Sample records for guinea pig heart

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

    PubMed

    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.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

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

    1987-09-01

    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{sup 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. Inmore » 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.« less

  3. The effect of restraining on the heart rate in guinea pigs

    NASA Technical Reports Server (NTRS)

    Mikiskova, H.

    1980-01-01

    The emotional effect of different applications of electrodes and the fixation for cariographic examination was investigated using guinea pigs. The effect of the stress is discussed in terms of heart rhythm and behavior.

  4. Chronic intermittent hypobaric hypoxia protects the heart against ischemia/reperfusion injury through upregulation of antioxidant enzymes in adult guinea pigs

    PubMed Central

    Guo, Hui-cai; Zhang, Zhe; Zhang, Li-nan; Xiong, Chen; Feng, Chen; Liu, Qian; Liu, Xu; Shi, Xiao-lu; Wang, Yong-li

    2009-01-01

    Aim: To investigate the protection and the anti-oxidative mechanism afforded by chronic intermittent hypobaric hypoxia (CIHH) against ischemia/reperfusion (I/R) injury in guinea pig hearts. Methods: Adult male guinea pigs were exposed to CIHH by mimicking a 5000 m high altitude (pB=404 mmHg, pO2=84 mmHg) in a hypobaric chamber for 6 h/day for 28 days. Langendorff-perfused isolated guinea pig hearts were used to measure variables of left ventricular function during baseline perfusion, ischemia and the reperfusion period. The activity and protein expression of antioxidant enzymes in the left myocardium were evaluated using biochemical methods and Western blotting, respectively. Intracellular reactive oxygen species (ROS) were assessed using ROS-sensitive fluorescence. Results: After 30 min of global no-flow ischemia followed by 60 min of reperfusion, myocardial function had better recovery rates in CIHH guinea pig hearts than in control hearts. The activity and protein expression of superoxide dismutase (SOD) and catalase (CAT) were significantly increased in the myocardium of CIHH guinea pigs. Pretreatment of control hearts with an antioxidant mixture containing SOD and CAT exerted cardioprotective effects similar to CIHH. The irreversible CAT inhibitor aminotriazole (ATZ) abolished the cardioprotection of CIHH. Cardiac contractile dysfunction and oxidative stress induced by exogenous hydrogen peroxide (H2O2) were attenuated by CIHH and CAT. Conclusions: These data suggest that CIHH protects the heart against I/R injury through upregulation of antioxidant enzymes in guinea pig. PMID:19543301

  5. [Effects of astragalus and its active ingredients on ischemia reperfusion injury in isolated guinea-pig heart].

    PubMed

    Zhang, Haining; Min, Dongyu; Fu, Mingyu; Tian, Jing; Wang, Qingwen; An, Xinjiang

    2014-09-01

    To explore the effects of astragalus (AST) , total flavone of astragalus (TFA), total saponins of astragalus (TSA) and astragalus polysaccharides (APS) on ischemia/reperfusion (40 min/60 min) injury in isolated guinea-pig heart. Isolated guinea-pig hearts underwent ischemia, then followed by K-H perfusion (I/R group), AST (60 mg/L),AST (60 mg/L), TFA (60 mg/L), TSA (60 mg/L) and APS (60 mg/L) perfusion (n = 6 each).Isolated hearts without ischemia serve as control group (n = 6). Activity of lactate dehydrogenas (LDH) and creatine kinase (CK) in effluent were measured.Infarct size, myocardial superoxide dismutase (SOD) activity and malondiadehyde (MDA) contents were also determined. Compared to control hearts, heart rate, coronary flow and myocardial superoxide dismutase (SOD) activity were significantly reduced, while LDH and CK in effluent as well as myocardial MDA were significantly increased in the I/R hearts during reperfusion (all P < 0.05), these changes could be partly reversed by AST and TFA perfusion.Infarct size was also significantly reduced in AST (11.9 ± 2.03) % and TFA (13.31 ± 1.17) % treated hearts compared to that in I/R group (18.9 ± 2.27) % (all P < 0.01). The findings indicate that AST and TFA could attenuate I/R injury in isolated guinea-pig heart possibly through enhancing the activity of SOD and reducing lipid peroxidation.

  6. Electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure.

    PubMed

    Fan, Ling; Chen, Li-Feng; Fan, Jing

    2017-12-01

    To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure. Guinea pigs model of iron deficiency anemia complicated with chronic heart failure in 10 guinea pigs of the experimental group was made by feeding a low iron diet, pure water and subcutaneous injection of isoproterenol. The control group consisting of 11 guinea pigs was given normal food, normal water and injected with normal saline. The left ventricular outflow tract model specimen was also prepared. The standard microelectrode technique was used to observe electrophysiological changes of autonomic cells in the outflow tract of left ventricular heart failure complicated with iron deficiency anemia in guinea pig model. The indicators of observation were maximal diastolic potential, action potential amplitude, 0 phase maximal depolarization velocity, 4 phase automatic depolarization velocity, repolarization 50% and 90%, and spontaneous discharge frequency. Compared with the control group, 4 phase automatic depolarization velocity, spontaneous discharge frequency and 0 phase maximal depolarization velocity decreased significantly (P < 0.01) and action potential amplitude reduced (P < 0.01) in model group. Moreover, repolarization 50% and 90% increased (P < 0.01). There are electrophysiological abnormalities of the left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with heart failure. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  7. Polydeoxyribonucleotides and nitric oxide release from guinea-pig hearts during ischaemia and reperfusion.

    PubMed Central

    Masini, E.; Lupini, M.; Mugnai, L.; Raspanti, S.; Mannaioni, P. F.

    1995-01-01

    1. Two polydeoxyribonucleotides, produced by the controlled hydrolysis of DNA of mammalian lung (defibrotide and its lower molecular weight fraction, P.O. 085 DV), were studied for their ability to modify the release of nitrite and the coronary flow in perfusates collected from isolated, normally perfused hearts of guinea-pigs and from hearts subjected to regional ischaemia and reperfusion. 2. In guinea-pig normally perfused hearts, both defibrotide (DFT) and its fraction, P.O. 085 DV, increase the amount of nitrite appearing in perfusates in a concentration-dependent fashion. At the highest concentration studied (10(-6) M), P.O. 085 DV was more effective than DFT. A concomitant increase in the coronary flow was observed. 3. The increase in nitrite in perfusates and the increase in coronary flow induced by both DFT and P.O. 085 DV were significantly reduced by NG-monomethyl-L-arginine (L-NMMA, 10(-4) M), an inhibitor of nitric oxide synthase (NOS). 4. The endothelium-dependent vasodilator, acetylcholine (ACh), enhances the formation of nitrite and the coronary flow. Both the increase in coronary flow and in the formation of nitrite were significantly reduced by L-NMMA (10(-4) M). 5. In guinea-pig hearts subjected to ischaemia and reperfusion, the effect of both compounds in increasing the amount of nitrite in perfusates was more evident and more pronounced with P.O. 085 DV. 6. Reperfusion-induced arrhythmias were significantly reduced by both compounds to the extent of complete protection afforded by compound P.O. 085 DV. 7. The cardioprotective and antiarrhythmic effects of DFT and P.O. 085 DV are discussed. PMID:7582482

  8. Dofetilide promotes repolarization abnormalities in perfused Guinea-pig heart.

    PubMed

    Osadchii, Oleg E

    2012-12-01

    Dofetilide is class III antiarrhythmic agent which prolongs cardiac action potential duration because of selective inhibition of I (Kr), the rapid component of the delayed rectifier K(+) current. Although clinical studies reported on proarrhythmic risk associated with dofetilide treatment, the contributing electrophysiological mechanisms remain poorly understood. This study was designed to determine if dofetilide-induced proarrhythmia may be attributed to abnormalities in ventricular repolarization and refractoriness. The monophasic action potential duration and effective refractory periods (ERP) were assessed at distinct epicardial and endocardial sites along with volume-conducted ECG recordings in isolated, perfused guinea-pig heart preparations. Dofetilide was found to produce the reverse rate-dependent prolongation of ventricular repolarization, increased the steepness of action potential duration rate adaptation, and amplified transepicardial variability in electrical restitution kinetics. Dofetilide also prolonged the T peak-to-end interval on ECG, and elicited a greater prolongation of endocardial than epicardial ERP, thereby increasing transmural dispersion of refractoriness. At epicardium, dofetilide prolonged action potential duration to a greater extent than ERP, thus extending the critical interval for ventricular re-excitation. This change was associated with triangulation of epicardial action potential because of greater dofetilide-induced prolonging effect at 90 % than 30 % repolarization. Premature ectopic beats and spontaneous short-lasting episodes of monomorphic ventricular tachycardia were observed in 44 % of dofetilide-treated heart preparations. Proarrhythmic potential of dofetilide in guinea-pig heart is attributed to steepened electrical restitution, increased transepicardial variability in electrical restitution kinetics, amplified transmural dispersion of refractoriness, increased critical interval for ventricular re-excitation, and

  9. Models of torsades de pointes: effects of FPL64176, DPI201106, dofetilide, and chromanol 293B in isolated rabbit and guinea pig hearts.

    PubMed

    Cheng, Hsien C; Incardona, Josephine

    2009-01-01

    For studying the torsades de pointes (TdP) liability of a compound, most high and medium throughput methods use surrogate markers such as HERG inhibition and QT prolongation. In this study, we have tested whether isolated hearts may be modified to allow TdP to be the direct readout. Isolated spontaneously beating rabbit and guinea pig hearts were perfused according to the Langendorff method in hypokalemic (2.1 mM) solution. The in vitro lead II ECG equivalent and the incidence of TdP were monitored for 1 h. In addition, heart rate, QTc, Tp-Te, short-term variability (STV), time to arrhythmia, and time to TdP were also analyzed. FPL64176, a calcium channel activator; and DPI201106, a sodium channel inactivation inhibitor, produced TdP in isolated rabbit and guinea pig hearts in a concentration dependent manner; guinea pig hearts were 3- to 5-fold more sensitive than rabbit hearts. Both compounds also increased QTc and STV. In contrast, dofetilide, an IKr inhibitor, produced no (or a low incidence of) TdP in both species, in spite of prolongation of QTc intervals. Chromanol 293B, an IKs inhibitor, did not produce TdP in rabbit hearts but elicited TdP concentration dependently in guinea pig hearts even though the compound had no effect on QTc intervals. IKs inhibition appears to be more likely to produce TdP in isolated guinea pig hearts than IKr inhibition. Chromanol 293B did not produce TdP in rabbit hearts presumably due to a low level of IKs channels in the heart. TdP produced in this study was consistent with the notion that its production was a consequence of reduced repolarization reserve, thereby causing rhythmic abnormalities. This isolated, perfused, and spontaneously beating rabbit and guinea pig heart preparation in hypokalemic medium may be useful as a preclinical test model for studying proarrhythmic liability of compounds in new drug development.

  10. Effects of anti-malarial drugs on the electrocardiographic QT interval modelled in the isolated perfused guinea pig heart system

    PubMed Central

    2010-01-01

    Background Concern over the potential cardiotoxicity of anti-malarial drugs inducing a prolonged electrocardiographic QT interval has resulted in the almost complete withdrawal from the market of one anti-malarial drug - halofantrine. The effects on the QT interval of four anti-malarial drugs were examined, using the guinea pig heart. Methods The guinea pig heart was isolated, mounted on a Langendorff apparatus, and was then perfused with pyruvate-added Klebs-Henseleit solutions containing graded concentrations of the four agents such as quinidine (0.15 - 1.2 μM), quinine (0.3 - 2.4 μM), halofantrine (0.1 - 2.0 μM) and mefloquine (0.1 - 2.0 μM). The heart rate-corrected QaTc intervals were measured to evaluate drug-induced QT prolongation effects. Results Quinidine, quinine, and halofantrine prolonged the QaTc interval in a dose-dependent manner, whereas no such effect was found with mefloquine. The EC50 values for the QaTc prolongation effects, the concentration that gives a half-maximum effect, were quinidine < quinine ≈ halofantrine. Conclusions In this study, an isolated, perfused guinea pig heart system was constructed to assess the cardiotoxic potential of anti-malarial drugs. This isolated perfused guinea pig heart system could be used to test newly developed anti-malarial drugs for their inherent QT lengthening potential. More information is required on the potential variation in unbound drug concentrations in humans, and their role in cardiotoxicity. PMID:21067575

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

    PubMed

    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.

  12. Inhibitory effects of sevoflurane on pacemaking activity of sinoatrial node cells in guinea-pig heart

    PubMed Central

    Kojima, Akiko; Kitagawa, Hirotoshi; Omatsu-Kanbe, Mariko; Matsuura, Hiroshi; Nosaka, Shuichi

    2012-01-01

    BACKGROUND AND PURPOSE The volatile anaesthetic sevoflurane affects heart rate in clinical settings. The present study investigated the effect of sevoflurane on sinoatrial (SA) node automaticity and its underlying ionic mechanisms. EXPERIMENTAL APPROACH Spontaneous action potentials and four ionic currents fundamental for pacemaking, namely, the hyperpolarization-activated cation current (If), T-type and L-type Ca2+ currents (ICa,T and ICa,L, respectively), and slowly activating delayed rectifier K+ current (IKs), were recorded in isolated guinea-pig SA node cells using perforated and conventional whole-cell patch-clamp techniques. Heart rate in guinea-pigs was recorded ex vivo in Langendorff mode and in vivo during sevoflurane inhalation. KEY RESULTS In isolated SA node cells, sevoflurane (0.12–0.71 mM) reduced the firing rate of spontaneous action potentials and its electrical basis, diastolic depolarization rate, in a qualitatively similar concentration-dependent manner. Sevoflurane (0.44 mM) reduced spontaneous firing rate by approximately 25% and decreased If, ICa,T, ICa,L and IKs by 14.4, 31.3, 30.3 and 37.1%, respectively, without significantly affecting voltage dependence of current activation. The negative chronotropic effect of sevoflurane was partly reproduced by a computer simulation of SA node cell electrophysiology. Sevoflurane reduced heart rate in Langendorff-perfused hearts, but not in vivo during sevoflurane inhalation in guinea-pigs. CONCLUSIONS AND IMPLICATIONS Sevoflurane at clinically relevant concentrations slowed diastolic depolarization and thereby reduced pacemaking activity in SA node cells, at least partly due to its inhibitory effect on If, ICa,T and ICa,L. These findings provide an important electrophysiological basis of alterations in heart rate during sevoflurane anaesthesia in clinical settings. PMID:22356456

  13. [Postmortem distribution of tetrodotoxin in tissues and body fluids of guinea pigs].

    PubMed

    Liu, Wei; Da, Qing; Shen, Min

    2012-06-01

    To investigate the postmortem distribution of tetrodotoxin in tissues and body fluids of guinea pig, and to provide method and evidence for forensic identification and clinical diagnosis and treatment. Guinea pigs were intragastric administrated with 100, 50, 15 microg/kg tetrodotoxin, respectively. The poisoning symptoms were observed. The samples of heart, liver, spleen, lung, kidney, brain, stomach, intestines, bile, heart blood and urine were collected. The concentrations of tetrodotoxin in tissues and body fluids were measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS). After administrated with tetrodotoxin, all guinea pigs came out poisoning signs including tachypnea, weary and dead finally. Tetrodotoxin concentrations in lung, stomach, intestines and urine were higher, followed by blood, heart and brain. The concentration in bile was the lowest. Postmortem distribution of tetrodotoxin in guinea pig is uneven. The concentration in the lung, stomach, intestines, urine and heart blood are higher, those tissues could be used for diagnosis of tetrodotoxin poisoning.

  14. Electrophysiological determinants of hypokalaemia-induced arrhythmogenicity in the guinea-pig heart.

    PubMed

    Osadchii, O E; Olesen, S P

    2009-12-01

    Hypokalaemia is an independent risk factor contributing to arrhythmic death in cardiac patients. In the present study, we explored the mechanisms of hypokalaemia-induced tachyarrhythmias by measuring ventricular refractoriness, spatial repolarization gradients, and ventricular conduction time in isolated, perfused guinea-pig heart preparations. Epicardial and endocardial monophasic action potentials from distinct left ventricular (LV) and right ventricular (RV) recording sites were monitored simultaneously with volume-conducted electrocardiogram (ECG) during steady-state pacing and following a premature extrastimulus application at progressively reducing coupling stimulation intervals in normokalaemic and hypokalaemic conditions. Hypokalaemic perfusion (2.5 mm K(+) for 30 min) markedly increased the inducibility of tachyarrhythmias by programmed ventricular stimulation and rapid pacing, prolonged ventricular repolarization and shortened LV epicardial and endocardial effective refractory periods, thereby increasing the critical interval for LV re-excitation. Hypokalaemia increased the RV-to-LV transepicardial repolarization gradients but had no effect on transmural dispersion of APD(90) and refractoriness across the LV wall. As determined by local activation time recordings, the LV-to-RV transepicardial conduction and the LV transmural (epicardial-to-endocardial) conduction were slowed in hypokalaemic heart preparations. This change was attributed to depressed diastolic excitability as evidenced by increased ventricular pacing thresholds. These findings suggest that hypokalaemia-induced arrhythmogenicity is attributed to shortened LV refractoriness, increased critical intervals for LV re-excitation, amplified RV-to-LV transepicardial repolarization gradients and slowed ventricular conduction in the guinea-pig heart.

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

    PubMed

    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.

  16. Protective effects of isorhynchophylline on cardiac arrhythmias in rats and guinea pigs.

    PubMed

    Gan, Runtao; Dong, Guo; Yu, Jiangbo; Wang, Xu; Fu, Songbin; Yang, Shusen

    2011-09-01

    As one important constituent extracted from a traditional Chinese medicine, Uncaria Rhynchophylla Miq Jacks, isorhynchophylline has been used to treat hypertension, epilepsy, headache, and other illnesses. Whether isorhynchophylline protects hearts against cardiac arrhythmias is still incompletely investigated. This study was therefore aimed to examine the preventive effects of isorhynchophylline on heart arrhythmias in guinea pigs and rats and then explore their electrophysiological mechanisms. In vivo, ouabain and calcium chloride were used to establish experimental arrhythmic models in guinea pigs and rats. In vitro, the whole-cell patch-lamp technique was used to study the effect of isorhynchophylline on action potential duration and calcium channels in acutely isolated guinea pig and rat cardiomyocytes. The dose of ouabain required to induce cardiac arrhythmias was much larger in guinea pigs administered with isorhynchophylline. Additionally, the onset time of cardiac arrhythmias induced by calcium chloride was prolonged, and the duration was shortened in rats pretreated with isorhynchophylline. The further study showed that isorhynchophylline could significantly decrease action potential duration and inhibit calcium currents in isolated guinea pig and rat cardiomyocytes in a dose-dependent manner. In summary, isorhynchophylline played a remarkably preventive role in cardiac arrhythmias through the inhibition of calcium currents in rats and guinea pigs. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Immune Response in Male Guinea Pigs Infected with the Guinea Pig Inclusion Conjunctivitis Agent of Chlamydia Psittaci

    DTIC Science & Technology

    1994-01-01

    Dist, ibution I Availability Codes Avail and/or Dist Special IMMUNE RESPONSE IN MALE GUINEA PIGS INFECTED WITH THE GUINEA PIG INCLUSION...CONJUNCTIVITIS AGENT OF CHLAM"DIA PSITTA CI At >- ~tu IMMUNE RESPONSE IN MALE GUINEA PIGS INFECTED WITH THE GUINEA PIG INCLUSION CONJUNCTIVITIS AGENT OF...Stock .................................................................... 15 Infection of Guinea Pigs with GPIC

  18. Effects of changes in vertical occlusal dimension on heart rate fluctuations in guinea pigs.

    PubMed

    Taga, Hitoshi; Azuma, Yukio; Maehara, Kiyoshi; Nomura, Shuichi

    2012-01-01

    We have previously reported that the decrease of the vertical occlusal dimension (VOD) led to heart failure and abnormalities in creatine phosphokinase (CPK) in guinea pigs. In the present study, we investigated the autonomic activity and the origin of the abnormality in CPK under different occlusal conditions. Guinea pigs were separated into the following five groups: untreated control, reduced VOD, slit, restored VOD and increased VOD groups and compared for their electrocardiogram and heart rate fluctuations for two weeks using Fluclet, computer software. The control group revealed no changes in heart rate fluctuations or posture. The reduced VOD group exhibited a two-phase wave of heart rate fluctuations, with the first peak 0-2 days after teeth grinding, and the second peak starting from 4 days after teeth grinding until sudden death (usually 12th day), accompanied by head drop. The slit and the restored VOD groups exhibited only the first peak. The increased VOD group, with approximately 3 mm-thick acrylic pellets bonded to the posterior teeth, showed no heart rate fluctuations. Body weight loss was most prominent in the reduced VOD group, and became much milder in the order of increased VOD, restored and slit groups. The reduced VOD group exhibited transient elevation of skeletal muscle type of CPK isozyme activity within two days after treatment. The present study suggests that the first peak of heart rate fluctuations is caused by pulpal stimulation, and the second peak by excessive contraction (excessive excitation of the motor output system and the autonomic nervous system) of the masticatory muscles. On the other hand, increased VOD did not influence either the motor or the autonomic nervous system.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

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

    1983-04-30

    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 virusmore » 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.« less

  20. New in vitro model for proarrhythmia safety screening: IKs inhibition potentiates the QTc prolonging effect of IKr inhibitors in isolated guinea pig hearts.

    PubMed

    Kui, Péter; Orosz, Szabolcs; Takács, Hedvig; Sarusi, Annamária; Csík, Norbert; Rárosi, Ferenc; Csekő, Csongor; Varró, András; Papp, Julius Gy; Forster, Tamás; Farkas, Attila S; Farkas, András

    2016-01-01

    Preclinical in vivo QT measurement as a proarrhythmia essay is expensive and not reliable enough. The aim of the present study was to develop a sensitive, cost-effective, Langendorff perfused guinea pig heart model for proarrhythmia safety screening. Low concentrations of dofetilide and cisapride (inhibitors of the rapid delayed rectifier potassium current, IKr) were tested alone and co-perfused with HMR-1556 (inhibitor of the slow delayed rectifier potassium current, IKs) in Langendorff perfused guinea pig hearts. The electrocardiographic rate corrected QT (QTc) interval, the Tpeak-Tend interval and the beat-to-beat variability and instability (BVI) of the QT interval were determined in sinus rhythm. Dofetilide and HMR-1556 alone or co-perfused, prolonged the QTc interval by 20±2%, 10±1% and 55±10%, respectively. Similarly, cisapride and HMR-1556 alone or co-perfused, prolonged the QTc interval by 11±3%, 11±4% and 38±6%, respectively. Catecholamine-induced fast heart rate abolished the QTc prolonging effects of the IKr inhibitors, but augmented the QTc prolongation during IKs inhibition. None of the drug perfusions increased significantly the Tpeak-Tend interval and the sinus BVI of the QT interval. IKs inhibition increased the QTc prolonging effect of IKr inhibitors in a super-additive (synergistic) manner, and the QTc interval was superior to other proarrhythmia biomarkers measured in sinus rhythm in isolated guinea pig hearts. The effect of catecholamines on the QTc facilitated differentiation between IKr and IKs inhibitors. Thus, QTc measurement in Langendorff perfused guinea pig hearts with pharmacologically attenuated repolarization reserve and periodic catecholamine perfusion seems to be suitable for preclinical proarrhythmia screening. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. The protective effect of H2-receptor activation against the duration of myocardial hypoxia/reoxygenation-induced ventricular fibrillation in sensitized guinea-pig hearts.

    PubMed

    Imajo, Naoki; Matsui, Saori; Yasui, Yumiko; Matsui, Nobuaki; Fukuishi, Nobuyuki; Akagi, Masaaki

    2005-12-01

    Patients with high serum immunoglobulin E levels were reported to be protected against sudden death during acute myocardial infarction. The protection mechanism might be attributed to the facilitation of histamine release from sensitized mast cells; however, this remains to be clarified. In this study, we examined the influence of sensitization on ventricular fibrillation (VF) induced by myocardial hypoxia/reoxygenation (H/R). Guinea pigs were actively sensitized by subcutaneous injection of ovalbumin in Bordetella pertussis vaccine. Hearts isolated from non-sensitized and sensitized guinea pigs were subjected to 30-min hypoxia / 30-min reoxygenation using a Langendorff apparatus. The amount of histamine released in the sensitized guinea-pig hearts was elevated, and the duration of VF was found to be reduced. The treatment with a histamine H2-receptor antagonist inhibited the reduction of VF duration. Treatment of the non-sensitized hearts with the histamine H2-receptor agonist resulted in the decrease of VF duration to the same level as that in the sensitized hearts. In conclusion, these results suggest that the risk of sudden death during myocardial H/R may be attenuated in the sensitized hearts and that histamine H2-receptor activation due to the released histamine may be involved in the protective effect.

  2. Reduced intrinsic heart rate is associated with reduced arrhythmic susceptibility in guinea-pig heart.

    PubMed

    Osadchii, Oleg E

    2014-12-01

    In the clinical setting, patients with slower resting heart rate are less prone to cardiovascular death compared with those with elevated heart rate. However, electrophysiological adaptations associated with reduced cardiac rhythm have not been thoroughly explored. In this study, relationships between intrinsic heart rate and arrhythmic susceptibility were examined by assessments of action potential duration (APD) rate adaptation and inducibility of repolarization alternans in sinoatrial node (SAN)-driven and atrioventricular (AV)-blocked guinea-pig hearts perfused with Langendorff apparatus. Electrocardiograms, epicardial monophasic action potentials, and effective refractory periods (ERP) were assessed in normokalemic and hypokalemic conditions. Slower basal heart rate in AV-blocked hearts was associated with prolonged ventricular repolarization during spontaneous beating, and with attenuated APD shortening at increased cardiac activation rates during dynamic pacing, when compared with SAN-driven hearts. During hypokalemic perfusion, the inducibility of repolarization alternans and tachyarrhythmia by rapid pacing was found to be lower in AV-blocked hearts. This difference was ascribed to prolonged ERP in the setting of reduced basal heart rate, which prevented ventricular capture at critically short pacing intervals required to induce arrhythmia. Reduced basal heart rate is associated with electrophysiological changes that prevent electrical instability upon an abrupt cardiac acceleration.

  3. Energetic study of cardioplegic hearts under ischaemia/reperfusion and [Ca(2+)] changes in cardiomyocytes of guinea-pig: mitochondrial role.

    PubMed

    Ragone, M I; Torres, N S; Consolini, A E

    2013-02-01

    To study the role of mitochondria in the recovery of guinea-pig hearts exposed to high-K(+)-cardioplegia (CPG) and ischaemia/reperfusion (I/R) METHODS: We measured contractility and heat release in perfused guinea-pig hearts and cytosolic and mitochondrial Ca(2+) by epifluorescence and confocal microscopy in isolated cardiomyocytes loaded with Fluo-4 or Rhod-2. In hearts, CPG increased the postischaemic contractile recovery, and this was potentiated by the mNCX blocker clonazepam and the mKATP opener diazoxide, which also prevented the fall in muscle economy. Moreover, CPG prevented the stunning induced by ouabain, which was reduced by clonazepam. In cardiomyocytes, CPG increased fluorescent signals of cytosolic and mitochondrial Ca(2+), while the addition of a mNCX blocker (CGP37157) increased cytosolic but reduced mitochondrial [Ca(2+)]. Ouabain in CPG increased cytosolic Ca(2+) and resting heat, but the addition of CGP37157 reduced them, as well as mitochondrial Ca(2+). CPG, diazoxide and clonazepam improve postischaemic recovery, respectively, by increasing the Ca(2+) cycling and by reducing the mitochondrial Ca(2+) uptake either by uniporter or by mNCX. The mitochondria compete with the leaky sarcoplasmic reticulum (SR) as sink of Ca(2+) in guinea-pig hearts, affecting the postischaemic contractility. CPG also prevented the ouabain-induced dysfunction by avoiding the Ca(2+) overload. Ouabain reduced the synergism between CPG and clonazepam suggesting that [Na(+)]i and SR load influence the mNCX role. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

  4. Flecainide-induced proarrhythmia is attributed to abnormal changes in repolarization and refractoriness in perfused guinea-pig heart.

    PubMed

    Osadchii, Oleg E

    2012-11-01

    Flecainide is nonselective Na(+) channel blocker which may also inhibit I(Kr), the rapid component of the delayed rectifier. This study was designed to explore if proarrhythmic responses to flecainide noted in cardiac patients may be partly attributed to abnormal changes in repolarization and refractoriness. Monophasic action potential duration (APD) and effective refractory periods (ERP) were assessed at distinct epicardial and endocardial sites along with volume-conducted ECG recordings in isolated perfused guinea-pig heart preparations. Flecainide was found to prolong ventricular repolarization, with effect being greater at the left ventricular compared with the right ventricular epicardium. This change translated to reversal of the normal right ventricular-to-left ventricular transepicardial APD difference determined before drug infusion. An inverse correlation between local epicardial APD and corresponding activation time values seen at baseline was eliminated in flecainide-treated hearts, indicating the activation-to-repolarization uncoupling. Over transmural plane, flecainide produced a greater ERP lengthening at endocardium than epicardium, thus markedly increasing ERP dispersion across ventricular wall. Spontaneous short-lasting episodes of monomorphic ventricular tachycardia were observed in 45% of heart preparations upon flecainide infusion. In conclusion, in nonischemic guinea-pig heart, flecainide-induced proarrhythmia may be partly attributed to abnormal spatial gradients in repolarization and refractoriness and impaired transepicardial activation-to-repolarization coupling.

  5. Protection of Lassa Virus-Infected Guinea Pigs with Lassa-Immune Plasma of Guinea Pig, Primate, and Human Origin

    DTIC Science & Technology

    1983-01-01

    DTICCS OCT 19 1983ora o ek Viroly 12-93-102 (1963) Protection of Lassa Virus-infected Guinea Pigs With Lassa-Immune Plasma of Guinea Pig , Primate...siotrain 13 guinea pigs were infected with a lethal dose of Lassa virus and treated with various Lassa-immune plasmas obtained from guinea pigs , primates...plaque-forming units (PFU) neutralization index (LNI). All guinea pigs treated with immune plasma 6 mI/kg/treatment on days 0, 3, and 6 after virus

  6. ON THE CARCINORESISTANCE OF THE GUINEA PIG. PART I. SPONTANEOUS TUMORS IN THE GUINEA PIG,

    DTIC Science & Technology

    Among the rodents, the guinea pig is known for its great carcino-resistance. In analyzing this phenomenon, it is best to study on the one hand the...spontaneous tumors of the guinea pig and on the other, the experimental tumors that one can obtain in the same animal. In this first work, only the spontaneous tumors of the guinea pig are studied. (Author)

  7. Guinea Pig Chymase Is Leucine-specific

    PubMed Central

    Caughey, George H.; Beauchamp, Jeremy; Schlatter, Daniel; Raymond, Wilfred W.; Trivedi, Neil N.; Banner, David; Mauser, Harald; Fingerle, Jürgen

    2008-01-01

    To explore guinea pigs as models of chymase biology, we cloned and expressed the guinea pig ortholog of human chymase. In contrast to rats and mice, guinea pigs appear to express just one chymase, which belongs to the α clade, like primate chymases and mouse mast cell protease-5. The guinea pig enzyme autolyzes at Leu residues in the loop where human chymase autolyzes at Phe. In addition, guinea pig α-chymase selects P1 Leu in a combinatorial peptide library and cleaves Ala-Ala-Pro-Leu-4-nitroanilide but has negligible activity toward substrates with P1 Phe and does not cleave angiotensin I. This contrasts with human chymase, which cleaves after Phe or Tyr, prefers P1 Phe in peptidyl 4-nitroanilides, and avidly hydrolyzes angiotensin I at Phe8 to generate bioactive angiotensin II. The guinea pig enzyme also is inactivated more effectively by α1-antichymotrypsin, which features P1 Leu in the reactive loop. Unlike mouse, rat, and hamster α-chymases, guinea pig chymase lacks elastase-like preference for P1 Val or Ala. Partially humanized A216G guinea pig chymase acquires human-like P1 Phe- and angiotensin-cleaving capacity. Molecular models suggest that the wild type active site is crowded by the Ala216 side chain, which potentially blocks access by bulky P1 aromatic residues. On the other hand, the guinea pig pocket is deeper than in Val-selective chymases, explaining the preference for the longer aliphatic side chain of Leu. These findings are evidence that chymase-like peptidase specificity is sensitive to small changes in structure and provide the first example of a vertebrate Leu-selective peptidase. PMID:18353771

  8. Endocrine tumours in the guinea pig.

    PubMed

    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.

  9. Prolactin family of the guinea pig, Cavia porcellus.

    PubMed

    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.

  10. Is digitalis compound-induced cardiotoxicity, mediated through guinea-pig cardiomyocytes apoptosis?

    PubMed

    Ramirez-Ortega, Margarita; Zarco, Gabriela; Maldonado, Vilma; Carrillo, Jose F; Ramos, Pilar; Ceballos, Guillermo; Melendez-Zajgla, Jorge; Garcia, Noemí; Zazueta, Cecilia; Chanona, Jose; Suarez, Jorge; Pastelin, Gustavo

    2007-07-02

    Our aim in performing this study was to analyze in vivo the cell death mechanism induced by toxic doses of digitalis compounds on guinea-pig cardiomyocytes. We analyzed three study groups of five male guinea pigs each. Guinea pigs were intoxicated under anesthesia with ouabain or digoxin (at a 50-60% lethal dose); the control group did not receive digitalis. A 5-hours period elapsed before guinea pig hearts were extracted to obtain left ventricle tissue. We carried out isolation of mitochondria and cytosol, cytochrome c and caspase-3 and -9 determination, and electrophoretic analysis of nuclear DNA. TdT-mediated DUTP-X nick end labeling (TUNEL) reaction was performed in histologic preparations to identify in situ apoptotic cell death. Ultrastructural analysis was performed by electron microscopy. Electrophoretic analysis of DNA showed degradation into fragments of 200-400 base pairs in digitalis-treated groups. TUNEL reaction demonstrated the following: in the control group, <10 positive nuclei per field; in the digoxin-treated group, 2-14 positive nuclei per field, while in the ouabain-treated group counts ranged from 9-30 positive nuclei per field. Extracts from ouabain-treated hearts had an elevation of cytochrome c in cytosol and a corresponding decrease in mitochondria; this release of cytochrome c provoked activation of caspase-9 and -3. Electron microscopy revealed presence of autophagic vesicles in cytoplasm of treated hearts. Toxic dosages of digitalis at 50-60% of the lethal dose are capable of inducing cytochrome c release from mitochondria, processing of procaspase-9 and -3, and DNA fragmentation; these observations are mainly indicative of apoptosis, although a mixed mechanism of cell death cannot be ruled out.

  11. Integrated Omic Analysis of a Guinea Pig Model of Heart Failure and Sudden Cardiac Death.

    PubMed

    Foster, D Brian; Liu, Ting; Kammers, Kai; O'Meally, Robert; Yang, Ni; Papanicolaou, Kyriakos N; Talbot, C Conover; Cole, Robert N; O'Rourke, Brian

    2016-09-02

    Here, we examine key regulatory pathways underlying the transition from compensated hypertrophy (HYP) to decompensated heart failure (HF) and sudden cardiac death (SCD) in a guinea pig pressure-overload model by integrated multiome analysis. Relative protein abundances from sham-operated HYP and HF hearts were assessed by iTRAQ LC-MS/MS. Metabolites were quantified by LC-MS/MS or GC-MS. Transcriptome profiles were obtained using mRNA microarrays. The guinea pig HF proteome exhibited classic biosignatures of cardiac HYP, left ventricular dysfunction, fibrosis, inflammation, and extravasation. Fatty acid metabolism, mitochondrial transcription/translation factors, antioxidant enzymes, and other mitochondrial procsses, were downregulated in HF but not HYP. Proteins upregulated in HF implicate extracellular matrix remodeling, cytoskeletal remodeling, and acute phase inflammation markers. Among metabolites, acylcarnitines were downregulated in HYP and fatty acids accumulated in HF. The correlation of transcript and protein changes in HF was weak (R(2) = 0.23), suggesting post-transcriptional gene regulation in HF. Proteome/metabolome integration indicated metabolic bottlenecks in fatty acyl-CoA processing by carnitine palmitoyl transferase (CPT1B) as well as TCA cycle inhibition. On the basis of these findings, we present a model of cardiac decompensation involving impaired nuclear integration of Ca(2+) and cyclic nucleotide signals that are coupled to mitochondrial metabolic and antioxidant defects through the CREB/PGC1α transcriptional axis.

  12. 9 CFR 113.38 - Guinea pig safety test.

    Code of Federal Regulations, 2010 CFR

    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...

  13. 9 CFR 113.38 - Guinea pig safety test.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 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...

  14. 9 CFR 113.38 - Guinea pig safety test.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 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...

  15. 9 CFR 113.38 - Guinea pig safety test.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 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...

  16. 9 CFR 113.38 - Guinea pig safety test.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 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...

  17. Temporal Progression of Lesions in Guinea Pigs Infected With Lassa Virus.

    PubMed

    Bell, T M; Shaia, C I; Bearss, J J; Mattix, M E; Koistinen, K A; Honnold, S P; Zeng, X; Blancett, C D; Donnelly, G C; Shamblin, J D; Wilkinson, E R; Cashman, K A

    2017-05-01

    Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100 000 to 300 000 persons in West Africa. This pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for Lassa fever. After experimental infection, guinea pigs ( Cavia porcellus; n = 67) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and serum chemistry and hematologic changes. Guinea pigs developed viremia on day 5 to 6 postexposure (PE), with clinical signs appearing by day 7 to 8 PE. Complete blood counts revealed lymphopenia and thrombocytopenia. Gross pathologic findings included skin lesions and congested lungs. Histologic lesions consisted of cortical lymphoid depletion by day 6 to 7 PE with lymphohistiocytic interstitial pneumonia at 7 to 8 days PE. Scattered hepatocellular degeneration and cell death were also noted in the liver and, to a lesser extent, in other tissues including the haired skin, lung, heart, adrenal gland, lymph nodes, thymus, and spleen. The first cell types to demonstrate staining for viral antigen were fibroblastic reticular cells and macrophages/dendritic cells in the lymph nodes on day 5 to 6 PE. This study demonstrates similarities between Lassa viral disease in human infections and experimental guinea pig infection. These shared pathologic characteristics support the utility of guinea pigs as an additional animal model for vaccine and therapeutic development under the Food and Drug Administration's Animal Rule.

  18. Some intrinsic neurons of the guinea-pig heart contain substance P.

    PubMed

    Bałuk, P; Gabella, G

    1989-10-09

    Whole-mount preparations of the posterior wall of the atria of the guinea pig heart containing intrinsic ganglion cells and nerve plexuses were stained for substance P-like immunoreactivity by the peroxidase-antiperoxidase method. Substance P-like nerve fibres are present as pericellular baskets around most, but not all, of the neuronal cell bodies, and are also found in the connecting nerve bundles, as perivascular nerve plexuses and in the myocardium and pericardium. The majority of ganglion cell bodies are negative for substance P, as reported previously, but we describe for the first time, a small subpopulation of intrinsic neuronal cell bodies which show immunoreactivity for substance P. Therefore, not all cardiac substance P nerves are extrinsic afferent fibres. At present, the physiological role of intrinsic substance P neurones is not clear.

  19. Intact nitric oxide production is obligatory for the sustained flow response during hypercapnic acidosis in guinea pig heart.

    PubMed

    Heintz, Anke; Koch, Thea; Deussen, Andreas

    2005-04-01

    The mechanisms underlying hypercapnic coronary dilation remain unsettled. This study tests the hypothesis that flow dependent NO production is obligatory for the hypercapnic flow response. In isolated, constant pressure (CP) perfused guinea pig hearts a step change of arterial pCO(2) from 38.6 to 61.4 mm Hg induced a bi-phasic flow response with an early transient (maximum 60 s) and a consecutive persisting flow rise (121.6+/-6.6 (S.D.) % after 10 min). In contrast, when perfused with constant flow (CF), perfusion pressure only transiently (2 min) fell by 7.4+/-4.8 % following the step change of arterial pCO(2). In CP perfused hearts L-NAME (100 micromol/l) specifically abolished the delayed flow rise during hypercapnic acidosis (102.37+/-2.9% after 10 min), whereas the inhibitor had no effect on perfusion pressure response in CF perfused hearts. Under CP perfusion arterial hypercapnia resulted in a transient rise of coronary cGMP release (from 0.69+/-0.35 to 1.12+/-0.68 pmol/ml), which was abolished after L-NAME. Surprisingly, the K(+)ATP channel blocker glibenclamide did not have any significant effect on the hypercapnic flow response but largely blunted reactive hyperemia after a 20 s flow stop. The delayed steady state hypercapnic flow response in guinea pig heart requires intact NO production. The absence of a persisting decrease in coronary resistance under CF perfusion points to an important role of shear stress dependent NO production.

  20. Unilateral flank ovariohysterectomy in guinea pigs (Cavia porcellus).

    PubMed

    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.

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

    PubMed Central

    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. PMID:25502875

  2. Electrophysiological determinants of arrhythmic susceptibility upon endocardial and epicardial pacing in guinea-pig heart.

    PubMed

    Osadchii, O E

    2012-08-01

    Endocardial pacing instituted to treat symptomatic bradycardia may nevertheless promote tachyarrhythmia in some pacemaker-implanted patients. We sought to determine the contributing electrophysiological mechanisms. Left ventricular (LV) monophasic action potential duration (APD(90)) and effective refractory periods were determined in perfused guinea-pig hearts along with volume-conducted ECG recordings during epicardial and endocardial stimulations. Consistent with electrotonic modulation of repolarization, APD(90) at a given (either epicardial or endocardial) recording site tended to be longer while pacing from the ipsilateral LV site as compared to stimulations applied at the opposite side of ventricular wall. As a result, the intrinsic transmural repolarization gradient was amplified during endocardial pacing while being significantly reduced upon epicardial stimulations. The maximum slope of APD(90) restitution was greater upon endocardial than epicardial pacing. The excitability was found to recur at earlier repolarization time point at endocardium than epicardium, thereby contributing to increased endocardial critical intervals for re-excitation. Premature extrasystolic beats could have been elicited at shorter coupling stimulation intervals and propagated with greater transmural conduction delay upon endocardial than epicardial stimulations. Endocardial site exhibited lower ventricular fibrillation thresholds and greater inducibility of tachyarrhythmia upon extrasystolic stimulations as compared to epicardium. Arrhythmic susceptibility in guinea-pig heart is greater during endocardial than epicardial pacing because of greater transmural APD(90) dispersion, steeper electrical restitution slopes, greater critical intervals for LV re-excitation and slower transmural conduction of the earliest premature ectopic beats. Further studies are warranted to determine whether these effects may contribute to proarrhythmia in paced human patients. © 2012 The Author Acta

  3. Development of a Guinea Pig Lung Deposition Model

    DTIC Science & Technology

    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

  4. Using guinea pigs in studies relevant to asthma and COPD

    PubMed Central

    Canning, Brendan J.; Chou, Yangling

    2010-01-01

    The guinea pig has been the most commonly used small animal species in preclinical studies related to asthma and COPD. The primary advantages of the guinea pig are the similar potencies and efficacies of agonists and antagonists in human and guinea pig airways and the many similarities in physiological processes, especially airway autonomic control and the response to allergen. The primary disadvantages to using guinea pigs are the lack of transgenic methods, limited numbers of guinea pig strains for comparative studies and a prominent axon reflex that is unlikely to be present in human airways. These attributes and various models developed in guinea pigs are discussed. PMID:18462968

  5. Functional analysis of guinea pig β1-adrenoceptor.

    PubMed

    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.

  6. Prenatal Nicotine Increases Matrix Metalloproteinase 2 (MMP-2) Expression in Fetal Guinea Pig Hearts

    PubMed Central

    Thompson, Loren P.; Liu, Hongshan; Evans, LaShauna; Mong, Jessica A.

    2011-01-01

    This study tested the hypothesis that maternal nicotine ingestion increases matrix metalloproteinase (MMP) expression in fetal hearts, which is mediated by the generation of reactive oxygen species. Timed pregnant guinea pigs were administered either water alone, nicotine (200 μg/mL), N-acetylcysteine (NAC), or nicotine plus NAC in their drinking water for 10 days at 52-day gestation (term = 65 days). Near-term (62 days), anesthetized fetuses were extracted, hearts were excised, and left cardiac ventricles snap frozen for analysis of MMP-2/-9/-13 protein and activity levels. Interstitial collagens were identified by Picrosirius red stain to assess changes in the extracellular matrix. Prenatal nicotine increased active MMP-2 forms and interstitial collagen but had no effect on either pro- or active MMP-9 or MMP-13 forms. In the presence of nicotine, NAC decreased active MMP-2 protein levels and reversed the nicotine-induced increase in collagen staining. We conclude that prenatal nicotine alters MMP-2 expression in fetal hearts that may be mediated by reactive oxygen species generation. PMID:21775771

  7. Gastric Volvulus in Guinea Pigs: Comparison with Other Species

    PubMed Central

    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 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. PMID:21838984

  8. Guinea Pig ID-Like Families of SINEs

    PubMed Central

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

    2009-01-01

    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. PMID:19232383

  9. Guinea pig ID-like families of SINEs.

    PubMed

    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.

  10. Flecainide attenuates rate adaptation of ventricular repolarization in guinea-pig heart.

    PubMed

    Osadchii, Oleg E

    2016-01-01

    Flecainide is class Ic antiarrhythmic agent that was found to increase the risk of sudden cardiac death. Arrhythmic responses to flecainide could be precipitated by exercise, suggesting a role played by inappropriate rate adaptation of ventricular repolarization. This study therefore examined flecainide effect on adaptation of the QT interval and ventricular action potential duration (APD) to abrupt reductions of the cardiac cycle length. ECG and ventricular epicardial and endocardial monophasic APD were recorded in isolated, perfused guinea-pig heart preparations upon a sustained cardiac acceleration (rapid pacing for 30 s), and following a single perturbation of the cycle length evoked by extrasystolic stimulation. Sustained increase in heart rate was associated with progressive bi-exponential shortening of the QT interval and APD. Flecainide prolonged ventricular repolarization, delayed its rate adaptation, and decreased the amplitude of QT interval and APD shortening upon rapid cardiac pacing. During extrasystolic stimulation, flecainide attenuated APD shortening in premature ventricular beats, with effect being greater upon using a longer basic drive cycle length (S1-S1=550 ms versus S1-S1=300 ms). Flecainide-induced arrhythmia may be partly accounted for by attenuated adaptation of ventricular repolarization to sudden changes in cardiac cycle length provoked by transient tachycardia or ectopic beats.

  11. Oxidative Damage in the Guinea Pig Hippocampal Slice

    DTIC Science & Technology

    1989-01-01

    Original Contribution OXIDATIVE DAMAGE IN THE GUINEA PIG HIPPOCAMPAL SLICE TIRRY C. Pnt.N1.iAR’ and KATIlRNN L. Nt-t-t- Physiology Department. Armed Forces...responses in the hippocampal slice isolated from the brains of guinea pigs . Electrical stim- ulation of afferents to neurons of the CA I region of...from the brains be secreted by the microglia invading a region of in- of euthanized male Hartley guinea pigs as previously Jury. ’ Another possible

  12. 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

    DTIC Science & Technology

    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.

  13. Gastric volvulus in guinea pigs: comparison with other species.

    PubMed

    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

  14. Iron does not cause arrhythmias in the guinea pig model of transfusional iron overload.

    PubMed

    Kaiser, Lana; Davis, John; Patterson, Jon; Boyd, Ryan F; Olivier, N Bari; Bohart, George; Schwartz, Kenneth A

    2007-08-01

    Cardiac events, including heart failure and arrhythmias, are the leading cause of death in patients with beta thalassemia. Although cardiac arrhythmias in humans are believed to result from iron overload, excluding confounding factors in the human population is difficult. The goal of the current study was to determine whether cardiac arrhythmias occurred in the guinea pig model of secondary iron overload. Electrocardiograms were recorded by using surgically implanted telemetry devices in guinea pigs loaded intraperitoneally with iron dextran (test animals) or dextran alone (controls). Loading occurred over approximately 6 wk. Electrocardiograms were recorded for 1 wk prior to loading, throughout loading, and for approximately 4 wk after loading was complete. Cardiac and liver iron concentrations were significantly increased in the iron-loaded animals compared with controls and were in the range of those reported for humans with thalassemia. Arrhythmias were rare in both iron-loaded and control guinea pigs. No life-threatening arrhythmias were detected in either group. These data suggest that iron alone may be insufficient to cause cardiac arrhythmias in the iron-loaded guinea pig model and that arrhythmias detected in human patients with iron overload may be the result of a complex interplay of factors.

  15. Guinea Pigs: Versatile Animals for the Classroom

    ERIC Educational Resources Information Center

    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)

  16. Combined selenium and vitamin C deficiency causes cell death in guinea pig skeletal muscle.

    PubMed

    Hill, Kristina E; Motley, Amy K; May, James M; Burk, Raymond F

    2009-03-01

    Combined antioxidant deficiencies of selenium and vitamin E or vitamin E and vitamin C in guinea pigs result in clinical illness. We hypothesized that combined selenium and vitamin C deficiency would have clinical consequences because in vitro interactions of these antioxidant nutrients have been reported. Because guinea pigs are dependent on dietary vitamin C, weanling male guinea pigs were fed selenium-deficient or control diet for 15 weeks before imposing vitamin C deficiency. Four dietary groups were formed and studied 3 weeks later: controls, vitamin C deficient, selenium deficient, and doubly deficient. Deficiencies were confirmed by determinations of glutathione peroxidase activity and vitamin C concentration in liver and skeletal muscle. Plasma creatine phosphokinase activity and liver, kidney, heart, and quadriceps histopathology were determined. Doubly deficient animals had moderately severe skeletal muscle cell death as judged by histopathology and plasma creatine phosphokinase activity of 6630 +/- 4400 IU/L (control, 70 + or - 5; vitamin C deficient, 95 + or - 110; selenium deficient, 280 + or - 250). Liver, kidney, and heart histology was normal in all groups. Muscle alpha-tocopherol levels were not depressed in the doubly deficient group, but muscle F2 isoprostane concentrations were elevated in them and correlated with markers of cell death. We conclude that combining selenium and vitamin C deficiencies in the guinea pig causes cell death in skeletal muscle that is more severe than the injury caused by selenium deficiency. The elevation of muscle F2 isoprostanes is compatible with the cell death being caused by oxidative stress.

  17. Sensitization of the Guinea Pig Myocardium through the Mucous Membrane of the Digestive Tract,

    DTIC Science & Technology

    Under certain conditions, sessile antibodies can be bound by the guinea - pig myocardium that had been sensitized by direct introduction of the allergen into the stomach. This is confirmed by the positive anaphylactic reaction in the isolated heart of animals treated in this manner, which reaction manifests itself in a modified heart rate when the isolated heart is challenged by the sensitizing allergen.

  18. [Spontaneous neoplasms in guinea pigs].

    PubMed

    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.

  19. Specific immune response genes of new inbred strains of guinea pigs.

    PubMed

    Chiba, J; Egashira, Y

    1978-01-01

    Distribution of specific immune-response (Ir) genes controlling responsiveness to synthetic polypeptide antigens, homopolymer of poly-L-lysine (PLL), copolymer of L-glutamic acid and L-alanine (GA) and copolymer of L-glutamic acid and L-tyrosine (GT), and limiting doses of 2,4-dinitrophenyl guinea pig serum albumin (DNP-GPA) was surveyed in new inbred strains of guinea pigs, JY 1, JY 2, JY 9 and JY 10, established in this Institute. The PLL gene was not found in any of the guinea pigs. The GA gene was found in JY 1 and JY 2 guinea pigs and the GT gene in all the guinea pigs. The gene controlling responsiveness to low doses (1 microgram) of DNP-GPA was found in JY 1, JY 9 and JY 10 guinea pigs. The associated (Ia) antigens was discussed.

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

    PubMed

    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

  1. A 2-D guinea pig lung proteome map

    USDA-ARS?s Scientific Manuscript database

    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...

  2. Hypervitaminosis D in Guinea Pigs with α-Mannosidosis

    PubMed Central

    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

  3. Hypervitaminosis D in guinea pigs with α-mannosidosis.

    PubMed

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

    2013-04-01

    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.

  4. A new assay system for guinea pig interferon biological activity.

    PubMed

    Yamamoto, Toshiko; Jeevan, Amminikutty; Ohishi, Kazue; Nojima, Yasuhiro; Umemori, Kiyoko; Yamamoto, Saburo; McMurray, David N

    2002-07-01

    We have developed an assay system for guinea pig interferon (IFN) based on reduction of viral cytopathic effect (CPE) in various cell lines. CPE inhibition was detected optimally in the guinea pig fibroblast cell line 104C1 infected with encephalomyocarditis virus (EMCV). The amount of biologically active guinea pig IFN was quantified by estimating viable cell numbers colorimetrically by means of a tetrazolium compound, 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt (WST-1) and 1-methoxy-5-methylphenazinium methylsulfate (PMS). WST-1 color developed until stopped by the addition of sulfuric acid. This had no effect on the colorimetric assay, and the color was stable for at least 24 h. The acid also inactivated the EMCV and, thus, eliminated the viral hazard. Inhibition of CPE activity was highly correlated with the concentration of culture supernatants from BCG-vaccinated guinea pig splenocytes stimulated in vitro with tuberculin or an immunostimulatory oligoDNA. This assay detected guinea pig IFN and human IFN-alpha, but not IFN-gamma from human, mouse, rat, pig, or dog. This assay system has proved useful for the titration of guinea pig IFN, being easy to perform, free from viral hazard, relatively species specific, highly reproducible, and inexpensive.

  5. ECG telemetry in conscious guinea pigs.

    PubMed

    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.

  6. SEA0400 fails to alter the magnitude of intracellular Ca2+ transients and contractions in Langendorff-perfused guinea pig heart.

    PubMed

    Szentandrássy, Norbert; Birinyi, Péter; Szigeti, Gyula; Farkas, Attila; Magyar, János; Tóth, András; Csernoch, László; Varró, András; Nánási, Péter P

    2008-07-01

    SEA0400 is a recently developed inhibitor of the Na+/Ca2+ exchanger (NCX) shown to suppress both forward and reverse mode operation of NCX. Present experiments were designed to study the effect of partial blockade of NCX on Ca handling and contractility in Langendorff-perfused guinea pig hearts loaded with the fluorescent Ca-sensitive dye fura-2. Left ventricular pressure and intracellular calcium concentration ([Ca2+]i) were synchronously recorded before and after cumulative superfusion with 0.3 and 1 muM SEA0400. SEA0400 caused no significant change in the systolic and diastolic values of left ventricular pressure and [Ca2+]i. Accordingly, pulse pressure and amplitude of the [Ca2+]i transient also remained unchanged in the presence of SEA0400. SEA0400 had no influence either on the time required to reach peak values of pressure and [Ca2+)]i or on half relaxation time. On the other hand, both 0.3 and 1 microM SEA0400 significantly increased the decay time constant of [Ca2+]i transients, obtained by fitting its descending limb between 30% and 90% of relaxation, from 127 +/- 7 to 165 +/- 7 and 177 +/- 14 ms, respectively (P < 0.05, n=6). In contrast to the guinea pig hearts, rat hearts responded to SEA0400 treatment with increased [Ca2+]i transients and contractility. These interspecies differences observed in the effect of SEA0400 can be explained by the known differences in calcium handling between the two species.

  7. Pig and guinea pig skin as surrogates for human in vitro penetration studies: a quantitative review.

    PubMed

    Barbero, Ana M; Frasch, H Frederick

    2009-02-01

    Both human and animal skin in vitro models are used to predict percutaneous penetration in humans. The objective of this review is a quantitative comparison of permeability and lag time measurements between human and animal skin, including an evaluation of the intra and inter species variability. We limit our focus to domestic pig and rodent guinea pig skin as surrogates for human skin, and consider only studies in which both animal and human penetration of a given chemical were measured jointly in the same lab. When the in vitro permeability of pig and human skin were compared, the Pearson product moment correlation coefficient (r) was 0.88 (P<0.0001), with an intra species average coefficient of variation of skin permeability of 21% for pig and 35% for human, and an inter species average coefficient of variation of 37% for the set of studied compounds (n=41). The lag times of pig skin and human skin did not correlate (r=0.35, P=0.26). When the in vitro permeability of guinea pig and human skin were compared, r=0.96 (P<0.0001), with an average intra species coefficient of variation of 19% for guinea pig and 24% for human, and an inter species coefficient of variation of permeability of 41% for the set of studied compounds (n=15). Lag times of guinea pig and human skin correlated (r=0.90, P<0.0001, n=12). When permeability data was not reported a factor of difference (FOD) of animal to human skin was calculated for pig skin (n=50) and guinea pig skin (n=25). For pig skin, 80% of measurements fell within the range 0.3guinea pig skin, 65% fell within that range. Both pig and guinea pig are good models for human skin permeability and have less variability than the human skin model. The skin model of choice will depend on the final purpose of the study and the compound under investigation.

  8. Immunoglobulin genomics in the guinea pig (Cavia porcellus).

    PubMed

    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 V(H) segments (94 potentially functional genes and 413 pseudogenes), 41 D(H) segments, six J(H) segments, four constant region genes (μ, γ, ε, and α), and one reverse δ remnant fragment were identified within the two scaffolds. Many V(H) 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 V(κ) (111 potentially functional genes and 238 pseudogenes), three J(κ) and one C(κ) genes. The Igλ locus spans 1,642 kb in scaffold 4 and consists of 142 V(λ) (58 potentially functional genes and 84 pseudogenes) and 11 J(λ) -C(λ) clusters. Phylogenetic analysis suggested the guinea pig's large germline V(H) 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.

  9. Sex Genotyping of Archival Fixed and Immunolabeled Guinea Pig Cochleas.

    PubMed

    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.

  10. Non-terminal blood sampling techniques in guinea pigs.

    PubMed

    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.

  11. L-dehydroascorbic acid can substitute l-ascorbic acid as dietary vitamin C source in guinea pigs.

    PubMed

    Frikke-Schmidt, Henriette; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2016-04-01

    Vitamin C deficiency globally affects several hundred million people and has been associated with increased morbidity and mortality in numerous studies. In this study, bioavailability of the oxidized form of vitamin C (l-dehydroascorbic acid or DHA)-commonly found in vitamin C containing food products prone to oxidation-was studied. Our aim was to compare tissue accumulation of vitamin C in guinea pigs receiving different oral doses of either ascorbate or DHA. In all tissues tested (plasma, liver, spleen, lung, adrenal glands, kidney, muscle, heart, and brain), only sporadic differences in vitamin C accumulation from ascorbate or DHA were observed except for the lowest dose of DHA (0.25mg/ml in the drinking water), where approximately half of the tissues had slightly yet significantly less vitamin C accumulation than from the ascorbate source. As these results contradicted data from rats, we continued to explore the ability to recycle DHA in blood, liver and intestine in guinea pigs, rats and mice. These investigations revealed that guinea pigs have similar recycling capacity in red blood cells as observed in humans, while rats and mice do not have near the same ability to reduce DHA in erythrocytes. In liver and intestinal homogenates, guinea pigs also showed a significantly higher ability to recycle DHA compared to rats and mice. These data demonstrate that DHA in guinea pigs-as in humans-is almost as effective as ascorbate as vitamin C source when it comes to taking up and storing vitamin C and further suggest that the guinea pig is superior to other rodents in modeling human vitamin C homeostasis. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Choline-modulated arsenic trioxide-induced prolongation of cardiac repolarization in Guinea pig.

    PubMed

    Sun, Hong-Li; Chu, Wen-Feng; Dong, De-Li; Liu, Yan; Bai, Yun-Long; Wang, Xiao-Hui; Zhou, Jin; Yang, Bao-Feng

    2006-04-01

    Arsenic trioxide (As(2)O(3)) has been found to be effective for relapsed or refractory acute promyelocytic leukaemia, but its clinical use is burdened by QT prolongation, Torsade de pointes tachycardias, and sudden cardiac death. The aim of the present study was to elucidate the ionic mechanisms of As(2)O(3)-induced abnormalities of cardiac electrophysiology and the therapeutic action of choline on As(2)O(3)-caused QT prolongation in guinea pig. Intravenous administration of As(2)O(3) prolonged the QT interval in a dose- and time-dependent manner in guinea pig hearts, and the QT prolongation could be modulated by choline. By using whole-cell patch clamp technique and confocal laser scanning microscopy, we found that As(2)O(3) significantly lengthened action potential duration measured at 50 and 90% of repolarization, enhanced L-type calcium currents (I(Ca-L)), inhibited delayed rectifier potassium currents (I(K)), and increased intracellular calcium concentration ([Ca(2+)](i)) in guinea pig ventricular myocytes. Choline corrected As(2)O(3)-mediated alterations of action potential duration, I(Ca-L) and [Ca(2+)](i), but had no effect on the I(K) inhibition. As(2)O(3) markedly disturbed the normal equilibrium of transmembrane currents (increasing I(Ca-L) and suppressing I(K)) in guinea pig cardiomyocyte, and induced prolongation of action potential duration, further degenerated into QT prolongation. Choline normalized QT interval abnormality and corrected lengthened action potential duration by inhibiting the elevated I(Ca-L) and [Ca(2+)](i) in ventricular myocytes during As(2)O(3) application.

  13. Glutathione oxidation unmasks proarrhythmic vulnerability of chronically hyperglycemic guinea pigs.

    PubMed

    Xie, Chaoqin; Biary, Nora; Tocchetti, Carlo G; Aon, Miguel A; Paolocci, Nazareno; Kauffman, Justin; Akar, Fadi G

    2013-04-01

    Chronic hyperglycemia in type-1 diabetes mellitus is associated with oxidative stress (OS) and sudden death. Mechanistic links remain unclear. We investigated changes in electrophysiological (EP) properties in a model of chronic hyperglycemia before and after challenge with OS by GSH oxidation and tested reversibility of EP remodeling by insulin. Guinea pigs survived for 1 mo following streptozotocin (STZ) or saline (sham) injection. A treatment group received daily insulin for 2 wk to reverse STZ-induced hyperglycemia (STZ + Ins). EP properties were measured using high-resolution optical action potential mapping before and after challenge of hearts with diamide. Despite elevation of glucose levels in STZ compared with sham-operated (P = 0.004) and STZ + Ins (P = 0.002) animals, average action potential duration (APD) and arrhythmia propensity were not altered at baseline. Diamide promoted early (<10 min) formation of arrhythmic triggers reflected by a higher arrhythmia scoring index in STZ (P = 0.045) and STZ + Ins (P = 0.033) hearts compared with sham-operated hearts. APD heterogeneity underwent a more pronounced increase in response to diamide in STZ and STZ + Ins hearts compared with sham-operated hearts. Within 30 min, diamide resulted in spontaneous incidence of ventricular tachycardia and ventricular fibrillation (VT/VF) in 3/6, 2/5, 1/5, and 0/4 STZ, STZ + Ins, sham-operated, and normal hearts, respectively. Hearts prone to VT/VF exhibited greater APD heterogeneity (P = 0.010) compared with their VT/VF-free counterparts. Finally, altered EP properties in STZ were not rescued by insulin. In conclusion, GSH oxidation enhances APD heterogeneity and increases arrhythmia scoring index in a guinea pig model of chronic hyperglycemia. Despite normalization of glycemic levels by insulin, these proarrhythmic properties are not reversed, suggesting the importance of targeting antioxidant defenses for arrhythmia suppression.

  14. Glutathione oxidation unmasks proarrhythmic vulnerability of chronically hyperglycemic guinea pigs

    PubMed Central

    Xie, Chaoqin; Biary, Nora; Tocchetti, Carlo G.; Aon, Miguel A.; Paolocci, Nazareno; Kauffman, Justin

    2013-01-01

    Chronic hyperglycemia in type-1 diabetes mellitus is associated with oxidative stress (OS) and sudden death. Mechanistic links remain unclear. We investigated changes in electrophysiological (EP) properties in a model of chronic hyperglycemia before and after challenge with OS by GSH oxidation and tested reversibility of EP remodeling by insulin. Guinea pigs survived for 1 mo following streptozotocin (STZ) or saline (sham) injection. A treatment group received daily insulin for 2 wk to reverse STZ-induced hyperglycemia (STZ + Ins). EP properties were measured using high-resolution optical action potential mapping before and after challenge of hearts with diamide. Despite elevation of glucose levels in STZ compared with sham-operated (P = 0.004) and STZ + Ins (P = 0.002) animals, average action potential duration (APD) and arrhythmia propensity were not altered at baseline. Diamide promoted early (<10 min) formation of arrhythmic triggers reflected by a higher arrhythmia scoring index in STZ (P = 0.045) and STZ + Ins (P = 0.033) hearts compared with sham-operated hearts. APD heterogeneity underwent a more pronounced increase in response to diamide in STZ and STZ + Ins hearts compared with sham-operated hearts. Within 30 min, diamide resulted in spontaneous incidence of ventricular tachycardia and ventricular fibrillation (VT/VF) in 3/6, 2/5, 1/5, and 0/4 STZ, STZ + Ins, sham-operated, and normal hearts, respectively. Hearts prone to VT/VF exhibited greater APD heterogeneity (P = 0.010) compared with their VT/VF-free counterparts. Finally, altered EP properties in STZ were not rescued by insulin. In conclusion, GSH oxidation enhances APD heterogeneity and increases arrhythmia scoring index in a guinea pig model of chronic hyperglycemia. Despite normalization of glycemic levels by insulin, these proarrhythmic properties are not reversed, suggesting the importance of targeting antioxidant defenses for arrhythmia suppression. PMID:23376824

  15. Electrophysiological effects of the aqueous extract of Averrhoa carambola L. leaves on the guinea pig heart.

    PubMed

    Vasconcelos, C M L; Araújo, M S; Conde-Garcia, E A

    2006-07-01

    This work aims to describe some electrophysiological changes promoted by the aqueous extract (AEx) from Averrhoa carambola leaves in guinea pig heart. The experiments were carried out on isolated heart or on right atrium-ventricle preparations. In 6 hearts, the extract induced many kinds of atrioventricular blocks (1st, 2nd, and 3rd degrees); increased the QT interval from 229+/-23 to 264+/-19 ms; increased the QRS complex duration from 27+/-3.1 to 59+/-11 ms, and depressed the cardiac rate from 136+/-17 to 89+/-14b pm. Furthermore, it decreased the conduction velocity of atrial impulse (17+/-3%); reduced the intraventricular pressure (86+/-6%), and increased the conduction time between the right atrium and the His bundle (27+/-6.5%). The conduction time from the His bundle to the right ventricle was not altered. Atropine sulfate did not change either the electrocardiographic parameters or the intraventricular pressure effects promoted by the A. carambola AEx. Based on these results, the popular use of such extracts should be avoided because it can promote electrical and mechanical changes in the normal heart.

  16. Histocompatibility type and immune responsiveness in random bred Hartley strain guinea pigs.

    PubMed

    Martin, W J; Ellman, L; Green, I; Benacerraf, B

    1970-12-01

    Outbred Hartley strain guinea pigs capable of responding immunologically to 2,4-dinitrophenylated poly-L-lysine were shown to display a histocompatibility specificity in common with inbred strain 2 guinea pigs. This histocompatibility specificity was not detected in guinea pigs unable to respond immunologically to DNP-PLL. The result suggests that the poly-L-lysine specific immune response gene is very closely linked or even identical with a gene determining a major histocompatibility antigen in guinea pigs.

  17. Arrangement of Renal Arteries in Guinea Pig.

    PubMed

    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.

  18. Chronic hypoxia alters maternal uterine and fetal hemodynamics in the full-term pregnant guinea pig.

    PubMed

    Turan, Sifa; Aberdeen, Graham W; Thompson, Loren P

    2017-10-01

    Placental hypoxia is associated with maternal hypertension, placental insufficiency, and fetal growth restriction. In the pregnant guinea pig, prenatal hypoxia during early gestation inhibits cytotrophoblast invasion of spiral arteries, increases maternal blood pressure, and induces fetal growth restriction. In this study the impact of chronic maternal hypoxia on fetal heart structure was evaluated using four-dimensional echocardiography with spatiotemporal image correlation and tomographic ultrasound, and uterine and umbilical artery resistance/pulsatility indexes and fetal heart function were evaluated using pulsed-wave Doppler ultrasound. Pregnant guinea pigs were exposed to normoxia ( n = 7) or hypoxia (10.5% O 2 , n = 9) at 28-30 days gestation, which was maintained until full term (65 days). At full term, fetal heart structure and outflow tracts were evaluated in the four-chamber view. Fetal heart diastolic function was assessed by E wave-to-A wave diastolic filling ratios (E/A ratios) of both ventricles and systolic function by the myocardial performance index (or Tie) of left ventricles of normoxic ( n = 21) and hypoxic ( n = 17) fetuses. There were no structural abnormalities in fetal hearts. However, hypoxia induced asymmetric fetal growth restriction and increased the placental/fetal weight compared with normoxic controls. Hypoxia increased Doppler resistance and pulsatility indexes in the uterine, but not umbilical, arteries, had no effect on the Tie index, and increased the E/A ratio in left, but not right, ventricles. Thus, prolonged hypoxia, starting at midgestation, increases uterine artery resistance and generates fetal growth restriction at full term. Furthermore, the enhanced cardiac diastolic filling with no changes in systolic function or umbilical artery resistance suggests that the fetal guinea pig systemic circulation undergoes a compensated, adaptive response to prolonged hypoxia exposure. Copyright © 2017 the American Physiological

  19. Crebanine inhibits voltage-dependent Na+ current in guinea-pig ventricular myocytes.

    PubMed

    Xiao-Shan, He; Qing, Lin; Yun-Shu, Ma; Ze-Pu, Yu

    2014-01-01

    To study the effects of crebanine on voltage-gated Na(+) channels in cardiac tissues. Single ventricular myocytes were enzymatically dissociated from adult guinea-pig heart. Voltage-dependent Na(+) current was recorded using the whole cell voltage-clamp technique. Crebanine reversibly inhibited Na(+) current with an IC50 value of 0.283 mmol·L(-1) (95% confidence range: 0.248-0.318 mmol·L(-1)). Crebanine at 0.262 mmol·L(-1) caused a negative shift (about 12 mV) in the voltage-dependence of steady-state inactivation of Na(+) current, and retarded its recovery from inactivation, but did not affect its activation curve. In addition to blocking other voltage-gated ion channels, crebanine blocked Na(+) channels in guinea-pig ventricular myocytes. Crebanine acted as an inactivation stabilizer of Na(+) channels in cardiac tissues. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

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

    DTIC Science & Technology

    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

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

    PubMed Central

    Zhang, Kun; wei Xu, 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

    2017-01-01

    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. PMID:28418930

  2. Albumin augmentation improves condition of guinea pig hearts after 4 hr of cold ischemia.

    PubMed

    Jacob, Matthias; Paul, Oliver; Mehringer, Laurenz; Chappell, Daniel; Rehm, Markus; Welsch, Ulrich; Kaczmarek, Ingo; Conzen, Peter; Becker, Bernhard F

    2009-04-15

    Major causes of death after heart transplantation are right ventricular pump failure and, chronically, cardiac allograft vasculopathy. Traditional preservation techniques focus on immediate cardioplegia, without particularly considering vascular demands. Recently, the endothelial surface layer, composed of the endothelial glycocalyx and plasma proteins, was discovered to play a major role in vascular barrier function, edema formation, and leukocyte-to-endothelial interaction. The impact of augmenting a traditional preservation solution with plasma colloid albumin was therefore investigated. Guinea pig hearts underwent cold ischemic storage for 4 hr using Bretschneider's solution (histidine-tryptophan-ketoglutarate [HTK]) without and with augmentation with 1 g% human albumin. After reperfusion, intracoronary adhesion of polymorphonuclear granulocytes, edema formation, left and right heart performance of pressure-to-volume work, and glycocalyx shedding were assessed. Intracoronary retention of leukocytes was doubled in the traditional group (36.4+/-6.6%), whereas it remained at basal values after albumin preservation (23.5+/-2.4%; P<0.05). Addition of albumin to HTK significantly decreased edema formation (wet to dry weight ratio 6.9+/-0.1 vs. 7.2+/-0.2; P<0.05). Although left heart performance was comparable, right heart cardiac output was doubled in hearts having received HTK containing albumin versus HTK alone (94+/-14 vs. 50+/-11 mL/min/g; P<0.05). Glycocalyx shedding was significantly reduced when the hearts were stored under albumin protection. Augmenting HTK with human albumin improves endothelial integrity and heart performance after 4 hr cold ischemia, because of a marked protection of the endothelial glycocalyx. For the prevention of acute and chronic graft failure, the glycocalyx might represent a new target.

  3. Guinea Pig Oxygen-Sensing and Carotid Body Functional Properties

    PubMed Central

    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

  4. Guinea Pig Oxygen-Sensing and Carotid Body Functional Properties.

    PubMed

    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.

  5. Differences in cholinergic responses from outer hair cells of rat and guinea pig.

    PubMed

    Chen, C; LeBlanc, C; Bobbin, R P

    1996-09-01

    A cholinergic receptor on outer hair cells (OHC) in guinea pig cochlea induces a K+ current when it is activated by acetylcholine and suberyldicholine but not by nicotine or muscarine (Bobbin, 1995). This unusual receptor may contain an alpha 9-subunit. However, the pharmacology of the alpha 9-subunit cloned from rat and expressed in Xenopus oocytes does not completely match that obtained for the ACh receptor in guinea pig OHCs. The response to 1,1-dimethyl-4-phenylpiperazinium (DMPP) is large in guinea pig OHCs and small in oocytes containing receptors of the alpha 9-subunit. Therefore, we compared the effects of cholinergic receptor agonists in rat and guinea pig OHCs using the whole-cell variant of the patch-clamp technique. ACh caused the largest outward K+ current in OHCs from both rat and guinea pig. Carbachol- and suberyldicholine-induced responses were similar in magnitude in OHCs of rat and guinea pig. However, DMPP produced a small response in OHCs from rat and a large response in OHCs from guinea pig. At a concentration of 100 microM, muscarine, oxotremorine M, nicotine and cytisine induced little response in guinea pig OHCs and none in rat OHCs. Results suggest that the ACh receptor on rat OHCs is similar to the alpha 9-subunit-containing receptor expressed in oocytes but different from the ACh receptor on guinea pig OHCs.

  6. A guinea pig model of Zika virus infection.

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:26010445

  9. [Ototoxicity study of netilmicin in pregnant guinea pigs and the embryo].

    PubMed

    Kawasaki, H; Yamada, Y; Takei, T; Akiyoshi, M

    1982-06-01

    The ototoxicity of netilmicin (NTL) in pregnant guinea pigs (Hartley strain) and the newborn was examined and compared to that of gentamicin (GM). NTL was administered intramuscularly at dose of 90 mg/kg to pregnant guinea pigs from day 0 to day 35 of pregnancy (the early period of pregnancy) or from day 42 of pregnancy to 1 day prior to delivery (the late period of pregnancy). GM at dose of 45 mg/kg or physiological saline were administered intramuscularly to pregnant guinea pigs during the late period of pregnancy. Four of 5 dams given NTL during the early period of pregnancy, 4 of 7 dams given TNL during the late period of pregnancy, and 2 of 4 dams given GM during the late period of pregnancy died. No pinna reflex loss in frequency range from 2 to 20 KHz were detected in mother guinea pigs treated with NTL either during the early period of pregnancy or during the late period of pregnancy. GM caused a loss of pinna reflex at 20 KHz in mother guinea pigs treated during the late period of pregnancy. Histopathologically, no damages were detected in the cochlea of mother guinea pigs treated with NTL during the early or late period of pregnancy, whereas slight scattered loss of hair cells was seen in the vestibulum. However, GM at dose of 45 mg/kg, caused an incomplete scattered loss of outer hair cells in the spiral organ, moderate atrophy of the spiral ganglion cells and a partial loss of hair cells in the vestibular organs in mother guinea pigs treated during the late period of pregnancy. In newborn guinea pig from the pregnant one treated with NTL during the early period of pregnancy, there was no loss of pinna reflex. The same results were obtained in newborn guinea pigs from the pregnant ones treated with either NTL or GM during the late period of pregnancy. No histopathological damages were detected. The present study suggests that NTL has a minimal effect on the auditory and vestibular organs in pregnant guinea pigs and the newborn and is considered to be 1

  10. Immunoglobulin Genomics in the Guinea Pig (Cavia porcellus)

    PubMed Central

    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

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

    PubMed Central

    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

  12. Brevetoxin Depresses Synaptic Transmission in Guinea Pig Hippocampal Slices

    DTIC Science & Technology

    1993-01-01

    Brevetoxin depresses synaptic transmission in guinea pig hippocampal slices. Brain Res Bull 31(1/2) 201-207, 1993.--Extracellular recordings were...obtained from area CA1 of guinea pig hippocampal slices. PbTx-3, a brevetoxin fraction isolated from the red tide dinoflagellate Ptychodiscus brevis, was

  13. Free Radicals Mediate Peroxidative Damage in Guinea Pig Hippocampus in vitro

    DTIC Science & Technology

    1989-01-01

    Peroxidative Damage in Guinea Pig Hippocampus In Vitro T.C. Pellmar, K.L. Neel, and K.H. Lee Physiology Department. Armed Forces Radiobiology Research...removed from brains of euthanized evaluate the free radical involvement in peroxidative guinea pigs . Electrical stimulation of an orthodromic damage to...Hartley guinea pigs as previously described (Pellmar, 1986, 1987). Animals were anesthetized with halothane and euthanized by cervical dislocation

  14. l-dehydroascorbic acid can substitute l-ascorbic acid as dietary vitamin C source in guinea pigs

    PubMed Central

    Frikke-Schmidt, Henriette; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2015-01-01

    Vitamin C deficiency globally affects several hundred million people and has been associated with increased morbidity and mortality in numerous studies. In this study, bioavailability of the oxidized form of vitamin C (l-dehydroascorbic acid or DHA)—commonly found in vitamin C containing food products prone to oxidation—was studied. Our aim was to compare tissue accumulation of vitamin C in guinea pigs receiving different oral doses of either ascorbate or DHA. In all tissues tested (plasma, liver, spleen, lung, adrenal glands, kidney, muscle, heart, and brain), only sporadic differences in vitamin C accumulation from ascorbate or DHA were observed except for the lowest dose of DHA (0.25 mg/ml in the drinking water), where approximately half of the tissues had slightly yet significantly less vitamin C accumulation than from the ascorbate source. As these results contradicted data from rats, we continued to explore the ability to recycle DHA in blood, liver and intestine in guinea pigs, rats and mice. These investigations revealed that guinea pigs have similar recycling capacity in red blood cells as observed in humans, while rats and mice do not have near the same ability to reduce DHA in erythrocytes. In liver and intestinal homogenates, guinea pigs also showed a significantly higher ability to recycle DHA compared to rats and mice. These data demonstrate that DHA in guinea pigs—as in humans—is almost as effective as ascorbate as vitamin C source when it comes to taking up and storing vitamin C and further suggest that the guinea pig is superior to other rodents in modeling human vitamin C homeostasis. PMID:26609560

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

    PubMed Central

    Kleven, Gale A; Joshi, Prianca

    2016-01-01

    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. PMID:27025807

  16. Brain and visceral involvement during congenital cytomegalovirus infection of guinea pigs.

    PubMed

    Griffith, B P; Lucia, H L; Hsiung, G D

    1982-06-01

    The virologic and histologic characteristics of congenital cytomegalovirus infection (CMV) were defined in 65 neonatal guinea pigs born from 27 mothers infected pregnancy. Infectious virus or tissue lesions were present in 54% of the neonates tested. Guinea pig CMV was detected most often in the salivary glands (72%) and spleen (33%) of infected guinea pigs. Less frequently, virus was also detected in the brain, lung, pancreas and liver. Tissue lesions were most frequently observed in the brain and kidney, but also occurred in the salivary glands, liver, pancreas, thymus and spleen. The histopathology was identical to that observed in infants with congenital CMV infection. Infectious virus and histopathology were present in newborn guinea pigs born from mothers infected at any time during gestation. Newborns from mothers infected during early stages of gestation and virus present most frequently in the salivary glands, whereas offspring of mothers infected in late pregnancy had virus present in several tissues. Acute maternal guinea pig CMV infection produced generalized CMV infection of the offspring which was followed by persistent infection in neonatal salivary glands. Lesions remained present in several neonatal tissues including the brain. The long term consequences of such lesions in affected guinea pigs remain to be determined. The results of the study emphasize the similarities between human congenital CMV infection and congenital guinea pig CMV infection, thereby underlining the utility of this animal model as a means of understanding human congenital CMV infection.

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

    PubMed

    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.

  18. Activation of apoptotic processes during transition from hypertrophy to heart failure in guinea pigs.

    PubMed

    Sharma, A K; Dhingra, S; Khaper, N; Singal, P K

    2007-09-01

    Changes in oxidative stress and apoptotic process were studied during the progression of a compensated hypertrophy to a decompensated heart failure in guinea pigs. Banding of the ascending aorta resulted in heart hypertrophy. At 10 wk, ventricle-to-body weight ratio and thickness of the interventricular septum as well as the left ventricular wall were increased significantly. Although fractional shortening and ejection fraction were decreased, there were no signs of heart failure. Furthermore, there was no increase in wet-to-dry weight ratios for the lungs and liver at this stage. However, at 20 wk, heart failure was characterized by a significant depression in heart function as indicated by a decrease in fractional shortening, and ejection fraction and a lesser increase in wall thickness from diastole to systole. Animals also showed clinical signs of heart failure, and the wet-to-dry weight ratios of the lungs and liver were significantly higher. Cardiomyocyte oxidative stress was significantly higher in the 20-wk aortic-banded group. The ratio of Bax to Bcl-xl showed an increase at 10 wk, and there was a further increase at 20 wk. Mitochondrial membrane potential in the aortic-banded animals was significantly decreased at 10 and 20 wk. Cytochrome c levels were higher in the cytosol compared with the mitochondria, leading to a considerable increase in the expression of p17 subunit of caspase-3. At 20 wk, both early and late stages of apoptosis were observed in isolated cardiomyocytes. It is suggested that an increase in oxidative stress initiates mitochondrial death pathway during the hypertrophic stage, leading to apoptosis and heart failure at a later stage.

  19. Electrophysiological effects of Chinese medicine Shen song Yang xin (SSYX) on Chinese miniature swine heart and isolated guinea pig ventricular myocytes.

    PubMed

    Feng, Li; Gong, Jing; Jin, Zhen-yi; Li, Ning; Sun, Li-ping; Wu, Yi-ling; Pu, Jie-lin

    2009-07-05

    Shen song Yang xin (SSYX) is a compound of Chinese medicine with the effect of increasing heart rate (HR). This study aimed to evaluate its electrophysiological properties at heart and cellular levels. The Chinese miniature swines were randomly assigned to two groups, administered with SSYX or placebo for 4 weeks (n = 8 per group). Cardiac electrophysiological study (EPS) was performed before and after drug administration. The guinea pig ventricular myocytes were enzymatically isolated and whole cell voltage-clamp technique was used to evaluate the effect of SSYX on cardiac action potential (AP). SSYX treatment accelerated the HR from (141.8 +/- 36.0) beats per minute to (163.0 +/- 38.0) beats per minute (P = 0.013) without changing the other parameters in surface electrocardiogram. After blockage of the autonomic nervous system with metoprolol and atropin, SSYX had no effect on intrinsic HR (IHR), but decreased corrected sinus node recovery time (CSNRT) and sinus atrium conducting time (SACT). Intra cardiac EPS showed that SSYX significantly decreased the A-H and A-V intervals as well as shortened the atrial (A), atrioventricular node (AVN) and ventricular (V) effective refractory period (ERP). In isolated guinea pig ventricular myocytes, the most obvious effect of SSYX on action potential was a shortening of the action potential duration (APD) without change in shape of action potential. The shortening rates of APD(30), APD(50) and APD(90) were 19.5%, 17.8% and 15.3%, respectively. The resting potential (Em) and the interval between the end of APD(30) and APD(90) did not significantly change. The present study demonstrates that SSYX increases the HR and enhances the conducting capacity of the heart in the condition of the intact autonomic nervous system. SSYX homogenously decreases the ERP of the heart and shortens the APD of the myocytes, suggesting its antiarrhythmic effect without proarrhythmia.

  20. Toluene-induced hearing loss in the guinea pig.

    PubMed

    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.

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

    PubMed Central

    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. PMID:25821613

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

    PubMed

    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.

  3. The Guinea Pigs of a Problem-Based Learning Curriculum

    ERIC Educational Resources Information Center

    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…

  4. β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure.

    PubMed

    Wang, Yao; Yuan, Jiamin; Qian, Zhiyong; Zhang, Xiwen; Chen, Yanhong; Hou, Xiaofeng; Zou, Jiangang

    2015-01-08

    β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways.

  5. β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure

    PubMed Central

    Wang, Yao; Yuan, Jiamin; Qian, Zhiyong; Zhang, Xiwen; Chen, Yanhong; Hou, Xiaofeng; Zou, Jiangang

    2015-01-01

    β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways. PMID:25567365

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

    PubMed

    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.

  7. Natural infection of guinea pigs exposed to patients with highly drug-resistant tuberculosis

    PubMed Central

    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

  8. SOME HISTOCHEMICAL RESPONSES OF GUINEA PIG TISSUES TO COLD,

    DTIC Science & Technology

    Guinea pigs weighing approximately 300 gm were kept in a cold room, held at 6C, for two weeks. Various organs were then studied histochemically...Liver glycogen is rapidly used up in cold-exposed guinea pigs . The fate of liver lipids is unknown. Lipids in the cortex of the adrenals appear to

  9. Guinea pig complement potently measures vibriocidal activity of human antibodies in response to cholera vaccines.

    PubMed

    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.

  10. Molecular cloning, expression, and in silico structural analysis of guinea pig IL-17.

    PubMed

    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.

  11. Hairless pigmented guinea pigs: a new model for the study of mammalian pigmentation.

    PubMed

    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.

  12. Interaction of Tacrine at M1 and M2 Cholinoceptors in Guinea Pig Brain

    DTIC Science & Technology

    1993-01-01

    NUMBERS cholinoceptors in Guinea Pig Brain 6 AUTHOR Maria Szilagyi and Wai-Man Lau 7 FOAMING ORG KES/eADORENESS DEFENCE SCIENCE AND S PEFORMING Wa REPO...rat heart muscarinic receptors using 3 Freeman SE, Lau W-M, Szilagyi M: M2 muscarinic receptors. Neurosci the new M2 selective antagonist Blockade of

  13. Electrophysiological and mechanical effects of caffeic acid phenethyl ester, a novel cardioprotective agent with antiarrhythmic activity, in guinea-pig heart.

    PubMed

    Chang, Gwo-Jyh; Chang, Chi-Jen; Chen, Wei-Jan; Yeh, Yung-Hsin; Lee, Hsiao-Yu

    2013-02-28

    Caffeic acid phenethyl ester (CAPE) is an active component of propolis that exhibits cardioprotective and antiarrhythmic effects. The detailed mechanisms underlying these effects, however, are not entirely understood. The aim of this study was to elucidate the electromechanical effects of CAPE in guinea-pig cardiac preparations. Intracardiac electrograms, left ventricular (LV) pressure, and the anti-arrhythmic efficacy were determined using isolated hearts. Action potentials of papillary muscles were assessed with microelectrodes, Ca(2+) transients were measured by fluorescence, and ion fluxes were measured by patch-clamp techniques. In a perfused heart model, CAPE prolonged the atrio-ventricular conduction interval, the Wenckebach cycle length, and the refractory periods of the AV node and His-Purkinje system, while shortening the QT interval. CAPE reduced the occurrence of reperfusion-induced ventricular fibrillation and decreased LV pressure in isolated hearts. In papillary muscles, CAPE shortened the action potential duration and reduced both the maximum upstroke velocity and contractile force. In fura-2-loaded single ventricular myocytes, CAPE decreased cell shortening and the Ca(2+) transient amplitude. Patch-clamp experiments revealed that CAPE produced a use-dependent decrease in L-type Ca(2+) current (ICa,L) (IC50=1.1 μM) and Na(+) current (INa) (IC50=0.43 μM), caused a negative-shift of the voltage-dependent inactivation and a delay of recovery from inactivation. CAPE decreased the delayed outward K(+) current (IK) slightly, without affecting the inward rectifier K(+) current (IK1). These results suggest that the preferential inhibition of Ca(2+) inward and Na(+) inward currents by CAPE may induce major electromechanical alterations in guinea-pig cardiac preparations, which may underlie its antiarrhythmic action. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Influence of lorcainide on microsomal Na+, K(+)-ATPase in guinea-pig isolated heart preparations.

    PubMed Central

    Almotrefi, A. A.; Dzimiri, N.

    1991-01-01

    1. The effects of lorcainide on the myocardial Mg2(+)-dependent, Na+ and K(+)-activated adenosine triphosphatase (Na+, K(+)-ATPase) were compared in guinea-pig heart preparations with those of ouabain, a specific inhibitor of the enzyme activity. 2. Both ouabain and lorcainide inhibited the microsomal Na+, K(+)-ATPase activity in a concentration-dependent fashion. Their inhibitory effective ranges were 0.05-100 microM and 0.15-125 microM, respectively, and the concentrations for half maximal inhibition (IC50 values) were 2.1 +/- 0.3 and 33.5 +/- 7.3 microM, respectively. 3. In a second series of experiments, the combined effects of the two drugs on the enzyme activity were studied. In these experiments, lorcainide produced a concentration-dependent potentiation of the inhibitory effects of ouabain on Na+, K(+)-ATPase activity. 4. The present study demonstrates that lorcainide is a potent inhibitor of myocardial Na+, K(+)-ATPase. PMID:1849773

  15. In Vitro Response of Guinea Pig Peritoneal Macrophages to Legionella pneumophila

    DTIC Science & Technology

    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

  16. Usefulness and limitations of various guinea-pig test methods in detecting human skin sensitizers-validation of guinea-pig tests for skin hypersensitivity.

    PubMed

    Marzulli, F; Maguire, H C

    1982-02-01

    Several guinea-pig predictive test methods were evaluated by comparison of results with those obtained with human predictive tests, using ten compounds that have been used in cosmetics. The method involves the statistical analysis of the frequency with which guinea-pig tests agree with the findings of tests in humans. In addition, the frequencies of false positive and false negative predictive findings are considered and statistically analysed. The results clearly demonstrate the superiority of adjuvant tests (complete Freund's adjuvant) in determining skin sensitizers and the overall superiority of the guinea-pig maximization test in providing results similar to those obtained by human testing. A procedure is suggested for utilizing adjuvant and non-adjuvant test methods for characterizing compounds as of weak, moderate or strong sensitizing potential.

  17. Characteristic plethysmographic findings in a guinea pig model of COPD.

    PubMed

    Ramírez-Ramírez, Edgar; Torres-Ramírez, Armando; Alquicira-Mireles, Jesús; Cañavera-Constantino, Abraham; Segura-Medina, Patricia; Montaño-Ramírez, Martha; Ramos-Abraham, Carlos; Vargas, Mario H; Arreola-Ramírez, José Luis

    2017-03-01

    Long-term exposure to cigarette smoke generates chronic obstructive pulmonary disease (COPD) in guinea pigs, but a comprehensive evaluation of changes in lung function, as assessed by barometric whole body plethysmography (WBP), is lacking. Female guinea pigs were exposed to the smoke of 20 cigarettes/day, 5 days/week, during 10 weeks (COPD group, n = 8), and were compared with unexposed female guinea pigs of the same age (control group, n = 8). WBP was performed in both groups, followed by lung histology. At the end of the exposure period, guinea pigs in the COPD group had higher respiratory frequency, while duty cycle (Ti/Ttot) was unaffected. There was a trend toward minute ventilation (MV) and expiratory flow at the mid-tidal volume (EF50) to be higher in the COPD group. Enhanced pause (Penh) was lower, while time of braking (TB) and time to PEF relative to Te (Rpef) were higher in the COPD group. All guinea pigs exposed to tobacco smoke developed emphysematous lesions in their lungs and gained less body weight than controls. In this COPD model, exposure to cigarette smoke produced changes in WBP characterized by a shallow breathing pattern with decreased Penh and a trend toward increasing EF50 (probably due to decreased elastic recoil), increased TB (suggesting dynamic laryngeal narrowing), and a trend of increasing MV (probably due to a higher metabolic rate). Many of these functional changes resemble those observed in patients with COPD and corroborate the suitability of this guinea pig model for the study of COPD.

  18. RELATIONSHIP BETWEEN BEHAVIORAL AND AUTONOMIC THERMOREGULATION IN THE GUINEA PIG

    EPA Science Inventory

    The study was conducted to correlate the preferred thermal environment of the unrestrained guinea pig with the activity of its thermoregulatory effectors when maintained under a wide range of ambient temperatures (Ta). Eight male guinea pigs were used in a series of experiments o...

  19. An ecologically relevant guinea pig model of fetal behavior.

    PubMed

    Bellinger, S A; Lucas, D; Kleven, G A

    2015-04-15

    The laboratory guinea pig, Cavia porcellus, shares with humans many similarities during pregnancy and prenatal development, including precocial offspring and social dependence. These similarities suggest the guinea pig as a promising model of fetal behavioral development as well. Using innovative methods of behavioral acclimation, fetal offspring of female IAF hairless guinea pigs time mated to NIH multicolored Hartley males were observed longitudinally without restraint using noninvasive ultrasound at weekly intervals across the 10 week gestation. To ensure that the ultrasound procedure did not cause significant stress, salivary cortisol was collected both before and after each observation. Measures of fetal spontaneous movement and behavioral state were quantified from video recordings from week 3 through the last week before birth. Results from prenatal quantification of Interlimb Movement Synchrony and state organization reveal guinea pig fetal development to be strikingly similar to that previously reported for other rodents and preterm human infants. Salivary cortisol readings taken before and after sonography did not differ at any observation time point. These results suggest this model holds translational promise for studying the prenatal mechanisms of neurobehavioral development, including those that may result from adverse events. Because the guinea pig is a highly social mammal with a wide range of socially oriented vocalizations, this model may also have utility for studying the prenatal origins and trajectories of developmental disabilities with social-emotional components, such as autism. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. An ecologically relevant guinea pig model of fetal behavior

    PubMed Central

    Bellinger, S. A.; Lucas, D.; Kleven, G. A.

    2015-01-01

    The laboratory guinea pig, Cavia porcellus, shares with humans many similarities during pregnancy and prenatal development, including precocial offspring and social dependence. These similarities suggest the guinea pig as a promising model of fetal behavioral development as well. Using innovative methods of behavioral acclimation, fetal offspring of female IAF hairless guinea pigs time mated to NIH multi-colored Hartley males were observed longitudinally without restraint using noninvasive ultrasound at weekly intervals across the 10 week gestation. To insure that the ultrasound procedure did not cause significant stress, salivary cortisol was collected both before and after each observation. Measures of fetal spontaneous movement and behavioral state were quantified from video recordings from week 3 through the last week before birth. Results from prenatal quantification of Interlimb Movement Synchrony and state organization reveal guinea pig fetal development to be strikingly similar to that previously reported for other rodents and preterm human infants. Salivary cortisol readings taken before and after sonography did not differ at any observation time point. These results suggest this model holds translational promise for studying the prenatal mechanisms of neurobehavioral development, including those that may result from adverse events. Because the guinea pig is a highly social mammal with a wide range of socially oriented vocalizations, this model may also have utility for studying the prenatal origins and trajectories of developmental disabilities with social-emotional components, such as autism. PMID:25655512

  1. Guinea pig models of asthma.

    PubMed

    McGovern, Alice E; Mazzone, Stuart B

    2014-12-01

    Described in this unit are methods for establishing guinea pig models of asthma. Sufficient detail is provided to enable investigators to study bronchoconstriction, cough, airway hyperresponsiveness, inflammation, and remodeling. Copyright © 2014 John Wiley & Sons, Inc.

  2. Cloning and characterization of the hamster and guinea pig nicotinic acid receptors.

    PubMed

    Torhan, April Smith; Cheewatrakoolpong, Boonlert; Kwee, Lia; Greenfeder, Scott

    2007-09-01

    In this study, we present the identification and characterization of hamster and guinea pig nicotinic acid receptors. The hamster receptor shares approximately 80-90% identity with the nucleotide and amino acid sequences of human, mouse, and rat receptors. The guinea pig receptor shares 76-80% identity with the nucleotide and amino acid sequences of these other species. [(3)H]nicotinic acid binding affinity at guinea pig and hamster receptors is similar to that in human (dissociation constant = 121 nM for guinea pig, 72 nM for hamster, and 74 nM for human), as are potencies of nicotinic acid analogs in competition binding studies. Inhibition of forskolin-stimulated cAMP production by nicotinic acid and related analogs is also similar to the activity in the human receptor. Analysis of mRNA tissue distribution for the hamster and guinea pig nicotinic acid receptors shows expression across a number of tissues, with higher expression in adipose, lung, skeletal muscle, spleen, testis, and ovary.

  3. [The phrenic nerve in the guinea pig (Cavia porcellus L. 1756)].

    PubMed

    Salgado, M C; Orsi, A M; Vicentini, C A; Mello Dias, S

    1983-01-01

    The aim of the present study was the ascertain in the mode of origin of the phrenic nerve and to provide a morphological basis for experimental studies of this nerve in the guinea pig. In sketches made of the dissections, in 10 male and 10 female guinea pigs adults, the modes of origin of the phrenic roots were demonstrated to arise from the fourth to the seventh cervical nerves. Four types of origin could be distinguished. The phrenic nerve of guinea pig has three or four roots.

  4. Effect of pregnancy on experimental allergic encephalomyelitis in guinea pigs and rats.

    PubMed

    Keith, A B

    1978-10-01

    Pregnancy in guinea pigs and rats exerted a suppressive influence on the development of experimental allergic encephalomyelitis (EAE). Early or late stages in pregnancy had a similar effect in delaying the onset of EAE, a greater delay being observed in pregnant guinea pigs with full term pregnancies. However, the suppressive effect in the majority of animals was only temporary and when they developed the disease the clinical severity was then similar to that in the controls. Clinical symptoms of EAE, in guinea pigs that did not maintain their pregnancy, developed soon after abortion or resorption and these animals deteriorated rapidly. Histologic lesions were markedly enhanced with prominent demyelination in the majority of guinea pigs that were sensitised when pregnant.

  5. Behavioural characterisation of the alpha-mannosidosis guinea pig.

    PubMed

    Robinson, A J; Crawley, A C; Auclair, D; Weston, P F; Hirte, C; Hemsley, K M; Hopwood, J J

    2008-01-25

    alpha-Mannosidosis is a lysosomal storage disorder resulting from a functional deficiency of the lysosomal enzyme alpha-mannosidase. This deficiency results in the accumulation of various oligosaccharides in the lysosomes of affected individuals, causing somatic pathology and progressive neurological degeneration that results in cognitive deficits, ataxia, and other neurological symptoms. We have a naturally occurring guinea pig model of this disease which exhibits a deficiency of lysosomal alpha-mannosidase and has a similar clinical presentation to human alpha-mannosidosis. Various tests were developed in the present study to characterise and quantitate the loss of neurological function in alpha-mannosidosis guinea pigs and to follow closely the progression of the disease. General neurological examinations showed progressive differences in alpha-mannosidosis animals from approximately 1 month of age. Significant differences were observed in hind limb gait width from 2 months of age and significant cognitive (memory and learning) deficits were observed from 3 months of age. Evoked response tests showed an increase in somatosensory P1 peak latency in alpha-mannosidosis guinea pigs from approximately 2 months of age, as well as progressive hearing loss using auditory brainstem evoked responses. The alpha-mannosidosis guinea pig therefore appears to exhibit many of the characteristics of the human disease, and will be useful in evaluating therapies for treatment of central nervous system pathology.

  6. Guinea Pig as a Model to Study the Carotid Body Mediated Chronic Intermittent Hypoxia Effects.

    PubMed

    Docio, Inmaculada; Olea, Elena; Prieto-LLoret, Jesus; Gallego-Martin, Teresa; Obeso, Ana; Gomez-Niño, Angela; Rocher, Asuncion

    2018-01-01

    promoted cardiovascular adjustments by increasing heart rate and mean arterial blood pressure without cardiac ventricle hypertrophy. In conclusion, CIH does not sensitize CB chemoreceptor response to hypoxia but promotes cardiovascular adjustments probably not mediated by the CB. Guinea pigs could represent an interesting model to elucidate the mechanisms that underlie the long-term effects of CIH exposure to provide evidence for the role of the CB mediating pathological effects in sleep apnea diseases.

  7. Demonstration of a specific C3a receptor on guinea pig platelets

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fukuoka, Y.; Hugli, T.E.

    1988-05-15

    Guinea pig platelets reportedly contain receptors specific for the anaphylatoxin C3a based on both ligand-binding studies and functional responses. A portion of the human 125I-C3a that binds to guinea pig platelets is competitively displaced by excess unlabeled C3a; however, the majority of ligand uptake was nonspecific. Uptake of 125I-C3a by guinea pig platelets is maximal in 1 min, and stimulation of guinea pig platelets by thrombin, ADP, or the Ca2+ ionophore A23187 showed little influence on binding of the ligand. Scatchard analysis indicated that approximately 1200 binding sites for C3a exist per cell with an estimated Kd of 8 xmore » 10(-10) M. Human C3a des Arg also binds to guinea pig platelets, but Scatchard analysis indicated that no specific binding occurred. Because the ligand-binding studies were complicated by high levels of nonspecific uptake, we attempted to chemically cross-link the C3a molecule to a specific component on the platelet surface. Cross-linkage of 125I-C3a to guinea pig platelets with bis(sulfosuccinimidyl)suberate revealed radioactive complexes at 105,000 and 115,000 m.w. on SDS-PAGE gels by autoradiographic analysis. In the presence of excess unlabeled C3a, complex formation was inhibited. No cross-linkage could be demonstrated between the inactive 125I-C3a des Arg and the putative C3a-R on guinea pig platelets. Human C3a, but not C3a des Arg induces serotonin release and aggregation of the guinea pig platelets. Human C3a was unable to induce either serotonin release or promote aggregation of human platelets. Uptake of human 125I-C3a by human platelets was not saturable, and Scatchard analysis was inconclusive. Attempts to cross-link 125I-C3a to components on the surface of human platelets also failed to reveal a ligand-receptor complex. Therefore, we conclude that guinea pig platelets have specific surface receptors to C3a and that human platelets appear devoid of receptors to the anaphylatoxin.« less

  8. 9 CFR 3.36 - Primary enclosures used to transport live guinea pigs and hamsters.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... live guinea pigs and hamsters. 3.36 Section 3.36 Animals and Animal Products ANIMAL AND PLANT HEALTH..., Care, Treatment, and Transportation of Guinea Pigs and Hamsters Transportation Standards § 3.36 Primary enclosures used to transport live guinea pigs and hamsters. No person subject to the Animal Welfare...

  9. 9 CFR 3.36 - Primary enclosures used to transport live guinea pigs and hamsters.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... live guinea pigs and hamsters. 3.36 Section 3.36 Animals and Animal Products ANIMAL AND PLANT HEALTH..., Care, Treatment, and Transportation of Guinea Pigs and Hamsters Transportation Standards § 3.36 Primary enclosures used to transport live guinea pigs and hamsters. No person subject to the Animal Welfare...

  10. 9 CFR 3.36 - Primary enclosures used to transport live guinea pigs and hamsters.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... live guinea pigs and hamsters. 3.36 Section 3.36 Animals and Animal Products ANIMAL AND PLANT HEALTH..., Care, Treatment, and Transportation of Guinea Pigs and Hamsters Transportation Standards § 3.36 Primary enclosures used to transport live guinea pigs and hamsters. No person subject to the Animal Welfare...

  11. 9 CFR 3.36 - Primary enclosures used to transport live guinea pigs and hamsters.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... live guinea pigs and hamsters. 3.36 Section 3.36 Animals and Animal Products ANIMAL AND PLANT HEALTH..., Care, Treatment, and Transportation of Guinea Pigs and Hamsters Transportation Standards § 3.36 Primary enclosures used to transport live guinea pigs and hamsters. No person subject to the Animal Welfare...

  12. 9 CFR 3.36 - Primary enclosures used to transport live guinea pigs and hamsters.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... live guinea pigs and hamsters. 3.36 Section 3.36 Animals and Animal Products ANIMAL AND PLANT HEALTH..., Care, Treatment, and Transportation of Guinea Pigs and Hamsters Transportation Standards § 3.36 Primary enclosures used to transport live guinea pigs and hamsters. No person subject to the Animal Welfare...

  13. Expressed sequence tag analysis of guinea pig (Cavia porcellus) eye tissues for NEIBank

    PubMed Central

    Simpanya, Mukoma F.; Wistow, Graeme; Gao, James; David, Larry L.; Giblin, Frank J.

    2008-01-01

    Purpose To characterize gene expression patterns in guinea pig ocular tissues and identify orthologs of human genes from NEIBank expressed sequence tags. Methods RNA was extracted from dissected eye tissues of 2.5-month-old guinea pigs to make three unamplified and unnormalized cDNA libraries in the pCMVSport-6 vector for the lens, retina, and eye minus lens and retina. Over 4,000 clones were sequenced from each library and were analyzed using GRIST for clustering and gene identification. Lens crystallin EST data were validated using two-dimensional electrophoresis (2-DE), matrix assisted laser desorption (MALDI), and electrospray ionization mass spectrometry (ESIMS). Results Combined data from the three libraries generated a total of 6,694 distinctive gene clusters, with each library having between 1,000 and 3,000 clusters. Approximately 60% of the total gene clusters were novel cDNA sequences and had significant homologies to other mammalian sequences in GenBank. Complete cDNA sequences were obtained for many guinea pig lens proteins, including αA/αAinsert-, γN-, and γS-crystallins, lengsin and GRIFIN. The ratio of αA- to αB-crystallin on 2-DE gels was 8: 1 in the lens nucleus and 6.5: 1 in the cortex. Analysis of ESTs, genome sequence, and proteins (by MALDI), did not reveal any evidence for the presence of γD-, γE-, and γF-crystallin in the guinea pig. Predicted masses of many guinea pig lens crystallins were confirmed by ESIMS analysis. For the retina, orthologs of human phototransduction genes were found, such as Rhodopsin, S-antigen (Sag, Arrestin), and Transducin. The guinea-pig ortholog of NRL, a key rod photoreceptor-specific transcription factor, was also represented in EST data. In the ‘rest-of-eye’ library, the most abundant transcripts included decorin and keratin 12, representative of the cornea. Conclusions Genomic analysis of guinea pig eye tissues provides sequence-verified clones for future studies. Guinea pig orthologs of many human

  14. Mechanism of resveratrol-induced relaxation of the guinea pig fundus.

    PubMed

    Tsai, Ching-Chung; Tey, Shu-Leei; Lee, Ming-Che; Liu, Ching-Wen; Su, Yu-Tsun; Huang, Shih-Che

    2018-04-01

    Resveratrol is a polyphenolic compound that can be isolated from plants and also is a constituent of red wine. Resveratrol induces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. Impaired gastric accommodation plays an important role in functional dyspepsia and fundic relaxation and is a therapeutic target of functional dyspepsia. Although drugs for fundic relaxation have been developed, these types of drugs are still rare. The purpose of this study was to investigate the relaxant effects of resveratrol in the guinea pig fundus. We studied the relaxant effects of resveratrol in the guinea pig fundus. In addition, we investigated the mechanism of resveratrol-induced relaxation on the guinea pig fundus by using tetraethylammonium (a non-selective potassium channel blocker), apamine (a selective inhibitor of the small conductance calcium-activated potassium channel), iberiotoxin (an inhibitor of large conductance calcium-activated potassium channels), glibenclamide (an ATP-sensitive potassium channel blocker), KT 5720 (a cAMP-dependent protein kinase A inhibitor), KT 5823 (a cGMP-dependent protein kinase G inhibitor), NG-nitro-L-arginine (a competitive inhibitor of nitric oxide synthase), tetrodotoxin (a selective neuronal Na + channel blocker), ω-conotoxin GVIA (a selective neuronal Ca 2+ channel blocker) and G-15 (a G-protein coupled estrogen receptor antagonist). The results of this study showed that resveratrol has potent and dose-dependent relaxant effects on the guinea pig fundic muscle. In addition, the results showed that resveratrol-induced relaxation of the guinea pig fundus occurs through nitric oxide and ATP-sensitive potassium channels. This study provides the first evidence concerning the relaxant effects of resveratrol in the guinea pig fundic muscle strips. Furthermore, resveratrol may be a potential drug to relieve gastrointestinal dyspepsia. Copyright © 2018 Elsevier GmbH. All rights reserved.

  15. Calcium antagonistic activity of Bacopa monniera in guinea-pig trachea.

    PubMed

    Channa, Shabana; Dar, Ahsana

    2012-01-01

    To demonstrate the calcium antagonistic property of ethanol extract of Bacopa monniera in guinea-pig trachea. The dose response curves of CaCl(2) (1 × 10(-5) to 1 × 10(-1) M) were constructed in the absence and presence of ethanol extract of Bacopa monniera (100, 500 and 700 μg/ml) or nifedipine (1 × 10(-6) M) in guinea-pig trachea in calcium free high K(+)-MOPS-PSS (3-(N-morpholino)-propanesulphonic acid physiological salt solution). The data was analyzed by ANOVA followed by least significant difference test or by Student's 't' test for unequal variance when appropriate. A probability of at least P < 0.05 was considered statistically significant. The plant extract (500 and 700 μg/ml) significantly (P < 0.05) depressed and shifted the calcium concentration-response curves (1 × 10(-3)- 1 × 10(-1) M) to rightward similar to that of nifedipine. Bacopa monniera extract exhibited calcium channel blocking activity in guinea-pig tracheal smooth muscles that may rationalize its relaxant action on guinea-pig trachea and its traditional use in respiratory disorders.

  16. Comparative analysis of detection methods for congenital cytomegalovirus infection in a Guinea pig model.

    PubMed

    Park, Albert H; Mann, David; Error, Marc E; Miller, Matthew; Firpo, Matthew A; Wang, Yong; Alder, Stephen C; Schleiss, Mark R

    2013-01-01

    To assess the validity of the guinea pig as a model for congenital cytomegalovirus (CMV) infection by comparing the effectiveness of detecting the virus by real-time polymerase chain reaction (PCR) in blood, urine, and saliva. Case-control study. Academic research. Eleven pregnant Hartley guinea pigs. Blood, urine, and saliva samples were collected from guinea pig pups delivered from pregnant dams inoculated with guinea pig CMV. These samples were then evaluated for the presence of guinea pig CMV by real-time PCR assuming 100% transmission. Thirty-one pups delivered from 9 inoculated pregnant dams and 8 uninfected control pups underwent testing for guinea pig CMV and for auditory brainstem response hearing loss. Repeated-measures analysis of variance demonstrated no statistically significantly lower weight for the infected pups compared with the noninfected control pups. Six infected pups demonstrated auditory brainstem response hearing loss. The sensitivity and specificity of the real-time PCR assay on saliva samples were 74.2% and 100.0%, respectively. The sensitivity of the real-time PCR on blood and urine samples was significantly lower than that on saliva samples. Real-time PCR assays of blood, urine, and saliva revealed that saliva samples show high sensitivity and specificity for detecting congenital CMV infection in guinea pigs. This finding is consistent with recent screening studies in human newborns. The guinea pig may be a good animal model in which to compare different diagnostic assays for congenital CMV infection.

  17. Protective effect of taurine on cardiotoxicity of the bufadienolides derived from toad (Bufo bufo gargarizans Canto) venom in guinea-pigs in vivo and in vitro.

    PubMed

    Ma, Hongyue; Jiang, Jiejun; Zhang, Junfeng; Zhou, Jing; Ding, Anwei; Lv, Gaohong; Xu, Huiqin; You, Fenqiang; Zhan, Zhen; Duan, Jinao

    2012-01-01

    In China, toad venom is an anti-inflammatory agent used in small doses for the treatment of various types of inflammation. Bufadienolides are cardioactive steroids responsible for the anti-inflammatory actions of toad venom. We studied the protective effect of taurine on the cardiotoxicity of bufadienolides in guinea-pigs. Bufadienolides (8 mg/kg) caused arrhythmias, cardiac dysfunction and death in guinea-pigs. Pretreatment with taurine (150, 300 mg/kg) significantly prevented bufadienolide-induced cardiotoxicity and reduced the mortality in vivo. Taurine markedly increased the cumulative doses of bufadienolides and resibufogenin required for lethal arrhythmia in ex vivo isolated guinea-pig heart. Taurine did not compromise the anti-inflammatory activity of the bufadienolides on concanavalin-A-stimulated proliferation of guinea-pig splenocytes in vitro. These data indicate that taurine can prevent bufadienolide-induced cardiotoxicity and could be a novel antidote in combination with bufadienolide therapy.

  18. Infection of guinea pigs with vesicular stomatitis New Jersey virus Transmitted by Culicoides sonorensis (Diptera: Ceratopogonidae).

    PubMed

    Pérez De León, Adalberto A; O'Toole, Donal; Tabachnick, Walter J

    2006-05-01

    Intrathoracically inoculated Culicoides sonorensis Wirth & Jones were capable of transmitting vesicular stomatitis New Jersey virus (family Rhabdoviridae, genus Vesiculovirus, VSNJV) during blood feeding on the abdomen of six guinea pigs. None of the guinea pigs infected in this manner developed clinical signs of vesicular stomatitis despite seroconversion for VSNJV. Guinea pigs infected by intradermal inoculations of VSNJV in the abdomen also failed to develop clinical signs of vesicular stomatitis. Three guinea pigs given intradermal inoculations of VSNJV in the foot pad developed lesions typical of vesicular stomatitis. Transmission by the bite of C. sonorensis may have facilitated guinea pig infection with VSNJV because a single infected C. sonorensis caused seroconversion and all guinea pigs infected by insect bite seroconverted compared with 50% of the guinea pigs infected by intradermal inoculation with a higher titer VSNJV inoculum. The role of C. sonorensis in the transmission of VSNJV is discussed.

  19. Transmission of Enterocytozoon bieneusi between a child and guinea pigs.

    PubMed

    Cama, Vitaliano A; Pearson, Julie; Cabrera, Lilia; Pacheco, Luz; Gilman, Robert; Meyer, Sarah; Ortega, Ynes; Xiao, Lihua

    2007-08-01

    An unusual Enterocytozoon bieneusi genotype was found in seven guinea pigs and a 2-year-old child in the same household. The genetic uniqueness of the parasite, its wide occurrence in other guinea pigs in the community, and its absence in other children in the community suggest the possibility of zoonotic transmission of the infection to the study child.

  20. Assessment of gastrointestinal pH, fluid and lymphoid tissue in the guinea pig, rabbit and pig, and implications for their use in drug development.

    PubMed

    Merchant, Hamid A; McConnell, Emma L; Liu, Fang; Ramaswamy, Chandrasekaran; Kulkarni, Rucha P; Basit, Abdul W; Murdan, Sudaxshina

    2011-01-18

    Laboratory animals are often used in drug delivery and research. However, basic information about their gastrointestinal pH, fluid volume, and lymphoid tissue is not completely known. We have investigated these post-mortem in healthy guinea pigs, rabbits and pigs, to assess their suitability for pre-clinical studies by comparing the results with reported human literature. The mean gastric pH (fed ad libitum) was 2.9 and 4.4 in guinea pig and pig, respectively. In contrast, a very low pH (1.6) was recorded in the rabbits. The small intestinal pH was found in the range of 6.4-7.4 in the guinea pigs and rabbits, whereas lower pH (6.1-6.7) was recorded in the pig, which may have consequences for ionisable or pH responsive systems when tested in pig. A relatively lower pH than in the small intestine was found in the caecum (6.0-6.4) and colon (6.1-6.6) of the guinea pig, rabbit and the pig. The water content in the gastrointestinal tract of guinea pig, rabbit and pig was 51g, 153g and 1546g, respectively. When normalized to the body weight, the guinea pig, had larger amounts of water compared to the rabbit and the pig (guinea pig>rabbit>pig); in contrast, a reverse order was found when normalized to per unit length of the gut (guinea pig). The lymphoid tissue distribution (lymphoid follicles, Peyer's patches and long strips) along the length of the gut in these animals is presented; in particular, an abundance of lymphoid tissue was found in pig's stomach, small intestine and caecum, and rabbit's appendix. Their ample presence indicated the potential utility of these animal species in oral and colonic vaccination. These differences in the gastrointestinal parameters of the guinea pig, rabbit and pig reiterates the crucial importance of correctly selecting animal models for pre-clinical studies. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Spontaneous occurrence of a potentially night blinding disorder in guinea pigs.

    PubMed

    Racine, Julie; Behn, Darren; Simard, Eric; Lachapelle, Pierre

    2003-07-01

    Several hereditary retinal disorders such as retinitis pigmentosa and congenital stationary night blindness compromise, sometimes exclusively, the activity of the rod pathway. Unfortunately, there are few animal models of these disorders that could help us better understand the pathophysiological processes involved. The purpose of this report is to present a pedigree of guinea pigs where, as a result of a consanguineous mating and subsequent selective breeding, we developed a new and naturally occurring animal model of a rod disorder. Analysis of the retinal function with the electroretinogram reveals that the threshold for rod-mediated electroretinograms (ERGs) is significantly increased by more than 2 log-units compared to that of normal guinea pigs. Furthermore, in response to a suprathreshold stimulus, also delivered under scotopic condition, which yield a mixed cone-rod response in normal guinea pigs, the ERG waveform in our mutant guinea pigs is almost identical (amplitude and timing of a- and b-waves) to that evoked in photopic condition. The above would thus suggest either a structural (abnormal development or absence) or a functional deficiency of the rod photoreceptors. We believe that our pedigree possibly represents a new animal model of a night blinding disorder, and that this condition is inherited as anautosomal recessive trait in the guinea pig population.

  2. Jejuno-jejunal intussusception in a guinea pig (Cavia porcellus)

    PubMed Central

    Fetzer, Tara J.; Mans, Christoph

    2017-01-01

    An approximately four-year-old male castrated guinea pig (Cavia porcellus) was presented for painful defecation with a 24-hour history of hyporexia and intermittent episodes of rolling behavior. Upon presentation the patient was quiet, alert, and responsive, and mildly hypothermic. Abdominal palpation revealed an approximately 2-cm long oblong mass within the caudal abdomen. Abdominal radiographs revealed gastric dilation without volvulus and a peritoneal mass effect. The patient was euthanized following gastric reflux of brown malodorous fluid from his nares and oral cavity. A necropsy was performed and revealed a jejuno-jejunal intussusception causing mechanical gastrointestinal ileus, and gastric dilatation without volvulus. While non-obstructive gastrointestinal stasis is common and obstructive ileus is uncommon in guinea pigs, this report shows that intestinal intussusception is a differential in guinea pigs with ileus and gastric dilatation. PMID:29038782

  3. The vascular supply of the thymus in the guinea-pig and pig

    PubMed Central

    Olson, I. A.; Poste, Mary E.

    1973-01-01

    A study of the blood supply of the thymus using intravascular carbon or silver shows that the pig and guinea-pig possess a more extensive vascular system than the current model taken from work on the mouse. ImagesFIG. 1FIG. 2FIG. 3 PMID:4120933

  4. Experimental Research Into High Barometric Oxygen Prevention of Guinea Pig Hearing Loss,

    DTIC Science & Technology

    1992-08-28

    PREVENTION OF GUINEA PIG HEARING LOSS by Yin Jiacai, Sun Fang ren, et al. DTIC MLECTE •<• EP 2 9 1992 Approved for public release, Distribution unlimited...PREVENTION OF GUINEA PIG HEARING LOSS By: Yin Jiacai, Sun Fang ren, et al. English pages: 9 Source: Chung-Hua I Shueh Tsa Chih, Vol. 65, Nr. 11, Nov.eember...Distributionf._DL~~~t .•b • / or __ Dlist szeccat .lef ’ ~1 EXPERIMENTAL RESEARCH INTO HIGH BAROMETRIC OXYGEN PREVENTION OF GUINEA PIG HEARING LOSS BY: Yin

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

    PubMed

    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 (p<0.0001-0.01) and a discrete lymphomonocytic infiltrate in cardiac and skeletal muscles was present. In the chronic phase, the histological view was normal. In contrast, control group revealed amastigote nests and typical histopathological alterations compatible with chagasic myocarditis, endocarditis and pericarditis. These results, together with previous works in our laboratory, show that T. rangeli induces immunoprotection in three species of animals: mice, guinea 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.

  6. Tamsulosin modulates, but does not abolish the spontaneous activity in the guinea pig prostate gland.

    PubMed

    Chakrabarty, Basu; Dey, Anupa; Lam, Michelle; Ventura, Sabatino; Exintaris, Betty

    2015-06-01

    To examine the effects of the α1A -adrenoceptor antagonist, tamsulosin, on spontaneous contractile and electrical activity in the guinea-pig prostate gland. The effects of tamsulosin (0.1 and 0.3 nM) were investigated in adult and ageing male guinea pig prostate glands using conventional tension recording and electrophysiological intracellular microelectrode recording techniques. Tamsulosin reduced spontaneous activity, and had different age-dependent effects on adult and ageing guinea pigs at different concentrations. 0.1 nM tamsulosin caused a significantly greater reduction of spontaneous contractile and electrical activity in ageing guinea pigs in comparison to adult guinea pigs. In contrast, 0.3 nM tamsulosin had a significantly greater reduction of spontaneous contractile and electrical activity in adult guinea pigs in comparison to ageing guinea pigs. This study demonstrates that tamsulosin can modulate spontaneous myogenic stromal contractility and the underlying spontaneous electrical activity; tamsulosin does not block spontaneous activity. This reduction in spontaneous activity suggests that downstream cellular mechanisms underlying smooth muscle tone are being targeted, and these may represent novel therapeutic targets to better treat benign prostatic hyperplasia. © 2014 Wiley Periodicals, Inc.

  7. Endogenous cannabinoid receptor agonists inhibit neurogenic inflammations in guinea pig airways.

    PubMed

    Yoshihara, Shigemi; Morimoto, Hiroshi; Ohori, Makoto; Yamada, Yumi; Abe, Toshio; Arisaka, Osamu

    2005-09-01

    Although neurogenic inflammation via the activation of C fibers in the airway must have an important role in the pathogenesis of asthma, their regulatory mechanism remains uncertain. The pharmacological profiles of endogenous cannabinoid receptor agonists on the activation of C fibers in airway tissues were investigated and the mechanisms how cannabinoids regulate airway inflammatory reactions were clarified. The effects of endogenous cannabinoid receptor agonists on electrical field stimulation-induced bronchial smooth muscle contraction, capsaicin-induced bronchoconstriction and capsaicin-induced substance P release in guinea pig airway tissues were investigated. The influences of cannabinoid receptor antagonists and K+ channel blockers to the effects of cannabinoid receptor agonists on these respiratory reactions were examined. Both endogenous cannabinoid receptor agonists, anandamide and palmitoylethanolamide, inhibited electrical field stimulation-induced guinea pig bronchial smooth muscle contraction, but not neurokinin A-induced contraction. A cannabinoid CB2 antagonist, SR 144528, reduced the inhibitory effect of endogenous agonists, but not a cannabinoid CB1 antagonist, SR 141716A. Inhibitory effects of agonists were also reduced by the pretreatment of large conductance Ca2+ -activated K+ channel (maxi-K+ channel) blockers, iberiotoxin and charybdotoxin, but not by other K+ channel blockers, dendrotoxin or glibenclamide. Anandamide and palmitoylethanolamide blocked the capsaicin-induced release of substance P-like immunoreactivity from guinea pig airway tissues. Additionally, intravenous injection of palmitoylethanolamide dose-dependently inhibited capsaicin-induced guinea pig bronchoconstriction, but not neurokinin A-induced reaction. However, anandamide did not reduce capsaicin-induced guinea pig bronchoconstriction. These findings suggest that endogenous cannabinoid receptor agonists inhibit the activation of C fibers via cannabinoid CB2 receptors and

  8. Expression Profile of the Integrin Receptor Subunits in the Guinea Pig Sclera.

    PubMed

    Wang, Kevin K; Metlapally, Ravikanth; Wildsoet, Christine F

    2017-06-01

    The ocular dimensional changes in myopia reflect increased scleral remodeling, and in high myopia, loss of scleral integrity leads to biomechanical weakening and continued scleral creep. As integrins, a type of cell surface receptors, have been linked to scleral remodeling, they represent potential targets for myopia therapies. As a first step, this study aimed to characterize the integrin subunits at the messenger RNA level in the sclera of the guinea pig, a more recently added but increasingly used animal model for myopia research. Primers for α and β integrin subunits were designed using NCBI/UCSC Genome Browser and Primer3 software tools. Total RNA was extracted from normal scleral tissue and isolated cultured scleral fibroblasts, as well as liver and lung, as reference tissues, all from guinea pig. cDNA was produced by reverse transcription, PCR was used to amplify products of predetermined sizes, and products were sequenced using standard methods. Guinea pig scleral tissue expressed all known integrin alpha subunits except αD and αE. The latter integrin subunits were also not expressed by cultured guinea pig scleral fibroblasts; however, their expression was confirmed in guinea pig liver. In addition, isolated cultured fibroblasts did not express integrin subunits αL, αM, and αX. This difference between results for cultured cells and intact sclera presumably reflects the presence in the latter of additional cell types. Both guinea pig scleral tissue and isolated scleral fibroblasts expressed all known integrin beta subunits. All results were verified through sequencing. The possible contributions of integrins to scleral remodeling make them plausible targets for myopia prevention. Data from this study will help guide future ex vivo and in vitro studies directed at understanding the relationship between scleral integrins and ocular growth regulation in the guinea pig model for myopia.

  9. Reproductive performance and fertility testing in strain 13 and Hartley guinea pigs.

    PubMed

    Doyle, R E; Sharp, G C; Irvin, W S; Berck, K

    1976-08-01

    A study to test the effects of certain experimental manipulation on the reproductive capacity of male guinea pigs required verifying the fertility of the male guinea pigs before and after manipulation. Methods of testing fertility were evaluated, and normal reproductive data from preexperimental and control groups were tabulated and analyzed. No data from the actual experiments were included. Virgin and proven fertile males were mated with 1 (1:1) or 2 (2:1) virgin or proven fertile females. Inbred (13/N Umm) and conventional (Mfi:CFDH-ML (DH) ) guinea pigs were used. Ninety-five percent of both groups of males were fertile. Eighty-four percent of both groups of females were fertile. Male guinea pigs previously proven fertile had the same subsequent fertility rate as virgin males. Over one-third of the conceptions did not take place during the first estrus cycle (16 da) during which the males and females were mated. Strain 13 and Hartley females had litters of approximately the same size (3.1 vs 3.0), but the neonatal mortality was statistically lower (P less than 0.001) in the Hartley stock (9.3%) than in the Strain 13 guinea pigs (28.4%).

  10. [Use of guinea pigs for assessing the efficacy of vaccines against Lassa fever].

    PubMed

    Firsova, I V; Shatokhina, I V; Borisevich, I V; Evseev, A A; Maksimov, V A; Pantiukhov, V B; Khmelev, A L

    2003-01-01

    The use of guinea pigs as a laboratory model was proven to be appropriate in investigating the vaccines developed against Lassa fever at the preclinical study stage. An adapted variant of Lassa virus was cultivated, which caused death of guinea pigs with respect for an agent's dose. Finally, it was shown to be possible to investigate the immunogenic and protective properties of the inactivated antigen of Lassa virus in experiments with guinea pigs.

  11. Detection of antibodies against Theiler's murine encephalomyelitis virus GDVII strain in experimental guinea pigs.

    PubMed

    Häger, C; Glage, S; Held, N; Bleich, E M; Burghard, A; Mähler, M; Bleich, André

    2016-10-01

    A disease affecting guinea pigs called 'guinea pig lameness' characterized by clinical signs of depression, lameness of limbs, flaccid paralysis, weight loss and death within a few weeks was first described by Römer in 1911. After a research group in our facility kept laboratory guinea pigs from two different origins together in one room, lameness was observed in two animals. Further investigations revealed a serological immune response against Theiler's murine encephalomyelitis virus (TMEV; GDVII strain) in these animals. Histopathology of the lumbar spinal cord of these animals showed mononuclear cell infiltration and necrotic neurons in the anterior horn. Therefore, all guinea pigs from this contaminated animal unit, from other units in our facility, as well as from different European institutions and breeding centres were screened for antibodies directed against GDVII. Our investigations showed that approximately 80% of all guinea pigs from the contaminated animal unit were seropositive for GDVII, whereas animals from other separate units were completely negative. In addition, 43% of tested sera from the different European institutions and breeding centres contained antibodies against GDVII. The present data confirm that an unknown viral infection causes an immune response in experimental guinea pigs leading to seroconversion against GDVII and that guinea pigs from a commercial breeder are the source of the infection. © The Author(s) 2015.

  12. Origin of platelet-derived growth factor in megakaryocytes in guinea pigs.

    PubMed Central

    Chernoff, A; Levine, R F; Goodman, D S

    1980-01-01

    Growth factor activity, as determined by the stimulation of [3H]thymidine incorporation into the DNA of quiescent 3T3 cells in culture, was found in lysates of guinea pig platelets and megakaryocytes. Quantitative dilution studies demonstrated that, of the cells present in the guinea pig bone marrow, only the megakaryocyte possessed quantitatively significant growth factor activity. The amount of activity present in one megakaryocyte was equivalent to that present in 1,000-5,000 platelets, a value approximately comparable to the number of platelets shed from a single megakaryocyte. It is suggested that guinea pig platelet-derived growth factor has its origin in the megakaryocyte. PMID:7358851

  13. Optic nerve head and intraocular pressure in the guinea pig eye.

    PubMed

    Ostrin, Lisa A; Wildsoet, Christine F

    2016-05-01

    The guinea pig is becoming an increasingly popular model for studying human myopia, which carries an increased risk of glaucoma. As a step towards understanding this association, this study sought to characterize the normal, developmental intraocular pressure (IOP) profiles, as well as the anatomy of the optic nerve head (ONH) and adjacent sclera of young guinea pigs. IOP was tracked in pigmented guinea pigs up to 3 months of age. One guinea pig was imaged in vivo with OCT and one with a fundus camera. The eyes of pigmented and albino guinea pigs (ages 2 months) were enucleated and sections from the posterior segment, including the ONH and surrounding sclera, processed for histological analyses - either hematoxylin and eosin (H&E) staining of paraffin embedded, sectioned tissue (n = 1), or cryostat sectioned tissue, processed for immunohistochemistry (n = 3), using primary antibodies against collagen types I-V, elastin, fibronectin and glial fibrillary acidic protein (GFAP). Transmission and scanning electron microscopy (TEM, SEM) studies of ONHs were also undertaken (n = 2 & 5 respectively). Mean IOPs ranged from 17.33 to 22.7 mmHg, increasing slightly across the age range studied, and the IOPs of individual animals also exhibited diurnal variations, peaking in the early morning (mean of 25.8, mmHg, ∼9 am), and decreasing across the day. H&E-stained sections showed retinal ganglion cell axons organized into fascicles in the prelaminar and laminar region of the ONHs, with immunostained sections revealing collagen types I, III, IV and V, as well as elastin, GFAP and fibronectin in the ONHs. SEM revealed a well-defined lamina cribrosa (LC), with radially-oriented collagen beams. TEM revealed collagen fibrils surrounding non-myelinated nerve fiber bundles in the LC region, with myelination and decreased collagen posterior to the LC. The adjacent sclera comprised mainly crimped collagen fibers in a crisscross arrangement. Both the sclera and LC were

  14. Calcium antagonistic activity of Bacopa monniera in guinea-pig trachea

    PubMed Central

    Channa, Shabana; Dar, Ahsana

    2012-01-01

    Objective: To demonstrate the calcium antagonistic property of ethanol extract of Bacopa monniera in guinea-pig trachea. Materials and Methods: The dose response curves of CaCl2 (1 × 10-5 to 1 × 10-1 M) were constructed in the absence and presence of ethanol extract of Bacopa monniera (100, 500 and 700 μg/ml) or nifedipine (1 × 10-6 M) in guinea-pig trachea in calcium free high K+-MOPS-PSS (3-(N-morpholino)-propanesulphonic acid physiological salt solution). The data was analyzed by ANOVA followed by least significant difference test or by Student's ‘t’ test for unequal variance when appropriate. A probability of at least P < 0.05 was considered statistically significant. Results: The plant extract (500 and 700 μg/ml) significantly (P < 0.05) depressed and shifted the calcium concentration-response curves (1 × 10-3- 1 × 10-1 M) to rightward similar to that of nifedipine. Conclusions: Bacopa monniera extract exhibited calcium channel blocking activity in guinea-pig tracheal smooth muscles that may rationalize its relaxant action on guinea-pig trachea and its traditional use in respiratory disorders. PMID:23087517

  15. Gallbladder motility and the sex of the guinea pig.

    PubMed

    Kline, Loren; Karpinski, Edward

    2016-06-01

    Progesterone (P), 17β-estradiol (E2), and dihydrotestosterone (DHT) affect gallbladder motility. When gallbladders were taken from women and men, women had more estrogen and P receptors than men. Both P and E2 had an inhibitory effect upon gallbladder contractility in men and premenopausal and postmenopausal women. Similar findings have been reported in gallbladder strips from male and female guinea pigs. In the present study, there was no significant difference in the amount of E2-, P-, or DHT-induced relaxation of CCK-induced tension when the responses in gallbladder strips from male and female guinea pigs were compared. Three metabolites of P were used: 17-hydroxyprogesterone (17-P), 20α-hydroxyprogesterone (20-P), and 21-hydroxyprogesterone (21-P). There was no significant difference in the responses from strips from male and female guinea pigs. In order to determine if the effects of E2 and P were additive, strips from male animals were exposed to either E2 or P and the amount of relaxation recorded. After recovery, the strips were exposed to E2 or P in reverse order to ensure the order of treatment had no effect. Then, the strips were treated with both E2 and P simultaneously and the relaxation recorded. This procedure was repeated with strips from female guinea pigs. The effect of E2 and P was found to be additive; however, the response of the strips from each sex were not significantly different. It is concluded that the sex of the guinea pig has no significant effect on the response to the sex hormones used. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  16. Vestibular morphology in the German Waltzing guinea pig.

    PubMed

    Kawaguchi, Sachie; Hultcrantz, Malou; Jin, Zhe; Ulfendahl, Mats; Suzuki, Mamoru

    2010-04-01

    The German waltzing guinea pig is a special strain of animal with a recessively inherited inner ear defect, resulting in deafness and a severe vestibular dysfunction. The hearing loss in the cochlea of the German strain is a result of a collapse of the Reissner membrane and the absence of scala media. The vestibular organ has not yet been described. German waltzing guinea pigs (homozygote and heterozygote) of different ages ranging from embryologic age 25 days to adulthood were investigated. The living animals were tested with four different vestibular tests, and the fetuses were controlled according to breeding. The morphology of the vestibular parts (ampulla, saccule, and utricle) was observed by using the light and transmission electron microscopy. Collapse of the membranous labyrinth was found already at embryologic age 50 days and progressed over time. Vestibular dysfunction was noted already from birth. Vestibular atelectasis has been shown to have the same morphology as the reported vestibular dysfunction in the German waltzing guinea pig. Owing to this similarity, this animal can be a good model for vestibular research.

  17. Wild genius - domestic fool? Spatial learning abilities of wild and domestic guinea pigs.

    PubMed

    Lewejohann, Lars; Pickel, Thorsten; Sachser, Norbert; Kaiser, Sylvia

    2010-03-25

    Domestic animals and their wild relatives differ in a wide variety of aspects. The process of domestication of the domestic guinea pig (Cavia aperea f. porcellus), starting at least 4500 years ago, led to changes in the anatomy, physiology, and behaviour compared with their wild relative, the wild cavy, Cavia aperea. Although domestic guinea pigs are widely used as a laboratory animal, learning and memory capabilities are often disregarded as being very scarce. Even less is known about learning and memory of wild cavies. In this regard, one striking domestic trait is a reduction in relative brain size, which in the domesticated form of the guinea pig amounts to 13%. However, the common belief, that such a reduction of brain size in the course of domestication of different species is accomplished by less learning capabilities is not at all very well established in the literature. Indeed, domestic animals might also even outperform their wild conspecifics taking advantage of their adaptation to a man-made environment.In our study we compared the spatial learning abilities of wild and domestic guinea pigs. We expected that the two forms are different regarding their learning performance possibly related to the process of domestication. Therefore wild cavies as well as domestic guinea pigs of both sexes, aged 35 to 45 days, were tested in the Morris water maze to investigate their ability of spatial learning. Both, wild cavies and domestic guinea pigs were able to learn the task, proving the water maze to be a suitable test also for wild cavies. Regarding the speed of learning, male as well as female domestic guinea pigs outperformed their wild conspecifics significantly. Interestingly, only domestic guinea pigs showed a significant spatial association of the platform position, while other effective search strategies were used by wild cavies. The results demonstrate that domestic guinea pigs do not at all perform worse than their wild relatives in tests of spatial

  18. Wild genius - domestic fool? Spatial learning abilities of wild and domestic guinea pigs

    PubMed Central

    2010-01-01

    Background Domestic animals and their wild relatives differ in a wide variety of aspects. The process of domestication of the domestic guinea pig (Cavia aperea f. porcellus), starting at least 4500 years ago, led to changes in the anatomy, physiology, and behaviour compared with their wild relative, the wild cavy, Cavia aperea. Although domestic guinea pigs are widely used as a laboratory animal, learning and memory capabilities are often disregarded as being very scarce. Even less is known about learning and memory of wild cavies. In this regard, one striking domestic trait is a reduction in relative brain size, which in the domesticated form of the guinea pig amounts to 13%. However, the common belief, that such a reduction of brain size in the course of domestication of different species is accomplished by less learning capabilities is not at all very well established in the literature. Indeed, domestic animals might also even outperform their wild conspecifics taking advantage of their adaptation to a man-made environment. In our study we compared the spatial learning abilities of wild and domestic guinea pigs. We expected that the two forms are different regarding their learning performance possibly related to the process of domestication. Therefore wild cavies as well as domestic guinea pigs of both sexes, aged 35 to 45 days, were tested in the Morris water maze to investigate their ability of spatial learning. Results Both, wild cavies and domestic guinea pigs were able to learn the task, proving the water maze to be a suitable test also for wild cavies. Regarding the speed of learning, male as well as female domestic guinea pigs outperformed their wild conspecifics significantly. Interestingly, only domestic guinea pigs showed a significant spatial association of the platform position, while other effective search strategies were used by wild cavies. Conclusion The results demonstrate that domestic guinea pigs do not at all perform worse than their wild

  19. [Analysis of the main components of inner ear antigens inducing autoimmune Meniere's disease in guinea pigs].

    PubMed

    Lu, Ling; Tan, Chang-Qiang; Cui, Yu-Gui; Ding, Gui-Peng; Ju, Xiao-Bin; Li, Yu-Jin; Cai, Wen-Jun

    2008-08-01

    To investigate the main components of inner ear antigens inducing autoimmune Meniere's disease (AIMD) in guinea pigs. The guinea pigs were immunized with isologous crude inner ear antigens (ICIEAg). Then, the hearing function was measured with auditory brainstem response (ABR), the vestibular function was measured with electronystagmography (including spontaneous nystagmus and caloric test), and inner ear histopathological changes were observed by inner ear celloidin section with haematoxylin-eosin staining and observed under light microscope. According to these results, the AIMD-model animals from non-AIMD-model ones were distinguished. The special antibodies against ICIEAg in sera were measured with ELISA. The antigen-antibody reactions against different components of ICIEAg were detected by Western blotting with sera of AIMD and non-AIMD guinea pigs respectively. Then, we analysed the contrast between them and found the main components of the ICIEAg that were positive reaction in AIMD guinea pigs and negative reaction in non-AIMD guinea pigs. The result of ELISA demonstrated that the sera of both the AIMD and non-AIMD guniea pigs contained the special antibodies against ICIEAg after immunized with ICIEAg. The difference of the amount of antibody against ICIEAg between AIMD guinea pig group and non-AIMD guinea pig group was not significant. Western blotting assay showed only the sera of AIMD guinea pig contained the antibodies against the specific antigens with the molecular of 68 000, 58 000, 42 000 and 28 000. ICIEAg contain many different components, the AIMD might only happen in the guinea pigs in which the special immunization against the main components that could induce this kind of disorder appeared. The inner ear antigens with molecular of 68 000, 58 000, 42 000 and 28 000 might be the main components inducing AIMD in guinea pigs.

  20. Effect of several compounds on biliary excretion of paclitaxel and its metabolites in guinea-pigs.

    PubMed

    Bun, Sok-Siya; Giacometti, Sarah; Fanciullino, Raphaëlle; Ciccolini, Joseph; Bun, Hot; Aubert, Claude

    2005-07-01

    The objective of this study was to evaluate the in vivo metabolic profile of paclitaxel and to examine the effect of potential co-administered drugs on the biliary secretion of paclitaxel and its metabolites in guinea-pigs. We first investigated in vitro paclitaxel metabolism using liver microsomes obtained from various species to identify the most suitable animal model with a similar metabolism to humans. Then, in vivo paclitaxel metabolism was investigated in male guinea-pigs. The levels of paclitaxel and its metabolites were measured by high-performance liquid chromatography in bile samples from guinea-pigs after paclitaxel i.v. injection (6 mg/kg). We further evaluated the effects of various drugs (quercetin, ketoconazole, dexamethasone, cotrimoxazole) on the biliary secretion of paclitaxel and its metabolites in guinea-pigs. This work demonstrated significant in vitro interspecies differences in paclitaxel metabolism. Our findings showed both in vitro and in vivo similarities between human and guinea-pig biotransformation of paclitaxel. 6alpha-Hydroxypaclitaxel, the main human metabolite of paclitaxel, was found in guinea-pig bile. After paclitaxel combination with ketoconazole or quercetin in guinea-pigs, the cumulative biliary excretion of paclitaxel and its metabolites up to 6 h was significantly decreased by 62 and 76%, respectively. The co-administration of cotrimoxazole or pretreatment with dexamethasone did not alter significantly cumulative biliary excretion. The guinea-pig is a suitable model to study metabolism and biliary excretion of paclitaxel, and to investigate in vivo drug interactions.

  1. Generation and Characterization of Inhibitory Antibodies Specific to Guinea Pig CXCR1 and CXCR2.

    PubMed

    Tanaka, Kento; Yoshimura, Chigusa; Shiina, Tetsuo; Terauchi, Tomoko; Yoshitomi, Tomomi; Hirahara, Kazuki

    2017-04-01

    CXCR1 and CXCR2 are chemokine receptors that have different selectivity of chemokine ligands, but the distinct role of each receptor is not clearly understood. This is due to the absence of specific inhibitors in guinea pigs, which are the appropriate species for investigation of CXCR1 and CXCR2 because of their functional similarity to humans. In this study, we generated and evaluated monoclonal antibodies that specifically bound to guinea pig CXCR1 (gpCXCR1) and guinea pig CXCR2 (gpCXCR2) for acquisition of specific inhibitors. To assess the activity of antibodies, we established CHO-K1 cells stably expressing either gpCXCR1 or gpCXCR2 (CHO/gpCXCR1 or CHO/gpCXCR2). CHO/gpCXCR1 showed migration in response to guinea pig interleukin (IL)-8, and CHO/gpCXCR2 showed migration in response to both guinea pig IL-8 and guinea pig growth-regulated oncogene α. The receptor selectivities of the chemokines of guinea pigs were the same as the human orthologs. The inhibitory activities of the anti-gpCXCR1 and anti-gpCXCR2 monoclonal antibodies on cell migration were observed in a concentration-dependent manner. In conclusion, we successfully obtained inhibitory antibodies specific to gpCXCR1 and gpCXCR2. These inhibitory antibodies will be useful to clarify the physiological roles of CXCR1 and CXCR2 in guinea pigs.

  2. Subacute Low Dose Nerve Agent Exposure Causes DNA Fragmentation in Guinea Pig Leukocytes

    DTIC Science & Technology

    2005-10-01

    1 SUBACUTE LOW DOSE NERVE AGENT EXPOSURE CAUSES DNA FRAGMENTATION IN GUINEA PIG LEUKOCYTES. Jitendra R. Dave1, John R. Moffett1, Sally M...DNA fragmentation in blood leukocytes from guinea pigs by ‘Comet’ assay after exposure to soman at doses ranging from 0.1LD50 to 0.4 LD50, once per...computer. Data obtained for exposure to soman demonstrated significant increases in DNA fragmentation in circulating leukocytes in CWNA treated guinea pigs as

  3. Immunohistopathology in the Guinea Pig Following Chronic Low-Level Exposure to Chemical Warfare Agents

    DTIC Science & Technology

    2005-11-01

    U.S. Army Medical Research Institute of Chemical Defense USAMRICD-TR-05-09 Immunohistopathology in the Guinea Pig Following Chronic Low...2005 2. REPORT TYPE Technical Report 3. DATES COVERED (From - To) May 2003 to April 2005 4. TITLE AND SUBTITLE Immunohistopathology in the Guinea Pig Following...release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Guinea pigs exposed repeatedly to low levels of chemical warfare nerve agents

  4. On the morality of Guinea-pig recruitment.

    PubMed

    Valdman, Mikhail

    2010-07-01

    ABSTRACT Can it be wrong to conduct medical research on human subjects even with their informed consent and even when the transaction between the subjects and researchers is expected to be mutually beneficial? This question is especially pressing today in light of the rise of a semi-professional class of 'guinea pigs'- human research subjects that sell researchers a right of access to their bodies in exchange for money. Can these exchanges be morally problematic even when they are consensual and mutually beneficial? I argue that there are two general kinds of concern one can have about such transactions - concerns about the nature of what is sold and concerns about the conditions in which the selling occurs. The former involves worries about degradation and the possible wrongness of selling a right of access to one's body. These worries, I argue, are not very serious. The latter involves worries about coercion, exploitation, and undue influence - about how, by virtue of their ignorance, impulsiveness, or desperation, guinea pigs can be taken advantage of by medical researchers. These worries are quite serious but I argue that, at least in cases where the exchange between guinea pigs and researchers is consensual and mutually beneficial, they do not raise insurmountable moral problems.

  5. Crataegus extract blocks potassium currents in guinea pig ventricular cardiac myocytes.

    PubMed

    Müller, A; Linke, W; Klaus, W

    1999-05-01

    Crataegus extract is used in cardiology for the treatment of mild to moderate heart failure (NYHA II) in Germany. However, little is known about the electrophysiological actions of Crataegus extract in the heart. Recently, it was shown that Crataegus extract prolongs the refractory period in isolated perfused hearts and increases action potential duration in guinea pig papillary muscle. It was the aim of this study to find out the mechanism of the increase in action potential duration caused by Crataegus extract. Using the patch-clamp technique, we measured the effects of Crataegus extract (10 mg/l; flavonoid content: 2.25%, total procyanidin content: 11.3 +/- 0.4%) on the inward rectifier and the delayed rectifier potassium current in isolated guinea pig ventricular myocytes. To get some insight into the mechanism underlying the positive inotropic effect of Crataegus extract, we also looked for effects on the L-type calcium current. Crataegus extract slightly blocked both the delayed and the inward rectifier potassium current. The inhibition amounted to 25% and about 15%, respectively. This amount of inhibition of these repolarising currents is sufficient to explain the prolongation of action potential duration caused by Crataegus extract. To our surprise we could not detect any influence of Crataegus extract on the L-type calcium current. In summary, our results show that Crataegus extract blocks repolarising potassium currents in ventricular myocytes. This effect is similar to the action of class III antiarrhythmic drugs and might be the basis of the antiarrhythmic effects described for Crataegus extract. Our measurements of the L-type calcium current indicate that Crataegus extract's positive inotropic effect is not caused by phosphodiesterase inhibition or a beta-sympathomimetic effect.

  6. Veterinarian Nominated Common Conditions of Rabbits and Guinea Pigs Compared with Published Literature

    PubMed Central

    Robinson, Natalie J.; Lyons, Emma; Grindlay, Douglas

    2017-01-01

    Rabbits and guinea pigs are increasingly popular pets in the UK, yet little is known about their common ailments, or how these relate to what appears in the published literature. The aim of this study was to characterise the common conditions of rabbits and guinea pigs, and to compare these with the topics found in the published literature. Information about the common conditions seen in rabbits and guinea pigs in clinical practice was obtained from a survey of UK veterinarians. The common conditions seen were compared with results from a structured literature search. Conditions relating to the dental (29.9%), and skin (37.6%) body systems were commonly nominated by veterinarians for rabbits and guinea pigs, respectively. A total of 655 rabbit and 1086 guinea pig citations were examined and there appeared to be a mismatch between the conditions nominated in the veterinary questionnaire, and those found in the literature. This is the first time that the published literature has been compared to the nominated caseload of veterinarians in practice, and there is concern that the literature about rabbits and guinea pigs may not be representative of, or relevant to the caseload seen in clinical practice. This is of importance for clinicians being able to apply an objective, evidence-based approach. The publishing of clinically-relevant, research-based evidence should be prioritised. PMID:29165371

  7. Direct negative chronotropic action of desflurane on sinoatrial node pacemaker activity in the guinea pig heart.

    PubMed

    Kojima, Akiko; Ito, Yuki; Kitagawa, Hirotoshi; Matsuura, Hiroshi; Nosaka, Shuichi

    2014-06-01

    Desflurane inhalation is associated with sympathetic activation and concomitant increase in heart rate in humans and experimental animals. There is, however, little information concerning the direct effects of desflurane on electrical activity of sinoatrial node pacemaker cells that determines the intrinsic heart rate. Whole-cell patch-clamp experiments were conducted on guinea pig sinoatrial node pacemaker cells to record spontaneous action potentials and ionic currents contributing to sinoatrial node automaticity, namely, hyperpolarization-activated cation current (If), T-type and L-type Ca currents (ICa,T and ICa,L, respectively), Na/Ca exchange current (INCX), and rapidly and slowly activating delayed rectifier K currents (IKr and IKs, respectively). Electrocardiograms were recorded from ex vivo Langendorff-perfused hearts and in vivo hearts. Desflurane at 6 and 12% decreased spontaneous firing rate of sinoatrial node action potentials by 15.9% (n = 11) and 27.6% (n = 10), respectively, which was associated with 20.4% and 42.5% reductions in diastolic depolarization rate, respectively. Desflurane inhibited If, ICa,T, ICa,L, INCX, and IKs but had little effect on IKr. The negative chronotropic action of desflurane was reasonably well reproduced in sinoatrial node computer model. Desflurane reduced the heart rate in Langendorff-perfused hearts. High concentration (12%) of desflurane inhalation was associated with transient tachycardia, which was totally abolished by pretreatment with the β-adrenergic blocker propranolol. Desflurane has a direct negative chronotropic action on sinoatrial node pacemaking activity, which is mediated by its inhibitory action on multiple ionic currents. This direct inhibitory action of desflurane on sinoatrial node automaticity seems to be counteracted by sympathetic activation associated with desflurane inhalation in vivo.

  8. Experimental Genital Infection of Male Guinea Pigs with the Agent of Guinea Pig Inclusion Conjunctivitis and Transmission to Females

    PubMed Central

    Mount, David T.; Bigazzi, Pierluigi E.; Barron, Almen L.

    1973-01-01

    Male guinea pigs were inoculated intraurethrally with the agent of guinea pig inclusion conjunctivitis (Gp-ic). Cytoplasmic inclusions were found in superficial epithelial cells of the urethra in smears and stained sections. Gp-ic antigen(s) was detected by immunofluorescent staining of sections. There was no marked urethral exudate, but many animals developed bullous lesions on the glans and the body of the penis and a severe inflammatory lesion of the hind leg. All males demonstrated an antibody response and most of them showed a positive skin test reaction. Venereal transmission to females of Gp-ic infection was shown to occur as determined by detection of inclusions in vaginal smears, antibody response, and positive skin tests. Images PMID:4594119

  9. Prokaryotic expression and in vitro functional analysis of IL-1β and MCP-1 from guinea pig.

    PubMed

    Dirisala, Vijaya R; Jeevan, Amminikutty; Ly, Lan H; McMurray, David N

    2013-06-01

    The Guinea pig (Cavia porcellus) is an excellent animal model for studying human tuberculosis (TB) and also for a number of other infectious and non-infectious diseases. One of the major roadblocks in effective utilization of this animal model is the lack of readily available immunological reagents. In order to address this issue, guinea pig interleukin 1 beta (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) were efficiently cloned and expressed in a prokaryotic expression vector, and the expressed proteins in soluble form from both the genes were confirmed by N-terminal sequencing. The biological activity of recombinant guinea pig IL-1β was demonstrated by its ability to drive proliferation in thymocytes, and the recombinant guinea pig MCP-1 exhibited chemotactic activity for guinea pig resident peritoneal macrophages. These biologically active recombinant guinea pig proteins will facilitate an in-depth understanding of the role they play in the immune responses of the guinea pig to TB and other diseases.

  10. Mitochondria-Targeted Antioxidant Mitoquinone Reduces Cisplatin-Induced Ototoxicity in Guinea Pigs.

    PubMed

    Tate, Alan D; Antonelli, Patrick J; Hannabass, Kyle R; Dirain, Carolyn O

    2017-03-01

    Objective To determine if mitoquinone (MitoQ) attenuates cisplatin-induced hearing loss in guinea pigs. Study Design Prospective and controlled animal study. Setting Academic, tertiary medical center. Subjects and Methods Guinea pigs were injected subcutaneously with either 5 mg/kg MitoQ (n = 9) or normal saline (control, n = 9) for 7 days and 1 hour before receiving a single dose of 10 mg/kg cisplatin. Auditory brainstem response thresholds were measured before MitoQ or saline administration and 3 to 4 days after cisplatin administration. Results Auditory brainstem response threshold shifts after cisplatin treatment were smaller by 28 to 47 dB in guinea pigs injected with MitoQ compared with those in the control group at all tested frequencies (4, 8, 16, and 24 kHz, P = .0002 to .04). Scanning electron microscopy of cochlear hair cells showed less outer hair cell loss and damage in the MitoQ group. Conclusion MitoQ reduced cisplatin-induced hearing loss in guinea pigs. MitoQ appears worthy of further investigation as a means of preventing cisplatin ototoxicity in humans.

  11. Gamma Radiation (5-10 Gy) Impairs Neuronal Function in the Guinea Pig Hippocampus

    DTIC Science & Technology

    1993-01-01

    Radiation (5-10 Gy) Impairs Neuronal Function in the Guinea Pig Hippocampus TERRY C. PELLMAR AND DENNIS L. LEPINSKI Ph.vsiology Department..Irmned Forces...L. Gamma Radiation ioral effects. Within hours of irradiation with 10 Gy and (5- 10 Gy) Impairs Neuronal Function in the Guinea Pig Hippo- less...acti v- Guinea pigs were exposed to 5 and 10 Gy ’y radiation. Hippo- ity (9) are evident. campal brain slices were isolated 30 min, I day, 3 days and 5

  12. Spontaneous axial myopia and emmetropization in a strain of wild-type guinea pig (Cavia porcellus).

    PubMed

    Jiang, Liqin; Schaeffel, Frank; Zhou, Xiangtian; Zhang, Sen; Jin, Xi; Pan, Miaozhen; Ye, Lingying; Wu, Xiaomin; Huang, Qinzhu; Lu, Fan; Qu, Jia

    2009-03-01

    To describe a wild-type guinea pig strain with an incidence of spontaneous axial myopia, minimal pupil responses, lack of accommodation, and apparently normal spatial vision. Such a strain is of interest because it may permit the exploration of defective emmetropization and mapping of the underlying quantitative trait loci. Twenty-eight guinea pigs were selected from 220 animals based on binocular myopia (exceeding -1.50 diopter [D]) or anisometropia (difference between both eyes exceeding 10 D) at 4 weeks of age. Refractions and pupil responses were measured with eccentric infrared photoretinoscopy, corneal curvature by modified conventional keratometer, and axial lengths by A-scan ultrasonography once a week. Twenty-one guinea pigs were raised under a normal 12-hour light/12-hour dark cycle. From a sample of 18 anisometropic guinea pigs, 11 were raised under normal light cycle and 7 were raised in the dark to determine the extent to which visual input guides emmetropization. Spatial vision was tested in an automated optomotor drum. In 10 guinea pigs with myopia in both eyes, refractive errors ranged from -15.67 D to -1.50 D at 3 weeks with a high interocular correlation (R = 0.82); axial length and corneal curvature grew almost linearly over time. Strikingly, two patterns of recovery were observed in anisometropic guinea pigs: in 12 (67%) anisometropia persisted, and in 6 (33%) it declined over time. These ratios remained similar in dark-reared guinea pigs. Unlike published strains, all guinea pigs of this strain showed weak pupil responses and no signs of accommodation but up to 3 cyc/deg of spatial resolution. This strain of guinea pigs has spontaneous axial refractive errors that may be genetically or epigenetically determined. Interestingly, it differs from other published strains that show no refractive errors, vivid accommodation, or pupil responses.

  13. Epizootic guinea pig herpes-like virus infection in a breeding colony.

    PubMed

    Connelly, B L; Keller, G L; Myers, M G

    1987-01-01

    A breeding colony of strain-2 guinea pigs which had been relatively free of indigenous caviid herpesviruses experienced an explosive outbreak of guinea pig herpes-like virus apparently as a consequence of intermixing groups and contamination of the water supply. A new breeding colony has been established and has been maintained apparently free of recognized caviid herpesviruses.

  14. The Potential Neurotoxic Effects of Low-Dose Sarin Exposure in a Guinea Pig Model

    DTIC Science & Technology

    2002-01-01

    1 THE POTENTIAL NEUROTOXIC EFFECTS OF LOW-DOSE SARIN EXPOSURE IN A GUINEA PIG MODEL Melinda R. Roberson, PhD, Michelle B. Schmidt...Proving Ground, MD 21010 USA ABSTRACT This study is assessing the effects in guinea pigs of repeated low-dose exposure to the nerve...COVERED - 4. TITLE AND SUBTITLE The Potential Neurotoxic Effects Of Low-Dose Sarin Exposure In A Guinea Pig Model 5a. CONTRACT NUMBER 5b

  15. Investigation Into the Humaneness of Slaughter Methods for Guinea Pigs (Cavia porcelus) in the Andean Region

    PubMed Central

    Limon, Georgina; Gonzales-Gustavson, Eloy A.; Gibson, Troy J.

    2016-01-01

    Guinea pigs (Cavia porcelus) are an important source of nonhuman animal protein in the Andean region of South America. Specific guidelines regarding the welfare of guinea pigs before and during slaughter have yet to be developed. This study critically assessed the humaneness of 4 different stunning/slaughter methods for guinea pigs: cervical neck dislocation (n = 60), electrical head-only stunning (n = 83), carbon dioxide (CO2) stunning (n = 21), and penetrating captive bolt (n = 10). Following cervical neck dislocation, 97% of guinea pigs had at least 1 behavioral or cranial/spinal response. Six percent of guinea pigs were classified as mis-stunned after electrical stunning, and 1% were classified as mis-stunned after captive bolt. Increased respiratory effort was observed during CO2 stunning. Apart from this finding, there were no other obvious behavioral responses that could be associated with suffering. Of the methods assessed, captive bolt was deemed the most humane, effective, and practical method of stunning guinea pigs. Cervical neck dislocation should not be recommended as a slaughter method for guinea pigs. PMID:26963642

  16. Anticonvulsant Effects of Memantine and MK-801 in Guinea Pig Hippocampal Neurons.

    DTIC Science & Technology

    investigation we compared the anticonvulsant properties of Mem to those of MK-801 in guinea pig hippocampal slices. Extracellular recordings were...obtained from area CA1 of guinea pig hippocampal slices in a total submersion chamber at 32 deg C in normal oxygenated artificial cerebrospinal fluid (ACSF

  17. Chlamydia caviae infection alters abundance but not composition of the guinea pig vaginal microbiota

    PubMed Central

    Neuendorf, Elizabeth; Gajer, Pawel; Bowlin, Anne K.; Marques, Patricia X.; Ma, Bing; Yang, Hongqiu; Fu, Li; Humphrys, Michael S.; Forney, Larry J.; Myers, Garry S.A.; Bavoil, Patrik M.; Rank, Roger G.; Ravel, Jacques

    2015-01-01

    In humans, the vaginal microbiota is thought to be the first line of defense again pathogens including Chlamydia trachomatis. The guinea pig has been extensively used as a model to study chlamydial infection because it shares anatomical and physiological similarities with humans, such as a squamous vaginal epithelium as well as some of the long-term outcomes caused by chlamydial infection. In this study, we aimed to evaluate the guinea pig-C. caviae model of genital infection as a surrogate for studying the role of the vaginal microbiota in the early steps of C. trachomatis infection in humans. We used culture-independent molecular methods to characterize the relative and absolute abundance of bacterial phylotypes in the guinea pig vaginal microbiota in animals non-infected, mock-infected or infected by C. caviae. We showed that the guinea pig and human vaginal microbiotas are of different bacterial composition and abundance. Chlamydia caviae infection had a profound effect on the absolute abundance of bacterial phylotypes but not on the composition of the guinea pig vaginal microbiota. Our findings compromise the validity of the guinea pig-C. caviae model to study the role of the vaginal microbiota during the early steps of sexually transmitted infection. PMID:25761873

  18. Chlamydia caviae infection alters abundance but not composition of the guinea pig vaginal microbiota.

    PubMed

    Neuendorf, Elizabeth; Gajer, Pawel; Bowlin, Anne K; Marques, Patricia X; Ma, Bing; Yang, Hongqiu; Fu, Li; Humphrys, Michael S; Forney, Larry J; Myers, Garry S A; Bavoil, Patrik M; Rank, Roger G; Ravel, Jacques

    2015-06-01

    In humans, the vaginal microbiota is thought to be the first line of defense again pathogens including Chlamydia trachomatis. The guinea pig has been extensively used as a model to study chlamydial infection because it shares anatomical and physiological similarities with humans, such as a squamous vaginal epithelium as well as some of the long-term outcomes caused by chlamydial infection. In this study, we aimed to evaluate the guinea pig-C. caviae model of genital infection as a surrogate for studying the role of the vaginal microbiota in the early steps of C. trachomatis infection in humans. We used culture-independent molecular methods to characterize the relative and absolute abundance of bacterial phylotypes in the guinea pig vaginal microbiota in animals non-infected, mock-infected or infected by C. caviae. We showed that the guinea pig and human vaginal microbiotas are of different bacterial composition and abundance. Chlamydia caviae infection had a profound effect on the absolute abundance of bacterial phylotypes but not on the composition of the guinea pig vaginal microbiota. Our findings compromise the validity of the guinea pig-C. caviae model to study the role of the vaginal microbiota during the early steps of sexually transmitted infection. © FEMS 2015.

  19. Effect of ribavirin on junin virus infection in guinea pigs.

    PubMed

    Salazar, M; Yun, N E; Poussard, A L; Smith, J N; Smith, J K; Kolokoltsova, O A; Patterson, M J; Linde, J; Paessler, S

    2012-06-01

    Junin virus (JUNV) is the aetiological agent of Argentine haemorrhagic fever. The pathogenesis of the infection is not well understood, no licensed vaccines exist and no specific antiviral therapy is available. Previous studies have demonstrated the ability of ribavirin to delay and reduce JUNV disease and virus burden in guinea pigs without preventing death. Based on available data, we performed three different studies to determine the efficacy of ribavirin against JUNV in the guinea pig model with a focus on survival. Different doses and treatment schedules of ribavirin were tested in a lethal model of JUNV infection. Our results show that prolonged treatment with high doses of ribavirin significantly reduces the mortality in guinea pigs infected with JUNV. These results may be useful in future experimental studies or clinical testing. © 2011 Blackwell Verlag GmbH.

  20. [Digestive disorders in rabbits and guinea pigs].

    PubMed

    Hollmann, P

    1992-12-01

    Numerous digestive tract diseases in pet rabbits and guinea pigs result from both an inherent physiological predisposition and from poor feeding and husbandry. A large proportion of digestive disturbances in rabbits and guinea pigs are secondary to changes in the oral cavity caused by inadequate teeth wear. The required regular trimming of the cheek teeth using a modified spatula and hollow pair of pincers is described and illustrated. The symptoms, diagnosis, prognosis and treatment of a selection of digestive disorders, as commonly encountered in small animal practice, are presented. The difficulties of using antibiotics in view of the gram positive intestinal flora and possible dysbacteria, dysentery and enterotoxaemia are considered. Finally, advice on feeding and on the rearing of orphan neonates is given.

  1. Comparison of human and guinea pig acetylcholinesterase sequences and rates of oxime-assisted reactivation.

    PubMed

    Cadieux, C Linn; Broomfield, Clarence A; Kirkpatrick, Melanie G; Kazanski, Meghan E; Lenz, David E; Cerasoli, Douglas M

    2010-09-06

    Poisoning via organophosphorus (OP) nerve agents occurs when the OP binds and inhibits the enzyme acetylcholinesterase (AChE). This enzyme is responsible for the metabolism of the neurotransmitter acetylcholine (ACh) which transmits signals between nerves and several key somatic regions. When AChE is inhibited, the signal initiated by ACh is not properly terminated. Excessive levels of ACh result in a cholinergic crisis, and in severe cases can lead to death. Current treatments for OP poisoning involve the administration of atropine, which blocks ACh receptors, and oximes, which reactivate AChE after inhibition. Efforts to improve the safety, efficacy, and broad spectrum utility of these treatments are ongoing and usually require the use of appropriate animal model systems. For OP poisoning, the guinea pig (Cavia porcellus) is a commonly used animal model because guinea pigs more closely mirror primate susceptibility to OP poisoning than do other animals such as rats and mice. This is most likely because among rodents and other small mammals, guinea pigs have a very low relative concentration of serum carboxylesterase, an enzyme known to bind OPs in vitro and to act as an 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 is substantially more resistant to oxime-mediated reactivation than human AChE. To examine the molecular basis for this difference, we reverse transcribed mRNA encoding guinea pig AChE, amplified the resulting cDNA, and sequenced this product. The nucleotide and deduced amino acid sequences of guinea pig AChE were then compared to the human version. Several amino acid differences were noted, and the predicted locations of these differences were mapped onto a structural model of human AChE. To examine directly how these differences affect oxime-mediated reactivation of AChE after inhibition by OPs, human and guinea pig red blood cell

  2. Enzyme replacement therapy in alpha-mannosidosis guinea-pigs.

    PubMed

    Crawley, Allison C; King, Barbara; Berg, Thomas; Meikle, Peter J; Hopwood, John J

    2006-01-01

    alpha-Mannosidosis is a lysosomal storage disorder caused by deficient activity of lysosomal alpha-mannosidase and is characterised by massive accumulation of mannose-containing oligosaccharides in affected individuals. Patients develop behaviour and learning difficulties, skeletal abnormalities, immune deficiency and hearing impairment. Disease in alpha-mannosidosis guinea-pigs resembles the clinical, histopathological, biochemical and molecular features of the human disease. We have used the guinea-pig model to investigate efficacy of enzyme replacement therapy as a treatment for alpha-mannosidosis. Intravenous recombinant human lysosomal alpha-mannosidase, administered at a dose of 1mg/kg, was cleared from circulation with a half-life of 53 h, with significant enzyme activity (1.4x normal levels) detected in circulation one week post-injection. alpha-Mannosidase administered to alpha-mannosidosis guinea-pigs at 1mg/kg (onset at birth or approximately 30 days) and 10mg/kg (at birth) was distributed widely amongst tissues, including to capillary depleted brain. By monitoring with tandem mass spectrometry, enzyme replacement therapy was found to be effective in reducing stored substrates in peripheral tissues at both dose rates, and in brain by up to 39% at the 10mg/kg dose, compared with untreated alpha-mannosidosis controls. Reductions of up to 60% of urinary mannose containing oligosaccharides were also observed. No histological improvements were seen in the brain at either dose, however marked decreases in lysosomal vacuolation in liver, kidney, spleen and endocrine pancreas, as well as a significant reduction in trigeminal ganglion neurons were observed. Multiple injections of 1mg/kg recombinant enzyme in alpha-mannosidosis guinea-pigs induced a very rapid humoral immune response precluding long-term intravenous treatment.

  3. Guinea Pig Ciliary Muscle Development

    PubMed Central

    Pucker, Andrew D.; Carpenter, Ashley R.; McHugh, Kirk M.; Mutti, Donald O.

    2014-01-01

    Purpose The purpose of this study was to develop a method for quantifying guinea pig ciliary muscle volume (CMV) and to determine its relationship to age and ocular biometric measurements. Methods Six albino guinea pigs eyes were collected at each of five ages (n=30 eyes). Retinoscopy and photography were used to document refractive error, eye size, and eye shape. Serial sections through the excised eyes were made and then labeled with an α-smooth muscle actin antibody. The CM was then visualized with an Olympus BX51 microscope, reconstructed with Stereo Investigator (MBF Bioscience) and analyzed using Neurolucida Explorer (MBF Bioscience). Full (using all sections) and partial (using a subset of sections) reconstruction methods were used to determine CMV. Results There was no significant difference between the full and partial volume determination methods (P = 0.86). The mean CMV of the 1, 10, 20, 30, and 90-day old eyes was 0.40 ± 0.16 mm3, 0.48 ± 0.13 mm3, 0.67 ± 0.15 mm3, 0.86 ± 0.35 mm3, and 1.09 ± 0.63 mm3, respectively. CMV was significantly correlated with log age (P = 0.001), ocular length (P = 0.003), limbal circumference (P = 0.01), and equatorial diameter (P = 0.003). It was not correlated with refractive error (P = 0.73) or eye shape (P = 0.60). Multivariate regression determined that biometric variables were not significantly associated with CMV after adjustment for age. Conclusions Three-dimensional reconstruction was an effective means of determining CMV. These data provide evidence that CM growth occurs with age in tandem with eye size in normal albino guinea pigs. Additional work is needed to determine the relationship between CMV and abnormal ocular growth. PMID:24901488

  4. Composition and characteristics of urinary calculi from guinea pigs.

    PubMed

    Hawkins, Michelle G; Ruby, Annette L; Drazenovich, Tracy L; Westropp, Jodi L

    2009-01-15

    To determine the mineral composition of calculi, anatomic locations of the calculi, and findings of urinalysis and bacteriologic culture of urine and calculi in guinea pigs with urolithiasis. Cross-sectional study. 127 guinea pigs. Records of urinary calculi that had been submitted to the University of California Stone Laboratory from 1985 through 2003 were reviewed. In addition, submissions of urinary calculi for evaluation by the laboratory were prospectively solicited from 2004 through 2007. Prospectively obtained calculi were accompanied by a urine sample for urinalysis and bacteriologic culture and a completed questionnaire. All calculi were analyzed by use of polarized light microscopy and infrared spectroscopy. A subset of calculi was examined by means of x-ray diffractometry (XRD). 83% (43/52) of calculi from the laboratory database and 93% (70/75) of calculi that were prospectively solicited were composed of 100% calcium carbonate. Analysis via XRD confirmed that 5 of 6 calculi from a subset that had the greatest gross morphologic variation were composed of 100% calcite. Although many guinea pigs had received anti-microbials before bacteriologic cultures of urine were performed, Corynebacterium renale was isolated from 5 urine samples. Contrary to findings of other studies, urinary calculi analyzed for the present study were most commonly composed of 100% calcium carbonate, and infrared spectroscopy or XRD was necessary to differentiate this mineral from others. Treatments, including diet and husbandry practices, should be developed to help prevent development of calcium carbonate calculi in guinea pigs.

  5. Adenosine transport systems on dissociated brain cells from mouse, guinea-pig, and rat

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Johnston, M.E.; Geiger, J.D.

    1990-09-01

    The kinetics and sodium dependence of adenosine transport were determined using an inhibitor-stop method on dissociated cell body preparations obtained from mouse, guinea-pig and rat brain. Transport affinity (KT) values for the high affinity adenosine transport systems KT(H) were significantly different between these three species; mean +/- SEM values were 0.34 +/- 0.1 in mouse, 0.9 +/- 0.2 in rat, and 1.5 +/- 0.5 microM in guinea-pig. The KT values for the low affinity transport system KT(L) were not different between the three species. Brain cells from rat displayed a significantly greater maximal capacity to accumulate (3H)adenosine (Vmax) than didmore » mouse or guinea-pig for the high affinity system, or than did mouse for the low affinity system. When sodium chloride was replaced in the transport medium with choline chloride, the KT(H) values for guinea-pig and rat were both increased by approximately 100%; only in rat did the change reach statistical significance. The sodium-dependence of adenosine transport in mouse brain was clearly absent. The differences between KT(H) values in mouse and those in guinea-pig or rat were accentuated in the absence of sodium. The differences in kinetic values, ionic requirements, and pharmacological characteristics between adenosine transporters in CNS tissues of mouse, guinea-pig and rat may help account for some of the variability noted among species in terms of their physiological responses to adenosine.« less

  6. Recombinant interleukin-12 and interleukin-18 antitumor therapy in a guinea-pig hepatoma cell implant model.

    PubMed

    Shiratori, Ikuo; Suzuki, Yasuhiko; Oshiumi, Hiroyuki; Begum, Nasim A; Ebihara, Takashi; Matsumoto, Misako; Hazeki, Kaoru; Kodama, Ken; Kashiwazaki, Yasuo; Seya, Tsukasa

    2007-12-01

    Interleukin (IL)-12 and IL-18 are secreted by myeloid cells activated with adjuvants such as Bacillus Calmette-Guérin (BCG) cell wall. They induce T-helper 1 polarization in the host immune system and upregulate production of lymphocyte interferon-gamma, which leads to the induction of an antitumor gene program. It has been reported that humans have an immune system that more closely resembles that of the guinea pig in adjuvant-response features rather than the mouse system, which prevents the mouse results being extrapolated to human immunotherapy. Here we have constructed a tumor-implant system in guinea pigs to evaluate the antitumor potential of guinea pig IL-12 (gpIL-12) and guinea pig IL-18 (gpIL-18). Purified recombinant gpIL-12 and gpIL-18 were prepared and applied intraperitoneally to tumor-bearing (line 10 hepatoma) guinea pigs as the basis of the adjuvant immunotherapy. Intraperitoneal administration of gpIL-12 and gpIL-18 led to retardation of primary tumor growth and suppression of lymph-node metastasis in tumor-bearing guinea pigs. The permissible range of IL-12 appeared wider in guinea pigs than in mice. Even at an IL-12 dose higher than that in mice, there was no evidence of side-effects until day 26, when the guinea pigs were killed. gpIL-18 augmented the antitumor effect of gpIL-12 but exerted less ability to suppress lymph-node metastasis. The effects of gpIL-12 and gpIL-18 on the tumors implanted in guinea pigs will encourage us to use IL-12- and IL-18-inducible adjuvants for immunotherapy in human patients with solid cancer.

  7. Long-term effects of substance P on the isolated guinea pig trachea.

    PubMed

    Schreiber, J; Slapke, J; Nieber, K; Oehme, P

    1988-01-01

    The undecapeptide substance P(SP) and its C-terminal sequence SP-5-11 induced a dose-dependent contraction of the isolated guinea pig trachea. SP-5-11 had a more potent bronchoconstrictive action than SP-1-11. The distal part of the isolated guinea pig trachea showed a greater reagibility to SP-5-11 than the proximal one. There was a continuous increase of the amplitude of the SP-1-11-induced contractions when the neuropeptide was added several times at one-hour intervals. Incubation with 10(-6) M SP-1-11 for 5 h reduced the reagibility of the isolated guinea pig trachea to acetylcholine.

  8. Comparison of the effects of histamine and tolazoline on adenylate cyclase activity from guinea pig heart.

    PubMed

    Weinryb, I; Michel, I M

    1975-01-01

    Both histamine and tolazoline (2-benzyl-2-imidazoline) stimulated particulate fractions of adenylate cyclase from guinea pig myocardium. Tolazoline was one-tenth as potent, and about two-thirds as active at maximally effective levels, as was histamine. Enhancement of cyclase activity by tolazoline was additive with that by isoproterenol, and the histamine and tolazoline concentration-response curves were parallel, suggesting that tolazoline acted at the same site as histamine. At maximally effective concentrations, tolazoline did not affect ATPase or cyclic AMP phosphodiesterase activities associated with the cyclase preparations. The H1-receptor antagonist mepyramine, and the H2 antagonist, burimamide, blocked stimulation of cyclase by tolazoline at one-tenth the molarity of agonist. Both antagonists were less effective vs. histamine stimulation of heart cyclase in particulate fractions or whole homogenates, with mepyramine being generally more potent. It is suggested that the molecular basis of the stimulatory effect of tolazoline on cardiac tissue may be histaminergic stimulation of adenylate cyclase. Furthermore, the lack of potency of burimamide as a histamine antagonist and its lack of specificity compared to mepyramine, at the subcellular level, indicate that histamine-responsive adenylate cyclase from heart may not be a satisfactory molecular model for the H2 receptor pharmacology of histamine in cardiac tissue.

  9. The OARSI Histopathology Initiative - Recommendations for Histological Assessments of Osteoarthritis in the Guinea Pig

    PubMed Central

    Kraus, Virginia B; Huebner, Janet L.; DeGroot, Jeroen; Bendele, Alison

    2010-01-01

    Objective This review focuses on the criteria for assessing osteoarthritis (OA) in the guinea pig at the macroscopic and microscopic levels, and recommends particular assessment criteria to assist standardization in the conduct and reporting of preclinical trails in guinea pig models of OA. Methods A review was conducted of all OA studies from 1958 until the present that utilized the guinea pig. The PubMed database was originally searched August 1, 2006 using the following search terms: guinea pig and osteoarthritis. We continued to check the database periodically throughout the process of preparing this chapter and the final search was conducted January 7, 2009. Additional studies were found in a review of abstracts from the OsteoArthritis Research Society International (OARSI) conferences, Orthopaedic Research Society (ORS) conferences, and literature related to histology in other preclinical models of OA reviewed for relevant references. Studies that described or used systems for guinea pig joint scoring on a macroscopic, microscopic, or ultrastructural basis were included in the final comprehensive summary and review. General recommendations regarding methods of OA assessment in the guinea pig were derived on the basis of a comparison across studies and an inter-rater reliability assessment of the recommended scoring system. Results A histochemical-histological scoring system (based on one first introduced by H. Mankin) is recommended for semi-quantitative histological assessment of OA in the guinea pig, due to its already widespread adoption, ease of use, similarity to scoring systems used for OA in humans, its achievable high inter-rater reliability, and its demonstrated correlation with synovial fluid biomarker concentrations. Specific recommendations are also provided for histological scoring of synovitis and scoring of macroscopic lesions of OA. Conclusions As summarized herein, a wealth of tools exist to aid both in the semi-quantitative and quantitative

  10. Estrogen and Hydroxysteroid Sulfotransterases in Guinea Pig Adrenal Cortex: Cellular and Subcellular Distributions

    DTIC Science & Technology

    1993-06-01

    hydroxysteroid substrate specificities (32 and 33 kilodaltons, respectively) were previously purified from guinea pig adrenal cortex and characterized. Western...labeling with these antisera revealed that the sulfortransferases were expressed only within the ACTH- responsive layers of the guinea pig adrenal cortex

  11. Strain difference in the immune response to hydralazine in inbred guinea-pigs

    PubMed Central

    Ellman, L.; Inman, J.; Green, Ira

    1971-01-01

    Guinea-pigs were immunized with hydralazine in Freund's complete adjuvant. A marked strain difference in the immune response involving both anti-hydralazine antibody and delayed hypersensitivity to hydralazine was observed in different strains of guinea-pigs: Hartley guinea-pigs and inbred strain 13 guinea-pigs were able to mount a vigorous immune response to the drug while inbred strain 2 guinea-pigs appeared to be `low or non-responders'. This difference could not be explained in terms of metabolism of the drug in that no differences in acetylation were observed. Breeding studies suggest that immune responsiveness to hydralazine is inherited in an autosomal dominant manner. The immune response to hydralazine may be controlled by a `specific immune response gene' which appears not to be linked to the major strain 13 histocompatibility gene. Anti-nuclear and anti-DNA antibodies could not be demonstrated at a time when the animals manifested a strong immune response to hydralazine. Thus, the development of auto-immune phenomena does not appear to be related to the development of an immune response to the drug in short term immunization. Hydralazine-protein conjugates were synthesized, radio-iodinated and used in a Farr technique for the measurement of anti-hydralazine antibody. These techniques for the assay of anti-hydralazine antibodies may be useful in clinical investigations. Imagesp933-a PMID:5316639

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

    PubMed

    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.

  13. [Effects of asphyxia on endocochlear direct-current potential in guinea pig].

    PubMed

    Liu, Xiuli; Ren, Zhong; Lü, Mei; Nakashima, Tsutomu

    2006-04-01

    To investigate the mechanism of auditory function disturbance due to asphyxiants. Guinea pigs with nice auricle reflex were selected in the experiment. The changes of endocochlear direct-current potential (EP) were detected when apnea and after artificial respiration, using the stria vascularis method. (1) The original EP of experimental group was (76.4+/-8.4) mV, and the original EP of control group was (80.8+/-8.4) mV, there was no significant difference between them. (2) During apnea, the EP of all the guinea pigs decreased precipitously after incubation period of 8 to 34 seconds. The decreasing rate of EP was positively correlated to the incubation period (P=0.008). (3) After 3 minutes of apnea, the mean minimum of EP was (-17.5+/-4.4) mV, which was positively correlated with decreasing rate and incubation period (P was 0.0002, 0.000 separately). (4) After artificial respiration, it needed the average time of (85.0+/-16.0) s to return original EP, and 7 cases got an overrun. The EP of all the guinea pigs decreased when apnea, which showed the abnormal living circumstance of acoustic hair cells. After 3 minutes of apnea, the EP of all the guinea pigs decreased to negative value, which demonstrated that the functions of acoustic hair cells had not lost within 3 minutes of apnea. After artificial respiration, all the guinea pigs' EP returned to original value, which indicated that the functions of the stria vascularis had not failed irreversibly.

  14. Distribution of cocaine- and amphetamine-regulated transcript in the hippocampal formation of the guinea pig and domestic pig.

    PubMed

    Kolenkiewicz, M; Robak, A; Równiak, M; Bogus-Nowakowska, K; Całka, J; Majewski, M

    2009-02-01

    This study provides a detailed description concerning the distribution of cocaineand amphetamine-regulated transcript (CART) subunits - CART(61-102) and rhCART(28-116) - in the hippocampal formation (HF) of the guinea pig and domestic pig, focussing on the dentate gyrus (DG) and hippocampus proper (HP). Although in both studied species CART-immunoreactive (CART-IR) neuronal somata and processes were present generally in the same layers, some species-specific differences were still found. In the granular layer (GL) of both species, the ovalshaped neurons and some thick varicose fibres were encountered. In the guinea pig there was an immunoreactive "band of dots", probably representing crosssectioned terminals within the DG molecular layer (MOL), whereas in the domestic pig, some varicose fibres were detected, thus suggesting a different orientation of, at least, some nerve terminals. Furthermore, some CART-positive cells and fibres were observed in the hilus (HL) of the guinea pig, whereas in the analogical part of the domestic pig only nerve terminals were labelled. In both species, in the pyramidal layer (PL) of the hippocampus proper, CART-IR triangular somata were observed in the CA3 sector, as well as some positive processes in MOL; however, a few immunoreactive perikarya were found only in the CA1 sector of the guinea pig. As regards the localization patterns of two isoforms of CART in the guinea pig, both peptide fragments were present simultaneously in each of the labelled neurons or fibres, whereas in the domestic pig three types of fibres may be distinguished within the area of the DG. In the hilus and MOL of the dentate gyrus, there were fibres expressing both isoforms of CART in their whole length (fibres of the first type). Fibres of the second type (in GL) coexpressed both peptides only on their short segments, and the last ones (in MOL) expressed solely rhCART(28-116). These results indicate that the distribution of the two CART isoforms are

  15. Development of a novel, guinea pig-specific IFN-γ ELISPOT assay and characterization of guinea pig cytomegalovirus GP83-specific cellular immune responses following immunization with a modified vaccinia virus Ankara (MVA)-vectored GP83 vaccine.

    PubMed

    Gillis, Peter A; Hernandez-Alvarado, Nelmary; Gnanandarajah, Josephine S; Wussow, Felix; Diamond, Don J; Schleiss, Mark R

    2014-06-30

    The guinea pig (Cavia porcellus) provides a useful animal model for studying the pathogenesis of many infectious diseases, and for preclinical evaluation of vaccines. However, guinea pig models are limited by the lack of immunological reagents required for characterization and quantification of antigen-specific T cell responses. To address this deficiency, an enzyme-linked immunospot (ELISPOT) assay for guinea pig interferon (IFN)-γ was developed to measure antigen/epitope-specific T cell responses to guinea pig cytomegalovirus (GPCMV) vaccines. Using splenocytes harvested from animals vaccinated with a modified vaccinia virus Ankara (MVA) vector encoding the GPCMV GP83 (homolog of human CMV pp65 [gpUL83]) protein, we were able to enumerate and map antigen-specific responses, both in vaccinated as well as GPCMV-infected animals, using a panel of GP83-specific peptides. Several potential immunodominant GP83-specific peptides were identified, including one epitope, LGIVHFFDN, that was noted in all guinea pigs that had a detectable CD8+ response to GP83. Development of a guinea pig IFN-γ ELISPOT should be useful in characterization of additional T cell-specific responses to GPCMV, as well as other pathogens. This information in turn can help focus future experimental evaluation of immunization strategies, both for GPCMV as well as for other vaccine-preventable illnesses studied in the guinea pig model. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Distribution and excretion of BisGMA in guinea pigs.

    PubMed

    Reichl, F X; Seiss, M; Kleinsasser, N; Kehe, K; Kunzelmann, K H; Thomas, P; Spahl, W; Hickel, R

    2008-04-01

    Bisphenol-A-glycidyldimethacrylate (BisGMA) is used in many resin-based dental materials. It was shown in vitro that BisGMA was released into the adjacent biophase from such materials during the first days after placement. In this study, the uptake, distribution, and excretion of [(14)C]BisGMA applied via gastric and intravenous administration (at dose levels well above those encountered in dental care) were examined in vivo in guinea pigs to test the hypothesis that BisGMA reaches cytotoxic levels in mammalian tissues. [(14)C]BisGMA was taken up rapidly from the stomach and intestine after gastric administration and was widely distributed in the body following administration by each route. Most [(14)C] was excreted within one day as (14)CO(2). The peak equivalent BisGMA levels in guinea pig tissues examined were at least 1000-fold less than known toxic levels. The peak urine level in guinea pigs that received well in excess of the body-weight-adjusted dose expected in humans was also below known toxic levels. The study therefore did not support the hypothesis.

  17. Genetic factors of Ebola virus virulence in guinea pigs.

    PubMed

    Subbotina, Ekaterina; Dadaeva, Alexandra; Kachko, Alla; Chepurnov, Alexander

    2010-10-01

    Zaire ebolavirus (ZEBOV) causes severe hemorrhagic fever in primates, whereas in guinea pigs it induces a nonlethal infection with a mild fever and subsequent recovery. We performed 7 selective passages in guinea pigs resulted in obtaining of guinea pig-adapted strain (GPA-P7) strain. By the 7th passage, the infection with EBOV induced a lethal disease in animals accompanied by the characteristic hematological changes: leukocytosis (primarily due to neutrophilia) as well as pronounced deficiencies in platelets, lymphocytes, monocytes and significant decrease of blood neutrophils phagocytic capacity. Increasing of virulence correlated with appearance of several nucleotide substitutions: in the genes NP, A2166G (N566S), VP24, U10784C (L147P), G10557A (M71I), G10805U (R154L), and L, G12286A (V236I). It has been theoretically calculated that the mutations associated with an increase in EBOV virulence can confer characteristic secondary structure on the proteins NP (C-terminal region) and full-sized VP24. (c) 2010 Elsevier B.V. All rights reserved.

  18. Crataegus extract prolongs action potential duration in guinea-pig papillary muscle.

    PubMed

    Müller, A; Linke, W; Zhao, Y; Klaus, W

    1996-11-01

    Crataegus extract is used in cardiology for the treatment of moderate heart failure (NYHA II). Recently it was shown that Crataegus extract prolongs the refractory period in isolated perfused guinea pig hearts. In order to find out what mechanism is responsible for this prolongation of refractory period, we investigated the effects of Crataegus extract (LI 132) on the action potential of guinea pig papillary muscle with the help of conventional microelectrode techniques. Crataegus extract, when put in a concentration (10 mg/l) capable of inducing an inotropic effect of about 20%, significantly increased action potential duration at all investigated levels of repolarisation. Maximum prolongation was 8.5±2.3 ms, 12.5±2.6 ms and 11.7±2.9 ms at 20%, 50% and 90% repolarisation, respectively (control APD(90): 172±4 ms). Experiments on the time course of recovery of the maximum upstroke velocity (V(max)) of the action potential revealed that Crataegus extract increased the time constant of recovery of V(max) from 8.80±2.33 ms to 22.60±5.77 ms, indicating a weak Class I-like antiarrhythmic action. In addition, we observed a small reduction in V(max). In summary, our results show that Crataegus extract prolongs action potential duration and delays recovery of V(max). We, therefore, suggest that Crataegus extract possesses certain antiarrhythmic properties. Copyright © 1996 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

  19. New Methods for Evaluating Skin Injury from Sulfur Mustard in the Hairless Guinea Pig

    DTIC Science & Technology

    1993-05-13

    MUSTARD IN THE HAIRLESS GUINEA PIG Ernest H. Braue, Jr., Catherine R. Bangledorf, and Robert G. Rieder "U.S. Army Medical Research Institute of Chemical...evaluating the skin hydration state. The skin of anesthetized hairless guinea pigs was exposed to saturated HD vapor (1.4mg/ml) at 4 sites for 3, 5, 7, or 9...assessment of skin damage following cutaneous exposure to HD vapor. EXPERIMENTAL METHODS Each hairless guinea pig (HGP) was exposed to saturated HD vapor

  20. Development of a guinea pig model of chorioamnionitis and fetal brain injury.

    PubMed

    Patrick, Lindsay A; Gaudet, Laura M; Farley, Anne E; Rossiter, John P; Tomalty, Lewis L; Smith, Graeme N

    2004-10-01

    The purpose of this study was to develop a guinea pig model of chorioamnionitis to study the mechanisms that lead to fetal brain injury. Study design Pregnant guinea pigs at 70% gestation were inoculated intracervically with 1000 to 2500 colony-forming units of Escherichia coli. Guinea pigs were killed 2 to 3 days after bacterial inoculation. Maternal blood and fetal amniotic fluid samples were analyzed for proinflammatory cytokine tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 levels with the use of enzyme-linked immunosorbent assay kits. Fetal brains were stained for evidence of cell death with NeuroTacs stain. Of 34 maternal guinea pigs that were given an intracervical inoculation of E coli, 8 guinea pigs showed microbiologic evidence of chorioamnionitis in the amniotic fluid. Tumor necrosis factor-alpha and interleukin-6 were significantly higher (P<.05) in amniotic fluid samples that were obtained from sows that were subjected to intracervical inoculation with bacteria as compared with control animals (n=6 control maternal animals). These results were observed even if no bacteria were found subsequently on culture of the amniotic fluid from inoculated animals, which indicated that indirect exposure to infectious agents was sufficient to cause an elevated inflammatory response in the fetus. Levels of white matter injury were greater in fetuses that were exposed to bacterial infection in utero, as compared with control animals (P<.05). This result was found in the staining of periventricular and cortical white matter for the immunolabeling of activated caspase 3 and NeuroTacs staining for cells that exhibited evidence of apoptotic cell death (positive stain with evidence of karyorrhexis). Intracervical inoculation with E coli results in chorioamnionitis in guinea pigs that is associated with fetal brain injury.

  1. Behavioral responses of deafened guinea pigs to intracochlear electrical stimulation: a new rapid psychophysical procedure.

    PubMed

    Agterberg, Martijn J H; Versnel, Huib

    2014-07-01

    In auditory research the guinea pig is often preferred above rats and mice because of the easily accessible cochlea and because the frequency range of its hearing is more comparable to that of humans. Studies of the guinea-pig auditory system primarily apply histological and electrophysiological measures. Behavioral animal paradigms, in particular in combination with these histological and electrophysiological methods, are necessary in the development of new therapeutic interventions. However, the guinea pig is not considered an attractive animal for behavioral experiments. Therefore, the purpose of this study was to develop a behavioral task suitable for guinea pigs, that can be utilized in cochlear-implant related research. Guinea pigs were trained in a modified shuttle-box in which a stream of air was used as unconditioned stimulus (UCS). A stream of air was preferred over conventionally used methods as electric foot-shocks since it produces less stress, which is a confounding factor in behavioral experiments. Hearing guinea pigs were trained to respond to acoustic stimuli. They responded correctly within only five sessions of ten minutes. The animals maintained their performance four weeks after the right cochlea was implanted with an electrode array. After systemic deafening, the animals responded in the first session immediately to intracochlear electrical stimulation. These responses were not affected by daily chronic electrical stimulation (CES). In conclusion, the present study demonstrates that guinea pigs can be trained relatively fast to respond to acoustic stimuli, and that the training has a lasting effect, which generalizes to intracochlear electrical stimulation after deafening. Furthermore, it demonstrates that bilaterally deafened guinea pigs with substantial (∼50%) loss of spiral ganglion cells (SGCs), detect intracochlear electrical stimulation. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Acute Inhalation Toxicity of T-2 Mycotoxin in the Rat and Guinea Pig

    DTIC Science & Technology

    1990-01-01

    2/kg body weight for the guinea pig . These data show that inhaled T-2 toxin is approximately 20 times more toxic to the rat (0.05 mg T-2/kg body wt...inhaled vs 1.0 mg T-2/kg body wt ip) and at least twice as toxic to the guinea pig (0.4 mg T-2/kg body wt inhaled vs 1-2 mg T-2/kg body wt ip) than ip...administered T-2 toxin. Histopathologic examination of major organs in both the rat and guinea pig after respiratory exposure to T-2 toxin indicated

  3. Inbred guinea pig model of intrauterine infection with cytomegalovirus.

    PubMed

    Griffith, B P; McCormick, S R; Booss, J; Hsiung, G D

    1986-01-01

    Outbred guinea pigs have previously been utilized in an experimental model for the study of congenital infection with cytomegalovirus (CMV). Development of an inbred model of intrauterine CMV infection would allow analysis of the cells involved in CMV immunity, studies of transplacental CMV transfer, and investigation of the cellular immune factors that participate in intrauterine CMV infections. This study was therefore designed to assess the inbred guinea pig as a model for the study of congenital CMV infection. Intrauterine fetal and placental infection with CMV was demonstrated in inbred Strain 2 guinea pigs, and the maternal factors influencing transplacental transmission of CMV were evaluated. Infectious virus was recovered from placentas and offspring of mothers that experienced primary CMV infection during pregnancy, but not from placentas and offspring of mothers that were inoculated with CMV prior to pregnancy. However, histologic lesions consisting of focal necrosis and inflammation were seen in tissues of offspring from both groups of mothers. Inoculation of seronegative pregnant Strain 2 animals with low doses of virus (2.5 to 3.5 log10 TCID50) resulted in both placental and fetal CMV infection without significant maternal death. Infection of placentas and offspring occurred in utero regardless of the stage of pregnancy. In addition, infectious virus was detectable in fetal tissues at the time of maternal viremia but also later during the course of maternal infection, ie, 4 weeks after inoculation. These findings indicate that the inbred guinea pig model can be used to investigate the pathogenesis of intrauterine CMV infections.

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

    PubMed

    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.

  5. Allogeneic guinea pig mesenchymal stem cells ameliorate neurological changes in experimental colitis.

    PubMed

    Stavely, Rhian; Robinson, Ainsley M; Miller, Sarah; Boyd, Richard; Sakkal, Samy; Nurgali, Kulmira

    2015-12-30

    The use of mesenchymal stem cells (MSCs) to treat inflammatory bowel disease (IBD) is of great interest because of their immunomodulatory properties. Damage to the enteric nervous system (ENS) is implicated in IBD pathophysiology and disease progression. The most commonly used model to study inflammation-induced changes to the ENS is 2,4,6-trinitrobenzene-sulfonate acid (TNBS)-induced colitis in guinea pigs; however, no studies using guinea pig MSCs in colitis have been performed. This study aims to isolate and characterise guinea pig MSCs and then test their therapeutic potential for the treatment of enteric neuropathy associated with intestinal inflammation. MSCs from guinea pig bone marrow and adipose tissue were isolated and characterised in vitro. In in vivo experiments, guinea pigs received either TNBS for the induction of colitis or sham treatment by enema. MSCs were administered at a dose of 1 × 10(6) cells via enema 3 h after the induction of colitis. Colon tissues were collected 24 and 72 h after TNBS administration to assess the level of inflammation and damage to the ENS. The secretion of transforming growth factor-β1 (TGF-β1) was analysed in MSC conditioned medium by flow cytometry. Cells isolated from both sources were adherent to plastic, multipotent and expressed some human MSC surface markers. In vitro characterisation revealed distinct differences in growth kinetics, clonogenicity and cell morphology between MSC types. In an in vivo model of TNBS-induced colitis, guinea pig bone marrow MSCs were comparatively more efficacious than adipose tissue MSCs in attenuating weight loss, colonic tissue damage and leukocyte infiltration into the mucosa and myenteric plexus. MSCs from both sources were equally neuroprotective in the amelioration of enteric neuronal loss and changes to the neurochemical coding of neuronal subpopulations. MSCs from both sources secreted TGF-β1 which exerted neuroprotective effects in vitro. This study is the first

  6. Developing guinea pig brain as a model for cortical folding.

    PubMed

    Hatakeyama, Jun; Sato, Haruka; Shimamura, Kenji

    2017-05-01

    The cerebral cortex in mammals, the neocortex specifically, is highly diverse among species with respect to its size and morphology, likely reflecting the immense adaptiveness of this lineage. In particular, the pattern and number of convoluted ridges and fissures, called gyri and sulci, respectively, on the surface of the cortex are variable among species and even individuals. However, little is known about the mechanism of cortical folding, although there have been several hypotheses proposed. Recent studies on embryonic neurogenesis revealed the differences in cortical progenitors as a critical factor of the process of gyrification. Here, we investigated the gyrification processes using developing guinea pig brains that form a simple but fundamental pattern of gyri. In addition, we established an electroporation-mediated gene transfer method for guinea pig embryos. We introduce the guinea pig brain as a useful model system to understand the mechanisms and basic principle of cortical folding. © 2017 Japanese Society of Developmental Biologists.

  7. Guinea pigs inbred for studies of respiratory anaphylaxis.

    PubMed

    Lundberg, L

    1979-02-01

    A selective inbreeding of approximately 24 generations of albino guinea pigs by brother x sister mating has resulted in two strains, registered IMM/S and IMM/R, with high and low responsiveness, respectively, to ovalbumin-induced respiratory anaphylaxis. The two guinea pig strains differed in their ability to be immunized by the inhalation of antigen and produce antibodies, as well as to develop respiratory anaphylaxis. A correlation between the strength of the anaphylactic reactions and the amount of hemagglutinating antibodies produced was observed. When immunization was carried out by an intradermal injection of ovalbumin (OA), even in small doses incorporated in FCA, guinea pigs from both strains produced hemagglutinating antibodies in nearly the same amount. These antibodies do not influence the ability of the animals to react with a high respectively low anaphylactic response on subsequent challenge by inhalation of OA, neither in the actively sensitized animals nor in passively sensitized animals. However, with repeated inhalations of OA, desensitization occurred in the intradermally immunized high-responders, while the passively immunized high-responders could be provoked several times without any signs of desensitization. No systematical differences between the two strains with regard to sensitivity to inhalations of histamine were demonstrated. The low responders were found to be less resistant to infections than high-responders.

  8. Efficacy of the Tertiary Oxime Monoisonitrosoacetone (MINA) Against Lethal Sarin Intoxication in the Guinea Pig

    DTIC Science & Technology

    2007-10-01

    Sarin 5a. CONTRACT NUMBER Intoxication in the Guinea Pig 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Koplovitz, I and...efficacy of MINA as a treatment for lethal sarin (GB) intoxication in guinea pigs . Male animals were challenged subcutaneously (s.c.) with 2 LD50s...oximes that are readily able to enter the brain. 15. SUBJECT TERMS oximes, brain, sarin, reactivation, nerve agents, guinea pigs 16. SECURITY

  9. Cryptosporidium homai n. sp. (Apicomplexa: Cryptosporidiiae) from the guinea pig (Cavia porcellus).

    PubMed

    Zahedi, Alireza; Durmic, Zoey; Gofton, Alexander W; Kueh, Susan; Austen, Jill; Lawson, Malcolm; Callahan, Lauren; Jardine, John; Ryan, Una

    2017-10-15

    The morphological, biological, and molecular characterisation of a new Cryptosporidium species from the guinea pig (Cavia porcellus) are described, and the species name Cryptosporidium homai n. sp. is proposed. Histological analysis conducted on a post-mortem sample from a guinea pig euthanised due to respiratory distress, identified developmental stages of C. homai n. sp. (trophozoites and meronts) along the intestinal epithelium. Molecular analysis at 18S rRNA (18S), actin and hsp70 loci was then conducted on faeces from an additional 7 guinea pigs positive for C. homai n. sp. At the 18S, actin and hsp70 loci, C. homai n. sp. exhibited genetic distances ranging from 3.1% to 14.3%, 14.4% to 24.5%, and 6.6% to 20.9% from other Cryptosporidium spp., respectively. At the 18S locus, C. homai n. sp. shared 99.1% similarity with a previously described Cryptosporidium genotype in guinea pigs from Brazil and it is likely that they are the same species, however this cannot be confirmed as actin and hsp70 sequences from the Brazilian guinea pig genotype are not available. Phylogenetic analysis of concatenated 18S, actin and hsp70 sequences showed that C. homai n. sp. exhibited 9.1% to 17.3% genetic distance from all other Cryptosporidium spp. This clearly supports the validity of C. homai n. sp. as a separate species. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed Central

    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

  11. Replication and Transmission of the Novel Bovine Influenza D Virus in a Guinea Pig Model

    PubMed Central

    Sreenivasan, Chithra; Thomas, Milton; Sheng, Zizhang; Hause, Ben M.; Collin, Emily A.; Knudsen, David E. B.; Pillatzki, Angela; Nelson, Eric; Wang, Dan; Kaushik, Radhey S.

    2015-01-01

    ABSTRACT Influenza D virus (FLUDV) is a novel influenza virus that infects cattle and swine. The goal of this study was to investigate the replication and transmission of bovine FLUDV in guinea pigs. Following direct intranasal inoculation of animals, the virus was detected in nasal washes of infected animals during the first 7 days postinfection. High viral titers were obtained from nasal turbinates and lung tissues of directly inoculated animals. Further, bovine FLUDV was able to transmit from the infected guinea pigs to sentinel animals by means of contact and not by aerosol dissemination under the experimental conditions tested in this study. Despite exhibiting no clinical signs, infected guinea pigs developed seroconversion and the viral antigen was detected in lungs of animals by immunohistochemistry. The observation that bovine FLUDV replicated in the respiratory tract of guinea pigs was similar to observations described previously in studies of gnotobiotic calves and pigs experimentally infected with bovine FLUDV but different from those described previously in experimental infections in ferrets and swine with a swine FLUDV, which supported virus replication only in the upper respiratory tract and not in the lower respiratory tract, including lung. Our study established that guinea pigs could be used as an animal model for studying this newly emerging influenza virus. IMPORTANCE Influenza D virus (FLUDV) is a novel emerging pathogen with bovine as its primary host. The epidemiology and pathogenicity of the virus are not yet known. FLUDV also spreads to swine, and the presence of FLUDV-specific antibodies in humans could indicate that there is a potential for zoonosis. Our results showed that bovine FLUDV replicated in the nasal turbinate and lungs of guinea pigs at high titers and was also able to transmit from an infected animal to sentinel animals by contact. The fact that bovine FLUDV replicated productively in both the upper and lower respiratory tracts

  12. [Preliminary pharmacodynamics study on antiasthmatic action of butylphthalide in guinea pig].

    PubMed

    Wang, Zhi-Wang; Wang, Yong-Hui; Ren, Yuan; Wang, Rui-Qiong; Lin, Xing-Yao; Duan, Hai-Jing

    2017-02-08

    To study the anti-asthmatic effects of butylphthalide in guinea pig. This research included isolated tra-cheal smooth muscle and in vivo animal experiments. Antispasmodic effects of butylphthalide at the concentrations of 1, 10, 100 mg/L were observed through spasmodical tracheal smooth muscle of guinea pig induced by acetylcholine or histamine ( n =10). After screened, the guinea pigs were divided into control group, model group, dexamethasone(DXM) group, high and low dose butylphthalide groups. The effects of butylphthalide on nitric oxide (NO), endothelin-1 (ET-1) and asthmatic behaviors were observed on the asthmatic guinea pigs that were stimu-lated six times by the excitation fluid (1% ACh:0.05% Hist=1:1). Butylphthalide at the concentrations of 1、10、100 mg/L had an-ti-spasmodic effects on spasmodical tracheal smooth muscle of guinea pig (15.08 ±7.68、42.41 ±13.54、77.56 ±24.82 to acetylcholine, 19.40 ±7.60、56.84 ±11.72、76.35 ±19.40 to histamine), which showed a certain dose-effect relationship. Butylphthalide could prolong asth-matic incubation period (53.3 ±13.2、33.1 ±13.0), improve asthmatic behaviors, reduce NO in serum (78.71 ±19.40、84.75 ±20.97) and ET-1 in bronchoalveolar lavage fluid (24.30 ±5.80、28.50 ±6.31) ( P < 0.05, 0.01). Butylphthalide has some effects of anti-asthma and one of the mechanisms is to relieve abnormal increase of NO and ET-1.

  13. Replication-defective lymphocytic choriomeningitis virus vectors expressing guinea pig cytomegalovirus gB and pp65 homologs are protective against congenital guinea pig cytomegalovirus infection.

    PubMed

    Cardin, Rhonda D; Bravo, Fernando J; Pullum, Derek A; Orlinger, Klaus; Watson, Elizabeth M; Aspoeck, Andreas; Fuhrmann, Gerhard; Guirakhoo, Farshad; Monath, Thomas; Bernstein, David I

    2016-04-12

    Congenital cytomegalovirus infection can be life-threatening and often results in significant developmental deficits and/or hearing loss. Thus, there is a critical need for an effective anti-CMV vaccine. To determine the efficacy of replication-defective lymphocytic choriomeningitis virus (rLCMV) vectors expressing the guinea pig CMV (GPCMV) antigens, gB and pp65, in the guinea pig model of congenital CMV infection. Female Hartley strain guinea pigs were divided into three groups: Buffer control group (n = 9), rLCMV-gB group (n = 11), and rLCMV-pp65 (n = 11). The vaccines were administered three times IM at 1.54 × 10(6)FFU per dose at 21-day intervals. At two weeks after vaccination, the female guinea pigs underwent breeding. Pregnant guinea pigs were challenged SQ at ∼ 45-55 days of gestation with 1 × 10(5)PFU of GPCMV. Viremia in the dams, pup survival, weights of pups at delivery, and viral load in both dam and pup tissues were determined. Pup survival was significantly increased in the LCMV-gB vaccine group. There was 23% pup mortality in the gB vaccine group (p = 0.044) and 26% pup mortality in the pp65 vaccine group (p = 0.054) compared to 49% control pup mortality. The gB vaccine induced high levels of gB binding and detectable neutralizing antibodies, reduced dam viremia, and significantly reduced viral load in dam tissues compared to control dams (p < 0.03). Reduced viral load and transmission in pups born to gB-vaccinated dams was observed compared to pups from pp65-vaccinated or control dams. The rLCMV-gB vaccine significantly improved pup survival and also increased pup weights and gestation time. The gB vaccine was also more effective at decreasing viral load in dams and pups and limiting congenital transmission. Thus, rLCMV vectors that express CMV antigens may be an effective vaccine strategy for congenital CMV infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. THE STATE OF IMMUNITY IN GUINEA-PIGS IMMUNIZED WITH LIVE BRUCELLOSIS VACCINE AND EXPOSED TO RADIATION

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shevtsova, Z.V.

    1960-01-01

    On immunization with 19-BA live brucellosis vaccine on the 3rd and 10th days after exposure to radiation in a dose of 200 r, guinea pigs died 4 and 2 times more frequently than unvaccinated guinea pigs. If immunization was carried out on the 30th day after irradiation the mortality among irradiated animals showed only a slight increase compared with the mortality among unvaccinated control animals. Immunization carried out before exposure to radiation had no influence upon the mortality of the animals caused by radiation sickness. Guinea pigs immunized after exposure to radiation were insusceptible when infected with the doses ofmore » virulent strains of Brucella usually employed to challenge immunity (2-4 infective doses). If, however, the animals were infected with a dose twice as high (8 infective doses) the degree of immunity proved to be lower in guinea pigs exposed to radiation, than in guinea pigs immunized and not exposed to radiation. Exposure of guinea pigs to radiation at a time when immunity had already developed had no influence upon the degree of immunity on infection with 4 infective doses of the virulent strain. (auth)« less

  15. The Potential Application of Hairless Guinea Pigs as a Replacement for the Yucatan Mini-pig in Animal Studies

    DTIC Science & Technology

    2009-02-01

    tissue. 4. The biopsy sample was removed using forceps . 5. The sample was placed into a pre-labeled holder and then inserted into a jar of 10% neutral...are excessive for projects using smaller beams. This experiment performed histological analysis of skin biopsies from pigmented Hairless Guinea Pigs...smaller beams. This experiment performed histological analysis of skin biopsies from pigmented Hairless Guinea Pigs (Cavia porcellus) for epidermal

  16. Differences in the distribution and characteristics of tachykinin NK1 binding sites between human and guinea pig lung.

    PubMed Central

    Walsh, D A; Salmon, M; Featherstone, R; Wharton, J; Church, M K; Polak, J M

    1994-01-01

    1. The distribution and characteristics of tachykinin NK1 binding sites have been compared in human and guinea pig lung using quantitative in vitro receptor autoradiography with [125I]-Bolton Hunter-labelled substance P ([125I]-BH-SP). In addition, the effects on these sites of ovalbumin sensitization and challenge have been determined in guinea pig lung. 2. [125I]-BH-SP bound specifically and with high affinity to microvascular endothelium in both human and guinea pig lung, but to bronchial smooth muscle and pulmonary artery media in only guinea pig lung. 3. Specific binding of [125I]-BH-SP to guinea pig bronchial smooth muscle was positively correlated with airway diameter in the range 150-800 microns and was less dense in trachea than in main bronchi. 4. [125I]-BH-SP binding was inhibited by tachykinins with rank orders of affinity of SP > NKA > NKB (human microvessels) and SP > NKA = NKB (guinea pig bronchi and pulmonary arteries). NKA displayed a higher affinity for [125I]-BH-SP binding sites in human microvessels than in guinea pig tissues (P < 0.0001), indicating differences in selectivity for tachykinins between human and guinea pig NK1 receptors. 5. In both human and guinea pig lung, [125I]-BH-SP binding was inhibited by the specific tachykinin receptor antagonists FK888 (NK1 selective antagonist) and FK224 (mixed NK1/NK2 antagonist), with FK888 displaying equal affinity to SP and > 500 times higher affinity than FK224. SP, NKA, NKB and FK888 exhibited similar affinities for [125I]-BH-SP binding sites in both guinea pig arteries and bronchi.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 2 PMID:7534186

  17. Plague in Guinea pigs and its prevention by subunit vaccines.

    PubMed

    Quenee, Lauriane E; Ciletti, Nancy; Berube, Bryan; Krausz, Thomas; Elli, Derek; Hermanas, Timothy; Schneewind, Olaf

    2011-04-01

    Human pneumonic plague is a devastating and transmissible disease for which a Food and Drug Administration-approved vaccine is not available. Suitable animal models may be adopted as a surrogate for human plague to fulfill regulatory requirements for vaccine efficacy testing. To develop an alternative to pneumonic plague in nonhuman primates, we explored guinea pigs as a model system. On intranasal instillation of a fully virulent strain, Yersinia pestis CO92, guinea pigs developed lethal lung infections with hemorrhagic necrosis, massive bacterial replication in the respiratory system, and blood-borne dissemination to other organ systems. Expression of the Y. pestis F1 capsule was not required for the development of pulmonary infection; however, the capsule seemed to be important for the establishment of bubonic plague. The mean lethal dose (MLD) for pneumonic plague in guinea pigs was estimated to be 1000 colony-forming units. Immunization of guinea pigs with the recombinant forms of LcrV, a protein that resides at the tip of Yersinia type III secretion needles, or F1 capsule generated robust humoral immune responses. Whereas LcrV immunization resulted in partial protection against pneumonic plague challenge with 250 MLD Y. pestis CO92, immunization with recombinant F1 did not. rV10, a vaccine variant lacking LcrV residues 271-300, elicited protection against pneumonic plague, which seemed to be based on conformational antibodies directed against LcrV. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  18. Plague in Guinea Pigs and Its Prevention by Subunit Vaccines

    PubMed Central

    Quenee, Lauriane E.; Ciletti, Nancy; Berube, Bryan; Krausz, Thomas; Elli, Derek; Hermanas, Timothy; Schneewind, Olaf

    2011-01-01

    Human pneumonic plague is a devastating and transmissible disease for which a Food and Drug Administration–approved vaccine is not available. Suitable animal models may be adopted as a surrogate for human plague to fulfill regulatory requirements for vaccine efficacy testing. To develop an alternative to pneumonic plague in nonhuman primates, we explored guinea pigs as a model system. On intranasal instillation of a fully virulent strain, Yersinia pestis CO92, guinea pigs developed lethal lung infections with hemorrhagic necrosis, massive bacterial replication in the respiratory system, and blood-borne dissemination to other organ systems. Expression of the Y. pestis F1 capsule was not required for the development of pulmonary infection; however, the capsule seemed to be important for the establishment of bubonic plague. The mean lethal dose (MLD) for pneumonic plague in guinea pigs was estimated to be 1000 colony-forming units. Immunization of guinea pigs with the recombinant forms of LcrV, a protein that resides at the tip of Yersinia type III secretion needles, or F1 capsule generated robust humoral immune responses. Whereas LcrV immunization resulted in partial protection against pneumonic plague challenge with 250 MLD Y. pestis CO92, immunization with recombinant F1 did not. rV10, a vaccine variant lacking LcrV residues 271-300, elicited protection against pneumonic plague, which seemed to be based on conformational antibodies directed against LcrV. PMID:21406168

  19. Guinea pig model for evaluating the potential public health risk of swine and avian influenza viruses.

    PubMed

    Sun, Yipeng; Bi, Yuhai; Pu, Juan; Hu, Yanxin; Wang, Jingjing; Gao, Huijie; Liu, Linqing; Xu, Qi; Tan, Yuanyuan; Liu, Mengda; Guo, Xin; Yang, Hanchun; Liu, Jinhua

    2010-11-23

    The influenza viruses circulating in animals sporadically transmit to humans and pose pandemic threats. Animal models to evaluate the potential public health risk potential of these viruses are needed. We investigated the guinea pig as a mammalian model for the study of the replication and transmission characteristics of selected swine H1N1, H1N2, H3N2 and avian H9N2 influenza viruses, compared to those of pandemic (H1N1) 2009 and seasonal human H1N1, H3N2 influenza viruses. The swine and avian influenza viruses investigated were restricted to the respiratory system of guinea pigs and shed at high titers in nasal tracts without prior adaptation, similar to human strains. None of the swine and avian influenza viruses showed transmissibility among guinea pigs; in contrast, pandemic (H1N1) 2009 virus transmitted from infected guinea pigs to all animals and seasonal human influenza viruses could also horizontally transmit in guinea pigs. The analysis of the receptor distribution in the guinea pig respiratory tissues by lectin histochemistry indicated that both SAα2,3-Gal and SAα2,6-Gal receptors widely presented in the nasal tract and the trachea, while SAα2,3-Gal receptor was the main receptor in the lung. We propose that the guinea pig could serve as a useful mammalian model to evaluate the potential public health threat of swine and avian influenza viruses.

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

    PubMed

    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.

  1. Impact of Hypokalemia on Electromechanical Window, Excitation Wavelength and Repolarization Gradients in Guinea-Pig and Rabbit Hearts

    PubMed Central

    Osadchii, Oleg E.

    2014-01-01

    Normal hearts exhibit a positive time difference between the end of ventricular contraction and the end of QT interval, which is referred to as the electromechanical (EM) window. Drug-induced prolongation of repolarization may lead to the negative EM window, which was proposed to be a novel proarrhythmic marker. This study examined whether abnormal changes in the EM window may account for arrhythmogenic effects produced by hypokalemia. Left ventricular pressure, electrocardiogram, and epicardial monophasic action potentials were recorded in perfused hearts from guinea-pig and rabbit. Hypokalemia (2.5 mM K+) was found to prolong repolarization, reduce the EM window, and promote tachyarrhythmia. Nevertheless, during both regular pacing and extrasystolic excitation, the increased QT interval invariably remained shorter than the duration of mechanical systole, thus yielding positive EM window values. Hypokalemia-induced arrhythmogenicity was associated with slowed ventricular conduction, and shortened effective refractory periods, which translated to a reduced excitation wavelength index. Hypokalemia also evoked non-uniform prolongation of action potential duration in distinct epicardial regions, which resulted in increased spatial variability in the repolarization time. These findings suggest that arrhythmogenic effects of hypokalemia are not accounted for by the negative EM window, and are rather attributed to abnormal changes in ventricular conduction times, refractoriness, excitation wavelength, and spatial repolarization gradients. PMID:25141124

  2. Effect of ozone exposure on antigen-induced airway hyperresponsiveness in guinea pigs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vargas, M.H.; Segura, P.; Campos, M.G.

    1994-12-31

    Airway hyperresponsiveness can be induced by several stimuli including antigen and ozone, both of which may be present in the air of polluted cities. Though the effect of ozone on the bronchoconstrictor response to antigen has been well described, the combined effect of these stimuli on airway hyperresponsiveness has not yet been studied. Sensitized guinea pigs with or without ozone exposure for 1 h at 3 ppm, 18 h prior to study, were challenged with a dose-response curve to histamine (0.01-1.8 {mu}g/kg, iv), and then by a second histamine dose-response curve 1 h later. Airway responses were measured as themore » increase in pulmonary insufflation pressure. In sensitized guinea pigs, the histamine ED50 significantly decreased after antigen challenge, demonstrating the development of airway hyperresponsiveness. Sensitized guinea pigs exposed to ozone showed airway hyperresponsiveness to histamine when compared with nonexposed animals, and such hyperresponsiveness was further enhanced after antigen challenge. We conclude that in this guinea pig model of acute allergic bronchoconstriction both antigen challenge and ozone induce airway hyperresponsiveness, while ozone exposure does not modify the development of antigen-induced hyperresponsiveness. 25 refs., 1 fig., 1 tab.« less

  3. Regeneration of guinea PIG facial nerve: the effect of hypergravity

    NASA Astrophysics Data System (ADS)

    Rosenzweig, E.; Horodiceanu, E.; Ishay, J. S.

    Exposure to moderate hypergravity improves the regenerative capacity of sectioned guinea-pig facial nerve. The improvement in regeneration is tri-directional as follows: a) an average 1.7 fold increase in rate of regeneration in guinea pigs subjected to hypergravity; b) a 25% enhancement of facial muscle activity following the exposure to hypergravity; and c) improvement in the quality of regeneration from an esthetic standpoint. A good correlation was recorded between the histological structure of the severed nerve at the end of the regeneration and the clinical results.

  4. [Construction of recombinant adenovirus and mediated reported gene expression in the guinea pig cochlea].

    PubMed

    Liu, Yingpeng; Wang, Guopeng; Shen, Anmin; Wang, Jianting; Chen, Pei; Li, Zeweng; Gong, Shusheng

    2007-08-01

    To purify P0 protein from guinea pig's inner ear by preparative SDS-PAGE and study the possible role it may play in the etiology of autoimmune inner ear disease. A mixture of membraneous proteins of inner ear was separated by preparative SDS-PAGE. The corresponding band at 30kd was cut and electrically eluted. The protein collected was identified by analytical SDS-PAGE and Western blot assay. A group of 20 guinea pigs were immunized with P0 protein emulsified in complete Freund's adjuvant, another 10 guinea pigs were immunized with complete Freund 's adjuvant only as control. The guinea pigs' hearing thresholds, serum IgG level and morphological changes in the inner ear were investigated. The distribution of P0 protein in the cochlear was detected by immunohistochemical technique. The purity of the protein was demonstrated by a single band at the 30 kD site in SDS-PAGE, which was identified as P0 protein by western blot analysis assay. About 17.5% P0-immunized guinea pigs showed increased hearing thresholds, elevated IgG level (F =6.48, P <0. 01), as well as a decreased number of spiral ganglion cells and inflammatory cell infiltration in the cochlear nerve region. The P0 protein is distributed in the cochlear nerve and spiral ganglion only. P0 protein from guinea pig's inner ear can be successfully purified by preparative SDS-PAGE and an animal model of experimental autoimmune inner ear disease induced by P0 protein is successfully established.

  5. Conjugated linoleic acid mitigates testosterone-related changes in body composition in male guinea pigs.

    PubMed

    Yang, Susan Q; DeGuire, Jason R; Lavery, Paula; Mak, Ivy L; Weiler, Hope A; Santosa, Sylvia

    2016-05-01

    We hypothesize that conjugated linoleic acid (CLA) may be effective in preventing the changes in total and regional body composition and increases in interleukin (IL) 6 that occur as a result of hypogonadism. Male guinea pigs (n = 40, 70- to 72-week retired breeders) were block randomized by weight into 4 groups: (1) sham surgery (SHAM)/control (CTRL) diet, (2) SHAM/conjugated linoleic acid (CLA) diet (1%), (3) orchidectomy (ORX)/CTRL diet, and (4) ORX/CLA diet. Dual-energy x-ray absorptiometry scans were performed at baseline and week 16 to assess body composition. Serum IL-6 was analyzed using an enzyme-linked immune sorbent assay. Fatty acids (FAs) from visceral and subcutaneous adipose tissue were analyzed using gas chromatography. In ORX/CTRL guinea pigs, percent total body fat increased by 6.1%, and percent lean mass decreased by 6.7% over the 16-week treatment period, whereas no changes were observed for either parameter in ORX/CLA guinea pigs. Guinea pigs fed the CLA diet gained less percent total, upper, and lower body fat than those fed the CTRL diet regardless of surgical treatment. Regional adipose tissue FA composition was reflective of dietary FAs. Serum IL-6 concentrations were not different among groups. In this study, we observed that, in male guinea pigs, hypogonadism resulted in increased fat mass and decreased lean mass. In addition, CLA was effective in reducing gains in body fat and maintaining lean mass in both hypogonadal and intact guinea pigs. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Pathology and pathophysiology of inhalational anthrax in a guinea pig model.

    PubMed

    Savransky, Vladimir; Sanford, Daniel C; Syar, Emily; Austin, Jamie L; Tordoff, Kevin P; Anderson, Michael S; Stark, Gregory V; Barnewall, Roy E; Briscoe, Crystal M; Lemiale-Biérinx, Laurence; Park, Sukjoon; Ionin, Boris; Skiadopoulos, Mario H

    2013-04-01

    Nonhuman primates (NHPs) and rabbits are the animal models most commonly used to evaluate the efficacy of medical countermeasures against anthrax in support of licensure under the FDA's "Animal Rule." However, a need for an alternative animal model may arise in certain cases. The development of such an alternative model requires a thorough understanding of the course and manifestation of experimental anthrax disease induced under controlled conditions in the proposed animal species. The guinea pig, which has been used extensively for anthrax pathogenesis studies and anthrax vaccine potency testing, is a good candidate for such an alternative model. This study was aimed at determining the median lethal dose (LD50) of the Bacillus anthracis Ames strain in guinea pigs and investigating the natural history, pathophysiology, and pathology of inhalational anthrax in this animal model following nose-only aerosol exposure. The inhaled LD50 of aerosolized Ames strain spores in guinea pigs was determined to be 5.0 × 10(4) spores. Aerosol challenge of guinea pigs resulted in inhalational anthrax with death occurring between 46 and 71 h postchallenge. The first clinical signs appeared as early as 36 h postchallenge. Cardiovascular function declined starting at 20 h postexposure. Hematogenous dissemination of bacteria was observed microscopically in multiple organs and tissues as early as 24 h postchallenge. Other histopathologic findings typical of disseminated anthrax included suppurative (heterophilic) inflammation, edema, fibrin, necrosis, and/or hemorrhage in the spleen, lungs, and regional lymph nodes and lymphocyte depletion and/or lymphocytolysis in the spleen and lymph nodes. This study demonstrated that the course of inhalational anthrax disease and the resulting pathology in guinea pigs are similar to those seen in rabbits and NHPs, as well as in humans.

  7. Developmental expression of Toll‑like receptors in the guinea pig lung.

    PubMed

    Ma, Lingjie; Yang, Jiali; Yang, Li; Shi, Juan; Xue, Jing; Li, Yong; Liu, Xiaoming

    2017-03-01

    The guinea pig is a useful model for investigating infectious and non‑infectious lung diseases due to the sensitivity of its respiratory system and susceptibility to infectious agents. Toll‑like receptors (TLRs) are important components of the innate immune response and are critical for lung immune function. In the present study, the differentiation of epithelial cells in the guinea pig lung was examined during gestation by studying anatomic morphology and the major epithelial cell types using cell type‑specific markers. The developmental expression of all 9 TLRs and the TLR signaling adaptors myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor associated factor 6 (TRAF‑6) were investigated by reverse transcription‑quantitative polymerase chain reaction and western blotting analysis. The formation of lung lobes in guinea pigs was observed at 45 days of gestation (dGA), along with the expression of the basal cell marker keratin 14 and the alveolar type II cell marker pro‑surfactant protein. However, the cube cell marker secretoglobin family1A member 1 and ciliated cell marker b‑tubulin IV were only detected in the lungs from 52 dGA onward. The expression levels of all TLRs, MyD88 and TRAF‑6 were determined in lung tissues harvested from embryos, newborn, postnatal and adult animals. The expression levels of all TLR signaling components displayed similar dynamic expression patterns with gestation age and postnatal maturation time, except for TLR‑4 and TLR‑7. mRNA expression levels of TLR components were significantly increased in the lungs at 45 and 52 dGA, compared with later developmental stages. These results suggest that TLR expression in the guinea pig lung is developmentally regulated, enhancing the understanding of lung biology in guinea pig models.

  8. Pathology and Pathophysiology of Inhalational Anthrax in a Guinea Pig Model

    PubMed Central

    Savransky, Vladimir; Sanford, Daniel C.; Syar, Emily; Austin, Jamie L.; Tordoff, Kevin P.; Anderson, Michael S.; Stark, Gregory V.; Barnewall, Roy E.; Briscoe, Crystal M.; Lemiale-Biérinx, Laurence; Park, Sukjoon; Ionin, Boris

    2013-01-01

    Nonhuman primates (NHPs) and rabbits are the animal models most commonly used to evaluate the efficacy of medical countermeasures against anthrax in support of licensure under the FDA's “Animal Rule.” However, a need for an alternative animal model may arise in certain cases. The development of such an alternative model requires a thorough understanding of the course and manifestation of experimental anthrax disease induced under controlled conditions in the proposed animal species. The guinea pig, which has been used extensively for anthrax pathogenesis studies and anthrax vaccine potency testing, is a good candidate for such an alternative model. This study was aimed at determining the median lethal dose (LD50) of the Bacillus anthracis Ames strain in guinea pigs and investigating the natural history, pathophysiology, and pathology of inhalational anthrax in this animal model following nose-only aerosol exposure. The inhaled LD50 of aerosolized Ames strain spores in guinea pigs was determined to be 5.0 × 104 spores. Aerosol challenge of guinea pigs resulted in inhalational anthrax with death occurring between 46 and 71 h postchallenge. The first clinical signs appeared as early as 36 h postchallenge. Cardiovascular function declined starting at 20 h postexposure. Hematogenous dissemination of bacteria was observed microscopically in multiple organs and tissues as early as 24 h postchallenge. Other histopathologic findings typical of disseminated anthrax included suppurative (heterophilic) inflammation, edema, fibrin, necrosis, and/or hemorrhage in the spleen, lungs, and regional lymph nodes and lymphocyte depletion and/or lymphocytolysis in the spleen and lymph nodes. This study demonstrated that the course of inhalational anthrax disease and the resulting pathology in guinea pigs are similar to those seen in rabbits and NHPs, as well as in humans. PMID:23357384

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

    PubMed

    Cappaert, Natalie L M; Klis, Sjaak F L; Muijser, Hans; Kulig, Beverly M; Ravensberg, Luco C; Smoorenburg, Guido 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 found in the corresponding cochlear regions. In contrast, guinea pigs showed no threshold shifts and no OHC loss after exposure to much higher ethyl benzene levels (2500 ppm, 6 h/day, 5 days). Subsequently, a limited study (four rats and four guinea pigs) was performed in an attempt to understand these differences in susceptibility. Ethyl benzene concentration in blood was determined in both species after exposure to 500-ppm ethyl benzene (8 h/day, 3 days). At the end of the first day, blood of the rats contained 23.2+/-0.8-microg/ml ethyl benzene, whereas the concentration in guinea pig blood was 2.8+/-0.1 microg/ml. After 3 days, the concentration in both species decreased with respect to the first day, but the ethyl benzene concentration in rat blood was still 4.3 times higher than that in guinea pig blood. Thus, the difference in susceptibility between the species may be related to the ethyl benzene concentration in blood.

  10. Replication and Transmission of the Novel Bovine Influenza D Virus in a Guinea Pig Model.

    PubMed

    Sreenivasan, Chithra; Thomas, Milton; Sheng, Zizhang; Hause, Ben M; Collin, Emily A; Knudsen, David E B; Pillatzki, Angela; Nelson, Eric; Wang, Dan; Kaushik, Radhey S; Li, Feng

    2015-12-01

    Influenza D virus (FLUDV) is a novel influenza virus that infects cattle and swine. The goal of this study was to investigate the replication and transmission of bovine FLUDV in guinea pigs. Following direct intranasal inoculation of animals, the virus was detected in nasal washes of infected animals during the first 7 days postinfection. High viral titers were obtained from nasal turbinates and lung tissues of directly inoculated animals. Further, bovine FLUDV was able to transmit from the infected guinea pigs to sentinel animals by means of contact and not by aerosol dissemination under the experimental conditions tested in this study. Despite exhibiting no clinical signs, infected guinea pigs developed seroconversion and the viral antigen was detected in lungs of animals by immunohistochemistry. The observation that bovine FLUDV replicated in the respiratory tract of guinea pigs was similar to observations described previously in studies of gnotobiotic calves and pigs experimentally infected with bovine FLUDV but different from those described previously in experimental infections in ferrets and swine with a swine FLUDV, which supported virus replication only in the upper respiratory tract and not in the lower respiratory tract, including lung. Our study established that guinea pigs could be used as an animal model for studying this newly emerging influenza virus. Influenza D virus (FLUDV) is a novel emerging pathogen with bovine as its primary host. The epidemiology and pathogenicity of the virus are not yet known. FLUDV also spreads to swine, and the presence of FLUDV-specific antibodies in humans could indicate that there is a potential for zoonosis. Our results showed that bovine FLUDV replicated in the nasal turbinate and lungs of guinea pigs at high titers and was also able to transmit from an infected animal to sentinel animals by contact. The fact that bovine FLUDV replicated productively in both the upper and lower respiratory tracts of guinea pigs

  11. Of guinea pigs and men--an unusual case of jaundice.

    PubMed

    Pischke, S; Ehmer, U; Schedel, I; Gratz, W F; Wedemeyer, H; Ziesing, S; Bange, F C; Burchard, G D; Manns, M P; Bahr, M J; Strassburg, C P

    2010-01-01

    A 21-year-old male presented at the emergency room with jaundice, itching, dry cough, malaise and weight loss of 10 kg during the preceding four weeks. Eighteen months earlier, the patient had suffered an automobile accident leading to polytrauma. Serological markers for viral or other causes of hepatitis were absent. For suspected secondary sclerosing cholangitis, ultrasound and ERCP were performed but failed to reveal pathological findings. A liver biopsy showed cholestatic liver disease without signs of portal field-associated hepatitis. Hepato-biliary scintigraphy demonstrated hepatocellular dysfunction. The patient finally mentioned his guinea pig farm with around 50 animals, 20 of which had recently died for unknown reasons. The patient and three of his guinea pigs were subsequently tested for serological evidence of leptospirosis. IgG and IgM antibodies reacting with Leptospira interrogans were detected in the patient's serum, and all 3 guinea pigs were serologically positive for serovar Bratislava. Bacterial culture was not successful, and also PCR tests remained negative. The clinical symptoms quickly resolved after the initiation of antibiotic therapy with amoxicillin.

  12. Guinea Pig Model for Evaluating the Potential Public Health Risk of Swine and Avian Influenza Viruses

    PubMed Central

    Pu, Juan; Hu, Yanxin; Wang, Jingjing; Gao, Huijie; Liu, Linqing; Xu, Qi; Tan, Yuanyuan; Liu, Mengda; Guo, Xin; Yang, Hanchun; Liu, Jinhua

    2010-01-01

    Background The influenza viruses circulating in animals sporadically transmit to humans and pose pandemic threats. Animal models to evaluate the potential public health risk potential of these viruses are needed. Methodology/Principal Findings We investigated the guinea pig as a mammalian model for the study of the replication and transmission characteristics of selected swine H1N1, H1N2, H3N2 and avian H9N2 influenza viruses, compared to those of pandemic (H1N1) 2009 and seasonal human H1N1, H3N2 influenza viruses. The swine and avian influenza viruses investigated were restricted to the respiratory system of guinea pigs and shed at high titers in nasal tracts without prior adaptation, similar to human strains. None of the swine and avian influenza viruses showed transmissibility among guinea pigs; in contrast, pandemic (H1N1) 2009 virus transmitted from infected guinea pigs to all animals and seasonal human influenza viruses could also horizontally transmit in guinea pigs. The analysis of the receptor distribution in the guinea pig respiratory tissues by lectin histochemistry indicated that both SAα2,3-Gal and SAα2,6-Gal receptors widely presented in the nasal tract and the trachea, while SAα2,3-Gal receptor was the main receptor in the lung. Conclusions/Significance We propose that the guinea pig could serve as a useful mammalian model to evaluate the potential public health threat of swine and avian influenza viruses. PMID:21124850

  13. Calcium-independent haemolysis via the lectin pathway of complement activation in the guinea-pig and other *

    PubMed Central

    Zhang, Y; Suankratay, C; Zhang, X-H; Jones, D R; Lint, T F; Gewurz, H

    1999-01-01

    We previously reported that complement-dependent haemolysis of sheep erythrocytes (E) coated with mannan (M) and sensitized with human mannan-binding lectin (MBL) via the lectin pathway in man occurs in Mg-EGTA and requires alternative pathway amplification. Calcium was required for MBL binding to E-M, but once the E-M-MBL intermediate was formed, MBL was retained and haemolysis occurred in the absence of calcium. Comparable or greater lectin pathway haemolysis in the absence of calcium was observed upon incubation of E-M-MBL in guinea-pig, rat, dog and pig sera, and was further investigated in the guinea-pig, in which titres were much higher (∼14-fold) than in man, and in contrast to humans, greater than classical pathway haemolytic activity. As in human serum, no lysis was observed in C4- or C2-deficient guinea-pig serum until purified C4 or C2, respectively, were restored. However, lectin pathway haemolytic activity in the guinea-pig did not require the alternative pathway. Removal (>98%) of factor D activity by three sequential passages through Sephadex G-75, resulting in serum which retained a normal classical pathway but no alternative pathway haemolytic activity, did not reduce the ability of guinea-pig serum to mediate haemolysis via the lectin pathway. Further, the C3-convertase formed via the lectin pathway (E-M-MBL-C4,2) lysed in C2-deficient guinea-pig but not human serum chelated with EDTA, a condition which precludes alternative pathway amplification. Thus, lectin pathway haemolysis occurs efficiently in guinea-pig serum, in the absence of calcium and without requirement for alternative pathway amplification. The guinea-pig provides a model for studying the assembly and haemolytic function of a lectin pathway which contrasts with the lectin pathway of man, and allows for comparisons that may help clarify the role of this pathway in complement biology. PMID:10457224

  14. The ototoxic effect of boric acid solutions applied into the middle ear of guinea pigs.

    PubMed

    Oztürkcan, Sedat; Dündar, Riza; Katilmis, Hüseyin; Ilknur, Ali Ekber; Aktaş, Sinem; Haciömeroğlu, Senem

    2009-05-01

    This study analyzed the ototoxic effects of boric acid solutions. Boric acid solutions have been used as otologic preparations for many years. Boric acid is commonly found in solutions prepared with alcohol or distilled water but can also be found in a powder form. These preparations are used for both their antiseptic and acidic qualities in external and middle ear infections. We investigated the ototoxic effect of boric acid solutions on guinea pigs. We are unaware of any similar, previously published study of this subject in English. The study was conducted on 28 young albino guinea pigs. Prior to application of the boric acid solution under general anesthesia, an Auditory Brainstem Response (ABRs) test was applied to the right ear of the guinea pigs. Following the test, a perforation was created on the tympanic membrane of the right ear of each guinea pig and small gelfoam pieces were inserted into the perforated area. Test solutions were administered to the middle ear for 10 days by means of a transcanal route. Fifteen days after inserting the gelfoams in all of the guinea pigs, we anasthesized the guinea pigs and removed the gelfoams from the perforated region of the ear and then performed an ABRs on each guinea pig. The ABRs were within the normal range before the applications. After the application, no significant changes were detected in the ABRs thresholds in neither the saline group nor the group administered boric acid and distilled water solution; however, significant changes were detected in the ABRs thresholds of the Gentamicine and boric acid and alcohol solution groups. We believe that a 4% boric acid solution prepared with distilled water can be a more reliable preparation than a 4% boric acid solution prepared with alcohol.

  15. Characterization of fetal growth by repeated ultrasound measurements in the wild guinea pig (Cavia aperea).

    PubMed

    Schumann, K; Guenther, A; Göritz, F; Jewgenow, K

    2014-08-01

    Fetal growth during pregnancy has previously been studied in the domesticated guinea pig (Cavia aperea f. porcellus) after dissecting pregnant females, but there are no studies describing the fetal growth in their wild progenitor, the wild guinea pig (C aperea). In this study, 50 pregnancies of wild guinea pig sows were investigated using modern ultrasound technique. The two most common fetal growth parameters (biparietal diameter [BPD] and crown-rump-length [CRL]) and uterine position were measured. Data revealed similar fetal growth patterns in the wild guinea pig and domesticated guinea pig in the investigated gestation period, although they differ in reproductive milestones such as gestation length (average duration of pregnancy 68 days), average birth weight, and litter mass. In this study, pregnancy lasted on average 60.2 days with a variance of less than a day (0.96 days). The measured fetal growth parameters are strongly correlated with each (R = 0.91; P < 0.001) other and with gestational age (BPD regression equation y = 0.04x - 0.29; P < 0.001 and CRL regression equation y = 0.17x - 2.21; P < 0.01). Furthermore, fetuses in the most frequent uterine positions did not differ in their growth parameters and were not influenced by the mother ID. Our results imply that ultrasound measurement of a single fetal growth parameter is sufficient to reliably estimate gestational age in the wild guinea pig. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Reduced noise susceptibility in littermate offspring from heterozygous animals of the German waltzing guinea pig.

    PubMed

    Skjönsberg, Åsa; Mannström, Paula

    2015-07-08

    The German waltzing guinea pig is a spontaneously mutated strain with severe auditory and vestibular impairment caused by a so far unknown genetic mutation. The animals are born deaf and show a circling behavior. The heterozygote animals of this guinea pig strain have functionally normal hearing and balance. However, these animals have, in earlier studies, shown an increased resistance to noise compared with normal wild-type guinea pigs. In the present study, we explored the functional hearing with auditory brainstem response thresholds before and at different time points after noise exposure. Symptom-free littermates from heterozygote couples of the German waltzing guinea pigs were exclusively used for the study, which, after the hearing test, were sent back for breeding to confirm their genotype (i.e. heterozygote or normal). The aim of this paper was to ascertain that the previously shown reduced susceptibility to noise trauma in the heterozygote animals of the German waltzing guinea pig was also evident when littermates were used as control animals. The findings are important for further analysis of the heterozygote animals of this strain and for future investigations of the underlying mechanisms behind the diverse susceptibility to exposures of loud sound.

  17. Generation and characterization of induced pluripotent stem cells from guinea pig fetal fibroblasts.

    PubMed

    Wu, Yuehong; Li, Ouyang; He, Chengwen; Li, Yong; Li, Min; Liu, Xiaoming Liu; Wang, Yujiong; He, Yulong

    2017-06-01

    Induced pluripotent stem cells (iPS) represent an important tool to develop disease‑modeling assays, drug testing assays and cell‑based replacement therapies. The application of iPS in these fields requires the development of suitable animal models. Of the suitable species, guinea pigs are particularly important and offer significant advantages. Successful iPS generation has been accomplished in a number of species; however, it has not been reported in the guinea pig. The present study successfully generated iPS from guinea pigs (giPS) using single polycistronic virus transduction with mouse octamer‑binding transcription factor 4 (Oct4), sex determining region Y‑box 2 (Sox2), Kruppel‑like factor 4 and c‑Myc. The giPS cell lines were cultured in media containing leukemia inhibitory factor and guinea pig fibroblast cells were used as feeder cells. These cultures were expanded under feeder‑free culture conditions using ESGRO Complete Plus Clonal Grade medium containing 15% fetal bovine serum on gelatin‑coated dishes. The resultant cells had a normal karyotype, exhibited alkaline phosphatase activity and expressed the pluripotency markers Oct4, Sox2 and Nanog. The cells differentiated in vivo to form teratomas that contained all three germ layers of the tissue cells. The generation of giPS may facilitate future studies investigating the mechanisms underlying innate immunity, particularly for tuberculosis. These experiments provide proof of principle that iPS technology may be adapted to use the guinea pig as a model of human diseases.

  18. Generation and characterization of induced pluripotent stem cells from guinea pig fetal fibroblasts

    PubMed Central

    Wu, Yuehong; Li, Ouyang; He, Chengwen; Li, Yong; Li, Min; Liu, Xiaoming; Wang, Yujiong; He, Yulong

    2017-01-01

    Induced pluripotent stem cells (iPS) represent an important tool to develop disease-modeling assays, drug testing assays and cell-based replacement therapies. The application of iPS in these fields requires the development of suitable animal models. Of the suitable species, guinea pigs are particularly important and offer significant advantages. Successful iPS generation has been accomplished in a number of species; however, it has not been reported in the guinea pig. The present study successfully generated iPS from guinea pigs (giPS) using single polycistronic virus transduction with mouse octamer-binding transcription factor 4 (Oct4), sex determining region Y-box 2 (Sox2), Kruppel-like factor 4 and c-Myc. The giPS cell lines were cultured in media containing leukemia inhibitory factor and guinea pig fibroblast cells were used as feeder cells. These cultures were expanded under feeder-free culture conditions using ESGRO Complete Plus Clonal Grade medium containing 15% fetal bovine serum on gelatin-coated dishes. The resultant cells had a normal karyotype, exhibited alkaline phosphatase activity and expressed the pluripotency markers Oct4, Sox2 and Nanog. The cells differentiated in vivo to form teratomas that contained all three germ layers of the tissue cells. The generation of giPS may facilitate future studies investigating the mechanisms underlying innate immunity, particularly for tuberculosis. These experiments provide proof of principle that iPS technology may be adapted to use the guinea pig as a model of human diseases. PMID:28393187

  19. Pathogenesis of a genotype C strain of bovine parainfluenza virus type 3 infection in albino guinea pigs.

    PubMed

    Shi, Hong-Fei; Zhu, Yuan-Mao; Dong, Xiu-Mei; Cai, Hong; Ma, Lei; Wang, Shu; Yan, Hao; Wang, Xue-Zhi; Xue, Fei

    2014-08-08

    Bovine parainfluenza virus type 3 (BPIV3) is one of the most important of the known viral respiratory tract agents of both young and adult cattle and widespread among cattle around the world. Up to present, three genotypes A, B and C of BPIV3 have been described on the basis of genetic and phylogenetic analysis and only limited studies on the pathogenesis of the genotype A of BPIV3 infection in calves and laboratory animals have been performed. The report about experimental infections of the genotypes B and C of BPIV3 in laboratory animals and calves was scant. Therefore, an experimental infection of guinea pigs with the Chinese BPIV3 strain SD0835 of the genotype C was performed. Sixteen guinea pigs were intranasally inoculated with the suspension of SD0835, while eight control guinea pigs were also intranasally inoculated with the same volume of supernatant from uninfected MDBK cells. The virus-inoculated guinea pigs displayed a few observable clinical signs that were related to the respiratory tract disease and two of the sixteen experimentally infected guinea pigs died at 2 and 3 days post inoculation (PI), respectively, and apparent gross pneumonic lesions were observed at necropsy. The gross pneumonic lesions in guinea pigs inoculated with SD0835 consisted of dark red, slightly depressed, irregular areas of consolidation in the lung lobes from the second to 9th day of infection at necropsy, and almost complete consolidation and atelectasis of the lung lobes were seen at 7 days PI. Histopathological changes including alveoli septa thickening and focal cellulose pneumonia were also observed in the lungs of guinea pigs experimentally infected with SD0835. Viral replication was detectable by virus isolation and titration, real-time RT-PCR and immunohistochemistry (IHC) staining in the respiratory tissues of guinea pigs as early as 24h after intranasal inoculation with SD0835. The results of virus isolation and titration showed that guinea pigs were permissive for

  20. Morphologic observation and classification criteria of atretic follicles in guinea pigs.

    PubMed

    Wang, Wei; Liu, Hong-Lin; Tian, Wei; Zhang, Fen-Fen; Gong, Yan; Chen, Jin-Wei; Mao, Da-Gan; Shi, Fang-Xiong

    2010-05-01

    There is a lack of appropriate classification criteria for the determination of atretic follicles in guinea pigs. In the present study, new criteria were established based on the latest morphologic criteria for cell death proposed by the Nomenclature Committee on Cell Death (NCCD) in 2009. Ovaries of guinea pigs were sampled on different stages of estrous cycle, and the morphologic observations of atretic follicles were investigated in serial sections. The results showed that the process of follicular atresia could be classified into four continuous stages: (1) the granulosa layer became loose, and some apoptotic bodies began to appear; (2) the granulosa cells were massively eliminated; (3) the theca interna cells differentiated; and (4) the residual follicular cells degenerated. In addition, the examination revealed that these morphologic criteria were accurate and feasible. In conclusion, this study provides new criteria for the classification of atretic follicles in guinea pigs, and this knowledge can inform future research in the area.

  1. Inotropic effects of extracts of Psidium guajava L. (guava) leaves on the guinea pig atrium.

    PubMed

    Conde Garcia, E A; Nascimento, V T; Santiago Santos, A B

    2003-05-01

    Many pharmacological effects have been ascribed to extracts of Psidium guajava L. (guava) leaves. However, in spite of its widespread use in Brazilian folk medicine and a reasonable number of scientific reports about it, we could not find any study dealing with its action on the mammalian myocardium. In the present study, by measuring isometric force, we observed that the crude extract of P. guajava (water-alcohol extract obtained by macerating dry leaves) depresses the guinea pig atrial contractility in a concentration-dependent fashion (N = 8 hearts, 15 trials). The compound with cardiac activity was concentrated by extraction in a Soxhlet apparatus using 17 M glacial acetic acid after removing the less polar fractions (hexane, chloroform, acetone, ethanol and methanol), suggesting that this compound is a highly polar substance. In the isolated guinea pig left atrium the acetic acid fraction (10-800 mg/l) of P. guajava 1) reversibly decreased myocardial force in a concentration-dependent fashion (EC50 = 0.07g/l, N = 5 hearts, 9 trials, P<0.05), 2) increased the atrial relaxation time measured at 20% of the force amplitude up to 35% (91 +/- 15 to 123 +/- 30 ms, N = 3 hearts, 6 trials, P<0.05), 3) abolished the positive staircase effect (Bowditch phenomenon) in a concentration-dependent fashion suggesting a decrease of the cellular inward calcium current (N = 4 hearts, 8 trials, P<0.05), and 4) its inotropic effect was abolished by cholinergic receptor blockade with 1.5 mM atropine sulfate, indicating a cholinergic involvement in the mechanism of action of the extract (N = 7 hearts, 15 trials, P<0.05). The acetic acid extract was 20 times more potent than crude extract (EC50 = 1.4 g/l). The results showed that extracts from P. guajava leaves depress myocardial inotropism.

  2. Modeling maternal fetal RSV F vaccine induced antibody transfer in guinea pigs.

    PubMed

    Glenn, Gregory M; Fries, Louis F; Smith, Gale; Kpamegan, Eloi; Lu, Hanxin; Guebre-Xabier, Mimi; Hickman, Somia P; Flyer, David

    2015-11-25

    Protection of newborns and young infants against RSV disease via maternal immunization mediated by transplacental transfer of antibodies is under evaluation in third-trimester pregnant women with the RSV recombinant F nanoparticle vaccine (RSV F vaccine). Since the hemichorial placental architecture in guinea pigs and humans is similar, the guinea pig model was employed to assess RSV F vaccine immunogenicity in pregnant sows and to compare RSV-specific maternal antibody levels in their pups. Thirty (30) presumptive pregnant guinea pigs were immunized on gestational day 25 and 46 with placebo (PBS), 30μg RSV F, or 30μg RSV F+400μg aluminum phosphate. Sera at delivery/birth (sows/pups) and 15 and 30 days post-partum (pups) were analyzed for the presence of anti-F IgG, palivizumab-competitive antibody (PCA) and RSV/A microneutralization (MN). The rates of pregnancy and stillbirth were similar between controls and vaccinees. The vaccine induced high levels of anti-F IgG, PCA and MN in sows, with the highest levels observed in adjuvanted vaccinees. Placental transfer to pups was proportional to the maternal antibody levels, with concentration effects observed for all immune measures. The RSV F vaccine was safe and immunogenic in pregnant guinea pigs and supported robust transplacental antibody transfer to their pups. Relative concentration of antibodies in the pups was observed even in the presence of high levels of maternal antibody. Guinea pigs may be an important safety and immunogenicity model for preclinical assessment of candidate vaccines for maternal immunization. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Evaluation of Mitoquinone for Protecting Against Amikacin-Induced Ototoxicity in Guinea Pigs.

    PubMed

    Dirain, Carolyn O; Ng, Maria Raye Ann V; Milne-Davies, Bailey; Joseph, Jerin K; Antonelli, Patrick J

    2018-01-01

    Mitoquinone (MitoQ) attenuates amikacin ototoxicity in guinea pigs. MitoQ, a mitochondria-targeted derivative of the antioxidant ubiquinone, has improved bioavailability and demonstrated safety in humans. Thus, MitoQ is a promising therapeutic approach for protecting against amikacin-induced ototoxicity. Both oral and subcutaneous administrations of MitoQ were tested. Amikacin-treated guinea pigs (n = 12-18 per group) received water alone (control) or MitoQ 30 mg/l-supplemented drinking water; or injected subcutaneously with 3 to 5 mg/kg MitoQ or saline (control). Auditory brainstem responses and distortion product otoacoustic emissions were measured before MitoQ or control solution administration and after amikacin injections. Cochlear hair cell damage was assessed using scanning electron microscopy and Western blotting. With oral administration, animals that received 30 mg/l MitoQ had better hearing than controls at only 24 kHz at 3-week (p = 0.017) and 6-week (p = 0.027) post-amikacin. With subcutaneous administration, MitoQ-injected guinea pigs had better hearing than controls at only 24 kHz, 2-week post-amikacin (p = 0.013). Distortion product otoacoustic emission (DPOAE) amplitudes were decreased after amikacin injections, but were not different between treatments (p > 0.05). Electron microscopy showed minor difference in outer hair cell loss between treatments. Western blotting demonstrated limited attenuation of oxidative stress in the cochlea of MitoQ-supplemented guinea pigs. Oral or subcutaneous MitoQ provided limited protection against amikacin-induced hearing loss and cochlear damage in guinea pigs. Other strategies for attenuating aminoglycoside-induced ototoxicity should be explored.

  4. The role of inhibition by phosphocitrate and its analogue in chondrocyte differentiation and subchondral bone advance in Hartley guinea pigs

    PubMed Central

    Sun, Yubo; Kiraly, Alex J.; Cox, Michael; Mauerhan, David R.; Hanley, Edward N.

    2018-01-01

    Phosphocitrate (PC) and its analogue, PC-β ethyl ester, inhibit articular cartilage degeneration in Hartley guinea pigs. However, the underlying molecular mechanisms remain unclear. The present study aimed to investigate the hypothesis that PC exerted its disease-modifying effect on osteoarthritis (OA), in part, by inhibiting a molecular program similar to that in the endochondral pathway of ossification. The results demonstrated that severe proteoglycan loss occurred in the superficial and middle zones, as well as in the calcified zone of articular cartilage in the Hartley guinea pigs. Subchondral bone advance was greater in the control Hartley guinea pigs compared with PC- or PC analogue-treated guinea pigs. Resorption of cartilage bars or islands and vascular invasion in the growth plate were also greater in the control guinea pigs compared with the PC- or PC analogue-treated guinea pigs. The levels of matrix metalloproteinase-13 and type X collagen within the articular cartilage and growth plate were significantly increased in the control guinea pigs compared with PC-treated guinea pigs (P<0.05). These results indicated that articular chondrocytes in Hartley guinea pigs exhibited a hypertrophic phenotype and recapitulated a developmental molecular program similar to the endochondral pathway of ossification. Activation of this molecular program resulted in resorption of calcified articular cartilage and subchondral bone advance. This suggests that PC and PC analogues exerted their OA disease-modifying activity, in part, by inhibiting this molecular program. PMID:29545850

  5. Guinea pig for meat production: A systematic review of factors affecting the production, carcass and meat quality.

    PubMed

    Sánchez-Macías, Davinia; Barba-Maggi, Lida; Morales-delaNuez, Antonio; Palmay-Paredes, Julio

    2018-09-01

    In developing countries, interest in guinea pig farming is growing exponentially because it provides a regular source of high quality animal protein for domestic consumption. Guinea pigs (Cavia porcellus) are prolific animals, grow and are capable of reproduction on a flexible diet, and are adaptable to a wide range of climates. This article mainly reviews findings on guinea pig meat production, including factors affecting raising guinea pigs, carcass and meat quality. We also present some studies that describe biological and pathologic effects on carcass component composition. During the last decades no standard procedure has been established for guinea pig carcass evaluation, which makes very difficult any comparison of results with other studies around the world. Herein we highlight a variety of factors that significantly affect carcass and meat quality. Some of these factors are production systems, environmental and genetic factors, management systems, the diet and health status, age, sex and reproductive management. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Cloning of guinea pig IL-4: reduced IL-4 mRNA after vaccination or Mycobacterium tuberculosis infection.

    PubMed

    Jeevan, Amminikutty; Yoshimura, Teizo; Ly, Lan H; Dirisala, Vijaya R; McMurray, David N

    2011-01-01

    Interleukin-4 (IL-4), a pleiotropic cytokine produced by T-helper type 2 (Th2) cells, is involved in promoting humoral immune responses, allergic reactions and asthma. Previous studies suggested an important role for IL-4 in susceptibility to pulmonary tuberculosis; however, the role of IL-4 has not been studied in the guinea pig, a highly relevant model for this disease. In the present study, we cloned a cDNA for guinea pig IL-4 and examined, for the first time, mRNA expression by real-time RT-PCR in cultured guinea pig cells. High levels of IL-4 mRNA expression were detected in spleen T cells of naïve animals after in vitro stimulation with PMA plus ionomycin for 4-24 h. The expression of IL-4 mRNA was low in spleen and lymph node cells immunized with ovalbumin (OVA) plus Complete Freund's Adjuvant (CFA) in response to OVA (Th1), but significantly higher in the guinea pigs immunized with OVA plus alum (Th2). BCG vaccination reduced the expression of IL-4 mRNA in both spleen and lung digest cells compared to naïve guinea pigs, while levels of IFN-γ were similar in both groups. Furthermore, lung cells from Mycobacterium tuberculosis-infected guinea pigs stimulated in vitro with PPD or MPT64 showed low levels of IL-4 mRNA expression. Thus, BCG vaccination or M. tuberculosis infection modulates IL-4 mRNA expression in the guinea pig. Cloning of guinea pig IL-4 will allow us to address the role of IL-4 in vaccine-induced resistance to pulmonary TB in a highly relevant animal model. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Spontaneous Behavior in Noise and Silence: A Possible New Measure to Assess Tinnitus in Guinea Pigs

    PubMed Central

    Heeringa, Amarins N.; Agterberg, Martijn J. H.; van Dijk, Pim

    2014-01-01

    This study describes two experiments that were conducted in search for a behavioral paradigm to test for tinnitus in guinea pigs. Conditioning paradigms are available to determine the presence of tinnitus in animals and are based on the assumption that tinnitus impairs their ability to detect silent intervals in continuous noise. Guinea pigs have not been subjected to these paradigms yet; therefore, we investigated whether guinea pigs could be conditioned in the two-way shuttle-box paradigm to respond to silent intervals in noise. Even though guinea pigs could be trained relatively easy to respond to the presence of a noise interval, training guinea pigs to silent intervals in noise was unsuccessful. Instead, it appeared that they became immobile when the continuous stimulus was suddenly stopped. This was confirmed by the next experiment, in which we subjected guinea pigs to alternating intervals of noise and silence with a random duration between 30 and 120 s. Indeed, guinea pigs were significantly longer immobile during silence compared to during noise. By interpreting immobility as a signature of perceiving silence, we hypothesized that the presence of tinnitus would reduce immobility in silence. Therefore, we unilaterally exposed one group of guinea pigs to an 11-kHz tone of 124 dB sound pressure level for 1 h. A subset of the exposed animals was significantly more active in silence, but also more active in noise, as compared to the control group. The increased mobility during silent intervals might represent tinnitus. However, the increased mobility in noise of this group implies that the observed behavior could have derived from, e.g., an overall increase in activity. Therefore, conducting validation experiments is very important before implementing this method as a new screening tool for tinnitus. Follow-up experiments are discussed to further elucidate the origin of the increased mobility in both silence and noise. PMID:25360130

  8. The Anticomplementary Activity of ’Fusobacterium polymorphum’ in Normal and C-4 Deficient Sources of Guinea Pig Complement.

    DTIC Science & Technology

    1977-01-12

    A complement consumption assay was used to show that the anticomplementary activity of a cell wall preparation from F. polymorphum in guinea pig complement...tests with C𔃾-deficient guinea pig sera confirmed that F. polymorphum cell walls were capable of generating alternate complement pathway activity in guinea pig sera.

  9. Prevalence and zoonotic risks of Trichophyton mentagrophytes and Cheyletiella spp. in guinea pigs and rabbits in Dutch pet shops.

    PubMed

    Overgaauw, P A M; Avermaete, K H A van; Mertens, C A R M; Meijer, M; Schoemaker, N J

    2017-06-01

    Young rabbits and guinea pigs are often purchased as pets for children and may be infected with zoonotic skin infections. To assess the risk of acquiring such an infection from rabbits or guinea pigs, this study investigated the prevalence of the fungus Trichophyton mentagrophytes and the fur mite Cheyletiella parasitovorax in asymptomatic rabbits and guinea pigs in Dutch pet shops. In 91 pet shops a total of 213 rabbits and 179 guinea pigs were sampled using the Mackenzie technique and cultured. Clean cultures were examined microscopically and a PCR was performed on at least one sample from each pet shop. All animals were investigated for fur mite using a flea comb, a magnifying glass and white paper. From the fur of 3.8% (8/213) of the rabbits and 16.8% (30/179) of the guinea pigs, T. mentagrophytes was isolated. From 1 guinea pig (0,6%) Chrysosporium keratinophilum was isolated. Dermatophyte-positive rabbits and guinea pigs originated from 5.6% (5/90) and 27.3% (24/88) of the investigated pet shops, respectively. Fur mites were not found. Pet shops can play an important role in preventing transmission of zoonotic ringworm infections (dermatophytosis) and educating their customers. Specific preventive measures such as routine screening examinations and (prophylactic) treatment of rabbits and guinea pigs are recommended next to regular hygiene when handling animals. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Biomechanical remodeling of obstructed guinea pig jejunum

    PubMed Central

    Zhao, Jingbo; Liao, Donghua; Yang, Jian; Gregersen, Hans

    2010-01-01

    Data on morphological and biomechanical remodeling are needed to understand the mechanisms behind intestinal obstruction. The effect of partial obstruction on mechanical properties with reference to the zero-stress state and on the histomorphological properties of the guinea pig small intestine was determined in this study. Partial obstruction and sham operation were surgically created in mid-jejunum of guinea pigs. The animals survived 2, 4, 7, and 14 days respectively. The age-matched guinea pigs that were not operated served as normal controls. The segment proximal to the obstruction site was used for histological analysis, no-load state and zero-stress state data, and distension test. The segment for distension was immersed in an organ bath and inflated to 10 cmH20. The outer diameter change during the inflation was monitored using a microscope with CCD camera. Circumferential stresses and strains were computed from the diameter, pressure and the zero-stress state data. The opening angle and absolute value of residual strain decreased (P<0.01 and P<0.001) whereas the wall thickness, wall cross-sectional area, and the wall stiffness increased after 7 days obstruction (P<0.05, P<0.01). Histologically, the muscle and submucosa layers, especially the circumferential muscle layer increased in thickness after obstruction. The opening angle and residual strain mainly depended on the thickness of the muscle layer whereas the wall stiffness mainly depended on the thickness of the submucosa layer. In conclusion, the histomorphological and biomechanical properties of small intestine (referenced for the first time to the zero-stress state) remodel proximal to the obstruction site in a time-dependent manner. PMID:20189575

  11. Similarities and differences among the chromosomes of the wild guinea pig Cavia tschudii and the domestic guinea pig Cavia porcellus (Rodentia, Caviidae)

    PubMed Central

    Walker, Laura I.; Soto, Miguel A.; Spotorno, Ángel E.

    2014-01-01

    Abstract Cavia tschudii Fitzinger, 1867 is a wild guinea pig species living in South America that according to the analysis of mitochondrial genes is the closest wild form of the domestic guinea pig. To investigate the genetic divergence between the wild and domestic species of guinea pigs from a cytogenetic perspective, we characterized and compared the C, G and AgNOR banded karyotypes of molecularly identified Cavia tschudii and Cavia porcellus Linnaeus, 1758 specimens for the first time. Both species showed 64 chromosomes of similar morphology, although C. tschudii had four medium size submetacentric pairs that were not observed in the C. porcellus karyotype. Differences in the C bands size and the mean number of AgNOR bands between the karyotypes of the two species were detected. Most of the two species chromosomes showed total G band correspondence, suggesting that they probably represent large syntenic blocks conserved over time. Partial G band correspondence detected among the four submetacentric chromosomes present only in the C. tschudii karyotype and their subtelocentric homologues in C. porcellus may be explained by the occurrence of four pericentric inversions that probably emerged and were fixed in the C. tschudii populations under domestication. The role of the chromosomal and genomic differences in the divergence of these two Cavia species is discussed. PMID:25147626

  12. MMP-2 participates in the sclera of guinea pig with form-deprivation myopia via IGF-1/STAT3 pathway.

    PubMed

    Liu, Y-X; Sun, Y

    2018-05-01

    To investigate the expression changes of MMP-2 (matrix metalloproteinases-2) mediated by IGF-1 (insulin-like growth factors-1) STAT3 (signal transducer and activator of transcription 3) pathway in the sclera of the form-deprivation myopia guinea pigs. Twenty-four three-week-old guinea pigs were randomly divided into 4 groups: group A (Control), B, C and D. Guinea pigs in group A were sacrificed after 21 days without any special treatment. Guinea pigs in group B were sacrificed 7 days after receiving stitch in the right eye. Guinea pigs in group C were sacrificed 14 days after receiving stitch in the right eye. Guinea pigs in group D were sacrificed 21 days after receiving stitch in the right eye. Eyeball refraction and axial length of guinea pigs were measured before sacrifice. Eyeballs of guinea pigs were enucleated after sacrifice. The expressions of IGF-1, STAT3 and MMP-2 in scleral tissue were detected by Western blot. Axial length extension and myopia appeared in the right eye of guinea pigs in group B. The expressions of IGF-1, STAT3 and MMP-2 in the sclera significantly increased after 7 days of occlusion compared with that in control group A (p<0.05). In the right eye of group C, the axial prolongation and myopia formation appeared after 14-day occlusion. The expressions of IGF-1, STAT3 and MMP-2 in sclera significantly increased compared with that in group A (p<0.05). In the right eye of group D, the axial extension and myopia formation occurred. IGF-1, STAT3 and MMP-2 in scleral significantly upregulated 21 days after occlusion (p<0.05). Furthermore, at different stages of deprivation, protein expressions of MMP-2 and IGF-1 in sclera were positively correlated (r = 0.962, p<0.01). Form-deprivation of guinea pigs lead to increased expressions of IGF-1, STAT3 and MMP-2 in the sclera and myopia of guinea pigs. The expressions of IGF-1, STAT3 and MMP-2 increased progressively over the time of deprivation. Additionally, overexpression of MMP-2 mediated by IGF

  13. Median Lethal Doses Associated with Intravenous Exposure to the Optically Pure Enantiomers of VX in Guinea Pigs

    DTIC Science & Technology

    2017-03-01

    highly toxic based on the U.S. Environmental Protection Agency’s Acute Toxicity Categories for Pesticide Products . 15. SUBJECT TERMS Guinea pig ...in Guinea Pigs 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Wright, Linnzi K. M.; Forster, Jeffry S...intravenous exposure of adult, male guinea pigs to the individual VX enantiomers, and we compared those potencies to that for a racemic mixture. The P

  14. Electrophysiological effects of calcitonin gene-related peptide in bull-frog and guinea-pig atrial myocytes.

    PubMed Central

    Ono, K; Giles, W R

    1991-01-01

    1. Electrophysiological effects of calcitonin gene-related peptide (CGRP) on action potentials and corresponding transmembrane currents in single myocytes from bull-frog and guinea-pig atria were studied using a whole-cell voltage-clamp method. 2. CGRP at relatively low concentrations increased the height of the action potential plateau in a dose-dependent manner in both bull-frog and guinea-pig myocytes. In addition, in bull-frog cells CGRP accelerated the early phase of repolarization, thus shortening the overall duration of the action potential. In contrast, in guinea-pig myocytes CGRP prolonged the action potential duration at all concentrations that were studied. 3. Voltage-clamp measurements demonstrated that CGRP increased transmembrane calcium current (ICa) in guinea-pig myocytes without a significant change in its voltage dependence. The ED50 value for this effect on ICa was 1.28 +/- 0.55 X 10(-8) M (n = 4). The time course of the inactivation of ICa was not affected by CGRP. 4. CGRP increased the delayed rectifier K+ current (IK) at relatively low concentrations in bull-frog atria, whereas relatively high concentrations were needed to increase IK in guinea-pig myocytes. This effect was observed even after complete inhibition of ICa. 5. CGRP had no significant effect on the inwardly rectifying background K+ current, IK1, even at very high concentrations. 6. Comparison of the time course of ICa augmentation in bull-frog and guinea-pig myocytes revealed an important difference in the effect of CGRP in these two types of cells. CGRP at maximal concentrations increased ICa transiently in bull-frog myocytes, whereas this response was sustained in guinea-pig myocytes. Isoprenaline (Iso) induced sustained increase in ICa in both species. When ICa was fully activated by Iso, CGRP at high concentrations strongly inhibited ICa in the bull-frog, whereas it had little effect on ICa in guinea-pig myocytes. 7. Intracellular application of GTP gamma S (guanosine 5'-O-(3

  15. [Use of guinea pigs to evaluate the efficacy of a heterological immunoglobulin against Bolivian hemorrhagic fever].

    PubMed

    Khmelev, A L; Borisevich, I V; Pantiukhov, V B; Pirozhkov, A P; Syromiatnikova, S I; Shatokhina, I V; Mel'nikov, S A; Shagarov, E E

    2009-01-01

    The use of guinea pigs as a laboratory model was proven to be appropriate in investigating the protective properties of a heterological immunoglobulin against Bolivian hemorrhagic fever at the preclinical stage of the study. A highly pathogenic Machupo virus strain that caused guinea pigs' death with respect with an agent's dose was cultivated. Injection of 1.0 ml of the immunoglobulin provided a 100% protective effect for the guinea pigs infected with the highly pathogenic Machupo virus strain in a dose of 10 LD50.

  16. Disruption of emmetropization and high susceptibility to deprivation myopia in albino guinea pigs.

    PubMed

    Jiang, Liqin; Long, Keli; Schaeffel, Frank; Zhang, Sen; Zhou, Xiangtian; Lu, Fan; Qu, Jia

    2011-08-03

    To compare emmetropization in albino and pigmented guinea pigs. Distributions of refractive state were examined in 214 albino and 234 pigmented guinea pigs. Albino (A) and pigmented (P) guinea pigs were divided into two groups, hyperopic (H) and myopic (M). Eye development was separately followed in 10 randomly selected animals from each group (AH, AM, PH, PM) from 2 to 10 weeks of age. In addition, deprivation myopia was induced in 36 age-matched albino (18 AH and 18 AM) and 36 pigmented (18 PH and 18 PM) guinea pigs by diffusers that were worn from 2 to 6 weeks of age. Finally, sclera fibril diameters were measured using transmission electron microscopy. Strikingly, the distributions of refractive errors were bimodal at 2 weeks of age, both in albino and pigmented animals, with clearly different averages (-2.86 ± 5.60 diopters [D] vs. 2.13 ± 5.27 D respectively; t = 9.712; P < 0.001). Spontaneous myopia was more common in albino animals: 70.1% were myopic (AM) and 29.9% hyperopic (AH), whereas only 28.6% were myopic (PM) and 71.4% hyperopic (PH) in pigmented guinea pigs. Different from PM and AM did not show any recovery from myopia. With diffusers, AH became more myopic (-7.61 ± 2.71 D and -11.17 ± 2.55 D) than PH (-4.48 ± 1.46 D and -8.28 ± 2.13 D) after 2 and 4 weeks, respectively. Deprivation myopia could still be induced in PM (-1.64 ± 1.44 D and -5.17 ± 1.88 D after 2 and 4 weeks, respectively; P < 0.01) but not in AM. Scleral fibril diameters were smaller in myopic animals, both albino and pigmented. Deprivation myopia could not be induced in spontaneously myopic but only in hyperopic albino guinea pigs, where it was even higher than in pigmented animals. The distinct effects of albinism on emmetropization will help to elucidate the mechanisms underlying the emmetropization.

  17. Differences in neurokinin receptor pharmacology between rat and guinea-pig superior cervical ganglia.

    PubMed

    Seabrook, G R; Main, M; Bowery, B; Wood, N; Hill, R G

    1992-04-01

    1. The depolarizations elicited by seven neurokinin receptor agonists were examined in both rat and guinea-pig superior cervical ganglia by use of grease-gap methodology in the presence of tetrodotoxin (0.1 microM). Responses were normalised with respect to 1 microM eledoisin. 2. The rank order of agonist potency in the rat ganglia was senktide greater than substance P greater than substance P methyl ester = eleidosin = Sar-Met-substance P greater than neurokinin B greater than neurokinin A, whereas in guinea-pig superior cervical ganglion (SCG) the rank order was senktide greater than Sar-Met-substance P greater than neurokinin B = eledoisin = substance P methyl ester. The concentration-effect curves for substance P and neurokinin A in guinea-pig ganglia were biphasic which precluded the determination of meaningful potency values. 3. The maximal depolarization achieved by subtype selective ligands was different between these two species. On rat and guinea-pig SCG, the NK3-selective ligand, senktide, produced a maximal depolarization of 27% and 274% respectively, whereas the NK1-selective ligand, substance P methyl ester, produced depolarizations of 77% and 64% respectively. 4. The depolarizations induced by substance P methyl ester and senktide in either species were unaffected by atropine (1 microM), suggesting a lack of involvement of presynaptic neurokinin receptors in the generation of the response. 5. The potency of substance P methyl ester, senktide, and neurokinin A were unaffected by pretreating ganglia with the peptidase inhibitors bacitracin (40 micrograms ml-1), leupeptin (4 micrograms ml-1), and chymostatin (2 micrograms ml-1). Similarly, these peptidase inhibitors had no effect on the maximal depolarizations achieved by any of these agonists.6. It is evident that rat and guinea-pig superior cervical ganglia possess both NK, and NK3 receptors, but that their net contribution to depolarizations are different between the two species. The depolarizations

  18. Catecholamine secretion by chemical hypoxia in guinea-pig, but not rat, adrenal medullary cells: differences in mitochondria.

    PubMed

    Harada, K; Endo, Y; Warashina, A; Inoue, M

    2015-08-20

    The effects of mitochondrial inhibitors (CN(-), a complex IV inhibitor and CCCP, protonophore) on catecholamine (CA) secretion and mitochondrial function were explored functionally and biochemically in rat and guinea-pig adrenal chromaffin cells. Guinea-pig chromaffin cells conspicuously secreted CA in response to CN(-) or CCCP, but rat cells showed a little, if any, secretory response to either of them. The resting metabolic rates in rat adrenal medullae did not differ from those in guinea-pig adrenal medullae. On the other hand, the time course of depolarization of the mitochondrial membrane potential (ΔΨm) in guinea-pig chromaffin cells in response to CN(-) was slower than that in rat chromaffin cells, and this difference was abolished by oligomycin, an F1F0-ATPase inhibitor. The extent of CCCP-induced decrease in cellular ATP in guinea-pig chromaffin cells, which was indirectly measured using a Mg(2+) indicator, was smaller than that in rat chromaffin cells. Relative expression levels of F1F0-ATPase inhibitor factor in guinea-pig adrenal medullae were smaller than in rat adrenal medullae, and the opposite was true for F1F0-ATPase α subunit. The present results indicate that guinea-pig chromaffin cells secrete more CA in response to a mitochondrial inhibitor than rat chromaffin cells and this higher susceptibility in the former is accounted for by a larger extent of reversed operation of F1F0-ATPase with the consequent decrease in ATP under conditions where ΔΨm is depolarized. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Optimization of Glial Fibrillary Acidic Protein Immunoreactivity in Formalin-fixed, Paraffin-Embedded Guinea Pig Brain Sections

    DTIC Science & Technology

    2003-09-01

    fixed, paraffin-embedded guinea pig brain sections using a variety of commercially available GFAP antibody clones. Of the 7 clones tested for cross...determining neuropathological consequences in the guinea pig following exposure to chemical warfare nerve agent.

  20. Interactions Between Macrophages of Guinea Pigs and Salmonellae III. Bactericidal Action and Cytophilic Antibodies of Macrophages of Infected Guinea Pigs

    PubMed Central

    Hsu, H. S.; Mayo, Donald R.

    1973-01-01

    The fate of virulent Salmonella typhimurium within macrophages of guinea pigs was assessed by a suspended cell culture procedure. The present study confirmed that macrophages of normal guinea pigs were capable of inactivating the ingested salmonellae. Macrophages of previously infected guinea pigs were not endowed with any significant increase in their ability to eliminate the ingested pathogen. However, the immune macrophages were observed to clump together tightly when they were exposed to salmonellae. This phenomenon was attributed to the presence of specific cytophilic antibodies on the immune macrophages. When immune macrophages were inactivated with Merthiolate, they agglutinated with both the H and the O antigens of S. typhimurium, but not with the O antigens of other species of Salmonella nor with the O antigens of Escherichia coli. Cytophilic antibodies could be eluted from immune macrophages by incubation in the absence of immune serum. Conversely, cytophilic antibodies could be passively transferred onto normal macrophages by incubation in the presence of immune serum. Furthermore, using immune serum previously adsorbed with the O antigens of S. typhimurium, cytophilic antibodies against the H antigens alone could be transferred onto normal macrophages, or those against the O antigens alone could be eluted from immune macrophages. These data suggest that immune macrophages possess specific cytophilic antibodies against both the H and the O antigens of S. typhimurium. It is proposed that the presence of cytophilic antibodies on immune macrophages represents an expression of antibacterial cellular immunity by enhanced clumping and phagocytic activities of the macrophages. PMID:4579899

  1. Comparison of cloned Kir2 channels with native inward rectifier K+ channels from guinea-pig cardiomyocytes

    PubMed Central

    Xin Liu, Gong; Derst, Christian; Schlichthörl, Günter; Heinen, Steffen; Seebohm, Guiscard; Brüggemann, Andrea; Kummer, Wolfgang; Veh, Rüdiger W; Daut, Jürgen; Preisig-Müller, Regina

    2001-01-01

    The aim of the study was to compare the properties of cloned Kir2 channels with the properties of native rectifier channels in guinea-pig (gp) cardiac muscle. The cDNAs of gpKir2.1, gpKir2.2, gpKir2.3 and gpKir2.4 were obtained by screening a cDNA library from guinea-pig cardiac ventricle. A partial genomic structure of all gpKir2 genes was deduced by comparison of the cDNAs with the nucleotide sequences derived from a guinea-pig genomic library. The cell-specific expression of Kir2 channel subunits was studied in isolated cardiomyocytes using a multi-cell RT-PCR approach. It was found that gpKir2.1, gpKir2.2 and gpKir2.3, but not gpKir2.4, are expressed in cardiomyocytes. Immunocytochemical analysis with polyclonal antibodies showed that expression of Kir2.4 is restricted to neuronal cells in the heart. After transfection in human embryonic kidney cells (HEK293) the mean single-channel conductance with symmetrical K+ was found to be 30.6 pS for gpKir2.1, 40.0 pS for gpKir2.2 and 14.2 pS for Kir2.3. Cell-attached measurements in isolated guinea-pig cardiomyocytes (n = 351) revealed three populations of inwardly rectifying K+ channels with mean conductances of 34.0, 23.8 and 10.7 pS. Expression of the gpKir2 subunits in Xenopus oocytes showed inwardly rectifying currents. The Ba2+ concentrations required for half-maximum block at -100 mV were 3.24 μm for gpKir2.1, 0.51 μm for gpKir2.2, 10.26 μm for gpKir2.3 and 235 μm for gpKir2.4. Ba2+ block of inward rectifier channels of cardiomyocytes was studied in cell-attached recordings. The concentration and voltage dependence of Ba2+ block of the large-conductance inward rectifier channels was virtually identical to that of gpKir2.2 expressed in Xenopus oocytes. Our results suggest that the large-conductance inward rectifier channels found in guinea-pig cardiomyocytes (34.0 pS) correspond to gpKir2.2. The intermediate-conductance (23.8 pS) and low-conductance (10.7 pS) channels described here may correspond to gpKir2

  2. The antigenicity in guinea pigs and monkeys of three mycobacterial polysaccharides purified by affinity chromatography with concanavalin A.

    PubMed

    Daniel, T M

    1975-06-01

    The antigenicity of 3 polysaccharides purified from culture filtrates of Mycobacterim tuberculosis by affinity chromatography using a concanavalin A-agarose absorbent was studied. All 3 purified polysaccharides were found to be potent elicitors of delayed skin test reactions in sensitized guinea pigs and in a tuberculos monkey. This antigenicity could not be attributed to contaminating protein. Small dermal reactions were also observed in control guinea pigs. All 3 polysaccharides reacted with precipitating antibody in guinea pig sera, the antigenic specificity observed with the guinea pig sera differing from that demonstrated with reference goat antiserum. The 3 polysaccharides were also demonstrated to contain hemagglutination antigenic sites.

  3. Further evidence from functional studies for somatostatin receptor heterogeneity in guinea-pig isolated ileum, vas deferens and right atrium.

    PubMed Central

    Feniuk, W.; Dimech, J.; Jarvie, E. M.; Humphrey, P. P.

    1995-01-01

    1. Somatostatin (SRIF) causes a concentration-dependent inhibition of neurotransmission in guinea-pig ileum and vas deferens as well as negative inotropy in guinea-pig isolated right atrium. The SRIF receptors mediating these effects have now been further characterized by use of the peptides BIM-23027, BIM-23056 and L-362855, reported as selective for the recombinant SRIF receptor types, sst2, sst3 and sst5, respectively. 2. BIM-23027 was a highly potent agonist at causing an inhibition of neurotransmission in the guinea-pig ileum (EC50 value 1.9 nM), being about 3 times more potent than SRIF (EC50 value 6.8 nM). In contrast, in both guinea-pig vas deferens and right atrial preparations, BIM-23027 was a relatively weak agonist being at least 30-100 times weaker than SRIF. In guinea-pig atria, BIM-23027 (3 microM) antagonized the negative inotropic action of SRIF28 (apparent pKB = 5.9 +/- 0.1) but had no effect on the negative inotropic action of cyclohexyladenosine. 3. The inhibitory effect of BIM-23027 in the guinea-pig ileum was readily desensitized. Prior exposure to BIM-23027 (0.3 microM) markedly attenuated the inhibitory effect of SRIF but had no effect on the inhibitory action of clonidine suggesting that BIM-23027 and SRIF act via a common receptor mechanism. 4. L-362855 caused a concentration-dependent inhibition of neurotransmission in both the guinea-pig ileum and vas deferens as well as causing negative inotropy in the guinea-pig atrium but was at least 30-100 times weaker than SRIF. In guinea-pig isolated atria, L-362855 (3 microM) did not antagonize the negative inotropic action of SRIF28.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7582529

  4. In Vitro Activity of the Ketolide HMR 3647 (RU 6647) for Legionella spp., Its Pharmacokinetics in Guinea Pigs, and Use of the Drug To Treat Guinea Pigs with Legionella pneumophila Pneumonia

    PubMed Central

    Edelstein, Paul H.; Edelstein, Martha A. C.

    1999-01-01

    The activities of HMR 3647, HMR 3004, erythromycin, clarithromycin, and levofloxacin for 97 Legionella spp. isolates were determined by microbroth dilution susceptibility testing. Growth inhibition of two Legionella pneumophila strains grown in guinea pig alveolar macrophages was also determined. The concentrations required to inhibit 50% of strains tested were 0.06, 0.02, 0.25, 0.03, and 0.02 μg/ml for HMR 3647, HMR 3004, erythromycin, clarithromycin, and levofloxacin, respectively. BYEα broth did not significantly inhibit the activities of the drugs tested, as judged by the susceptibility of the control Staphylococcus aureus strain; however, when Escherichia coli was used as the test strain, levofloxacin activity tested in BYEα broth was fourfold lower. HMR 3647, HMR 3004, erythromycin, and clarithromycin (0.25 and 1 μg/ml) reduced bacterial counts of two L. pneumophila strains grown in guinea pig alveolar macrophages by 0.5 to 1 log10, but regrowth occurred over a 2-day period. HMR 3647, erythromycin, and clarithromycin appeared to have equivalent intracellular activities which were solely static in nature. HMR 3004 was more active than all drugs tested except levofloxacin. In contrast, levofloxacin (1 μg/ml) was bactericidal against intracellular L. pneumophila and significantly more active than the other drugs tested. Therapy studies with HMR 3647 and erythromycin were performed in guinea pigs with L. pneumophila pneumonia. When HMR 3647 was given (10 mg/kg of body weight) by the intraperitoneal route to infected guinea pigs, mean peak plasma levels were 1.4 μg/ml at 0.5 h and 1.0 μg/ml at 1 h postinjection. The terminal half-life phase of elimination from plasma was 1.4 h. All 16 L. pneumophila-infected guinea pigs treated with HMR 3647 (10 mg/kg/dose given intraperitoneally once daily) for 5 days survived for 9 days after antimicrobial therapy, as did all 16 guinea pigs treated with the same dose of HMR 3647 given twice daily. Fourteen of 16

  5. Development of a Method to Determine the Audiogram of the Guinea Pig for Threshold Shift Studies,

    DTIC Science & Technology

    1984-01-01

    AD-A139 717 DEVELOPENI OF A MEHO 10O DEUUUINE tHE AU0IOOGAB Of II THE GUINEA PIG FP0.6 I ARM AEOICAL RESEARCH LAO FORT RUICKER AL. C COMPEIIAIOAE It...tS4 USAARL REPORT NO. 84 - 4 RESU DEVELOPMENT OF A METHOD TO DETERMINE THE AUDIOGRAM OF THE GUINEA PIG FOR THRESHOLD SHIFT STUDIES By Carlos Comperatore...Determine the Audiogram of the Guinea Pig for Threshold Shift Studies G. PERFORMING ORo. REPORT MummaR 7. AUTHOR(e) S. CONTRACT OR GRANT NUMSERa) Carlos

  6. Combined deficiency of vitamins E and C causes paralysis and death in guinea pigs.

    PubMed

    Hill, Kristina E; Montine, Thomas J; Motley, Amy K; Li, Xia; May, James M; Burk, Raymond F

    2003-06-01

    On the basis of in vitro studies, the antioxidant nutrients vitamins E and C are postulated to interact in vivo. We developed a guinea pig model to evaluate the combined deficiency of vitamins E and C in vivo. Weanling guinea pigs were fed a control diet or a vitamin E-deficient diet for 14 d, after which one-half of each group had vitamin C removed from their diet, thus creating 4 diet groups. Some animals were observed for clinical signs. Others were killed for evaluation. Of 21 guinea pigs that were observed after being fed the diet deficient in both vitamins, 8 died 9 +/- 2 d (x +/- SD) after starting the diet. Eight additional guinea pigs developed a characteristic syndrome at 11 +/- 3 d. First, they became paralyzed in the hind limbs. Within a few hours, the paralysis progressed to include all 4 limbs and caused difficulty in breathing, which would have caused death had the animals not been euthanized. Histopathologic evaluation did not identify a lesion in the muscles or nervous system that could account for the paralysis. Biochemical measurements confirmed the deficiencies and indicated that the double deficiency caused lipid peroxidation in the central nervous system. A distinct clinical syndrome of combined vitamin E and vitamin C deficiency occurs in guinea pigs. This syndrome indicates that these antioxidant vitamins are related in vivo. We speculate that acute oxidative injury in the central nervous system underlies the clinical syndrome.

  7. Sudden death in the presence of overt beta-adrenergic receptor activation in guinea pigs immediately following isoflurane anesthesia.

    PubMed

    Overholser, Brian R; Zheng, Xiaomei; Pell, Carrie; Blickman, Andrew

    2010-05-01

    A case series of sudden death is reported in five consecutive guinea pigs following anesthesia with inhalational isoflurane during beta-adrenergic receptor stimulation with isoproterenol. Sustained-release isoproterenol pellets or mini-osmotic pumps were implanted subcutaneously in male Dunkin-Hartley guinea pigs as part of a research study to assess the interplay of adrenergic receptor activation and the development of atrial arrhythmias. The continuous exposure to isoproterenol resulted in a similar presentation and eventual sudden death in all guinea pigs exposed to inhalational isoflurane between 15 to 40 minutes after discontinuation of anesthesia. Death occurred in guinea pigs in this case series despite the fact that doses of isoproterenol used were more than 10-fold lower than previously reported in guinea pigs in the absence of isoflurane anesthesia. The cause of death was suspected to be due to an interaction of isoproterenol with isoflurane anesthesia, as placebo implantation or anesthesia alone did not result in cardiac arrest. Of four subsequent guinea pigs anesthetized with the combination of xylazine and ketamine (X/K), three survived isoproterenol implantation for the full 21-day study period while one died perioperatively. There was an increased rate of post-anesthetic mortality associated with isoproterenol pellet implantation in guinea pigs anesthetized with isoflurane compared to X/K. This may be due to the detrimental effects of the combination of isoflurane during overt beta-adrenergic receptor activation or cardioprotective effects of X/K anesthesia during beta-adrenergic receptor hyperactivity.

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

    PubMed

    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.

  9. Influence of body condition on reproductive output in the guinea pig.

    PubMed

    Michel, Catherine Louise; Bonnet, Xavier

    2012-01-01

    Reproduction is expensive. Substantial body reserves (i.e. high body condition) are usually required for females to undertake offspring production. In many vertebrates, maternal body condition positively influences reproductive output, and emaciated individuals skip reproduction. However, the impact of extremely high body condition, more specifically obesity, on animal reproductive performance remains poorly understood and research has generated contradictory results. For instance, obesity negatively affects fertility in women, but does not influence reproductive capacity or reproductive output in laboratory rodents. We examined the influence of high body condition on reproductive status and reproductive output in the guinea pig. In captivity, when fed ad libitum, guinea pigs store large amounts of fat tissues and exhibit a tendency for obesity. Our results show that obesity negatively affected reproduction in this species: both the proportion of fertile females and litter size were lower in the fattest females. Therefore, guinea pigs may represent suitable organisms to better understand the negative effect of obesity on reproduction. Copyright © 2011 Wiley Periodicals, Inc., A Wiley Company.

  10. DNA vaccines elicit durable protective immunity against individual or simultaneous infections with Lassa and Ebola viruses in guinea pigs.

    PubMed

    Cashman, Kathleen A; Wilkinson, Eric R; Wollen, Suzanne E; Shamblin, Joshua D; Zelko, Justine M; Bearss, Jeremy J; Zeng, Xiankun; Broderick, Kate E; Schmaljohn, Connie S

    2017-12-02

    We previously developed optimized DNA vaccines against both Lassa fever and Ebola hemorrhagic fever viruses and demonstrated that they were protective individually in guinea pig and nonhuman primate models. In this study, we vaccinated groups of strain 13 guinea pigs two times, four weeks apart with 50 µg of each DNA vaccine or a mock vaccine at discrete sites by intradermal electroporation. Five weeks following the second vaccinations, guinea pigs were exposed to lethal doses of Lassa virus, Ebola virus, or a combination of both viruses simultaneously. None of the vaccinated guinea pigs, regardless of challenge virus and including the coinfected group, displayed weight loss, fever or other disease signs, and all survived to the study endpoint. All of the mock-vaccinated guinea pigs that were infected with Lassa virus, and all but one of the EBOV-infected mock-vaccinated guinea pigs succumbed. In order to determine if the dual-agent vaccination strategy could protect against both viruses if exposures were temporally separated, we held the surviving vaccinates in BSL-4 for approximately 120 days to perform a cross-challenge experiment in which guinea pigs originally infected with Lassa virus received a lethal dose of Ebola virus and those originally infected with Ebola virus were infected with a lethal dose of Lassa virus. All guinea pigs remained healthy and survived to the study endpoint. This study clearly demonstrates that DNA vaccines against Lassa and Ebola viruses can elicit protective immunity against both individual virus exposures as well as in a mixed-infection environment.

  11. DNA vaccines elicit durable protective immunity against individual or simultaneous infections with Lassa and Ebola viruses in guinea pigs

    PubMed Central

    Cashman, Kathleen A.; Wilkinson, Eric R.; Wollen, Suzanne E.; Shamblin, Joshua D.; Zelko, Justine M.; Bearss, Jeremy J.; Zeng, Xiankun; Broderick, Kate E.; Schmaljohn, Connie S.

    2017-01-01

    ABSTRACT We previously developed optimized DNA vaccines against both Lassa fever and Ebola hemorrhagic fever viruses and demonstrated that they were protective individually in guinea pig and nonhuman primate models. In this study, we vaccinated groups of strain 13 guinea pigs two times, four weeks apart with 50 µg of each DNA vaccine or a mock vaccine at discrete sites by intradermal electroporation. Five weeks following the second vaccinations, guinea pigs were exposed to lethal doses of Lassa virus, Ebola virus, or a combination of both viruses simultaneously. None of the vaccinated guinea pigs, regardless of challenge virus and including the coinfected group, displayed weight loss, fever or other disease signs, and all survived to the study endpoint. All of the mock-vaccinated guinea pigs that were infected with Lassa virus, and all but one of the EBOV-infected mock-vaccinated guinea pigs succumbed. In order to determine if the dual-agent vaccination strategy could protect against both viruses if exposures were temporally separated, we held the surviving vaccinates in BSL-4 for approximately 120 days to perform a cross-challenge experiment in which guinea pigs originally infected with Lassa virus received a lethal dose of Ebola virus and those originally infected with Ebola virus were infected with a lethal dose of Lassa virus. All guinea pigs remained healthy and survived to the study endpoint. This study clearly demonstrates that DNA vaccines against Lassa and Ebola viruses can elicit protective immunity against both individual virus exposures as well as in a mixed-infection environment. PMID:29135337

  12. Studies of guinea pig immunoglobulin isotype, idiotype and antiidiotype

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tirrell, S.M.

    1988-01-01

    Immunization of Guinea pigs with diphtheria toxoid generated antibodies of the IgG class that were capable of neutralizing native toxin in vivo. Sera from these animals were used to affinity purify idiotypic antibodies (AB1). AB1 vaccines derived from the IgG1 class and from F(ab{prime}){sub 2} of IgG1 + IgG2 (IgG1/2) classes were effective in inducing a syngeneic anti-idiotype (AB2) response. Animals immunized with AB1 consisting of both IgG1/2 did not elicit a detectable AB2 response. Binding of homologous {sup 125}I-F(ab{prime}){sub 2} (AB1) to the antiidiotype was inhibited 90% in the presence of DT.F(ab{prime}){sub 2} derived from preimmune serum or hadmore » no inhibitory effects on the idiotype-antiidiotype interactions. Two groups of outbred guinea pigs were vaccinated with alum absorbed F(ab{prime}){sub 2} of anti-idiotype IgG1/2 (AB2). Of the ten animals inoculated with AB2, three tested positive by RIA against {sup 125}I-DT. Two of the RIA positive sera contained antibodies that neutralized diphtheria toxin in a rabbit intracutaneous assay. Purification of guinea pig IgG by protein A-Sepharose affinity chromatography resulted in the separation of three distinct IgG populations.« less

  13. Prevention of abnormal pulmonary mechanics in the postmortem guinea pig lung.

    PubMed

    Reynolds, A M; McEvoy, R D

    1988-04-01

    Severe postmortem bronchoconstriction has been shown previously in guinea pig lungs and linked to pulmonary blood loss during exsanguination (Lai et al., J. Appl. Physiol. 56: 308-314, 1984). To reexamine this phenomenon we measured postmortem airway function in anesthetized open-chest guinea pigs after sudden circulatory arrest. Animals were divided into 4 groups of 10 and ventilated for 15 min postmortem with different gases: 1) room air, 2) conditioned air, 3) dry 5% CO2-21% O2-74% N2, and 4) conditioned 5% CO2-21% O2-74% N2. In room air-ventilated lungs there was a 50% decrease in dynamic compliance (Cdyn) by 15 min and marked gas trapping compared with control lungs. Conditioning the room air did not attenuate these changes, but when 5% CO2 was added to the conditioned postmortem inspirate, gas trapping was eliminated and the fall in Cdyn was almost abolished. Ventilation with a dry 5% CO2 gas mixture at room temperature resulted in a 31% fall in Cdyn at 15 min but no gas trapping. We conclude that marked abnormalities of airway function occur postmortem in room air-ventilated guinea pig lungs in the absence of pulmonary blood loss. The changes are mainly due to airway hypocarbia, a known cause of bronchoconstriction, but a reduction in Cdyn can also occur if there is marked airway cooling and drying. Acute postmortem airway dysfunction can be prevented in the guinea pig by maintaining normal airway gas composition.

  14. Monovalent virus-like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple Marburg viruses.

    PubMed

    Swenson, Dana L; Warfield, Kelly L; Larsen, Tom; Alves, D Anthony; Coberley, Sadie S; Bavari, Sina

    2008-05-01

    Virus-like particle (VLP)-based vaccines have the advantage of being morphologically and antigenically similar to the live virus from which they are derived. Expression of the glycoprotein and VP40 matrix protein from Lake Victoria marburgvirus (MARV) results in spontaneous production of VLPs in mammalian cells. Guinea pigs vaccinated with Marburg virus VLPs (mVLPs) or inactivated MARV (iMARV) develop homologous humoral and T-cell responses and are completely protected from a lethal homologous MARV challenge. To determine whether mVLPs based on the Musoke (aka Lake Victoria) isolate of MARV could broadly protect against diverse isolates of MARV, guinea pigs were vaccinated with mVLPs or iMARV-Musoke and challenged with MARV-Musoke, -Ravn or -Ci67. Prior to challenge, the mVLP- and iMARV-vaccinated guinea pigs had high levels of homologous MARV-Musoke and heterologous MARV-Ravn and -Ci67 antibodies. The Musoke-based mVLPs and iMARV vaccines provided complete protection in guinea pigs against viremia, viral replication and pathological changes in tissues, and lethal disease following challenge with MARV-Musoke, -Ravn or -Ci67. Guinea pigs vaccinated with RIBI adjuvant alone and infected with guinea pig-adapted MARV-Musoke, -Ravn or -Ci67 had histopathologic findings similar to those seen in the nonhuman primate model for MARV infection. Based on the strong protection observed in guinea pigs, we next vaccinated cynomolgus macaques with Musoke-based mVLPs and showed the VLP-vaccinated monkeys were broadly protected against three isolates of MARV (Musoke, Ravn and Ci67). Musoke mVLPs are effective at inducing broad heterologous immunity and protection against multiple MARV isolates.

  15. Direct adenovirus-mediated gene delivery to the temporomandibular joint in guinea-pigs.

    PubMed

    Kuboki, T; Nakanishi, T; Kanyama, M; Sonoyama, W; Fujisawa, T; Kobayashi, K; Ikeda, T; Kubo, T; Yamashita, A; Takigawa, M

    1999-09-01

    Adenovirus vector system is expected to be useful for direct gene therapy for joint disease. This study first sought to confirm that foreign genes can be transferred to articular chondrocytes in primary culture. Next, recombinant adenovirus vectors harbouring beta-galactosidase gene (LacZ) was injected directly into the temporomandibular joints of Hartley guinea-pigs to clarify the in vivo transfer availability of the adenovirus vectors. Specifically, recombinant adenovirus harbouring LacZ gene (AxlCALacZ) was injected into the upper joint cavities of both mandibular joints of four male 6-week-old Hartley guinea-pigs. Either the same amount of recombinant adenovirus without LacZ gene (Axlw) suspension (placebo) or the same amount of phosphate-buffered saline solution (control) were injected into the upper joint cavities of both joints of another four male guinea-pigs. At 1, 2, 3 and 4 weeks after injection, the joints were dissected and the expression of delivered LacZ was examined by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining and reverse transcriptase-polymerase chain reaction (RT-PCR). To investigate the expression of transferred gene in other organs, total RNA was extracted from liver, kidney, heart and brain and the expression of LacZ mRNA and 18 S ribosomal RNA were analysed by RT-PCR. Clear expression of LacZ was observed in the articular surfaces of the temporal tubercle, articular disc and synovium of the temporomandibular joints even 4 weeks after injection in the AxlCALacZ-injected group, while no expression was detected in placebo and control groups. Histological examination confirmed that LacZ activity was clearly detected in a few cell layers of the articular surface tissues, which is much more efficient than in a previously study of the knee joint. In the other organs, expression of the delivered transgene was not observed. Based on these findings, direct gene delivery into the articular surface of the temporomandibular joint

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

    PubMed

    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.

  17. Disseminated disease severity as a measure of virulence of Mycobacterium tuberculosis in the guinea pig model.

    PubMed

    Palanisamy, Gopinath S; Smith, Erin E; Shanley, Crystal A; Ordway, Diane J; Orme, Ian M; Basaraba, Randall J

    2008-07-01

    Virulence is the measure of pathogenicity of a microorganism as determined by its ability to invade host tissues and to produce severe disease. In the low-dose aerosol guinea pig model the virulence of multiple strains of Mycobacterium tuberculosis was determined by measuring time of survival, bacterial loads in target organs, and the severity of pulmonary and extra-pulmonary lesions. Erdman K01, CSU93/CDC1551 and HN878 had shorter survival times compared to the common laboratory strain H37Rv. After 30 days of the infection bacilli had disseminated from the lungs resulting in microscopically visible lesions in peribronchial lymph nodes, peripancreatic lymph nodes, spleen, liver, pancreas, adrenal and heart. The extent of the lesion necrosis paralleled virulence when survival times were used as a measure as Erdman K01 and the two clinical isolates caused more necrosis and resulted in sooner death in infected animals than the H37Rv. The extent of extra-pulmonary lesion necrosis was a better predictor of virulence than the number of viable bacilli in the tissue. Overall, this study emphasizes the point that extra-pulmonary disease is a prominent feature of the guinea pig model and dissemination to organs not normally assayed such as the heart and adrenal glands should be taken into account in the assessment of the disease process.

  18. Ocular disease in the guinea pig (Cavia porcellus): a survey of 1000 animals.

    PubMed

    Williams, David; Sullivan, Ann

    2010-09-01

    Anecdotal evidence has suggested that guinea pigs have a high prevalence of ocular lesions. Here we undertook a survey of 1000 guinea pigs from populations of animals kept as laboratory animals, breeding show cavies, animals kept as pets and those from rescue and rehoming centers. Each animal was examined to assess for ocular abnormalities. A full ophthalmic examination was performed on each animal with direct and indirect ophthalmoscopy and with slit lamp biomicroscopy. Measurement of tear production using the Schirmer tear test 1 and intraocular pressure using the Tonopen applanation tonometer after topical anesthesia was undertaken in selected animals. Forty-five percent of animals examined had some ocular abnormality. The majority were lens lesions including 17% with cataract and 21% with subclinical lens abnormalities such as nuclear sclerosis. Other abnormalities included conjunctivitis in 4.7% and keratitis in 3.6%. Lipid deposition in conjunctiva was observed in 2.3% of guinea pigs and ciliary body heterotopic bone formation in 0.8% of animals. This study shows a high proportion of eyes with some degree of abnormality in animals otherwise considered healthy. Information on diseases of the guinea pig eye is important given the use of the species as a laboratory rodent and also the number kept as pets and show animals.

  19. Modeling production functions and economic weights in intensive meat production of guinea pigs.

    PubMed

    Pascual, Mariam; Cruz, Danny Julio; Blasco, Agustín

    2017-10-01

    A profit function for a typical commercial farm of intensive guinea pig production was designed. The simulated farm contained 86 cages with a ratio of 7:1 females/males, with continuous mating. Kits were weaned at 15 days of age and slaughtered for meat production at 90 days of age. The absolute (EW) and relative economic weights of the main traits were calculated. The highest EW were kits produced per kindling (US$25), kits weaned per kindling (US$22), kits born alive per kindling (US$20), and the number of kindlings per female and year (US$12). Profit, returns, and costs per female and year were US$15, 68, and 53, respectively. Returns came from the production of young guinea pigs and discarded reproductive adults for meat production, 90 and 10% of the total returns. The highest costs were feeding and labor, 44 and 23% of the total cost. The EW and profit did not substantially change when simulating variations of ±20% in the prices of kilograms of fattening feed and kilograms of live weight of guinea pig, showing their robustness to future variations in market prices or to variations in prices between countries. The results obtained highlight the importance of the feeding costs in the guinea pig meat production.

  20. Hypochlorite Solution as a Decontaminant in Sulfur Mustard Contaminated Skin Defects in the Euthymic Hairless Guinea Pig

    DTIC Science & Technology

    1993-05-13

    AD-P008 792 Hyochlorte Solution as a Decossitamrsrl nan Sultur Mustard Contaminated Skin Defects in the Euthymesc Hailess Guinea Pig Mark B. Gol, OVM...euthymic hairles guinea pigs (EHGP) (n--6) were exposed tn 0 4 LD50 HO in a hA-thickntss 8 mm surgical bmop~sy skin deflect (ioe wound) Each animal was...in a animal model of an HO contaminated wound. The euthymic hairless guinea pig (EHGP) has been extensrvely studied and aicepted as the model of

  1. Determining Optimal Microwave Antigen Retrieval Conditions for Microtubule-Associated Protein 2 Immunohistochemistry in the Guinea Pig Brain

    DTIC Science & Technology

    2002-12-01

    sections of formalin-fixed guinea pig brains using different MAP-2 monoclonal antibodies. Brain sections were boiled in sodium citrate, citric acid...citric acid solution at pH 6.0 is the optimal microwave-assisted AR method for immunolabeling MAP-2 in formalin-fixed, paraffin-processed guinea pig brain...studies on archival guinea pig brain paraffin blocks, ultimately relaxing the use of additional animals to evaluate changes in MAP-2 expression between chemical warfare nerve agent-treated and control samples.

  2. Antitussive and antibronchoconstriction actions of fenspiride in guinea-pigs.

    PubMed

    Laude, E A; Bee, D; Crambes, O; Howard, P

    1995-10-01

    Fenspiride is a nonsteroidal anti-inflammatory agent, which we have previously shown to have an in vivo antibronchoconstrictor action in guinea pigs. We have currently studied this action using the constrictors Substance P, neurokinin A, citric acid and capsaicin in anaesthetized guinea-pigs. Fenspiride has also been reported to produce a subjective improvement in cough in patients. We have used a conscious guinea-pig model of cough as a more definitive method to study the effect of fenspiride on capsaicin- and citric acid-induced cough. Aerosolized fenspiride (1 mg.mL-1) caused a 58% reversal of capsaicin-induced bronchoconstriction; and i.v. fenspiride (1mg.kg-1) a 45% reversal of citric acid induced bronchoconstriction. Substance P- and neurokinin A-induced bronchoconstriction were unaffected by 1 mg.kg-1 i.v. fenspiride. Aerosolized fenspiride (1, 3 and 10 mg.mL-1) administered for 4 min reduced citric acid (300 mM) induced cough, but 0.1 mg.mL-1 was without effect. Pretreatment with aerosolized fenspiride (10 mg.mL-1) caused a shift in the citric acid dose response curve to the right. For citric acid-induced cough, the duration of action of aerosolized fenspiride (10 mg.mL-1) was found to be 5 and 15 min post-treatment. Aerosolized capsaicin (30 microM) induced cough was also reduced by 3 and 10 mg.mL-1 aerosolized fenspiride, but no significant effect was found with 1 mg.mL-1. We conclude that aerosolized fenspiride reduces capsaicin- and citric acid-induced bronchoconstriction as well as induced cough in guinea-pigs in vivo. Whether a pathway common to both cough and bronchoconstriction is the site of action of fenspiride remains to be established. We postulate that fenspiride, acting as an antitussive and antibronchoconstrictor agent, would be beneficial in the clinical situation for those patients with hyperresponsive airways.

  3. Bcl-2 upregulation and neuroprotection in guinea pig brain following chronic simvastatin treatment.

    PubMed

    Franke, Cornelia; Nöldner, Michael; Abdel-Kader, Reham; Johnson-Anuna, Leslie N; Gibson Wood, W; Müller, Walter E; Eckert, Gunter P

    2007-02-01

    The present study determined if chronic simvastatin administration in vivo would provide neuroprotection in brain cells isolated from guinea pigs after challenge with the Bcl-2 inhibitor HA 14-1 or the NO donor sodium nitroprusside (SNP). Bcl-2 levels were significantly increased in brains of simvastatin-treated guinea pigs while levels of the pro-apoptotic protein Bax were significantly reduced. The ratio of Bax/Bcl-2, being a critical factor of the apoptotic state of cells, was significantly reduced in simvastatin-treated animals. Cholesterol levels in the brain remained unchanged in the simvastatin group. Brain cells isolated from simvastatin-treated guinea pigs were significantly less vulnerable to mitochondrial dysfunction and caspase-activation. These results provide new insight into potential mechanisms for the protective actions of statins within the CNS where programmed cell death has been implicated.

  4. Pathogenesis of Bolivian Hemorrhagic Fever in Guinea Pigs.

    PubMed

    Bell, T M; Bunton, T E; Shaia, C I; Raymond, J W; Honnold, S P; Donnelly, G C; Shamblin, J D; Wilkinson, E R; Cashman, K A

    2016-01-01

    Machupo virus, the cause of Bolivian hemorrhagic fever, is a highly lethal viral hemorrhagic fever with no Food and Drug Administration-approved vaccines or therapeutics. This study evaluated the guinea pig as a model using the Machupo virus-Chicava strain administered via aerosol challenge. Guinea pigs (Cavia porcellus) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and sequential changes in serum chemistry and hematology. The incubation period was 5 to 12 days, and complete blood counts revealed leukopenia with lymphopenia and thrombocytopenia. Gross pathologic findings included congestion and hemorrhage of the gastrointestinal mucosa and serosa, noncollapsing lungs with fluid exudation, enlarged lymph nodes, and progressive pallor and friability of the liver. Histologic lesions consisted of foci of degeneration and cell death in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, renal pelvis, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system, interpreted as nonsuppurative encephalitis, was histologically apparent approximately 16 days postexposure and was generally progressive. Macrophages in the tracheobronchial lymph node, on day 5 postexposure, were the first cells to demonstrate visible viral antigen. Viral antigen was detected throughout the lymphoid system by day 9 postexposure, followed by prominent spread within epithelial tissues and then brain. This study provides insight into the course of Machupo virus infection and supports the utility of guinea pigs as an additional animal model for vaccine and therapeutic development. © The Author(s) 2015.

  5. Testing Experimental Therapies in a Guinea Pig Model for Hemorrhagic Fever.

    PubMed

    Wong, Gary; Bi, Yuhai; Kobinger, Gary; Gao, George F; Qiu, Xiangguo

    2018-01-01

    Hemorrhagic fever viruses are among the deadliest pathogens known to humans, and often, licensed medical countermeasures are unavailable to prevent or treat infections. Guinea pigs are a commonly used animal for the preclinical development of any experimental candidates, typically to confirm data generated in mice and as a way to validate and support further testing in nonhuman primates. In this chapter, we use Sudan virus (SUDV), a lethal filovirus closely related to Ebola virus, as an example of the steps required for generating a guinea pig-adapted isolate that is used to test a monoclonal antibody-based therapy against viral hemorrhagic fevers.

  6. An Investigation into the Relationship between Owner Knowledge, Diet, and Dental Disease in Guinea Pigs (Cavia porcellus)

    PubMed Central

    Norman, Rosemary; Wills, Alison P.

    2016-01-01

    Simple Summary Dental disease is a serious problem in small mammals, with cases in rabbits well documented. Guinea pigs also suffer from this condition, yet the literature investigating the underlying causes in guinea pigs is limited. Owners of guinea pigs were surveyed to investigate what they fed their animals. It was discovered that there was no relationship between the overall diet of the animals and whether or not they had been diagnosed with dental disease or displayed clinical signs of the disease. However, the environment was important, with animals that had access to the outside, including the use of runs on both concrete and grass, less likely to display clinical signs of disease. Some of the clinical signs of dental disease in guinea pigs, including difficulty eating, were related to dental problems. These findings are important, as many guinea pigs may not have continuous access to the outdoors. Dental disease is a serious welfare concern, as many owners may not pick up on the clinical signs, leaving animals susceptible to pain, dysphagia, malnutrition, and secondary infection. It is important that owners are aware of key clinical signs, particularly in multi-animal households where monitoring food consumption may be challenging. Abstract Recent studies have highlighted a high prevalence of dental disease in domestic guinea pigs, yet the aetiology of this multi-factorial disease is still unclear. Factors that have been associated with dental disease include feeding a diet that is high in energy but low in fibre, feeding an insufficiently abrasive diet, a lack of dietary calcium, and genetics. As many of these factors relate to the husbandry requirements of guinea pigs, owner awareness of dietary requirements is of the utmost importance. An online questionnaire was created based on previous research into the husbandry and feeding of rabbits. Guinea pig owners were asked to answer questions on the clinical history of their animals and their diet and

  7. Adeno-associated virus transformation into the normal miniature pig and the normal guinea pigs cochlea via scala tympani.

    PubMed

    Shi, Xunbei; Wu, Nan; Zhang, Yue; Guo, Weiwei; Lin, Chang; Yang, Shiming

    2017-09-01

    To investigate the expression of the miniature pig cochlea after AAV1 transfect into the cochlea via round window membrane (RWM). Twenty miniature pigs are equally divided into four experimental groups. Twelve miniature pigs are equally divided into four control groups. Each pig was transfected with the AAV1 in the experimental group via RWM and each pig was transduced with the artificial perilymph in the control group. The expression of green fluorescent protein (GFP) was observed at 2 weeks, 3 weeks and 4 weeks, respectively. Likewise, AAV1 was delivered into the guinea pigs cochleas using the same method, and the results were compared with that of the miniature pigs. The expression was mainly in the inner hair cells of the miniature pig. The expression of GFP began to appear at 2 weeks, reached the peak at 3 weeks. It also expressed in Hensen's cells, inner pillar cells, outer pillar cells, spiral limbus, and spiral ligament. In the meanwhile, AAV1 was delivered into guinea pig cochlea via the same method, and AAV1 was also expressed in the inner hair cells. But the expression peaked at 2 weeks, and the efficiency of the inner hair cell transfection was higher than that of the pig. AAV1 can be transformed into miniature pig cochlea via scala tympani by the RWM method efficiently.

  8. [Lethal anaphylactic shock model induced by human mixed serum in guinea pigs].

    PubMed

    Ren, Guang-Mu; Bai, Ji-Wei; Gao, Cai-Rong

    2005-08-01

    To establish an anaphylactic shock model induced by human mixed serum in guinea pigs. Eighteen guinea pigs were divided into two groups: sensitized and control, The sensitized group were immunized intracutaneously with human mixed serum and then induced by endocardiac injection after 3 weeks. Symptoms of anaphylactic shock appeared in the sensitized group. The level of serum IgE were increased in the sensitized group significantly. An animal model of anaphylactic shock wer established successfully. It provide a tool for both forensic study and anaphylactic shock therapy.

  9. [Effect of down-regulation of IKs repolarization-reserve on ventricular arrhythmogenesis in a guinea pig model of cardiac hypertrophy].

    PubMed

    Wang, Hegui; Huang, Ting; Wang, Zheng; Ge, Nannan; Ke, Yongsheng

    2018-04-28

    To observe the changes of rapidly activated delayed rectifier potassium channel (IKr) and slowly activated delayed rectifier potassium channel (IKs) in cardiac hypertrophy and to evaluate the effects of IKr and IKs blocker on the incidence of ventricular arrhythmias in guinea pigs with left ventricular hypertrophy (LVH).
 Methods: Guinea pigs were divided into a sham operation group and a left ventricular hypertrophy (LVH) group. LVH model was prepared. Whole cell patch-clamp technique was used to record IKr and IKs tail currents in a guinea pig model with LVH. The changes of QTc and the incidence rate of ventricular arrhythmias in LVH guinea pigs were observed by using the IKr and IKs blockers.
 Results: Compared with cardiac cells in the control group, the interventricular septal thickness at end systole (IVSs), left ventricular posterior wall thickness at end systole (LVPWs), QTc interval and cell capacitance in guinea pigs with LVH were significantly increased (P<0.05); while IKs densities were significantly reduced [+60 mV: (0.36±0.03) pA/pF vs (0.58±0.05) pA/pF, P<0.01]. However, LVH exerted no significant effect on IKr densities. IKr blocker markedly prolonged the QTc interval (P<0.01) and increased the incidence of ventricular arrhythmias in guinea pigs with LVH compared with the control guinea pigs. In contrast, IKs blocker produced modest increase in QTc interval in guinea pigs of control group with no increase in LVH animals. IKs blocker did not induce ventricular arrhythmias incidence in either control or LVH animals.
 Conclusion: The cardiac hypertrophy-induced arrhythmogenesis is due to the down-regulation 
of IKs.

  10. Effects of omega-conotoxin GVIA on the activation of capsaicin-sensitive afferent sensory nerves in guinea pig airway tissues.

    PubMed

    Morimoto, H; Matsuda, A; Ohori, M; Fujii, T

    1996-06-01

    We examined the effects of Ca2+ channel antagonists on various respiratory reactions induced by the activation of capsaicin-sensitive afferent sensory nerves. Intravenous (i.v.) injection of the N-type Ca2+ channel antagonist omega-conotoxin GVIA (CgTX) (1-20 micrograms/kg) dose-dependently inhibited capsaicin-induced guinea pig bronchoconstriction, whereas i.v. administration of the L-type antagonist nicardipine (100 micrograms/kg), the P-type antagonist omega-agatoxin IVA (AgaTX) (20 micrograms/kg) or the OPQ family-type antagonist omega-conotoxin MVIIC (CmTX) (20 micrograms/kg) had no effect. However, CgTX (20 micrograms/kg) failed to inhibit substance P-induced guinea pig bronchoconstriction. CgTX (20 micrograms/kg) significantly inhibited cigarette smoke-induced guinea pig tracheal plasma extravasation, but not the substance P-induced reaction. CgTX also reduced electrical field stimulation-induced guinea pig bronchial smooth muscle contraction (0.01-10 microM) and capsaicin-induced substance P-like immunoreactivity release from guinea pig lung (0.14 microM). This evidence suggests that N-type Ca2+ channels modulate tachykinin release from capsaicin-sensitive afferent sensory nerve endings in guinea pig airway tissue.

  11. GENETIC CONTROL IN GUINEA PIGS OF IMMUNE RESPONSE TO CONJUGATES OF HAPTENS AND POLY-L-LYSINE.

    PubMed

    LEVINE, B B; BENACERRAF, B

    1965-01-29

    Random-bred Hartley strain guinea pigs which do not respond immunologically to conjugates of hapten and poly-L-lysine mere mated with heterozygous guinea pigs which do. These responders were considered heterozygous for this trait since their mating resulted in at least one nonresponder offspring. Of 31 offspring from 10 breeding pairs (nonresponder x heterozygous responder) 14 were responders. There was no evidence that this trait is sex-linked. This finding confirms the view that, in guinea pigs, development of an immune response to the aforementioned conjugates is a genetically transmitted autosomal, unigenic Mendelian dominant trait.

  12. Malformation of stria vascularis in the developing inner ear of the German waltzing guinea pig.

    PubMed

    Jin, Zhe; Mannström, Paula; Järlebark, Leif; Ulfendahl, Mats

    2007-05-01

    Auditory function and cochlear morphology have previously been described in the postnatal German waltzing guinea pig, a strain with recessive deafness. In the present study, cochlear histopathology was further investigated in the inner ear of the developing German waltzing guinea pig (gw/gw). The lumen of the cochlear duct diminished progressively from embryonic day (E) 35 to E45 and was absent at E50 because of the complete collapse of Reissner's membrane onto the hearing organ. The embryonic stria vascularis, consisting of a simple epithelium, failed to transform into the complex trilaminar tissue seen in normal animals and displayed signs of degeneration. Subsequent degeneration of the sensory epithelium was observed from E50 and onwards. Defective and insufficient numbers of melanocytes were observed in the developing gw/gw stria vascularis. A gene involved in cochlear melanocyte development, Pax3, was markedly reduced in lateral wall tissue of the cochlea of both E40 and adult gw/gw individuals, whereas its expression was normal in the skin and diaphragm muscle of adult gw/gw animals. The Pax3 gene may thus be involved in the pathological process but is unlikely to be the primary mutated gene in the German waltzing guinea pig. TUNEL assay showed no signs of apoptotic cell death in the developing stria vascularis of this type of guinea pig. Thus, malformation of the stria vascularis appears to be the primary defect in the inner ear of the German waltzing guinea pig. Defective and insufficient numbers of melanocytes might migrate to the developing stria vascularis but fail to provide the proper support for the subsequent development of marginal and basal cells, thereby leading to stria vascularis malformation and dysfunction in the inner ear of the German waltzing guinea pig.

  13. Morphological and immunohistochemical characterization of spontaneous thyroid gland neoplasms in guinea pigs (Cavia porcellus).

    PubMed

    Gibbons, P M; Garner, M M; Kiupel, M

    2013-03-01

    Reports of thyroid gland neoplasms in guinea pigs (Cavia porcellus) are rare, but thyroid tumors are among the most common neoplasms seen in cases submitted to Northwest ZooPath. This report describes the histological and immunohistochemical characteristics of thyroid neoplasms and lists the concurrent conditions found in guinea pig cases submitted to Northwest ZooPath during 1998 to 2008. Of 526 guinea pig case submissions, 19 had thyroid neoplasms. The most common clinical findings included a palpable mass on the ventral neck and progressive weight loss. Neoplasms were removed as an excisional biopsy from 7 guinea pigs, and 3 of these animals died within a few days after surgery. Radiographic mineral density was detected in 2 masses. Five of the neoplasms were reported as cystic; 5 were black or a dark color. Histologically, the neoplasms were classified as macrofollicular thyroid adenoma (8), thyroid cystadenoma (1), papillary thyroid adenoma (3), follicular thyroid carcinoma (5), follicular-compact thyroid carcinoma (1), and small-cell thyroid carcinoma (1). Osseous metaplasia was present in 8 neoplasms, and myeloid hyperplasia was present in 1 neoplasm. All 19 neoplasms were positive for thyroid transcription factor 1 and thyroglobulin but negative for parathyroid hormone and calcitonin. Numerous concurrent diseases, including hepatopathies, cardiomyopathies, and nephropathies, were present and considered to be the cause of death in many cases. Research is needed to determine the appropriate modalities for antemortem diagnosis and treatment and whether thyroid disease plays a role in the pathogenesis of chronic degenerative diseases in guinea pigs.

  14. Mechanisms and roles of muscarinic activation in guinea-pig adrenal medullary cells.

    PubMed

    Inoue, Masumi; Harada, Keita; Matsuoka, Hidetada; Nakamura, Jun; Warashina, Akira

    2012-09-15

    Muscarinic receptors are expressed in the adrenal medullary (AM) cells of various mammals, but their physiological roles are controversial. Therefore, the ionic mechanism for muscarinic receptor-mediated depolarization and the role of muscarinic receptors in neuronal transmission were investigated in dissociated guinea-pig AM cells and in the perfused guinea-pig adrenal gland. Bath application of muscarine induced an inward current at -60 mV. This inward current was partially suppressed by quinine with an IC(50) of 6.1 μM. The quinine-insensitive component of muscarine-induced currents changed the polarity at -78 mV and was inhibited by bupivacaine, a TWIK-related acid-sensitive K(+) (TASK) channel inhibitor. Conversely, the current-voltage relationship for the bupivacaine-insensitive component of muscarine currents showed a reversal potential of -5 mV and a negative slope below -40 mV. External application of La(3+) had a double action on muscarine currents of both enhancement and suppression. Immunoblotting and immunocytochemistry revealed expression of TASK1 channels and cononical transient receptor potential channels 1, 4, 5, and 7 in guinea-pig AM cells. Retrograde application of atropine reversibly suppressed transsynaptically evoked catecholamine secretion from the adrenal gland. The results indicate that muscarinic receptor stimulation in guinea-pig AM cells induces depolarization through inhibition of TASK channels and activation of nonselective cation channels and that muscarinic receptors are involved in neuronal transmission from the splanchnic nerve.

  15. Mechanisms and roles of muscarinic activation in guinea-pig adrenal medullary cells

    PubMed Central

    Harada, Keita; Matsuoka, Hidetada; Nakamura, Jun; Warashina, Akira

    2012-01-01

    Muscarinic receptors are expressed in the adrenal medullary (AM) cells of various mammals, but their physiological roles are controversial. Therefore, the ionic mechanism for muscarinic receptor-mediated depolarization and the role of muscarinic receptors in neuronal transmission were investigated in dissociated guinea-pig AM cells and in the perfused guinea-pig adrenal gland. Bath application of muscarine induced an inward current at −60 mV. This inward current was partially suppressed by quinine with an IC50 of 6.1 μM. The quinine-insensitive component of muscarine-induced currents changed the polarity at −78 mV and was inhibited by bupivacaine, a TWIK-related acid-sensitive K+ (TASK) channel inhibitor. Conversely, the current-voltage relationship for the bupivacaine-insensitive component of muscarine currents showed a reversal potential of −5 mV and a negative slope below −40 mV. External application of La3+ had a double action on muscarine currents of both enhancement and suppression. Immunoblotting and immunocytochemistry revealed expression of TASK1 channels and cononical transient receptor potential channels 1, 4, 5, and 7 in guinea-pig AM cells. Retrograde application of atropine reversibly suppressed transsynaptically evoked catecholamine secretion from the adrenal gland. The results indicate that muscarinic receptor stimulation in guinea-pig AM cells induces depolarization through inhibition of TASK channels and activation of nonselective cation channels and that muscarinic receptors are involved in neuronal transmission from the splanchnic nerve. PMID:22744007

  16. Comparison of Four Skin Decontamination Procedures Using Reactive Skin Decontamination Lotion (RSDL) Following Cutaneous VX Exposure in Guinea Pigs

    DTIC Science & Technology

    2016-01-01

    DC) product following cutaneous exposure to VX was affected by the DC procedure. Fur-clipped, male, unanesthetized guinea pigs were used as subjects...RSDL) Following Cutaneous VX Exposure in Guinea Pigs Irwin Koplovitz Susan Schulz Julia Morgan Robert Reed Edward Clarkson C. Gary Hurst...Decontamination Procedures Using Reactive Skin 5a. CONTRACT NUMBER Decontamination Lotion (RSDL) Following Cutaneous VX Exposure in Guinea Pigs 5b

  17. A combined deficiency of vitamins E and C causes severe central nervous system damage in guinea pigs.

    PubMed

    Burk, Raymond F; Christensen, Joani M; Maguire, Mark J; Austin, Lori M; Whetsell, William O; May, James M; Hill, Kristina E; Ebner, Ford F

    2006-06-01

    A short period of combined deficiency of vitamins E and C causes profound central nervous system (CNS) dysfunction in guinea pigs. For this report, CNS histopathology was studied to define the nature and extent of injury caused by this double deficiency. Weanling guinea pigs were fed a vitamin E-deficient or -replete diet for 14 d. Then vitamin C was withdrawn from the diet of some guinea pigs. Four diet groups were thus formed: replete, vitamin E deficient, vitamin C deficient, and both vitamin E and C deficient. From 5 to 11 d after institution of the doubly deficient diet, 9 of 12 guinea pigs developed paralysis, and 2 more were found dead. The remaining guinea pig in the doubly deficient group and all animals in the other 3 groups survived without clinical impairment until the experiment was terminated at 13-15 d. Brains and spinal cords were serially sectioned and stained for examination. Only the combined deficiency produced damage in the CNS. The damage consisted mainly of nerve cell death, axonal degeneration, vascular injury, and associated glial cell responses. The spinal cord and the ventral pons in the brainstem were most severely affected, often exhibiting asymmetric cystic lesions. Several features of the lesions suggest that the primary damage was to blood vessels. These results indicate that the paralysis and death caused by combined deficiency of vitamins E and C in guinea pigs is caused by severe damage in the brainstem and spinal cord.

  18. The pathology of halothane hepatotoxicity in a guinea-pig model: a comparison with human halothane hepatitis.

    PubMed Central

    Lunam, C. A.; Hall, P. M.; Cousins, M. J.

    1989-01-01

    The pathology of halothane hepatotoxicity is described in detail in a guinea-pig model. Twenty-two of 40 guinea-pigs developed liver damage after exposure to 1% halothane in 21% O2 for 4 h. The other 18 animals showed no evidence of hepatic injury. Two distinct patterns of damage were identified: mild damage, in which livers had focal areas of necrosis, and severe damage, where necrosis was confluent around the terminal hepatic venules, often extending to the portal tracts. Serum alanine aminotransferase activity was significantly elevated in guinea-pigs with severe liver damage. Hepatocytes in the damaged areas showed degenerative changes ranging from vacuolization to ballooning degeneration and necrosis. Inflammatory cells, predominantly lymphocytes, were often present in the areas of necrosis. The pathology of mild and severe liver injury in the guinea-pig closely resembles the spectrum of injury observed in non-fatal halothane hepatitis in man. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:2818932

  19. The extraneuronal accumulation of isoprenaline in trachea and atria of guinea-pig and cat

    PubMed Central

    Anning, Elizabeth N.; Bryan, Lesley J.; O'Donnell, Stella R.

    1979-01-01

    1 The Falck-Hillarp histochemical technique was used to locate extraneuronal sites of accumulation of isoprenaline in trachea and atria from guinea-pig and cat. With a tissue exposure time to formaldehyde gas of 3 h, isoprenaline was located as green fluorescence. 2 Quantitative microphotometry was used to measure fluorescence intensity within cells in the trachealis smooth muscle and the atrial myocardium of both species. 3 After incubation of tissues in 50 μM isoprenaline, specific fluorescence was seen in trachealis smooth muscle of both species and in the atrial myocardium of cat but not guinea-pig. In both species, fluorescence was also seen in the chondroblasts of the tracheal cartilage and in blood vessels in all tissues. 4 In trachealis smooth muscle of both species and in cat atrial myocardium, fluorescence brightness, resulting from incubation of tissues in 50 μM isoprenaline was significantly increased by 200 μM β-thujaplicin, an inhibitor of catechol-O-methyl transferase (COMT). In the presence of β-thujaplicin, fluorescence was not visible in guinea-pig atrial myocardium with 50 μM isoprenaline, although fluorescence brightness measured in myocardial cells was now greater than that in corresponding controls. 5 The fluorescence intensity seen in cat and guinea-pig trachealis smooth muscle cells and in cat atrial myocardial cells after incubation in 50 μM isoprenaline was decreased significantly in the presence of phenoxybenzamine (100 μM). In guinea-pig atria, phenoxybenzamine had no effect on myocardial fluorescence. Fluorescence intensity was also decreased if the incubation with isoprenaline was carried out at 0°C or if the post-incubation washing temperature was 37°C instead of 0 to 2°C. 6 The results demonstrate that the fluorescence histochemical technique can be used to locate isoprenaline in tissues. They also indicate that guinea-pig and cat trachealis smooth muscle cells and cat atrial myocardial cells can accumulate isoprenaline (a

  20. Computed tomography analysis of guinea pig bone: architecture, bone thickness and dimensions throughout development.

    PubMed

    Witkowska, Agata; Alibhai, Aziza; Hughes, Chloe; Price, Jennifer; Klisch, Karl; Sturrock, Craig J; Rutland, Catrin S

    2014-01-01

    The domestic guinea pig, Cavia aperea f. porcellus, belongs to the Caviidae family of rodents. It is an important species as a pet, a source of food and in medical research. Adult weight is achieved at 8-12 months and life expectancy is ∼5-6 years. Our aim was to map bone local thickness, structure and dimensions across developmental stages in the normal animal. Guinea pigs (n = 23) that had died of natural causes were collected and the bones manually extracted and cleaned. Institutional ethical permission was given under the UK Home Office guidelines and the Veterinary Surgeons Act. X-ray Micro Computed Tomography (microCT) was undertaken on the left and right scapula, humerus and femur from each animal to ascertain bone local thickness. Images were also used to undertake manual and automated bone measurements, volumes and surface areas, identify and describe nutrient, supratrochlear and supracondylar foramina. Statistical analysis between groups was carried out using ANOVA with post-hoc testing. Our data mapped a number of dimensions, and mean and maximum bone thickness of the scapula, humerus and femur in guinea pigs aged 0-1 month, 1-3 months, 3-6 months, 6 months-1 year and 1-4 years. Bone dimensions, growth rates and local bone thicknesses differed between ages and between the scapula, humerus and femur. The microCT and imaging software technology showed very distinct differences between the relative local bone thickness across the structure of the bones. Only one bone showed a singular nutrient foramen, every other bone had between 2 and 5, and every nutrient canal ran in an oblique direction. In contrast to other species, a supratrochlear foramen was observed in every humerus whereas the supracondylar foramen was always absent. Our data showed the bone local thickness, bone structure and measurements of guinea pig bones from birth to 4 years old. Importantly it showed that bone development continued after 1 year, the point at which most guinea pigs have

  1. Inhibiting mitochondrial Na+/Ca2+ exchange prevents sudden death in a Guinea pig model of heart failure.

    PubMed

    Liu, Ting; Takimoto, Eiki; Dimaano, Veronica L; DeMazumder, Deeptankar; Kettlewell, Sarah; Smith, Godfrey; Sidor, Agnieszka; Abraham, Theodore P; O'Rourke, Brian

    2014-06-20

    In cardiomyocytes from failing hearts, insufficient mitochondrial Ca(2+) accumulation secondary to cytoplasmic Na(+) overload decreases NAD(P)H/NAD(P)(+) redox potential and increases oxidative stress when workload increases. These effects are abolished by enhancing mitochondrial Ca(2+) with acute treatment with CGP-37157 (CGP), an inhibitor of the mitochondrial Na(+)/Ca(2+) exchanger. Our aim was to determine whether chronic CGP treatment mitigates contractile dysfunction and arrhythmias in an animal model of heart failure (HF) and sudden cardiac death (SCD). Here, we describe a novel guinea pig HF/SCD model using aortic constriction combined with daily β-adrenergic receptor stimulation (ACi) and show that chronic CGP treatment (ACi plus CGP) attenuates cardiac hypertrophic remodeling, pulmonary edema, and interstitial fibrosis and prevents cardiac dysfunction and SCD. In the ACi group 4 weeks after pressure overload, fractional shortening and the rate of left ventricular pressure development decreased by 36% and 32%, respectively, compared with sham-operated controls; in contrast, cardiac function was completely preserved in the ACi plus CGP group. CGP treatment also significantly reduced the incidence of premature ventricular beats and prevented fatal episodes of ventricular fibrillation, but did not prevent QT prolongation. Without CGP treatment, mortality was 61% in the ACi group <4 weeks of aortic constriction, whereas the death rate in the ACi plus CGP group was not different from sham-operated animals. The findings demonstrate the critical role played by altered mitochondrial Ca(2+) dynamics in the development of HF and HF-associated SCD; moreover, they reveal a novel strategy for treating SCD and cardiac decompensation in HF. © 2014 American Heart Association, Inc.

  2. Pre- and postjunctional inhibitory effects of fenspiride on guinea-pig bronchi.

    PubMed

    Girard, V; Naline, E; Crambes, O; Malbezin, M; Malmström, R E; Lundberg, J M; Advenier, C

    1997-05-01

    Fenspiride is a drug with potential benefits in the treatment of obstructive airways disease. It has antibronchoconstriction and anti-inflammatory properties. The aim of this study was to investigate the effect of this drug on the contractions induced in the guinea-pig isolated main bronchus and perfused lung by electrical field stimulation (EFS) or exogenously added agents. Bronchi were stimulated transmurally in the presence of indomethacin 10(-6) M and propranolol 10(-6) M, and isometric tension was measured. In the perfused lung model calcitonin gene-related peptide (CGRP) release was determined in the perfusate fractions as a measure of neuropeptide production. Two successive contractile responses were observed: a rapid cholinergic contraction, followed by a long-lasting contraction due to local release of neuropeptides from C-fibre endings. Fenspiride (10(-6) to 10(-4) M) inhibited the nonadrenergic, noncholinergic (NANC) component of the contraction of the guinea-pig isolated main bronchus induced by EFS. Fenspiride significantly affected contractions induced by exogenously added substance P or [Nle10]-NKA(4-10) only at concentrations higher than 10(-3) M. In the guinea-pig perfused lung, fenspiride inhibited low pH- but not capsaicin-evoked release of CGRP. At higher concentrations (10(-4) M to 3x10(-4) M) fenspiride exhibited a significant inhibitory effect both on the cholinergic component of contractile response induced by EFS in the guinea-pig isolated main bronchus and on exogenously added acetylcholine. In conclusion, the result of this study suggests that fenspiride, in moderate concentrations, reduces the release of neuropeptides, including tachykinins, from sensory nerve endings at a prejunctional level. At higher concentrations, postjunctional actions on bronchial smooth muscle are also present.

  3. Diseases of guinea-pigs.

    PubMed

    Sebesteny, A

    1976-05-22

    Information on diseases of guinea-pigs is generally available in research institutes and breeding establishments. When dealing with an individual patient it is tempting to extrapolate from this pool of information, without realising that a number of factors can affect the disease situation in a colony which need not apply to the individual animal kept as a pet--or vice versa. Thus diseases may appear as an explosive outbreak in a group of cavies kept under uniform conditions while a single animal may be exposed to amateur management (Townsend 1975) and suffer in consequence. The diseases generally encountered in this species are dealt with here as they appear clinically.

  4. Some effects of mastectomy on reproductive success in the guinea-pig.

    PubMed

    Peaker, M; Taylor, E

    1990-07-01

    Virgin guinea-pigs were mastectomized in two stages between 11 and 18 weeks of age and then mated, starting 19 weeks after final surgery. In the subsequent first pregnancy, the incidence of still-births and neonatal deaths was significantly higher in the mastectomized animals (6 out of 12 mothers (50%) and 14 out of 49 young (29%) compared with intact guinea-pigs (1 out of 15 mothers (7%) and 1 out of 58 young (2%)). There was no significant effect of mastectomy on litter size and weight or on gestation period. The still-born were not significantly different in weight from those born alive. A significant relation was found between maternal weight changes in the period 20 to 5 days before parturition and the occurrence of still-births and neonatal deaths; still-births were associated with a period of reduced weight gain. No effect of mastectomy on the length of the oestrous cycle was apparent but a significant increase in the incidence of non-pregnancy was found. The results provide further evidence that mastectomy influences reproductive success in the guinea-pig and suggest that parturition is a key process affected.

  5. Effects of Dithiothreitol, a Sulfhydryl Reducing Agent, on CA1 Pyramidal Cells of the Guinea Pig Hippocampus in Vitro

    DTIC Science & Technology

    1988-01-01

    pyramidal cells of the guinea pig hippocampus in vitro J.M. Tolliver* and T.C. Pellmar Physiology Department. Armed Forces Radiohiology Research...Hartley guinea pigs as scavenging free radicals’K3 ). 32 and by donating hy- previously described&𔃾t . Slices were incubated at drogen to damaged...Dithiothreitol-induced al- 29 Pellmar, T.C.. Electrophysiological correlates of peroxide teration in histamine H,-agonist binding in guinea - pig cere

  6. Effects of Potassium Channel Blockers on the Negative Inotropic Responses Induced by Cromakalim and Pinacidil in Guinea Pig Atrium

    DTIC Science & Technology

    1992-01-01

    RD-A2•4 875 EFFECTS OF POTASSIUM CHANNEL BLOCKERS ON THE NEGATIVE 1/1 INOTROPIC RESPONSES INDUCED BY CRONAKALIM RND PINACIDIL IN GUINEA PIG ATRIUM(U...INOTROPICTRSPONSES INDUCED BY CROMAKAUM AND PINACIDILIN GUINEA PIG ATRIUM a AUTHOR WAI-MAN LAU 7 FORMING ORG NAMES/ADDRESSES DEFENCE SCIENCE AND a...and Technology Organisaio Aot Val. Negative Inotropic Responses Victoria. Australia Induced by Cromakalim and Pinacidil in Guinea Pig Atrium Key

  7. DEMONSTRATION IN VITRO OF ANAPHYLACTOID RESPONSE OF THE UTERUS AND ILEUM OF GUINEA PIGS INJECTED WITH TESTIS OR SPERM

    PubMed Central

    Katsh, Seymour

    1958-01-01

    Female guinea pigs were injected with the following materials: homogenates of guinea pig testis in saline or in adjuvant; suspensions of washed guinea pig sperm in saline or in adjuvant; homogenates of rabbit testis in adjuvant; guinea pig sperm and rabbit sperm in adjuvant. Control animals were not injected or were injected with adjuvant alone. At various times between 15 and 39 days after injection, the animals were sacrificed. Their ilea and uterine horns were removed and tested in vitro for reaction to washed epididymal sperm of the guinea pig, rabbit, or bull. It was found that the animals which were injected with homologous testis or sperm in adjuvant possessed organs which responded strongly to the challenge with homologous sperm. The response was a contracture which began 10 to 30 seconds after the sperm were injected into the bath and lasted for 5 minutes to 4 hours, the longest period of observation. Responses which lasted for periods of 5 minutes to 30 minutes were obtained with the uteri of the animals injected with guinea pig testis in saline or with guinea pig sperm in saline. Animals which were injected with rabbit testis and adjuvant responded to rabbit sperm, and animals injected with guinea pig sperm and rabbit sperm in adjuvant reacted to both gametes. A large proportion of the control animals possessed organs which reacted weakly to the challenge with homologous sperm. Retesting the organ which had contracted following exposure to sperm indicated that desensitization had occurred. Testing with heterologous sperm indicated a species selectivity. The evidence is interpreted to mean that injections of sperm or testis induce a hypersensitivity which is similar in some respects but differs from true anaphylaxis. The findings are discussed from the point of view of the nature of the response and the implications regarding natural immunity to sperm. PMID:13481258

  8. A model of type 2 diabetes in the guinea pig using sequential diet-induced glucose intolerance and streptozotocin treatment

    PubMed Central

    Ackart, David F.; Richardson, Michael A.; DiLisio, James E.; Pulford, Bruce; Basaraba, Randall J.

    2017-01-01

    ABSTRACT Type 2 diabetes is a leading cause of morbidity and mortality among noncommunicable diseases, and additional animal models that more closely replicate the pathogenesis of human type 2 diabetes are needed. The goal of this study was to develop a model of type 2 diabetes in guinea pigs, in which diet-induced glucose intolerance precedes β-cell cytotoxicity, two processes that are crucial to the development of human type 2 diabetes. Guinea pigs developed impaired glucose tolerance after 8 weeks of feeding on a high-fat, high-carbohydrate diet, as determined by oral glucose challenge. Diet-induced glucose intolerance was accompanied by β-cell hyperplasia, compensatory hyperinsulinemia, and dyslipidemia with hepatocellular steatosis. Streptozotocin (STZ) treatment alone was ineffective at inducing diabetic hyperglycemia in guinea pigs, which failed to develop sustained glucose intolerance or fasting hyperglycemia and returned to euglycemia within 21 days after treatment. However, when high-fat, high-carbohydrate diet-fed guinea pigs were treated with STZ, glucose intolerance and fasting hyperglycemia persisted beyond 21 days post-STZ treatment. Guinea pigs with diet-induced glucose intolerance subsequently treated with STZ demonstrated an insulin-secretory capacity consistent with insulin-independent diabetes. This insulin-independent state was confirmed by response to oral antihyperglycemic drugs, metformin and glipizide, which resolved glucose intolerance and extended survival compared with guinea pigs with uncontrolled diabetes. In this study, we have developed a model of sequential glucose intolerance and β-cell loss, through high-fat, high-carbohydrate diet and extensive optimization of STZ treatment in the guinea pig, which closely resembles human type 2 diabetes. This model will prove useful in the study of insulin-independent diabetes pathogenesis with or without comorbidities, where the guinea pig serves as a relevant model species. PMID:28093504

  9. A model of type 2 diabetes in the guinea pig using sequential diet-induced glucose intolerance and streptozotocin treatment.

    PubMed

    Podell, Brendan K; Ackart, David F; Richardson, Michael A; DiLisio, James E; Pulford, Bruce; Basaraba, Randall J

    2017-02-01

    Type 2 diabetes is a leading cause of morbidity and mortality among noncommunicable diseases, and additional animal models that more closely replicate the pathogenesis of human type 2 diabetes are needed. The goal of this study was to develop a model of type 2 diabetes in guinea pigs, in which diet-induced glucose intolerance precedes β-cell cytotoxicity, two processes that are crucial to the development of human type 2 diabetes. Guinea pigs developed impaired glucose tolerance after 8 weeks of feeding on a high-fat, high-carbohydrate diet, as determined by oral glucose challenge. Diet-induced glucose intolerance was accompanied by β-cell hyperplasia, compensatory hyperinsulinemia, and dyslipidemia with hepatocellular steatosis. Streptozotocin (STZ) treatment alone was ineffective at inducing diabetic hyperglycemia in guinea pigs, which failed to develop sustained glucose intolerance or fasting hyperglycemia and returned to euglycemia within 21 days after treatment. However, when high-fat, high-carbohydrate diet-fed guinea pigs were treated with STZ, glucose intolerance and fasting hyperglycemia persisted beyond 21 days post-STZ treatment. Guinea pigs with diet-induced glucose intolerance subsequently treated with STZ demonstrated an insulin-secretory capacity consistent with insulin-independent diabetes. This insulin-independent state was confirmed by response to oral antihyperglycemic drugs, metformin and glipizide, which resolved glucose intolerance and extended survival compared with guinea pigs with uncontrolled diabetes. In this study, we have developed a model of sequential glucose intolerance and β-cell loss, through high-fat, high-carbohydrate diet and extensive optimization of STZ treatment in the guinea pig, which closely resembles human type 2 diabetes. This model will prove useful in the study of insulin-independent diabetes pathogenesis with or without comorbidities, where the guinea pig serves as a relevant model species. © 2017. Published by

  10. Late effects of radiation on the lumbar spinal cord of guinea pigs: Re-treatment tolerance

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mason, K.A.; Withers, H.R.; Chiang, Chi-Shiun

    Using a guinea pig model of lumbar myelopathy, various factors affecting the tolerance of spinal cord to irradiation were assessed: (a) extent of initial injury; (b) time interval between priming and test doses; and (c) animal age at the time of initial radiation treatment. A 3 cm section of lumbar spinal cord of guinea pigs was irradiated with fractionated doses of 4.5 Gy gamma rays given as 9 fractions per week. Guinea pigs were primed with 9 x 4.5 Gy in 7 days which is 60% of the ED[sub 50] for a continuous course of treatment. After 28 or 40more » weeks, animal were retreated with 6-14 fractions of 4.5 Gy. Animals were observed for 2 years following the priming dose and both the incidence and latency of myelopathy recorded. Young adult guinea pigs (8 wk old) showed both a decreased radiation tolerance and latency compared to old individuals (40 wk old). At 28 or 40 wk after 9 x 4.5 Gy, only about 8% of the initial injury was remembered in young adult guinea pigs. The amount of residual injury was dependent on the initial damage as a proportion of the tolerance dose. The spinal cord shows a greater capacity for long-term recovery than generally appreciated and re-treatment doses clinically prescribed may be lower than necessary. 8 refs., 3 figs., 2 tabs.« less

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

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

    1989-06-01

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

  12. The effect of substance P on the antigen-induced bronchoconstriction in guinea pigs.

    PubMed

    Nagai, H; Tsuji, F; Koda, A

    1990-03-01

    The effect of substance P (SP) on the antigen-induced bronchoconstriction in vitro and in vivo was investigated in guinea pigs. SP caused the contraction of isolated non-sensitized guinea pig tracheal muscle at concentrations between 10(-9) to 10(-7) g/ml. The elimination of epithelium in the tracheal muscle produced a slight enhancement of SP response as compared to control. Antigen-induced contraction of isolated sensitized guinea pig tracheal muscle was slightly enhanced by the pretreatment with SP at a concentration of 10(-9) g/ml. The SP-induced enhancement of antigen-induced contraction was significantly augmented by the elimination of epithelium of sensitized tracheal muscle. Moreover, the clear bronchoconstriction was observed by the infusion of SP (1 micrograms/min) intravenously, but not by the infusion of SP at the rates between 0.1 and 0.01 micrograms/min. Antigen-induced asthmatic respiratory disorder was accelerated temporarily by the infusion of subthreshold SP (0.1 microgram/min). The reactivity of bronchial smooth muscle measured by repeated injection of acetylcholine was significantly potentiated by the infusion of subthreshold SP (0.1 microgram/min). These results suggest that SP has dual actions in the contractile response of guinea pig airway smooth muscle. One is the direct contractile activity, and the other one is enhancing activity of antigen- and acetylcholine-induced bronchoconstriction.

  13. Micro-endoscopic ear anatomy of guinea pig applied to experimental surgery.

    PubMed

    Barros, Bruno Borges de Carvalho; Andrade, José Santos Cruz de; Garcia, Leandro Borborema; Pifaia, Gustavo Ribeiro; Cruz, Oswaldo Laércio Mendonça; Onishi, Ektor Tsuneo; Penido, Norma de Oliveira

    2014-01-01

    To describe topographic and endoscopic anatomy of guinea pig ear for development of surgical approaches in experimental studies. Experimental study. Eight adult guinea pigs (Cavia porcellus) were used in this study. Four animals were described through endoscopic view and four animals were used to describe topographic anatomy. The main structures of middle ear were well identified through endoscopy view: oval and round window, ossicles and vascular structures. Temporal bone position, landmarks and its relations to skull are perceived with topographic description. Topographic anatomic description allowed exposition of temporal bone relations for external surgical approaches. Alternatively, grooves and middle ear structures were identified and may be used to transcanal accesses.

  14. Phosphoramidon potentiates the bronchoconstriction induced by inhaled bombesin in guinea pigs.

    PubMed

    Lagente, V; Boichot, E; Mencia-Huerta, J M; Braquet, P

    1993-01-01

    The effect of the neutral endopeptidase inhibitor, phosphoramidon, on the bronchoconstriction induced by aerosolized bombesin in the guinea pig was investigated. Administered by aerosol for 1 min, bombesin (0.01 or 0.1 mg/ml) induced a dose-dependent increase in pulmonary inflation pressure. Pretreatment of the guinea-pigs with phosphoramidon (0.1 mM), administered by aerosol for 15 min, 15 min prior to challenge, markedly potentiated the increase in pulmonary inflation pressure induced by bombesin (0.01 mg/ml) and substance P (0.1 mg/ml). This result suggests a local hydrolysis of bombesin by airway neutral endopeptidase reducing the activity of this peptide on smooth muscle.

  15. [The experimental study of guinea pig cytomegalovirus infection in the kidney of the pup of guinea pig].

    PubMed

    Wang, Xin-rong; Chen, Su-hua; Liu, Hai-zhi; Xiong, Jin-wen; Ling, Xia-zhen

    2004-02-01

    To study the relationship of guinea pig cytomegalovirus (GPCMV) infection with the outcome of pregnancy by the kidney of guinea pig (GP). Twenty first-trimester gestation GPs were randomly selected, intraperitoneally inoculated with GPCMV. Then female GPs and the pups were killed within 24 h after delivery. By in situ hybridization (ISH) with three phases GPCMV late-mRNA probes labeled by digoxin, the virus load and its distribution were screened inside the pup's kidney. Twenty GPs totally conceived 63 pups. Among them, 42 had normal outcome and lived longer than 24 h; 21 had abnormal outcome such as abortion, fetal death, et al. By in situ hybridization, the infection rate of normal pups was 7.1% (3/42) and the average optical density (A) was 0.105 +/- 0.052. The infection rate of abnormal pups was 28. 6% (6/21) and the A was 0.158 +/- 0.047. The difference of the A was significant (t = 2.57, P < 0.05). The positive signal of ISH was mainly distributed in the epithelium of renal tubule and collecting duct. It is concluded that the late-mRNA mainly expressed in the epithelium of renal tubule and collecting duct and the expression level was related with the abnormal pregnancy outcome.

  16. Experimental hyperphenylalaninemia in the pregnant guinea pig: possible phenylalanine teratogenesis and p-chlorophenylalanine embryotoxicity.

    PubMed

    Kronick, J B; Whelan, D T; McCallion, D J

    1987-10-01

    Maternal hyperphenylalaninemia (HPH) due to deficient phenylalanine (Phe) hydroxylation is a recognized human teratogen associated with an increased incidence of intrauterine growth retardation, microcephaly, congenital heart disease, and mental retardation. There are no previous reports of experimental HPH during organogenesis. Sustained HPH was produced in pregnant guinea pigs by adding 3.5% Phe and 1.0% parachlorophenylalanine (pCPA), an inhibitor of Phe hydroxylase, to standard guinea pig chow. Animals consumed the supplemented test diets from gestation day 1 until killed on gestation day 17. Examination of day 17 embryos revealed that embryonic mortality was associated only with maternal pCPA administration and was independent of the degree of maternal HPH. Embryonic malformation was associated with maternal HPH as well as maternal pCPA administration. Both maternal HPH and pCPA administration were associated with embryonic growth retardation. There was no association between maternal food intake or plasma tyrosine levels and embryonic abnormality or mortality. Both Phe and tyrosine were found to be concentrated in gestation day 17 yolk sac fluid when compared to maternal plasma Phe and tyrosine. The association of embryonic malformation and maternal HPH is consistent with human data. The embryotoxicity of pCPA requires further study and highlights the necessity of appropriate controls in models of experimental HPH.

  17. Tachykinin receptors in the guinea-pig isolated bronchi.

    PubMed

    Maggi, C A; Patacchini, R; Quartara, L; Rovero, P; Santicioli, P

    1991-05-17

    The aim of the study was to assess which tachykinin receptors mediate the contractile response in the guinea-pig isolated bronchi. Experiments with natural tachykinins and receptor-selective tachykinin agonists were performed in the absence or presence of peptidase inhibitors and in bronchi pretreated with phenoxybenzamine. Both NK-1 (substance P, substance P methylester and septide) and NK-2 (neurokinin A, [beta-Ala8]neurokinin A-(4-10) and MDL 28,564) receptor agonists produced concentration-dependent contraction. NK-3 agonists (senktide and [MePhe7]neurokinin B) were active only at high concentrations. Phenoxybenzamine pretreatment reduced the maximal response to NK-1 agonists and produced a rightward shift of the curve to NK-2 agonists, without depression of the maximum. Five tachykinin antagonists selective for the NK-1 (L 668,169) or the NK-2 (MEN 10,207, MEN 10,376, L 659,877 and R 396) receptor were tested against substance P methylester and [beta-Ala8]neurokinin A-(4-10). The results indicated that these receptor-selective antagonists maintain their characteristic even when tested in a multireceptor assay such as the guinea-pig bronchus. The rank order of potency of NK-2 antagonists against [beta-Ala8]neurokinin A-(4-10) was MEN 10,207 = MEN 10,376 greater than L 659,877 much greater than R 396. This pattern, with the observation of the full agonist activity of MDL 28,564, indicates that in addition to NK-1 receptors, NK-2 receptors also are present in the guinea-pig bronchi and belong to the same subtype (NK-2A) as present in the rabbit pulmonary artery.

  18. Fate and Distribution of 3H-Labeled T-2 Mycotoxin in Guinea Pigs

    DTIC Science & Technology

    1984-08-03

    HPLC as well as TLC. . . of T-2 sycotox in guinea pigs. To establish the toxicity of an im injection of T-2 mycotoxin in the guinea pig, si:: ;A...that remained at the origin with p- glucuronidase , two additional less-polar radiolabeled peaks were smnarated by HPLC. This suggests that at least one...all tissues within 30 min - ’af.ter, an a injection" of, thr toxin. The rapi& reationff label suggests that toxic effects could begin shortly after

  19. Intraocular Pressure, Tear Production, and Ocular Echobiometry in Guinea Pigs (Cavia porcellus)

    PubMed Central

    Rajaei, Seyed Mehdi; Mood, Maneli Ansari; Sadjadi, Reza; Azizi, Farzaneh

    2016-01-01

    The purpose of this study was to evaluate intraocular pressure (IOP) by means of rebound tonometry, to assess tear production by using the endodontic absorbent paper point tear test (EAPTT) and phenol red thread test (PRTT), and to determine the effects of time of day on IOP and tear production in guinea pigs. The study population comprised 24 healthy adult guinea pigs (12 male, 12 female; 48 eyes) of different breeds and ranging in age from 12 to 15 mo. IOP and tear production were measured at 3 time points (0700, 1500, and 2300) during a 24-h period. Overall values (mean ± 1 SD) were: IOP, 6.81 ± 1.41 mm Hg (range, 4.83 to 8.50); PRTT, 14.33 ± 1.35 mm (range, 12.50 to 16.83); and EAPTT, 8.54 ± 1.08 mm (range, 7.17 to 10.0 mm). In addition, ultrasound biometry was performed by using a B-mode system with linear 8-MHz transducer. This study reports reference values for IOP and tear production in guinea pigs. PMID:27423156

  20. C-Kit expression in the gallbladder of guinea pig with chronic calculous cholecystitis and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal.

    PubMed

    Feng, Hua; Wang, Fang; Wang, Changmiao

    2016-07-01

    To study the c-Kit expression in the gallbladder of cholesterol lithogenic guinea pig model and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal (ICCs). A total of 45 guinea pigs were randomly assigned into three groups: the control group (guinea pigs fed a standard diet, normal group); the model group (guinea pigs fed a cholesterol gallstone-inducing diet); and the Chinese medicine group (guinea pigs fed the cholesterol gallstone-inducing diet and treated with A. capillaris through intragastric administration, therapy group). Each group had 15 guinea pigs. The gallbladders of the guinea pigs were harvested after 8 weeks. C-Kit expression was detected using an immunohistochemistry staining, real-time PCR, and Western blot analyses. The effect of A. capillaris on ICCs was evaluated by muscle strip contraction experiments. C-Kit expression significantly decreased in the gallbladder of model group, but increased in the Chinese medicine group. The Contractility of guinea pig gallbladder muscle strip significantly improved in the Chinese medicine group. Our results indicated that A. capillaris improves gallbladder impairment by up-regulating c-Kit expression, and it also can improve the contractile response of in vitro guinea pig gallbladder muscle strips.

  1. The guinea-pig expresses functional CYP2C and P-glycoprotein: further validation of its usefulness in drug biotransformation/transport studies.

    PubMed

    Hasibu, Ibrahim; Patoine, Dany; Pilote, Sylvie; Drolet, Benoit; Simard, Chantale

    2015-04-01

    The guinea-pig is an excellent animal model for studying cardiopulmonary physiology/pharmacology. Interestingly, it also possesses a number of drug-metabolizing enzymes found in humans, such as CYP1A, CYP2D and CYP3A. To evaluate the hypothesis that the guinea-pig also expresses a functional CYP2C drug-metabolizing enzyme and the P-glycoprotein (P-gp) drug transporter in various tissues. cDNAs encoding CYP2C and P-gp were obtained from guinea-pig liver or small intestine and sequenced. Western blotting was performed to confirm the expression of CYP2C and P-gp. The functional enzymatic activity of guinea-pig CYP2C was evaluated with microsomal preparations using diclofenac and tolbutamide as specific drug substrates in HPLC analyses. To further study both P-gp and CYP2C functional activities, the guinea-pig ABCB1/MDR1 and CYP2C genes were cloned. The recombinant plasmids were then transfected in HEK293 (human embryonic kidney) cells and either calcein-acetoxymethyl ester (AM) accumulation assays or 14,15-EET/DHET formation experiments were performed to evaluate either P-gp transport activity or CYP2C epoxygenase activity, respectively. The guinea-pig tissue distribution of P-gp was studied by Western blotting. Functional expression of CYP2C was demonstrated in guinea-pig liver microsomal preparations. CYP2C-mediated biotransformation of diclofenac and tolbutamide were shown. Expression of P-gp protein was detected in guinea-pig liver and small intestine. Functional activity of guinea-pig P-gp was demonstrated in ABCB1/MDR1-transfected cells. GP-CYP2C-transfected cells also showed functional epoxygenase activity. The guinea-pig expresses functional CYP2C and P-gp, thus suggesting its usefulness for further validating data obtained with other animal models in drug biotransformation/transport studies. Copyright © 2015 John Wiley & Sons, Ltd.

  2. Rapid non-genomic effects of glucocorticoids on oxidative stress in a guinea pig model of asthma.

    PubMed

    Long, Fei; Wang, Yan; Qi, Hui-Hui; Zhou, Xin; Jin, Xian-Qiao

    2008-03-01

    Glucocorticoids (GC) may exert therapeutic effects in asthma by a rapid non-genomic mechanism. The lungs of asthmatic patients are exposed to oxidative stress, which is believed to be critical in the pathogenesis of asthma. The aim of this study was to investigate whether GC exert a rapid non-genomic effect on oxidative stress in asthmatic guinea pigs. The guinea pig asthma model was used to assess inhibitory effects of budesonide (BUD) on oxidative stress. BAL fluid (BALF), trolox equivalent antioxidant capacity and lung manganese superoxide dismutase (MnSOD) activity were measured by spectrophotometry. Superoxide anion production was measured by cytochrome c reduction assay. Oxidative stress occurred within minutes following antigen challenge and BUD reduced the severity of oxidative stress in asthmatic guinea pigs within 15 min. BUD significantly decreased BALF trolox equivalent antioxidant capacity and lung MnSOD activity, as compared with those of vehicle-treated asthmatic guinea pigs (P < 0.05). Additionally, BUD rapidly inhibited in vitro superoxide anion production by BALF cells and bronchi harvested from sensitized animals. These rapid effects were not blocked by the GC receptor antagonist RU486 and/or the protein synthesis inhibitor cycloheximide. BUD reduced oxidative stress in a guinea pig model of asthma by a rapid non-genomic mechanism. These data suggest new mechanisms whereby GC treatments may benefit asthma.

  3. Development of a guinea pig cutaneous radiation injury model using low penetrating X-rays.

    PubMed

    Rodgers, Kathleen E; Tan, Alick; Kim, Lila; Espinoza, Theresa; Meeks, Christopher; Johnston, William; Maulhardt, Holly; Donald, Melissa; Hill, Colin; diZerega, Gere S

    2016-08-01

    A guinea pig skin model was developed to determine the dose-dependent response to soft X-ray radiation into the dermis. X-ray exposure (50 kVp) was defined to a 4.0 × 4.0 cm area on the lateral surface of a guinea pig using lead shielding. Guinea pigs were exposed to a single fraction of X-ray irradiation ranging from 25-79 Gy via an XRAD320ix Biological Irradiator with the collimator removed. Gross skin changes were measured using clinical assessments defined by the Kumar scale. Skin contracture was assessed, as well as histological evaluations. Loss of dermal integrity was shown after a single dose of soft X-ray radiation at or above 32 Gy with the central 2.0 × 2.0 cm of the exposed site being the most affected. Hallmarks of the skin injury included moist desquamation, ulceration and wound contracture, as well as alterations in epithelium, dermis, muscle and adipose. Changes in the skin were time- and radiation dose-dependent. Full-thickness injury occurred without animal mortality or gross changes in the underlying organs. The guinea pig is an appropriate small animal model for the short-term screening of countermeasures for cutaneous radiation injury (CRI).

  4. Acrolein increases airway sensitivity to substance P and decreases NEP activity in guinea pigs.

    PubMed

    Turner, C R; Stow, R B; Hubbs, S J; Gomes, B C; Williams, J C

    1993-04-01

    The effects of acrolein exposure on airway responses to intravenous substance P were determined in guinea pigs exposed to vehicle or 1.6 ppm acrolein for 7.5 h on 2 consecutive days and examined 1, 4, 8, 15, and 28 days after exposure by use of pulmonary mechanics and bronchoalveolar lavage (BAL). Lung, trachea, liver, and BAL fluid were also assayed for neutral endopeptidase (NEP) activity 1, 7, and 28 days after exposure. Pulmonary inflammation and epithelial damage were prominent 1 day after acrolein exposure. NEP activity was decreased in the lungs, trachea, and liver 1 and 7 days after acrolein. Twenty-eight days after exposure, NEP activity in the lungs and liver was not significantly different in vehicle- and acrolein-exposed guinea pigs but was still reduced in tracheal tissue. The BAL NEP activity in acrolein-exposed guinea pigs was approximately twice that of vehicle control guinea pigs at all three time points. Acrolein caused a prolonged increase in airway sensitivity to substance P. Experiments performed in the presence of thiorphan suggested that the acrolein-induced reduction in NEP may contribute to increased airway sensitivity to aerosolized substance P, but the increase in airway sensitivity to intravenous substance P may occur by additional mechanisms.

  5. External Genital Development, Urethra Formation, and Hypospadias Induction in Guinea Pig: A Double Zipper Model for Human Urethral Development.

    PubMed

    Wang, Shanshan; Shi, Mingxin; Zhu, Dongqing; Mathews, Ranjiv; Zheng, Zhengui

    2018-03-01

    To determine whether the guinea pig phallus would be an appropriate model of human penile development, we characterized the embryology and sexual differentiation of guinea pig external genitalia and attended to induce hypospadias in males and tubular urethra formation in females pharmacologically. The external genitalia of guinea pig were collected from genital swelling initiation to newborn stages, and scanning electronic microscopy and histology were performed to visualize the morphology and structure. Immunohistochemistry was used to determine the androgen receptor localization. Bicalutamide and methyltestosterone were given to pregnant dams to reveal the role and timing of androgen in guinea pig penile masculinization. Canalization and dorsal-to-ventral movement of the urethral canal develops the urethral groove in both sexes, and then the males perform distal-opening-proximal-closing to form tubular urethra. More nuclear-localized androgen receptor is found in proximal genital tubercles of males than in females at (E) 29. Antiandrogen treatment at E26-E30 can cause hypospadias, and methyltestosterone administration at E27-E31 can induce tubular urethra formation in females. Fetal development of the guinea pig phallus is homologous to that of humans. Although guinea pig has structures similar to mouse, the urethral groove and the tubular urethra formation are more similar to humans. Antiandrogen treatment causes hypospadias in males and additional androgen induces tubular urethra formation in females. Thus, guinea pig is an appropriate model for further study of cellular and molecular mechanisms involved in distal-opening-proximal-closing in tubular urethra formation and the evaluation of the pathophysiological processes of hypospadias. Published by Elsevier Inc.

  6. Vaccination for the prevention of maternal and fetal infection with guinea pig cytomegalovirus.

    PubMed

    Bia, F J; Griffith, B P; Tarsio, M; Hsiung, G D

    1980-11-01

    Live guinea pig cytomegalovirus (CMV) vaccine was prepared after 11 serial passages in tissue culture; noninfectious envelope antigen vaccine was prepared by n-octyl glucoside treatment of CMV-derived dense bodies and virions. Hartley strain guinea pigs immunized with either vaccine were compared with guinea pigs inoculated with virulent, salivary gland-passaged CMV (approximating natural infection), with passively immunized animals, and with nonimmune controls. All vaccinated animals had neutralizing antibodies to CMV. After challenge with virulent CMV, animals previously inoculated with either tissue culture-passaged or virulent CMV were protected against acute viremia and death; pregnant animals previously inoculated with live CMV vaccine had lower incidences of viremia and generalized maternal and fetal infection. Envelope antigen-vaccinated and passively immunized pregnant animals showed acute viremia after similar challenge with virulent virus; however, infection was less generalized than that in control animals, and CMV was not isolated from the fetuses of these vaccinated mothers.

  7. Spot-on Treatments of Diflubenzuron and Permethrin to Control a Guinea Pig Louse, Gliricola Porcelli (Phthiraptera: Gyropidae)

    USDA-ARS?s Scientific Manuscript database

    Guinea pigs (Cavia porcellus (L.)) (Rodentia: Caviidae) are pets and laboratory animals. They can be infested by a chewing louse, Gliricola porcelli (Schrank) (Phthiraptera: Gyropidae), which is fairly common in some animal rearing facilities, pet stores, and on wild guinea pigs. Infestation with G....

  8. Characterization of two strains of selectively bred guinea-pigs. 2. Differences in immune response to synthetic polypeptides.

    PubMed

    Lundberg, L; Koch, C; Magnusson, M; Bertelsen, C

    1983-06-01

    Two strains of guinea-pigs selectively bred for either high (IMM/S) or low (IMM/R) responsiveness to ovalbumin-induced respiratory anaphylaxis were examined for their immune response to a copolymer of L-glutamic acid and L-alanine (GA), a copolymer of L-glutamic acid and L-tyrosine (GT), and to a dinitro-phenyl derivative of a homopolymer of L-lysine (DNP-PLL). Considerable differences between the strains in development of cellular hypersensitivity and in the production of antibodies were observed. Guinea-pigs from IMM/S were all responders to GA and DNP-PLL and non-responders to GT, while guinea-pigs from two of three lines from IMM/R were responders to GT and non-responders to GA and DNP-PLL. The third IMM/R line showed an immune response pattern similar to guinea-pigs of strain IMM/S. Preliminary breeding studies confirmed that the immune response to these three antigens is under the control of dominant autosomal genes, since (IMM/S x IMM/R) F1 animals responded to all three antigens. It is concluded that these three antigens may serve as immune response markers in genetic studies of the differences between guinea-pigs from IMM/S and IMM/R in their ability to develop respiratory anaphylaxis.

  9. In vivo evaluation of antiviral efficacy against genital herpes using mouse and guinea pig models.

    PubMed

    Valencia, Frances; Veselenak, Ronald L; Bourne, Nigel

    2013-01-01

    Both the guinea pig and mouse are important animal models for the study of genital herpes. The murine model has been used extensively to evaluate vaccines and antiviral agents by measuring the incidence of infection and the magnitude of viral replication; however, this model is limited with regard to distinguishing between candidate vaccines or treatments. In contrast, the guinea pig closely mimics human infection and provides an excellent model of both primary and recurrent genital herpes disease. This animal model is especially important in the study of viral transmission through the evaluation of latent viral reactivation and virus shedding into the genital tract. Here, we describe methodologies to determine viral infection, severity of primary disease, and quantification of primary viral replication in the genital tract for both the guinea pig and murine models of genital herpes. Additionally, we detail the evaluation of the onset of primary disease and progression to the day of death in the mouse model. Further, we summarize methods to assess the frequency of recurrences, frequency and magnitude of virus shedding, and latent viral load in the sensory nerve ganglia of the guinea pig.

  10. The role of substance P and bradykinin in the cough reflex and bronchoconstriction in guinea-pigs.

    PubMed

    El-Hashim, Ahmed Z; Amine, Sanaa A

    2005-04-18

    In this study we investigated the ability of aerosolized substance P to induce either cough or bronchoconstriction in guinea-pigs. We have also examined whether pre-treatment, by the inhaled route, of animals with a combination of the neutral endopeptidase inhibitor, phosphoramidon (10(-3) M), and the diaminopeptidase IV inhibitor, diprotin A (10(-3) M), enhances the airway response to substance P. Moreover, we also assessed whether aerosol pre-treatment of guinea-pigs with either substance P or bradykinin, at 10(-4) M, affects the citric acid-induced cough and/or bronchoconstriction. Challenge of guinea-pigs with substance P only at 10(-3) M resulted in significant bronchconstriction but only a weak and variable cough response (1.1+/-0.6; P>0.05). Pre-treatment of guinea-pigs with both phosphoramidon and diprotin A resulted in a small non-significant increase in the cough response (2.8+/-0.9 vs. 1.1+/-0.6; P>0.05) but significantly enhanced substance P-induced bronchoconstriction (P<0.05). Moreover, exposure of guinea-pigs to substance P (10(-4) M) prior to citric acid challenge (0.6 M) resulted in a significant (P<0.05) enhancement of the citric acid-induced bronchoconstriction but not the citric acid-induced cough (11.7+/-1.8 vs. 12.8+/-1.5; P>0.05). In contrast, exposure of guinea-pigs to bradykinin (10(-4) M) prior to the citric acid challenge resulted in a significant enhancement of the cough response (9.2+/-1.9 vs. 25.8+/-2.5; P<0.05) but not the bronchoconstriction (P>0.05). These data do not support a major peripheral role for substance P in the cough reflex, although bradykinin is able to sensitize the cough reflex. Furthermore, these data suggest that bronchoconstriction, induced by citric acid, is not responsible for the cough associated with this irritant.

  11. Characterization of guinea pig T cell responses elicited after EP-assisted delivery of DNA vaccines to the skin

    PubMed Central

    Schultheis, Katherine; Schaefer, Hubert; Yung, Bryan S.; Oh, Janet; Muthumani, Karuppiah; Humeau, Laurent; Broderick, Kate E.

    2016-01-01

    The skin is an ideal target tissue for vaccine delivery for a number of reasons. It is highly accessible, and most importantly, enriched in professional antigen presenting cells. Possessing strong similarities to human skin physiology and displaying a defined epidermis, the guinea pig is an appropriate model to study epidermal delivery of vaccine. However, whilst we have characterized the humoral responses in the guinea pig associated with skin vaccine protocols we have yet to investigate the T cell responses. In response to this inadequacy, we developed an IFN-γ ELISpot assay to characterize the cellular immune response in the peripheral blood of guinea pigs. Using a nucleoprotein (NP) influenza pDNA vaccination regimen, we characterized host T cell responses. After delivery of the DNA vaccine to the guinea pig epidermis we detected robust and rapid T cell responses. The levels of IFN-γ spot-forming units averaged approximately 5000 per million cells after two immunizations. These responses were broad in that multiple regions across the NP antigen elicited a T cell response. Interestingly, we identified a number of NP immunodominant T cell epitopes to be conserved across an outbred guinea pig population, a phenomenon which was also observed after immunization with a RSV DNA vaccine. We believe this data enhances our understanding of the cellular immune response elicited to a vaccine in guinea pigs, and globally, will advance the use of this model for vaccine development, especially those targeting skin as a delivery site. PMID:27894716

  12. Computed tomography analysis of guinea pig bone: architecture, bone thickness and dimensions throughout development

    PubMed Central

    Witkowska, Agata; Alibhai, Aziza; Hughes, Chloe; Price, Jennifer; Klisch, Karl; Sturrock, Craig J.

    2014-01-01

    The domestic guinea pig, Cavia aperea f. porcellus, belongs to the Caviidae family of rodents. It is an important species as a pet, a source of food and in medical research. Adult weight is achieved at 8–12 months and life expectancy is ∼5–6 years. Our aim was to map bone local thickness, structure and dimensions across developmental stages in the normal animal. Guinea pigs (n = 23) that had died of natural causes were collected and the bones manually extracted and cleaned. Institutional ethical permission was given under the UK Home Office guidelines and the Veterinary Surgeons Act. X-ray Micro Computed Tomography (microCT) was undertaken on the left and right scapula, humerus and femur from each animal to ascertain bone local thickness. Images were also used to undertake manual and automated bone measurements, volumes and surface areas, identify and describe nutrient, supratrochlear and supracondylar foramina. Statistical analysis between groups was carried out using ANOVA with post-hoc testing. Our data mapped a number of dimensions, and mean and maximum bone thickness of the scapula, humerus and femur in guinea pigs aged 0–1 month, 1–3 months, 3–6 months, 6 months–1 year and 1–4 years. Bone dimensions, growth rates and local bone thicknesses differed between ages and between the scapula, humerus and femur. The microCT and imaging software technology showed very distinct differences between the relative local bone thickness across the structure of the bones. Only one bone showed a singular nutrient foramen, every other bone had between 2 and 5, and every nutrient canal ran in an oblique direction. In contrast to other species, a supratrochlear foramen was observed in every humerus whereas the supracondylar foramen was always absent. Our data showed the bone local thickness, bone structure and measurements of guinea pig bones from birth to 4 years old. Importantly it showed that bone development continued after 1 year, the point at which most

  13. Effects of imatinib mesylate on the spontaneous activity generated by the guinea-pig prostate.

    PubMed

    Lam, Michelle; Dey, Anupa; Lang, Richard J; Exintaris, Betty

    2013-08-01

    What's known on the subject? and what does the study add?: Several studies have examined the functional role of tyrosine kinase receptors in the generation of spontaneous activity in various segments of the gastrointestinal and urogenital tracts through the application of its inhibitor, imatinib mesylate (Glivec®), but results are fairly inconsistent. This is the first study detailing the effects of imatinib mesylate on the spontaneous activity in the young and ageing prostate gland. As spontaneous electrical activity underlies the spontaneous rhythmic prostatic contractions that occur at rest, elucidating the mechanisms involved in the regulation of the spontaneous electrical activity and the resultant phasic contractions could conceivably lead to the identification of better targets and the development of more specific therapeutic agents to treat prostate conditions. To investigate the effect of imatinib mesylate, a tyrosine kinase receptor inhibitor, in the generation of spontaneous electrical and contractile activity in the young and ageing guinea-pig prostate. Standard tension and intracellular recording were used to measure spontaneous contractions and slow waves, respectively from the guinea-pig prostate at varying concentrations of imatinib mesylate (1-50 μm). Imatinib mesylate (1-10 μm), did not significantly affect slow waves recorded in the prostate of both age groups but at 50 μm, the amplitude of slow waves from the ageing guinea-pig prostate was significantly reduced (P < 0.05, n = 5). In contrast, the amplitude of contractions across all concentrations in the young guinea-pig prostate was reduced to between 35% and 41% of control, while the frequency was reduced to 15.7% at 1 μm (n = 7), 49.8% at 5 μm (n = 10), 46.2% at 10 μm (n = 7) and 53.1% at 50 μm (n = 5). Similarly, imatinib mesylate attenuated the amplitude and slowed the frequency of contractions in ageing guinea-pigs to 5.15% and 3.3% at 1 μm (n = 6); 21.1% and 20.8% at 5 μm (n = 8

  14. Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts.

    PubMed

    Stracina, Tibor; Slaninova, Iva; Polanska, Hana; Axmanova, Martina; Olejnickova, Veronika; Konecny, Petr; Masarik, Michal; Krizanova, Olga; Novakova, Marie

    2015-07-01

    Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

  15. Differences in the effects of Na+-H+ exchange inhibitors on cardiac function and apoptosis in guinea-pig ischemia-reperfused hearts.

    PubMed

    Hotta, Yoshihiro; Nishimaki, Haruaki; Takeo, Tomohiro; Itoh, Gen; Yajima, Michio; Otsuka-Murakami, Hidetsugu; Ishikawa, Naohisa; Kawai, Norio; Huang, Lei; Yamada, Kazuto; Yamamoto, Setsuko; Matsui, Kazuki; Ohashi, Naohito

    2004-10-25

    The protective effects of the Na+-H+ exchange (NHE) inhibitors SM-198110 (2-[[(aminoiminomethyl) amino] carbonyl]-4-chloro-1H-indole-1-propanesulfonic acid monohydrate) and SM-197378 (N-(aminoiminomethyl)-1-methyl-7-(sulfooxy)-4-(trifluoromethyl)-1H-indole-2-carboxamide monohydrate) were investigated in perfused Langendorff guinea-pig hearts subjected to ischemia (40 min) and reperfusion (40 min). The recovery of left ventricular developed pressure (LVDP) from ischemia by reperfusion was 39.0% in the control, while in the hearts pretreated with SM-198110 or SM-197378 (10(-7) M), it was about 100%. The ATP level, monitored simultaneously by (31)P-nuclear magnetic resonance spectrometry, was already higher than the control value at the end of the ischemic period, and the elevation in Na+ or Ca2+ fluorometric signals induced during ischemia was suppressed. In post-treated hearts, the LVDP recovery rate was significantly higher with SM-198110 than with SM-197378. By in vitro electron paramagnetic resonance spectrometry, SM-197378 was found to directly quench the active oxygen radical, whereas SM-198110 had no effect. Numbers of apoptotic cardiomyocytes after ischemia (1 h) followed by reperfusion (5 h) were significantly lower in SM-197378-treated than in SM-198110-treated hearts, consistent with the level of activity of caspase-3. These results suggest that the antioxidant effects of NHE inhibitors have an important role in apoptosis during ischemia-reperfusion, but apoptosis is not a major manifestation of cardiac function during postischemic recovery, and that NHE-sensitive mechanisms of reperfusion injury promote both necrotic and apoptotic processes death.

  16. [Hematological and immunological parameters during Ebola virus passages in guinea-pigs].

    PubMed

    Dadaeva, A A; Sizikova, L P; Subbotina, E L; Chepurnov, A A

    2006-01-01

    The trend in hematological and immunological parameters during Ebola virus passages in guinea-pigs indicated that pathophysiological changes occurred just during the second passage and further became stronger. The increase of some parameters and their correlation with the occurrence of fatal outcomes allowed the authors to reveal the most significant changes as increased juvenile platelets, whole blood virus appearance, higher echinocytes, a rise in the pro mil of blast cells and megakaryocytes in the bone marrow, and decreased neutrophilic phagocytic activity. Viral acquisition of the properties of lethality to guinea-pigs depends on the fine mechanisms responsible for viral interaction with host cells, which may lead to viral genetic changes during passages.

  17. Immunogenicity, Protective Efficacy, and Non-Replicative Status of the HSV-2 Vaccine Candidate HSV529 in Mice and Guinea Pigs

    PubMed Central

    Bernard, Marie-Clotilde; Barban, Véronique; Pradezynski, Fabrine; de Montfort, Aymeric; Ryall, Robert; Caillet, Catherine; Londono-Hayes, Patricia

    2015-01-01

    HSV-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. A replication-deficient mutant virus (dl5-29) has demonstrated promising efficacy in animal models of genital herpes. However, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (HSV529) derived from dl5-29 have not been evaluated. Humoral and cellular immune responses were measured in mice and guinea pigs immunized with HSV529. Protection against acute and recurrent genital herpes, mortality, latent infection, and viral shedding after vaginal HSV-2 infection was determined in mice or in naïve and HSV-1 seropositive guinea pigs. HSV529 replication and pathogenicity were investigated in three sensitive models of virus replication: severe combined immunodeficient (SCID/Beige) mice inoculated by the intramuscular route, suckling mice inoculated by the intracranial route, and vaginally-inoculated guinea pigs. HSV529 immunization induced HSV-2-neutralizing antibody production in mice and guinea pigs. In mice, it induced production of specific HSV-2 antibodies and splenocytes secreting IFNγ or IL-5. Immunization effectively prevented HSV-2 infection in all three animal models by reducing mortality, acute genital disease severity and frequency, and viral shedding. It also reduced ganglionic viral latency and recurrent disease in naïve and HSV-1 seropositive guinea pigs. HSV529 replication/propagation was not detected in the muscles of SCID/Beige mice, in the brains of suckling mice, or in vaginal secretions of inoculated guinea pigs. These results confirm the non-replicative status, as well as its immunogenicity and efficacy in mice and guinea pigs, including HSV-1 seropositive guinea pigs. In mice, HSV529 produced Th1/Th2 characteristic immune response thought to be necessary for an effective vaccine. These results further support the clinical investigation of HSV529 in human subjects as a prophylactic vaccine

  18. Ozone-Induced Hypertussive Responses in Rabbits and Guinea Pigs

    PubMed Central

    Clay, Emlyn; Patacchini, Riccardo; Trevisani, Marcello; Preti, Delia; Branà, Maria Pia; Spina, Domenico

    2016-01-01

    Cough remains a major unmet clinical need, and preclinical animal models are not predictive for new antitussive agents. We have investigated the mechanisms and pharmacological sensitivity of ozone-induced hypertussive responses in rabbits and guinea pigs. Ozone induced a significant increase in cough frequency and a decrease in time to first cough to inhaled citric acid in both conscious guinea pigs and rabbits. This response was inhibited by the established antitussive drugs codeine and levodropropizine. In contrast to the guinea pig, hypertussive responses in the rabbit were not inhibited by bronchodilator drugs (β2 agonists or muscarinic receptor antagonists), suggesting that the observed hypertussive state was not secondary to bronchoconstriction in this species. The ozone-induced hypertussive response in the rabbit was inhibited by chronic pretreatment with capsaicin, suggestive of a sensitization of airway sensory nerve fibers. However, we could find no evidence for a role of TRPA1 in this response, suggesting that ozone was not sensitizing airway sensory nerves via activation of this receptor. Whereas the ozone-induced hypertussive response was accompanied by a significant influx of neutrophils into the airway, the hypertussive response was not inhibited by the anti-inflammatory phosphodiesterase 4 inhibitor roflumilast at a dose that clearly exhibited anti-inflammatory activity. In summary, our results suggest that ozone-induced hypertussive responses to citric acid may provide a useful model for the investigation of novel drugs for the treatment of cough, but some important differences were noted between the two species with respect to sensitivity to bronchodilator drugs. PMID:26837703

  19. Immunohistochemical demonstration of enkephalin-containing nerve fibers in guinea pig and rat lungs.

    PubMed

    Shimosegawa, T; Foda, H D; Said, S I

    1989-08-01

    Met-enkephalin (Met-Enk) and Leu-enkephalin (Leu-Enk), the opioid peptides originally isolated from the brain, are believed to act as inhibitory neuromodulators at various synaptic sites. In this immunohistochemical study, we have investigated the localization and distribution of Met- and Leu-Enk immunoreactivities in airways and pulmonary vessels of guinea pigs and rats. Immunoreactivities to both peptides were found in nerve fibers and nerve terminals distributed mainly to the trachea and major bronchi, and were especially prevalent in the smooth muscle layer, in the lamina propria, and around tracheal and bronchial glands, but not in the epithelium. Few immunoreactive nerve fibers were detected in smaller bronchi, bronchioles, and alveoli. Enkephalin-immunoreactive nerve fibers were also localized in the walls of pulmonary and bronchial vessels. Within airway microganglia, immunoreactivity was observed in a few nerve terminals, but not in ganglion cell bodies. Met- and Leu-Enk immunoreactive nerve fibers showed similar distribution patterns, though minor differences were noted between the two species: Enk-immunoreactive nerve fibers in the smooth muscle layer were more abundant in guinea pigs than in rats, whereas those in mucous glands were richer in rats than in guinea pigs. These results document the presence of Met- and Leu-Enk immunoreactivity in nerve fibers supplying guinea pig and rat airways and pulmonary vessels, and provide a morphologic basis for the view that enkephalins are likely neurotransmitters or neuromodulators in the lung.

  20. Guinea-pig productivity under traditional management.

    PubMed

    Manjeli, Y; Tchoumboue, J; Njwe, R M; Teguia, A

    1998-04-01

    Results of a 12 month study of traditional guinea-pig production in the western highlands of Cameroon are reported. The mean age of guinea-pigs (Cavia porcellus L.) at first parturition, kidding interval and litter size at birth were 126.30 +/- 10.40 d, 64.8 +/- 1.70 d and 1.63 +/- 0.26 kids respectively. The annual reproductive rate was 9.18 kids/breeding doe while the doe post-partum weight was 530 g. Mean body weights at birth, presumed weaning (21 d) and 15 weeks of age were 78.36 +/- 3.20, 147.51 +/- 8.10 and 418.88 +/- 32 g respectively. Type of birth and sex had a significant effect on body weight at all ages. Birth weight dropped significantly from 83.88 +/- 2.87 g for singles to 81.57 +/- 3.40 g for twins, 74.25 +/- 2.39 g for triplets and 73.75 +/- 4.12 g for quadruplets. These differences were maintained to maturity (15 weeks). Males were generally heavier than females. Mortality rates were relatively high among kids: 24% at birth, 39% at 3 weeks and 40% at 15 weeks. Productivity indices were 0.827 kg of young weaned per doe per year, 1560 g of young weaned per kg of doe per year and 2.52 kg of young weaned per kg metabolic weight (kg 0.75) of female per year.

  1. Spontaneous Transitional Cell Carcinoma in the Urinary Bladder of a Strain 13 Guinea Pig.

    DTIC Science & Technology

    1985-05-01

    less than I of all canine neoplasms. In the feline , the extremely low incidence of bladder tumors observed may well be due to a difference in...factor of age. Prog Exp Tumor Res 1967;9:261-85. ..................... , 12. Ediger R D, Rabstein M M. Spontaneous leukemia in a Hartley strain guinea pig...Intracisternal virus -like particles in two guinea pig mammary adenocarcinomas. Lab Anim Sci 1976;26:607-9. 17.. Yoshida A, Iqbal Z M, Epstein. S S

  2. Analysis of anabolic steroids in hair: time courses in guinea pigs.

    PubMed

    Shen, Min; Xiang, Ping; Yan, Hui; Shen, Baohua; Wang, Mengye

    2009-09-01

    Sensitive, specific, and reproducible methods for the quantitative determination of eight anabolic steroids in guinea pig hair have been developed using LC/MS/MS and GC/MS/MS. Methyltestosterone, stanozolol, methandienone, nandrolone, trenbolone, boldenone, methenolone and DHEA were administered intraperitoneally in guinea pigs. After the first injection, black hair segments were collected on shaved areas of skin. The analysis of these segments revealed the distribution of anabolic steroids in the guinea pig hair. The major components in hair are the parent anabolic steroids. The time courses of the concentrations of the steroids in hair (except methenolone, which does not deposit in hair) demonstrated that the peak concentrations were reached on days 2-4, except stanozolol, which peaked on day 10 after administration. The concentrations in hair appeared to be related to the physicochemical properties of the drug compound and to the dosage. These studies on the distribution of drugs in the hair shaft and on the time course of their concentration changes provide information relevant to the optimal time and method of collecting hair samples. Such studies also provide basic data that will be useful in the application of hair analysis in the control of doping and in the interpretation of results.

  3. Characterization of the receptors for mycobacterial cord factor in Guinea pig.

    PubMed

    Toyonaga, Kenji; Miyake, Yasunobu; Yamasaki, Sho

    2014-01-01

    Guinea pig is a widely used animal for research and development of tuberculosis vaccines, since its pathological disease process is similar to that present in humans. We have previously reported that two C-type lectin receptors, Mincle (macrophage inducible C-type lectin, also called Clec4e) and MCL (macrophage C-type lectin, also called Clec4d), recognize the mycobacterial cord factor, trehalose-6,6'-dimycolate (TDM). Here, we characterized the function of the guinea pig homologue of Mincle (gpMincle) and MCL (gpMCL). gpMincle directly bound to TDM and transduced an activating signal through ITAM-bearing adaptor molecule, FcRγ. Whereas, gpMCL lacked C-terminus and failed to bind to TDM. mRNA expression of gpMincle was detected in the spleen, lymph nodes and peritoneal macrophages and it was strongly up-regulated upon stimulation of zymosan and TDM. The surface expression of gpMincle was detected on activated macrophages by a newly established monoclonal antibody that also possesses a blocking activity. This antibody potently suppressed TNF production in BCG-infected macrophages. Collectively, gpMincle is the TDM receptor in the guinea pig and TDM-Mincle axis is involved in host immune responses against mycobacteria.

  4. Pulmonary effects of inhaled zinc oxide in human subjects, guinea pigs, rats, and rabbits

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gordon, T.; Chen, L.C.; Fine, J.M.

    1992-08-01

    Occupational exposure to freshly formed zinc oxide (ZnO) particles (less than 1.0 micron aerodynamic diameter) produces a well-characterized response known as metal fume fever. An 8-hr threshold limit value (TLV) of 5 mg/m3 has been established to prevent adverse health effects because of exposure to ZnO fumes. Because animal toxicity studies have demonstrated pulmonary effects near the current TLV, the present study examined the time course and dose-response of the pulmonary injury produced by inhaled ZnO in guinea pigs, rats, rabbits, and human volunteers. The test animals were exposed to 0, 2.5, or 5.0 mg/m3 ZnO for up to 3more » hr and their lungs lavaged. Both the lavage fluid and recovered cells were examined for evidence of inflammation or altered cell function. The lavage fluid from guinea pigs and rats exposed to 5 mg/m3 had significant increases in total cells, lactate dehydrogenase, beta-glucuronidase, and protein content. These changes were greatest 24 hr after exposure. Guinea pig alveolar macrophage function was depressed as evidenced by in vitro phagocytosis of opsonized latex beads. Significant changes in lavage fluid parameters were also observed in guinea pigs and rats exposed to 2.5 mg/m3 ZnO. In contrast, rabbits showed no increase in biochemical or cellular parameters following a 2-hr exposure to 5 mg/m3 ZnO. Differences in total lung burden of ZnO, as determined in additional animals by atomic absorption spectroscopy, appeared to account for the observed differences in species responses. Although the lungs of guinea pigs and rats retained approximately 20% and 12% of the inhaled dose, respectively, rabbits retained only 5%.« less

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

    PubMed

    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.

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

    PubMed

    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.

  7. High-dose ascorbic acid decreases cholesterolemic factors of an atherogenic diet in guinea pigs.

    PubMed

    Filis, Konstantinos; Anastassopoulou, Aikaterini; Sigala, Fragiska; Theodorou, Dimitrios; Manouras, Andreas; Leandros, Emanouel; Sigalas, Panagiotis; Hepp, Wolfgang; Bramis, John

    2007-03-01

    The study evaluates the effect of a high supplemental dose of ascorbic acid (AA) on plasma concentrations of total cholesterol (TC), triglycerides (TG), total lipids (TL), and lipoprotein fractions high-density, very-low-density-, and low-density lipoprotein (HDL, VLDL, LDL) in guinea pigs fed with atherogenic diet. Group I consisted of 5 normally fed guinea pigs plus a low dose of AA (1 mg/100 g/day), group II consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a low dose of AA (1 mg/100 g/day), and group III consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a high dose of AA (30 mg/100 g/day). Cholesterolemic factors concentrations were determined after nine weeks. Concentrations of TC, TG, TL, LDL, and VLDL were increased in group II compared to group I (p < 0.01 for all differences). Supplementation with a high dose of AA resulted in decreased concentrations of TC (p < 0.01), TG (p < 0.01), TL (p < 0.01), and LDL (p < 0.01) in group III compared to group II. Additionally, concentration of HDL was increased in group III compared to group II (p < 0.01). High-dose AA supplementation to an atherogenic diet decreases concentrations of TC, TG, TL, and LDL and increases concentration of HDL compared to low-dose AA.

  8. Newly divided eosinophils limit ozone-induced airway hyperreactivity in nonsensitized guinea pigs

    PubMed Central

    Jacoby, David B.

    2017-01-01

    Ozone causes vagally mediated airway hyperreactivity and recruits inflammatory cells, including eosinophils, to lungs, where they mediate ozone-induced hyperreactivity 1 day after exposure but are paradoxically protective 3 days later. We aimed to test the role of newly divided eosinophils in ozone-induced airway hyperreactivity in sensitized and nonsensitized guinea pigs. Nonsensitized and sensitized guinea pigs were treated with 5-bromo-2-deoxyuridine (BrdU) to label newly divided cells and were exposed to air or ozone for 4 h. Later (1 or 3 days later), vagally induced bronchoconstriction was measured, and inflammatory cells were harvested from bone marrow, blood, and bronchoalveolar lavage. Ozone induced eosinophil hematopoiesis. One day after ozone, mature eosinophils dominate the inflammatory response and potentiate vagally induced bronchoconstriction. However, by 3 days, newly divided eosinophils have reached the lungs, where they inhibit ozone-induced airway hyperreactivity because depleting them with antibody to IL-5 or a TNF-α antagonist worsened vagally induced bronchoconstriction. In sensitized guinea pigs, both ozone-induced eosinophil hematopoiesis and subsequent recruitment of newly divided eosinophils to lungs 3 days later failed to occur. Thus mature eosinophils dominated the ozone-induced inflammatory response in sensitized guinea pigs. Depleting these mature eosinophils prevented ozone-induced airway hyperreactivity in sensitized animals. Ozone induces eosinophil hematopoiesis and recruitment to lungs, where 3 days later, newly divided eosinophils attenuate vagally mediated hyperreactivity. Ozone-induced hematopoiesis of beneficial eosinophils is blocked by a TNF-α antagonist or by prior sensitization. In these animals, mature eosinophils are associated with hyperreactivity. Thus interventions targeting eosinophils, although beneficial in atopic individuals, may delay resolution of airway hyperreactivity in nonatopic individuals. PMID:28258108

  9. Newly divided eosinophils limit ozone-induced airway hyperreactivity in nonsensitized guinea pigs.

    PubMed

    Wicher, Sarah A; Jacoby, David B; Fryer, Allison D

    2017-06-01

    Ozone causes vagally mediated airway hyperreactivity and recruits inflammatory cells, including eosinophils, to lungs, where they mediate ozone-induced hyperreactivity 1 day after exposure but are paradoxically protective 3 days later. We aimed to test the role of newly divided eosinophils in ozone-induced airway hyperreactivity in sensitized and nonsensitized guinea pigs. Nonsensitized and sensitized guinea pigs were treated with 5-bromo-2-deoxyuridine (BrdU) to label newly divided cells and were exposed to air or ozone for 4 h. Later (1 or 3 days later), vagally induced bronchoconstriction was measured, and inflammatory cells were harvested from bone marrow, blood, and bronchoalveolar lavage. Ozone induced eosinophil hematopoiesis. One day after ozone, mature eosinophils dominate the inflammatory response and potentiate vagally induced bronchoconstriction. However, by 3 days, newly divided eosinophils have reached the lungs, where they inhibit ozone-induced airway hyperreactivity because depleting them with antibody to IL-5 or a TNF-α antagonist worsened vagally induced bronchoconstriction. In sensitized guinea pigs, both ozone-induced eosinophil hematopoiesis and subsequent recruitment of newly divided eosinophils to lungs 3 days later failed to occur. Thus mature eosinophils dominated the ozone-induced inflammatory response in sensitized guinea pigs. Depleting these mature eosinophils prevented ozone-induced airway hyperreactivity in sensitized animals. Ozone induces eosinophil hematopoiesis and recruitment to lungs, where 3 days later, newly divided eosinophils attenuate vagally mediated hyperreactivity. Ozone-induced hematopoiesis of beneficial eosinophils is blocked by a TNF-α antagonist or by prior sensitization. In these animals, mature eosinophils are associated with hyperreactivity. Thus interventions targeting eosinophils, although beneficial in atopic individuals, may delay resolution of airway hyperreactivity in nonatopic individuals. Copyright

  10. Cholinergic agonists increase intracellular calcium concentration in guinea pig vestibular hair cells.

    PubMed

    Han, W; Zhang, S; Han, D; Jiang, S; Yang, W

    2001-07-01

    To better understand the cholinergic receptors in vestibular hair cells (VHC) and their subtypes, and to investigate the effects of cholinergic agonists on intracellular calcium concentration ([Ca2+]i) in guinea pig VHCs. VHCs were isolated from guinea pig crista ampullaris by enzymatic and mechanical methods. The effect of cholinergic agonists on [Ca2+]i was examined using laser scanning confocal microscopy and the Ca2+ sensitive dye Fluo-3. The results showed that the addition of acetylcholine (ACh) and carbachol (CCh), muscamic and nicotinic agonists, induced [Ca2+]i increases in all the VHCs, whereas acetylcholine bromide (ACh-Br), a nicotinic agonist, induced the [Ca2+]i increase in only a small percentage of VHCs. The ACh or CCh-induced Ca2+ response could be partially suppressed by atropine. In the presence of 0.1 mmol/L atropine, the amplitudes of ACh or CCh-induced [Ca2+]i responses became significantly smaller than those in atropine free medium (P < 0.01). The results suggest the existence of cholinergic receptors in guinea pig VHCs. It is the muscamic agonists rather than nicontic receptors that dominate [Ca2+]i variation. Atropine can suppress muscamic agonist-induced Ca2+ responses.

  11. Fever: exchange of shivering by nonshivering pyrogenesis in cold-acclimated guinea pigs.

    PubMed

    Blatteis, C M

    1976-01-01

    The pyrogenic response of adult, unanesthetized guinea pigs to 2 mug/kg iv of Salmonella enteritidis endotoxin was measured at 27 and 7 degrees C ambient temperatures, both before and after an 8-wk exposure to 7 degrees C. There were no significant differences between the onset, maximum height, and total duration of the fevers produced before and after cold acclimation in both thermal environments. However, in 27 degrees C, before cold acclimation, fever production was associated with vigorous shivering activity; two temperature maxima typically developed. After cold acclimation, visible shivering was not detectable during pyrogenesis; moreover, only a single maximum occurred, culminating during the interval between the two rises previously. In 7 degrees C, shivering occurred in both the non-cold- and cold-acclimated endotoxin-treated guinea pigs, but the increase in oxygen consumption was significantly greater in the latter. These results indicated, therefore, that nonshivering (NST) replaces shivering thermogenesis (ST) in a thermoneutral, while ST is added onto NST in a cold, environment in cold-acclimated guinea pigs in supplying the necessary heat for fever production, and that these effects involve alterations in the character of the febrile course.

  12. Twenty-four–Hour Measurement of Intraocular Pressure in Guinea Pigs (Cavia porcellus)

    PubMed Central

    Ansari-Mood, Maneli; Mehdi-Rajaei, Seyed; Sadjadi, Reza; Selk-Ghaffari, Masoud; Williams, David L

    2016-01-01

    The objective of this study was to measure intraocular pressure (IOP) in intact, healthy guinea pigs (15 male, 15 female) every 2 h for a 24-h period. First, IOP was measured by using rebound tonometry (RBT). After a 1-min rest period, 0.5% proparacaine ophthalmic solution, a topical anesthetic, was applied to both eyes; 4 min after anesthetic instillation, IOP was measured by using applanation tonometry (APT). The IOP was lower during the light period (0700 to 1900) than during the dark phase (2000 to 0600). The lowest IOP by both RBT and APT (3.68 and 13.37 mm Hg, respectively) occurred at 0700, whereas maximal IOP occurred at 2300 for RBT (8.12 mm Hg) but at 2100 for APT (20.62 mm Hg). No significant differences in IOP between the left and right eyes or between RBT and APT were noted. In addition, daily variations in the IOP of guinea pigs seem to be independent of sex and body weight. The results of this study may be beneficial in the diagnosis and observation of glaucoma in guinea pigs. PMID:26817986

  13. Improved Method for Culturing Guinea-Pig Macrophage Cells

    NASA Technical Reports Server (NTRS)

    Savage, J.

    1982-01-01

    Proper nutrients and periodic changes in culture medium maintain cell viability for a longer period. New method uses a thioglycolate solution, instead of mineral oil, to induce macrophage cells in guinea pigs and also uses an increased percent of fetal-calf bovine serum in cultivation medium. Macrophage cells play significant roles in the body's healing and defense systems.

  14. The non-nucleoside antiviral, BAY 38-4766, protects against cytomegalovirus (CMV) disease and mortality in immunocompromised guinea pigs

    PubMed Central

    Schleiss, Mark R.; Bernstein, David I.; McVoy, Michael A.; Stroup, Greg; Bravo, Fernando; Creasy, Blaine; McGregor, Alistair; Henninger, Kristin; Hallenberger, Sabine

    2008-01-01

    New antiviral drugs are needed for the treatment of cytomegalovirus (CMV) infections, particularly in immunocompromised patients. These studies evaluated the in vitro and in vivo activity of the non-nucleosidic CMV inhibitor, BAY 38-4766, against guinea pig cytomegalovirus (GPCMV). Plaque reduction assays indicated that BAY 38-4766 was active against GPCMV, with an IC50 of 0.5 μM. Yield reduction assays demonstrated an ED90 and ED99 of 0.4 and 0.6 μM, respectively, of BAY 38-4766 against GPCMV. Guinea pigs tolerated oral administration of 50 mg/kg/day of BAY 38-4766 without evidence of biochemical or hematologic toxicity. Plasma concentrations of BAY 38-4766 were high following oral dosing, with a mean peak level at 1-h post-dose of 26.7 mg/ml (n = 6; range, 17.8-35.4). Treatment with BAY 38-4766 reduced both viremia and DNAemia, as determined by a real-time PCR assay, following GPCMV infection of cyclophosphamide-immunosuppressed strain 2 guinea pigs (p < 0.05, Mann-Whitney test). BAY 38-4766 also reduced mortality following lethal GPCMV challenge in immunosuppressed Hartley guinea pigs, from 83% (20/24) in placebo-treated guinea pigs, to 17% (4/24) in BAY 38-4766-treated animals (p < 0.0001, Fisher’s exact test). Mortality differences were accompanied by reduction in DNAemia in Hartley guinea pigs. Based upon its favorable safety, pharmacokinetic, and therapeutic profiles, BAY 38-4766 warrants further investigation in the GPCMV model. PMID:15652969

  15. Characterization of guinea pig T cell responses elicited after EP-assisted delivery of DNA vaccines to the skin.

    PubMed

    Schultheis, Katherine; Schaefer, Hubert; Yung, Bryan S; Oh, Janet; Muthumani, Karuppiah; Humeau, Laurent; Broderick, Kate E; Smith, Trevor R F

    2017-01-03

    The skin is an ideal target tissue for vaccine delivery for a number of reasons. It is highly accessible, and most importantly, enriched in professional antigen presenting cells. Possessing strong similarities to human skin physiology and displaying a defined epidermis, the guinea pig is an appropriate model to study epidermal delivery of vaccine. However, whilst we have characterized the humoral responses in the guinea pig associated with skin vaccine protocols we have yet to investigate the T cell responses. In response to this inadequacy, we developed an IFN-γ ELISpot assay to characterize the cellular immune response in the peripheral blood of guinea pigs. Using a nucleoprotein (NP) influenza pDNA vaccination regimen, we characterized host T cell responses. After delivery of the DNA vaccine to the guinea pig epidermis we detected robust and rapid T cell responses. The levels of IFN-γ spot-forming units averaged approximately 5000 per million cells after two immunizations. These responses were broad in that multiple regions across the NP antigen elicited a T cell response. Interestingly, we identified a number of NP immunodominant T cell epitopes to be conserved across an outbred guinea pig population, a phenomenon which was also observed after immunization with a RSV DNA vaccine. We believe this data enhances our understanding of the cellular immune response elicited to a vaccine in guinea pigs, and globally, will advance the use of this model for vaccine development, especially those targeting skin as a delivery site. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Guinea pig and chinchilla care and husbandry.

    PubMed

    Donnelly, Thomas M; Brown, Cynthia J

    2004-05-01

    This article reviews breeds and coat colors of guinea pigs and chinchillas, their husbandry, care and anatomy. The unusual reproductive physiology and reproductive diseases of these animals are described. We cover nutrition, the potential for disease on poor diets, and the vocalization of hystricomorph rodents. Skills such as handling, sexing, blood collection and drug administration, including antibiotic toxicity are described. The conclusion lists recommended textbooks, pet owner manuals, and websites.

  17. Adenoviral vector gene delivery via the round window membrane in guinea pigs.

    PubMed

    Suzuki, Mitsuya; Yamasoba, Tatsuya; Suzukawa, Keigo; Kaga, Kimitaka

    2003-10-27

    We have found that damage from a local anesthetic solution containing phenol permitted beta-galactosidase (beta-gal) gene delivery to the guinea pig inner ear via the round window membrane (RWM). RWM damage was evident as degeneration of the outer epithelium. After adenovirus lacZ vector was applied to the damaged RWM, immunohistochemistry showed strong beta-gal expression in the RWM, mesothelial cells, organ of Corti, spiral limbus, spiral ligament and spiral ganglion. In the vestibular labyrinth, expression was seen in the sensory and supporting cells, transitional cells, and the dark-cell area. Thus, adenovirus can transfect a variety of inner ear cells in the guinea pig through a damaged RWM.

  18. Studies of foetal death and foetal weight in guinea pigs fed polychlorinated biphenyls (PCB).

    PubMed

    Brunström, B; Kihlström, I; Lundkvist, U

    1982-02-01

    Pregnant guinea pigs were fed a total dose of 100 mg of the commercial PCB preparation Clophen A50 during days 16 to 60 of gestation. This treatment caused severe foetal, but no maternal, death. Contrarily, a total dose of 25 mg or 100 mg of 2,2',4,4',5,5'-hexachlorobiphenyl (HCB) did not cause foetal death in the guinea pig. The prenatal growth rate was increased by a total dose of 25 mg, but not by 100 mg, of HCB.

  19. Mammary gland tumors in irradiated and untreated guinea pigs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hoch-Ligeti, C.; Liebelt, A.G.; Congdon, C.C.

    1986-01-01

    This is a report of mammary gland tumors from 62 guinea pigs. The tumors arose in the terminal ductal-lobular units as either lobular acinar carcinoma or cystadenocarcinoma or as papillary carcinomas within large ducts near the mammilla. About half the number of the males had terminal ductal-lobular carcinomas and all but 2 of the papillary duct carcinomas also arose in males. Large tumors frequently exhibited squamous, chondromatous, osseous, fatty and myoepitheliomatous types of tissues. In 2 irradiated males and 1 female the tumors metastasized. Whole-body irradiation did not produce significant changes in the number or sex distribution or in themore » morphology of mammary gland tumors in inbred or outbred guinea pigs. All females had cystic ovaries without increase in granulosa cells, 24 (66.6%) had uterine tumors and 13 (34.2%) had adrenal gland tumors; all males had atrophic testes, 5 (16.5%) had testicular and 6 (22.2%) had adrenal gland tumors.« less

  20. Monovalent Virus-Like Particle Vaccine Protects Guinea Pigs and Nonhuman Primates Against Infection with Multiple Marburg Viruses

    DTIC Science & Technology

    2008-05-01

    illness and death. Guinea pig necropsy, histology & immunohistochemistry Two animals randomly selected from each group were eutha- nized on 6–7 days... Gastritis , neutrophilic - - - - - - +/++ +/++ - Intestine Cellular lysis - - - - - - + + + Enteritis, neutrophilic...isolates in both guinea pigs and NHPs. Clinical, histological and immunohisto- logical findings, restricted to six animals in the three RIBI-vaccinated

  1. Mitochondrial pyruvate transport in working guinea-pig heart. Work-related vs. carrier-mediated control of pyruvate oxidation.

    PubMed

    Bünger, R; Mallet, R T

    1993-09-19

    Myocardial pyruvate oxidation is work- or calcium-load-related, but control of pyruvate dehydrogenase (PDH) by the specific mitochondrial pyruvate transporter has also been proposed. To test the transport hypothesis distribution of pyruvate across the cell membrane as well as rates of mitochondrial pyruvate net transport plus oxidation were examined in isolated perfused but stable and physiologically working guinea-pig hearts. 150 microM-1.2 mM alpha-cyanohydroxycinnamate proved to specifically block mitochondrial pyruvate uptake in these hearts. When perfusate glucose as cytosolic pyruvate precursor was supplied in combination with octanoate (0.2 or 0.5 mM) as diffusible alternative fatty acid substrate, alpha-cyanohydroxycinnamate produced up to 20- and 3-fold increases in pyruvate and lactate efflux, respectively. Cinnamates did not alter myocardial hemodynamics nor sarcolemmal pyruvate and lactate export. In contrast the tested concentrations of cinnamate produced reversible, dose-dependent decreases in 14CO2 production from [1-14C]pyruvate or [U-14C]glucose by inhibiting mitochondrial pyruvate uptake. Linear least-squares estimates of available cinnamate-sensitive total pyruvate transport potential yielded rates close to 110 mumol/min per g dry mass at S0.5 approximately 120 microM, which compared reasonably well with literature values from isolated cardiac mitochondria. This transport potential was severalfold larger than total extractable myocardial PDH activity of approximately 32 mumol/min per g dry mass at 37 degrees C. Even when cytosolic pyruvate levels were in the lower physiologic range of about 90 microM, pyruvate oxidation readily kept pace with mitochondrial respiration over a wide range of workload and inotropism. Furthermore, dichloroacetate, a selective activator of PDH, stimulated pyruvate oxidation without affecting myocardial O2 consumption, regardless of the metabolic or inotropic state of the hearts. Consequently, little or no regulatory

  2. Antagonist profile of ibodutant at the tachykinin NK2 receptor in guinea pig isolated bronchi.

    PubMed

    Santicioli, Paolo; Meini, Stefania; Giuliani, Sandro; Lecci, Alessandro; Maggi, Carlo Alberto

    2013-10-24

    In this study we have characterized the pharmacological profile of the non-peptide tachykinin NK 2 receptor antagonist ibodutant (MEN15596) in guinea pig isolated main bronchi contractility. The antagonist potency of ibodutant was evaluated using the selective NK 2 receptor agonist [βAla 8 ]NKA(4-10)-mediated contractions of guinea pig isolated main bronchi. In this assay ibodutant (30, 100 and 300nM) induced a concentration-dependent rightward shift of the [βAla 8 ]NKA(4-10) concentration-response curves without affecting the maximal contractile effect. The analysis of the results yielded a Schild-plot linear regression with a slope not different from unity (0.95, 95% c.l. 0.65-1.25), thus indicating a surmountable behaviour. The calculated apparent antagonist potency as pK B value was 8.31±0.05. Ibodutant (0.3-100nM), produced a concentration-dependent inhibition of the nonadrenergic-noncholinergic (NANC) contractile response induced by electrical field stimulation (EFS) of intrinsic airway nerves in guinea pig isolated main bronchi. At the highest concentration tested (100nM) ibodutant almost abolished the EFS-induced bronchoconstriction (95±4% inhibition), the calculated IC 50 value was 2.98nM (95% c.l. 1.73-5.16nM). In bronchi from ovalbumin (OVA) sensitized guinea pigs ibodutant (100nM) did not affect the maximal contractile response to OVA, but completely prevented the slowing in the fading of the motor response induced by phosphoramidon pretreatment linked to the endogenous neurokinin A release. Altogether, the present study demonstrate that ibodutant is a potent NK 2 receptor antagonist in guinea pig airways. © 2013 Published by Elsevier B.V.

  3. Ebola GP-specific monoclonal antibodies protect mice and guinea pigs from lethal Ebola virus infection.

    PubMed

    Qiu, Xiangguo; Fernando, Lisa; Melito, P Leno; Audet, Jonathan; Feldmann, Heinz; Kobinger, Gary; Alimonti, Judie B; Jones, Steven M

    2012-01-01

    Ebola virus (EBOV) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90%. So far there are no effective treatments available. This study evaluates the protective efficacy of 8 monoclonal antibodies (MAbs) against Ebola glycoprotein in mice and guinea pigs. Immunocompetent mice or guinea pigs were given MAbs i.p. in various doses individually or as pools of 3-4 MAbs to test their protection against a lethal challenge with mouse- or guinea pig-adapted EBOV. Each of the 8 MAbs (100 µg) protected mice from a lethal EBOV challenge when administered 1 day before or after challenge. Seven MAbs were effective 2 days post-infection (dpi), with 1 MAb demonstrating partial protection 3 dpi. In the guinea pigs each MAb showed partial protection at 1 dpi, however the mean time to death was significantly prolonged compared to the control group. Moreover, treatment with pools of 3-4 MAbs completely protected the majority of animals, while administration at 2-3 dpi achieved 50-100% protection. This data suggests that the MAbs generated are capable of protecting both animal species against lethal Ebola virus challenge. These results indicate that MAbs particularly when used as an oligoclonal set are a potential therapeutic for post-exposure treatment of EBOV infection.

  4. Comparison of effects of glass fibre and glass powder on guinea-pig lungs

    PubMed Central

    Botham, Susan K.; Holt, P. F.

    1973-01-01

    Botham, Susan K., and Holt, P. F. (1973).British Journal of Industrial Medicine,30, 232-236. Comparison of effects of glass fibre and glass powder on guinea-pig lungs. Following 24 hours inhalation by guinea-pigs of powdered glass dust, the pulmonary effects over the succeeding month differed from those previously observed to follow inhalation of glass fibre in that (1) fewer erythrocytes escaped from the capillaries, (2) very few giant cells were produced, (3) erythrocytes and intracellular glass particles were cleared more readily because junctions between respiratory and terminal bronchioles were not blocked by giant cells, (4) intracellular granules containing Perls-positive material did not appreciably increase in number or intensity of staining during the month, and (5) particles were not coated with Perls-positive material during the time that pseudo-asbestos bodies would be formed from glass fibres. The difference between the effects of chemically similar glass powder and fibre during a month in a guinea-pig lung is considered to be due to the morphology of the inhaled particle. Images PMID:4124978

  5. Pharmacologic effects of grain weevil extract on isolated guinea pig tracheal smooth muscle.

    PubMed

    Schachter, E Neil; Zuskin, Eugenija; Arumugam, Uma; Goswami, Satindra; Castranova, Vincent; Whitmer, Mike; Chiarelli, Angelo

    2008-01-01

    The grain weevil, an insect (pest) that infects grain, is a frequent contaminant of processed wheat, and its presence may contribute to respiratory abnormalities in grain workers. We studied the in vitro effects of an extract of grain weevil (GWE) on airway smooth muscle. Pharmacologic studies included in vitro challenge of guinea pig trachea with GWE, in parallel organ baths, pretreated with mediator-modifying agents or a control solution. Dose-related contractions of nonsensitized guinea pig trachea (GPT) were demonstrated using this extract. Pharmacologic studies were performed by pretreating guinea pig tracheal tissue with drugs known to modulate smooth muscle contraction: atropine, indomethacin, pyrilamine, acivicin, NDGA, BPB, TMB8, captopril, and capsaicin. Atropine, pyrilamine, BPB, and capsaicin significantly reduced the contractile effects of the extract at most of the challenge doses (p < 0.01 or p < 0.05). Inhibition of GWE-induced contraction by blocking of other mediators was less complete. We suggest that GWE causes dose-related airway smooth muscle constriction of the GPT by nonimmunologic mechanisms involving a variety of airway mediators and possibly cholinergic receptors.

  6. Typhlitis Caused by Intestinal Serpulina-Like Bacteria in Domestic Guinea Pigs (Cavia porcellus)

    PubMed Central

    Vanrobaeys, Mia; De Herdt, Peter; Ducatelle, Richard; Devriese, Luc A.; Charlier, Gerard; Haesebrouck, Freddy

    1998-01-01

    Between January 1992 and December 1996, Serpulina-like bacteria were demonstrated in intestinal tract lesions from 37 of 88 guinea pigs submitted to the University of Ghent in Ghent, Belgium, for necropsy because of disease and death from different unknown causes. All infected animals had a history of sudden death with minimal introductory clinical signs. Occasionally, they produced yellow, slimy feces or showed nervous signs, but the condition always had a fatal outcome within 24 h. When larger colonies of guinea pigs were involved, the disease spread very rapidly unless treatment with ronidazole was initiated. Lesions consisted of a catarrhal or hemorrhagic inflammation of the colon and cecum (typhlitis). Electron microscopy demonstrated the presence of large numbers of Serpulina-like organisms adhering to the cecal mucosae of these animals. Attempts to isolate the agents failed. The organisms did not stain by an immunofluorescence technique for the detection of Serpulina hyodysenteriae. The present data provide evidence that intestinal Serpulina-like organisms can be important as a cause of disease in guinea pigs. PMID:9508297

  7. Guinea pig adenovirus infection does not inhibit cochlear transfection with human adenoviral vectors in a model of hearing loss.

    PubMed

    Hankenson, F Claire; Wathen, Asheley B; Eaton, Kathryn A; Miyazawa, Toru; Swiderski, Donald L; Raphael, Yehoash

    2010-04-01

    Routine surveillance of guinea pigs maintained within a barrier facility detected guinea pig adenovirus (GPAdV) in sentinel animals. These guinea pigs served as models of induced hearing loss followed by regeneration of cochlear sensory (hair) cells through transdifferentiation of nonsensory cells by using human adenoviral (hAV) gene therapy. To determine whether natural GPAdV infection affected the ability of hAV vectors to transfect inner ear cells, adult male pigmented guinea pigs (n = 7) were enrolled in this study because of their prolonged exposure to GPAdV-seropositive conspecifics. Animals were deafened chemically (n = 2), received an hAV vector carrying the gene for green fluorescent protein (hAV-GFP) surgically without prior deafening (n = 2), or were deafened chemically with subsequent surgical inoculation of hAV-GFP (n = 3). Cochleae were evaluated by using fluorescence microscopy, and GFP expression in supporting cells indicated that the hAV-GFP vector was able to transfect inner ears in GPAdV-seropositive guinea pigs that had been chemically deafened. Animals had histologic evidence of interstitial pneumonia, attributable to prior infection with GPAdV. These findings confirmed that the described guinea pigs were less robust animal models with diminished utility for the overall studies. Serology tests confirmed that 5 of 7 animals (71%) were positive for antibodies against GPAdV at necropsy, approximately 7 mo after initial detection of sentinel infection. Control animals (n = 5) were confirmed to be seronegative for GPAdV with clinically normal pulmonary tissue. This study is the first to demonstrate that natural GPAdV infection does not negatively affect transfection with hAV vectors into guinea pig inner ear cells, despite the presence of other health complications attributed to the viral infection.

  8. [Study of the effect of JNK signal transduction pathway in intense noise-induced apoptosis in cochlea of guinea pig].

    PubMed

    Xue, Qiuhong; Chen, Jia; Gong, Shusheng; Xie, Jing; He, Jian; Chen, Xiaolin

    2009-12-01

    To investigate the mechanism of intense noise-induced cochlea cells death in guinea pig, and the effect of JNK signal transduction pathway in the procedure of cochlea cells apoptosis by intense noise-induced. Thirty-two guinea pigs were randomly divided into 4 groups. The guinea pigs in the experiment groups were exposed to 4 kHz narrow band noise at 120 dB SPL for 4 h. After the noise expose for 1, 4, 14 days of the experiment guinea pigs, ABR of the guinea pigs on experiment and control groups were tested before put them to death. Four guinea pig's cochleas of every group were taken to paraffin section, and the rest was extracted the total cochlear's protein. Apoptosis was tested by terminal deoxynucleotidyl Transferase (TdT)-mediated deoxyuridine triphosphate (d-UTP) nick and labeling method (TUNEL). The phosphorylation of JNK and c-Jun were tested by immunohistochemistry and western blot methods. Tunel-Positive cells in the Corti's, SGC and SV of experiment groups, and there have significant differences compared with the control group (P<0.01) and Tunel-Positive cells are most in 1 d experiment group. The positive cells of P-JNK and P-c-Jun could be detected in guinea pig's cochleas after noise exposed, but no positive cells were found in the control. Protein levels of P-JNK and P-c-Jun were risen up and activated quickly after noise exposed, and achieved peak in 1 d, 4 d and then fallen-offs, but still maintained higher levels within 14 d. Intense noise causes cochlea cell lesion by inducing apoptosis to result in and JNK signal transduction pathway plays an important role in the procedure of apoptosis.

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

    PubMed

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

    2002-01-01

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

  10. Development and morphology of the inverted yolk sac in the guinea pig (Cavia porcellus).

    PubMed

    Vasconcelos, Bruno Gomes; Favaron, Phelipe Oliveira; Miglino, Maria Angelica; Mess, Andrea Maria

    2013-10-01

    Although the guinea pig is an important animal model for human placentation, aspects of fetal nutrition are not fully understood, especially in regard to the yolk sac that is regarded to be essential for early development of the embryo. We investigated differentiation by means of histology, histochemistry, immunohistochemistry, and transmission electron microscopy. Data suggest that the guinea pig's yolk sac was not sufficiently developed to facilitate substantial fetal nutrition in early pregnancy. On Day 12, it was a flat, inverted, but avascular structure. This was followed by differentiation to form the typical, highly villous and vascularized condition of advanced gestation. Finally, the yolk sac degenerated toward term. We suggest that the guinea pig and other caviomorphs rely predominantly on hemotrophic nutrition via the placenta even in very early pregnancy. In contrast to the general pattern of mammals, histiotrophic nutrition via yolk sac routes seems to be most essential during mid-gestation. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Relaxation of isolated guinea-pig trachea by apigenin, a constituent of celery, via inhibition of phosphodiesterase.

    PubMed

    Chen, Junn-Lain; Ko, Wun-Chang

    2017-09-15

    Apigenin, was reported to have vasodilatory effects by inhibiting Ca 2+ influx through both voltage- and receptor-operated calcium channels, but not by inhibiting cAMP- or cGMP-phosphodiesterases (PDEs) in rat thoracic aorta. However, apigenin was reported to inhibit PDE1, 2 and 3 in guinea-pig lung and heart. The aim of this study was to clarify that guinea-pig tracheal relaxation by apigenin whether via PDE inhibition. We isometrically recorded the tension of isolated guinea-pig tracheal segments on a polygraph. Antagonistic effects of apigenin against cumulative contractile agents or Ca 2+ induced contractions of the trachealis in normal or isotonic high-K + , Ca 2+ -free Krebs solution, respectively. Effects of apigenin (15 and 30μM) on the cumulative forskolin- and nitroprusside-induced relaxations to histamine (30μM)-induced precontraction were performed. The inhibitory effects of 30-300μM apigenin and 3-isobutyl-1-methylxanthine (IBMX, positive control) on the cAMP- and cGMP-PDEs were determined. Apigenin concentration-dependently but non-competitively inhibited cumulative histamine-, carbachol- or Ca 2+ -induced contractions in normal or in the depolarized (K + , 60mM) trachealis, suggesting that Ca 2+ influx through voltage-dependent calcium channels is inhibited. However, apigenin (15-30μM) parallel leftward shifted the concentration-response curves of forskolin and nitroprusside, and significantly increased the pD 2 values of these two cyclase activators. Both apigenin and IBMX, a reference drug, concentration (10-300μM)-dependently and significantly, but non-selectively inhibited the activities of cAMP- and cGMP-PDEs in the trachealis. In conclusion, the relaxant effect of apigenin may be due to inhibition of both enzyme activities and reduction of intracellular Ca 2+ by inhibiting Ca 2+ influx in the trachealis. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. [Breeding and management of mycobacteria-free guinea pigs (author's transl)].

    PubMed

    Kazda, J

    1976-08-01

    A number of mycobacterial species are detectable under conventional holding condition of guinea pigs. These mycobacteria originating in drinking water and litter caused cross reactions in the Jones-Mote hypersensitivity test. Using suitable precautions it was possible to breed and hold the animals mycobacteria-free. The precautions depend mainly in alteration of the wire mesh floor in cages to avoide the contact of the animals with the litter, in cleaning and desinfection of water bottles, in using of heated water and food and in the prevention of mycobacterial contamination from the staff. The control examination on mycobacteria without treating is given in details. Cases are refered in which a oral rece ption of mycobacteria can alter the immune response. The modification of guinea pigs management to the mycobacteria-free ones is possible in a short time and with minimal cost.

  13. [Dermatophyte colonization on guinea pigs (Cavia porcellus) kept in pet stores. First report from Santiago, Chile].

    PubMed

    Thomson, Pamela; Monsalves, Pamela; Maier, Liliana; Silva, Víctor

    2015-01-01

    Dermatophytes are pathogenic fungi that can be present in the flora of mammals, such as dogs, cats and rodents, which can be a source and transmission vehicle to other hosts, including humans. In Chile, there is a steady increase of acquiring guinea pigs (Cavia porcellus) as pets, with no local studies on their colonization by dermatophytes. To determine the presence of dermatophytes on clinically healthy guinea pigs, kept in pet stores in Santiago, Chile. A total of 52 clinically healthy animals were studied using the method by Mariat and Tapia (1966). The specimen culture and identification of the dermatophytes were performed using classical mycological procedures. Four guinea pigs (7.7%) out of 52 were colonized by dermatophytes, and were identified as Trichophyton mentagrophytes (3 cases) and Trichophyton verrucosum (one case). This study shows, for the first time in Chile, that guinea pigs can be colonized by dermatophytes, which should alert administrators of pet stores, veterinarians and physicians, to keep this in mind when purchasing or looking after this type of pet in a veterinary office. Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  14. Do β3-adrenergic receptors play a role in guinea pig detrusor smooth muscle excitability and contractility?

    PubMed Central

    Afeli, Serge A. Y.; Hristov, Kiril L.

    2012-01-01

    In many species, β3-adrenergic receptors (β3-ARs) have been reported to play a primary role in pharmacologically induced detrusor smooth muscle (DSM) relaxation. However, their role in guinea pig DSM remains controversial. The aim of this study was to investigate whether β3-ARs are expressed in guinea pig DSM and to evaluate how BRL37344 and L-755,507, two selective β3-AR agonists, modulate guinea pig DSM excitability and contractility. We used a combined experimental approach including RT-PCR, patch-clamp electrophysiology, and isometric DSM tension recordings. β3-AR mRNA message was detected in freshly isolated guinea pig DSM single cells. BRL37344 but not L-755,507 caused a slight decrease in DSM spontaneous phasic contraction amplitude and frequency in a concentration-dependent manner. In the presence of atropine (1 μM), only the spontaneous phasic contractions frequency was inhibited by BRL37344 at higher concentrations. Both BRL37344 and L-755,507 significantly decreased DSM carbachol-induced phasic and tonic contractions in a concentration-dependent manner. However, only BRL37344 inhibitory effect was partially antagonized by SR59230A (10 μM), a β3-AR antagonist. In the presence of atropine, BRL37344 and L-755,507 had no inhibitory effect on electrical field stimulation-induced contractions. Patch-clamp experiments showed that BRL37344 (100 μM) did not affect the DSM cell resting membrane potential and K+ conductance. Although β3-ARs are expressed at the mRNA level, they play a minor to no role in guinea pig DSM spontaneous contractility without affecting cell excitability. However, BRL37344 and L-755,507 have pronounced inhibitory effects on guinea pig DSM carbachol-induced contractions. The study outlines important DSM β3-ARs species differences. PMID:21993887

  15. Reflections on the Fiftieth Reunion of the Guinea Pigs.

    ERIC Educational Resources Information Center

    Loud, Oliver

    1988-01-01

    A member of the original faculty of the experimental Ohio State University Laboratory High School reflects at a fiftieth reunion of the first graduating class. Students were used as guinea pigs to determine the effects of providing teenagers with liberating, interesting, and customized education from university faculty. (SM)

  16. Mouse and Guinea Pig Models of Tuberculosis.

    PubMed

    Orme, Ian M; Ordway, Diane J

    2016-08-01

    This article describes the nature of the host response to Mycobacterium tuberculosis in the mouse and guinea pig models of infection. It describes the great wealth of information obtained from the mouse model, reflecting the general availability of immunological reagents, as well as genetic manipulations of the mouse strains themselves. This has led to a good understanding of the nature of the T-cell response to the infection, as well as an appreciation of the complexity of the response involving multiple cytokine- and chemokine-mediated systems. As described here and elsewhere, we have a growing understanding of how multiple CD4-positive T-cell subsets are involved, including regulatory T cells, TH17 cells, as well as the subsequent emergence of effector and central memory T-cell subsets. While, in contrast, our understanding of the host response in the guinea pig model is less advanced, considerable strides have been made in the past decade in terms of defining the basis of the immune response, as well as a better understanding of the immunopathologic process. This model has long been the gold standard for vaccine testing, and more recently is being revisited as a model for testing new drug regimens (bedaquiline being the latest example).

  17. Absorption of the nerve agent VX (O-ethyl-S-[2(di-isopropylamino)ethyl] methyl phosphonothioate) through pig, human and guinea pig skin in vitro.

    PubMed

    Dalton, Christopher H; Hattersley, Ian J; Rutter, Stephen J; Chilcott, Robert P

    2006-12-01

    The physico-chemical properties of VX make the skin the most likely route of absorption into the human body. The development of effective medical countermeasures against such percutaneous threat agents relies on the use of appropriate animal models, as the inherent toxicity of nerve agents precludes the use of human volunteers. Previous studies have characterised the mechanism of nerve agent toxicity in rodent models, however, it is generally accepted that one of the most appropriate animal models for human skin absorption is the domestic pig. The purpose of the present study was to measure and compare the skin absorption kinetics of VX in vitro using pig, human and guinea pig skin to highlight any potential species differences in skin permeability. When undiluted VX was applied directly to the skin, the permeability of guinea pig skin was approximately 7-fold greater than human skin. There was no significant difference in the permeability of pig and human skin. When VX diluted with isopropyl alcohol was applied to the skin, the permeability of guinea pig skin was approximately 4-fold greater than human skin. There was no significant difference in the permeability of pig and human skin. From this data it may be inferred that dermatomed, abdominal pig skin is an appropriate model for the human skin absorption of VX.

  18. SULFAMETHOXAZOLE-TRIMETHOPRIM TREATMENT OF GUINEA PIGS INFECTED WITH 'LEGIONELLA PNEUMPOPHILA'

    EPA Science Inventory

    Legionnaires' disease is a bacterial pneumonia caused by Legionella pneumophila. Many antibiotics inhibit the growth of L. pneumophila in vitro, but only erythromycin and rifampin have been clinically effective. Parallel results have been observed in guinea pigs infected ip with ...

  19. Pharmacokinetics and Adverse Effects of 3 Sustained-release Buprenorphine Dosages in Healthy Guinea Pigs (Cavia porcellus)

    PubMed Central

    Zanetti, Andrea S; Putta, Sumanth K; Casebolt, Donald B; Louie, Stan G

    2017-01-01

    In guinea pigs, studies addressing the efficacy, safety, and pharmacokinetic profiles of different sustained-release buprenorphine (SRB) formulations are still in their infancy. Here we assessed the pharmacokinetic profiles of 3 SRB dosages (SR-LAB, ZooPharm; SRBLow, 0.15 mg/kg; SRBMedium, 0.3 mg/kg; and SRBHigh, 0.6 mg/kg) for 72 h after a single subcutaneous administration to 8 (4 male and 4 female) healthy guinea pigs. Body weight, fecal output, and cortisol levels were also monitored and the results compared with those of the sham group. Within the first h after administration, the maximal plasma concentration (Cmax) of the drug was 64.3 ± 9.2 ng/mL (males) and 71.3 ± 3.7 ng/mL (females) in the SRBHigh group; 11.5 ± 3.2 ng/mL (males) and 6.9 ± 0.9 ng/mL (females) in the SRBMedium group; and 2.3 ± 0.8 ng/mL (males) and 2.0 ± 0.5 ng/mL (females) in the SRBLow group. After 72 h, therapeutic levels of the drug (>1 ng/mL) were observed only in guinea pigs treated with SRBHigh (both sexes) and males treated with SRBMediu cm. Fecal output (quantity and distribution) and body weight were significantly lower in the SRB groups as compared with the sham group, and with the SRBHigh group showing larger reductions. Baseline levels of serum cortisol in healthy females (1440 ± 106 ng/mL) were significantly greater than in males (550 ± 66 ng/mL). But, independent of the sex, SRB administration significantly reduced those levels. In conclusion, the data indicate that all 3 SRB dosages can be safely used in guinea pigs. However, therapeutic levels of the drug were observed for at least 48 h only guinea pigs treated with SRBHigh and SRBMedium. Further investigation is needed to determine if these dosages can alleviate pain in guinea pigs. PMID:29256372

  20. [Experiences with cage combinations for guinea pigs].

    PubMed

    von Zychlinski, J

    1989-01-01

    Special cage units described in 1982 for guinea pigs have been used either as cages for small groups of breeding animals or for caging of growing animals. By using these cages the following advantages have been noted; the cage size can be adapted to number, age and body weight of the animals; aggression and panic are avoided by corners, walls and tunnels; economic use of breeding males by mating with more females.

  1. Development and characterization of a guinea pig model for Marburg virus.

    PubMed

    Wong, Gary; Cao, Wen-Guang; He, Shi-Hua; Zhang, Zi-Rui; Zhu, Wen-Jun; Moffat, Estella; Ebihara, Hideki; Embury-Hyatt, Carissa; Qiu, Xiang-Guo

    2018-01-18

    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 LD 50 was calculated to be 1.1×10 -1 TCID 50 (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.

  2. alpha-Mannosidosis in the guinea pig: cloning of the lysosomal alpha-mannosidase cDNA and identification of a missense mutation causing alpha-mannosidosis.

    PubMed

    Berg, Thomas; Hopwood, John J

    2002-03-16

    alpha-Mannosidosis is a lysosomal storage disorder caused by deficient activity of the lysosomal alpha-mannosidase. We report here the sequencing and expression of the lysosomal alpha-mannosidase cDNA from normal and alpha-mannosidosis guinea pigs. The amino acid sequence of the guinea pig enzyme displayed 82-85% identity to the lysosomal alpha-mannosidase in other mammals. The cDNA of the alpha-mannosidosis guinea pig contained a missense mutation, 679C>T, leading to substitution of arginine by tryptophan at amino acid position 227 (R227W). The R227W allele segregated with the alpha-mannosidosis genotype in the guinea pig colony and introduction of R227W into the wild-type sequence eliminated the production of recombinant alpha-mannosidase activity in heterologous expression studies. Furthermore, the guinea pig mutation has been found in human patients. Our results strongly indicate that the 679C>T mutation causes alpha-mannosidosis and suggest that the guinea pig will be an excellent model for investigation of pathogenesis and evaluation of therapeutic strategies for human alpha-mannosidosis.

  3. Aerosolized polymerized type I collagen reduces airway inflammation and remodelling in a guinea pig model of allergic asthma.

    PubMed

    Moreno-Alvarez, Paola; Sánchez-Guerrero, Edgar; Martínez-Cordero, Erasmo; Hernández-Pando, Rogelio; Campos, María G; Cetina, Lucely; Bazán-Perkins, Blanca

    2010-04-01

    Collagen-polyvinylpyrrolidone (Collagen-PVP) has been demonstrated to elicit immunomodulatory properties in different chronic inflammatory diseases. Nevertheless, its effects on asthma are still unknown. We have evaluated whether collagen-PVP could modulate airway inflammation and remodelling in a guinea pig model of allergic asthma. Sensitized guinea pigs were challenged with the allergen (ovalbumin) six times (at 10-day intervals). From the third challenge on, animals were treated every 5 days with saline aerosols containing 0.16, 0.33, or 0.66 mg/ml of collagen-PVP (n = 5, respectively). Some guinea pigs, sensitized and challenged with saline as well as treated with 0 or 0.66 mg/ml collagen-PVP, were included in the study as control (n = 7) and sham groups (n = 5), respectively. From the first challenge on, ovalbumin induced a transient airway obstruction, measured by barometric plethysmography, which was not modified by collagen-PVP treatments. After the last allergen challenge, guinea pigs were anesthetized to obtain bronchoalveolar lavage (BAL) and the left lung caudal lobe. As expected, BAL cell count from allergen-challenged guinea pigs showed abundant neutrophils and eosinophils, as well as numerous tumor necrosis factor (TNF)-alpha-expressing granulocytes and macrophages in airway wall (determined by immunohistochemical assay). Neutrophilia and TNF-alpha-expressing leukocytes, from collagen-PVP treated animals, diminished from 0.16 mg/ml, and eosinophilia from 0.66 mg/ml of collagen-PVP doses. Histological changes induced by allergen challenges include thickening of connective tissue below airway epithelium and vascular wall widening of airway adjacent vessels; these changes were reduced by collagen-PVP treatment. Collagen-PVP seems to have anti-inflammatory and antifibrotic properties in this guinea pig asthma model.

  4. Treatment and control of Trixacarus caviae infestation in a conventional guinea pig (Cavia porcellus) breeding colony.

    PubMed

    Nath, Anjan Jyoti

    2016-12-01

    A case of sarcoptic mange caused by Trixacarus caviae in a conventional guinea pig breeding colony is reported. The infestation was reported in a large colony of guinea pigs during the month of July, 2013 affecting 30 breeder guinea pigs. Severely infested animals were treated individually with subcutaneous injection of ivermectin 1 % w/v (Neomec ® ) at the rate of 400 µg/kg body weight 10 days apart. Three doses of ivermectin were sufficient to eliminate the parasite which tested negative after 30 days of the first treatment. The entire colony was given preventive dose of ivermectin spray (2 mg/ml solution) following the same schedule. Strict hygienic measures were followed. New hair growth in the severely affected animals was evidenced on 30th day of treatment.

  5. Activities of tigecycline (GAR-936) against Legionella pneumophila in vitro and in guinea pigs with L. pneumophila pneumonia.

    PubMed

    Edelstein, Paul H; Weiss, William J; Edelstein, Martha A C

    2003-02-01

    The activities of tigecycline (Wyeth Research) against extracellular and intracellular Legionella pneumophila and for the treatment of guinea pigs with L. pneumophila pneumonia were studied. The tigecycline MIC at which 50% of strains are inhibited for 101 different Legionella sp. strains was 4 micro g/ml versus 0.125 and 0.25 micro g/ml for azithromycin and erythromycin, respectively. Tigecycline was about as active as erythromycin (tested at 1 micro g/ml) against the F889 strain of L. pneumophila grown in guinea pig alveolar macrophages and more active than erythromycin against the F2111 strain. Azithromycin (0.25 micro g/ml) was more active than (F889) or as active as (F2111) tigecycline (1 micro g/ml) in the macrophage model. When tigecycline was given (7.5 mg/kg of body weight subcutaneously once) to guinea pigs with L. pneumophila pneumonia, the mean peak serum and lung levels were 2.3 and 1.8 micro g/ml (1.2 and 1.5 micro g/g) at 1 and 2 h postinjection, respectively. The serum and lung areas under the concentration time curve from 0 to 24 h were 13.7 and 15.8 micro g. h/ml, respectively. Thirteen of 16 guinea pigs with L. pneumophila pneumonia treated with tigecycline (7.5 mg/kg subcutaneously once daily for 5 days) survived for 7 days post-antimicrobial therapy, as did 11 of 12 guinea pigs treated with azithromycin (15 mg/kg intraperitoneally once daily for 2 days). None of 12 guinea pigs treated with saline survived. Tigecycline-treated guinea pigs had average end of therapy lung counts of 1 x 10(6) CFU/g (range, 2.5 x 10(4) to 3.2 x 10(6) CFU/g) versus <1 x 10(2) CFU/g for azithromycin (range, undetectable to 100 CFU/g). A second guinea pig study examined the ability of tigecycline to clear L. pneumophila from the lung after 5 to 9 days of therapy; bacterial concentrations 1 day posttherapy ranged from log(10) 4.2 to log(10) 5.5 CFU/g for four different dosing regimens. Tigecycline is about as effective as erythromycin against intracellular L

  6. Activities of Tigecycline (GAR-936) against Legionella pneumophila In Vitro and in Guinea Pigs with L. pneumophila Pneumonia

    PubMed Central

    Edelstein, Paul H.; Weiss, William J.; Edelstein, Martha A. C.

    2003-01-01

    The activities of tigecycline (Wyeth Research) against extracellular and intracellular Legionella pneumophila and for the treatment of guinea pigs with L. pneumophila pneumonia were studied. The tigecycline MIC at which 50% of strains are inhibited for 101 different Legionella sp. strains was 4 μg/ml versus 0.125 and 0.25 μg/ml for azithromycin and erythromycin, respectively. Tigecycline was about as active as erythromycin (tested at 1 μg/ml) against the F889 strain of L. pneumophila grown in guinea pig alveolar macrophages and more active than erythromycin against the F2111 strain. Azithromycin (0.25 μg/ml) was more active than (F889) or as active as (F2111) tigecycline (1 μg/ml) in the macrophage model. When tigecycline was given (7.5 mg/kg of body weight subcutaneously once) to guinea pigs with L. pneumophila pneumonia, the mean peak serum and lung levels were 2.3 and 1.8 μg/ml (1.2 and 1.5 μg/g) at 1 and 2 h postinjection, respectively. The serum and lung areas under the concentration time curve from 0 to 24 h were 13.7 and 15.8 μg · h/ml, respectively. Thirteen of 16 guinea pigs with L. pneumophila pneumonia treated with tigecycline (7.5 mg/kg subcutaneously once daily for 5 days) survived for 7 days post-antimicrobial therapy, as did 11 of 12 guinea pigs treated with azithromycin (15 mg/kg intraperitoneally once daily for 2 days). None of 12 guinea pigs treated with saline survived. Tigecycline-treated guinea pigs had average end of therapy lung counts of 1 × 106 CFU/g (range, 2.5 × 104 to 3.2 × 106 CFU/g) versus <1 × 102 CFU/g for azithromycin (range, undetectable to 100 CFU/g). A second guinea pig study examined the ability of tigecycline to clear L. pneumophila from the lung after 5 to 9 days of therapy; bacterial concentrations 1 day posttherapy ranged from log10 4.2 to log10 5.5 CFU/g for four different dosing regimens. Tigecycline is about as effective as erythromycin against intracellular L. pneumophila, but tigecycline inactivation by

  7. Influence of feeding hay on the alopecia of breeding guinea pigs.

    PubMed

    Gerold, S; Huisinga, E; Iglauer, F; Kurzawa, A; Morankic, A; Reimers, S

    1997-08-01

    Animals with partial alopecia were seen frequently in a breeding colony of guinea pigs. No pathologic aetiology could be determined. An influence of nutrition on the density of the hair coat was considered. Breeding groups were fed one of the commercial guinea pig diets of differing composition, with or without the addition of hay. Observation occurred over a period of months and the quality of the hair coat was evaluated periodically using a semi-quantitative scoring system. More extensive and more frequent fur defects were found is guinea pigs receiving a breeding diet with a high content of crude protein (23%) and a low level of crude fibre (12%), offered hay only restrictively compared with animals receiving a diet with a lower content of crude protein (15.5%) and a higher level of crude fibre (19.5%), offered the same amount of hay. The amount of hay offered is of paramount importance. Animals fed only the diet with the higher level of crude fibre (19.5%), according to the manufacturer's instructions as a complete food, without the addition of hay, showed a less dense hair coat within 4 weeks. In our colony a group of five breeding animals and their young required 200 g of hay daily in order to improve their hair coat quality to normal. Conversely, animals receiving less hay had progressively deteriorating hair coat density. Not only the amount of hay offered, but also the accessibility for all animals plays a role in preventing alopecia in guinea pigs. In larger cages (twice the usual ground surface area) fur defects were seen when the same amount of hay (200 g) was offered in only one central area, rather than spread out evenly throughout the cage. Hair loss was observed to be the result of trichophagia between adult animals kept in the same cage. The need for crude fibre of breeding animals does not appear to be completely met by pellets rich in fibre segments.

  8. Levodopa inhibits the development of form-deprivation myopia in guinea pigs.

    PubMed

    Mao, Junfeng; Liu, Shuangzhen; Qin, Wenjuan; Li, Fengyun; Wu, Xiaoying; Tan, Qian

    2010-01-01

    It has been shown that visual deprivation leads to a myopic refractive error and also reduces the retinal concentration of dopamine. Exogenously 3,4-dihydroxy-L-phenylalanine (levodopa, L-DOPA) can be converted into dopamine in vivo, which safely and effectively treats Parkinson disease. Moreover, L-DOPA was also used in the treatment of amblyopia in clinical studies. However, the effect of L-DOPA on the development of myopia has not been studied. The aim of this study was to investigate whether intraperitoneal injection of L-DOPA could inhibit form-deprivation myopia in guinea pigs and to explore a new strategy for drug treatment of myopia. Sixty guinea pigs, at age of 4 weeks, were randomly divided into six groups: normal control, L-DOPA group, saline group, deprived group, deprived plus L-DOPA group, and deprived plus saline group. Form deprivation was induced with translucent eye shields on the right eye and lasted for 10 days. L-DOPA was injected intraperitoneally into the guinea pig once a day. The corneal radius of curvature, refraction, and axial length were measured in all animals. Subsequently, retinal dopamine content was evaluated by high-performance liquid chromatography with electrochemical detection. Ten days of eye occlusion caused the form-deprived eyes to elongate and become myopic, and retinal dopamine content to decrease, but the corneal radius of curvature was not affected. Repeated intraperitoneal injection of L-DOPA could inhibit the myopic shift (from -3.62 +/- 0.98 D to -1.50 +/- 0.38 D; p < 0.001) due to goggles occluding and compensate retinal dopamine (from 0.65 +/- 0.10 ng to 1.33 +/- 0.23 ng; p < 0.001). Administration of L-DOPA to the unoccluded animals had no effect on its ocular refraction. There was no effect of intraperitoneal saline on the ocular refractive state and retinal dopamine. Systemic L-DOPA was partly effective in this guinea pig model and, therefore, is worth testing for effectiveness in progressing human myopes.

  9. Contact allergy to a contaminant in Kathon CG in the guinea pig.

    PubMed

    Bruze, M; Gruvberger, B; Persson, K

    1987-01-01

    Kathon CG is a commercial preservative, consisting of the two active ingredients, 2-methyl-4-isothiazolin-3-one and 5-chloro-2-methyl-4-isothiazolin-3-one (5243-K-CG) and other components. 4,5-dichloro-2-methyl-4-isothiazolin-3-one (45243-K-CG) is a contaminant in Kathon CG. The chemically related active ingredients are known to be contact sensitizers in humans and guinea pigs. Aims of this study were to determine the sensitizing capacity of this contaminant and also to investigate the cross-reaction pattern by guinea pig sensitization tests. 45243-K-CG was demonstrated to be a strong sensitizer; all animals reacting to 45243-K-CG also reacted to 5243-K-CG when rechallenged.

  10. Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs

    DOE PAGES

    Kim, Hwan Keun; Falugi, Fabiana; Thomer, Lena; ...

    2015-01-06

    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 V H3 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 V H3 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 suppressesmore » host B cell responses. Immunization with SpA KKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity.« less

  11. Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Hwan Keun; Falugi, Fabiana; Thomer, Lena

    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 V H3 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 V H3 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 suppressesmore » host B cell responses. Immunization with SpA KKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity.« less

  12. Adaptation of H9N2 AIV in guinea pigs enables efficient transmission by direct contact and inefficient transmission by respiratory droplets

    PubMed Central

    Sang, Xiaoyu; Wang, Airong; Ding, Jie; Kong, Huihui; Gao, Xiaolong; Li, Lin; Chai, Tongjie; Li, Yuanguo; Zhang, Kun; Wang, Chengyu; Wan, Zhonghai; Huang, Geng; Wang, Tiecheng; Feng, Na; Zheng, Xuexing; Wang, Hualei; Zhao, Yongkun; Yang, Songtao; Qian, Jun; Hu, Guixue; Gao, Yuwei; Xia, Xianzhu

    2015-01-01

    H9N2 avian influenza viruses circulate worldwide in poultry and have sporadically infected humans, raising concern whether H9N2 viruses have pandemic potential. Here, we use a guinea pig model to examine whether serial passage results in adaptive viral changes that confer a transmissible phenotype to a wild-type H9N2 virus. After nine serial passages of an H9N2 virus through guinea pigs, productive transmission by direct contact occurred in 2/3 guinea pig pairs. The efficiency of transmission by direct contact increased following the fifteenth passage and occurred in 3/3 guinea pig pairs. In contrast, airborne transmission of the passaged virus was less efficient and occurred in 1/6 guinea pig pairs and 0/6 ferret pairs after the fifteenth passage. Three amino acid substitutions, HA1-Q227P, HA2-D46E, and NP-E434K, were sufficient for contact transmission in guinea pigs (2/3 pairs). The two HA amino acid substitutions enhanced receptor binding to α2,3-linked sialic acid receptors. Additionally, the HA2-D46E substitution increased virus thermostability whereas the NP-E434K mutation enhanced viral RNA polymerase activity in vitro. Our findings suggest that adaptive changes that enhance viral receptor binding, thermostability, and replicative capacity in mammalian cells can collectively enhance the transmissibility of H9N2 AIVs by direct contact in the guinea pig model. PMID:26552719

  13. Bilirubin attenuates bufadienolide-induced ventricular arrhythmias and cardiac dysfunction in guinea-pigs by reducing elevated intracellular Na(+) levels.

    PubMed

    Ma, Hongyue; Zhang, Junfeng; Jiang, Jiejun; Zhou, Jing; Xu, Huiqin; Zhan, Zhen; Wu, Qinan; Duan, Jinao

    2012-03-01

    Bufadienolides, known ligands of the sodium pump, have been shown to inhibit the proliferation of several cancer cell types. However, their development to date as anticancer agents has been impaired by a narrow therapeutic margin resulting from their potential to induce cardiotoxicity. In the present study, we examined the effects of bilirubin, an endogenous antioxidant, on the cardiotoxicity of bufadienolides (derived from toad venom) in guinea-pigs. The results showed that bufadienolides (8 mg/kg) caused ventricular arrhythmias, conduction block, cardiac dysfunction and death in guinea-pigs. Pretreatment with bilirubin (75 and 150 mg/kg) significantly prevented bufadienolide-induced premature ventricular complexes, ventricular tachycardia, ventricular fibrillation and death. Bilirubin also markedly improved the inhibition of cardiac contraction in bufadienolide-treated guinea-pigs as evidenced by increases in left ventricular systolic pressure and decreases in left ventricular diastolic pressure in vivo. Furthermore, bilirubin significantly reduced the intracellular sodium content ([Na(+)]( i )) in ex vivo bufadienolide-stimulated guinea-pig ventricular myocytes loaded with the sodium indicator Sodium Green. An antitumor study showed that bilirubin did not compromise the ability of bufadienolides to inhibit gastric cancer cell MGC-803 proliferation. These results suggested that bilirubin can attenuate bufadienolide-induced arrhythmias and cardiac dysfunction in guinea-pigs by reducing elevated [Na(+)]( i ) and may improve bufadienolide therapeutic index in cancer treatment.

  14. THE BACTERICIDAL ACTIVITY OF NORMAL GUINEA PIG SERUM AGAINST LISTERIA MONOCYTOGENES AND ITS INHIBITION BY A LISTERIAL CELL EXTRACT,

    DTIC Science & Technology

    Normal guinea pig serum contains bactericidins active against Listeria monocytogenes. The listeriocidal activity of the serum did not increase after...factor. Lysozyme was not implicated in the bactericidal system. It was suggested that the bactericidal activity of guinea pig serum might be due either to

  15. Clinical and pathologic changes in a guinea pig aerosol challenge model of acute Q fever.

    PubMed

    Russell-Lodrigue, K E; Zhang, G Q; McMurray, D N; Samuel, J E

    2006-11-01

    Acute Q fever is a zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii and can manifest as a flu-like illness, pneumonia, or hepatitis. A need exists in Q fever research for animal models mimicking both the typical route of infection (inhalation) and the clinical illness seen in human cases of Q fever. A guinea pig aerosol challenge model was developed using C. burnetii Nine Mile phase I (RSA 493), administered using a specialized chamber designed to deliver droplet nuclei directly to the alveolar spaces. Guinea pigs were given 10(1) to 10(6) organisms and evaluated for 28 days postinfection. Clinical signs included fever, weight loss, respiratory difficulty, and death, with the degree and duration of response corresponding to the dose of organism delivered. Histopathologic evaluation of the lungs of animals infected with a high dose showed coalescing panleukocytic bronchointerstitial pneumonia at 7 days postinfection that resolved to multifocal lymphohistiocytic interstitial pneumonia by 28 days. Guinea pigs receiving a killed whole-cell vaccine prior to challenge with the highest dose of C. burnetii were protected against lethal infection and did not develop fever. Clinical signs and pathological changes noted for these guinea pigs were comparable to those seen in human acute Q fever, making this an accurate and valuable animal model of human disease.

  16. An attenuated quadruple gene mutant of Mycobacterium tuberculosis imparts protection against tuberculosis in guinea pigs

    PubMed Central

    Chauhan, Priyanka

    2018-01-01

    ABSTRACT Previously we had developed a triple gene mutant of Mycobacterium tuberculosis (MtbΔmms) harboring disruption in three genes, namely mptpA, mptpB and sapM. Though vaccination with MtbΔmms strain induced protection in the lungs of guinea pigs, the mutant strain failed to control the hematogenous spread of the challenge strain to the spleen. Additionally, inoculation with MtbΔmms resulted in some pathological damage to the spleens in the early phase of infection. In order to generate a strain that overcomes the pathology caused by MtbΔmms in spleen of guinea pigs and controls dissemination of the challenge strain, MtbΔmms was genetically modified by disrupting bioA gene to generate MtbΔmmsb strain. Further, in vivo attenuation of MtbΔmmsb was evaluated and its protective efficacy was assessed against virulent M. tuberculosis challenge in guinea pigs. MtbΔmmsb mutant strain was highly attenuated for growth and virulence in guinea pigs. Vaccination with MtbΔmmsb mutant generated significant protection in comparison to sham-immunized animals at 4 and 12 weeks post-infection in lungs and spleen of infected animals. However, the protection imparted by MtbΔmmsb was significantly less in comparison to BCG immunized animals. This study indicates the importance of attenuated multiple gene deletion mutants of M. tuberculosis for generating protection against tuberculosis. PMID:29242198

  17. Effect of Altered Retinal Cones/Opsins on Refractive Development under Monochromatic Lights in Guinea Pigs

    PubMed Central

    Zou, Leilei; Zhu, Xiaoyu; Liu, Rui; Ma, Fei; Yu, Manrong

    2018-01-01

    Purpose To analyze the changes of refraction and metabolism of the retinal cones under monochromatic lights in guinea pigs. Methods Sixty guinea pigs were randomly divided into a short-wavelength light (SL) group, a middle-wavelength light (ML) group, and a white light (WL) group. Refraction and axial length were measured before and after 10-week illumination. The densities of S-cones and M-cones were determined by retinal cone immunocytochemistry, and the expressions of S-opsins and M-opsins were determined by real-time PCR and Western blot. Results After 10-week illumination, the guinea pigs developed relative hyperopia in the SL group and relative myopia in the ML group. Compared with the WL group, the density of S-cones and S-opsins increased while M-cones and M-opsins decreased in the SL group (all, p < 0.05); conversely, the density of S-cones and S-opsins decreased while M-cones and M-opsins increased in the ML group (all, p < 0.05). Increased S-cones/opsins and decreased M-cones/opsins were induced by short-wavelength lights. Decreased S-cones/opsins and increased M-cones/opsins were induced by middle-wavelength lights. Conclusions Altered retinal cones/opsins induced by monochromatic lights might be involved in the refractive development in guinea pigs. PMID:29675275

  18. The electro-mechanical window in anaesthetized guinea pigs: a new marker in screening for Torsade de Pointes risk

    PubMed Central

    Guns, P-J; Johnson, DM; Van Op den bosch, J; Weltens, E; Lissens, J

    2012-01-01

    BACKGROUND AND PURPOSE QT prolongation is commonly used as a surrogate marker for Torsade de Pointes (TdP) risk of non-cardiovascular drugs. However, use of this indirect marker often leads to misinterpretation of the realistic TdP risk, as tested compounds may cause QT prolongation without evoking TdP in humans. A negative electro-mechanical (E-M) window has recently been proposed as an alternative risk marker for TdP in a canine LQT1 model. Here, we evaluated the E-M window in anaesthetized guinea pigs as a screening marker for TdP in humans. EXPERIMENTAL APPROACH The effects of various reference drugs and changes in body temperature on the E-M window were assessed in instrumented guinea pigs. The E-M window was defined as the delay between the duration of the electrical (QT interval) and mechanical (QLVPend) systole. KEY RESULTS Drugs with known TdP liability (quinidine, haloperidol, domperidone, terfenadine, thioridazine and dofetilide), but not those with no TdP risk in humans (salbutamol and diltiazem) consistently decreased the E-M window. Interestingly, drugs with known clinical QT prolongation, but with low risk for TdP (amiodarone, moxifloxacin and ciprofloxacin) did not decrease the E-M window. Furthermore, the E-M window was minimally affected by changes in heart rate or body temperature. CONCLUSIONS AND IMPLICATIONS A decreased E-M window was consistently observed with drugs already known to have high TdP risk, but not with drugs with low or no TdP risk. These results suggest that the E-M window in anaesthetized guinea pigs is a risk marker for TdP in humans. PMID:22122450

  19. Electrical Integration of Human Embryonic Stem Cell-Derived Cardiomyocytes in a Guinea Pig Chronic Infarct Model

    PubMed Central

    Shiba, Yuji; Filice, Dominic; Fernandes, Sarah; Minami, Elina; Dupras, Sarah K.; Van Biber, Benjamin; Trinh, Peter; Hirota, Yusuke; Gold, Joseph D.; Viswanathan, Mohan; Laflamme, Michael A.

    2014-01-01

    Background Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were recently shown to be capable of electromechanical integration following their direct injection into intact or recently injured guinea pig hearts, and hESC-CM transplantation in recently injured hearts correlated with improvements in contractile function and a reduction in the incidence of arrhythmias. The present study was aimed at determining the ability of hESC-CMs to integrate and modulate electrical stability following transplantation in a chronic model of cardiac injury. Methods & Results At 28 days following cardiac cryoinjury, guinea pigs underwent intra-cardiac injection of hESC-CMs, non-cardiac hESC-derivatives (non-CMs) or vehicle. Histology confirmed partial remuscularization of the infarct zone in hESC-CM recipients, while non-CM recipients showed heterogeneous xenografts. The three experimental groups showed no significant difference in the left ventricular dimensions or fractional shortening by echocardiography or in the incidence of spontaneous arrhythmias by telemetric monitoring. While recipients of hESC-CMs and vehicle showed a similar incidence of arrhythmias induced by programmed electrical stimulation at 4-weeks post-transplantation, non-CM recipients proved to be highly inducible, with a ~3-fold greater incidence of induced arrhythmias. In parallel studies, we investigated the ability of hESC-CMs to couple with host myocardium in chronically injured hearts by the intravital imaging of hESC-CM grafts that stably expressed a fluorescent reporter of graft activation, the genetically-encoded calcium sensor GCaMP3. In this work, we found that only ~38% (5 of 13) of recipients of GCaMP3+ hESC-CMs showed fluorescent transients that were coupled to the host electrocardiogram. Conclusions hESC-CMs engraft in chronically injured hearts without increasing the incidence of arrhythmias, but their electromechanical integration is more limited than was previously reported following

  20. Recurrent apnea induces neuronal apoptosis in the guinea pig forebrain.

    PubMed

    Zhang, Jian-Hua; Fung, Simon J; Xi, Mingchu; Sampogna, Sharon; Chase, Michael H

    2009-04-01

    Obstructive sleep apnea (OSA) and sleep-disordered breathing (SDB) can result in impaired cognition and mental acuity, and the generation of mood disorders, including depression. However, the mechanisms of neuronal damage for these complications have not been elucidated. Accordingly, using immunohistochemical technique with monoclonal antibody against single-stranded DNA, we examined the morphological effects of chronic recurrent apnea on neurons in the hippocampus and related forebrain sites in guinea pigs. Our results show that a large number of neurons labeled by anti-ssDNA antibody were present in the cingulate, insular and frontal cortices, the hippocampus and the amygdala in conjunction with periods of recurrent apnea. However, no labeling was observed in comparable regions of the brain in control guinea pigs. In the cortices of experimental animals, labeled neurons were detected mainly in the superficial layers (II-III) in the frontal, insular and cingulate cortex. In the hippocampus, most labeled neurons were located in the CA1 region, in which most of stained neurons were observed in strata pyramidal, while only a few positive neurons were located in the strata radiatum and the strata oriens. In addition, a large number of labeled neurons were also detected in the central nucleus of amygdala in the guinea pigs underwent recurrent periods of apnea. The present data indicate that recurrent apnea results in cell death in the hippocampus and related forebrain regions via mechanisms of apoptosis, which may represent the basis for the clinical complications of obstructive sleep apnea and sleep-disordered breathing.

  1. Characterization of the guinea pig animal model and subsequent comparison of the behavioral effects of selective dopaminergic drugs and methamphetamine

    PubMed Central

    Lee, Kiera-Nicole; Pellom, Samuel T.; Oliver, Ericka; Chirwa, Sanika

    2014-01-01

    Though not commonly used in behavior tests guinea pigs may offer subtle behavior repertoires that better mimic human activity and warrant study. To test this, 31 Hartley guinea pigs (male, 200–250 g) were evaluated in PhenoTyper cages using the video-tracking EthoVision XT 7.0 software. Results showed that guinea pigs spent more time in the hidden zone (small box in corner of cage) than the food/water zone, or arena zone. Guinea pigs exhibited thigmotaxis (a wall following strategy) and were active throughout the light and dark phases. Eating and drinking occurred throughout the light and dark phases. An injection of 0.25 mg/kg SCH23390, the dopamine D1 receptors (D1R) antagonist, produced significant decreases in time spent in the hidden zone. There were insignificant changes in time spent in the hidden zone for guinea pigs treated with 7.5 mg SKF38393 (D1R agonist), 1.0 mg/kg sulpiride (D2R antagonist), and 1.0 or 10.0 mg/kg methamphetamine. Locomotor activity profiles were unchanged after injections of saline, SKF38393, SCH23390 and sulpiride. By contrast, a single injection or repeated administration for 7 days of low-dose methamphetamine induced transient hyperactivity but this declined to baseline levels over the 22-hour observation period. Guinea pigs treated with high-dose methamphetamine displayed sustained hyperactivity and travelled significantly greater distances over the circadian cycle. Subsequent 7-day treatment with high-dose methamphetamine induced motor sensitization and significant increases in total distances moved relative to single drug injections or saline controls. These results highlight the versatility and unique features of the guinea pig for studying brain-behavior interactions. PMID:24436154

  2. Fatty acid ethyl esters (FAEE); comparative accumulation in human and guinea pig hair as a biomarker for prenatal alcohol exposure.

    PubMed

    Kulaga, Vivian; Caprara, Daniela; Iqbal, Umar; Kapur, Bhushan; Klein, Julia; Reynolds, James; Brien, James; Koren, Gideon

    2006-01-01

    To compare the incorporation rate (ICR) of fatty acid ethyl esters (FAEE) in hair between guinea pigs and humans, and to assess the relationship between ethanol exposure and FAEE concentrations in hair. Published data from pregnant guinea pigs, including maximum blood ethanol concentration (BEC), dosage regimen, and total hair FAEE concentration, were compared with published data from alcoholic patients, where dose of ethanol consumed and total hair FAEE concentration were reported. Mean values of ethanol Vmax for pregnant guinea pigs and humans were obtained from published data (26.2 and 24 mg/dl/h, respectively). Total and individual FAEE ICRs, defined as the ratio of hair FAEE to the area under the BEC-time curve (total systemic ethanol exposure), were found to be on average an order of magnitude lower in the guinea pig than in the human. The profiles of ester incorporation also differed slightly between species, with ethyl stearate being highly incorporated in guinea pig hair and less so in human hair. The results may reflect in the human greater FAEE production, greater FAEE deposition in hair, slower FAEE catabolism, differential sebum production and composition, or a combination thereof. Also, ethyl oleate was found to correlate with total systemic ethanol exposure for both guinea pigs and humans, correlation coefficients equalling 0.67 (P < 0.05) and 0.49 (P < 0.05), respectively. No other ethyl esters, nor total FAEE, were found to correlate with systemic ethanol exposure. When extrapolating FAEE concentrations in hair from guinea pigs to humans, an order of magnitude difference should be considered, with humans incorporating more FAEE per unit of ethanol exposure. Also, the results suggest caution should be taken when interpreting values of single esters because of their differential incorporation among species. Lastly, our findings suggest ethyl oleate may be of keen interest in FAEE hair analysis, particularly across species.

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

    PubMed

    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.

  4. Cloning and functional characterization of the guinea pig apoptosis inhibitor protein Survivin.

    PubMed

    Habtemichael, Negusse; Wünsch, Desiree; Bier, Carolin; Tillmann, Sarah; Unruhe, Britta; Frauenknecht, Katrin; Heinrich, Ulf-Rüdiger; Mann, Wolf J; Stauber, Roland H; Knauer, Shirley K

    2010-12-01

    The guinea pig is widely used as a model to study (patho)physiological processes, such as neurodegenerative disorders. Survivin's dual function as an apoptosis inhibitor and a mitotic regulator is crucial not only for ordered development but its modulation seems crucial also under disease conditions. However, data on the expression and function of the guinea pig Survivin protein (Survivin(Gp)) are currently lacking. Here, we here report the cloning and functional characterization of Survivin(Gp). The respective cDNA was cloned from spleen mRNA, containing a 426 bp open reading frame encoding for a protein of 142aa. Survivin(Gp) displays a high homology to the human and murine orthologue, especially in domains critical for function, such as binding sites for chromosomal passenger complex (CPC) proteins and the nuclear export signal (NES). Notably, phylogenetic analyses revealed that Survivin(Gp) is more related to humans than to rodents. Ectopic expression studies of a Survivin(Gp)-GFP fusion confirmed its dynamic intracellular localization, analogous to the human and murine counterparts. In interphase cells, Survivin(Gp)-GFP was predominantly cytoplasmic and accumulated in the nucleus following export inhibition with leptomycin B (LMB). A typical CPC protein localization during mitosis was observed for Survivin(Gp)-GFP. Microinjection experiments together with genetic knockout demonstrated that the NES is essential for the anti-apoptotic and regulatory role of Survivin(Gp) during cell division. In vivo protein interaction assays further demonstrated its dimerization with human Survivin and its interaction with human CPC proteins. Importantly, RNAi-depletion studies show that Survivin(Gp) can fully substitute for human Survivin as an apoptosis inhibitor and a mitotic effector. Immunohistochemistry, immunofluorescence, and western blotting were employed to detect Survivin expression in guinea pig tissues. Besides its expression in proliferating tissues, such as

  5. Comparison of cannabinoid binding sites in guinea-pig forebrain and small intestine

    PubMed Central

    Ross, Ruth A; Brockie, Heather C; Fernando, Susanthi R; Saha, Bijali; Razdan, Raj K; Pertwee, Roger G

    1998-01-01

    We have investigated the nature of cannabinoid receptors in guinea-pig small intestine by establishing whether this tissue contains cannabinoid receptors with similar binding properties to those of brain CB1 receptors. The cannabinoids used were the CB1-selective antagonist SR141716A, the CB2-selective antagonist SR144528, the novel cannabinoid receptor ligand, 6′-azidohex-2′-yne-Δ8-tetrahydrocannabinol (O-1184), and the agonists CP55940, which binds equally well to CB1 and CB2 receptors, and WIN55212-2, which shows marginal CB2 selectivity.[3H]-CP55940 (1 nM) underwent extensive specific binding both to forebrain membranes (76.3%) and to membranes obtained by sucrose density gradient fractionation of homogenates of myenteric plexus-longitudinal muscle of guinea-pig small intestine (65.2%).Its binding capacity (Bmax) was higher in forebrain (4281 fmol mg−1) than in intestinal membranes (2092 fmol mg−1). However, the corresponding KD values were not significantly different from each other (2.29 and 1.75 nM respectively). Nor did the Ki values for its displacement by CP55940, WIN55212-2, O-1184, SR141716A and SR144528 from forebrain membranes (0.87, 4.15, 2.85, 5.32 and 371.9 respectively) differ significantly from the corresponding Ki values determined in experiments with intestinal membranes (0.99, 5.03, 3.16, 4.95 and 361.5 nM respectively).The Bmax values of [3H]-CP55940 and [3H]-SR141716A in forebrain membranes did not differ significantly from each other (4281 and 5658 fmol mg−1) but were both greater than the Bmax of [3H]-WIN55212-2 (2032 fmol mg−1).O-1184 (10 or 100 nM) produced parallel dextral shifts in the log concentration-response curves of WIN55212-2 and CP55940 for inhibition of electrically-evoked contractions of the myenteric plexus-longitudinal muscle preparation, its KD values being 0.20 nM (against WIN55212-2) and 0.89 nM (against CP55940).We conclude that cannabinoid binding sites in guinea-pig small

  6. Effects of polypeptide from Chlamys farreri on amino acid content in guinea pig skin irradiated by chronic ultraviolet A and B

    NASA Astrophysics Data System (ADS)

    Yu, Guoying; Cao, Pengli; Guo, Kun; Wang, Yuejun; Sun, Mi; Wang, Chunbo

    2004-12-01

    We examined the effects of polypeptide from Chlamys farreri (PCF) on the amount of hydroxyproline in guinea pig skin irradiated by chronic ultraviolet A (UVA) and ultraviolet B (UVB) radiation. PCF was applied locally before repeated exposure of guinea pig to UVA and UVB. The contents of hydroxyproline and other amino acids in guinea pig skin were determined by automatic amino acid analyzer. Our results showed that: (1) long-time UVA and UVB radiation can reduce dramatically the amounts of hydroxyproline, aspartic acid, threonine, glycine, phenylalanine and lysine in guinea pig skin in comparison with the control group ( P<0.05); (2) Compared with model group, pre-treatment with 5% and 20% PCF prior to UVA and UVB radiation can inhibit the decline of amino acids content in guinea pig skin in a dose-dependent manner ( P<0.05). As the decrease of hydroxyproline, glycine and lysine contents in the skin directly reflexes type I collagen degeneration, our results indicated that the chronic application of PCF can protect skin type I collagen against UV radiation, and thus protect skin from photoaging.

  7. Myocarditis in mice and guinea pigs experimentally infected with a canine-origin Borrelia isolate from Florida.

    PubMed

    Breitschwerdt, E B; Geoly, F J; Meuten, D J; Levine, J F; Howard, P; Hegarty, B C; Stafford, L C

    1996-04-01

    To characterize the pathogenic potential of a unique Borrelia isolate obtained from a dog from Florida (FCB isolate). Prospective experimental infection. 32 preweanling Swiss Webster mice and 12 adult male Hartley guinea pigs were injected intraperitoneally with 10(5) spirochetes. Mice were used as controls and blood recipients, and at 3- to 4-day intervals, 1 control mouse and 2 infected mice were necropsied, tissues were cultured, and a recipient mouse was inoculated with blood. Guinea pigs were randomized to 4 groups and inoculated intradermally with 10(0), 10(2), 10(3), or 10(4) spirochetes. For 48 days, clinical, hematologic, serologic, and microbiologic tests were performed on them, after which they were necropsied. In mice, spirochetemia was detectable between postinoculation days (PID) 3 and 13, and seroreactivity to homologous antigen was detectable during PID 10 through 31. Compared with control mice, infected mouse spleens were 2 to 3 times larger. Histologic lesions included lymphoid hyperplasia, neutrophilic panniculitis, epicarditis, and myocarditis, with intralesional spirochetes detected from PID 3 through 6. During PID 10 through 31, nonsuppurative epicarditis developed. Signs of illness and hematologic abnormalities were not observed in guinea pigs, despite isolating spirochetes from blood during PID 7 to 27. When necropsied on PID 48, histologic lesions included lymphoid hyperplasia and lymphocytic plasmacytic epicarditis. The FCB isolate causes spirochetemia, lymphoid hyperplasia, dermatitis, and myocardial injury in Swiss Webster mice and can be transmitted by blood inoculation. In Hartley guinea pigs, the isolate causes spirochetemia, lymphoid hyperplasia, and epicarditis. Documentation of disease in mice, guinea pigs, and, presumably, dogs raises the level of concern that the FCB isolate might be pathogenic for man and other animal species.

  8. Inhibiting Mitochondrial Na+/Ca2+ Exchange Prevents Sudden Death in a Guinea Pig Model of Heart Failure

    PubMed Central

    Liu, Ting; Takimoto, Eiki; Dimaano, Veronica L.; DeMazumder, Deeptankar; Kettlewell, Sarah; Smith, Godfrey; Sidor, Agnieszka; Abraham, Theodore P.; O’Rourke, Brian

    2014-01-01

    Rationale In cardiomyocytes from failing hearts, insufficient mitochondrial Ca2+ ([Ca2+]m) accumulation secondary to cytoplasmic Na+ overload decreases NAD(P)H/NAD(P)+ redox potential and increases oxidative stress when workload increases. These effects are abolished by enhancing [Ca2+]m with acute treatment with CGP-37157 (CGP), an inhibitor of the mitochondrial Na+/Ca2+ exchanger. Objective To determine if chronic CGP treatment mitigates contractile dysfunction and arrhythmias in an animal model of heart failure (HF) and sudden cardiac death (SCD). Methods and Results Here, we describe a novel guinea-pig HF/SCD model employing aortic constriction combined with daily β-adrenergic receptor stimulation (ACi) and show that chronic CGP treatment (ACi+CGP) attenuates cardiac hypertrophic remodeling, pulmonary edema, and interstitial fibrosis and prevents cardiac dysfunction and SCD. In the ACi group 4 weeks after pressure-overload, fractional shortening and the rate of left ventricular pressure development decreased by 36% and 32%, respectively, compared to sham-operated controls; in contrast, cardiac function was completely preserved in the ACi+CGP group. CGP treatment also significantly reduced the incidence of premature ventricular beats and prevented fatal episodes of ventricular fibrillation, but did not prevent QT prolongation. Without CGP treatment, mortality was 61% in the ACi group within 4 weeks of aortic constriction, while the death rate in the ACi+CGP group was not different from sham-operated animals. Conclusions The findings demonstrate the critical role played by altered mitochondrial Ca2+ dynamics in the development of HF and HF-associated SCD; moreover, they reveal a novel strategy for treating SCD and cardiac decompensation in HF. PMID:24780171

  9. In vivo effects of the IKr agonist NS3623 on cardiac electrophysiology of the guinea pig.

    PubMed

    Hansen, Rie Schultz; Olesen, Søren-Peter; Rønn, Lars Christian B; Grunnet, Morten

    2008-07-01

    The long QT syndrome is characterized by a prolongation of the QT interval measured on the surface electrocardiogram. Prolonging the QT interval increases the risk of dangerous ventricular fibrillations, eventually leading to sudden cardiac death. Pharmacologically induced QT interval prolongations are most often caused by antagonizing effects on the repolarizing cardiac current called IKr. In humans IKr is mediated by the human ether-a-go-go related gene (hERG) potassium channel. We recently presented NS3623, a compound that selectively activates this channel. The present study was dedicated to examining the in vivo effects of NS3623. Injection of 30 mg/kg NS3623 shortened the corrected QT interval by 25 +/- 4% in anaesthetized guinea pigs. Accordingly, 50 mg/kg of NS3623 shortened the QT interval by 30 +/- 6% in conscious guinea pigs. Finally, pharmacologically induced QT prolongation by a hERG channel antagonist (0.15 mg/kg E-4031) could be reverted by injection of NS3623 (50 mg/kg) in conscious guinea pigs. In conclusion, the present in vivo study demonstrates that injection of the hERG channel agonist NS3623 results in shortening of the QTc interval as well as reversal of a pharmacologically induced QT prolongation in both anaesthetized and conscious guinea pigs.

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

    PubMed

    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.

  11. Passive smoke effects on cough and airways in young guinea pigs: role of brainstem substance P.

    PubMed

    Joad, Jesse P; Munch, Paul A; Bric, John M; Evans, Samuel J; Pinkerton, Kent E; Chen, Chao-Yin; Bonham, Ann C

    2004-02-15

    Children raised with extended exposure to environmental tobacco smoke (ETS) experience increased cough and wheeze. This study was designed to determine whether extended ETS exposure enhances citric acid-induced cough and bronchoconstriction in young guinea pigs via a neurokinin-1 (NK-1) receptor mechanism at the first central synapse of lung afferent neurons, the nucleus tractus solitarius. Guinea pigs were exposed to ETS from 1 to 6 weeks of age. At 5 weeks of age, guide cannulae were implanted bilaterally in the medial nucleus tractus solitarius at a site that produced apnea in response to the glutamate agonist D,L-homocysteic acid. At 6 weeks of age, either vehicle or a NK-1 receptor antagonist, SR 140333, was injected into the nucleus tractus solitarius of the conscious guinea pigs who were then exposed to citric acid aerosol. ETS exposure significantly enhanced citric acid-induced cough by 56% and maximal Penh (a measure of airway obstruction) by 43%, effects that were attenuated by the NK-1 receptor antagonist in the nucleus tractus solitarius. We conclude that in young guinea pigs extended exposure to ETS increases citric acid-induced cough and bronchoconstriction in part by an NK-1 receptor mechanism in the nucleus tractus solitarius.

  12. Differential growth of allogeneic bone marrow and leukemia cells in irradiated guinea pigs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bhan, A,K.; Kumar, V.; Bennett, M.

    1979-11-01

    Growth of normal bone marrow and L/sub 2/C leukemia cell grafts was studied in lethally irradiated strain 2 and strain 13 guinea pigs. Allogeneic bone marrow cells proliferated as well as syngeneic cells in both strain 2 and 13 animals. This observation indicates that Ia disparities are not relevant to marrow graft rejection in the guinea pig. Both Ia positive and Ia negative L/sub 2/C leukemia cells of strain 2 origin grew well in the spleen of irradiated strain 2 animals. However, irradiated strain 13 animals showed resistance to the growth of both leukemia cell lines. F/sub 1/ hybrids (2more » x 13) also showed resistance to the growth of the leukemia cells. These observations suggest the existence of an effector system capable of mediating natural resistance to L/sub 2/C cells in unimmunized strain 13 and F/sub 1/ guinea pigs. The nature of antigens recognized by these radiation resistant effector cells are not entirely clear. However, Ia antigens, or tumor-associated antigens dependent upon Ia antigens for immunogenicity, do not seem to be the primary targets in this phenomenon.« less

  13. Trichinella spiralis infection enhances protein kinase C phosphorylation in guinea pig alveolar macrophages.

    PubMed

    Dzik, J M; Zieliński, Z; Cieśla, J; Wałajtys-Rode, E

    2010-03-01

    To learn more about the signalling pathways involved in superoxide anion production in guinea pig alveolar macrophages, triggered by Trichinella spiralis infection, protein level and phosphorylation of mitogen activated protein (MAP) kinases and protein kinase C (PKC) were investigated. Infection with T. spiralis, the nematode having 'lung phase' during colonization of the host, enhances PKC phosphorylation in guinea pig alveolar macrophages. Isoenzymes beta and delta of PKC have been found significantly phosphorylated, although their location was not changed as a consequence of T. spiralis infection. Neither in macrophages from T. spiralis-infected guinea pig nor in platelet-activating factor (PAF)-stimulated macrophages from uninfected animals, participation of MAP kinases in respiratory burst activation was statistically significant. The parasite antigens seem to act through macrophage PAF receptors, transducing a signal for enhanced NADPH oxidase activity, as stimulating effect of newborn larvae homogenate on respiratory burst was abolished by specific PAF receptor antagonist CV 6209. A suppressive action of T. spiralis larvae on host alveolar macrophage innate immunological response was reflected by diminished protein level of ERK2 kinase and suppressed superoxide anion production, in spite of high level of PKC phosphorylation.

  14. A SKIN TEST FOR DETECTING GROUP C HEMOLYTIC STREPTOCOCCAL INFECTION CAUSING EPIZOOTIC LYMPHADENITIS IN GUINEA PIGS

    PubMed Central

    Moen, Johannes K.

    1936-01-01

    1. A skin test with a crude bacterial extract prepared from group C (Lancefield) hemolytic streptococci was used as a means of detecting possible carriers of the streptococcus causing epizootic lymphadenitis in guinea pigs. A positive test similar to a positive tuberculin reaction was considered presumptive evidence of present or recent infection with this streptococcus. 2. 20 positive reactors were found in 330 supposedly normal guinea pigs. 3. 195 negatively reacting animals were used as a breeding stock which yielded 1,296 progeny over a period of 15 months. None of the breeding stock or their progeny showed evidence of spontaneous lymphadenitis. Skin tests of 100 of the progeny were all negative. 4. The use of this skin test as a means of obtaining guinea pig breeding stock free of the streptococcus causing spontaneous lymphadenitis is suggested. PMID:19870552

  15. Use of the hyperinsulinemic euglycemic clamp to assess insulin sensitivity in guinea pigs: dose response, partitioned glucose metabolism, and species comparisons.

    PubMed

    Horton, Dane M; Saint, David A; Owens, Julie A; Gatford, Kathryn L; Kind, Karen L

    2017-07-01

    The guinea pig is an alternate small animal model for the study of metabolism, including insulin sensitivity. However, only one study to date has reported the use of the hyperinsulinemic euglycemic clamp in anesthetized animals in this species, and the dose response has not been reported. We therefore characterized the dose-response curve for whole body glucose uptake using recombinant human insulin in the adult guinea pig. Interspecies comparisons with published data showed species differences in maximal whole body responses (guinea pig ≈ human < rat < mouse) and the insulin concentrations at which half-maximal insulin responses occurred (guinea pig > human ≈ rat > mouse). In subsequent studies, we used concomitant d-[3- 3 H]glucose infusion to characterize insulin sensitivities of whole body glucose uptake, utilization, production, storage, and glycolysis in young adult guinea pigs at human insulin doses that produced approximately half-maximal (7.5 mU·min -1 ·kg -1 ) and near-maximal whole body responses (30 mU·min -1 ·kg -1 ). Although human insulin infusion increased rates of glucose utilization (up to 68%) and storage and, at high concentrations, increased rates of glycolysis in females, glucose production was only partially suppressed (~23%), even at high insulin doses. Fasting glucose, metabolic clearance of insulin, and rates of glucose utilization, storage, and production during insulin stimulation were higher in female than in male guinea pigs ( P < 0.05), but insulin sensitivity of these and whole body glucose uptake did not differ between sexes. This study establishes a method for measuring partitioned glucose metabolism in chronically catheterized conscious guinea pigs, allowing studies of regulation of insulin sensitivity in this species. Copyright © 2017 the American Physiological Society.

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

    PubMed

    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.

  17. Endogenous gamma-aminobutyric acid modulates tonic guinea pig airway tone and propofol-induced airway smooth muscle relaxation.

    PubMed

    Gallos, George; Gleason, Neil R; Virag, Laszlo; Zhang, Yi; Mizuta, Kentaro; Whittington, Robert A; Emala, Charles W

    2009-04-01

    Emerging evidence indicates that an endogenous autocrine/paracrine system involving gamma-aminobutyric acid (GABA) is present in airways. GABAA channels, GABAB receptors, and the enzyme that synthesizes GABA have been identified in airway epithelium and smooth muscle. However, the endogenous ligand itself, GABA, has not been measured in airway tissues. The authors sought to demonstrate that GABA is released in response to contractile agonists and tonically contributes a prorelaxant component to contracted airway smooth muscle. The amount and cellular localization of GABA in upper guinea pig airways under resting and contracted tone was determined by high pressure liquid chromatography and immunohistochemistry, respectively. The contribution that endogenous GABA imparts on the maintenance of airway smooth muscle acetylcholine-induced contraction was assessed in intact guinea pig airway tracheal rings using selective GABAA antagonism (gabazine) under resting or acetylcholine-contracted conditions. The ability of an allosteric agent (propofol) to relax a substance P-induced relaxation in an endogenous GABA-dependent manner was assessed. GABA levels increased and localized to airway smooth muscle after contractile stimuli in guinea pig upper airways. Acetylcholine-contracted guinea pig tracheal rings exhibited an increase in contracted force upon addition of the GABAA antagonist gabazine that was subsequently reversed by the addition of the GABAA agonist muscimol. Propofol dose-dependently relaxed a substance P contraction that was blocked by gabazine. These studies demonstrate that GABA is endogenously present and increases after contractile stimuli in guinea pig upper airways and that endogenous GABA contributes a tonic prorelaxant component in the maintenance of airway smooth muscle tone.

  18. Endogenous γ-aminobutyric Acid Modulates Tonic Guinea Pig Airway Tone and Propofol-induced Airway Smooth Muscle Relaxation

    PubMed Central

    Gallos, George; Gleason, Neil R.; Virag, Laszlo; Zhang, Yi; Mizuta, Kentauro; Whittington, Robert A.; Emala, Charles W.

    2009-01-01

    Background Emerging evidence indicates that an endogenous autocrine/paracrine system involving γ-aminobutyric acid (GABA) is present in airways. GABAA channels, GABAB receptors and the enzyme that synthesizes GABA have been identified in airway epithelium and smooth muscle. However, the endogenous ligand itself, GABA, has not been measured in airway tissues. We sought to demonstrate that GABA is released in response to contractile agonists and tonically contributes a pro-relaxant component to contracted airway smooth muscle. Methods The amount and cellular localization of GABA in upper guinea pig airways under resting and contracted tone was determined by high pressure liquid chromatography and immunohistochemistry, respectively. The contribution that endogenous GABA imparts on the maintenance of airway smooth muscle acetylcholine-induced contraction was assessed in intact guinea pig airway tracheal rings using selective GABAA antagonism (gabazine) under resting or acetylcholine-contracted conditions. The ability of an allosteric agent (propofol) to relax a substance P-induced relaxation in an endogenous GABA-dependent manner was assessed. Results GABA levels increased and localized to airway smooth muscle following contractile stimuli in guinea pig upper airways. Acetylcholine-contracted guinea pig tracheal rings exhibited an increase in contracted force upon addition of the GABAA antagonist gabazine which was subsequently reversed by the addition of the GABAA agonist muscimol. Propofol dose-dependently relaxed a substance P contraction that was blocked by gabazine. Conclusion These studies demonstrate that GABA is endogenously present and increases following contractile stimuli in guinea pig upper airways and that endogenous GABA contributes a tonic pro-relaxant component in the maintenance of airway smooth muscle tone. PMID:19322939

  19. Evaluation of Pain Assessment Techniques and Analgesia Efficacy in a Female Guinea Pig (Cavia porcellus) Model of Surgical Pain

    PubMed Central

    Oliver, Vanessa L; Athavale, Stephanie; Simon, Katherine E; Kendall, Lon V; Nemzek, Jean A; Lofgren, Jennifer L

    2017-01-01

    Guinea pigs (Cavia porcellus) are a frequently used species in research, often involving potentially painful procedures. Therefore, evidence-based recommendations regarding analgesia are critically needed to optimize their wellbeing. Our laboratory examined the efficacy of carprofen and extended-release (ER) buprenorphine, alone and as a multimodal combination, for relieving postsurgical pain in guinea pigs. Animals were assessed by using evoked (mechanical hypersensitivity), nonevoked (video ethogram, cageside ethogram, time-to-consumption test), and clinical (weight loss) measurements for 96 h during baseline, anesthesia–analgesia, and hysterectomy conditions. In addition, ER buprenorphine was evaluated pharmacologically. Guinea pigs treated with a single analgesic showed increased mechanical sensitivity for at least 96 h and indices of pain according to the video ethogram for as long as 8 h, compared with levels recorded during anesthesia–analgesia. In contrast, animals given both analgesics demonstrated increased mechanical sensitivity and behavioral evidence of pain for only 2 h after surgery compared with anesthesia–analgesia. The cageside ethogram and time-to-consumption tests failed to identify differences between conditions or treatment groups, highlighting the difficulty of identifying pain in guinea pigs without remote observation. Guinea pigs treated with multimodal analgesia or ER buprenorphine lost at least 10% of their baseline weights, whereas weight loss in carprofen animals was significantly lower (3%). Plasma levels for ER buprenorphine exceeded 0.9 ng/mL from 8 to 96 h after injection. Of the 3 analgesia regimens evaluated, multimodal analgesia provided the most effective pain control in guinea pigs. However the weight loss in the ER buprenorphine–treated animals may need to be considered during analgesia selection. PMID:28724492

  20. Role of αA-crystallin-derived αA66-80 peptide in guinea pig lens crystallin aggregation and insolubilization

    PubMed Central

    Raju, Murugesan; Mooney, Brian P.; Thakkar, Kavi M.; Giblin, Frank J.; Schey, Kevin L.; Sharma, K. Krishna

    2015-01-01

    Earlier we reported that low molecular weight (LMW) peptides accumulate in aging human lens tissue and that among the LMW peptides, the chaperone inhibitor peptide αA66-80, derived from α-crystallin protein, is one of the predominant peptides. We showed that in vitro αA66-80 induces protein aggregation. The current study was undertaken to determine whether LMW peptides are also present in guinea pig lens tissue subjected to hyperbaric oxygen (HBO) in vivo. The nuclear opacity induced by HBO in guinea pig lens is the closest animal model for studying age-related cataract formation in humans. A LMW peptide profile by mass spectrometry showed the presence of an increased amount of LMW peptides in HBO-treated guinea pig lenses compared to age-matched controls. Interestingly, the mass spectrometric data also showed that the chaperone inhibitor peptide αA66-80 accumulates in HBO-treated guinea pig lens. Following incubation of synthetic chaperone inhibitor peptide αA66-80 with α-crystallin from guinea pig lens extracts, we observed a decreased ability of α-crystallin to inhibit the amorphous aggregation of the target protein alcohol dehydrogenase and the formation of large light scattering aggregates, similar to those we have observed with human α-crystallin and αA66-80 peptide. Further, time-lapse recordings showed that a preformed complex of α-crystallin and αA66-80 attracted additional crystallin molecules to form even larger aggregates. These results demonstrate that LMW peptide–mediated cataract development in aged human lens and in HBO-induced lens opacity in the guinea pig may have common molecular pathways. PMID:25639202

  1. Role of αA-crystallin-derived αA66-80 peptide in guinea pig lens crystallin aggregation and insolubilization.

    PubMed

    Raju, Murugesan; Mooney, Brian P; Thakkar, Kavi M; Giblin, Frank J; Schey, Kevin L; Sharma, K Krishna

    2015-03-01

    Earlier we reported that low molecular weight (LMW) peptides accumulate in aging human lens tissue and that among the LMW peptides, the chaperone inhibitor peptide αA66-80, derived from α-crystallin protein, is one of the predominant peptides. We showed that in vitro αA66-80 induces protein aggregation. The current study was undertaken to determine whether LMW peptides are also present in guinea pig lens tissue subjected to hyperbaric oxygen (HBO) in vivo. The nuclear opacity induced by HBO in guinea pig lens is the closest animal model for studying age-related cataract formation in humans. A LMW peptide profile by mass spectrometry showed the presence of an increased amount of LMW peptides in HBO-treated guinea pig lenses compared to age-matched controls. Interestingly, the mass spectrometric data also showed that the chaperone inhibitor peptide αA66-80 accumulates in HBO-treated guinea pig lens. Following incubation of synthetic chaperone inhibitor peptide αA66-80 with α-crystallin from guinea pig lens extracts, we observed a decreased ability of α-crystallin to inhibit the amorphous aggregation of the target protein alcohol dehydrogenase and the formation of large light scattering aggregates, similar to those we have observed with human α-crystallin and αA66-80 peptide. Further, time-lapse recordings showed that a preformed complex of α-crystallin and αA66-80 attracted additional crystallin molecules to form even larger aggregates. These results demonstrate that LMW peptide-mediated cataract development in aged human lens and in HBO-induced lens opacity in the guinea pig may have common molecular pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. [The improvement of mixed human serum-induced anaphylactic reaction death model in guinea pigs].

    PubMed

    Chen, Jiong-Yuan; Lai, Yue; Li, Dang-Ri; Yue, Xia; Wang, Hui-Jun

    2012-12-01

    To increase the death rate of fatal anaphylaxis in guinea pigs and the detectahie level of the tryptase of mast cell in hlood serum. Seventy-four guinea pigs were randomly divided into five groups: original model group, original model control group, improved model group, improved model control group, improved model with non-anaphylaxis group. Using mixed human serum as the allergen, the way of injection, sensitization and induction were improved. ELISA was used to detect the serum mast cell tryptase and total IgE in guinea pigs of each group. The death rate of fatal anaphylaxis in original model group was 54.2% with the different degree of hemopericardium. The severe pericardial tamponade appeared in 9 guinea pigs in original model group and original model control group. The death rate of fatal anaphylaxis in improved model group was 75% without pericardial tamponade. The concentration of the serum total IgE showed no statistically difference hetween original model group and original model control group (P > 0.05), hut the serum mast cell tryptase level was higher in the original model group than that in the original model control group (P > 0.05). The concentration of the serum total IgE and the serum mast cell tryptase level were significantly higher in improved model group than that in the improved model control group (P < 0.05). The death rate of the improved model significantly increases, which can provide effective animal model for the study of serum total IgE and mast cell tryptase.

  3. Validation of a Behavioral Ethogram for Assessing Postoperative Pain in Guinea Pigs (Cavia porcellus)

    PubMed Central

    Dunbar, Misha L; David, Emily M; Aline, Marian R; Lofgren, Jennifer L

    2016-01-01

    Although guinea pigs (Cavia porcellus) have been used in research for more than a century and remain the most prevalent USDA-covered species, little has been elucidated regarding the recognition of clinical pain or analgesic efficacy in this species. We sought to assess pain in guinea pigs by using newer, clinically relevant methods that have been validated in other rodent species: the behavioral ethogram and cageside proxy indicator. In this study, 10 male guinea pigs underwent electronic von Frey testing of nociception, remote videorecording of behavior, and cageside assessment by using time-to-consumption (TTC) of a preferred treat test. These assessments were performed across 2 conditions (anesthesia only and castration surgery under anesthesia) at 3 time points (2, 8, and 24 h after the event). The anesthesia only condition served to control for the nonpainful but potentially distressing components of the surgical experience. Compared with those after anesthesia only conditions, subtle body movements were increased and nociceptive thresholds were decreased at 2 and 8 h after surgery. At 24 h, neither subtle body movement behaviors nor nociceptive thresholds differed between the 2 conditions. In contrast, TTC scores did not differ between the anesthesia only and surgery conditions at any time point, underscoring the challenge of identifying pain in this species through cageside evaluation. By comparing ethogram scores with measures of nociception, we validated select behaviors as pain-specific. Therefore, our novel ethogram allowed us to assess postoperative pain and may further serve as a platform for future analgesia efficacy studies in guinea pigs. PMID:26817977

  4. Ascorbate in the guinea pig lens: dependence on drinking water supplementation.

    PubMed

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

    2005-04-01

    To investigate whether lens ascorbate concentration can be elevated with drinking water supplementation. Pigmented guinea pigs received drinking water supplemented with L-ascorbate, concentration 0.00, 2.84, 5.68 or 8.52 mm for a duration of 4 weeks. In addition, the chow fed to all animals contained 125 mmol L-ascorbate per kg of chow. At the end of the supplementation period, the guinea pigs were killed. Each lens was extracted. The lens was processed and ascorbate concentration was measured using high performance liquid chromatography (HPLC) with 254 nm ultraviolet radiation detection. The data were analysed with regression. At the end of the test period, all lenses were devoid of cataract as observed by slit-lamp examination. All lenses contained a detectable concentration of ascorbate. Estimated 95% confidence intervals for mean animal-averaged lens ascorbate concentrations (micromol/g wet weight of whole lens) per group were 0.51 +/- 0.04 (0.00 mm; n = 6), 0.70 +/- 0.18 (2.84 mm; n = 6), 0.71 +/- 0.11 (5.68 mm; n = 5), and 0.71 +/- 0.06 (8.52 mm; n = 6). Animal-averaged lens ascorbate concentration [Asc(lens)] (micromol/g wet weight lens) increased with ascorbate supplementation in drinking water [Asc(water)] (M), in agreement with the model: [Asc(lens)] = A - Be(-kAsc(water)]. Lens ascorbate concentration increases with drinking water supplementation in the guinea pig without cataract development. The currently presented method for measurement of whole lens ascorbate content is suitable.

  5. Genetic predisposition to liver damage after halothane anesthesia in guinea pigs.

    PubMed

    Lunam, C A; Cousins, M J; Hall, P M

    1986-11-01

    Three 4-hr normoxic (21% oxygen) exposures to 1% halothane administered 3 days apart were associated with elevations in serum alanine aminotransferase (ALT) activity in four of 20 guinea pigs after the initial and third exposures. Serum alanine aminotransferase values were not measured after the second anesthetic. Susceptibility was defined as an ALT level greater than 300 IU/L after halothane. Nonsusceptible animals, that is, animals without significant increases in ALT values after halothane, remained nonsusceptible after reexposure. Serum alanine aminotransferase values after the first and third anesthesias were significantly correlated (rs = 0.86, P less than 0.001). Two exposures of another 30 guinea pigs at a 5-week interval resulted in high elevations of ALT in the same eight animals after both anesthetics. In contrast, after an initial exposure nonsusceptible animals remained nonsusceptible upon reexposure. Serum alanine aminotransferase levels after the first and second anesthetics were significantly correlated (rs = 0.85, P less than 0.001). The proportion of first generation (F1) males with elevated ALTs whose parents were susceptible to halothane hepatotoxicity (HH) was significantly higher than the proportion of males with elevated ALTs in a random group of 90 males (P less than 0.005). First generation males and females of nonsusceptible parents had ALTs within the normal range after halothane exposure. These studies suggest that in the guinea pig genetic predisposition is an important determinant of susceptibility to HH, although other contributing factors are not excluded.

  6. Loop diuretics inhibit cholinergic and noncholinergic nerves in guinea pig airways.

    PubMed

    Elwood, W; Lötvall, J O; Barnes, P J; Chung, K F

    1991-06-01

    Furosemide, a loop diuretic, is known to inhibit the response to a variety of indirect bronchial challenges in humans but does not inhibit bronchoconstriction induced by inhaled methacholine or histamine. We have investigated the effects of the two loop diuretics, furosemide (10(-6) to 10(-3) M) and bumetanide (10(-7) to 10(-4) M), on airway smooth muscle contraction in vitro induced by electrical field stimulation (EFS), or exogenously applied acetylcholine (ACh) or substance P (SP) in guinea pig tracheal and bronchial smooth muscle strips pretreated with indomethacin (10(-5) M) and propranolol (10(-6) M). Both furosemide and bumetanide caused a concentration-dependent inhibition of cholinergically mediated neural contraction in the trachea. The effect of furosemide was not influenced by the presence of airway epithelium. Furthermore, both furosemide and bumetanide inhibited in a concentration-dependent fashion nonadrenergic, noncholinergic (NANC) contraction induced by electrical field stimulation of bronchi pretreated with atropine (10(-5) M). Neither drug at the highest concentration inhibited the responses to exogenous acetylcholine (10(-8) to 10(-2) M) or substance P (10(-9) to 10(-5) M). Thus loop diuretics inhibit the neurally induced contraction of guinea pig airways without a direct effect on airway smooth muscle. We conclude that loop diuretics inhibit both cholinergic and excitatory NANC neurotransmission in guinea pig airways and that this effect may be related to their inhibitory effects on the sodium-potassium-chloride cotransporter.

  7. Tachykinin receptors and noncholinergic bronchoconstriction in the guinea-pig isolated bronchi.

    PubMed

    Maggi, C A; Patacchini, R; Rovero, P; Santicioli, P

    1991-08-01

    The aim of the study was to assess which type(s) of tachykinin receptor mediate the noncholinergic bronchoconstriction produced by activation (electrical field stimulation) of capsaicin-sensitive primary afferents in epithellum-denuded guinea-pig isolated bronchi. Experiments with natural and synthetic tachykinin agonists indicated the presence of both NK-1 and NK-2 receptors at this level. Experiments with the putative NK-1 (L668, 169) or NK-2 (MEN 10,207, MEN 10,376, L659,877, and R396) selective antagonists against NK-1 and NK-2 selective agonists further supported this conclusion. All the tachykinin antagonists tested reduced the noncholinergic bronchoconstriction to field stimulation with the order of potency MEN 10,207 = MEN 10,376 greater than L659,877 greater than L668,169 congruent to R396. In the presence of peptidase inhibitors, the activity of MEN 10,376 toward the noncholinergic bronchoconstriction was slightly reduced, whereas that of L668,169 was increased. These findings demonstrate that both NK-1 and NK-2 receptors mediate the noncholinergic constriction produced by endogenous tachykinins in guinea-pig bronchi and that the relative contribution of NK-2 receptors is greater than that of NK-1. These findings implicate a major role for neurokinin A rather than for substance P as an endogenous bronchoconstrictor in the guinea-pig isolated bronchi. In the presence of peptidase inhibitors, the relative contribution of NK-1 receptors is increased.

  8. Review of gastric torsion in eight guinea pigs (Cavia porcellus).

    PubMed

    Nógrádi, Anna Linda; Cope, Iain; Balogh, Márton; Gál, János

    2017-12-01

    The authors present eight cases of gastric dilatation and volvulus (GDV) in guinea pigs from the Department and Clinic of Exotic Animal and Wildlife Medicine, University of Veterinary Medicine, Budapest, Hungary between 2012 and 2016. Seven animals were operated on and two survived. Gastric torsion has been noted in many mammalian species. Gastric volvulus has a high morbidity and high mortality rate with a guarded to poor prognosis in all of these species. How GDV develops is still not widely understood. Postmortem examinations, in both our cases and previously reported cases, have failed to reveal the exact causes of the gastric torsions. The aetiology of gastric torsion in guinea pigs is probably multifactorial. Feeding fewer meals per day, eating rapidly, decreased food particle size, exercise, stress after a meal, competition, age, and an aggressive or fearful temperament, are all likely and potential risk factors for GDV development in a similar fashion to dogs. Sex, breeding, dental diseases, anatomical abnormalities, pain and pregnancy may also be contributing factors.

  9. Guinea pig ductus arteriosus. II - Irreversible closure after birth.

    NASA Technical Reports Server (NTRS)

    Fay, F. S.; Cooke, P. H.

    1972-01-01

    To investigate the mechanism underlying irreversibility of ductal closure after birth, studies were undertaken to determine the exact time course for the onset of irreversible closure of the guinea pig ductus arteriosus. Parallel studies of the reactivity of ductal smooth muscle to oxygen and studies of the postpartum cellular changes within the vessel were also carried out.

  10. Effects of Perfluoroisobutene on Guinea Pig Isolated Lung Preparations.

    DTIC Science & Technology

    guinea pigs showed increased sensitivity to 5-hydroxytryptamine, bradykinin, isoprenaline and a thromboxane A2 analogue, but not to carbachol, histamine, prostaglandin D2, adenosine or potassium. These changes were not detected in the TS. If PFIB-induced changes in lung pharmacology contribute to oedema, antagonists of identified mediators may be useful as pretreatments/therapies to pulmonary

  11. A contrastive analysis of laser heating between the human and guinea pig cochlea by numerical simulations.

    PubMed

    Zhang, Kaiyin; Zhang, Yulong; Li, Ji; Wang, Qiuling

    2016-05-23

    The photo-thermal effect has been hypothesised to be one of the most possible biophysical mechanisms for laser-cochlea stimulation. However, there is a lack of studies to date for direct assessing laser heating in humans due to the large body of evidence required to demonstrate safety and efficacy. Instead, the majority focus on animals like the guinea pig, from which a number of valuable results have been gained. However, in light of the increasing need to improve laser safety, it has became necessary to find out whether studies on animals can shed light on safe laser parameters in the human cochlea. Hence, we conducted this contrastive analysis of laser heating between the human and guinea pig cochlea with the aim of assisting further investigations in this field. In this work, a 3D symmetrical model was adopted to simplify the spiraled cochlea. With attention focused on the effect of heat conduction, the time-dependent heat equation was solved using finite element method with the COMSOL Script. In the simulations, cochleae with different sizes and various boundary thermal conditions were utilized. Laser heating in both cochleae has a similar trend. In the first stage, or at the beginning of the laser heating, both cochleae increased their temperatures rapidly. In the second stage in which the laser heating reached a quasi-steady stage, the peak temperatures began to rise slowly as more laser pulses were applied. However, three differences of the laser heating were observed. The first is regarding the temperature rise. The results show that laser heating in guinea pig is higher than that in human under the same laser parameters. The second difference is the fluctuation of temperature rise at the center of the modiolus. There is a larger fluctuation of temperature rise in the guinea pig cochlea, compared with that in the human cochlea. The third one is the time for reaching a steady thermal state. The results show that the guinea pig cochlea takes longer time to

  12. Toxicokinetic of HEMA in guinea pigs.

    PubMed

    Reichl, F-X; Durner, J; Kehe, K; Manhart, J; Folwaczny, M; Kleinsasser, N; Hume, W R; Hickel, R

    2002-01-01

    Unconverted 2-hydroxyethylmethacrylate (HEMA) can be released from dental resin materials and can enter the body in humans. In the present study the uptake, distribution and excretion of 14C-HEMA applied via different routes were examined in vivo in guinea pigs. HEMA (0.02 mmol/kg bw labelled with a tracer dose 14C-HEMA 0.3 Bq/g bw) was administered by gastric tube or by subcutaneous injection. Urine, feces, and exhaled carbon dioxide were collected for 24 h after administration. Guinea pigs were killed 24 h after the beginning of the experiment and various organs removed and 14C radioactivity measured. Low fecal 14C levels (about 2% of the dose) and urinary levels of about 15% after 24 h were noted with either route of administration. Direct measurement of exhaled CO(2) showed that about 70% of the dose left the body via the lungs. Two pathways for the metabolism of 14C-HEMA can be described. It is likely that 14C-pyruvate is formed in vivo resulting in the formation of toxic 14C-HEMA intermediates. 14C-HEMA was taken up rapidly from the stomach and small intestine after gastric administration and was widely distributed in the body following administration by each of the routes. Clearance from most tissues following gastric and intradermal administration was essentially complete within one day. The peak HEMA levels in all tissues examined after 24 h were at least onemillion-fold less than known toxic levels. Copyright 2002 Elsevier Science Ltd.

  13. Glucagon effects on 3H-histamine uptake by the isolated guinea-pig heart during anaphylaxis.

    PubMed

    Rosic, Mirko; Parodi, Oberdan; Jakovljevic, Vladimir; Colic, Maja; Zivkovic, Vladimir; Jokovic, Vuk; Pantovic, Suzana

    2014-01-01

    We estimated the influence of acute glucagon applications on (3)H-histamine uptake by the isolated guinea-pig heart, during a single (3)H-histamine passage through the coronary circulation, before and during anaphylaxis, and the influence of glucagon on level of histamine, NO, O2 (-), and H2O2 in the venous effluent during anaphylaxis. Before anaphylaxis, glucagon pretreatment does not change (3)H-histamine Umax and the level of endogenous histamine. At the same time, in the presence of glucagon, (3)H-histamine Unet is increased and backflux is decreased when compared to the corresponding values in the absence of glucagon. During anaphylaxis, in the presence of glucagon, the values of (3)H-histamine Umax and Unet are significantly higher and backflux is significantly lower in the presence of glucagon when compared to the corresponding values in the absence of glucagon. The level of endogenous histamine during anaphylaxis in the presence of glucagon (6.9-7.38 × 10(-8) μM) is significantly lower than the histamine level in the absence of glucagon (10.35-10.45 × 10(-8) μM). Glucagon pretreatment leads to a significant increase in NO release (5.69 nmol/mL) in comparison with the period before glucagon administration (2.49 nmol/mL). Then, in the presence of glucagon, O2 (-) level fails to increase during anaphylaxis. Also, our results show no significant differences in H2O2 levels before, during, and after anaphylaxis in the presence of glucagon, but these values are significantly lower than the corresponding values in the absence of glucagon. In conclusion, our results show that glucagon increases NO release and prevents the increased release of free radicals during anaphylaxis, and decreases histamine level in the venous effluent during cardiac anaphylaxis, which may be a consequence of decreased histamine release and/or intensified histamine capturing by the heart during anaphylaxis.

  14. Guinea Pig-Adapted Foot-and-Mouth Disease Virus with Altered Receptor Recognition Can Productively Infect a Natural Host▿

    PubMed Central

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

    2007-01-01

    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 (I248→T in 2C, Q44→R in 3A, and L147→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 L147→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 L147→P, and this infection was inhibited by antibodies to αvβ6 and by an FMDV-derived RGD-containing peptide, suggesting that integrin αvβ6 may be used as a receptor for these mutants in the animal (porcine, guinea pig, and suckling mice) host. Substitution T248→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. PMID:17522230

  15. Assessing Zika virus replication and the development of Zika-specific antibodies after a mid-gestation viral challenge in guinea pigs

    PubMed Central

    Fernández-Alarcón, Claudia; Hernandez-Alvarado, Nelmary; Zabeli, Jason C.; Janus, Bradley C.; Putri, Dira S.; Schleiss, Mark R.

    2017-01-01

    Primary Zika virus (ZIKV) infections that occur during pregnancy can cause spontaneous abortion and profoundly disrupt fetal development. While the full range of developmental abnormalities associated with congenital Zika syndrome is not yet known, severe cases of the syndrome can present with microcephaly, extensive neurologic and ocular damage, and pronounced joint malformations. Animal models that accurately recapitulate congenital Zika syndrome are urgently needed for vaccine development and for the study of ZIKV pathogenesis. As guinea pigs have successfully been used to model transplacental infections by cytomegalovirus, syphilis, and Listeria monocytogenes, we sought to test whether ZIKV could productively infect guinea pigs and whether viral transmission with attendant fetal pathology would occur after a mid-gestation viral challenge. We found that guinea pig cells supported ZIKV replication in vitro. Experimental infection of non-pregnant animals did not result in overt disease but low-level, detectable viremia was observed. When pregnant guinea pigs were challenged with ZIKV at between 18 and 21 days gestational age, ZIKV was not detected in maternal or pup blood, plasma, or tissues and no significant differences in maternal weight gain or pup size were observed following challenge. Nonetheless, a robust antibody response against ZIKV was detected in both the pups and dams. These results suggest that, while guinea pigs can model aspects of the immune response to ZIKV infection during pregnancy, naturally circulating ZIKV strains are not pathogenic during the pregnancy of immunocompetent guinea pigs and do not interfere with normal pup development. PMID:29099873

  16. Neuropeptide Y in the guinea-pig biliary tract.

    PubMed

    Allen, J M; Gu, J; Adrian, T E; Polak, J M; Bloom, S R

    1984-07-15

    High concentrations of neuropeptide Y (NPY) have been demonstrated in the gall bladder (16.7 +/- 5.4 pmol/g), cystic duct (25.4 +/- 9.2 pmol/g) and common bile duct (54.7 +/- 11.5 pmol/g) of the guinea-pig using a recently developed radioimmunoassay. Immunoreactive NPY containing nerves were demonstrated in all layers of the biliary tree using immunocytochemistry, being particularly dense in the myenteric and mucosal plexuses.

  17. Exchange protein directly activated by cAMP mediates slow delayed-rectifier current remodeling by sustained β-adrenergic activation in guinea pig hearts.

    PubMed

    Aflaki, Mona; Qi, Xiao-Yan; Xiao, Ling; Ordog, Balazs; Tadevosyan, Artavazd; Luo, Xiaobin; Maguy, Ange; Shi, Yanfen; Tardif, Jean-Claude; Nattel, Stanley

    2014-03-14

    β-Adrenoceptor activation contributes to sudden death risk in heart failure. Chronic β-adrenergic stimulation, as occurs in patients with heart failure, causes potentially arrhythmogenic reductions in slow delayed-rectifier K(+) current (IKs). To assess the molecular mechanisms of IKs downregulation caused by chronic β-adrenergic activation, particularly the role of exchange protein directly activated by cAMP (Epac). Isolated guinea pig left ventricular cardiomyocytes were incubated in primary culture and exposed to isoproterenol (1 μmol/L) or vehicle for 30 hours. Sustained isoproterenol exposure decreased IKs density (whole cell patch clamp) by 58% (P<0.0001), with corresponding decreases in potassium voltage-gated channel subfamily E member 1 (KCNE1) mRNA and membrane protein expression (by 45% and 51%, respectively). Potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) mRNA expression was unchanged. The β1-adrenoceptor antagonist 1-[2-((3-Carbamoyl-4-hydroxy)phenoxy)ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)phenoxy]-2-propanol dihydrochloride (CGP-20712A) prevented isoproterenol-induced IKs downregulation, whereas the β2-antagonist ICI-118551 had no effect. The selective Epac activator 8-pCPT-2'-O-Me-cAMP decreased IKs density to an extent similar to isoproterenol exposure, and adenoviral-mediated knockdown of Epac1 prevented isoproterenol-induced IKs/KCNE1 downregulation. In contrast, protein kinase A inhibition with a cell-permeable highly selective peptide blocker did not affect IKs downregulation. 1,2-Bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetate-AM acetoxymethyl ester (BAPTA-AM), cyclosporine, and inhibitor of nuclear factor of activated T cell (NFAT)-calcineurin association-6 (INCA6) prevented IKs reduction by isoproterenol and INCA6 suppressed isoproterenol-induced KCNE1 downregulation, consistent with signal-transduction via the Ca(2+)/calcineurin/NFAT pathway. Isoproterenol induced nuclear NFATc3/c4

  18. M/sub r/ 25,000 heparin-binding protein from guinea pig brain is a high molecular weight form of basic fibroblast growth factor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moscatelli, D.; Joseph-Silverstein, J.; Manejias, R.

    1987-08-01

    A M/sub r/ 25,000 form of basic fibroblast growth factor (bFGF) has been isolated from guinea pig grain along with the typical M/sub r/ 18,000 form. Both forms were purified to homogeneity by a combination of heparin-affinity chromatography and ion-exchange chromatography on an FPLC Mono S column. The M/sub r/ 25,000 form, like the M/sub r/ 18,000 form was not eluted from the heparin-affinity column with 0.95 M NaCl, but was eluted with 2 M NaCl. The M/sub r/ 25,000 guinea pig protein stimulated plasminogen activator production by cultured bovine capillary endothelial cells in a dose-dependent manner at concentration ofmore » 0.1-10 ngml, the same range that was effective for guinea pig and human M/sub r/ 18,000 bFGFs. The binding of human /sup 125/I-labeled bFGF to baby hamster kidney cells is inhibited equally by the M/sub r/ 25,000 guinea pig protein and the M/sub r/ 18,000 guinea pig and human bFGFs. Polyclonal antibodies raised against human bFGF recognize both the M/sub r/ 25,000 and 18,000 guinea pig proteins in an immunoblot analysis. In a radioimmunoassay, both the M/sub r/ 25,000 and M/sub r/ 18,000 guinea pig proteins compete equally well with iodinated human bFGF for binding to the anti-human bFGF antibodies. When treated with low concentrations of trypsin, the M/sub r/ 25,000 guinea pig bFGF was converted to a M/sub r/ 18,000 protein. These results show that the two molecules are closely related and suggest that the M/sub r/ 25,000 protein shares substantial homology with the M/sub r/ 18,000 bFGF« less

  19. Evaluation of respiratory effects of thermal decomposition products following single and repeated exposures of guinea pigs.

    PubMed

    Detwiler-Okabayashi, K; Schaper, M

    1995-01-01

    Groups of guinea pigs were exposed to the thermal decomposition products (TDP) released from acrylonitrile butadiene styrene (ABS), polypropylene-polyethylene copolymer (CP), polypropylene homopolymer (HP), or plasticized polyvinyl chloride (PVC). In single 50-min exposures to the TDP, guinea pigs exhibited sensory irritation, coughing, and airways constriction. Significant decreases in respiratory frequency (f) occurred during TDP exposure which were magnified during CO2 challenge conducted immediately post-exposure. For each resin, it was possible to demonstrate a linear relationship between the logarithm of heated mass and the percent decrease in f during CO2 challenge. From these relationships, the mass of each resin producing a 50% decrease in f during CO2 challenge (RD50 mass) was obtained. RD50 masses of 2744, 25.2, 16.0, and 6.7 g were obtained for ABS, CP, HP, and PVC, respectively. Thus, the relative potency of their TDP was PVC > CP approximately HP > ABS. Using the RD50 mass of each resin, guinea pigs were exposed to TDP for 50 min/day on 5 consecutive days. These repeated exposures also resulted in sensory irritation, coughing, and airways constriction. However, deaths occurred during exposures, and there was evidence of cumulative respiratory effects, and slower recoveries among survivors. Data obtained in guinea pigs were compared to a previous study with mice exposed to the TDP of the same four resins (Schaper et al. 1994). On the basis of heated mass, mice were 20-500 times more sensitive to the acute respiratory effects of TDP than guinea pigs. Thus, the exposure limits of 0.63, 0.11, 0.08, and 0.35 mg/m3 proposed by Schaper et al. (1994) on the basis of particulates released from ABS, CP, HP and PVC should prevent not only irritation, but also possible coughing, and airways constriction in workers.

  20. Development of the first oligonucleotide microarray for global gene expression profiling in guinea pigs: defining the transcription signature of infectious diseases.

    PubMed

    Jain, Ruchi; Dey, Bappaditya; Tyagi, Anil K

    2012-10-02

    The Guinea pig (Cavia porcellus) is one of the most extensively used animal models to study infectious diseases. However, despite its tremendous contribution towards understanding the establishment, progression and control of a number of diseases in general and tuberculosis in particular, the lack of fully annotated guinea pig genome sequence as well as appropriate molecular reagents has severely hampered detailed genetic and immunological analysis in this animal model. By employing the cross-species hybridization technique, we have developed an oligonucleotide microarray with 44,000 features assembled from different mammalian species, which to the best of our knowledge is the first attempt to employ microarray to study the global gene expression profile in guinea pigs. To validate and demonstrate the merit of this microarray, we have studied, as an example, the expression profile of guinea pig lungs during the advanced phase of M. tuberculosis infection. A significant upregulation of 1344 genes and a marked down regulation of 1856 genes in the lungs identified a disease signature of pulmonary tuberculosis infection. We report the development of first comprehensive microarray for studying the global gene expression profile in guinea pigs and validation of its usefulness with tuberculosis as a case study. An important gap in the area of infectious diseases has been addressed and a valuable molecular tool is provided to optimally harness the potential of guinea pig model to develop better vaccines and therapies against human diseases.

  1. Cyclic cidofovir (cHPMPC) prevents congenital cytomegalovirus infection in a guinea pig model

    PubMed Central

    Schleiss, Mark R; Anderson, Jodi L; McGregor, Alistair

    2006-01-01

    Background Congenital cytomegalovirus (CMV) infection is a major public health problem. Antiviral therapies administered during pregnancy might prevent vertical CMV transmission and disease in newborns, but these agents have not been evaluated in clinical trials. The guinea pig model of congenital CMV infection was therefore used to test the hypothesis that antiviral therapy, using the agent agent cyclic cidofovir (cHPMPC), could prevent congenital CMV infection. Results Pregnant outbred Hartley guinea pigs were challenged in the early-third trimester with guinea pig CMV (GPCMV) and treated with placebo, or the antiviral agent, cyclic cidofovir. To optimize detection of vertical infection, an enhanced green fluorescent protein (eGFP)-tagged virus was employed. Compared to placebo, cyclic cidofovir-treated dams and pups had reduced mortality following GPCMV challenge. The magnitude of GPCMV-induced maternal and fetal mortality in this study was reduced from 5/25 animals in the placebo group to 0/21 animals in the treatment group (p = 0.05, Fisher's exact test). By viral culture assay, antiviral therapy was found to completely prevent GPCMV transmission to the fetus. In control pups, 5/19 (26%) were culture-positive for GPCMV, compared to 0/16 of pups in the cyclic cidofovir treatment group (p < 0.05, Fisher's exact test). Conclusion Antiviral therapy with cyclic cidofovir improves pregnancy outcomes in guinea pigs, and eliminates congenital CMV infection, following viral challenge in the third trimester. This study also demonstrated that an eGFP-tagged recombinant virus, with the reporter gene inserted into a dispensable region of the viral genome, retained virulence, including the potential for congenital transmission, facilitating tissue culture-based detection of congenital infection. These observations provide support for clinical trials of antivirals for reduction of congenital CMV infection. PMID:16509982

  2. Expression and function of human hemokinin-1 in human and guinea pig airways.

    PubMed

    Grassin-Delyle, Stanislas; Naline, Emmanuel; Buenestado, Amparo; Risse, Paul-André; Sage, Edouard; Advenier, Charles; Devillier, Philippe

    2010-10-07

    Human hemokinin-1 (hHK-1) and endokinins are peptides of the tachykinin family encoded by the TAC4 gene. TAC4 and hHK-1 expression as well as effects of hHK-1 in the lung and airways remain however unknown and were explored in this study. RT-PCR analysis was performed on human bronchi to assess expression of tachykinin and tachykinin receptors genes. Enzyme immunoassay was used to quantify hHK-1, and effects of hHK-1 and endokinins on contraction of human and guinea pig airways were then evaluated, as well as the role of hHK-1 on cytokines production by human lung parenchyma or bronchi explants and by lung macrophages. In human bronchi, expression of the genes that encode for hHK-1, tachykinin NK1-and NK2-receptors was demonstrated. hHK-1 protein was found in supernatants from explants of human bronchi, lung parenchyma and lung macrophages. Exogenous hHK-1 caused a contractile response in human bronchi mainly through the activation of NK2-receptors, which blockade unmasked a NK1-receptor involvement, subject to a rapid desensitization. In the guinea pig trachea, hHK-1 caused a concentration-dependant contraction mainly mediated through the activation of NK1-receptors. Endokinin A/B exerted similar effects to hHK-1 on both human bronchi and guinea pig trachea, whereas endokinins C and D were inactive. hHK-1 had no impact on the production of cytokines by explants of human bronchi or lung parenchyma, or by human lung macrophages. We demonstrate endogenous expression of TAC4 in human bronchi, the encoded peptide hHK-1 being expressed and involved in contraction of human and guinea pig airways.

  3. Differences in neurokinin receptor pharmacology between rat and guinea-pig superior cervical ganglia.

    PubMed Central

    Seabrook, G. R.; Main, M.; Bowery, B.; Wood, N.; Hill, R. G.

    1992-01-01

    1. The depolarizations elicited by seven neurokinin receptor agonists were examined in both rat and guinea-pig superior cervical ganglia by use of grease-gap methodology in the presence of tetrodotoxin (0.1 microM). Responses were normalised with respect to 1 microM eledoisin. 2. The rank order of agonist potency in the rat ganglia was senktide greater than substance P greater than substance P methyl ester = eleidosin = Sar-Met-substance P greater than neurokinin B greater than neurokinin A, whereas in guinea-pig superior cervical ganglion (SCG) the rank order was senktide greater than Sar-Met-substance P greater than neurokinin B = eledoisin = substance P methyl ester. The concentration-effect curves for substance P and neurokinin A in guinea-pig ganglia were biphasic which precluded the determination of meaningful potency values. 3. The maximal depolarization achieved by subtype selective ligands was different between these two species. On rat and guinea-pig SCG, the NK3-selective ligand, senktide, produced a maximal depolarization of 27% and 274% respectively, whereas the NK1-selective ligand, substance P methyl ester, produced depolarizations of 77% and 64% respectively. 4. The depolarizations induced by substance P methyl ester and senktide in either species were unaffected by atropine (1 microM), suggesting a lack of involvement of presynaptic neurokinin receptors in the generation of the response. 5. The potency of substance P methyl ester, senktide, and neurokinin A were unaffected by pretreating ganglia with the peptidase inhibitors bacitracin (40 micrograms ml-1), leupeptin (4 micrograms ml-1), and chymostatin (2 micrograms ml-1). Similarly, these peptidase inhibitors had no effect on the maximal depolarizations achieved by any of these agonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1380375

  4. Neuronally mediated non-cholinergic contraction of guinea-pig bronchial smooth muscle is inhibited by a substance P antagonist.

    PubMed

    Leander, S; Grundström, N; Andersson, R G; Håkanson, R

    1984-04-01

    The isolated main bronchi of the guinea-pig respond to electrical field stimulation with a twitch followed by a slow contraction. Atropine blocked the slow contraction. The substance P antagonist, (D-Pro2, D- Trp7 ,9)-SP, greatly reduced the atropine-resistant contraction. The results suggest the involvement of substance P in non-cholinergic neurotransmission in the guinea-pig airways.

  5. Elucidation of Distinct Roles of Guinea Pig CXCR1 and CXCR2 in Neutrophil Migration toward IL-8 and GROα by Specific Antibodies.

    PubMed

    Tanaka, Kento; Yoshitomi, Tomomi; Hirahara, Kazuki

    2017-01-01

    Chemokine receptors CXCR1 and CXCR2 are conserved between guinea pigs and humans, but the distinct role of each receptor in chemotactic responses of neutrophils against chemokine ligands has not been elucidated due in part to the lack of specific inhibitors against these receptors in guinea pigs. In this study, we investigated the roles of guinea pig CXCR1 and CXCR2 on neutrophils in chemotactic responses to guinea pig interleukin (IL)-8 and growth-regulated oncogene (GRO)α by using specific inhibitory antibodies against these receptors. Neutrophil migration induced by IL-8 was partially inhibited by either anti-CXCR1 antibody or anti-CXCR2 antibody. In addition, the migration was inhibited completely when both anti-CXCR1 and anti-CXCR2 antibodies were combined. On the other hand, neutrophil migration induced by GROα was not inhibited by anti-CXCR1 antibody while inhibited profoundly by anti-CXCR2 antibody. These results indicated that CXCR1 and CXCR2 mediated migration induced by the IL-8 synergistically and only CXCR2 mediated migration induced by GROα in guinea pig neutrophils. Our findings on ligand selectivity of CXCR1 and CXCR2 in guinea pigs are consistent with those in humans.

  6. Inhibitors of ATP-sensitive potassium channels in guinea pig isolated ischemic hearts.

    PubMed

    Weyermann, A; Vollert, H; Busch, A E; Bleich, M; Gögelein, H

    2004-04-01

    During heart ischemia, ATP-sensitive potassium channels in the sarcolemmal membrane (sarcK(ATP)) open and cause shortening of the action potential duration. This creates heterogeneity of repolarization, being responsible for the development of re-entry arrhythmias and sudden cardiac death. Therefore, the aim is to develop selective blockers of the cardiac sarcK(ATP) channel. In the present study we established an in vitro model and classified 5 K(ATP) channel inhibitors with respect to their potency and selectivity between cardiomyocytes and the coronary vasculature and compared the results with inhibition of Kir6.2/SUR2A channels expressed in HEK293 cells, recorded with the Rb(+)-efflux methods. We used Langendorff-perfused guinea pig hearts, where low-flow ischemia plus hypoxia was performed by reducing the coronary flow (CF) to 1.2 ml/min and by gassing the perfusion solution with N(2) instead of O(2). Throughout the experiment, the monophasic action potential duration at 90% repolarization (MAPD(90)) was recorded. In separate experiments, high-flow hypoxia was produced by oxygen reduction in the perfusate from 95% to 20%, which caused an increase in the coronary flow. Under normoxic conditions, the substances glibenclamide, repaglinide, meglitinide, HMR 1402 and HMR 1098 (1 microM each) reduced the CF by 34%, 38%, 19%, 12% and 5%, respectively. The hypoxia-induced increase in CF was inhibited by the compounds half-maximally at 25 nM, approximately 200 nM, 600 nM, approximately 9 microM and >100 microM, respectively. In control experiments after 5 min low-flow ischemia plus hypoxia, the MAPD(90) shortened from 121+/-2 to 99+/-2 ms ( n=29). This shortening was half-maximally inhibited by the substances at concentrations of 95 nM, 74 nM, 400 nM, 110 nM and 550 nM, respectively. In HEK293 cells the Rb(+)-efflux through KIR6.2/SUR2A channels was inhibited by the compounds with IC(50) values of 21 nM, 67 nM, 205 nM, 60 nM and 181 nM, respectively. In summary, the

  7. Hypervitaminosis D and Metastatic Calcification in a Colony of Inbred Strain 13 Guinea Pigs, Cavia porcellus.

    PubMed

    Holcombe, H; Parry, N M; Rick, M; Brown, D E; Albers, T M; Refsal, K R; Morris, J; Kelly, R; Marko, S T

    2015-07-01

    A commercial diet fed to a colony of inbred strain 13 guinea pigs for approximately 6 weeks was subsequently recalled for excessive levels of vitamin D. Twenty-one of 62 animals exhibited clinical signs, including anorexia, lethargy, and poor body condition. Nine affected and 4 clinically normal animals were euthanized for further evaluation, including serum chemistry, urinalysis, and gross and/or histopathology. Macroscopic findings included white discoloration in multiple organs in 8 animals, and microscopic evaluation confirmed multiorgan mineralization in tissues from 7 animals. Serum 25-hydroxyvitamin D levels were elevated in 10 animals. Serum inorganic phosphorus and alkaline phosphatase levels were increased in all exposed animals; however, total calcium and ionized calcium levels were not significantly higher in exposed animals than in control strain 13 guinea pigs from a different institution. The data support a diagnosis of hypervitaminosis D with metastatic calcification. Following the diet recall, the remaining guinea pigs increased their food intake and regained body condition. Diagnostic testing of 8 animals euthanized approximately 3 months after returning to a normal diet demonstrated that serum parathyroid hormone remained significantly lower, and ionized calcium and ionized magnesium were significantly higher, in recovered animals compared to controls and exposed animals. These results indicate that diagnostic tests other than serum calcium are necessary for a diagnosis of hypervitaminosis D in guinea pigs. © The Author(s) 2014.

  8. Post-exposure therapy with human butyrylcholinesterase following percutaneous VX challenge in guinea pigs.

    PubMed

    Mumford, Helen; E Price, Matthew; Lenz, David E; Cerasoli, Douglas M

    2011-04-01

    Human butyrylcholinesterase (huBuChE) has potential utility as a post-exposure therapy following percutaneous nerve agent poisoning as there is a slower absorption of agent by this route and hence a later onset of poisoning. METHODS. We used surgically implanted radiotelemetry devices to monitor heart rate, EEG, body temperature and locomotor activity in guinea pigs challenged with VX via the percutaneous route. RESULTS. Treatment with huBuChE (24.2 mg/kg, i.m.) at 30 or 120 min following percutaneous VX (~2.5 × LD(50)) protected 9 out of 10 animals from lethality. When i.m. huBuChE administration was delayed until the onset of observable signs of systemic cholinergic poisoning, only one out of six animals survived to 7 days. Survival increased to 50% when the same dose of huBuChE was given intravenously at the onset of signs of poisoning. This dose represents approximately 1/10th the stoichiometric equivalent of the dose of VX administered (0.74 mg/kg). Intramuscular administration of huBuChE (24.2 mg/kg) alone did not produce any changes in heart rate, brain electrical activity, temperature or locomotion compared to saline control. Survival following VX and huBuChE treatment was associated with minimal incapacitation and observable signs of poisoning, and the mitigation or prevention of detrimental physiological changes (e.g. seizure, bradycardia and hypothermia) observed in VX + saline-treated animals. At 7 days, cholinesterase activity in the erythrocytes and most brain areas of guinea pigs that received huBuChE at either 18 h prior to or 30 min following VX was not significantly different from that of naïve, weight-matched control animals. CONCLUSION. Percutaneous VX poisoning was successfully treated using post-exposure therapy with huBuChE bioscavenger. The opportunity for post-exposure treatment may have particular relevance in civilian settings, and this is a promising indication for the use of huBuChE.

  9. Biphasic kill curve of isoniazid reveals the presence of drug-tolerant, not drug-resistant, Mycobacterium tuberculosis in the guinea pig.

    PubMed

    Ahmad, Zahoor; Klinkenberg, Lee G; Pinn, Michael L; Fraig, Mostafa M; Peloquin, Charles A; Bishai, William R; Nuermberger, Eric L; Grosset, Jacques H; Karakousis, Petros C

    2009-10-01

    The marked reduction in the potent early bactericidal activity of isoniazid during the initial phase of antituberculosis (anti-TB) therapy has been attributed not only to the depletion of logarithmically growing bacilli but also to the emergence of isoniazid resistance. We studied the anti-TB activity of isoniazid and its ability to select for drug-resistant mutant strains in guinea pigs, in which the histopathology of TB closely resembles that of human TB. Prior mouse passage did not appear to enhance the virulence of Mycobacterium tuberculosis in guinea pigs. The human-equivalent dose of isoniazid was determined to be 60 mg/kg. Although isoniazid therapy caused rapid killing of bacilli in guinea pig lungs during the first 14 days of administration and rescued guinea pigs from acute death, its activity was dramatically reduced thereafter. This reduction in activity was not associated with the emergence of isoniazid-resistant mutant strains but, rather, with the selection of phenotypically tolerant "persisters."

  10. [The effects of infrasound on the blood coagulation function of guinea pigs].

    PubMed

    Ma, Wen-min; Qi, Peng; Zhang, Jian-zhong; Yi, Yong; Chen, Xing-ming; Zhang, Jun; Han, Rui-gang

    2011-03-01

    To study the change of the blood coagulation function of guinea pigs exposed to 16 Hz/120 dB, 16 Hz/125 dB infrasound and to explore the mechanism of circulation system damage. Seventy-two guinea pigs were divided into 3 groups: the control group, the group exposed to 16 Hz/120 dB infrasound for 1.5 h a day and the group exposed to 16 Hz/125 dB infrasound for 1.5 h a day. Each exposure group was divided into 4 sub-groups (8 guinea pigs a sub-group) which were exposed to infrasound for 1, 7, 14 and 21 d, respectively. The coagulation function and serum nitric oxide (NO) were measured for control group and all sub-groups after exposure to infrasound. The prothrombin time (PT), international normalized ratio (INR) and serum NO of group exposed to 16 Hz/125 dB infrasound were (31.16 ± 3.05) s, 2.53 ± 1.21 and (88.304 ± 52.601) µmol/L, respectively, which were significantly higher than those [(21.36 ± 0.10) s, 1.65 ± 0.07 and (30.943 ± 26.864) µmol/L] of control group (P < 0.05). PT and INR of sub-groups exposed to 16 Hz/125 dB infrasound for 14 and 21 d were significantly higher than those of control group. NO of sub-groups exposed to 16 Hz/125 dB infrasound for 1 week and 2 weeks were significantly higher than that of control group (P < 0.05), but NO of sub-group exposed to 16 Hz/125 dB infrasound for 3 weeks decreased slightly. The blood coagulation function of guinea pigs exposed to 16 Hz/125 dB infrasound decreased, PT and INR may be used as the indexes to assess of blood coagulation function change induced by the infrasound exposure.

  11. Interaction Between Daidzein and Hesperetin on Antispasmodic Action in Isolated Sensitized and Non-sensitized Guinea-Pig Tracheas.

    PubMed

    Shih, Chung-Hung; Chang, Tsu-Ya; Ko, Wun-Chang

    2016-01-01

    In traditional Chinese medicine (TCM), a combination of kudzu and Chen-Pi is frequently prescribed for relieving colds, fever, bronchitis, and cough. It contains daidzein and hesperetin, selective inhibitors of family 3 (PDE3), and 4 (PDE4) of phosphodiesterases (PDEs), respectively. In passively sensitized human airways, allergen-induced contraction was reported to be inhibited only by the simultaneous inhibition of PDE3 and PDE4, but not by single inhibition of either isozyme. Therefore, we are interested in investigating the interaction between daidzein and hesperetin on their antispasmodic effects in the isolated sensitized and non-sensitized guinea-pig tracheas, to clarify the difference between these two tissues, because effects of TCM prescription on patients with or without allergic asthma are often different. Guinea-pigs were sensitized by subcutaneous injection of ovalbumin (OVA) into legs. After sensitization, the baseline and cumulative OVA-induced contractions of the sensitized trachea were isometrically recorded on a polygraph. In the same way, the histamine (30 μM)-induced tonic contraction of non-sensitized guinea-pig trachea was recorded. The isobole method was used to analyze the antagonism and synergism between daidzein and hesperetin. The isoboles showed antagonism between daidzein and hesperetin on baseline relaxant effect and OVA (100 μg/ml)-induced contraction in the sensitized guinea-pig trachea. In contrast, the isobole showed synergism between daidzein and hesperetin on the relaxant effect of histamine-induced tonic contraction in non-sensitized guinea-pig trachea. These results suggest that the combination of kudzu and Chen-Pi for relieving colds, fever, bronchitis and cough is effective in patients without, but might show little effect in patients with allergic asthma.

  12. Interaction Between Daidzein and Hesperetin on Antispasmodic Action in Isolated Sensitized and Non-sensitized Guinea-Pig Tracheas

    PubMed Central

    Shih, Chung-Hung; Chang, Tsu-Ya; Ko, Wun-Chang

    2016-01-01

    In traditional Chinese medicine (TCM), a combination of kudzu and Chen-Pi is frequently prescribed for relieving colds, fever, bronchitis, and cough. It contains daidzein and hesperetin, selective inhibitors of family 3 (PDE3), and 4 (PDE4) of phosphodiesterases (PDEs), respectively. In passively sensitized human airways, allergen-induced contraction was reported to be inhibited only by the simultaneous inhibition of PDE3 and PDE4, but not by single inhibition of either isozyme. Therefore, we are interested in investigating the interaction between daidzein and hesperetin on their antispasmodic effects in the isolated sensitized and non-sensitized guinea-pig tracheas, to clarify the difference between these two tissues, because effects of TCM prescription on patients with or without allergic asthma are often different. Guinea-pigs were sensitized by subcutaneous injection of ovalbumin (OVA) into legs. After sensitization, the baseline and cumulative OVA-induced contractions of the sensitized trachea were isometrically recorded on a polygraph. In the same way, the histamine (30 μM)-induced tonic contraction of non-sensitized guinea-pig trachea was recorded. The isobole method was used to analyze the antagonism and synergism between daidzein and hesperetin. The isoboles showed antagonism between daidzein and hesperetin on baseline relaxant effect and OVA (100 μg/ml)-induced contraction in the sensitized guinea-pig trachea. In contrast, the isobole showed synergism between daidzein and hesperetin on the relaxant effect of histamine-induced tonic contraction in non-sensitized guinea-pig trachea. These results suggest that the combination of kudzu and Chen-Pi for relieving colds, fever, bronchitis and cough is effective in patients without, but might show little effect in patients with allergic asthma. PMID:27064479

  13. Immunoreactivities for glutathione S-transferases and glutathione peroxidase in the lateral wall of pigmented and albino guinea pig cochlea.

    PubMed

    Fujimura, Takeyuki; Suzuki, Hideaki; Udaka, Tsuyoshi; Shiomori, Teruo; Mori, Takanori; Inaba, Tsuyoshi; Hiraki, Nobuaki; Kayashima, Kotaro; Doi, Yoshiaki

    2008-09-01

    Dark-skinned people are known to be more tolerant of ototraumatic noise than are light-skinned people, and pigmented animals are more tolerant of ototraumatic noise and aminoglycoside ototoxicity than are albino animals. Such tolerance may be dependent on the local ability of detoxification and antioxidant enzymes, including glutathione S-transferase (GST) and glutathione peroxidase (GSPx). In the present study, we examined the difference in GST/GSPx expression in the lateral wall of the cochlea between pigmented and albino guinea pigs. Eight-week-old male pigmented and albino guinea pigs were killed by transcardiac perfusion with 2% paraformaldehyde. The cochlear ducts were isolated, further fixed with 4% paraformaldehyde, decalcified, and then embedded in paraffin. Sections prepared at 5-microm thickness were incubated with anti-GST-alpha,-mu,-pi, or anti-GSPx antibody, reacted with Alexa Fluorconjugated secondary antibody, and examined under a Carl Zeiss Axioskop 2 plus fluorescence microscope. The cochlea ducts were also subjected to immunoelectron microscopy for GST-pi by the postembedment method. The stria vascularis of pigmented guinea pigs was strongly immunoreactive for GST-alpha,-mu,-pi, and GSPx, whereas no or only weak immunoreactivities were seen in the stria vascularis of albino guinea pigs. The spiral ligament showed positive but different immunoreactivities for these enzymes between the strains. Double-stained immunofluorescence micrographs for GST-pi and GSPx showed a close resemblance of localization between the two enzymes in both pigmented and albino guinea pigs. At the ultrastructural level, immunoreactivity for GST-pi was localized preferentially in the melanin cells of pigmented guinea pigs. These results suggest that correlation between pigmentation and inner ear susceptibility is, at least partially, attributed to the different distribution of GST/GSPx in the stria vascularis.

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

    PubMed

    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.

  15. The role of TRPM8 in the Guinea-pig bladder-cooling reflex investigated using a novel TRPM8 antagonist.

    PubMed

    Gardiner, Jennifer C; Kirkup, Anthony J; Curry, John; Humphreys, Sian; O'Regan, Paul; Postlethwaite, Michael; Young, Kimberley C; Kitching, Linda; Ethell, Brian T; Winpenny, David; McMurray, Gordon

    2014-10-05

    Patients with overactive bladder often exhibit abnormal bladder contractions in response to intravesical cold saline (positive ice-water test). The molecular entity involved in cold sensation within the urinary bladder is unknown, but a potential candidate is the ion channel, transient receptor potential (melastatin)-8 (TRPM8). The objective of the present study was to investigate the role of TRPM8 in a bladder-cooling reflex evoked in anaesthetised guinea-pigs that is comparable to the positive ice-water test seen in patients. Guinea-pig TRPM8 was cloned from L6 dorsal root ganglia (DRG) and expressed in HEK293 cells. Functional agonist- and cold-induced Ca2+ influx and electrophysiology assays were performed in these cells, and for comparison in HEK293 cells expressing human TRPM8, using a novel TRPM8 antagonist, the S-enantiomer of 1-phenylethyl 4-(benzyloxy)-3-methoxybenzyl (2-aminoethyl) carbamate hydrochloride (PBMC). Potency data from these assays was used to calculate intravenous infusion protocols for targeted plasma concentrations of PBMC in studies on micturition reflexes evoked by intravesical infusion of menthol or cold saline in anaesthetised guinea-pigs. Tissue expression of TRPM8 in guinea-pig bladder, urethra and in dorsal root ganglia neurones traced from the bladder was also investigated. TRPM8 mRNA and protein were detected in L6 dorsal root ganglia, bladder urothelium and smooth muscle. PBMC antagonised in vitro activation of human and guinea-pig TRPM8 and reversed menthol and cold-induced facilitation of the micturition reflex at plasma concentrations consistent with in vitro potencies. The present data suggest that the bladder-cooling reflex in the guinea-pig involves TRPM8. The potential significance of TRPM8 in bladder disease states deserves future investigation. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Species differences in the negative inotropic effect of acetylcholine and soman in rat, guinea pig, and rabbit hearts. (Reannouncement with new availability information)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Maxwell, D.M.; Thomsen, R.H.; Baskin, S.I.

    1991-12-31

    Acetylcholine reduced atrial contractions by 82.5% in guinea pig, 50.8% in rat, and 41.5% in rabbit. 2. The EC50, values for the negative inotropic effect of acetylcholine were 3.3 x 10(-7) M in rat and guinea pig atria and 4.1 x 10(-6) M in rabbit atria. 3. There was no correlation between the species differences in the negative inotropic effect of acetylcholine in atria and the density or affinity of acetylcholinesterase or muscarinic receptors. 4. Inhibition of atrial acetylcholinesterase with soman reduced the EC50 of acetylcholine three-fold in all species, but did not change the maximal inotropic effect of acetylcholine.more » 5. Species differences in the negative inotropic effect of acetylcholine may be caused by differences in the coupling between myocardial muscarinic receptors and the ion channels that mediate negative inotropy. Acetylcholine, cardiovascular response, species variation negative inotropic response.« less

  17. Kinetics of IFN-gamma and TNF-alpha gene expression and their relationship with disease progression after infection with Mycobacterium tuberculosis in guinea pigs.

    PubMed

    Roh, In Soon; Cho, Sungae; Eum, Seok-Yong; Cho, Sang-Nae

    2013-05-01

    Guinea pig is one of the most suitable animal models for Mycobacterium tuberculosis (M. tb) infection since it shows similarities to pulmonary infection in humans. Although guinea pig shows hematogenous spread of M. tb infection into the whole body, immunological studies have mainly focused on granulomatous tissues in lungs and spleens. In order to investigate the time-course of disease pathogenesis and immunological profiles in each infected organ, we performed the following approaches with guinea pigs experimentally infected with M. tb over a 22-week post-infection period. We examined body weight changes, M. tb growth curve, cytokine gene expression (IFN-γ and TNF-α), and histopathology in liver, spleen, lungs and lymph nodes of infected guinea pigs. The body weights of infected guinea pigs did not increase as much as uninfected ones and the number of M. tb bacilli in their organs increased except bronchotracheal lymph node during the experimental period. The gene expression of IFN-γ and TNF-α was induced between 3 and 6 weeks of infection; however, kinetic profiles of cytokine gene expression showed heterogeneity among organs over the study period. Histophathologically granulomatous lesions were developed in all four organs of infected guinea pigs. Although IFN-γ and TNF-α gene expression profiles showed heterogeneity, the granuloma formation was clearly observed in every organ regardless of whether the number of bacilli increased or decreased. However, this protective immunity was accompanied with severe tissue damage in all four organs, which may lead to the death of guinea pigs.

  18. Effect of aldosterone on cochlear Af9 expression and hearing in guinea pig.

    PubMed

    Qin, Li; Zhang, Biyun; Wang, Qianying; Li, Duanchao; Luo, Xiaoli; Zhong, Shixun

    2017-09-01

    Af9 protein in cochlea may be closely related to endolymph regulation by aldosterone and thus may be involved in pathogenesis of endolymphatic hydrops (EH). EH is the pathological characteristic of Ménière's disease (MD). Aldosterone could induce EH, but its relationship with MD is still controversial. The aim of the present study is to investigate the Af9 protein expression in guinea pig cochlea and regulation of Af9 expression and cochlear function by aldosterone. The role of Af9 in pathogenesis of EH is discussed. Thirty guinea pigs were randomly divided into two groups. The treatment group was intraperitoneally injected with aldosterone 0.1 mg/kg/d for 5 days, while the control group was done with saline. Hearing and histomorphology of cochlea were examined. In addition, expression of Af9 protein was studied. The hearing threshold of the treatment group was increased. EH was induced in 73% of guinea pigs in the treatment group, and no EH was found in the control group. Af9 protein was found in spiral limbus, stria vascularis, Reissner's membrane, organ of Corti and spiral ganglion in both groups. Af9 expression in cochlea decreased significantly at protein level after treatment by aldosterone.

  19. Two dimensional vibrations of the guinea pig apex organ of Corti measured in vivo using phase sensitive Fourier domain optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Ramamoorthy, Sripriya; Zhang, Yuan; Petrie, Tracy; Fridberger, Anders; Ren, Tianying; Wang, Ruikang; Jacques, Steven L.; Nuttall, Alfred L.

    2015-02-01

    In this study, we measure the in vivo apical-turn vibrations of the guinea pig organ of Corti in both axial and radial directions using phase-sensitive Fourier domain optical coherence tomography. The apical turn in guinea pig cochlea has best frequencies around 100 - 500 Hz which are relevant for human speech. Prior measurements of vibrations in the guinea pig apex involved opening the otic capsule, which has been questioned on the basis of the resulting changes to cochlear hydrodynamics. Here this limitation is overcome by measuring the vibrations through bone without opening the otic capsule. Furthermore, we have significantly reduced the surgery needed to access the guinea pig apex in the axial direction by introducing a miniature mirror inside the bulla. The method and preliminary data are discussed in this article.

  20. Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells.

    PubMed

    Sirenko, Syevda G; Yang, Dongmei; Maltseva, Larissa A; Kim, Mary S; Lakatta, Edward G; Maltsev, Victor A

    2017-01-01

    Uptake and release calcium from the sarcoplasmic reticulum (SR) (dubbed "calcium clock"), in the form of spontaneous, rhythmic, local diastolic calcium releases (LCRs), together with voltage-sensitive ion channels (membrane clock) form a coupled system that regulates the action potential (AP) firing rate. LCRs activate Sodium/Calcium exchanger (NCX) that accelerates diastolic depolarization and thus participating in regulation of the time at which the next AP will occur. Previous studies in rabbit SA node cells (SANC) demonstrated that the basal AP cycle length (APCL) is tightly coupled to the basal LCR period (time from the prior AP-induced Ca2+ transient to the diastolic LCR occurrence), and that this coupling is further modulated by autonomic receptor stimulation. Although spontaneous LCRs during diastolic depolarization have been reported in SANC of various species (rabbit, cat, mouse, toad), prior studies have failed to detect LCRs in spontaneously beating SANC of guinea-pig, a species that has been traditionally used in studies of cardiac pacemaker cell function. We performed a detailed investigation of whether guinea-pig SANC generate LCRs and whether they play a similar key role in regulation of the AP firing rate. We used two different approaches, 2D high-speed camera and classical line-scan confocal imaging. Positioning the scan-line beneath sarcolemma, parallel to the long axis of the cell, we found that rhythmically beating guinea-pig SANC do, indeed, generate spontaneous, diastolic LCRs beneath the surface membrane. The average key LCR characteristics measured in confocal images in guinea-pig SANC were comparable to rabbit SANC, both in the basal state and in the presence of β-adrenergic receptor stimulation. Moreover, the relationship between the LCR period and APCL was subtended by the same linear function. Thus, LCRs in guinea-pig SANC contribute to the diastolic depolarization and APCL regulation. Our findings indicate that coupled-clock system

  1. Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells

    PubMed Central

    Sirenko, Syevda G.; Yang, Dongmei; Maltseva, Larissa A.; Kim, Mary S.; Lakatta, Edward G.

    2017-01-01

    Uptake and release calcium from the sarcoplasmic reticulum (SR) (dubbed “calcium clock”), in the form of spontaneous, rhythmic, local diastolic calcium releases (LCRs), together with voltage-sensitive ion channels (membrane clock) form a coupled system that regulates the action potential (AP) firing rate. LCRs activate Sodium/Calcium exchanger (NCX) that accelerates diastolic depolarization and thus participating in regulation of the time at which the next AP will occur. Previous studies in rabbit SA node cells (SANC) demonstrated that the basal AP cycle length (APCL) is tightly coupled to the basal LCR period (time from the prior AP-induced Ca2+ transient to the diastolic LCR occurrence), and that this coupling is further modulated by autonomic receptor stimulation. Although spontaneous LCRs during diastolic depolarization have been reported in SANC of various species (rabbit, cat, mouse, toad), prior studies have failed to detect LCRs in spontaneously beating SANC of guinea-pig, a species that has been traditionally used in studies of cardiac pacemaker cell function. We performed a detailed investigation of whether guinea-pig SANC generate LCRs and whether they play a similar key role in regulation of the AP firing rate. We used two different approaches, 2D high-speed camera and classical line-scan confocal imaging. Positioning the scan-line beneath sarcolemma, parallel to the long axis of the cell, we found that rhythmically beating guinea-pig SANC do, indeed, generate spontaneous, diastolic LCRs beneath the surface membrane. The average key LCR characteristics measured in confocal images in guinea-pig SANC were comparable to rabbit SANC, both in the basal state and in the presence of β-adrenergic receptor stimulation. Moreover, the relationship between the LCR period and APCL was subtended by the same linear function. Thus, LCRs in guinea-pig SANC contribute to the diastolic depolarization and APCL regulation. Our findings indicate that coupled

  2. The effect of statins on performance in the Morris water maze in guinea pig.

    PubMed

    Maggo, Simran; Clark, David; Ashton, John C

    2012-01-15

    Statins play a crucial role in reducing the risk of death from cardiovascular disease in millions of people worldwide. Recently, pharmacovigilance data has suggested that statin drugs may have rare but significant adverse psychiatric effects, such as amnesia, anxiety and even aggression. In order to investigate the effects of statins on cognitive function in an animal model, we studied the effect of 6 weeks of daily administration of oral simvastatin (1 mg/kg) or atorvastatin (0.5mg/kg) in guinea pig on performance in the Morris water maze (MWM). Animals were also re-tested in the MWM, 2 weeks after drug cessation, to test for any changes in performance as a result of drug de-challenge. Guinea pigs treated with either statin showed a significant (P<0.001) decrease in total cholesterol and low density lipoprotein-cholesterol (LDL-C), which remained partially reduced after the 2 week drug washout period. Guinea pigs receiving either statin did not show any difference in latency to reach the platform, nor any difference in total distance travelled during testing. Also, analysis of probe trials revealed no significant differences between drug and vehicle groups. However, both groups spent a significantly (P<0.01) greater proportion of time in the outer zone of the maze (indication of increased anxiety) and showed an increase in swimming speed (P<0.05) compared with the vehicle group. Differences between groups for swimming speed, and time spent in the outer zone, were not retained in the drug de-challenge phase. Our results show that low dose treatment with statins can induce mild but significant anxiety in guinea pigs. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Minimal In Vivo Efficacy of Iminosugars in a Lethal Ebola Virus Guinea Pig Model

    PubMed Central

    Dowall, Stuart D.; Taylor, Irene; Rule, Antony; Alonzi, Dominic S.; Sayce, Andrew C.; Wright, Edward; Bentley, Emma M.; Thom, Ruth; Hall, Graham; Dwek, Raymond A.; Hewson, Roger; Zitzmann, Nicole

    2016-01-01

    The antiviral properties of iminosugars have been reported previously in vitro and in small animal models against Ebola virus (EBOV); however, their effects have not been tested in larger animal models such as guinea pigs. We tested the iminosugars N-butyl-deoxynojirimycin (NB-DNJ) and N-(9-methoxynonyl)-1deoxynojirimycin (MON-DNJ) for safety in uninfected animals, and for antiviral efficacy in animals infected with a lethal dose of guinea pig adapted EBOV. 1850 mg/kg/day NB-DNJ and 120 mg/kg/day MON-DNJ administered intravenously, three times daily, caused no adverse effects and were well tolerated. A pilot study treating infected animals three times within an 8 hour period was promising with 1 of 4 infected NB-DNJ treated animals surviving and the remaining three showing improved clinical signs. MON-DNJ showed no protective effects when EBOV-infected guinea pigs were treated. On histopathological examination, animals treated with NB-DNJ had reduced lesion severity in liver and spleen. However, a second study, in which NB-DNJ was administered at equally-spaced 8 hour intervals, could not confirm drug-associated benefits. Neither was any antiviral effect of iminosugars detected in an EBOV glycoprotein pseudotyped virus assay. Overall, this study provides evidence that NB-DNJ and MON-DNJ do not protect guinea pigs from a lethal EBOV-infection at the dose levels and regimens tested. However, the one surviving animal and signs of improvements in three animals of the NB-DNJ treated cohort could indicate that NB-DNJ at these levels may have a marginal beneficial effect. Future work could be focused on the development of more potent iminosugars. PMID:27880800

  4. Antigen challenge induces pulmonary airway eosinophil accumulation and airway hyperreactivity in sensitized guinea-pigs: the effect of anti-asthma drugs.

    PubMed Central

    Sanjar, S.; Aoki, S.; Kristersson, A.; Smith, D.; Morley, J.

    1990-01-01

    1. Guinea-pigs were sensitized with 3 injections of ovalbumin (OA) (1 or 10 micrograms per animal) using Al(OH)3 and pertussis vaccine as adjuvants at two week intervals. 2. Sensitized guinea-pigs were challenged with an aerosol of OA (0.1%) over a one hour period and both airway reactivity and cellular content of bronchoalveolar lavage (BAL) fluid were assessed at intervals for up to 7 days. 3. Guinea-pigs sensitized with 1 microgram of ovalbumin responded to an aerosol of OA with increased pulmonary airway eosinophilia, which was evident 1 day after challenge and was present for up to 7 days. Airway hyperreactivity was not detectable in these animals. 4. Guinea-pigs sensitized with 10 micrograms of ovalbumin responded to an aerosol of OA with increased pulmonary airway neutrophilia and eosinophilia and with increased airway reactivity which was maximal between 8 and 24 h after exposure to OA. 5. Depletion of circulating platelets or neutrophils, by use of selective antisera, did not alter either the magnitude of eosinophilia or the intensity of airway reactivity in sensitized guinea-pigs (10 micrograms) exposed to an aerosol of OA. 6. Pretreatment of sensitized guinea-pigs (10 micrograms) for 6 days with AH 21-132, aminophylline, dexamethasone or ketotifen inhibited pulmonary airway eosinophilia, but did not diminish airway hyperreactivity. Neither eosinophil accumulation nor development of airway hyperreactivity was influenced by treatment with mepyramine or salbutamol over a 6 day period before OA inhalation. 7. Although eosinophilia may occur in association with increased airway reactivity in this animal model, there is no evidence of a causal relationship. PMID:2361168

  5. Involvement of cell proliferation in the process of follicular atresia in the guinea pig.

    PubMed

    Wang, Wei; Liu, Honglin; Ding, Wei; Gong, Yan; Chen, Jingwei; Hutz, Reinhold J; Mao, Dagan; Shi, Fangxiong

    2010-08-01

    Cell morphology and proliferation was investigated in the atretic follicles during estrous cycles in the guinea pig. Ovarian samples on days 1, 4, 8, 12 and 16 of the estrous cycle in the guinea pig were taken in the morning for histologic staining with hematoxylin and eosin (HE), and immunohistochemical staining of the protein proliferating cell nuclear antigen (PCNA). The results indicated that the granulosa cells degenerated and eliminated first in atretic follicles, while the fibroblast-like cells appeared in the innermost layer of theca interna cells. When the fibroblast-like cells migrated to the antrum, they proliferated and formed a new tissue in peripheral to the zona pellucida of the oocyte. Our results also revealed that the orientation of the theca interna cell arrangement changed twice during the process of atresia, and the loose connective tissue in the antrum was critical for follicular atresia. Therefore, follicular atresia was not a simple process of cell death and elimination, but coexisted with cell proliferation. To our knowledge, we have for the first time confirmed cell proliferation and the presence of new tissue in atretic follicles in guinea pigs. Copyright 2010 Elsevier Ltd. All rights reserved.

  6. [Analysis of biochemical markers in serum of guinea pigs after death caused by hypothermia].

    PubMed

    Li, Shi-ying; Deng, Kai-fei; Shao, Yu; Li, Zheng-dong; Qin, Zhi-qiang; Chen, Yi-jiu; Huang, Ping

    2014-08-01

    To explore the changes and rules of biochemical markers in serum of guinea pigs after death caused by hypothermia and to provide references for fatal hypothermia diagnosis by serum biochemical markers. Twenty guinea pigs were randomly divided into experimental group and control group. The guinea pigs in the experimental group were kept at -30 °C until death, while the ones in control group were decapitated after same survival intervals at 25 °C. The serum was extracted from the whole blood of right ventricular immediately. Subsequently, a series of serum biochemical markers were analyzed by auto bio-chemical analyzer. The levels of glucose, uric acid, creatinine and urea nitrogen in the experimental group were significantly higher than those in control group, respectively (P<0.05). Compared with the control group, the levels of total protein and albumin were significantly lower in the experimental group (P<0.05). There were no significantly differences of the levels of other markers such as serum enzymes and ions observed between the two groups. There are characteristic changes of some specific serum biochemical markers in fatal hypothermia, which may be potentially useful for auxiliary diagnosis of fatal hypothermia.

  7. Betahistine metabolites, aminoethylpyridine, and hydroxyethylpyridine increase cochlear blood flow in guinea pigs in vivo.

    PubMed

    Bertlich, Mattis; Ihler, Fritz; Sharaf, Kariem; Weiss, Bernhard G; Strupp, Michael; Canis, Martin

    2014-10-01

    Betahistine is a histamine-like drug that is used in the treatment of Ménière's disease. It is commonly believed that betahistine increases cochlear blood flow and thus decreases the endolymphatic hydrops that is the cause of Ménière's. Despite common clinical use, there is little understanding of the kinetics or effects of its metabolites. This study investigated the effect of the betahistine metabolites aminoethylpyridine, hydroxyethylpyridine, and pyridylacetic acid on cochlear microcirculation. Guinea pigs were randomly assigned to one of the groups: placebo, betahistine, or equimolar amounts of aminoethylpyridine, hydroxyethylpyridine, or pyridylacetic acid. Cochlear blood flow and mean arterial pressure were recorded for three minutes before and 15 minutes after treatment. Thirty Dunkin-Hartley guinea pigs assigned to one of five groups with six guinea pigs per group. Betahistine, aminoethylpyridine, and hydroxyethylpyridine caused a significant increase in cochlear blood flow in comparison to placebo. The effect seen under aminoethylpyridin was greatest. The group treated with pyridylacetic acid showed no significant effect on cochlear blood flow. Aminoethylpyridine and hydroxyethylpyridine are, like betahistine, able to increase cochlear blood flow significantly. The effect of aminoethylpyridine was greatest. Pyridylacetic acid had no effect on cochlear microcirculation.

  8. Infected Peripheral Blood Mononuclear Cells Transmit Latent Varicella Zoster Virus Infection to the Guinea Pig Enteric Nervous System

    PubMed Central

    Gan, Lin; Wang, Mingli; Chen, Jason J.; Gershon, Michael D.; Gershon, Anne A.

    2014-01-01

    Latent wild-type (WT) and vaccine (vOka) varicella-zoster virus (VZV) are found in the human enteric nervous system (ENS). VZV also infects guinea pig enteric neurons in vitro, establishes latency and can be reactivated. We therefore determined whether lymphocytes infected in vitro with VZV secrete infectious virions and can transfer infection in vivo to the ENS of recipient guinea pigs. T lymphocytes (CD3-immunoreactive) were preferentially infected following co-culture of guinea pig or human peripheral blood mononuclear cells with VZV-infected HELF. VZV proliferated in the infected T cells and expressed immediate early and late VZV genes. Electron microscopy confirmed that VZV-infected T cells produced encapsulated virions. Extracellular virus, however, was pleomorphic, suggesting degradation occurred prior to release, which was confirmed by the failure of VZV-infected T cells to secrete infectious virions. Intravenous injection of WT- or vOka-infected PBMCs, nevertheless, transmitted VZV to recipient animals (guinea pig > human lymphocytes). Two days post-inoculation, lung and liver, but not gut, contained DNA and transcripts encoding ORFs 4, 40, 66 and 67. Twenty-eight days after infection, gut contained DNA and transcripts encoding ORFs 4 and 66 but neither DNA nor transcripts could any longer be found in lung or liver. In situ hybridization revealed VZV DNA in enteric neurons, which also expressed ORF63p (but not ORF68p) immunoreactivity. Observations suggest that VZV infects T cells, which can transfer VZV to and establish latency in enteric neurons in vivo. Guinea pigs may be useful for studies of VZV pathogenesis in the ENS. PMID:24965252

  9. Comparative glycopattern analysis of mucins in the Brunner's glands of the guinea-pig and the house mouse (Rodentia).

    PubMed

    Scillitani, Giovanni; Mentino, Donatella

    2015-09-01

    The mucins secreted by the Brunner's glands and the duodenal goblet cells of the Guinea-pig and the house mouse were compared by conventional and FITC-conjugated lectin histochemistry. Methylation/saponification and sialidase digestion were performed prior to lectin binding to detect the residues subterminal to sulfated groups and sialic acid, respectively. In the Guinea-pig the Brunner's glands produce class-III stable sulfosialomucins. Sialic acid is mostly 2,6-linked to galactose or to N-acetylgalactosamine and is in part O-acetylated in C7, C8, and C9. Sulfated groups are probably linked to sialic acid and N-acetylgalactosamine. Terminal residuals of N-acetylglucosamine, galactose, N-acetylgalactosamine and fucose linked in α1,2, α1,3, and α1,4 are also present. Duodenal goblet cells of the Guinea-pig present a lower number of residuals in respect to the Brunner's glandular ones, with sialic acid and N-acetylgalactosamine subterminal to sulfated groups. In the house mouse the Brunner's glands produce class-III stable neutral mucins, binding to same lectins as in the Guinea-pig except for those specific to sialic acid. A diversity of fucosylated residuals higher than in the Guinea-pig is observed. The mouse duodenal goblet cells lack stable class-III mucins, have little sialic acid and present a lower number of residuals in respect to the correspondent Brunner's glands. Regulation of the acidic intestinal microenvironment, prevention of pathologies and hosting of microflora can explain the observed results and the differences observed between the two rodents. Copyright © 2015 Elsevier GmbH. All rights reserved.

  10. Effect of active sensitization on the bronchopulmonary responses to tachykinins in the guinea pig. Modulation by peptidase inhibitors.

    PubMed

    Capaz, F R; Ruffié, C; Lefort, J; Manzini, S; Vargaftig, B B; Pretolani, M

    1993-08-01

    The i.v. administration of substance P (SP, 0.25-16 micrograms/kg) or of the selective metabolic stable NK-1 agonist, [Glp6,Pro9]SP-(6-11) (septide, 0.03-0.25 microgram) to atropine-treated guinea pigs or to isolated perfused lungs triggered a dose-dependent bronchoconstriction, which was enhanced in animals actively sensitized to ovalbumin. In vivo, bronchial hyper-responsiveness was restricted to SP and to septide, inasmuch as neurokinin A (0.06-1 microgram/kg)- or capsaicin (0.5-32 micrograms/kg)-induced bronchoconstriction were not modified. In contrast, isolated lungs from sensitized guinea pigs exhibited an increased bronchoconstriction also in response to capsaicin (0.01-10 micrograms), which was inhibited by atropine in the medium. Pretreatment of actively sensitized guinea pigs either with indomethacin plus mepyramine, the lipoxygenase inhibitor BW A4C or with the platelet-activating factor antagonist SR 27417, did not modify bronchial hyper-reactivity to SP. Captopril (5 mg/kg i.v.), but not thiorphan (0.8 mg/kg i.v.), increased the SP-induced bronchoconstriction in actively sensitized animals, whereas both inhibitors were equally effective in nonsensitized guinea pigs. Thiorphan, however, did not modify the in vivo response to septide. Our results demonstrate that guinea pigs sensitized to ovalbumin exhibit bronchial hyperreactivity to SP, but not to neurokinin A, as compared to nonsensitized animals, suggesting a decrease in the neutral endopeptidase activity in the airways brought by the immunization. However, the results obtained by using septide indicate that other mechanisms may be involved in the bronchial hyper-reactivity to SP.

  11. An active site mutation increases the polymerase activity of the guinea pig-lethal Marburg virus.

    PubMed

    Koehler, Alexander; Kolesnikova, Larissa; Becker, Stephan

    2016-10-01

    Marburg virus (MARV) causes severe, often fatal, disease in humans and transient illness in rodents. Sequential passaging of MARV in guinea pigs resulted in selection of a lethal virus containing 4 aa changes. A D184N mutation in VP40 (VP40D184N), which leads to a species-specific gain of viral fitness, and three mutations in the active site of viral RNA-dependent RNA polymerase L, which were investigated in the present study for functional significance in human and guinea pig cells. The transcription/replication activity of L mutants was strongly enhanced by a substitution at position 741 (S741C), and inhibited by other substitutions (D758A and A759D) in both species. The polymerase activity of L carrying the S741C substitution was eightfold higher in guinea pig cells than in human cells upon co-expression with VP40D184N, suggesting that the additive effect of the two mutations provides MARV a replicative advantage in the new host.

  12. Enhanced effect of VEGF165 on L-type calcium currents in guinea-pig cardiac ventricular myocytes.

    PubMed

    Xing, Wenlu; Gao, Chuanyu; Qi, Datun; Zhang, You; Hao, Peiyuan; Dai, Guoyou; Yan, Ganxin

    2017-01-01

    The mechanisms of vascular endothelial growth factor 165 (VEGF165) on electrical properties of cardiomyocytes have not been fully elucidated. The aim of this study is to test the hypothesis that VEGF165, an angiogenesis-initiating factor, affects L-type calcium currents (I Ca,L ) and cell membrane potential in cardiac myocytes by acting on VEGF type-2 receptors (VEGFR2). I Ca,L and action potentials (AP) were recorded by the whole-cell patch clamp method in isolated guinea-pig ventricular myocytes treated with different concentrations of VEGF165 proteins. Using a VEGFR2 inhibitor, we also tested the receptor of VEGF165 in cardiomyocytes. We found that VEGF165 increased I Ca,L in a concentration-dependent manner. SU5416, a VEGFR2 inhibitor, almost completely eliminated VEGF165-induced I Ca,L increase. VEGF165 had no significant influence on action potential 90 (APD90) and other properties of AP. We conclude that in guinea-pig ventricular myocytes, I Ca,L can be increased by VEGF165 in a concentration-dependent manner through binding to VEGFR2 without causing any significant alteration to action potential duration. Results of this study may further expound the safety of VEGF165 when used in the intervention of heart diseases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Spontaneous Healing of Mycobacterium ulcerans Lesions in the Guinea Pig Model

    PubMed Central

    Silva-Gomes, Rita; Marcq, Elly; Trigo, Gabriela; Gonçalves, Carine M.; Longatto-Filho, Adhemar; Castro, António G.; Pedrosa, Jorge; Fraga, Alexandra G.

    2015-01-01

    Buruli Ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans infection. BU is characterized by a wide range of clinical forms, including non-ulcerative cutaneous lesions that can evolve into severe ulcers if left untreated. Nevertheless, spontaneous healing has been reported to occur, although knowledge on this process is scarce both in naturally infected humans and experimental models of infection. Animal models are useful since they mimic different spectrums of human BU disease and have the potential to elucidate the pathogenic/protective pathway(s) involved in disease/healing. In this time-lapsed study, we characterized the guinea pig, an animal model of resistance to M. ulcerans, focusing on the macroscopic, microbiological and histological evolution throughout the entire experimental infectious process. Subcutaneous infection of guinea pigs with a virulent strain of M. ulcerans led to early localized swelling, which evolved into small well defined ulcers. These macroscopic observations correlated with the presence of necrosis, acute inflammatory infiltrate and an abundant bacterial load. By the end of the infectious process when ulcerative lesions healed, M. ulcerans viability decreased and the subcutaneous tissue organization returned to its normal state after a process of continuous healing characterized by tissue granulation and reepethelialization. In conclusion, we show that the experimental M. ulcerans infection of the guinea pig mimics the process of spontaneous healing described in BU patients, displaying the potential to uncover correlates of protection against BU, which can ultimately contribute to the development of new prophylactic and therapeutic strategies. PMID:26625302

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

    PubMed

    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.

  15. The Multidrug Resistance 1 Gene Abcb1 in Brain and Placenta: Comparative Analysis in Human and Guinea Pig

    PubMed Central

    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. PMID:25353162

  16. Ultrasound-induced temperature increase in guinea-pig fetal brain in utero: third-trimester gestation.

    PubMed

    Horder, M M; Barnett, S B; Vella, G J; Edwards, M J; Wood, A K

    1998-11-01

    Temperature increase was measured at various depths in the brain of living fetal guinea pigs during in utero exposure to unscanned pulsed ultrasound at ISPTA 2.8 W/cm2. Mean temperature increases of 4.9 degrees C close to parietal bone and 1.2 degrees C in the midbrain were recorded after 2-min exposures. When exposures were repeated on the same sites in each fetus after death, the corresponding mean temperature increases were 4.9 degrees C and 1.3 degrees C, respectively. Cerebral blood perfusion had little cooling effect on ultrasound-induced heating in the guinea pig fetus of 57-61 days gestational age.

  17. T helper 1 background protects against airway hyperresponsiveness and inflammation in guinea pigs with persistent respiratory syncytial virus infection.

    PubMed

    Sutton, Troy C; Tayyari, Farnoosh; Khan, M Aatif; Manson, Heather E; Hegele, Richard G

    2007-05-01

    A family history of allergy has been implicated in children who develop post-bronchiolitis wheezing and asthma. In a guinea pig model of respiratory syncytial virus (RSV) lung infection, we evaluated the role of host Th1 background (either genetic or induced) on the development of a persistent infection, nonspecific airway hyperresponsiveness (AHR) and airway inflammation. Allergy resistant/T helper 1 (Th1)-skewed strain 2 guinea pigs (STR2) and cytosine phosphate guanine oligodeoxynucleotides (CpG-ODN) (Th1 stimuli) pretreated Cam Hartley guinea pigs (CH) were inoculated with RSV and compared with virus-inoculated allergy-susceptible/Th2-skewed CHs and to sham-inoculated STR2 and CH, 60 d post-inoculation. We measured titers of intrapulmonary RSV, lung interferon (IFN)-gamma and interleukin (IL)-5 mRNA expression, AHR and airway T cells and eosinophils. All virus-inoculated groups of animals showed evidence of persistent RSV lung infection; however, Th2-skewed guinea pigs had virus-associated AHR and significantly greater levels of airway T cells and eosinophils. In conclusion, RSV can establish persistent infection of the guinea pig lung regardless of host Th1/Th2 background; however; a host Th1 background limits the extent of virus-associated AHR and airway inflammation. Heterogeneity in virus-host interactions may be relevant to understanding why some children hospitalized for RSV bronchiolitis go on to develop recurrent wheezing/asthma symptoms.

  18. Evaluation of Inhaled Versus Deposited Dose Using the Exponential Dose-Response Model for Inhalational Anthrax in Nonhuman Primate, Rabbit, and Guinea Pig.

    PubMed

    Gutting, Bradford W; Rukhin, Andrey; Mackie, Ryan S; Marchette, David; Thran, Brandolyn

    2015-05-01

    The application of the exponential model is extended by the inclusion of new nonhuman primate (NHP), rabbit, and guinea pig dose-lethality data for inhalation anthrax. Because deposition is a critical step in the initiation of inhalation anthrax, inhaled doses may not provide the most accurate cross-species comparison. For this reason, species-specific deposition factors were derived to translate inhaled dose to deposited dose. Four NHP, three rabbit, and two guinea pig data sets were utilized. Results from species-specific pooling analysis suggested all four NHP data sets could be pooled into a single NHP data set, which was also true for the rabbit and guinea pig data sets. The three species-specific pooled data sets could not be combined into a single generic mammalian data set. For inhaled dose, NHPs were the most sensitive (relative lowest LD50) species and rabbits the least. Improved inhaled LD50 s proposed for use in risk assessment are 50,600, 102,600, and 70,800 inhaled spores for NHP, rabbit, and guinea pig, respectively. Lung deposition factors were estimated for each species using published deposition data from Bacillus spore exposures, particle deposition studies, and computer modeling. Deposition was estimated at 22%, 9%, and 30% of the inhaled dose for NHP, rabbit, and guinea pig, respectively. When the inhaled dose was adjusted to reflect deposited dose, the rabbit animal model appears the most sensitive with the guinea pig the least sensitive species. © 2014 Society for Risk Analysis.

  19. Specific immune response genes of the guinea pig. II. Relationship between the poly-L-lysine gene and the genes controlling immune responsiveness to copolymers of L-glutamic acid and L-alanine and L-glutamic acid and L-tyrosine in random-bred Hartley guinea pigs.

    PubMed

    Bluestein, H G; Green, I; Benacerraf, B

    1971-08-01

    The ability of guinea pigs to make immune responses to GA, a linear random copolymer of L-glutamic acid and L-alanine, GT, a random linear copolymer of L-glutamic acid and L-tyrosine, and PLL, a linear homopolymer of L-lysine, is controlled by different autosomal dominant genes specific for each of those polymers. We have investigated the relationship between the PLL gene and the GA and GT immune response genes by simultaneously immunizing random-bred Hartley strain guinea pigs with GA and PLL, GT and PLL, or GA and GT. In most Hartley guinea pigs the ability to respond immunologically to GA and to PLL is inherited together; that is, most animals responding to GA respond to PLL and vice versa. However, a few animals respond to either GA or to PLL but not both, demonstrating that the GA and PLL immune response genes are not identical but linked in most Hartley animals. Conversely, when simultaneously immunized with GT and PLL, most Hartley guinea pigs respond to either PLL or GT but not both, indicating that GT and PLL responsiveness tends to segregate away from each other. Thus, the GT and PLL immune response genes also are not inherited independently but, rather, behave as alleles or pseudoalleles. Similar results are observed when Hartley guinea pigs are simultaneously immunized with GA and GT. The ability to respond to GA segregates away from the ability to respond to GT. Our studies demonstrated that the specific immune response genes thus far identified in guinea pigs controlling the ability to respond to GA, GT, and PLL, respectively, are found on the same chromosome. In most Hartley animals, the GA and PLL immune response genes are often linked, i.e. occur on the same chromosome strand, and tend to behave as alleles or pseudoalleles to the GT immune response gene.

  20. Adenovirus-mediated in utero gene transfer in mice and guinea pigs: tissue distribution of recombinant adenovirus determined by quantitative TaqMan-polymerase chain reaction assay.

    PubMed

    Senoo, M; Matsubara, Y; Fujii, K; Nagasaki, Y; Hiratsuka, M; Kure, S; Uehara, S; Okamura, K; Yajima, A; Narisawa, K

    2000-04-01

    Fetal somatic cell gene therapy could become an attractive solution for some congenital genetic diseases or the disorders which manifest themselves during the fetal period. We performed adenovirus-mediated gene transfer to mice and guinea pig fetuses in utero and evaluated the efficiency of gene transfer by histochemical analysis and a quantitative TaqMan-polymerase chain reaction (TaqMan-PCR) assay. We first injected a replication-deficient recombinant adenovirus containing the Escherichia coli LacZ gene driven by a CAG promoter (AxCALacZ) into pregnant mice through the amniotic space, placenta, or intraperitoneal space of the fetus. Histochemical analysis showed limited transgene expression in fetal tissues. We then administered AxCALacZ to guinea pig fetuses in the late stage of pregnancy through the umbilical vein. The highest beta-galactosidase expression was observed in liver followed by moderate expression in heart, spleen, and adrenal gland. The transgene expression was also present in kidney, intestine, and placenta to a lesser degree. No positively stained cells were observed in lung, muscle, or pancreas except in the vascular endothelium of these organs. Quantitative measurement of recombinant adenoviral DNA by the TaqMan-PCR assay showed that the vast majority of the injected viruses was present in liver. The current study indicated that adenovirus-mediated gene transfer into guinea pig fetus through the umbilical vein is feasible and results in efficient transgene expression in fetal tissues. The experimental procedures using pregnant guinea pigs might serve as a good experimental model for in utero gene transfer. Since our TaqMan-PCR assay detects the LacZ gene, one of the most widely used reporter genes, it may be generally applicable to adenovirus quantification in various gene transfer experiments.

  1. Effect of water extract of Turkish propolis on tuberculosis infection in guinea-pigs.

    PubMed

    Yildirim, Zeki; Hacievliyagil, Süleyman; Kutlu, Nurettin Onur; Aydin, Nasuhi Engin; Kurkcuoglu, Mine; Iraz, Mustafa; Durmaz, Riza

    2004-03-01

    Mycobacterium tuberculosis (H(37)R(v))-infected guinea-pig model was used to investigate the effect of water extract of propolis (WEP). After subcutaneous inoculation of tubercle bacilli, each animal received oral WEP (n=9), isoniazid (n=5) or saline (n=6) as placebo and were sacrificed 30 days later. Formation of necrosis was less prominent in the group treated with WEP, but was not statistically significant (P>0.05). The granuloma formation in the same group was more prominent than the placebo and isoniazid groups; however, this finding failed to reach statistical significance by the Kruskal-Wallis test (P>0.05). These findings suggest that Turkish WEP may have a limited effect on the development of tuberculosis infection in this guinea-pig model.

  2. Effect of lipid emulsions on the plasma lecithin: cholesterol acyltransfer in guinea pigs.

    PubMed

    Drevon, C A; Norum, K R

    1975-01-01

    Addition of triglyceride/phospholipid emulsion to adult guinea pig plasma more than doubled the cholesteryl ester (CE) production. Plasma from newborn guinea pigs was stimulated to a lower degree. The increase in CE production was dependant on the type and amount of phospholipids in the lipid emulsions. Egg phospholipids stimulated the cholesterol esterification while partially hydrogenated soy phospholipids (with high content of saturated fatty acids) inhibited the reaction. The stimulation of CE formation was probably due to transfer of phosphatidyl choline (PC) from the emulsion to the high density lipoproteins since the stimulation was: (a) dependant on a preincubation time, (b) less pronounced in newborn animals with high plasma PC levels, and (c) detected in plasma fractions from which the lipid emulsion had been removed.

  3. A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus.

    PubMed

    Coleman, Stewart; Choi, K Yeon; Root, Matthew; McGregor, Alistair

    2016-07-01

    In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenital CMV. Guinea pig cytomegalovirus (GPCMV) potentially encodes a UL128-131 HCMV PC homolog locus (GP128-GP133). In transient expression studies, GPCMV gH and gL glycoproteins interacted with UL128, UL130 and UL131 homolog proteins (designated GP129 and GP131 and GP133 respectively) to form PC or subcomplexes which were determined by immunoprecipitation reactions directed to gH or gL. A natural GP129 C-terminal deletion mutant (aa 107-179) and a chimeric HCMV UL128 C-terminal domain swap GP129 mutant failed to form PC with other components. GPCMV infection of a newly established guinea pig epithelial cell line required a complete PC and a GP129 mutant virus lacked epithelial tropism and was attenuated in the guinea pig for pathogenicity and had a low congenital transmission rate. Individual knockout of GP131 or 133 genes resulted in loss of viral epithelial tropism. A GP128 mutant virus retained epithelial tropism and GP128 was determined not to be a PC component. A series of GPCMV mutants demonstrated that gO was not strictly essential for epithelial infection whereas gB and the PC were essential. Ectopic expression of a GP129 cDNA in a GP129 mutant virus restored epithelial tropism, pathogenicity and congenital infection. Overall, GPCMV forms a PC similar to HCMV which enables evaluation of PC based vaccine strategies in the guinea pig model.

  4. A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus

    PubMed Central

    McGregor, Alistair

    2016-01-01

    In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenital CMV. Guinea pig cytomegalovirus (GPCMV) potentially encodes a UL128-131 HCMV PC homolog locus (GP128-GP133). In transient expression studies, GPCMV gH and gL glycoproteins interacted with UL128, UL130 and UL131 homolog proteins (designated GP129 and GP131 and GP133 respectively) to form PC or subcomplexes which were determined by immunoprecipitation reactions directed to gH or gL. A natural GP129 C-terminal deletion mutant (aa 107–179) and a chimeric HCMV UL128 C-terminal domain swap GP129 mutant failed to form PC with other components. GPCMV infection of a newly established guinea pig epithelial cell line required a complete PC and a GP129 mutant virus lacked epithelial tropism and was attenuated in the guinea pig for pathogenicity and had a low congenital transmission rate. Individual knockout of GP131 or 133 genes resulted in loss of viral epithelial tropism. A GP128 mutant virus retained epithelial tropism and GP128 was determined not to be a PC component. A series of GPCMV mutants demonstrated that gO was not strictly essential for epithelial infection whereas gB and the PC were essential. Ectopic expression of a GP129 cDNA in a GP129 mutant virus restored epithelial tropism, pathogenicity and congenital infection. Overall, GPCMV forms a PC similar to HCMV which enables evaluation of PC based vaccine strategies in the guinea pig model. PMID:27387220

  5. Sympathetic Nervous Regulation of Calcium and Action Potential Alternans in the Intact Heart.

    PubMed

    Winter, James; Bishop, Martin J; Wilder, Catherine D E; O'Shea, Christopher; Pavlovic, Davor; Shattock, Michael J

    2018-01-01

    Rationale: Arrhythmogenic cardiac alternans are thought to be an important determinant for the initiation of ventricular fibrillation. There is limited information on the effects of sympathetic nerve stimulation (SNS) on alternans in the intact heart and the conclusions of existing studies, focused on investigating electrical alternans, are conflicted. Meanwhile, several lines of evidence implicate instabilities in Ca handling, not electrical restitution, as the primary mechanism underpinning alternans. Despite this, there have been no studies on Ca alternans and SNS in the intact heart. The present study sought to address this, by application of voltage and Ca optical mapping for the simultaneous study of APD and Ca alternans in the intact guinea pig heart during direct SNS. Objective : To determine the effects of SNS on APD and Ca alternans in the intact guinea pig heart and to examine the mechanism(s) by which the effects of SNS are mediated. Methods and Results : Studies utilized simultaneous voltage and Ca optical mapping in isolated guinea pig hearts with intact innervation. Alternans were induced using a rapid dynamic pacing protocol. SNS was associated with rate-independent shortening of action potential duration (APD) and the suppression of APD and Ca alternans, as indicated by a shift in the alternans threshold to faster pacing rates. Qualitatively similar results were observed with exogenous noradrenaline perfusion. In contrast with previous reports, both SNS and noradrenaline acted to flatten the slope of the electrical restitution curve. Pharmacological block of the slow delayed rectifying potassium current (I Ks ), sufficient to abolish I Ks -mediated APD-adaptation, partially reversed the effects of SNS on pacing-induced alternans. Treatment with cyclopiazonic acid, an inhibitor of the sarco(endo)plasmic reticulum ATPase, had opposite effects to that of SNS, acting to increase susceptibility to alternans, and suggesting that accelerated Ca reuptake

  6. Inhibitory effect of harmane on morphine-dependent Guinea pig ileum.

    PubMed

    Aricioglu, Feyza; Utkan, Tijen

    2003-12-01

    Studies on the occurrence and properties of b-carbolines structurally related to harmala alkaloids have gained attention since it was hypothesized that some of these compounds play a role in processes of substance abuse and dependence. This study investigates the effects of harmane on naloxone-precipitated withdrawal syndrome in morphine-dependent guinea pig ileum. Segments of ilea from starved male guinea pigs were obtained and fixed at a resting tension of 1 g in an organ bath containing 10(-6) M morphine in Tyrode solution at 37 degrees C, which was bubbled with 95% O(2) and 5% CO(2). Tissues were incubated in 10(-6) M morphine containing Tyrode solution for 4 hours before harmane was added. Naloxone and harmane had no effect on naive ilea. Naloxone (10(-6) M) contracted morphine-dependent ilea. Harmane significantly inhibited the contractile response to naloxone in a dose-dependent manner (10(-7) M = 24%; 10(-6) M = 49.3%; 10(-5) = 70%). These results suggest that harmane may have beneficial effects on morphine withdrawal syndrome.

  7. Postexposure protection of guinea pigs against a lethal ebola virus challenge is conferred by RNA interference.

    PubMed

    Geisbert, Thomas W; Hensley, Lisa E; Kagan, Elliott; Yu, Erik Zhaoying; Geisbert, Joan B; Daddario-DiCaprio, Kathleen; Fritz, Elizabeth A; Jahrling, Peter B; McClintock, Kevin; Phelps, Janet R; Lee, Amy C H; Judge, Adam; Jeffs, Lloyd B; MacLachlan, Ian

    2006-06-15

    Ebola virus (EBOV) infection causes a frequently fatal hemorrhagic fever (HF) that is refractory to treatment with currently available antiviral therapeutics. RNA interference represents a powerful, naturally occurring biological strategy for the inhibition of gene expression and has demonstrated utility in the inhibition of viral replication. Here, we describe the development of a potential therapy for EBOV infection that is based on small interfering RNAs (siRNAs). Four siRNAs targeting the polymerase (L) gene of the Zaire species of EBOV (ZEBOV) were either complexed with polyethylenimine (PEI) or formulated in stable nucleic acid-lipid particles (SNALPs). Guinea pigs were treated with these siRNAs either before or after lethal ZEBOV challenge. Treatment of guinea pigs with a pool of the L gene-specific siRNAs delivered by PEI polyplexes reduced plasma viremia levels and partially protected the animals from death when administered shortly before the ZEBOV challenge. Evaluation of the same pool of siRNAs delivered using SNALPs proved that this system was more efficacious, as it completely protected guinea pigs against viremia and death when administered shortly after the ZEBOV challenge. Additional experiments showed that 1 of the 4 siRNAs alone could completely protect guinea pigs from a lethal ZEBOV challenge. Further development of this technology has the potential to yield effective treatments for EBOV HF as well as for diseases caused by other agents that are considered to be biological threats.

  8. Defining the Hook Region Anatomy of the Guinea Pig Cochlea for Modeling of Inner Ear Surgery.

    PubMed

    Lo, Jonathon; Sale, Phillip; Wijewickrema, Sudanthi; Campbell, Luke; Eastwood, Hayden; O'leary, Stephen John

    2017-07-01

    The aim of this study was to describe the hook region anatomy of the guinea pig cochlea to identify the optimal surgical approach for cochlear implantation and to determine what anatomical structures are at risk. Animal studies investigating hearing loss after cochlear implantation surgery are currently constrained by the lack of a reproducible implantation model. Guinea pig cochleae were imaged using thin-sheet laser imaging microscopy. Images were stitched, reconstructed, and segmented for analysis. Insertion vectors were determined by tracing their paths to the outer wall and converting to Cartesian coordinates. Spherical surface and multiplane views were generated to analyze outer wall and radial forces of the insertion vector. Thin-sheet laser imaging microscopy enabled quantitative, whole specimen analysis of the soft and bony tissue relationships of the complex cochlear hook region in any desired plane without loss of image quality. Round window or cochleostomy approaches in the anteroinferior plane avoided direct damage to cochlear structures. Cochleostomy approach had large interindividual variability of angular depth and outer wall forces but predictable radial force. The guinea pig hook region and lower basal turn have similar structural relationships to humans. Careful cochleostomy placement is essentially for minimizing cochlear trauma and for ensuring a straight insertion vector that successfully advances around the outer wall. Experiments with guinea pigs that control for the surgical approach are likely to provide useful insights into the aetiology and the development of therapies directed at postimplantation hearing loss.

  9. Role of connexin 43 in the maintenance of spontaneous activity in the guinea pig prostate gland

    PubMed Central

    Dey, Anupa; Kusljic, Snezana; Lang, Richard J; Exintaris, Betty

    2010-01-01

    BACKGROUND AND PURPOSE To investigate the role of connexin 43 in the maintenance of spontaneous activity in prostate tissue from young and old guinea pigs. EXPERIMENTAL APPROACH Conventional intracellular microelectrode and tension recording techniques, coupled with Western blot analysis and immunohistochemistry for connexin 43 (CX43) were used. The effects of three gap junction uncouplers, 18β glycyrrhetinic acid (10 µM, 40 µM), carbenoxolone (10 µM, 50 µM) and octanol (0.5 mM, 1 mM), were studied in cells displaying slow wave activity and on spontaneously contracting tissue from prostate glands of young (2–5 months) and old (9–16 months) guinea pigs. KEY RESULTS 18β Glycyrrhetinic acid (40 µM), carbenoxolone (50 µM) or octanol (0.5 mM) abolished slow wave activity in prostate tissue from young and old guinea pigs and depolarized membrane potential by approximately 5 mV. These treatments also abolished all contractions in both sets of prostate tissue. These effects were reversed upon washout. Western blot analysis and CX43 immunohistochemistry showed that there was no age-related difference in the expression and distribution of CX43 in prostate tissues. CONCLUSION AND IMPLICATIONS When gap junctional communication via CX43 was disrupted, spontaneous activity was abolished at a cellular and whole tissue level; CX43 is therefore essential for the maintenance of spontaneous slow wave activity and subsequent contractile activity in the guinea pig prostate gland. PMID:20735413

  10. The in vitro isolated whole guinea pig brain as a model to study epileptiform activity patterns.

    PubMed

    de Curtis, Marco; Librizzi, Laura; Uva, Laura

    2016-02-15

    Research on ictogenesis is based on the study of activity between seizures and during seizures in animal models of epilepsy (chronic condition) or in in vitro slices obtained from naïve non-epileptic brains after treatment with pro-convulsive drugs, manipulations of the extracellular medium and specific stimulation protocols. The in vitro isolated guinea pig brain retains the functional connectivity between brain structures and maintains interactions between neuronal, glial and vascular compartments. It is a close-to-in vivo preparation that offers experimental advantages not achieved with the use of other experimental models. Neurophysiological and imaging techniques can be utilized in this preparation to study brain activity during and between seizures induced by pharmacological or functional manipulations. Cellular and network determinants of interictal and ictal discharges that reproduce abnormal patterns observed in human focal epilepsies and the associated changes in extracellular ion and blood-brain permeability can be identified and analyzed in the isolated guinea pig brain. Ictal and interictal patterns recorded in in vitro slices may show substantial differences from seizure activity recorded in vivo due to slicing procedure itself. The isolated guinea pig brain maintained in vitro by arterial perfusion combines the typical facilitated access of in vitro preparations, that are difficult to approach during in vivo experiments, with the preservation of larger neuronal networks. The in vitro whole isolated guinea pig brain preparation offers an unique experimental model to study systemic and neurovascular changes during ictogenesis. Published by Elsevier B.V.

  11. Negative inotropism of terpenes on guinea pig left atrium: structure-activity relationships.

    PubMed

    Vasconcelos, Carla M L; Oliveira, Ingrid S N; Santos, José N A; Souza, Américo A; Menezes-Filho, José E R; Silva Neto, Júlio A; Lima, Tamires C; de Sousa, Damião P

    2018-06-01

    The aim of this work was to evaluate the pharmacological effect of seven structurally related terpenes on the contractility of cardiac muscle. The effect of terpenes was studied on isolated electrically driven guinea pig left atrium. From concentration-response curves for inotropic effect were determined the EC 50 and relative potency of such terpenes. Our results revealed that all terpenes, except phytol, showed ability to reduce the contractile response of guinea pig left atrium. Further, relative potency was directly related to the number of isoprene units and to the lipophilicity of the compounds. For example, sesquiterpenes farnesol and nerolidol showed higher relative potency when compared with the monoterpenes citronellol, geraniol and nerol. We can conclude that most of the evaluated terpenes showed a promising negative inotropism on the atrial muscle. Future studies are necessary to investigate their action mechanism.

  12. Goats' milk of defective alpha(s1)-casein genotype decreases intestinal and systemic sensitization to beta-lactoglobulin in guinea pigs.

    PubMed

    Bevilacqua, C; Martin, P; Candalh, C; Fauquant, J; Piot, M; Roucayrol, A M; Pilla, F; Heyman, M

    2001-05-01

    Contradictory results have been reported on the use of goats' milk in cows' milk allergy. In this study the hypothesis was tested, using a guinea pig model of cows' milk allergy, that these discrepancies could be due to the high genetic polymorphism of goats' milk proteins. Forty guinea pigs were fed over a 20 d period with pelleted diets containing one of the following: soyabean proteins (group S), cows' milk proteins (group CM), goats' milk proteins with high (group GM1) or low (group GM2) alpha(s1)-casein content. Parenteral sensitization to GM1 and GM2 proteins as also assessed. The sensitization was measured (1) by systemic IgG1 antibodies directed against bovine or caprine beta-lactoglobulin (beta-lg), alpha-lactalbumin (alpha-la) and whole caseins, and (2) by intestinal anaphylaxis measured in vitro in Ussing chambers, by the rise in short-circuit current (delta Isc) in response to milk proteins. Guinea pigs fed on CM and GM1 developed high titres (> 1500) of anti-beta-lg IgG1, with an important cross reactivity between goat and cow beta-lg. However, in guinea pigs fed on GM2, anti-goat beta-lg IgG1 antibodies were significantly decreased compared with GM1 guinea pigs (mean IgG1 titres were 546 and 2046 respectively), and the intestinal anaphylaxis was significantly decreased (3.5+/-4.5 microA/cm2) compared with that observed in GM1 guinea pigs (8.3+/-7.6 microA/cm2). Animals receiving GM1 or GM2 proteins via the parenteral route developed a marked sensitization. These results suggest that the discrepancies observed in the use of goats milk in cows' milk allergy could be due, at least in part, to the high genetic polymorphism of goats' milk proteins.

  13. Characterization of Guinea Pig Antibody Responses to Salivary Proteins of Triatoma infestans for the Development of a Triatomine Exposure Marker

    PubMed Central

    Dorňáková, Veronika; Salazar-Sanchez, Renzo; Borrini-Mayori, Katty; Carrion-Navarro, Oscar; Levy, Michael Z.; Schaub, Günter A.; Schwarz, Alexandra

    2014-01-01

    Background Salivary proteins of Triatoma infestans elicit humoral immune responses in their vertebrate hosts. These immune responses indicate exposure to triatomines and thus can be a useful epidemiological tool to estimate triatomine infestation. In the present study, we analyzed antibody responses of guinea pigs to salivary antigens of different developmental stages of four T. infestans strains originating from domestic and/or peridomestic habitats in Argentina, Bolivia, Chile and Peru. We aimed to identify developmental stage- and strain-specific salivary antigens as potential markers of T. infestans exposure. Methodology and Principal Findings In SDS-PAGE analysis of salivary proteins of T. infestans the banding pattern differed between developmental stages and strains of triatomines. Phenograms constructed from the salivary profiles separated nymphal instars, especially the 5th instar, from adults. To analyze the influence of stage- and strain-specific differences in T. infestans saliva on the antibody response of guinea pigs, twenty-one guinea pigs were exposed to 5th instar nymphs and/or adults of different T. infestans strains. Western blot analyses using sera of exposed guinea pigs revealed stage- and strain-specific variations in the humoral response of animals. In total, 27 and 17 different salivary proteins reacted with guinea pig sera using IgG and IgM antibodies, respectively. Despite all variations of recognized salivary antigens, an antigen of 35 kDa reacted with sera of almost all challenged guinea pigs. Conclusion Salivary antigens are increasingly considered as an epidemiological tool to measure exposure to hematophagous arthropods, but developmental stage- and strain-specific variations in the saliva composition and the respective differences of immunogenicity are often neglected. Thus, the development of a triatomine exposure marker for surveillance studies after triatomine control campaigns requires detailed investigations. Our study resulted

  14. Luliconazole Retention in Stratum Corneum and Prevention of Fungal Infection in a Guinea Pig Tinea Pedis Model.

    PubMed

    Koga, Hiroyasu; Nanjoh, Yasuko; Toga, Tetsuo; Pillai, Radhakrishnan; Jo, William; Tsuboi, Ryoji

    2016-01-01

    To compare drug concentrations in the stratum corneum following daily application of luliconazole and terbinafine cream in a guinea pig tinea pedis model. Luliconazole 1% cream or terbinafine 1% cream were topically applied once daily to hind limbs of guinea pigs for 14 days. Drug concentration in stratum corneum of plantar skin was measured by HPLC-UV on days 1, 3, 7, 10, and 14. Separately, creams were applied daily for 5 days to the hind limbs of guinea pigs and skin drug release determined. In addition, drug retention in the stratum corneum was assessed by infecting guinea pigs with Trichophyton mentagrophytes, 14 and 21 days after a single application of luliconazole or terbinafine creams. Luliconazole stratum corneum concentrations were higher than those of terbinafine throughout the study. Concentrations of luliconazole and terbinafine were 71.6μg/g and 36.6μg/g, respectively, after a single application (P<.05), reaching steady state after 10 days. Cumulative release of luliconazole from the stratum corneum was 4.5 times greater than with terbinafine. Unlike terbinafine, no fungal invasion of the stratum corneum was seen 14 days post-treatment with luliconazole. Drug concentrations of luliconazole in the stratum corneum and subsequent release are greater than those achieved with terbinafine and may contribute to clinical efficacy. Luliconazole may also provide greater protection against disease recurrence.

  15. Identification and structural analysis of an L-asparaginase enzyme from guinea pig with putative tumor cell killing properties.

    PubMed

    Schalk, Amanda M; Nguyen, Hien-Anh; Rigouin, Coraline; Lavie, Arnon

    2014-11-28

    The initial observation that guinea pig serum kills lymphoma cells marks the serendipitous discovery of a new class of anti-cancer agents. The serum cell killing factor was shown to be an enzyme with L-asparaginase (ASNase) activity. As a direct result of this observation, several bacterial L-asparaginases were developed and are currently approved by the Food and Drug Administration for the treatment of the subset of hematological malignancies that are dependent on the extracellular pool of the amino acid asparagine. As drugs, these enzymes act to hydrolyze asparagine to aspartate, thereby starving the cancer cells of this amino acid. Prior to the work presented here, the precise identity of this guinea pig enzyme has not been reported in the peer-reviewed literature. We discovered that the guinea pig enzyme annotated as H0W0T5_CAVPO, which we refer to as gpASNase1, has the required low Km property consistent with that possessed by the cell-killing guinea pig serum enzyme. Elucidation of the ligand-free and aspartate complex gpASNase1 crystal structures allows a direct comparison with the bacterial enzymes and serves to explain the lack of L-glutaminase activity in the guinea pig enzyme. The structures were also used to generate a homology model for the human homolog hASNase1 and to help explain its vastly different kinetic properties compared with gpASNase1, despite a 70% sequence identity. Given that the bacterial enzymes frequently present immunogenic and other toxic side effects, this work suggests that gpASNase1 could be a promising alternative to these bacterial enzymes. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Gestation age dependent transfer of human immunoglobulins across placenta in timed-pregnant guinea pigs.

    PubMed

    Xu, Yanqun; Ma, Li; Norton, Malgorzata G; Stuart, Christine; Zhao, Zhong; Toibero, Denise; Dahlen, Shelby; Zhong, Lilin; Zhang, Pei; Struble, Evi B

    2015-12-01

    When administered during pregnancy, antibodies and other biologic drugs that contain the Fc part of the IgG molecule can traverse the placenta. Although it is generally accepted that the FcRn receptor mediates this process, gaps remain in our understanding of underlying details in humans and in common laboratory animal species. We expanded our previous studies in timed-pregnant guinea pigs to both measure the transport of human (h) IgG at earlier gestation ages in vivo and evaluate FcRn function in vitro using Surface Plasmon Resonance (SPR) and Madin-Darby canine kidney cells (MDCK) that express guinea pig (gp) FcRn. In timed-pregnant guinea pigs both the average concentration of hIgG in the fetus and its ratio to maternal hIgG concentration increase exponentially with gestation age. Thus, hIgG fetal:maternal concentration ratios increase from an average of 1% to 3%, 17%, and 76% on GD ∼26, 35, 46, and 54, respectively. In vitro, gpFcRn immobilized on a solid surface can bind hIgG and gpIgG preparations in a similar manner. All engineered human Fc isotype-specific constructs were internalized by MDCK-gpFcRn cells at significant levels. While not significant, their recycling and hIgG transcytosis by this cell line also trend higher than background controls. Pregnant guinea pigs exhibit similarities with humans in the degree and timing of transplacental transfer as well as the ability of their FcRn to bind and internalize hIgG in vitro. Further studies are needed to guide building appropriate systems for the evaluation of FcRn mediated function of human immunoglobulin therapies. Published by Elsevier Ltd.

  17. Guinea pig (Cavia porcellus) drinking preferences: do nipple drinkers compensate for behaviourally deficient diets?

    PubMed

    Balsiger, A; Clauss, M; Liesegang, A; Dobenecker, B; Hatt, J-M

    2017-10-01

    When offered diets with hay ad libitum, rabbits (Oryctolagus cuniculus) clearly prefer open dishes over nipple drinkers, but whether this preference also applies in guinea pigs (Cavia porcellus) is unsure. We tested the drinker preference of 10 guinea pigs when offered open dishes (OD) and nipple drinkers (ND) simultaneously and measured the amount of water consumed by each animal on four different diets (grass hay 100%, or as 10% of intake on diets of fresh parsley, seed mix or pelleted complete feed, respectively) on either of the drinking systems. All animals ingested the hay portion of the combined diets first. The amount of water consumed differed significantly between individual animals. Animals drank less water on parsley than on the other diets. Nine of 10 animals clearly preferred ND when having a choice, and eight of these drank more when on ND only. The difference between the drinking systems was not consistent across all diets: on hay, similar amounts of water were drunk when on OD or ND only. Differences in water intake were reflected in urine production. Because drinking from ND in guinea pigs involves jaw movements similar to those in chewing, the results could suggest that when motivation for oral processing behaviour is not satisfied by a diet, animals may respond in using ND beyond physiological water necessity. Whereas physiological water requirements are probably better investigated with other drinking systems due to a possible overestimation when using ND, offering ND to pet guinea pigs most likely offers a form of behavioural enrichment that at the same time may increase water intake and hence act as prophylaxis against urolithiasis. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  18. The recombinant fusion protein CFP10-ESAT6-dIFN has protective effect against tuberculosis in guinea pigs.

    PubMed

    Permyakova, Natalya V; Belavin, Pavel A; Pirozhkova, Dariya S; Ufimtseva, Elena G; Rozov, Sergey M; Mursalimov, Sergey R; Sidorchuk, Yuriy V; Uvarova, Elena A; Zagorskaya, Alla A; Marenkova, Tatiana V; Bannikova, Svetlana V; Demidov, Evgeniy A; Starostin, Konstantin V; Kravchenko, Marionella A; Vakhrusheva, Diana V; Berdnikov, Roman B; Eremeeva, Natalya I; Skornyakov, Sergey N; Peltek, Sergey E; Deineko, Elena V

    2018-03-01

    Development of effective vaccine candidates against tuberculosis (TB) is currently the most important challenge in the prevention of this disease since the BCG vaccine fails to guarantee a lifelong protection, while any other approved vaccine with better efficiency is still absent. The protective effect of the recombinant fusion protein CFP10-ESAT6-dIFN produced in a prokaryotic expression system (Escherichia coli) has been assessed in a guinea pig model of acute TB. The tested antigen comprises the Mycobacterium tuberculosis (Mtb) proteins ESAT6 and CFP10 as well as modified human γ-interferon (dIFN) for boosting the immune response. Double intradermal immunization of guinea pigs with the tested fusion protein (2 × 0.5 µg) induces a protective effect against subsequent Mtb infection. The immunized guinea pigs do not develop the symptoms of acute TB and their body weight gain was five times more as compared with the non-immunized infected guinea pigs. The animal group immunized with this dose of antigen displays the minimum morphological changes in the internal organs and insignificant inflammatory lesions in the liver tissue, which complies with a decrease in the bacterial load in the spleen and average Mtb counts in macrophages.

  19. Transcriptional profiling of TLR-4/7/8-stimulated guinea pig splenocytes and whole blood by bDNA assay

    PubMed Central

    Ching, Lance K.; Mompoint, Farah; Guderian, Jeffrey A.; Picone, Alex; Orme, Ian M.; Coler, Rhea N.; Reed, Steven G.; Baldwin, Susan L.

    2011-01-01

    Toll-like receptor (TLR) agonists are currently being examined as adjuvants for vaccines, with several lead candidates now in licensed products or in late-stage clinical development. Guinea pigs are widely used for preclinical testing of drugs and vaccines; however, evaluation of TLR agonists in this model is hindered by the limited availability of immunological tools and reagents. In this study, we validated the use of a branched-chain DNA (bDNA) assay known as the QuantiGene Plex 2.0 Reagent System for measuring innate cytokine and chemokine mRNA levels following TLR stimulation of guinea pig cells. Gene expression for T-helper-1 (Th1) polarizing cytokines (TNF-α, IL-1β, IL-12) and chemokines (CXCL1, CCL2) was upregulated following ex vivo stimulation of guinea pig splenocytes and whole blood with TLR-4 or TLR-7/8 agonists. These data confirm the utility of the QuantiGene system both as an alternative to RT-PCR for measuring transcript levels and as a high-throughput screening tool for dissecting the immunological response to TLR stimulation in guinea pigs. Overall, the QuantiGene platform is reliable, reproducible, and sensitive. These agonists have the potential to be used as adjuvant components in vaccines against various pathogens. PMID:21839740

  20. [Effects of genistein on contractility of isolated right ventricular muscles in guinea pig].

    PubMed

    Wu, Jin-xia; Li, Hong-fang; Liu, Chong-bin; Tian, Zhi-feng

    2008-11-01

    To study the effect of genistein (GEN) on contractility of isolated right ventricular muscles in guinea pig and its mechanisms. Isolated guinea pig ventricular muscles were suspended in organ baths containing K-H solution.After an equilibration period, the effect of GEN on contraction of myocardium was observed. GEN and isoprenaline hydrochloride had the positive inotropic effects on contractity of myocardium. Meanwhile, the effect of GEN (1-100 micromol x L(-1)) was in dose-dependent manner. Propranolol (1 micromol x L(-1)) and verapamil hydrochloride (0.5 micromol x L(-1)) attenuated the positive inotropic effect of isoprenaline hydrochloride (1 micromol x L(-1)), but did not change the effect of GEN (50 micromol x L(-1)). Further more, the enhancement of the contraction induced by elevation of extracellular Ca2+ concentration in ventricular muscles had no change after pretreatment with GEN (1.10 micromol x L(-1)). In addition,the positive inotropic effect of GEN was inhibited partially by tamoxifen (1 micromol x L(-1)) and SQ22536 (1 micromol x L(-1)), also, could be attenuated by bpV (1 micromol x L(-1)). GEN has the positive inotropic effect on guinea pig ventricular muscles, which is not related to the activation of beta adrenoceptor, Ca2+ channel on cell membrane,but may involve in cAMP of intracellular signal transduction and tyrosine kinase pathway.