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.

[Low extracellular pH increases the persistent sodium current in guinea pig ventricular myocytes].

PubMed

Ma, Ji-Hua; Luo, An-Tao; Wang, Wei-Ping; Zhang, Pei-Hua

2007-04-25

Whole-cell and cell-attached patch-clamp techniques were used to record the changes of persistent sodium current (I(Na.P)) in ventricular myocytes of guinea pig to investigate the effect of low extracellular pH on I(Na.P) and its mechanism. The results showed that low extracellular pH (7.0, 6.8 and 6.5) obviously increased the amplitude of whole-cell I(Na.P) in a [H(+)] concentration-dependent manner. Under the condition of extracellular pH 6.5, I(Na.P) was markedly augmented from control (pH 7.4) value of (0.347+/-0.067) pA/pF to (0.817+/- 0.137) pA/pF (P<0.01, n=6), whereas the reducing agent dithiothreitiol (DTT, 1 mmol/L) reversed the increased IN(Na.P) from (0.817+/-0.137) pA/pF to (0.233+/-0.078) pA/pF (P<0.01 vs pH 6.5, n=6). Decreasing extracellular pH to 6.5 also increased the persistent sodium channel activity in cell-attached patches. The mean open probability and mean open time were increased from control value of 0.021+/-0.007 and (0.899+/-0.074) ms to 0.205+/-0.023 and (1.593+/-0.158) ms, respectively (both P<0.01, n=6), and such enhancement was reversed by application of 1 mmol/L DTT [to 0.019+/-0.005 and (0.868+/-0.190) ms, both P<0.01 vs pH 6.5, n=6]. Furthermore, protein kinase C (PKC) inhibitor bisindolylmaleimide (BIM, 5 micromol/L) reduced the enhanced mean open probability and mean open time at pH 6.5 from 0.214+/-0.024 and (1.634+/-0.137) ms to 0.025+/-0.006 and (0.914+/-0.070) ms, respectively (both P<0.01 vs pH 6.5, n=6). The results demonstrate that low extracellular pH markedly increases I(Na.P) in guinea pig ventricular myocytes, in which activation of PKC may be involved.

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.

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.

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

Effects of Xinjining extract on inward rectifier potassium current in ventricular myocytes of guinea pig.

PubMed

Zhu, Ming-jun; Wang, Guo-juan; Wang, Yong-xia; Pu, Jie-lin; Liu, Hong-jun; Yu, Hai-bin

2010-02-01

To study the effect of Xinjining extract (, XJN) on inward rectifier potassium current (I(K1)) in ventricular myocyte (VMC) of guinea pigs and its anti-arrhythmic mechanism on ion channel level. Single VMC was enzymatically isolated by zymolisis, and whole-cell patch clamp recording technique was used to record the I(k1) in VMC irrigated with XJN of different concentrations (1.25, 2.50, 5.00 g/L; six samples for each). The stable current and conductance of the inward component of I(K1) as well as the outward component of peak I(K1) and conductance of it accordingly was recorded when the test voltage was set on -110 mV. The suppressive rate of XJN on the inward component of I(K1) was 9.54% + or - 5.81%, 34.82% + or - 15.03%, and 59.52% + or - 25.58% with a concentration of 1.25, 2.50, and 5.00 g/L, respectively, and that for the outward component of peak I(K1) was 23.94% + or - 7.45%, 52.98% + or - 19.62%, and 71.42% + or - 23.01%, respectively (all P<0.05). Moreover, different concentrations of XJN also showed effects for reducing I(K1) conductance. XJN has inhibitory effect on I(K1) in guinea pig's VMC, and that of the same concentration shows stronger inhibition on outward component than on inward component, which may be one of the mechanisms of its anti-arrhythmic effect.

Inhibitory Effects of Glycyrrhetinic Acid on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes and HERG Channel

PubMed Central

Wu, Delin; Jiang, Linqing; Wu, Hongjin; Wang, Shengqi; Zheng, Sidao; Yang, Jiyuan; Liu, Yuna; Ren, Jianxun; Chen, Xianbing

2013-01-01

Background. Licorice has long been used to treat many ailments including cardiovascular disorders in China. Recent studies have shown that the cardiac actions of licorice can be attributed to its active component, glycyrrhetinic acid (GA). However, the mechanism of action remains poorly understood. Aim. The effects of GA on the delayed rectifier potassium current (I K), the rapidly activating (I Kr) and slowly activating (I Ks) components of I K, and the HERG K+ channel expressed in HEK-293 cells were investigated. Materials and Methods. Single ventricular myocytes were isolated from guinea pig myocardium using enzymolysis. The wild type HERG gene was stably expressed in HEK293 cells. Whole-cell patch clamping was used to record I K (I Kr, I Ks) and the HERG K+ current. Results. GA (1, 5, and 10 μM) inhibited I K (I Kr, I Ks) and the HERG K+ current in a concentration-dependent manner. Conclusion. GA significantly inhibited the potassium currents in a dose- and voltage-dependent manner, suggesting that it exerts its antiarrhythmic action through the prolongation of APD and ERP owing to the inhibition of I K (I Kr, I Ks) and HERG K+ channel. PMID:24069049

A key role for peroxynitrite-mediated inhibition of cardiac ERG (Kv11.1) K+ channels in carbon monoxide–induced proarrhythmic early afterdepolarizations

PubMed Central

Al-Owais, Moza M.; Hettiarachchi, Nishani T.; Kirton, Hannah M.; Hardy, Matthew E.; Boyle, John P.; Scragg, Jason L.; Steele, Derek S.; Peers, Chris

2017-01-01

Exposure to CO causes early afterdepolarization arrhythmias. Previous studies in rats have indicated that arrhythmias arose as a result of augmentation of the late Na+ current. The purpose of the present study was to examine the basis for CO-induced arrhythmias in guinea pig myocytes in which action potentials (APs) more closely resemble those of human myocytes. Whole-cell current- and voltage-clamp recordings were made from isolated guinea pig myocytes as well as from human embryonic kidney 293 (HEK293) cells that express wild-type or a C723S mutant form of ether-a-go-go–related gene (ERG; Kv11.1). We also monitored the formation of peroxynitrite (ONOO−) in HEK293 cells fluorimetrically. CO—applied as the CO-releasing molecule, CORM-2—prolonged the APs and induced early afterdepolarizations in guinea pig myocytes. In HEK293 cells, CO inhibited wild-type, but not C723S mutant, Kv11.1 K+ currents. Inhibition was prevented by an antioxidant, mitochondrial inhibitors, or inhibition of NO formation. CO also raised ONOO− levels, an effect that was reversed by the ONOO− scavenger, FeTPPS [5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrinato-iron(III)], which also prevented the CO inhibition of Kv11.1 currents and abolished the effects of CO on Kv11.1 tail currents and APs in guinea pig myocytes. Our data suggest that CO induces arrhythmias in guinea pig cardiac myocytes via the ONOO−-mediated inhibition of Kv11.1 K+ channels.—Al-Owais, M. M., Hettiarachchi, N. T., Kirton, H. M., Hardy, M. E., Boyle, J. P., Scragg, J. L., Steele, D. S., Peers, C. A key role for peroxynitrite-mediated inhibition of cardiac ERG (Kv11.1) K+ channels in carbon monoxide–induced proarrhythmic early afterdepolarizations. PMID:28743763

Enhanced basal late sodium current appears to underlie the age-related prolongation of action potential duration in guinea pig ventricular myocytes.

PubMed

Song, Yejia; Belardinelli, Luiz

2017-12-14

Aging hearts have prolonged QT interval and are vulnerable to oxidative stress. Because the QT interval indirectly reflects the action potential duration (APD), we examined the hypotheses that 1) the APD of ventricular myocytes increases with age; 2) the age-related prolongation of APD is due to an enhancement of basal late Na + current (I NaL ); 3) inhibition of I NaL may protect aging hearts from arrhythmogenic effects of hydrogen peroxide (H 2 O 2 ). Experiments were performed on ventricular myocytes isolated from one-month (young) and one-year (old) guinea pigs (GPs). The APD of myocytes from old GPs was significantly longer than that from young GPs and was shortened by the I NaL inhibitors GS967 and tetrodotoxin. The magnitude of I NaL was significantly larger in myocytes from old than from young GPs. The CaMKII inhibitors KN-93 and AIP and the Na V 1.5-channel blocker MTSEA blocked the I NaL . There were no significant differences between myocytes from young and old GPs in L-type Ca 2+ current and the rapidly- and slowly-activating delayed rectifier K + currents, although the inward rectifier K + current was slightly decreased in myocytes from old GPs. H 2 O 2 induced more early afterdepolarizations in myocytes from old than from young GPs. The effect of H 2 O 2 was attenuated by GS967. The results suggest that 1) the APD of myocytes from old GPs is prolonged, 2) a CaMKII-mediated increase in Na V 1.5-channel I NaL is responsible for the prolongation of APD, and 3) Inhibition of I NaL may be beneficial for maintaining electrical stability under oxidative stress in myocytes of old GPs.

Relationship between intracellular pH and proton mobility in rat and guinea-pig ventricular myocytes.

PubMed

Swietach, Pawel; Vaughan-Jones, Richard D

2005-08-01

Intracellular H+ ion mobility in eukaryotic cells is low because of intracellular buffering. We have investigated whether Hi+ mobility varies with pHi. A dual microperfusion apparatus was used to expose guinea-pig or rat myocytes to small localized doses (3-5 mm) of ammonium chloride (applied in Hepes-buffered solution). Intracellular pH (pHi) was monitored confocally using the fluorescent dye, carboxy-SNARF-1. Local ammonium exposure produced a stable, longitudinal pHi gradient. Its size was fed into a look-up table (LUT) to give an estimate of the apparent intracellular proton diffusion coefficient (D(app)H). LUTs were generated using a diffusion-reaction model of Hi+ mobility based on intracellular buffer diffusion. To examine the pHi sensitivity of D(app)H, whole-cell pHi was initially displaced using a whole-cell ammonium or acetate prepulse, before locally applying the low dose of ammonium. In both rat and guinea-pig, D(app)H decreased with pHi over the range 7.5-6.5. In separate pipette-loading experiments, the intracellular diffusion coefficient for carboxy-SNARF-1 (a mobile-buffer analogue) exhibited no significant pHi dependence. The pHi sensitivity of D(app)H is thus likely to be governed by the mobile fraction of intrinsic buffering capacity. These results reinforce the buffer hypothesis of Hi+ mobility. The pHi dependence of D(app)H was used to characterize the mobile and fixed buffer components, and to estimate D(mob) (the average diffusion coefficient for intracellular mobile buffer). One consequence of a decline in Hi+ mobility at low pHi is that it will predispose the myocardium to pHi nonuniformity. The physiological relevance of this is discussed.

Transcriptional Reversion of Cardiac Myocyte Fate During Mammalian Cardiac Regeneration

PubMed Central

O’Meara, Caitlin C.; Wamstad, Joseph A.; Gladstone, Rachel; Fomovsky, Gregory M.; Butty, Vincent L.; Shrikumar, Avanti; Gannon, Joseph; Boyer, Laurie A.; Lee, Richard T.

2014-01-01

Rationale Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective The objectives of our study were to determine if myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results We derived a core transcriptional signature of injury-induced cardiac myocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiac myocyte differentiation, in vitro cardiac myocyte explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of cardiac myocyte differentiation processes including reactivation of latent developmental programs similar to those observed during de-stabilization of a mature cardiac myocyte phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13 (IL13), which induced cardiac myocyte cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of IL13 signaling in cardiac myocytes. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration. PMID:25477501

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.

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.

Amiodarone inhibits sarcolemmal but not mitochondrial KATP channels in Guinea pig ventricular cells.

PubMed

Sato, Toshiaki; Takizawa, Taichi; Saito, Tomoaki; Kobayashi, Satoru; Hara, Yukio; Nakaya, Haruaki

2003-12-01

ATP-sensitive K(+) (KATP) channels are present on the sarcolemma (sarcKATP channels) and mitochondria (mitoKATP channels) of cardiac myocytes. Amiodarone, a class III antiarrhythmic drug, reduces sudden cardiac death in patients with organic heart disease. The objective of the present study was to investigate the effects of amiodarone on sarcKATP and mitoKATP channels. Single sarcKATP channel current and flavoprotein fluorescence were measured in guinea pig ventricular myocytes to assay sarcKATP and mitoKATP channel activity, respectively. Amiodarone inhibited the sarcKATP channel currents in a concentration-dependent manner without affecting its unitary amplitude. The IC50 values were 0.35 microM in the inside-out patch exposed to an ATP-free solution and 2.8 microM in the cell-attached patch under metabolic inhibition, respectively. Amiodarone (10 microM) alone did not oxidize the flavoprotein. In addition, the oxidative effect of the mitoKATP channel opener diazoxide (100 microM) was unaffected by amiodarone. Exposure to ouabain (1 mM) for 30 min produced mitochondrial Ca(2+) overload, and the intensity of rhod-2 fluorescence increased to 246 +/- 16% of baseline (n = 9). Amiodarone did not alter the ouabain-induced mitochondrial Ca(2+) overload (236 +/- 10% of baseline, n = 7). Treatment with diazoxide significantly reduced the ouabain-induced mitochondrial Ca(2+) overload (158 +/- 15% of baseline, n = 8, p < 0.05 versus ouabain); this effect was not abolished by amiodarone (154 +/- 10% of baseline, n = 8, p < 0.05 versus ouabain). These results suggest that amiodarone inhibits sarcKATP but not mitoKATP channels in cardiac myocytes. Such an action of amiodarone may effectively prevent ischemic arrhythmias without causing ischemic damage.

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.

Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig

PubMed Central

Beaumont, Eric; Wright, Gary L.; Southerland, Elizabeth M.; Li, Ying; Chui, Ray; KenKnight, Bruce H.; Armour, J. Andrew

2016-01-01

Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15–20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling. PMID:26993230

Sarcolemmal mechanisms for pHi recovery from alkalosis in the guinea-pig ventricular myocyte

PubMed Central

Leem, Chae-Hun; Vaughan-Jones, Richard D

1998-01-01

The mechanism of pHi recovery from an intracellular alkali load (induced by acetate prepulse or by reduction/removal of ambient PCO2) was investigated using intracellular SNARF fluorescence in the guinea-pig ventricular myocyte. In Hepes buffer (pHo 7.40), pHi recovery was inhibited by removal of extracellular Cl−, but not by removal of Na+o or elevation of K+o. Recovery was unaffected by the stilbene drug DIDS (4,4-diisothiocyanatostilbene-disulphonic acid), but was slowed dose dependently by the stilbene drug DBDS (dibenzamidostilbene-disulphonic acid). In 5 % CO2/HCO3− buffer (pHo 7.40), pHi recovery was faster than in Hepes buffer. It consisted of an initial rapid recovery phase followed by a slow phase. Much of the rapid phase has been attributed to CO2-dependent buffering. The slow phase was inhibited completely by Cl− removal but not by Na+o removal or K+o elevation. At a test pHi of 7.30 in CO2/HCO3− buffer, the slow phase was inhibited 70 % by DIDS. The mean DIDS-inhibitable acid influx was equivalent in magnitude to the HCO3−-stimulated acid influx. Similarly, the DIDS-insensitive influx was equivalent to that estimated in Hepes buffer. We conclude that two independent sarcolemmal acid-loading carriers are stimulated by a rise of pHi and account for the slow phase of recovery from an alkali load. The results are consistent with activation of a DIDS-sensitive Cl−-HCO3− anion exchanger (AE) to produce HCO3− efflux, and a DIDS-insensitive Cl−-OH− exchanger (CHE) to produce OH− efflux. H+-Cl− co-influx as the alternative configuration for CHE is not, however, excluded. The dual acid-loading system (AE plus CHE), previously shown to be activated by a fall of extracellular pH, is thus activated by a rise of intracellular pH. Activity of the dual-loading system is therefore controlled by pH on both sides of the cardiac sarcolemma. PMID:9575297

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

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

Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig.

PubMed

Beaumont, Eric; Wright, Gary L; Southerland, Elizabeth M; Li, Ying; Chui, Ray; KenKnight, Bruce H; Armour, J Andrew; Ardell, Jeffrey L

2016-05-15

Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15-20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling. Copyright © 2016 the American Physiological Society.

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

Cardiac myosin binding protein C regulates postnatal myocyte cytokinesis

PubMed Central

Jiang, Jianming; Burgon, Patrick G.; Wakimoto, Hiroko; Onoue, Kenji; Gorham, Joshua M.; O’Meara, Caitlin C.; Fomovsky, Gregory; McConnell, Bradley K.; Lee, Richard T.; Seidman, J. G.; Seidman, Christine E.

2015-01-01

Homozygous cardiac myosin binding protein C-deficient (Mybpct/t) mice develop dramatic cardiac dilation shortly after birth; heart size increases almost twofold. We have investigated the mechanism of cardiac enlargement in these hearts. Throughout embryogenesis myocytes undergo cell division while maintaining the capacity to pump blood by rapidly disassembling and reforming myofibrillar components of the sarcomere throughout cell cycle progression. Shortly after birth, myocyte cell division ceases. Cardiac MYBPC is a thick filament protein that regulates sarcomere organization and rigidity. We demonstrate that many Mybpct/t myocytes undergo an additional round of cell division within 10 d postbirth compared with their wild-type counterparts, leading to increased numbers of mononuclear myocytes. Short-hairpin RNA knockdown of Mybpc3 mRNA in wild-type mice similarly extended the postnatal window of myocyte proliferation. However, adult Mybpct/t myocytes are unable to fully regenerate the myocardium after injury. MYBPC has unexpected inhibitory functions during postnatal myocyte cytokinesis and cell cycle progression. We suggest that human patients with homozygous MYBPC3-null mutations develop dilated cardiomyopathy, coupled with myocyte hyperplasia (increased cell number), as observed in Mybpct/t mice. Human patients, with heterozygous truncating MYBPC3 mutations, like mice with similar mutations, have hypertrophic cardiomyopathy. However, the mechanism leading to hypertrophic cardiomyopathy in heterozygous MYBPC3+/− individuals is myocyte hypertrophy (increased cell size), whereas the mechanism leading to cardiac dilation in homozygous Mybpc3−/− mice is primarily myocyte hyperplasia. PMID:26153423

Cardiac Myocyte Cell Cycle Control in Development, Disease and Regeneration

PubMed Central

Ahuja, Preeti; Sdek, Patima; Maclellan, W. Robb

2009-01-01

Cardiac myocytes rapidly proliferate during fetal life but exit the cell cycle soon after birth in mammals. Although the extent to which adult cardiac myocytes are capable of cell cycle reentry is controversial and species-specific differences may exist, it appears that for the vast majority of adult cardiac myocytes the predominant form of growth postnatally is an increase in cell size (hypertrophy) not number. Unfortunately, this limits the ability of the heart to restore function after any significant injury. Interst in novel regenerative therapies has led to the accumulation of much information on the mechanisms that regulate the rapid proliferation of cardiac myocytes in utero, their cell cycle exit in the perinatal period and the permanent arrest (terminal differentiation) in adult myocytes. The recent identification of cardiac progenitor cells capable of giving rise to cardiac myocyte-like cells has challenged the dogma that the heart is a terminally differentiated organ and opened new prospects for cardiac regeneration. In this review, we summarize the current understanding of cardiomyocyte cell cycle control in normal development and disease. In addition, we also discuss the potential usefulness of cardiomyocyte self-renewal as well as feasibility of therapeutic manipulation of the cardiac myocyte cell cycle for cardiac regeneration. PMID:17429040

Out-of-equilibrium pH transients in the guinea-pig ventricular myocyte

PubMed Central

Leem, Chae-Hun; Vaughan-Jones, Richard D

1998-01-01

Following an intracellular alkali load (imposed by acetate prepulsing in CO2/HCO3− buffer), intracellular pH (pHi) of the guinea-pig ventricular myocyte (recorded from intracellular SNARF fluorescence) recovers to control levels. Recovery has two phases. An initial rapid phase (lasting up to 2 min) is followed by a later slow phase (several minutes). Inhibition of sarcolemmal acid-loading carriers (by removal of extracellular Cl−) inhibits the later, slow phase but the initial rapid recovery phase persists. It also persists in the absence of extracellular Na+ and in the presence of the HCO3− transport inhibitor DIDS (4,4-di-isothiocyanatostilbene-2,2-disulphonic acid). The rapid recovery phase is not evident if the alkali load has been induced by reducing PCO2 (from 10 to 5 %), and it is inhibited in the absence of CO2/HCO3− buffer (i.e. Hepes buffer). It is also slowed by the carbonic anhydrase (CA) inhibitor acetazolamide (ATZ). We conclude that it is caused by buffering of the alkali load through the hydration of intracellular CO2 (CO2-dependent buffering). The time course of rapid recovery is consistent with an intracellular CO2 hydration rate constant (k1) of 0.36 s−1 in the presence of CA activity, and 0.14 s−1 in the absence of CA activity. This latter k1 value matches the literature value for uncatalysed CO2 hydration in free solution. Natural CO2 hydration is accelerated 2.6-fold in the ventricular myocyte by endogenous CA. The rapid recovery phase represents a period when the intracellular CO2/HCO3− buffer is out of equilibrium (OOE). Modelling of the recovery phase using our k1 value, indicates that OOE conditions will normally extend for at least 2 min following a step rise in pHi (at constant PCO2). If CA is inactive, this period can be as long as 5 min. During normal pHi regulation, the recovery rate during these periods cannot be used as a measure of sarcolemmal acid loading since it is a mixture of slow CO2-dependent buffering and

Effects of itopride hydrochloride on the delayed rectifier K+ and L-type CA2+ currents in guinea-pig ventricular myocytes.

PubMed

Morisawa, T; Hasegawa, J; Hama, R; Kitano, M; Kishimoto, Y; Kawasaki, H

1999-01-01

The effects of itopride hydrochloride, a new drug used to regulate motility in the gastrointestinal tract, on the delayed rectifier K+ current (I(K)) and the L-type Ca2+ current (I(Ca)) were evaluated in guinea-pig ventricular myocytes at concentrations of 1, 10 and 100 microM to determine whether the drug has a proarrhythmic effect through blockade of I(K). Itopride did not affect I(K) at concentrations of 100 microM or less, and no significant effects of 1, 10 or 100 microM itopride were observed on the inward rectifier K+ current (I(K1)) responsible for the resting potential and final repolarization phase of the action potential. We next investigated the effects of itopride on L-type Ca2+ current (I(Ca)). Significant inhibition of I(Ca) was observed at itopride concentrations greater than 10 microM. These results suggested that itopride hydrochloride has an inhibitory effect on I(Ca) at concentrations much higher than those in clinical use.

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)

Inotropic effects of diadenosine tetraphosphate (AP4A) in human and animal cardiac preparations.

PubMed

Vahlensieck, U; Bokník, P; Gombosová, I; Huke, S; Knapp, J; Linck, B; Lüss, H; Müller, F U; Neumann, J; Deng, M C; Scheld, H H; Jankowski, H; Schlüter, H; Zidek, W; Zimmermann, N; Schmitz, W

1999-02-01

Diadenosine tetraphosphate (AP4A) is an endogenous compound and exerts diverse physiological effects in animal systems. However, the effects of AP4A on inotropy in ventricular cardiac preparations have not yet been studied. The effects of AP4A on force of contraction (FOC) were studied in isolated electrically driven guinea pig and human cardiac preparations. Furthermore, the effects of AP4A on L-type calcium current and [Ca]i were studied in isolated guinea pig ventricular myocytes. In guinea pig left atria, AP4A (0.1-100 microM) reduced FOC maximally by 36.5 +/- 4.3%. In guinea pig papillary muscles, AP4A (100 microM) alone was ineffective, but reduced isoproterenol-stimulated FOC maximally by 29.3 +/- 3.4%. The negative inotropic effects of AP4A in atria and papillary muscles were abolished by the A1-adenosine receptor antagonist 1, 3-dipropyl-cyclopentylxanthine. In guinea pig ventricular myocytes, AP4A (100 microM) attenuated isoproterenol-stimulated L-type calcium current and [Ca]i. In human atrial and ventricular preparations, AP4A (100 microM) alone increased FOC to 158.3 +/- 12.4% and 167.5 +/- 25.1%, respectively. These positive inotropic effects were abolished by the P2-purinoceptor antagonist suramin. On the other hand, AP4A (100 microM) reduced FOC by 27.2 +/- 7.4% in isoproterenol-stimulated human ventricular trabeculae. The latter effect was abolished by 1,3-dipropyl-cyclopentylxanthine. In summary, after beta adrenergic stimulation AP4A exerts negative inotropic effects in animal and human ventricular preparations via stimulation of A1-adenosine receptors. In contrast, AP4A alone can exert positive inotropic effects via P2-purinoceptors in human ventricular myocardium. Thus, P2-purinoceptor stimulation might be a new positive inotropic principle in the human myocardium.

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.

Alpha 1-acid glycoprotein reverses cocaine-induced sodium channel blockade in cardiac myocytes.

PubMed

Ma, Yu-Ling; Peters, Nicholas S; Henry, John A

2006-03-01

Alpha 1-acid glycoprotein (AAG) is an acute phase protein capable of binding basic drugs. This action explains its reversal of sodium channel blockade by drugs such as amitriptyline and quinidine. We report here the reversal of cocaine-induced sodium channel blockade by AAG. The sodium channel blocking property of cocaine is a major mechanism behind cocaine-induced sudden cardiac death, since sodium channels play a key role in the initiation and regulation of the heart beat. Voltage-gated sodium current (I(Na)) was recorded using whole-cell patch-clamp techniques. Guinea-pig cardiac ventricular myocytes were isolated and continuously perfused at room temperature with physiological solutions. At concentrations ranging from 5 to 320 microM cocaine showed a dose-dependent and reversible blockade of I(Na) with an IC50 of 45.9 microM. The addition of equimolar amounts of AAG to cocaine produced almost complete reversal of cocaine's effects, suggesting a single binding site for cocaine on the AAG molecule. With changes of peak I(Na) normalized against control as 1, cocaine at 20 and 40 microM reduced I(Na) to 0.62+/-0.042 (n = 6) and 0.57+/-0.052 (n = 9), respectively, and the addition of an equimolar concentration of AAG reversed I(Na) to 0.86+/-0.022 and 0.91+/-0.060, respectively. AAG reverses cocaine-induced sodium channel blockade in a dose-dependent manner, indicating a therapeutic potential to reverse acute cocaine cardiac toxicity.

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

Cardiac safety of lacosamide: the non-clinical perspective.

PubMed

Delaunois, A; Colomar, A; Depelchin, B O; Cornet, M

2015-11-01

Lacosamide is indicated for the adjunctive treatment of partial-onset seizures in adult patients. Unlike other sodium channel-blocking antiepileptic drugs, lacosamide selectively enhances sodium channel slow inactivation. Potential effects of lacosamide on cardiac sodium channels and their cardiovascular consequences were comprehensively assessed. This manuscript presents the non-clinical cardiac safety profile of lacosamide. Lacosamide was tested in vitro on sodium and L-type calcium currents from isolated human atrial myocytes and on hERG-mediated potassium currents from stably transfected HEK293 cells. Cardiac action potentials were recorded in guinea pig ventricular myocytes. In vivo, hemodynamic and ECG parameters were evaluated in anesthetized dogs and monkeys receiving acute cumulative intravenous doses of lacosamide. Following intravenous dosing with lacosamide, dose-dependent PR and QRS prolongation and ECG abnormalities (loss of P waves, atrioventricular and intraventricular blocks, junctional premature contractions) were observed in anesthetized dogs and monkeys. In vitro, lacosamide reduced human cardiac sodium currents in a concentration-, voltage- and state-dependent manner. Lacosamide reductions in Vmax in guinea pig myocytes were similar to lamotrigine and carbamazepine. Lacosamide showed no relevant inhibitory effects on hERG and L-type calcium channels and did not prolong QTc in vivo. ECG findings in anesthetized animals correlate well with in vitro sodium channel-related effects and are also consistent with those (PR prolongation, first-degree atrioventricular block) reported in healthy volunteers and patients with epilepsy. Both in vivo and in vitro effects were detected from exposure levels 1.5- to 2-fold above those achieved with the maximum-recommended human lacosamide dose (400 mg/day). © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

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.

Inhibitory Effect of Vascular Endothelial Growth Factor on the Slowly Activating Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes.

PubMed

Lin, Zhenhao; Xing, Wenlu; Gao, Chuanyu; Wang, Xianpei; Qi, Datun; Dai, Guoyou; Zhao, Wen; Yan, Ganxin

2018-01-26

Vascular endothelial growth factor (VEGF) exerts a number of beneficial effects on ischemic myocardium via its angiogenic properties. However, little is known about whether VEGF has a direct effect on the electrical properties of cardiomyocytes. In the present study, we investigated the effects of different concentrations of VEGF on delayed rectifier potassium currents (I K ) in guinea pig ventricular myocytes and their effects on action potential (AP) parameters. I K and AP were recorded by the whole-cell patch clamp method in ventricular myocytes. Cells were superfused with control solution or solution containing VEGF at different concentrations for 10 minutes before recording. Some ventricular myocytes were pretreated with a phosphatidylinositol 3-kinase inhibitor for 1 hour before the addition of VEGF. We found that VEGF inhibited the slowly activating delayed rectifier potassium current (I K s ) in a concentration-dependent manner (18.13±1.04 versus 12.73±0.34, n=5, P =0.001; 12.73±0.34 versus 9.05±1.20, n=5, P =0.036) and prolonged AP duration (894.5±36.92 versus 746.3±33.71, n=5, P =0.021). Wortmannin, a phosphatidylinositol 3-kinase inhibitor, eliminated these VEGF-induced effects. VEGF had no significant effect on the rapidly activating delayed rectifier potassium current (I K r ), resting membrane potential, AP amplitude, or maximal velocity of depolarization. VEGF inhibited I K s in a concentration-dependent manner through a phosphatidylinositol 3-kinase-mediated signaling pathway, leading to AP prolongation. The results indicate a promising therapeutic potential of VEGF in prevention of ventricular tachyarrhythmias under conditions of high sympathetic activity and ischemia. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Increased Cardiac Myocyte Progenitors in Failing Human Hearts

PubMed Central

Kubo, Hajime; Jaleel, Naser; Kumarapeli, Asangi; Berretta, Remus M.; Bratinov, George; Shan, Xiaoyin; Wang, Hongmei; Houser, Steven R.; Margulies, Kenneth B.

2009-01-01

Background Increasing evidence, derived mainly from animal models, supports the existence of endogenous cardiac renewal and repair mechanisms in adult mammalian hearts that could contribute to normal homeostasis and the responses to pathological insults. Methods and Results Translating these results, we isolated small c-kit+ cells from 36 of 37 human hearts using primary cell isolation techniques and magnetic cell sorting techniques. The abundance of these cardiac progenitor cells was increased nearly 4-fold in patients with heart failure requiring transplantation compared with nonfailing controls. Polychromatic flow cytometry of primary cell isolates (<30 μm) without antecedent c-kit enrichment confirmed the increased abundance of c-kit+ cells in failing hearts and demonstrated frequent coexpression of CD45 in these cells. Immunocytochemical characterization of freshly isolated, c-kit–enriched human cardiac progenitor cells confirmed frequent coexpression of c-kit and CD45. Primary cardiac progenitor cells formed new human cardiac myocytes at a relatively high frequency after coculture with neonatal rat ventricular myocytes. These contracting new cardiac myocytes exhibited an immature phenotype and frequent electric coupling with the rat myocytes that induced their myogenic differentiation. Conclusions Despite the increased abundance and cardiac myogenic capacity of cardiac progenitor cells in failing human hearts, the need to replace these organs via transplantation implies that adverse features of the local myocardial environment overwhelm endogenous cardiac repair capacity. Developing strategies to improve the success of endogenous cardiac regenerative processes may permit therapeutic myocardial repair without cell delivery per se. PMID:18645055

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...

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...

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...

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...

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...

Regulation of ATP sensitive potassium channel of isolated guinea pig ventricular myocytes by sarcolemmal monocarboxylate transport.

PubMed

Coetzee, W A

1992-11-01

The aim was to describe the effects of extracellular application of monocarboxylates (pyruvate, lactate, or acetate) on current through KATP channels (iK,ATP) in isolated guinea pig ventricular myocytes. The iK,ATP was elicited during whole cell voltage clamping by application of metabolic poisons, 2,4-dinitrophenol (150 microM) or glucose free cyanide (1 mM) and could be blocked by glibenclamide (3 microM). Extracellular application of monocarboxylates, pyruvate (0.1-10 mM), L-lactate (0.1-10 mM), and acetate (10 mM) led to a rapid inhibition of iK,ATP--an effect which was fully reversible upon washout. Substances without any effect on iK,ATP were (10 mM each) gluconate, citrate, glutamate, creatine, succinate, and glycine. The mechanism underlying the effects of monocarboxylates on iK,ATP was unlikely to be related to an increased ATP production, since D-lactate (10 mM) essentially had the same effect on iK,ATP as the L-isomer of lactate. Furthermore, with intracellular dialysis of alpha-cyano-4-hydroxycinnamate (0.1-0.5 mM), which inhibits pyruvate uptake into mitochondria, extracellular pyruvate exerted the same inhibitory effect on iK,ATP. High concentrations of extracellular alpha-cyano-4-hydroxycinnamate (4 mM), which blocks the sarcolemmal monocarboxylate carrier, prevented the effects on iK,ATP by pyruvate, L-lactate, D-lactate, and acetate. Furthermore, intracellular dialysis with D-lactate (10 mM) led to a more rapid onset of iK,ATP when activated by ATP free dialysis. Activity of isolated KATP channels, measured in isolated membrane patches in the inside out or outside out configuration, typically had a single channel conductance of around 80 pS and was blocked by glibenclamide (3-9 microM). No significant effect of pyruvate was observed in either patch configuration. In cardiac tissue there may be some modulatory role involving monocarboxylate transport on KATP channel activity, the nature of which is unclear at present but which may involve cytosolic

Hypertrophic cardiomyopathy mutation in cardiac troponin T (R95H) attenuates length-dependent activation in guinea pig cardiac muscle fibers.

PubMed

Mickelson, Alexis V; Chandra, Murali

2017-12-01

The central region of cardiac troponin T (TnT) is important for modulating the dynamics of muscle length-mediated cross-bridge recruitment. Therefore, hypertrophic cardiomyopathy mutations in the central region may affect cross-bridge recruitment dynamics to alter myofilament Ca 2+ sensitivity and length-dependent activation of cardiac myofilaments. Given the importance of the central region of TnT for cardiac contractile dynamics, we studied if hypertrophic cardiomyopathy-linked mutation (TnT R94H )-induced effects on contractile function would be differently modulated by sarcomere length (SL). Recombinant wild-type TnT (TnT WT ) and the guinea pig analog of the human R94H mutation (TnT R95H ) were reconstituted into detergent-skinned cardiac muscle fibers from guinea pigs. Steady-state and dynamic contractile measurements were made at short and long SLs (1.9 and 2.3 µm, respectively). Our results demonstrated that TnT R95H increased pCa 50 (-log of free Ca 2+ concentration) to a greater extent at short SL; TnT R95H increased pCa 50 by 0.11 pCa units at short SL and 0.07 pCa units at long SL. The increase in pCa 50 associated with an increase in SL from 1.9 to 2.3 µm (ΔpCa 50 ) was attenuated nearly twofold in TnT R95H fibers; ΔpCa 50 was 0.09 pCa units for TnT WT fibers but only 0.05 pCa units for TnT R95H fibers. The SL dependency of rate constants of cross-bridge distortion dynamics and tension redevelopment was also blunted by TnT R95H Collectively, our observations on the SL dependency of pCa 50 and rate constants of cross-bridge distortion dynamics and tension redevelopment suggest that mechanisms underlying the length-dependent activation cardiac myofilaments are attenuated by TnT R95H NEW & NOTEWORTHY Mutant cardiac troponin T (TnT R95H ) differently affects myofilament Ca 2+ sensitivity at short and long sarcomere length, indicating that mechanisms underlying length-dependent activation are altered by TnT R95H TnT R95H enhances myofilament Ca 2

Block of HERG human K(+) channel and IKr of guinea pig cardiomyocytes by chlorpromazine.

PubMed

Lee, So-Young; Choi, Se-Young; Youm, Jae Boum; Ho, Won-Kyung; Earm, Yung E; Lee, Chin O; Jo, Su-Hyun

2004-05-01

Chlorpromazine, a commonly used antipsychotic drug, has been known to induce QT prolongation and torsades de pointes, which can cause sudden death. We studied the effects of chlorpromazine on the human ether-a-go-go-related gene (HERG) channel expressed in Xenopus oocytes and on delayed rectifier K current of guinea pig ventricular myocytes. Application of chlorpromazine showed a dose-dependent decrease in the amplitudes of steady-state currents and tail currents of HERG. The decrease became more pronounced at increasingly positive potential, suggesting that the blockade of HERG by chlorpromazine is voltage dependent. IC50 for chlorpromazine block of HERG current was progressively decreased according to depolarization: IC50 values at -30, 0, and +30 mV were 10.5, 8.8, and 4.9 microM, respectively. The block of HERG current during the voltage step increased with time starting from a level 89% of the control current. In guinea pig ventricular myocytes, bath application of 2 and 5 microM chlorpromazine at 36 degree C blocked rapidly activating delayed rectifier K current (IKr) by 31 and 83%, respectively. How-ever, the same concentrations of chlorpromazine failed to significantly block slowly activating delayed rectifier K current (IKs). Our findings suggest that the arrhythmogenic side effect of chlorpromazine is caused by blockade of HERG and rapid component of delayed rectifier K current rather than by blockade of the slow component.

[Image processing applying in analysis of motion features of cultured cardiac myocyte in rat].

PubMed

Teng, Qizhi; He, Xiaohai; Luo, Daisheng; Wang, Zhengrong; Zhou, Beiyi; Yuan, Zhirun; Tao, Dachang

2007-02-01

Study of mechanism of medicine actions, by quantitative analysis of cultured cardiac myocyte, is one of the cutting edge researches in myocyte dynamics and molecular biology. The characteristics of cardiac myocyte auto-beating without external stimulation make the research sense. Research of the morphology and cardiac myocyte motion using image analysis can reveal the fundamental mechanism of medical actions, increase the accuracy of medicine filtering, and design the optimal formula of medicine for best medical treatments. A system of hardware and software has been built with complete sets of functions including living cardiac myocyte image acquisition, image processing, motion image analysis, and image recognition. In this paper, theories and approaches are introduced for analysis of living cardiac myocyte motion images and implementing quantitative analysis of cardiac myocyte features. A motion estimation algorithm is used for motion vector detection of particular points and amplitude and frequency detection of a cardiac myocyte. Beatings of cardiac myocytes are sometimes very small. In such case, it is difficult to detect the motion vectors from the particular points in a time sequence of images. For this reason, an image correlation theory is employed to detect the beating frequencies. Active contour algorithm in terms of energy function is proposed to approximate the boundary and detect the changes of edge of myocyte.

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.

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

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

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

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.

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.

Cardiac myocyte exosomes: stability, HSP60, and proteomics.

PubMed

Malik, Z A; Kott, K S; Poe, A J; Kuo, T; Chen, L; Ferrara, K W; Knowlton, A A

2013-04-01

Exosomes, which are 50- to 100-nm-diameter lipid vesicles, have been implicated in intercellular communication, including transmitting malignancy, and as a way for viral particles to evade detection while spreading to new cells. Previously, we demonstrated that adult cardiac myocytes release heat shock protein (HSP)60 in exosomes. Extracellular HSP60, when not in exosomes, causes cardiac myocyte apoptosis via the activation of Toll-like receptor 4. Thus, release of HSP60 from exosomes would be damaging to the surrounding cardiac myocytes. We hypothesized that 1) pathological changes in the environment, such as fever, change in pH, or ethanol consumption, would increase exosome permeability; 2) different exosome inducers would result in different exosomal protein content; 3) ethanol at "physiological" concentrations would cause exosome release; and 4) ROS production is an underlying mechanism of increased exosome production. We found the following: first, exosomes retained their protein cargo under different physiological/pathological conditions, based on Western blot analyses. Second, mass spectrometry demonstrated that the protein content of cardiac exosomes differed significantly from other types of exosomes in the literature and contained cytosolic, sarcomeric, and mitochondrial proteins. Third, ethanol did not affect exosome stability but greatly increased the production of exosomes by cardiac myocytes. Fourth, ethanol- and hypoxia/reoxygenation-derived exosomes had different protein content. Finally, ROS inhibition reduced exosome production but did not completely inhibit it. In conclusion, exosomal protein content is influenced by the cell source and stimulus for exosome formation. ROS stimulate exosome production. The functions of exosomes remain to be fully elucidated.

Can optical recordings of membrane potential be used to screen for drug-induced action potential prolongation in single cardiac myocytes?

PubMed

Hardy, M E L; Lawrence, C L; Standen, N B; Rodrigo, G C

2006-01-01

Potential-sensitive dyes have primarily been used to optically record action potentials (APs) in whole heart tissue. Using these dyes to record drug-induced changes in AP morphology of isolated cardiac myocytes could provide an opportunity to develop medium throughout assays for the pharmaceutical industry. Ideally, this requires that the dye has a consistent and rapid response to membrane potential, is insensitive to movement, and does not itself affect AP morphology. We recorded the AP from isolated adult guinea-pig ventricular myocytes optically using di-8-ANEPPS in a single-excitation dual-emission ratiometric system, either separately in electrically field stimulated myocytes, or simultaneously with an electrical AP recorded with a patch electrode in the whole-cell bridge mode. The ratio of di-8-ANEPPS fluorescence signal was calibrated against membrane potential using a switch-clamp to voltage clamp the myocyte. Our data show that the ratio of the optical signals emitted at 560/620 nm is linearly related to voltage over the voltage range of an AP, producing a change in ratio of 7.5% per 100 mV, is unaffected by cell movement and is identical to the AP recorded simultaneously with a patch electrode. However, the APD90 recorded optically in myocytes loaded with di-8-ANEPPS was significantly longer than in unloaded myocytes recorded with a patch electrode (355.6+/-13.5 vs. 296.2+/-16.2 ms; p<0.01). Despite this effect, the apparent IC50 for cisapride, which prolongs the AP by blocking IKr, was not significantly different whether determined optically or with a patch electrode (91+/-46 vs. 81+/-20 nM). These data show that the optical AP recorded ratiometrically using di-8-ANEPPS from a single ventricular myocyte accurately follows the action potential morphology. This technique can be used to estimate the AP prolonging effects of a compound, although di-8-ANEPPS itself prolongs APD90. Optical dyes require less technical skills and are less invasive than

Loss of Adult Cardiac Myocyte GSK-3 Leads to Mitotic Catastrophe Resulting in Fatal Dilated Cardiomyopathy

PubMed Central

Zhou, Jibin; Ahmad, Firdos; Parikh, Shan; Hoffman, Nichole E.; Rajan, Sudarsan; Verma, Vipin K.; Song, Jianliang; Yuan, Ancai; Shanmughapriya, Santhanam; Guo, Yuanjun; Gao, Erhe; Koch, Walter; Woodgett, James R.; Muniswamy, Madesh; Kishore, Raj; Lal, Hind; Force, Thomas

2016-01-01

Rationale Cardiac myocyte-specific deletion of either Glycogen Synthase Kinase (GSK)3A or GSK3B leads to cardiac protection following myocardial infarction, suggesting that deletion of both isoforms may provide synergistic protection. This is an important consideration due to the fact that all GSK-3–targeted drugs including the drugs already in clinical trial target both isoforms of GSK-3 and none are isoform specific. Objective To identify the consequences of combined deletion of cardiac myocyte GSK3A and GSK3B in heart function. Methods and Results We generated tamoxifen-inducible cardiac myocyte-specific mice lacking both GSK-3 isoforms (double knockout, DKO). We unexpectedly found that cardiac myocyte GSK-3 is essential for cardiac homeostasis and overall survival. Serial echocardiographic analysis reveals that within 2 weeks of tamoxifen treatment, DKO hearts leads to excessive dilatative remodeling and ventricular dysfunction. Further experimentation with isolated adult cardiac myocytes and fibroblasts from DKO implicated cardiac myocytes intrinsic factors responsible for observed phenotype. Mechanistically, loss of GSK-3 in adult cardiac myocytes resulted in induction of mitotic catastrophe, a previously unreported event in cardiac myocytes. DKO cardiac myocytes showed cell cycle progression resulting in increased DNA content and multi-nucleation. However, increased cell cycle activity was rivaled by marked activation of DNA damage, cell cycle checkpoint activation, and mitotic catastrophe induced apoptotic cell death. Importantly, mitotic catastrophe was also confirmed in isolated adult cardiac myocytes. Conclusion Together, our findings suggest that cardiac myocyte GSK-3 is required to maintain normal cardiac homeostasis and its loss is incompatible with life due to cell cycle dysregulation that ultimately results in a severe fatal dilated cardiomyopathy. PMID:26976650

Loss of Adult Cardiac Myocyte GSK-3 Leads to Mitotic Catastrophe Resulting in Fatal Dilated Cardiomyopathy.

PubMed

Zhou, Jibin; Ahmad, Firdos; Parikh, Shan; Hoffman, Nichole E; Rajan, Sudarsan; Verma, Vipin K; Song, Jianliang; Yuan, Ancai; Shanmughapriya, Santhanam; Guo, Yuanjun; Gao, Erhe; Koch, Walter; Woodgett, James R; Madesh, Muniswamy; Kishore, Raj; Lal, Hind; Force, Thomas

2016-04-15

Cardiac myocyte-specific deletion of either glycogen synthase kinase (GSK)-3α and GSK-3β leads to cardiac protection after myocardial infarction, suggesting that deletion of both isoforms may provide synergistic protection. This is an important consideration because of the fact that all GSK-3-targeted drugs, including the drugs already in clinical trial target both isoforms of GSK-3, and none are isoform specific. To identify the consequences of combined deletion of cardiac myocyte GSK-3α and GSK-3β in heart function. We generated tamoxifen-inducible cardiac myocyte-specific mice lacking both GSK-3 isoforms (double knockout). We unexpectedly found that cardiac myocyte GSK-3 is essential for cardiac homeostasis and overall survival. Serial echocardiographic analysis reveals that within 2 weeks of tamoxifen treatment, double-knockout hearts leads to excessive dilatative remodeling and ventricular dysfunction. Further experimentation with isolated adult cardiac myocytes and fibroblasts from double-knockout implicated cardiac myocytes intrinsic factors responsible for observed phenotype. Mechanistically, loss of GSK-3 in adult cardiac myocytes resulted in induction of mitotic catastrophe, a previously unreported event in cardiac myocytes. Double-knockout cardiac myocytes showed cell cycle progression resulting in increased DNA content and multinucleation. However, increased cell cycle activity was rivaled by marked activation of DNA damage, cell cycle checkpoint activation, and mitotic catastrophe-induced apoptotic cell death. Importantly, mitotic catastrophe was also confirmed in isolated adult cardiac myocytes. Together, our findings suggest that cardiac myocyte GSK-3 is required to maintain normal cardiac homeostasis, and its loss is incompatible with life because of cell cycle dysregulation that ultimately results in a severe fatal dilated cardiomyopathy. © 2016 American Heart Association, Inc.

Nickel suppresses the PACAP-induced increase in guinea pig cardiac neuron excitability

PubMed Central

Tompkins, John D.; Merriam, Laura A.; Girard, Beatrice M.; May, Victor

2015-01-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent intercellular signaling molecule involved in multiple homeostatic functions. PACAP/PAC1 receptor signaling increases excitability of neurons within the guinea pig cardiac ganglia, making them a unique system to establish mechanisms underlying PACAP modulation of neuronal function. Calcium influx is required for the PACAP-increased cardiac neuron excitability, although the pathway is unknown. This study tested whether PACAP enhancement of calcium influx through either T-type or R-type channels contributed to the modulation of excitability. Real-time quantitative polymerase chain reaction analyses indicated transcripts for Cav3.1, Cav3.2, and Cav3.3 T-type isoforms and R-type Cav2.3 in cardiac neurons. These neurons often exhibit a hyperpolarization-induced rebound depolarization that remains when cesium is present to block hyperpolarization-activated nonselective cationic currents (Ih). The T-type calcium channel inhibitors, nickel (Ni2+) or mibefradil, suppressed the rebound depolarization, and treatment with both drugs hyperpolarized cardiac neurons by 2–4 mV. Together, these results are consistent with the presence of functional T-type channels, potentially along with R-type channels, in these cardiac neurons. Fifty micromolar Ni2+, a concentration that suppresses currents in both T-type and R-type channels, blunted the PACAP-initiated increase in excitability. Ni2+ also blunted PACAP enhancement of the hyperpolarization-induced rebound depolarization and reversed the PACAP-mediated increase in excitability, after being initiated, in a subset of cells. Lastly, low voltage-activated currents, measured under perforated patch whole cell recording conditions and potentially flowing through T-type or R-type channels, were enhanced by PACAP. Together, our results suggest that a PACAP-enhanced, Ni2+-sensitive current contributes to PACAP-induced modulation of neuronal excitability. PMID:25810261

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.

Essential oil from Xylopia frutescens Aubl. reduces cytosolic calcium levels on guinea pig ileum: mechanism underlying its spasmolytic potential.

PubMed

Souza, Iara Leão Luna de; Correia, Ana Carolina de Carvalho; Araujo, Layanne Cabral da Cunha; Vasconcelos, Luiz Henrique César; Silva, Maria da Conceição Correia; Costa, Vicente Carlos de Oliveira; Tavares, Josean Fechine; Paredes-Gamero, Edgar Julian; Cavalcante, Fabiana de Andrade; Silva, Bagnólia Araújo da

2015-09-16

Xylopia frutescens Aubl. (embira, semente-de-embira or embira-vermelha), is used in folk medicine as antidiarrheal. The essential oil from its leaves (XF-EO) has been found to cause smooth muscle relaxation. Thus, the aim of this study was to investigate the spasmolytic action by which XF-EO acts on guinea pig ileum. The components of the XF-EO were identified by gas chromatography-mass spectrometry. Segments of guinea pig ileum were suspended in organ bath containing modified Krebs solution at 37 °C, bubbled with carbogen mixture under a resting tension of 1 g. Isotonic contractions were registered using kymographs and isometric contractions using force transducer coupled to an amplifier and computer. Fluorescence measurements were obtained with a microplate reader using Fluo-4. Forty-three constituents were identified in XF-EO, mostly mono- and sesquiterpenes. XF-EO has been found to cause relaxation on guinea pig ileum. The essential oil inhibited in a concentration-dependent manner both CCh- and histamine-induced phasic contractions, being more potent on histamine-induced contractions as well as antagonized histamine-induced cumulative contractions in a non-competitive antagonism profile. XF-EO relaxed in a concentration-dependent manner the ileum pre-contracted with KCl and histamine. Since the potency was smaller in organ pre-contracted with KCl, it was hypothesized that XF-OE would be acting as a K(+) channel positive modulator. In the presence of CsCl (non-selective K(+) channel blocker), the relaxant potency of XF-OE was not altered, indicating a non-participation of these channels. Moreover, XF-EO inhibited CaCl2-induced cumulative contractions in a depolarizing medium nominally without Ca(2+) and relaxed the ileum pre-contracted with S-(-)-Bay K8644 in a concentration-dependent manner, thus, was confirmed the inhibition of Ca(2+) influx through Cav1 by XF-EO. In cellular experiments, the viability of longitudinal layer myocytes from guinea pig ileum was

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

Electrophysiological effects of haloperidol on isolated rabbit Purkinje fibers and guinea pigs papillary muscles under normal and simulated ischemia.

PubMed

Yan, Dong; Cheng, Lu-feng; Song, Hong-Yan; Turdi, Subat; Kerram, Parhat

2007-08-01

Overdoses of haloperidol are associated with major ventricular arrhythmias, cardiac conduction block, and sudden death. The aim of this experiment was to study the effect of haloperidol on the action potentials in cardiac Purkinje fibers and papillary muscles under normal and simulated ischemia conditions in rabbits and guinea pigs. Using the standard intracellular microelectrode technique, we examined the effects of haloperidol on the action potential parameters [action potential amplitude (APA), phase 0 maximum upstroke velocity (V(max)), action potential amplitude at 90% of repolarization (APD(90)), and effective refractory period (ERP)] in rabbit cardiac Purkinje fibers and guinea pig cardiac papillary cells, in which both tissues were under simulated ischemic conditions. Under ischemic conditions, different concentrations of haloperidol depressed APA and prolonged APD(90) in a concentration-dependent manner in rabbit Purkinje fibers. Haloperidol (3 micromol/L) significantly depressed APA and prolonged APD(90), and from 1 micromol/L, haloperidol showed significant depression on V(max); ERP was not significantly affected. In guinea pig cardiac papillary muscles, the thresholds of significant reduction in APA, V(max), EPR, and APD(90) were 10, 0.3, 1, and 1 mumol/L, respectively, for haloperidol. Compared with cardiac conductive tissues, papillary muscles were more sensitive to ischemic conditions. Under ischemia, haloperidol prolonged ERP and APD(90) in a concentration-dependent manner and precipitated the decrease in V(max) induced by ischemia. The shortening of ERP and APD(90) in papillary muscle action potentials may be inhibited by haloperidol.

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

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.

Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes

PubMed Central

He, Quan; Harris, Nicole; Ren, Jun; Han, Xianlin

2014-01-01

Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS) have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress. PMID:25247053

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

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.

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

Inhibition of the calcium channel by intracellular protons in single ventricular myocytes of the guinea-pig.

PubMed Central

Kaibara, M; Kameyama, M

1988-01-01

1. The inhibitory effects of intracellular protons (Hi+) on the L-type Ca2+ channel activity were investigated in single ventricular myocytes of guinea-pigs by using the patch-clamp method in the open-cell-attached patch configuration, where 'run down' of the channel was partially prevented. 2. Hi+ reduced the unitary Ba2+ current of the Ca2+ channel by 10-20% without changing the maximum slope conductance. 3. Hi+ did not alter the number of channels in patches containing one or two channels. 4. Hi+ markedly reduced the mean current normalized by the unitary current, which gave the open-state probability multiplied by the number of channels in the patch. The dose-response curve between Hi+ and the open-state probability indicated half-maximum inhibition at pHi 6.6 and an apparent Hill coefficient of 1. 5. Hi+ shifted both the steady-state activation and inactivation curves in a negative direction by 10-15 mV, and the effects were reversible. 6. Hi+ did not affect the fast open-closed kinetics represented by the C-C-O scheme, apart from increasing the slow time constant of the closed time. 7. Hi+ increased the percentage of blank sweeps and reduced that of non-blank sweeps resulting in a decreased probability of channel opening. 8. Photo-oxidation with Rose Bengal abolished the reducing effect of Hi+ on the open-state probability (Po) in two out of ten experiments, suggesting the possible involvement of histidine residues in the Hi+ effect. 9. The above results indicate that Hi+ inhibits the Ba2+ current mainly by affecting the slow gating mechanism of the channel. PMID:2855346

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)

[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.

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.

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.

Signaling Pathways in Cardiac Myocyte Apoptosis

PubMed Central

Xia, Peng; Liu, Yuening

2016-01-01

Cardiovascular diseases, the number 1 cause of death worldwide, are frequently associated with apoptotic death of cardiac myocytes. Since cardiomyocyte apoptosis is a highly regulated process, pharmacological intervention of apoptosis pathways may represent a promising therapeutic strategy for a number of cardiovascular diseases and disorders including myocardial infarction, ischemia/reperfusion injury, chemotherapy cardiotoxicity, and end-stage heart failure. Despite rapid growth of our knowledge in apoptosis signaling pathways, a clinically applicable treatment targeting this cellular process is currently unavailable. To help identify potential innovative directions for future research, it is necessary to have a full understanding of the apoptotic pathways currently known to be functional in cardiac myocytes. Here, we summarize recent progress in the regulation of cardiomyocyte apoptosis by multiple signaling molecules and pathways, with a focus on the involvement of these pathways in the pathogenesis of heart disease. In addition, we provide an update regarding bench to bedside translation of this knowledge and discuss unanswered questions that need further investigation. PMID:28101515

Heart repair by reprogramming non-myocytes with cardiac transcription factors

PubMed Central

Song, Kunhua; Nam, Young-Jae; Luo, Xiang; Qi, Xiaoxia; Tan, Wei; Huang, Guo N.; Acharya, Asha; Smith, Christopher L.; Tallquist, Michelle D.; Neilson, Eric G.; Hill, Joseph A.; Bassel-Duby, Rhonda; Olson, Eric N.

2012-01-01

The adult mammalian heart possesses little regenerative potential following injury. Fibrosis due to activation of cardiac fibroblasts impedes cardiac regeneration and contributes to loss of contractile function, pathological remodeling and susceptibility to arrhythmias. Cardiac fibroblasts account for a majority of cells in the heart and represent a potential cellular source for restoration of cardiac function following injury through phenotypic reprogramming to a myocardial cell fate. Here we show that four transcription factors, GATA4, Hand2, MEF2C and Tbx5 can cooperatively reprogram adult mouse tail-tip and cardiac fibroblasts into beating cardiac-like myocytes in vitro. Forced expression of these factors in dividing non-cardiomyocytes in mice reprograms these cells into functional cardiac-like myocytes, improves cardiac function and reduces adverse ventricular remodeling following myocardial infarction. Our results suggest a strategy for cardiac repair through reprogramming fibroblasts resident in the heart with cardiogenic transcription factors or other molecules. PMID:22660318

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

Bepridil differentially inhibits two delayed rectifier K+ currents, IKr and IKs, in guinea-pig ventricular myocytes

PubMed Central

Wang, Jin-Cheng; Kiyosue, Tatsuto; Kiriyama, Kuninori; Arita, Makoto

1999-01-01

We investigated the effects of bepridil on the two components of the delayed rectifier K+ current, i.e., the rapidly activating (IKr) and the slowly activating (IKs) currents using tight-seal whole-cell patch-clamp techniques in guinea-pig ventricular myocytes, under blockade of L-type Ca2+ current with nitrendipine (5 μM) or D600 (1 μM).Bepridil decreased IKs under blockade of IKr with E4031 (5 μM), in a concentration-dependent manner. The concentration-dependent inhibition of IKs by bepridil was fitted by a curve, assuming one-to-one interactions between the channel and the drug molecule. The concentration of half-maximal inhibition (IC50) was found to be 6.2 μM.The effect of bepridil on IKr was assessed using an envelope-of-tails test. In the control condition, a ratio of the tail current to the time-dependent current measured during depolarization was large (>1) at shorter pulses (<200 ms), and it decreased to a steady state value of ∼0.4 with increases in the pulse duration. Bepridil at a concentration of 2 μM did not decrease this ratio at shorter pulses.In a short-pulse (duration=50 ms) experiment that largely activates IKr, the drug was found to block IKr in a cooperative manner (Hill coefficient=3.03) and the IC50 was 13.2 μM.These results suggest that bepridil at a clinical therapeutic concentration (∼2 μM) selectively blocks IKs but does not inhibit IKr. This may relate to the characteristic frequency-dependent effects of bepridil on the action potential duration (APD), e.g., the non-reverse use-dependent prolongation of APD. PMID:10588929

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.

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...

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

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.

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.

Purification of cardiac myocytes from human heart biopsies for gene expression analysis.

PubMed

Kosloski, L M; Bales, I K; Allen, K B; Walker, B L; Borkon, A M; Stuart, R S; Pak, A F; Wacker, M J

2009-09-01

The collection of gene expression data from human heart biopsies is important for understanding the cellular mechanisms of arrhythmias and diseases such as cardiac hypertrophy and heart failure. Many clinical and basic research laboratories conduct gene expression analysis using RNA from whole cardiac biopsies. This allows for the analysis of global changes in gene expression in areas of the heart, while eliminating the need for more complex and technically difficult single-cell isolation procedures (such as flow cytometry, laser capture microdissection, etc.) that require expensive equipment and specialized training. The abundance of fibroblasts and other cell types in whole biopsies, however, can complicate gene expression analysis and the interpretation of results. Therefore, we have designed a technique to quickly and easily purify cardiac myocytes from whole cardiac biopsies for RNA extraction. Human heart tissue samples were collected, and our purification method was compared with the standard nonpurification method. Cell imaging using acridine orange staining of the purified sample demonstrated that >98% of total RNA was contained within identifiable cardiac myocytes. Real-time RT-PCR was performed comparing nonpurified and purified samples for the expression of troponin T (myocyte marker), vimentin (fibroblast marker), and alpha-smooth muscle actin (smooth muscle marker). Troponin T expression was significantly increased, and vimentin and alpha-smooth muscle actin were significantly decreased in the purified sample (n = 8; P < 0.05). Extracted RNA was analyzed during each step of the purification, and no significant degradation occurred. These results demonstrate that this isolation method yields a more purified cardiac myocyte RNA sample suitable for downstream applications, such as real-time RT-PCR, and allows for more accurate gene expression changes in cardiac myocytes from heart biopsies.

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.

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.

Enhanced functional expression of transient outward current in hypertrophied feline myocytes.

PubMed

Ten Eick, R E; Zhang, K; Harvey, R D; Bassett, A L

1993-08-01

Cardiac hypertrophy can decrease myocardial contractility and alter the electrophysiological activity of the heart. It is well documented that action potentials recorded from hypertrophied feline ventricular cells can exhibit depressed plateau voltages and prolonged durations. Similar findings have been made by others in rabbit, rat, guinea pig, and human heart. Whole-cell patch voltage-clamp studies designed to explain these changes in the action potential suggest that the only component of the membrane current recorded from feline right ventricular (RV) myocytes found to be substantially different from normal is the 4-amino-pyridine-sensitive transient outward current (I(to)). However, it was not clear if the change in I(to) could explain the changes in the action potential of hypertrophied cardiocytes, nor was it clear if these changes reflect an alteration in the electrophysiological character of the channels underlying I(to). A kinetic comparison of I(to) elicited by hypertrophied RV myocytes with that elicited by comparable normal RV myocytes previously revealed no differences, suggesting that the increased magnitude of the peak I(to) recorded from hypertrophied myocytes arises because the current density increases and not because of any alteration in the kinetic parameters governing the current. This finding suggests that in hypertrophy additional normal channels are expressed rather than a kinetically different channel subtype emerging. Investigations designed to determine if enhancement of I(to) could explain the hypertrophy-induced changes in plateau voltage and action potential duration suggest that a change in I(to) density can indeed explain the entire effect of hypertrophy on RV action potentials. If this notion is correct, the likelihood of "sudden death" in patients with myocardial hypertrophy might be decreased by a blocker selective for cardiac I(to).

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.

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.

Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction

PubMed Central

Beaumont, Eric; Southerland, Elizabeth M.; Hardwick, Jean C.; Wright, Gary L.; Ryan, Shannon; Li, Ying; KenKnight, Bruce H.; Armour, J. Andrew

2015-01-01

This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions. PMID:26276818

Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction.

PubMed

Beaumont, Eric; Southerland, Elizabeth M; Hardwick, Jean C; Wright, Gary L; Ryan, Shannon; Li, Ying; KenKnight, Bruce H; Armour, J Andrew; Ardell, Jeffrey L

2015-10-01

This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions. Copyright © 2015 the American Physiological Society.

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

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.

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.

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.

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

α4-Integrin Mediates Neutrophil-Induced Free Radical Injury to Cardiac Myocytes

PubMed Central

Poon, Betty Y.; Ward, Christopher A.; Cooper, Conan B.; Giles, Wayne R.; Burns, Alan R.; Kubes, Paul

2001-01-01

Previous work has demonstrated that circulating neutrophils (polymorphonuclear leukocytes [PMNs]) adhere to cardiac myocytes via β2-integrins and cause cellular injury via the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme system. Since PMNs induced to leave the vasculature (emigrated PMNs) express the α4-integrin, we asked whether (a) these PMNs also induce myocyte injury via NADPH oxidase; (b) β2-integrins (CD18) still signal oxidant production, or if this process is now coupled to the α4-integrin; and (c) dysfunction is superoxide dependent within the myocyte or at the myocyte–PMN interface. Emigrated PMNs exposed to cardiac myocytes quickly induced significant changes in myocyte function. Myocyte shortening was decreased by 30–50% and rates of contraction and relaxation were reduced by 30% within the first 10 min. Both α4-integrin antibody (Ab)-treated PMNs and NADPH oxidase–deficient PMNs were unable to reduce myocyte shortening. An increased level of oxidative stress was detected in myocytes within 5 min of PMN adhesion. Addition of an anti–α4-integrin Ab, but not an anti-CD18 Ab, prevented oxidant production, suggesting that in emigrated PMNs the NADPH oxidase system is uncoupled from CD18 and can be activated via the α4-integrin. Addition of exogenous superoxide dismutase (SOD) inhibited all parameters of dysfunction measured, whereas overexpression of intracellular SOD within the myocytes did not inhibit the oxidative stress or the myocyte dysfunction caused by the emigrated PMNs. These findings demonstrate that profound molecular changes occur within PMNs as they emigrate, such that CD18 and associated intracellular signaling pathways leading to oxidant production are uncoupled and newly expressed α4-integrin functions as the ligand that signals oxidant production. The results also provide pathological relevance as the emigrated PMNs have the capacity to injure cardiac myocytes through the α4-integrin–coupled NADPH

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

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

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.

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.

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.

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.

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

[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

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

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

Mechanically induced orientation of adult rat cardiac myocytes in vitro

NASA Technical Reports Server (NTRS)

Samuel, J.-L.; Vandenburgh, H. H.

1990-01-01

The present study describes the spatial orientation of a population of freshly isolated adult rat cardiac myocytes using a computerized mechanical cell stimulator device for tissue cultured cells. A continuous unidirectional stretch of the substratum at 60 to 400 microns/min for 120 to 30 min, respectively, during the cell attachment period in a serum-free medium was found to induce a significant threefold increase in the number of rod-shaped myocytes oriented parallel to the direction of movement. The myocytes orient less well with unidirectional substratum stretching after their adhesion to the substratum. Adult myocytes plated onto a substratum undergoing continuous 10-percent stretch-relaxation cycling show no significant change in the myocyte orientation or cytoskeletal organization. In addition to the type of mechanical activity, orientation of rod-shaped myocytes is dependent on the speed of the substratum, the final stretch amplitude, and the timing between initiation of substratum stretching and adhesion of myocytes to the substratum.

Interleukin 1 and Tumor Necrosis Factor Inhibit Cardiac Myocyte β -adrenergic Responsiveness

NASA Astrophysics Data System (ADS)

Gulick, Tod; Chung, Mina K.; Pieper, Stephen J.; Lange, Louis G.; Schreiner, George F.

1989-09-01

Reversible congestive heart failure can accompany cardiac allograft rejection and inflammatory myocarditis, conditions associated with an immune cell infiltrate of the myocardium. To determine whether immune cell secretory products alter cardiac muscle metabolism without cytotoxicity, we cultured cardiac myocytes in the presence of culture supernatants from activated immune cells. We observed that these culture supernatants inhibit β -adrenergic agonist-mediated increases in cultured cardiac myocyte contractility and intracellular cAMP accumulation. The myocyte contractile response to increased extracellular Ca2+ concentration is unaltered by prior exposure to these culture supernatants, as is the increase in myocyte intracellular cAMP concentration in response to stimulation with forskolin, a direct adenyl cyclase activator. Inhibition occurs in the absence of alteration in β -adrenergic receptor density or ligand binding affinity. Suppressive activity is attributable to the macrophage-derived cytokines interleukin 1 and tumor necrosis factor. Thus, these observations describe a role for defined cytokines in regulating the hormonal responsiveness and function of contractile cells. The effects of interleukin 1 and tumor necrosis factor on intracellular cAMP accumulation may be a model for immune modulation of other cellular functions dependent upon cyclic nucleotide metabolism. The uncoupling of agonist-occupied receptors from adenyl cyclase suggests that β -receptor or guanine nucleotide binding protein function is altered by the direct or indirect action of cytokines on cardiac muscle cells.

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

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

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

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.

Recruitment of endosomal signaling mediates the forskolin modulation of guinea pig cardiac neuron excitability.

PubMed

Hardwick, Jean C; Clason, Todd A; Tompkins, John D; Girard, Beatrice M; Baran, Caitlin N; Merriam, Laura A; May, Victor; Parsons, Rodney L

2017-08-01

Forskolin, a selective activator of adenylyl cyclase (AC), commonly is used to establish actions of G protein-coupled receptors (GPCRs) that are initiated primarily through activation of AC/cAMP signaling pathways. In the present study, forskolin was used to evaluate the potential role of AC/cAMP, which is a major signaling mechanism for the pituitary adenylate cyclase-activating polypeptide (PACAP)-selective PAC1 receptor, in the regulation of guinea pig cardiac neuronal excitability. Forskolin (5-10 µM) increases excitability in ~60% of the cardiac neurons. The forskolin-mediated increase in excitability was considered related to cAMP regulation of a cyclic nucleotide gated channel or via protein kinase A (PKA)/ERK signaling, mechanisms that have been linked to PAC1 receptor activation. However, unlike PACAP mechanisms, forskolin enhancement of excitability was not significantly reduced by treatment with cesium to block currents through hyperpolarization-activated nonselective cation channels ( I h ) or by treatment with PD98059 to block MEK/ERK signaling. In contrast, treatment with the clathrin inhibitor Pitstop2 or the dynamin inhibitor dynasore eliminated the forskolin-induced increase in excitability; treatments with the inactive Pitstop analog or PP2 treatment to inhibit Src-mediated endocytosis mechanisms were ineffective. The PKA inhibitor KT5702 significantly suppressed the forskolin-induced change in excitability; further, KT5702 and Pitstop2 reduced the forskolin-stimulated MEK/ERK activation in cardiac neurons. Collectively, the present results suggest that forskolin activation of AC/cAMP/PKA signaling leads to the recruitment of clathrin/dynamin-dependent endosomal transduction cascades, including MEK/ERK signaling, and that endosomal signaling is the critical mechanism underlying the forskolin-induced increase in cardiac neuron excitability. Copyright © 2017 the American Physiological Society.

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.

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

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.

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…

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.

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

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

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.

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.

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.

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.

Length dependence of force generation exhibit similarities between rat cardiac myocytes and skeletal muscle fibres.

PubMed

Hanft, Laurin M; McDonald, Kerry S

2010-08-01

According to the Frank-Starling relationship, increased ventricular volume increases cardiac output, which helps match cardiac output to peripheral circulatory demand. The cellular basis for this relationship is in large part the myofilament length-tension relationship. Length-tension relationships in maximally calcium activated preparations are relatively shallow and similar between cardiac myocytes and skeletal muscle fibres. During twitch activations length-tension relationships become steeper in both cardiac and skeletal muscle; however, it remains unclear whether length dependence of tension differs between striated muscle cell types during submaximal activations. The purpose of this study was to compare sarcomere length-tension relationships and the sarcomere length dependence of force development between rat skinned left ventricular cardiac myocytes and fast-twitch and slow-twitch skeletal muscle fibres. Muscle cell preparations were calcium activated to yield 50% maximal force, after which isometric force and rate constants (k(tr)) of force development were measured over a range of sarcomere lengths. Myofilament length-tension relationships were considerably steeper in fast-twitch fibres compared to slow-twitch fibres. Interestingly, cardiac myocyte preparations exhibited two populations of length-tension relationships, one steeper than fast-twitch fibres and the other similar to slow-twitch fibres. Moreover, myocytes with shallow length-tension relationships were converted to steeper length-tension relationships by protein kinase A (PKA)-induced myofilament phosphorylation. Sarcomere length-k(tr) relationships were distinct between all three cell types and exhibited patterns markedly different from Ca(2+) activation-dependent k(tr) relationships. Overall, these findings indicate cardiac myocytes exhibit varied length-tension relationships and sarcomere length appears a dominant modulator of force development rates. Importantly, cardiac myocyte length

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

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.

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.

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.

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...

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.

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

Inhibitory effects of psychotropic drugs on the acetylcholine receptor-operated potassium current (IK.ACh) in guinea-pig atrial myocytes.

PubMed

Okada, Muneyoshi; Watanabe, Shinya; Matada, Takashi; Asao, Yoko; Hamatani, Ramu; Yamawaki, Hideyuki; Hara, Yukio

2013-01-01

Influences of psychotropic drugs, six antipsychotics and three antidepressants, on acetylcholine receptor-operated potassium current (IK.ACh) were examined by a whole-cell patch clamp method in freshly isolated guinea-pig atrial myocyte. IK.ACh was induced by a superfusion of carbachol (CCh) or by an intracellular application of guanosine 5'-[thio] triphosphate (GTPγS). To elucidate mechanism for anticholinergic action, IC50 ratio, the ratio of IC50 for GTPγS-activated IK.ACh to CCh-induced IK.ACh, was calculated. Antipsychotics and antidepressants inhibited CCh-induced IK.ACh in a concentration-dependent manner. The IC50 values were as follows; chlorpromazine 0.53 μM, clozapine 0.06 μM, fluphenazine 2.69 μM, haloperidol 2.66 μM, sulpiride 42.3 μM, thioridazine 0.07 μM, amitriptyline 0.03 μM, imipramine 0.22 μM and maprotiline 1.81 μM. The drugs, except for sulpiride, inhibited GTPγS-activated IK.ACh with following IC50 values; chlorpromazine 1.71 μM, clozapine 14.9 μM, fluphenazine 3.55 μM, haloperidol 2.73 μM, thioridazine 1.90 μM, amitriptyline 7.55 μM, imipramine 7.09 μM and maprotiline 5.93 μM. The IC50 ratio for fluphenazine and haloperidol was close to unity. The IC50 ratio for chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine and maprotiline was much higher than unity. The present findings suggest that the psychotropics studied suppress IK.ACh. Chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine, maprotiline and sulpiride are preferentially acting on muscarinic receptor. Fluphenazine and haloperidol may act on G protein and/or potassium channel.

Nuclear accumulation of myocyte muscle LIM protein is regulated by heme oxygenase 1 and correlates with cardiac function in the transition to failure

PubMed Central

Paudyal, Anju; Dewan, Sukriti; Ikie, Cindy; Whalley, Benjamin J; de Tombe, Pieter P.

2016-01-01

Key points The present study investigated the mechanism associated with impaired cardiac mechanosensing that leads to heart failure by examining the factors regulating muscle LIM protein subcellular distribution in myocytes.In myocytes, muscle LIM protein subcellular distribution is regulated by cell contractility rather than passive stretch via heme oxygenase‐1 and histone deacetylase signalling. The result of the present study provide new insights into mechanotransduction in cardiac myocytes.Myocyte mechanosensitivity, as indicated by the muscle LIM protein ratio, is also correlated with cardiac function in the transition to failure in a guinea‐pig model of disease. This shows that the loss mechanosensitivity plays an important role during the transition to failure in the heart.The present study provides the first indication that mechanosensing could be modified pharmacologically during the transition to heart failure. Abstract Impaired mechanosensing leads to heart failure and a decreased ratio of cytoplasmic to nuclear CSRP3/muscle LIM protein (MLP ratio) is associated with a loss of mechanosensitivity. In the present study, we tested whether passive or active stress/strain was important in modulating the MLP ratio and determined whether this correlated with heart function during the transition to failure. We exposed cultured neonatal rat myocytes to a 10% cyclic mechanical stretch at 1 Hz, or electrically paced myocytes at 6.8 V (1 Hz) for 48 h. The MLP ratio decreased by 50% (P < 0.05, n = 4) only in response to electrical pacing, suggesting impaired mechanosensitivity. Inhibition of contractility with 10 μm blebbistatin resulted in an ∼3‐fold increase in the MLP ratio (n = 8, P < 0.05), indicating that myocyte contractility regulates nuclear MLP. Inhibition of histone deacetylase (HDAC) signalling with trichostatin A increased nuclear MLP following passive stretch, suggesting that HDACs block MLP nuclear accumulation. Inhibition of heme

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.

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

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.

[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.

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.

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.

Changes in Ca(2+) cycling proteins underlie cardiac action potential prolongation in a pressure-overloaded guinea pig model with cardiac hypertrophy and failure.

PubMed

Ahmmed, G U; Dong, P H; Song, G; Ball, N A; Xu, Y; Walsh, R A; Chiamvimonvat, N

2000-03-17

Ventricular arrhythmias are common in both cardiac hypertrophy and failure; cardiac failure in particular is associated with a significant increase in the risk of sudden cardiac death. We studied the electrophysiologic changes in a guinea pig model with aortic banding resulting in cardiac hypertrophy at 4 weeks and progressing to cardiac failure at 8 weeks using whole-cell patch-clamp and biochemical techniques. Action potential durations (APDs) were significantly prolonged in banded animals at 4 and 8 weeks compared with age-matched sham-operated animals. APDs at 50% and 90% repolarization (APD(50) and APD(90) in ms) were the following: 4 week, banded, 208+/-51 and 248+/-49 (n = 15); 4 week, sham, 189+/-68 and 213+/-69 (n = 16); 8 week, banded, 197+/-40 and 226+/-40 (n = 21); and 8 week, sham, 156+/-42 and 189+/-45 (n = 22), respectively; P<0.05 comparing banded versus sham-operated animals. We observed no significant differences in the K(+) currents between the 2 groups of animals at 4 and 8 weeks. However, banded animals exhibited a significant increase in Na(+) and Na(+)-Ca(2+) exchange current densities compared with controls. Furthermore, we have found a significant attenuation in the Ca(2+)-dependent inactivation of the L-type Ca(2+) current in the banded compared with sham-operated animals, likely as a result of the significant downregulation of the sarcoplasmic reticulum Ca(2+) ATPase, which has been documented previously in the heart failure animals. Our data provide an alternate mechanism for APD prolongation in cardiac hypertrophy and failure and support the notion that there is close interaction between Ca(2+) handling and action potential profile.

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

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 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...

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...

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...

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...

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

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.

Activation of MEK/ERK signaling contributes to the PACAP-induced increase in guinea pig cardiac neuron excitability

PubMed Central

Tompkins, John D.; Clason, Todd A.; Hardwick, Jean C.; Girard, Beatrice M.; Merriam, Laura A.; May, Victor

2016-01-01

Pituitary adenylate cyclase (PAC)-activating polypeptide (PACAP) peptides (Adcyap1) signaling at the selective PAC1 receptor (Adcyap1r1) participate in multiple homeostatic and stress-related responses, yet the cellular mechanisms underlying PACAP actions remain to be completely elucidated. PACAP/PAC1 receptor signaling increases excitability of neurons within the guinea pig cardiac ganglia, and as these neurons are readily accessible, this neuronal system is particularly amenable to study of PACAP modulation of ionic conductances. The present study investigated how PACAP activation of MEK/ERK signaling contributed to the peptide-induced increase in cardiac neuron excitability. Treatment with the MEK inhibitor PD 98059 blocked PACAP-stimulated phosphorylated ERK and, in parallel, suppressed the increase in cardiac neuron excitability. However, PD 98059 did not blunt the ability of PACAP to enhance two inward ionic currents, one flowing through hyperpolarization-activated nonselective cationic channels (Ih) and another flowing through low-voltage-activated calcium channels (IT), which support the peptide-induced increase in excitability. Thus a PACAP- and MEK/ERK-sensitive, voltage-dependent conductance(s), in addition to Ih and IT, modulates neuronal excitability. Despite prior work implicating PACAP downregulation of the KV4.2 potassium channel in modulation of excitability in other cells, treatment with the KV4.2 current blocker 4-aminopyridine did not replicate the PACAP-induced increase in excitability in cardiac neurons. However, cardiac neurons express the ERK target, the NaV1.7 sodium channel, and treatment with the selective NaV1.7 channel inhibitor PF-04856264 decreased the PACAP modulation of excitability. From these results, PACAP/PAC1 activation of MEK/ERK signaling may phosphorylate the NaV1.7 channel, enhancing sodium currents near the threshold, an action contributing to repetitive firing of the cardiac neurons exposed to PACAP. PMID:27488668

The Permeability Transition Pore Controls Cardiac Mitochondrial Maturation and Myocyte Differentiation

PubMed Central

Hom, Jennifer R.; Quintanilla, Rodrigo A.; Hoffman, David L.; Karen L., de Mesy Bentley; Molkentin, Jeffery D.; Sheu, Shey-Shing; Porter, George A.

2011-01-01

SUMMARY Although mature myocytes rely on mitochondria as the primary source of energy, the role of mitochondria in the developing heart is not well known. Here, we find closure of the mitochondrial permeability transition pore (mPTP) drives maturation of mitochondrial structure and function and myocyte differentiation. Cardiomyocytes at embryonic day (E) 9.5, when compared to E13.5, displayed fragmented mitochondria with few cristae, a less polarized mitochondrial membrane potential, higher reactive oxygen species (ROS) levels, and an open mPTP. Pharmacologic and genetic closing of the mPTP yielded maturation of mitochondrial structure and function, lowered ROS, and increased myocyte differentiation (measured by counting Z-bands). Furthermore, myocyte differentiation was inhibited and enhanced with oxidant and antioxidant treatment, respectively, suggesting that redox signaling pathways lie downstream of mitochondria to regulate cardiac myocyte differentiation. PMID:21920313

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.

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.

Azithromycin/chloroquine combination does not increase cardiac instability despite an increase in monophasic action potential duration in the anesthetized guinea pig.

PubMed

Fossa, Anthony A; Wisialowski, Todd; Duncan, J Neil; Deng, Shibing; Dunne, Michael

2007-11-01

Prolongation of the electrocardiogram QT interval by some, but not all drugs, has been associated with increased incidence of sudden cardiac death. Current preclinical regulatory assays cannot discriminate the arrhythmia liability of these drugs. Consequently, many new medications that prolong the QT interval are not developed despite their potential therapeutic benefit. Alternans (action potential duration alternations) is a measure of cardiac instability in humans and animals associated with the onset of ventricular fibrillation. Due to potential arrhythmia risk from observed QT prolongation, alternans was assessed in the anesthetized guinea pig after azithromycin or chloroquine alone and after combination treatment at clinically relevant concentrations proposed for the management of malaria. Chloroquine alone, but not azithromycin, caused a profound increase in action potential duration but with only minimal effects on alternans (approximately 10 ms). Azithromycin alone and in combination with chloroquine showed no increase in alternans beyond vehicle baseline responses indicating no additional arrhythmia liability.

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.

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.

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.

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.

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

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

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.

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

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

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

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.

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

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.

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%).

[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.

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.

Cardiac myocyte-protective effect of microRNA-22 during ischemia and reperfusion through disrupting the caveolin-3/eNOS signaling

PubMed Central

Chen, Zhenfei; Qi, Yinliang; Gao, Chao

2015-01-01

MicroRNA-22 (miR-22) was previously reported to elicit cardiac myocyte hypertrophy and had an anti-apoptotic effect on neurons. However, its effects on cardiac myocyte apoptosis and cardiac function during ischemia and reperfusion (I/R) are not clear. In the present study, we demonstrate that pre-administration of miR-22 mimic reduced I/R-induced cardiac dysfunction significantly in a rat model. We found that miR-22 overexpression inhibited cardiac myocyte apoptosis, and reduced cardiac remodeling during I/R. Significant cardiac myocyte apoptosis was also observed in a cardiac myocyte model after hypoxia/reoxygenation (H/R), a representative process of I/R. Further experiments showed that eNOS activity and the following NO production were significantly decreased during I/R and H/R, while such decrease was inhibited by overexpression of miR-22. Mechanistically, overexpression of miR-22 had little effect on the total protein level of eNOS, but restored the level of p-eNOS (Ser1177) which was down-regulated during H/R. Further RT-PCR results demonstrated that Caveolin 3 (Cav3), an upstream negative regulator of eNOS, was upregulated during H/R, resulting in a decrease of p-eNOS. However, such upregulation of Cav3 transcript level was inhibited directly by miR-22 during H/R, leading to a restored p-eNOS level and followed NO production in cardiac myocytes. Together, the present study revealed that miR-22 down-regulated Cav3, leading to restored eNOS activity and NO production, which further inhibited cardiac myocyte apoptosis and promoted cardiac function after I/R. Of clinical interest, the present study may highlight miR-22 as a potential therapeutic agent for reducing I/R induced cardiac injury. PMID:26191152

Blockade of HERG human K+ channel and IKr of guinea pig cardiomyocytes by prochlorperazine.

PubMed

Kim, Moon-Doo; Eun, Su-Yong; Jo, Su-Hyun

2006-08-21

Prochlorperazine, a drug for the symptomatic control of nausea, vomiting and psychiatric disorders, can induce prolonged QT, torsades de pointes and sudden death. We studied the effects of prochlorperazine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and also in the delayed rectifier K+ current of guinea pig cardiomyocytes. Prochlorperazine induced a concentration-dependent decrease in current amplitudes at the end of the voltage steps and tail currents of HERG. The IC50 for a prochlorperazine block of HERG current in Xenopus oocytes progressively decreased relative to the degree of depolarization, from 42.1 microM at -40 mV to 37.4 microM at 0 mV to 22.6 microM at +40 mV. The block of HERG by prochlorperazine was use-dependent, exhibiting a more rapid onset and a greater steady-state block at higher frequencies of activation, while there was partial relief of the block with reduced frequencies. In guinea pig ventricular myocytes, bath applications of 0.5 and 1 muM prochlorperazine at 36 degrees C blocked rapidly activating delayed rectifier K+ current by 38.9% and 76.5%, respectively, but did not significantly block slowly activating delayed rectifier K+ current. Our findings suggest that the arrhythmogenic side effects of prochlorperazine are caused by a blockade of HERG and the rapid component of the delayed rectifier K+ current rather than by a blockade of the slow component.

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

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

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

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.

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.

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

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

[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.

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.

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.

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

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

Ultrasonic destruction of albumin microbubbles enhances gene transfection and expression in cardiac myocytes.

PubMed

Wang, Guo-zhong; Liu, Jing-hua; Lü, Shu-zheng; Lü, Yun; Guo, Cheng-jun; Zhao, Dong-hui; Fang, Dong-ping; He, Dong-fang; Zhou, Yuan; Ge, Chang-jiang

2011-05-01

It has been proven that ultrasonic destruction of microbubbles can enhance gene transfection efficiency into the noncardiac cells, but there are few reports about cardiac myocytes. Moreover, the exact mechanisms are not yet clear; whether the characteristic of microbubbles can affect the gene transfection efficiency or not is still controversial. This study was designed to investigate whether the ultrasound destruction of gene-loaded microbubbles could enhance the plasmids carried reporter gene transfection in primary cultured myocardial cell, and evaluate the effects of microbubbles characteristics on the transgene expression in cardiac myocytes. The β-galactosidase plasmids attached to the two types of microbubbles, air-contained sonicated dextrose albumin (ASDA) and perfluoropropane-exposed sonicated dextrose albumin (PESDA) were prepared. The gene transfection into cardiac myocytes was performed in vitro by naked plasmids, ultrasound exposure, ultrasonic destruction of gene-loaded microbubbles and calcium phosphate precipitation, and then the gene expression and cell viability were analyzed. The ultrasonic destruction of gene-loaded microbubbles enhanced gene expression in cardiac myocytes compared with naked plasmid transfection ((51.95 ± 2.41) U/g or (29.28 ± 3.65) U/g vs. (0.84 ± 0.21) U/g, P < 0.01), and ultrasonic destruction PESDA resulted in more significant gene expression than ASDA ((51.95 ± 2.41) U/g vs. (29.28 ± 3.65) U/g, P < 0.05). Ultrasonic destruction of microbubbles during calcium phosphate precipitation gene transfection enhanced β-galactosidase activity nearly 8-fold compared with calcium phosphate precipitation gene transfection alone ((111.35 ± 11.21) U/g protein vs. (14.13 ± 2.58) U/g protein, P < 0.01). Even 6 hours after calcium phosphate precipitation gene transfection, ultrasound-mediated microbubbles destruction resulted in more intense gene expression ((35.63 ± 7.65) U/g vs. (14.13 ± 2.58) U/g, P < 0.05). Ultrasonic

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.

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

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

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.

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.

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

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.

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.

Sarcolemmal cardiac K(ATP) channels as a target for the cardioprotective effects of the fluorine-containing pinacidil analogue, flocalin.

PubMed

Voitychuk, Oleg I; Strutynskyi, Ruslan B; Yagupolskii, Lev M; Tinker, Andrew; Moibenko, Olexiy O; Shuba, Yaroslav M

2011-02-01

A class of drugs known as K(ATP) -channel openers induce cardioprotection. This study examined the effects of the novel K(ATP) -channel opener, the fluorine-containing pinacidil derivative, flocalin, on cardiac-specific K(ATP) -channels, excitability of native cardiac myocytes and on the ischaemic heart. The action of flocalin was investigated on: (i) membrane currents through cardiac-specific K(ATP) -channels (I(KATP) ) formed by K(IR) 6.2/SUR2A heterologously expressed in HEK-293 cells (HEK-293(₆.₂/₂A) ); (ii) excitability and intracellular Ca²(+) ([Ca²(+) ](i) ) transients of cultured rat neonatal cardiac myocytes; and (iii) functional and ultrastructural characteristics of isolated guinea-pig hearts subjected to ischaemia-reperfusion. Flocalin concentration-dependently activated a glibenclamide-sensitive I(KATP) in HEK-293(₆.₂/₂A) cells with an EC₅₀= 8.1 ± 0.4 µM. In cardiac myocytes, flocalin (5 µM) hyperpolarized resting potential by 3-5 mV, markedly shortened action potential duration, reduced the amplitude of [Ca²(+) ](i) transients by 2-3-fold and suppressed contraction. The magnitude and extent of reversibility of these effects depended on the type of cardiac myocytes. In isolated hearts, perfusion with 5 µmol·L⁻¹ flocalin, before inducing ischaemia, facilitated restoration of contraction during reperfusion, decreased the number of extrasystoles, prevented the appearance of coronary vasoconstriction and reduced damage to the cardiac tissue at the ultrastructural level (state of myofibrils, membrane integrity, mitochondrial cristae structure). Flocalin induced potent cardioprotection by activating cardiac-type K(ATP) -channels with all the benefits of the presence of fluorine group in the drug structure: higher lipophilicity, decreased toxicity, resistance to oxidation and thermal degradation, decreased metabolism in the organism and prolonged therapeutic action. © 2011 The Authors. British Journal of Pharmacology © 2011 The

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

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

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

[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.

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

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.

Myocyte-Derived Hsp90 Modulates Collagen Upregulation via Biphasic Activation of STAT-3 in Fibroblasts during Cardiac Hypertrophy

PubMed Central

Datta, Ritwik; Bansal, Trisha; Rana, Santanu; Datta, Kaberi; Datta Chaudhuri, Ratul; Chawla-Sarkar, Mamta

2016-01-01

ABSTRACT Signal transducer and activator of transcription 3 (STAT-3)-mediated signaling in relation to upregulated collagen expression in fibroblasts during cardiac hypertrophy is well defined. Our recent findings have identified heat shock protein 90 (Hsp90) to be a critical modulator of fibrotic signaling in cardiac fibroblasts in this disease milieu. The present study was therefore intended to analyze the role of Hsp90 in the STAT-3-mediated collagen upregulation process. Our data revealed a significant difference between in vivo and in vitro results, pointing to a possible involvement of myocyte-fibroblast cross talk in this process. Cardiomyocyte-targeted knockdown of Hsp90 in rats (Rattus norvegicus) in which the renal artery was ligated showed downregulated collagen synthesis. Furthermore, the results obtained with cardiac fibroblasts conditioned with Hsp90-inhibited hypertrophied myocyte supernatant pointed toward cardiomyocytes' role in the regulation of collagen expression in fibroblasts during hypertrophy. Our study also revealed a novel signaling mechanism where myocyte-derived Hsp90 orchestrates not only p65-mediated interleukin-6 (IL-6) synthesis but also its release in exosomal vesicles. Such myocyte-derived exosomes and myocyte-secreted IL-6 are responsible in unison for the biphasic activation of STAT-3 signaling in cardiac fibroblasts that culminates in excess collagen synthesis, leading to severely compromised cardiac function during cardiac hypertrophy. PMID:28031326

Myocyte-Derived Hsp90 Modulates Collagen Upregulation via Biphasic Activation of STAT-3 in Fibroblasts during Cardiac Hypertrophy.

PubMed

Datta, Ritwik; Bansal, Trisha; Rana, Santanu; Datta, Kaberi; Datta Chaudhuri, Ratul; Chawla-Sarkar, Mamta; Sarkar, Sagartirtha

2017-03-15

Signal transducer and activator of transcription 3 (STAT-3)-mediated signaling in relation to upregulated collagen expression in fibroblasts during cardiac hypertrophy is well defined. Our recent findings have identified heat shock protein 90 (Hsp90) to be a critical modulator of fibrotic signaling in cardiac fibroblasts in this disease milieu. The present study was therefore intended to analyze the role of Hsp90 in the STAT-3-mediated collagen upregulation process. Our data revealed a significant difference between in vivo and in vitro results, pointing to a possible involvement of myocyte-fibroblast cross talk in this process. Cardiomyocyte-targeted knockdown of Hsp90 in rats ( Rattus norvegicus ) in which the renal artery was ligated showed downregulated collagen synthesis. Furthermore, the results obtained with cardiac fibroblasts conditioned with Hsp90-inhibited hypertrophied myocyte supernatant pointed toward cardiomyocytes' role in the regulation of collagen expression in fibroblasts during hypertrophy. Our study also revealed a novel signaling mechanism where myocyte-derived Hsp90 orchestrates not only p65-mediated interleukin-6 (IL-6) synthesis but also its release in exosomal vesicles. Such myocyte-derived exosomes and myocyte-secreted IL-6 are responsible in unison for the biphasic activation of STAT-3 signaling in cardiac fibroblasts that culminates in excess collagen synthesis, leading to severely compromised cardiac function during cardiac hypertrophy. Copyright © 2017 American Society for Microbiology.

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.

[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.

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

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.

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

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.

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

Shear fluid-induced Ca2+ release and the role of mitochondria in rat cardiac myocytes.

PubMed

Belmonte, Steve; Morad, Martin

2008-03-01

Cardiac myocyte contraction occurs when Ca2+ influx through voltage-gated L-type Ca2+ channels causes Ca2+ release from ryanodine receptors of the sarcoplasmic reticulum (SR). Although mitochondria occupy about 35% of the cell volume in rat cardiac myocytes, and are thought to be located <300 nm from the junctional SR, their role in the beat-to-beat regulation of cardiac Ca2+ signaling remains unclear. We have recently shown that rapid ( approximately 20 ms) application of shear fluid forces ( approximately 25 dynes/cm2) to rat cardiac myocytes triggers slowly ( approximately 300 ms) developing Cai transients that were independent of activation of all transmembrane Ca2+ transporting pathways, but were suppressed by FCCP, CCCP, and Ru360, all of which are known to disrupt mitochondrial function. We have here used rapid 2-D confocal microscopy to monitor fluctuations in mitochondrial Ca2+ levels ([Ca2+]m) and mitochondrial membrane potential (Delta Psi m) in rat cardiac myocytes loaded either with rhod-2 AM or tetramethylrhodamine methyl ester (TMRM), respectively. Freshly isolated intact rat cardiac myocytes were plated on glass coverslips and incubated in 5 mM Ca2+ containing Tyrode's solution and 40 mM 2,3-butanedione monoxime (BDM) to inhibit cell contraction. Alternatively, myocytes were permeabilized with 10 microM digitonin and perfused with an "intracellular" solution containing 10 microM free [Ca2+], 5 mM EGTA, and 15 mM BDM. Direct [Ca2+]m measurements showed transient mitochondrial Ca2+ accumulation after exposure to 10 mM caffeine, as revealed by a 66% increase in the rhod-2 fluorescence intensity. Shear fluid forces, however, produced a 12% decrease in signal, suggesting that application of a mechanical force releases Ca2+ from the mitochondria. In addition, caffeine and CCCP or FCCP strongly reduced Delta Psi m, while application of a pressurized solution produced a transient Delta Psi m hyperpolarization in intact ventricular myocytes loaded with TMRM

Sphingosine mediates the immediate negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian cardiac myocyte.

PubMed

Oral, H; Dorn, G W; Mann, D L

1997-02-21

To determine whether activation of the neutral sphingomyelinase pathway was responsible for the immediate (<30 min) negative inotropic effects of tumor necrosis factor-alpha (TNF-alpha), we examined sphingosine levels in diluent and TNF-alpha-stimulated cardiac myocytes. TNF-alpha stimulation of adult feline cardiac myocytes provoked a rapid (<15 min) increase in the hydrolysis of [14C]sphingomyelin in cell-free extracts, as well as an increase in ceramide mass, consistent with cytokine-induced activation of the neutral sphingomyelinase pathway. High performance liquid chromatographic analysis of lipid extracts from TNF-alpha-stimulated cardiac myocytes showed that TNF-alpha stimulation produced a rapid (<30 min) increase in free sphingosine levels. Moreover, exogenous D-sphingosine mimicked the effects of TNF-alpha on intracellular calcium homeostasis, as well as the negative inotropic effects of TNF-alpha in isolated contracting myocytes; time course studies showed that exogenous D-sphingosine produced abnormalities in cell shortening that were maximal at 5 min. Finally, blocking sphingosine production using an inhibitor of ceramidase, n-oleoylethanolamine, completely abrogated the negative inotropic effects of TNF-alpha in isolated contracting cardiac myocytes. Additional studies employing biologically active ceramide analogs and sphingosine 1-phosphate suggested that neither the immediate precursor of sphingosine nor the immediate metabolite of sphingosine, respectively, were likely to be responsible for the immediate negative inotropic effects of TNF-alpha. Thus, these studies suggest that sphingosine mediates the immediate negative inotropic effects of TNF-alpha in isolated cardiac myocytes.

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.

Targeted Gene Silencing of Tumor Necrosis Factor Attenuates the Negative Inotropic Effects of Lipopolysaccharide in Isolated Contracting Cardiac Myocytes

PubMed Central

Ramabadran, R. S.; Chancey, Amanda; Vallejo, Jesus G.; Barger, Philip M.; Sivasubramanian, Natarajan; Mann, Douglas L.

2008-01-01

Bacterial endotoxin (lipopolysaccharide) depresses cardiovascular function; however, the mediators and signaling pathways that are responsible for the negative inotropic effects of lipopolysaccharide are not fully known. We used RNA interference to determine the relative role of tumor necrosis factor with respect to mediating the negative inotropic effects of lipopolysaccharide in isolated cardiac myocytes. Cardiac myocyte cultures were treated with lipopolysaccharide in the presence or absence of small interfering RNAs (siRNA) for tumor necrosis factor. We examined the effects of tumor necrosis factor siRNA on lipopolysaccharide-induced tumor necrosis factor messenger RNA (mRNA) and protein biosynthesis, as well as the negative inotropic effects of lipopolysaccharide in isolated contracting cardiac myocytes. Treatment of adult cardiac myocyte cultures with tumor necrosis factor siRNA significantly attenuated lipopolysaccharide-induced tumor necrosis factor mRNA and protein biosynthesis, whereas transfection with a double-stranded RNA that does not target mammalian mRNA had no effect. Pretreatment with tumor necrosis factor siRNA significantly attenuated, but did not abrogate, the lipopolysaccharide-induced decrease in sarcomere shortening in isolated contracting cardiac myocytes. In contrast, tumor necrosis factor siRNA had a comparatively smaller effect on improving sarcomere shortening once the negative inotropic effects of lipopolysaccharide were fully established. These results suggest that tumor necrosis factor plays an important upstream role in lipopolysaccharide-induced negative inotropic effects in isolated contracting cardiac myocytes and that other molecular mechanisms are responsible for the decrease in sarcomere shortening after sustained lipopolysaccharide signaling. PMID:18427645

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.

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

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

A Simplified, Langendorff-Free Method for Concomitant Isolation of Viable Cardiac Myocytes and Nonmyocytes From the Adult Mouse Heart

PubMed Central

Ackers-Johnson, Matthew; Li, Peter Yiqing; Holmes, Andrew P.; O’Brien, Sian-Marie; Pavlovic, Davor; Foo, Roger S.

2018-01-01

Rationale Cardiovascular disease represents a global pandemic. The advent of and recent advances in mouse genomics, epigenomics, and transgenics offer ever-greater potential for powerful avenues of research. However, progress is often constrained by unique complexities associated with the isolation of viable myocytes from the adult mouse heart. Current protocols rely on retrograde aortic perfusion using specialized Langendorff apparatus, which poses considerable logistical and technical barriers to researchers and demands extensive training investment. Objective To identify and optimize a convenient, alternative approach, allowing the robust isolation and culture of adult mouse cardiac myocytes using only common surgical and laboratory equipment. Methods and Results Cardiac myocytes were isolated with yields comparable to those in published Langendorff-based methods, using direct needle perfusion of the LV ex vivo and without requirement for heparin injection. Isolated myocytes can be cultured antibiotic free, with retained organized contractile and mitochondrial morphology, transcriptional signatures, calcium handling, responses to hypoxia, neurohormonal stimulation, and electric pacing, and are amenable to patch clamp and adenoviral gene transfer techniques. Furthermore, the methodology permits concurrent isolation, separation, and coculture of myocyte and nonmyocyte cardiac populations. Conclusions We present a novel, simplified method, demonstrating concomitant isolation of viable cardiac myocytes and nonmyocytes from the same adult mouse heart. We anticipate that this new approach will expand and accelerate innovative research in the field of cardiac biology. PMID:27502479

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

Protection of adult rat cardiac myocytes from ischemic cell death: role of caveolar microdomains and delta-opioid receptors.

PubMed

Patel, Hemal H; Head, Brian P; Petersen, Heidi N; Niesman, Ingrid R; Huang, Diane; Gross, Garrett J; Insel, Paul A; Roth, David M

2006-07-01

The role of caveolae, membrane microenvironments enriched in signaling molecules, in myocardial ischemia is poorly defined. In the current study, we used cardiac myocytes prepared from adult rats to test the hypothesis that opioid receptors (OR), which are capable of producing cardiac protection in vivo, promote cardiac protection in cardiac myocytes in a caveolae-dependent manner. We determined protein expression and localization of delta-OR (DOR) using coimmunohistochemistry, caveolar fractionation, and immunoprecipitations. DOR colocalized in fractions with caveolin-3 (Cav-3), a structural component of caveolae in muscle cells, and could be immunoprecipitated by a Cav-3 antibody. Immunohistochemistry confirmed plasma membrane colocalization of DOR with Cav-3. Cardiac myocytes were subjected to simulated ischemia (2 h) or an ischemic preconditioning (IPC) protocol (10 min ischemia, 30 min recovery, 2 h ischemia) in the presence and absence of methyl-beta-cyclodextrin (MbetaCD, 2 mM), which binds cholesterol and disrupts caveolae. We also assessed the cardiac protective effects of SNC-121 (SNC), a selective DOR agonist, on cardiac myocytes with or without MbetaCD and MbetaCD preloaded with cholesterol. Ischemia, simulated by mineral oil layering to inhibit gas exchange, promoted cardiac myocyte cell death (trypan blue staining), a response blunted by SNC (37 +/- 3 vs. 59 +/- 3% dead cells in the presence and absence of 1 muM SNC, respectively, P < 0.01) or by use of the IPC protocol (35 +/- 4 vs. 62 +/- 3% dead cells, P < 0.01). MbetaCD treatment, which disrupted caveolae (as detected by electron microscopy), fully attenuated the protective effects of IPC or SNC, resulting in cell death comparable to that of the ischemic group. By contrast, SNC-induced protection was not abrogated in cells incubated with cholesterol-saturated MbetaCD, which maintained caveolae structure and function. These findings suggest a key role for caveolae, perhaps through enrichment of

Electrical coupling of single cardiac rat myocytes to field-effect and bipolar transistors.

PubMed

Kind, Thomas; Issing, Matthias; Arnold, Rüdiger; Müller, Bernt

2002-12-01

A novel bipolar transistor for extracellular recording the electrical activity of biological cells is presented, and the electrical behavior compared with the field-effect transistor (FET). Electrical coupling is examined between single cells separated from the heart of adults rats (cardiac myocytes) and both types of transistors. To initiate a local extracellular voltage, the cells are periodically stimulated by a patch pipette in voltage clamp and current clamp mode. The local extracellular voltage is measured by the planar integrated electronic sensors: the bipolar and the FET. The small signal transistor currents correspond to the local extracellular voltage. The two types of sensor transistors used here were developed and manufactured in the laboratory of our institute. The manufacturing process and the interfaces between myocytes and transistors are described. The recordings are interpreted by way of simulation based on the point-contact model and the single cardiac myocyte model.

[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.

Voltage sensitivity of M2 muscarinic receptors underlies the delayed rectifier-like activation of ACh-gated K(+) current by choline in feline atrial myocytes.

PubMed

Navarro-Polanco, Ricardo A; Aréchiga-Figueroa, Iván A; Salazar-Fajardo, Pedro D; Benavides-Haro, Dora E; Rodríguez-Elías, Julio C; Sachse, Frank B; Tristani-Firouzi, Martin; Sánchez-Chapula, José A; Moreno-Galindo, Eloy G

2013-09-01

Choline (Ch) is a precursor and metabolite of the neurotransmitter acetylcholine (ACh). In canine and guinea pig atrial myocytes, Ch was shown to activate an outward K(+) current in a delayed rectifier fashion. This current has been suggested to modulate cardiac electrical activity and to play a role in atrial fibrillation pathophysiology. However, the exact nature and identity of this current has not been convincingly established. We recently described the unique ligand- and voltage-dependent properties of muscarinic activation of ACh-activated K(+) current (IKACh) and showed that, in contrast to ACh, pilocarpine induces a current with delayed rectifier-like properties with membrane depolarization. Here, we tested the hypothesis that Ch activates IKACh in feline atrial myocytes in a voltage-dependent manner similar to pilocarpine. Single-channel recordings, biophysical profiles, specific pharmacological inhibition and computational data indicate that the current activated by Ch is IKACh. Moreover, we show that membrane depolarization increases the potency and efficacy of IKACh activation by Ch and thus gives the appearance of a delayed rectifier activating K(+) current at depolarized potentials. Our findings support the emerging concept that IKACh modulation is both voltage- and ligand-specific and reinforce the importance of these properties in understanding cardiac physiology.

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

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.

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.

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.

Functional subcellular distribution of β1- and β2-adrenergic receptors in rat ventricular cardiac myocytes

PubMed Central

Cros, Caroline; Brette, Fabien

2013-01-01

β-adrenergic stimulation is a key regulator of cardiac function. The localization of major cardiac adrenergic receptors (β1 and β2) has been investigated using biochemical and biophysical approaches and has led to contradictory results. This study investigates the functional subcellular localization of β1- and β2-adrenergic receptors in rat ventricular myocytes using a physiological approach. Ventricular myocytes were isolated from the hearts of rat and detubulated using formamide. Physiological cardiac function was measured as Ca2+ transient using Fura-2-AM and cell shortening. Selective activation of β1- and β2-adrenergic receptors was induced with isoproterenol (0.1 μmol/L) and ICI-118,551 (0.1 μmol/L); and with salbutamol (10 μmol/L) and atenolol (1 μmol/L), respectively. β1- and β2-adrenergic stimulations induced a significant increase in Ca2+ transient amplitude and cell shortening in intact rat ventricular myocytes (i.e., surface sarcolemma and t-tubules) and in detubulated cells (depleted from t-tubules, surface sarcolemma only). Both β1- and β2-adrenergic receptors stimulation caused a greater effect on Ca2+ transient and cell shortening in detubulated myocytes than in control myocytes. Quantitative analysis indicates that β1-adrenergic stimulation is ∼3 times more effective at surface sarcolemma compared to t-tubules, whereas β2- adrenergic stimulation occurs almost exclusively at surface sarcolemma (∼100 times more effective). These physiological data demonstrate that in rat ventricular myocytes, β1-adrenergic receptors are functionally present at surface sarcolemma and t-tubules, while β2-adrenergic receptors stimulation occurs only at surface sarcolemma of cardiac cells. PMID:24303124

Negative Inotropic Effects of High Mobility Box Group 1 Protein in Isolated Contracting Cardiac Myocytes

PubMed Central

Tzeng, Huei-Ping; Fan, Jinping; Vallejo, Jesus G.; Dong, Jian Wen; Chen, Xiongwen; Houser, Steven R.; Mann, Douglas L.

2013-01-01

HMGB1 released from necrotic cells or macrophages functions as a late inflammatory mediator, and has been shown to induce cardiovascular collapse during sepsis. Thus far, however, the effect(s) of HMGB1 in the heart are not known. We determined the effects of HMGB1 on isolated feline cardiac myocytes by measuring sarcomere shortening in contracting cardiac myocytes, intracellular Ca2+ transients using fluo-3, and L-type calcium currents using whole cell perforate configuration of the patch clamp technique. Treatment of isolated myocytes with HMGB1 (100 ng/ml) resulted in a 70% decrease in sarcomere shortening and a 50% decrease in the height of the peak Ca++ transient within 5 min (p <0.01). The immediate negative inotropic effects HMGB1 on cell contractility and calcium homeostasis were partially reversible upon washout of HMGB1. A significant inhibition of the inward L-type calcium currents also was documented by the patch clamp technique. HMGB1 induced the PKCε translocation and a PKC inhibitor significantly attenuated the negative inotropic effects of HMGB1. These studies show for the first time that HMGB1 impairs sarcomere shortening by decreasing calcium availability in cardiac myocytes through modulating membrane calcium influx, and suggest that HMGB1 maybe act as a novel myocardial depressant factor during cardiac injury. PMID:18223193

Matrix elasticity regulates the optimal cardiac myocyte shape for contractility

PubMed Central

McCain, Megan L.; Yuan, Hongyan; Pasqualini, Francesco S.; Campbell, Patrick H.

2014-01-01

Concentric hypertrophy is characterized by ventricular wall thickening, fibrosis, and decreased myocyte length-to-width aspect ratio. Ventricular thickening is considered compensatory because it reduces wall stress, but the functional consequences of cell shape remodeling in this pathological setting are unknown. We hypothesized that decreases in myocyte aspect ratio allow myocytes to maximize contractility when the extracellular matrix becomes stiffer due to conditions such as fibrosis. To test this, we engineered neonatal rat ventricular myocytes into rectangles mimicking the 2-D profiles of healthy and hypertrophied myocytes on hydrogels with moderate (13 kPa) and high (90 kPa) elastic moduli. Actin alignment was unaffected by matrix elasticity, but sarcomere content was typically higher on stiff gels. Microtubule polymerization was higher on stiff gels, implying increased intracellular elastic modulus. On moderate gels, myocytes with moderate aspect ratios (∼7:1) generated the most peak systolic work compared with other cell shapes. However, on stiffer gels, low aspect ratios (∼2:1) generated the most peak systolic work. To compare the relative contributions of intracellular vs. extracellular elasticity to contractility, we developed an analytical model and used our experimental data to fit unknown parameters. Our model predicted that matrix elasticity dominates over intracellular elasticity, suggesting that the extracellular matrix may potentially be a more effective therapeutic target than microtubules. Our data and model suggest that myocytes with lower aspect ratios have a functional advantage when the elasticity of the extracellular matrix decreases due to conditions such as fibrosis, highlighting the role of the extracellular matrix in cardiac disease. PMID:24682394

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

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.

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.

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

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.

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.

The Electrophysiological Effects of Qiliqiangxin on Cardiac Ventricular Myocytes of Rats

PubMed Central

Wei, Yidong; Liu, Xiaoyu; Wei, Haidong; Hou, Lei; Che, Wenliang; The, Erlinda; Li, Gang; Jhummon, Muktanand Vikash; Wei, Wanlin

2013-01-01

Qiliqiangxin, a Chinese herb, represents the affection in Ca channel function of cardiac myocytes. It is unknown whether Qiliqiangxin has an effect on Na current and K current because the pharmacological actions of this herb's compound are very complex. We investigated the rational usage of Qiliqiangxin on cardiac ventricular myocytes of rats. Ventricular myocytes were exposed acutely to 1, 10, and 50 mg/L Qiliqiangxin, and whole cell patch-clamp technique was used to study the acute effects of Qiliqiangxin on Sodium current (I Na), outward currents delayed rectifier outward K+ current (I K), slowly activating delayed rectifier outward K+ current (I Ks), transient outward K+ current (I to), and inward rectifier K+ current (I K1). Qiliqiangxin can decrease I Na by 28.53% ± 5.98%, and its IC50 was 9.2 mg/L. 10 and 50 mg/L Qiliqiangxin decreased by 37.2% ± 6.4% and 55.9% ± 5.5% summit current density of I to. 10 and 50 mg/L Qiliqiangxin decreased I Ks by 15.51% ± 4.03% and 21.6% ± 5.6%. Qiliqiangxin represented a multifaceted pharmacological profile. The effects of Qiliqiangxin on Na and K currents of ventricular myocytes were more profitable in antiarrhythmic therapy in the clinic. We concluded that the relative efficacy of Qiliqiangxin was another choice for the existing antiarrhythmic therapy. PMID:24250713

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

Cell contact as an independent factor modulating cardiac myocyte hypertrophy and survival in long-term primary culture

NASA Technical Reports Server (NTRS)

Clark, W. A.; Decker, M. L.; Behnke-Barclay, M.; Janes, D. M.; Decker, R. S.

1998-01-01

Cardiac myocytes maintained in cell culture develop hypertrophy both in response to mechanical loading as well as to receptor-mediated signaling mechanisms. However, it has been shown that the hypertrophic response to these stimuli may be modulated through effects of intercellular contact achieved by maintaining cells at different plating densities. In this study, we show that the myocyte plating density affects not only the hypertrophic response and features of the differentiated phenotype of isolated adult myocytes, but also plays a significant role influencing myocyte survival in vitro. The native rod-shaped phenotype of freshly isolated adult myocytes persists in an environment which minimizes myocyte attachment and spreading on the substratum. However, these conditions are not optimal for long-term maintenance of cultured adult cardiac myocytes. Conditions which promote myocyte attachment and spreading on the substratum, on the other hand, also promote the re-establishment of new intercellular contacts between myocytes. These contacts appear to play a significant role in the development of spontaneous activity, which enhances the redevelopment of highly differentiated contractile, junctional, and sarcoplasmic reticulum structures in the cultured adult cardiomyocyte. Although it has previously been shown that adult cardiac myocytes are typically quiescent in culture, the addition of beta-adrenergic agonists stimulates beating and myocyte hypertrophy, and thereby serves to increase the level of intercellular contact as well. However, in densely-plated cultures with intrinsically high levels of intercellular contact, spontaneous contractile activity develops without the addition of beta-adrenergic agonists. In this study, we compare the function, morphology, and natural history of adult feline cardiomyocytes which have been maintained in cultures with different levels of intercellular contact, with and without the addition of beta-adrenergic agonists

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

T-type Ca2+ channels regulate the exit of cardiac myocytes from the cell cycle after birth

PubMed Central

Wang, Fang; Gao, Hui; Kubo, Hajime; Fan, Xiaoxuan; Zhang, Hongyu; Berretta, Remus; Chen, Xiongwen; Sharp, Thomas; Starosta, Timothy; Makarewich, Catherine; Li, Ying; Molkentin, Jeffrey D.; Houser, Steven R.

2013-01-01

T-type Ca2+ channels (TTCCs) are expressed in the fetal heart and then disappear from ventricular myocytes after birth. The hypothesis examined in this study was the α1G TTCCs' influence in myocyte maturation and their rapid withdrawal from the cell cycle after birth. Methods Cardiac myocytes were isolated from neonatal and adult wild type (WT), α1G−/− and α1G over expressing (α1GDT) mice. Bromodeoxyuridine (BrdU) uptake, myocyte nucleation, cell cycle analysis, and T-type Ca2+ currents were measured. Results All myocytes were mono-nucleated at birth and 35% of WT myocytes expressed functional TTCCs. Very few neonatal myocytes had functional TTCCs in α1G−/− hearts. By the end of the first week after birth no WT or α1G−/− had functional TTCCs. During the first week after birth about 25% of WT myocytes were BrdU+ and became bi-nucleated. Significantly fewer α1G−/− myocytes became bi-nucleated and fewer of these myocytes were BrdU+. Neonatal α1G−/− myocytes were also smaller than WT. Adult WT and α1G−/− hearts were similar in size, but α1G−/− myocytes were smaller and a greater % were mono-nucleated. α1G over expressing hearts were smaller than WT but their myocytes were larger. Conclusions The studies performed show that loss of functional TTCCs is associated with bi-nucleation and myocyte withdrawal from the cell cycle. Loss of α1G TTCCs slowed the transition from mono- to bi-nucleation and resulted in an adult heart with a greater number of small cardiac myocytes. These results suggest that TTCCs are involved in the regulation of myocyte size and the exit of myocytes from the cell cycle during the first week after birth. PMID:23743021

Optimisation of a Generic Ionic Model of Cardiac Myocyte Electrical Activity

PubMed Central

Guo, Tianruo; Al Abed, Amr; Lovell, Nigel H.; Dokos, Socrates

2013-01-01

A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented. The model provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation. PMID:23710254

Gene therapy to develop a genetically engineered cardiac pacemaker.

PubMed

Glenn, Christopher M; Pogwizd, Steven M

2003-01-01

While cardiac pacemakers are frequently used for the treatment of bradydysrhythmias (from diseases of the cardiac conduction system), their use is still limited by complications that can be life-threatening and expensive. Genetic engineering approaches offer an opportunity to modulate cellular automaticity in a manner that could have significant therapeutic potential. It is well known that ventricular myocytes exhibit a more negative diastolic potential than do pacemaker cells, in large part because of the inward rectifying potassium current/K1 (which pacemaker cells lack). Taking advantage of these intrinsic electrophysiological differences, a biological pacemaker has recently been developed by Miake et al (Nature 2002; 419:132-133) using adenoviral gene transfer approaches. By isolating the gene responsible for/K1 (the Kir2.1 gene), mutating it to make it a dysfunctional channel (a dominant-negative), inserting the mutated gene into an adenoviral vector, and delivering the virus to the hearts of guinea pigs, the investigators were able to successfully convert some ventricular myocytes to pacemaker cells. While issues of safety and long-term efficacy need to be further established, the results of these experiments provide proof of principle that gene transfer offers great promise for treatment of electrophysiological disorders including conduction system disease.

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.

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.

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

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.

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

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

[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.

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.

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

Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays

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

Morton, M.J., E-mail: michael.morton@astrazeneca.com; Armstrong, D.; Abi Gerges, N.

2014-09-01

Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies – radioligand-binding or automated electrophysiology – was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity inmore » the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost. - Highlights: • The L-type calcium channel is a significant safety liability during drug discovery. • Radioligand-binding to the L-type calcium channel can be measured in vitro. • The assay can be run at a single test concentration as part of a screening cascade. • This measurement is highly predictive of changes in cardiac myocyte contractility.« less

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

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

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.

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.

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

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.

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.

Infrasound exposure induces apoptosis of rat cardiac myocytes by regulating the expression of apoptosis-related proteins.

PubMed

Pei, Zhao-Hui; Chen, Bao-Ying; Tie, Ru; Zhang, Hai-Feng; Zhao, Ge; Qu, Ping; Zhu, Xiao-Xing; Zhu, Miao-Zhang; Yu, Jun

2011-12-01

It has been reported that exposure to infrasound causes cardiac dysfunction. Allowing for the key role of apoptosis in the pathogenesis of cardiovascular diseases, the objective of this study was to investigate the apoptotic effects of infrasound. Cardiac myocytes cultured from neonatal rats were exposed to infrasound of 5 Hz at 130 dB. The apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Also, the expression levels of a series of apoptosis-related proteins were detected. As a result, infrasound induced apoptosis of cultured rat cardiac myocytes in a time-dependant manner. The expression of proapoptotic proteins such as Bax, caspase-3, caspase-8, caspase-9, and FAS was significantly up-regulated, with concomitant down-regulated expression of antiapoptotic proteins such as Bcl-x, and the inhibitory apoptosis proteins family proteins including XIAP, cIAP-1, and cIAP-2. The expression of poly (ADP-ribose) polymerase and β-catenin, which are the substrate proteins of caspase-3, was significantly decreased. In conclusion, infrasound is an apoptotic inducer of cardiac myocytes.

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

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.

[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.

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.

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.

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.

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

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.

Reversal of cardiac myocyte dysfunction as a unique mechanism of rescue by P2X4 receptors in cardiomyopathy.

PubMed

Shen, Jian-Bing; Shutt, Robin; Agosto, Mariela; Pappano, Achilles; Liang, Bruce T

2009-04-01

Binary cardiac transgenic (Tg) overexpression of P2X(4) receptors (P2X(4)R) improved the survival of the cardiomyopathic calsequestrin (CSQ) mice. Here we studied the mechanism of rescue using binary P2X(4)R/CSQ Tg and CSQ Tg mice as models. Cellular and intact heart properties were determined by simultaneous sarcomere shortening (SS) and Ca(2+) transients in vitro and echocardiography in vivo. Similar to a delay in death, binary mice exhibited a slowed heart failure progression with a greater left ventricular (LV) fractional shortening (FS) and thickness and a concomitant lesser degree of LV dilatation in both systole and diastole at 8 or 12 wk. By 16 wk, binary hearts showed similarly depressed FS and thinned out LV and equal enlargement of LV as did 12-wk-old CSQ hearts. Binary cardiac myocytes showed higher peak basal cell shortening (CS) and SS as well as greater basal rates of shortening and relaxation than did the CSQ myocytes at either 8 or 12 wk. Similar data were obtained in comparing the Ca(2+) transient. At 16 wk, binary myocytes were like the 12-wk-old CSQ myocytes with equally depressed CS, SS, and Ca(2+) transient. CSQ myocytes were longer than myocytes from wild-type and binary mice at 12 wk of age. At 16 wk, the binary myocyte length increased to that of the 12-wk-old CSQ myocyte, parallel to LV dilatation. The data suggest a unique mechanism, which involves a reversal of cardiac myocyte dysfunction and a delay in heart failure progression. It represents an example of targeting the abnormal failing myocyte in treating heart failure.

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

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.

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

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

Minocycline suppresses oxidative stress and attenuates fetal cardiac myocyte apoptosis triggered by in utero cocaine exposure

PubMed Central

Sinha-Hikim, Indrani; Shen, Ruoqing; Nzenwa, Ify; Gelfand, Robert; Mahata, Sushil K.

2015-01-01

This study investigates the molecular mechanisms by which minocycline, a second generation tetracycline, prevents cardiac myocyte death induced by in utero cocaine exposure. Timed mated pregnant Sprague-Dawley (SD) rats received one of the following treatments twice daily from embryonic (E) day 15–21 (E15–E21): (i) intraperitoneal (IP) injections of saline (control); (ii) IP injections of cocaine (15 mg/kg BW); and (iii) IP injections of cocaine + oral administration of 25 mg/kg BW of minocycline. Pups were killed on postnatal day 15 (P15). Additional pregnant dams received twice daily IP injections of cocaine (from E15–E21) + oral administration of a relatively higher (37.5 mg/kg BW) dose of minocycline. Minocycline treatment continued from E15 until the pups were sacrificed on P15. In utero cocaine exposure resulted in an increase in oxidative stress and fetal cardiac myocyte apoptosis through activation of c-Jun-NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK)-mediated mitochondria-dependent apoptotic pathway. Continued minocycline treatment from E15 through P15 significantly prevented oxidative stress, kinase activation, perturbation of BAX/BCL-2 ratio, cytochrome c release, caspase activation, and attenuated fetal cardiac myocyte apoptosis after prenatal cocaine exposure. These results demonstrate in vivo cardioprotective effects of minocycline in preventing fetal cardiac myocyte death after prenatal cocaine exposure. Given its proven clinical safety and ability to cross the placental barrier and enter into the fetal circulation, minocycline may be an effective therapy for preventing cardiac consequences of in utero cocaine exposure. PMID:21424555

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.

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.

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.

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.

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

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

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.

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.

Overexpression of connexin 43 using a retroviral vector improves electrical coupling of skeletal myoblasts with cardiac myocytes in vitro

PubMed Central

Tolmachov, Oleg; Ma, Yu-Ling; Themis, Michael; Patel, Pravina; Spohr, Hilmar; MacLeod, Kenneth T; Ullrich, Nina D; Kienast, Yvonne; Coutelle, Charles; Peters, Nicholas S

2006-01-01

Background Organ transplantation is presently often the only available option to repair a damaged heart. As heart donors are scarce, engineering of cardiac grafts from autologous skeletal myoblasts is a promising novel therapeutic strategy. The functionality of skeletal muscle cells in the heart milieu is, however, limited because of their inability to integrate electrically and mechanically into the myocardium. Therefore, in pursuit of improved cardiac integration of skeletal muscle grafts we sought to modify primary skeletal myoblasts by overexpression of the main gap-junctional protein connexin 43 and to study electrical coupling of connexin 43 overexpressing myoblasts to cardiac myocytes in vitro. Methods To create an efficient means for overexpression of connexin 43 in skeletal myoblasts we constructed a bicistronic retroviral vector MLV-CX43-EGFP expressing the human connexin 43 cDNA and the marker EGFP gene. This vector was employed to transduce primary rat skeletal myoblasts in optimised conditions involving a concomitant use of the retrovirus immobilising protein RetroNectin® and the polycation transduction enhancer Transfectam®. The EGFP-positive transduced cells were then enriched by flow cytometry. Results More than four-fold overexpression of connexin 43 in the transduced skeletal myoblasts, compared with non-transduced cells, was shown by Western blotting. Functionality of the overexpressed connexin 43 was demonstrated by microinjection of a fluorescent dye showing enhanced gap-junctional intercellular transfer in connexin 43 transduced myoblasts compared with transfer in non-transduced myoblasts. Rat cardiac myocytes were cultured in multielectrode array culture dishes together with connexin 43/EGFP transduced skeletal myoblasts, control non-transduced skeletal myoblasts or alone. Extracellular field action potential activation rates in the co-cultures of connexin 43 transduced skeletal myoblasts with cardiac myocytes were significantly higher than

Overexpression of connexin 43 using a retroviral vector improves electrical coupling of skeletal myoblasts with cardiac myocytes in vitro.

PubMed

Tolmachov, Oleg; Ma, Yu-Ling; Themis, Michael; Patel, Pravina; Spohr, Hilmar; Macleod, Kenneth T; Ullrich, Nina D; Kienast, Yvonne; Coutelle, Charles; Peters, Nicholas S

2006-06-06

Organ transplantation is presently often the only available option to repair a damaged heart. As heart donors are scarce, engineering of cardiac grafts from autologous skeletal myoblasts is a promising novel therapeutic strategy. The functionality of skeletal muscle cells in the heart milieu is, however, limited because of their inability to integrate electrically and mechanically into the myocardium. Therefore, in pursuit of improved cardiac integration of skeletal muscle grafts we sought to modify primary skeletal myoblasts by overexpression of the main gap-junctional protein connexin 43 and to study electrical coupling of connexin 43 overexpressing myoblasts to cardiac myocytes in vitro. To create an efficient means for overexpression of connexin 43 in skeletal myoblasts we constructed a bicistronic retroviral vector MLV-CX43-EGFP expressing the human connexin 43 cDNA and the marker EGFP gene. This vector was employed to transduce primary rat skeletal myoblasts in optimised conditions involving a concomitant use of the retrovirus immobilising protein RetroNectin and the polycation transduction enhancer Transfectam. The EGFP-positive transduced cells were then enriched by flow cytometry. More than four-fold overexpression of connexin 43 in the transduced skeletal myoblasts, compared with non-transduced cells, was shown by Western blotting. Functionality of the overexpressed connexin 43 was demonstrated by microinjection of a fluorescent dye showing enhanced gap-junctional intercellular transfer in connexin 43 transduced myoblasts compared with transfer in non-transduced myoblasts. Rat cardiac myocytes were cultured in multielectrode array culture dishes together with connexin 43/EGFP transduced skeletal myoblasts, control non-transduced skeletal myoblasts or alone. Extracellular field action potential activation rates in the co-cultures of connexin 43 transduced skeletal myoblasts with cardiac myocytes were significantly higher than in the co-cultures of non

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.

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.

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

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.

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.

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

The lethal effects of cytokine-induced nitric oxide on cardiac myocytes are blocked by nitric oxide synthase antagonism or transforming growth factor beta.

PubMed Central

Pinsky, D J; Cai, B; Yang, X; Rodriguez, C; Sciacca, R R; Cannon, P J

1995-01-01

Inducible nitric oxide (NO) produced by macrophages is cytotoxic to invading organisms and has an important role in host defense. Recent studies have demonstrated inducible NO production within the heart, and that cytokine-induced NO mediates alterations in cardiac contractility, but the cytotoxic potential of nitric oxide with respect to the heart has not been defined. To evaluate the role of inducible nitric oxide synthase (iNOS) on cardiac myocyte cytotoxicity, we exposed adult rat cardiac myocytes to either cytokines alone or to activated J774 macrophages in coculture. Increased expression of both iNOS message and protein was seen in J774 macrophages treated with IFN gamma and LPS and cardiac myocytes treated with TNF-alpha, IL-1 beta, and IFN gamma. Increased NO synthesis was confirmed in both the coculture and isolated myocyte preparations by increased nitrite production. Increased NO synthesis was associated with a parallel increase in myocyte death as measured by CPK release into the culture medium as well as by loss of membrane integrity, visualized by trypan blue staining. Addition of the competitive NO synthase inhibitor L-NMMA to the culture medium prevented both the increased nitrite production and the cytotoxicity observed after cytokine treatment in both the isolated myocyte and the coculture experiments. Because transforming growth-factor beta modulates iNOS expression in other cell types, we evaluated its effects on cardiac myocyte iNOS expression and NO-mediated myocyte cytotoxicity. TGF-beta reduced expression of cardiac myocyte iNOS message and protein, reduced nitrite production, and reduced NO-mediated cytotoxicity in parallel. Taken together, these experiments show the cytotoxic potential of endogenous NO production within the heart, and suggest a role for TGF-beta or NO synthase antagonists to mute these lethal effects. These findings may help explain the cardiac response to sepsis or allograft rejection, as well as the progression of

Na+ channel regulation by Ca2+/calmodulin and Ca2+/calmodulin-dependent protein kinase II in guinea-pig ventricular myocytes†

PubMed Central

Aiba, Takeshi; Hesketh, Geoffrey G.; Liu, Ting; Carlisle, Rachael; Villa-Abrille, Maria Celeste; O'Rourke, Brian; Akar, Fadi G.; Tomaselli, Gordon F.

2010-01-01

Aims Calmodulin (CaM) regulates Na+ channel gating through binding to an IQ-like motif in the C-terminus. Ca2+/CaM-dependent protein kinase II (CaMKII) regulates Ca2+ handling, and chronic overactivity of CaMKII is associated with left ventricular hypertrophy and dysfunction and lethal arrhythmias. However, the acute effects of Ca2+/CaM and CaMKII on cardiac Na+ channels are not fully understood. Methods and results Purified NaV1.5–glutathione-S-transferase fusion peptides were phosphorylated in vitro by CaMKII predominantly on the I–II linker. Whole-cell voltage-clamp was used to measure Na+ current (INa) in isolated guinea-pig ventricular myocytes in the absence or presence of CaM or CaMKII in the pipette solution. CaMKII shifted the voltage dependence of Na+ channel availability by ≈+5 mV, hastened recovery from inactivation, decreased entry into intermediate or slow inactivation, and increased persistent (late) current, but did not change INa decay. These CaMKII-induced changes of Na+ channel gating were completely abolished by a specific CaMKII inhibitor, autocamtide-2-related inhibitory peptide (AIP). Ca2+/CaM alone reproduced the CaMKII-induced changes of INa availability and the fraction of channels undergoing slow inactivation, but did not alter recovery from inactivation or the magnitude of the late current. Furthermore, the CaM-induced changes were also completely abolished by AIP. On the other hand, cAMP-dependent protein kinase A inhibitors did not abolish the CaM/CaMKII-induced alterations of INa function. Conclusion Ca2+/CaM and CaMKII have distinct effects on the inactivation phenotype of cardiac Na+ channels. The differences are consistent with CaM-independent effects of CaMKII on cardiac Na+ channel gating. PMID:19797425

Minocycline suppresses oxidative stress and attenuates fetal cardiac myocyte apoptosis triggered by in utero cocaine exposure.

PubMed

Sinha-Hikim, Indrani; Shen, Ruoqing; Nzenwa, Ify; Gelfand, Robert; Mahata, Sushil K; Sinha-Hikim, Amiya P

2011-06-01

This study investigates the molecular mechanisms by which minocycline, a second generation tetracycline, prevents cardiac myocyte death induced by in utero cocaine exposure. Timed mated pregnant Sprague-Dawley (SD) rats received one of the following treatments twice daily from embryonic (E) day 15-21 (E15-E21): (i) intraperitoneal (IP) injections of saline (control); (ii) IP injections of cocaine (15 mg/kg BW); and (iii) IP injections of cocaine + oral administration of 25 mg/kg BW of minocycline. Pups were killed on postnatal day 15 (P15). Additional pregnant dams received twice daily IP injections of cocaine (from E15-E21) + oral administration of a relatively higher (37.5 mg/kg BW) dose of minocycline. Minocycline treatment continued from E15 until the pups were sacrificed on P15. In utero cocaine exposure resulted in an increase in oxidative stress and fetal cardiac myocyte apoptosis through activation of c-Jun-NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK)-mediated mitochondria-dependent apoptotic pathway. Continued minocycline treatment from E15 through P15 significantly prevented oxidative stress, kinase activation, perturbation of BAX/BCL-2 ratio, cytochrome c release, caspase activation, and attenuated fetal cardiac myocyte apoptosis after prenatal cocaine exposure. These results demonstrate in vivo cardioprotective effects of minocycline in preventing fetal cardiac myocyte death after prenatal cocaine exposure. Given its proven clinical safety and ability to cross the placental barrier and enter into the fetal circulation, minocycline may be an effective therapy for preventing cardiac consequences of in utero cocaine exposure.

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.

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.

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

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

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

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

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

[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.

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.

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

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.

The Interplay of Rogue and Clustered Ryanodine Receptors Regulates Ca2+ Waves in Cardiac Myocytes.

PubMed

Chen, Xudong; Feng, Yundi; Huo, Yunlong; Tan, Wenchang

2018-01-01

Ca 2+ waves in cardiac myocytes can lead to arrhythmias owing to delayed after-depolarisations. Based on Ca 2+ regulation from the junctional sarcoplasmic reticulum (JSR), a mathematical model was developed to investigate the interplay of clustered and rogue RyRs on Ca 2+ waves. The model successfully reproduces Ca 2+ waves in cardiac myocytes, which are in agreement with experimental results. A new wave propagation mode of "spark-diffusion-quark-spark" is put forward. It is found that rogue RyRs greatly increase the initiation of Ca 2+ sparks, further contribute to the formation and propagation of Ca 2+ waves when the free Ca 2+ concentration in JSR lumen ([Ca 2+ ] lumen ) is higher than a threshold value of 0.7 mM. Computational results show an exponential increase in the velocity of Ca 2+ waves with [Ca 2+ ] lumen . In addition, more CRUs of rogue RyRs and Ca 2+ release from rogue RyRs result in higher velocity and amplitude of Ca 2+ waves. Distance between CRUs significantly affects the velocity of Ca 2+ waves, but not the amplitude. This work could improve understanding the mechanism of Ca 2+ waves in cardiac myocytes.

The Interplay of Rogue and Clustered Ryanodine Receptors Regulates Ca2+ Waves in Cardiac Myocytes

PubMed Central

Chen, Xudong; Feng, Yundi; Huo, Yunlong; Tan, Wenchang

2018-01-01

Ca2+ waves in cardiac myocytes can lead to arrhythmias owing to delayed after-depolarisations. Based on Ca2+ regulation from the junctional sarcoplasmic reticulum (JSR), a mathematical model was developed to investigate the interplay of clustered and rogue RyRs on Ca2+ waves. The model successfully reproduces Ca2+ waves in cardiac myocytes, which are in agreement with experimental results. A new wave propagation mode of “spark-diffusion-quark-spark” is put forward. It is found that rogue RyRs greatly increase the initiation of Ca2+ sparks, further contribute to the formation and propagation of Ca2+ waves when the free Ca2+ concentration in JSR lumen ([Ca2+]lumen) is higher than a threshold value of 0.7 mM. Computational results show an exponential increase in the velocity of Ca2+ waves with [Ca2+]lumen. In addition, more CRUs of rogue RyRs and Ca2+ release from rogue RyRs result in higher velocity and amplitude of Ca2+ waves. Distance between CRUs significantly affects the velocity of Ca2+ waves, but not the amplitude. This work could improve understanding the mechanism of Ca2+ waves in cardiac myocytes. PMID:29755362

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.

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

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.

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

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

An Experimental Model Using Cultured Cardiac Myocytes for a Study of the Generation of Premature Ventricular Contractions Under Ultrasound Exposure

NASA Astrophysics Data System (ADS)

Kudo, Nobuki; Yamamoto, Masaya

2011-09-01

It is known that use of a contrast agents in echocardiography increases the probability of generation of premature ventricular contractions (PVCs). As a basic study to elucidate the mechanisms and to reduce adverse effects, the generation of PVCs was investigated using cultured cardiac myocytes instead of the intact heart in vivo. Cardiac myocytes were isolated from neonatal rats and cultured on a cover slip. The myocyte sample was exposed to pulsed ultrasound with microbubbles adjacent to the myocytes, and generation of PVCs was examined with ultrasound exposure at various delay times after onset of myocyte contraction. The experimental results showed that generation of PVCs had a stable threshold delay time and that PVCs were generated only when myocytes were exposed to ultrasound with delay times longer than the threshold. The results indicate that the model used in this study is useful for revealing the mechanisms by which PVCs are induced by ultrasound exposure.

Actions and mechanisms of action of novel analogues of sotalol on guinea-pig and rabbit ventricular cells.

PubMed Central

Connors, S. P.; Gill, E. W.; Terrar, D. A.

1992-01-01

1. The actions and mechanisms of action of novel analogues of sotalol which prolong cardiac action potentials were investigated in guinea-pig and rabbit isolated ventricular cells. 2. In guinea-pig and rabbit cells the compounds significantly prolonged action potential duration at 20% and 90% repolarization levels without affecting resting membrane potential. In guinea-pig but not rabbit cells there was an increase in action potential amplitude and in rabbit cells there was no change in the shape or position of the 'notch' in the action potential. 3. Possible mechanisms of action were studied in more detail in the case of compound II (1-(4-methanesulphonamidophenoxy)-3-(N-methyl 3,4 dichlorophenylethylamino)-2-propanol). Prolongation of action potential duration continued to occur in the presence of nisoldipine, and calcium currents recorded under voltage-clamp conditions were not reduced by compound II (1 microM). Action potential prolongation by compound II was also unaffected in the presence of 10 microM tetrodotoxin. 4. Compound II (1 microM) did not influence IK1 assessed from the current during ramp changes in membrane potential (20 mV s-1) over the range -90 to -10 mV. 5. Compound II (1 microM) blocked time-dependent delayed rectifier potassium current (IK) activated by step depolarizations and recorded as an outward tail following repolarization. When a submaximal concentration (50 nM) was applied there was no change in the apparent reversal potential of IK.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1393293

Increased Response to β2-Adrenoreceptor Stimulation Augments Inhibition of IKr in Heart Failure Ventricular Myocytes

PubMed Central

Wang, Hegui; Chen, Yanhong; Zhu, Hongjun; Wang, Sen; Zhang, Xiwen; Xu, Dongjie; Cao, Kejiang; Zou, Jiangang

2012-01-01

Background Increasing evidence indicates that the rapid component of delayed rectifier potassium current (IKr) is modulated by α- and β-adrenergic stimulation. However, the role and mechanism regulating IKr through β2-adrenoreceptor (β-AR) stimulation in heart failure (HF) are unclear. Methodology/Principal Findings In the present study, we investigated the effects of fenoterol, a highly selective β2-AR agonist, on IKr in left ventricular myocytes obtained from control and guinea pigs with HF induced by descending aortic banding. IKr was measured by using whole cell patch clamp technique. In control myocytes, superfusion of fenoterol (10 µM) caused a 17% decrease in IKr. In HF myocytes, the same concentration of fenoterol produced a significantly greater decrease (33%) in IKr. These effects were not modified by the incubation of myocytes with CGP-20712A, a β1-AR antagonist, but were abolished by pretreatment of myocytes with ICI-118551, a β2-AR antagonist. An inhibitory cAMP analog, Rp-cAMPS and PKA inhibitor significantly attenuated fenoterol-induced inhibition of IKr in HF myocytes. Moreover, fenoterol markedly prolonged action potential durations at 90% (APD90) repolarization in HF ventricular myocytes. Conclusions The results indicate that inhibition of IKr induced by β2-AR stimulation is increased in HF. The inhibitory effect is likely to be mediated through a cAMP/PKA pathway in HF ventricular myocytes. PMID:23029432

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

Direct, Differential Effects of Tamoxifen, 4-Hydroxytamoxifen, and Raloxifene on Cardiac Myocyte Contractility and Calcium Handling

PubMed Central

Asp, Michelle L.; Martindale, Joshua J.; Metzger, Joseph M.

2013-01-01

Tamoxifen (Tam), a selective estrogen receptor modulator, is in wide clinical use for the treatment and prevention of breast cancer. High Tam doses have been used for treatment of gliomas and cancers with multiple drug resistance, but long QT Syndrome is a side effect. Tam is also used experimentally in mice for inducible gene knockout in numerous tissues, including heart; however, the potential direct effects of Tam on cardiac myocyte mechanical function are not known. The goal of this study was to determine the direct, acute effects of Tam, its active metabolite 4-hydroxytamoxifen (4OHT), and related drug raloxifene (Ral) on isolated rat cardiac myocyte mechanical function and calcium handling. Tam decreased contraction amplitude, slowed relaxation, and decreased Ca2+ transient amplitude. Effects were primarily observed at 5 and 10 μM Tam, which is relevant for high dose Tam treatment in cancer patients as well as Tam-mediated gene excision in mice. Myocytes treated with 4OHT responded similarly to Tam-treated cells with regard to both contractility and calcium handling, suggesting an estrogen-receptor independent mechanism is responsible for the effects. In contrast, Ral increased contraction and Ca2+ transient amplitudes. At 10 μM, all drugs had a time-dependent effect to abolish cellular contraction. In conclusion, Tam, 4OHT, and Ral adversely and differentially alter cardiac myocyte contractility and Ca2+ handling. These findings have important implications for understanding the Tam-induced cardiomyopathy in gene excision studies and may be important for understanding effects on cardiac performance in patients undergoing high-dose Tam therapy. PMID:24205315

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.

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.

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.

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.

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

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

Redox signaling in cardiac myocytes

PubMed Central

Santos, Celio X.C.; Anilkumar, Narayana; Zhang, Min; Brewer, Alison C.; Shah, Ajay M.

2011-01-01

The heart has complex mechanisms that facilitate the maintenance of an oxygen supply–demand balance necessary for its contractile function in response to physiological fluctuations in workload as well as in response to chronic stresses such as hypoxia, ischemia, and overload. Redox-sensitive signaling pathways are centrally involved in many of these homeostatic and stress-response mechanisms. Here, we review the main redox-regulated pathways that are involved in cardiac myocyte excitation–contraction coupling, differentiation, hypertrophy, and stress responses. We discuss specific sources of endogenously generated reactive oxygen species (e.g., mitochondria and NADPH oxidases of the Nox family), the particular pathways and processes that they affect, the role of modulators such as thioredoxin, and the specific molecular mechanisms that are involved—where this knowledge is available. A better understanding of this complex regulatory system may allow the development of more specific therapeutic strategies for heart diseases. PMID:21236334

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.

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.

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.

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

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.

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.

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

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.

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.

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.

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.

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.