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Sample records for guinea pig ventricular

  1. Chamber-specific effects of hypokalaemia on ventricular arrhythmogenicity in isolated, perfused guinea-pig heart.

    PubMed

    Osadchii, Oleg E; Bentzen, Bo Hjorth; Olesen, Soren Peter

    2009-04-01

    Diuretic-induced hypokalaemia has been shown to promote cardiac arrhythmias in hypertensive patients. The present study was designed to determine whether hypokalaemia increases arrhythmic susceptibility of the left ventricle (LV) or the right ventricle (RV), or both. Proarrhythmic effects of hypokalaemic perfusion (2.5 mm K(+) for 30 min) were assessed in isolated guinea-pig heart preparations using simultaneous recordings of volume-conducted electrocardiogram and monophasic action potentials from six ventricular epicardial sites. Effective refractory periods, ventricular fibrillation thresholds and inducibility of tachyarrhythmias by programmed electrical stimulation and tachypacing were determined at the LV and the RV epicardial stimulation sites. Hypokalaemia promoted spontaneous ventricular ectopic activity, an effect attributed to non-uniform prolongation of ventricular repolarization resulting in increased RV-to-LV transepicardial dispersion of refractoriness and action potential duration. Furthermore, hypokalaemic perfusion was associated with reduced ventricular fibrillation threshold and increased inducibility of tachyarrhythmias by programmed electrical stimulation and tachypacing as determined at the LV stimulation site. In contrast, the RV stimulation revealed no change in arrhythmic susceptibility of the RV chamber. Consistently, hypokalaemia reduced the LV effective refractory period but had no effect on the RV refractoriness. This change enabled generation of premature propagating responses by extrastimulus application at earlier time points during LV repolarization. Increased prematurity of extrastimulus-evoked propagating responses was associated with exaggerated local inhomogeneities in intraventricular conduction and action potential duration in hypokalaemic LV, thus creating a favourable stage for re-entrant tachyarrhythmias. Taken together, these findings suggest that proarrhythmic effects of hypokalaemia are mostly attributed to increased LV

  2. Effects of acetylcholine on the Na(+)-K+ pump current in guinea-pig ventricular myocytes.

    PubMed Central

    Gao, J; Mathias, R T; Cohen, I S; Baldo, G J

    1997-01-01

    1. The whole-cell patch clamp technique was used to study the effects of acetylcholine (ACh) on Na(+)-K+ pump current (Ip) in acutely isolated guinea-pig ventricular myocytes. Studies were performed in the absence and presence of the beta-agonist isoprenaline (Iso). 2. ACh had no effect on Ip at low or high [Ca2+]i at any voltage in the absence of Iso. Iso alone inhibited Ip at low [Ca2+]i and shifted the Ip-V relationship at high [Ca2+]i in a negative direction. Addition of 1 microM ACh reversed these effects of Iso. K0.5 for the effects of ACh was about 16 nM, regardless of [Ca2+]i. 3. The actions of ACh on the heart are usually mediated via muscarinic receptors. Atropine, a muscarinic antagonist, blocked the effects of ACh on Ip in the presence of Iso, suggesting that these effects are also mediated by muscarinic receptors. 4. Muscarinic receptors are usually coupled to a Gi protein, leading to inhibition of adenylyl cyclase and a reduction of cAMP levels. We have shown previously that basal levels of cAMP are very low in guinea-pig ventricular myocytes, and that a membrane-permeant cAMP analogue, chlorophenylthio-cAMP (CPTcAMP), mimics the effects of Iso. ACh did not reverse the effects of CPTcAMP, supporting the hypothesis that the effects of ACh on Ip are also mediated via inhibition of adenylyl cyclase. 5. The present results suggest that a high level of parasympathetic tone alone does not affect the activity of ventricular Na(+)-K+ pumps. However, if sympathetic tone is high, then muscarinic stimulation can reciprocally modulate Na(+)-K+ pump activity. PMID:9218213

  3. Quinidine elicits proarrhythmic changes in ventricular repolarization and refractoriness in guinea-pig.

    PubMed

    Osadchii, Oleg E

    2013-04-01

    Quinidine is a class Ia Na(+) channel blocker that prolongs cardiac repolarization owing to the inhibition of I(Kr), the rapid component of the delayed rectifier current. Although quinidine may induce proarrhythmia, the contributing mechanisms remain incompletely understood. This study examined whether quinidine may set proarrhythmic substrate by inducing spatiotemporal abnormalities in repolarization and refractoriness. The monophasic action potential duration (APD), effective refractory periods (ERPs), and volume-conducted electrocardiograms (ECGs) were assessed in perfused guinea-pig hearts. Quinidine was found to produce the reverse rate-dependent prolongation of ventricular repolarization, which contributed to increased steepness of APD restitution. Throughout the epicardium, quinidine elicited a greater APD increase in the left ventricular chamber compared with the right ventricle, thereby enhancing spatial repolarization heterogeneities. Quinidine prolonged APD to a greater extent than ERP, thus extending the vulnerable window for ventricular re-excitation. This change was attributed to increased triangulation of epicardial action potential because of greater APD lengthening at 90% repolarization than at 30% repolarization. Over the transmural plane, quinidine evoked a greater ERP prolongation at endocardium than epicardium and increased dispersion of refractoriness. Premature ectopic beats and monomorphic ventricular tachycardia were observed in 50% of quinidine-treated heart preparations. In summary, abnormal changes in repolarization and refractoriness contribute greatly to proarrhythmic substrate upon quinidine infusion.

  4. Sarcolemmal hydraulic conductivity of guinea-pig and rat ventricular myocytes.

    PubMed

    Ogura, Toshitsugu; Matsuda, Hiroyuki; Imanishi, Sunao; Shibamoto, Toshishige

    2002-06-01

    Osmotic gradient-induced volume change and sarcolemmal water permeability of cardiac myocytes were evaluated to characterize the mechanism of water flux across the plasma membranes. Cell surface dimensions were measured from isolated guinea-pig and rat ventricular myocytes by digital videomicroscopy, and membrane hydraulic conductivity (L(p)) was obtained by analyzing the time course of cell swelling and shrinkage in response to osmotic gradients. Superfusion with anisosmotic solution (0.5-4 times normal osmolality) caused a rapid (<3 min to steady states) and reversible myocyte swelling or shrinkage. L(p) was approximately 1.9 x 10(-10) l N(-1) s(-1) for guinea-pig myocytes and approximately 1.7 x 10(-10) l N(-1) s(-1) for rat myocytes at 35 degrees C. Arrhenius activation energy (E(a)), a measure of the energy barrier to water flux, was approximately 3.7 (guinea-pig) and approximately 3.6 kcal mol(-1) (rat) between 11 and 35 degrees C; these values are equivalent to E(a) of self-diffusion of water in bulk solution ( approximately 4 kcal mol(-1)). Treatment with 0.1 mM Hg(2+), a sulfhydryl-oxidizing reagent that blocks membrane water channels, reduced L(p) by approximately 80%, and the sulfhydryl-reducing reagent dithiothreitol (10 mM) antagonized the inhibitory action of Hg(2+). Inhibition of the volume-sensitive cation (30 microM Gd3+) and anion (1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonate) channels and Na+-K+ pump (10 microM ouabain) modified the size of osmotic swelling but had little effect on L(p). Although the observed L(p) is relatively small in magnitude, the low E(a) and the sulfhydryl reagent-induced modification of L(p) are characteristic of channel-mediated water transport. These data suggest that water flux across the sarcolemma of guinea-pig and rat heart cells occurs through parallel pathways, i.e., the majority passing through water channels and the remainder penetrating the lipid bilayers.

  5. Electrophysiological effects of CRE-1087 in guinea-pig ventricular muscles.

    PubMed Central

    Delpón, E.; Valenzuela, C.; Pérez, O.; Tamargo, J.

    1992-01-01

    1. The electrophysiological effects of CRE-1087, a new antiarrhythmic drug, were studied in guinea-pig papillary muscles. 2. CRE-1087 (10(-7) M-10(-4) M) produced a concentration-dependent decrease in the action potential amplitude and Vmax of the upstroke without altering the action potential duration or the resting membrane potential. 3. At 5 x 10(-6) M, CRE-1087 produced a 5.0 +/- 1.0% tonic Vmax block and this value was not modified at the different rates of stimulation tested. In the presence of CRE-1087, trains of stimuli at rates between 0.5 and 3 Hz led to an exponential decline in Vmax (frequency-dependent Vmax block) which augmented at higher rates of stimulation. At 2 Hz the onset kinetics of the frequency-dependent Vmax block was fitted by a monoexponential function being the K value 0.099 +/- 0.012 AP-1. The time constant for the recovery of Vmax from the frequency-dependent block was prolonged to 18.3 +/- 1.5 s. 4. CRE-1087 (5 x 10(-6) M) did not shift the membrane responsiveness curve. 5. CRE-1087 had no effect on the characteristics of the slow action potentials elicited by isoprenaline in ventricular fibres depolarized by 27 mM KCl, which suggested that CRE-1087 did not exhibit class IV (Ca antagonist) antiarrhythmic actions. 6. The slow onset and the slow offset kinetics of frequency-dependent Vmax block during repetitive activity suggested that in guinea-pig ventricular muscle fibres CRE-1087 exhibited class Ic antiarrhythmic actions. PMID:1422597

  6. A Na+-activated K+ current (IK,Na) is present in guinea-pig but not rat ventricular myocytes.

    PubMed

    Lawrence, C; Rodrigo, G C

    1999-05-01

    The effects of removing extracellular Ca2+ and Mg2+ on the membrane potential, membrane current and intracellular Na+ activity (aiNa) were investigated in guinea-pig and rat ventricular myocytes. Membrane potential was recorded with a patch pipette and whole-cell membrane currents using a single-electrode voltage clamp. Both guinea-pig and rat cells depolarize when the bathing Ca2+ and Mg2+ are removed and the steady-state aiNa increases rapidly from a resting value of 6.4+/- 0.6 mM to 33+/-3.8 mM in guinea-pig (n=9) and from 8.9+/-0.8 mM to 29.3+/-3.0 mM (n=5) in rat ventricular myocytes. Guinea-pig myocytes partially repolarized when, in addition to removal of the bathing Ca2+ and Mg2+, K+ was also removed, however rat cells remained depolarized. A large diltiazem-sensitive inward current was recorded in guinea-pig and rat myocytes, voltage-clamped at -20 mV, when the bathing divalent cations were removed. When the bathing K+ was removed after Ca2+ and Mg2+ depletion, a large outward K+ current developed in guinea-pig, but not in rat myocytes. This current had a reversal potential of -80+/-0.7 mV and was not inhibited by high Mg2+ or glybenclamide indicating that it is not due to activation of non-selective cation or adenosine triphosphate (ATP)-sensitive K channels. The current was not activated when Li+ replaced the bathing Na+ and was blocked by R-56865, suggesting that it was due to the activation of KNa channels.

  7. Physiological role of endogenous amines in the modulation of ventricular automaticity in the guinea-pig.

    PubMed

    Hume, J; Katzung, B G

    1980-12-01

    1. Current-clamp experiments were carried out with guinea-pig papillary muscles to determine the dependence of depolarization-induced automaticity on endogenous catecholamines. 2. Catecholamine depletion was produced by pre-treatment of animals with 6-hydroxydopamine and confirmed by fluorimetric assay of right ventricular tissue. Papillary muscles from depleted animals demonstrated a marked suppression of depolarization-induced automaticity for maximum diastolic potentials less negative than -55 mV. This suppression was completely reversed by noradrenaline but not by tyramine. 3. In normal tissue, noradrenaline and tyramine had much smaller effects on automaticity arising from maximum diastolic potentials negative to -55 mV than on repetitive activity arising positive to this level. 4. L-propranolol in concentrations of 2-3 x 10(-7) M reduced repetitive activity in the less negative range of maximum diastolic potential. No evidence of direct membrane depression was observed at these doses and the effect was reversed by application of noradrenaline. 5. D-propranolol, the isomer with much lower beta-receptor blocking potency, required twentyfold higher concentrations to depress automaticity and this was accompanied by evidence of direct membrane depression, i.e. reduction of upstroke velocity of action potentials. 6. These results show that automaticity induced in guinea-pig papillary muscles by depolarization positive to -55 mV is strongly dependent upon endogenous catecholamines. 7. The hypothesis that endogenous catecholamines facilitate depolarization-induced automaticity through an increase in calcium conductance was modelled using numerical techniques. It was found that changes in calcium conductance caused changes in the model which closely parallelled the experimental effects of catecholamine depletion and beta-blockade. The effects of changes in delayed rectification in the model did not accurately reproduce the experimental results.

  8. Physiological role of endogenous amines in the modulation of ventricular automaticity in the guinea-pig.

    PubMed Central

    Hume, J; Katzung, B G

    1980-01-01

    1. Current-clamp experiments were carried out with guinea-pig papillary muscles to determine the dependence of depolarization-induced automaticity on endogenous catecholamines. 2. Catecholamine depletion was produced by pre-treatment of animals with 6-hydroxydopamine and confirmed by fluorimetric assay of right ventricular tissue. Papillary muscles from depleted animals demonstrated a marked suppression of depolarization-induced automaticity for maximum diastolic potentials less negative than -55 mV. This suppression was completely reversed by noradrenaline but not by tyramine. 3. In normal tissue, noradrenaline and tyramine had much smaller effects on automaticity arising from maximum diastolic potentials negative to -55 mV than on repetitive activity arising positive to this level. 4. L-propranolol in concentrations of 2-3 x 10(-7) M reduced repetitive activity in the less negative range of maximum diastolic potential. No evidence of direct membrane depression was observed at these doses and the effect was reversed by application of noradrenaline. 5. D-propranolol, the isomer with much lower beta-receptor blocking potency, required twentyfold higher concentrations to depress automaticity and this was accompanied by evidence of direct membrane depression, i.e. reduction of upstroke velocity of action potentials. 6. These results show that automaticity induced in guinea-pig papillary muscles by depolarization positive to -55 mV is strongly dependent upon endogenous catecholamines. 7. The hypothesis that endogenous catecholamines facilitate depolarization-induced automaticity through an increase in calcium conductance was modelled using numerical techniques. It was found that changes in calcium conductance caused changes in the model which closely parallelled the experimental effects of catecholamine depletion and beta-blockade. The effects of changes in delayed rectification in the model did not accurately reproduce the experimental results. PMID:7252866

  9. Effects of mitoxantrone on excitation-contraction coupling in guinea pig ventricular myocytes.

    PubMed

    Wang, G X; Zhou, X B; Korth, M

    2000-05-01

    The mechanisms of the inotropic effect of mitoxantrone (MTO), a synthetic dihydroxyanthracenedione derivative with antineoplastic activity, was investigated in guinea pig ventricular myocytes using whole-cell patch-clamp methods combined with fura-2 fluorescence and cell-edge tracking techniques. In right ventricular papillary muscles, 30 microM MTO increased isometric force of contraction as well as action potential duration (APD) in a time-dependent manner. The force of contraction was increased approximately 3-fold within 4 h. This positive inotropic effect was accompanied by a prolongation of time to peak force and relaxation time. In current-clamped single myocytes treated with 30 microM MTO for 30 min, an increase of cell shortening by 77% and a prolongation of APD by 19% was observed. Peak amplitude of the intracellular Ca(2+) transients was also increased by 10%. The contribution of APD prolongation to the enhancement of cell shortening induced by MTO was assessed by clamping control myocytes with action potentials of various duration. Prolongation of APD(90) (ADP measured at 90% of repolarization) by 24% led to an increase of cell shortening by 13%. When the cells were clamped by an action potential with constant APD, MTO still caused an increase of cell shortening by 59% within 30 min. No increase of the peak intracellular Ca(2+) transients, however, was observed under this condition. We conclude that both the APD prolongation and a direct interaction with the contractile proteins contributed to the positive inotropic effect of MTO.

  10. Biphasic effects of acetylstrophanthidin on automaticity in guinea pig ventricular muscle.

    PubMed

    Karagueuzian, H S; Katzung, B G

    1982-04-23

    The effects of acetylstrophanthidin (AS) on depolarization-induced automaticity and contractility of guinea pig papillary muscle were studied in a single sucrose gap chamber with microelectrode and current-clamp techniques. The concentration used, 1.4-1.8 microM, never induced automaticity in preparations at their normal resting potential. Twenty min after superfusion with AS, action potential duration (APD) was prolonged and the force of contraction increased. These were associated with an increase in slope of phase 4 depolarization and an increase in the membrane resistance (Rm) of muscles depolarized with small constant current pulses. With longer (50-80 min) periods of AS superfusion, APD became shorter, Rm decreased to less than predrug values, and in depolarized preparations, the slope of phase 4 decreased. Contractility remained unchanged throughout this second phase. All of these effects were fully reversible upon 60 min of superfusion with AS-free Tyrode solution. We suggest that the biphasic effects of AS on the automaticity of depolarized ventricular muscle cells are caused by an initial decrease followed by a later increase in transmembrane potassium conductance.

  11. Use-dependent block of single sodium channels by lidocaine in guinea pig ventricular myocytes.

    PubMed Central

    McDonald, T V; Courtney, K R; Clusin, W T

    1989-01-01

    Single sodium channel openings have been recorded from cell-attached patches of isolated guinea pig ventricular myocytes. A paired pulse protocol was used to test the hypothesis that channel openings are required for lidocaine block. While the averaged ensemble current during the test pulse was much reduced, there was no correlation between the appearance of channel openings during the conditioning pulse and the subsequent test pulse. Analysis of single channel records demonstrated that the unit conductance of open channels was not changed by lidocaine. The block of ensemble INa was explained by roughly equal reductions in number of open channel events, and in the average duration of opening for each event. These results suggest that lidocaine binding to Na+ channels is dependent upon voltage, but may occur before channel opening. A lidocaine-modified channel can still open, but will be less likely to remain open than a drug-free channel. These results are consistent with block of a pre-open state of the channel. PMID:2548633

  12. Effects of propafenone on calcium currents in single ventricular myocytes of guinea-pig.

    PubMed Central

    Fei, L.; Gill, J. S.; McKenna, W. J.; Camm, A. J.

    1993-01-01

    1. The effects of propafenone on the inward calcium current (ICa) were investigated in isolated single ventricular myocytes of the guinea-pig by the whole-cell clamp method. Propafenone inhibited ICa in a dose-dependent manner at concentrations of propafenone ranging from 1 x 10(-8) to 1 x 10(-3) M and half maximal block of ICa occurred at a propafenone concentration of 1.5 x 10(-6) M. Propafenone did not change the current-voltage relation of ICa other than a reduction in amplitude and showed no clear use- or frequency-dependent effects upon ICa (stimulation frequencies from 0.03 to 2 Hz). Propafenone did not alter the steady-state inactivation process: the half maximal activation potentials were 18.5 +/- 2.2 mV in the control state and 20.9 +/- 5.0 mV in the presence of 1 x 10(-6) M propafenone (n = 12, NS). Propafenone (1 x 10(-6) M) increased the half-time of reactivation by 73.9% (n = 6, 212.3 +/- 1.2 ms vs 369.2 +/- 1.5 ms, P < 0.05). 2. We conclude that propafenone blocks ICa in a concentration-dependent and a channel state-, use- or frequency-independent manner. The ICa blockade elicited by propafenone at clinically therapeutic plasma concentration is significant and may be involved in its anti-arrhythmic effects. PMID:8388297

  13. Electrophysiological effects of E-3753, a new antiarrhythmic drug, in guinea-pig ventricular muscle.

    PubMed Central

    Delpón, E.; Valenzuela, C.; Tamargo, J.

    1989-01-01

    1. The electrophysiological effects of E-3753, a new antiarrhythmic drug, were studied in guinea-pig papillary muscles. 2. E-3753 (10(-7) - 10(-4) M) produced a concentration-dependent decrease in the action potential amplitude and Vmax of the upstroke, shortened the action potential duration (APD) and shifted the resting membrane potential to less negative values. E-3753 also shortened the effective refractory period (ERP), lengthening the ERP relative to APD. 3. E-3753 (10(-5) M) shifted the membrane responsiveness curve along the voltage axis to more negative potentials. 4. In the presence of E-3753 (10(-5) M) trains of stimuli at rates between 0.5 and 3 Hz led to an exponential decline in Vmax (onset rate at 3 Hz, 0.05 +/- 0.009 per action potential), to a new steady-state level. This use-dependent Vmax block was augmented at higher rates of stimulation. The time constant for the recovery of Vmax from the use-dependent block was 41.1 +/- 4.8 s. 5. E-3753 (10(-5) - 10(-4) M) had no effect on the characteristics of the slow action potentials elicited by isoprenaline in ventricular fibres depolarized by 27 mM KCl. 6. The slow onset of use-dependent block during repetitive activity and the slow offset kinetics of use-dependent Vmax block suggest that E-3753 exhibits class Ic antiarrhythmic actions in ventricular muscle fibres but does not exhibit class IV (Ca antagonist) antiarrhythmic actions. PMID:2743087

  14. Oxidative metabolism in guinea pig ventricular myocytes protected from proteolytic enzyme activity.

    PubMed

    Bailey, L E; Carlos, H; Amian, A; Moon, K E

    1987-07-01

    Surface structures on guinea pig ventricular myocytes were protected from proteolytic enzyme activity with 100 KIU.ml-2 aprotinin during mechanical disaggregation. Intact myocytes, approximately 7.5 X 10(6) cells.g-1 ventricular wet weight, were separated from debris and damaged cells using Cytodex I tissue culture supports. Cellular ultrastructure did not differ from that observed in intact tissue. Neither spontaneous contractions nor contracture were ever observed in these myocytes in calcium concentrations of 10 mmol.litre-1. Dinitrophenol (0.2 mmol. litre-1) uncoupled respiration in the myocytes but only after the sarcolemma had been disrupted with Triton X100. The adenosine diphosphate to oxygen ratio of mitochondria isolated from the myocytes was 2.4(0.2) and the respiratory control index 2.6(0.3). Calcium (1.8 mmol.litre-1) increased oxygen uptake in the presence of 10 mmol.litre-1 pyruvate or 11 mmol.litre-1 glucose but not 17 mmol. litre-1 succinate. Succinate dependent oxygen consumption was greater than pyruvate dependent oxygen consumption (1090.0(190.0) and 40.1(0.8) nl.min-1.mg-1 protein respectively). The Crabtree effect was present. Oxidative metabolism was normal in cells stored at 10 degrees C for seven days but deteriorated rapidly thereafter. The results indicate that myocytes disaggregated by this procedure retain many of the morphological and metabolic characteristics of intact cardiac muscle cells and are relatively homogeneous with respect to calcium tolerance and metabolic function.

  15. An analysis of the delayed outward current in single ventricular cells of the guinea-pig.

    PubMed

    Matsuura, H; Ehara, T; Imoto, Y

    1987-12-01

    Properties of the delayed outward current (IK) in ventricular myocytes of the guinea-pig were studied using the whole cell clamp method. The experiments were performed under conditions in which IK was enhanced by application of isoproterenol while the Ca2+ current was eliminated by Ca2+-removal and by the addition of Cd2+. The reversal potential (Erev) of IK, determined from the current tails, was about 10 mV less negative than the K+ equilibrium potential. This was estimated by examining the reversal potential of the inward rectifier K+ current in Ba2+-containing solution, or from the Nernst equation. The Erev--log[K+]o relationship had a slope of 49 mV per tenfold change in [K+]o. In Na+-free solution, Erev became more negative. Thus, although the major charge carriers in IK are K+ ions, Na+ ions may also contribute in part to this current. The PNa/PK ratio in IK, calculated by applying a Goldman-Hodgkin-Katz relation to the reversal potential, was 0.016. The activation of IK during depolarization showed a sigmoidal time course at the onset, while the time course of the current tails was monoexponential at voltages more negative than-50 mV, but biexponential at more positive voltages. These observations can be explained by the conductance equation of the Hodgkin-Huxley type in which the kinetic variable is raised to the second power. These and other features of IK observed in the ventricular cells are discussed in comparison to the properties of similar current systems reported in other cardiac preparations.

  16. M1 muscarinic receptors increase calcium current and phosphoinositide turnover in guinea-pig ventricular cardiocytes.

    PubMed Central

    Gallo, M P; Alloatti, G; Eva, C; Oberto, A; Levi, R C

    1993-01-01

    1. Physiological and molecular evidence for the presence and functional role of M1 muscarinic cholinergic receptors (mAChRs) in adult guinea-pig ventricular cells is presented. 2. Whole-cell clamp measurements of the L-type calcium current (ICa) in isolated myocytes were performed. Caesium was used to suppress potassium currents. ICa was increased by the muscarinic agonist carbachol in cells pretreated with pertussis toxin which blocked the M2 mAChR-triggered cascade of intracellular signalling, while it was not changed in untreated cells. 3. If the M2-mediated regulation of ICa was blocked by directly saturating the cell with cyclic adenosine monophosphate (cAMP) through the patch pipette, application of carbachol induced a further small increase of the current above the level reached after cAMP perfusion. This increase was more pronounced in cells pretreated with pertussis toxin. 4. The carbachol-induced increase of ICa was blocked by the selective M1 mAChR antagonist pirenzepine. 5. The application of high concentrations of carbachol increased the accumulation of [3H]inositol monophosphate up to 240% above control levels. This increase was reduced by application of pirenzepine. 6. The expression of M1 receptor mRNA in ventricular cardiocytes was shown by reverse transcriptase-polymerase chain reaction. 7. These results suggest that M1 mAChR regulation of ICa can be a component of the paradoxical positive inotropism induced by high concentrations of muscarinic agonists. Images Fig. 11 PMID:8120813

  17. Regional differences in action potential characteristics and membrane currents of guinea-pig left ventricular myocytes.

    PubMed

    Main, M C; Bryant, S M; Hart, G

    1998-11-01

    Regional differences in action potential characteristics and membrane currents were investigated in subendocardial, midmyocardial and subepicardial myocytes isolated from the left ventricular free wall of guinea-pig hearts. Action potential duration (APD) was dependent on the region of origin of the myocytes (P < 0.01, ANOVA). Mean action potential duration at 90 % repolarization (APD90) was 237 +/- 8 ms in subendocardial (n = 30 myocytes), 251 +/- 7 ms in midmyocardial (n = 30) and 204 +/- 7 ms in subepicardial myocytes (n = 36). L-type calcium current (ICa) density and background potassium current (IK1) density were similar in the three regions studied. Delayed rectifier current (IK) was measured as deactivating tail current, elicited on repolarization back to -45 mV after 2 s step depolarizations to test potentials ranging from -10 to +80 mV. Mean IK density (after a step to +80 mV) was larger in subepicardial myocytes (1.59 +/- 0.16 pA pF-1, n = 16) than in either subendocardial (1.16 +/- 0.12 pA pF-1, n = 17) or midmyocardial (1. 13 +/- 0.11 pA pF-1, n = 21) myocytes (P < 0.05, ANOVA). The La3+-insensitive current (IKs) elicited on repolarization back to -45 mV after a 250 ms step depolarization to +60 mV was similar in the three regions studied. The La3+-sensitive tail current, (IKr) was greater in subepicardial (0.50 +/- 0.04 pA pF-1, n = 11) than in subendocardial (0.25 +/- 0.05 pA pF-1, n = 9) or in midmyocardial myocytes (0.38 +/- 0.05 pA pF-1, n = 11, P < 0.05, ANOVA). The contribution of a Na+ background current to regional differences in APD was assessed by application of 0.1 microM tetrodotoxin (TTX). TTX-induced shortening of APD90 was greater in subendocardial myocytes (35.7 +/- 7.1 %, n = 11) than in midmyocardial (15.7 +/- 3. 8 %, n = 10) and subepicardial (20.2 +/- 4.3 %, n = 11) myocytes (P < 0.05, ANOVA). Regional differences in action potential characteristics between subendocardial, midmyocardial, and subepicardial myocytes isolated from

  18. Electrophysiological effects of diprafenone, a dimethyl congener of propafenone on guinea-pig ventricular cells.

    PubMed Central

    Kodama, I.; Suzuki, R.; Honjo, H.; Toyama, J.

    1992-01-01

    1. The effects of diprafenone and propafenone on transmembrane action potential were examined and compared in papillary muscles and single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, both diprafenone and propafenone > or = 10(-6) M caused a significant and dose-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential. 3. In the presence of either drug, trains of stimuli at rates > or = 0.1 Hz led to an exponential decline in Vmax. A time constant (tau R) for Vmax recovery from the use-dependent block was 15.5 s for diprafenone and 8.8 s for propafenone. 4. The use-dependent block of Vmax with diprafenone was enhanced when the resting potential was depolarized by high (8, 10 mM) [K+]o, whereas that with propafenone was virtually unchanged. tau R with diprafenone was shortened by the depolarization, while that with propafenone was rather prolonged. 5. In single myocytes perfused with diprafenone or propafenone, 10 ms conditioning clamp to 0 mV caused a significant decrease in Vmax of subsequent action potential. A prolongation of the clamp pulse duration resulted in a modest enhancement of the Vmax inhibition with diprafenone, while a large enhancement of the Vmax inhibition occurred with propafenone. 6. These findings suggest that diprafenone, like propafenone, may block the sodium channel during both the activated and inactivated states. The relative contribution of inactivation block is less important for diprafenone than for propafenone. The different voltage-dependence of use-dependent block with diprafenone from propafenone would contribute to its high antiarrhythmic potency. PMID:1335340

  19. Blockade of Na+ current by promethazine in guinea-pig ventricular myocytes.

    PubMed Central

    Tanaka, H.; Habuchi, Y.; Nishimura, M.; Sato, N.; Watanabe, Y.

    1992-01-01

    1. To elucidate the antiarrhythmic mechanism of promethazine, its effects on the fast Na+ current (INa) were examined in single guinea-pig ventricular myocytes by whole-cell voltage clamp methods. 2. Promethazine blocked INa with a KD of 42.6 microM and Hill's coefficient of 1.1 at a holding potential of -140 mV. 3. The INa blockade was enhanced at a less negative holding potential of -80 mV with a change of KD to 4.4 microM. Although 10 microM promethazine did not change the inactivation time constants of INa, it shifted the steady-state inactivation curve (h infinity curve) toward more negative potentials by 19.5 mV with the slope factor unaffected. 4. Double pulse experiments revealed that the development of blockade followed two-exponential functions having time constants of 7 and 220 ms at -20 mV. 5. Promethazine slowed the repriming of INa. This was associated with the development of slow phase having a time constant of 1160 +/- 59 ms. 6. Promethazine produced a profound use-dependent block when the cell was repeatedly stimulated with interpulse intervals shorter than 1 s. However, short pulses of 2 ms duration hardly produced such a use-dependent block. Hence, open channel blockade is considered to play a minor role in the promethazine action on INa. 7. These results suggest that promethazine blocks cardiac INa in a manner similar to class I antiarrhythmic drugs and that this effect may account for its antiarrhythmic action. PMID:1327391

  20. Activation of the ATP-sensitive K+ channel by decavanadate in guinea-pig ventricular myocytes.

    PubMed

    Nakashima, H; Kakei, M; Tanaka, H

    1993-03-23

    To evaluate the effects of decavanadate on the ATP-sensitive K+ (KATP) channel, we applied the inside-out membrane patch-clamp technique to ventricular myocytes isolated from guinea-pig hearts. Decavanadate increased the probability of the KATP channel being open in a dose-dependent manner over the range of 0.1 to 5 mM in the presence of 0.3 mM ATP. Half-maximal activation occurred at 540 microM decavanadate and a Hill coefficient of 1.3 was obtained when the Hill equation was used to fit the dose-dependent activation for the channel by decavanadate. The half-maximum inhibition for the channel by ATP (K1/2) in the presence of 2 mM Mg2+ was 19 and 74 microM in its absence. In the presence of decavanadate, both curves shifted toward the higher concentration of ATP without a change in steepness of the slope (Hill coefficient = 2). The effect of decavanadate could be expressed by a model in which its binding prevents ATP binding from closing the channel. The estimated dissociation constant of decavanadate was 1.5 microM in the presence and 22.8 microM in the absence of Mg2+. Decavanadate reactivated the rundown channel in the absence of Mg2+ and ATP. Neither the single channel slope conductance nor the mean open and closed lifetime within the bursts of channel openings were affected by decavanadate. We conclude that internal Mg2+ is not required for the modulation produced by decavanadate, but this ion influences the channel and changes the dissociation constant of both ATP and decavanadate to the channel.

  1. Distinguishing between overdrive excited and suppressed ventricular beats in guinea pig ventricular myocardium.

    PubMed

    Greer-Short, Amara; Poelzing, Steven

    2015-01-01

    Rapid ventricular pacing rates induces two types of beats following pacing cessation: recovery cycle length (RCL) prolongation (overdrive suppression) and RCL shortening (overdrive excitation). The goals of this study were to compare common experimental protocols for studying triggered activity in whole-heart preparations and differentiate between recovery beats using a new methodology. Post-pacing recovery beat cycle length (RCL) and QRS were normalized to pre-paced R-R and QRS intervals and analyzed using a K-means clustering algorithm. Control hearts only produced suppressed beats: RCL ratio increased with rapid pacing (25 ± 4.0%, n = 10) without changing QRS duration. Rapid pacing during hypercalcemia + hypothermia (5.5 mM and 34°C) produced significantly earlier excited beats (53 ± 14%, n = 5) with wider QRS durations (58 ± 6.3%, n = 5) than suppressed beats. Digoxin + hypothermia (0.75 μM) produced the most excited beats with significantly earlier RCL (44 ± 3.2%, n = 6) and wider QRS (60 ± 3.1%, n = 6) ratios relative to suppressed beats. Increasing pacing further shortened RCL (30 ± 7.8%, n = 6). In a prospective study, TTX (100 nM) increased RCL ratio (15 ± 6.0%, n = 10) without changing the QRS duration of excited beats. The algorithm was compared to a cross-correlation analysis with 93% sensitivity and 94% specificity. This ECG based algorithm distinguishes between triggered and automatic activity.

  2. Distinguishing between overdrive excited and suppressed ventricular beats in guinea pig ventricular myocardium

    PubMed Central

    Greer-Short, Amara; Poelzing, Steven

    2015-01-01

    Rapid ventricular pacing rates induces two types of beats following pacing cessation: recovery cycle length (RCL) prolongation (overdrive suppression) and RCL shortening (overdrive excitation). The goals of this study were to compare common experimental protocols for studying triggered activity in whole-heart preparations and differentiate between recovery beats using a new methodology. Post-pacing recovery beat cycle length (RCL) and QRS were normalized to pre-paced R-R and QRS intervals and analyzed using a K-means clustering algorithm. Control hearts only produced suppressed beats: RCL ratio increased with rapid pacing (25 ± 4.0%, n = 10) without changing QRS duration. Rapid pacing during hypercalcemia + hypothermia (5.5 mM and 34°C) produced significantly earlier excited beats (53 ± 14%, n = 5) with wider QRS durations (58 ± 6.3%, n = 5) than suppressed beats. Digoxin + hypothermia (0.75 μM) produced the most excited beats with significantly earlier RCL (44 ± 3.2%, n = 6) and wider QRS (60 ± 3.1%, n = 6) ratios relative to suppressed beats. Increasing pacing further shortened RCL (30 ± 7.8%, n = 6). In a prospective study, TTX (100 nM) increased RCL ratio (15 ± 6.0%, n = 10) without changing the QRS duration of excited beats. The algorithm was compared to a cross-correlation analysis with 93% sensitivity and 94% specificity. This ECG based algorithm distinguishes between triggered and automatic activity. PMID:25741282

  3. Enhanced effect of VEGF165 on L-type calcium currents in guinea-pig cardiac ventricular myocytes.

    PubMed

    Xing, Wenlu; Gao, Chuanyu; Qi, Datun; Zhang, You; Hao, Peiyuan; Dai, Guoyou; Yan, Ganxin

    2017-01-01

    The mechanisms of vascular endothelial growth factor 165 (VEGF165) on electrical properties of cardiomyocytes have not been fully elucidated. The aim of this study is to test the hypothesis that VEGF165, an angiogenesis-initiating factor, affects L-type calcium currents (ICa,L) and cell membrane potential in cardiac myocytes by acting on VEGF type-2 receptors (VEGFR2). ICa,L and action potentials (AP) were recorded by the whole-cell patch clamp method in isolated guinea-pig ventricular myocytes treated with different concentrations of VEGF165 proteins. Using a VEGFR2 inhibitor, we also tested the receptor of VEGF165 in cardiomyocytes. We found that VEGF165 increased ICa,L in a concentration-dependent manner. SU5416, a VEGFR2 inhibitor, almost completely eliminated VEGF165-induced ICa,L increase. VEGF165 had no significant influence on action potential 90 (APD90) and other properties of AP. We conclude that in guinea-pig ventricular myocytes, ICa,L can be increased by VEGF165 in a concentration-dependent manner through binding to VEGFR2 without causing any significant alteration to action potential duration. Results of this study may further expound the safety of VEGF165 when used in the intervention of heart diseases.

  4. Characterization of intracellular pH regulation in the guinea-pig ventricular myocyte

    PubMed Central

    Leem, Chae Hun; Lagadic-Gossmann, Dominique; Vaughan-Jones, Richard D

    1999-01-01

    Intracellular pH was recorded fluorimetrically by using carboxy-SNARF-1, AM-loaded into superfused ventricular myocytes isolated from guinea-pig heart. Intracellular acid and base loads were induced experimentally and the changes of pHi used to estimate intracellular buffering power (β). The rate of pHi recovery from acid or base loads was used, in conjunction with the measurements of β, to estimate sarcolemmal transporter fluxes of acid equivalents. A combination of ion substitution and pharmacological inhibitors was used to dissect acid effluxes carried on Na+-H+ exchange (NHE) and Na+-HCO3− cotransport (NBC), and acid influxes carried on Cl−-HCO3− exchange (AE) and Cl−-OH− exchange (CHE). The intracellular intrinsic buffering power (βi), estimated under CO2/HCO3−-free conditions, varied inversely with pHi in a manner consistent with two principal intracellular buffers of differing concentration and pK. In CO2/HCO3−-buffered conditions, intracellular buffering was roughly doubled. The size of the CO2-dependent component (βCO2) was consistent with buffering in a cell fully open to CO2. Because the full value of βCO2 develops slowly (2·5 min), it had to be measured under equilibrium conditions. The value of βCO2 increased monotonically with pHi. In 5 % CO2/HCO3−-buffered conditions (pHo 7·40), acid extrusion on NHE and NBC increased as pHi was reduced, with the greater increase occurring through NHE at pHi < 6·90. Acid influx on AE and CHE increased as pHi was raised, with the greater increase occurring through AE at pHi > 7·15. At resting pHi (7·04-7·07), all four carriers were activated equally, albeit at a low rate (about 0·15 mM min−1). The pHi dependence of flux through the transporters, in combination with the pHi and time dependence of intracellular buffering (βi+βCO2), was used to predict mathematically the recovery of pHi following an intracellular acid or base load. Under several conditions the mathematical predictions

  5. Intracellular Ca2+ transients during rapid cooling contractures in guinea-pig ventricular myocytes.

    PubMed Central

    Bers, D M; Bridge, J H; Spitzer, K W

    1989-01-01

    1. We measured intracellular Ca2+ transients during rapid cooling contractures (RCCs) in guinea-pig ventricular myocytes using the fluorescent Ca2+ indicator, Indo-1. 2. Rapid cooling of myocytes from 22 to 0-1 degrees C induced a rapid increase in [Ca2+]i which preceded the peak of the contraction and was sometimes large enough to saturate Indo-1. This indicates that [Ca2+]i may reach greater than 10 microM during an RCC. 3. The [Ca2+]i during the RCC slowly declined from its peak value and most of this decline in [Ca2+]i can be attributed to slow reaccumulation of Ca2+ by the sarcoplasmic reticulum (SR) in the cold. RCCs induced in the absence of Cao2+, were not different from control, supporting previous conclusions that RCCs depend exclusively on intracellular Ca2+ stores. 4. RCCs are depressed by long rest periods (rest decay) or by exposure to ryanodine or caffeine, which supports conclusions that RCCs are due to Ca2+ release from the SR. The rest decay of RCCs can be almost completely prevented by applying Nao(+)-free solution during the rest period. This implies that the loss of SR Ca2+ during rest depends on the sarcolemmal Na(+)-Ca2+ exchange (and not the sarcolemmal Ca2(+)-ATPase pump). 5. Rapid rewarming during an RCC normally leads to an additional transient contraction (or rewarming spike), without any increase in [Ca2+]i. Thus, the rewarming spike might be attributable to an increase in myofilament Ca2+ sensitivity induced by rewarming. 6. A second RCC is used to assess the fraction of Ca2+ which is re-sequestered by the SR during relaxation from the first RCC. In control solution progressive RCCs decline in amplitude, but in Na(+)-free, Ca2(+)-free solution they are of constant amplitude. We conclude that the SR Ca2+ pump and Na(+)-Ca2+ exchange are responsible for relaxation and that the latter may account for 20-50% of relaxation. 7. These results support the use of RCCs as a useful means of assessing SR Ca2+ content in intact cardiac muscle cells

  6. Measuring and Modeling Chloride-Hydroxyl Exchange in the Guinea-Pig Ventricular Myocyte

    PubMed Central

    Niederer, S. A.; Swietach, P.; Wilson, D. A.; Smith, N. P.; Vaughan-Jones, R. D.

    2008-01-01

    Protons are powerful modulators of cardiac function. Their intracellular concentration is regulated by sarcolemmal ion transporters that export or import H+-ions (or their ionic equivalent: \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{HCO}}_{3}^{-},\\hspace{.167em}{\\mathrm{OH}}^{-}\\end{equation*}\\end{document}). One such transporter, which imports H+-equivalents, is a putative Cl−/OH− exchanger (CHE). A strong candidate for CHE is SLC26A6 protein, a product of the SLC26A gene family of anion transporters, which has been detected in murine heart. SLC26A6 protein is suggested to be an electrogenic \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}1{\\mathrm{Cl}}^{-}/2{\\mathrm{OH}}^{-}(2{\\mathrm{HCO}}_{3}^{-}\\end{equation*}\\end{document}) exchanger. Unfortunately, there is insufficient characterization of cardiac CHE against which the properties of heterologously expressed SLC26A6 can be matched. We therefore investigated the proton, Cl−, and voltage dependence of CHE activity in guinea-pig ventricular myocytes, using voltage-clamp, intracellular pH fluorescence, and mathematical modeling techniques. We find that CHE activity is tightly regulated by intracellular and extracellular pH, is voltage-insensitive over a wide range (±80 mV), and displays substrate dependence suggestive of electroneutral 1Cl−/1OH− exchange. These properties exclude electrogenic SLC26A6 as sole contributor to CHE. Either the SLC26A6 product in heart is electroneutral, or CHE comprises at

  7. Inward current related to contraction in guinea-pig ventricular myocytes.

    PubMed Central

    Fedida, D; Noble, D; Shimoni, Y; Spindler, A J

    1987-01-01

    1. A component of inward current has been identified in isolated guinea-pig ventricular cells that is closely correlated with the contraction of the cell and not with the rapidly activated calcium current. This is a delayed current most clearly seen as a current 'tail' after 50-200 ms depolarizing pulses. At 22 degrees C the delayed current has a maximum amplitude of approximately 0.5 nA at -40 mV (consistently 10-20% of the peak amplitude of the calcium current) and decays with a half time of approximately 150 ms. 2. Paired-pulse protocols show that at pulse intervals (300-400 ms) at which the calcium current is nearly fully reprimed, the delayed component is very small. It recovers over a time course of several seconds, as does the contraction. Adrenaline speeds the decay of the delayed current (approximately 50%) and similarly accelerates cell relaxation. Adrenaline also shortens the recovery time of both the contraction and the delayed current. 3. During long trains of repetitive pulses, the delayed current amplitude follows that of the contraction 'staircase'. The half-time of the decay of the current 'tail' also matches that of contraction and suggests that both may reflect the time course of the underlying intracellular calcium transient. 4. The half-time of decay of the delayed current is only moderately voltage dependent over the potential range -80 to 0 mV. The amplitude of the delayed current normally reaches a minimum around -20 mV and increases at more negative potentials. 5. The voltage dependence and kinetics of decay of the current show that it should flow and decay largely during the action potential plateau and repolarization rather than during diastole. 6. Diffusion of high concentrations of EGTA into cells abolishes the delayed current and cell contraction. Under these conditions the fast calcium current is increased and its inactivation delayed. 7. When calcium is replaced by strontium, the delayed current amplitude is greatly reduced even

  8. Phorbol ester activation of chloride current in guinea-pig ventricular myocytes.

    PubMed Central

    Shuba, L. M.; Asai, T.; McDonald, T. F.

    1996-01-01

    1. Although earlier studies with phorbol esters indicate that protein kinase C (PKC) may be an important regulator of Cl- current (Icl) in cardiac cells, there is a need for additional quantitative data and investigation of conflicting findings. Our objectives were to measure the magnitude, time course, and concentration-dependence of Icl activated in guinea-pig ventricular myocytes by phorbol 12-myristate 13-acetate (PMA), evaluate its PKC dependence, and examine its modification by external and internal ions. 2. The whole-cell patch clamp technique was used to apply short depolarizing and hyperpolarizing pulses to myocytes superfused with Na(+)-, K(+)-, Ca(2+)-free solution (36 degrees C) and dialysed with Cs+ solution. Stimulation of membrane currents by PMA (threshold < or = 1nM, EC50 approximately equal to 14 nM, maximal 40% increase with > or = 100 nM) plateaued within 6-10 min. 3. PMA-activated current was time-independent, and suppressed by l mM 9-anthracenecarboxylic acid (9-AC). Its reversal potential (Erev) was sensitive to changes in the Cl- gradient, and outward rectification of the current-voltage (I-V) relationship was more pronounced with 30 mM than 140 mM Cl- dialysate. 4. The relative permeability of PMA-activated channels estimated from Erev measurements was I- > Cl- > > aspartate. Channel activation was independent of external Na+. 5. PMA failed to activate Icl in myocytes pretreated with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) or dialysed with pCa 10.5 solution. Lack of response to 4 alpha-phorbol 12, 13-didecanoate (alpha PDD) was a further indication of mediation by PKC. 6. Icl induced by 2 microM forskolin was far larger than that induced by PMA, suggesting that endogenous protein kinase A is a much stronger Cl- channel activator than endogenous PKC in these myocytes. 7. The macroscopic properties of PMA-induced Icl appear to be indistinguishable from those of PKA-activated Icl. We discount stimulation of PKA by PMA as an

  9. Sodium-calcium exchange during the action potential in guinea-pig ventricular cells.

    PubMed Central

    Egan, T M; Noble, D; Noble, S J; Powell, T; Spindler, A J; Twist, V W

    1989-01-01

    1. Slow inward tail currents attributable to electrogenic sodium-calcium exchange can be recorded by imposing hyperpolarizing voltage clamp pulses during the normal action potential of isolated guinea-pig ventricular cells. The hyperpolarizations return the membrane to the resting potential (between -65 and -88 m V) allowing an inward current to be recorded. This current usually has peak amplitude when repolarization is imposed during the first 50 ms after the action potential upstroke, but becomes negligible once the final phase of repolarization is reached. The envelope of peak current tail amplitudes strongly resembles that of the intracellular calcium transient recorded in other studies. 2. Repetitive stimulation producing normal action potentials at a frequency of 2 Hz progressively augments the tail current recorded immediately after the stimulus train. Conversely, if each action potential is prematurely terminated at 0.1 Hz, repetitive stimulation produces a tail current much smaller than the control value. The control amplitude of inward current is only maintained if interrupted action potentials are separated by at least one full 'repriming' action potential. These effects mimic those on cell contraction (Arlock & Wohlfart, 1986) and suggest that progressive changes in tail current are controlled by variations in the amplitude and time course of the intracellular calcium transient. 3. When intracellular calcium is buffered sufficiently to abolish contraction, the tail current is abolished. Substitution of calcium with strontium greatly reduces the tail current. 4. The inward tail current can also be recorded at more positive membrane potentials using standard voltage clamp pulse protocols. In this way it was found that temperature has a large effect on the tail current, which can change from net inward at 22 degrees C to net outward at 37 degrees C. The largest inward currents are usually recorded at about 30 degrees C. It is shown that this effect is

  10. Isoprenaline, Ca2+ and the Na(+)-K+ pump in guinea-pig ventricular myocytes.

    PubMed Central

    Gao, J; Mathias, R T; Cohen, I S; Baldo, G J

    1992-01-01

    1. The whole-cell patch clamp technique was employed to study the effects of the beta-agonist isoprenaline (ISO) on the Na(+)=K+ pump current, Ip, in acutely isolated ventricular myocytes from guinea-pig hearts. Propranolol, a beta-adrenergic antagonist, was used to demonstrate that all of the effects of ISO, stimulatory or inhibitory, are mediated by beta-receptors. 2. Below about 150 nM [Ca2+]i, we find that ISO reduces Ip, while above this [Ca2+]i ISO increases Ip. The stimulatory and inhibitory effects of ISO on Ip are independent of either intracellular sodium ([Na+]i) or extracellular potassium ([K+]o). These results suggest that the end-effect of ISO is directly on the maximum pump turnover rate (Vmax) rather than indirectly through changes in [Na+]i or [K+]o or modulatory effects on Na+ or K+ affinity. 3. The maximum effect of ISO increases Ip by 25% when [Ca2+] is buffered at 1.4 microM. A half-maximal effect is reached at roughly 10 nM-ISO and a near-maximal effect by 0.5 microM. 4. The permeabilized patch technique, using amphotericin B (Horn & Marty, 1988; Rae, Cooper, Gates & Watsky, 1991), was employed to minimize changes in the normal second messenger systems and calcium buffers. In these experiments, we used a high intracellular sodium solution (pipette sodium was 50 mM), thus sodium-calcium exchange was depressed and we expected [Ca2+]i to be above 150 nM. ISO increases Ip in these conditions as in the dialysed cells. 5. Our results suggest that beta-stimulation can increase Ip, but only if [Ca2+]i is above about 150 nM. In the beating heart [Ca2+]i rises well above this value during systole and the average [Ca2+]i, which depends on heart rate, is expected to normally be above this level. During beta-stimulation, the increase in Ip along with a concomitant increase in IK (Giles, Nakajima, Ono & Shibata, 1989; Duchatelle-Gourdon, Hartzell & Lagrutta, 1989) helps prevent action potential lengthening and allows an increase in heart rate even in the

  11. Two classes of gating current from L-type Ca channels in guinea pig ventricular myocytes

    PubMed Central

    1992-01-01

    Intramembrane charge movement was recorded in guinea pig ventricular myocytes at 19-22 degrees C using the whole-cell patch clamp technique. From a holding potential of -110 mV, the dependence of intramembrane charge moved on test voltage (Q(V)) followed the sum of two Boltzmann components. One component had a transition voltage (V) of -48 mV and a total charge (Qmax) of congruent to 3 nC/microF. The other had a V of - 18 mV and a Qmax of 11 nC/microF. Ba2+ currents through Ca channels began to activate at -45 mV and peaked at congruent to -15 mV. Na+ current peaked at -35 to -30 mV. Availability of charge (in pulses from -70 to +10 mV) depended on the voltage of conditioning depolarizations as two Boltzmann terms plus a constant. One term had a V of -88 mV and a Qmax of 2.5 nC/microF; the other had a V of -29 mV and a Qmax of 6.3 nC/microF. From the Q(V) dependence, the voltage dependence of the ionic currents, and the voltage dependence of the availability of charge, the low voltage term of Q(V) and availability was identified as Na gating charge, at a total of 3.5 nC/microF. The remainder, 11 nC/microF, was attributed to Ca channels. After pulses to -40 mV and above, the OFF charge movement had a slow exponentially decaying component. Its time constant had a bell-shaped dependence on OFF voltage peaking at 11 ms near -100 mV. Conditioning depolarizations above -40 mV increased the slow component exponentially with the conditioning duration (tau approximately equal to 480 ms). Its magnitude was reduced as the separation between conditioning and test pulses increased (tau approximately equal to 160 ms). The voltage distribution of the slow component of charge was measured after long (5 s) depolarizations. Its V was -100 mV, a shift of -80 mV from the value in normally polarized cells. This voltage was the same at which the time constant of the slow component peaked. Qmax and the steepness of the voltage distribution were unchanged by depolarization. This indicates

  12. Resting, and rate-dependent depression of Vmax of guinea-pig ventricular action potentials by amiodarone and desethylamiodarone.

    PubMed Central

    Pallandi, R. T.; Campbell, T. J.

    1987-01-01

    1 The cellular electrophysiological effects of amiodarone and its metabolite desethylamiodarone (DEA) were studied in guinea-pig ventricular myocardium by use of standard microelectrode techniques. 2 Both compounds produced significant increases in action potential duration (Class III antiarrhythmic effect) and decreases in maximum rate of depolarization (Class I effect), at clinically relevant concentrations. 3 The Class I effects were rate-dependent, with small (0-16%) falls in maximum depolarization rate in the absence of stimulation ('resting block') and progressively larger effects at decreasing interstimulus intervals (range 1200-300 ms). 4 The kinetics of onset and offset of the Class I effect in response to a step change in driving rate were quite fast for both drugs (comparable to those reported for Class Ib agents). 5 It is concluded that this unique combination of Class III action plus Class I effects with fast onset and offset kinetics may help explain the great efficacy of amiodarone in antiarrhythmic therapy. PMID:3664094

  13. Kinetic evidence distinguishing volume-sensitive chloride current from other types in guinea-pig ventricular myocytes.

    PubMed Central

    Shuba, L M; Ogura, T; McDonald, T F

    1996-01-01

    1. Kinase-mediated chloride currents (ICl) in guinea-pig ventricular myocytes were activated by application of phorbol ester or forskolin, and compared with currents induced by hyposmotic swelling. Swelling-activated current was identified as ICl from changes in reversal potential, outward rectification and conductance when the Cl-gradient was modified. 2. Kinase-stimulated currents were relatively time and voltage independent, whereas hyposmotic swelling-stimulated (hyposmotic-stimulated) currents inactivated during 100 ms pulses to positive potentials. Forskolin stimulated time-independent ICl in myocytes with current unresponsive to hyposmotic superfusion, and superimposed a similar pedestal on time-dependent ICl in swollen myocytes. 3. Less negative holding potentials depressed hyposmotic-stimulated ICl tested at +80 mV; inhibition was half-maximal at -25 mV. Pulses from -80 to +80 mV inactivated up to 75% of ICl along a multi-exponential time course; repolarization elicited inwardly developing tail currents whose time courses suggest complex gating. 4. Hyperpolarizations, after strongly-inactivating depolarizations, triggered reactivating tail currents whose amplitude and configuration were dependent on voltage and Cl-gradients; tails were large and inwardly developing at potentials negative to the calculated Cl-equilibrium potential (ECl), small and outwardly developing at potentials positive to ECl, and time independent near ECl. 5. These results suggest that the volume-sensitive Cl- channels investigated here are distinct from other Cl- channels in guinea-pig ventricular myocytes. However, their voltage-dependent properties strongly resemble those of volume-sensitive Cl- channels in certain epithelial cells. PMID:9011623

  14. The effects of quinidine and verapamil on electrically induced automaticity in the ventricular myocardium of guinea pig.

    PubMed

    Grant, A O; Katzung, B G

    1976-02-01

    The effects of 2 to 10 muM verapamil (1-5 mg/l) and 3.8 to 7.6 muM quinidine (2-4 mg/l) on automaticity in ventricular myocardial fibers were examined. Papillary muscles from guinea pigs were mounted in a sucrose gap chamber and transmembrane potential was recorded by standard microelectrode techniques. Automaticity was induced with depolarizing currents of various strengths. Verapamil reduced phase 4 slope at all maximum diastolic membrane potentials. It also caused a selective reduction of the overshoot of action potentials arising from less negative maximum diastolic potentials. During exposure to verapamil, increased [Ca]0 partially restored action potential overshoot, but phase 4 slope was further reduced. Epinephrine caused a partial or complete reversal of verapamil-induced phase 4 slope depression but usually did not restore action potential overshoot. Quinidine reduced phase 4 slope at all maximum diastolic potentials. There was less marked reduction of action potential overshoot than in the case of verapamil. Epinephrine caused a partial reversal of the reduction of phase 4 slope produced by quinidine. It is concluded that although both verapamil and quinidine reduce automaticity in ventricular fibers, verapamil may be more effective in reducing the amplitude and occurrence of action potentials arising from low maximum diastolic potentials.

  15. Effects of L-propionylcarnitine on electrical and mechanical alterations induced by amphiphilic lipids in isolated guinea pig ventricular muscle.

    PubMed

    Aomine, M; Arita, M; Shimada, T

    1988-01-01

    We examined the effects of L-propionylcarnitine (Prop. C), a short-chain acylcarnitine, on amphiphile (L-lysophosphatidylcholine or L-palmitoylcarnitine)-induced electrophysiological and ultrastructural changes in isolated guinea pig ventricular papillary muscles, under acidic conditions (pH 6.9). Conventional microelectrode, tension-recording, and electron microscope techniques were used. Both amphiphiles, at a concentration of 10(-4) M, significantly decreased the resting membrane potential, action potential amplitude, and action potential duration, but increased the developed and resting tension. Such amphiphile-induced electrical changes were not observed in muscles pretreated with the beta-blocker, atenolol, although the mechanical changes remained unaffected. The application of Prop. C (10(-2) M), in the continued presence of the amphiphiles caused a return of the action potential duration and the developed tension to the control level. However, the resting potential and action potential amplitude remained unaffected; in fact, the maximum upstroke velocity (Vmax) of the action potential tended to decrease further. Pretreatment with Prop. C prevented all the amphiphile-induced electrophysiological and mechanical changes, except for Vmax. Electron microscopic studies revealed that amphiphile-induced ultrastructural changes were prevented, at least in part, in the presence of Prop. C. Thus, Prop. C antagonizes some of deleterious effects of amphiphiles, such as lysophosphatidylcholine and palmitoylcarnitine, upon the electrical and mechanical activities of the ventricular muscle, under acidic conditions.

  16. Effects of the fluoroquinolone antibacterial drug ciprofloxacin on ventricular repolarization in the halothane-anesthetized Guinea pig.

    PubMed

    Matsuo, Kazuhiro; Fujiwara, Kaori; Omuro, Naoki; Kimura, Itsuki; Kobayashi, Kazuko; Yoshio, Takashi; Takahara, Akira

    2013-01-01

    The fluoroquinolone antibiotic ciprofloxacin has been reported to block delayed rectifier K(+) channels at much higher concentrations than those at which it exerts its bactericidal activity. In this study using the halothane-anesthetized guinea pig, we assessed whether ciprofloxacin has a proarrhythmic activity. Ciprofloxacin at a clinically relevant dose of 3 mg/kg, i.v. did not affect any electrocardiographic parameters. At 10 mg/kg, it prolonged the QT interval and the duration of the monophasic action potential of the ventricle under sinus rhythm and constant ventricular pacing (n = 6). The extents of its effects on the ventricular repolarization phase were comparable to those of another fluoroquinolone antibiotic moxifloxacin at a clinically relevant dose of 3 mg/kg (n = 6). Meanwhile, the PR interval and QRS width were also increased by ciprofloxacin at 10 mg/kg, suggesting that the drug inhibited cardiac K(+) channels as well as Na(+) and Ca(2+) channels in vivo. These results suggest that ciprofloxacin exerted a multi-ion channel-blocking action in the heart within the supra-therapeutic dose range. Therefore, careful observation may be necessary for patients with heart disease receiving a higher dose of ciprofloxacin in order to prevent the emergence of resistance.

  17. Temporal response of ectopic activity in guinea pig ventricular myocardium in response to isoproterenol and acetylcholine

    PubMed Central

    Greer-Short, Amara; Poelzing, Steven

    2015-01-01

    Both β adrenergic and muscarinic receptor stimulation independently potentiate arrhythmogenesis. However, the effect of simultaneous stimulation on arrhythmogenesis is not well known. The purpose of this study was to determine the temporal response of arrhythmia risk to individual and combined autonomic agonists. Guinea pig hearts were excised and Langendorff-perfused. The β adrenergic receptor and muscarinic receptor agonists were isoproterenol (ISO, 0.6 μM) and acetylcholine (ACh, 10 μM), respectively. All measurements with agonists occurred over 21 min. ISO induced ectopic activity for the first 8 min. ISO also transiently shortened and then prolonged R-R interval over a similar time course. ACh added after ISO transiently induced ectopic activity for 12 min, while R-R interval invariantly prolonged. ACh alone produced few ectopic beats, while invariantly prolonging R-R interval. In contrast to ISO alone, ISO following ACh significantly increased ectopic activity and shortened R-R interval for the duration of the experiment. Animals aged 17–19 months exhibited sustained arrhythmogenesis while those aged 11–14 did not. When ACh was removed in older hearts while ISO perfused, a transient increase in ectopic activity and decreased R-R interval was observed, similar to ISO alone. These data suggest that pre-treating with and maintaining ACh perfusion can sustain ISO sensitivity, in contrast to ISO perfusion alone. PMID:26539122

  18. Anti-adrenergic effect of adenosine on Na(+)-Ca(2+) exchange current recorded from guinea-pig ventricular myocytes.

    PubMed

    Zhang, Y H; Hinde, A K; Hancox, J C

    2001-05-01

    The Na(+)-Ca(2+) exchanger is a protein present in the cell membrane of many cell types. In heart it plays important roles in Ca homeostasis and ionic current generation. Recently, it has been reported that the beta-adrenergic agonist isoprenaline (ISO) can increase directly Na(+)-Ca(2+) exchanger activity in guinea-pig ventricular myocytes. Adenosine (ADO) exerts anti-adrenergic properties that make it effective against some arrhythmias and the aim of the present study was to determine whether or not ADO can antagonize the direct modulatory effect of ISO on the exchanger.Whole-cell patch clamp measurements of Na(+)-Ca(2+) exchanger current (I(NaCa)) were made from guinea-pig ventricular myocytes, with major interfering currents inhibited. I(NaCa) was measured at 378 degrees C as current sensitive to external nickel (Ni(2+), 10 mM) during an applied descending voltage ramp. ISO (1 microM) significantly increased both inward and outward I(NaCa). This effect was abolished in the presence of ADO (200 microM). ADO alone did not significantly alter the amplitude of I(NaCa). The effect of ADO on the response of I(NaCa) to ISO was mimicked by the A(1)ADO receptor agonist N(6)-cyclopentyladenosine (CPA, 10 microM), whereas the effect of ADO on the response of I(NaCa) to ISO was inhibited by the A(1)ADO receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 2 microM). These data suggest that the A(1)ADO receptor mediated the response. The anti-adrenergic effects on I(NaCa) of ADO were not affected by the protein kinase C (PKC) inhibitor, chelerythrine (CLT, 1 microM), nor by the nitric oxide (NO) synthase inhibitor, N (G)-nitro-L-arginine methyl ester((L)-NAME, 0.5 mM). Moreover, in the presence of PKC activator phorbol 12-myristate 13-acetate (PMA, 1 microM) or exogenous NO donor sodium nitroprusside (SNP, 100 microM), ISO preserved its stimulatory effect on I(NaCa). However, prior incubation of myocytes with pertussis toxin (PTX, 5 microg ml(-1) did prevent the

  19. Perforated patch recording of L-type calcium current with beta-escin in guinea pig ventricular myocytes.

    PubMed

    Fu, Li-Ying; Wang, Fang; Chen, Xue-Song; Zhou, Hong-Yi; Yao, Wei-Xing; Xia, Guo-Jin; Jiang, Ming-Xing

    2003-11-01

    To establish a perforated patch recording (PPR) mode with beta-escin and compare L-type calcium current (I(Ca,L)) recorded under PPR and normal whole-cell recording (WCR) condition in isolated guinea-pig ventricular myocytes. Single myocytes were dissociated by enzymatic dissociation method. beta-escin was added to the pipette solution to perforate the cell membrane and obtain PPR mode. I(Ca,L) was recorded using PPR and WCR techniques. beta-Escin 20, 25, and 30 micromol/L could permeabilize the cell membrane and obtain PPR mode. With beta-escin 25 micromol/L, the success rate was highest (16/17, 94 %) and the time required for permibilization was 2-15 (8+/-4) min. Run-down of I(Ca,L) was considerably slower in PPR than in WCR condition. The amplitude of I(Ca,L) was decreased by 36 % at 20 min after the formation of WCR, while it was slowly decreased by 8 % at 30 min after the formation of PPR. The current-voltage relation (I-V) curves, activation and inactivation curves of I(Ca,L) were not significantly different between WCR and PPR. The inactivation rate of ICa,L was slower in PPR than in WCR, the faster inactivation time constant (tau(f)) was longer in PPR than in WCR at membrane potentials of -20 mV -- +10 mV (n=6, P<0.05), and the slower time constant (tau(s)) was also longer in PPR than in WCR at membrane potentials of -10 mV to +10 mV (n=6, P<0.05). There was no significant difference between the activation rate in WCR and PPR. Using beta-escin 25 micromol/L can easily obtain stable PPR in isolated guinea-pig ventricular myocytes, and this method is useful in dealing with channels, which show run-down under normal WCR such as L-type Ca channel.

  20. The arrhythmogenic transient inward current iTI and related contraction in isolated guinea-pig ventricular myocytes.

    PubMed Central

    Fedida, D; Noble, D; Rankin, A C; Spindler, A J

    1987-01-01

    1. The arrhythmogenic transient inward current, iTI, and contractions were recorded in isolated guinea-pig ventricular myocytes, after exposure to strophanthidin or low external K+ (0.5 mM), using a single-microelectrode voltage-clamp technique and an optical measure of contraction. 2. The inward current, iTI, and after-contraction occurred on repolarization after a depolarizing pre-pulse. Longer pre-pulses to more positive potentials increased the size and reduced the latency of iTI. Oscillatory currents and contractions also occurred during pulses to positive potentials. 3. The voltage dependence of iTI was studied by repolarizing to different potentials after a constant depolarizing pulse. Inward currents preceded after-contractions at all potentials. The iTI was maximal at about -50 mV, diminishing in magnitude at more negative and positive potentials. It remained inward at potentials up to +47 mV. The contraction exhibited a similar voltage dependence. The current-voltage relation varied in the same cell with longer exposure to glycosides. Thus, the voltage dependence of iTI reflected not only that of an underlying ionic mechanism but also the effects of potential on intracellular Ca2+ oscillations which trigger iTI. 4. Uniformity of internal Ca2+ transients was achieved by clamping to different potentials at the peak of an inward current. The iTI remained inward at positive potentials. An inward tail current, seen on repolarizing during iTI at the end of a depolarizing pre-pulse, progressively increased at negative potentials. This voltage dependence may be close to that of the Ca2+-activated inward current responsible for iTI. 5. Replacement of Na+ by Li+ initially increased the magnitude of iTI, but further exposure abolished the inward current, while the after-contractions continued to increase. The potential dependence of iTI was not affected by exposure to zero Na+. Replacement of Ca2+ by Sr2+ also abolished iTI and the after-contraction, but the main

  1. [Guinea pigs and dermatophytosis].

    PubMed

    Khettar, L; Contet-Audonneau, N

    2012-10-01

    The current trend of keeping "exotic" pets has led to the emergence of new types of fungal species that may be transmitted to humans [1]. We describe a form of dermatophytosis transmitted by a Guinea pig and caused by a new variety of dermatophyte. A 13-year-old girl developed multiple erythematosquamous and vesicular lesions with a highly inflammatory edge several weeks after acquiring a Guinea pig of apparently healthy appearance. Direct examination and culture tests demonstrated the presence of a dermatophyte closely related to the erinacei variant of Trichophyton mentagrophytes, from which it differed in terms of microscopic and macroscopic characteristics. The condition resolved on therapy with topical imidazole. This new type of dermatophyte has been identified in many patients coming into close contact with Guinea pigs in the region of Nancy. We would suggest the emergence of a novel variety of T. mentagrophytes, which has adapted to its new host following transmission to Guineas pigs from hedgehogs. We propose that it be named T. mentagrophytes var. porcellae. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  2. Alteration of the L-type calcium current in guinea-pig single ventricular myocytes by heptaminol hydrochloride.

    PubMed Central

    Peineau, N.; Mongo, K. G.; Le Guennec, J. Y.; Garnier, D.; Argibay, J. A.

    1992-01-01

    1. The effects of heptaminol on calcium current amplitude and characteristics were studied in single ventricular myocytes of guinea-pig by use of the whole cell configuration of the patch clamp technique. 2. A concentration-dependent decrease in ICa amplitude was observed. At heptaminol concentration as low as 10(-6) M, this effect was observed in only two cells (n = 6). At 10(-5) M the reduction of ICa was of 30 +/- 15% (n = 11). 3. The current recovery from inactivation at -40 mV holding potential (HP) seemed less sensitive to perfusion with heptaminol (greater than 10(-6) M). However, at -80 mV HP the overshoot of the recovery curve was decreased by heptaminol. 4. Both at -40 mV and -80 mV HP, heptaminol (10(-5) M) significantly increased the steady state inactivation of ICa. 5. As previously proposed by others to explain the effects of membrane active substances, the effects of heptaminol may result from alterations in cell membrane properties and possibly from an increase in intracellular free calcium ion concentration. PMID:1422567

  3. Use-dependent block of Na+ currents by mexiletine at the single channel level in guinea-pig ventricular myocytes.

    PubMed Central

    Sunami, A.; Fan, Z.; Sawanobori, T.; Hiraoka, M.

    1993-01-01

    1. The mechanism of use-dependent block of Na+ current by mexiletine was studied at the single channel level in guinea-pig ventricular myocytes by the patch-clamp techniques. All experiments were performed using stimulation protocols to enable us to analyze the strict dependence of changes in channel properties on channel use. 2. In cell-attached patches, bath or pipette application of mexiletine (40 microM) produced a use-dependent reduction of the peak average current without changes in single channel conductance. Null sweeps were increased and the number of openings per sweep decreased with successive pulses, whereas no significant change in the mean open time was detected during the train. 3. Block by mexiletine became greater when pulse duration was extended beyond the period in which channels were open, suggesting that block progressed without channel opening. 4. At near threshold potentials, mexiletine decreased the later occurrence of first openings. Additionally, late openings were reduced in a use-dependent way. 5. We conclude that mexiletine binds to the inactivated closed states of the Na+ channel and then causes a failure of late openings as well as early, which results in null sweeps on subsequent depolarization. PMID:8220878

  4. Effects of propafenone on electrical and mechanical activities of single ventricular myocytes isolated from guinea-pig hearts.

    PubMed Central

    Honjo, H.; Watanabe, T.; Kamiya, K.; Kodama, I.; Toyama, J.

    1989-01-01

    1. The effects of propafenone on the transmembrane action potential and sarcomere shortening during twitch contraction were investigated in single ventricular myocytes isolated from guinea-pig hearts. 2. Propafenone at low concentrations (3-5 x 10(-7) M) slightly lengthened action potential duration (APD), but shortened it at higher concentrations. The shortening of APD was accompanied by an attenuation of sarcomere shortening during twitch contraction. 3. Propafenone (greater than 10(-6) M) caused a concentration-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential. In the presence of propafenone (3 x 10(-6) M), trains of stimuli led to an exponential decline in Vmax. A time constant for the recovery of Vmax from the use-dependent block was 4.8 s. 4. In myocytes treated with propafenone (3 x 10(-6) M), the Vmax of test action potentials preceded by the conditioning clamp pulses to 0 mV was progressively decreased by increasing the duration of single clamp pulse or by increasing the number of multiple brief clamp pulses. 5. These findings suggest that propafenone has use-dependent inhibitory action on the sodium channel by binding to the channel during both activated and inactivated states, and that the unbinding rate is comparable to that of Class-I antiarrhythmic drugs with intermediate kinetics. Propafenone may also have an inhibitory action on calcium and potassium channels. PMID:2758239

  5. Supersensitivity to tetrodotoxin and lignocaine of sea anemone toxin II-treated sodium channel in guinea-pig ventricular muscle.

    PubMed Central

    Nishio, M.; Ohmura, T.; Kigoshi, S.; Muramatsu, I.

    1991-01-01

    1. Sea anemone toxin II (ATX II, 20-30 nM) doubled the action potential duration in guinea-pig papillary muscles without affecting the maximum rate of rise of the action potential (Vmax) and the resting potential. 2. Tetrodotoxin and lignocaine shortened the prolonged action potential in the ATX II-treated papillary muscles in concentrations (30 nM - 3 microM) at which these drugs did not suppress the Vmax. 3. Whole-cell voltage-clamp experiments with single ventricular cells showed that ATX II produced a slowly decaying inward sodium current following a transient sodium current upon depolarization. 4. The ATX II-induced slowly decaying current was reduced by tetrodotoxin or lignocaine in concentrations (300 nM-1 microM for tetrodotoxin, 3-10 microM for lignocaine) at which these drugs failed to affect the Vmax in cells not treated with ATX II. 5. These results suggest that sodium channel modification by ATX II not only changes its kinetics but also increases the susceptibility of the channel to block by tetrodotoxin and lignocaine. PMID:1686737

  6. [Inhibition of guan-fu base A on delayed rectifier current (Ik) in guinea pig ventricular myocytes].

    PubMed

    Wang, Y P; Chen, W Z; Wang, X L; Hua, Z

    1996-01-01

    Guan-fu base A (GFA) is a terpenoid alkaloid isolated from the tuber of Aconitum coreanum, which has been shown to prolong cardiac repolarization in vivo and in vitro. In the present study, the effects of GFA on the delayed rectifier current (Ik) were investigated using the whole cell patch-clamp technique in isolated guinea pig ventricular myocytes. In the presence of CdCl2 100 mumol.L-1, Ik was observed upon depolarizing pulses to +50 mV from a holding potential -40 mV for variable duration (550, 1100, 1650, 2200, 2750, 3300, 3850 ms). The magnitude of Ik after a 2200 ms pulse was 293 +/- 90 pA prior to drug and 227 +/- 59 pA in the presence of GFA 100 mumol.L-1. In a 3850 ms pulse, the magnitude of Ik decreased from 290 +/- 90 to 231 +/- 66 pA after exposure to GFA. The inhibitory effects of GFA on Ik was not dependent on the duration of depolarization. The inward rectifier current (Ik1) was not affected by GFA 100 mumol.L-1. It is concluded that GFA has inhibitory effects on Ik, which may contribute to its prolongation of cardiac repolarization.

  7. Synergistic action of cyclic GMP on catecholamine-induced chloride current in guinea-pig ventricular cells.

    PubMed Central

    Ono, K; Tareen, F M; Yoshida, A; Noma, A

    1992-01-01

    1. Effects of cyclic GMP on the catecholamine-induced chloride current (ICl) were studied using the whole-cell patch-clamp technique combined with internal perfusion in single ventricular myocytes dispersed from guinea-pig heart. 2. When ICl was activated by submaximal doses of isoprenaline (0.01-0.1 microM), adrenaline (0.5-1 microM) and histamine (0.2-0.5 microM), intracellular dialysis with cyclic GMP (10-100 microM) induced an extra increase of ICl. No further increase of ICl was induced by cyclic GMP when ICl was maximally activated. In the absence of agonists, cyclic GMP failed to induce ICl. 3. The enhancement by cyclic GMP was also observed when ICl was activated by external application of 0.2-1.0 microM-forskolin or by internal dialysis with a pipette solution containing 50-200 microM-cyclic AMP. 4. In contrast to cyclic GMP, 10-1000 microM-dibutyryl cyclic GMP and 8-bromo-cyclic GMP were ineffective in modifying ICl. 5. Milrinone (1-10 microM), a specific inhibitor of a kind of phosphodiesterase which is inhibited by cyclic GMP, also enhanced ICl activated by submaximal doses of isoprenaline. Milrinone itself did not activate ICl. 6. When ICl was enhanced by 5 microM-milrinone, an additional application of cyclic GMP failed to increase ICl. In the presence of cyclic GMP, milrinone failed to enhance ICl. 7. The above findings on ICl are analogous to the enhancement by cyclic GMP of the beta-adrenergic stimulation of the Ca2+ current reported in the same preparation, and support the hypothesis that in mammalian cardiac cells cyclic GMP potentiates elevation of cyclic AMP induced by beta-adrenergic agents, and thereby increases the amplitudes of ionic currents. PMID:1281506

  8. The nonlinear elastic and viscoelastic passive properties of left ventricular papillary muscle of a guinea pig heart.

    PubMed

    Hassan, M A; Hamdi, M; Noma, A

    2012-01-01

    The mechanical behavior of the heart muscle tissues is the central problem in finite element simulation of the heart contraction, excitation propagation and development of an artificial heart. Nonlinear elastic and viscoelastic passive material properties of the left ventricular papillary muscle of a guinea pig heart were determined based on in-vitro precise uniaxial and relaxation tests. The nonlinear elastic behavior was modeled by a hypoelastic model and different hyperelastic strain energy functions such as Ogden and Mooney-Rivlin. Nonlinear least square fitting and constrained optimization were conducted under MATLAB and MSC.MARC in order to obtain the model material parameters. The experimental tensile data was used to get the nonlinear elastic mechanical behavior of the heart muscle. However, stress relaxation data was used to determine the relaxation behavior as well as viscosity of the tissues. Viscohyperelastic behavior was constructed by a multiplicative decomposition of a standard Ogden strain energy function, W, for instantaneous deformation and a relaxation function, R(t), in a Prony series form. The study reveals that hypoelastic and hyperelastic (Ogden) models fit the tissue mechanical behaviors well and can be safely used for heart mechanics simulation. Since the characteristic relaxation time (900 s) of heart muscle tissues is very large compared with the actual time of heart beating cycle (800 ms), the effect of viscosity can be reasonably ignored. The amount and type of experimental data has a strong effect on the Ogden parameters. The in vitro passive mechanical properties are good initial values to start running the biosimulation codes for heart mechanics. However, an optimization algorithm is developed, based on clinical intact heart measurements, to estimate and re-correct the material parameters in order to get the in vivo mechanical properties, needed for very accurate bio-simulation and for the development of new materials for the

  9. Effects of acidosis and NO on nicorandil-activated KATP channels in guinea-pig ventricular myocytes

    PubMed Central

    Moncada, Gustavo A; Kishi, Yukio; Numano, Fujio; Hiraoka, Masayasu; Sawanobori, Tohru

    2000-01-01

    Nicorandil is a hybrid compound of K+ channel opener and nitrate. We investigated a possible interaction of acidosis and nitric oxide (NO)-donors on the nicorandil-activated ATP-sensitive K+ channel (KATP) in guinea-pig ventricular myocytes using the patch-clamp technique.In whole-cell recordings, external application of 300 μM nicorandil activated KATP in the presence of 2 mM intracellular ATP concentration ([ATP]i) at external pH (pHo) 7.4, but the activated current was decreased by reducing pHo to 6.5–6.0.Single-channel recordings of inside-out patches revealed decreased open-state probability (Po) of KATP activated by nicorandil with reducing internal pH (pHi) from 7.2 to 6.0, whilst the channel activity increased at low pHi in the absence of nicorandil.Application of NO donors, 1 mM-sodium nitroprusside (SNP) or -NOR-3 to the membrane cytoplasmic side at pHi 7.2 increased the channel activity but decreased it at pHi 6.5–6.0. Neither removal of the drugs nor application of NO-scavengers reversed depression of channel activity induced by NO-donors.We conclude that an increase in pHo and pHi depresses rather than stimulates the nicorandil-activated KATP. Since NO-donors at low pHi exhibited a similar trend, involvement of H+ and NO interaction can be considered as a mechanism of decreased KATP activated by nicorandil. PMID:11082116

  10. Low sodium inotropy is accompanied by diastolic Ca2+ gain and systolic loss in isolated guinea-pig ventricular myocytes

    PubMed Central

    Même, William; O'Neill, S C; Eisner, D A

    2001-01-01

    We measured sarcolemmal Ca2+ fluxes responsible for the positive inotropic effects of solutions with reduced Na+ concentration in voltage-clamped guinea-pig ventricular myocytes; intracellular Ca2+ concentration ([Ca2+]i) was measured with Indo-1. Reduction of external Na+ concentration by 50 % (to 67 mM) produced an increase in systolic [Ca2+]i accompanied by a decrease in Ca2+ entry via the L-type Ca2+ current. With reduced Na+ concentration, there was an initial decrease in the Na+–Ca2+ exchange current on repolarization followed by an increase to greater than control. We attribute this initial decrease to a decrease in the Na+ gradient and the subsequent increase to a fall in intracellular Na+ concentration and increase in systolic [Ca2+]i. The decreased L-type Ca2+ current and increased Ca2+ efflux on Na+–Ca2+ exchange resulted in a calculated systolic loss of Ca2+. The calculated systolic loss of Ca2+ was accompanied by a measured increase in sarcoplasmic reticulum (SR) Ca2+ content. Reduction of the external Na+ concentration also produced an outward shift of holding current which was blocked by Ni2+. This is taken to represent Ca2+ influx via Na+–Ca2+ exchange. When diastolic influx is taken into account, the observed gain in SR Ca2+ content can be predicted. The measurements show that, in reduced Na+, much of the entry of Ca2+ into the cell occurs during diastole (via Na+–Ca2+ exchange) rather than in systole (via the L-type Ca2+ current). PMID:11158278

  11. Isometric force development, isotonic shortening, and elasticity measurements from Ca(2+)-activated ventricular muscle of the guinea pig

    PubMed Central

    Maughan, DW; Low, ES; Alpert, NR

    1978-01-01

    Isometric tension and isotonic shortening were measured at constant levels of calcium activation of varying magnitude in mechanically disrupted EGTA-treated ventricular bundles from guinea pigs. The results were as follows: (a) The effect of creatine phosphate (CP) on peak tension and rate of shortening saturated at a CP concentration more than 10 mM; below that level tension was increased and shortening velocity decreased. We interpreted this to mean that CP above 10 mM was sufficient to buffer MgATP(2-) intracellularly. (b) The activated bundles exhibited an exponential stress-strain relationship and the series elastic properties did not vary appreciably with degree of activation or creatine phosphate level. (c) At a muscle length 20 percent beyond just taut, peak tension increased with Ca(2+) concentration over the range slightly below 10(-6) to slightly above 10(-4)M. (d) By releasing the muscle length-active tension curves were constructed. Force declined to 20 percent peak tension with a decrease in muscle length (after the recoil) of only 11 percent at 10(-4)M Ca(2+) and 6 percent at 4x10(-6)M Ca(2+). (e) The rate of shortening after a release was greater at lower loads. At identical loads (relative to maximum force at a given Ca(2+) level), velocity at a given time after the release was less at lower Ca(2+) concentrations; at 10 M(-5), velocity was 72 percent of that at 10(-4)M, and at 4x10(-6)M, active shortening was usually delayed and was 40 percent of the velocity at 10(-4) M. Thus, under the conditions of these experiments, both velocity and peak tension depend on the level of Ca(2+) activation over a similar range of Ca(2+) concentration. PMID:149182

  12. Modulation by stimulation rate of basal and cAMP-elevated Ca2+ channel current in guinea pig ventricular cardiomyocytes

    PubMed Central

    1995-01-01

    The modulation of L-type Ca2+ current (ICa) by changes in stimulation frequency was investigated in single ventricular cardiomyocytes isolated from guinea pig hearts. Electrical recordings were carried out at 21-25 degrees C and at 33-37 degrees C with the whole-cell patch clamp method, under K(+)-free conditions. A comparison is made between the response to frequency changes for ICa in the basal state and after the application of drugs which elevate the level of adenosine-3',5'- cyclic monophosphate (cAMP) within the cells. Peak basal ICa was reduced with an increase in stimulation rate from 0.5 Hz to 1, 2, 3, 4, or 5 Hz. This frequency-induced reduction of ICa was enhanced by reduced temperature, was unchanged when Na+ or Ba2+ carried the basal Ca2+ channel current, and was greatly enhanced after elevating cAMP levels with forskolin, isoprenaline, or 8-(4-chlorophenylthio)-cyclic AMP. We examined the mechanism of the enhancement of the frequency- induced reduction of ICa by cAMP, and found two conditions which abolished it: (a) application of isoprenaline when Na+ carried the Ca2+ channel current in Ca(2+)-free solution, or (b) application of 3- isobutyl-1-methylxanthine, a broad-spectrum phosphodiesterase inhibitor. It was further shown that an elevation of both ICa and cAMP (induced by isoprenaline), and not an increase of ICa alone (induced by Bay K 8644), is required to produce the extra component of reduction by frequency. It is concluded that Ca2+ entry results in feedback regulation of ICa, through the activation of Ca(2+)-dependent phosphodiesterase(s). This is important in the context of sympathetic stimulation, which produces the companion conditions of an elevated heart rate and increases in cAMP levels and Ca2+ entry. PMID:8537815

  13. The effects of sodium substitution on currents determining the resting potential in guinea-pig ventricular cells.

    PubMed

    Spindler, A J; Noble, S J; Noble, D; LeGuennec, J Y

    1998-03-01

    It has recently been shown that a sodium background current, ib,Na, exists in cardiac muscle cells whose effect is to depolarize the membrane so that the resting potential, Vm, is positive to the potassium equilibrium potential, EK. In ventricular cells, where ib,Na is smallest, Vm is about 10 mV positive to EK (EK = -87 mV at 37 degrees C). Yet, replacement of Na+ ions by large impermeant cations does not cause the expected hyperpolarization. We have studied this problem in guinea-pig myocytes using a single microelectrode recording technique in combination with a rapid external solution switch. Cells depolarized < or = 0.5 mV from potentials between -80 and -73 mV and hyperpolarized up to 5 mV from potentials between -73 and -64 mV when 70 mM choline chloride or N-methyl-D-glucamine chloride were used to replace 70 mM Na+ in the bathing solution. Replacement by 70 mM lithium chloride, however, only caused hyperpolarization in very depolarized cells when the voltage change was much smaller. The changes were complete almost as soon as the solution change, i.e. within 250 ms, indicating that the actions are attributable to the external solution change rather than to secondary changes in intracellular concentrations. Patch clamp recording was used to investigate the mechanism involved. These experiments showed that the presence or absence of the inward rectifier current iK1 determines in which direction Na+ removal acts. In the absence of iK1 the changes are attributable to removal of ib,Na, whereas in the presence of iK1 the changes resemble the i(V) relation for iK1, implying that Na+ regulates iK1 in a way that can mask the changes in ib,Na. These results explain why removal of Na+ does not lead to hyperpolarization in ventricular cells as would be expected if changes in ib,Na were solely responsible. Computer reconstruction shows that the effects may be attributed to actions of sodium removal on the conductance and gating of iK1.

  14. Amrinone effects on electromechanical coupling and depolarization-induced automaticity in ventricular muscle of guinea pigs and ferrets.

    PubMed

    Malécot, C O; Arlock, P; Katzung, B G

    1985-01-01

    The effects of the cardiotonic agent, amrinone (0.05-4 mM), on electrical and mechanical activities of ferret and guinea-pig papillary muscles were studied using current and voltage clamp (single sucrose gap) techniques. In current clamp studies, amrinone increased, in a dose-dependent manner, contractile force elicited by action potential in both species. Depolarization-induced automaticity was facilitated in ferret muscles at all maximum diastolic potentials between -70 and -15 mV. Facilitation of automaticity in guinea-pig muscles occurred only at potentials more negative than -35 mV and was suppressed at more positive potentials. Cimetidine (10 microM) partially reversed the effects of amrinone on automaticity in both species. In voltage clamp studies, amrinone increased the slow inward current. Steady-state outward current was increased in guinea-pig but not in ferret muscles. A dual effect of amrinone on tension was observed. Amrinone was found to increase phasic tension of ferret papillary muscles only for depolarizations lasting less than 250 to 300 msec. For longer depolarizations, amrinone decreased the phasic tension (in a dose-dependent manner), whereas the tonic tension was not modified. The decrease as well as the increase in tension was associated with an increase of the slow inward current. The results suggest that amrinone may be arrhythmogenic and may have an intracellular action at the sarcoplasmic reticulum level (partial inhibition) in addition to its action on the calcium current.

  15. Effects of droperidol on depolarization-induced automaticity, maximum upstroke velocity (Vmax) and the kinetics of recovery of Vmax in guinea-pig ventricular myocardium.

    PubMed

    Grant, A O; Hondeghem, L M; Katzung, B G

    1978-04-01

    The neuroleptic drug droperidol has been shown to have clinically useful antiarrhythmic activity. Prior reports have resulted in conflicting conclusions regarding actions on ventricular myocardial fibers. The present study was carried out to determine whether droperidol did in fact affect the electrophysiological properties of guinea-pig papillary muscle fibers. By means of microelectrode recordings from preparations mounted in a single sucrose gap, the effects of concentrations from 10(-6) to 4 X 10(-5) M were studied on depolarization-induced automaticity, and on Vmax and its recovery time under several conditions of membrane potential, stimulation rate and external ion concentration. The results showed that at clinically relevant concentrations, droperidol significantly slows ventricular pacemaker activity, a depression reversible by epinephrine. Furthermore, Vmax was decreased and the time constant for Vmax recovery was significantly prolonged under several conditions which pertain to clinical arrhythmias, i.e., reduced membrane potential, elevated extracellular potassium concentrations and increased stimulation rate.

  16. A xanthine derivative denbufylline inhibits negative inotropic response to verapamil in guinea pig ventricular papillary muscles, independent of its phosphodiesterase inhibitory activity.

    PubMed

    Sanae, F; Ohmae, S; Takagi, K; Miyamoto, K

    1995-11-01

    A phosphodiesterase (PDE) III inhibitor, amrinone, inhibited both the negative inotropic actions of verapamil and nicardipine in guinea pig ventricular papillary muscle; this effect was canceled by the protein kinase A inhibitor H-89. The PDE IV inhibitor 1,3-di-n-butyl-7-(2'-oxopropyl)xanthine (denbufylline), which elicited a negative inotropic action by itself, attenuated the action of verapamil up to 10 microM, without any interaction with nicardipine. The attenuation by denbufylline was not influenced by H-89. This suggests that in the ventricular papillary muscle, denbufylline acts on some verapamil-sensitive site(s) in the membrane and interferes with the calcium channel function without involvement of its PDE inhibitory activity.

  17. Voltage-dependent magnesium block of adenosine-triphosphate-sensitive potassium channel in guinea-pig ventricular cells.

    PubMed Central

    Horie, M; Irisawa, H; Noma, A

    1987-01-01

    1. The adenosine-5'-triphosphate (ATP)-sensitive K+ channel of guinea-pig ventricular cells was examined in the presence and absence of internal Mg2+ or Na+ using an open cell-attached configuration of the patch-clamp technique. 2. Millimolar concentrations of internal Mg2+ ([Mg2+]i) produced marked fluctuations in the outward current, and the amplitude of the open-channel current was reduced with increasing [Mg2+]i. Millimolar Na+ applied internally also decreased the mean amplitude of the outward current, but the increase in current noise was not obvious. These effects became larger when the membrane potential was shifted to be more positive from the K+ equilibrium potential (EK). At potentials negative to EK the inward current was affected by neither internal Mg2+ nor Na+. 3. The external application of Na+, Mg2+ or Ca2+, however, failed to affect the single-channel current. 4. After removal of both internal Mg2+ and Na+, the mean open-channel current-voltage relationship became virtually linear. Referring to these unblocked values, relative amplitudes were determined at different levels of [Mg2+]i or [Na+]i. The dose-response relations gave a Hill coefficient of approximately 1 for Mg2+ block and approximately 2 for Na+ block. The half-maximum concentrations (Kh) for both Mg2+ and Na+ block were shifted to lower values with increasing positive potentials. 5. The power-density spectrum of the open-channel current noise induced by internal Mg2+ showed a Lorentzian function with a corner frequency above 1 kHz, suggesting that the current noise is due to rapid fluctuations of open-channel current between blocked and unblocked states. The corner frequencies gave Mg2+ block and unblock rate constants which were of the order of 10(7) M-1 s-1 and 10(4) s-1, respectively. 6. With increasing external K+ concentration ([K+]o) from 0 to 140 mM the current fluctuations became less prominent, and Kh for Mg2+ block was shifted to higher values. Raising [K+]o enhanced the

  18. Characterization of (/sup 3/H)leukotriene D4 binding sites in guinea-pig ventricular myocardium

    SciTech Connect

    Hogaboom, G.K.; Mong, S.; Stadel, J.M.; Crooke, S.T.

    1985-06-01

    (/sup 3/H)Leukotriene (LT) D4 was used to identify specific LTD4 binding sites in guinea-pig ventricular myocardial membranes. High-performance liquid chromatography analyses indicated that, in the presence of the gamma-glutamyl transpeptidase inhibitor L-serine-borate (80 mM), less than 3% of membrane-bound (/sup 3/H)LTD4 was converted to (/sup 3/H)LTC4 or (/sup 3/H)LTE4 at 30 degrees C. The specific (/sup 3/H) LTD4 binding, assayed in the presence of 80 mM L-serine-borate, reached a stable steady state within 45 min at 30 degrees C (pH 7.5). A monophasic Scatchard plot of saturation binding data yielded an apparent dissociation constant (Kd) of 3.4 +/- 2.1 nM and a maximum number of binding sites of 850 +/- 91 fmol/mg of protein. Competition binding studies with (/sup 3/H)LTD4, synthetic 5S, 6R-LTD4 (LTD4) and its diastereoisomer 5R,6S-LTD4, LTE4, LTC4 and the putative LT antagonists FPL 55712, 4R-hydroxy-5S-1-cysteinylglycine-6Z-nonadecanoic acid (2-nor-LTD1) and SKF 88046 demonstrated a potency order of LTD4 greater than LTE4 greater than LTC4 greater than 5R,6S-LTD4 much greater than 2-nor-LTD1. FPL 55712 and SKF 88046 were ineffective in displacing the specific (/sup 3/H)LTD4 binding. Pretreatment of the heart membranes with the sulfhydryl reducing reagent dithiothreitol decreased the specific (/sup 3/H)LTD4 binding in a concentration-dependent manner. Scatchard analyses of saturation isotherms indicated that 0.3 mM dithiothreitol pretreatment of heart membranes decreased the maximum number of binding sites of the (/sup 3/H)LTD4 binding to 368 +/- 61 fmol/mg of protein with minimal effects on the apparent Kd.

  19. Calcium-activated non-selective cation channel in ventricular cells isolated from adult guinea-pig hearts.

    PubMed Central

    Ehara, T; Noma, A; Ono, K

    1988-01-01

    1. A class of Ca2+-activated non-selective cation channel was identified in ventricular cells, which were dissociated from adult guinea-pig hearts using collagenase. 2. Under cell-attached conditions the patch electrode filled with a Na+-rich solution recorded no obvious single-channel current at the resting membrane potential. Subsequent superfusion of the ventricular cell with a Na+-free Tyrode solution induced an inward-going single-channel current as well as contracture of the cell. Kinetics of this channel were not affected by varying the membrane potential. 3. Single-channel currents showing a conductance similar to those observed in the cell-attached patches were recorded in isolated inside-out membrane patches when the inner side of the membrane was exposed to a free Ca2+ concentration ([Ca2+]i) higher than 0.3 microM. The slope conductance of the channel was 14.8 +/- 2.9 pS (mean +/- S.D., n = 17) at 20-25 degrees C. 4. The reversal potential examined in the inside-out patch was about 0 mV irrespective of the Na+-rich, K+-rich, Li+-rich or Cs+-rich solutions on either side of the membrane, thereby indicating that the channel was almost equally permeable to these cations. 5. The open probability of the channel was increased by raising [Ca2+]i with the maximum value of 0.93 +/- 0.17 (n = 4) at about 10 microM [Ca2+]i. The dose-response relation was fitted to the saturation kinetics with a Hill coefficient of 3.0 and a half-maximum concentration of 1.2 microM [Ca2+]i. 6. The gating kinetics were complex; both the open and closed time histograms showed at least two exponential components with time constants of 3.8 +/- 1.3 ms and 140 +/- 110 ms for open time and 1.8 +/- 1.1 ms and 14.9 +/- 5.3 ms for closed time (n = 4) at 10 microM [Ca2+]i. Reduction of [Ca2+]i resulted in both a decrease of the time constant of the slow component in the open time histogram and an increase of the two time constants of the closed time histogram. 7. Contribution of the channel

  20. [Na] and [K] dependence of the Na/K pump current-voltage relationship in guinea pig ventricular myocytes

    PubMed Central

    1989-01-01

    Na/K pump current was determined between -140 and +60 mV as steady- state, strophanthidin-sensitive, whole-cell current in guinea pig ventricular myocytes, voltage-clamped and internally dialyzed via wide- tipped pipettes. Solutions were designed to minimize all other components of membrane current. A device for exchanging the solution inside the pipette permitted investigation of Na/K pump current-voltage (I-V) relationships at several levels of pipette [Na] [( Na]pip) in a single cell; the effects of changes in external [Na] [( Na]o) or external [K] [( K]o) were also studied. At 50 mM [Na]pip, 5.4 mM [K]o, and approximately 150 mM [Na]o, Na/K pump current was steeply voltage dependent at negative potentials but was approximately constant at positive potentials. Under those conditions, reduction of [Na]o enhanced pump current at negative potentials but had little effect at positive potentials: at zero [Na]o, pump current was only weakly voltage dependent. At 5.4 mM [K]o and approximately 150 mM [Na]o, reduction of [Na]pip from 50 mM scaled down the sigmoid pump I-V relationship and shifted it slightly to the right (toward more positive potentials). Pump current at 0 mV was activated by [Na]pip according to the Hill equation with best-fit K0.5 approximately equal to 11 mM and Hill coefficient nH approximately equal to 1.4. At zero [Na]o, reduction of [Na]pip seemed to simply scale down the relatively flat pump I-V relationship: Hill fit parameters for pump activation by [Na]pip at 0 mV were K0.5 approximately equal to 10 mM, nH approximately equal to 1.4. At 50 mM [Na]pip and high [Na]o, reduction of [K]o from 5.4 mM scaled down the sigmoid I-V relationship and shifted it slightly to the right: at 0 mV, K0.5 approximately equal to 1.5 mM and nH approximately equal to 1.0. At zero [Na]o, lowering [K]o simply scaled down the flat pump I-V relationships yielding, at 0 mV, K0.5 approximately equal to 0.2 mM, nH approximately equal to 1.1. The voltage

  1. Modulation of beta-adrenergic responses of chloride and calcium currents by external cations in guinea-pig ventricular cells.

    PubMed Central

    Tareen, F M; Yoshida, A; Ono, K

    1992-01-01

    1. The catecholamine-induced Cl- current and the Ca2+ current were recorded in the single ventricular cells of guinea-pig hearts, using the whole-cell patch clamp technique combined with internal perfusion. Dependence of the beta-adrenergic responses on external monovalent cations was investigated. The Cl- current was recognized by measuring the reversal potential of the agonist-induced current. 2. The amplitude of the Cl- current, activated by 1 microM adrenaline or 0.01-0.1 microM isoprenaline, was decreased when the external Na+ concentration ([Na+]o) was reduced by replacement with Tris+. The conductance of the catecholamine-induced Cl- current was proportional to the logarithm of the [Na+]o over a range of 15-140 mM. When the conductance was plotted against the concentration of Tris+, a dose-dependent inhibition of the Cl- response by Tris+ was suggested with a half-maximum concentration of 95 mM. 3. The inhibitory effect of the Na+ substitute TEA+ on the Cl- current was not affected by either increasing the buffer for the internal Ca2+ (10 mM BAPTA) or for the pH (50 mM HEPES). 4. In the relationship between agonist concentration and the Cl- conductance, the half-maximum concentration (K1/2) of isoprenaline was 0.013 microM in the control Na+ solution, and was shifted to 0.07, 0.08, 0.1 and 0.3 microM in the Li+, Cs+, TEA+ and Tris+ external solutions, respectively. The maximum slope conductance was not significantly affected, except for a slight depression on the Tris+ solution. When the current was induced by adrenaline, qualitatively the same finding was obtained; K1/2 was 0.15 and 3.2 microM in the Na+ and Tris+ solutions, respectively. 5. As a substitute for the external Na+, sucrose seemed to be inert. The activation of the inward Cl- current was conserved in the 300 mM sucrose solution ([Cl-]o = 8 mM) with a K1/2 value of 0.015 microM isoprenaline. 6. The Cl- current, when activated by either an external application of forskolin (0.2-10 microM) or an

  2. beta-adrenergic and cholinergic modulation of the inwardly rectifying K+ current in guinea-pig ventricular myocytes.

    PubMed Central

    Koumi, S; Wasserstrom, J A; Ten Eick, R E

    1995-01-01

    1. Whole-cell patch-clamp technique was used to study the beta-adrenergic and cholinergic regulation of the inwardly rectifying K+ conductance (gK1) in isolated guinea-pig ventricular myocytes. 2. In Cl(-)-free solutions or in the presence of 9-anthracenecarboxylic acid or Co2+, bath-applied isoprenaline (Iso) partially inhibited the steady-state whole-cell conductance (gss) calculated from the steady-state current (Iss)-voltage (Iss-V) curve at membrane voltages (Vm) negative to the equilibrium potential for potassium (EK). Iss was also inhibited at Vm positive to EK when the extracellular [K+] was 20 mM. The Iso-sensitive component of gss exhibited the characteristics of the inwardly rectifying K+ conductance (gK1). 3. The Iso-induced inhibition of gK1 was reversible, concentration dependent, blocked by propranolol, mimicked by both forskolin and dibutyryl cAMP, and prevented by including a cAMP-dependent protein kinase (PKA) inhibitor in the pipette solution. These findings suggest that PKA mediates the Iso-induced inhibition of gK1. 4. The apparent dissociation constant (KD) for the concentration dependence of Iso-induced inhibition was 0.035 microM and the Hill coefficient was approximately 1.0. A maximal Iso concentration (1 microM) inhibited gK1 by 40 +/- 4.1% (mean +/- S.E.M.; n = 13). 5. Bath application of acetylcholine (ACh, 0.1 microM or more) antagonized the Iso-induced (1 microM) inhibition of gK1; [ACh] > 1.0 microM antagonized 88 +/- 2.1% (n = 10) of the inhibition. ACh increased the KD for Iso to inhibit Iso-sensitive gK1 and also reduced the maximal Iso-induced inhibition. 6. ACh-induced antagonism could be abolished by pre-incubating myocytes with pertussis toxin (PTX), suggesting that a muscarinic receptor-coupled, PTX-sensitive G protein, Gi, is involved. 7. ACh (10 microM) also antagonized approximately 70% of the dibutyryl cyclic AMP (1 mM)-induced inhibition of gK1 (n = 3), suggesting that the ACh-induced antagonism involves more than simply

  3. Low oxygen tension induces positive inotropy and decreases a(i)Na in isolated guinea-pig cardiac ventricular papillary muscles.

    PubMed

    Jao, M J; Yang, J M

    1998-06-30

    Effects of low oxygen on contractile force, intracellular Na+ activity (aiNa), and action potential were simultaneously measured in isolated guinea-pig ventricular papillary muscles. Reduction of oxygen from control 488 to 150 mmHg biphasically increased and decreased the twitch tension, and decreased aiNa in muscles driven at 60 beats/min. The action potential duration (APD) was decreased but the maximum rate of upstroke (Vmax) was increased. In control, 1 microM epinephrine significantly increased the the action potential amplitude and twitch tension with decreases in the time to twitch peak (TTP), time for 50% relaxation (RT50), and aiNa. After exposure to low oxygen for 10 min, with twitch tension elevated and TTP and RT90 increased, 1 microM epinephrine significantly increased the twitch tension and Vmax, and decreased the APD and aiNa. Pretreatment with reserpine inhibited the twitch tension, both at control and in the presence of epinephrine. But changes of action potential and aiNa in response to low oxygen and epinephrine were similar to those in control. Our results indicate that the isolated guinea-pig ventricular muscle needs a high oxygen tension to maintain a normal contractile function. Reduction of oxygen deteriorates the electrical and mechanical activities, most likely, by a coaxial graded hypoxia. The decreased aiNa, not associated with endogenous catecholamines, suggests that the activity of the Na(+)-K+ pump can be maintained in the superficial muscle cells despite of core-central hypoxia.

  4. Insulinoma in 2 guinea pigs (Cavia porcellus)

    PubMed Central

    2005-01-01

    Abstract This paper describes an insulinoma in 2 guinea pigs (Cavia porcellus). Both guinea pigs presented with neurologic signs and low blood glucose readings. The neurologic signs resolved with dextrose administration. Insulinoma was confirmed on postmortem examination. PMID:15943120

  5. Guinea-pig reaginic antibody

    PubMed Central

    Margni, R. A.; Hajos, Silvia E.

    1973-01-01

    The physicochemical and biological properties of purified guinea-pig reaginic antibody were studied. It is a labile protein different to γ1. Its antibody activity is completely destroyed by heating at 56° for 6 hours and by treatment with mercaptoethanol. The capacity to give PCA is decreased by repeated freezing and thawing. It is a bivalent antibody, haemagglutinating, does not fix complement and is capable of sensitizing guinea-pig skin for PCA reaction after a latent period of a week but not after 3 hours. Reaginic antibody appears on day 7–8 after the first inoculation and the higher levels (PCA reaction) are obtained at the eleventh to thirteenth days. After the fifteenth to seventeenth days the PCA is negative. The reaginic antibody does not pass the placenta. Higher levels of reaginic antibody were obtained when the guinea-pigs were inoculated with the antigen in saline with simultaneous inoculation, intraperitoneally, of killed Bordetella pertussis, phase I. PMID:4354828

  6. Guinea-pig reaginic antibody

    PubMed Central

    Margni, R. A.; Hajos, Silvia E.

    1973-01-01

    The methods for isolation and purification of a guinea-pig serum protein with homocytotropic antibody activity and characteristics of IgE are described. By precipitation in the equivalence zone or immunoadsorption and chromatography on DEAE-cellulose, we isolated an homocytotropic antibody, that was not able to give a precipitin line when it was reacted directly with the antigen. It was capable of sensitizing guinea-pig skin for PCA after a latent period of 24–48 hours but not after 3 hours; it was sensitive to treatment with mercaptoethanol. It had antigenic determinants present in the other guinea-pig immunoglobulins and particular antigenic determinants. All these properties make us believe that this protein belongs to an immunoglobulin different from γ1 and similar to the reaginic antibody (IgE) described in other species. ImagesFIG. 3FIG. 4FIG. 5 PMID:4126261

  7. Effects of 2,4-dinitrophenol or low [ATP]i on cell excitability and action potential propagation in guinea pig ventricular myocytes.

    PubMed

    Morley, G E; Anumonwo, J M; Delmar, M

    1992-10-01

    Inhibition of aerobic metabolism leads to a major disruption of cardiac cell homeostasis. The purpose of the present study was twofold: 1) We determined the relative importance of junctional and nonjunctional membrane resistance (Rj and Rm, respectively) in the development of propagation failure during inhibition of aerobic metabolism in guinea pig ventricular cell pairs. 2) We used the patch-action potential clamp technique in single ventricular myocytes to study some of the properties of the membrane channels that are responsible for shortening of action potential duration and eventual failure of cell excitation after metabolic blockade. In most experiments, whole-cell patch pipettes were filled with a solution containing 1 mM EGTA, 5 mM HEPES, and 5 mM ATP. Our results in cell pairs showed that pharmacological inhibition of aerobic metabolism with the mitochondrial uncoupler 2,4-dinitrophenol (DNP) led to a drop in Rm followed by an increase in Rj. The increase in Rj was not sufficient to cause a measurable delay in cell-to-cell propagation, whereas the drop in Rm consistently led to failure of cell excitation. Similar results were obtained in additional experiments in which the EGTA concentration in the pipette was reduced to 50 microM. Similar results were also obtained by loading the recording patch pipettes with a solution containing only 0.1 mM ATP. Our patch-action potential clamp experiments, on the other hand, revealed that DNP induced the opening of time- and voltage-independent membrane channels, with a unitary conductance of 23 pS. The channels allowed for the passage of outward current in the voltage range of the action potential, and the increase in membrane patch conductance correlated with the observed shortening of action potential duration during DNP superfusion. Our experiments provide the first simultaneous recordings of action potentials and DNP-induced channel currents in guinea pig ventricular myocytes. Overall, the data provide new

  8. Electrophysiological effects of OPC-88117, a new antiarrhythmic agent on papillary muscles and single ventricular myocytes isolated from guinea-pig hearts.

    PubMed Central

    Toyama, J.; Kodama, I.; Honjo, H.; Kamiya, K.

    1989-01-01

    1. The effects of OPC-88117, a new antiarrhythmic agent, on transmembrane action potentials were examined in right ventricular papillary muscles and in single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, OPC-88117 above 3 x 10(-6) M caused a dose-dependent prolongation of action potential duration (APD). 3. OPC-88117 above 3 x 10(-5) M caused a significant decrease in the maximum upstroke velocity (Vmax) of the action potential without affecting the resting membrane potential. The inhibition of Vmax was enhanced at higher stimulation frequencies. 4. In the presence of OPC-88117, trains of stimuli at rates greater than or equal to 1.0 Hz led to a use-dependent inhibition of Vmax with rapid onset. The time constant for the recovery of Vmax from the use-dependent block was 456 ms. 5. The curves relating membrane potential and Vmax were shifted by OPC-88117 to the direction of more negative potentials (9 mV at 10(-4) M). 6. In single ventricular myocytes treated with OPC-88117 (1-3 x 10(-4) M), the Vmax of test action potentials preceded by conditioning clamp pulses to 0 mV was decreased progressively as the clamp pulse duration was prolonged. 7. These findings suggest that the primary electrophysiological effect of OPC-88117 on the cardiac muscle cell is prolongation of APD (Class III action) and that at high concentrations, it may also possess a lignocaine-like sodium channel inhibitory effect (Class I action). PMID:2553186

  9. Genistein directly induces cardiac CFTR chloride current by a tyrosine kinase-independent and protein kinase A-independent pathway in guinea pig ventricular myocytes.

    PubMed

    Chiang, C E; Chen, S A; Chang, M S; Lin, C I; Luk, H N

    1997-06-09

    With one-suction electrode voltage-clamp technique, we demonstrated that genistein, a tyrosine kinase (TK) inhibitor, could directly activate cystic fibrosis transmembrane regulator (CFTR) chloride current in guinea pig ventricular myocytes. The activation showed concentration-dependent effect with the estimated IC50 of 39.7 microM. Tyrphostin 51, another TK inhibitor, had no effect, suggesting that genistein's effect might be unrelated to TK inhibition. After the chloride current had been activated by the maximally elevated intracellular cAMP content by saturating concentration of isoproterenol, forskolin and IBMX, genistein could further enhance the current. Pre-treatment with saturating concentration of a specific protein kinase A (PKA) inhibitor, H-89, or other protein kinase inhibitors H-8 and H-9 in the perfusate or intracellularly could not prevent the activation of the current by genistein, suggesting a PKA-independent activity. Furthermore, saturating concentration of calyculin A, a specific inhibitor of phosphotase 1 and 2A, in the perfusate or intracellularly could not block genistein's action. It is possible that genistein opens the channels directly or inhibits the dephosphorylation process of CFTR, which is not sensitive calyculin A.

  10. 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)

  11. 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)

  12. Temperature dependence of Na+-H+ exchange, Na+-HCO3- co-transport, intracellular buffering and intracellular pH in guinea-pig ventricular myocytes.

    PubMed

    Ch'en, Frederick F-T; Dilworth, Emma; Swietach, Pawel; Goddard, Ruth S; Vaughan-Jones, Richard D

    2003-11-01

    Almost all aspects of cardiac function are sensitive to modest changes of temperature. We have examined the thermal sensitivity of intracellular pH regulation in the heart. To do this we determined the temperature sensitivity of pHi, intracellular buffering capacity, and the activity of sarcolemmal acid-extrusion proteins, Na+-H+ exchange (NHE) and Na+-HCO3- co-transport (NBC) in guinea-pig isolated ventricular myocytes. pHi was recorded fluorimetrically with acetoxymethyl (AM)-loaded carboxy-SNARF-1 at either 27 or 37 degrees C. At 27 degrees C, intrinsic (non-CO2-dependent) buffering power (betai) was approximately 60% of that at 37 degrees C. Acid-extrusion (Je) through NHE was approximately 50% slower than at 37 degrees C, consistent with a Q10 of approximately 2. In 5% CO2/HCO3--buffered conditions, in the presence of 30 microM cariporide to inhibit NHE, acid extrusion via NBC was also slowed at 27 degrees C, suggestive of a comparable Q10. Resting pHi at 27 degrees C was similar in Hepes- or 5% CO2/HCO3--buffered superfusates but, in both cases, was approximately 0.1 pH units lower at 37 degrees C. The higher the starting pHi, the larger was the thermally induced fall of pHi, consistent with a mathematical model where intrinsic buffers with a low principal pKa (e.g. close to 6.0) are less temperature-sensitive than those with a higher pKa. The high temperature sensitivity of pHi regulation in mammalian cardiac cells has implications for experimental work conducted at room temperature. It also has implications for the ability of intracellular acidosis to generate intracellular Na+ and Ca2+ overload, cardiac injury and arrhythmia in the heart.

  13. Inhibitory effect of YM-244769, a novel Na(+)/Ca(2+) exchanger inhibitor on Na(+)/Ca(2+) exchange current in guinea pig cardiac ventricular myocytes.

    PubMed

    Yamashita, Kanna; Watanabe, Yasuhide; Kita, Satomi; Iwamoto, Takahiro; Kimura, Junko

    2016-11-01

    Recently, YM-244769 (N-(3-aminobenzyl)-6-{4-[(3-fluorobenzyl)oxy]phenoxy} nicotinamide) has been reported as a new potent and selective Na(+)/Ca(2+) exchange (NCX) inhibitor by using various cells transfected with NCX using the (45)Ca(2+) fluorescent technique. However, the electrophysiological study of YM-244769 on NCX had not been performed in the mammalian heart. We examined the effects of YM-244769 on NCX current (INCX) in single cardiac ventricular myocytes of guinea pigs by using the whole-cell voltage clamp technique. YM-244769 suppressed the bidirectional INCX in a concentration-dependent manner. The IC50 values of YM-244769 for the bidirectional outward and inward INCX were both about 0.1 μM. YM-244769 suppressed the unidirectional outward INCX (Ca(2+) entry mode) with an IC50 value of 0.05 μM. The effect on the unidirectional inward INCX (Ca(2+) exit mode) was less potent, with 10 μM of YM-244769 resulting in the inhibition of only about 50 %. At 5 mM intracellular Na(+) concentration, YM-244769 suppressed INCX more potently than it did at 0 mM [Na(+)]i. Intracellular application of trypsin via the pipette solution did not change the blocking effect of YM-244769. In conclusion, YM-244769 inhibits the Ca(2+) entry mode of NCX more potently than the Ca(2+) exit mode, and inhibition by YM-244769 is [Na(+)]i-dependent and trypsin-insensitive. These characteristics are similar to those of other benzyloxyphenyl derivative NCX inhibitors such as KB-R7943, SEA0400, and SN-6. The potency of YM-244769 as an NCX1 inhibitor is higher than those of KB-R7943 and SN-6 and is similar to that of SEA0400.

  14. Bepridil differentially inhibits two delayed rectifier K(+) currents, I(Kr) and I(Ks), in guinea-pig ventricular myocytes.

    PubMed

    Wang, J C; Kiyosue, T; Kiriyama, K; Arita, M

    1999-12-01

    1. We investigated the effects of bepridil on the two components of the delayed rectifier K(+) current, i.e., the rapidly activating (I(Kr)) and the slowly activating (I(Ks)) currents using tight-seal whole-cell patch-clamp techniques in guinea-pig ventricular myocytes, under blockade of L-type Ca(2+) current with nitrendipine (5 microM) or D600 (1 microM). 2. Bepridil decreased I(Ks) under blockade of I(Kr) with E4031 (5 microM), in a concentration-dependent manner. The concentration-dependent inhibition of I(Ks) 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 (IC(50)) was found to be 6.2 microM. 3. The effect of bepridil on I(Kr) 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 approximately 0.4 with increases in the pulse duration. Bepridil at a concentration of 2 microM did not decrease this ratio at shorter pulses. 4. In a short-pulse (duration=50 ms) experiment that largely activates I(Kr), the drug was found to block I(Kr) in a cooperative manner (Hill coefficient=3.03) and the IC(50) was 13.2 microM. 5. These results suggest that bepridil at a clinical therapeutic concentration ( approximately 2 microM) selectively blocks I(Ks) but does not inhibit I(Kr). 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.

  15. Regulation of the beta-stimulation of the Na(+)-K+ pump current in guinea-pig ventricular myocytes by a cAMP-dependent PKA pathway.

    PubMed Central

    Gao, J; Cohen, I S; Mathias, R T; Baldo, G J

    1994-01-01

    1. The whole-cell patch-clamp technique was employed with the free intracellular [Ca2+] fixed at 1.4 microM in order to study the isoprenaline (Iso)-induced increase in the Na(+)-K+ pump current (Ip) in acutely isolated guinea-pig ventricular myocytes. 2. The non-specific protein kinase inhibitor, H-7, eliminated the stimulatory effect of Iso, suggesting a phosphorylation step is involved in the beta-agonist stimulation of Ip. 3. H-7 or the phosphatase inhibitor calyculin A individually had no effect on basal Ip; however, when Ip was first increased by Iso, H-7 inhibited and calyculin A further increased Ip. This suggests phosphorylation is not important to the basal regulation of Ip, but does have an effect during beta-stimulation. 4. The Iso-induced increase in Ip could be mimicked by adding the membrane-permanent cAMP analogue chlorophenylthio-cAMP, blocking cAMP degradation with IBMX or stimulating cAMP production with forskolin. Alternatively the protein kinase A inhibitor PKI blocked the stimulatory effect of Iso. This suggests the Iso-induced phosphorylation responsible for increasing Ip is mediated by cAMP, which then activates protein kinase A (PKA). 5. We conclude that the beta-agonist-induced increase in Ip in the presence of high intracellular [Ca2+] is mediated by a phosphorylation step via the cAMP-dependent PKA pathway. During beta-stimulation, this increase in active Na(+)-K+ transport can serve to offset the effects of increases in passive membrane conductances. PMID:7932227

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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

  2. 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.

  3. Regulation by endothelin-1 of Na+-Ca2+ exchange current (I(NaCa)) from guinea-pig isolated ventricular myocytes.

    PubMed

    Zhang, Y H; James, A F; Hancox, J C

    2001-11-01

    The cardiac Na+-Ca2+ exchanger participates in Ca homeostasis, and Na+-Ca2+ exchanger-mediated ionic current (I(NaCa)) also contributes to the regulation of cardiac action potential duration. Moreover, I(NaCa) can contribute to arrhythmogenesis under conditions of cellular Ca overload. Although it has been shown that the peptide hormone endothelin-1 (ET-1) can phosphorylate the cardiac Na+-Ca2+ exchanger via protein kinase C (PKC), little is known about the effect of ET-1 on I(NaCa). In order to examine the effects of ET-1 on I(NaCa), whole-cell patch clamp measurements were made at 378C from guinea-pig isolated ventricular myocytes. With major interfering currents inhibited, I(NaCa) was measured as the current sensitive to nickel (Ni; 10mM) during a descending voltage ramp. ET-1 (10 nM) significantly increased I(NaCa) ( approximately 2-fold at -100 mV). Application of a PKC activator (PMA; 1mM: phorbol 12-myristate 13-acetate), mimicked the effect of ET-1. In contrast, the PKC inhibitor chelerythrine (CLT, 1mM) abolished the stimulatory effect of ET-1. An inactive phorbol ester, 4-alpha-phorbol-12,13-didecanoate (4a-PDD, 1mM) had no effect on I(NaCa). Collectively, these data indicate that ET-1 activated I(NaCa) through a PKC-dependent pathway. In additional experiments, isoprenaline (ISO; which has also been reported to activate I(NaCa) ) was applied. The increase in I(NaCa) density with ISO (1mM) was similar to that induced by ET-1 (10nM). When I(NaCa) was pre-stimulated by ET-1, application of ISO elicited no further increase in current and vice versa. ISO also had no additional effect on I(NaCa) when the cells were pretreated with PMA. Application of CLT did not alter the response of I(NaCa) to ISO. We conclude that ET-1 stimulated ventricular I(NaCa) via a PKC-dependent mechanism under our recording conditions. Concentrations of ET-1 and ISO that stimulated I(NaCa) to similar extents when applied separately were not additive when co-applied. The lack of

  4. Chlorthalidone inhibits the KvLQT1 potassium current in guinea-pig ventricular myocytes and oocytes from Xenopus laevis

    PubMed Central

    Mancilla-Simbro, C; López, A; Martinez-Morales, E; Soto-Perez-de-Celis, E; Millan-PerezPeña, L; Tsushima, R; Salinas-Stefanon, E M

    2007-01-01

    Background and purpose: Chlorthalidone is used for the treatment of hypertension as it produces a lengthening of the cardiac action potential. However, there is no experimental evidence that chlorthalidone has electrophysiological effects on the potassium currents involved in cardiac repolarization. Experimental approach: Ventricular myocytes and oocytes, transfected with human ionic channels that produce IK current, were exposed to different concentrations of chlorthalidone. Action potentials and potassium currents were recorded using a patch clamp technique. To determine which component of the current was affected by chlorthalidone, human channel proteins (hERG, minK and KvLQT1) were used. Key results: Chlorthalidone prolonged the ventricular action potential at 50 and 90% by 13 and 14%, respectively. The cardiac potassium currents I to and IK1 were not affected by chlorthalidone at any concentration, whereas the delayed rectifier potassium current, IK, was blocked in a dose-response, voltage-independent fashion. In our preparation, 100 μM chlorthalidone blocked the two components of the delayed rectifier potassium current with the same potency (50.1±5% for IKr and 54.6±6% for IKs) (n=7, P<0.05). The chlorthalidone-sensitive current was slow and saturated at potentials greater than +30 mV. In our conditions only the KvLQT1 potassium current was affected by the drug, by 14%. Conclusions and implications: Chlorthalidone was demonstrated to have a direct effect on cardiac ventricular myocytes; it blocked the delayed rectifier potassium current (IK), specifically the KvLQT1 component of the potassium current. These results indicate that it has potential for use as an antiarrhythmic but further studies are needed. PMID:18037918

  5. Differential effects of L-propionylcarnitine on the electrical and mechanical properties of guinea pig ventricular muscle in normal and acidic conditions.

    PubMed

    Aomine, M; Arita, M

    1987-11-01

    We studied the effects of L-propionylcarnitine (PC) on transmembrane action potentials and isometric contractile tension in isolated guinea pig ventricular papillary muscles. The effects of 5 concentrations of PC (10(-5), 10(-4), 10(-3), 10(-2) and 3 X 10(-2)M) were examined in both normal (pH 7.4) and acidic (pH 6.9) conditions. The concentrations of 10(-5) to 10(-2)M had no significant effect on action potential amplitude, maximum upstroke velocity of phase 0 and resting potential, in either condition. At pH 7.4, action potential duration (ADP) was significantly (P less than 0.05) or insignificantly shortened by the drug depending upon the concentration used. At pH 6.9, however, the APD was prolonged by moderate PC concentrations (10(-3) and 10(-2)M), in which the effective refractory period (ERP) was also lengthened, associated with an increased ERP/APD ratio. In both pH conditions, the highest concentration (3 X 10(-2)M) significantly (P less than 0.05) decreased all these action potential parameters. PC had a biphasic effect on the developed tension. In both pH conditions, low PC concentrations (10(-5) to 10(-3)M) produced an initial augmentation of the contraction, followed by subsequent reduction. The initial augmentation disappeared by pretreatment with reserpine or propranolol, suggesting the involvement of beta-adrenoceptors. In the steady state, all PC concentrations produced a negative inotropic effect at pH 7.4, while at pH 6.9 only high concentrations (10(-2)M and 3 X 10(-2)M) had this effect. These results suggest that the effects of PC in an acidic condition differ considerably from those in a normal pH condition and that limited concentrations of PC (10(-3) to 10(-2)M) may prevent re-entrant arrhythmias from developing under acidic conditions via lengthening of the ERP, without deleterious effects on the contractile force.

  6. Animal Models of Tuberculosis: Guinea Pigs

    PubMed Central

    Clark, Simon; Hall, Yper; Williams, Ann

    2015-01-01

    The progression of the disease that follows infection of guinea pigs with Mycobacterium tuberculosis displays many features of human tuberculosis (TB), and the guinea pig model of TB has been used for more than 100 years as a research tool to understand and describe disease mechanisms. Changes in the bacterial burden and pathology following infection can be readily monitored and used to evaluate the impact of TB interventions. Demonstration of the protective efficacy of vaccines in the low-dose aerosol guinea pig model is an important component of the preclinical data package for novel vaccines in development, and there is a continual need to improve the model to facilitate progression of vaccines to the clinic. Development of better tools with which to dissect the immune responses of guinea pigs is a focus of current research. PMID:25524720

  7. [Dermophytes and guinea pigs : An underestimated danger?

    PubMed

    Kupsch, C; Berlin, M; Gräser, Y

    2017-06-14

    For several years, an increasing number of human infections, mainly affecting children, with the zoophilic dermatophyte Trichophyton benhamiae has been observed. It is predominantly transmitted by pet guinea pigs. The prevalence of the dermatophyte on guinea pigs which are for sale in pet shops is unknown. Therefore, the aim of this study was to analyze the frequency of T. benhamiae on symptomatic and asymptomatic guinea pigs from pet shops in Berlin. We sampled 59 guinea pigs from 15 pet shops using toothbrushes (MacKenzie brush technique) and FLOQswabs™ and analyzed the material for the presence of T. benhamiae with polymerase chain reaction (PCR) and culture. We detected T. benhamiae on more than 90% of the guinea pigs; 9% of which showed visible tinea symptoms. The majority was identified as asymptomatic carriers of the dermatophyte. Pet shop guinea pigs have a high risk of being carriers of T. benhamiae, which can be transmitted to humans via physical contact, even though there is no visible infection in most cases. It is therefore recommended to have newly purchased animals examined by a veterinarian.

  8. 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

  9. DOCA-salts induce heart failure in the guinea pig.

    PubMed

    Tiritilli, A

    2001-10-01

    Heart failure (HF) is a common clinical problem confronting physicians and is often the final manifestation of many cardiovascular disorders. Despite recent advances in the pharmacological management of HF, it remains a highly lethal and disabling disorder. A number of animal models have been developed to study both the pathophysiology of HF and new therapeutic approaches to this complex syndrome. Only through an improved understanding of the basic biology of the early stages of the syndrome can HF be prevented or at least anticipated. With this in view, we have developed an easily realisable and inexpensive model in the guinea pig, which presents numerous structural, metabolic and biochemical similarities compared with the human heart. Thirty guinea pigs, aged 5 weeks and weighing 300 g were used. After anaesthesia, left nephrectomy was performed. After 1 week the guinea pigs were divided into: (a) control group (n=15), which received an injection of vehicle as well as tap water for 10 weeks; (b) DOCA-salts group (n=15), where the animals were treated with an IM injection of 10 mg DOCA 5 days a week for 10 weeks and with drinking water containing 9 g/l(-1) NaCl and 2 g/l(-1) KCl. Our results demonstrate that the administration of DOCA-salts to guinea pigs for 10 weeks caused a significant increase in blood pressure (BP+30%) associated with left ventricular hypertrophy (LVH), evaluated by LV weight (+37%), LV wall (+36%), by the ratio LV weight/Body weight (+23%) and by an increase in LV volume (+51%). Concerning HF, the latter was clinically evident through an increase in body weight, heart rate and dyspnoea. Indeed, guinea pigs presented pleural and/or pericardial effusion often associated with ascite. This model, which combines pressure and volume overload, results in a slow evolution towards HF. This allows a better understanding of the mechanisms in early LV remodelling which has the potential to develop into HF. Some recent studies have emphasised the value

  10. Influenza virus infection in guinea pigs raised as livestock, Ecuador.

    PubMed

    Leyva-Grado, Victor H; Mubareka, Samira; Krammer, Florian; Cárdenas, Washington B; Palese, Peter

    2012-07-01

    To determine whether guinea pigs are infected with influenza virus in nature, we conducted a serologic study in domestic guinea pigs in Ecuador. Detection of antibodies against influenza A and B raises the question about the role of guinea pigs in the ecology and epidemiology of influenza virus in the region.

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

    SciTech Connect

    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 virus 40 (SV40). These cell lines also formed colonies in soft agarose and induced sarcomas in nude mice. It is concluded that (i) GPCMV can malignantly transform guinea pig cells; (ii) cloning of GPCMV-transformed cells in soft agarose produced cells that induced tumors with a shorter latency period but with no alteration in growth rate or final tumor size; and (iii) the tumors produced by GPCMV-and HCMV-transformed guinea pig cells were more similar to each other in growth rate than to those induced by SV40-transformed guinea pig cells.

  12. Skin toxicity of propranolol in guinea pigs.

    PubMed

    Kobayashi, I; Hosaka, K; Maruo, H; Saeki, Y; Kamiyama, M; Konno, C; Gemba, M

    1999-05-01

    The skin toxicities of propranolol were studied in guinea pigs. In the primary and cumulative skin irritation studies, the skin reactions and the histopathological changes were observed in all animals treated with propranolol, and those tended to increase with the increase of propranolol dosage. The skin reactions increased with the application times of propranolol up to 7 days in the cumulative skin irritation study. In the skin sensitization, the phototoxicity and the skin photosensitization studies, no skin reactions were observed in any animals used in the studies. These results indicate that propranolol caused skin irritation, but was negative for skin sensitization, phototoxicity and skin photosensitization in guinea pigs.

  13. Prolactin Family of the Guinea Pig, Cavia porcellus

    PubMed Central

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

    2010-01-01

    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. PMID:20534723

  14. 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.

  15. New guinea pig model of Cryptococcal meningitis.

    PubMed

    Kirkpatrick, William R; Najvar, Laura K; Bocanegra, Rosie; Patterson, Thomas F; Graybill, John R

    2007-08-01

    We developed a guinea pig model of cryptococcal meningitis to evaluate antifungal agents. Immunosuppressed animals challenged intracranially with Cryptococcus neoformans responded to fluconazole and voriconazole. Disease was monitored by serial cerebrospinal fluid (CSF) cultures and quantitative organ cultures. Our model produces disseminating central nervous system disease and responds to antifungal therapy.

  16. 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.

  17. Watch out guinea pigs, here I come.

    PubMed

    Norton, T

    2001-04-01

    We live in an age of increasing emphasis of do-it-yourself, as a mere glance at the TV schedule will prove. Why not apply this same principle to your research? By becoming the guinea pig of your own experimentation you will be following a noble precedent--though maybe not a sane one!

  18. Synthesis of factor VIII antigen by cultured guinea pig megakaryocytes.

    PubMed

    Nachman, R; Levine, R; Jaffe, E A

    1977-10-01

    Immunoprecipitates containing guinea pig Factor VIII antigen were prepared from guinea pig plasma with a cross-reacting rabbit anti-human Factor VIII. Monospecific antisera to guinea pig Factor VIII antigen were produced in rabbits by using these washed immunoprecipitates as immunogens. The resulting antisera to guinea pig Factor VIII antigen detected Factor VIII antigen in guinea pig plasma and inhibited the von Willebrand factor activity in guinea pig plasma. This antibody also detected Factor VIII antigen in a solubilized protein mixture prepared from isolated cultured guinea pig megakaryocytes. Cultured guinea pig megakaryocytes were labeled with radio-active leucine. By radioautography, 96.2% of the radio-activity was present in megakaryocytes. The radio-active Factor VIII antigen present in the solubilized cell protein mixture was isolated by immunoprecipitation and characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results demonstrate that cultured guinea pig megakaryocytes synthesize Factor VIII antigen which contains the same polypeptide subunit (mol wt 200,000) present in guinea pig plasma Factor VIII antigen.

  19. Voltage- and time-dependent depression of maximum rate of depolarization of guinea-pig ventricular action potentials by two steroidal antiarrhythmic drugs, CCI 22277 and ORG 6001.

    PubMed Central

    Campbell, T. J.

    1982-01-01

    1 The voltage- and time-dependence of the depression of the maximum rate of depolarization (Vmax) by two steroidal anti-arrhythmic drugs, CCI22277 and Org 6001 were studied in guinea-pig ventricle. 2 At normal resting potentials CCI22277 (2 microM and 4 microM) produced very little depression of Vmax at very low driving rates (resting block) but trains of stimuli at interstimulus intervals (ISI) of less than 10,000 ms led to an exponential decline in Vmax to a new plateau over 100-200 beats. 3 This 'rate-dependent block' (RDB) increased with rate over the range ISI=4800 to ISI=200 ms. 4 Org 6001 30 microM and 60 microM produced a similar degree of RDB over the same range of frequencies but the new plateau level of Vmax was reached much more rapidly (20-30 beats) and there was a moderate degree of depression of Vmax in the resting tissue. 5 Recovery from RDB in the presence of both drugs was an exponential process with time constants (tau re) of 80.4 +/- 7.4 s for CCI22277 and 4.6 +/- 0.5 s for Org 6001. 6 Both drugs shifted the steady-state inactivation curve, relating Vmax to resting membrane potential, in the hyperpolarizing direction, implying selective depression of depolarized cells. PMID:7139201

  20. Effect of lidocaine and quinidine on steady-state characteristics and recovery kinetics of (dV/dt)max in guinea pig ventricular myocardium.

    PubMed

    Chen, C M; Gettes, L S; Katzung, B G

    1975-07-01

    We studied the effects of quinidine and lidocaine on the steady-state relationship between membrane potential and the maximum rate of rise of the action potential, (dV/dt)max, and on the recovery kinetics of (dV/dt)max in guinea pig papillary muscles. The steady-state relationships were determined in fibers stimulated at 0.2/sec and depolarized with KCl. Recovery kinetics were determined at various resting membrane potentials by assessing (dV/dt)max in progressively earlier premature action potentials. Lidocaine caused a dose-dependent decrease in (dV/dt)max, shifted the curve defining the steady-state relationship along the voltage axis in the direction of more negative potentials, and slowed the recovery kinetics of (dV/dt)max. Quinidine caused a dose-dependent decrease in (dV/dt)max but did not alter the shape of the curves defining either the steady-state relationship or the recovery kinetics of (dV/dt)max. Both drugs depressed membrane responsiveness as determined in premature action potentials originating from incompletely repolarized fibers. Our study indicates that the mechanisms whereby quinidine and lidocaine influence (dV/dt)max are different. It is possible that this difference may underlie some of the differences in the clinical effects of these two drugs.

  1. Spontaneous reproductive pathology in female guinea pigs.

    PubMed

    Veiga-Parga, Tamara; La Perle, Krista M D; Newman, Shelley J

    2016-11-01

    Reproductive pathology of domestic guinea pigs is underreported to date. To provide a comprehensive review of uterine disease in guinea pigs, we performed a retrospective study of the pathology archives of the University of Tennessee, College of Veterinary Medicine. By histology, 13 of 37 uterine lesions in 23 animals were neoplastic; the other 24 nonneoplastic lesions included cystic endometrial hyperplasia (16 of 24), endometrial hemorrhage (3 of 24), pyometra (2 of 24), polyp (2 of 24), and mucometra (1 of 24). The most common guinea pig uterine neoplasms were uterine leiomyomas (6 of 13), followed by adenomas (3 of 13) and leiomyosarcomas (1 of 13). Other neoplasms included anaplastic tumors of unknown origin (2 of 13) and choriocarcinoma (1 of 13). Both anaplastic tumors and the choriocarcinoma were positive for vimentin. The choriocarcinoma was positive for HSD83B1, indicating a trophoblastic origin and its final diagnosis. All were negative for cytokeratin and smooth muscle. In multiple animals, more than 1 tumor or lesion was reported. Estrogen receptor and progesterone receptor expression was nearly 100% in uterine neoplasms. Nearly all animals for which data were available had cystic rete ovarii (18 of 19); the animal with no cystic rete ovarii had paraovarian cysts. In our study, female pet guinea pigs had a tendency to develop cystic endometrial hyperplasia and uterine neoplasia. Factors for the development of these lesions could be cystic rete ovarii, hormone dysregulation, and/or age. Other factors could contribute to the development of uterine lesions. As in other species, early ovariohysterectomy could decrease the prevalence of uterine lesions. © 2016 The Author(s).

  2. 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…

  3. Heterogeneous infectiousness in guinea pigs experimentally infected with Trypanosoma cruzi.

    PubMed

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

    2016-02-01

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

  4. 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...

  5. 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…

  6. Streptococcus equi subsp. zooepidemicus Infections Associated with Guinea Pigs

    PubMed Central

    Young, Andrea; Levine, Seth J.; Garvin, Joseph P.; Brown, Susan; Turner, Lauren; Fritzinger, Angela; Gertz, Robert E.; Murphy, Julia M.; Vogt, Marshall; Beall, Bernard

    2015-01-01

    Streptococcus equi subsp. zooepidemicus is a known zoonotic pathogen. In this public health investigation conducted in Virginia, USA, in 2013, we identified a probable family cluster of S. zooepidemicus cases linked epidemiologically and genetically to infected guinea pigs. S. zooepidemicus infections should be considered in patients who have severe clinical illness and report guinea pig exposure. PMID:25531424

  7. 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.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-01-01

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

  10. Temperature dependence of Na+−H+ exchange, Na+−HCO3− co-transport, intracellular buffering and intracellular pH in guinea-pig ventricular myocytes

    PubMed Central

    Ch'en, Frederick F-T; Dilworth, Emma; Swietach, Pawel; Goddard, Ruth S; Vaughan-Jones, Richard D

    2003-01-01

    Almost all aspects of cardiac function are sensitive to modest changes of temperature. We have examined the thermal sensitivity of intracellular pH regulation in the heart. To do this we determined the temperature sensitivity of pHi, intracellular buffering capacity, and the activity of sarcolemmal acid-extrusion proteins, Na+-H+ exchange (NHE) and Na+-HCO3− co-transport (NBC) in guinea-pig isolated ventricular myocytes. pHi was recorded fluorimetrically with acetoxymethyl (AM)-loaded carboxy-SNARF-1 at either 27 or 37°C. At 27°C, intrinsic (non-CO2-dependent) buffering power (βi) was ˜60 % of that at 37°C. Acid-extrusion (Je) through NHE was ˜50 % slower than at 37°C, consistent with a Q10 of ˜2. In 5 % CO2/HCO3−-buffered conditions, in the presence of 30 μm cariporide to inhibit NHE, acid extrusion via NBC was also slowed at 27°C, suggestive of a comparable Q10. Resting pHi at 27°C was similar in Hepes- or 5 % CO2/HCO3−-buffered superfusates but, in both cases, was ˜0.1 pH units lower at 37°C. The higher the starting pHi, the larger was the thermally induced fall of pHi, consistent with a mathematical model where intrinsic buffers with a low principal pKa (e.g. close to 6.0) are less temperature-sensitive than those with a higher pKa. The high temperature sensitivity of pHi regulation in mammalian cardiac cells has implications for experimental work conducted at room temperature. It also has implications for the ability of intracellular acidosis to generate intracellular Na+ and Ca2+ overload, cardiac injury and arrhythmia in the heart. PMID:12923205

  11. Ebola virus transmission in guinea pigs.

    PubMed

    Wong, Gary; Qiu, Xiangguo; Richardson, Jason S; Cutts, Todd; Collignon, Brad; Gren, Jason; Aviles, Jenna; Embury-Hyatt, Carissa; Kobinger, Gary P

    2015-01-15

    Ebola virus (EBOV) transmission is currently poorly characterized and is thought to occur primarily by direct contact with infectious material; however transmission from swine to nonhuman primates via the respiratory tract has been documented. To establish an EBOV transmission model for performing studies with statistical significance, groups of six guinea pigs (gps) were challenged intranasally (i.n.) or intraperitoneally (i.p.) with 10,000 times the 50% lethal dose (LD50) of gp-adapted EBOV, and naive gps were then introduced as cage mates for contact exposure at 1 day postinfection (p.i.). The animals were monitored for survival and clinical signs of disease and quantitated for virus shedding postexposure. Changes in the duration of contact of naive gps with infected animals were evaluated for their impact on transmission efficiency. Transmission was more efficient from i.n.- than from i.p.-challenged gps, with 17% versus 83% of naive gps surviving exposure, respectively. Virus shedding was detected beginning at 3 days p.i. from both i.n.- and i.p.-challenged animals. Contact duration positively correlated with transmission efficiency, and the abrogation of direct contact between infected and naive animals through the erection of a steel mesh was effective at stopping virus spread, provided that infectious animal bedding was absent from the cages. Histopathological and immunohistochemical findings show that i.n.-infected gps display enhanced lung pathology and EBOV antigen in the trachea, which supports increased virus transmission from these animals. The results suggest that i.n.-challenged gps are more infectious to naive animals than their systemically infected counterparts and that transmission occurs through direct contact with infectious materials, including those transported through air movement over short distances. Ebola is generally thought to be spread between humans though infectious bodily fluids. However, a study has shown that Ebola can be spread

  12. Pathogenesis of Lassa Virus Infection in Guinea Pigs

    DTIC Science & Technology

    1982-08-01

    INFECTION AND IMMUNITY. Aug. 1982. p. 771-778 Vol. 37. No. 2 0019-9567/82/080771-08$02.00/0 Pathogenesis of Lassa Virus Infection in Guinea Pigs... virus strain Josiah. In contrast, no more than 30% of the Hartley guinea pigs died regardless of the virus rdose. In lethally infected strain 13 guinea...pigs, peak titers of virus (107 to 10 PFU) occurred in the spleen and lymph nodes at 8 to 9 days, in the salivary glands at 11 days, and in the lung at

  13. 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.

  14. Radiation-induced micrencephaly in guinea pigs

    SciTech Connect

    Wagner, L.K.; Johnston, D.A.; Felleman, D.J.

    1992-11-01

    The effect of x rays on brain weight of guinea pig pups at birth was studied for 21-day old embroys exposed in utero to doses of 75 and 100 mGy. When compared to controls and when corrected for body weight, gestation time, litter size, sex, and examiner differences the brains of irradiated pups weighed approximately 46 mg less than those of controls (p<0.001) for the 75-mGy group and about 55 mg less for the 100-mGy group. Brains of females weighed 51 mg less than those of males of the same body weight. Dam weight and caging conditions had no observed effect on brain weight.

  15. Radiation-induced micrencephaly in guinea pigs

    SciTech Connect

    Wagner, L.K.; Johnston, D.A.; Felleman, D.J.

    1992-01-01

    The effect of x rays on brain weight of guinea pig pups at birth was studied for 21-day old embroys exposed in utero to doses of 75 and 100 mGy. When compared to controls and when corrected for body weight, gestation time, litter size, sex, and examiner differences the brains of irradiated pups weighed approximately 46 mg less than those of controls (p<0.001) for the 75-mGy group and about 55 mg less for the 100-mGy group. Brains of females weighed 51 mg less than those of males of the same body weight. Dam weight and caging conditions had no observed effect on brain weight.

  16. Reversing the objective: Adding guinea pig pedagogies

    NASA Astrophysics Data System (ADS)

    Weinstein, Matthew

    2004-03-01

    This article explores objectification in science and science education, i.e., the way material is turned into an object of interest to scientists. Drawing on sociological and anthropological drama theory, it examines how objectification does and does not occur in classrooms and schools. To understand the role and relationship of the object to the scientist, I look at current literature from the social studies of science concerning human and nonhuman objects as well as my own ethnographic work on the activism of politicized human research subjects. The paper concludes by how and why a more self-conscious focus on the object of science is important for those concerned with equity in science education, suggesting that such guinea pig pedagogies restore missing historical and ethical dimensions to science education.

  17. Transglutaminase from Hair Follicle of Guinea Pig

    PubMed Central

    Chung, S. I.; Folk, J. E.

    1972-01-01

    Two transglutaminases are found in homogenates of the inner root sheaths of guinea pig hair-follicles. One is indistinguishable from the well-characterized liver transglutaminase [J. Biol. Chem., 246, 1093 (1971)]. The other, which is present in far greater quantity, has not been detected in other organs or tissues. Gel filtration and polyacrylamide gel electrophoresis studies indicate that the native hair-follicle enzyme, of molecular weight 54,000, is composed of two subunits of identical molecular weight. Specificity studies suggest that the intermolecular cross-linking of fibrin and fibrinogen that is catalyzed by this enzyme is a result of the formation of ε(γ-glutamyl)lysine bonds. The probable participation of hair-follicle transglutaminase in the formation of these cross-links in the proteins of hair is discussed. Images PMID:4501114

  18. Electrocardiographic toxicity in the guinea pig.

    PubMed

    Lacroix, Pierre

    2002-11-01

    Abnormalities of cardiac rhythm are one of the most common clinical problems in cardiology and arise as the result of either disorders of cardiac impulse formation or conduction, or a combination of both. It has been established that some classes of drugs, such as tricyclic antidepressants (e.g., imipramine), cardiac glycosides (e.g., digoxin), and Class I or Class III antiarrhythmic drugs (e.g., quinidine or amiodarone) can produce electrocardiographic toxicity in humans. It is therefore highly advisable to assess the effect of any new compound in this respect, during the early phases of drug development. This unit presents a protocol to detect the electrocardiographic toxicity of compounds in the anesthetized guinea pig.

  19. Establishment of a Salmonella-Free Guinea Pig Colony

    PubMed Central

    Pivnick, Hilliard; Stuart, Philip F.; Walcroft, M.

    1966-01-01

    Salmonellosis due to Salmonella typhimurium was enzootic in a guinea pig breeding colony for over 25 years. A Salmonella-free auxiliary colony was established by removing weanlings from the infected colony to a clean area, and preventing infection. Examination of agglutinin titers and necropsy specimens indicated that the auxiliary colony was still free from Salmonella 18 months after its establishment while 24% of the guinea pigs dying in the infected colony yielded Salmonella typhimurium. PMID:17649571

  20. Antitussive effects of memantine in guinea pigs.

    PubMed

    Smith, Jaclyn A; Hilton, Emma C Y; Saulsberry, Loren; Canning, Brendan J

    2012-04-01

    The treatment of cough is a significant clinical unmet need because there is little evidence that current therapies are effective. Based on evidence supporting a role for N-methyl D-aspartate receptors (NMDARs) in cough, we hypothesized that memantine, a low-affinity, uncompetitive NMDAR channel blocker in routine use for the treatment of Alzheimer disease, could be an effective, well-tolerated, antitussive therapy. The aim of this study was to establish preclinical evidence that memantine has antitussive effects. We studied the influence of memantine on experimentally induced coughing in response to citric acid and bradykinin inhalation in guinea pigs. We also compared the potency and efficacy of memantine as an antitussive to other NMDAR antagonists, dextromethorphan and ketamine, and to the γ-aminobutyric acid class B receptor agonist baclofen. Compared with control subjects, 10 mg/kg memantine significantly reduced the cumulative number of coughs evoked by both citric acid (median, 24.0 [interquartile range (IQR), 13.0-25.5] vs 1.5 [IQR, 0.3-10.3] coughs; P = .012) and bradykinin aerosols (median, 16.0 [IQR, 9.5-18.5] vs 0.0 [IQR, 0-0.75] coughs; P = .002). Memantine 10 mg/kg produced a similar reduction in the cumulative number of coughs to baclofen 3 mg/kg and demonstrated comparatively greater cough suppression than 30 mg/kg dextromethorphan or 30 mg/kg ketamine. This dose of memantine produced no sedative or respiratory depressive effects. This study illustrates that memantine has marked antitussive effects in guinea pigs, most likely mediated through NMDAR channel blockade. Memantine, therefore, has the potential to be a safe, effective, and well-tolerated antitussive agent.

  1. The complementary deoxyribonucleic acid sequence of guinea pig endometrial prorelaxin.

    PubMed

    Lee, Y A; Bryant-Greenwood, G D; Mandel, M; Greenwood, F C

    1992-03-01

    The nucleotide sequence of the relaxin gene transcript in the endometrium of the late pregnant guinea pig has been determined. The strategy used was a combination of polymerase chain reaction (PCR) with primers designed from the mRNA sequence of porcine preprorelaxin, rapid amplification of cDNA ends-PCR, and blunt end cloning in M13 mp18. With heterologous primers, a 226-basepair (bp) segment of the guinea pig relaxin gene sequence was obtained and was used to design a guinea pig-specific primer for use with the rapid amplification of cDNA ends-PCR method. The latter allowed completion of the sequence of 336 bp, with a 96-bp overlap. The sequence obtained shows greater homology at both the nucleotide and amino acid levels with porcine and human relaxins H1 and H2 than with rat relaxin, supporting the thesis that the guinea pig is not a rodent. The transcription of the guinea pig endometrial relaxin gene during pregnancy was confirmed by Northern analysis of guinea pig endometrial tissues with a species-specific cDNA probe. The endometrial relaxin gene is transcribed during pregnancy, but not in lactation, consistent with the observed immunostaining for relaxin.

  2. [Experimental study of infectious hepatitis in guinea pigs].

    PubMed

    Asharafova, R A; Tuliaganov, P D; Kasymkhodzhaev, E S

    1976-04-01

    The authors carried out a comparative study of morphological changes in the liver of guinea-pigs in various times following intraperitoneal administration of the serum taken from a patient with infectious hepatitis (1st group), administration of the serum in combination with the urine (2nd group), administration of the serum in combination with the patient's duodenal juice (3rd group), and administration of the serum in combination with a hepatic antigen prepared of the liver of a healthy guinea-pig (4th group). Observations over the behaviour of the animals and morphological investigations showed a high sensitivity of guinea-pigs to virus-containing materials. The reaction was particularly pronounced in animals which were given the serum taken from a patient with infectious hepatitis in combination with a hepatic antigen, and the microscopic picture of the liver almost similar to that of the patient with Botkin's disease. Moreover, in the course of the study it was found possible to re-inoculate the virus obtained from the guinea-pigs subjected to a combined exposure to the serum from a patient with infectious hepatits and hepatic antigen. Comparing the results of the study on guinea-pigs with those obtained previously in the experimental study of viral hepatitis on white rats (1970), the authors have come to the conclusion that guinea-pigs may be used for modelling and experimental investigation of Botkin's disease.

  3. Effects of the Anemonia sulcata toxin (ATX II) on intracellular sodium and contractility in rat and guinea-pig myocardium.

    PubMed

    Hoey, A; Harrison, S M; Boyett, M R; Ravens, U

    1994-12-01

    The effects of the Anemonia sulcata toxin ATX II on action potentials and contractility of isolated papillary muscles and single myocytes from rat and guinea-pig hearts have been studied. ATX II prolonged the action potential in both rat and guinea-pig papillary muscle. Although it produced a positive inotropic effect in guinea-pig papillary muscle, it failed to do so in rat papillary muscle. However, in single rat and guinea-pig ventricular cells, it both prolonged the action potential and had a positive inotropic effect. We suggest that ATX II does not cause a positive inotropic effect in rat papillary muscle, because it induces Ca2+ overload. In single cells the positive inotropic effect was reduced by approximately 50% when the contractions were triggered by voltage clamp pulses of constant duration rather than by action potentials. This suggests that the inotropic effect of ATX II is in part the result of the prolongation of the action potential. The intracellular Na+ activity (a(i)Na) in single ventricular cells was measured with the Na(+)-sensitive fluorescent dye SBFI. After exposure of the cells to ATX II, a(i)Na was increased by a maximum of 1.9 +/- 0.3 and 2.2 +/- 0.3 mM in rat and guinea-pig cells, respectively. It is suggested that the positive inotropic effect of ATX II is also in part the result of the rise in a(i)Na.

  4. Antiarrhythmic Effect of Either Negative Modulation or Blockade of Small Conductance Ca2+-activated K+ Channels on Ventricular Fibrillation in Guinea Pig Langendorff-perfused Heart.

    PubMed

    Diness, Jonas G; Kirchhoff, Jeppe E; Sheykhzade, Majid; Jespersen, Thomas; Grunnet, Morten

    2015-09-01

    During recent years, small conductance Ca-activated K (SK) channels have been reported to play a role in cardiac electrophysiology. SK channels seem to be expressed in atria and ventricles, but from a functional perspective, atrial activity is predominant. A general notion seems to be that cardiac SK channels are predominantly coming into play during arrhythmogenic events where intracellular concentration of Ca is increased. During ventricular fibrillation (VF), a surge of [Ca]i has the potential to bind to and open SK channels. To obtain mechanistic insight into possible roles of SK channels during VF, we conducted experiments with an SK channel pore blocker (ICA) and a negatively allosteric modulator (NS8395) in a Langendorff-perfused heart model. Both compounds increased the action potential duration, effective refractory period, and Wenckebach cycle length to comparable extents. Despite these similarities, the SK channel modulator was found to revert and prevent VF more efficiently than the SK channel pore blocker. In conclusion, either negative allosteric modulation of the SK channel with NS8593 is more favorable than pure channel block with ICA or the 2 compounds have different selectivity profiles that makes NS8593 more antiarrhythmic than ICA in a setting of VF.

  5. [Renal pleomorphic sarcoma in four guinea pigs (Cavia porcellus)].

    PubMed

    Hankel, Julia; Hewicker-Trautwein, Marion; Warschau, Martina; Thöle, Anna Milena; Fehr, Michael

    2017-09-20

    Renal tumours apparently are rare not only in cats and dogs, but also in guinea pigs and can be difficult to diagnose. The aim of this study is to describe the clinical, pathological and immunohistochemical findings in guinea pigs with renal tumours. Furthermore, the symptoms, diagnostic possibilities and therapy are compared with renal tumours in other small animals, including cats and dogs. During a period of 4 years and 4 months the data of guinea pigs that had been presented in the clinic were retrospectively analysed. The analysis comprised guinea pigs that underwent a macroscopical and histopathological postmortem examination, and were diagnosed to have a renal neoplasm. Four guinea pigs had a renal tumour. The percentage of renal neoplasms in relation to the overall necropsied carcasses and the number of organs originating from guinea pigs was 4.7 % and the percentage of renal neoplasms in relation to the overall diagnosed tumours of the abdominal and pelvic cavities was 30.7 %. Histology and immunohistochemistry revealed the presence of renal pleomorphic sarcomas in all four cases. In two of the four guinea pigs, the classical triad, as described for cats and dogs with renal tumours (weight loss, abdominal mass and haematuria), was observed. During clinical examination a prominent, apparently painful abdominal mass in the region of the kidneys was palpable in all four cases. Applying radiography the suspected diagnosis of a mass in the area of the kidney was confirmed in three cases, in two animals the renal origin of the masses was determined by ultrasound examination. Because a renal neoplasm is a pain-inducing disease with a high risk of metastases in domestic animals, a prompt nephrectomy should be performed when azotaemia is absent.

  6. Radiation induced micrencephaly in guinea pigs

    SciTech Connect

    Wagner, L.K.; Johnston, D.A.; Felleman, D.J.

    1991-01-01

    A brain weight deficit of about 70 mg was induced at doses of approximately 75-mGy and a deficit of 60 mg was induced at 100 mGy. This confirms the effects projected and observed by Wanner and Edwards. Although the data do not demonstrate a clear dose-response relationship between the 75-mGy and 100-mGy groups, the data are statistically consistent with a dose-response effect because of the overlapping confidence intervals. The lack of a statistically significant observation is most likely related to the small difference in doses and the limited numbers of animals examined. There are several factors that can influence the brain weight of guinea pig pups, such as caging and housing conditions, the sex of the animal, and litter size. These should be taken into account for accurate analysis. Dam weight did not appear to have a significant effect. The confirmation of a micrencephalic effect induced x rays at doses of 75-mGy during this late embryonic stage of development is consistent with the findings of small head size induced in those exposed prior to the eight week of conception at Hiroshima. This implies a mechanism for micrencephaly different from those previously suggested and lends credence to a causal relation between radiation and small head size in humans at low doses as reported by Miller and Mulvihill. 16 refs., 13 tabs.

  7. Evaluation of Ebola Virus Countermeasures in Guinea Pigs.

    PubMed

    Marzi, Andrea

    2017-01-01

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

  8. 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

  9. Pharmacologically Stimulated Pupil and Accommodative Changes in Guinea Pigs

    PubMed Central

    Ostrin, Lisa A.; Garcia, Mariana B.; Choh, Vivian; Wildsoet, Christine F.

    2014-01-01

    Purpose. The guinea pig is being used increasingly as a model of human myopia. As accommodation may influence the effects of manipulations used in experimental myopia models, understanding the accommodative ability of guinea pigs is important. Here, nonselective muscarinic agonists were used as pharmacological tools to study guinea pig accommodation. Methods. Measurements were made on 15 pigmented guinea pigs. For in vivo testing, animals were anesthetized and, following baseline measurements, 2% pilocarpine was applied topically. Measurements included A-scan ultrasonography, optical coherence tomography (OCT) imaging, corneal topography, and refraction. In vitro lens scanning experiments were performed using anterior segment preparations, with measurements before and during exposure to carbachol. Anterior segment structures were examined histologically and immunohistochemistry was done to characterize the muscarinic receptor subtypes present. Results. In vivo, pilocarpine induced a myopic shift in refractive error coupled to a small, but consistent decrease in anterior chamber depth (ACD), a smaller and more variable increase in lens thickness, and a decrease in pupil size. Lens thickness increases were short-lived (10 minutes), while ACD and pupil size decreased over 20 minutes. Corneal curvature was not significantly affected. Carbachol tested on anterior segment preparations in vitro was without effect on lens back vertex distance, but did stimulate pupil constriction. Immunohistochemistry indicated the presence of muscarinic receptor subtypes 1 to 5 in the iris and ciliary body. Conclusions. The observed pilocarpine-induced changes in ACD, lens thickness, and refraction are consistent with active accommodation in the guinea pig, through cholinergic muscarinic stimulation. PMID:25097245

  10. [Phototoxicity of Bergamot oil. Comparison between humans and guinea pigs].

    PubMed

    Girard, J; Unkovic, J; Delahayes, J; Lafille, C

    1979-01-01

    Phototoxicity of bergamot oil in solar simulating radiation (SSR greater than or equal to 290 nm) and in long ultraviolet radiation (LUV greater than or equal to 320 nm) has been compared by studying photoaugmentation of erythema in the guinea pig after 24 h and pigmentary photoaugmentation in man on the 8th day. The results show that a close relationship exists between guinea pig and human responses, with both radiations used, and that man seems to be slightly more sensitive to phototoxic effects of bergamot oil than the guinea pig. This difference of sensitivity necessarily implies the participation of UVA (320--400 nm) in the phototoxic reaction of bergamot oil with solar radiation. This UVA participation is particularly obvious in the guinea pig; in man, the results are less clear and a certain synergy of UVB rays (290--320 nm) may be involved in the phototoxic UVA-induced reaction of bergamot oil. Despite these slight differences, the erythematous reaction in the guinea pig appears to be a remarkable experimental model to show out potential phototoxic reactions of products containing psoralens in man.

  11. 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.

  12. 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

  13. 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.

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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

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

    PubMed

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

    2014-01-01

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

  1. Induction and properties of guinea pig serum interferon. Preliminary report.

    PubMed

    Nolewajka, E; Mikolajski, K; Kapp-Burzyńska, Z; Trzeciak, J; Wrona, M

    1977-01-01

    Guinea pigs, 250-350 g body weight, both sexes, were injected with 5X10(8.5) EID50 NDV (Radom strain) intracardially and intraperitoneally simultaneously. The animals were bled by cardiac puncture 0, 3, 6, 12, 24 and 48 hours after injection. After virus inactivation, serum interferon titration was performed in cultures of guinea pig embryo kidney cells with 50 percent plaque inhibition test using VSV. The highest interferon titer (64 u./ml) was found after 6 hours of inductor injection. Interferon titer decreased quickly and after 12 hours it was lower than 16 u./ml. Guinea pig serum interferon induced by NDV was resistant to pH 2 and 56 degrees C during 1 hour. Interferon was inactivated by trypsin. The decribed interferon did not protect heterologous species cells (swine) against Teschen Disease Virus infection. Other properties of this interferon are being studied.

  2. Inhaled Bordetella pertussis vaccine decreases airway responsiveness in guinea pigs.

    PubMed

    Vargas, M H; Bazán-Perkins, B; Segura, P; Campos, M G; Selman, M; Montaño, L M

    1995-01-01

    Bordetella pertussis (BP) has been used as adjuvant for experimental animal immunization, but its effects on airway responsiveness are uncertain. Three groups of guinea pigs were used: animals with a single exposure to inhaled BP vaccine (strain 134, total dose 1.24 x 10(12) germs), animals submitted to a sensitization procedure through inhalation of ovalbumin plus BP, and healthy control animals. Four weeks after inhalation of BP or after the beginning of sensitization, dose- or concentration-response curves to histamine were constructed in vivo and in vitro (tracheal and parenchymal preparations). We found that BP alone produced lower responses to histamine than control guinea pigs in vivo (insufflation pressure, p = 0.0003) and in tracheal tissues (p = 0.04), but not in parenchymal preparations. Sensitization did not modify the responsiveness compared with their respective controls. These results suggest that some BP component(s), probably pertussis toxin, causes a long lasting airway hyporesponsiveness in guinea pigs.

  3. PSITTACOSIS : III. EXPERIMENTALLY INDUCED INFECTIONS IN RABBITS AND GUINEA PIGS.

    PubMed

    Rivers, T M; Berry, G P

    1931-06-30

    1. Rabbits and guinea pigs are susceptible to psittacosis virus introduced intracerebrally. By means of brain to brain passages in these animals the active agent is capable of propagation indefinitely. 2. Serial passages of the virus through rabbits and guinea pigs do not cause the active agent to lose its pathogenicity for parrots and mice. 3. The chief clinical evidences of infection in rabbits and guinea pigs following intracranial inoculation of the virus are fever and loss of weight. The pathological changes are characterized by a mild meningo-encephalitis, and fatty degeneration, focal necrosis, and infarction of the liver. 4. Rabbits upon recovery from an attack of psittacosis are actively immune. 5. Two strains of virus, human and parrot, were found to be immunologically similar. 6. No evidence was obtained to show that human convalescent serum possesses an appreciable amount of neutralizing substances.

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

    PubMed

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

    2017-01-01

    Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the carotid body (CB) chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial 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 Ca(2+) levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied.

  5. 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.

  6. Spontaneous cyclic embryonic movements in humans and guinea pigs.

    PubMed

    Felt, Renée H M; Mulder, Eduard J H; Lüchinger, Annemarie B; van Kan, Colette M; Taverne, Marcel A M; de Vries, Johanna I P

    2012-08-01

    Motility assessment before birth can be used to evaluate the integrity of the nervous system. Sideways bending (SB) of head and/or rump, the earliest embryonic motility in both humans and guinea pigs, can be visualized sonographically. We know from other species that early embryonic motility is cyclic. This study explores the distribution of SB-to-SB intervals in human and guinea pig embryos before the appearance of more complex movements such as general movements. We hypothesized that the activity in both species is cyclic. We made 15-min sonographic recordings of SBs between 5 weeks and 0 days (5wk0d) and 7wk0d conceptional age (CA) in 18 human embryos of uncomplicated IVF pregnancies (term 38 weeks) and in 20 guinea pig embryos between 3wk4d and 4wk0d CA (term 9 weeks). SB-to-SB interval durations were categorized as long (≥10 s) or short (<10 s) intervals. For human embryos, the median values for long and short intervals were 61 s (range, 10-165 s) and 3 s (range, 1-9 s) respectively; for guinea pigs 38 s (range, 10-288 s) and 5 s (range, 1-9 s), respectively. During development, the duration of long intervals decreased while the number of short intervals increased for both species. The earliest embryonic motility in the human and guinea pig is performed cyclically with distinct developmental milestones. The resemblance of their interval development offers promising possibilities to use the guinea pig as a noninvasive animal model of external influences on motor and neural development.

  7. 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

  8. Guinea Pig ID-Like Families of SINEs

    PubMed Central

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

    2009-01-01

    Previous studies have indicated a paucity of SINEs within the genomes of the guinea pig and nutria, representatives of the Hystricognathi suborder of rodents. More recent work has shown that the guinea pig genome contains a large number of B1 elements, expanding to various levels among different rodents. In this work we utilized A–B PCR and screened GenBank with sequences from isolated clones to identify potentially uncharacterized SINEs within the guinea pig genome, and identified numerous sequences with a high degree of similarity (>92%) specific to the guinea pig. The presence of A-tails and flanking direct repeats associated with these sequences supported the identification of a full-length SINE, with a consensus sequence notably distinct from other rodent SINEs. Although most similar to the ID SINE, it clearly was not derived from the known ID master gene (BC1), hence we refer to this element as guinea pig ID-like (GPIDL). Using the consensus to screen the guinea pig genomic database (Assembly CavPor2) with Ensembl BlastView, we estimated at least 100,000 copies, which contrasts markedly to just over 100 copies of ID elements. Additionally we provided evidence of recent integrations of GPIDL as two of seven analyzed conserved GPIDL-containing loci demonstrated presence/absence variants in Cavia porcellus and C. aperea. Using intra-IDL PCR and sequence analyses we also provide evidence that GPIDL is derived from a hystricognath-specific SINE family. These results demonstrate that this SINE family continues to contribute to the dynamics of genomes of hystricognath rodents. PMID:19232383

  9. Guinea pig ID-like families of SINEs.

    PubMed

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

    2009-05-01

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

  10. The Guinea Pig as a Model of Infectious Diseases

    PubMed Central

    Padilla-Carlin, Danielle J; McMurray, David N; Hickey, Anthony J

    2008-01-01

    The words ‘guinea pig’ are synonymous with scientific experimentation, but much less is known about this species than many other laboratory animals. This animal model has been used for approximately 200 y and was the first to be used in the study of infectious diseases such as tuberculosis and diphtheria. Today the guinea pig is used as a model for a number of infectious bacterial diseases, including pulmonary, sexually transmitted, ocular and aural, gastrointestinal, and other infections that threaten the lives of humans. Most studies on the immune response to these diseases, with potential therapies and vaccines, have been conducted in animal models (for example, mouse) that may have less similarity to humans because of the large number of immunologic reagents available for these other species. This review presents some of the diseases for which the guinea pig is regarded as the premier model to study infections because of its similarity to humans with regard to symptoms and immune response. Furthermore, for diseases in which guinea pigs share parallel pathogenesis of disease with humans, they are potentially the best animal model for designing treatments and vaccines. Future studies of immune regulation of these diseases, novel therapies, and preventative measures require the development of new immunologic reagents designed specifically for the guinea pig. PMID:18724774

  11. Isolated perfused liver model: the rat and guinea pig compared.

    PubMed

    Chaïb, Samira; Charrueau, Christine; Neveux, Nathalie; Coudray-Lucas, Colette; Cynober, Luc; De Bandt, Jean-Pascal

    2004-05-01

    Although the rat is the most commonly used species for the study of hepatic metabolism, the physiology of the guinea pig is closer to human physiology. We compared the model of isolated perfused guinea pig liver with the classic model of isolated perfused rat liver, especially with respect to amino acid metabolism. After validation of an anesthetic mixture of ketamine, diazepam, and xylazine for the guinea pig, isolated perfused livers were harvested for both species. Three groups of animals were compared for the study of liver metabolic fluxes: 6-wk-old male Sprague-Dawley rats (R; 230 +/- 10 g, n = 5), young male Hartley guinea pigs (YG; 223 +/- 8 g, n = 6) matched to rats by liver weight, and adult male Hartley guinea pigs (AG; 389 +/- 5 g, n = 6) matched to rats by age. Results (mean +/- standard error of the mean) were compared by analysis of variance and Newman-Keuls tests. Both models displayed a satisfactory hepatic viability, but differences were noted, with higher portal flows (R: 3.1 +/- 0.3 versus YG: 4.5 +/- 0.3 and AG: 4.2 +/- 0.3 mL. min(-1). g(-1); P < 0.05, YG and AG versus R) and bile flows (R: 0.34 +/- 0.01 versus YG: 2.38 +/- 0.22 versus AG: 3.17 +/- 0.28 microL. min(-1). g(-1); P < 0.05, YG and AG versus R, and YG versus AG) and higher amino acid fluxes (P < 0.05) leading to greater nitrogen uptake (P < 0.05) in guinea pigs. We performed a second set of experiments to evaluate the influence of anesthesia and portal flow on this last parameter. In these experiments, rats were anesthetized with ketamine, diazepam, and xylazine and guinea pig livers were perfused at rat blood flow. Apart from a 50% anesthesia-related mortality for rats, bile flow and metabolic parameters were only slightly modified. However, some amino acid fluxes were statistically different (aspartate, serine, and histidine; P < 0.05), as confirmed by a higher transfer constant. Our results indicate that the isolated perfused guinea pig liver is a suitable model for the study of

  12. [Effects of Yanggan Lidan Granule on insulin resistance in guinea pigs with induced cholesterol gallstones].

    PubMed

    Fang, Bang-jiang; Zhou, Shuang; Pei, Xin-jun; Huang, Jin-yang; Chen, Bao-jin; Geng, Yun; Yang, Li-kun

    2009-12-01

    To observe the effects of Yanggan Lidan Granule (YGLDG), a compound traditional Chinese herbal medicine, on insulin resistance in guinea pigs with induced cholesterol gallstones. Eighty guinea pigs were randomly divided into normal control group, untreated group, YGLDG group and ursodeoxycholic acid (UDCA) group, with 20 guinea pigs in each group. Except the normal control group, gallstones were induced by high-cholesterol diet in the guinea pigs. The guinea pigs in the normal control group and the untreated group were administered with normal saline. UDCA and YGLDG were given to the guinea pigs in the corresponding groups for seven weeks. Eight guinea pigs of each group were used to measure the glucose infusion rate (GIR) by using hyperinsulinemic-euglycemic clamp technique. At the end the guinea pigs were killed and their gallstone formation was observed. The gallstones in guinea pigs were identified as cholesterol stones by qualitative analysis through infrared spectrum. The incidence rate of cholelithiasis of the untreated group was 82.35% . The GIR of guinea pigs in the untreated group was obviously lowered down as compared with the normal control group. Compared with the untreated group, the GIRs of the YGLDG group and the UDCA group were obviously increased, especially in the YGLDG group. YGLDG may improve insulin resistance in guinea pigs with cholesterol gallstones by elevating GIR obviously.

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

    PubMed

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

  14. 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

  15. Analysis of normal and denerved laryngeal vocalization in guinea pigs (Cavia porcellus).

    PubMed

    Arch-Tirado, Emilio; Verduzco-Mendoza, Antonio; Taboada-Picazo, Verónica; Mota-Rojas, Daniel; Alonso-Spilsbury, Maria de Lourdes; Alfaro-Rodríguez, Alfonso

    2009-01-01

    Paralysis of the left vocal chord is frequent in human clinical practice; because of its anatomic similarity with human, the guinea pig might be a suitable biological model to analyze the phoniatric behavior in denerved animals. Forty newborn guinea pigs were used (20 control and 20 experimental); an incision was made in the ventricular region with the animals under general anesthesia over the middle line of the neck, until the lower left laryngeal nerve was found, the same was secured with alligator clips so that afterward a two-part dissection could be performed and the middle section could be removed (1cm) from the nerve endings (distal and proximal) before they were separated from the laryngeal structure. After recovery from surgery, vocal emissions were recorded in solitary for 6 minutes. The animals that had nerves removed showed an increase in fundamental vocalization frequency compared with the controls. F test was carried out (P=0.05) and no significant difference was found. When analyzing functional recovery, we found that the guinea pigs compensated vocal emissions at 20 days. With regard to the unilateral paralysis, the motility was frequently compensated by the healthy vocal chord, improving voice emission, and loss of air inhalation.

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

    SciTech Connect

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

    1985-03-01

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

  17. Development of a Guinea Pig Lung Deposition Model

    DTIC Science & Technology

    2016-01-01

    6 3.4. MECHANISTIC MODEL OF PARTICLE DEPOSITION IN THE LUNG ................................. 7 4.0 SOFTWARE IMPLEMENTATION...4 Figure 2. Particle deposition in the lung of the guinea pig via endotracheal breathing...10 Figure 3. Deposition fraction of various size particles at different lung depths. ..................................... 11 Figure 4

  18. 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.

  19. Guinea pig ductus arteriosus. II - Irreversible closure after birth.

    NASA Technical Reports Server (NTRS)

    Fay, F. S.; Cooke, P. H.

    1972-01-01

    To investigate the mechanism underlying irreversibility of ductal closure after birth, studies were undertaken to determine the exact time course for the onset of irreversible closure of the guinea pig ductus arteriosus. Parallel studies of the reactivity of ductal smooth muscle to oxygen and studies of the postpartum cellular changes within the vessel were also carried out.

  20. 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

  1. EFFECTS OF METHYLNALTREXONE ON GUINEA PIG GASTROINTESTINAL MOTILITY

    PubMed Central

    Anselmi, Laura; Huynh, Jennifer; Vegezzi, Gaia; Sternini, Catia

    2013-01-01

    The purpose of the present study was to compare the effects of methylnaltrexone (MNTX), a peripherally acting μ opioid receptor (μOR) antagonist, on gastrointestinal (GI) motility in naïve vs. opiate-chronically treated guinea pigs in vitro and in vivo. We have used the electrically stimulated muscle twitch contractions of longitudinal muscle-myenteric plexus (LMMP) preparations and total GI transit as measure of GI motility. In LMMP preparations of naïve guinea pigs, MNTX (1–30 μM) induced a significant, dose-response reduction of morphine-induced inhibition of electrically stimulated muscle twitch contractions, with an IC50 of 9.4 10−8M. By contrast, MNTX abolished the inhibitory effect of acute morphine at any concentration tested (1–30 μM) in the guinea pigs chronically treated with opiates. In vivo, MNTX (10–50 mg s.c.) did not affect GI transit in naïve guinea pigs when administered acutely or for 5 consecutive days, but reversed the GI transit delay induced by chronic morphine treatment. These findings show that MNTX is effective in reversing opiate-induced inhibition of GI motility acting at peripheral μORs, but does not exert a pharmacologic effect on GI transit in the absence of opiate stimulation. PMID:23361094

  2. Ototoxic drugs: difference in sensitivity between mice and guinea pigs.

    PubMed

    Poirrier, A L; Van den Ackerveken, P; Kim, T S; Vandenbosch, R; Nguyen, L; Lefebvre, P P; Malgrange, B

    2010-03-01

    The development of experimental animal models has played an invaluable role in understanding the mechanisms of neurosensory deafness and in devising effective treatments. The purpose of this study was to develop an adult mouse model of ototoxic drug-induced hearing loss and to compare the ototoxicity in the adult mouse to that in the well-described guinea pig model. Mice are a powerful model organism, especially due to the large availability of antibodies, probes and genetic mutants. In this study, mice (n=114) and guinea pigs (n=35) underwent systemic treatment with either kanamycin or cisplatin. Auditory brainstem responses showed a significant threshold shift in guinea pigs 2 weeks after the beginning of the ototoxic treatment, while there was no significant hearing impairment recorded in mice. Hair cells and neuronal loss were correlated with hearing function in both guinea pigs and mice. These results indicate that the mouse is not a good model for ototoxicity, which should be taken into consideration in all further investigations concerning ototoxicity-induced hearing loss.

  3. Improved Method for Culturing Guinea-Pig Macrophage Cells

    NASA Technical Reports Server (NTRS)

    Savage, J.

    1982-01-01

    Proper nutrients and periodic changes in culture medium maintain cell viability for a longer period. New method uses a thioglycolate solution, instead of mineral oil, to induce macrophage cells in guinea pigs and also uses an increased percent of fetal-calf bovine serum in cultivation medium. Macrophage cells play significant roles in the body's healing and defense systems.

  4. Calcium influx and postjunctional supersensitivity in guinea pig aortic strips.

    PubMed

    Kaiman, M; Shibata, S

    1976-05-01

    Both reserpine and 6-hydroxydopamine (6-OHDA) pretreatment potentiated the sensitivity of guinea pig aortic strips to norepinephrine (NE), barium, methoxamine and potassium indicating postjunctional supersensitivity. However, cocaine treatmetn only potentiated the NE response indicating prejunctional supersensitivity. 6-OHDA and reserpine-induced supersensitivity but not cocaine-induced supersensitivity was accompanied by an increase in 45Ca influx.

  5. Reflections on the Fiftieth Reunion of the Guinea Pigs.

    ERIC Educational Resources Information Center

    Loud, Oliver

    1988-01-01

    A member of the original faculty of the experimental Ohio State University Laboratory High School reflects at a fiftieth reunion of the first graduating class. Students were used as guinea pigs to determine the effects of providing teenagers with liberating, interesting, and customized education from university faculty. (SM)

  6. Reflections on the Fiftieth Reunion of the Guinea Pigs.

    ERIC Educational Resources Information Center

    Loud, Oliver

    1988-01-01

    A member of the original faculty of the experimental Ohio State University Laboratory High School reflects at a fiftieth reunion of the first graduating class. Students were used as guinea pigs to determine the effects of providing teenagers with liberating, interesting, and customized education from university faculty. (SM)

  7. Improved Method for Culturing Guinea-Pig Macrophage Cells

    NASA Technical Reports Server (NTRS)

    Savage, J.

    1982-01-01

    Proper nutrients and periodic changes in culture medium maintain cell viability for a longer period. New method uses a thioglycolate solution, instead of mineral oil, to induce macrophage cells in guinea pigs and also uses an increased percent of fetal-calf bovine serum in cultivation medium. Macrophage cells play significant roles in the body's healing and defense systems.

  8. Guinea pig ductus arteriosus. II - Irreversible closure after birth.

    NASA Technical Reports Server (NTRS)

    Fay, F. S.; Cooke, P. H.

    1972-01-01

    To investigate the mechanism underlying irreversibility of ductal closure after birth, studies were undertaken to determine the exact time course for the onset of irreversible closure of the guinea pig ductus arteriosus. Parallel studies of the reactivity of ductal smooth muscle to oxygen and studies of the postpartum cellular changes within the vessel were also carried out.

  9. Purinergic regulation of guinea pig suburothelial myofibroblasts

    PubMed Central

    Wu, C; Sui, G P; Fry, C H

    2004-01-01

    The Ca2+-regulating and electrophysiological properties of guinea-pig suburothelial myofibroblasts have been measured in order to investigate their potential role in the sensation of bladder fullness, due to their strategic position between the urothelium and afferent fibres. Previous work has shown that stretch of the bladder wall releases ATP. Cells that stain positively for vimentin were isolated. About 45% of cells (median membrane capacitance 13.3 pF) exhibited spontaneous depolarizations to about −25 mV with a physiological Cl− gradient (frequency 2.6 ± 1.5 min−1, duration 14.5 ± 2.2 s, n = 15). Under voltage-clamp spontaneous inward currents (frequency 1.5 ± 0.2 min−1, duration 14.5 ± 7.0 s, n = 18) were recorded, with a similar reversal potential. The spontaneous currents were preceded by intracellular Ca2+ transients with a magnitude that was independent of membrane potential. All cells tested responded to ATP by generating an intracellular Ca2+ transient, followed by inward currents; the currents had a similar reversal potential and slope conductance to their spontaneous counterparts. ATP-generated transients were mimicked by UTP and ADP but not by α,β-methylene-ATP (1–10 μm) or CTP (30 μm), indicating that ATP acts via a P2Y receptor. Transients were partially attenuated by 1 mm suramin but PPADS (80 μm) had no effect. These data indicate that ATP acts via a P2Y receptor, but responses were resistant to the P2Y1 antagonist MRS2179. ATP-generated transients were abolished by intracellular perfusion with heparin and TMB-8 indicating that IP3 was the intracellular second messenger. The reversal potentials of the spontaneous and ATP-generated currents were shifted by about +45 mV by a 12-fold reduction of the extracellular [Cl−] and the currents were greatly attenuated by 1 mm DIDS. No transients were generated on exposure to the muscarinic agonist carbachol. We propose that these cells may play a regulatory step in the sensation of

  10. Antibodies to spermatozoa. III. Responses in rabbits and guinea-pigs to immunization with guinea-pig sperm cells

    PubMed Central

    Hekman, Annemarie; Shulman, S.

    1971-01-01

    The antigens of guinea-pig sperm cells, of both the epididymal and ejaculated (or seminal) types, have been studied, using rabbit and guinea-pig antisera. Several antigens could be revealed by gel diffusion studies, using well-washed but non-ruptured sperm cells, indicating that intentional cell breaking is not essential for demonstrating the antigens. This release of soluble antigen was followed as a function of time and temperature, both as total protein in supernatants and in increasing strength of precipitation. With rabbit antiserum, epididymal sperm showed two antigens, that were also demonstrated in epididymal and testicular extract and in seminal sperm. These other materials revealed additional antigens with these antisera. Immunofluorescent staining was limited to the acrosomes. With guinea-pig antibodies, no precipitating antigen that was characteristic of sperm could be seen. These antisera showed immunofluorescent staining of the acrosomes. The staining could be distinguished, in terms of thermostability, from the staining produced by normal serum. No evidence was found for the occurrence of any sperm-coating antigens in the guinea-pig, especially since both antiseminal plasma and antivesicular fluid antisera failed to give immunofluorescent staining of the sperm cells. ImagesFig. 1Fig. 3Fig. 4Fig. 5Fig. 6 PMID:4998924

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

    PubMed

    d'Ovidio, Dario; Santoro, Domenico

    2014-04-01

    Chirodiscoides caviae is the most common fur mite affecting guinea pigs; infestation is generally asymptomatic. No studies have been published on the prevalence of such mites in guinea pigs in southern Italy. We sought to evaluate the prevalence and the clinical signs of C. caviae infestation in guinea pigs in southern Italy. Clinical records of guinea pigs evaluated from August 2012 to July 2013 were retrospectively searched. In this retrospective matched case-control study, records of guinea pigs with evidence of C. caviae infestation were selected. The prevalence of C. caviae infestation was evaluated and exposure variables were assessed among guinea pigs with and without infestation using stepwise conditional logistic regression. Guinea pigs seen during the same time period, but without a diagnosis of C. caviae, were included as control animals. The prevalence of C. caviae was 32% (42 of 131); 66.6% of affected guinea pigs (28 of 42) originated from pet shops, whereas 28% (14 of 42) were privately owned. Thirty-one guinea pigs (73.8%) were asymptomatic, whereas 11 (26.1%) showed clinical signs (pruritus, alopecia, erythema and scaling). The most frequently affected area was the lumbosacral region (38 of 42). Guinea pigs in pet shops were more likely to be affected by C. caviae than owned guinea pigs (odds ratio, 5.12; 95% confidence interval, 2.32-11.29; P < 0.0001). The results of this study indicate a high prevalence of C. caviae infestation in guinea pigs in southern Italy. Chirodiscoides mites should be sought in guinea pigs, particularly in animals coming from pet shops. © 2014 ESVD and ACVD.

  12. Cytoarchitecture, Proliferative Activity and Neuroblast Migration in the Subventricular Zone and Lateral Ventricle Extension of the Adult Guinea Pig Brain.

    PubMed

    Jara, Nery; Cifuentes, Manuel; Martínez, Fernando; Salazar, Katterine; Nualart, Francisco

    2016-10-01

    In the mouse brain, neuroblasts generated in the subventricular zone (SVZ) migrate to the olfactory bulb (OB) through the rostral migratory stream (RMS). Although the RMS is not present in the human brain, a migratory pathway that is organized around a ventricular cavity that reaches the OB has been reported. A similar cavity, the lateral ventricle extension (LVE), is found in the adult guinea pig brain. Therefore, we analyzed cytoarchitecture, proliferative activity and precursor cell migration in the SVZ and LVE of 1-, 6- and 12-month-old guinea pigs. In young animals, we used confocal spectral and transmission electron microscopy to identify neuroblasts, astrocytes, and progenitor cells in the SVZ and LVE. Analysis of peroxidase diffusion demonstrated that the LVE was a continuous cavity lined by ependymal cells and surrounded by neuroblasts. Precursor cells were mostly located in the SVZ and migrated from the SVZ to the OB through the LVE. Finally, analysis of 6- and 12-month-old guinea pigs revealed that the LVE was preserved in older animals; however, the number of neurogenic cells was significantly reduced. Consequently, we propose that the guinea pig brain may be used as a new neurogenic model with increased similarity to humans, given that the LVE connects the LV with the OB, as has been described in humans, and that the LVE works a migratory pathway. Stem Cells 2016;34:2574-2586.

  13. Effect of Hypergravity Stress on Gaseous Exchange and Survival of Young and Old Guinea Pigs

    NASA Astrophysics Data System (ADS)

    Muradian, Kh. K.; Timchenko, A. N.

    Hypergravity tolerance decreases in aging Guinea pigs, the range being lower than in other studied species of laboratory mammals - mice, hamsters, and rats. Moreover, for the gaseous exchange rate and body temperature, the decline during the stress is not characteristic for Guinea pigs of both age groups, in contrast to other species. In general, hypergravity tolerance of Guinea pigs could be more appropriate experimental models.

  14. [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.

  15. Injuries caused by pigs in Papua New Guinea.

    PubMed

    Barss, P; Ennis, S

    Pigs are intelligent animals that can be formidable adversaries to humans because of their sharp tusks and their ability to attack swiftly. Domestic and feral pigs have an important role in the ecology of village life in Melanesia. A six-year review of all injuries that were caused by pigs that were referred from the villages in Milne Bay Province, Papua New Guinea, to the Provincial Hospital was completed. Some of the injuries that were seen among the 20 patients who were studied included: three penetrating abdominal injuries with prolapse and strangulation of the intestine; a "sucking" chest wound; bilateral pneumothoraces; two infected open fractures of the radius and the ulna; a perforating injury of the knee with septic arthritis; a hand injury with laceration of multiple tendons; an arterial injury of the wrist; injury of a tibial nerve with foot drop; and a severe scrotal injury with exposure of the testicles. Most injuries resulted from the hunting of feral pigs. Adult male hunters who used dogs and carried only one spear were injured most frequently. Wounds from injuries by pigs are deep, often involve multiple critical structures, and are grossly contaminated. Resuscitation requires the administration of fluid and often blood. Treatment includes irrigation, debridement and closure of the wound. The principles of managing such injuries, the prevention of injuries, the ecology of pigs and humans, human infections originating from pigs, and safer methods of hunting pigs are discussed.

  16. Mammary gland tumors in irradiated and untreated guinea pigs

    SciTech Connect

    Hoch-Ligeti, C.; Liebelt, A.G.; Congdon, C.C.; Stewart, H.L.

    1986-01-01

    This is a report of mammary gland tumors from 62 guinea pigs. The tumors arose in the terminal ductal-lobular units as either lobular acinar carcinoma or cystadenocarcinoma or as papillary carcinomas within large ducts near the mammilla. About half the number of the males had terminal ductal-lobular carcinomas and all but 2 of the papillary duct carcinomas also arose in males. Large tumors frequently exhibited squamous, chondromatous, osseous, fatty and myoepitheliomatous types of tissues. In 2 irradiated males and 1 female the tumors metastasized. Whole-body irradiation did not produce significant changes in the number or sex distribution or in the morphology of mammary gland tumors in inbred or outbred guinea pigs. All females had cystic ovaries without increase in granulosa cells, 24 (66.6%) had uterine tumors and 13 (34.2%) had adrenal gland tumors; all males had atrophic testes, 5 (16.5%) had testicular and 6 (22.2%) had adrenal gland tumors.

  17. Mandibular condylectomy in the guinea pig: quantitative triple fluorochrome study.

    PubMed

    Soni, N N; Malloy, R B

    1976-01-01

    Different-colored fluorochromes were administered sequentially to guinea pigs and the rate of bone formation measured in their condylectomized control contralateral hemimandibles. The values for labeled bone for condylectomized hemimandibles were lower than for the control contralateral hemimandibles of the same guinea pig. The differences in values of condylectomized and control contralateral sides for DCTC- and total surface area-labeled bone were statistically significant, but were not statistically significant for DCAF- and hematoporphyrin-labeled bone. There was partial regeneration of the condylar process. Although the condylectomized area was nearly normal in shape, its size and proportions were different from those of the contralateral hemimandibles that were not operated on. The greatest differences were noted in the length, height, and the distances measured between the inferior alveolar foramen and the mental foramen and the posterior border of the condyle.

  18. Spontaneous Ameloblastic Fibroma in a Young Guinea Pig

    PubMed Central

    Tanaka, Makoto; Sawamoto, Osamu

    2013-01-01

    A spontaneous ameloblastic fibroma was found in a 9-week-old guinea pig. Histopathologically, neoplastic cells consisted of two components: an odontogenic epithelium and odontogenic mesenchyme. The odontogenic epithelium formed strands, nests and islands that were interspersed within the odontogenic mesenchyme. In the marginal region, odontoblasts and scant dysplastic eosinophilic material were seen between these two components. Immunohistochemically, the odontogenic epithelium was positive for cytokeratin AE1/AE3, and the odontogenic mesenchyme and odontoblast were positive for vimentin, in the same manner as in the normal tooth germ (control). We could not obtain conclusive data suggesting that the eosinophilic material was dental hard tissue because the eosinophilic material was not stained specifically by any methods. Based on these histological characteristics, the tumor in the present case was diagnosed as an ameloblastic fibroma. This is the first report of ameloblastic fibroma in guinea pigs. PMID:24155567

  19. Spontaneous ameloblastic fibroma in a young Guinea pig.

    PubMed

    Tanaka, Makoto; Sawamoto, Osamu

    2013-09-01

    A spontaneous ameloblastic fibroma was found in a 9-week-old guinea pig. Histopathologically, neoplastic cells consisted of two components: an odontogenic epithelium and odontogenic mesenchyme. The odontogenic epithelium formed strands, nests and islands that were interspersed within the odontogenic mesenchyme. In the marginal region, odontoblasts and scant dysplastic eosinophilic material were seen between these two components. Immunohistochemically, the odontogenic epithelium was positive for cytokeratin AE1/AE3, and the odontogenic mesenchyme and odontoblast were positive for vimentin, in the same manner as in the normal tooth germ (control). We could not obtain conclusive data suggesting that the eosinophilic material was dental hard tissue because the eosinophilic material was not stained specifically by any methods. Based on these histological characteristics, the tumor in the present case was diagnosed as an ameloblastic fibroma. This is the first report of ameloblastic fibroma in guinea pigs.

  20. Form-deprivation myopia in the guinea pig (Cavia porcellus).

    PubMed

    Howlett, Marcus H C; McFadden, Sally A

    2006-01-01

    Form deprivation (FD) was induced in 61 guinea pigs with a diffuser worn on one eye. The form-deprived eye elongated and developed myopia within 6 days in animals raised under a 12:12 h light/dark cycle, but not when reared in darkness. After 11 days of FD, the average eye was -6.6 D more myopic and 146 microm longer than its fellow eye. Initially the myopia was mostly from vitreous chamber elongation, but with longer periods of FD, corneal power increases predominated. These effects were confirmed in schematic eyes. After a delay, FD also elongated the vitreous chamber of the non-deprived eye. The myopia rapidly abated once the diffusers were removed (65% within 24 h) due to inhibition of elongation and choroidal thickening. The guinea pig provides a fast mammalian model of FD myopia and corneal curvature regulation.

  1. Role of leukotrienes in airway hyperresponsiveness in guinea-pigs.

    PubMed Central

    Ishida, K.; Thomson, R. J.; Schellenberg, R. R.

    1993-01-01

    1. Repeated aerosolization of leukotriene C4 (LTC4) to guinea-pigs produced leftward shift in their pulmonary resistance (RL) dose-response curves to inhaled acetylcholine (ACh) without increasing the maximum responses. 2. Repeated LTC4 aerosolization did not increase airway eosinophils. 3. The 5-lipoxygenase-activating protein (FLAP) inhibitor, MK-886, prevented the leftward shift in RL dose-response curves to ACh following repeated antigen challenge in guinea-pigs. 4. MK-886 did not inhibit the increased maximal RL produced by repeated antigen challenge, nor inhibit the airway eosinophilia induced by repeated antigen challenge. 5. Our findings suggest that leukotrienes may account for the leftward shift in pulmonary resistance responses caused by antigen but do not cause the airway eosinophilia nor enhanced maximum broncho-constrictor response to antigen. PMID:8467358

  2. Interstitial pneumonitis induced in guinea pigs by Triatoma infestans antigens.

    PubMed

    Alonso, A; Caccuri, R L; Scavini, L M; Rodríguez, S M; Marino, G A

    1994-01-01

    Data concerning the experimental induction of hypersensitivity pneumonitis in guinea pigs with a Triatoma infestans antigen are presented. Glycoproteins obtained from the chitinous structures of T. infestans (79 kd + 11 kd) were aerosolized daily to guinea pigs during 7 weeks. The presence of specific antibodies (IgG and IgE) was detected by serological techniques; histopathological studies of the lungs showed interstitial infiltrates of macrophages and T-cells. Single non-necrotizing granulomas were seen at the seventh week of the experiment. The results from this animal model suggest that this hypersensitivity pneumonitis is a typical delayed-type reaction due to chronic contact with the heterologous glycoproteins of T. infestans.

  3. RELEASE OF KALLIKREIN FROM GUINEA PIG LUNG DURING ANAPHYLAXIS

    PubMed Central

    Jonasson, O.; Becker, E. L.

    1966-01-01

    An antigen-antibody reaction occurring in the perfused sensitized guinea pig lung, has been demonstrated to release kallikrein, a proteolytic enzyme related to the formation of kinins. This lung kallikrein is similar to plasma kallikrein in all properties studied, including susceptibility to the same inhibitors, electrophoretic mobility, and heterogeneity in molecular size. The release of kallikrein during anaphylaxis in the guinea pig lung occurs in the presence of ethylenediaminetetraacetate. Perfusion of ellagic acid into nonsensitized lungs will also release kallikrein, presumably through activation of Hageman factor. On the basis of these findings the hypothesis is suggested that the kallikrein in perfused lung activated by the antigen-antibody reaction is, in fact, plasma kallikrein. It is further suggested that activation of such kallikrein by the antigen-antibody reaction proceeds through Hageman factor. PMID:5937059

  4. Preliminary pharmacokinetic study of repeated doses of rifampin and rifapentine in guinea pigs.

    PubMed

    Dutta, Noton K; Alsultan, Abdullah; Peloquin, Charles A; Karakousis, Petros C

    2013-03-01

    Substitution of rifapentine (RFP) for rifampin (RIF) in the standard antituberculous regimen reduces the time required to cure chronic tuberculosis (TB) infection in mice, but not in guinea pigs. In order to gain insight into these discrepant findings, we conducted a steady-state pharmacokinetic (PK) study in healthy guinea pigs to study the metabolism and autoinduction of RIF and RFP. Both RFP and RIF 25-desacetyl metabolites (desRFP and desRIF, respectively), were detected at low concentrations in the serum of guinea pigs. The metabolite concentrations in guinea pigs are much lower than those seen in humans at steady state.

  5. Preliminary Pharmacokinetic Study of Repeated Doses of Rifampin and Rifapentine in Guinea Pigs

    PubMed Central

    Dutta, Noton K.; Alsultan, Abdullah; Peloquin, Charles A.

    2013-01-01

    Substitution of rifapentine (RFP) for rifampin (RIF) in the standard antituberculous regimen reduces the time required to cure chronic tuberculosis (TB) infection in mice, but not in guinea pigs. In order to gain insight into these discrepant findings, we conducted a steady-state pharmacokinetic (PK) study in healthy guinea pigs to study the metabolism and autoinduction of RIF and RFP. Both RFP and RIF 25-desacetyl metabolites (desRFP and desRIF, respectively), were detected at low concentrations in the serum of guinea pigs. The metabolite concentrations in guinea pigs are much lower than those seen in humans at steady state. PMID:23295923

  6. Hyperthyroidism in four guinea pigs: clinical manifestations, diagnosis, and treatment.

    PubMed

    Künzel, F; Hierlmeier, B; Christian, M; Reifinger, M

    2013-12-01

    Hyperthyroidism was diagnosed in four guinea pigs by demonstration of an increased serum total thyroxine concentration. The main clinical signs were comparable with those observed in feline hyperthyroidism and included weight loss despite maintenance of appetite and a palpable mass in the ventral cervical region. Three animals were treated successfully with methimazole for between 13 and 28 months. Clinical signs and regular measurement of circulating total thyroxine concentrations appear to be convenient parameters for monitoring response to medical therapy.

  7. Brevetoxin Depresses Synaptic Transmission in Guinea Pig Hippocampal Slices

    DTIC Science & Technology

    1993-01-01

    literature publication 4. TITLE AND SUBTITLE IS. FUNDING NUMBERS Brevetoxin depresses synpatic transmission in guinea pig hippocampal slices 61102A...The toxin produced a concentration -dependent depression of the orlhodroiiiicallk esoked population spl, , i~h an EC50 of 37 5 nM. Brevetoxin...precise mechanism b) which PbTx-3 depresses evoked responses is not certain, depolarization of the presynaptic nerve terminals leading to failure of

  8. Suppressed tuberculin reaction in guinea pigs following laser irradiation

    SciTech Connect

    Inoue, K.; Nishioka, J.; Hukuda, S.

    1989-01-01

    Tuberculin reactions were tested at the bilateral sites of the backs of sensitized guinea pigs. Laser irradiation at an energy fluence of 3.6 J at one site of reaction suppressed the reaction not only at the irradiated site but also at the contralateral nonirradiated site. These phenomena were observed when mononuclear cells were dominant in the perivascular cellular infiltration. The results indicate that local irradiation with a low-power laser has systemic inhibitory effects on delayed hypersensitivity reactions.

  9. Acute Oral Toxicity of Physostigmine Salicylate in Guinea Pigs

    DTIC Science & Technology

    1988-11-01

    of animals that died during the study presented with a serous oral discharge, perianal staining, and intussusception , observations consistent with the...receiving the lower doses. The two cases of ileocolic intussusceptions observed in animals 87E00239 and 87E00257 at necropsy is probably related to the...perioral staining and intussusception ) or common incidental findings (hepatic necrosis) of little clinical significance in guinea pigs. No evidence of direct

  10. Pharmacokinetics and pharmacodynamics of 4-aminopyridine in awake guinea pigs.

    PubMed

    Capacio, B R; Chang, F C; Spriggs, D; Byers, C E; Matthews, R L; Benton, B J

    1997-08-01

    The selective blockade of potassium channels on excitable membranes by 4-aminopyridine (4-AP) leads to facilitation of neurotransmitter release at a wide variety of synapses. This compound has been shown to be efficacious against lethality induced by saxitoxin (STX) and tetrodotoxin (TTX) in guinea pigs. To characterize the actions of 4-AP in guinea pigs we have investigated its pharmacokinetics (PK) and pharmacodynamics following a 2 mg/kg, intramuscular (im) dose in awake chronically instrumented (IN) animals. Animals were chronically instrumented for electrophysiologic recordings of diaphragmatic electromyogram (DEMG), lead II electrocardiogram (ECGII) and electrocorticogram (ECoG). Also, PK studies were carried out in uninstrumented (UN) guinea pigs. Blood and electrophysiologic data were collected at predetermined time intervals up to 4 hours post 4-AP administration. High performance liquid chromatography was used to determine plasma 4-AP concentrations. For IN and UN animals, plasma concentration-time data best fit a one-compartment model, and PK parameter estimates were similar for both groups. Peak plasma levels were found to occur between 16 and 17 min, and the half-lives of elimination were 65 and 71 min for IN and UN animals respectively. Heart and respiratory rates were elevated as early as 5 and 15 min respectively in response to 4-AP administration. The duration of action was approximately 1-1.5 half-lives of elimination beyond peak plasma levels. Maximum ECoG responses were observed between 12-15 min after 4-AP injection; some residual drug effects were still apparent at 240 min. The difference between the heart and respiratory rates and ECoG profiles suggests that these different physiological systems respond with varying degrees of sensitivity to plasma 4-AP concentrations. The stimulation of these systems is consistent with the action of 4-AP in reversing STX- and TTX-induced cardiorespiratory depression and decreased ECoG power in guinea pigs.

  11. Common Emergencies in Rabbits, Guinea Pigs, and Chinchillas.

    PubMed

    DeCubellis, Julie

    2016-05-01

    Rabbits, guinea pigs, and chinchillas are some of the more common exotic pets seen in emergency clinics. They frequently present with acute illnesses that are the result of several chronic conditions, most related to inadequate diet and husbandry. This article reviews the diagnosis and treatment of some of the more common acute illnesses. It also discusses the predisposing factors that culminate in acute presentations, so that emergency providers can recognize and be mindful of underlying causes of disease before treatment of acute illnesses.

  12. A guinea pig model of bovine pneumonic pasteurellosis.

    PubMed Central

    Morck, D W; Costerton, J W; Bolingbroke, D O; Ceri, H; Boyd, N D; Olson, M E

    1990-01-01

    The induction of pneumonic pasteurellosis in guinea pigs (Cavia porcellus) was examined. Specific pathogen free male guinea pigs were anesthetized and a tracheostomy performed to introduce 10(5), 10(4) or 10(3) Pasteurella haemolytica-A1 into the left principal bronchus. The surgical site was closed with tissue adhesive and staples and the animals were monitored for signs of respiratory tract infection. Within 24 hours after inoculation they became depressed, anorectic, pyretic and dyspneic. Fibrinous pleuropneumonia with prominent areas of necrosis and hemorrhage was present. Pericardial effusion was a frequent finding. There was infiltration of the pleura and alveoli with degenerate heterophils and macrophages, a hyperplastic mesothelium and fibrin exudation on the pleura and within alveoli. Hemorrhage, congestion, consolidation, edema and fibrin exudation were prominent in the hilar region of the lungs. Bacterial colonies were evident in all airways. More bacteria were recovered from infected lungs than were inoculated (p less than 0.05) indicating P. haemolytica was actively multiplying in the lungs. Hematological and clinical chemistry data were consistent with fibrinous pneumonia, however, blood cultures were positive for P. haemolytica in 61% (11/18) of animals sampled. Examination of pneumonic pasteurellosis in guinea pigs may be useful in studying pathogenetic and pathological features applicable to bovine pneumonic pasteurellosis (shipping fever pneumonia). Images Fig. 1. Fig. 2. Fig. 4. Fig. 5. Fig. 7. Fig. 8. Fig. 9. PMID:2306663

  13. Novel antitussive effect of suplatast tosilate in guinea pigs.

    PubMed

    Zhou, Jian-Rong; Syono, Ryo-ichi; Fukumi, Syu-ichi; Kimoto, Kenji; Shirasaki, Tetsuya; Soeda, Fumio; Takahama, Kazuo

    2015-01-01

    We studied the antitussive effects of suplatast, a Th2 cytokine inhibitor, and compared them with the effects of codeine using an experimental cough model in guinea pigs. Suplatast and codeine dose-dependently inhibited cough caused by mechanical stimulation of the larynx, but they did not inhibit cough caused by mechanical stimulation of the bifurcation of the trachea. In guinea pigs with bronchitis, suplatast had an antitussive effect on cough caused by stimulation of the larynx, whereas codeine did not inhibit such cough. In SO2-exposed guinea pigs, suplatast tended to inhibit cough caused by mechanical stimulation of the tracheal bifurcation. Further, suplatast inhibited citric acid-induced cough augmented by pretreatment with an angiotensin-converting enzyme inhibitor, whereas codeine did not inhibit such cough. Suplatast also inhibited bradykinin-induced discharges of airway vagal afferent nerves and significantly inhibited 4-aminopyridine-induced discharges of airway vagal afferent nerves. These findings indicate that the antitussive effects of suplatast are mediated by a novel mechanism involving the peripheral nervous system. © 2015 S. Karger AG, Basel.

  14. 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.

  15. Acute inhalation exposure of azodicarbonamide in the guinea pig.

    PubMed

    Shopp, G M; Cheng, Y S; Gillett, N A; Bechtold, W E; Medinsky, M A; Hobbs, C H; Birnbaum, L S; Mauderly, J L

    1987-02-01

    Humans have been exposed to azodicarbonamide (ADA) by inhalation where bulk quantities of ADA are handled in the workplace. Responses of some workers have led to concern for the potential irritant and sensitizing properties of inhaled ADA. This study examined the effects of inhaling ADA on lung structure and function of guinea pigs during and after an acute exposure. Groups of 20 guinea pigs were exposed to each of 3 concentrations of ADA (19, 58, and 97 mg/m3), plus air as a control, for 1 hr. Pulmonary function was measured before exposure (baseline), during exposure, immediately after exposure and 24 hr after exposure. Dynamic compliance (Cdyn), total pulmonary resistance (RL), tidal volume (VT), respiratory frequency and minute volume were measured. In addition, gross necropsies and histological examinations of respiratory tract tissues were done either immediately following the exposure or 24 hr after exposure. There were no effects of ADA exposure on gross necropsy, histology, Cdyn, or RL. Some significant, concentration-related decreases in VT, respiratory frequency and minute volume were seen. The magnitudes of these changes were small: the largest change was seen in minute volume, amounting to a 24% decrease in the high concentration group. Inhalation exposure of guinea pigs to ADA at concentrations of up to 97 mg/m3 resulted in minor changes in pulmonary function without any changes in lung histology.

  16. 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.

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

    SciTech Connect

    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 had 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.

  18. The origin of SFOAE microstructure in the guinea pig.

    PubMed

    Goodman, Shawn S; Withnell, Robert H; Shera, Christopher A

    2003-09-01

    Human stimulus-frequency otoacoustic emissions (SFOAEs) evoked by low-level stimuli have previously been shown to have properties consistent with such emissions arising from a linear place-fixed reflection mechanism with SFOAE microstructure thought to be due to a variation in the effective reflectance with position along the cochlea [Zweig and Shera, J. Acoust. Soc. Am. 98 (1995) 2018-2047]. Here we report SFOAEs in the guinea pig obtained using a nonlinear extraction paradigm from the ear-canal recording that show amplitude and phase microstructure akin to that seen in human SFOAEs. Inverse Fourier analysis of the SFOAE spectrum indicates that SFOAEs in the guinea pig are a stimulus level-dependent mix of OAEs arising from linear-reflection and nonlinear-distortion mechanisms. Although the SFOAEs are dominated by OAE generated by a linear-reflection mechanism at low and moderate stimulus levels, nonlinear distortion can dominate some part of, or all of, the emission spectrum at high levels. Amplitude and phase microstructure in the guinea pig SFOAE is evidently a construct of (i). the complex addition of nonlinear-distortion and linear-reflection components; (ii). variation in the effective reflectance with position along the cochlea; and perhaps (iii). the complex addition of multiple intra-cochlear reflections.

  19. Peptidoleukotriene binding in guinea pig uterine membrane preparations.

    PubMed

    Levinson, S L

    1984-08-01

    Peptidoleukotrienes are known to be potent smooth muscle contractile agents in many tissues, including guinea pig uterus. In order to characterize the receptors at which the leukotrienes interact, guinea pig uteri were homogenized in 50mM Tris-HCl, pH 7.4 at 4 degrees C and centrifuged at 1000xg for 10 min. The supernatant was centrifuged at 40,000 xg and the washed pellet was used to measure the binding of 3H-LTC4 and 3H-LTD4. Specific binding of 3H-LTD4 was not detected, but specific, saturable binding of 3H-LTC4 was measured at 4 degrees C, was complete in 10 min. and was rapidly reversible on addition of unlabeled LTC4. Binding was linear with protein concentration and stimulated by CaCl2 and L-serine borate. Scatchard and kinetic analysis of binding in the presence of calcium suggested a Kd of 10-12 nM. LTC4 was a more potent competitor of binding than LTD4 (IC50 - 40nM and 30 microM, respectively). FPL 55712 inhibited binding from 10-100 microM but stimulated binding at lower concentrations. Thus, the guinea pig uterus has specific receptors for LTC4, but not LTD4, that can be demonstrated by radioligand binding.

  20. Protection of Lassa virus-infected guinea pigs with Lassa-immune plasma of guinea pig, primate, and human origin.

    PubMed

    Jahrling, P B

    1983-01-01

    Lassa virus-immune plasma has been used to treat human Lassa fever patients; however, criteria for plasma selection were based arbitrarily on available serologic tools and protective efficacy was never directly assessed. To test the validity of plasma therapy for Lassa virus infections in an animal model, and to develop biologically relevant criteria for selection of protective immune plasma, inbred, strain 13 guinea pigs were infected with a lethal dose of Lassa virus and treated with various Lassa-immune plasmas obtained from guinea pigs, primates, and convalescent human patients. Neutralizing antibody titers were determined in a virus dilution, plaque reduction test, and were expressed as a log10 plaque-forming units (PFU) neutralization index (LNI). All guinea pigs treated with immune plasma 6 ml/kg/treatment on days 0, 3, and 6 after virus inoculation were protected, provided the LNI exceeded 2.0. Plasmas obtained from donors in early convalescence (32-45 days) had low titers of N-antibody (LNI less than 2) and failed to confer protection, despite high titers of Lassa antibody measured in the indirect fluorescent antibody (IFA) test. Higher doses of marginally titered plasma conferred increased protection. The degree of protection and suppression of viremia was closely associated with LNI an not IFA titers. Administration of low-titered plasma did not result in immune enhancement. A high dose of human plasma from Liberia (12 ml/kg/treatment) was required to confer complete protection to guinea pigs infected with a Lassa virus strain from Sierra Leone (LNI = 1.6), while a lower dose (3 ml/kg/treatment) was sufficient for protection against a Liberian strain (LNI = 2.8), suggesting that a geographic matching of immune plasma and Lassa virus strain origin may increase treatment success. These studies support the concept of plasma therapy for Lassa infection and suggest that the plaque reduction neutralization test is more appropriate than the IFA test for

  1. Hematology and clinical chemistry values of normal and euthymic hairless adult male Dunkin-Hartley guinea pigs (Cavia porcellus).

    PubMed

    Waner, Trevor; Avidar, Yaakov; Peh, Hao-Chang; Zass, Rosa; Bogin, Eitan

    1996-01-01

    Hematology and serum chemistry measurements were performed on blood specimens from 12 male Dunkin-Hartley hairless guinea pigs Crl:IAF(HA)BR and 10 haired Dunkin-Hartley male guinea pigs Crl:(HA)BR. Significantly higher activities of alanine aminotransferase, aspartate aminotransferase, amylase, and creatine kinase were observed in the hairless guinea pigs as compared to the haired strain. Alkaline phosphatase activity was found to be lower in the hairless guinea pig. The hairless guinea pigs were found to have serum urea concentrations approximately 46% higher than the normal guinea pig strain. The erythrocytic mean cell volume of the hairless strain was found to be smaller, with a greater hemoglobin content. Hairless guinea pigs were found to have approximately 40% fewer leukocytes with a reversed lymphocyte:neutrophil ratio compared to the haired guinea pigs which had much higher lymphocyte counts.

  2. Biosynthesis of factor V in isolated guinea pig megakaryocytes.

    PubMed Central

    Chiu, H C; Schick, P K; Colman, R W

    1985-01-01

    Although platelets contain Factor V, localized primarily in the alpha-granules, the origin of this coagulation cofactor in these cells is not known. We therefore explored whether isolated megakaryocytes could biosynthesize Factor V. Guinea pig plasma Factor V coagulant activity was demonstrated to be neutralized by human monoclonal and rabbit polyclonal antibodies directed monospecifically against human Factor V. These antibodies had been used earlier to purify human Factor V. These antibodies had been used earlier to purify human Factor V and to quantify Factor V antigen concentration, respectively (1983. Chiu, H. C., E. Whitaker, and R. W. Colman. J. Clin. Invest. 72:493-503). As determined by a competitive enzyme-linked immunosorbent assay with guinea pig plasma as a standard, Factor V solubilized from guinea pig megakaryocytes was present at 0.098 +/- 0.018 micrograms/10(5) cells. Each megakaryocyte contained about 500 times as much Factor V as is in a platelet (0.234 +/- 0.180 micrograms/10(8) platelets). The content of Factor V antigen in guinea pig plasma was greater (27.0 +/- 3.0 micrograms/ml) than that of Factor V antigen in human plasma (11.1 +/- 0.4 micrograms/ml). In contrast, human platelets contain ninefold more Factor V antigen (2.01 +/- 1.09 micrograms/10(8) platelets) than do guinea pig were 2.85 +/- 0.30 U/ml plasma, 0.022 +/- 0.012 U/10(8) platelets, and 0.032 +/- 0.03 U/10(5) megakaryocytes, compared with human values of 0.98 +/- 0.02 U/ml plasma and 0.124 +/- 0.064 U/10(8) platelets. Isolated megakaryocytes were found to contain Factor V by cytoimmunofluorescence. The megakaryocytes were incubated with [35S]methionine, and radiolabeled intracellular proteins purified were on a human anti-Factor V immunoaffinity column. The purified protein exhibited Factor V coagulant activity and neutralized the inhibitory activity of a rabbit antihuman Factor V antibody, which suggests that megakaryocyte Factor V is functionally and antigenically intact

  3. The video technique developed for measuring epicardial strains on guinea pig's left ventricle.

    PubMed

    Kirn, Borut; Starc, Vito

    2005-01-01

    Single-plain video used for measurements of epicardial strains is a technique that yields minor interference with the studied mechanical properties of the ventricle. Due to its low temporal resolution, the existing technique is, however, not appropriate for small animals. We questioned whether the technique could be improved enough to cope with higher heart rates and miniaturization necessary for experiments on rats, mice and guinea pigs. Therefore, we developed a high-speed video system and used it for measuring epicardial strains in guinea pig hearts in situ with the open chest. The improvement was achieved in video hardware (camera: Dalsa D6-0256; framegraber: EPIX PIXCI D32) and software, the markers (glowing acrylate crystals; diameter approximately 0.15 mm) and illumination (UVA light, OSRAM L). Three markers were attached onto the epicardium in the equatorial region of the left ventricular free wall, 1.5 mm apart, with fibrin glue. From their coordinates, we calculated two-dimensional finite strains with end diastole as the reference point. The accuracy of the displacement measurement of the technique and the error introduced by approximate-visual estimation of the left ventricle coordinate system were evaluated. The accuracy of the displacement measurement was +/-1.6 microm and the temporal resolution was 2 ms. Error due to approximate coordinate system orientation was +/-3% of the strain amplitude. The typical amplitude of strains was -0.06, -0.11 and 0.04 in circumferential, axial direction and in-plane shear, respectively. The improvements enable us to perform physiologically relevant measurements of epicardial deformations on guinea pig heart.

  4. Renal failure in a guinea pig (Cavia porcellus) following ingestion of oxalate containing plants

    PubMed Central

    Holowaychuk, Marie K.

    2006-01-01

    A 1-year-old guinea pig presented with anorexia, lethargy, and weight loss, 1 week after ingesting a peace lily leaf. Laboratory findings were suggestive of renal failure and included elevated blood urea nitrogen and creatinine with concurrent isosthenuria. The guinea pig was euthanized 1 month later due to worsening clinical signs. PMID:16933558

  5. THE EFFECT OF 6-MERCAPTOPURINE ON DELAYED HYPERSENSITIVITY IN GUINEA PIGS

    PubMed Central

    Hoyer, John R.; Hoyer, Leon W.; Good, Robert A.; Condie, Richard M.

    1962-01-01

    The development of tuberculin hypersensitivity in guinea pigs after BCG stimulation was suppressed by intramuscular administration of 50 mg/kg/day of 6-mercaptopurine started at the time of stimulation. Fasting of guinea pigs after BCG stimulation had no effect on the development of tuberculin hypersensitivity. PMID:13955205

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

    DTIC Science & Technology

    1984-01-01

    52 kHz by using a positive reinforcement training method. In this procedure, tones served as discriminative stimuli for a report response. Guinea pigs...and Stebbins, W. C. 1978. Auditory thresholds and kanamycin-induced hearing loss in the guinea pig assessed by a positive reinforcement procedure

  7. Attempt to immunize guinea pigs against leukemia by skin scarification with leukemic cell suspensions.

    PubMed

    Gross, L

    1973-12-01

    An attempt was made to immunize "strain 2" guinea pigs by superficial skin scarification with small doses of L2C leukemic cell suspensions. Among 203 scarified guinea pigs, 32 developed progressively growing leukemic tumors at the site of skin scarification. In 35 guinea pigs small intradermal tumors that appeared at the site of scarification regressed spontaneously; however, 15 guinea pigs in which the intradermal tumor regressed later developed generalized leukemia. In addition, 13 other animals developed generalized leukemia, without an apparent local tumor formation at the site of scarification. A total of 60 out of 203 scarified guinea pigs (30%) died from leukemia.143 Guinea pigs that survived the scarification were challenged by subcutaneous inoculation of massive doses (0.5 ml each of a 10-fold dilution from a 10% extract) of leukemic cell extracts and only 48 (34%) developed leukemia; 95 guinea pigs (66%) resisted the challenge and remained in good health. In a control experiment, 156 untreated "strain 2" guinea pigs were inoculated subcutaneously (0.5 ml each) with L2C leukemic cell suspensions of 10(-2) or 10(-3) dilution, and all but two (99%) developed generalized leukemia.

  8. Attempt to Immunize Guinea Pigs Against Leukemia by Skin Scarification with Leukemic Cell Suspensions

    PubMed Central

    Gross, Ludwik

    1973-01-01

    An attempt was made to immunize “strain 2” guinea pigs by superficial skin scarification with small doses of L2C leukemic cell suspensions. Among 203 scarified guinea pigs, 32 developed progressively growing leukemic tumors at the site of skin scarification. In 35 guinea pigs small intradermal tumors that appeared at the site of scarification regressed spontaneously; however, 15 guinea pigs in which the intradermal tumor regressed later developed generalized leukemia. In addition, 13 other animals developed generalized leukemia, without an apparent local tumor formation at the site of scarification. A total of 60 out of 203 scarified guinea pigs (30%) died from leukemia. 143 Guinea pigs that survived the scarification were challenged by subcutaneous inoculation of massive doses (0.5 ml each of a 10-fold dilution from a 10% extract) of leukemic cell extracts and only 48 (34%) developed leukemia; 95 guinea pigs (66%) resisted the challenge and remained in good health. In a control experiment, 156 untreated “strain 2” guinea pigs were inoculated subcutaneously (0.5 ml each) with L2C leukemic cell suspensions of 10-2 or 10-3 dilution, and all but two (99%) developed generalized leukemia. Images PMID:4519636

  9. Rapid Accumulation of Eosinophils in Lung Lesions in Guinea Pigs Infected with Mycobacterium tuberculosis

    PubMed Central

    Lasco, Todd M.; Turner, Oliver C.; Cassone, Lynne; Sugawara, Isamu; Yamada, Hiroyuki; McMurray, David N.; Orme, Ian M.

    2004-01-01

    Guinea pig eosinophils were positively identified in bronchoalveolar lavage populations and in the lung granulomas of Mycobacterium tuberculosis-infected guinea pigs. It is possible that the rapid influx of these cells, and their subsequent degranulation during acute pulmonary tuberculosis, may play a key role in the susceptibility of this animal model. PMID:14742563

  10. Identification of guinea pig gammadelta T cells and characterization during pulmonary tuberculosis.

    PubMed

    Xiong, Xiaowei; Morita, Craig T; Bukowski, Jack F; Brenner, Michael B; Dascher, Christopher C

    2004-11-01

    Guinea pigs are an alternative small animal model for many disease studies. Here we describe a pan-gammadelta monoclonal antibody (anti-TCRdelta1) specific for the constant region of human T cell receptor delta chains that cross-reacts with a subpopulation of guinea pig (Cavia porcellus) lymphocytes. The phenotype and distribution of this subpopulation is consistent with the guinea pig gammadelta T cell subset. FACS analysis of fresh PBMC and splenocytes from naïve guinea pigs revealed the presence of a subset of cells that stained with the anti-TCRdelta1 mAb. The relative percentage of anti-TCRdelta1 positive cells in PBMC and tissues is similar to that described for gammadelta T cells in other species. Immunohistochemistry of tissues also revealed a distribution of anti-TCRdelta1 positive cells consistent with gammadelta T cells. These data are further supported by staining of a polyclonal guinea pig T cell line that became progressively CD4 and CD8 negative in long-term culture. Analysis of PBMC from guinea pigs following aerosol infection with virulent Mycobacterium tuberculosis revealed no apparent changes in the steady-state percentage of blood gammadelta+ T cells. Taken together, these data suggest that the anti-TCRdelta1 antibody recognizes the gammadelta T cell subset in guinea pigs. This reagent may be useful for examining gammadelta T cells in various disease models where the guinea pig is a more desirable model for study.

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

    PubMed

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

    2017-05-02

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

  12. Dioxin in soil: bioavailability after ingestion by rats and guinea pigs

    SciTech Connect

    McConnell, E.E.; Lucier, G.W.; Rumbaugh, R.C.; Albro, P.W.; Harvan, D.J.; Hass, J.R.; Harris, M.W.

    1984-03-09

    Soil environmentally contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was given by gavage to guinea pigs and rats. The development of a characteristic clinicopathologic syndrome in guinea pigs, the induction of aryl hydrocarbon hydroxylase in rats, and the presence of TCDD in the livers of both species show that TCDD in soil exhibits high biological availability after ingestion.

  13. 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

  14. Morphologic investigations of the guinea pig model of iron overload.

    PubMed

    Schwartz, K A; Fisher, J; Adams, E T

    1993-01-01

    We have developed a guinea pig model of iron overload toxicity. Animals were administered intraperitoneal iron dextran 3 times a week to achieve total body iron load of 0.25, 0.5, 1.0, 1.5, and 2.0 g Fe/kg body weight in less than 30 days. Quantitation of tissue iron levels with atomic absorption indicated increased iron deposition in liver and heart of the iron-loaded guinea pigs (p < 0.001). Additionally, the iron-loaded pigs demonstrated decreased nuclear magnetic resonance spectroscopy T1 relaxation times in both liver and heart (p < 0.001). Serum iron, total body iron capacity, and transferrin saturation values were also determined in guinea pigs treated with 0.25, 0.5, and 1.0 g Fe/kg body weight. Serum iron and total iron-binding capacity were significantly increased at 0.5 and 1.0 g Fe/kg; transferrin saturation was elevated at 0.25 and 1.0 g Fe/kg. kg. Histologic examination of liver, heart, and bone marrow as well as ultrastructural studies on liver and heart confirmed increased iron deposition in treated animals. At the low iron dose level of 0.5 g Fe/kg, liver iron particles were primarily confined to Kupffer cells with minimal hepatocellular localization. Increased hepatocellular iron deposition was observed with larger doses of loaded iron. Myocardial iron was most prominent in interstitial cells of the epicardium, endocardium, myocardium, and coronary adipose tissue. Ultrastructurally, the presence of iron particles in perinuclear, membrane-bound structures (consistent with lysosomes) was confirmed using x-ray microanalysis. These morphological studies suggest that in this animal model siderosis of hepatic mononuclear phagocyte and myocardial interstitial cells may be the initial lesions leading to further biochemical and functional abnormalities. Correlation between tissue iron measurements and both light and electron microscopic changes, presented in this report, serve to introduce the iron-loaded guinea pig as a model for the study of iron

  15. Cardiac mechanical and electrophysiologic modulations of guinea-pig by caffeine and thapsigargin.

    PubMed

    Nario, K; Satoh, H

    1996-10-01

    1. The effects of caffeine and thapsigargin on the contractile force and the action potential in guinea-pig papillary muscles were examined. 2. Caffeine (1 to 10 mM) initially increased contractile force in a concentration-dependent manner. Subsequently, 1 mM caffeine decreased it as compared with precaffeine level (but not significantly). At 5 mM or 10 mM, caffeine also decreased contractile force, but the decrease was still positive as compared with control level. 3. Exchange to low [Ca]o (0.9 mM) or high [K]o (8 mM) decreased steady-state value during exposure to 1 mM caffeine. Addition of 1 microM thapsigargin (TG) decreased the steady-state value during exposure to 1 mM caffeine, but enhanced it with 5 mM and 10 mM caffeine. TG (1 microM) alone increased the force. 4. In electrophysiologic, studies, caffeine shortened the action potential duration (APD) in a concentration-dependent manner. In the presence of caffeine (1 mM), high [K]o shortened APD and decreased the action potential amplitude and resting potential. 5. These results suggest that in the presence of caffeine and/or thapsigargin calcium overload might not occur in the left ventricular papillary muscles of the guinea-pig heart.

  16. 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

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

    PubMed

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

    2016-04-01

    Cough remains a major unmet clinical need, and preclinical animal models are not predictive for new antitussive agents. We have investigated the mechanisms and pharmacological sensitivity of ozone-induced hypertussive responses in rabbits and guinea pigs. Ozone induced a significant increase in cough frequency and a decrease in time to first cough to inhaled citric acid in both conscious guinea pigs and rabbits. This response was inhibited by the established antitussive drugs codeine and levodropropizine. In contrast to the guinea pig, hypertussive responses in the rabbit were not inhibited by bronchodilator drugs (β2 agonists or muscarinic receptor antagonists), suggesting that the observed hypertussive state was not secondary to bronchoconstriction in this species. The ozone-induced hypertussive response in the rabbit was inhibited by chronic pretreatment with capsaicin, suggestive of a sensitization of airway sensory nerve fibers. However, we could find no evidence for a role of TRPA1 in this response, suggesting that ozone was not sensitizing airway sensory nerves via activation of this receptor. Whereas the ozone-induced hypertussive response was accompanied by a significant influx of neutrophils into the airway, the hypertussive response was not inhibited by the anti-inflammatory phosphodiesterase 4 inhibitor roflumilast at a dose that clearly exhibited anti-inflammatory activity. In summary, our results suggest that ozone-induced hypertussive responses to citric acid may provide a useful model for the investigation of novel drugs for the treatment of cough, but some important differences were noted between the two species with respect to sensitivity to bronchodilator drugs. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

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

    PubMed Central

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

    2016-01-01

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

  19. Ciliary Muscle Cell Changes During Guinea Pig Development

    PubMed Central

    Pucker, Andrew D.; Jackson, Ashley R.; Morris, Hugh J.; Fischer, Andrew J.; McHugh, Kirk M.; Mutti, Donald O.

    2015-01-01

    Purpose Guinea pig ciliary muscle (CM) increases robustly in volume, length, and thickness with age. We wanted to characterize CM cells during development to determine the contributions of hypertrophy (cell size increase) and hyperplasia (cell number increase) during development. Methods Six pigmented guinea pig eyes were collected at each of five ages: 1, 10, 20, 30, and 90 days. Refractive errors and axial lengths were determined. Eyes were temporally marked, enucleated, hemisected, and fixed. Nasal and temporal eye segments were embedded and 30-μm serial sections were collected; the two most central slides from each hemisection were analyzed with an epifluorescence microscope and Stereo Investigator software to determine normal morphologic parameters. Results Refractive errors became less hyperopic (P = 0.0001) while axial lengths and CM lengths, cross-sectional areas, volumes, and cell sizes all increased linearly with log age (all P < 0.00001). Ciliary muscle cell numbers increased only during the first 20 days of life (P = 0.02). Nasal and temporal CM lengths (P = 0.07), cross-sectional areas (P = 0.18), and cell numbers (P = 0.70) were not different, but CM cell sizes were initially larger temporally and became larger nasally after age 30 days. Conclusions The mechanism of guinea pig CM cell growth during the first 90 days of life was characterized by early hyperplasia combined with hypertrophic cell growth throughout development that results in larger CM lengths, cross-sectional areas, and volumes. Nasal-temporal CM development was generally symmetric, but there was more CM hypertrophy nasally at older ages. PMID:26641547

  20. Bronchodilator action of inhaled nitric oxide in guinea pigs.

    PubMed Central

    Dupuy, P M; Shore, S A; Drazen, J M; Frostell, C; Hill, W A; Zapol, W M

    1992-01-01

    The effects of inhaling nitric oxide (NO) on airway mechanics were studied in anesthetized and mechanically ventilated guinea pigs. In animals without induced bronchoconstriction, breathing 300 ppm NO decreased baseline pulmonary resistance (RL) from 0.138 +/- 0.004 (mean +/- SE) to 0.125 +/- 0.002 cmH2O/ml.s (P less than 0.05). When an intravenous infusion of methacholine (3.5-12 micrograms/kg.min) was used to increase RL from 0.143 +/- 0.008 to 0.474 +/- 0.041 cmH2O/ml.s (P less than 0.05), inhalation of 5-300 ppm NO-containing gas mixtures produced a dose-related, rapid, consistent, and reversible reduction of RL and an increase of dynamic lung compliance. The onset of bronchodilation was rapid, beginning within 30 s after commencing inhalation. An inhaled NO concentration of 15.0 +/- 2.1 ppm was required to reduce RL by 50% of the induced bronchoconstriction. Inhalation of 100 ppm NO for 1 h did not produce tolerance to its bronchodilator effect nor did it induce substantial methemoglobinemia (less than 2%). The bronchodilating effects of NO were additive with the effects of inhaled terbutaline, irrespective of the sequence of NO and terbutaline administration. Inhaling aerosol generated from S-nitroso-N-acetylpenicillamine also induced a rapid and profound decrease of RL from 0.453 +/- 0.022 to 0.287 +/- 0.022 cmH2O/ml.s, which lasted for over 15 min in guinea pigs broncho-constricted with methacholine. Our results indicate that low levels of inhaled gaseous NO, or an aerosolized NO-releasing compound are potent bronchodilators in guinea pigs. PMID:1644915

  1. Attenuation of streptomycin ototoxicity by tetramethylpyrazine in guinea pig cochlea.

    PubMed

    Cui, Cheng; Liu, Dajun; Qin, Xin

    2015-05-01

    Tetramethylpyrazine has been suggested to have a therapeutic effect on impaired hearing that is induced by aminoglycoside antibiotics. However, its effectiveness on streptomycin ototoxicity and its cellular mechanisms are relatively unknown. Here we investigate the protective effect of tetramethylpyrazine on streptomycin-induced ototoxicity in guinea pig cochlea. Prospective randomized laboratory study. Hearing Research Laboratory of China Medical University. Adult guinea pigs were randomized to 4 groups. Hearing sensitivity of guinea pigs was tested by auditory brainstem response measurements before streptomycin exposure and again 10 days later. The cochlear tissues were prepared for electron microscopy and immunohistochemical staining of heat shock protein 70 (HSP70). The effect of tetramethylpyrazine on streptomycin-induced activation of caspase-3 was evaluated by Western blotting. Co-therapy with tetramethylpyrazine reduced a profound streptomycin-induced auditory threshold shift compared with streptomycin treatment alone (P = .0002 or P = .00008). Tetramethylpyrazine also attenuated the structural disruption in streptomycin-treated outer hair cells and marginal cells of vascular stria by transmission electronic microscopy and scanning electronic microscopy, respectively. Moreover, tetramethylpyrazine decreased the streptomycin-stimulated expressions of HSP70 and caspase-3. The correlation analysis demonstrated that HSP70 expression had a positive correlation with auditory brainstem response thresholds (|R| = 0.6-0.9, P = .0073 or P = .0169). Our data suggest that the protective effect of tetramethylpyrazine on hearing function is associated with the reduction of stress response and inhibition of apoptosis. Tetramethylpyrazine may have therapeutic potential for patients with ototoxicity diseases. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.

  2. Auditory effects of noise on infant and adult guinea pigs.

    PubMed

    Danto, J; Caiazzo, A J

    1977-01-01

    This pilot study compared the susceptibility of the infant (48 hr) and adult (120 days) guinea pig to the effects of noise. Subjects were exposed to a narrow band of noise (center frequency 4 kHz) at an intensity of 115 dB sound pressure level (SPL) for 1 hr. Postexposure thresholds were obtained by a conditioned suppression technique. Results indicated that the infant animals displayed a mean hearing threshold of 25 dB SPL that significantly differed from the adult mean threshold of 7.5 dB SPL.

  3. Antimicrobial therapy of experimental Legionella micdadei pneumonia in guinea pigs.

    PubMed Central

    Pasculle, A W; Dowling, J N; Frola, F N; McDevitt, D A; Levi, M A

    1985-01-01

    Several antimicrobial agents were evaluated for activity against experimental Legionella micdadei pneumonia in guinea pigs. Erythromycin, rifampin, doxycycline, and sulfamethoxazole-trimethoprim produced significant reductions in mortality. Penicillin, cefazolin, cefoxitin, chloramphenicol, and gentamicin were not efficacious even though, at the doses administered, the peak concentrations of these agents in serum substantially exceeded their MICs for the test strain. It is suggested that the poor performance of the latter group of agents resulted from poor penetration into cells in which L. micdadei was multiplying. PMID:3878688

  4. Early histological maturation in the hippocampus of the guinea pig.

    PubMed

    Nacher, J; Palop, J J; Ramirez, C; Molowny, A; Lopez-Garcia, C

    2000-06-01

    The vesicular zinc-rich synaptic systems of the principal neurons of the hippocampus are well developed in newborn guinea pigs, a precocial species. In addition, alvear and fimbrial myelinated fibers as well as significant inhibitory interneurons (i.e. somatostatin, parvalbumin and opioid immunoreactive hippocampal interneurons) are also well developed. On the contrary, neither vesicular zinc synapses nor myelinated fibers nor the above mentioned immunoreactive interneurons are detectable in newborn specimens of other related altricial species such as rats or rabbits. These data suggest that early maturation of a highly integrative center related to cognitive map building such as the hippocampus is characteristic of precocial species.

  5. The present use of guinea pigs for chiropractic research *

    PubMed Central

    McGregor, Marion; Wiles, Michael R.; Grice, Adrian S.

    1980-01-01

    The necessity for an animal model in chiropractic research is considered and a short review of previous experimentation of manipulation on animals is presented. The guinea pig is proposed as a suitable animal model, and research into its suitability is presented. Analysis includes the animal’s physical characteristics, the choice of anesthetic and parametric and roentgenographic evaluation. A device for supporting the anesthetized animal during standard and motion roentgenographic examination is described. We conclude that this animal model fulfills the requirements necessary for successful investigation in chiropractic research, and the need for such investigation is emphasized. ImagesFigure 1Figure 2

  6. Microbial flora of odontogenic abscesses in pet guinea pigs.

    PubMed

    Minarikova, A; Hauptman, K; Knotek, Z; Jekl, V

    2016-10-01

    Abscesses of odontogenic origin in guinea pigs pose a serious health problem and need to be treated with a combination of surgical and medical therapy. The aim of this prospective study was to describe the microbial flora of odontogenic abscesses associated with osteomyelitis in 24 pet guinea pigs, to perform antibiotic sensitivity testing, and to make recommendations for practitioners on the antibiotics of first choice. Inclusion criteria for the study included the animal being diagnosed with an odontogenic abscess which underwent surgery and was not pre-treated with an antibiotic. Inclusion criteria matched for 24 guinea pigs. Samples (pus, capsule and affected tooth/bone) for bacteriological examination were collected under sterile conditions during the surgical procedure. The most commonly isolated bacteria from abscesses of odontogenic origin were Bacteroides fragilis in 12.8 per cent (6/47) of cases, Pasteurella multocida in 10.6 per cent (5/47) and Peptostreptococcus anaerobius in 8.5 per cent (4/47). Aerobic bacterial species only were isolated in 29.2 per cent (7/24) of cases, anaerobic bacteria only were isolated in 33.3 per cent (8/24), and mixed infection with anaerobic and aerobic bacterial species was seen in 37.5 per cent (9/24). Aerobes (n=20) were sensitive to enrofloxacin and marbofloxacin in 100 per cent of samples, benzylpenicillin potassium (penicillin G, PNCG) in 90 per cent, cephalotin in 85 per cent, amoxicillin-clavulanate in 75 per cent, doxycycline in 70 per cent, gentamicin in 65 per cent and trimethoprim-sulfamethoxazole in 55 per cent. Anaerobes (n=27) were sensitive to amoxicillin-clavulanate in 100 per cent of cases, clindamycin in 96.3 per cent, metronidazole in 92.6 per cent, PNCG in 92.6 per cent and cephalotin in 74.1 per cent. As guinea pigs are strictly herbivorous animals, based on the results of this study the recommended antibiotic treatment for odontogenic abscesses is a combination of fluoroquinolones and metronidazole

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

    PubMed

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

    2012-04-25

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

  8. Effects of extracellular calcium and sodium on depolarization-induced automaticity in guinea pig papillary muscle.

    PubMed

    Katzung, B G

    1975-07-01

    Regenerative discharge of action potentials is induced in mammalian papillary muscles by passage of small depolarizing currents. In this paper, the effects of various extracellular calcium and sodium concentrations and of tetrodotoxin on this phenomenon were studied in guinea pig papillary muscles in a sucrose gap chamber. Phase 4 diastolic depolarization was found to be associated with an increase in membrane resistance. The slope of phase 4 depolarization was decreased by reductions in extracellular calcium or sodium concentration. The range of maximum diastolic potentials and the thresholds from which regenerative potentials arose were reduced, especially at the positive limit of potentials, by a reduction in either ion. It was concluded that both calcium and sodium influence diastolic depolarization and participate in the regenerative action potentials of depolarization-induced ventricular automaticity.

  9. Antimony-induced cardiomyopathy in guinea-pig and protection by L-carnitine

    PubMed Central

    Alvarez, Marco; Malécot, Claire O; Gannier, François; Lignon, Jacques M

    2004-01-01

    Antimony (Sb) is the mainstay for the treatment of Leishmaniasis. It has serious, often lethal, cardiovascular side effects. The objective of this study was to examine the effects of Sb treatment upon the electrocardiogram (ECG), myocyte contractility (assessed by monitoring sarcomere length during field stimulation), whole-cell action potential (AP) and calcium current (ICa) of the guinea-pig and to evaluate L-carnitine as a cardioprotective agent. Guinea-pigs received daily injections of either saline, Sb(V), Sb(III), L-carnitine or L-carnitine with Sb(III). Eight lead ECGs were recorded under halothane anaesthesia every 4 days. At the end of each treatment regime, animals were killed and ventricular myocytes were enzymatically isolated. Treatment with Sb(V) for 26 days prolonged the QT interval of the ECG. Treatment with Sb(III) was lethal within 2 days for ∼50% of the animals. The survivors showed ECG alterations similar to those described in man: T wave flattening and/or inversion, depression of the ST segment, and elongation of RR and QT intervals. Their ventricular myocytes showed impaired contraction responses to changes in stimulus frequency, elongated AP and reduced ICa. Combined treatment with L-carnitine and Sb(III) delayed mortality. Prior treatment with L-carnitine followed by combined treatment with L-carnitine and Sb(III) reduced mortality to <10% over 12 days and these animals showed normal ECG. Their myocytes showed normal contractility and AP. It is concluded that L-carnitine has a preventive cardioprotective role against antimony-induced cardiomyopathy. The mechanism of action of L-carnitine may be to counter oxidative stress caused by Sb(III). PMID:15644865

  10. Cutaneous sensitization to some polyisocyanate prepolymers in guinea pigs.

    PubMed

    Zissu, D; Binet, S; Limasset, J C

    1998-11-01

    Isocyanates are used extensively in the polyurethane industry. Pulmonary and dermal sensitization resulting from exposure to diisocyanates has frequently been reported, but the potential effects of polyisocyanates on health are less well known. Thus, since 1978, occupational exposure limits have been established for diisocyanates only. Nevertheless, respiratory diseases and dermatitis have been reported in the polyurethane industry after accidental isocyanate contact during spills or splashes. The aim of this experimental work was to assess the dermal hypersensitivity of guinea pigs to some polyisocyanate prepolymers by means of a well-conducted standard predictive Buehler test. Our results showed that dicyclohexylmethane 4,4'-diisocyanate (HMDI), toluylene 2,4-diisocyanate (TDI), TDI adduct triol, TDI isocyanurate, 1,6-hexamethylene diisocyanate (HDI), HDI isocyanurate, HDI biuret and isophorone diisocyanate (IPDI) induced dermal sensitization while IPDI isocyanurate did not. In conclusion, the dermal hypersensitivity of guinea pigs to some polyisocyanates was similar to those of their corresponding monomers except for IPDI isocyanurate, suggesting that the results from diisocyanate monomers could not be a valuable approach for the detection of the sensitization potency of the corresponding prepolymers.

  11. Acid secretion by guinea-pig isolated stomach.

    PubMed Central

    Holton, P; Spencer, J

    1976-01-01

    An isolated stomach preparation from the guinea-pig is described. 2. Both histamine acid phosphate (1-4 mug/ml.) and theophylline hydrate (0-2-3-2 mg/ml.) separately stimulated hydrochloric acid, HCl, secretion from the guinea-pig stomach preparation. A linear dose-response relationship was obtained for theophylline. 3. Addition of theophylline (0-2 and 1-6 mg/ml.) during maximal response to histamine increased the secretion further, whereas addition of histamine during maximal response to theophylline did not cause further secretion. 4. The secretory activities of Nalpha-MeH (0-3-5-0 muM), Nalpha-Me2H (1-2-9-5 muM) and 5-MeH (1-5-12 muM) were compared with histamine (0-9-13 muM) on a threshold background secretion induced by theophylline (0-2 mg/ml.). Linear log.-dose response relationships were obtained for each test drug. The results confirm that Nalpha-MeH is a more potent secretagogue than histamine. 5. Pentagastrin (0-3-1-0 mug/ml.) stimulated HCl secretion in approximately half the experiments. The response was often transitory. In the other experiments, pentagastrin had no effect on HCl secretion although subsequent administration of histamine did stimulate HCl secretion. PMID:3644

  12. Pulmonary effects of acid sulfate inhalation in the guinea pig

    SciTech Connect

    Silbaugh, S.A.; Mauderly, J.L.; Wolff, R.K.; Carpenter, R.L.; Brownstein, D.G.; Harkema, J.R.; Rothenberg, S.J.

    1982-07-01

    Guinea pigs were exposed by inhalation for 1 to 8 hours to sulfuric acid aerosols of various sizes and concentrations in order to provide quantitative information for standards setting. The effects of sulfuric acid aerosols were examined to determine acute mortality, changes in respiratory function and morphology, response mechanisms, differences in individual sensitivity and changes in airway response to bronchoconstrictors. An aerosol generator for another sulfur-containing pollutant, ammonium bisulfite, was developed for use in animal exposures. Also, lung lesions which simulate human emphysema were produced by intratracheal elastase instillation to investigate a potential impaired animal model for sulfur pollutant exposures. Pulmonary mechanics, lung morphology, and histamine sensitivity data all suggest that the guinea pig reacts to sulfuric acid aerosols with a nearly all-or-none airway constrictive response. Results also indicate that the concentration at which this response occurs is affected by aerosol size, exposure profile and individual animal sensitivity. No acute pulmonary function changes were noted at concentrations below 15 mg/m/sup 3/. The reason for these differences is unknown.

  13. Noninvasive detection of airway constriction in awake guinea pigs

    SciTech Connect

    Silbaugh, S.A.; Mauderly, J.L.

    1984-01-01

    Tidal volume measured by the barometric method is very sensitive to increases in compression and expansion of alveolar gas, such as would be expected to occur during airway narrowing or closure. By comparing a barometric method tidal volume signal (VT') with a reference tidal volume (VT) obtained with a head-out pressure plethysmograph, a simple index related to gas compressibility effects was calculated (VT/VT'). Changes in this index were compared with decreases in dynamic compliance (Cdyn) during histamine aerosol challenge of 15 Charles River Hartley guinea pigs. Decreases in VT/VT' occurred during all aerosol challenges and were correlated with decreases in Cdyn. Decreases in VT/VT' were most marked at Cdyn values of less than 50% of base line. At Cdyn of less than 15% of base line, VT' was 3.1-4.8 times the VT reference signal. No increase in total pulmonary resistance was noted, and Cdyn and VT/VT' returned to base line after histamine exposure was stopped. The authors conclude that gas compressibility effects become substantial during histamine-induced airway constriction in the guinea pig and that the VT/VT' ratio appears to provide a simple noninvasive method of detecting these changes.

  14. Synaptic localization of. kappa. opioid receptors in guinea pig neostriatum

    SciTech Connect

    Jomary, C.; Beaudet, A. ); Gairin, J.E. )

    1992-01-15

    Distribution of {kappa} opioid receptors was examined by EM radioautography in sections of guinea pig neostriatum with the selective {sup 125}I-labeled dynorphin analog (D-Pro{sup 10})dynorphin-(1-11). Most specifically labeled binding sites were found by probability circle analysis to be associated with neuronal membrane appositions. Because of limitations in resolution of the method, the radioactive sources could not be ascribed directly to either one of the apposed plasma membranes. Nevertheless, three lines of evidence favored a predominant association of ligand with dendrites of intrinsic striatal neurons: (1) the high frequency with which labeled interfaces implicated a dendrite, (2) the enrichment of dendrodendritic interfaces, and (3) the occurrence of dendritic profiles labeled at several contact points along their plasma membranes. A small proportion of labeled sites was associated with axo-axonic interfaces, which may subserve the {kappa} opioid-induced regulation of presynaptic dopamine and acetylcholine release documented in guinea pig neostriatum. These results support the hypothesis that in mammalian brain {kappa} opioid receptors are conformationally and functionally distinct from {mu} and {delta} types.

  15. Synaptic localization of kappa opioid receptors in guinea pig neostriatum.

    PubMed Central

    Jomary, C; Gairin, J E; Beaudet, A

    1992-01-01

    Distribution of kappa opioid receptors was examined by EM radioautography in sections of guinea pig neostriatum with the selective 125I-labeled dynorphin analog [D-Pro10]dynorphin-(1-11). Most specifically labeled binding sites were found by probability circle analysis to be associated with neuronal membrane appositions. Because of limitations in resolution of the method, the radioactive sources could not be ascribed directly to either one of the apposed plasma membranes. Nevertheless, three lines of evidence favored a predominant association of ligand with dendrites of intrinsic striatal neurons: (i) the high frequency with which labeled interfaces implicated a dendrite, (ii) the enrichment of dendro-dendritic interfaces, and (iii) the occurrence of dendritic profiles labeled at several contact points along their plasma membranes. A small proportion of labeled sites was associated with axo-axonic interfaces, which may subserve the kappa opioid-induced regulation of presynaptic dopamine and acetylcholine release documented in guinea pig neostriatum. Although most membrane-associated kappa sites were found at extrasynaptic locations, approximately 23% were associated with synaptic specializations. This proportion is markedly higher than that previously reported for either mu or delta sites in rat neostriatum. Whether labeled synapses represent preferential sites of action for kappa ligands remains to be established. In any event, these results support the hypothesis that in mammalian brain kappa opioid receptors are conformationally and functionally distinct from mu and delta types. Images PMID:1346233

  16. Spasmolytic effect of traditional herbal formulation on guinea pig ileum

    PubMed Central

    Kumar, Dushyant; Ganguly, Kuntal; Hegde, H. V.; Patil, P. A.; Kholkute, S. D.

    2015-01-01

    Background: The herbal formulation consisting of Andrographis paniculata Nees., Cassia fistula L., Foeniculum vulgare Mill. and Cuminum cyminum L. is widely used by the local traditional practitioners in rural Northern Karnataka for spasmodic abdominal pain. Objective: The present study was undertaken to evaluate safety and spasmolytic effect of poly-herbal formulation. Materials and Methods: Acute toxicity studies were carried out in Swiss mice, as per the Organization for Economic Co-operation and Development (OECD) guidelines. The spasmolytic activity of the formulation was studied in isolated guinea pig ileum model using histamine and acetylcholine as agonists. The data were analyzed by one-way ANOVA, followed by Dunnetts post-hoc test and P ≤ 0.05 was considered as significant. Results: The formulation did not show any adverse toxic effects and found to be safe. It also showed significant (P < 0.05) relaxation in different agonist like histamine and acetylcholine-induced contractions in guinea pig ileum. Conclusion: Antispasmodic activity of the herbal formulation can be attributed to its atropine-like activity. The present findings, therefore, support its utility in spasmodic abdominal pain. PMID:26604555

  17. Synaptic localization of kappa opioid receptors in guinea pig neostriatum.

    PubMed

    Jomary, C; Gairin, J E; Beaudet, A

    1992-01-15

    Distribution of kappa opioid receptors was examined by EM radioautography in sections of guinea pig neostriatum with the selective 125I-labeled dynorphin analog [D-Pro10]dynorphin-(1-11). Most specifically labeled binding sites were found by probability circle analysis to be associated with neuronal membrane appositions. Because of limitations in resolution of the method, the radioactive sources could not be ascribed directly to either one of the apposed plasma membranes. Nevertheless, three lines of evidence favored a predominant association of ligand with dendrites of intrinsic striatal neurons: (i) the high frequency with which labeled interfaces implicated a dendrite, (ii) the enrichment of dendro-dendritic interfaces, and (iii) the occurrence of dendritic profiles labeled at several contact points along their plasma membranes. A small proportion of labeled sites was associated with axo-axonic interfaces, which may subserve the kappa opioid-induced regulation of presynaptic dopamine and acetylcholine release documented in guinea pig neostriatum. Although most membrane-associated kappa sites were found at extrasynaptic locations, approximately 23% were associated with synaptic specializations. This proportion is markedly higher than that previously reported for either mu or delta sites in rat neostriatum. Whether labeled synapses represent preferential sites of action for kappa ligands remains to be established. In any event, these results support the hypothesis that in mammalian brain kappa opioid receptors are conformationally and functionally distinct from mu and delta types.

  18. Enzymic synthesis of leukotriene B4 in guinea pig brain.

    PubMed

    Shimizu, T; Takusagawa, Y; Izumi, T; Ohishi, N; Seyama, Y

    1987-05-01

    Leukotriene B4 [5(S), 12(R)-dihydroxy-6, 14-cis-8,10-trans-eicosatetraenoic acid] was obtained from endogenous arachidonic acid when slices of the guinea pig brain cortex were incubated with the calcium ionophore A 23187. Enzymes involved in its synthesis, arachidonate 5-lipoxygenase [arachidonic acid to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid and subsequently to leukotriene A4] and leukotriene A4 hydrolase (leukotriene A4 to B4), were present in the cytosol fraction. Arachidonate 5-lipoxygenase was Ca2+-dependent, and was stimulated by ATP and the microsomal membrane, as was noted for the enzyme from mast cells. The lipid hydroperoxides stimulated 5-lipoxygenase by four- to sixfold. The leukotriene A4 hydrolase activity was rich in brain, and the specific activity (0.4 nmol/min/mg of protein) was much the same as that of guinea pig leukocytes. High activities of these enzymes were detected in the olfactory bulb, pituitary gland, hypothalamus, and cerebral cortex. Since leukotriene B4 is enzymically synthesized in the brain, possible roles related to neuronal functions or dysfunctions deserve to be examined.

  19. ACTION OF DIPHTHERIA TOXIN IN THE GUINEA PIG

    PubMed Central

    Baseman, Joel B.; Pappenheimer, A. M.; Gill, D. M.; Harper, Annabel A.

    1970-01-01

    The blood clearance and distribution in the tissues of 125I after intravenous injection of small doses (1.5–5 MLD or 0.08–0.25 µg) of 125I-labeled diphtheria toxin has been followed in guinea pigs and rabbits and compared with the fate of equivalent amounts of injected 125I-labeled toxoid and bovine serum albumin. Toxoid disappeared most rapidly from the blood stream and label accumulated and was retained in liver, spleen, and especially in kidney. Both toxin and BSA behaved differently. Label was found widely distributed among all the organs except the nervous system and its rate of disappearance from the tissues paralleled its disappearance from the circulation. There was no evidence for any particular affinity of toxin for muscle tissue or for a "target" organ. Previous reports by others that toxin causes specific and selective impairment of protein synthesis in muscle tissue were not confirmed. On the contrary, both in guinea pigs and rabbits, a reduced rate of protein synthesis was observed in all tissues that had taken up the toxin label. In tissues removed from intoxicated animals of both species there was an associated reduction in aminoacyl transferase 2 content. It is concluded that the primary action of diphtheria toxin in the living animal is to effect the inactivation of aminoacyl transferase 2. The resulting inhibition in rate of protein synthesis leads to morphologic damage in all tissues reached by the toxin and ultimately to death of the animal. PMID:5511567

  20. Prokaryotic Expression and In vitro Functional Analysis of IL-1 and MCP-1 from Guinea Pig

    PubMed Central

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

    2012-01-01

    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 chemo attractant protein-1 (MCP-1) were efficiently cloned and expressed in a prokaryotic expression vector (pET-30a) 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. PMID:22744745

  1. 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.

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

    PubMed

    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.

  3. Diseases in pet guinea pigs: a retrospective study in 1000 animals.

    PubMed

    Minarikova, A; Hauptman, K; Jeklova, E; Knotek, Z; Jekl, V

    2015-08-22

    Guinea pigs are commonly kept as pet animals; however, information about particular disease prevalence is lacking. The objective of this article was to present disease prevalence in 1000 pet guinea pigs from private owners divided into three age groups: under two years; between two and five years; and above five years. Medical records of guinea pigs (Cavia aperea f. porcellus) that were presented to the authors' clinic in the period from January 2008 to August 2013 were reviewed. The most commonly diagnosed disease in guinea pigs was dental disease (36.3 per cent), with higher prevalence in the middle age group (P<0.001) and in males (P<0.001) rather than females. Skin problems were seen as the second most common disease (33.3 per cent), with higher prevalence in male guinea pigs (P<0.001) and in animals younger than two years (P<0.001). Ovarian cystic disease was the third most commonly seen disorder, with higher prevalence in females older than two years (P<0.001). Other common health disorders included gastrointestinal stasis, heterotopic ciliary body calcifications, fatty eye and tibiofemoral osteoarthritis. Only 81 guinea pigs from a total of 1000 animals were healthy. This is the first study to describe the disease prevalence in three age groups of pet guinea pigs. British Veterinary Association.

  4. 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

  5. Prevalence of dermatophytes and other superficial fungal organisms in asymptomatic guinea pigs in Southern Italy.

    PubMed

    d'Ovidio, D; Grable, S L; Ferrara, M; Santoro, D

    2014-07-01

    Guinea pigs have been indicated as a potential source of zoophilic dermatophytes that cause human dermatomycosis. The purpose of this study was to evaluate the prevalence of dermatophytes as well as saprophytic fungi in asymptomatic pet guinea pigs in Southern Italy. Two-hundred pet guinea pigs were enrolled from both private veterinary clinics and pet shops in the Campania region, Italy, from August 2012 to September 2013. Samples were collected using the MacKenzie's toothbrush technique. The plates were incubated for four weeks at 25°C and identification of the fungal colonies was based on both macroscopic and microscopic characteristics. Two pathogenic dermatophytes were isolated in 9 (4·5%) of 200 guinea pigs; Epidermophyton species in 2 (1%) and Scopulariopsis species in 7 (3·5%). Saprophytic dermatophytes were isolated from 151 (75·5%) animals enrolled. No fungal growth was observed in 40 (20%) guinea pigs. The results of this study indicate a low prevalence of pathogenic dermatophytes in pet guinea pigs in Southern Italy but the presence of Epidermophyton and Scopulariopsis species in asymptomatic pet guinea pigs. © 2014 British Small Animal Veterinary Association.

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

    PubMed

    Kleven, Gale A; Joshi, Prianca

    2016-03-01

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

  7. 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.

  8. 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

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

    PubMed

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

    2013-03-01

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

  10. 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

  11. β-adrenoceptor activation plays a role in the reverse rate-dependency of effective refractory period lengthening by dofetilide in the guinea-pig atrium, in vitro

    PubMed Central

    Kovács, Anikó; Magyar, János; Bányász, Tamás; Nánási, Péter P; Szénási, Gábor

    2003-01-01

    Blockers of the rapid component of the delayed rectifier potassium current (IKr) prolong cardiac action potential duration (APD) and effective refractory period (ERP) in a reverse rate-dependent manner. Since activation of β-adrenoceptors attenuates prolongation of APD evoked by IKr blockers, rate-dependent neuronal noradrenaline liberation in the myocardium may contribute to the reverse rate-dependent nature of the effects of IKr blockers. In order to test this hypothesis, we studied the effects of dofetilide, a pure IKr blocker, on ERP after activation or blockade of β-adrenoceptors and after catecholamine depletion in guinea-pig left atrial myocardium paced at 3, 2 and 1 Hz, in vitro.Dofetilide (100 nM) lengthened ERP in a reverse rate-dependent manner in the left atrial myocardium of guinea-pigs. Strong activation of β-adrenoceptors using 10 nM isoproterenol abolished the dofetilide-induced lengthening of ERP at all pacing rates.Blockade of the β-adrenoceptors with metoprolol (1 μM), atenolol (3 μM) or propranolol (300 nM) increased the dofetilide-evoked prolongation of ERP at 3 and 2 Hz, but not at 1 Hz. As a consequence, metoprolol attenuated while propranolol and atenolol fully eliminated the reverse rate-dependent nature of the dofetilide-induced ERP lengthening. In catecholamine-depleted atrial preparations of the guinea-pig (24 h pretreatment with 5 mg kg−1 reserpine i.p.), the effect of dofetilide on ERP was not frequency dependent, and propranolol did not alter the effects of dofetilide.In contrast to results obtained in guinea-pig atrial preparations, propranolol failed to change the reverse rate-dependent effect of dofetilide on ERP in the right ventricular papillary muscles of rabbits and guinea-pigs.As an indication of the functional consequences of rate-dependent noradrenaline liberation, propranolol decreased twitch tension at 3 and 2 Hz but not at 1 Hz in the atrial myocardium of control guinea-pigs, whereas no such effect was detected in

  12. Beta-adrenoceptor activation plays a role in the reverse rate-dependency of effective refractory period lengthening by dofetilide in the guinea-pig atrium, in vitro.

    PubMed

    Kovács, Anikó; Magyar, János; Bányász, Tamás; Nánási, Péter P; Szénási, Gábor

    2003-08-01

    1. Blockers of the rapid component of the delayed rectifier potassium current (I(Kr)) prolong cardiac action potential duration (APD) and effective refractory period (ERP) in a reverse rate-dependent manner. Since activation of beta-adrenoceptors attenuates prolongation of APD evoked by I(Kr) blockers, rate-dependent neuronal noradrenaline liberation in the myocardium may contribute to the reverse rate-dependent nature of the effects of I(Kr) blockers. In order to test this hypothesis, we studied the effects of dofetilide, a pure I(Kr) blocker, on ERP after activation or blockade of beta-adrenoceptors and after catecholamine depletion in guinea-pig left atrial myocardium paced at 3, 2 and 1 Hz, in vitro. 2. Dofetilide (100 nM) lengthened ERP in a reverse rate-dependent manner in the left atrial myocardium of guinea-pigs. Strong activation of beta-adrenoceptors using 10 nM isoproterenol abolished the dofetilide-induced lengthening of ERP at all pacing rates. 3. Blockade of the beta-adrenoceptors with metoprolol (1 micro M), atenolol (3 micro M) or propranolol (300 nM) increased the dofetilide-evoked prolongation of ERP at 3 and 2 Hz, but not at 1 Hz. As a consequence, metoprolol attenuated while propranolol and atenolol fully eliminated the reverse rate-dependent nature of the dofetilide-induced ERP lengthening. In catecholamine-depleted atrial preparations of the guinea-pig (24 h pretreatment with 5 mg kg(-1) reserpine i.p.), the effect of dofetilide on ERP was not frequency dependent, and propranolol did not alter the effects of dofetilide. 4. In contrast to results obtained in guinea-pig atrial preparations, propranolol failed to change the reverse rate-dependent effect of dofetilide on ERP in the right ventricular papillary muscles of rabbits and guinea-pigs. 5. As an indication of the functional consequences of rate-dependent noradrenaline liberation, propranolol decreased twitch tension at 3 and 2 Hz but not at 1 Hz in the atrial myocardium of control guinea-pigs

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

    PubMed

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

    2014-12-01

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

  14. 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

  15. Cysteinyl leucotriene receptor type 1 mediates contraction in human and guinea-pig oesophagus.

    PubMed

    Chang, B-S; Chang, J-C; Wang, Y-S; Huang, S-C

    2008-10-01

    Leucotriene D(4) (LTD(4)) causes contraction of the guinea-pig and cat oesophagus. Effects of cysteinyl leucotrienes in the human oesophagus were unknown. To investigate and compare the cysteinyl leucotriene effects in the human oesophagus with those in the guinea-pig oesophagus, we measured contraction of muscularis mucosae strips isolated from the human and guinea-pig oesophagus caused by cysteinyl leucotrienes, LTC(4), LTD(4) and LTE(4), as well as the dihydroxy leucotriene, LTB(4). Effects of leucotrienes in human were similar to those in guinea-pig oesophagus. LTC(4) and LTD(4) caused moderate, whereas LTE(4) caused mild, concentration-dependent contraction. LTE(4) was a partial agonist. In contrast, LTB(4) did not cause any contraction. The relative potencies for cysteinyl leucotrienes to cause contraction were LTD(4) = LTC(4) > LTE(4). The LTD(4)-induced contraction was moderately inhibited by two selective CysLT(1) receptor antagonists, montelukast and zafirlukast, in both human and guinea-pig oesophagus. In addition, the LTD(4)-induced contraction was not and only slightly inhibited by BAY u9773, the CysLT(1) and CysLT(2) receptor antagonist, in the human and guinea-pig oesophageal muscularis mucosae respectively. These indicate the existence of the CysLT(1) mediating oesophageal contraction in both human and guinea-pig oesophagus. The LTD(4)-induced contraction was not affected by tetrodotoxin, atropine or capsaicin, suggesting a direct effect. These results demonstrate that cysteinyl leucotrienes but not the dihydroxy leucotriene cause contraction in the human and guinea-pig oesophagus. CysLT(1) mediates contraction in both human and guinea-pig oesophagus.

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

    DTIC Science & Technology

    1984-08-03

    Interim Mycotoxin in Guinea Pigs 6. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(a) B. CONTRACT OR GRANT NUMBER(-) J. G. Pace2, M. R. Watts, E. P. Burrows...on ,eveeae -Ide If necessary and Identify by block number) ś-2 mycotoxin , distribution, metabolism, guinea pigs, TLC ri 9ST-PAc’r rccit ue. a re! s...Ttl4e: F08te 2n4 s,, , ,H-T-2 t07in 84 08 24 077 zate anc Distribution of 3 H-Labeled T-2 Mycotoxin in Guinea Pigs. Face. J. G.. Watts, M. R

  17. Hematological assessment in pet guinea pigs (Cavia porcellus): blood sample collection and blood cell identification.

    PubMed

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

    2015-01-01

    Pet guinea pigs are presented to veterinary clinics for routine care and treatment of clinical diseases. In addition to obtaining clinical history and exam findings, diagnostic testing may be required, including hematological assessments. This article describes common blood collection methods, including venipuncture sites, the volume of blood that can be safely collected, and handling of the blood. Hematological parameters for normal guinea pigs are provided for comparison with in-house or commercial test results. A description of the morphology of guinea pig leukocytes is provided to assist in performing a differential count.

  18. Immunogenicity of heterologous Fc and Fab immunoglobulin fragments in rabbits, guinea-pigs and rats

    PubMed Central

    Binaghi, R. A.; Oriol, R.; Boussac-Aron, Yolande

    1967-01-01

    Rabbits, guinea-pigs and rats were immunized with various heterologous 7S and 19S immunoglobulins from each other and man, and the antisera obtained were studied by immunoelectrophoresis. Rabbits produced antibodies against the Fc and the Fab fragments of the immunoglobulin injected, while guinea-pigs and rats only produced anti-Fc antibodies. The fact that guinea-pigs and rats only respond to the specific determinants of each class of immunoglobulin provides a simple method for the preparation of class-specific antisera. ImagesFIG. 1FIG. 2 PMID:6027784

  19. Hematological Assessment in Pet Guinea Pigs (Cavia porcellus): Blood Sample Collection and Blood Cell Identification.

    PubMed

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

    2015-09-01

    Pet guinea pigs are presented to veterinary clinics for routine care and treatment of clinical diseases. In addition to obtaining clinical history and exam findings, diagnostic testing may be required, including hematological assessments. This article describes common blood collection methods, including venipuncture sites, the volume of blood that can be safely collected, and handling of the blood. Hematological parameters for normal guinea pigs are provided for comparison with in-house or commercial test results. A description of the morphology of guinea pig leukocytes is provided to assist in performing a differential count.

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

    PubMed

    Guo, Hui-Cai; Zhang, Zhe; Zhang, Li-Nan; Xiong, Chen; Feng, Chen; Liu, Qian; Liu, Xu; Shi, Xiao-Lu; Wang, Yong-Li

    2009-07-01

    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. Adult male guinea pigs were exposed to CIHH by mimicking a 5000 m high altitude (p(B)=404 mmHg, p(O2)=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. 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 (H(2)O(2)) were attenuated by CIHH and CAT. These data suggest that CIHH protects the heart against I/R injury through upregulation of antioxidant enzymes in guinea pig.Acta Pharmacologica Sinica (2009) 30: 947-955; doi: 10.1038/aps.2009.57; published online 22 June 2009.

  1. 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

  2. Expression of Endogenous Retroviral Genes in Leukemic Guinea Pig Cells

    PubMed Central

    Davis, A. R.; Nayak, D. P.

    1977-01-01

    The expression of guinea pig retrovirus (5-bromodeoxyuridine[BUdR]-induced GPV) was studied in guinea pig L2C leukemic lymphoblasts by use of molecular hybridization of viral complementary DNA (cDNA) to cellular RNA. It was found that L2C leukemic lymphoblasts, leukemic spleen, and BUdR-induced virus-producing cells contain virus-specific RNA: 0.05% (800 to 960 copies per cell), 0.02% (360 copies per cell), and 0.3% (5,120 copies per cell), respectively. Adult normal liver and spleen, on the other hand, contain less than 0.2 copy of viral RNA per cell. Both BUdR-induced cells and L2C leukemic lymphoblasts contained 14S, 22S, 35S, and 70S RNA species of total and cytoplasmic virus-specific RNA as determined by sucrose velocity gradient analysis and hybridization of sucrose gradient fractions to cDNA. Virus-specific mRNA was identified in both BUdR-induced cells and L2C leukemic lymphoblasts by the criterion that it cosedimented with purified polyribosomes in a sucrose gradient and that it changed to a lower sedimentation value if polyribosomes were disaggregated with EDTA prior to centrifugation. Virus-specific mRNA obtained from either the polyribosome region of purified polyribosomes or the released messenger region of EDTA-disaggregated purified polyribosomes consisted of 14S, 20S, and 35S species in both BUdR-induced cells and L2C leukemic lymphoblasts. Hybridization of cDNA to the RNA of L2C leukemic lymphoblasts and BUdR-induced cells was essentially complete. Additionally, leukemic lymphoblast RNA could displace 95% of the hybridization of BUdR-induced GPV 70S RNA to guinea pig DNA. The midpoints of thermal denaturation of hybrids formed between GPV cDNA and the RNA of either L2C leukemic lymphoblasts or the 70S RNA of BUdR-induced GPV were both 89°C in 2× concentrated 0.15 M NaCl plus 0.015 M sodium citrate. These results show that BUdR-induced GPV genes are essentially completely expressed in L2C leukemic lymphoblasts and that virus-specific mRNA is

  3. Leukotriene B4 receptors on guinea pig alveolar eosinophils

    SciTech Connect

    Maghni, K.; de Brum-Fernandes, A.J.; Foeldes-Filep, E.G.; Gaudry, M.; Borgeat, P.; Sirois, P. )

    1991-09-01

    The existence of receptors for LTB4 on highly purified guinea pig alveolar eosinophils was investigated. Massive infiltration of eosinophils in alveolar spaces was induced in guinea pigs by i.v. injections of Sephadex beads G50 (16 mg/kg). Alveolar eosinophils (50 {times} 10(6) cells) were purified to approximately 98% by Percoll continuous density gradient centrifugation. The binding studies indicated that alveolar eosinophils bind LTB4 in a saturable, reversible and specific manner. Scatchard analysis indicated the existence of high-affinity binding sites (Kd1 = 1.00 {plus minus} 0.22 nM; Bmax1 = 966 {plus minus} 266 sites/cell) and low-affinity binding sites (Kd2 = 62.5 {plus minus} 8.9 nM; Bmax2 = 5557 {plus minus} 757 sites/cell). The metabolism of LTB4 by alveolar eosinophils in binding conditions was assessed by RP-HPLC and no significant degradation of (3H)LTB4 was observed. LTB4 dose-dependently stimulated eosinophil migration in both chemokinesis and chemotaxis assays with an EC50 value of 1.30 {plus minus} 0.14 and 18.14 {plus minus} 1.57 nM, respectively. LTB4 caused a dose-dependent increase in the production of superoxide anion with an apparent EC50 value of 50 {times} 10(-9) M in the authors experimental conditions. LTB4 also induced a dose-dependent increase in the generation of TxA2 with an EC50 value of 46.2 {times} 10(-9) M. Taken together, their results demonstrated that guinea pig alveolar eosinophils express two classes of specific receptors for LTB4. The high-affinity binding sites seem associated to chemokinesis and chemotaxis whereas the low-affinity binding sites seem associated to superoxide anion production and generation of TxA2. The existence of LTB4 receptors in eosinophils could explain the presence of these cells in hypersensitivity reactions.

  4. Ontogeny of fetal movements in the guinea pig.

    PubMed

    van Kan, C M; de Vries, J I P; Lüchinger, A B; Mulder, E J H; Taverne, M A M

    2009-09-07

    Assessment of fetal motility is an approach to evaluate the development and function of the nervous system before birth. Reference values for the time of first occurrence and the incidence of normal fetal movements are indispensable for studies in which prenatal motor activity is applied as a model to study the central and peripheral nervous systems. Studies on fetal motility have been performed in a few species, particularly in the human. The aim of the present study is to describe the ontogeny of fetal motility in the guinea pig, a precocious polytocous species. After a pilot study to establish procedures for repeated ultasonographic scanning of guinea pigs, 10 domesticated animals were scanned (5.0 or 7.5 MHz convex transducer) at 2-4 day intervals between day 24 and 63 of gestation (term age 68 days). Per animal two selected fetuses were each scanned for 15 min. Images were stored on videotape and analyzed off-line for the first onset, presence and quality of fetal movement patterns, and quantity of sideway bendings, general movements, breathing movements and periods of fetal rest. Twenty-five different movement patterns could be characterized, 6 emerging at the onset of motor activity were performed only temporarily. The very first fetal movement was observed on day 24 gestational age, and subsequently most other movements developed during a period of only 5 days. Interfetal difference in onset of the frequently occurring sideway bendings, general movements, and front and hind limb movements was only 2 days. Sideway bendings and general movements co-existed during days 29 to 43. There were developmental trends in the course of pregnancy. Sideway bendings increased rapidly between 24 and 30 days and declined hereafter. General movements and fetal breathing increased during midpregnancy and declined towards parturition. Conversely, fetal rest was observed for approximately 60% of time at midgestation and a marked increase was found towards parturition. There

  5. Citicoline retards myopia progression following form deprivation in guinea pigs

    PubMed Central

    Liu, Shuangzhen; Fu, Chunyan

    2016-01-01

    The retinal dopaminergic system is involved in the myopic shift following form deprivation. Citicoline has been demonstrated to stimulate the dopaminergic system in the brain and retina. Furthermore, citicoline has been used in many neurogenic diseases, such as senile cognitive impairment, stroke and Parkinson's disease as well as in amblyopia and glaucoma. Our aim was to investigate the effect of citicoline on the refractive state and retinal dopamine level in form deprivation myopia of guinea pigs. Guinea pigs, at an age of four weeks, were randomly divided into normal control, deprivation, deprived + citicoline and deprived + vehicle groups. Form deprivation myopia was induced by a translucent eye shield covering the right eye. Citicoline was injected intraperitoneally twice a day (500 mg/kg, 9 am and 9 pm) for 10 days. In vitro, retinal explants were cultured with citicoline for 24 h, with a final citicoline concentration of 100 µmol/L. The ocular refractive parameters and retinal dopamine content were measured. After occlusion for 10 days, the form-deprived eyes became myopic with an increase in axial length and a decrease in retinal dopamine content. The intraperitoneal injection of citicoline reduced the myopic degree (from −3.25 ± 0.77D to −0.62 ± 0.47D, P < 0.001) and partially raised retinal dopamine levels (from 0.55 ± 0.21 ng to 0.81 ± 0.24 ng, P < 0.01) in the form-deprived eyes. After 24 h of culturing retinal explants with citicoline, retinal dopamine content increased significantly (from 0.42 ± 0.14 ng to 0.62 ± 0.21 ng, P < 0.05). These results demonstrated that an intraperitoneal injection of citicoline could retard the myopic shift induced by form deprivation in guinea pigs, which was mediated by an increase in the retinal dopamine levels. PMID:26979720

  6. Antispasmodic effect of hydroalcoholic extract of Thymus vulgaris on the guinea-pig ileum.

    PubMed

    Babaei, Mehdi; Abarghoei, Mitra Emmami; Ansari, Reza; Vafaei, Abbas Ali; Taherian, Abbas Ali; Akhavan, Maziar Mohammad; Toussy, Gafar; Mousavi, Shahrokh

    2008-01-01

    The effects of Thymus vulgaris hydroalcoholic extract on the contractile responses of the isolated guinea-pig ileum were investigated. Contraction changes in the terminal ileum of guinea pigs were monitored using a force displacement transducer amplifier connected to a physiograph. Thymus vulgaris extract inhibited the contractile responses in a dose-dependent manner and also decreased the amplitude of peristaltic waves. It is concluded that T. vulgaris has an antispasmodic action on guinea pig ileum by decreasing the amplitudes of the muscle contractions during peristalsis. The EC50 was calculated as 1.7 mg mL(-1). In guinea-pig ileum the extract led to an antispasmodic effect, possibly by affecting the anticholinergic and serotoninergic pathways.

  7. Pathogenesis of XJ and Romero strains of Junin virus in two strains of guinea pigs.

    PubMed

    Yun, Nadezhda E; Linde, Nathaniel S; Dziuba, Natallia; Zacks, Michele A; Smith, Jeanon N; Smith, Jennifer K; Aronson, Judy F; Chumakova, Olga V; Lander, Heather M; Peters, Clarence J; Paessler, Slobodan

    2008-08-01

    Argentine hemorrhagic fever (AHF), a systemic infectious disease caused by infection with Junin virus, affects several organs, and patients can show hematologic, cardiovascular, renal, or neurologic symptoms. We compared the virulence of two Junin virus strains in inbred and outbred guinea pigs with the aim of characterizing this animal model better for future vaccine/antiviral efficacy studies. Our data indicate that this passage of the XJ strain is attenuated in guinea pigs. In contrast, the Romero strain is highly virulent in Strain 13 as well as in Hartley guinea pigs, resulting in systemic infection, thrombocytopenia, elevated aspartate aminotransferase levels, and ultimately, uniformly lethal disease. We detected viral antigen in formalin-fixed, paraffin-embedded tissues. Thus, both guinea pig strains are useful animal models for lethal Junin virus (Romero strain) infection and potentially can be used for preclinical trials in vaccine or antiviral drug development.

  8. Oxidative and glycolytic metabolism of semen components by washed guinea pig spermatozoa.

    PubMed

    Frenkel, G; Peterson, R N; Freund, M

    1975-02-01

    The concentration of several potentially metabolizable substances in guinea pig semen and the ability of these substances to support ATP synthesis and the motility of guinea pig sperm have been determined. Both glucose and fructose were present in high concentration in semen and were equipotent at the concentration tested in maintaining high levels of ATP and a high rate of motility. Lactic and pyruvic acids also supported a high rate of sperm motility but maintained lower levels of ATP. These constituents of guinea pig semen, as well as the metabolites alpha-glycerophosphate, succinic acid, and beta-hydroxybutyric acid, are oxidized at unusually high rates. The active oxidative metabolism of guinea pig sperm is compared with that of human sperm which is primarily glycolytic.

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

    NASA Technical Reports Server (NTRS)

    Mikiskova, H.

    1980-01-01

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

  10. Papular dermatitis induced in guinea pigs by the biting midge Culicoides sonorensis (Diptera: Ceratopogonidae)

    USDA-ARS?s Scientific Manuscript database

    Histological, ultrastructural, and virological examinations were performed on abdominal skin from guinea pigs after a blood meal by colony-bred biting midges, Culicoides sonorensis. Small, superficial, cutaneous, crateriform ulcers with necrosis of superficial dermis developed at feeding sites and ...

  11. Induction of follicular luteinization by equine chorionic gonadotropin in cyclic guinea pigs.

    PubMed

    Li, Jun-rong; Wang, Wei; Shi, Fang-xiong

    2015-12-01

    The effects of equine chorionic gonadotropin (eCG) on follicular development and ovulation in cyclic guinea pigs were investigated by histological and immunohistochemical analyses. Three groups of guinea pigs (n=12) were administrated subcutaneously with saline, 20 or 50 IU of eCG, respectively, on cyclic Day 12 (Day 1=vaginal openings). Ovaries were collected at 4 and 8 d after administration (6 animals per group each time). The eCG administration induced significant and distinct morphological changes in the ovaries, as it promoted the luteinization of granulosa cells, but not follicular development. In addition, proliferating cell nuclear antigen (PCNA) and steroidogenic acute regulatory protein (StAR) were immunolocalized specifically in luteinized follicles. Our experiments together indicate that eCG administration can induce follicular luteinization but not superovulation in guinea pigs. The eCG in cyclic guinea pigs functions similar to that of luteinizing hormone (LH), but not follicle-stimulating hormone (FSH).

  12. Pathogenesis of XJ and Romero Strains of Junin Virus in Two Strains of Guinea Pigs

    PubMed Central

    Yun, Nadezhda E.; Linde, Nathaniel S.; Dziuba, Natallia; Zacks, Michele A.; Smith, Jeanon N.; Smith, Jennifer K.; Aronson, Judy F.; Chumakova, Olga V.; Lander, Heather M.; Peters, Clarence J.; Paessler, Slobodan

    2008-01-01

    Argentine hemorrhagic fever (AHF), a systemic infectious disease caused by infection with Junin virus, affects several organs, and patients can show hematologic, cardiovascular, renal, or neurologic symptoms. We compared the virulence of two Junin virus strains in inbred and outbred guinea pigs with the aim of characterizing this animal model better for future vaccine/antiviral efficacy studies. Our data indicate that this passage of the XJ strain is attenuated in guinea pigs. In contrast, the Romero strain is highly virulent in Strain 13 as well as in Hartley guinea pigs, resulting in systemic infection, thrombocytopenia, elevated apartate aminotransferase levels, and ultimately, uniformly lethal disease. We detected viral antigen in formalin-fixed, paraffin-embedded tissues. Thus, both guinea pig strains are useful animal models for lethal Junin virus (Romero strain) infection and potentially can be used for preclinical trials in vaccine or antiviral drug development. PMID:18689636

  13. Induction of follicular luteinization by equine chorionic gonadotropin in cyclic guinea pigs*

    PubMed Central

    Li, Jun-rong; Wang, Wei; Shi, Fang-xiong

    2015-01-01

    The effects of equine chorionic gonadotropin (eCG) on follicular development and ovulation in cyclic guinea pigs were investigated by histological and immunohistochemical analyses. Three groups of guinea pigs (n=12) were administrated subcutaneously with saline, 20 or 50 IU of eCG, respectively, on cyclic Day 12 (Day 1=vaginal openings). Ovaries were collected at 4 and 8 d after administration (6 animals per group each time). The eCG administration induced significant and distinct morphological changes in the ovaries, as it promoted the luteinization of granulosa cells, but not follicular development. In addition, proliferating cell nuclear antigen (PCNA) and steroidogenic acute regulatory protein (StAR) were immunolocalized specifically in luteinized follicles. Our experiments together indicate that eCG administration can induce follicular luteinization but not superovulation in guinea pigs. The eCG in cyclic guinea pigs functions similar to that of luteinizing hormone (LH), but not follicle-stimulating hormone (FSH). PMID:26642181

  14. [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.

  15. Characterization of a novel parainfluenza virus, caviid parainfluenza virus 3, from laboratory guinea pigs (Cavia porcellus).

    PubMed

    Simmons, Joe H; Purdy, Gregory A; Franklin, Craig L; Trottier, Pierre; Churchill, Anthony E; Russell, Robert J; Besch-Williford, Cynthia L; Riley, Lela K

    2002-12-01

    A novel Respirovirus was isolated from nasopharyngeal swab specimens from clinically normal laboratory guinea pigs, and was characterized and named caviid parainfluenza virus 3 (CavPIV-3). The CavPIV-3 is enveloped, is 100 to 300 nm in diameter, and has a characteristic 15-nm-diameter chevron-shaped virus ribonucleocapsid protein. Sequence analysis of the fusion glycoprotein of CavPIV-3 revealed it to be 94% identical to human and guinea pig parainfluenza 3 (PIV-3) viruses and 80% identical to bovine PIV-3. To determine whether CavPIV-3 causes clinical disease in laboratory guinea pigs and to compare the serologic response of guinea pigs to CavPIV-3 and to other paramyxoviruses, an infection study was performed, in which groups of guinea pigs were inoculated with CavPIV-3, Sendai virus, simian virus 5 (SV-5), murine pneumonia virus (PVM), or bovine PIV-3 virus. During the course of the study, guinea pigs were maintained in an infectious disease suite, housed in Micro-Isolator cages, and were only manipulated under a laminar flow hood. Clinical signs of disease were not observed in any of the paramyxovirus-inoculated guinea pigs during the eight-week course of the study, and histologic signs of disease were not evident at necropsy eight weeks after inoculation. Guinea pigs inoculated with CavPIV-3, Sendai virus, PVM, and bovine PIV-3 developed robust homologous or heterologous serologic responses. In contrast, guinea pigs inoculated with SV-5 developed modest or equivocal serologic responses, as assessed by use of an enzyme-linked immunosorbent assay. Further, use of the SV-5 enzyme-linked immunosorbent assay resulted in the highest degree of non-specific reactivity among all of the paramyxovirus assays. In summary, CavPIV-3 is a novel guinea pig Respirovirus that subclinically infects laboratory guinea pigs, resulting in a robust serologic response, but no observed clinical or histologic disease. The CavPIV-3 fusion glycoprotein gene sequence is available from Gen

  16. Infrared neural stimulation: beam path in the guinea pig cochlea

    PubMed Central

    Moreno, Laura E; Rajguru, Suhrud M; Matic, Agnella Izzo; Yerram, Nitin; Robinson, Alan M; Hwang, Margaret; Stock, Stuart; Richter, Claus-Peter

    2011-01-01

    It has been demonstrated INS can be utilized to stimulate spiral ganglion cells in the cochlea. Although neural stimulation can be achieved without direct contact of the radiation source and the tissue, the presence of fluids or bone between the target structure and the radiation source may lead to absorption or scattering of the radiation, which may limit the efficacy of INS. The present study demonstrates the neural structures in the radiation beam path that can be stimulated. Histological reconstructions and microCT of guinea pig cochleae stimulated with an infrared laser suggest that the orientation of the beam from the optical fiber determined the site of stimulation in the cochlea. Best frequencies of the INS-evoked neural responses obtained from the central nucleus of the inferior colliculus matched the histological sites in the spiral ganglion. PMID:21763410

  17. Mycoplasma pneumoniae induces cytotoxic activity in guinea pig bronchoalveolar cells

    SciTech Connect

    Kist, M.; Koester, H.; Bredt, W.

    1985-06-01

    Precultured guinea pig alveolar macrophages (AM) and freshly harvested alveolar cells (FHAC) activated by interaction with Mycoplasma pneumoniae were cytotoxic for xenogeneic /sup 75/selenomethionine-labeled tumor target cells. Phagocytosis of whole opsonized or nonopsonized M. pneumoniae cells was more effective in eliciting cytotoxicity than uptake of sonicated microorganisms. The addition of living mycoplasma cells to the assay system enhanced the cytotoxic effect considerably. Target cells were significantly more susceptible to the cytotoxic action of phagocytes if they were coated with mycoplasma antigen or cocultured together with M. pneumoniae. The activation of the phagocytes could be inhibited by 2-deoxy-D-glucose but not by antimicrobial substances suppressing mycoplasma protein synthesis. It was accompanied by /sup 51/Cr release without detectable signs of cell damage. The supernatants of activated cells were cytotoxic for approximately 24 h. Inhibition, release, and cytotoxic activity indicate the necessity of an intact metabolism of the effector cells and suggest a secretion of cytotoxic substances.

  18. Middle ear overpressure treatment of endolymphatic hydrops in guinea pigs.

    PubMed

    Sakikawa, Y; Kimura, R S

    1997-01-01

    Guinea pigs placed outside or inside a pressure chamber and exposed to 49.2 cm H2O overpressure continuously for 24 h immediately after blockage of the endolymphatic duct showed no significant difference in the magnitude of endolymphatic hydrops when compared to controls, although there was a slight indication of a volume decrease in the outside-treatment group and an increase in the inside-treatment group. A pressure increase of 49.2 cm H2O in the external auditory canal for 1 h twice a day for 2 weeks outside the chamber significantly inhibited the development of hydrops. The latter result supports the merit of pressure application through the external auditory canal as a treatment for Meniere's disease.

  19. [Micro-CT imaging of guinea pig cochlear].

    PubMed

    Sun, Cheng-cheng; Jiang, Zi-dong; Zhang, Kai

    2012-12-25

    To employ micro-CT equipment for nondestructive three-dimensional (3D) imaging of internal ear. The guinea pigs were anesthetized by napental and bilateral cochleas harvested. Cochlea was fixed in glutaraldehyde before scanning of micro-CT. Two-dimensional (2D) images were acquired for a 3D model of reconstruction. The 2D images was distinct enough to visualize vestibular gallery, scala media, scala tympani, Reissner's membrane, velum, organ of Corti and spiral ganglion, etc. The 3D structure model was excellent for viewing and free to revolve in any axial direction. Micro-CT may allow nondestructive three-dimensional imaging of internal ear. As compared with the traditional method of morphology, this approach is able to save samples, easy to operate and has a high resolution. And it is more easily popularized than the synchrotron radiation approach.

  20. Transmission of influenza B viruses in the guinea pig.

    PubMed

    Pica, Natalie; Chou, Yi-Ying; Bouvier, Nicole M; Palese, Peter

    2012-04-01

    Epidemic influenza is typically caused by infection with viruses of the A and B types and can result in substantial morbidity and mortality during a given season. Here we demonstrate that influenza B viruses can replicate in the upper respiratory tract of the guinea pig and that viruses of the two main lineages can be transmitted with 100% efficiency between inoculated and naïve animals in both contact and noncontact models. Our results also indicate that, like in the case for influenza A virus, transmission of influenza B viruses is enhanced at colder temperatures, providing an explanation for the seasonality of influenza epidemics in temperate climates. We therefore present, for the first time, a small animal model with which to study the underlying mechanisms of influenza B virus transmission.

  1. Experimental infection with Treponema hyodysenteriae in guinea pigs.

    PubMed Central

    Joens, L A; Songer, J G; Harris, D L; Glock, R D

    1978-01-01

    Outbred and inbred (Hartley strain) guinea pigs (GP) were inoculated intragastrically with pathogenic and nonpathogenic Treponema hyodysenteriae. GP 3 to 16 weeks old received T. hyodysenteriae after a fasting period of 36 to 72 h. Infected GP with pathogenic T. hyodysenteriae developed a diarrheal and/or depressive condition, with mucus but not blood in the feces. Of 88 GP, 40 had gross lesions resembling those of swine dysentery. Lesions were limited mainly to the large intestine. TP used as controls or inoculated with nonpathogenic T. hyodysenteriae did not develop these lesions in the large intestine. These studies suggest that the GP may be used as an animal model for swine dysentery. PMID:730345

  2. Investigation of Guinea Pig Performance on an Eight-Lane Treadmill

    DTIC Science & Technology

    1991-11-01

    exercise model . Training was conducted over a twelve- day period at speeds ranging from 0.08 mph (1.93 mpm) to 0.50 mph (11.61 mpin) and session lengths from...conditioning, similar requirements when testing pretreatmant and therapy compounds should reflect this conditioned state. The guinea pig model is...standard guinea pig exercise model is the swim test devised by Rylands [3). This test has proven unsatisfactory for two reasons: a fairly large number

  3. A Pilot Study of Uterine Artery Embolization with Tris-Acryl Gelatin Microspheres in Guinea Pigs

    SciTech Connect

    Zhuang Wenquan; Tan Guosheng; Guo Wenbo; Yang Jianyong

    2012-06-15

    Objective: This study was designed to establish guinea pigs as an animal model for uterine artery embolization (UAE) with tris-acryl gelatin microspheres (TAGM). Methods: Twenty-five female adult guinea pigs were randomly divided into two groups, including a uterine artery casting mould group (n = 10) and a UAE group (n = 15). Pelvic angiography and vascular casting mould were performed in the first group. The anatomical characters of the pelvic cavity in guinea pigs were described. In the second group, the technical feasibility of performing UAE with TAGM in guinea pigs was investigated. The histopathological slides of the uterus of guinea pigs after UAE were examined to inspect the outcomes of UAE. Results: The uterine artery springs from the internal iliac artery, ascends tortuously along the cervix, and gives off vertically 8-10 branches to the cervix uteri and uterine horns. The diameters of the trunk of the uterine artery and its first branch were 0.32 {+-} 0.027 mm and 0.14 {+-} 0.01 mm, respectively. For UAE animals, the dosages of 40-120 and 100-300 {mu}m TAGM were 0.033 {+-} 0.003 ml and 0.015 {+-} 0.002 ml, respectively. On histopathological slides, embosphere particles were found in the first branches of the uterine artery, the subserous arteries, and the intramural arteries. Inflammatory reactions in the uterus were common in guinea pigs after UAE. Local or dispersed areas of necrosis in uterus also were observed in a few guinea pigs. Conclusions: Guinea pigs are an appropriate and feasible model for UAE with TAGM.

  4. Bitter avoidance in guinea pigs (Cavia porcellus) and mice (Mus musculus and Peromyscus leucopus).

    PubMed

    Field, Kristin L; Beauchamp, Gary K; Kimball, Bruce A; Mennella, Julie A; Bachmanov, Alexander A

    2010-11-01

    Rejection of bitter substances is common in many species and may function to protect an animal from ingestion of bitter-tasting toxins. Since many plants are bitter, it has been proposed that high tolerance for bitterness would be adaptive for herbivores. Earlier studies conducted on herbivorous guinea pigs (Cavia porcellus) have been used to support this proposal. We tested guinea pigs with bitter plant secondary metabolites (salicin, caffeine, quinine hydrochloride) and bitter protein hydrolysates (two types of hydrolyzed casein, hydrolyzed soy) in a series of two-choice preference tests. For comparison, we tested two nonherbivorous mouse species (Mus musculus and Peromyscus leucopus). Guinea pigs did show weaker avoidance of quinine hydrochloride than did the mice, confirming predictions generated from earlier work. However, guinea pigs had similar responses to caffeine as did Peromyscus. Both of these species showed weaker avoidance responses than Mus to 10 mM caffeine. For salicin, guinea pigs were the only species to avoid it at 10 mM and their preference scores at this concentration were significantly lower than for the two mice species. Guinea pigs avoided all of the protein hydrolysates more strongly than the other species. Responses to the protein hydrolysates did not reflect the patterns observed with the simple bitter compounds, suggesting that other properties of these complex stimuli may be responsible for guinea pig avoidance of them. Our results suggest caution in accepting, without further empirical support, the premise that guinea pigs (and herbivores in general) have a generalized reduced bitter sensitivity. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  5. SB223412, a neurokinin-3 receptor-selective antagonist, suppresses testosterone secretion in male guinea pigs.

    PubMed

    Nakamura, Sho; Ito, Yoshiko; Yamamoto, Koki; Takahashi, Chudai; Dai, Mingdao; Tanahashi, Miyu; Uenoyama, Yoshihisa; Tsukamura, Hiroko; Oishi, Shinya; Maeda, Kei-Ichiro; Matsuda, Fuko

    2017-10-15

    Guinea pigs are important zoo animals and have been recommended for animal-assisted activities or therapy, however there are problems concerning testosterone inducing aggressive or sexual behaviors in male guinea pigs. Testicular testosterone secretion is regulated by pulsatile gonadotropin releasing hormone (GnRH)/luteinizing hormone (LH) release in mammals. The mechanism generating GnRH/LH pulses is thought to be governed by kisspeptin neurons, which coexpress neurokinin B (NKB) and dynorphin A (Dyn), in the arcuate nucleus (ARC). Kisspeptin neurons in the ARC are frequently referred to as KNDy neurons. The purpose of this study was to examine whether the antagonization of NKB-neurokinin-3 receptor (NK3R) signaling can manipulate testosterone secretion in male guinea pigs. A single subcutaneous administration or 7 days of oral administration of an NK3R-selective antagonist, SB223412 (50 mg/body), significantly decreased plasma testosterone levels in male guinea pigs. In vitro binding assays confirmed that SB223412 has a high affinity to guinea pig NK3R. These results suggest that SB223412 could be used as an orally-available compound to suppress testosterone levels in male guinea pigs. Double labeling in situ hybridization of kisspeptin and either NKB or Dyn showed that kisspeptin-expressing neurons contained NKB (77.9%) or Dyn (62.3%) in the ARC, suggesting the presence of KNDy neurons in the ARC of guinea pigs. In conclusion, the present study shows that SB223412 could be a candidate compound to suppress testosterone secretion in male guinea pigs for controlling sexual and aggressive behaviors in the species. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. 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.

  7. Spontaneous behavior in noise and silence: a possible new measure to assess tinnitus in Guinea pigs.

    PubMed

    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.

  8. [Measurement of airway resistance and reactivity in guinea pigs using double-chamber plethysmography].

    PubMed

    Yao, Wei-min; Lai, Ke-fang; Luo, Yuan-ming; Liu, Chun-li; Chen, Ru-chong; Luo, Wei; Zhong, Nan-shan

    2009-05-01

    To establish a method for measurement of airway resistance (sRaw) and reactivity in guinea pigs. Methacholine spray at gradient concentrations was given to guinea pigs. PC100 was defined as the concentration of methacholine when the sRaw doubled in the guinea pigs using a double-chamber plethysmograph. The time for the recovery of PC100 resistance to baseline levels was measured. The sRaw and PC100 were measured twice on days 1 and 15 (4 time points) in the guinea pigs before and after OVA challenge. PC100 in a normal guinea pig airway was shown to recover the baseline level within 1 h. Double-chamber plethysmographical measurement of the sRaw and PC100 in normal guinea pigs did not show significant differences between the time points [sRaw: 3.25-/+0.67, 3.33-/+0.58, 3.30-/+0.56, and 3.32-/+0.75 cm H2O.s; log2PC100: 8.48-/+0.94, 8.64-/+1.04, 8.56-/+0.67, and 8.64-/+0.60, respectively, P>0.05]. The sRaw and airway reactivity were significantly increased in guinea pigs challenged with OVA [sRaw: 7.08-/+1.82 vs 2.87-/+0.53 cmH2O.s, P<0.01; log2PC100: 6.64-/+1.26 vs 8.48-/+1.17, P<0.01]. A double-chamber plethysmography for measurement of sRaw and airway reactivity in guinea pig is established successfully.

  9. 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

  10. Differential release of guinea pig sperm acrosomal components during exocytosis.

    PubMed

    Kim, K S; Foster, J A; Gerton, G L

    2001-01-01

    The contents of the sperm acrosome are compartmentalized at the biochemical and morphological levels. Biochemically, the acrosome can be considered to be comprised of two compartments: one consisting of readily soluble proteins and one containing a particulate acrosomal matrix. To test the hypothesis that compartmentalization affects the release of acrosomal components during the course of secretion in guinea pig sperm, we examined the relationship between the presence of specific proteins and acrosomal status and monitored the recovery of acrosomal constituents in the medium surrounding sperm induced to undergo exocytosis with the ionophore A23187. Cysteine-rich secretory protein 2 (CRISP-2), a soluble component of the acrosome, was rapidly lost from the acrosome soon after ionophore treatment. However, acrosomal matrix components remained associated with the sperm for longer periods. AM67, a matrix component and the guinea pig orthologue of the mouse sperm zona pellucida-binding protein sp56, was released at a slower rate than was CRISP-2 but at a faster rate than were two other matrix proteins, AM50 and proacrosin. Coincident with their release from the sperm, AM50 and proacrosin were posttranslationally modified, probably by proteolysis. The release of proacrosin from the matrix appears associated with the conversion of this protein to the enzymatically active acrosin protease. These results provide strong support for the hypothesis that compartmentalization plays a significant role in regulating the release of proteins during the course of acrosomal exocytosis. Acrosomal matrix proteins remain associated with the sperm for prolonged periods of time following the induction of acrosomal exocytosis, suggesting that transitional acrosomal intermediates may have significant functions in the fertilization process.

  11. Transduction sites of vagal mechanoreceptors in the guinea pig esophagus.

    PubMed

    Zagorodnyuk, V P; Brookes, S J

    2000-08-15

    Extrinsic afferent neurons play an essential role in both sensation and reflex control of visceral organs, but their specialized morphological peripheral endings have never been functionally identified. Extracellular recordings were made from fine nerve trunks running between the vagus nerve and esophagus of the guinea pig. Mechanoreceptors, which responded to esophageal distension, fired spontaneously, had low thresholds to circumferential stretch, and were slowly adapting. Calibrated von Frey hairs (0.12 mN) were used to probe the serosal surface at 100-200 sites, which were mapped on a video image of the live preparation. Each stretch-sensitive unit had one to three highly localized receptive fields ("hot spots"), which were marked with Indian ink applied on the tip of the von Frey hair. Recorded nerve trunks were then filled anterogradely, using biotinamide in an artificial intracellular solution. Receptive fields were consistently associated with intraganglionic laminar endings (IGLEs) in myenteric ganglia, but not with other filled neuronal structures. The average distance of receptive fields to IGLEs was 73 +/- 14 microm (24 receptive fields, from 12 units; n = 5), compared to 374 +/- 17 microm for 240 randomly generated sites (n = 5; p < 0.001). After maintained probing on a single receptive field, spontaneous discharge of units was inhibited, as were responses to distension. During adapted discharge to maintained distension, interspike intervals were distributed in a narrow range. This indicates that multiple receptive fields interact to encode mechanical distortion in a graded manner. IGLEs are specialized transduction sites of mechanosensitive vagal afferent neurons in the guinea pig esophagus.

  12. Acute and subchronic dermal toxicity of nanosilver in guinea pig.

    PubMed

    Korani, M; Rezayat, S M; Gilani, K; Arbabi Bidgoli, S; Adeli, S

    2011-01-01

    Silver has been used as an antimicrobial agent for a long time in different forms, but silver nanoparticles (nanosilver) have recently been recognized as potent antimicrobial agents. Although nanosilver is finding diverse medical applications such as silver-based dressings and silver-coated medical devices, its dermal and systemic toxicity via dermal use has not yet been identified. In this study, we analyzed the potential toxicity of colloidal nanosilver in acute and subchronic guinea pigs. Before toxicity assessments, the size of colloidal nanosilver was recorded in sizes <100 nm by X-ray diffraction and transmission electron microscopy. For toxicological assessments, male guinea pigs weighing 350 to 400 g were exposed to two different concentrations of nanosilver (1000 and 10,000 μg/mL) in an acute study and three concentrations of nanosilver (100, 1000, and 10,000 μg/mL) in a subchronic study. Toxic responses were assessed by clinical and histopathologic parameters. In all experimental animals the sites of exposure were scored for any type of dermal toxicity and compared with negative control and positive control groups. In autopsy studies during the acute test, no significant changes in organ weight or major macroscopic changes were detected, but dose-dependent histopathologic abnormalities were seen in skin, liver, and spleen of all test groups. In addition, experimental animals subjected to subchronic tests showed greater tissue abnormalities than the subjects of acute tests. It seems that colloidal nanosilver has the potential to provide target organ toxicities in a dose- and time-dependent manner.

  13. Blast cells transfer experimental hypersensitivity pneumonitis in guinea pigs

    SciTech Connect

    Schuyler, M.; Cook, C.; Listrom, M.; Fengolio-Preiser, C.

    1988-06-01

    We previously demonstrated that experimental hypersensitivity pneumonitis (HP) can be transferred by lymph node cells (LNC) cultured in vitro with antigen. The purpose of this study was to identify the cells responsible for transfer and to determine if pulmonary cells can transfer HP. We cultured LNC from sensitized Strain 2 guinea pigs with a soluble extract of Micropolyspora faeni for 72 h, separated lymphoblasts from small lymphocytes, and transferred both subpopulations intravenously to syngeneic recipients. We also transferred irradiated lymphoblasts (1,500 rads), macrophage-depleted, lymphoblast-enriched populations, and pulmonary cells either without culture or after culture with M. faeni. Control animals received an equal volume of medium. All recipient animals were challenged intratracheally (i.t.) with M. faeni 48 h after the cell transfer, and they were killed 4 days after i.t. challenge. Randomly selected microscopic fields of the lung (250/animal) were judged to be normal or abnormal without knowledge of treatment. This measurement was reproducible (r = 0.95 for duplicate measurements, n = 55). All guinea pigs were maintained in HEPA-filtered air. There was a low level of pulmonary response to an i.t. challenge of M. faeni in animals that received medium. Animals that received pulmonary cells, either cultured or noncultured, did not differ from those in the control group. There was a substantial increase (p less than 0.01) in the extent of pulmonary abnormalities in the recipients of the lymphoblast population, with significant correlation (r = 0.87, p less than 0.01) between the number of lymphoblasts transferred and the extent of pulmonary abnormalities.

  14. Different roles of retinal dopamine in albino Guinea pig myopia.

    PubMed

    Mao, Junfeng; Liu, Shuangzhen

    2017-02-03

    To investigate whether the different role of ocular dopamine was involved in the myopic development between spontaneous myopia (SM) and form deprivation myopia (FDM) in albino guinea pigs. 55 myopic animals were randomly divided into SM, Levodapa (L-DOPA), L-DOPA+carbidopa and vehicle. 70 non-myopic animals were randomly divided into normal control, FDM, L-DOPA+FDM, L-DOPA+carbidopa+FDM and vehicle. Once per day, for 14days, L-DOPA (10mg/kg) was injected intraperitoneally, and carbidopa (1μg) was injected at the same time into the peribulbar space of the right eye. Refractive parameters and dopamine content in neural retina and RPE/choroid complex were measured. In SM animals, high myopia was formed at 5 week of ages. L-DOPA treatment could reduce its myopic degree, and inhibit the increase of axial length and vitreous chamber depth with the increase of retinal dopamine in both eyes. Administration of carbidopa could prevent the increase of retinal dopamine induced by L-DOPA, but no influenced on its refractive state in the injected eyes. In non-SM animals, intraperitoneal L-DOPA could inhibit FDM, accompanied by the increase of retinal dopamine. Carbidopa treatment diminished the inhibition of FDM and prevented the increase in retinal dopamine by L-Dopa. Retinal dopamine was highly correlated with ocular refraction in FDM, but not in SM. There was no significant difference in dopamine content of RPE/choroid complex among all groups. The role of retinal dopamine was different between SM and FDM in albino guinea pigs. Although systemic L-DOPA could inhibit the development of SM and FDM, retinal dopamine was only involved in the L-DOPA inhibition on FDM, but not on SM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Involvement of chymase in allergic conjunctivitis of guinea pigs.

    PubMed

    Nabe, Takeshi; Kijitani, Yurie; Kitagawa, Yuriko; Sakano, Emi; Ueno, Tomoko; Fujii, Masanori; Nakao, Shintaro; Sakai, Masaru; Takai, Shinji

    2013-08-01

    It has been reported that chymase activity was increased in allergic conjunctivitis patients and this activity was correlated with the severity of the disease. However, the precise roles of chymase in allergic conjunctivitis are unclear, and whether chymase inhibitors are effective for allergic conjunctivitis has not been reported even in experimental animal models. In this study, the roles of chymase in the pathogenesis were evaluated using a selective chymase inhibitor, ONO-WH-236, in a guinea pig model of allergic conjunctivitis induced by cedar pollen. Sensitized guinea pigs were challenged by the pollen, followed by assessing redness and edema in the conjuntiva, and counting the frequency of eye scratching as an itch-associated response. Treatment with the ONO-WH-236 (40 and 80 mg/kg, p.o.) dose-dependently inhibited the induction of redness, edema and scratching behavior. An anti-histaminic drug, ketotifen (3 mg/kg, p.o.), also significantly inhibited conjunctivitis symptoms. Chymase activity was increased in ophthalmic lavage fluid immediately after the pollen challenge. The increase in chymase activity was inhibited by in vivo treatment with ONO-WH-236. Interestingly, increased histamine in the ophthalmic lavage fluid immediately after the challenge was also inhibited by the chymase inhibitor. Administration of human recombinant chymase by eye dropping (0.09 and 0.9 μg/eye) dose-dependently induced scratching behavior, which was inhibited by not only ONO-WH-236 but also ketotifen; however, chymase administration induced only weak redness in the conjunctiva, which was resistant to treatment with anti-histaminic drugs. In conclusion, it was suggested that chymase was released from mast cells after antigen challenge, followed by the induction of conjunctivitis symptoms through histamine release from mast cells. Thus, chymase could be a potential target for pharmacotherapy for allergic conjunctivitis.

  16. Ototoxicity of acetic acid on the guinea pig cochlea.

    PubMed

    Yamano, Takafumi; Higuchi, Hitomi; Nakagawa, Takashi; Morizono, Tetsuo

    2015-12-14

    To evaluate the ototoxicity of acetic acid solutions. Compound action potentials (CAPs) of the eighth nerve were measured in guinea pigs before and after the application of acetic acid in the middle ear cavity. The pH values of the acetic acid solutions were pH 3.0, 4.0, and 5.0, and the application times were 30 min, 24 h, and 1 week. Acetic acid solution (pH 3.0, N = 3) for 30 min caused no significant elevation in CAP threshold at 4 kHz, but a significant elevation in the threshold was noted for 8 kHz and clicks. Acetic acid solutions (pH 4.0 N = 6, 5.0 N = 5) for 30 min caused no significant elevation in CAP. Acetic acid solution (pH 4.0) for 24 h (N = 5) caused significant elevations of the CAP threshold for 8 kHz, 4 kHz, and for clicks. Acetic acid (pH 5.0) for 24 h (N = 3) caused a significant elevation of the CAP threshold for 4 kHz, but not for 8 kHz or clicks. Acetic acid (pH 5.0) for 1 week (N = 3) caused a small but significant elevation CAP the threshold for 8 kHz and 4 kHz tone bursts, but no significant change was noted for clicks. We found a significant toxic effect of acetic acid in guinea pigs on eighth-nerve compound action potentials when the pH was 5.0 or lower. Clearly, the stronger the acidity, and longer the exposure time, the more the CAP threshold was elevated.

  17. Methadone-induced respiratory depression in the neonatal guinea pig.

    PubMed

    Nettleton, Rosemary T; Ransom, Ty A; Abraham, Stephanie L; Nelson, Cole S; Olsen, George D

    2007-12-01

    Respiratory depression, the most serious side-effect of opioid treatment, is well documented for morphine, the most commonly used opioid in neonatal care. Less is known about methadone, a clinically relevant opioid analgesic, especially during neonatal development. This study was undertaken to determine the neonatal respiratory effects of methadone. We hypothesize that methadone is equipotent to morphine, compared to our previous morphine results in the same animal model, but has a much longer duration of action, due to its longer elimination half-life. Neonatal guinea pigs (3-14 days old) randomly received a single subcutaneous dose of methadone or saline. Using a non-invasive plethysmographic method, we measured ventilatory and metabolic parameters before injection and at intervals for 32 hr after injection while pups breathed "room air" or 5% CO(2) gas mixtures. Methadone-induced depression of ventilation was most evident during 5% CO(2) challenge. The onset of drug effects was within 15 min for all ages and doses, but the duration of action decreased with age. While the depth of methadone-induced respiratory depression did not depend on pup age, the control of breathing was different in 3-day-old pups, where inspiratory time increased fourfold; twice that of older pups. We conclude that methadone induces a naloxone reversible respiratory depression in guinea pig neonates and, in the very young, causes an abnormal breathing pattern due to changes in respiratory timing. Methadone is more potent than morphine with respect to neonatal respiratory depression, but surprisingly, the duration of methadone action was not longer than morphine.

  18. Evaluation of rhesus monkey and guinea pig hepatic cytosol fractions as models for human aldehyde oxidase.

    PubMed

    Choughule, Kanika V; Barr, John T; Jones, Jeffrey P

    2013-10-01

    Aldehyde oxidase (AOX) is a cytosolic enzyme expressed across a wide range of species, including guinea pig and rhesus monkey. These species are believed to be the best preclinical models for studying human AOX-mediated metabolism. We compared AOX activity in rhesus monkeys, guinea pigs, and humans using phthalazine and N-[2-(dimethylamino)ethyl]acridone-4-carboxamide (DACA) as substrates and raloxifene as an inhibitor. Michaelis-Menten kinetics was observed for phthalazine oxidation in rhesus monkey, guinea pig, and human liver cytosol, whereas substrate inhibition was seen with DACA oxidase activity in all three livers. Raloxifene inhibited phthalazine and DACA oxidase activity uncompetitively in guinea pig, whereas mixed-mode inhibition was seen in rhesus monkey. Our analysis of the primary sequence alignment of rhesus monkey, guinea pig, and human aldehyde oxidase isoform 1 (AOX1) along with homology modeling has led to the identification of several amino acid residue differences within the active site and substrate entrance channel of AOX1. We speculate that some of these residues might be responsible for the differences observed in activity. Overall, our data indicate that rhesus monkeys and guinea pigs would overestimate intrinsic clearance in humans and would be unsuitable to use as animal models. Our study also showed that AOX metabolism in species is substrate-dependent and no single animal model can be reliably used to predict every drug response in humans.

  19. Evaluation of Rhesus Monkey and Guinea Pig Hepatic Cytosol Fractions as Models for Human Aldehyde Oxidase

    PubMed Central

    Choughule, Kanika V.; Barr, John T.

    2013-01-01

    Aldehyde oxidase (AOX) is a cytosolic enzyme expressed across a wide range of species, including guinea pig and rhesus monkey. These species are believed to be the best preclinical models for studying human AOX-mediated metabolism. We compared AOX activity in rhesus monkeys, guinea pigs, and humans using phthalazine and N-[2-(dimethylamino)ethyl]acridone-4-carboxamide (DACA) as substrates and raloxifene as an inhibitor. Michaelis-Menten kinetics was observed for phthalazine oxidation in rhesus monkey, guinea pig, and human liver cytosol, whereas substrate inhibition was seen with DACA oxidase activity in all three livers. Raloxifene inhibited phthalazine and DACA oxidase activity uncompetitively in guinea pig, whereas mixed-mode inhibition was seen in rhesus monkey. Our analysis of the primary sequence alignment of rhesus monkey, guinea pig, and human aldehyde oxidase isoform 1 (AOX1) along with homology modeling has led to the identification of several amino acid residue differences within the active site and substrate entrance channel of AOX1. We speculate that some of these residues might be responsible for the differences observed in activity. Overall, our data indicate that rhesus monkeys and guinea pigs would overestimate intrinsic clearance in humans and would be unsuitable to use as animal models. Our study also showed that AOX metabolism in species is substrate-dependent and no single animal model can be reliably used to predict every drug response in humans. PMID:23918666

  20. 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.

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

    PubMed

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

    2011-09-01

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

  2. A novel guinea pig macrophage-specific polymorphic molecule. I. Biochemistry, genetics, and tissue distribution.

    PubMed

    Jensen, L A; Schwartz, B D

    1988-02-15

    In the course of studying Ia molecules from strain 2 and strain 13 guinea pig macrophages, with the intent of comparing them to B cell Ia molecules, it was observed that guinea pig alloserum prepared by cross-immunization of guinea pig lymphocyte Ag non-identical inbred guinea pigs immunoprecipitated not only conventional class I and class II molecules, but also a 98,000-Da molecule, termed gp98. Two different forms of the molecule were detected, indicating it is polymorphic. The genes encoding gp98 were shown not to be linked to the guinea pig lymphocyte Ag complex. The molecule gp98 was found on macrophages within populations of peritoneal exudate cells, resident peritoneal cells, bone marrow cells, and spleen. All gp98-bearing macrophages were also Ia-positive. However, only a subpopulation of macrophages bore gp98. The gp98 was not found on Ly-1 or Ig-bearing cells, indicating that B and T cells do not bear Ia. Thus, gp98 appears to be a highly immunogenic polymorphic macrophage-specific molecule that allows the characterization of guinea pig macrophage subsets.

  3. Effects of ascorbic acid deficiency on methyl mercury dicyandiamide toxicosis in guinea pigs.

    PubMed

    Yamini, B; Sleight, S D

    1984-07-01

    Methylmercury dicyandiamide (MMD) when given intraperitoneally at a dosage of 4 mg/kg of body weight at weekly intervals for 3 weeks resulted in death of guinea pigs fed an ascorbic acid deficient diet. Controls fed an ascorbic acid deficient diet survived during this period as did guinea pigs given MMD and fed an ascorbic acid adequate diet. In a second experiment, guinea pigs fed an ascorbic acid deficient diet containing 22 ppm of MMD died within 26 days and had severe hemorrhagic and ulcerative gastroenteritis and coagulative necrosis of the liver. Ascorbic acid deficient controls died at 34 days. The MMD-containing ascorbic acid adequate diet killed guinea pigs in 150 days. Guinea pigs fed an ascorbic acid deficient diet with 44 ppm of MMD died within 20 days with acute neurologic signs. Pathologic changes were mostly in the gray matter. Guinea pigs fed MMD and a diet with adequate ascorbic acid survived for 38 days whereas the ascorbic acid deficient controls survived for 47 days. Results indicate that ascorbic acid deficiency can be a factor in the location and severity of clinical signs and lesions of MMD.

  4. Anti-anaphylactic action of nordihydroguaiaretic acid in antigen sensitized guinea pigs.

    PubMed

    Bergren, Dale R; Valentine, Jimmie L

    2016-12-01

    Therapeutic natural products and medicinal herbs has gained popularity. The anti-antigenic action of the plant alkaloid nordihydroguaiaretic acid (NDGA) was studied in ovalbumin (OA)-sensitized guinea pigs. In one series of experiments conscious, non-sedated guinea pigs were challenged with OA aerosol. Specific airway resistance (SRAW) was monitored using a two-chambered whole-body plethysmograph. OA aerosol increased SRAW above that produced by vehicle administration. Prior NDGA administration by a 1min 0.9% aerosol (w/vol) attenuated the increase in SRAW resulting from OA challenge. In the anesthetized guinea pig pretreated with indomethacin, pyrilamine and propranolol, intravenous OA injection increased intra-tracheal pressure above vehicle injection. Intravenous NDGA administration (5mg/kg) reduced the intra-tracheal pressure increases. In a third series of experiments plasma leukotriene C4 was measured by radio-immunoassay in 3 groups challenged with OA aerosol: vehicle-treated OA-sensitized, OA-sensitized receiving NDGA and vehicle treated guinea pigs. NDGA pretreatment reduced plasma LTC4 in response to OA challenge in OA sensitized guinea pigs. This study demonstrates that NDGA is an effective antigenic agent when given by aerosol or intravenous injection in either conscious or anesthetized guinea pigs, respectively. The mechanism of action of NDGA is presumed primarily be due to the blockage of 5-lipoxygenase and therefore the synthesis of leukotrienes. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Increased Severity of Tuberculosis in Guinea Pigs with Type 2 Diabetes

    PubMed Central

    Podell, Brendan K.; Ackart, David F.; Obregon-Henao, Andres; Eck, Sarah P.; Henao-Tamayo, Marcela; Richardson, Michael; Orme, Ian M.; Ordway, Diane J.; Basaraba, Randall J.

    2015-01-01

    Impaired glucose tolerance and type 2 diabetes were induced in guinea pigs to model the emerging comorbidity of Mycobacterium tuberculosis infection in diabetic patients. Type 2 diabetes mellitus was induced by low-dose streptozotocin in guinea pigs rendered glucose intolerant by first feeding a high-fat, high-carbohydrate diet before M. tuberculosis exposure. M. tuberculosis infection of diabetic guinea pigs resulted in severe and rapidly progressive tuberculosis (TB) with a shortened survival interval, more severe pulmonary and extrapulmonary pathology, and a higher bacterial burden compared with glucose-intolerant and nondiabetic controls. Compared with nondiabetics, diabetic guinea pigs with TB had an exacerbated proinflammatory response with more severe granulocytic inflammation and higher gene expression for the cytokines/chemokines interferon-γ, IL-17A, IL-8, and IL-10 in the lung and for interferon-γ, tumor necrosis factor-α, IL-8, and monocyte chemoattractant protein-1 in the spleen. TB disease progression in guinea pigs with impaired glucose tolerance was similar to that of nondiabetic controls in the early stages of infection but was more severe by day 90. The guinea pig model of type 2 diabetes–TB comorbidity mimics important features of the naturally occurring disease in humans. This model will be beneficial in understanding the complex pathogenesis of TB in diabetic patients and to test new strategies to improve TB and diabetes control when the two diseases occur together. PMID:24492198

  6. Efficacy of doramectin in Trixacarus caviae infestation in guinea pigs (Cavia porcellus).

    PubMed

    Singh, Shanker K; Dimri, Umesh; Ahmed, Quazi Shahir; Sayedda, Kauser; Singh, Krishna Veer

    2013-04-01

    The present study was intended to evaluate the efficacy of doramectin against seven naturally Trixacarus caviae infested male guinea pigs. Multiple skin scrapings of all the seven guinea pigs were found microscopically positive for T. caviae mites. Clinically these animals revealed, more or less denuded, very red often thickened, and crustated cutaneous lesions restricted at the sacral region and back. Doramectin 1 % (w/v) was administered intramuscularly at a dose rate of 400 μg/kg once weekly, which resulted in profound improvements in clinical conditions within 14 days after the first doramectin application. It took almost 28 days for the cutaneous lesions to disappear and to witness partial hair coat regrowth. Two moderately infested guinea pigs required only single injection of doramectin to achieve complete parasitological cure, while remaining five (one moderately infested and four severely infested) guinea pigs required two injections of doramectin to achieve complete parasitological cure. No adverse effects were revealed by any of the doramectin treated guinea pigs during the study period. Thus, it can be concluded from the present study that guinea pigs naturally infested by T. caviae mites can be cured safely using two doses of doramectin once in a week.

  7. 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.

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

    SciTech Connect

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

    1981-12-01

    The immunogenicity of inbred strain 2/N guinea pig fibroblasts transformed to the malignant state in vitro by chemical carcinogens was evaluated with the use of a variety of in vivo and in vitro methods including delayed-type hypersensitivity skin and tumor transplantation tests and analysis of antibody production by immunofluorescence, complement fixation, and staphylococcal protein A binding tests. Neoplastic transformation was induced by direct treatment of cells in culture with benzo(a)pyrene, 3-methylcholanthrene, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or by the host-mediated method by which fetuses were exposed to diethylnitrosamine or MNNG in vivo prior to cell culture. Rabbits and syngeneic guinea pigs were inoculated with unirradiated and X-irradiated clonally derived cells. Delayed hypersensitivity skin reactions to immunizing or other cells were equivalent in immunized or control guinea pigs, and no protection to tumor outgrowth from a challenge inoculum of immunizing cells was observed. Antibody activity induced in the sera of immunized guinea pigs was cross-reactive and removed by absorption with nontumorigenic cells. Rabbit anitsera after absorption with fetal guinea pig cells were nonreactive with the specific immunizing or other cultured cells. Chemical carcinogen-induced neoplastic transformation of guinea pig cells can, therefore, occur without formation of detectable, individually distinct cell surface tumor-specific neoantigens.

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

    SciTech Connect

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

    1981-12-01

    The immunogenicity of inbred strain 2/N guinea pig fibroblasts transformed to the malignant state in vitro by chemical carcinogens was evaluated with the use of a variety of in vivo and in vitro methods including delayed-type hypersensitivity skin and tumor transplantation tests and analysis of antibody production by immunofluorescence, complement fixation, and staphylococcal protein A binding tests. Neoplastic transformation was induced by direct treatment of cells in culture with benzo(a)pyrene, 3-methylcholanthrene, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or by the host-mediated method by which fetuses were exposed to diethylnitrosamine or MNNG in vivo prior to cell culture. Rabbits and syngeneic guinea pigs were inoculated with unirradiated and X-irradiated clonally derived cells. Delayed hypersensitivity skin reactions to immunizing or other cells were equivalent in immunized or control guinea pigs, and no protection to tumor outgrowth from a challenge inoculum of immunizing cells was observed. Antibody activity induced in the sera of immunized guinea pigs was cross-reactive and removed by absorption with nontumorigenic cells. Rabbit antisera after absorption with fetal guinea pig cells were nonreactive with the specific immunizing or other culture cells. Chemical carcinogen-induced neoplastic transformation of guinea pig cells can, therefore, occur without formation of detectable, individually distinct cell surface tumor-specific neoantigens.

  10. [Establishing an experimental guinea pig model of dermatophytosis Using Trichophyton rubrum].

    PubMed

    Chen, Xian-Jin; Shen, Yong-Nian; Lü, Gui-Xia; Liu, Wei-Da

    2008-10-01

    To construct an animal model infected by Trichophyton rubrum. Three different strains of Trichophyton rubrum were separated from clinical specimen for the infection of guinea pigs. Corticosteroids were given before and after the construction of animal model to facilitate the infection. Direct microscopy, culture, and histopathologic methods were adopted to verify the construction. Ten days after the inoculation of Trichophyton rubrum, with the intervention of corticosteroid, the guinea pigs were examined. Prominent scales and inflammation could be seen on the inoculation site of the Trichophyton rubrum infected guinea pig. Scales and hairs of Trichophyton rubrum infected guinea pig dealt with 10% potassium hydroxide, hypha out of the hair and microconidia or hypha in the hair shaft could be seen. Seven days after the inoculation of scales and hair on SDA plate, cultures of Trichophyton rubrum showed that the colonial morphology were identical to the original dermatophytes. PAS staining of infected guinea pig skin tissue showed that hypha and microconidia could be seen in the infundibula and hair root. With the intervention of corticosteroid, a stable guinea pig model infected by Trichophyton rubrum were successfully constructed.

  11. 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

  12. Renal denervation suppresses ventricular arrhythmias during acute ventricular ischemia in pigs.

    PubMed

    Linz, Dominik; Wirth, Klaus; Ukena, Christian; Mahfoud, Felix; Pöss, Janine; Linz, Benedikt; Böhm, Michael; Neuberger, Hans-Ruprecht

    2013-10-01

    Increased sympathetic activation during acute ventricular ischemia is involved in the occurrence of life-threatening arrhythmias. To test the effect of sympathetic inhibition by renal denervation (RDN) on ventricular ischemia/reperfusion arrhythmias. Anesthetized pigs, randomized to RDN or SHAM treatment, were subjected to 20 minutes of left anterior descending coronary artery (LAD) occlusion followed by reperfusion. Infarct size, hemodynamics, premature ventricular contractions, and spontaneous ventricular tachyarrhythmias were analyzed. Monophasic action potentials were recorded with an epicardial probe at the ischemic area. Ventricular ischemia resulted in an acute reduction of blood pressure (-29%) and peak left ventricular pressure rise (-40%), which were not significantly affected by RDN. However, elevation of left ventricular end-diastolic pressure (LVEDP) during LAD ligation was attenuated by RDN (ΔLVEDP: +1.8 ± 0.6 mm Hg vs +9.7 ± 1 mm Hg in the SHAM group; P = .046). Infarct size was not affected by RDN compared to SHAM. RDN significantly reduced spontaneous ventricular extrabeats (160 ± 15/10 min in the RDN group vs 422 ± 36/10 min in the SHAM group; P = .021) without affecting coupling intervals. In 5 of 6 SHAM-treated animals, ventricular fibrillation (VF) occurred during LAD occlusion. By contrast, only 1 of 7 RDN-treated animals experienced VF (P = .029). Beta-receptor blockade by atenolol showed comparable effects. Neither VF nor transient shortening of monophasic action potential duration during reperfusion was inhibited by RDN. RDN reduced the occurrence of ventricular arrhythmias/fibrillation and attenuated the rise in LVEDP during left ventricular ischemia without affecting infarct size, changes in ventricular contractility, blood pressure, and reperfusion arrhythmias. Therefore, RDN may protect from ventricular arrhythmias during ischemic events. © 2013 Heart Rhythm Society. All rights reserved.

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

    PubMed

    Osadchii, Oleg E

    2014-12-01

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

  14. Effects of HNS-32, a novel antiarrhythmic agent, on guinea-pig myocardium.

    PubMed

    Noguchi, Kazuo; Kase, Junya; Saitoh, Mariko; Masumiya, Haruko; Saitoh, Masaki; Nakazawa, Tomoo; Tanaka, Yoshio; Tanaka, Hikaru; Hashimoto, Keitaro; Shigenobu, Koki

    2002-01-01

    The electrophysiological and mechanical effects of HNS-32, a novel azulene-1-carboxamidine derivative with antiarrhythmic activity, were studied in isolated guinea-pig myocardial preparations. HNS-32 (10(-6)-10(-4) mol/l) concentration-dependently decreased the maximum rate of rise (V(max)) of action potential in isolated papillary muscle; the potency was the same or slightly higher than that of disopyramide. At 10(-4) mol/l, HNS-32 also shortened the action potential duration (APD) and depolarized the resting membrane potential; these effects were similar to those of 10(-5) mol/l verapamil. HNS-32 (10(-7)-10(-4) mol/l), as well as verapamil (10(-8)-10(-5) mol/l) and disopyramide (10(-6)-10(-3) mol/l), had concentration-dependent negative chronotropic and negative inotropic effects on isolated right atrial and right ventricular papillary muscle preparations, respectively. The concentration-response relationship for the positive chronotropic effect of isoproterenol was not affected by HNS-32 (10(-5) mol/l). In isolated ventricular myocytes, HNS-32 (10(-6)-10(-4) mol/l) concentration-dependently inhibited the peak amplitude of the L-type Ca(2+) current. These results suggest that NHS-32 has V(max) reducing activity on myocardial tissue, which may be responsible for antiarrhythmic effect. The drug may also have additional effect on the Ca(2+) channel at higher concentrations. Copyright 2002 S. Karger AG, Basel

  15. Attenuation of Ca paradox injury in guinea pig heart by K+ channel blocker, d-sotalol.

    PubMed

    Tribulova, N; Sosner, I; Varon, D; Manoach, M

    1999-01-01

    D-sotalol was shown to prevent Ca overload and intermyocyte uncoupling. The aim of this study was to investigate the effect of d-sotalol in Ca paradox conditions. Guinea pig hearts were perfused at 37 degrees C and constant pressure with oxygenated Tyrode solution. Ca paradox was induced by 10 min Ca free perfusion followed by 10 min Ca repletion. 10(-6) M d-sotalol was administered either during Ca depletion or during Ca repletion period. Electrical activity and ventricular contraction were simultaneously recorded and subcellular alterations were analysed. The contraction terminated in 5 min of Ca free perfusion and electrical activity disappeared within 5 min of Ca repletion. Nonuniform injury of myocardial tissue was observed. The majority of cardiomyocytes were irreversibly injured and profound dissociation of intercellular junctions was detected. Administration of d-sotalol during Ca free period preserved electrical activity and restored ventricular contraction accompanied by apparent protection of the ultrastructure, including intercellular connections. Uniform patterns of sarcomeres reflected synchronous contraction and protection of junctional couplings. In conclusion, d-sotalol attenuates Ca paradox injury. It seems that the protective effect of d-sotalol is most likely related to inhibition of potassium efflux antagonizing Na loading during Ca depletion period, as well as to attenuation of excess of [Ca2+]i via acceleration of sarcoplasmic Ca exchange during Ca repletion.

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

    PubMed

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

    2017-09-01

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

  17. 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.

  18. 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

  19. 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

  20. Analysis of humoral immune responses to LM1 ganglioside in guinea pigs.

    PubMed

    Gu, Yajuan; Chen, Zi-Wei; Siegel, Allan; Koshy, Ranie; Ramirez, Cristhian; Raabe, Timothy D; Devries, George H; Ilyas, Amjad A

    2012-05-15

    Guillain-Barré syndrome (GBS) is an autoimmune-mediated disease triggered by a preceding infection. A substantial body of evidence implicates antibodies to various gangliosides in subtypes of GBS. A significant proportion of patients with acute demyelinating subset of GBS have IgG antibodies against peripheral nervous system myelin specific neolactogangliosides such as LM1 and Hex-LM1. Although anti-neolactoganglioside antibodies in GBS were described more than two decades ago, their pathogenic role in neuropathy remains unknown due to the lack of suitable experimental models. In this study, we immunized ten guinea pigs with purified LM1 ganglioside mixed with keyhole limpet hemocyanin (KLH) and emulsified in complete Freund's adjuvant (CFA). Control guinea pigs were injected with KLH emulsified in CFA only. The animals were bled every four week intervals. The animals were boosted 3 times every four weeks. Experiments were terminated four months after initial immunization. Nine of 10 guinea pigs immunized with LM1 exhibited antibody responses to LM1. Anti-LM1 IgG titers in nine guinea pigs ranged from 1:400 to 1:12,800 at 16-weeks after initial immunization. Anti-LM1 antibodies were predominantly of IgG2 subclass. One guinea pig with the highest levels of IgG antibodies exhibited mild signs of neuropathy. There was no evidence of demyelination or inflammation in the sciatic nerves of LM1-immunized guinea pigs. Anti-LM1 antibodies bound to rat sciatic nerve myelin and to isolated rat Schwann cells. In summary, our findings suggest that relatively high levels of anti-LM1 IgG antibodies can be induced in guinea pigs and that LM1 is localized in peripheral nerve myelin and in Schwann cells. Further studies are needed to determine the pathogenic potential of anti-neolactoganglioside antibodies in neuropathy.

  1. Deterioration of epithelium mediated mechanisms in diabetic-antigen sensitized airways of guinea pigs.

    PubMed

    Bano, Saidullah; Swati, Omanwar; Kambadur, Muralidhar; Mohammad, Fahim

    2016-01-01

    The onset of diabetes causes disruption of respiratory epithelial mediators. The present study investigates whether diabetes modifies the epithelium mediated bronchial responses in hyper-reactive airway smooth muscle (ASM) primarily through nitric oxide (NO), cyclooxygenase (COX), and epithelium derived hyperpolarizing factor (EpDHF) pathways. Experimental model of guinea pigs having hyper-reactive airways with or without diabetes were developed. The responses of tracheal rings to cumulative concentrations of acetylcholine (ACh) and isoproterenol (IP) in the presence and absence of epithelium and before and after incubation with NO, K(+)ATP and COX inhibitors, N-(ω)-Nitro-L-arginine methyl ester (L-NAME; 100 μM), glybenclamide (10 μM) and indomethacin (100 μM) were assessed. In diabetic guinea pigs with hyper-reactive airways, a decrease in ACh induced bronchoconstriction was observed after epithelium removal and after incubation with L-NAME/indomethacin, suggesting damage to NO/COX pathways. Hyper-reactivity did not alter the response of trachea to ACh but affected the response to IP which was further reduced in hyper-reactive animals with diabetes. The ASM response to IP after glybenclamide treatment did not alter in hyper-reactive guinea pigs and diabetic guinea pigs with hyper-reactive airways, suggesting damage to the EpDHF pathway. Treatment with indomethacin reduced IP response in the hyper-reactive model, and did not produce any change in diabetic model with hyper-reactive airways, indicating further disruption of the COX pathway. EpDHF pathway is damaged in hyper-reactive guinea pigs and in diabetic guinea pigs with hyper-reactive airways. Diabetes further aggravates the NO and COX mediated pathways in diabetic guinea pigs with hyper-reactive airways.

  2. Airway hyperresponsiveness induced by repeated esophageal infusion of HCl in guinea pigs.

    PubMed

    Cheng, Yan-Mei; Cao, Ai-Li; Zheng, Jian-Pu; Wang, Hong-Wei; Sun, Yong-Shun; Liu, Chun-Fang; Zhang, Bei-Bei; Wang, Yi; Zhu, Sheng-Liang; Wu, Da-Zheng

    2014-11-01

    Gastroesophageal reflux is a common disorder closely related to chronic airway diseases, such as chronic cough, asthma, chronic bronchitis, and chronic obstructive disease. Indeed, gastroesophageal acid reflux into the respiratory tract causes bronchoconstriction, but the underlying mechanisms have still not been clarified. This study aimed to elucidate functional changes of bronchial smooth muscles (BSMs) isolated from guinea pigs in an animal model of gastroesophageal reflux. The marked airway inflammation, hyperresponsiveness and remodeling were observed after guinea pigs were exposed to intraesophageal HCl infusion for 14 days. In addition, contractile responses to acetylcholine (ACh), KCl, electrical field stimulation, and extracellular Ca(2+) were greater in guinea pigs infused with HCl compared with control groups. The L-type voltage-dependent Ca(2+) channels (L-VDCC) blocker, nicardipine, significantly inhibited ACh- and Ca(2+)-enhanced BSM contractions in guinea pigs infused with HCl. The Rho-kinase inhibitor, Y27632, attenuated ACh-enhanced BSM contractions in guinea pigs infused with HCl. Moreover, mRNA and protein expressions for muscarinic M2 and M3 receptors, RhoA, and L-VDCC in BSM were detected by real-time PCR and Western blot. Expressions of mRNA and protein for muscarinic M3 receptors, RhoA, and L-VDCC were greater than in BSM of HCl-infused guinea pigs, whereas levels of muscarinic M2 receptors were unchanged. We demonstrate that acid infusion to the lower esophagus and, subsequently, microaspiration into the respiratory tract in guinea pigs leads to airway hyperresponsiveness and overactive BSM. Functional and molecular results indicate that overactive BSM is the reason for enhancement of extracellular Ca(2+) influx via L-VDCC and Ca(2+) sensitization through Rho-kinase signaling.

  3. 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.

  4. Novel organization and processing of the guinea pig pancreatic polypeptide precursor.

    PubMed

    Blackstone, C D; Seino, S; Takeuchi, T; Yamada, T; Steiner, D F

    1988-02-25

    Studies on New World hystricomorph rodents have revealed interesting structural divergences in the peptide hormones of the islets of Langerhans, particularly with respect to insulin and glucagon. Herein we report the isolation and sequencing of a cDNA encoding the precursor of pancreatic polypeptide (PP) from a guinea pig pancreas cDNA library. The 126-residue precursor sequence is predicted to include a 26-residue NH2-terminal signal peptide followed by the 36-amino acid PP hormonal sequence and a large COOH-terminal extension. The sequence identity between guinea pig and human PP is 89% (32/36 residues), and the predicted sequence is in agreement with that reported by Eng et al. (Eng, J., Huang, C.-G., Pan, Y.-C. E., Hulmes, J. D., and Yalow, R. S. (1987) Peptides 8, 165-168). In contrast, the icosapeptide domain in the guinea pig precursor exhibits only 40% (8/20) identity with the corresponding human precursor domain, and the COOH-terminal extension differs greatly in both sequence and size. The guinea pig precursor lacks the monobasic processing site (Pro-Arg) found at the COOH terminus of the icosapeptide domain in human, ovine, canine, and feline proPP. An icosapeptide is thus not likely to be liberated as such from this precursor. Of particular interest in guinea pig proPP is the substitution of serine for arginine at the dibasic amino acid processing site on the COOH-terminal side of the PP domain. Results of radioimmunoassays of gel-filtered protein fractions from a guinea pig pancreas extract indicate that efficient proteolytic cleavage takes place at this Lys-Ser site and that mature guinea pig PP is normally carboxyamidated.

  5. 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.

  6. Contractile effects of cysteamine on the guinea-pig ileum.

    PubMed Central

    Bakich, V.; Brown, J.; Kwok, Y. N.; McIntosh, C.; Nishimura, E.

    1984-01-01

    Cysteamine (beta-mercaptoethylamine HCl) (1.0-40.0 mM) induced a concentration-dependent increase in tonic and phasic contractions of segments of guinea-pig ileum in vitro. Myenteric plexus-longitudinal muscle (MPLM) preparations also responded with an increase in tonic contractions but phasic contractions were either greatly reduced or absent, indicating that these were a response of the circular muscle. Atropine (5 microM) inhibited the cysteamine-induced contractions, whereas hexamethonium and guanethidine had no effect, suggesting that cysteamine was acting at least partly via a cholinergic mechanism involving muscarinic receptors. Tetrodotoxin increased the phasic contractions of ileal segments, but had no effect on the tonic component. Treatment of MPLM preparations with morphine (1 microM) resulted in a small reduction in responsiveness to cysteamine, and blocked electrically-induced contractions by at least 90%. Since morphine acts by inhibiting acetylcholine release via hyperpolarization of intrinsic neurones, a small but significant part of the cysteamine-induced contractions probably resulted from stimulation of acetylcholine release from intrinsic neurones. Following a response to high cysteamine concentrations (greater than 15 mM) tissues were refractory to subsequent cysteamine administration. Cross-desensitization between cysteamine and acetylcholine also occurred, as short-term (1-3 min) incubation of MPLM preparations with high concentrations of either compound (1-10 microM acetylcholine or 20 mM cysteamine) resulted in a reduced responsiveness to both. A reduced sensitivity to acetylcholine or cysteamine was obtained following long-term (45 min) incubation with acetylcholine (1 microM). Removal of Na+ from the incubation medium negated this effect. In contrast, the refractoriness to acetylcholine or cysteamine following long-term (45 min) incubation with cysteamine (20 mM) was accentuated in low Na+ medium. It is suggested that cysteamine induces

  7. Electrophysiological effects of CI-980, a tubulin binding agent, on guinea-pig papillary muscles

    PubMed Central

    Pérez, Onésima; Valenzuela, Carmen; Delpón, Eva; Tamargo, Juan

    1997-01-01

    The electrophysiological effects of CI-980, a new tubulin-binding agent that inhibits assembly of cytoplasmic microtubules, on transmembrane action potential characteristics were studied in right ventricular papillary muscles from guinea-pig hearts. In papillary muscles driven at 1 Hz, CI-980 at concentrations ⩾10−5 M produced a concentration-dependent increase in the maximum upstroke velocity (Vmax) and a lengthening of the action potential duration at 50% (APD50) and 90% (APD90) of repolarization without affecting the resting membrane potential. Prolongation of the APD90 was accompanied by a parallel lengthening of the effective refractory period (ERP) so that the ERP/APD90 ratio remained unaltered at all drug concentrations tested. CI-980 exhibits a reverse use-dependent effect on APD90 values, that is, drug-induced APD90 prolongation become exagerated at slow rates and attenuated at fast rates. CI-980 at concentrations ⩾10−6 M lengthened the APD of the slow action potentials elicited by isoprenaline in papillary muscles depolarized by high K+ (27 mM) solution. At 10−5 M, CI-980 produced a small tonic Vmax block. However, in muscles driven at rates between 0.5 and 3 Hz it produced an exponential decline in Vmax (use-dependent Vmax block) which was augmented at higher rates of stimulation. At 3 Hz the onset kinetics of the use-dependent Vmax block was fitted by a monoexponential function with a K value 0.07±0.01 per AP. The recovery time constant (τre) from the use-dependent Vmax block was prolonged from 21.6±2.6 ms to 3.5±0.2 s. The curve relating membrane potential and Vmax was shifted by CI-980 (10−5 M) in the hyperpolarizing direction by 2.3±1.1 mV. It is concluded that in guinea-pig papillary muscles, CI-980 produces a use-dependent inhibition of Vmax and a reverse use-dependent prolongation of the ventricular action potential, thus exhibiting class I and class III antiarrhythmic actions, respectively. From the onset

  8. Inhibition of some aspects of acute inflammation of guinea-pig lung by intraperitoneal dexamethasone and mifepristone: demonstration of agonist activity of mifepristone in the guinea-pig.

    PubMed

    Whelan, C J; Hughes, S C; Wren, G P

    1995-03-01

    We have determined the inhibitory activity of dexamethasone as an inhibitor of histamine-induced plasma protein extravasation (PPE) in guinea-pig lung and skin, and of lipopolysaccharide (LPS)-induced neutrophilia and platelet activating factor (PAF)-induced eosinophilia in guinea-pig lungs. Dexamethasone inhibited PAF-induced eosinophilia in guinea-pig lung (ED50 1.4 mg/kg i.p.). Higher doses of dexamethasone were required to inhibit LPS-induced neutrophilia (ED50 10.8 mg/kg i.p.). However, at doses up to 150 mg/kg i.p. dexamethasone did not inhibit histamine-induced plasma protein extravasation (PPE) in guinea-pig lung, but did inhibit PPE in guinea-pig skin. These preparations have previously been shown to be equally sensitive to inhibition by the beta 2-adrenoceptor agonist salmeterol. Dexamethasone inhibited PAF-induced eosinophilia (5 mg/kg) or LPS-induced neutrophilia (50 mg/kg) when given 3 h or 1 h prior to challenge. Inhibitory activity was lost when dexamethasone was administered 23 h prior to LPS or 1 h after PAF. The glucocorticoid antagonist mifepristone (1-100 mg/kg i.p.) caused dose-related inhibition of PAF-induced eosinophilia but not of LPS-induced neutrophilia. The highest dose of mifepristone used (100 mg/kg) did not reverse the inhibitory actions of dexamethasone (50 mg/kg) on LPS-induced neutrophilia. We suggest that the different inhibitory activity of dexamethasone in the preparations studied indicates differences in the sensitivity of the target cells involved to inhibition by dexamethasone. We also suggest that inhibition of PAF-induced eosinophilia by mifepristone reflects the partial agonist activity of this agent, demonstrated by others in different experimental systems.

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

    SciTech Connect

    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 x 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.

  10. 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

  11. 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

  12. In vivo imaging and vibration measurement of Guinea pig cochlea

    NASA Astrophysics Data System (ADS)

    Choudhury, Niloy; Chen, Fangyi; Zheng, Jiefu; Nuttall, Alfred L.; Jacques, Steven L.

    2008-02-01

    An optical coherence tomography (OCT) system was built to acquire in vivo, both images and vibration measurements of the organ of Corti of the guinea pig. The organ of Corti was viewed through a ~500-μm diameter hole in the bony wall of the scala tympani of the first cochlear turn. In imaging mode, the image was acquired as reflectance R(x,z). In vibration mode, the basilar membrane (BM) or reticular lamina (RL) was selected based on the image. Under software control, the system would move the scanning mirrors to bring the sensing volume of the measurement to the desired tissue location. To address the gain stability problem of the homodyne OCT system, arising from the system moving in and out of the quadrature point and also to resolve the 180 degree ambiguity in the phase measurement using an interferometer, a vibration calibration method is developed by adding a vibrating source to the reference arm to monitor the operating point of the interferometric system. Amplitude gain and phase of various cochlear membranes was measured for different sound pressure level (SPL) varying from 65dB SPL to 93 dB SPL.

  13. Antispasmodic effect of 4'-methylepigallocatechin on guinea pig ileum.

    PubMed

    da Rocha, Marcelly Barbosa; Souza, Fábia Valéria Menezes; dos Santos Estevam, Charlez; Pizza, Cosimo; Sant'ana, Antônio Euzébio Goulart; Marçal, Rosilene Moretti

    2012-10-01

    The antispasmodic effect of 4'-methylepigallocatechin (MEC), which was isolated from Maytenus rigida Mart (Celestraceae), was investigated in vitro in guinea pig intestinal segments. In the isolated ileum, MEC (1 nM-100 μM) did not modify the ileal spontaneous tonus or the electrically elicited contractions. MEC (8 μM) significantly (p<0.01) reduced the submaximal contractions induced by histamine (2 μM), carbachol (100 μM) and BaCl₂ (0.03 M). An additive relaxing action (p<0.001) was observed by co-incubation of verapamil (10 nM) and MEC (8 μM). Although MEC (1 nM-100 μM) did not modify the contractions elicited by 60 mM KCl, it significantly reduced the CaCl₂ contractile response without changing the EC₅₀ (effective concentration of CaCl₂ causing 50% of maximum response). In brief, these results show that MEC has a potent ileal spasmolytic effect and blocks spasms induced by specific and nonspecific stimuli. Importantly, the spasmolytic effects were attained at low concentrations and might be related to the symptomatic relief of abdominal pain that is obtained from the use of the M. rigida stem bark. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum.

    PubMed

    Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

    2015-05-10

    Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain.

  15. Acquired chemotactic inhibitors during infection with guinea pig cytomegalovirus.

    PubMed Central

    Tannous, R; Myers, M G

    1983-01-01

    Factors involved in neutrophil and monocyte migrations were serially studied in strain 2 guinea pigs undergoing initial cytomegalovirus infection and sham-inoculated controls. All studies remained unchanged in uninfected animals. Monocyte migrations and neutrophil spontaneous migration remained unchanged in infected animals. However, transient abnormalities occurred early in infection, comprising a decrease in neutrophil-directed migration towards C5-derived chemotactic fractions (C5-fr) and a decrease in the chemotactic activity of zymosan-activated plasma. Consequently, the presence of neutrophil- and chemotaxin-directed inhibitors in plasma was investigated. Normal neutrophils, C5-fr, Escherichia coli-derived bacterial factor, and the synthetic peptide F-met-leu-phe were first incubated with control or infected plasmas and then assayed for directed migration and lysosomal enzyme release. Results indicated the de novo appearance of both neutrophil- and chemotaxin-directed inhibitory activities in plasma during early infection. The neutrophil-directed inhibition was heat stable (56 degrees C for 120 min) and nonspecific (responses to all chemotaxins were inhibited). The chemotaxin-directed inhibition was heat stable and C5-fr specific. The cytomegalovirus-induced inhibitors may be important in the enhanced susceptibility to concurrent opportunistic infections. PMID:6305847

  16. Immune modulation in the guinea pig using cortisone acetate.

    PubMed

    Scipioni, R L; Baggs, R B; Kraus, A L

    1991-01-01

    Cortisone acetate was administered to a group of guinea pigs (Cavia porcellus) at 0 (control), 20 (low) or 200 (high) mg/kg. Steroid was given daily for two individual 7 day periods, separated by 7 days of no treatment. The effects of this steroid on body weight gain, thymic weight, total and differential leukocyte counts, serum antibody titer against a bacterin, dermal hypersensitivity response to a sensitizing agent and histological evaluation of lymphoid and other tissues were evaluated. Significant differences in body weight gain (p less than 0.05) and thymic weight (p less than .01) were noted. For total leukocyte count, no significant difference among treatment groups at individual time points was noted (p greater than .10), while significant differences were seen in lymphocyte and neutrophil counts (p less than .01). A significant difference in antibody titer among the treatment groups was observed (p less than .01). For the dermal hypersensitivity response, there was no consistent pattern among the treatment groups in gross (macroscopic) skin reactions. Microscopically, differences were seen in the inflammatory response among the treatment groups. Histologically, steroid related changes were seen in thymus, spleen, lymph node and liver. At necropsy, 24 of 40 animals had lesions of focal necrotizing hepatitis. Three affected animals died and remaining animals showed no clinical illness. The cause of the necrotizing hepatitis could not be determined by culture, special stains, electron microscopy, serology or by attempts at transmission with affected liver samples.

  17. Experimental zinc deficiency in guinea-pigs: biochemical changes.

    PubMed

    Gupta, R P; Verma, P C; Gupta, R K

    1986-05-01

    1. Zinc deficiency was produced experimentally in guinea-pigs fed on a diet containing 1.25 mg Zn/kg diet over a period of 60 d. In addition, the response of the Zn-deficient (ZnD) animals to Zn supplementation was studied for 15 d. 2. In the ZnD group a significant reduction was found in serum Zn and protein concentrations and in alkaline phosphatase (EC 3.1.3.1; AP) activity from day 24 onwards. 3. Paper electrophoretic studies on serum revealed a significant decrease in relative values, as well as absolute values, of albumin and gamma-globulin and an increase in beta-globulin. 4. Albumin:globulin increased on day 24 but decreased significantly from day 48 onwards. 5. The kidney and testis of the ZnD group showed a reduction in Zn and protein contents, and AP activity. 6. Zn supplementation of the previously ZnD group resulted in marked although incomplete improvement in the biochemical indices studied.

  18. [Study of Magnolia grandiflora extracts in guinea pigs cardiac muscle].

    PubMed

    del Valle Mondragón, Leonardo; Tenorio López, Fermín Alejandro; Torres Narváez, Juan Carlos; Zarco Olvera, Gabriela; Pastelín Hernández, Gustavo

    2004-01-01

    Several extracts from diverse Magnolia grandiflora varieties were pharmacological evaluated in the cardiac muscle. From March to July, flowers and leaves from Magnolia grandiflora, native from the National Institute of Cardiology "Ignacio Chávez", from north, west, and orient zones from Mexico City, and from Puebla, Colima and Chiapas states were collected. They were separately processed and the extracts were obtained by maceration with ethanol-water (1:3 v/v) at 4 degrees C during two weeks. Qualitative analysis was accomplished with thin-layer, column and high-performance liquid chromatographies (HPLC). Functional and molecular analysis was made by specific chemical reactivity and by protonic magnetic resonance (RMN 1H). Pharmacological evaluation was completed in isolated and perfused male guinea pigs hearts. Extracts, fractions, and compounds were administrated by serial bolus in a gradual dose-response curves study in which left intraventricular pressure and coronary perfusion pressure were recorded, evaluating by such the positive inotropic and vasodilator effects of Magnolia grandiflora extracts. Vulgarenol and 2-p-hydroxyphenyl-2-hydroxy-ethylamine were isolated and identified, and the obtained results suggest that its positive inotropic and vasodilator effects are owed to these substances, being complemented by magnograndiolide and tyramine.

  19. Surface immunoglobulin of guinea-pig leukaemic lymphocytes.

    PubMed Central

    Stevenson, G T; Eady, R P; Hough, D W; Jurd, R D; Stevenson, F K

    1975-01-01

    The surface immunoglobulin of the transplantable L2C leukaemia of strain 2 guinea-pigs has been investigated. The immunoglobulin is seen to be synthesized when the cells are maintained in culture, indicating its intrinsic origin. Immunolabelling of the cell surface and immunochemical study of the Fab released by limited surface proteolysis indicate the presence of immunoglobulin of class IgM. IgG and free light chains were not detected, and there is unlikely to be an appreciable amount of immunoglobulin of any other class. The amount of immunoglobulin present, in terms of 4-chain monomers, is approximately 100,000 molecules per cell. Its half-life, calculated from the rate of reappearance in vitro of surface Fab after proteolytic clearing, is approximately 5 hours. Immunoglobulin secreted into the environment appears to arise predominantly or entirely from the cell surface: there is no evidence of an appreciable export of immunoglobulin which does not have a surface phase. Papain at 0.06 mg/ml rapidly removes the surface Fab. Residual Fcmu can then be detected by immunofluorescence, suggesting that papain cleaves surface IgM at a hinge region with the molecule in situ on the membrane. The released Fab is only moderately susceptible to degradation by papain at the enzyme: substrate ratio prevailing. It has been possible to isolate it from the papain digest by immuno-adsorption, with a notional yield of 75 mug per 10-10 cells, and then to prepare antisera against it. PMID:48498

  20. Sulfur Mustard Induces Immune Sensitization in Hairless Guinea Pigs

    PubMed Central

    Mishra, Neerad C.; Rir-sima-ah, Jules; March, Thomas; Weber, Waylon; Benson, Janet; Jaramillo, Richard; Seagrave, Jean-Clare; Schultz, Gregory; Grotendorst, Gary; Sopori, Mohan

    2009-01-01

    Sulfur mustard (SM, bis-(2-chloroethyl) sulfide) is a well known chemical warfare agent that may cause long-term debilitating injury. Because of the ease of production and storage, it has a strong potential for chemical terrorism; however, the mechanism by which SM causes chronic tissue damage is essentially unknown. SM is a potent protein alkylating agent, and we tested the possibility that SM modifies cellular antigens, leading to an immunological response to “altered self” and a potential long-term injury. To that end, in this communication, we show that dermal exposure of euthymic hairless guinea pigs induced infiltration of both CD4+ and CD8+ T cells into the SM-exposed skin and strong upregulated expression of proinflammatory cytokines and chemokines (TNF-α, IFN-γ, and IL-8) in distal tissues such as the lung and the lymph nodes. Moreover, we present evidence for the first time that SM induces a specific delayed-type hypersensitivity response that is associated with splenomegaly, lymphadenopathy, and proliferation of cells in these tissues. These results clearly suggest that dermal exposure to SM leads to immune activation, infiltration of T cells into the SM-exposed skin, delayed-type hypersensitivity response, and molecular imprints of inflammation in tissues distal from the site of SM exposure. These immunological responses may contribute to the long-term sequelae of SM toxicity. PMID:19887117

  1. Sulfur mustard induces immune sensitization in hairless guinea pigs.

    PubMed

    Mishra, Neerad C; Rir-sima-ah, Jules; March, Thomas; Weber, Waylon; Benson, Janet; Jaramillo, Richard; Seagrave, Jean-Clare; Schultz, Gregory; Grotendorst, Gary; Sopori, Mohan

    2010-02-01

    Sulfur mustard (SM, bis-(2-chloroethyl) sulfide) is a well known chemical warfare agent that may cause long-term debilitating injury. Because of the ease of production and storage, it has a strong potential for chemical terrorism; however, the mechanism by which SM causes chronic tissue damage is essentially unknown. SM is a potent protein alkylating agent, and we tested the possibility that SM modifies cellular antigens, leading to an immunological response to "altered self" and a potential long-term injury. To that end, in this communication, we show that dermal exposure of euthymic hairless guinea pigs induced infiltration of both CD4(+) and CD8(+) T cells into the SM-exposed skin and strong upregulated expression of proinflammatory cytokines and chemokines (TNF-alpha, IFN-gamma, and IL-8) in distal tissues such as the lung and the lymph nodes. Moreover, we present evidence for the first time that SM induces a specific delayed-type hypersensitivity response that is associated with splenomegaly, lymphadenopathy, and proliferation of cells in these tissues. These results clearly suggest that dermal exposure to SM leads to immune activation, infiltration of T cells into the SM-exposed skin, delayed-type hypersensitivity response, and molecular imprints of inflammation in tissues distal from the site of SM exposure. These immunological responses may contribute to the long-term sequelae of SM toxicity.

  2. Antitussive effect of Carum copticum in guinea pigs.

    PubMed

    Boskabady, M H; Jandaghi, P; Kiani, S; Hasanzadeh, L

    2005-02-10

    Several therapeutic effects including anti-asthma and dyspnea have been described for the seeds of Carum copticum In previous studies the relaxant and anticholinergic (functional antagonism) effects, histamine (H(1)) inhibitory effect of Carum copticum have been demonstrated on guinea pig tracheal chains. In the present study the antitussive effect of this plant was evaluated. The antitussive effects of aerosols of two different concentrations of aqueous and macerated extracts and carvacrol, codeine, and saline were tested by counting the number of coughs produced due to aerosol of citric acid 10 min after exposing animals to aerosols of different solutions (for carvacrol n=5 and for other solutions n=6). The results showed significant reduction of cough number obtained in the presence of both concentrations of aqueous and macerated extracts and codeine (p<0.001 for extracts and p<0.01 for codeine). The cough number obtained in the presence of higher concentration of aqueous and macerated extracts was significantly less than those of lower concentrations (p<0.05 for both extracts). In addition the cough number obtained in the presence of both concentrations of aqueous and macerated extracts was significantly lower than that of codeine (p<0.05 to 0.001). However, carvacrol did not show any antitussive effect. These results indicated an antitussive effect of Carum copticum which was even greater than that of codeine at concentrations used. In addition the antitussive effect of Carum copticum was not due to its main constituent, carvacrol.

  3. Superoxide Production by Digitonin-Stimulated Guinea Pig Granulocytes

    PubMed Central

    Cohen, Harvey J.; Chovaniec, Margaret E.

    1978-01-01

    N-ethylmaleimide, divalent cations, ethylene glycol bis (β aminoethyl ether) N,N,N′,N′,-tetraacetate, 2-deoxyglucose, cyanide, and dinitrophenol were examined for their effect on the ability of guinea pig granulocytes to generate superoxide (O2−) when stimulated by digitonin. N-ethylmaleimide (1 mM) inhibits only when added before complete activation of the O2− generating system, and at lower concentrations (0.05-0.2 mM) slows the activation process. Ca++ is required for maximum O2− generation, and Mg++ decreases the amount of Ca++ required. Ethylene glycol bis (β aminoethyl ether) N,N,N′,N′,-tetraacetate (10 mM) inhibits only if added before complete activation. Incubation of cells in 2-DOG causes a time- and concentration-dependent inhibition of O2− generation. It also increases the time required for activation of this system. Cyanide and dinitrophenol increase the rate of O2− production. However, when these compounds are added to cells whose O2− production is partially inhibited by incubation in 2-deoxyglucose, complete inhibition results. If cyanide or dinitrophenol is added after activation of 2-deoxyglucose-treated cells, no further inhibition occurs. On the basis of the above results, we conclude that the activation of the O2− generating system is N-ethylmaleimide sensitive, Ca++ dependent, and energy requiring, but that the activity of the enzyme system in the cell is not. PMID:207722

  4. Epidermal cell proliferation in guinea pigs with experimental dermatophytosis

    SciTech Connect

    Tagami, H.

    1985-08-01

    To elucidate the mechanisms underlying the self-healing process of experimental dermatophytosis produced in guinea pigs by an occlusive method with Trichophyton mentagrophytes, epidermal proliferative activity was evaluated by the in vivo tritiated thymidine-labeling technique performed at various intervals after the first and second infections. Determination of labeling indices disclosed that an increased epidermal proliferation correlated well with the severity of inflammatory changes, i.e., a peak activity was noted after 10 days in primary infection and at 2 days in reinfection, respectively, and was followed by subsequent spontaneous lesion clearance after 10 days. Application of a heat-killed spore suspension produced inflammatory changes with enhanced epidermopoiesis, similar to those induced by reinoculation of living spores, only in immune animals. The present results indicate that the dermatitic changes occurring in experimental dermatophytosis increase epidermopoiesis which facilitates elimination of the fungus from the stratum corneum and that host immune activity, particularly contact sensitivity to fungal antigen, exerts a crucial role to induce these changes.

  5. Low protein diets improve survival from peritonitis in guinea pigs.

    PubMed Central

    Peck, M D; Alexander, J W; Gonce, S J; Miskell, P W

    1989-01-01

    Enteral diets with different protein content were tested to determine their effect on outcome in a model of protracted bacterial peritonitis. Hartley guinea pigs were provided with gastrostomies, and 1 week later, osmotic pumps were implanted into the peritoneal cavity to allow for continuous release of live bacteria over the course of 1 week. Three days after pump implantation, the animals began receiving isocaloric enteral diets that contained 5%, 10%, 15%, or 20% of total calories as protein. After 2 weeks of observation, the survivors were killed. All animals lost weight during the 2-weeks period, but there was no difference in weight lost. Nitrogen balance correlated with dietary protein. The mortality rate was significantly higher in the groups that received 15% and 20% of total calories compared with the group that received 5% (p less than 0.05). Although dietary protein in the 5% group was insufficient for meeting the nutritional needs of the animal, survival was best in this group. Possible explanations are that protein restriction in this model may either augment host defence or impair bacterial virulence. PMID:2494959

  6. Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum

    PubMed Central

    Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R.; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

    2015-01-01

    Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain. PMID:25871402

  7. Dendrodendritic connections between the cochlear efferent neurons in guinea pig.

    PubMed

    Szabó, Zs; Bácskai, T; Deák, Á; Matesz, K; Veress, G; Sziklai, I

    2011-10-31

    The outer hair cells of organ of Corti are innervated by the efferent neurons of medial olivocochlear neurons (MOC) of the brainstem which modify the cochlear auditory processing and sensitivity. Most of the MOC neurons are excited by a dominant ear and only a small portion of them is excited by both ears resulting in a binaural facilitation. The functional role of the feedback system between the organ of Corti and the cochlear efferent neurons is the protection of the ear from acoustic injury. The rapid impulse propagation in the bilateral olivocochlear system is suggestive of an electrotonic interaction between the bilateral olivocochlear neurons. The morphological background of the MOC pathway is not yet completely characterized. Therefore, we have labeled the bilateral cochlear nerves with different neuronal tracers in guinea pigs. In the anesthetized animals the cochlear nerves were exposed in the basal part of the modiolus and labeled simultaneously with different retrograde fluorescent tracers. By using confocal laser scanning microscope we could detect close appositions between the dendrites of the neurons of bilateral MOC. The distance between the neighboring profiles suggested close membrane appositions without interposing glial elements. These connections might serve as one of the underlying mechanisms of the binaural facilitation mediated by the olivocochlear system. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Macrominerals in guinea pig milk during 21 days of lactation.

    PubMed

    Anderson, R R; Sheffield, L G

    1988-02-01

    Milk samples were obtained daily from English short-hair albino guinea pigs for 21 d. Analyses included six macrominerals: Ca, P, K, chloride, Na, and Mg (in order of decreasing concentration). All minerals except K gradually increased in concentration from the beginning to the end of lactation. Calcium concentration began at 38 mM on d 1 and was 78 mM on d 21. The pattern of increase was quadratic: Y (mM) = 39 -.48X (day of lactation) + .11 X2. Phosphorus concentration was 38 mM on d 1 and highest at 51 mM on d 21. Chloride was 19 mM on d 1 and 68 mM on d 21. Sodium was 13 mM on d 1 and highest at 42 mM on d 21. Magnesium was 11 mM on d 1 and was highest on d 18 (13 mM). However, K was 31 mM on d 1, reached a high of 33 mM on d 3, and was lowest on d 19 (12 mM). These changes in concentration and previously reported volume changes suggest alterations in functional capacities of ionic transport mechanisms of secretory cell membranes in this species.

  9. Comparison of guinea pig and protozoan models for determining virulence of Legionella species.

    PubMed Central

    Fields, B S; Barbaree, J M; Shotts, E B; Feeley, J C; Morrill, W E; Sanden, G N; Dykstra, M J

    1986-01-01

    Legionella pneumophila organisms are able to infect and multiply within the ciliated protozoan Tetrahymena pyriformis. This ability may be associated with virulence, because an attenuated strain of L. pneumophila fails to multiply within this protozoan, whereas a virulent strain increases 10,000-fold in number when coincubated with T. pyriformis. Seventeen strains (11 species) of legionellae were evaluated for virulence by intraperitoneal injection of guinea pigs and inoculation of protozoan cultures. Analysis of the data indicates that there are four categories of legionellae with respect to virulence as follows: organisms that infect and kill guinea pigs and multiply in T. pyriformis; organisms that infect but do not kill guinea pigs and multiply in T. pyriformis; organisms that do not infect guinea pigs but are lethal at high concentrations and multiply in T. pyriformis; and organisms that neither infect nor kill guinea pigs and fail to multiply in T. pyriformis. Evidence suggests that these distinctions are based on two virulence factors: intracellular multiplication in a host and toxic activity. Images PMID:3744550

  10. Stereoselective pharmacokinetics of cetirizine in the guinea pig: role of protein binding.

    PubMed

    Gupta, Anubha; Hammarlund-Udenaes, Margareta; Chatelain, Pierre; Massingham, Roy; Jonsson, E Niclas

    2006-09-01

    To characterize the pharmacokinetics of cetirizine enantiomers in the guinea pig including protein binding in both the guinea pig and human plasma. Plasma concentrations of cetirizine enantiomers in the guinea pig were determined using a LC-MS/MS method after a short i.v. infusion (1, 2 and 4 mg/kg) of racemic cetirizine. Protein binding was determined using an in vitro equilibrium dialysis technique. A pharmacokinetic model was developed using NONMEM and the differences in pharmacokinetic parameters of levocetirizine and dextrocetirizine were estimated. The plasma concentration time data of both the enantiomers were best described by a three-compartment pharmacokinetics model. The clearance (CL) of levocetirizine and dextrocetirizine was 1.2 and 2.7 ml/min, respectively, and the volume of distribution at steady state (Vss) was 457 ml and 996 ml, respectively. The fraction unbound (fu) in guinea pig plasma for levocetirizine and dextrocetirizine was 7-10% and 16-21% while in human plasma, it was 8% and 12%, respectively. The factor describing the difference in the pharmacokinetic parameters of the cetirizine enantiomers was estimated to be 2.26. Cetirizine pharmacokinetics is stereoselective in the guinea pig. For levocetirizine, fu, CL and Vss were half those of dextrocetirizine, indicating that protein binding is an important factor affecting the pharmacokinetics of cetirizine. The effect of protein binding on the pharmacokinetics of the cetirizine enantiomers could be extrapolated to humans. Copyright 2006 John Wiley & Sons, Ltd.

  11. Tachykinins activate guinea-pig alveolar macrophages: involvement of NK2 and NK1 receptors.

    PubMed Central

    Brunelleschi, S.; Vanni, L.; Ledda, F.; Giotti, A.; Maggi, C. A.; Fantozzi, R.

    1990-01-01

    1. The effects of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) were evaluated on superoxide anion (O2-.) production by guinea-pig alveolar macrophages (AM). 2. SP dose-dependently (ED50 = 0.7 nM) evoked O2-. production from guinea-pig AM; the N-terminal heptapeptide, SP(1-7), was ineffective. In the presence of thiorphan (10(-5) M), an enkephalinase inhibitor, the stimulating effects of SP were not significantly modified. NKA and NKB were both able to induce O2-. production from guinea-pig AM, ED50 values being 0.1 and 1.3 nM, respectively. Therefore, the rank order of activity of natural tachykinins was NKA greater than SP greater than NKB. Tachykinin-evoked effects were quantitatively similar to those elicited by the autacoid mediator PAF-acether and less than those induced by the synthetic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP). 3. The NK2 receptor agonist [beta-Ala8]-NKA (4-10) dose-dependently evoked O2-. production from guinea-pig AM; the NK1 receptor agonist [Pro9]-SP sulphone acted only at high concentrations, while the NK3 receptor agonist [Me,Phe7]-NKB was ineffective. 4. These findings indicate that guinea-pig AM possess NK2 and possibly some NK1 tachykinin receptors and further suggest tachykinin involvement in lung pathophysiology. PMID:1697194

  12. Breathing responses of unanesthetized man and guinea pigs to increased transrespiratory pressure.

    PubMed

    Gillespie, J R; Bruce, E; Alexander, J; Mead, J

    1979-07-01

    We compared the breathing responses of unanesthetized men and guinea pigs to externally imposed shifts in lung volume produced by steady pressures applied to the body surface while the mouth remained near atmospheric pressure. Lung inflation caused no consistent or significant changes either in frequency or end-tidal CO2 in the three men. In contrast, during lung inflation the guinea pigs breathed at low frequencies and smaller tidal volumes and showed consistent increases in arterial PCO2 lasting up to 10 min. The changes seen immediately on application of pressure, namely apneic periods followed by breathing in which inspiratory duration was shortened while expiratory duration was substantially increased, indicates that conscious guinea pigs have active inflation reflexes. We concluded that the reflex responses rather than mechanical factors probably account for the underventilation in the guinea pigs and that guinea pigs are not nearly as well equipped as is man to defend gas exchange in the face of nonmetabolic shifts in lung volume.

  13. Incorporation of intravenously injected albumin, immunoglobulin G, and fibrinogen in guinea pig megakaryocyte granules.

    PubMed Central

    Handagama, P J; Shuman, M A; Bainton, D F

    1989-01-01

    In a previous study we provide evidence for a circuitous pathway by which circulating plasma proteins enter megakaryocyte granules by an endocytic mechanism and are returned to the circulation in platelets (1987. Proc. Natl. Acad. Sci. USA. 84:861-865). Horseradish peroxidase (40,000 mol wt) was injected into guinea pigs and its uptake into megakaryocyte organelles examined by electron microscopy and cytochemistry. In the present study we tested the ability of guinea pig megakaryocytes to take up intravenously injected albumin, IgG, and fibrinogen. We used two types of proteins to study the endocytic pathway: (a) heterologous human proteins, which were detected immunohistochemically using antibodies that do not crossreact with the native guinea pig counterparts; and (b) human and guinea pig proteins labeled with the small (250 mol wt), inert molecule, biotin, which were detected using an antibody against biotin. We detected all three of the injected proteins in bone marrow megakaryocytes in patterns identical to those of native counterparts. The injected protein consistently appeared in platelets 24 h later and was secreted in response to thrombin. We conclude that there are at least two mechanisms by which guinea pig megakaryocyte granules acquire proteins (a) endogenous synthesis, as demonstrated by others, and (b) endocytosis of plasma proteins synthesized by other types of cells. Images PMID:2738161

  14. Effects of Changing to Individually Ventilated Caging on Guinea Pigs (Cavia porcellus)

    PubMed Central

    Giral, Marta; Armengol, Clara; Sánchez-Gómez, Sonia; Gavaldà, Amadeu

    2015-01-01

    The goal of this study was to evaluate the effect of changing to IVC housing on guinea pigs by recording several physiologic parameters in guinea pigs housed sequentially in open-top cages (OTC) and IVC. To register heart rate and locomotor activity, 10 male Dunkin–Hartley guinea pigs implanted with telemetric transmitters were moved from OTC to new, freshly prepared OTC or IVC and subsequently monitored by telemetry during the 4 d after the first cage change. Body weight and food consumption were measured twice during the study. Comparison of data from OTC- and IVC-housed guinea pigs showed no relevant differences in heart rate (mean ± 1 SD; 213 ± 10 bpm and 207 ± 9 bpm, respectively) at any time point. In contrast, locomotor activity varied: whereas activity during the first 4 h after the change of cage type was greater in IVC-housed animals, that during the following 24 h was greater in OTC but was similar between groups thereafter. Animals housed in OTC consumed more food than did those in IVC and, under both conditions, consumption was statistically related to body weight changes. Together, these results show that a change to IVC housing induced only transient increases in locomotor activity in guinea pigs without a marked increase in heart rate but with a decrease in food consumption. Because decreased food consumption was the only stress-associated sign during the 4-d observation, longer studies are needed to ascertain the importance of this finding. PMID:26045451

  15. 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.

  16. [Delayed hypersensitivity after anthrax vaccination. I--Study of guinea pigs vaccinated against anthrax].

    PubMed

    Shlyakhov, E; Rubinstein, E

    1994-01-01

    To evaluate delayed hypersensitivity after anthrax vaccination, an Anthraxin skin test was performed in 682 guinea pigs at various times after immunization with veterinary unencapsulated active anthrax vaccine. Results were compared with those obtained in unimmunized control guinea pigs (n = 216), in guinea pigs that received a non-immunizing dose of live vaccine (n = 183) and in guinea pigs inoculated with inactivated vaccine (n = 120). Anthraxin skin tests were positive in the first postvaccination days. The incidence and intensity of positive tests peaked between two weeks and one month after vaccination and then gradually decreased during the first year. Study of resistance of guinea pigs to an inoculum at a lethal dose of a virulent strain of Bacillus anthracis showed a close correlation between positive tests and resistance. These findings demonstrate development of cell-mediated immunity after anthrax vaccination. The Anthraxin skin test should have practical applications for the production of vaccines and for evaluation of the immune status of vaccinated livestock [corrected].

  17. [Isobutane driven salbutamol sulfate metered dose inhaler: formulation selection and respiratory tract absorption in guinea pigs].

    PubMed

    Ding, Li; Zhang, Jun-Shou

    2009-09-01

    This paper is to study the iso-butane (A-31)-driven salbutamol sulfate (SS) metered dose inhaler (MDI) formulations and inhaling status in guinea pigs. Solubility determination and orthogonal design were used to screen non-chlorofluorocarbon (CFC) SS MDI formulations. Intubation inhalation of MDI in guinea pigs was used as a main administration method. Fluorescence HPLC detection method was testified as a potential method in assaying the concentration of SS in plasma of guinea pigs after inhaling various SS MDI formulations. Analysis of the data was executed with statistical moment calculation from which pharmacokinetic parameters were obtained. The results show that A-31 based on SS MDI formulations were screened and the guinea pigs in vivo determination method after inhaling SS MDI was established. The zero-moment rations of SS/A-31 MDI formulation to contrast sample and CFC SS MDI was 143.26% and 147.01%, respectively. The first moment value of SS/A-31 MDI formulation was the highest. It is a preliminary conclusion that the absorption result of SS/A-31 MDI formulation inhaled by guinea pigs is equivalent to HFA-134a formulation in sale and better than CFC formulation. A-31 could be used as a potential substitute candidate for CFC MDI propellant.

  18. 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.

  19. Effects of Changing to Individually Ventilated Caging on Guinea Pigs (Cavia porcellus).

    PubMed

    Giral, Marta; Armengol, Clara; Sánchez-Gómez, Sonia; Gavaldà, Amadeu

    2015-05-01

    The goal of this study was to evaluate the effect of changing to IVC housing on guinea pigs by recording several physiologic parameters in guinea pigs housed sequentially in open-top cages (OTC) and IVC. To register heart rate and locomotor activity, 10 male Dunkin-Hartley guinea pigs implanted with telemetric transmitters were moved from OTC to new, freshly prepared OTC or IVC and subsequently monitored by telemetry during the 4 d after the first cage change. Body weight and food consumption were measured twice during the study. Comparison of data from OTC- and IVC-housed guinea pigs showed no relevant differences in heart rate (mean ± 1 SD; 213 ± 10 bpm and 207 ± 9 bpm, respectively) at any time point. In contrast, locomotor activity varied: whereas activity during the first 4 h after the change of cage type was greater in IVC-housed animals, that during the following 24 h was greater in OTC but was similar between groups thereafter. Animals housed in OTC consumed more food than did those in IVC and, under both conditions, consumption was statistically related to body weight changes. Together, these results show that a change to IVC housing induced only transient increases in locomotor activity in guinea pigs without a marked increase in heart rate but with a decrease in food consumption. Because decreased food consumption was the only stress-associated sign during the 4-d observation, longer studies are needed to ascertain the importance of this finding.

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

    SciTech Connect

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

    1993-07-15

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

  1. Expression of matrix metalloproteinases and ovarian morphological changes in androgenized cyclic female guinea pigs.

    PubMed

    Li, Jun-rong; Shen, Ting; Wang, Yan-li; Wei, Quan-wei; Shi, Fang-xiong

    2016-02-01

    This study was conducted to investigate expression of matrix metalloproteinases (MMPs) and ovarian morphological changes in androgenized cyclic female guinea pigs. Adult cyclic female guinea pigs were injected daily for 28 days with medium doses of testosterone propionate (TP; 1 mg/100g), high doses of TP (2 mg/100g), or saline (control). Serum concentrations of testosterone, estradiol (E2), and progesterone (P4) were measured. Histologic sections of ovaries were stained with hematoxylin-eosin and by immunohistochemistry. Expressions of steroidogenic acute regulatory protein, proliferating cell nuclear antigen, and MMP-2 and MMP-9 in the ovary were characterized by immunohistochemistry. After 28 days of TP injection, serum testosterone concentrations were increased dose-dependently. An appropriate dosage of TP could induce permanent anovulation in guinea pigs, making them a potential model for human polycystic ovary syndrome. MMP-2 and MMP-9 are jointly involved in the growth and atresia of ovarian follicles in cyclic guinea pigs. Increased numbers of atretic antral follicles in the ovary might be associated with the observed high expression of MMP-2 in androgenized cyclic guinea pigs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Congenital malformations caused by Stryphnodendron fissuratum (Leg. Mimosoideae) in guinea pigs (Cavia porcellus).

    PubMed

    Macedo, Josenaldo S; Rocha, Brena P; Colodel, Edson M; Freitas, Sílvio H; Dória, Renata G S; Riet-Correa, Franklin; Evêncio-Neto, Joaquim; Mendonça, Fábio S

    2015-11-01

    The aim of this study was to evaluate the toxicity of Stryphnodendron fissuratum pods in guinea pigs (Cavia porcellus) and test the hypothesis that this plant has teratogenic effects. Thus, sixteen guinea pigs were randomly divided into four groups of four animals each. Groups 10, 20 and 40 consisted of guinea pigs that received commercial food that contained crushed pods of S. fissuratum at concentrations of 10, 20 and 40 g/kg, respectively, during the period of organogenesis. Control group consisted of guinea pigs under the same management conditions that did not receive crushed pods of S. fissuratum in their food. In all experimental groups, the main clinical signs of poisoning consisted of anorexia, prostration, absence of vocalizations, alopecia, diarrhea, and abortions within the adult guinea pigs. Those that did not abort gave birth to weak, malnourished pups, some of which had fetal malformations. The main teratogenic changes consisted of eventration, arthrogryposis, amelia of the forelimbs, anophthalmia, microphthalmia, anotia and agnathia. The reductions in the number of offspring and the malformations observed in the experimental groups suggest that S. fissuratum affects fetal development and is teratogenic. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. A guinea pig model of hypersensitivity to allergenic fractions of natural rubber latex.

    PubMed

    Aamir, R; Safadi, G S; Mandelik, J; Cornish, K; Melton, A L; Pien, L C; Wagner, W O; Battisto, J R

    1996-06-01

    Allergy to natural rubber latex is a growing medical problem with life-threatening aspects. The aim of this study was to learn if guinea pigs could serve as a suitable model for immediate-type hypersensitivity to latex. Guinea pigs were immunized either with whole non-ammoniated latex extract, or with one of nine SDS-PAGE-separated components. Other animals were injected with electroeluted latex components localized on gel at 14, 24 and a cluster around 45 kD. Before and after immunization, sera from the animals were examined by ELISA, immunoblots, passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis. Latex-specific antibodies were detected by ELISA and immunoblots in sera from all immunized animals. PCA assays showed that the guinea pigs had homocytotropic antibodies dilutable to 1:250. PCA was abolished when sera from animals immunized with allergens in alum were heated at 56 degrees C for 30 min indicating the antibodies were of the E isotype. Passive systemic anaphylaxis was induced in 4 of 10 guinea pigs. The results show that guinea pigs are capable of making antibodies to latex protein components that mediate dermal and systemic anaphylaxis, paralleling the spectrum of clinical and laboratory findings of humans with immediate-type clinical latex hypersensitivity.

  4. Isolation and characterization of guinea-pig serum amyloid P component.

    PubMed Central

    Maudsley, S; Hind, C R; Munn, E A; Buttress, N; Pepys, M B

    1986-01-01

    A pentraxin was isolated from acute-phase guinea-pig serum by calcium-dependent affinity chromatography on agarose. It was immunochemically identical to guinea-pig amyloid P component and therefore has been called guinea-pig serum amyloid P component (SAP). Guinea-pig SAP has an apparent MW of between 265,000 and 300,000 by different techniques, and is composed of 10 noncovalently associated subunits arranged in two pentameric annular discs interacting face-to-face. It is apparently composed of two types of subunit, which run as a closely spaced doublet on reduced sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). At least one type of subunit is glycosylated. The serum concentration was 16 +/- 4 mg/l in outbred animals, rising to 25 +/- 4 mg/l in an acute-phase response. Binding to agarose correlated with the agarose pyruvate content and was completely abolished by diazomethane treatment of the agarose, which methylates the pyruvate carboxylic moiety. Binding was also inhibited in the presence of free methyl 4,6-o-(carboxyethylidine)-beta-D-galactopyranoside. No protein resembling C-reactive protein (CRP) was obtained by calcium-dependent affinity chromatography of acute-phase guinea-pig serum on phosphorylcholine (PC)-Sepharose, and it not clear whether a counterpart of CRP exists in this species. Images Figure 1 Figure 2 PMID:3770806

  5. A protease-like permeability factor in guinea pig skin: immunologic identity with plasma Hageman factor.

    PubMed Central

    Yamamoto, T.; Cochrane, C. G.

    1982-01-01

    Vascular permeability enhancement activity of the protease-like permeability factor derived from guinea pig skin and of active guinea pig Hageman factor (beta HFa) were both inhibited by anti-guinea pig Hageman factor rabbit F(ab')2 antibody. The permeability activity of both factors was also absorbed on anti-Hageman factor F(ab')2-Sepharose beads. The latent form of the permeability factor derived from skin extracts produced a single immunoprecipitation line with anti-Hageman factor and gave a reaction of identity with a precipitation band developing between purified Hageman factor and anti-Hageman factor. The latent permeability factor in the fraction corrected the clotting activity of Hageman-factor-deficient human plasma. The clotting activity was also blocked by anti-Hageman factor F(ab')2 antibody. From these results, it was concluded that the skin permeability factor was immunologically and functionally indistinguishable from Hageman factor of plasma. Extracts were obtained from skin of guinea pigs given intravenous injections of 125I-guinea pig Hageman factor immediately before sacrifice to calculate the amount of Hageman factor in the extravascular tissue space of the skin. The pseudoglobulin fractions of the extracts containing a concentration of Hageman factor of approximately 9 microgram of Hageman factor per gram of skin. This was determined both by immunologic means and procoagulant activity. Only 4% of the Hageman factor in the extract was obtained from the intravascular plasma volume of the skin. Images Figure 1 PMID:7044129

  6. 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.

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

    PubMed

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

    2013-03-01

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

  8. Inhibition of converting enzyme and neointima formation after vascular injury in rabbits and guinea pigs.

    PubMed

    Clozel, J P; Hess, P; Michael, C; Schietinger, K; Baumgartner, H R

    1991-10-01

    Recently, it has been shown that cilazapril could suppress neointima formation after vascular injury in rats. The goal of the present study was to confirm these findings in guinea pigs and rabbits. Vascular injury was produced by ballooning the right carotid artery of guinea pigs and the right iliac artery of rabbits. The animals were treated with either placebo or cilazapril (30 mg/kg/day and 3 mg/kg/day in guinea pigs and rabbits, respectively). Cilazapril decreased by 42% (p less than 0.001) the neointima area in the guinea pig but was ineffective in rabbits. However, in rabbits, doses of cilazapril higher than 3 mg/kg could not be given because of known toxicological effects in the rabbit. We conclude that the protective effect of cilazapril described in rats also is observed in guinea pigs. However, in rabbits, the maximal tolerated dose of cilazapril was ineffective. These results underline the importance of ongoing clinical studies to evaluate if, in humans, cilazapril inhibits restenosis after coronary angioplasty.

  9. Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

    PubMed

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-05

    We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. The role of the anaesthetised guinea-pig in the preclinical cardiac safety evaluation of drug candidate compounds

    SciTech Connect

    Marks, Louise; Borland, Samantha; Philp, Karen; Ewart, Lorna; Lainée, Pierre; Skinner, Matthew; Kirk, Sarah; Valentin, Jean-Pierre

    2012-09-01

    Despite rigorous preclinical and clinical safety evaluation, adverse cardiac effects remain a leading cause of drug attrition and post-approval drug withdrawal. A number of cardiovascular screens exist within preclinical development. These screens do not, however, provide a thorough cardiac liability profile and, in many cases, are not preventing the progression of high risk compounds. We evaluated the suitability of the anaesthetised guinea-pig for the assessment of drug-induced changes in cardiovascular parameters. Sodium pentobarbitone anaesthetised male guinea-pigs received three 15 minute intravenous infusions of ascending doses of amoxicillin, atenolol, clonidine, dobutamine, dofetilide, flecainide, isoprenaline, levosimendan, milrinone, moxifloxacin, nifedipine, paracetamol, verapamil or vehicle, followed by a 30 minute washout. Dose levels were targeted to cover clinical exposure and above, with plasma samples obtained to evaluate effect/exposure relationships. Arterial blood pressure, heart rate, contractility function (left ventricular dP/dt{sub max} and QA interval) and lead II electrocardiogram were recorded throughout. In general, the expected reference compound induced effects on haemodynamic, contractility and electrocardiographic parameters were detected confirming that all three endpoints can be measured accurately and simultaneously in one small animal. Plasma exposures obtained were within, or close to the expected clinical range of therapeutic plasma levels. Concentration–effect curves were produced which allowed a more complete understanding of the margins for effects at different plasma exposures. This single in vivo screen provides a significant amount of information pertaining to the cardiovascular risk of drug candidates, ultimately strengthening strategies addressing cardiovascular-mediated compound attrition and drug withdrawal. -- Highlights: ► Evaluation of the anaesthetised guinea-pig to determine cardiac liability.

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

    USDA-ARS?s Scientific Manuscript database

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

  12. 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.

  13. A comparative analysis of the intestinal metagenomes present in guinea pigs (Cavia porcellus) and humans (Homo sapiens)

    PubMed Central

    2012-01-01

    Background Guinea pig (Cavia porcellus) is an important model for human intestinal research. We have characterized the faecal microbiota of 60 guinea pigs using Illumina shotgun metagenomics, and used this data to compile a gene catalogue of its prevalent microbiota. Subsequently, we compared the guinea pig microbiome to existing human gut metagenome data from the MetaHIT project. Results We found that the bacterial richness obtained for human samples was lower than for guinea pig samples. The intestinal microbiotas of both species were dominated by the two phyla Bacteroidetes and Firmicutes, but at genus level, the majority of identified genera (320 of 376) were differently abundant in the two hosts. For example, the guinea pig contained considerably more of the mucin-degrading Akkermansia, as well as of the methanogenic archaea Methanobrevibacter than found in humans. Most microbiome functional categories were less abundant in guinea pigs than in humans. Exceptions included functional categories possibly reflecting dehydration/rehydration stress in the guinea pig intestine. Finally, we showed that microbiological databases have serious anthropocentric biases, which impacts model organism research. Conclusions The results lay the foundation for future gastrointestinal research applying guinea pigs as models for humans. PMID:23020652

  14. Understanding the anatomy of ears from guinea pigs and rats and its use in basic otologic research.

    PubMed

    Albuquerque, Agnes Afrodite Sumarelli; Rossato, Maria; Oliveira, José Antonio Apparecido de; Hyppolito, Miguel Angelo

    2009-01-01

    The use of animal samples is important in otologic research and understanding the anatomy of their ears help make proper use of them in research projects. to study guinea pig's and rat's ears under light microscopy(LM) and scanning electron microscopy(SEM) and understand their anatomical advantages in basic otologic research. The temporal bones, tympanic bullas and cochleas from three albino guinea pigs and rats were photographed and analyzed under LM and SEM. Rats aren't as simple to handle as guinea pigs, and often present with otitis media. Rats have a fragile junction of the tympanic bulla, two and half turns in the cochlea, and their tympanic membranes do not seal off the entire external auditory canal. Guinea pigs have full bullas, their incus and malleus are fused and they have three and half cochlear turns. Under SEM, guinea pigs and rats have Tectori Membrane, Raissner's Membrane and the Organ of Corti. Only guinea pigs have Hensen's Cells. Guinea pigs were considered easy to handle for microdissection purposes because of the size and robustness of their temporal bones, and for surgical experiments involving the stapes, the oval window and the tympanic membrane. Under SEM there are similarities guinea pigs and rats, and both can be used in inner ear studies.

  15. A comparative analysis of the intestinal metagenomes present in guinea pigs (Cavia porcellus) and humans (Homo sapiens).

    PubMed

    Hildebrand, Falk; Ebersbach, Tine; Nielsen, Henrik Bjørn; Li, Xiaoping; Sonne, Si Brask; Bertalan, Marcelo; Dimitrov, Peter; Madsen, Lise; Qin, Junjie; Wang, Jun; Raes, Jeroen; Kristiansen, Karsten; Licht, Tine Rask

    2012-09-28

    Guinea pig (Cavia porcellus) is an important model for human intestinal research. We have characterized the faecal microbiota of 60 guinea pigs using Illumina shotgun metagenomics, and used this data to compile a gene catalogue of its prevalent microbiota. Subsequently, we compared the guinea pig microbiome to existing human gut metagenome data from the MetaHIT project. We found that the bacterial richness obtained for human samples was lower than for guinea pig samples. The intestinal microbiotas of both species were dominated by the two phyla Bacteroidetes and Firmicutes, but at genus level, the majority of identified genera (320 of 376) were differently abundant in the two hosts. For example, the guinea pig contained considerably more of the mucin-degrading Akkermansia, as well as of the methanogenic archaea Methanobrevibacter than found in humans. Most microbiome functional categories were less abundant in guinea pigs than in humans. Exceptions included functional categories possibly reflecting dehydration/rehydration stress in the guinea pig intestine. Finally, we showed that microbiological databases have serious anthropocentric biases, which impacts model organism research. The results lay the foundation for future gastrointestinal research applying guinea pigs as models for humans.

  16. 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

  17. 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

  18. Immunological relationships of an endogenous guinea pig retrovirus with prototype mammalian type B and type D retroviruses.

    PubMed Central

    Dahlberg, J E; Tronick, S R; Aaronson, S A

    1980-01-01

    A retrovirus endogenous to guinea pig cells was earlier shown to be morphologically similar to type B and type D prototype retroviruses. Molecular hybridization techniques were used to show that guinea pig virus nucleotide sequences are endogenous to both domestic (Cavia porcellus) and indigenous (Cavia aperea) guinea pigs, but cannot be detected in the DNA of either other hystricomorph rodents or other mammals tested. Using radioimmunological techniques designed to detect interspecies relationships, the major internal polypeptide of guinea pig virus (p26) was shown to share three different sets of interspecies antigenic determinants with squirrel monkey retrovirus, viper retrovirus, and mouse mammary tumor virus. Thus, guinea pig virus appears to provide an evolutionary link between type B and D retroviruses. Images PMID:6154150

  19. Worm recovery and precipitin antibody response in guinea pigs and rats infected with Clonorchis sinensis.

    PubMed

    Su, K E; Wang, F Y; Chi, P Y

    1998-12-01

    Guinea pigs (Hartley strain) and rats (Wistar strain) were each fed 200 and 100 Clonorchis sinensis metacercariae, respectively. Five animals from each species were sacrificed weekly between 1-8 weeks postinfection (WPI) and then at 12, 16, 20 and 30 WPI for collection of worms, bile and sera. The overall worm recovery rates for guinea pigs and rats were 18.7% and 12.4%, respectively. Only one of the five rats examined at 20 WPI still harbored one worm, while all were worm-free at 30 WPI. By a double diffusion test, no antibodies were detected against C. sinensis adult antigens in the bile juice. Serum antibodies were detected in at least 95% of the infected guinea pigs between 4-30 WPI and rats between 3-16 WPI. Precipitin antibodies seemed to be correlated with the presence of live worms in rats that had been infected for more than 12 weeks.

  20. Comparative study of 2 surgical techniques for castration of guinea pigs (Cavia porcellus)

    PubMed Central

    Guilmette, Josée; Langlois, Isabelle; Hélie, Pierre; de Oliveira El Warrak, Alexander

    2015-01-01

    The objective of this study was to compare 2 surgical approaches (scrotal or abdominal) for castration of guinea pigs and to investigate post-operative infection rates with either technique. Forty-eight guinea pigs were castrated by scrotal or abdominal technique after being randomly assigned to 1 of 2 groups (n = 24). Individuals were either castrated by an experienced exotic animal surgeon (n = 12) or by an experienced small animal surgeon (n = 12). Surgical wounds were evaluated daily before euthanasia for histological evaluation 2 wks after surgery. Post-operative infection rate was significantly higher in the scrotal group than in the abdominal group, with a higher rate for the experienced small animal surgeon. Castration of guinea pigs with the abdominal technique is significantly faster and has a significantly lower post-operative infection rate than the scrotal technique. PMID:26424914

  1. Naturally occurring Parelaphostrongylus tenuis-associated choriomeningitis in a guinea pig with neurologic signs.

    PubMed

    Southard, T; Bender, H; Wade, S E; Grunenwald, C; Gerhold, R W

    2013-05-01

    An adult male guinea pig (Cavia porcellus) with a 1-month history of hind limb paresis, torticollis, and seizures was euthanized and submitted for necropsy. Gross examination was unremarkable, but histologic examination revealed multifocal eosinophilic and lymphoplasmacytic choriomeningitis and cross sections of nematode parasites within the leptomeninges of the midbrain and diencephalon. Morphologic features of the nematode were consistent with a metastrongyle, and the parasite was identified as Parelaphostrongylus tenuis by polymerase chain reaction testing and nucleotide sequencing. Further questioning of the owner revealed that the guinea pig was fed grass from a yard often grazed by white-tailed deer (Odocoileus virginianus). To the authors' knowledge, this is the first report of a naturally occurring P. tenuis infection in a guinea pig.

  2. Automaintenance in guinea pigs: effects of feeding regimen and omission training1

    PubMed Central

    Poling, Alan; Poling, Teresa

    1978-01-01

    Behavior maintained by stimulus-reinforcer pairings was examined. Guinea pigs maintained at 85 per cent of free-feeding weights reliably contacted a retractable lever presented before delivery of a single piece of guinea-pig chow or a 45-milligram guinea-pig pellet. When animals were given free access to one food and received the second food preceded by the lever, contact responses persisted. Such responses seldom occurred when a single food was freely available and was also delivered after lever presentation. Introduction of an omission training (negative automaintenance) procedure, in which lever contacts resulted in lever retraction and prevented food delivery, strongly reduced lever contacts. Observation indicated that mouthing the food cup, instead of the lever, became the prominent behavior during the prefood stimulus under the omission training procedure. PMID:16812086

  3. Effect of experimental zinc deficiency and repletion on some immunological variables in guinea-pigs.

    PubMed

    Verma, P C; Gupta, R P; Sadana, J R; Gupta, R K

    1988-01-01

    1. Cellular and humoral immune responses were studied in guinea-pigs fed on zinc-deficient (ZnD), Zn-adequate (control) and Zn-replete diets containing 1.25, 50 and 100 mg Zn/kg diet respectively. 2. It was found that the ZnD guinea-pigs had significantly decreased ability to elicit delayed-type hypersensitivity (DTH) response against sheep erythrocytes as compared with controls on the 9th day of immunization. This was further substantiated by histological examination of DTH-positive skin sections. 3. A significant reduction in direct splenic plaque-forming-cell response and haemagglutinating-antibody titre was also observed in ZnD guinea-pigs. 4. Serum electrophoretic studies revealed a highly disordered protein profile with a significantly depressed value for gamma-globulin. 5. Zn repletion of the previously ZnD group resulted in marked, though incomplete, restoration of immunological responses.

  4. [Occurrence and distribution of ectoparasites in guinea pigs (Cavia spp.) in Peru, South America].

    PubMed

    de la Cruz, Katharina Dittmar; Ribbeck, Regine; Daugschies, Arwio

    2003-01-01

    Studies on the prevalence and distribution of ectoparasites in Peru were carried out during a period of 2 1/2 years. The survey included 17,421 domesticated guinea pigs (Cavia aperea f. porcellus) from 14 departments in all bioregions and altitude levels and 143 wild guinea pigs (Cavia aperea) from three areas (El Paramo, Junin and La Raya) in the Andes and the Cordillera. The guinea pig is an important source of food, especially for the rural population, the infestation with ectoparasites, such as fleas, lice or mites greatly contributes to a decrease in production and low performance. Ectoparasites can be vectors for a variety of pathogens, which is particularly problematic due to the close association of this animal with humans. Twenty one ectoparasite species have been recovered. New knowledge about host associations and distributions could be obtained. The results of the studies are presented under faunistic and ecological aspects.

  5. Spasmolytic activity of a herbal drug isolated from Tephrosia purpurea in guinea pigs.

    PubMed

    Soni, Kapil K; Khare, M L; Saxena, R C

    2004-04-01

    We investigated the spasmolytic activity of herbal drugs isolated from Tephrosia purpurea on guinea pigs for the treatment of asthma in India. For this investigation, the herbal drug was extracted with 70% ethanol in soxhlet apparatus. After purification and isolution, the drug was used in experimental animals to observe prophylactic activity. For anaphylactic activity, horse serum 0.5 ml along with triple antigen (0.5 ml) was induced in guinea pigs. To observe prophylactic activity, male guinea pigs weighing about 250-450 gms were killed by cervical dislocation and the trachea was isolated. Each trachea was cut in to six segments. Each segment consists of three cartilage rings. Each end of tracheal muscles was attached to the bronchospasm transducers for isometric recording of the tension charges on a polygraph. The results of experiments clearly showed the spasmolytic activity of the drug. The preliminary phytochemical investigation, however shows the presence of glycoside saponins.

  6. Inhibition of gastric secretion in guinea pig by relatively low dose ionizing radiation

    SciTech Connect

    Batzri, S.; Catravas, G.

    1988-11-01

    We evaluated the effect of a single dose of ionizing radiation on gastric secretion in awake guinea pigs equipped with a permanent gastric cannula. Changes in gastric secretion were measured using a dye dilution technique. Infusion of histamine increased acid and fluid output and there was a positive correlation (r = 0.93) between the two. Total body irradiation with 400 cGy, like cimetidine, suppressed acid and fluid secretion under basal conditions and during histamine stimulation by 50-90%. Recovery from the radiation damage was only partial after one week. Irradiation inhibited the rise in gastric juice volume during histamine stimulation and also reduced the normal gain in body weight of the guinea pig. These results demonstrate that ionizing radiations have an immediate and long lasting effects on the gastric mucosal function of the guinea pig.

  7. Pathological and virological features of arenavirus disease in guinea pigs. Comparison of two Pichinde virus strains.

    PubMed

    Aronson, J F; Herzog, N K; Jerrells, T R

    1994-07-01

    A guinea pig passage-adapted strain of the arena-virus Pichinde (adPIC) is highly virulent in inbred guinea pigs, whereas the related strain PIC3739 is attenuated. Both viruses were macrophage tropic and infected peritoneal, splenic, liver, and alveolar macrophages during experimental Pichinde virus infection. Infection with the virulent strain was associated with unlimited viral replication in the face of exaggerated delayed-type hypersensitivity response, manifested by the macrophage disappearance reaction. Histopathological lesions unique to adPIC-infected guinea pigs included intestinal villus blunting with mucosal infiltration by pyknotic debris-laden macrophages and apoptosis of crypt epithelial cells. Splenic red pulp necrosis was also significantly associated with adPIC infection but not PIC3739 infection. These findings may provide clues to the pathogenesis of a group of poorly understood human viral hemorrhagic fevers.

  8. Pathological and virological features of arenavirus disease in guinea pigs. Comparison of two Pichinde virus strains.

    PubMed Central

    Aronson, J. F.; Herzog, N. K.; Jerrells, T. R.

    1994-01-01

    A guinea pig passage-adapted strain of the arena-virus Pichinde (adPIC) is highly virulent in inbred guinea pigs, whereas the related strain PIC3739 is attenuated. Both viruses were macrophage tropic and infected peritoneal, splenic, liver, and alveolar macrophages during experimental Pichinde virus infection. Infection with the virulent strain was associated with unlimited viral replication in the face of exaggerated delayed-type hypersensitivity response, manifested by the macrophage disappearance reaction. Histopathological lesions unique to adPIC-infected guinea pigs included intestinal villus blunting with mucosal infiltration by pyknotic debris-laden macrophages and apoptosis of crypt epithelial cells. Splenic red pulp necrosis was also significantly associated with adPIC infection but not PIC3739 infection. These findings may provide clues to the pathogenesis of a group of poorly understood human viral hemorrhagic fevers. Images Figure 6 Figure 7 PMID:8030751

  9. [In vitro inhibition of celastrol on spermatozoa fertilization ability of guinea pig].

    PubMed

    Yuan, Y Y; Gu, Z P; Shi, Q X; Qin, G W; Xu, R S; Cao, L

    1995-01-01

    The effects of celastrol (Cel), isolated from Tripterygium wilfordii, on guinea pig sperm forward motility (FM), capacitation (Cap), the acrosome reaction (AR) and sperm penetration assay (SPA) were assessed in vitro. Cel (5 micrograms.ml-1) was found to inhibit these spermatozoal functions, and the inhibitions were proportional to the concentrations of Cel used. The potency of inhibition of Cel on the fertilizing ability in guinea pig spermatozoa in vitro seems to follow the order: Cap > FM > SPA > AR. The inhibitory effect appeared to be reversible after washing away Cel if the duration of exposure of spermatozoa to Cel was shorter than 3 h. In a comparative study, the inhibitory effects of Cel on guinea pig sperm FM and AR were significantly stronger than those of gossypol acetic acid.

  10. Development of isolation-induced vocal behavior in normal-hearing and deafened guinea pig infants.

    PubMed

    Arch-Tirado, E; McCowan, B; Saltijeral-Oaxaca, J; Zarco de Coronado, I; Licona-Bonilla, J

    2000-04-01

    Infants in many different animal species require auditory information from conspecifics to learn appropriate responses to important environmental and social cues. Isolation calls are emitted by infant guinea pigs in contexts of social separation from their mothers. The aim of the present study was to examine the ontogeny of the isolation calls in normal-hearing and deafened infant guinea pigs, from 2 to 40 days postpartum and to determine the role of hearing maternal vocalization in infant guinea pig vocal responses in contexts of social proximity and isolation. Female newborn pigmented guinea pigs (Cavia porcellus) were housed with their birth mother and siblings. Water and dry food were available ad libitum. One day postpartum, the cochlea of infants in the experimental group was destroyed. The control group consisted of normal-hearing female siblings. Vocalizations from infants in the experimental and control groups were recorded for 6 minutes when with the mother before isolation, 6 minutes when alone, and then 6 minutes when with the mother after reunion. Recordings were made 5 days per week from 2 to 40 days after birth. The duration of calling was calculated for each 6-minute period of recording. Results demonstrated that deaf infants vocalize more than normal-hearing infants during social isolation from their mothers. Vocal activity of isolated deaf and normal-hearing infants decreased substantially over development, almost disappearing by the end of the study period. These results indicate that maternal vocal behavior modulates the vocal responses of guinea pigs early in infant development and supports other evidence that the guinea pig offers a viable model for investigating audition in deaf and normal-hearing human infants.

  11. Effects of oral administration of trimethoprim-sulfamethoxazole on tear production in clinically normal guinea pigs.

    PubMed

    Asadi, Faezeh; Rajaei, Seyed Mehdi; Golabdar, Salar

    2016-09-01

    To determine the effects of short-term oral administration of trimethoprim-sulfamethoxazole on tear production in clinically normal guinea pigs. Thirty-two healthy adult Abyssinian guinea pigs were used in this study. One day before the start of the trial, the pretreatment baseline phenol red thread test (PRTT) values were recorded. Sixteen guinea pigs in the treated group received 25 mg/kg trimethoprim-sulfamethoxazole orally twice a day for 14 days. The other sixteen guinea pigs were used as untreated controls and received a placebo during the study. All the ophthalmic tests were performed without chemical restraint. PRTT values were evaluated in both eyes of all the guinea pigs using a commercial PRTT strip of a single lot number on days 0 (baseline), 15, and 21 after starting the trial. The pretreatment baseline mean ± SD PRTT values for the treatment and control groups were 11.12 ± 3.82 mm/15 s and 11.93 ± 2.73 mm/15 s, respectively. After 14 days of drug administration, the mean ± SD PRTT values for the treatment and control groups were 10.87 ± 3.11 mm/15 s and 13.00 ± 2.47 mm/15 s, respectively. On Day 21, the mean ± SD PRTT values for the treatment and control groups were 12.62 ± 4.05 mm/15 s and 12.87 ± 2.99 mm/15 s, respectively. Significant decreases in the PRTT values, compared with the pretreatment baseline values, were not observed in the treatment group on Day 15 (P = 0.14) and Day 21 (P = 0.31). Trimethoprim-sulfamethoxazole did not decrease tear production in the guinea pigs in this study. © 2015 American College of Veterinary Ophthalmologists.

  12. 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.

  13. 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.

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

    SciTech Connect

    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 did 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.

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

    SciTech Connect

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

    1989-06-01

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

  16. Rifapentine is not more active than rifampin against chronic tuberculosis in guinea pigs.

    PubMed

    Dutta, Noton K; Illei, Peter B; Peloquin, Charles A; Pinn, Michael L; Mdluli, Khisimuzi E; Nuermberger, Eric L; Grosset, Jacques H; Karakousis, Petros C

    2012-07-01

    Rifamycins are key sterilizing drugs in the current treatment of active tuberculosis (TB). Daily dosing of rifapentine (P), a potent rifamycin with high intracellular accumulation, in place of rifampin (R) in the standard antitubercular regimen significantly shortens the duration of treatment needed to prevent relapse in a murine model of active TB. We undertook the current study to compare directly the activities of human-equivalent doses of P and R in a guinea pig model of chronic TB, in which bacilli are predominantly extracellular within human-like necrotic granulomas. Hartley strain guinea pigs were aerosol infected with ~200 bacilli of Mycobacterium tuberculosis H37Rv, and treatment given 5 days/week was initiated 6 weeks later. R at 100 mg/kg of body weight and P at 100 mg/kg were given orally alone or in combination with isoniazid (H) at 60 mg/kg and pyrazinamide (Z) at 300 mg/kg. Culture-positive relapse was assessed in subgroups of guinea pigs after completion of 1 and 2 months of treatment. Human-equivalent doses of R and P showed equivalent bactericidal activity when used alone and in combination therapy. In guinea pigs treated with rifampin, isoniazid, and pyrazinamide (RHZ) or PHZ, microbiological relapse occurred in the lungs of 8/10 animals treated for 1 month and in 0/10 animals treated for 2 months. Substitution of P for R in the standard antitubercular regimen did not shorten the time to cure in this guinea pig model of chronic TB. Data from ongoing clinical trials comparing the activity of these two drugs are awaited to determine the relevance of the guinea pig TB model in preclinical drug screening.

  17. Rifapentine Is Not More Active than Rifampin against Chronic Tuberculosis in Guinea Pigs

    PubMed Central

    Dutta, Noton K.; Illei, Peter B.; Peloquin, Charles A.; Pinn, Michael L.; Mdluli, Khisimuzi E.; Nuermberger, Eric L.; Grosset, Jacques H.

    2012-01-01

    Rifamycins are key sterilizing drugs in the current treatment of active tuberculosis (TB). Daily dosing of rifapentine (P), a potent rifamycin with high intracellular accumulation, in place of rifampin (R) in the standard antitubercular regimen significantly shortens the duration of treatment needed to prevent relapse in a murine model of active TB. We undertook the current study to compare directly the activities of human-equivalent doses of P and R in a guinea pig model of chronic TB, in which bacilli are predominantly extracellular within human-like necrotic granulomas. Hartley strain guinea pigs were aerosol infected with ∼200 bacilli of Mycobacterium tuberculosis H37Rv, and treatment given 5 days/week was initiated 6 weeks later. R at 100 mg/kg of body weight and P at 100 mg/kg were given orally alone or in combination with isoniazid (H) at 60 mg/kg and pyrazinamide (Z) at 300 mg/kg. Culture-positive relapse was assessed in subgroups of guinea pigs after completion of 1 and 2 months of treatment. Human-equivalent doses of R and P showed equivalent bactericidal activity when used alone and in combination therapy. In guinea pigs treated with rifampin, isoniazid, and pyrazinamide (RHZ) or PHZ, microbiological relapse occurred in the lungs of 8/10 animals treated for 1 month and in 0/10 animals treated for 2 months. Substitution of P for R in the standard antitubercular regimen did not shorten the time to cure in this guinea pig model of chronic TB. Data from ongoing clinical trials comparing the activity of these two drugs are awaited to determine the relevance of the guinea pig TB model in preclinical drug screening. PMID:22547623

  18. The protective effect of Nigella sativa on lung injury of sulfur mustard-exposed Guinea pigs.

    PubMed

    Hossein, Boskabady Mohammad; Nasim, Vahedi; Sediqa, Amery

    2008-05-01

    The lung is one of the most exposable organs to chemical warfare agents such as sulfur mustard (SM) gas. Airway hyperresponsiveness and lung inflammation are reported in chemical warfare victims. There is no definite treatment for respiratory disorders induced by SM exposure. However, the protective effect of Nigella sativa on inflammatory process was shown. In the present study, the protective effect of Nigella sativa on tracheal responsiveness and lung inflammation of SM exposed guinea pigs was examined. Guinea pigs were exposed to diluent's solution (ethanol, control group), 100 mg/m(3) inhaled sulfur mustard (SME group), and SME treated with Nigella sativa, 0.08 g daily (SME+N), n = 6 for each group. Tracheal responsiveness (TR) to methacholine, total white blood cell (WBC) count of lung lavage, and differential WBC were done 14 days post exposure. The weigh of animal were measured at the beginning, middle (day 7), and the end (day 14) of the study. The TR of SM-exposed guinea pigs was significantly (P < .001) and WBC nonsignificantly higher than those of controls. In SME guinea pigs, there was a weight loss but in the case of SME+N guinea pigs, no obvious weight change thought the study was seen. The eosinophl, monocyte, and lympocytes in SME animals were significantly changed compared to control group (P < .001 for all cases). Monocyte, lymphocyte, and neutrophil number were decreased in SME+N group compared to SME animals, which was significant only for neutrophil (P < .05). These results showed a preventive effect of Nigella sativa on TR of SM-exposed guinea pigs.

  19. Role of interleukin-5 in enhanced migration of eosinophils from airways of immunized guinea-pigs.

    PubMed Central

    Coëffier, E; Joseph, D; Vargaftig, B B

    1994-01-01

    1. Platelet activating factor (PAF), leukotriene B4 (LTB4) and interleukin-5 (IL-5) are potent chemoattractants for guinea-pig eosinophils, which may be involved in eosinophil recruitment and up-regulation in allergic diseases. Eosinophils from the bronchoalveolar lavage fluid (BALF) of ovalbumin-sensitized guinea-pigs were collected 24 h after antigen provocation and migration induced by PAF, LTB4 and rhIL-5 was studied. 2. Total BALF content and distribution of eosinophils were greater in immunized, ovalbumin-challenged guinea-pigs (5.0 +/- 0.8 x 10(6)/guinea-pig; 12 +/- 1%) than in immunized, saline-challenged animals (3.0 +/- 0.7 x 10(6)/guinea-pig; 7 +/- 1%). 3. The chemoattraction of eosinophils isolated on a metrizamide gradient was studied in micro-Boyden chambers, results being expressed as the number of migrating cells (mean +/- s.e. mean). PAF and LTB4-induced migration of eosinophils from immunized and OA-challenged guinea-pigs were significantly enhanced, as compared to immunized and saline-challenged animals (170 +/- 36 vs 35 +/- 9 migrating eosinophils for 10 nM PAF; 271 +/- 60 vs 110 +/- 19 for 1 nM LTB4). 4. The IL-5 antibody TRFK-5, in vivo, reduced eosinophil recruitment in BALF of antigen-challenged immunized animals as well as the enhanced responsiveness of eosinophils from the challenged animals, suggesting a role for IL-5 in the priming of eosinophils in vivo. 5. In contrast to TRFK-5, nedocromil sodium reduced to a similar extent eosinophil, macrophage and lymphocyte recruitment into the BALF of antigen-challenged, but failed to down-regulate the enhanced responsiveness of eosinophils from the challenged animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7858864

  20. Onset and duration of immunity in guinea pigs and mice induced with different Q fever vaccines.

    PubMed

    Kazár, J; Votruba, D; Propper, P; Schramek, S

    1986-11-01

    Protective effects of different types of Q fever vaccines, namely untreated Coxiella burnetii phase I cells (Cb I) or Cb I cells treated with chloroform-methanol (CM) mixture (Cb I-CM) and of a Q fever chemovaccine obtained by trichloroacetic acid extraction (TCAE) from intact Cb I cells, were compared in mice and guinea pigs at different intervals after intraperitoneal (i.p.) or subcutaneous (s.c.) immunizations. The highest degree of protection at all intervals studied was achieved with Cb I cells, irrespective of the route of immunization and i.p. or aerosol challenge. This vaccine exerted a protective effect in guinea pigs and mice as early as after one or two weeks post-immunization, the effect lasting for at least 40 weeks in mice (i.p. challenge) and 12 months in guinea pigs (aerosol challenge). Addition of small amount of Cb I cells to TCAE increased resistance of guinea pigs to aerosol challenge. Degree, onset and duration of protection to either type of virulent challenge afforded by Cb I-CM cells and TCAE was similar, but when compared with that of Cb I cells it was lower, started later (from the 2nd week in guinea pigs and the 3rd week in mice), and in mice it lasted for a shorter period (20 weeks only). The resistance to virulent challenge in guinea pigs did not depend on the levels of microagglutination (MA) antibodies and in mice it was reflected by delayed type hypersensitivity (DTH) reaction and adoptively transferred splenocytes, rather than by MA antibody titres and passive transfer of immune sera to recipient mice.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Excitatory motor and electrical effects produced by tachykinins in the human and guinea-pig isolated ureter and guinea-pig renal pelvis

    PubMed Central

    Patacchini, Riccardo; Santicioli, Paolo; Zagorodnyuk, Vladimir; Lazzeri, Massimo; Turini, Damiano; Alberto Maggi, Carlo

    1998-01-01

    In isolated tissue experiments, neurokinin A (NKA) produced concentration-dependent contraction of human and guinea-pig ureter (pD2=6.7 and 7.2, respectively); an effect greatly reduced (>80% inhibition) by the tachykinin NK2 receptor-selective antagonist MEN 11420 (0.1 μM). The tachykinin NK1 and NK3 receptor agonists septide and senktide, respectively, were ineffective.Electrical field stimulation (EFS) of the guinea-pig isolated renal pelvis produced an inotropic response blocked by MEN 11420 (0.01–1 μM). In the same preparation MEN 11420 (0.1 μM) blocked (apparent pKB=8.2) the potentiation of spontaneous motor activity produced by the NK2 receptor-selective agonist [βAla8]NKA(4–10).In sucrose-gap experiments, EFS evoked action potentials (APs) accompanied by phasic contractions of human and guinea-pig ureter, which were unaffected by tetrodotoxin or MEN 11420 (3 μM), but were blocked by nifedipine (1–10 μM). NKA (1–3 μM) produced a slow membrane depolarization with superimposed APs and a tonic contraction with superimposed phasic contractions. NKA prolonged the duration of EFS-evoked APs and potentiated the accompanying contractions. MEN 11420 completely prevented the responses to NKA in both the human and guinea-pig ureter.Nifedipine (1–10 μM) suppressed the NKA-evoked APs and phasic contractions in both human and guinea-pig ureter, and slightly reduced the membrane depolarization induced by NKA. A tonic-type contraction of the human ureter in response to NKA persisted in the presence of nifedipine.In conclusion, tachykinins produce smooth muscle excitation in both human and guinea-pig ureter by stimulating receptors of the NK2 type only. NK2 receptor activation depolarizes the membrane to trigger the firing of APs from latent pacemakers. PMID:9846636

  2. Toward an Integrative Computational Model of the Guinea Pig Cardiac Myocyte

    PubMed Central

    Gauthier, Laura Doyle; Greenstein, Joseph L.; Winslow, Raimond L.

    2012-01-01

    The local control theory of excitation-contraction (EC) coupling asserts that regulation of calcium (Ca2+) release occurs at the nanodomain level, where openings of single L-type Ca2+ channels (LCCs) trigger openings of small clusters of ryanodine receptors (RyRs) co-localized within the dyad. A consequence of local control is that the whole-cell Ca2+ transient is a smooth continuous function of influx of Ca2+ through LCCs. While this so-called graded release property has been known for some time, its functional importance to the integrated behavior of the cardiac ventricular myocyte has not been fully appreciated. We previously formulated a biophysically based model, in which LCCs and RyRs interact via a coarse-grained representation of the dyadic space. The model captures key features of local control using a low-dimensional system of ordinary differential equations. Voltage-dependent gain and graded Ca2+ release are emergent properties of this model by virtue of the fact that model formulation is closely based on the sub-cellular basis of local control. In this current work, we have incorporated this graded release model into a prior model of guinea pig ventricular myocyte electrophysiology, metabolism, and isometric force production. The resulting integrative model predicts the experimentally observed causal relationship between action potential (AP) shape and timing of Ca2+ and force transients, a relationship that is not explained by models lacking the graded release property. Model results suggest that even relatively subtle changes in AP morphology that may result, for example, from remodeling of membrane transporter expression in disease or spatial variation in cell properties, may have major impact on the temporal waveform of Ca2+ transients, thus influencing tissue level electromechanical function. PMID:22783206

  3. Evidence for a non-opioid sigma binding site din the guinea-pig myenteric plexus

    SciTech Connect

    Roman, F.; Pascaud, X.; Vauche, D.; Junien, J.

    1988-01-01

    The presence of a binding site to (+)-(/sup 3/H)SKF 10,047 was demonstrated in a guinea-pig myenteric plexus (MYP) membrane preparation. Specific binding to this receptor was saturable, reversible, linear with protein concentration and consisted of two components, a high affinity site and a low affinity site. Morphine and naloxone 10/sup -4/M were unable to displace (+)-(/sup 3/H)SKF 10,047 binding. Haloperidol, imipramine, ethylketocyclazocine and propranolol were among the most potent compounds to inhibit this specific binding. These results suggest the presence of a non-opioid haloperidol sensitive sigma receptor in the MYP of the guinea-pig.

  4. The role of pheromones in the regulation of estrous cycle duration in the guinea pig.

    PubMed

    Jesel, L; Aron, C L

    1976-01-01

    A decrease in estrous cycle duration, due to shortening of the period of vaginal closure (VC), has been observed in female guinea pigs exposed to the odor of urine from males of the same species. VC shortening was also observed in females exposed to the odor of female urine collected during the period of vaginal opening (VO). No alteration in VC duration occurred, however, in females exposed to urine collected in the 1st 7 days of VC. Also VC shortening did not occur in bulbectomized females exposed to the odor of male urine. Therefore, it was concluded that guinea pig urine, when highly concentrated, contains pheromones capable of shortening estrous cycle VC.

  5. Vesicular Lesions Produced in Guinea Pigs by a Staphylococcus aureus Strain

    PubMed Central

    Tessler, J.

    1973-01-01

    A bacterium isolated from vesicular lesions on foot pads of guinea pigs reproduced lesions similar to those seen in experimental infections of guinea pigs with foot-and-mouth disease virus. (FMDV). These bacterial lesions were produced with an inactivated FMDV suspension. Identification as Staphylococcus aureus was determined by growth characteristics on nutrient and blood agar, Gram staining, fermentation of mannitol and coagulase positive reactions. In addition, the organism was sensitive to concentrations of penicillin and streptomycin commonly used in laboratory diluents. PMID:4355472

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

    PubMed

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

    2014-01-01

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

  7. 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

  8. BCG vaccination enhances resistance to M. tuberculosis infection in guinea pigs fed a low casein diet.

    PubMed

    Sugawara, Isamu; Yamada, Hiroyuki; Mizuno, Satoru

    2007-03-01

    In order to examine the relationship between malnutrition and tuberculosis development in vivo, a malnourished guinea pig model fed with a low casein (5%) diet was developed. After being fed with the low casein diet, the guinea pigs were infected with Mycobacterium (M.) tuberculosis Kurono strain by aerosol infection, and seven weeks later were subjected to histopathologic examination, colony-forming unit (CFU) assay, fluorescence-activated cell sorter (FACS) analysis and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12 and inducible nitric oxide synthase (iNOS) mRNA. Another group of guinea pigs were vaccinated subcutaneously with 10(6) CFU BCG Tokyo for three weeks and then similarly infected by aerosol. Eighty-eight% (7/8) of the malnourished guinea pigs succumbed to mycobacterial infection within 85 days after infection, while the malnourished guinea pigs vaccinated with BCG Tokyo survived. CFU assay showed that lung and splenic CFUs were higher in the low casein diet-fed groups than in the control diet (20% casein)-fed groups, although both groups had significantly lower CFUs after vaccination with BCG Tokyo (p<0.01). Examination of lung histopathology revealed that pulmonary granulomas were large and disorganized in the groups fed the low casein diet. The number of visible lesions on the surfaces of the fixed lungs in guinea pigs fed control diet+BCG and low casein diet+BCG was low significantly. Pan T-, CD4-, CD8- and Mac antigen-positive cells were also recognized in the infected lung tissues of low casein-fed guinea pigs and Pan T-, CD4- and Mac antigen-positive cells increased after vaccination with BCG Tokyo. Expression of IFN-gamma, TNF-alpha, IL-12 and iNOS mRNA was also recognized in the infected lung tissues of low casein-fed guinea pigs and IFN-gamma and TNF-alpha mRNA expression was enhanced with BCG vaccination. These results indicate that

  9. Beam-Beam Interaction Simulations with Guinea Pig (LCC-0125)

    SciTech Connect

    Sramek, C

    2003-11-20

    At the interaction point of a particle accelerator, various phenomena occur which are known as beam-beam effects. Incident bunches of electrons (or positrons) experience strong electromagnetic fields from the opposing bunches, which leads to electron deflection, beamstrahlung and the creation of electron/positron pairs and hadrons due to two-photon exchange. In addition, the beams experience a ''pinch effect'' which focuses each beam and results in either a reduction or expansion of their vertical size. Finally, if a beam's disruption parameter is too large, the beam can develop a sinusoidal distortion, or two-stream (kink) instability. This project simulated and studied these effects as they relate to luminosity, deflection angles and energy loss in order to optimize beam parameters for the Next Linear Collider (NLC). Using the simulation program Guinea Pig, luminosity, deflection angle and beam energy data was acquired for different levels of beam offset and distortion. Standard deflection curves and luminosity plots agreed with theoretical models but also made clear the difficulties of e-e- feedback. Simulations emphasizing kink instability in modulated and straight beam collisions followed qualitative behavioral predictions and roughly fit recent analytic calculations. A study of e-e- collisions under design constraints for the NLC provided new estimates of how luminosity, beamstrahlung energy loss, upsilon parameter and deflection curve width scale with beam cross-sections ({sigma}{sub x}, {sigma}{sub y}, {sigma}{sub z}) and number of particles per bunch (N). Finally, this same study revealed luminosity maxima at large N and small {sigma}{sub y} which may merit further investigation.

  10. Pharmacometabolomic approach to predict QT prolongation in guinea pigs.

    PubMed

    Park, Jeonghyeon; Noh, Keumhan; Lee, Hae Won; Lim, Mi-sun; Seong, Sook Jin; Seo, Jeong Ju; Kim, Eun-Jung; Kang, Wonku; Yoon, Young-Ran

    2013-01-01

    Drug-induced torsades de pointes (TdP), a life-threatening arrhythmia associated with prolongation of the QT interval, has been a significant reason for withdrawal of several medicines from the market. Prolongation of the QT interval is considered as the best biomarker for predicting the torsadogenic risk of a new chemical entity. Because of the difficulty assessing the risk for TdP during drug development, we evaluated the metabolic phenotype for predicting QT prolongation induced by sparfloxacin, and elucidated the metabolic pathway related to the QT prolongation. We performed electrocardiography analysis and liquid chromatography-mass spectroscopy-based metabolic profiling of plasma samples obtained from 15 guinea pigs after administration of sparfloxacin at doses of 33.3, 100, and 300 mg/kg. Principal component analysis and partial least squares modelling were conducted to select the metabolites that substantially contributed to the prediction of QT prolongation. QTc increased significantly with increasing dose (r = 0.93). From the PLS analysis, the key metabolites that showed the highest variable importance in the projection values (>1.5) were selected, identified, and used to determine the metabolic network. In particular, cytidine-5'-diphosphate (CDP), deoxycorticosterone, L-aspartic acid and stearic acid were found to be final metabolomic phenotypes for the prediction of QT prolongation. Metabolomic phenotypes for predicting drug-induced QT prolongation of sparfloxacin were developed and can be applied to cardiac toxicity screening of other drugs. In addition, this integrative pharmacometabolomic approach would serve as a good tool for predicting pharmacodynamic or toxicological effects caused by changes in dose.

  11. Pharmacometabolomic Approach to Predict QT Prolongation in Guinea Pigs

    PubMed Central

    Lee, Hae Won; Lim, Mi-sun; Seong, Sook Jin; Seo, Jeong Ju; Kim, Eun-Jung; Kang, Wonku; Yoon, Young-Ran

    2013-01-01

    Drug-induced torsades de pointes (TdP), a life-threatening arrhythmia associated with prolongation of the QT interval, has been a significant reason for withdrawal of several medicines from the market. Prolongation of the QT interval is considered as the best biomarker for predicting the torsadogenic risk of a new chemical entity. Because of the difficulty assessing the risk for TdP during drug development, we evaluated the metabolic phenotype for predicting QT prolongation induced by sparfloxacin, and elucidated the metabolic pathway related to the QT prolongation. We performed electrocardiography analysis and liquid chromatography–mass spectroscopy-based metabolic profiling of plasma samples obtained from 15 guinea pigs after administration of sparfloxacin at doses of 33.3, 100, and 300 mg/kg. Principal component analysis and partial least squares modelling were conducted to select the metabolites that substantially contributed to the prediction of QT prolongation. QTc increased significantly with increasing dose (r = 0.93). From the PLS analysis, the key metabolites that showed the highest variable importance in the projection values (>1.5) were selected, identified, and used to determine the metabolic network. In particular, cytidine-5′-diphosphate (CDP), deoxycorticosterone, L-aspartic acid and stearic acid were found to be final metabolomic phenotypes for the prediction of QT prolongation. Metabolomic phenotypes for predicting drug-induced QT prolongation of sparfloxacin were developed and can be applied to cardiac toxicity screening of other drugs. In addition, this integrative pharmacometabolomic approach would serve as a good tool for predicting pharmacodynamic or toxicological effects caused by changes in dose. PMID:23593245

  12. Opioid receptors on guinea-pig intestinal crypt epithelial cells.

    PubMed Central

    Lang, M E; Davison, J S; Bates, S L; Meddings, J B

    1996-01-01

    1. Opioid peptides promote net intestinal absorption via two mechanisms: stimulation of Na+ and Cl- absorption and inhibition of Cl- secretion. Although these transport changes are predominantly mediated by submucosal neurones, it is currently unclear whether opioid peptides can regulate enterocyte function directly. We therefore tested the hypothesis that enterocytes have specific opioid receptors. 2. Villus and crypt jejunal epithelial cells were isolated by the distended sac method from anaesthetized guinea-pigs. Flow cytometry was used to resolve enterocytes from other cell types and to determine whether binding of a fluorescently labelled opioid antagonist, naltrexone-FITC, could be prevented by unlabelled mu- and delta-opioid receptor agonists. A population of crypt enterocytes (approximately 21%) exhibited high-affinity naltrexone-FITC binding to both mu- and delta-type binding sites that was stereoselective and sodium dependent. Villus enterocytes did not exhibit any of these characteristics. 3. Basal cAMP production was elevated in both villus and crypt cells treated with IBMX (3-isobutyl-1-methylxanthine). Villus cells did not respond to 100 nM vasoactive intestinal peptide (VIP), nor were they affected by opioid peptides. In contrast, 100 nM VIP significantly increased cAMP production in crypt epithelial cells, which was significantly reduced by both morphiceptin and D-Ser2-Leu-Enk-Thr. This opioid-mediated effect was stereoselective and blocked by the opioid receptor antagonist naltrexone. 4. These experiments suggest that enterocytes isolated from the crypt epithelium of guineapigs have both mu- and delta-types of opioid receptors. It is possible that these cells participate in opioid-mediated regulation of intestinal secretion. Images Figure 12 PMID:8951719

  13. Angiotensin receptors and actions in guinea pig enteric nervous system.

    PubMed

    Wang, Guo-Du; Wang, Xi-Yu; Hu, Hong-Zhen; Fang, Xiu-Cai; Liu, Sumei; Gao, Na; Xia, Yun; Wood, Jackie D

    2005-09-01

    Actions of ANG II on electrical and synaptic behavior of enteric neurons in the guinea pig small intestine were studied. Exposure to ANG II depolarized the membrane potential and elevated neuronal excitability. The number of responding neurons was small, with responses to ANG II in 32% of submucosal neurons and 25% of myenteric neurons. Hyperpolarizing responses were evoked by ANG II in 45% of the neurons. The hyperpolarizing responses were suppressed by alpha2-noradrenergic receptor antagonists, which suggested that the hyperpolarizing responses reflected stimulation of norepinephrine release from sympathetic neurons. Exposure to ANG II enhanced the amplitude and prolonged the duration of noradrenergic inhibitory postsynaptic potentials and suppressed the amplitude of both fast and slow excitatory postsynaptic potentials. The selective ANG II(1) receptor (AT1R) antagonists, ZD-7115 and losartan, but not a selective AT2R antagonist (PD-123319), suppressed the actions of ANG II. Western blot analysis and RT-PCR confirmed expression of AT1R protein and the mRNA transcript for the AT1R in the enteric nervous system. No expression of AT2R protein or mRNA was found. Immunoreactivity for AT1R was expressed by the majority of neurons in the gastric antrum and small and large intestine. AT1R immunoreactivity was coexpressed with calbindin, choline acetyltransferase, calretinin, neuropeptide Y, and nitric oxide synthase in subpopulations of neurons. The results suggest that formation of ANG II might have paracrine-like actions in the enteric nervous system, which include alterations in neuronal excitability and facilitated release of norepinephrine from sympathetic postganglionic axons. The enhanced presence of norepinephrine is expected to suppress fast and slow excitatory neurotransmission in the enteric microcircuits and to suppress neurogenic mucosal secretion.

  14. [+]-Huperzine A protects against soman toxicity in guinea pigs.

    PubMed

    Wang, Ying; Wei, Yanling; Oguntayo, Samuel; Jensen, Neil; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2011-12-01

    The chemical warfare nerve agent (CWNA) soman irreversibly inhibits acetylcholinesterase (AChE) causing seizure, neuropathology and neurobehavioral deficits. Pyridostigmine bromide (PB), the currently approved pretreatment for soman, is a reversible AChE inhibitor that does not cross the blood-brain barrier (BBB) to protect against central nervous system damage. [-]-Huperzine A, a natural reversible AChE inhibitor, rapidly passes through the BBB and has numerous neuroprotective properties that are beneficial for protection against soman. However, [-]-Huperzine A is toxic at higher doses due to potent AChE inhibition which limits the utilization of its neuroprotective properties. [+]-Huperzine A, a synthetic stereoisomer of [-]-Huperzine A and a weak inhibitor of AChE, is non-toxic. In this study, we evaluated the efficacy of [+]-Huperzine A for protection against soman toxicity in guinea pigs. Pretreatments with [+]-Huperzine A, i.m., significantly increased the survival rate in a dose-dependent manner against 1.2× LD(50) soman exposures. Behavioral signs of soman toxicity were significantly reduced in 20 and 40 mg/kg [+]-Huperzine A treated animals at 4 and 24 h compared to vehicle and PB controls. Electroencephalogram (EEG) power spectral analysis showed that [+]-Huperzine A significantly reduces soman-induced seizure compared to PB. [+]-Huperzine A (40 mg/kg) preserved higher blood and brain AChE activity compared to PB in soman exposed animals. These data suggest that [+]-Huperzine A protects against soman toxicity stronger than PB and warrant further development as a potent medical countermeasure against CWNA poisoning.

  15. Neurogenic mucosal bicarbonate secretion in guinea pig duodenum

    PubMed Central

    Fei, G; Fang, X; Wang, GD; Liu, S; Wang, XY; Xia, Y; Wood, JD

    2013-01-01

    Background and Purpose To test a hypothesis that: (i) duodenal pH and osmolarity are individually controlled at constant set points by negative feedback control centred in the enteric nervous system (ENS); (ii) the purinergic P2Y1 receptor subtype is expressed by non-cholinergic secretomotor/vasodilator neurons, which represent the final common excitatory pathway from the ENS to the bicarbonate secretory glands. Experimental Approach Ussing chamber and pH-stat methods investigated involvement of the P2Y1 receptor in neurogenic stimulation of mucosal bicarbonate (HCO3−) secretion in guinea pig duodenum. Key Results ATP increased HCO3− secretion with an EC50 of 160 nM. MRS2179, a selective P2Y1 purinergic receptor antagonist, suppressed ATP-evoked HCO3− secretion by 47% and Cl− secretion by 63%. Enteric neuronal blockade by tetrodotoxin or exposure to a selective vasoactive intestinal peptide (VIP, VPAC1) receptor antagonist suppressed ATP-evoked HCO3− secretion by 61 and 41%, respectively, and Cl- by 97 and 70% respectively. Pretreatment with the muscarinic antagonist, scopolamine did not alter ATP-evoked HCO3− or Cl− secretion. Conclusion and Implications Whereas acid directly stimulates the mucosa to release ATP and stimulate HCO3− secretion in a cytoprotective manner, neurogenically evoked HCO3− secretion accounts for feedback control of optimal luminal pH for digestion. ATP stimulates duodenal HCO3− secretion through an excitatory action at purinergic P2Y1 receptors on neurons in the submucosal division of the ENS. Stimulation of the VIPergic non-cholinergic secretomotor/vasodilator neurons, which are one of three classes of secretomotor neurons, accounts for most, if not all, of the neurogenic secretory response evoked by ATP. PMID:22994306

  16. Stability of the guinea pigs personality - cognition - linkage over time.

    PubMed

    Brust, Vera; Guenther, Anja

    2017-01-01

    In human psychological research, personality traits as well as cognitive traits are usually validated for both, their stability over time and contexts. While stability over time gives an estimate on how genetically fixated a trait can be, correlations across traits have the power to reveal linkages or trade - offs. In animals, these validations have widely been done for personality but not for cognitive traits. We tested guinea pigs in four consecutive discrimination tasks using four unique pairs of objects with two objects of the same form but different size in each pair. The same animals were tested twice each for three personality traits, i.e. boldness, aggression and sociopositive behaviour. The animals did not learn to "always choose the larger item" in the cognitive task but learned to discriminate the two objects of each stimulus pair anew, so that we did test for learning speed in four slightly different task setups. Performance over the four tasks was significantly repeatable as well as all tested personality traits. A stable linkage over time was found between sociopositive behaviour and learning performance, probably indicating an ecological relevance for a correlation between these two traits. Still, not all traits seem to be connected amongst each other, as in our case boldness and aggression are both not linked to individual learning performance. Future studies will hopefully further investigate the repeatability of various cognitive traits in several species and thus lead to a better understanding of the interdependence of personality and cognition. This will help to unravel which suites of traits facilitate individual life histories and hence improve our understanding of the emergence and maintenance of individual differences. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Biomechanical analysis of fracture healing in guinea-pigs.

    PubMed

    Kdolsky, Richard; Reihsner, Roland; Beer, Rudolf

    2008-01-01

    To validate the hypothesis that healing of fractures can be accelerated by oral administered L-arginine a guinea-pig model was chosen. A diaphyseal defect fracture was established in the right femur of each of the 32 small animals and stabilized. According to randomization groups the oral administration was realized (2 or 4 weeks medication / solvent). The following biomechanical variables were measured after 4 weeeks in 32 right femora and the corresponding uninjured left femora. The measurement for the healed femur was individually compared with that of the uninjured femur in each animal; bending, force (necessary for refracture) and energy (necessary for refracture). To apply the bending moment in a measurable and reproducible way each end of the femur was secured using a special device. For each femur a strain/momentum graph of the measurements and the essential parameters were drawn (stiffness, end of the linear range, and failure-point). The bending moment was always applied with the same loading rate. The following three variables were used for the biomechanical evaluation; bending stiffness, force until failure and energy necessary for refracture. The bending stiffness reached 73% by the control group and 88% by the 4-week treatment group. The force necessary for refracture was 52% in the control compared with 65% in the 4-week treatment group. The energy necessary for refracture was 36% in the control compared with 73% in the group treated for 4 weeks. The 2 week treatment group showed no statistical significant differences to the control, but the femora from the 4 week treatment group required statistically significant higher energy for refracture than the femora from the control.

  18. Macroscopic electrical propagation in the guinea pig urinary bladder.

    PubMed

    Hammad, F T; Stephen, B; Lubbad, L; Morrison, J F B; Lammers, W J

    2014-07-15

    There is little knowledge about macroscopic electrical propagation in the wall of the urinary bladder. Recording simultaneously from a large number of extracellular electrodes is one technology that could be used to study the patterns of macroscopic electrical propagations. The urinary bladders from 14 guinea pigs were isolated and placed in an organ bath. A 16 × 4-electrode array was positioned at various sites on the serosal bladder surface, and recordings were performed at different intravesical volumes. In four experiments, carbachol (CCH; 10(-6) M), nifedipine (10 mM), or tetrodotoxin (TTX; 10(-6) M) was added to the superfusing fluid. After the experiments, the extracellular signals were analyzed and propagation maps were constructed. Electrical waves were detected at all sites on the bladder surface and propagated for a limited distance before terminating spontaneously. The majority of waves (>90%) propagated in the axial direction (i.e., from dome to base or vice versa). An increase in vesicle volume significantly decreased the conduction velocity (from 4.9 ± 1.5 to 2.7 ± 0.7 cm/s; P < 0.05). CCH increased, nifedipine decreased, while TTX had little effect on electrical activities. In addition, a new electrical phenomenon, termed a "patch," was discovered whereby a simultaneous electrical deflection was detected across an area of the bladder surface. Two types of electrical activities were detected on the bladder surface: 1) electrical waves propagating preferentially in the axial direction and 2) electrical patches. The propagating electrical waves could form the basis for local spontaneous contractions in the bladder during the filling phase.

  19. Schirmer tear test, phenol red thread tear test, eye blink frequency and corneal sensitivity in the guinea pig.

    PubMed

    Trost, Katrin; Skalicky, M; Nell, Barbara

    2007-01-01

    To establish reference values for Schirmer tear tests (STT) I and II, phenol red thread (PRT) tear test and eye blink frequency, and to determine corneal sensitivity for normal guinea pigs. One hundred and eight eyes of 54 adult Duncan-Hartley guinea pigs. Schirmer tear test (STT) I and then STT II were performed in 36 guinea pigs. PRT and STT I were compared in 18 adult Duncan-Hartley guinea pigs. Corneal sensitivity was determined in 23 guinea pigs by evaluating the corneal touch threshold (CTT) of five different regions using a Cochet-Bonnet esthesiometer. Eye blink frequency was measured in 10 guinea pigs over a period of 20 min and in 17 guinea pigs over a period of 10 min. Mean STT I was 0.36 mm +/- 1.09 mm (wetting/min) and mean STT II was 0.43 mm +/- 1.29 mm (wetting/min). There was no significant difference between mean STT I and mean STT II (P = 0.79). The mean PRT-value was 16 +/- 4.7 mm (wetting/15 s), and the mean STT I-value in the same guinea pigs was 0.6 +/- 1.83 mm (wetting/min). Corneal sensitivity was significantly higher in the center than in the four limbal regions. The mean CTT for central, ventral, nasal, temporal and dorsal regions was 2, 1.7, 1.7, 1.7 and 1.6 cm or 3.7, 5.2, 5.6, 5.7 and 6.4 g/mm(2), respectively. Eye blink frequency was between two to five (mean 3.4 +/- 1.04) blinks per eye over 20 min in guinea pigs in their home environment, while in handheld and restrained guinea pigs eye blink frequency showed a variation between 0 and 17 blinks per eye (mean 3.24 +/- 3.64 blinks per eye) over 10 min. As there were no significant differences between STT I and STT II results, reflex tear secretion in the guinea pig may not exist. The most likely explanation is a lower corneal sensitivity in the guinea pig than in other species, such as cats, dogs and horses. Because of the small amount of tears, PRT is the preferred test for tear measurement in the guinea pig.

  20. Assessment of the effects of changes in body temperature on cardiac electrophysiology in anaesthetised guinea pigs.

    PubMed

    Kågström, Jens; Laumola, Eva-Lena; Poijes, Niklas; Johansson, Maria; Ericson, Ann-Christin

    2012-01-01

    Anaesthetised guinea pigs are commonly used within Safety Pharmacology to evaluate drug effects on cardiac electrophysiology. However, anesthesia compromises the ability to thermoregulate, which can be further challenged when more invasive surgery is required. As anaesthetised animals are often used when screening for cardiotoxicity, thereby influencing go/no-go decisions, we wanted to quantify the impact of small temperature changes on the recorded electrophysiological parameters. Male guinea pigs were anaesthetised by pentobarbital, placed on a pre-heated table and a rectal thermistor inserted for monitoring of body temperature. After intubation animals were vagotomised and β-blocked, and lead II ECG needle electrodes attached. Following thoracotomy an atrial pacing electrode was attached and a suction MAP electrode positioned on the ventricular epicardium. In control animals temperature was kept constant (38.1±0.1°C) over the duration of the experiment. Animals in one group were slowly warmed to 41.9°C by a heating plate and a heating lamp, and in another group slowly cooled to 34.4°C by turning off all heating equipment. MAP duration at 90% repolarisation (MAPD90), AV conduction, ECG and body temperature were recorded during cardiac pacing every 5min up to 50min. No time-dependent changes were seen in the control group. In contrast, a linear correlation was found between changes in body temperature and MAPD90, AV conduction, QTc and QRS intervals. For each degree temperature fell below 38°C MAPD90 was prolonged by 6.1ms, and for each degree above 38°C MAPD90 was shortened by 5.3ms. Corresponding changes were seen for QTc interval and AV conduction time, while effects on the QRS interval were smaller. The data highlights the importance of carefully controlling body temperature when performing electrophysiological recordings in laboratory animals. A change by a single degree can affect electrophysiological parameters by 5-10%, thus increasing the risk for

  1. 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.

  2. 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 Central

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

    2014-01-01

    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. PMID:24856783

  3. Cell-mediated and humoral immune responses to chlamydial antigens in guinea pigs infected ocularly with the agent of guinea pig inclusion conjunctivitis.

    PubMed

    Senyk, G; Kerlan, R; Stites, D P; Schanzlin, D J; Ostler, H B; Hanna, L; Keshishyan, H; Jawetz, E

    1981-04-01

    Cell-mediated immune response and humoral response to chlamydial antigens were investigated in guinea pigs infected with the agent of guinea pig inclusion conjunctivitis (GPIC). Pronounced cell-mediated immune response to the homologous antigen, as well as to two other chlamydial antigens, 6BC (Chlamydia psittaci) and LB-1 (C. trachomatis), occurred in all infected animals. Cell-mediated immune response to GPIC, and to a lesser extent to 6BC and LB-1 as well, was enhanced with time after infection even without the re-inoculation of the infectious agent. Extensive cross-reactions among the three chlamydial antigens during the cell-mediated immune response appeared to be due to shared species-specific and group-reactive antigens. Serum antibody response was pronounced and uniform to GPIC; it was less marked to 6BC and LB-1, with fewer cross-reactions than seen in tests for cell-mediated immunity.

  4. 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

  5. Kinetics of rate-dependent shortening of action potential duration in guinea-pig ventricle; effects of IK1 and IKr blockade.

    PubMed

    Williams, B A; Dickenson, D R; Beatch, G N

    1999-03-01

    1. The kinetics of shortening of action potential duration (APD) following an increase in pacing rate, from 2 to 3.3 Hz, was characterized in guinea-pig ventricular preparations. Terikalant (RP62719), an inhibitor of the inwardly rectifying K+ current (IK1), and dofetilide, a specific inhibitor of the rapidly activating delayed-rectifier current (IKr), were applied to determine the effect of inhibition of these ion currents on slow APD shortening. 2. Action potentials were recorded from isolated guinea-pig ventricular myocytes using the perforated-patch patch-clamp technique, and monophasic action potentials were recorded from Langendorff-perfused guinea-pig ventricles using a contact epicardial probe. 3. Under control conditions, after an increase in pacing rate, APD immediately decreased, and then shortened slowly with an exponential time course. In ventricular myocytes, the time constant of this exponential shortening was 28+/-4 s and the amount of slow shortening was 21.9+/-0.9 ms (n=8) for an increase in rate from 2 to 3.3 Hz. Similar values were observed in Langendorff-perfused ventricles. 4. Terikalant dose-dependently increased APD and the increase was enhanced by rapid pacing ('positive' rate-dependence). The drug dose-dependently decreased the time constant of shortening and amount of slow APD shortening. In contrast, dofetilide, an inhibitor of IKr, which shows 'reverse' rate-dependent APD widening, had no significant effect on the time constant or amount of slow shortening. 5. These observations suggest that IK1 plays a role in rate-dependent shortening of APD. The results appear to support the hypothesis that 'reverse' rate-dependent effects of IKr blockers are due to these drugs not affecting the ion current(s) mediating intrinsic rate-dependent slow shortening of APD.

  6. 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.

  7. The conventional antihistamine drug cyproheptadine lacks QT-interval-prolonging action in halothane-anesthetized guinea pigs: comparison with hydroxyzine.

    PubMed

    Kobayashi, Kazuko; Omuro, Naoki; Takahara, Akira

    2014-01-01

    Antihistamines are known to belong to the chemical class that may induce long QT syndrome. Among them, cyproheptadine has been shown to exert multifaceted actions on the ventricular repolarization phase; namely, shortening of the action potential duration at supra-therapeutic concentrations of 2 - 8 μM and prolongation of the QT interval at ≥ 10 μM. Since information is limited regarding the in vivo electrophysiological effects of cyproheptadine, we assessed it using the halothane-anesthetized guinea-pig model, which was compared with effects of another antihistamine drug, hydroxyzine. Sub-therapeutic to therapeutic doses of hydroxyzine at 1 and 10 mg/kg, i.v. prolonged the QT interval and duration of monophasic action potential, whereas therapeutic to supra-therapeutic doses of cyproheptadine at 0.1 and 1 mg/kg, i.v. hardly affected the indices of ventricular repolarization. These results suggest that cyproheptadine may be categorized into antihistamines with little effect on the ventricular repolarization.

  8. Effect of estradiol on chlamydial genital infection of female guinea pigs.

    PubMed Central

    Rank, R G; White, H J; Hough, A J; Pasley, J N; Barron, A L

    1982-01-01

    Female guinea pigs were treated daily with 1 mg of beta-estradiol-3-benzoate intramuscularly beginning 14 days before intravaginal inoculation with the chlamydial agent of guinea pig inclusion conjunctivitis and continuing during the course of the infection. Treatment with estradiol was found to markedly influence the course of genital infection with the chlamydial agent of guinea pig inclusion conjunctivitis, producing infections of greater intensity and longer duration than those in control animals. Moreover, pathogenesis was altered in that ascending infection was observed, resulting in endometritis, cystic salpingitis, and cystitis. Infection in the controls was limited to the cervix and vagina. Estradiol treatment increased the apparent number of infected cells in the cervix and vagina as detected by histopathology and immunofluorescent staining. Humoral and cell-mediated immune responses to the chlamydial agent of guinea pig inclusion conjunctivitis were comparable in estradiol-treated and untreated animals. These data indicate that hormonal manipulation may have profound effects on the course of chlamydial genital infections. Images PMID:7141709

  9. Development and duration of BCG-induced allergy in the guinea-pig*

    PubMed Central

    Tolderlund, Knud; Bunch-Christensen, Kirsten; Waaler, Hans

    1960-01-01

    In assessing the biological activity of BCG vaccine by tuberculin testing of vaccinated guinea-pigs, it is necessary to take into account the rates of development and waning of allergy, and also the boosting effect on waning allergy caused by the tuberculin test itself. Using Danish liquid vaccine (in approximately standard dose), the authors have carried out two series of tests, involving more than six hundred guinea-pigs, to evaluate the significance of these factors. Post-vaccination tuberculin sensitivity was found to reach a maximum within 1-2 months. Three months after vaccination the BCG-induced allergy began to wane, and after 12 months it had dropped almost to the level observed in non-vaccinated guinea-pigs. The tuberculin test had a strong boosting effect, however, and even 12 months after vaccination the waning sensitivity could be considerably increased by a single injection of 10 TU of tuberculin. An analysis of the results showed that the waning of the level of allergy takes place gradually over several months. This is not an effect of aging, however, as the response to vaccination was found to be independent of the age of the animals. The indications of this study are that tuberculin testing of guinea-pigs used for the laboratory control of BCG vaccine is best performed about 6 weeks after vaccination. PMID:20604065

  10. Possible formation of nitrosamine in guinea pigs following exposure to nitrogen dioxide and dimethylamine

    SciTech Connect

    Chaudhari, A.; Dutta, S.

    1981-05-01

    The possibility of formation of nitrosamine was investigated in animals exposed to a combination of dimethylamine (DMA) and NO/sub 2/. First, the distribution and covalent binding of DMA and dimethylnitrosamine (DMN) in rats and guinea pigs were determined. The apparent volume of distribution and biological half-life for (/sup 14/C)-DMA or (/sup 14/C) DMN did not reveal any species difference. In general, there were no marked differences in accumulation of radioactivity in tissues of guinea pigs and rats 4 h after the administration of DMA, while the guinea pig tissues showed higher accumulation after DMN administration. Nucleic acid fractions prepared from liver and lungs of both species following administration of DMN or DMA in vivo showed much higher covalent binding with DMN than with DMA. Since guinea pig liver showed a higher degree of covalent binding than rat liver, this species was used to investigate the possible increase in covalent binding in the presence of NO/sub 2/ and DMA as a reflection of DMN formation. There was no evidence of enhancement of covalent binding when animals pretreated with (/sup 14/C)-DMA were exposed for vaious lengths of time to different concentrations of NO/sub 2/.

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

    PubMed

    Meza, Graciela; Aguilar-Maldonado, Beatriz

    2007-01-01

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

  12. Antispasmodic effects of Persea cordata bark fractions on guinea pig ileum.

    PubMed

    Cechinel-Filho, Valdir; Zampirolo, Júlio A; Stulzer, Hellen K; Schlemper, Valfredo

    2007-02-01

    The present study describes the antispasmodic activity of some fractions from the bark of Persea cordata, against guinea pig ileum contracted by acetylcholine and histamine. Hexane and dichloromethane fractions demonstrated the most promising biological effects, having similar potency to that of papaverine, a well-known antispasmodic agent.

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

    PubMed

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

    2009-03-01

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

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

    PubMed

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

    2016-08-01

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

  15. [Gallbladder contractility in early stages of lithogenesis in the lithogenic fed guinea pig].

    PubMed

    Lange, K; Gottschalk, M

    1995-07-01

    The main aim of our study was the investigation of gallbladder motility prior to gallstone formation in vivo in guinea pigs fed a lithogenic diet. In a first experiment guinea pigs were fed a lithogenic diet for 5, 15, 30 and 45 days. First gallstones (pigment calculi) appeared after 30 days diet application. The in vitro contractility after lithogenic diet remained unchanged. In a second experimental part the in vivo gallbladder contractility was measured in two experimental animal groups (control group and 21 days lithogenic fed guinea pigs). The isovolumetric pressure rise inside the gallbladder following the intravenous injection of 10(-9) mol/kg body weight ceruletid was the essential contractility parameter (intraluminal basal pressure 5 mm hg). Due to lithogenic feeding of 21 days--that means prior to gallstone formation--the isovolumetric pressure rise was significantly elevated (p < 0.01). Moreover we observed passive distensibility changes of gallbladder muscle due to muscular hyperplasia. The main result of this investigation is the fact that gallbladder muscle in guinea pigs fed a lithogenic diet response to ceruletid application with hypercontractility prior to provable pigment gallstone formation. However gallbladder hypomotility--believed to be a causal factor in cholelithogenesis--was not observed in our experimental conditions.

  16. Evaluation of bioactive glass for mastoid obliteration: a guinea pig model.

    PubMed

    Jang, Chul Ho; Cho, Yong Bum; Bae, Chun Sik

    2007-01-01

    Mastoid obliteration seeks to replace an open mastoid cavity with material that will become viable and free of infection and cholesteatoma. The purpose of this study was to evaluate the efficacy of bioactive glass ceramic particles for mastoid obliteration using a guinea pig animal model. Ten male guinea pigs (weighing 250-300 g) with normal eardrums and Preyer reflexes were used. Bulla obliteration using bioactive glass was performed on the left side in all guinea pigs. The implanted bioactive glass ceramic particles were examined clinically and radiologically by computed tomography (CT) and histologically. Clinically, there were no signs of inflammation, infection or implant exposure in all guinea pigs. The CT scans showed hyperintense areas that represented new bone formation. Histological evidence of new bone formation was observed in the implant specimens that included: active osteoblasts, osteocytes, chondrocytes and osteoid tissue. There was a definite bond between the implant and the bone interface at the areas of new bone formation. No inflammatory or foreign body reactions, caused by the bioactive glass ceramic particle implantation, were observed in the surrounding tissue. Our results suggest that bioactive glass ceramic particles are an ideal implant material. Further studies on bioactive glass ceramic particles should include a larger animal trial to lay the groundwork for human studies.

  17. Human mast cell mediator cocktail excites neurons in human and guinea-pig enteric nervous system.

    PubMed

    Schemann, M; Michel, K; Ceregrzyn, M; Zeller, F; Seidl, S; Bischoff, S C

    2005-04-01

    Neuroimmune interactions are an integral part of gut physiology and involved in the pathogenesis of inflammatory and functional bowel disorders. Mast cells and their mediators are important conveyors in the communication from the innate enteric immune system to the enteric nervous system (ENS). However, it is not known whether a mediator cocktail released from activated human mast cells affects neural activity in the ENS. We used the Multi-Site Optical Recording Technique to image single cell activity in guinea-pig and human ENS after application of a mast cell mediator cocktail (MCMC) that was released from isolated human intestinal mucosa mast cells stimulated by IgE-receptor cross-linking. Local application of MCMC onto individual ganglia evoked an excitatory response consisting of action potential discharge. This excitatory response occurred in 31%, 38% or 11% neurons of guinea-pig submucous plexus, human submucous plexus, or guinea-pig myenteric plexus, respectively. Compound action potentials from nerve fibres or fast excitatory synaptic inputs were not affected by MCMC. This study demonstrates immunoneural signalling in the human gut and revealed for the first time that an MCMC released from stimulated human intestinal mast cells induces excitatory actions in the human and guinea-pig ENS.

  18. Studies on vertical transmission of Trichinella spiralis in experimentally infected guinea pigs (Cavia porcellus).

    PubMed

    Riva, Eliana; Fiel, Cesar; Bernat, Gisele; Muchiut, Sebastián; Steffan, Pedro

    2017-08-01

    An experimental study to enhance knowledge on the capability of Trichenella spiralis to pass from guinea pigs to progeny at different periods of pregnancy or lactation was performed. For this purpose, 18 female adult guinea pigs were inoculated with 100 or 1000 T. spiralis muscle larvae (ML) during early, late gestation and during lactation period. The presence of T. spiralis (ML) in mothers and newborns was studied through enzymatic digestion from muscle samples. ML were observed in 9 of 42 newborn guinea pigs and levels of infection were significantly higher when infections of mothers were done during late gestation (p = 0.0046) with the high infective dose (p = 0.0043). T. spiralis ML were not recovered from any of the newborns from mothers infected in the lactation period. Ten out of 18 infected mothers presented larvae 1 in their mammary glands. Muscle samples from the tongue and the masseter showed the highest larval burdens. These observations confirm previous reports on that ML of T. spiralis are capable to pass through placental tissues to reach and encyst in striated muscle groups of newborn guinea pigs. This study may also reinforce the importance of preventive programs to control trichinellosis in those endemic areas where pregnant women would have high risk of infection.

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

    EPA Science Inventory

    Comparative genotoxic responses to arsenite in guinea pig, mouse, rat and human
    lymphocytes.

    Inorganic arsenic is a known human carcinogen causing skin, lung, and bladder cancer following chronic exposures. Yet, long-term laboratory animal carcinogenicity studies have ...

  20. THE PREPARATION OF SECTIONS OF GUINEA PIG LIVER FOR ELECTRON MICROSCOPY

    PubMed Central

    Claude, Albert; Fullam, Ernest F.

    1946-01-01

    1. A method is described whereby sections of guinea pig liver cells can be prepared for electron microscopy after fixation. 2. The high resolving powerof the electron microscope reveals the presence of two components, one particulate, the other apparently of fibrous texture, in the ground substance of the cells. PMID:19871546

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2017-06-15

    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.

  3. Effects of disodium cromoglycate (DSCG) on the guinea pig trachea and ileum.

    PubMed

    González Alvarez, R; Arruzazabala, M L

    1983-01-01

    Disodium cromoglycate (DSCG) (10(-2)M) significantly inhibits contractions induced by potassium chloride and barium chloride on guinea pig ileum and trachea. The effects of DSCG against these spasmogens are greater on the guinea pig ileum than on its trachea, which may be related with the calcium ion if we take into account that the contraction of the latter preparation seems to be less dependent on the extracellular calcium concentration than the first one. DSCG (10(-2)M) inhibits contractions induced by electrical stimulation (0.1 Hz) but the action of exogenous acetylcholine is not affected. This effect supports a neural site of action for DSCG in the ileum. DSCG (10(-2)M) also suppresses contractions induced by electrical stimulation (20 Hz) on isolated guinea pig trachea. This effect of DSCG is concentration and time dependent. The fact that DSCG inhibits contractions induced by electrical stimulation in both, guinea pig ileum and trachea as well as atropine does, constitute evidence that either an inhibition of acetylcholine release from postganglionic parasympathetic fibers or an anticholinergic effect is involved in the mode of action of DSCG. These effects can be ascribed to membrane stabilizing properties of this antiallergic drug.

  4. Cutaneous Uptake of 14C-HD Vapor by the Hairless Guinea Pig.

    DTIC Science & Technology

    1996-10-01

    The hairless guinea pig ( HGP ) is used by our laboratory to model the human cutaneous response to sulfur mustard (HD) exposure. We have determined the...other aspects of the experimental model. These results contribute to a better understanding of the cutaneous response to HD in the HGP model.

  5. Endogenous histamine and promethazine-induced gastric ulcers in the guinea pig

    NASA Technical Reports Server (NTRS)

    Djahanguiri, B.; Hemmati, M.

    1978-01-01

    Experiments performed with an inhibitor of diaminoxydase, aminoguanidine and an inhibitor of histidine decarboxylase, NSD 1055, showed that the frequency of gastric ulcers induced by promethazine was increased with the first inhibitor and decreased with the second. It is suggested that ulcers induced by promethazine in guinea pigs might be due to histamino-liberator effect of the antihistaminio compound.

  6. Contractile properties of synthetic cationic polypeptides in guinea-pig isolated trachea.

    PubMed Central

    Spina, D.; Goldie, R. G.

    1994-01-01

    1. The synthetic polypeptides, poly-L-arginine, poly-L-lysine and poly-D-lysine contract guinea-pig isolated trachea in a concentration-dependent, epithelium-independent manner. Indomethacin augmented the contractile response to poly-L-arginine. 2. The contractile response to poly-L-arginine was not significantly inhibited by nicardipine, a selective L-type calcium channel blocker or by the histamine H1-receptor antagonist, mepyramine nor significantly augmented by the neutral endopeptidase inhibitor, phosphoramidon. 3. The contractile response to poly-L-arginine was inhibited in a concentration-dependent manner by prior incubation of guinea-pig tracheal rings with a number of anionic polypeptides including, low molecular weight heparin, poly-L-aspartic acid and bovine serum albumin. 4. In vitro capsaicin-induced desensitization failed to attenuate the contractile response to poly-L-arginine, suggesting little, if any role for sensory neuropeptides in the functional response in the guinea-pig. 5. Synthetic polypeptides induce an epithelium-independent, charge-dependent contraction of guinea-pig isolated trachea. PMID:8012709

  7. Combined Selenium and Vitamin C Deficiency Causes Cell Death in Guinea Pig Skeletal Muscle1

    PubMed Central

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

    2009-01-01

    Combined antioxidant deficiencies of selenium and vitamin E or vitamin E and vitamin C in guinea pigs result in clinical illness. We hypothesized that combined selenium and vitamin C deficiency would have clinical consequences because in vitro interactions of these antioxidant nutrients have been reported. Since guinea pigs are dependent on dietary vitamin C, weanling male guinea pigs were fed selenium-deficient or control diet for 15 weeks prior to imposing vitamin C deficiency. Four dietary groups were formed and studied 3 weeks later: controls, vitamin C deficient, selenium deficient, and doubly deficient. Deficiencies were confirmed by determinations of glutathione peroxidase activity and vitamin C concentration in liver and skeletal muscle. Plasma creatine phosphokinase (CPK) activity and liver, kidney, heart, and quadriceps histopathology were determined. Doubly deficient animals had moderately severe skeletal muscle cell death as judged by histopathology and plasma CPK activity of 6630 ± 4400 IU/L (control 70 ± 5; vitamin C deficient 95 ± 110; selenium deficient 280 ± 250). Liver, kidney, and heart histology was normal in all groups. Muscle α-tocopherol levels were not depressed in the doubly deficient group but muscle F2 isoprostane concentrations were elevated in them and correlated with markers of cell death. We conclude that combining selenium and vitamin C deficiencies in the guinea pig causes cell death in skeletal muscle that is more severe than the injury caused by selenium deficiency. The elevation of muscle F2 isoprostanes is compatible with the cell death being caused by oxidative stress. PMID:19358936

  8. Diet Restriction and Fasting Exacerbate the Toxicity of Soman in Young and Old Guinea Pigs

    DTIC Science & Technology

    2012-09-01

    young and old guinea pigs Todd M . Myers Jeffrey L. Langston September 2012 Approved for public release; distribution...PAGES 19a. NAME OF RESPONSIBLE PERSON Todd M . Myers a. REPORT UNCLASSIFIED b. ABSTRACT UNCLASSIFIED c. THIS PAGE UNCLASSIFIED Unlimited 20...clip ( Vallejo -Freire, 1951) prior to soman or saline administration (at minus 1 week and at 0 h) and analyzed for acetylcholinesterase

  9. Synthesis by guinea pig megakaryocytes of platelet glycoprotein receptors for fibrinogen and von Willebrand factor.

    PubMed

    Kupinski, J M; Miller, J L

    1986-08-01

    In the preceding paper, we described two monoclonal antibodies, PG-1 and PG-2, that selectively blocked the binding of von Willebrand factor (PG-1) or of fibrinogen (PG-2) to guinea pig platelets. In this study we examine the structures and site of synthesis of these receptors. NP-40 lysates of radiolabeled guinea pig platelets were immunoprecipitated with monoclonal antibodies PG-1 or PG-2, and the precipitates analyzed by SDS-PAGE. PG-1 recognized a single polypeptide with reduced Mr of 143,000 daltons, while PG-2 precipitated two chains with reduced Mr of 121,000 and 93,000 daltons. Periodate-[3H]borohydride labeling of platelets, in conjunction with two-dimensional SDS-PAGE, showed that all three of the polypeptides are glycoproteins and that the 143,000 and 121,000 dalton chains are linked by disulfide bond(s) to smaller, approximately 25,000 dalton polypeptides. Guinea pig megakaryocytes synthesized polypeptides immunoprecipitable by PG-1 and PG-2, with molecular weights similar to polypeptides found associated with platelet membranes. These studies demonstrate that guinea pig platelets have functional receptors for fibrinogen and von Willebrand factor that are structurally homologous to human platelet glycoproteins Ib, IIb and IIIa, and that these glycoproteins are synthesized by megakaryocytes.

  10. The in vitro isolated whole guinea pig brain as a model to study epileptiform activity patterns.

    PubMed

    de Curtis, Marco; Librizzi, Laura; Uva, Laura

    2016-02-15

    Research on ictogenesis is based on the study of activity between seizures and during seizures in animal models of epilepsy (chronic condition) or in in vitro slices obtained from naïve non-epileptic brains after treatment with pro-convulsive drugs, manipulations of the extracellular medium and specific stimulation protocols. The in vitro isolated guinea pig brain retains the functional connectivity between brain structures and maintains interactions between neuronal, glial and vascular compartments. It is a close-to-in vivo preparation that offers experimental advantages not achieved with the use of other experimental models. Neurophysiological and imaging techniques can be utilized in this preparation to study brain activity during and between seizures induced by pharmacological or functional manipulations. Cellular and network determinants of interictal and ictal discharges that reproduce abnormal patterns observed in human focal epilepsies and the associated changes in extracellular ion and blood-brain permeability can be identified and analyzed in the isolated guinea pig brain. Ictal and interictal patterns recorded in in vitro slices may show substantial differences from seizure activity recorded in vivo due to slicing procedure itself. The isolated guinea pig brain maintained in vitro by arterial perfusion combines the typical facilitated access of in vitro preparations, that are difficult to approach during in vivo experiments, with the preservation of larger neuronal networks. The in vitro whole isolated guinea pig brain preparation offers an unique experimental model to study systemic and neurovascular changes during ictogenesis. Published by Elsevier B.V.

  11. Effects of ozone and sulfuric acid aerosol on gas trapping in the guinea pig lung

    SciTech Connect

    Silbaugh, S.A.; Mauderly, J.L.

    1986-01-01

    Four groups of 20 guinea pigs were sequentially exposed by inhalation to either air followed by sulfuric acid aerosol, ozone followed by sulfuric acid aerosol, ozone followed by air, or air followed by air to determine whether ozone preexposure sensitizes guinea pigs to the airway constrictive effects of sulfuric acid aerosol. All first exposures to ozone or air were 2 h in duration; all second exposures to sulfuric acid or air were for 1 h. All ozone and sulfuric acid exposures were 0.8 ppm and 12 mg/m3, respectively. Animals were observed for respiratory distress during exposure, and excised lungs were quantitated for trapped gas and wet/dry ratios. None of the guinea pigs developed dyspnea, and wet/dry ratios were not altered. Ozone significantly (p less than 0.05) increased trapped gas volumes, which were 44% (ozone-acid) to 68% (ozone-air) greater than in the air-air group. Trapped gas volume was 23% greater in the ozone-acid group than in the air-acid group, but the difference was not statistically significant (p less than 0.20). Thus, ozone increased gas trapping but did not significantly sensitize guinea pigs to the bronchoconstrictive action of sulfuric acid.

  12. Effect of systemic clarithromycin and prednisolone on histamine-induced otitis media in guinea pigs.

    PubMed

    Kozan, Günay; Aktan, Bülent; Sakat, Muhammed Sedat; Kurt, Sezgin; Öner, Fatih; Kara, Adem

    2015-01-01

    The results of the study showed that clarithromycin has anti-inflammatory and antioxidant effects and, when it is combined with prednisolone, those effects gain strength. The present study aims to investigate the effects that the antioxidant and anti-inflammatory activities of clarithromycin and/or prednisolone have on experimental otitis media in effusion-induced guinea-pigs. In this study, 35-male guinea pigs were randomly divided into five-groups. For the experimental otitis media, intra-tympanic histamine (0.1 ml) was injected into the guinea pigs in all of the groups except the control group. Then, 24-h after the intra-tympanic injections, clarithromycin (15 mg/kg/day) and/or prednisolone (1 mg/kg/day) were applied intraperitoneally to the guinea-pigs for 7-days. The biochemical analysis showed an increase in antioxidant capacity and a decrease in oxidant status and malondialdehyde (MDA) levels in the clarithromycin group and the prednisolone group and especially in the clarithromycin+prednisolone group, as compared to the experimental group (p < 0.05). In the cytokine analysis, lower levels of interleukin (IL)-6 and IL-17A and higher IL-10 were found in the clarithromycin, prednisolone, and clarithromycin+prednisolone groups than in the experimental group (p < 0.05). Furthermore, the histologic analyses showed histopathologic changes in the middle ear mucosa of the experimental group, but comparatively fewer-histopathologic changes were observed in the clarithromycin, prednisolone, and clarithromycin+prednisolone groups.

  13. Hypervitaminosis D and Metastatic Calcification in a Colony of Inbred Strain 13 Guinea Pigs, Cavia porcellus.

    PubMed

    Holcombe, H; Parry, N M; Rick, M; Brown, D E; Albers, T M; Refsal, K R; Morris, J; Kelly, R; Marko, S T

    2015-07-01

    A commercial diet fed to a colony of inbred strain 13 guinea pigs for approximately 6 weeks was subsequently recalled for excessive levels of vitamin D. Twenty-one of 62 animals exhibited clinical signs, including anorexia, lethargy, and poor body condition. Nine affected and 4 clinically normal animals were euthanized for further evaluation, including serum chemistry, urinalysis, and gross and/or histopathology. Macroscopic findings included white discoloration in multiple organs in 8 animals, and microscopic evaluation confirmed multiorgan mineralization in tissues from 7 animals. Serum 25-hydroxyvitamin D levels were elevated in 10 animals. Serum inorganic phosphorus and alkaline phosphatase levels were increased in all exposed animals; however, total calcium and ionized calcium levels were not significantly higher in exposed animals than in control strain 13 guinea pigs from a different institution. The data support a diagnosis of hypervitaminosis D with metastatic calcification. Following the diet recall, the remaining guinea pigs increased their food intake and regained body condition. Diagnostic testing of 8 animals euthanized approximately 3 months after returning to a normal diet demonstrated that serum parathyroid hormone remained significantly lower, and ionized calcium and ionized magnesium were significantly higher, in recovered animals compared to controls and exposed animals. These results indicate that diagnostic tests other than serum calcium are necessary for a diagnosis of hypervitaminosis D in guinea pigs. © The Author(s) 2014.

  14. THE IMPACT OF ULTRAVIOLET IRRADIATION ON MORPHO-FUNCTIONAL STATE OF SKIN IN GUINEA PIGS.

    PubMed

    Myronchenko, S; Naumova, O; Zvyagintseva, T

    2016-11-01

    The purpose of this study was to assess the impact of ultraviolet irradiation (UV) on morphological and functional condition of the skin in guinea pigs. The study involved 30 albino guinea pigs weighing 400-500 g subjected to local exposure to UV irradiation. Control group consisted of intact guinea pigs. Histological studies of the skin were carried out at different stages of the trial (2 hours, 4 hours, 3 days, 8 days following the exposure). Microscopic examination showed morphological signs of acute inflammation in the skin of animals within the first three days following the exposure to UV irradiation. Within 2 hours following the exposure to UV irradiation these changes were minimal with signs of mild exudative changes. In 4 hours after the exposure histological changes increased. The specimens were also found to contain altered apoptotic keratinocytes (sunburn cells). Histopathological changes persisted and reached maximum severity by the 3rd day. Within post-erythema period (the 8th day) proliferative, hyperplastic, degenerative and dystrophic changes in the skin persisted. The prolonged nature of the changes in the skin is suggestive of the development of chronic inflammation in the skin of guinea pigs subjected to local exposure to UV irradiation.

  15. 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.

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

    SciTech Connect

    Vargas, M.H.; Segura, P.; Campos, M.G.; Hong, E.; Montano, L.M.

    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 the 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.

  17. Effect of estradiol on chlamydial genital infection of female guinea pigs.

    PubMed

    Rank, R G; White, H J; Hough, A J; Pasley, J N; Barron, A L

    1982-11-01

    Female guinea pigs were treated daily with 1 mg of beta-estradiol-3-benzoate intramuscularly beginning 14 days before intravaginal inoculation with the chlamydial agent of guinea pig inclusion conjunctivitis and continuing during the course of the infection. Treatment with estradiol was found to markedly influence the course of genital infection with the chlamydial agent of guinea pig inclusion conjunctivitis, producing infections of greater intensity and longer duration than those in control animals. Moreover, pathogenesis was altered in that ascending infection was observed, resulting in endometritis, cystic salpingitis, and cystitis. Infection in the controls was limited to the cervix and vagina. Estradiol treatment increased the apparent number of infected cells in the cervix and vagina as detected by histopathology and immunofluorescent staining. Humoral and cell-mediated immune responses to the chlamydial agent of guinea pig inclusion conjunctivitis were comparable in estradiol-treated and untreated animals. These data indicate that hormonal manipulation may have profound effects on the course of chlamydial genital infections.

  18. Experimental Chagas' disease in complement-deficient mice and guinea pigs.

    PubMed Central

    Dalmasso, A P; Jarvinen, J A

    1980-01-01

    The course of infection with trypomastigotes of Trypanosoma cruzi (House 510 strain) in mice and guinea pigs with genetic complement deficiencies was compare