, procurement, food supply, human resource supply, etc. The Gulf of Guinea comprises of countries from west and central Africa. This project was limited to Nigeria, Equatorial Guinea and Cameroon. This area holds the largest petroleum reserves in Africa and plays a vital role in the global supply of petroleum. The Oil and Industrial Services Group (OIS), plans to establish herself as one of the leading petroleum service companies in this gulf. To manage this expansion, I have taken the role of Gulf of Guinea manager to apply my background as a petroleum engineer as well as my business skills to build a successful division of the company. This work provides a record of study of the management of services, projects and contracts carried out by the OIS group in the gulf of Guinea. The following are the specific projects in the Gulf of Guinea that I participated in: Managing delivering, maintenance and marketing of offshore vessels, Offshore pipe laying project, Integrated pipeline maintenance project, Development a petroleum technical training facilities, Agbami pipe insulation project, Engineering lift project and Capital budgeting analysis for potential investments. The details of the specific

Use of permethrin eradicated the tropical rat mite (Ornithonyssus bacoti) from a colony of mutagenized and transgenic mice.

Science.gov (United States)

Hill, William A; Randolph, Mildred M; Boyd, Keli L; Mandrell, Timothy D

2005-09-01

The tropical rat mite, Ornithonyssus bacoti, was identified in a colony of mutagenized and transgenic mice at a large academic institution. O. bacoti is an obligate, blood-feeding ectoparasite with an extensive host range. Although the source of the infestation was likely feral rodents, none were found in the room housing infested mice. We hypothesize that construction on the floor above the vivarium and compromised ceiling integrity within the animal room provided for vermin entry and subsequent O. bacoti infestation. O. bacoti infestation was eliminated by environmental decontamination with synthetic pyrethroids and weekly application of 7.4% permethrin-impregnated cotton balls to mouse caging for five consecutive weeks. Visual examination of the macroenvironment, microenvironment, and colony for 38 days confirmed the efficacy of treatment. We noted no treatment-related toxicities or effects on colony production.

Direct behavioral and neurophysiological evidence for retronasal olfaction in mice.

Directory of Open Access Journals (Sweden)

Michelle R Rebello

Full Text Available The neuroscience of flavor perception is hence becoming increasingly important to understand food flavor perception that guides food selection, ingestion and appreciation. We recently provided evidence that rats can use the retronasal mode of olfaction, an essential element of human flavor perception. We showed that in rats, like humans, odors can acquire a taste. We and others also defined how the input of the olfactory bulb (OB -not functionally imageable in humans- codes retronasal smell in anesthetized rat. The powerful awake transgenic mouse, however, would be a valuable additional model in the study of flavor neuroscience. We used a go/no-go behavioral task to test the mouse's ability to detect and discriminate the retronasal odor amyl acetate. In this paradigm a tasteless aqueous odor solution was licked by water-restricted head-fixed mice from a lick spout. Orthonasal contamination was avoided. The retronasal odor was successfully discriminated by mice against pure distilled water in a concentration-dependent manner. Bulbectomy removed the mice's ability to discriminate the retronasal odor but not tastants. The OB showed robust optical calcium responses to retronasal odorants in these awake mice. These results suggest that mice, like rats, are capable of smelling retronasally. This direct neuro-behavioral evidence establishes the mouse as a useful additional animal model for flavor research.

Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models.

Science.gov (United States)

Oesch, F; Fabian, E; Guth, K; Landsiedel, R

2014-12-01

The exposure of the skin to medical drugs, skin care products, cosmetics, and other chemicals renders information on xenobiotic-metabolizing enzymes (XME) in the skin highly interesting. Since the use of freshly excised human skin for experimental investigations meets with ethical and practical limitations, information on XME in models comes in the focus including non-human mammalian species and in vitro skin models. This review attempts to summarize the information available in the open scientific literature on XME in the skin of human, rat, mouse, guinea pig, and pig as well as human primary skin cells, human cell lines, and reconstructed human skin models. The most salient outcome is that much more research on cutaneous XME is needed for solid metabolism-dependent efficacy and safety predictions, and the cutaneous metabolism comparisons have to be viewed with caution. Keeping this fully in mind at least with respect to some cutaneous XME, some models may tentatively be considered to approximate reasonable closeness to human skin. For dermal absorption and for skin irritation among many contributing XME, esterase activity is of special importance, which in pig skin, some human cell lines, and reconstructed skin models appears reasonably close to human skin. With respect to genotoxicity and sensitization, activating XME are not yet judgeable, but reactive metabolite-reducing XME in primary human keratinocytes and several reconstructed human skin models appear reasonably close to human skin. For a more detailed delineation and discussion of the severe limitations see the "Overview and Conclusions" section in the end of this review.

Gastric Volvulus in Guinea Pigs: Comparison with Other Species

OpenAIRE

Dudley, Emily S; Boivin, Gregory P

2011-01-01

Gastric volvulus has been documented in several species of animals and is associated with high morbidity and mortality. We report 2 cases of gastric volvulus in guinea pigs that died without detection of prior clinical signs. Both guinea pigs were adult female guinea pigs in a breeding colony and had given birth to multiple litters; one was pregnant at the time of death. Gastric rotations of 540° and 360° were identified at necropsy examination. These cases include the first known report of g...

Salmonella arizonaeInfection In A Guinea Pig Breeding Unit

OpenAIRE

GÜREL, Aydın; AYYILDIZ, Gülbin

1998-01-01

Salmonella arizonae infection was detected in guinea pigs kept for breeding. Two months old 50 quinea pigs were died in the breedig unit. Three death and 2 live guinea pigs were brought to Veterinary Faculty of İstanbul. The live 2 were euthanasied and necropcy was performed on all guinea pigs. The fluid about 50 cc. in the abdomen, the necrosis and pseudomembranes in the liver and spleen were observed. On histopathology, the foci of various coagulative necrosis were seen in the liver. The...

Crossed Looks: Globalisations and Curriculum in Guinea-Bissau

Science.gov (United States)

da Silva, Rui; dos Santos, Júlio Gonçalves; Pacheco, José Augusto

2015-01-01

This article focuses on education in Guinea-Bissau in the context of globalisations, examining the concept of globalisation and its relation to education and the curriculum. It focuses on the relatively neglected area of national education policies in Guinea-Bissau, comparing differences and common points of interference/influence of multilateral…

Passive Immunization of Anti bZP3 (Zone Pellucida3 in Wistar Rat (Rattus novergicus and Mouse (Mus musculus

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Y. Pantiwati

2012-12-01

Full Text Available This study was aimed at comparing the influence of anti bZP3’s passive immunization on anti-anti bZP3’s titer and pregnancy level on Wistar rats and mice. This study employed factorial design experiment with completely randomized design. The first factor was immunogenic type. The treated rats were immunized with 100 L anti bZP3 in 100 L Complete Freund’s Adjuvant (CFA, while the treated mice were injected with 50 L anti bZP3 in 50 L CFA. Control Wistar rats and mice were immunized with CFA and Incomplete Freund’s Adjuvant (IFA without anti bZP3. The second factor was animal type. The third factor was the length of serum incubation, i.e. 38, 49, 63, 86, 100, and 126 d. Dot blot on the treated Wistar rats and mice showed positive response proven by blue gradation; pre-immune mice as well as control Wistar rats and mice showed negative response proven by white gradation. The highest antibody titer in treated mouse serum was shown in 63 d incubation. The pregnancy on treated mice, control mice and Wistar rat occurred 100% until day 126; while the failure percentage on the treated mice was 4.5%. The pregnancy on treated mice occurred in 86 d incubation (1 rat, 100 d incubation (1 rat, and 126 d incubation (3 rats. Effective passive immunization on similar hospes occurred until day 63; while different hospes was ineffective. Antibodi anti-bZP3 was potential as a contraception through passive immunization on similar hospes.

Effect of fructo-oligosaccharide on nitrogen utilization in guinea pigs.

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Kawasaki, Kiyonori; Min, Xiao; Nishiyama, Ai; Sakaguchi, Ei

2013-04-01

The present study was conducted to determine the effects of fructo-oligosaccharide (FOS) on the nitrogen (N) utilization and digestibilities of dietary nutrients through cecotrophy in guinea pigs. Adult male guinea pigs that were housed or not housed in wooden frames to prevent cecotrophy were fed a commercial pellet diet (50 g/day) with 3% and 5% glucose or FOS for 8 days in individual metabolism cages. In the guinea pigs allowed cecotrophy, addition of FOS to the diet had no significant effects on body weight gain or apparent digestibility of N, but showed significantly lower value for the urinary N excretion and acid-detergent fiber digestibility (P guinea pigs prevented from cecotrophy, FOS had no effect on N retention, but showed tendencies toward a higher value for fecal N excretion and a lower value for urinary N excretion. These results suggest that FOS stimulates cecal microbial proliferation, thereby improving N utilization in guinea pigs. © 2012 Japanese Society of Animal Science.

Sex Genotyping of Archival Fixed and Immunolabeled Guinea Pig Cochleas.

Science.gov (United States)

Depreux, Frédéric F; Czech, Lyubov; Whitlon, Donna S

2018-03-26

For decades, outbred guinea pigs (GP) have been used as research models. Various past research studies using guinea pigs used measures that, unknown at the time, may be sex-dependent, but from which today, archival tissues may be all that remain. We aimed to provide a protocol for sex-typing archival guinea pig tissue, whereby past experiments could be re-evaluated for sex effects. No PCR sex-genotyping protocols existed for GP. We found that published sequence of the GP Sry gene differed from that in two separate GP stocks. We used sequences from other species to deduce PCR primers for Sry. After developing a genomic DNA extraction for archival, fixed, decalcified, immunolabeled, guinea pig cochlear half-turns, we used a multiplex assay (Y-specific Sry; X-specific Dystrophin) to assign sex to tissue as old as 3 years. This procedure should allow reevaluation of prior guinea pig studies in various research areas for the effects of sex on experimental outcomes.

α7-Nicotinic acetylcholine receptor: role in early odor learning preference in mice.

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Jennifer L Hellier

Full Text Available Recently, we have shown that mice with decreased expression of α7-nicotinic acetylcholine receptors (α7 in the olfactory bulb were associated with a deficit in odor discrimination compared to wild-type mice. However, it is unknown if mice with decreased α7-receptor expression also show a deficit in early odor learning preference (ELP, an enhanced behavioral response to odors with attractive value observed in rats. In this study, we modified ELP methods performed in rats and implemented similar conditions in mice. From post-natal days 5-18, wild-type mice were stroked simultaneously with an odor presentation (conditioned odor for 90 s daily. Control mice were only stroked, exposed to odor, or neither. On the day of testing (P21, mice that were stroked in concert with a conditioned odor significantly investigated the conditioned odor compared to a novel odor, as observed similarly in rats. However, mice with a decrease in α7-receptor expression that were stroked during a conditioned odor did not show a behavioral response to that odorant. These results suggest that decreased α7-receptor expression has a role in associative learning, olfactory preference, and/or sensory processing deficits.

Unexpected gender difference in sensitivity to the acute toxicity of dioxin in mice

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Pohjanvirta, Raimo, E-mail: raimo.pohjanvirta@helsinki.fi [Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland); Miettinen, Hanna, E-mail: hanna.miettinen@crl.com [Department of Environmental Health, National Institute for Health and Welfare, P.O. Box 95, FI-70701 Kuopio (Finland); Sankari, Satu, E-mail: satu.sankari@helsinki.fi [Central Laboratory of the Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, FI-00014 University of Helsinki (Finland); Hegde, Nagabhooshan [Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland); Lindén, Jere, E-mail: jere.linden@helsinki.fi [Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland); Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki (Finland)

2012-07-15

The acute toxicity of the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) varies widely among species and strains. Previous studies in rats have established that females are approximately 2-fold more sensitive to TCDD lethality than males. However, there is a surprising gap in the literature regarding possible gender-related sensitivity differences in mice. In the present study, by using three substrains of TCDD-sensitive C57BL/6 mice and transgenic mice on this background, we demonstrated that: 1) in contrast to the situation in rats, female mice are the more resistant gender; 2) the magnitude of the divergence between male and female mice depends on the substrain, but can amount to over 10-fold; 3) AH receptor protein expression levels or mutations in the primary structure of this receptor are not involved in the resistance of female mice of a C57BL/6 substrain, despite their acute LD{sub 50} for TCDD being over 5000 μg/kg; 4) transgenic mice that globally express the rat wildtype AH receptor follow the mouse type of gender difference; 5) in gonadectomized mice, ovarian estrogens appear to enhance TCDD resistance, whereas testicular androgens seem to augment TCDD susceptibility; and 6) the gender difference correlates best with the severity of liver damage, which is also reflected in hepatic histopathology and the expression of pro-inflammatory cytokines, especially IL-6. Hence, the two closely related rodent species most often employed in toxicological risk characterization studies, rat and mouse, represent opposite examples of the influence of gender on dioxin sensitivity, further complicating the risk assessment of halogenated aromatic hydrocarbons. -- Highlights: ► In contrast to rats, male mice are more sensitive to TCDD toxicity than female mice. ► The resistance of female C57BL/6Kuo mice matches or exceeds that of male DBA/2 mice. ► The resistance of female C57BL/6Kuo mice is not based on AHR structure or abundance. �

Unexpected gender difference in sensitivity to the acute toxicity of dioxin in mice

International Nuclear Information System (INIS)

Pohjanvirta, Raimo; Miettinen, Hanna; Sankari, Satu; Hegde, Nagabhooshan; Lindén, Jere

2012-01-01

The acute toxicity of the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) varies widely among species and strains. Previous studies in rats have established that females are approximately 2-fold more sensitive to TCDD lethality than males. However, there is a surprising gap in the literature regarding possible gender-related sensitivity differences in mice. In the present study, by using three substrains of TCDD-sensitive C57BL/6 mice and transgenic mice on this background, we demonstrated that: 1) in contrast to the situation in rats, female mice are the more resistant gender; 2) the magnitude of the divergence between male and female mice depends on the substrain, but can amount to over 10-fold; 3) AH receptor protein expression levels or mutations in the primary structure of this receptor are not involved in the resistance of female mice of a C57BL/6 substrain, despite their acute LD 50 for TCDD being over 5000 μg/kg; 4) transgenic mice that globally express the rat wildtype AH receptor follow the mouse type of gender difference; 5) in gonadectomized mice, ovarian estrogens appear to enhance TCDD resistance, whereas testicular androgens seem to augment TCDD susceptibility; and 6) the gender difference correlates best with the severity of liver damage, which is also reflected in hepatic histopathology and the expression of pro-inflammatory cytokines, especially IL-6. Hence, the two closely related rodent species most often employed in toxicological risk characterization studies, rat and mouse, represent opposite examples of the influence of gender on dioxin sensitivity, further complicating the risk assessment of halogenated aromatic hydrocarbons. -- Highlights: ► In contrast to rats, male mice are more sensitive to TCDD toxicity than female mice. ► The resistance of female C57BL/6Kuo mice matches or exceeds that of male DBA/2 mice. ► The resistance of female C57BL/6Kuo mice is not based on AHR structure or abundance. �

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

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

2011-01-01

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

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

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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.

Mechanism of toxicity of MPTP: A cause of Parkinsonism in human beings

International Nuclear Information System (INIS)

Denton, T.L.

1988-01-01

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was found in 1983 to cause a syndrome virtually identical to Parkinson's Disease in humans and other primates. The symptoms, as in idiopathic Parkinson's syndrome, are due to destruction of dopaminergic neurons in the pars compacta of the substantia nigra resulting in depletion of dopamine in the basal ganglia. The mechanism of toxicity was investigated with a dopamine containing cell line, PC12, a MPTP resistant variant (MPTP r ), and synaptosomes from the striate cortex of mice, rats, guinea pigs and a monkey. The mechanism of acute effects was studied with membrane preparations from human and rat striate cortex. MPTP displaced [ 3 H]haloperidol from binding sites in human and rat striate cortex, but could not displace [ 3 H]flupenthixol, suggesting that MPTP is a D2 receptor ligand of equivalent potency in both species. MPTP was a competitive inhibitor of uptake of [ 3 H]dopamine in PC12 but did not accumulate in PC12 or in synaptosomes of rat, guinea pig, mouse or monkey striate cortex. 100 uM MPTP depleted catecholamine levels in PC12 cells by about 50%, without killing

Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge

Science.gov (United States)

Konduru, Krishnamurthy; Shurtleff, Amy C.; Bradfute, Steven B.; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

2016-01-01

Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105−106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge.

Science.gov (United States)

Konduru, Krishnamurthy; Shurtleff, Amy C; Bradfute, Steven B; Nakamura, Siham; Bavari, Sina; Kaplan, Gerardo

2016-01-01

Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105-106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV) pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data further support

Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge.

Directory of Open Access Journals (Sweden)

Krishnamurthy Konduru

Full Text Available Ebola virus (EBOV, a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc protected mice against EBOV lethal challenge. Here, we show that the EBOVgp-Fc vaccine formulated with QS-21, alum, or polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC adjuvants induced strong humoral immune responses in guinea pigs. The vaccinated animals developed anti-GP total antibody titers of approximately 105-106 and neutralizing antibody titers of approximately 103 as assessed by a BSL-2 neutralization assay based on vesicular stomatitis virus (VSV pseudotypes. The poly-ICLC formulated EBOVgp-Fc vaccine protected all the guinea pigs against EBOV lethal challenge performed under BSL-4 conditions whereas the same vaccine formulated with QS-21 or alum only induced partial protection. Vaccination with a mucin-deleted EBOVgp-Fc construct formulated with QS-21 adjuvant did not have a significant effect in anti-GP antibody levels and protection against EBOV lethal challenge compared to the full-length GP construct. The bulk of the humoral response induced by the EBOVgp-Fc vaccine was directed against epitopes outside the EBOV mucin region. Our findings indicate that different adjuvants can eliciting varying levels of protection against lethal EBOV challenge in guinea pigs vaccinated with EBOVgp-Fc, and suggest that levels of total anti-GP antibodies elicit by protein-based GP subunit vaccines do not correlate with protection. Our data

Species and gender differences in the metabolism and distribution of tertiary amyl methyl ether in male and female rats and mice after inhalation exposure or gavage administration.

Science.gov (United States)

Sumner, Susan C J; Janszen, Derek B; Asgharian, Bahman; Moore, Timothy A; Parkinson, Horace D; Fennell, Timothy R

2003-01-01

Tertiary amyl methyl ether (TAME) is a gasoline fuel additive used to reduce emissions. Understanding the metabolism and distribution of TAME is needed to assess potential human health issues. The effect of dose level, duration of exposure and route of administration on the metabolism and distribution of TAME were investigated in male and female F344 rats and CD-1 mice following inhalation or gavage administration. By 48 h after exposure, >96% of the administered radioactivity was expired in air (16-71%) or eliminated in urine and feces (28-72%). Following inhalation exposure, mice had a two- to threefold greater relative uptake of [14C]TAME compared with rats. Metabolites were excreted in urine of rats and mice that are formed by glucuronide conjugation of tertiary amyl alcohol (TAA), oxidation of TAA to 2,3-dihydroxy-2-methylbutane and glucuronide conjugation of 2,3-dihydroxy-2-methylbutane. A saturation in the uptake and metabolism of TAME with increased exposure concentration was indicated by a decreased relative uptake of total [14C]TAME equivalents and an increase in the percentage expired as volatiles. A saturation of P-450 oxidation of TAA was indicated by a disproportional decrease of 2,3-dihydroxy-2-methylbutane and its glucuronide conjugate with increased exposure concentration. Copyright 2003 John Wiley & Sons, Ltd.

Molecular cloning and expression of the IL-10 gene from guinea pigs.

Science.gov (United States)

Dirisala, Vijaya R; Jeevan, Amminikutty; Bix, Gregory; Yoshimura, Teizo; McMurray, David N

2012-04-25

The Guinea pig (Cavia porcellus) is one of the most relevant small animals for modeling human tuberculosis (TB) in terms of susceptibility to low dose aerosol infection, the organization of granulomas, extrapulmonary dissemination and vaccine-induced protection. It is also considered to be a gold standard for a number of other infectious and non-infectious diseases; however, this animal model has a major disadvantage due to the lack of readily available immunological reagents. In the present study, we successfully cloned a cDNA for the critical Th2 cytokine, interleukin-10 (IL-10), from inbred Strain 2 guinea pigs using the DNA sequence information provided by the genome project. The complete open reading frame (ORF) consists of 537 base pairs which encodes a protein of 179 amino acids. This cDNA sequence exhibited 87% homology with human IL-10. Surprisingly, it showed only 84% homology with the previously published IL-10 sequence from the C4-deficient (C4D) guinea pig, leading us to clone IL-10 cDNA from the Hartley strain of guinea pig. The IL-10 gene from the Hartley strain showed 100% homology with the IL-10 sequence of Strain 2 guinea pigs. In order to validate the only published IL-10 sequence existing in Genbank reported from C4D guinea pigs, genomic DNA was isolated from tissues of C4D guinea pigs. Amplification with various sets of primers showed that the IL-10 sequence reported from C4D guinea pigs contained numerous errors. Hence the IL-10 sequence that is being reported by us replaces the earlier sequence making our IL-10 sequence to be the first one accurate from guinea pig. Recombinant guinea pig IL-10 proteins were subsequently expressed in both prokaryotic and eukaryotic cells, purified and were confirmed by N-terminal sequencing. Polyclonal anti-IL-10 antibodies were generated in rabbits using the recombinant IL-10 protein expressed in this study. Taken together, our results indicate that the DNA sequence information provided by the genome project

Heterogeneity of Opioid Binding Sites in Guinea Pig Spinal Cord

Science.gov (United States)

1984-11-30

MEDICAL CENTER WILFORD HALL AIR FORCE MEDICAL CENTER Title of Thesis: "Heterogeneity of Opioid Binding Sites in Guinea Pig Spinal Cord" Name of...that the use of any copyrighted material in the dissertation manuscript entitled: "Heterogeneity of Opioid Binding Sites in Guinea Pig Spinal Cord...University of the Health Sciences 11 Abstract Title of Thesis: Heterogenity of Opioid Binding Sites In Guinea Pig Spinal Cord Gary Dean Zarr MAJ/ANC

Acute cognitive impact of antiseizure drugs in naive rodents and corneal-kindled mice.

Science.gov (United States)

Barker-Haliski, Melissa L; Vanegas, Fabiola; Mau, Matthew J; Underwood, Tristan K; White, H Steve

2016-09-01

Some antiseizure drugs (ASDs) are associated with cognitive liability in patients with epilepsy, thus ASDs without this risk would be preferred. Little comparative pharmacology exists with ASDs in preclinical models of cognition. Few pharmacologic studies exist on the acute effects in rodents with chronic seizures. Predicting risk for cognitive impact with preclinical models may supply valuable ASD differentiation data. ASDs (phenytoin [PHT]; carbamazepine [CBZ]; valproic acid [VPA]; lamotrigine [LTG]; phenobarbital [PB]; tiagabine [TGB]; retigabine [RTG]; topiramate [TPM]; and levetiracetam [LEV]) were administered equivalent to maximal electroshock median effective dose ([ED50]; mice, rats), or median dose necessary to elicit minimal motor impairment (median toxic dose [TD50]; rats). Cognition models with naive adult rodents were novel object/place recognition (NOPR) task with CF-1 mice, and Morris water maze (MWM) with Sprague-Dawley rats. Selected ASDs were also administered to rats prior to testing in an open field. The effect of chronic seizures and ASD administration on cognitive performance in NOPR was also determined with corneal-kindled mice. Mice that did not achieve kindling criterion (partially kindled) were included to examine the effect of electrical stimulation on cognitive performance. Sham-kindled and age-matched mice were also tested. No ASD (ED50) affected latency to locate the MWM platform; TD50 of PB, RTG, TPM, and VPA reduced this latency. In naive mice, CBZ and VPA (ED50) reduced time with the novel object. Of interest, no ASD (ED50) affected performance of fully kindled mice in NOPR, whereas CBZ and LEV improved cognitive performance of partially kindled mice. Standardized approaches to the preclinical evaluation of an ASD's potential cognitive impact are needed to inform drug development. This study demonstrated acute, dose- and model-dependent effects of therapeutically relevant doses of ASDs on cognitive performance of naive mice and

Effect of ghrelin on mortality and cardiovascular outcomes in experimental rat and mice models of heart failure: a systematic review and meta-analysis.

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Mahalaqua Nazli Khatib

Full Text Available Heart failure (HF continues to be a challenging condition in terms of prevention and management of the disease. Studies have demonstrated various cardio-protective effects of Ghrelin. The aim of the study is to determine the effect of Ghrelin on mortality and cardiac function in experimental rats/mice models of HF.Data sources: PUBMED, Scopus. We searched the Digital Dissertations and conference proceedings on Web of Science. Search methods: We systematically searched for all controlled trials (upto November 2014 which assessed the effects of Ghrelin (irrespective of dose, form, frequency, duration and route of administration on mortality and cardiac function in rats/ mice models of HF. Ghrelin administration irrespective of dose, form, frequency, duration and route of administration. Data collection and analysis: Two authors independently assessed each abstract for eligibility and extracted data on characteristics of the experimental model used, intervention and outcome measures. We assessed the methodological quality by SYRCLE's risk of bias tool for all studies and the quality of evidence by GRADEpro. We performed meta-analysis using RevMan 5.3.A total of 325 animals (rats and mice were analyzed across seven studies. The meta-analysis revealed that the mortality in Ghrelin group was 31.1% and in control group was 40% (RR 0.83, 95% CI 0.46 to 1.47 i.e Ghrelin group had 68 fewer deaths per 1000 (from 216 fewer to 188 more as compared to the control group. The meta-analysis reveals that the heart rate in rats/mice on Ghrelin was higher (MD 13.11, 95% CI 1.14 to 25.08, P=0.66 while the mean arterial blood pressure (MD -1.38, 95% CI -5.16 to 2.41, P=0.48 and left ventricular end diastolic pressure (MD -2.45, 95% CI -4.46 to -0.43, P=0.02 were lower as compared to the those on placebo. There were insignificant changes in cardiac output (SMD 0.28, 95% CI -0.24 to 0.80, P=0.29 and left ventricular end systolic pressure (MD 1.48, 95% CI -3.86 to 6

Infecção via oral por Trypanosoma evansi em animais de laboratório Oral infection by Trypanosoma evansi in rats and mice

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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

Arrangement of Renal Arteries in Guinea Pig.

Science.gov (United States)

Mazensky, David; Flesarova, Slavka

2017-03-01

The aim of this study was to describe origin, localization, and variations of renal arteries in guinea pig. The study was carried out on 26 adult guinea pigs. We prepared corrosion casts of the guinea pig arterial system. Batson's corrosion casting kit no. 17 was used as the casting medium. In 57.7% of specimens, a. renalis dextra was present as a single vessel with different level of its origin from aorta abdominalis. In 38.5% of specimens, two aa. renales dextrae were present with variable origin and arrangement. The presence of three aa. renales dextrae we found in one specimen. In 76.9% of specimens, a. renalis sinistra was present as a single vessel with different level of its origin from aorta abdominalis and variable arrangement. In 23.1% of specimens, we found two aa. renales sinistrae with variable origin and arrangement. The anatomical knowledge of the renal arteries, and its variations are of extreme importance for the surgeon that approaches the retroperitoneal region in several experiments, results of which are extrapolated in human. This is the first work dealing with the description of renal arteries arrangement in guinea pig. Anat Rec, 300:556-559, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Comparison of Human and Guinea Pig Acetylcholinesterase Sequences and Rates of Oxime-Assisted Reactivation

Science.gov (United States)

2010-01-01

of appropriate animal model systems. For OP poisoning, the guinea pig (Cavia porcellus) is a commonly used animal model because guinea pigs more...endogenous bioscavenger in vivo. Although guinea pigs historically have been used to test OP poisoning therapies, it has been found recently that guinea pig AChE...transcribed mRNA encoding guinea pig AChE, amplified the resulting cDNA, and sequenced this product. The nucleotide and deduced amino acid sequences of

NTP Toxicology and Carcinogenesis Studies of Barium Chloride Dihydrate (CAS No. 10326-27-9) in F344/N Rats and B6C3F1 Mice (Drinking Water Studies).

Science.gov (United States)

1994-01-01

Barium chloride dihydrate, a white crystalline granule or powder, is used in pigments, aluminum refining, leather tanning and coloring, the manufacture of magnesium metal, ceramics, glass, and paper products, as a pesticide, and in medicine as a cardiac stimulant. Toxicology and carcinogenicity studies were conducted by administering barium chloride dihydrate (99% pure) in drinking water to F344/N rats and B6C3F1 mice for 15 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse lymphoma cells. 15-DAY STUDY IN RATS: Groups of five males and five females received barium chloride dihydrate in the drinking water at concentrations of 0, 125, 250, 500, 1,000, or 2,000 ppm for 15 days, corresponding to average daily doses of 10, 15, 35, 60, or 110 mg barium/kg body weight to males and females. No chemical-related deaths, differences in final mean body weights, or clinical findings of toxicity were observed. Water consumption by male and female rats exposed to 2,000 ppm was slightly less (S16%) than controls during week 2. There were no significant differences in absolute or relative organ weights between exposed and control rats. No biologically significant differences in hematology, clinical chemistry, or neurobehavioral parameters occurred in rats. 15-DAY STUDY IN MICE: Groups of five males and five females received barium chloride dihydrate in the drinking water at concentrations of 0, 40, 80,173, 346, or 692 ppm for 15 days, corresponding to average daily doses of 5,10, 20, 40, or 70 mg barium/kg body weight to males and 5, 10, 15, 40, or 85 mg barium/kg body weight to females. No chemical-related deaths, differences in mean body weights or in water consumption, or clinical findings of toxicity were observed in mice. The relative liver weight of males receiving 692 ppm was significantly greater than that of the controls. The absolute and relative liver weights of females that

The innate immunity of guinea pigs against highly pathogenic avian influenza virus infection.

Science.gov (United States)

Zhang, Kun; Xu, Wei Wei; Zhang, Zhaowei; Liu, Jing; Li, Jing; Sun, Lijuan; Sun, Weiyang; Jiao, Peirong; Sang, Xiaoyu; Ren, Zhiguang; Yu, Zhijun; Li, Yuanguo; Feng, Na; Wang, Tiecheng; Wang, Hualei; Yang, Songtao; Zhao, Yongkun; Zhang, Xuemei; Wilker, Peter R; Liu, WenJun; Liao, Ming; Chen, Hualan; Gao, Yuwei; Xia, Xianzhu

2017-05-02

H5N1 avian influenza viruses are a major pandemic concern. In contrast to the highly virulent phenotype of H5N1 in humans and many animal models, guinea pigs do not typically display signs of severe disease in response to H5N1 virus infection. Here, proteomic and transcriptional profiling were applied to identify host factors that account for the observed attenuation of A/Tiger/Harbin/01/2002 (H5N1) virulence in guinea pigs. RIG-I and numerous interferon stimulated genes were among host proteins with altered expression in guinea pig lungs during H5N1 infection. Overexpression of RIG-I or the RIG-I adaptor protein MAVS in guinea pig cell lines inhibited H5N1 replication. Endogenous GBP-1 expression was required for RIG-I mediated inhibition of viral replication upstream of the activity of MAVS. Furthermore, we show that guinea pig complement is involved in viral clearance, the regulation of inflammation, and cellular apoptosis during influenza virus infection of guinea pigs. This work uncovers features of the guinea pig innate immune response to influenza that may render guinea pigs resistant to highly pathogenic influenza viruses.

Animal metabolism

International Nuclear Information System (INIS)

Walburg, H.E.

1977-01-01

Studies on placental transport included the following: clearance of tritiated water as a baseline measurement for transport of materials across perfused placentas; transport of organic and inorganic mercury across the perfused placenta of the guinea pig in late gestation; and transport of cadmium across the perfused placenta of the guinea pig in late gestation. Studies on cadmium absorption and metabolism included the following: intestinal absorption and retention of cadmium in neonatal rats; uptake and distribution of an oral dose of cadmium in postweanling male and female, iron-deficient and normal rats; postnatal viability and growth in rat pups after oral cadmium administration during gestation; and the effect of calcium and phosphorus on the absorption and toxicity of cadmium. Studies on gastrointestinal absorption and mineral metabolism included: uptake and distribution of orally administered plutonium complex compounds in male mice; gastrointestinal absorption of 144 Ce in the newborn mouse, rat, and pig; and gastrointestinal absorption of 95 Nb by rats of different ages. Studies on iodine metabolism included the following: influence of thyroid status and thiocyanate on iodine metabolism in the bovine; effects of simulated fallout radiation on iodine metabolism in dairy cattle; and effects of feeding iodine binding agents on iodine metabolism in the calf

A First Generation Comparative Chromosome Map between Guinea Pig (Cavia porcellus) and Humans.

Science.gov (United States)

Romanenko, Svetlana A; Perelman, Polina L; Trifonov, Vladimir A; Serdyukova, Natalia A; Li, Tangliang; Fu, Beiyuan; O'Brien, Patricia C M; Ng, Bee L; Nie, Wenhui; Liehr, Thomas; Stanyon, Roscoe; Graphodatsky, Alexander S; Yang, Fengtang

2015-01-01

The domesticated guinea pig, Cavia porcellus (Hystricomorpha, Rodentia), is an important laboratory species and a model for a number of human diseases. Nevertheless, genomic tools for this species are lacking; even its karyotype is poorly characterized. The guinea pig belongs to Hystricomorpha, a widespread and important group of rodents; so far the chromosomes of guinea pigs have not been compared with that of other hystricomorph species or with any other mammals. We generated full sets of chromosome-specific painting probes for the guinea pig by flow sorting and microdissection, and for the first time, mapped the chromosomal homologies between guinea pig and human by reciprocal chromosome painting. Our data demonstrate that the guinea pig karyotype has undergone extensive rearrangements: 78 synteny-conserved human autosomal segments were delimited in the guinea pig genome. The high rate of genome evolution in the guinea pig may explain why the HSA7/16 and HSA16/19 associations presumed ancestral for eutherians and the three syntenic associations (HSA1/10, 3/19, and 9/11) considered ancestral for rodents were not found in C. porcellus. The comparative chromosome map presented here is a starting point for further development of physical and genetic maps of the guinea pig as well as an aid for genome assembly assignment to specific chromosomes. Furthermore, the comparative mapping will allow a transfer of gene map data from other species. The probes developed here provide a genomic toolkit, which will make the guinea pig a key species to unravel the evolutionary biology of the Hystricomorph rodents.

A guinea pig model of Zika virus infection.

Science.gov (United States)

Kumar, Mukesh; Krause, Keeton K; Azouz, Francine; Nakano, Eileen; Nerurkar, Vivek R

2017-04-11

Animal models are critical to understand disease and to develop countermeasures for the ongoing epidemic of Zika virus (ZIKV). Here we report that immunocompetent guinea pigs are susceptible to infection by a contemporary American strain of ZIKV. Dunkin-Hartley guinea pigs were inoculated with 10 6 plaque-forming units of ZIKV via subcutaneous route and clinical signs were observed. Viremia, viral load in the tissues, anti-ZIKV neutralizing antibody titer, and protein levels of multiple cytokine and chemokines were analyzed using qRT-PCR, plaque assay, plaque reduction neutralization test (PRNT) and multiplex immunoassay. Upon subcutaneous inoculation with PRVABC59 strain of ZIKV, guinea pigs demonstrated clinical signs of infection characterized by fever, lethargy, hunched back, ruffled fur, and decrease in mobility. ZIKV was detected in the whole blood and serum using qRT-PCR and plaque assay. Anti-ZIKV neutralizing antibody was detected in the infected animals using PRNT. ZIKV infection resulted in a dramatic increase in protein levels of multiple cytokines, chemokines and growth factors in the serum. ZIKV replication was observed in spleen and brain, with the highest viral load in the brain. This data demonstrate that after subcutaneous inoculation, the contemporary ZIKV strain is neurotropic in guinea pigs. The guinea pig model described here recapitulates various clinical features and viral kinetics observed in ZIKV-infected patients, and therefore may serve as a model to study ZIKV pathogenesis, including pregnancy outcomes and for evaluation of vaccines and therapeutics.

Cartilage Degeneration, Subchondral Mineral and Meniscal Mineral Densities in Hartley and Strain 13 Guinea Pigs

Science.gov (United States)

Sun, Yubo; Scannell, Brian P; Honeycutt, Patrick R; Mauerhan, David R; H, James Norton; Hanley Jr, Edward N

2015-01-01

Osteoarthritis is a joint disease involved in articular cartilage, subchondral bone, meniscus and synovial membrane. This study sought to examine cartilage degeneration, subchondral bone mineral density (BMD) and meniscal mineral density (MD) in male Hartley, female Hartley and female strain 13 guinea pigs to determine the association of cartilage degeneration with subchondral BMD and meniscal MD. Cartilage degeneration, subchondral BMD and meniscal MD in 12 months old guinea pigs were examined with histochemistry, X-ray densitometry and calcium analysis. We found that male Hartley guinea pigs had more severe cartilage degeneration, subchondral BMD and meniscal MD than female Hartley guinea pigs, but not female strain 13 guinea pigs. Female strain 13 guinea pigs had more severe cartilage degeneration and higher subchondral BMD, but not meniscal MD, than female Hartley guinea pigs. These findings indicate that higher subchondral BMD, not meniscal MD, is associated with more severe cartilage degeneration in the guinea pigs and suggest that abnormal subchondral BMD may be a therapeutic target for OA treatment. These findings also indicate that the pathogenesis of OA in the male guinea pigs and female guinea pigs are different. Female strain 13 guinea pig may be used to study female gender-specific pathogenesis of OA. PMID:26401159

Prevalence of fur mites (Chirodiscoides caviae) in pet guinea pigs (Cavia porcellus) in southern Italy.

Science.gov (United States)

d'Ovidio, Dario; Santoro, Domenico

2014-04-01

Chirodiscoides caviae is the most common fur mite affecting guinea pigs; infestation is generally asymptomatic. No studies have been published on the prevalence of such mites in guinea pigs in southern Italy. We sought to evaluate the prevalence and the clinical signs of C. caviae infestation in guinea pigs in southern Italy. Clinical records of guinea pigs evaluated from August 2012 to July 2013 were retrospectively searched. In this retrospective matched case-control study, records of guinea pigs with evidence of C. caviae infestation were selected. The prevalence of C. caviae infestation was evaluated and exposure variables were assessed among guinea pigs with and without infestation using stepwise conditional logistic regression. Guinea pigs seen during the same time period, but without a diagnosis of C. caviae, were included as control animals. The prevalence of C. caviae was 32% (42 of 131); 66.6% of affected guinea pigs (28 of 42) originated from pet shops, whereas 28% (14 of 42) were privately owned. Thirty-one guinea pigs (73.8%) were asymptomatic, whereas 11 (26.1%) showed clinical signs (pruritus, alopecia, erythema and scaling). The most frequently affected area was the lumbosacral region (38 of 42). Guinea pigs in pet shops were more likely to be affected by C. caviae than owned guinea pigs (odds ratio, 5.12; 95% confidence interval, 2.32-11.29; P guinea pigs in southern Italy. Chirodiscoides mites should be sought in guinea pigs, particularly in animals coming from pet shops. © 2014 ESVD and ACVD.

(+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate (SNI-2011, cevimeline hydrochloride) induces saliva and tear secretions in rats and mice: the role of muscarinic acetylcholine receptors.

Science.gov (United States)

Iga, Y; Arisawa, H; Ogane, N; Saito, Y; Tomizuka, T; Nakagawa-Yagi, Y; Masunaga, H; Yasuda, H; Miyata, N

1998-11-01

We investigated effects of (+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate (SNI-2011, cevimeline hydrochloride), a rigid analogue of acetylcholine, on saliva and tear secretions in rats and mice to evaluate its therapeutical efficacy for xerostomia and xerophthalmia in patients with Sjogren's syndrome and X-ray exposure in the head and neck. Intraduodenal administrations of SNI-2011 increased saliva secretion in a dose-dependent manner at doses ranging from 3 to 30 mg/kg in normal rats and mice, two strains of autoimmune disease mice and X-irradiated saliva secretion defective rats. The salivation elicited by SNI-2011 was completely inhibited by atropine. A similar atropine-sensitive response was observed in tear secretion. In rat submandibular/sublingual gland membranes, [3H]quinuclidinyl benzilate (QNB) binding was saturable, and Scatchard plot analysis revealed a single population of binding sites with a Kd of 22 pM and a maximal binding capacity of 60 fmol/mg protein. The competitive inhibition curve of the [3H]QNB binding by SNI-2011 was obtained, and its dissociation constant value calculated from IC50 was 1-2 microM. These results suggest that SNI-2011 increases saliva and tear secretions through a direct stimulation to muscarinic receptors in salivary and lacrimal glands, and they suggest that SNI-2011 should be beneficial to patients with Sjögren's syndrome and X-ray exposure in the head and neck.

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.

Temperature Preference in IAF Hairless and Hartley Guinea Pigs (Cavia porcellus).

Science.gov (United States)

Kleven, Gale A; Joshi, Prianca

2016-03-01

The Hairless strain of guinea pigs (Cavia porcellus) is the result of a spontaneous recessive mutation first identified at the Institute Armand Frappier (IAF) in 1978. Despite the longstanding availability of this strain, little is known about its thermoregulatory behavior. The aim of this study was to determine temperature preference in Hartley and Hairless guinea pigs by observing each strain in a ring-shaped apparatus containing a nonlinear temperature gradient. Temperatures were maintained by separately controlled heating mats lining the apparatus. Set point temperatures ranged from 24 to 38 °C. Guinea pigs (Hartley female, Hairless female, and Hairless male guinea pigs; n = 8 each group) were placed either singly or in pairs at 1 of the 8 randomized starting points within the apparatus. Subjects were observed for 30 min and coded for location within the temperature gradient by both frequency and duration. When placed singly in the apparatus, all 3 groups spent more time in the 30 °C zones. However, when placed as pairs with a cagemate, Hartley female guinea pigs spent more time in the cooler range of temperatures from 24 to 30 °C, whereas Hairless guinea pigs preferred a range of 30 to 38 °C. These results confirm a temperature preference of 30 ± 2 °C for both Hartley and Hairless guinea pigs when singly housed. However, data from the paired housing condition suggest that context plays an important role in thermoregulatory behavior.

Clinical signs, therapy and zoonotic risk of pet guinea pigs with dermatophytosis.

Science.gov (United States)

Kraemer, A; Hein, J; Heusinger, A; Mueller, R S

2013-03-01

Systematic studies about pet guinea pigs with dermatophytosis are rare. The aim of this study was to evaluate clinical signs, therapy and zoonotic risk of pet guinea pigs with dermatophytosis. Questionnaires from both owners (n = 74) of pet guinea pigs with dermatophytosis and their veterinarians (n = 101) were analysed regarding clinical signs, therapy and data pertinent to zoonotic potential. Trichophyton (T.) mentagrophytes was found in 97% of cases. In the weeks preceding the onset of the clinical signs, a new guinea pig joined the household in 43% of cases. One third of the affected guinea pigs had lived in the household for less than 3 months. Predominant clinical signs were alopecia (83%), scaling (73%) and crusting (70%). The most commonly affected body site was the head (75%). In approximately one quarter of the cases humans showed clinical signs of dermatophytosis, in half the households, only children were affected. Skin lesions were seen most often on the face, the neck and the arms. Pet guinea pigs carrying dermatophytes must be considered a serious zoonotic risk for their owners, especially for children. A major risk factor for dermatophytosis seems to be a recent acquisition of a new guinea pig. © 2012 Blackwell Verlag GmbH.

On the western fringe of baboon distribution: mitochondrial D-loop diversity of Guinea Baboons (Papio papio Desmarest, 1820 (Primates: Cercopithecidae in Coastal Guinea-Bissau, western Africa

Directory of Open Access Journals (Sweden)

M.J. Ferreira da Silva

2013-06-01

Full Text Available Like many primate species in West Africa, habitat loss and intensive hunting are threatening the poorly studied Guinea Baboon (Papio papio. These factors contributed to a significant population contraction during the last 30 years. Our study presents genetic diversity estimates for the Guinea Baboon based on a 391 base pair fragment of the mitochondrial DNA D-loop hypervariable region I. We used non-invasively collected genetic samples from two locations in Guinea-Bissau: Cufada Lagoons Natural Park and Cantanhez Forest National Park. Although most sampling was opportunistic, we observed and collected samples from two dames (social units. Among the 25 sequences obtained, we found seven closely related mtDNA haplotypes and one highly different haplotype. The presence of this divergent haplotype suggests a contact area between genetically differentiated populations in Cufada Lagoons Natural Park, or dispersal of individuals. The samples gathered from both regions share two of the most common haplotypes in different frequencies, but also exhibit unique haplotypes. No significant genetic differentiation was found between social units from both regions, possibly due to common ancestral origin or frequent dispersal between sampling locations. The presence of different maternal lineages in the same social unit and a higher percentage of variation within social units suggest historical female-biased dispersal for Guinea-Bissau Baboons. We further compared mitochondrial genetic diversity of Guinea and Hamadryas Baboons. We found lower haplotype, nucleotide and theta diversity for Guinea Baboons, which points to different demographic histories of these species. This work supports the need for additional genetic studies within the full Guinea Baboon range.

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.

Damage of guinea pig heart and arteries by a trioleate-enriched diet and of cultured cardiomyocytes by oleic acid.

Directory of Open Access Journals (Sweden)

Josef Krieglstein

2010-03-01

Full Text Available Mono-unsaturated fatty acids (MUFAs like oleic acid have been shown to cause apoptosis of cultured endothelial cells by activating protein phosphatase type 2C alpha and beta (PP2C. The question arises whether damage of endothelial or other cells could be observed in intact animals fed with a trioleate-enriched diet.Dunkin-Hartley guinea pigs were fed with a trioleate-enriched diet for 5 months. Advanced atherosclerotic changes of the aorta and the coronary arteries could not be seen but the arteries appeared in a pre-atherosclerotic stage of vascular remodelling. However, the weight and size of the hearts were lower than in controls and the number of apoptotic myocytes increased in the hearts of trioleate-fed animals. To confirm the idea that oleic acid may have caused this apoptosis by activation of PP2C, cultured cardiomyocytes from guinea pigs and mice were treated with various lipids. It was demonstrable that oleic acid dose-dependently caused apoptosis of cardiomyocytes from both species, yet, similar to previous experiments with cultured neurons and endothelial cells, stearic acid, elaidic acid and oleic acid methylester did not. The apoptotic effect caused by oleic acid was diminished when PP2C alpha and beta were downregulated by siRNA showing that PP2C was causally involved in apoptosis caused by oleic acid.The glycerol trioleate diet given to guinea pigs for 5 months did not cause marked atherosclerosis but clearly damaged the hearts by activating PP2C alpha and beta. The diet used with 24% (wt/wt glycerol trioleate is not comparable to human diets. The detrimental role of MUFAs for guinea pig heart tissue in vivo is shown for the first time. Whether it is true for humans remains to be shown.

Identification of rat Rosa26 locus enables generation of knock-in rat lines ubiquitously expressing tdTomato.

Science.gov (United States)

Kobayashi, Toshihiro; Kato-Itoh, Megumi; Yamaguchi, Tomoyuki; Tamura, Chihiro; Sanbo, Makoto; Hirabayashi, Masumi; Nakauchi, Hiromitsu

2012-11-01

Recent discovery of a method for derivation and culture of germline-competent rat pluripotent stem cells (PSCs) enables generation of transgenic rats or knock-out rats via genetic modification of such PSCs. This opens the way to use rats, as is routine in mice, for analyses of gene functions or physiological features. In mouse or human, one widely used technique to express a gene of interest stably and ubiquitously is to insert that gene into the Rosa26 locus via gene targeting of PSCs. Rosa26 knock-in mice conditionally expressing a reporter or a toxin gene have contributed to tracing or ablation of specific cell lineages. We successfully identified a rat orthologue of the mouse Rosa26 locus. Insertion of tdTomato, a variant of red fluorescent protein, into the Rosa26 locus of PSCs of various rat strains allows ubiquitous expression of tdTomato. Through germline transmission of one Rosa26-tdTomato knock-in embryonic stem cell line, we also obtained tdTomato knock-in rats. These expressed tdTomato ubiquitously throughout their bodies, which indicates that the rat Rosa26 locus conserves functions of its orthologues in mouse and human. The new tools described here (targeting vectors, knock-in PSCs, and rats) should be useful for a variety of research using rats.

Towards global Guinea worm eradication in 2015: the experience of South Sudan.

Science.gov (United States)

Awofeso, Niyi

2013-08-01

For centuries, the Guinea worm parasite (Dracunculus medinensis) has caused disabling misery, infecting people who drink stagnant water contaminated with the worm's larvae. In 2012, there were 542 cases of Guinea worm reported globally, of which 521 (96.1%) were reported in South Sudan. Protracted civil wars, an inadequate workforce, neglect of potable water provision programs, suboptimal Guinea worm surveillance and case containment, and fragmented health systems account for many of the structural and operational factors encumbering South Sudan's Guinea worm eradication efforts. This article reviews the impacts of six established Guinea worm control strategies in South Sudan: (1) surveillance to determine actual caseload distribution and trends in response to control measures; (2) educating community members from whom worms are emerging to avoid immersing affected parts in sources of drinking water; (3) filtering potentially contaminated drinking water using cloth filters or filtered drinking straws; (4) treating potentially contaminated surface water with the copepod larvicide temephos (Abate); (5) providing safe drinking water from boreholes or hand-dug wells; and (6) containment of transmission through voluntary isolation of each patient to prevent contamination of drinking water sources, provision of first aid, and manual extraction of the worm. Surveillance, community education, potable water provision, and case containment remain weak facets of the program. Abate pesticide is not a viable option for Guinea worm control in South Sudan. In light of current case detection and containment trends, as well as capacity building efforts for Guinea worm eradication, South Sudan is more likely to eradicate Guinea worm by 2020, rather than by 2015. The author highlights areas in which substantial improvements are required in South Sudan's Guinea worm eradication program, and suggests improvement strategies. Copyright © 2013 International Society for Infectious

Family Outbreaks of Nontyphoidal Salmonellosis following a Meal of Guinea Pigs.

Science.gov (United States)

Fournier, John B; Knox, Kimberly; Harris, Maureen; Newstein, Michael

2015-01-01

Salmonella outbreaks have been linked to a wide variety of foods, including recent nationwide outbreaks. Guinea pig (Cavia porcellus), also known as cuy or cobayo, has long been a popular delicacy and ceremonial food in the Andean region in South America. This case report describes three family outbreaks of nontyphoidal salmonellosis, each occurring after a meal of guinea pigs. We believe this case report is the first to describe a probable association between the consumption of guinea pig meat and human salmonellosis. Physicians should be aware of the association of Salmonella and the consumption of guinea pigs, given the increasing immigration of people from the Andean region of South America and the increasing travel to this region.

Epidemiological evidence of listeriosis in guinea pigs fed with ...

African Journals Online (AJOL)

Listeria monocytogenes is a bacterium that infects livestock and humans. We report the first outbreak of invasive listeriosis caused by L. monocytogenes in a guinea pig breeding colony. Eighty to 100% mortality rate was recorded in the colony of 80 guinea pigs within four weeks outbreak. On epidemiologic investigation ...

The Guinea Pigs of a Problem-Based Learning Curriculum

Science.gov (United States)

Reddy, Sarasvathie; McKenna, Sioux

2016-01-01

Participants in a study on learning the clinical aspects of medicine in a problem-based learning (PBL) curriculum repeatedly referred to themselves as "Guinea pigs" at the mercy of a curriculum experiment. This article interrogates and problematises the "Guinea pig" identity ascribed to and assumed by the first cohort of…

Spleens and holoendemic malaria in West New Guinea.

Science.gov (United States)

METSELAAR, D

1956-01-01

The author describes the results obtained in recent malaria surveys in West New Guinea, where what is essentially holoendemic malaria prevails. However, the spleen-rate in adults differs markedly from what is regarded as normal under holoendemic conditions according to the definition put forward at the Malaria Conference in Equatorial Africa in 1950. The author therefore concludes that that definition is not properly applicable to New Guinea.

Guinea pig maximization test

DEFF Research Database (Denmark)

Andersen, Klaus Ejner

1985-01-01

Guinea pig maximization tests (GPMT) with chlorocresol were performed to ascertain whether the sensitization rate was affected by minor changes in the Freund's complete adjuvant (FCA) emulsion used. Three types of emulsion were evaluated: the oil phase was mixed with propylene glycol, saline...

Inner ear test battery in guinea pig models - a review.

Science.gov (United States)

Young, Yi-Ho

2018-06-01

This study reviewed the development of the inner ear test battery comprising auditory brainstem response (ABR), and caloric, ocular vestibular-evoked myogenic potential (oVEMP), and cervical vestibular-evoked myogenic potential (cVEMP) tests in guinea pig models at our laboratory over the last 20 years. Detailed description of the methodology for testing the small animals is also included. Inner ear disorders, i.e. ototoxicity, noise exposure, or perilymph fistula were established in guinea pig models first. One to four weeks after operation, each animal underwent ABR, oVEMP, cVEMP, and caloric tests. Then, animals were sacrificed for morphological study in the temporal bones. Inner ear endorgans can be comprehensively evaluated in guinea pig models via an inner ear test battery, which provides thorough information on the cochlea, saccule, utricle, and semicircular canal function of guinea pigs. Coupled with morphological study in the temporal bones of the animals may help elucidate the mechanism of inner ear disorders in humans. The inner ear test battery in guinea pig models may encourage young researchers to perform basic study in animals and stimulate the progress of experimental otology which is in evolution.

Immunogenicity of guinea pig cells transformed in culture by chemical carcinogens.

Science.gov (United States)

Ohanian, S H; McCabe, R P; Evans, C H

1981-12-01

The immunogenicity of inbred strain 2/N guinea pig fibroblasts transformed to the malignant state in vitro by chemical carcinogens was evaluated with the use of a variety of in vivo and in vitro methods including delayed-type hypersensitivity skin and tumor transplantation tests and analysis of antibody production by immunofluorescence, complement fixation, and staphylococcal protein A binding tests. Neoplastic transformation was induced by direct treatment of cells in culture with benzo[a]pyrene, 3-methylcholanthrene, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or by the host-mediated method by which fetuses were exposed to diethylnitrosamine or MNNG in vivo prior to cell culture. Rabbits and syngeneic guinea pigs were inoculated with unirradiated and X-irradiated clonally derived cells. Delayed hypersensitivity skin reactions to immunizing or other cells were equivalent in immunized or control guinea pigs, and no protection to tumor outgrowth from a challenge inoculum of immunizing cells was observed. Antibody activity induced in the sera of immunized guinea pigs was cross-reactive and removed by absorption with nontumorigenic cells. Rabbit antisera after absorption with fetal guinea pig cells were nonreactive with the specific immunizing or other culture cells. Chemical carcinogen-induced neoplastic transformation of guinea pig cells can, therefore, occur without formation of detectable, individually distinct cell surface tumor-specific neoantigens.

Immunogenicity of guinea pig cells transformed in culture by chemical carcinogens

International Nuclear Information System (INIS)

Ohanian, S.H.; McCabe, R.P.; Evans, C.H.

1981-01-01

The immunogenicity of inbred strain 2/N guinea pig fibroblasts transformed to the malignant state in vitro by chemical carcinogens was evaluated with the use of a variety of in vivo and in vitro methods including delayed-type hypersensitivity skin and tumor transplantation tests and analysis of antibody production by immunofluorescence, complement fixation, and staphylococcal protein A binding tests. Neoplastic transformation was induced by direct treatment of cells in culture with benzo[a]pyrene, 3-methylcholanthrene, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or by the host-mediated method by which fetuses were exposed to diethylnitrosamine or MNNG in vivo prior to cell culture. Rabbits and syngeneic guinea pigs were inoculated with unirradiated and X-irradiated clonally derived cells. Delayed hypersensitivity skin reactions to immunizing or other cells were equivalent in immunized or control guinea pigs, and no protection to tumor outgrowth from a challenge inoculum of immunizing cells was observed. Antibody activity induced in the sera of immunized guinea pigs was cross-reactive and removed by absorption with nontumorigenic cells. Rabbit anitsera after absorption with fetal guinea pig cells were nonreactive with the specific immunizing or other cultured cells. Chemical carcinogen-induced neoplastic transformation of guinea pig cells can, therefore, occur without formation of detectable, individually distinct cell surface tumor-specific neoantigens

Natural infection of guinea pigs exposed to patients with highly drug-resistant tuberculosis

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Dharmadhikari, Ashwin S.; Basaraba, Randall J.; Van Der Walt, Martie L.; Weyer, Karin; Mphahlele, Matsie; Venter, Kobus; Jensen, Paul A.; First, Melvin W.; Parsons, Sydney; McMurray, David N.; Orme, Ian M.; Nardell, Edward A.

2012-01-01

A natural TB infection model using guinea pigs may provide useful information for investigating differences in transmission efficiency and establishment of active disease by clinical TB strains in a highly susceptible host under controlled environmental conditions. We sought to examine the capacity of naturally transmitted multidrug-resistant M. tuberculosis to establish infection and produce active disease in guinea pigs. Guinea pigs were continuously exposed for 4 months to the exhaust air of a 6-bed multidrug-resistant tuberculosis inpatient hospital ward in South Africa. Serial tuberculin skin test reactions were measured to determine infection. All animals were subsequently evaluated for histologic disease progression at necropsy. Although 75% of the 362 exposed guinea pigs had positive skin test reactions [≥6mm], only 12% had histopathologic evidence of active disease. Reversions (≥ 6 mm change) in skin test reactivity were seen in 22% of animals, exclusively among those with reactions of 6 to 13 mm. Only two of 86 guinea pigs with reversion had histological evidence of disease compared to 47% (31/66) of guinea pigs with large, non-reverting reactions. Immunosuppression of half the guinea pigs across all skin test categories did not significantly accelerate disease progression. In guinea pigs that reverted a skin test, a second positive reaction in 27 (33%) of them strongly suggested re-infection due to ongoing exposure. These results show that a large majority of guinea pigs naturally exposed to human-source strains of multidrug-resistant tuberculosis became infected, but that many resolved their infection and a large majority failed to progress to detectable disease. PMID:21478054

Guinea pig Ia antigens are not derivatised on trinitrophenyl-modified cells

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Clement, L T; Thomas, D W; Kask, A M; Shevach, E M [National Inst. of Allergy and Infectious Diseases, Bethesda, MD (USA)

1978-08-10

In an effort to clarify the nature of the trinitrophenyl (TNP) specific immunogen recognised by hapten-reactive guinea pig T lymphocytes, the membrane proteins of TNP-modified guinea pig macrophages have been analysed by chemical methods using nitrobenzene sulphonic acid surface labelled with /sup 125/I. The experiments provided strong evidence that the TNP specific immunogen which T lymphocytes recognise on guinea pig macrophages does not consist of directly haptenated Ia antigens.

Guinea pig complement potently measures vibriocidal activity of human antibodies in response to cholera vaccines.

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Kim, Kyoung Whun; Jeong, Soyoung; Ahn, Ki Bum; Yang, Jae Seung; Yun, Cheol-Heui; Han, Seung Hyun

2017-12-01

The vibriocidal assay using guinea pig complement is widely used for the evaluation of immune responses to cholera vaccines in human clinical trials. However, it is unclear why guinea pig complement has been used over human complement in the measurement of vibriocidal activity of human sera and there have not been comparison studies for the use of guinea pig complement over those from other species. Therefore, we comparatively investigated the effects of complements derived from human, guinea pig, rabbit, and sheep on vibriocidal activity. Complements from guinea pig, rabbit, and human showed concentration-dependent vibriocidal activity in the presence of quality control serum antibodies. Of these complements, guinea pig complement was the most sensitive and effective over a wide concentration range. When the vibriocidal activity of complements was measured in the absence of serum antibodies, human, sheep, and guinea pig complements showed vibriocidal activity up to 40-fold, 20-fold, and 1-fold dilution, respectively. For human pre- and post-vaccination sera, the most potent vibriocidal activity was observed when guinea pig complement was used. In addition, the highest fold-increases between pre- and post- vaccinated sera were obtained with guinea pig complement. Furthermore, human complement contained a higher amount of V. cholerae- and its lipopolysaccharide-specific antibodies than guinea pig complement. Collectively, these results suggest that guinea pig complements are suitable for vibriocidal assays due to their high sensitivity and effectiveness to human sera.

Molecular cloning, expression, and in silico structural analysis of guinea pig IL-17.

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Dirisala, Vijaya R; Jeevan, Amminikutty; Ramasamy, Suresh K; McMurray, David N

2013-11-01

Interleukin-17A (IL-17A) is a potent proinflammatory cytokine and the signature cytokine of Th17 cells, a subset which is involved in cytokine and chemokine production, neutrophil recruitment, promotion of T cell priming, and antibody production. IL-17 may play an important role in tuberculosis and other infectious diseases. In preparation for investigating its role in the highly relevant guinea pig model of pulmonary tuberculosis, we cloned guinea pig IL-17A for the first time. The complete coding sequence of the guinea pig IL-17A gene (477 nucleotides; 159 amino acids) was subcloned into a prokaryotic expression vector (pET-30a) resulting in the expression of a 17 kDa recombinant guinea pig IL-17A protein which was confirmed by mass spectrometry analysis. Homology modeling of guinea pig IL-17A revealed that the three-dimensional structure resembles that of human IL-17A. The secondary structure predicted for this protein showed the presence of one extra helix in the N-terminal region. The expression profile of IL-17A was analyzed quantitatively in spleen, lymph node, and lung cells from BCG-vaccinated guinea pigs by real-time PCR. The guinea pig IL-17A cDNA and its recombinant protein will serve as valuable tools for molecular and immunological studies in the guinea pig model of pulmonary TB and other human diseases.

Gastroesophageal reflux leads to esophageal cancer in a surgical model with mice

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Chen Xiaoxin

2009-07-01

Full Text Available Abstract Background Esophago-gastroduodenal anastomosis with rats mimics the development of human Barrett's esophagus and esophageal adenocarcinoma by introducing mixed reflux of gastric and duodenal contents into the esophagus. However, use of this rat model for mechanistic and chemopreventive studies is limited due to lack of genetically modified rat strains. Therefore, a mouse model of esophageal adenocarcinoma is needed. Methods We performed reflux surgery on wild-type, p53A135V transgenic, and INK4a/Arf+/- mice of A/J strain. Some mice were also treated with omeprazole (1,400 ppm in diet, iron (50 mg/kg/m, i.p., or gastrectomy plus iron. Mouse esophagi were harvested at 20, 40 or 80 weeks after surgery for histopathological analysis. Results At week 20, we observed metaplasia in wild-type mice (5%, 1/20 and p53A135V mice (5.3%, 1/19. At week 40, metaplasia was found in wild-type mice (16.2%, 6/37, p53A135V mice (4.8%, 2/42, and wild-type mice also receiving gastrectomy and iron (6.7%, 1/15. Esophageal squamous cell carcinoma developed in INK4a/Arf+/- mice (7.1%, 1/14, and wild-type mice receiving gastrectomy and iron (21.4%, 3/14. Among 13 wild-type mice which were given iron from week 40 to 80, twelve (92.3% developed squamous cell carcinoma at week 80. None of these mice developed esophageal adenocarcinoma. Conclusion Surgically induced gastroesophageal reflux produced esophageal squamous cell carcinoma, but not esophageal adenocarcinoma, in mice. Dominant negative p53 mutation, heterozygous loss of INK4a/Arf, antacid treatment, iron supplementation, or gastrectomy failed to promote esophageal adenocarcinoma in these mice. Further studies are needed in order to develop a mouse model of esophageal adenocarcinoma.

Hairless pigmented guinea pigs: a new model for the study of mammalian pigmentation.

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Bolognia, J L; Murray, M S; Pawelek, J M

1990-09-01

A stock of hairless pigmented guinea pigs was developed to facilitate studies of mammalian pigmentation. This stock combines the convenience of a hairless animal with a pigmentary system that is similar to human skin. In both human and guinea pig skin, active melanocytes are located in the basal layer of the interfollicular epidermis. Hairless albino guinea pigs on an outbred Hartley background (CrI:IAF/HA(hr/hr)BR; designated hr/hr) were mated with red-haired guinea pigs (designated Hr/Hr). Red-haired heterozygotes from the F1 generation (Hr/hr) were then mated with each other or with hairless albino guinea pigs. The F2 generation included hairless pigmented guinea pigs that retained their interfollicular epidermal melanocytes and whose skin was red-brown in color. Following UV irradiation, there was an increase in cutaneous pigmentation as well as an increase in the number of active epidermal melanocytes. An additional strain of black hairless guinea pigs was developed using black Hr/Hr animals and a similar breeding scheme. These two strains should serve as useful models for studies of the mammalian pigment system.

Family Outbreaks of Nontyphoidal Salmonellosis following a Meal of Guinea Pigs

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John B. Fournier

2015-01-01

Full Text Available Salmonella outbreaks have been linked to a wide variety of foods, including recent nationwide outbreaks. Guinea pig (Cavia porcellus, also known as cuy or cobayo, has long been a popular delicacy and ceremonial food in the Andean region in South America. This case report describes three family outbreaks of nontyphoidal salmonellosis, each occurring after a meal of guinea pigs. We believe this case report is the first to describe a probable association between the consumption of guinea pig meat and human salmonellosis. Physicians should be aware of the association of Salmonella and the consumption of guinea pigs, given the increasing immigration of people from the Andean region of South America and the increasing travel to this region.

Effects of intranasal corticosteroids on radiated nasal mucosa of guinea pig

International Nuclear Information System (INIS)

Zhu Xinhua; Liu Yuehui

2009-01-01

Objective: To investigate a mechanism protected radiation-induce injure for radiated guinea pigs'nasal mucosa treated with intranasal corticosteroids(fluticasone nasal cavity spray). Methods: 50 health guinea pigs were divided into 2 groups randomly: the irradiated group (control group) with 25 guinea pigs and the administration group after irradiation (test group)with 25 guinea pigs. The nasal part of all guinea pigs were performed irradiation by the 6 MV X-ray with single 5 Gy, one time each week for three weeks. The guinea pigs of test group received intranasal corticosteroids with one time every day and one spray each side nasal cavity on the second day after three weeks irradiation. Five guinea pigs in each group were sacrificed randomly at 1 week, 1 month, 2 months, 3 months and 4 months after irradiation, and the histopathologic changes were observed under optical microscope and electron microscope. At the same time, blood were drawn from the heart and the concentration of IL-1, IL-6 and TNF-α in serum were measured by ELISA. Results: The early nasal mucosa inflammatory reaction of the test group was less than the control group. The coverage rate of cilia of the test group was much than that of the control group (72.9% vs 50.2%) at four months after irradiation. The atrophy of submucosal glandular organ was lessened and they displayed some extent secretory function. The concentration of IL-1 in serum was increased very much in the test group compared with the control group after irradiation and kept higher level in the first two months. After two months, it began to decrease; on four months, it still kept equivalency level with the control group. The concentration of IL-6 and TNF-α in serum were reduced all the while. Conclusions: The intranasal corticosteroids with fluticasone nasal cavity spray can reduce radiation- induced injury of guinea pigs' nasal mucosa. The concentration change of IL-1, IL-6 and TNF-α in serum may be one of mechanism protected

Lin28a Is Dormant, Functional, and Dispensable During Mouse Oocyte-to-Embryo Transition

Czech Academy of Sciences Publication Activity Database

Flemr, Matyáš; Moravec, Martin; Libová, Veronika; Sedláček, Radislav; Svoboda, Petr

2014-01-01

Roč. 90, č. 6 (2014), s. 1-9 ISSN 0006-3363 R&D Projects: GA MŠk LH13084; GA MŠk(CZ) LM2011032; GA ČR(CZ) GBP305/12/G034 Institutional support: RVO:68378050 Keywords : early development * genome activation * guinea pigs * Let-7 * LIN28 * mice * microRNA * oocyte * rats * RNAi * rodents * transgenic/ knockout model * voles * zygote Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.318, year: 2014

Survey of endoparasites in pet guinea pigs in Italy.

Science.gov (United States)

d'Ovidio, Dario; Noviello, Emilio; Ianniello, Davide; Cringoli, Giuseppe; Rinaldi, Laura

2015-03-01

Little information is available on the occurrence of endoparasites in pet guinea pigs (Cavia porcellus). The purpose of this study was to evaluate the prevalence of intestinal parasites in cavies kept as pets in southern Italy. Fresh fecal samples were randomly collected from 60 guinea pigs housed in pet shops or privately owned. All fecal samples were processed using the FLOTAC pellet technique to identify and count helminthic eggs/larvae and protozoan cysts/oocysts. In addition, the specimens were analyzed also by the Remel Xpect® Giardia/Cryptosporidium immunoassay. Intestinal parasites were detected in 19 out of 60 guinea pigs (31.7 %). Paraspidodera uncinata eggs were found in 13.3 % (8/60) of the rodents examined, Nippostrongylus-like eggs in 10 % (6/60), and finally Eimeria caviae oocysts were found in 10 % (6/60) of the animals. In one case, both E. caviae oocysts and P. uncinata eggs were found. None of the samples was positive for Cryptosporidium or Giardia. To the authors' knowledge, this is the first survey of endoparasites in pet guinea pigs in Italy.

In Vitro Response of Guinea Pig Peritoneal Macrophages to Legionella pneumophila

Science.gov (United States)

1981-03-01

In Vitro Responlse of Guinea Pig Peritoneal Macrophages to Legionella pneumophila It. A. KISIIIMi~O~’ .1. Ii.,W11ITE, F. G. SIREY, V. (U.1 Mc(GANN, R...Tlhe inter- act ion between L. lincumnophila andl( peritoneal macrophages front normial guinea pigs or front animials that had survived infection was...roagglujtiniat titer) guinea pig serum to The purp~ose of this study "as to investigate contain approximately 108 organisms per ml. the phagocytic and

Erythropoietin and erythropoietin receptor expression in the guinea pig inner ear

DEFF Research Database (Denmark)

Cayé-Thomasen, Per; Wagner, Niels; Lidegaard Frederiksen, Birgitte

2005-01-01

, this study determines expression of EPO and EPOR in the inner ear of the guinea pig. Normal guinea pig inner ears were processed for immunohistochemistry, using poly-clonal antibodies against EPO and the EPO receptor. EPO expression was exclusively found in most, but not all spiral ganglion neurons...... expressed by several cell types within the guinea pig cochlea. We hypothesize on the existence of a local paracrine system and that EPO treatment may be feasible following inner ear damage....

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

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

2017-09-03

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

The preparation of recombinant interleukin-6 and its protection for irradiated guinea-pigs

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