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Sample records for guinea-pig vascular smooth

  1. Actions of 4-aminopyridine on vascular smooth muscle tissues of the guinea-pig

    PubMed Central

    Hara, Yusuke; Kitamura, Kenji; Kuriyama, Hirosi

    1980-01-01

    1 Effects of 4-aminopyridine (4-AP) and procaine on the membrane and contractile properties of smooth muscle cells of the guinea-pig pulmonary artery and portal vein were observed. 2 The membrane potential and length constant of smooth muscle cells of the guinea-pig pulmonary artery were -53.2 mV and 1.2 mm, respectively, and those of the portal vein were -52.6 mV and 0.71 mm, respectively. The membrane was electrically quiescent in the pulmonary artery and it was electrically active in the portal vein. 3 Both 4-AP and procaine depolarized the membrane, increased the membrane resistance and suppressed the rectifying properties in both tissues. Both agents evoked a graded response from the muscle membranes of the pulmonary artery by outward current pulse. Procaine had a greater effect than 4-AP on the above membrane properties. 4 4-AP (10-5 M) produced contraction without depolarization of the membrane. The contraction evoked by 10-5 M 4-AP was completely suppressed but that evoked by 5 × 10-4 M 4-AP was only partly suppressed by phentolamine (10-7 M). However, the contraction evoked by procaine was not suppressed by phentolamine. 5 4-AP enhanced but procaine suppressed the amplitude of 118 mM [K]0-induced contraction. 6 The results suggest that 4-AP and procaine suppress K-conductance of the muscle membrane, and 4-AP but not procaine increases noradrenaline release from the nerve terminal. Presumably intracellular free Ca concentrations are also modified by these agents. The effects of 4-AP and procaine on the vascular muscle were compared with those on other excitable tissues. PMID:7357204

  2. The effects of cannabidiol on the antigen-induced contraction of airways smooth muscle in the guinea-pig.

    PubMed

    Dudášová, A; Keir, S D; Parsons, M E; Molleman, A; Page, C P

    2013-06-01

    (-)-Δ(9)-Tetrahydrocannabinol has been demonstrated to have beneficial effects in the airways, but its psychoactive effects preclude its therapeutic use for the treatment of airways diseases. In the present study we have investigated the effects of (-)-cannabidiol, a non-psychoactive component of cannabis for its actions on bronchial smooth muscle in vitro and in vivo. Guinea-pig bronchial smooth muscle contractions induced by exogenously applied spasmogens were measured isometrically. In addition, contractile responses of bronchial smooth muscle from ovalbumin-sensitized guinea-pigs were investigated in the absence or presence of (-)-cannabidiol. Furthermore, the effect of (-)-cannabidiol against ovalbumin-induced airway obstruction was investigated in vivo in ovalbumin-sensitized guinea-pigs. (-)-Cannabidiol did not influence the bronchial smooth muscle contraction induced by carbachol, histamine or neurokinin A. In contrast, (-)-cannabidiol inhibited anandamide- and virodhamine-induced responses of isolated bronchi. A fatty acid amide hydrolase inhibitor, phenylmethanesulfonyl fluoride reversed the inhibitory effect of (-)-cannabidiol on anandamide-induced contractions. In addition, (-)-cannabidiol inhibited the contractile response of bronchi obtained from allergic guinea-pigs induced by ovalbumin. In vivo, (-)-cannabidiol reduced ovalbumin-induced airway obstruction. In conclusion, our results suggest that cannabidiol can influence antigen-induced airway smooth muscle tone suggesting that this molecule may have beneficial effects in the treatment of obstructive airway disorders. PMID:23428645

  3. Electrical properties of purinergic transmission in smooth muscle of the guinea-pig prostate.

    PubMed

    Lam, Michelle; Mitsui, Retsu; Hashitani, Hikaru

    2016-01-01

    Prostatic smooth muscle develops spontaneous myogenic tone which is modulated by autonomic neuromuscular transmission. This study aimed to investigate the role of purinergic transmission in regulating electrical activity of prostate smooth muscle and whether its contribution may be altered with age. Intracellular recordings were simultaneously made with isometric tension recordings in smooth muscle preparations of the guinea-pig prostate. Immunostaining for P2X1 receptors on whole mount preparations was also performed. In prostate preparations which generated spontaneous slow waves, electrical field stimulation (EFS)-evoked excitatory junction potentials (EJPs) which were abolished by guanethidine (10 μM), α-β-methylene ATP (10 μM) or pyridoxal phosphate-6-azophenyl-2,4-disulfonic acid (PPADS, 10 μM) but not phentolamine (1 μM). Consistently, immunostaining revealed the expression of P2X1 receptors on prostatic smooth muscle. EJPs themselves did not cause contractions, but EJPs could sum to trigger a slow wave and associated contraction. Yohimbine (1 μM) and 3,7-dimethyl-1-propargylxanthine (DMPX, 10 μM) but not propranolol (1 μM) potentiated EJPs. Although properties of EJPs were not different between young and aging guinea-pig prostates, ectoATPase inhibitor ARL 67156 (100 μM) augmented EJP amplitudes by 64.2 ± 29.6% in aging animals, compared to 22.1 ± 19.9% in young animals. These results suggest that ATP released from sympathetic nerves acts on P2X1 purinoceptors located on prostate smooth muscle to evoke EJPs, while pre-junctional α2-adrenergic and adenosine A2 receptors may play a role in preventing excessive transmitter release. Age-related up-regulation of enzymatic ATP breakdown may be a compensatory mechanism for the enhanced purinergic transmission which would cause hypercontractility arising from increased ATP release in older animals. PMID:26657181

  4. Constitutively active PKA regulates neuronal acetylcholine release and contractility of guinea pig urinary bladder smooth muscle.

    PubMed

    Xin, Wenkuan; Li, Ning; Fernandes, Vitor S; Petkov, Georgi V

    2016-06-01

    Autonomic and somatic motor neurons that innervate the urinary bladder and urethra control the highly coordinated functions of the lower urinary tract, the storage, and the emptying of urine. ACh is the primary excitatory neurotransmitter in the bladder. Here, we aimed to determine whether PKA regulates neuronal ACh release and related nerve-evoked detrusor smooth muscle (DSM) contractions in the guinea pig urinary bladder. Isometric DSM tension recordings were used to measure spontaneous phasic and electrical field stimulation (EFS)- and carbachol-induced DSM contractions with a combination of pharmacological tools. The colorimetric method was used to measure ACh released by the parasympathetic nerves in DSM isolated strips. The pharmacological inhibition of PKA with H-89 (10 μM) increased the spontaneous phasic contractions, whereas it attenuated the EFS-induced DSM contractions. Intriguingly, H-89 (10 μM) attenuated the (primary) cholinergic component, whereas it simultaneously increased the (secondary) purinergic component of the nerve-evoked contractions in DSM isolated strips. The acetylcholinesterase inhibitor, eserine (10 μM), increased EFS-induced DSM contractions, and the subsequent addition of H-89 attenuated the contractions. H-89 (10 μM) significantly increased DSM phasic contractions induced by the cholinergic agonist carbachol. The inhibition of PKA decreased the neuronal release of ACh in DSM tissues. This study revealed that PKA-mediated signaling pathways differentially regulate nerve-evoked and spontaneous phasic contractions of guinea pig DSM. Constitutively active PKA in the bladder nerves controls synaptic ACh release, thus regulating the nerve-evoked DSM contractions, whereas PKA in DSM cells controls the spontaneous phasic contractility. PMID:27029424

  5. Effect of gamma-aminobutyric acid on neurally mediated contraction of guinea pig trachealis smooth muscle.

    PubMed

    Tamaoki, J; Graf, P D; Nadel, J A

    1987-10-01

    To determine whether gamma-aminobutyric acid (GABA) affects the contractile properties of airway smooth muscle and, if so, what the mechanism of action is, the authors studied guinea pig tracheal rings under isometric conditions in vitro. GABA and related substances, baclofen and muscimol, had no effect on the resting tension but reversibly depressed contractions induced by electrical field stimulation in a dose-dependent fashion, IC50 values (mean +/- S.E.) being 5.6 +/- 1.4 X 10(-6) M, 6.8 +/- 0.9 X 10(-6) M and 8.5 +/- 1.5 X 10(-5) M, respectively. In contrast, GABA did not alter the response to exogenous acetylcholine or the nonadrenergic noncholinergic inhibitory component. Pretreatment of tissues with bicuculline antagonized the inhibitory effect of GABA as well as that of baclofen. This inhibitory effect was not modified by propranolol, phentolamine, hemicholinium-3 or naloxone, but it was blocked by the Cl channel blocker furosemide and by the substitution of external Cl. These results suggest that GABA decreases the contractile response of airway smooth muscle to cholinergic nerve stimulation by inhibiting the evoked release of acetylcholine and that this effect is exerted by activating Cl-dependent, bicuculline-sensitive GABA receptors. PMID:3668869

  6. Membrane properties of the smooth-muscle fibres of the guinea-pig portal vein.

    PubMed

    Ito, Y; Kuriyama, H

    1971-05-01

    The membrane activities and the various characteristic constants of the smooth-muscle membrane of the guinea-pig portal vein were investigated with the micro-electrode technique.1. The mean membrane potential was -37 mV. Spontaneous discharges appeared as regular bursts of short trains of spikes alternating with silent periods, as a mixture of single spikes and bursts of spikes appearing continuously, or as regular spikes with low frequency.2. Spontaneous spikes with overshoot were frequently observed. The maximum rate of rise of the spike was 3.7 V/sec. The shapes of the spikes were classified into three different types, i.e. pace-maker type of spike, monophasic spike and spike with a hump during the falling phase.3. Tetrodotoxin (10(-5) g/ml.) did not influence the patterns of the spontaneous train discharges nor the shape of the spike.4. Extracellularly applied outward current elicited spikes which were either monophasic or had a hump on the falling phase. Inward current elicited break excitation of the spike.5. Current-voltage relations, produced by application of inward current pulses to the tissue and measured at various distances from the stimulating partition, were linear.6. The smooth-muscle membrane of portal vein showed cable-like properties. The mean space constant of the membrane was 0.52 mm; the mean time constant of the membrane calculated from the electrotonic potential was 330 msec.7. Conduction velocity of the spike measured by insertion of two micro-electrodes was 0.58 cm/sec.8. The time constant of the foot of the propagated spike was 27 msec. The time constant of the membrane calculated from the time constant of the foot of the spike and the conduction velocity was 310 msec.9. The membrane properties of longitudinal smooth muscle of the portal vein were discussed in comparison with other veins and various visceral smooth muscles. PMID:5580862

  7. Ovalbumin sensitization of guinea pig at birth prevents the ontogenetic decrease in airway smooth muscle responsiveness

    PubMed Central

    Chitano, Pasquale; Wang, Lu; Degan, Simone; Worthington, Charles L.; Pozzato, Valeria; Hussaini, Syed H.; Turner, Wesley C.; Dorscheid, Delbert R.; Murphy, Thomas M.

    2014-01-01

    Abstract Airway smooth muscle (ASM) displays a hyperresponsive phenotype at young age and becomes less responsive in adulthood. We hypothesized that allergic sensitization, which causes ASM hyperresponsiveness and typically occurs early in life, prevents the ontogenetic loss of the ASM hyperresponsive phenotype. We therefore studied whether neonatal allergic sensitization, not followed by later allergen challenges, alters the ontogenesis of ASM properties. We neonatally sensitized guinea pigs to ovalbumin and studied them at 1 week, 3 weeks, and 3 months (adult). A Schultz‐Dale response in isolated tracheal rings confirmed sensitization. The occurrence of inflammation was evaluated in the blood and in the submucosa of large airways. We assessed ASM function in tracheal strips as ability to produce force and shortening. ASM content of vimentin was also studied. A Schultz‐Dale response was observed in all 3‐week or older sensitized animals. A mild inflammatory process was characterized by eosinophilia in the blood and in the airway submucosa. Early life sensitization had no effect on ASM force generation, but prevented the ontogenetic decline of shortening velocity and the increase in resistance to shortening. Vimentin increased with age in control but not in sensitized animals. Allergic sensitization at birth without subsequent allergen exposures is sufficient to prevent normal ASM ontogenesis, inducing persistence to adulthood of an ASM hyperresponsive phenotype. PMID:25501429

  8. Effects of trimebutine maleate (TM-906) on the smooth muscles of isolated guinea pig gallbladder.

    PubMed

    Takenaga, H; Magaribuchi, T; Tamaki, H

    1984-08-01

    Effects of trimebutine maleate (TM-906) on the smooth muscles of isolated guinea pig gallbladder were investigated. TM-906 inhibited the contractile responses to cholinergic nerve stimulation (5 Hz) and to acetylcholine (3 X 10(-8) g/ml) to the same extent, both of which produced much the same amplitude of contraction. TM-906 noncompetitively antagonized the contractile response to methacholine, and it caused a parallel shift of dose-response curves for the contractile response to CaCl2 to higher concentrations. Moreover, TM-906 inhibited the contractile response to 50 mM KCl in a dose-dependent manner. On the other hand, TM-906 itself evoked a slight contractile response in a dose-dependent manner. The contractile response induced by TM-906 was prevented by exposure to Ca++-free solution, but not by tetrodotoxin or atropine. From these results, it was suggested that TM-906 inhibited the contractile responses to cholinergic nerve stimulation, acetylcholine, methacholine and 50 mM KCl by reducing the influx of calcium ion across the cell membrane, while it was assumed that TM-906 itself evoked a slight contractile response by increasing in some way the concentration of the intracellular free calcium ion available for the contractile systems. PMID:6503039

  9. A comparison of the electrical properties and morphological characteristics of the smooth muscle of the rat and guinea-pig vas deferens.

    PubMed

    Goto, K; Millecchia, L L; Westfall, D P; Fleming, W W

    1977-04-25

    Microelectrodes were used to compare a variety of electrophysiological parameters of the rat and guinea-pig vas deferens. In comparison to the guinea pig, spontaneous junction potentials in the rat tissue were of shorter duration and occurred with greater frequency and amplitude. Action potentials induced by nerve stimulation could be observed in the smooth muscle of both species. However, in the rat tissue the majority of action potentials were generated in the impaled cell while 60% of the action potentials in the guinea-pig vas deferens were propagated. When current was intracellularly applied, spike potentials could be induced in approximately 90% of the cells of the rat vas deferens but in less than 10% of the cells of the guinea-pig vas deferens. The space constant was 1.48 mm for the guinea-pig vas deferens, but less than 0.5 mm for the rat vas deferens. Electromicroscopic examination of the homologous tissues indicates that the differences in electrical properties can be accounted for in part by differences in morphology. The incidence and intimacy of neuromuscular contacts was greater in the rat vas deferens while the incidence of nexuses between smooth muscle cells was greater in the guinea-pig tissue. PMID:559295

  10. Novel role for the transient potential receptor melastatin 4 channel in guinea pig detrusor smooth muscle physiology

    PubMed Central

    Smith, Amy C.; Hristov, Kiril L.; Cheng, Qiuping; Xin, Wenkuan; Parajuli, Shankar P.; Earley, Scott; Malysz, John

    2013-01-01

    Members of the transient receptor potential (TRP) channel superfamily, including the Ca2+-activated monovalent cation-selective TRP melastatin 4 (TRPM4) channel, have been recently identified in the urinary bladder. However, their expression and function at the level of detrusor smooth muscle (DSM) remain largely unexplored. In this study, for the first time we investigated the role of TRPM4 channels in guinea pig DSM excitation-contraction coupling using a multidisciplinary approach encompassing protein detection, electrophysiology, live-cell Ca2+ imaging, DSM contractility, and 9-phenanthrol, a recently characterized selective inhibitor of the TRPM4 channel. Western blot and immunocytochemistry experiments demonstrated the expression of the TRPM4 channel in whole DSM tissue and freshly isolated DSM cells with specific localization on the plasma membrane. Perforated whole cell patch-clamp recordings and real-time Ca2+ imaging experiments with fura 2-AM, both using freshly isolated DSM cells, revealed that 9-phenanthrol (30 μM) significantly reduced the cation current and decreased intracellular Ca2+ levels. 9-Phenanthrol (0.1–30 μM) significantly inhibited spontaneous, 0.1 μM carbachol-induced, 20 mM KCl-induced, and nerve-evoked contractions in guinea pig DSM-isolated strips with IC50 values of 1–7 μM and 70–80% maximum inhibition. 9-Phenanthrol also reduced nerve-evoked contraction amplitude induced by continuous repetitive electrical field stimulation of 10-Hz frequency and shifted the frequency-response curve (0.5–50 Hz) relative to the control. Collectively, our data demonstrate the novel finding that TRPM4 channels are expressed in guinea pig DSM and reveal their critical role in the regulation of guinea pig DSM excitation-contraction coupling. PMID:23302778

  11. Effect of airway inflammation on smooth muscle shortening and contractility in guinea pig trachealis.

    PubMed

    Mitchell, R W; Ndukwu, I M; Arbetter, K; Solway, J; Leff, A R

    1993-12-01

    We studied the effect of either 1) immunogenic inflammation caused by aerosolized ovalbumin or 2) neurogenic inflammation caused by aerosolized capsaicin in vivo on guinea pig tracheal smooth muscle (TSM) contractility in vitro. Force-velocity relationships were determined for nine epithelium-intact TSM strips from ovalbumin-sensitized (OAS) vs. seven sham-sensitized controls and TSM strips for seven animals treated with capsaicin aerosol (Cap-Aer) vs. eight sham controls. Muscle strips were tethered to an electromagnetic lever system, which allowed isotonic shortening when load clamps [from 0 to maximal isometric force (Po)] were applied at specific times after onset of contraction. Contractions were elicited by supramaximal electrical field stimulation (60 Hz, 10-s duration, 18 V). Optimal length for each muscle was determined during equilibration. Maximal shortening velocity (Vmax) was increased in TSM from OAS (1.72 +/- 0.46 mm/s) compared with sham-sensitized animals (0.90 +/- 0.15 mm/s, P < 0.05); Vmax for TSM from Cap-Aer (0.88 +/- 0.11 mm/s) was not different from control TSM (1.13 +/- 0.08 mm/s, P = NS). Similarly, maximal shortening (delta max) was augmented in TSM from OAS (1.01 +/- 0.15 mm) compared with sham-sensitized animals (0.72 +/- 0.14 mm, P < 0.05); delta max for TSM from Cap-Aer animals (0.65 +/- 0.11 mm) was not different from saline aerosol controls (0.71 +/- 0.15 mm, P = NS). We demonstrate Vmax and delta max are augmented in TSM after ovalbumin sensitization; in contrast, neurogenic inflammation caused by capsaicin has no effect on isolated TSM contractility in vitro. These data suggest that airway hyperresponsiveness in vivo that occurs in association with immunogenic or neurogenic inflammation may result from different effects of these types of inflammation on airway smooth muscle. PMID:8279571

  12. Hypoxia-induced inhibition of calcium channels in guinea-pig taenia caeci smooth muscle cells.

    PubMed

    Rekalov, V; Juránek, I; Máleková, L; Bauer, V

    1997-11-15

    1. The effects of hypoxia on whole-cell current in single smooth muscle cells and on a high K(+)-induced contraction of strips of the guinea-pig taenia caeci were studied. 2. In physiological salt solution (PSS) and K(+)-based pipette solution, hypoxia (PO2 = 20 mmHg) reversibly inhibited both the inward Ca2+ current (ICa) and outward Ca(2+)-activated K+ current (IK(Ca)) components of the whole-cell current. 3. In PSS and Cs(+)-based pipette solution, hypoxia reversibly suppressed ICa by 30 +/- 5% at 0 mV. 4. When Ba2+ was used as a charge carrier, the IBa was suppressed by hypoxia in a potential-dependent manner, with the maximum of 40 +/- 7% at +10 mV. Alterations of concentrations of EGTA, GDB beta S or ATP in the pipette solution did not change the inhibitory effects of hypoxia on ICa and IBa. 5. In PSS with 2 mM CaCl2 replaced by CoCl2, hypoxia did not affect the Ca2+ influx-independent potassium current. 6. In cells voltage clamped at -20 mV hypoxia reversibly inhibited the spontaneous transient outward currents. 7. The response of high K(+)-contracted taenia caeci to hypoxia was composed of an initial rapid relaxation followed by a small transient contraction and slow relaxation. The transient contraction was blocked by atropine (1-10 microM), while relaxations were unaffected by atropine and guanethidine (10 microM). 8. The results show that hypoxia reversibly inhibits ICa and secondarily suppresses IK(Ca) due to decreased Ca2+ influx through Ca2+ channels. 9. It is suggested that inhibition of ICa was responsible for the rapid relaxation, whereas transient contraction may have been due to release of acetylcholine from nerve terminals upon hypoxia. PMID:9409475

  13. Three Paradigms of Airway Smooth Muscle Hyperresponsiveness in Young Guinea Pigs

    PubMed Central

    Chitano, Pasquale; Wang, Lu; Murphy, Thomas M.

    2008-01-01

    Evidence for contributions of airway smooth muscle (ASM) to the hyperresponsiveness of newborn and juvenile airways continues to accumulate. In our laboratory three novel paradigms of hyperresponsiveness of newborn and young ASM have recently emerged using a guinea pig model of maturation in three age groups-- 1 week (newborn); 3 week (juvenile) and 2−3 months (adult). These include 1) evidence for a natural decline after newborn and juvenile life of the shortening velocity of ASM shortening associated with a decrease in regulatory myosin light chain (MLC) phosphorylation and a parallel decline in the content of MLC kinase. Associated with the decrease in ASM shortening with age is an increase in the internal resistance to shortening. This relationship can be approximated as dP/dtmax ≈ dP/dLpassive × dL/dtmax (the maximal rate of increase of active stress generation ≈ the passive stiffness × the maximal shortening velocity V0). 2) The second paradigm demonstrates that newborn ASM, unlike that in adults, does not relax with prolonged electrical field stimulation. The impaired relaxation is related to changes in prostaglandin synthesis and acetylcholinesterase function; 3) the third paradigm demonstrates that while oscillatory strain serves to relax adult ASM, the response in newborns is the potentiation of active stress. This is related to developmental changes in the cytoskeleton. Oscillatory stiffness is shown to relate inversely to the expression of myosin light chain kinase. This suggests that developmental changes in shortening relate inversely to the stiffness of the ASM early in shortening, suggesting a dynamic role for the cytoskeleton in facilitating and opposing ASM shortening. Together these paradigms demonstrate that ASM contributes by multiple mechanisms to the natural hyperresponsiveness of newborn and juvenile airways. Future studies will elaborate the mechanisms and extend these paradigms relate to ASM hyperresponsiveness that is increased

  14. Nonadrenergic, noncholinergic responses stabilize smooth muscle tone, with and without parasympathetic activation, in guinea-pig isolated airways.

    PubMed

    Lindén, A; Löfdahl, C G; Ullman, A; Skoogh, B E

    1993-03-01

    In guinea-pig isolated airways, nonadrenergic, noncholinergic (NANC) neural responses converge towards a similar level of smooth muscle tone, via a contraction when the tone is low prior to stimulation, and via a relaxation when the tone is high prior to stimulation. We wanted to assess the effect of simultaneous parasympathetic activation on these converging NANC responses, with and without the addition of sympathetic activation. In guinea-pig isolated airways, the spontaneous airway tone was initially abolished by indomethacin (10 microM). In one series, adrenergic depletion by guanethidine (10 microM) was then established, with and without cholinergic blockade by atropine (1 microM). In another series, either cholinergic blockade by atropine (1 microM) or no blockade was utilized. Responses to electrical field stimulation (1,200 mA, 0.5 ms, 3 Hz for 240 s) were studied with no induced tone, at a moderate (0.3 microM) and at a near-maximum (6 microM), histamine-induced tone. The mean level of the tonus equilibrium (% of maximum tone) was higher with the simultaneous NANC and parasympathetic activation than with NANC activation alone (75% compared with 44%, in the main bronchus, n = 8). The level of the tonus equilibrium was also higher with the simultaneous NANC, sympathetic and parasympathetic activation than with NANC and sympathetic activation only (49% compared with 21%, in the main bronchus, n = 8). The pattern was similar in the distal trachea. In conclusion, NANC neural responses can stabilize smooth muscle tone, and this stabilizing effect can be modulated by both parasympathetic and sympathetic activation, in guinea-pig isolated airways. PMID:8472834

  15. Muscarinic receptor subtypes controlling the cationic current in guinea-pig ileal smooth muscle

    PubMed Central

    Zholos, Alexander V; Bolton, Thomas B

    1997-01-01

    The effects of muscarinic antagonists on cationic current evoked by activating muscarinic receptors with the stable agonist carbachol were studied by use of patch-clamp recording techniques in guinea-pig single ileal smooth muscle cells. Ascending concentrations of carbachol (3–300 μM) activated the cationic conductance in a concentration-dependent manner with conductance at a maximally effective carbachol concentration (Gmax) of 27.4±1.4 nS and a mean −log EC50 of 5.12±0.03 (mean±s.e.mean) (n=114). Muscarinic antagonists with higher affinity for the M2 receptor, methoctramine, himbacine and tripitramine, produced a parallel shift of the carbachol concentration-effect curve to the right in a concentration-dependent manner with pA2 values of 8.1, 8.0 and 9.1, respectively. All M3 selective muscarinic antagonists tested, 4-DAMP, p-F-HHSiD and zamifenacin, reduced the maximal response in a concentration-dependent and non-competitive manner. This effect could be observed even at concentrations which did not produce any increase in the EC50 for carbachol. At higher concentrations M3 antagonists shifted the agonist curve to the right, increasing the EC50, and depressed the maximum conductance response. Atropine, a non-selective antagonist, produced both reduction in Gmax (M3 effect) and significant increase in the EC50 (M2 effect) in the same concentration range. The depression of the conductance by 4-DAMP, zamifenacin and atropine could not be explained by channel block as cationic current evoked by adding GTPγS to the pipette (without application of carbachol) was unaffected. The results support the hypothesis that carbachol activates M2 muscarinic receptors so initiating the opening of cationic channels which cause depolarization; this effect is potentiated by an unknown mechanism when carbachol activates M3 receptors. As an increasing fraction of M3 receptors are blocked by an antagonist, the effects on cationic current of an increasing proportion of

  16. Effects of cicletanine on whole-cell currents of single smooth muscle cells from the guinea-pig portal vein.

    PubMed Central

    Noack, T.; Deitmer, P.

    1993-01-01

    1. Smooth muscle cells of the guinea-pig portal vein were dispersed by enzymatic treatment and recordings of membrane currents were made in the whole-cell mode by the patch-clamp technique. The effects of extracellular application of cicletanine-hydrochloride on the whole-cell currents of isolated smooth muscle cells from the guinea-pig portal vein were studied in solutions containing a normal concentration of calcium (2.5 mM). 2. Cicletanine, 10 to 100 microM, reduced the voltage-dependent inward calcium current with an IC50 of 250 microM. These effects of cicletanine were reversible. 3. The action of cicletanine on calcium currents can be interpreted as a decrease of the availability of calcium channels but not by an alteration of the time course or voltage-dependency of inactivation. 4. The control calcium current was enhanced by application of Bay K 8644. On this enhanced inward current, cicletanine also exerted inhibitory effects which were not use-dependent. 5. Cicletanine, 1 to 100 microM, did not enhance outward potassium currents. 6. It is concluded that at least one component of the vasorelaxant effects of cicletanine is produced by inhibition of calcium currents. PMID:7684299

  17. Synthesis and calcium antagonist activity of new 1,4-dihydropyridines containing nitrobenzylimidazolyl substituent in guinea-pig ileal smooth muscle.

    PubMed

    Zarghi, A; Derakhshandeh, K; Roshanzamir, F; Jorjani, M; Rastegar, H; Varmazyari, M; Shafiee, A

    2002-01-01

    New alkyl ester analogues of nifedipine, in which the ortho-nitrophenyl group of position 4 is replaced by 1-(4-nitrobenzyl)-5-imidazolyl or 2-methylthio-1-(4-nitrobenzyl)-5-imidazolyl substituent, were synthesized and evaluated as calcium-channel antagonists using the electrically induced contraction of guinea-pig ileal longitudinal smooth muscle. Our results demonstrate that all compounds inhibited the contractile response of guinea-pig ileum to electrical stimulation and the IC50 value of the most potent compounds 6a and 6f were significantly lower than that of nifedipine. Therefore, they are more potent than nifedipine. PMID:12064052

  18. ATP induces guinea pig gallbladder smooth muscle excitability via the P2Y4 receptor and COX-1 activity.

    PubMed

    Bartoo, Aaron C; Nelson, Mark T; Mawe, Gary M

    2008-06-01

    The purpose of this study was to elucidate the mechanisms by which ATP increases guinea pig gallbladder smooth muscle (GBSM) excitability. We evaluated changes in membrane potential and action potential (AP) frequency in GBSM by use of intracellular recording. Application of ATP (100 microM) caused membrane depolarization and a significant increase in AP frequency that were not sensitive to block by tetrodotoxin (0.5 microM). The nonselective P2 antagonist, suramin (100 microM), blocked the excitatory response, resulting in decreased AP frequency in the presence of ATP. The excitatory response to ATP was not altered by pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (30 microM), a nonselective P2X antagonist. UTP also caused membrane depolarization and increased AP frequency, with a similar dose-response relationship as ATP. RT-PCR demonstrated that the P2Y(4), but not P2Y(2), receptor subtype is expressed in guinea pig gallbladder muscularis. ATP induced excitation was blocked by indomethacin (10 microM) and the cyclooxygenase (COX)-1 inhibitor SC-560 (300 nM), but not the COX-2 inhibitor nimesulide (500 nM). These data suggest that ATP stimulates P2Y(4) receptors within the gallbladder muscularis and, in turn, stimulate prostanoid production via COX-1 leading to increased excitability of GBSM. PMID:18436624

  19. Comparison of polyurethane with cyanoacrylate in hemostasis of vascular injury in guinea pigs

    PubMed Central

    Kubrusly, Luiz Fernando; Formighieri, Marina Simões; Lago, José Vitor Martins; Graça, Yorgos Luiz Santos de Salles; Sobral, Ana Cristina Lira; Lago, Marianna Martins

    2015-01-01

    Objective To evaluate the behavior of castor oil-derived polyurethane as a hemostatic agent and tissue response after abdominal aortic injury and to compare it with 2-octyl-cyanoacrylate. Methods Twenty-four Guinea Pigs were randomly divided into three groups of eight animals (I, II, and III). The infrarenal abdominal aorta was dissected, clamped proximally and distally to the vascular puncture site. In group I (control), hemostasis was achieved with digital pressure; in group II (polyurethane) castor oil-derived polyurethane was applied, and in group III (cyanoacrylate), 2-octyl-cyanoacrylate was used. Group II was subdivided into IIA and IIB according to the time of preparation of the hemostatic agent. Results Mean blood loss in groups IIA, IIB and III was 0.002 grams (g), 0.008 g, and 0.170 g, with standard deviation of 0.005 g, 0.005 g, and 0.424 g, respectively (P=0.069). The drying time for cyanoacrylate averaged 81.5 seconds (s) (standard deviation: 51.5 seconds) and 126.1 s (standard deviation: 23.0 s) for polyurethane B (P=0.046). However, there was a trend (P=0.069) for cyanoacrylate to dry more slowly than polyurethane A (mean: 40.5 s; SD: 8.6 s). Furthermore, polyurethane A had a shorter drying time than polyurethane B (P=0.003), mean IIA of 40.5 s (standard deviation: 8.6 s). In group III, 100% of the animals had mild/severe fibrosis, while in group II only 12.5% showed this degree of fibrosis (P=0.001). Conclusion Polyurethane derived from castor oil showed similar hemostatic behavior to octyl-2-cyanoacrylate. There was less perivascular tissue response with polyurethane when compared with cyanoacrylate. PMID:25859876

  20. Cellular mechanisms of nitric oxide-induced relaxation of corporeal smooth muscle in the guinea-pig

    PubMed Central

    Hashitani, Hikaru; Fukuta, Hiroyasu; Dickens, Emma J; Suzuki, Hikaru

    2002-01-01

    The cellular mechanism of nitric oxide (NO)-induced relaxation in corporeal smooth muscle (CSM) of the guinea-pig was investigated. Changes in the intracellular concentration of calcium ions ([Ca2+]i), membrane potential and isometric tension were measured. CSM cells exhibited spontaneous depolarizations and transient increases in [Ca2+]i (Ca2+ transients) which were accompanied by contractions. This spontaneous activity was abolished by nifedipine (10 μm). NO released by 3-morpholino-sydnonimine (SIN-1, 10 μm) hyperpolarized the membrane and prevented the generation of spontaneous depolarizations. SIN-1 also abolished Ca2+ transients and associated contractions. These effects of SIN-1 were blocked by 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ, 10 μm), an inhibitor of guanylate cyclase. Noradrenaline (NA, 1 μm) increased [Ca2+]i to levels similar to those produced by high potassium-containing solution (high K+ solution, [K+]o = 40 mm), however, NA-induced contractions were three times greater in amplitude than those induced by high K+ solution. In NA precontracted preparations, SIN-1 inhibited 80 % of the contraction and decreased [Ca2+]i by 20 %. In contrast, nifedipine reduced [Ca2+]i by 80 %, while the level of contraction was decreased by only 20 %. SIN-1-induced reduction in [Ca2+]i but not the tension effect, was abolished by pretreatment with cyclopiazonic acid (CPA, 10 μm). In high K+ precontracted preparations, SIN-1 inhibited 80 % of the contraction and reduced [Ca2+]i by 20 %. Nifedipine, however, largely abolished increases in both [Ca2+]i and tension under these circumstances. These results suggest that decreasing the sensitivity of contractile proteins to Ca2+ is probably the key mechanism of NO-induced relaxation in CSM of the guinea-pig. PMID:11790820

  1. Effects of trimebutine maleate (TM-906) on electrical and mechanical activities of smooth muscles of the guinea-pig stomach.

    PubMed

    Furukawa, K; Kimoto, Y

    1984-07-01

    The effects of trimebutine maleate (TM-906) on electrical and mechanical activities of smooth muscles of the guinea-pig stomach were investigated using a microelectrode and isometric tension recording methods. TM-906 (2 X 10(-5) M) depolarized the membrane of smooth muscles in the antrum to about 10 mV. From the current-voltage relationship and changes in membrane potentials in various [K]0, the TM-906-induced depolarization is considered to be mainly due to a decrease in the K-conductance. TM-906 increased the amplitude of the first spike potential and regularized the rhythm of slow waves. These excitatory effects are presumably due to the K-channel-blocking action during the repolarizing phase of the spikes and to the depolarization. TM-906 reduced the amplitudes of mechanical activities and slow waves. These inhibitory effects are presumably due to the inhibition of Ca-release from storage sites and to the block of Ca-influx. The biphasic effects are possibly due to the local anesthetic properties. TM-906 modified neither the membrane potential nor the membrane conductance of circular muscles in the fundus. This may mean that the circular muscles in the fundus lack the K-channel sensitive to TM-906. PMID:6482091

  2. Dual excitatory and smooth muscle-relaxing effect of Sideritis montana extract on guinea-pig ileum.

    PubMed

    Tóth, Barbara; Bartho, Loránd; Vasas, Andrea; Sándor, Zsolt; Jedlinszki, Nikoletta; Pinke, Gyula; Hohmann, Judit

    2015-03-01

    The neuronal and smooth muscle effects of a methanol extract prepared from the air-dried flowering aerial parts of Sideritis montana L. (SME) was tested in vitro on Guinea-pig ileum. The chemical composition of the investigated extract was analysed by HPLC-MS, and chrysoeriol, chlorogenic acid and caffeic acid were detected as main constituents. The isolated organ assay showed that S. montana extract caused an immediate contraction and a more slowly developing inhibitory response in the ileum. The SME-induced contractions were strongly inhibited by the acetylcholine muscarinic receptor antagonist atropine (0.5 μM), but not by either the Na+ channel blocker tetrodotoxin (TTX; 0.5 μM) or the histamine H1 receptor antagonist chloropyramine (0.5 μM). Selective desensitization of capsaicin-sensitive neurons by the sensory neuron stimulant and blocker capsaicin did not influence the contractile effect of SME. As to the spasmolytic effect, SME inhibited the effects of electrical field stimulation, exogenous acetylcholine, and histamine. These smooth muscle-relaxing effects were reversible in 40 min by repeated renewals of the bathing solution. PMID:25924535

  3. Role of membrane potential in endothelium-dependent relaxation of guinea-pig coronary arterial smooth muscle.

    PubMed

    Parkington, H C; Tonta, M A; Coleman, H A; Tare, M

    1995-04-15

    was similar to that which was due to EDHF in intact tissues stimulated with acetylcholine. 7. It is concluded that the ability of NO or Iloprost to relax guinea-pig coronary artery does not depend upon hyperpolarization of the smooth muscle. In contrast, hyperpolarization is likely to play a major, if not the only, role in the relaxation in response to EDHF in this tissue. PMID:7541469

  4. Comparative Study of Protective Effects of Salbutamol and Beclomethasone against Insulin Induced Airway Hyper-reactivity on Isolated Tracheal Smooth Muscle of Guinea Pig

    PubMed Central

    Sharif, Mahjabeen; Tayyaba Khan, Bushra; Bakhtiar, Salman; Anwar, Mohammad Asim

    2015-01-01

    Inhalational insulin was withdrawn from the market due to its potential to produce airway hyper-reactivity and bronchoconstriction. So the present study was designed to explore the acute effects of insulin on airway reactivity of guinea pigs and protective effects of salbutamol and beclomethasone against insulin induced airway hyper-responsiveness on isolated tracheal smooth muscle of guinea pig. Effects of varying concentrations of insulin (10-7 to 10-3 M), insulin pretreated with fixed concentration of salbutamol (10-7 M) and beclomethasone (10-6 M) were studied on isolated tracheal tissue of guinea pig by constructing cumulative concentration response curves. Changes in tracheal smooth muscle contractions were recorded on four channel oscillograph. The mean ± SEM of maximum amplitudes of contraction with increasing concentrations of insulin, insulin pretreated with fixed concentration of salbutamol and beclomethasone were 35 ± 1.13 mm, 14.55 ± 0.62 mm and 22 ± 1.154 mm respectively. Although salbutamol and beclomethasone both had a profound inhibitory effect on insulin induced airway hyper-reactivity, yet salbutamol is more efficacious than beclomethasone. So we suggest that pretreatment of inhaled insulin with salbutamol may be preferred over beclomethasone in amelioration of its potential respiratory adverse effects such as bronchoconstriction. PMID:25901165

  5. Relationship between stimulated phosphatidic acid production and inositol lipid hydrolysis in intestinal longitudinal smooth muscle from guinea pig.

    PubMed Central

    Mallows, R S; Bolton, T B

    1987-01-01

    Accumulation of [32P]phosphatidic acid (PA) and total [3H]inositol phosphates (IPs) was measured in the longitudinal smooth-muscle layer from guinea-pig small intestine. Stimulation with carbachol, histamine and substance P produced increases in accumulation of both [3H]IPs and [32P]PA over the same concentration range. The increase in [32P]PA accumulation in response to carbachol (1 microM-0.1 mM) was inhibited in the presence of atropine (0.5 microM). Buffering the external free [Ca2+] to 10 nM did not prevent the carbachol-stimulated increase in [32P]PA accumulation. Carbachol and Ca2+ appear to act synergistically to increase accumulation of [32P]PA. In contrast, although incubation with noradrenaline also increased accumulation of [3H]IPs, no increase in accumulation of [32P]PA could be detected. These results suggest that an increase in formation of IPs is not necessarily accompanied by an increase in PA formation, and imply the existence of receptor-modulated pathways regulating PA concentrations other than by phospholipase-C-catalysed inositol phospholipid hydrolysis. PMID:2451504

  6. Effects of magnesium pyrophosphate on mechanical properties of skinned smooth muscle from the guinea pig taenia coli.

    PubMed Central

    Arheden, H; Arner, A

    1992-01-01

    Effects of the non-hydrolyzable nucleotide analogue magnesium pyrophosphate (MgPPi) on cross-bridge properties were investigated in skinned smooth muscle of the guinea pig Taenia coli. A "high" rigor state was obtained by removing MgATP at the plateau of an active contraction. Rigor force decayed slowly towards an apparent plateau of approximately 25-35% of maximal active force. MgPPi markedly increased the rate of force decay. The initial rate of the force decay depended on [MgPPi] and could be described by the Michaelis-Menten equation with a dissociation constant of 1.6 mM. The decay was irreversible amounting to approximately 50% of the rigor force. Stiffness decreased by 20%, suggesting that the major part of the cross-bridges were still attached. The results can be interpreted as "slippage" of PPi-cross-bridges to positions of lower strain. The initial rate of MgPPi-induced force decay decreased with decreasing ionic strength in the range 45-150 mM and was approximately 25% lower in thiophosphorylated fibers. MgADP inhibited the MgPPi-induced force decay with an apparent Ki of 2 microM. The apparent Km of MgATP for the maximal shortening velocity in thiophosphorylated fibers was 32 microM. This low Km of MgATP suggests that steps other than MgATP-induced detachment are responsible for the low shortening velocity in smooth muscle. No effects were observed of 4 mM MgPPi on the force-velocity relation, suggesting that cross-bridges with bound MgPPi do not constitute an internal load or that binding of MgPPi is weaker in negatively strained cross-bridges during shortening. PMID:1319761

  7. Free-calcium and force transients during depolarization and pharmacomechanical coupling in guinea-pig smooth muscle.

    PubMed Central

    Himpens, B; Somlyo, A P

    1988-01-01

    1. Fura2 was loaded by permeation and hydrolysis of the acetoxymethyl ester into smooth muscle cells of intact thin sheets of the longitudinal layer of the small intestine of the guinea-pig, to record Ca2+ transients during contraction. 2. Cytoplasmic Ca2+ ([Ca2+]i) was monitored by computing the ratio of the fluorescence signal excited at 340 and 380 nm wavelengths. The dye loading and the exposure to UV light required for the experiments had no significant effect on the contractile parameters observed. 3. Spontaneous, rhythmic increases in [Ca2+]i were often observed, preceding the onset of force. Removal of extracellular Ca2+ caused a very transient increase in [Ca2+]i accompanied by a phasic force transient; this was followed by a decline in [Ca2+]i and tension below control levels. Elevated Ca2+ from 1.2 to 15 mM also caused a fall in [Ca2+]i and a relaxation of basal tension. 4. Elevation of [K+]o increased [Ca2+]i. Graded concentrations of K+ caused graded changes in both fluorescence ratio and tension. 5. Carbachol evoked a transient increase in [Ca2+]i and contraction. Thereafter, in spite of the continued presence of the drug, both signals declined, presumably as the result of cholinergic desensitization. The initial phasic force response to carbachol was usually followed by an 'after-contraction', that was only occasionally accompanied by a similar (small) secondary rise in the fluorescence signal. 6. In depolarized smooth muscle, both in the presence and in the absence of extracellular Ca2+, carbachol induced a transient increase in [Ca2+]i, indicating that Ca2+ release from intracellular stores is a major mechanism of pharmacomechanical coupling. 7. In some preparations an applied stretch caused, after a few seconds, a rise in [Ca2+]i and force development. PMID:3137325

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

    SciTech Connect

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

    1985-06-01

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

  9. Leukotriene C4 induces bronchoconstriction and airway vascular hyperpermeability via the cysteinyl leukotriene receptor 2 in S-hexyl glutathione-treated guinea pigs.

    PubMed

    Yonetomi, Yasuo; Sekioka, Tomohiko; Kadode, Michiaki; Kitamine, Tetsuya; Kamiya, Akihiro; Matsumura, Naoya; Fujita, Manabu; Kawabata, Kazuhito

    2015-05-01

    Cysteinyl leukotrienes act through G-protein-coupled receptors termed cysteinyl leukotriene 1 (CysLT1) and cysteinyl leukotriene 2 (CysLT2) receptors. However, little is known about the pathophysiological role of CysLT2 receptors in asthma. To elucidate the possible involvement of CysLT2 receptors in bronchoconstriction and airway vascular hyperpermeability, we have established a novel guinea pig model of asthma. In vitro study confirmed that CHO-K1 cells, expressing guinea pig CysLT2 and CysLT1 receptors are selectively stimulated by LTC4 and LTD4, respectively. However, when LTC4 was intravenously injected to guinea pigs, the resulting bronchoconstriction was fully abrogated by montelukast, a CysLT1 receptor antagonist, indicating rapid metabolism of LTC4 to LTD4 in the lung. We found that treatment with S-hexyl glutathione (S-hexyl GSH), an inhibitor of gamma-glutamyl transpeptidase, significantly increased LTC4 content and LTC4/(LTD4 plus LTE4) ratio in the lung. Under these circumstances, LTC4-induced bronchoconstriction became resistant to montelukast, but sensitive to Compound A, a CysLT2 receptor antagonist, depending on the dose of S-hexyl GSH. Combination with montelukast and Compound A completely abrogated this spasmogenic response. Additionally, we confirmed that LTC4 elicits airway vascular hyperpermeability via CysLT2 receptors in the presence of high dose of S-hexyl GSH as evidenced by complete inhibition of LTC4-induced hyperpermeability by Compound A, but not montelukast. These results suggest that CysLT2 receptors mediate bronchoconstriction and airway vascular hyperpermeability in guinea pigs and that the animal model used in this study may be useful to elucidate the functional role of CysLT2 receptors in various diseases, including asthma. PMID:25704617

  10. Mechanism of carbachol-evoked contractions of guinea-pig ileal smooth muscle close to freezing point.

    PubMed Central

    Blackwood, A. M.; Bolton, T. B.

    1993-01-01

    1. The effect of lowering the temperature to near freezing-point upon the contractions and [3H]-inositol phosphate responses to carbachol were investigated in longitudinal smooth muscle from the guinea-pig ileum. 2. The peak amplitude of the contraction to a single application of 100 microM carbachol was the same at 37 degrees C and temperatures near freezing-point. However, the sensitivity to carbachol was reduced upon lowering the temperature and the time to peak contraction was increased from 5-10 s to 2-10 min. Even when the temperature was maintained near freezing-point, washing off carbachol produced a relaxation and eventual return of tension to basal levels. 3. Incubating the tissue in 140 mM K+, calcium-free solution or in calcium channel antagonists significantly reduced the carbachol-induced contraction to 10-30% of the control at 37 degrees C and also at 3 degrees C. Thus the majority of the activator calcium required for contraction entered the tissue via voltage-dependent calcium channels (VDCs) at both 37 degrees C and 3 degrees C. 4. The contractions produced by high potassium solutions were less at temperatures close to freezing-point than those at 37 degrees C suggesting that voltage-dependent calcium entry was inhibited as the temperature was lowered. 5. A small part of the contractile response to 100 microM carbachol was resistant to the removal of extracellular calcium at both 37 degrees C and 3 degrees C and this component was increased under depolarizing conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8401915

  11. Tumor Necrosis Factor Alpha Inhibits L-Type Ca2+ Channels in Sensitized Guinea Pig Airway Smooth Muscle through ERK 1/2 Pathway

    PubMed Central

    Reyes-García, Jorge; Flores-Soto, Edgar; Solís-Chagoyán, Héctor; Sommer, Bettina; Díaz-Hernández, Verónica; García-Hernández, Luz María

    2016-01-01

    Tumor necrosis factor alpha (TNF-α) is a potent proinflammatory cytokine that plays a significant role in the pathogenesis of asthma by inducing hyperresponsiveness and airway remodeling. TNF-α diminishes the L-type voltage dependent Ca2+ channel (L-VDCC) current in cardiac myocytes, an observation that seems paradoxical. In guinea pig sensitized tracheas KCl responses were lower than in control tissues. Serum from sensitized animals (Ser-S) induced the same phenomenon. In tracheal myocytes from nonsensitized (NS) and sensitized (S) guinea pigs, an L-VDCC current (ICa) was observed and diminished by Ser-S. The same decrease was detected in NS myocytes incubated with TNF-α, pointing out that this cytokine might be present in Ser-S. We observed that a small-molecule inhibitor of TNF-α (SMI-TNF) and a TNF-α receptor 1 (TNFR1) antagonist (WP9QY) reversed ICa decrease induced by Ser-S in NS myocytes, confirming the former hypothesis. U0126 (a blocker of ERK 1/2 kinase) also reverted the decrease in ICa. Neither cycloheximide (a protein synthesis inhibitor) nor actinomycin D (a transcription inhibitor) showed any effect on the TNF-α-induced ICa reduction. We found that CaV1.2 and CaV1.3 mRNA and proteins were expressed in tracheal myocytes and that sensitization did not modify them. In cardiac myocytes, ERK 1/2 phosphorylates two sites of the L-VDCC, augmenting or decreasing ICa; we postulate that, in guinea pig tracheal smooth muscle, TNF-α diminishes ICa probably by phosphorylating the L-VDCC site that reduces its activity through the ERK1/2 MAP kinase pathway. PMID:27445440

  12. Tumor Necrosis Factor Alpha Inhibits L-Type Ca(2+) Channels in Sensitized Guinea Pig Airway Smooth Muscle through ERK 1/2 Pathway.

    PubMed

    Reyes-García, Jorge; Flores-Soto, Edgar; Solís-Chagoyán, Héctor; Sommer, Bettina; Díaz-Hernández, Verónica; García-Hernández, Luz María; Montaño, Luis M

    2016-01-01

    Tumor necrosis factor alpha (TNF-α) is a potent proinflammatory cytokine that plays a significant role in the pathogenesis of asthma by inducing hyperresponsiveness and airway remodeling. TNF-α diminishes the L-type voltage dependent Ca(2+) channel (L-VDCC) current in cardiac myocytes, an observation that seems paradoxical. In guinea pig sensitized tracheas KCl responses were lower than in control tissues. Serum from sensitized animals (Ser-S) induced the same phenomenon. In tracheal myocytes from nonsensitized (NS) and sensitized (S) guinea pigs, an L-VDCC current (ICa) was observed and diminished by Ser-S. The same decrease was detected in NS myocytes incubated with TNF-α, pointing out that this cytokine might be present in Ser-S. We observed that a small-molecule inhibitor of TNF-α (SMI-TNF) and a TNF-α receptor 1 (TNFR1) antagonist (WP9QY) reversed ICa decrease induced by Ser-S in NS myocytes, confirming the former hypothesis. U0126 (a blocker of ERK 1/2 kinase) also reverted the decrease in ICa. Neither cycloheximide (a protein synthesis inhibitor) nor actinomycin D (a transcription inhibitor) showed any effect on the TNF-α-induced ICa reduction. We found that CaV1.2 and CaV1.3 mRNA and proteins were expressed in tracheal myocytes and that sensitization did not modify them. In cardiac myocytes, ERK 1/2 phosphorylates two sites of the L-VDCC, augmenting or decreasing ICa; we postulate that, in guinea pig tracheal smooth muscle, TNF-α diminishes ICa probably by phosphorylating the L-VDCC site that reduces its activity through the ERK1/2 MAP kinase pathway. PMID:27445440

  13. The membrane properties of the smooth muscle of the guinea-pig portal vein in isotonic and hypertonic solutions.

    PubMed

    Kuriyama, H; Oshima, K; Sakamoto, Y

    1971-08-01

    The membrane properties of the longitudinal smooth muscle of the guinea-pig portal vein were investigated under various experimental conditions.1. In isotonic Krebs solution, the membrane potential (-48.7 mV), the maximum rates of rise and fall of the spike (4.6 and 2.3 V/sec respectively), the space constant (0.61 mm), the conduction velocity of excitation (0.97 cm/sec) and the time constant of the foot of the propagated spike (18.4 msec) were measured.2. The various parameters of the muscle membrane in the isotonic solution were compared with those in the hypertonic solution prepared by the addition of solid sucrose (twice the normal tonicity).3. When the muscles were perfused with hypertonic solution, marked depolarization of the membrane and increased membrane resistance occurred. These were probably due to reduction of the K permeability, increased internal resistance of the muscle and shrinkage of the muscle fibre.4. The membrane potential in isotonic and hypertonic solutions was analysed into two components, i.e. the metabolic (electrogenic Na-pump) and the ionic (electrical diffusion potential) component in the various environmental conditions.(a) In isotonic and hypertonic solutions, the membrane was depolarized by lowering the temperature or by removal of K ion from the solutions. When the tissues were rewarmed or on readdition of K ion, the membrane was markedly hyperpolarized. These hyperpolarizations of the membrane were suppressed by treatment with ouabain (10(-5) g/ml.), by warming to only 20 degrees C and by K-free solution.(b) The relationships between the membrane potential and the [K](o) in isotonic Krebs, in the hypertonic (sucrose) Krebs, in the Na-free (Tris) Krebs and in the Cl-deficient (C(6)H(5)SO(3)) Krebs were observed. The maximum slopes of the membrane depolarization against tenfold changes of [K](o) were much lower than that expected if it behaved like a K electrode.(c) In Na-free (Tris) solution, the membrane was not depolarized in

  14. Mechanism of carbachol-evoked contractions of guinea-pig ileal smooth muscle close to freezing point.

    PubMed

    Blackwood, A M; Bolton, T B

    1993-08-01

    1. The effect of lowering the temperature to near freezing-point upon the contractions and [3H]-inositol phosphate responses to carbachol were investigated in longitudinal smooth muscle from the guinea-pig ileum. 2. The peak amplitude of the contraction to a single application of 100 microM carbachol was the same at 37 degrees C and temperatures near freezing-point. However, the sensitivity to carbachol was reduced upon lowering the temperature and the time to peak contraction was increased from 5-10 s to 2-10 min. Even when the temperature was maintained near freezing-point, washing off carbachol produced a relaxation and eventual return of tension to basal levels. 3. Incubating the tissue in 140 mM K+, calcium-free solution or in calcium channel antagonists significantly reduced the carbachol-induced contraction to 10-30% of the control at 37 degrees C and also at 3 degrees C. Thus the majority of the activator calcium required for contraction entered the tissue via voltage-dependent calcium channels (VDCs) at both 37 degrees C and 3 degrees C. 4. The contractions produced by high potassium solutions were less at temperatures close to freezing-point than those at 37 degrees C suggesting that voltage-dependent calcium entry was inhibited as the temperature was lowered. 5. A small part of the contractile response to 100 microM carbachol was resistant to the removal of extracellular calcium at both 37 degrees C and 3 degrees C and this component was increased under depolarizing conditions. This suggests that the release of stored calcium contributes to a minor degree to contraction at both 37 degrees C and 3 degrees C.6. Although 100 microM carbachol produced a statistically significant rise in several [3H]-inositol phosphate isomers at both 37 degrees C and 3 degrees C, the production of [3H]-inositol phosphates was less at 3 degrees C than at 37 degrees C and the increase in their production caused by carbachol was much slower.7. These results suggest that the

  15. Relation between muscarinic receptor cationic current and internal calcium in guinea-pig jejunal smooth muscle cells.

    PubMed Central

    Pacaud, P; Bolton, T B

    1991-01-01

    1. The action of carbachol, which activates muscarinic receptors, was studied in single patch-clamped cells where free internal calcium concentration in the cell (Cai2+) was estimated using the emission from the dye Indo-1. Cells were dialysed with potassium-free caesium solution to block any Ca(2+)-activated K(+)-current. 2. Carbachol applied to the cell evoked an initial peak in Cai2+ followed by a smaller sustained rise (plateau) upon which several oscillations in Cai2+ were often superimposed; the changes in inward, cationic current (icarb) followed changes in Cai2+ closely. Calcium entry blocker did not affect these responses. 3. The initial peak in Cai2+ produced by carbachol was due to calcium store release: it was essentially unchanged at +50 mV, and abolished by prior application of caffeine (10 mM) to the cell or by inclusion of heparin (which blocks D-myoinositol 1,4,5-trisphosphate receptors) in the pipette. In contrast, the rise in Cai2+ produced by ATP in rabbit ear artery smooth muscle cells was unaffected by caffeine or heparin as it was due to calcium entry into the cell. 4. The later sustained rise (plateau) in Cai2+ produced by carbachol was due to the entry of calcium into the cell down its electrochemical gradient as it was affected by changing the cell membrane potential or the calcium concentration of the bathing solution. As the sustained rise in Cai2+ produced by caffeine had similar properties, it was suggested that depletion of calcium stores can evoke an increased calcium entry into the cell through some pathway. 5. The cationic current evoked by carbachol was strongly dependent on Cai2+. It was small if any rise in Cai2+ due to calcium store release was prevented by the inclusion of heparin in the pipette solution and increased greatly if calcium entry was provoked through voltage-dependent channels by applying a depolarizing pulse or if calcium was released from stores by caffeine. 6. In the longitudinal muscle of guinea-pig small

  16. Force response to rapid length change during contraction and rigor in skinned smooth muscle of guinea-pig taenia coli.

    PubMed Central

    Arheden, H; Hellstrand, P

    1991-01-01

    1. Mechanical transients in fibre bundles of skinned smooth muscle of guinea-pig taenia coli at 21-22 degrees C were investigated by recording tension responses to length changes of up to 9%, complete within 0.3 ms. 2. The length-force relationship, recorded continuously during rapid stretch of a Ca(2+)-activated contracted muscle, was linear up to at least 2.5 times the isometric force, corresponding to a stretch of about 1%. The slope of the relationship (stiffness) increased with the velocity of stretch. 3. During rapid release (about 120 muscle lengths s-1) the length-force relationship was linear down to about 50% of the initial isometric force, reached at about 80 microseconds after the beginning of the release. At lower force the length-force relationship was concave upwards. The linear portion extrapolated to zero force at about -0.008 muscle lengths. In large releases the length-force plot approached the force baseline under an acute angle, and negative force was transiently exerted. 4. When the muscle was stretched back to the initial length after a shortening step, force transiently rose above the isometric force, but decayed back within a few milliseconds. Stiffness at the time of restretch was compared with that in the initial shortening step by plotting force vs. length, and was found to be decreased to 63% within 0.3 ms of a step to zero force. Stiffness decreased further with time at zero force, and after 256 ms was about 29% of the isometric value. 5. In rigor, caused by the introduction of ATP-free solution during the plateau of isometric contraction, fibre tension decreased to about 30% of the active tension, whereas stiffness relative to force increased; 82% of the initial stiffness in rigor was detected in a restretch immediately after a shortening step, decreasing to 59% at 256 ms. When the fibre was activated at suboptimal [Ca2+] to cause the same force as in rigor, stiffness was lower than in rigor and decreased more after a release. 6

  17. Activity of the oxidation products of oleum terebinthinae "Landes" on guinea pig airway smooth muscle in vivo and in vitro.

    PubMed

    Bermudez, J; Burgess, M F; Cassidy, F; Clarke, G D

    1987-11-01

    The oxidation products of Oleum Terebinthinae "Landes" (Ozothin; in the following briefly called Ox. O. T. L.) have been described in many studies as being of benefit in the treatment of disturbed tracheobronchial function in obstructive airways diseases. Previous literature has dealt mainly with the influence of Ox. O. T. L. on the visco-elastic properties of mucus. However, the purpose of the present work was to study the bronchospasmolytic component. Using a standard methodology for the measurement of bronchospasmolytic effects, it could be demonstrated that Ox.O.T.L., given orally or as an aerosol, protected conscious guinea pigs against histamine-induced bronchoconstriction. The potency was lower than that of isoprenaline but was significant and reproducible. These results in vivo are paralleled by effects observed on guinea pig lung strips and tracheal spiral preparations. Ox.O.T.L. relaxed, in a dose-dependent fashion, guinea pig lung strip preparations contracted with histamine. Potency and efficacy was, however, less than that of isoprenaline. Similarly, in guinea pig tracheal spiral preparations, Ox.O.T.L. was less potent than isoprenaline in counteracting carbachol-elevated tone. However, efficacy equalled that of isoprenaline. Ox.O.T.L. was approximately 3 times more potent in the isolated tracheal spiral preparation than in lung strips. The activity of non-oxidised turpentine oil and terpin hydrate against histamine-induced bronchoconstriction in conscious animals and in the isolated organ preparations was substantially lower than that of the oxidation products of O.T.L. PMID:3440034

  18. The effect of hyperpolarization-activated cyclic nucleotide-gated ion channel inhibitors on the vagal control of guinea pig airway smooth muscle tone

    PubMed Central

    McGovern, Alice E; Robusto, Jed; Rakoczy, Joanna; Simmons, David G; Phipps, Simon; Mazzone, Stuart B

    2014-01-01

    BACKGROUND AND PURPOSE Subtypes of the hyperpolarization-activated cyclic nucleotide-gated (HCN) family of cation channels are widely expressed on nerves and smooth muscle cells in many organ systems, where they serve to regulate membrane excitability. Here we have assessed whether HCN channel inhibitors alter the function of airway smooth muscle or the neurons that regulate airway smooth muscle tone. EXPERIMENTAL APPROACH The effects of the HCN channel inhibitors ZD7288, zatebradine and Cs+ were assessed on agonist and nerve stimulation-evoked changes in guinea pig airway smooth muscle tone using tracheal strips in vitro, an innervated tracheal tube preparation ex vivo or in anaesthetized mechanically ventilated guinea pigs in vivo. HCN channel expression in airway nerves was assessed using immunohistochemistry, PCR and in situ hybridization. KEY RESULTS HCN channel inhibition did not alter airway smooth muscle reactivity in vitro to exogenously administered smooth muscle spasmogens, but significantly potentiated smooth muscle contraction evoked by the sensory nerve stimulant capsaicin and electrical field stimulation of parasympathetic cholinergic postganglionic neurons. Sensory nerve hyperresponsiveness was also evident in in vivo following HCN channel blockade. Cs+, but not ZD7288, potentiated preganglionic nerve-dependent airway contractions and over time induced autorhythmic preganglionic nerve activity, which was not mimicked by inhibitors of potassium channels. HCN channel expression was most evident in vagal sensory ganglia and airway nerve fibres. CONCLUSIONS AND IMPLICATIONS HCN channel inhibitors had a previously unrecognized effect on the neural regulation of airway smooth muscle tone, which may have implications for some patients receiving HCN channel inhibitors for therapeutic purposes. PMID:24762027

  19. The action of acetylcholine and other drugs on the efflux of potassium and rubidium from smooth muscle of the guinea-pig intestine

    PubMed Central

    Burgen, A. S. V.; Spero, L.

    1968-01-01

    1. A method is described for measuring continuously the efflux of potassium or rubidium from smooth muscle of the guinea-pig. 2. Muscarinic drugs cause at maximum a 100-fold increase in the efflux rate, due to a direct increase in permeability and only to a minor extent secondary to depolarization. With acetylcholine the dose response curve for producing efflux is displaced to 1,000 times higher concentrations than that for contraction. 3. The shift varies with different agonists. The efflux and contractile responses to agonists are antagonized to an equivalent extent by atropine and several other reversible antagonists but benzhexol has a relatively greater effect on efflux. An estimate of spare receptors was obtained with benzilylcholine mustard and was similar for both responses. Dibenamine and local anaesthetics led to a parallel shift of the contraction dose response curve but a depression without shift in the efflux response. 4. The most satisfactory explanation of these results is that there are two types of the muscarinic receptor in the smooth muscle of the guinea-pig intestine. PMID:19108279

  20. Effect of quercetin on colon contractility and L-type Ca(2+) channels in colon smooth muscle of guinea-pig.

    PubMed

    Huang, Wei-Feng; Ouyang, Shou; Li, Shi-Ying; Lin, Yan-Fei; Ouyang, Hui; Zhang, Hui; Lu, Chun-Jing

    2009-12-25

    The aim of the present study was to investigate the effects of quercetin on colon contractility and voltage-dependent Ca(2+) channels in the single smooth muscle cell isolated from the proximal colon of guinea-pig and to clarify whether its effect on L-type Ca(2+) current (I(Ca,L)) would be related to its myorelaxing properties. Colon smooth muscle strips were used to take contractile tension recordings. Smooth muscle cells were freshly isolated from the proximal colon of guinea-pig by means of papain treatment. I(Ba,L) (barium instead of calcium as current carrier) was measured by using whole-cell patch-clamp techniques. The results showed that quercetin relaxed colon muscle strips in a concentration-dependent manner and antagonized the contractile effect of acetylcholine and neostigmine. Preincubation with indomethcin [cyclooxygenase (COX) inhibitor] and methylene blue [guanylate cyclase (GC) inhibitor] significantly attenuated the relaxing effect of quercetin, respectively. Quercetin increased I(Ba,L) in a concentration- [EC(50)= (7.59+/-0.38) mumol/L] and voltage-dependent pattern, and shifted the maximum of the current-voltage curve by 10 mV in the depolarizing direction without modifying the threshold potential for Ca(2+) influx. Quercetin shifted the steady-state inactivation curve toward more positive potentials by approximately 3.75 mV without affecting the slope of activation and inactivation curve. H-89 (PKA inhibitor) abolished quercetin-induced I(Ba,L) increase, while cAMP enhanced the quercetin-induced I(Ba,L) increase. The patch-clamp results proved that quercetin increased I(Ba,L) via PKA pathway. It is therefore suggested that the relaxing effect of quercetin attributes to the interaction of GC and COX stimulation, as well as the antagonism effect on acetylcholine, which hierarchically prevails over the increase in the Ca(2+) influx to be expected from I(Ca,L) stimulation. PMID:20029691

  1. Effect of removing the endothelium on the vascular responses induced by leukotrienes C4 and D4 in guinea-pig isolated heart.

    PubMed

    McLeod, J D; Piper, P J

    1992-02-25

    The coronary vascular endothelium of the guinea-pig isolated perfused heart was removed by treatment with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS), a zwitterionic detergent. After CHAPS treatment of the heart the vasoconstrictor responses of leukotriene (LT) C4, LTD4 and angiotensin II (AII) were significantly attenuated whereas the vascular actions of U46619, a thromboxane (Tx) A2 mimetic, and endothelin-1 (ET-1) were unaltered. The endothelium-dependent vasoconstrictor response of LTC4 and LTD4 could not be attributed to the release of TxA2, platelet-activating factor or AII since indomethacin, WEB 2086 and captopril had no effect on LT actions. However, in the presence of cromakalim, a potassium channel activator, the vasoconstrictor effects induced by LTC4, LTD4 and AII were significantly attenuated to a greater extent than the responses of U46619 and ET-1. The results suggest that in the coronary vasculature of the guinea-pig isolated heart the vasoconstrictor responses of LTC4, LTD4 and AII are endothelium-dependent and may involve a cromakalim-sensitive mechanism. PMID:1555641

  2. Suppression of the increasing level of acetylcholine-stimulated intracellular Ca2+ in guinea pig airway smooth muscle cells by mabuterol

    PubMed Central

    SONG, XIRUI; ZHAO, CHAO; DAI, CAILING; REN, YANXIN; AN, NAN; WEN, HUIMIN; PAN, LI; CHENG, MAOSHENG; ZHANG, YUYANG

    2015-01-01

    The present study aimed to establish an effective method for the in vitro culture of guinea pig airway smooth muscle (ASM) cells, and also investigate the suppressive effect of mabuterol hydrochloride (Mab) on the increased level of intracellular Ca2+ in ASM cells induced with acetylcholine (Ach). Two different methods, i.e. with or without collagenase to pretreat tracheal tissues, were applied to the manufacture of ASM cells. Cell viability was determined with the 3-(4,5-dimethylthinazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Immunocytochemistry and immunofluorescence were used for the identification of ASM cells. Different concentration levels (10−3, 10−4, 10−5, 10−6 and 10−7 mmol/l) of Mab were administered 5 min before Ach (10−4 M) treatment, respectively. The Ca2+ fluorescent probe, Fura-2/AM or Fluo-3/AM were applied to the inspection of Ca2+ fluorescent intensity with Varioskan Flash, immunocytometry systems and an inverted system microscope, respectively. The results showed that the fresh method, in which isolated tracheal tissues were previously treated with collagenase for 20 min, was more advantageous for the preparation of guinea pig ASM cells compared to when the enzyme was not used. The time for the ASM cells to initially migrate out of the ‘tissue blocks’ and the culture having to be generated due to the thick cell density was significantly less. On identification with immunocytochemistry or immunofluorescent staining, >95% of the cells were ASM cells. Mab (10−3−10−7 mmol/l) significantly suppressed the elevation of intracellular Ca2+ induced by Ach in a concentration-dependent manner. The inhibitory rates of intracellular Ca2+ by different concentrations of Mab, from low to high, were 14.93, 24.73, 40.06, 48.54 and 57.13%, respectively, when Varioskan Flash was used for determination. In conclusion, this novel method has a shorter harvesting period for ASM cells. Mab can suppress the increasing level of intracellular Ca2

  3. Spontaneous reproductive tract leiomyomas in aged guinea-pigs.

    PubMed

    Field, K J; Griffith, J W; Lang, C M

    1989-10-01

    Seven of 83 female guinea-pigs were found to have reproductive tract leiomyomas at necropsy. Sixty-three of these guinea-pigs also had cystic rete ovarii. Eleven separate leiomyomas were identified, the most common site of formation being the uterine body or horn. The tumours contained histological evidence of smooth muscle, abundant fibrous connective tissue and occasional foci of fibrocartilage and bone. Mitotic figures were identified in only one tumour. The mean age of guinea-pigs with leiomyomas was 47.6 months, and the mean age of the study population was 33.1 months. Two other reproductive tract tumours identified in the 83 guinea-pigs were an ovarian teratoma and a cavernous haemangioma. These data indicate that leiomyomas are the most common reproductive tract tumour in this colony of aged female guinea-pigs and that they are frequently seen in conjunction with cystic rete ovarii. PMID:2584448

  4. 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

  5. Molecular Expression and Pharmacological Evidence for a Functional Role of Kv7 Channel Subtypes in Guinea Pig Urinary Bladder Smooth Muscle

    PubMed Central

    Afeli, Serge A. Y.; Malysz, John; Petkov, Georgi V.

    2013-01-01

    Voltage-gated Kv7 (KCNQ) channels are emerging as essential regulators of smooth muscle excitability and contractility. However, their physiological role in detrusor smooth muscle (DSM) remains to be elucidated. Here, we explored the molecular expression and function of Kv7 channel subtypes in guinea pig DSM by RT-PCR, qRT-PCR, immunohistochemistry, electrophysiology, and isometric tension recordings. In whole DSM tissue, mRNAs for all Kv7 channel subtypes were detected in a rank order: Kv7.1~Kv7.2Kv7.3~Kv7.5Kv7.4. In contrast, freshly-isolated DSM cells showed mRNA expression of: Kv7.1~Kv7.2Kv7.5Kv7.3~Kv7.4. Immunohistochemical confocal microscopy analyses of DSM, conducted by using co-labeling of Kv7 channel subtype-specific antibodies and α-smooth muscle actin, detected protein expression for all Kv7 channel subtypes, except for the Kv7.4, in DSM cells. L-364373 (R-L3), a Kv7.1 channel activator, and retigabine, a Kv7.2-7.5 channel activator, inhibited spontaneous phasic contractions and the 10-Hz electrical field stimulation (EFS)-induced contractions of DSM isolated strips. Linopiridine and XE991, two pan-Kv7 (effective at Kv7.1-Kv7.5 subtypes) channel inhibitors, had opposite effects increasing DSM spontaneous phasic and 10 Hz EFS-induced contractions. EFS-induced DSM contractions generated by a wide range of stimulation frequencies were decreased by L-364373 (10 µM) or retigabine (10 µM), and increased by XE991 (10 µM). Retigabine (10 µM) induced hyperpolarization and inhibited spontaneous action potentials in freshly-isolated DSM cells. In summary, Kv7 channel subtypes are expressed at mRNA and protein levels in guinea pig DSM cells. Their pharmacological modulation can control DSM contractility and excitability; therefore, Kv7 channel subtypes provide potential novel therapeutic targets for urinary bladder dysfunction. PMID:24073284

  6. Mechanisms of relaxant action of a crude hexane extract of Gnaphalium liebmannii in guinea pig tracheal smooth muscle.

    PubMed

    Sánchez-Mendoza, María Elena; Torres, Gabriela; Arrieta, Jesús; Aguilar, Abigail; Castillo-Henkel, Carlos; Navarrete, Andrés

    2007-04-20

    We investigated the mechanisms of action of Gnaphalium liebmannii which is used as a folk medicine in México for treating various respiratory diseases such as gripe, fever, asthma, cough, cold, bronchitis, expectorating, and bronchial affections. The tension changes of guinea pig tracheal segments were isometrically recorder on a polygraph. Hexane extract of Gnaphalium liebmannii was the most active relaxant extract (IC(30)=54.23+/-19.79 microg/mL with 99.5+/-3.2 % of relaxation), followed by dichloromethane extract (IC(30)=120.22+/-5.27 microg/mL) and methanol extract (IC(30)=190.25+/-30.02 microg/mL). Hexane extract produced a parallel rightward shift of the concentration-response curve of carbachol in a competitive manner (pA(2)=-2.4), but did not modify the concentration-response curves for histamine. The relaxant effect of hexane extract of Gnaphalium liebmannii was unaffected by the presence of propranolol (3x10(-6)M) or glibenclamide (10 microM). However hexane extract produced a leftward shifts of the concentration-response curve of forskolin (10(-8) to 10(-3)M), nitroprusside (10(-10) to 10(-6)M), isoproterenol (3x10(-10) to 3x10(-5)M) and aminophylline (10(-11) to 10(-2)M). The above results suggest that Gnaphalium liebmannii induce relaxation of the tracheal muscle, probably via phosphodiesterase inhibition. The bronchodilator effect of Gnaphalium liebmannii might explain in part their traditional use as anti-asthmatic remedy. PMID:17141995

  7. Protein kinase C requirement of Ca2+ channel stimulation by intracellular ATP in guinea-pig basilar artery smooth muscle cells.

    PubMed Central

    McHugh, D; Beech, D J

    1997-01-01

    1. Smooth muscle cells were isolated from guinea-pig basilar artery and conventional whole-cell recordings of Ca2+ channel activity were made at room temperature within 7 h of the isolation procedure. The purpose of the study was to investigate the mechanism of the stimulatory action of intracellular ATP on Ca2+ channels. 2. High (millimolar) concentrations of ATP were needed to produce stimulation of Ca2+ channels, and neither ADP nor AMP mimicked the action of ATP. 3.The ATP effect was not mimicked by stable ATP derivatives (AMP-PNP or AMP-PCP) and was abolished by incubation of cells in non-specific protein kinase inhibitors (staurosporine or H-7) or specific protein kinase C inhibitors (GF109203x, calphostin C or chelerythrine) but not by tyrosine kinase inhibitors (tyrphostin B42 and genistein). 4. The data suggest that ATP-induced stimulation of L-type Ca2+ channels requires functional activity of a protein kinase C isozyme. PMID:9147319

  8. Exercise enclosures for guinea pigs.

    PubMed

    Brown, Cyndi

    2009-11-01

    Exercise and exploration are important to the health and happiness of guinea pigs. Laboratory housing does not always provide the space necessary for such opportunities. This article presents an inexpensive, versatile option for an enclosed exercise area for the laboratory guinea pig. PMID:19847177

  9. The effect of S-(+)-boldine on the alpha 1-adrenoceptor of the guinea-pig aorta.

    PubMed Central

    Chuliá, S.; Moreau, J.; Naline, E.; Noguera, M. A.; Ivorra, M. D.; D'Ocón, M. P.; Advenier, C.

    1996-01-01

    .1-100 microM). 7. These results provide evidence that S-(+)-boldine, an aporphine alkaloid, has interesting properties as an alpha 1-adrenoceptor blocker in vascular smooth muscle, and acts as a competitive antagonist of the alpha 1-adrenoceptor present in the guinea pig aorta. PMID:8968536

  10. Low birth weight followed by postnatal over-nutrition in the guinea pig exposes a predominant player in the development of vascular dysfunction

    PubMed Central

    Thompson, Jennifer A; Sarr, Ousseynou; Piorkowska, Karolina; Gros, Robert; Regnault, Timothy R H

    2014-01-01

    The association between intrauterine growth restriction (IUGR) and hypertension is well established, yet the interaction between IUGR and other pathogenic contributors remains ill-defined. This study examined the independent and interactive effects of fetal growth reduction resulting in low birth weight (LBW), and postnatal Western diet (WD) on vascular function. Growth reduction was induced in pregnant guinea pigs by uterine artery ablation. LBW and normal birth weight (NBW) offspring were randomly assigned to a control diet (CD) or a WD. In young adulthood, length–tension curves were generated in aortic rings and responses to methacholine (MCh) were evaluated in the carotid and aorta using wire myography. Relative to NBW/CD, aortae of NBW/WD offspring were stiffer, as determined by a leftward shift in the length–tension curve, yet the shift in the LBW/CD curve was considerably greater. Aortic stiffening was most severe in LBW/WD (slope: NBW/CD, 1.97 ± 0.04; NBW/WD, 2.16 ± 0.04; LBW/CD, 2.28 ± 0.05; LBW/WD, 2.34 ± 0.07). Maximal responses (Emax) to MCh were significantly blunted in the aorta of LBW/CD vs. NBW/CD (P < 0.05) and in LBW/WD vs. NBW/WD offspring (P < 0.05); but WD alone had no influence on MCh responses. Emax values for carotid responses to MCh were reduced in LBW/CD vs. NBW/CD (P < 0.05). Thus, aortic stiffening was influenced more by LBW than by a postnatal WD and the most severe stiffening was observed in LBW/WD offspring. In contrast, blunted endothelial responses in LBW/CD offspring were not exacerbated by WD. IUGR may have a greater independent impact on vascular function than a postnatal WD. PMID:25362153

  11. Elodontoma in Two Guinea Pigs.

    PubMed

    Capello, Vittorio; Lennox, Angela; Ghisleni, Gabriele

    2015-01-01

    Elodontoma was diagnosed in two pet guinea pigs, one involving a maxillary premolar tooth and the other affecting a mandibular incisor tooth. Diagnostic imaging, including radiographs, computed tomography, and oral endoscopy was performed in order to quantify dental disease. Diagnostic imaging was also used to guide treatment of acquired dental disease, which included intraoral restoration of normal occlusal plane and tooth extraction using an extraoral approach. These are the first histologically confirmed cases of elodontoma in guinea pigs. PMID:26415388

  12. Role of mitochondria in spontaneous rhythmic activity and intracellular calcium waves in the guinea pig gallbladder smooth muscle.

    PubMed

    Balemba, Onesmo B; Bartoo, Aaron C; Nelson, Mark T; Mawe, Gary M

    2008-02-01

    Mitochondrial Ca(2+) handling has been implicated in spontaneous rhythmic activity in smooth muscle and interstitial cells of Cajal. In this investigation we evaluated the effect of mitochondrial inhibitors on spontaneous action potentials (APs), Ca(2+) flashes, and Ca(2+) waves in gallbladder smooth muscle (GBSM). Disruption of the mitochondrial membrane potential with carbonyl cyanide 3-chlorophenylhydrazone, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone, rotenone, and antimycin A significantly reduced or eliminated APs, Ca(2+) flashes, and Ca(2+) waves in GBSM. Blockade of ATP production with oligomycin did not alter APs or Ca(2+) flashes but significantly reduced Ca(2+) wave frequency. Inhibition of mitochondrial Ca(2+) uptake and Ca(2+) release with Ru360 and CGP-37157, respectively, reduced the frequency of Ca(2+) flashes and Ca(2+) waves in GBSM. Similar to oligomycin, cyclosporin A did not alter AP and Ca(2+) flash frequency but significantly reduced Ca(2+) wave activity. These data suggest that mitochondrial Ca(2+) handling is necessary for the generation of spontaneous electrical activity and may therefore play an important role in gallbladder tone and motility. PMID:18048480

  13. 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.

  14. Studies on dioctyl sodium sulfosuccinate toxicity: clinical, gross and microscopic pathology in the horse and guinea pig.

    PubMed

    Moffatt, R E; Kramer, L L; Lerner, D; Jones, R

    1975-10-01

    Concentrations of dioctyl sodium sulfosuccinate (DSS) ranging from three to five times the recommended dosage produced severe diarrhea, rapid dehydration and death in seven horses and 66 guinea pigs when administered experimentally per os. Clinicopathological findings indicated hemoconcentration in both horses and guinea pigs. There was a leucocytosis in the guinea pigs given the highest dosages. In all cases the principal finding at necropsy was extreme fluid distention of the intestinal tract. There was histopathological evidence of epithelial denudation and vascular stasis. The LD50 in the guinea pig was approximately 0.65 g DSS/kg body weight. PMID:1175077

  15. Nitric oxide pathway-mediated relaxant effect of aqueous sesame leaves extract (Sesamum radiatum Schum. & Thonn.) in the guinea-pig isolated aorta smooth muscle

    PubMed Central

    Konan, André B; Datté, Jacques Y; Yapo, Paul A

    2008-01-01

    Background Sesamum radiatum Schum. & Thonn. (Pedaliaceae) is an annual herbaceous plant, which belongs to the family Pedaliaceae and genus Sesamum. Sesame is used in traditional medicine in Africa and Asia for many diseases treatment. Sesame plant especially the leaves, seed and oil are consumed locally as a staple food by subsistence farmers. The study analyses the relaxation induced by the aqueous extract of leaves from sesame (ESera), compared with those of acetylcholine (ACh) in the guinea-pig aortic preparations (GPAPs), in order to confirm the use in traditional medicine for cardiovascular diseases. Methods The longitudinal strips of aorta of animals were rapidly removed from animals. The aorta was immediately placed in a Mac Ewen solution. Experiments were performed in preparations with intact endothelium as well as in aortae where the endothelium had been removed. The preparations were suspended between two L-shaped stainless steel hooks in a 10 ml organ bath with Mac Ewen solution. The isometric contractile force of the aorta strips of guinea-pig were recorded by using a strain gauge. All both drugs caused concentration-dependent relaxations responses. Results The aqueous extract of leaves from sesame ESera (1 × 10-7 – 0.1 μg/ml) caused a graded relaxation in GPAPs with intact endothelium, with a EC50-value of 1 × 10-4 μg/ml. The same effect was observed with ACh (7 × 10-2 nM – 7 × 10-1 μM), which caused relaxation in a concentration-dependent manner. The relaxation in response to ESera and, like that to ACh in GPAPs without endothelium, was fully abolished. Destruction of the endothelium or incubation with the nitric oxyde synthase inhibitor (L-NNA) significantly enhanced the inhibition of the relaxation response to ESera. Moreover, all concentrations induced vasoconstrictions. However, L-NNA produced a significant displacement to the right (about 65-fold) of the relaxation response to ESera. Similar results were obtained with ACh. Both

  16. Tissue distribution of the guinea-pig decay-accelerating factor.

    PubMed Central

    Nishikawa, K; Matsuo, S; Tamai, H; Okada, N; Okada, H

    1998-01-01

    MCA44 is a monoclonal antibody (mAb) to guinea-pig decay-accelerating factor (DAF) and, using this mAb, tissue distribution of guinea-pig DAF was studied by immunofluorescence. Guinea-pig DAF was found to be expressed not only on the vascular endothelium but also on different types of cells, such as the tubular epithelium of the kidney, epidermal cells of the skin and synovial lining cells. As there was no significant reduction in staining intensity with MCA44 following treatment with phosphatidylinositol-specific phospholipase C, many guinea-pig DAF molecules expressed in these tissues may be of the transmembrane form. Images Figure 1 Figure 2 Figure 3 PMID:9824490

  17. Effect of hydrogen peroxide on guinea-pig tracheal smooth muscle in vitro: role of cyclo-oxygenase and airway epithelium.

    PubMed Central

    Rhoden, K. J.; Barnes, P. J.

    1989-01-01

    1. Hydrogen peroxide (H2O2) (0.1 microM-3 mM) induced variable contractions of guinea-pig isolated trachea which were attenuated by catalase (100 u ml-1) and mannitol (15 mM) suggesting that contractions were induced by H2O2 and/or the hydroxyl anion. 2. Epithelial removal potentiated contractile responses of tracheal preparations to H2O2 with a leftward shift of the concentration-response curve and an increase in the maximal response. 3. Indomethacin (3 microM) inhibited contractions to H2O2 of intact preparations and preparations without epithelium suggesting that contractions may be mediated by cyclo-oxygenase products. Intact preparations (but not preparations without epithelium) contracted in response to high concentrations (greater than 0.1 mM) of H2O2 in the presence of indomethacin suggesting that other excitatory factor(s) released by the epithelium may induce contraction. 4. Preincubation of intact tracheal preparations with H2O2 (1 mM) for 1 h had no effect on responses to histamine or isoprenaline. 5. These results suggest that hydrogen peroxide generated during the inflammatory process may play a role in bronchoconstriction. PMID:2508982

  18. 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)

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

    PubMed Central

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

    1994-01-01

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

  20. 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.

  1. Comparison of the Ca2+ entry channels responsible for mechanical responses of guinea-pig aorta to noradrenaline and thapsigargin using SK&F 96365 and LOE 908.

    PubMed

    Tanaka, Y; Imai, T; Igarashi, T; Takayanagi, K; Otsuka, K; Yamaki, F; Tanaka, H; Shigenobu, K

    2000-08-01

    Noradrenaline (NA) produces sustained contractions in conduit arteries such as aorta isolated from various animal species. In guinea-pig aorta, NA-produced sustained contraction is largely dependent upon the influx of extracellular Ca2+, but is refractory to the treatment with organic Ca2+ entry blockers. In the present study, we attempted to characterize pharmacologically the Ca2+ entry channel responsible for NA-produced sustained contraction of guinea-pig aorta using SK&F 96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenylethyl]-1H-imi dazole) and LOE 908 ((R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-[2- (2,3,4-trimethoxyphenyl)ethyl]-acetamide), both of which block voltage-independent Ca2+ channels. The effects of SK&F 96365 and LOE 908 on NA-produced contraction were compared with those on extracellular Ca2+-dependent contractile and endothelium-dependent relaxant responses to thapsigargin (TSG), an inhibitor of Ca2+-pump Ca2+-ATPase. NA (3x10(-6) M)-produced sustained contraction of guinea-pig aorta without endothelium exhibited a strong dependency on the extracellular Ca2+. Nicardipine (10(-7) M), diltiazem (10(-5) M) and verapamil (10(-5) M) did not show any appreciable inhibitory effects on NA-produced sustained contraction. SK&F 96365 concentration-dependently (10(-6)-10(-4) M) attenuated the NA-produced sustained contraction whereas LOE 908 did not affect it at concentrations up to 10(-4) M. Similarly, extracellular Ca2+-dependent contraction of guinea-pig aorta without endothelium in response to TSG was also diminished by SK&F 96365 but was unaffected by LOE 908. In fura-PE3-loaded vascular preparations, SK&F 96365 decreased both cytoplasmic Ca2+ level ([Ca2+]i) and muscle tension elevated by NA and TSG. Both SK&F 96365 and LOE 908 did not affect an endothelium-dependent relaxation of guinea-pig aorta in response to TSG. These findings suggest that in guinea-pig aortic smooth muscle cells, NA activates Ca2+ influx across

  2. Animal models of tuberculosis: Guinea pigs.

    PubMed

    Clark, Simon; Hall, Yper; Williams, Ann

    2015-05-01

    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

  3. 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

  4. Furosemide-induced airway relaxation in guinea pigs: relation to Na-K-2Cl cotransporter function.

    PubMed

    Lavallee, S L; Iwamoto, L M; Claybaugh, J R; Dressel, M V; Sato, A K; Nakamura, K T

    1997-07-01

    This study tested the hypothesis that airway relaxation to furosemide is mediated via the Na-K-2Cl cotransporter. If this mechanism exists in airway smooth muscle like in vascular smooth muscle, changes in airway relaxation should be associated with changes in Na-K-2Cl cotransporter function, and both should be substrate dependent. Tracheal rings from newborn guinea pigs were bathed in standard (STD) or varying low Cl- concentration ([Cl-]) N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES). Isometric relaxation to 300 microM furosemide or 10(-8) to 10(-5) M salbutamol was measured. Airway segments were incubated with rubidium-86 (86Rb) in STD or varying low [Cl-] HEPES, with and without 300 microM furosemide or 25 microM salbutamol. Furosemide was unable to reduce 86Rb uptake at 10 mM [Cl-], although relaxation was still observed in 10 mM [Cl-]. Salbutamol did not affect 86Rb uptake. This study demonstrated that there is a furosemide-sensitive Na-K-2Cl cotransporter in newborn guinea pig trachea. However, the effect of furosemide on cotransporter function did not always directly correspond to differences in relaxation, suggesting that the Na-K-2Cl cotransporter may play a major, but not exclusive, role in furosemide-induced airway relaxation. PMID:9252558

  5. Studies on dioctyl sodium sulfosuccinate toxicity: clinical, gross and microscopic pathology in the horse and guinea pig.

    PubMed Central

    Moffatt, R E; Kramer, L L; Lerner, D; Jones, R

    1975-01-01

    Concentrations of dioctyl sodium sulfosuccinate (DSS) ranging from three to five times the recommended dosage produced severe diarrhea, rapid dehydration and death in seven horses and 66 guinea pigs when administered experimentally per os. Clinicopathological findings indicated hemoconcentration in both horses and guinea pigs. There was a leucocytosis in the guinea pigs given the highest dosages. In all cases the principal finding at necropsy was extreme fluid distention of the intestinal tract. There was histopathological evidence of epithelial denudation and vascular stasis. The LD50 in the guinea pig was approximately 0.65 g DSS/kg body weight. Images Fig. 1a. Fig. 1b. Fig. 2a. Fig. 2b. PMID:1175077

  6. Disodium cromoglycate prevents ileum hyperreactivity to histamine in Toxocara canis-infected guinea pigs.

    PubMed

    Sá-Nunes, A; Corrado, A P; Baruffi, M D; Faccioli, L H

    2003-11-01

    The aim of this study was to investigate whether Toxocara canis infection in guinea pigs provokes changes in ileum responsiveness to histamine. Ileum segments from control and T. canis-infected groups were placed at isometric conditions and submitted to various doses of histamine. No changes were observed between controls and T. canis-infected groups at days 3, 6 and 12 after infection. However, at days 18 and 24 after infection, there was a significant increase in ileum responsiveness to histamine in T. canis-infected group. Pre-incubation of ileum segments with 1mgml(-1) disodium cromoglycate (DSCG) prevented the increased responsiveness to histamine in T. canis-infected guinea pigs and did not affect ileum contractility in non-infected animals. These results indicate that T. canis-infected guinea pigs develop increased intestinal responsiveness to histamine and that DSCG prevents alterations in smooth-muscle contractility. PMID:12967589

  7. Contractile responses in bladder body, bladder neck and prostate from rat, guinea pig and cat.

    PubMed

    Cohen, M L; Drey, K

    1989-03-01

    Lower urinary tract smooth muscle displays marked heterogeneity in pharmacologic responsiveness to contractile agents. The present study details differences among species with regard to muscarinic, adrenergic, histaminergic and serotonergic agonists in the bladder body, bladder neck and prostate from guinea pig, rat and cat. Under in vitro conditions, all smooth muscle preparations contracted to potassium chloride. The muscarinic agonist, carbamylcholine, produced maximal contraction, whereas alpha receptor agonists exerted only minimal, if any, effect in bladder body preparations from all three species. In contrast, alpha receptor-mediated responses predominated relative to muscarinic responses in bladder neck preparations from all three species. Prostatic contractility was examined in tissue from guinea pig and rat and contraction occurred to both alpha and muscarinic receptor agonists. Contractile response to norepinephrine in bladder neck and prostate was potentiated by neuronal uptake inhibition but not by beta receptor blockade. Serotonin and histamine exhibited more diverse effects among species and tissues. In general, histamine contracted all three tissues from guinea pig with minimal contraction occurring in tissues from rat or cat. On the other hand, serotonin markedly contracted the cat bladder body and rat prostate, but exerted no effect on tissues from the guinea pig. These data reinforce and detail the heterogeneity of pharmacologic contractile responses in lower urinary tract smooth muscle. Furthermore, the studies document the relative similarity among species in cholinergic and adrenergic responsiveness and the dissimilarity among species in serotonergic and histaminergic responsiveness of lower urinary tract smooth muscle. PMID:2539454

  8. Vascular smooth muscle in hypertension.

    PubMed

    Winquist, R J; Webb, R C; Bohr, D F

    1982-06-01

    The cause of the elevated arterial pressure in most forms of hypertension is an increase in total peripheral resistance. This brief review is directed toward an assessment of recent investigations contributing information about the factors responsible for this increased vascular resistance. Structural abnormalities in the vasculature that characterize the hypertensive process are 1) changes in the vascular media, 2) rarefication of the resistance vessels, and 3) lesions of the intimal vascular surface. These abnormalities are mainly the result of an adaptive process and are secondary to the increase in wall stress and/or to pathological damage to cellular components in the vessel wall. Functional alterations in the vascular smooth muscle are described as changes in agonist-smooth muscle interaction or plasma membrane permeability. These types of changes appear to play a primary, initiating role in the elevation of vascular resistance of hypertension. These alterations are not the result of an increase in wall stress and they often precede the development of high blood pressure. The functional changes are initiated by abnormal function of neurogenic, humoral, and/or myogenic changes that alter vascular smooth muscle activity. PMID:6282652

  9. Transmural distribution of extracellular purines in isolated guinea pig heart.

    PubMed Central

    Zhu, Q Y; Headrick, J P; Berne, R M

    1991-01-01

    The purine adenosine appears to be involved in regulation of coronary vascular tone. Little is known concerning the levels and distribution of adenosine and related purines in the extracellular fluid of the heart. We have measured epicardial and endocardial levels of adenosine, inosine, hypoxanthine, AMP, and IMP in isolated constant flow perfused guinea pig hearts by using a recently developed technique with porous nylon sampling discs. Venous effluent purine levels were also measured. Concentrations of all purines measured, excluding IMP, were significantly higher in endocardial fluid samples than in epicardial fluid samples (P less than 0.05). Conversely, IMP levels were significantly lower in endocardial than in epicardial samples. The magnitude of the endocardial/epicardial ratios for adenosine, inosine, hypoxanthine, AMP, and IMP were approximately 12:1, 4:1, 5:1, 4:1, and 1:2, respectively. To assess cellular damage, lactate dehydrogenase activity was measured in all fluid samples and was not significantly different in endocardial and epicardial fluid. These data support the existence of significant transmural gradients for extracellular purine levels in crystalloid perfused guinea pig hearts. Transmural differences in vasoactive adenosine levels may be partially due to the greater endocardial oxygen consumption and metabolism and may be involved in maintaining relatively high subendocardial blood flows in the face of high intramyocardial pressures. Images PMID:1988961

  10. The flavonoid chrysin, an endocrine disrupter, relaxes cholecystokinin- and KCl-induced tension in male guinea pig gallbladder strips through multiple signaling pathways.

    PubMed

    Kline, Loren W; Karpinski, Edward

    2014-01-01

    The bioflavonoids have effects on vascular smooth muscle and gastrointestinal smooth muscle. The flavone and phytoestrogen, chrysin, has been shown to have a vasorelaxant effect on resistance blood vessels. This effect was mediated by nitric oxide (NO). Chrysin inhibited aromatase/estrogen biosynthesis in postmenopausal women. The purpose of this study was to determine if chrysin had an effect on cholecystokinin- or KCl-induced tension in male guinea pig gallbladder strips. In addition, the second messenger(s) system(s) that mediated the effect were to be determined. A pharmacologic approach was used. Male guinea pig gallbladder strips were placed in in vitro chambers filled with Krebs solution, maintained at 37 °C, and gassed with 95% O2-5% CO2. Changes in tension were recorded using a polygraph. It was shown that the PKA/cAMP second messenger system mediated part of the observed chrysin-induced relaxation of cholecystokinin-induced tension, the PKC system also mediated part of the relaxation, and the inhibition of both extracellular Ca(2+) entry and intracellular Ca(2+) release also mediated the chrysin-induced relaxation. This is the first report of chrysin having an effect on gallbladder smooth muscle contraction. PMID:24291637

  11. The cochleogram of the guinea pig.

    PubMed

    Linss, Volker; Linss, Werner; Emmerich, Edeltraut; Richter, Frank

    2007-04-01

    The cochleogram is an important tool to relate properties of the cochlea (e.g. hair cell loss, damaged hair cells) to their position in the cochlear turns, to calculate the average hair cell density, and to measure the length of the whole cochlea. In this work different methods of plotting cochleograms are compared. We suggest that a sector-wise division of the cochlea for counting a cochleogram has advantages over line diagrams that provide a higher spatial resolution but might lead to misinterpretations of the degree of missing hair cells. The scanning electron microscopic analysis of 171 guinea pig cochleas revealed a mean basilar membrane length of 16.4 +/- 1.4 mm (mean +/- standard deviation) with sector lengths of 6.9, 4.2, 3.2, and 1.9 mm, thus adding relevant information to the morphology of the guinea pig cochlea. PMID:17082943

  12. Endogenous prostaglandin in guinea pig taenia coli.

    PubMed

    Yamaguchi, T; Hitzig, B; Coburn, R F

    1976-01-01

    Prostaglandin (PGE) is synthesized in the guinea pig taenia coli. A low threshold concentration for an effect of exogenous PGE1 or PGE2 on spontaneous mechanical activity was demonstrated. The PG synthetase inhibitors aspirin, indomethacin, and 5,8,11,14-eicosatetraynoic acid, at concentrations that inhibited PGE efflux, had effects on spontaneous mechanical activity, membrane potential, membrane resistance, and evoked and spontaneous action potentials (single and double sucrose-gap methods) that were consistent with an action due to inhibition of membrane PGE concentration. The threshold concentration of indomethacin, which inhibited PGE efflux, was the same as the concentration that inhibited spontaneous mechanical activity. Pretreatment with ouabain (10(-6)-10(-5) g/ml) or elevated extracellular K+ (29 and 126 mM) made the guinea pig taenia coli entirely refractory to exogenous PGE1 or PGE2; the mechanical effects of the three prostaglandin synthetase inhibitors also were absent in the presence of elevated K+ or ouabain. The data are consistent with a hypothesis that, under conditions of our experiments, endogenous PGE has an effect on resting tension and spontaneous mechanical activity and on properties of the surface membrane of the guinea pig taenia coli. PMID:1251900

  13. A 2-D guinea pig lung proteome map

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  14. 9 CFR 113.38 - Guinea pig safety test.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Guinea pig safety test. 113.38 Section 113.38 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Standard Procedures § 113.38 Guinea pig safety...

  15. 9 CFR 113.38 - Guinea pig safety test.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals... pigs during the observation period, the serial or subserial is unsatisfactory. If unfavorable reactions... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Guinea pig safety test. 113.38...

  16. 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…

  17. 9 CFR 113.38 - Guinea pig safety test.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the animals... pigs during the observation period, the serial or subserial is unsatisfactory. If unfavorable reactions... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Guinea pig safety test. 113.38...

  18. Effect of nanodisperse ferrite cobalt (CoFe2O4) particles on contractile reactions in guinea pigs airways.

    PubMed

    Kapilevich, L V; D'yakova, E Yu; Nosarev, A V; Zaitseva, T N; Petlina, Z R; Ogorodova, L M; Ageev, B G; Magaeva, A A; Itin, V I; Terekhova, O G

    2010-07-01

    The effect of nanopowder CoFe(2)O(4)on contractile responses of smooth-muscle segments of guinea pigs airways was studied by mechanography. Both in vivo inhalation of nanopowder aerosol or in vitro application of nanopowder to isolated airway segments increased the amplitude of contractile responses to histamine and potentiated the dilatory reaction to adrenergic salbutamol. PMID:21113462

  19. Localization of quantitative changes in pulmonary beta-receptors in ovalbumin-sensitized guinea pigs

    SciTech Connect

    Gatto, C.; Green, T.P.; Johnson, M.G.; Marchessault, R.P.; Seybold, V.; Johnson, D.E.

    1987-07-01

    Impaired beta-receptor function has been postulated as one factor contributing to airway hyperreactivity in asthmatic patients. Although numerous indirect studies have cast doubt on this theory, none of these previous investigations has been able to directly measure changes in beta-receptor number on intrapulmonary structures capable of affecting the physiologic changes seen in this disease state. To help clarify the intrapulmonary location of such changes, a model of allergic bronchoconstriction was prepared by sensitizing guinea pigs to ovalbumin intraperitoneally (ip) 2 wk prior to testing (Group S). A second group of animals was sensitized to ovalbumin, then 2 wk later partially desensitized (Group D) during a 4- to 6-wk period by repeated exposure to increasing doses of nebulized ovalbumin with epinephrine rescue. Control animals received ip administered and nebulized normal saline alone. Pulmonary function assessed by plethysmography revealed an increase in airway resistance to 294 +/- 42% (SE) of control in Group S (p less than 0.005) and a decrease in dynamic compliance to 76 +/- 8% of control in Group D and 39 +/- 10% of control in Group S (p less than 0.002) after exposure to nebulized ovalbumin. Using L-(/sup 3/H) dihydroalprenolol ((/sup 3/H) DHA), beta-receptors were autoradiographically localized and quantitated in lung sections from all 3 groups. Significant decreases (p less than 0.02) in /sup 3/H-DHA binding were noted in alveolar and conducting airway epithelium, and bronchiolar and vascular smooth muscle in ovalbumin-exposed animals.

  20. Ultrastructural and Metabolic Determinants of Resistance to Azo-dye and Susceptibility to Nitrosamine Carcinogenesis of the Guinea-pig

    PubMed Central

    Bryant, G. M.; Sohal, R. S.; Argus, M. F.; Arcos, J. C.

    1977-01-01

    During diethylnitrosamine (DEN) administration, a distinctive difference was observed between rats and guinea-pigs in the sequence of ultrastructural changes in the hepatic endoplasmic reticulum (ER). In DEN-induced hepatic tumour cells in the guinea-pig there was extensive proliferation of the rough ER, while the smooth ER was quite sparse; in the premalignant liver the opposite was noted. This is in contrast to the rat, in which administration of either DEN or 3′-methyl-4-dimethylaminoazobenzene (3′-Me-DAB) brings about, in both premalignant and malignant hepatic tissue, proliferation of the smooth ER and sparsity of the rough ER. Yet, as in the rat, the number of ribosomes on the outer surface of the guinea-pig liver rough ER is greatly reduced and this is paralleled by a 49% decrease of the RNA/protein ratio as early as 4 weeks of nitrosamine administration. The decrease of RNA/protein ratio and ultrastructurally observed loss of ribosomes from the ER, following nitrosamine administration, correlate with a decrease of photometric response of microsomal suspensions to the sulphydryl probe, p-chloromercuribenzoate. While azo-dye-reductase activity is higher in untreated rats than in untreated guinea-pigs, feeding 3′-Me-DAB for 6 weeks brings about a 76% decrease in the rat, but no significant decrease in the guinea-pig, which is refractory to azo-dye carcinogenesis. Thus, the ability of the liver to inactivate the dye is greatly decreased in the rat, but not in the guinea-pig, as administration progresses toward the threshold dose for tumorigenesis. On the other hand, constitutive levels of nitrosamine dealkylase are identical in the 2 species and remain essentially unchanged following administration of DEN for 10 weeks. Inasmuch as nitrosamine dealkylation represents activating metabolism, this provides a rationale for the comparable susceptibility of the rat and guinea-pig to DEN carcinogenesis. Of the 2 enzymes in the 2 species, it is only azo

  1. Mechanics of Vascular Smooth Muscle.

    PubMed

    Ratz, Paul H

    2015-01-01

    Vascular smooth muscle (VSM; see Table 1 for a list of abbreviations) is a heterogeneous biomaterial comprised of cells and extracellular matrix. By surrounding tubes of endothelial cells, VSM forms a regulated network, the vasculature, through which oxygenated blood supplies specialized organs, permitting the development of large multicellular organisms. VSM cells, the engine of the vasculature, house a set of regulated nanomotors that permit rapid stress-development, sustained stress-maintenance and vessel constriction. Viscoelastic materials within, surrounding and attached to VSM cells, comprised largely of polymeric proteins with complex mechanical characteristics, assist the engine with countering loads imposed by the heart pump, and with control of relengthening after constriction. The complexity of this smart material can be reduced by classical mechanical studies combined with circuit modeling using spring and dashpot elements. Evaluation of the mechanical characteristics of VSM requires a more complete understanding of the mechanics and regulation of its biochemical parts, and ultimately, an understanding of how these parts work together to form the machinery of the vascular tree. Current molecular studies provide detailed mechanical data about single polymeric molecules, revealing viscoelasticity and plasticity at the protein domain level, the unique biological slip-catch bond, and a regulated two-step actomyosin power stroke. At the tissue level, new insight into acutely dynamic stress-strain behavior reveals smooth muscle to exhibit adaptive plasticity. At its core, physiology aims to describe the complex interactions of molecular systems, clarifying structure-function relationships and regulation of biological machines. The intent of this review is to provide a comprehensive presentation of one biomachine, VSM. PMID:26756629

  2. Characterization of an atypical muscarinic cholinoceptor mediating contraction of the guinea-pig isolated uterus

    PubMed Central

    Boxall, Donna K; Ford, Anthony P D W; Choppin, Agnes; Nahorski, Stefan R; Challiss, R A John; Eglen, Richard M

    1998-01-01

    In many smooth muscle tissues a minor M3-muscarinic acetylcholine (mACh) receptor population mediates contraction, despite the presence of a larger M2-mACh receptor population. However, this is not the case for guinea-pig uterus where radioligand binding and functional studies exclude a dominant role for M3-mACh receptors. Using tissue from animals pre-treated with diethylstilboestrol, estimates of antagonist affinity were made before and after selective alkylation procedures, together with estimates of agonist affinity to characterise the mACh receptor population mediating carbachol-induced contraction of guinea-pig isolated uterus. Antagonist affinity estimates made at `protected' receptors were not significantly different from those made in untreated tissues. However all estimations were significantly different from those reported in guinea-pig ileum and atria. The rank order of affinities were atropine>zamifenacin=tripitramine>methoctramine. Carbachol-induced contractions were insensitive to the M4-selective muscarinic toxin MTx-3, or PD102807 (0.1 μM) ruling out a role for M4-mACh receptors. The agonist affinity value for L-660,863, a putative `M2-selective' agonist of 5.44±0.30 (n=6) was significantly different from that reported in guinea-pig atria. In contrast, the pKA value for carbachol (4.22±0.17; n=8) agrees with that reported for guinea-pig ileum. Carbachol-induced contractions were insensitive to pertussis toxin although carbachol-induced inhibition of forskolin-stimulated cyclic AMP production was attenuated, ruling out the involvement of Gi-proteins in contraction. Radioligand binding studies revealed a KD for N-[3H]-methylscopolamine of 0.12±0.05 nM and a Bmax of 147±18 fmol mg protein−1. Antagonist affinity estimates made using competition binding studies supported previous data suggesting the presence of a homogenous population of M2-mACh receptors. These data suggest a small population of mACh receptors with an atypical

  3. Biosynthesis of plasmenylcholine in guinea pig heart

    SciTech Connect

    Wientzek, M.; Choy, P.C.

    1986-05-01

    In some mammalian hearts, up to 40% of the choline phosphoglyceride (CPG) exists as plasmenylcholine (1-alkenyl-2-acyl-glycero-3-phosphocholine). Although the majority of diacylphosphatidylcholine (PC) in mammalian hearts is synthesized from choline via the CDP-choline pathway, the formation of plasmenylcholine from choline was not known. In this study, they investigated the biosynthesis of plasmenyl-choline in the isolated guinea pig heart by perfusion with (/sup 3/H)choline. Labelled choline containing metabolites and labelled plasmenylcholine were isolated and determined at different perfusion time points. Significant amounts of labelling were found only in choline, phosphocholine, CDP-choline, plasmenyl-choline and PC. In addition, a precursor-product relationship was observed between the labelling of CDP-choline and plasmenylcholine. Such a relationship was not observed between choline and plasmenylcholine. Hence, they postulate that the incorporation of choline into plasmenylcholine is via the CDP-choline pathway and not via base exchange. The ability to condense 1-alkenyl-2-acyl-glycerol with CDP-choline was also demonstrated in vitro with guinea pig heart microsomes.

  4. Experimental poisoning of guinea pig (Cavia porcellus) with Indigofera suffruticosa.

    PubMed

    Salvador, I S; Medeiros, R M T; Pessoa, C R M; Oliveira, D M; Duarte, A L A; Fighera, R A; Riet-Correa, F

    2011-05-01

    Indigofera suffruticosa causes hemolytic anemia and hemoglobinuria in cattle. The plant was administered to six groups of two guinea pigs each, at the daily dose of 10 g/kg body weight, for periods of 2, 4, 6, 8, 10 and 15 days. The guinea pigs progressively developed reduced hematocrits and hemoglobin concentrations, and finally presented anemia, without hemoglobinuria. Urine passed by guinea pigs that had ingested the plant for more than 24 h acquired a turquoise blue pigmentation 8-10 h after urination. It is suggested that the anemia is caused by the aniline contained in I. suffruticosa. PMID:21396390

  5. Intimal permeability evaluated in a short-term organ culture of diabetic guinea pig aorta

    SciTech Connect

    Schlosser, M.J.; Verlangieri, A.J.

    1988-01-01

    A novel short-term organ culture system was used to evaluate intimal permeability changes by measuring aortic (/sup 14/C)methylated albumin accumulation. Aortic plugs were removed from the upper thoracic aorta of male guinea pigs and maintained in serum-free media. The accumulation of (/sup 14/C)albumin in the intimal-medial layer was determined after a 5 h incubation. In preliminary studies, albumin recovered from intimal-injured aortic plugs was significantly greater than those from non-injured plugs. Aortic plugs from streptozotocin-treated guinea pigs, diabetic for 3 weeks, also accumulated significantly more (/sup 14/C)albumin than plugs from nondiabetic controls. Histological changes were not observed in the aorta of either the diabetic or control group. A strong significant inverse correlation was found between plasma ascorbic acid levels and (/sup 14/C)-activity recovered from aortic plugs. This study demonstrates a simple and rapid method for assessing aortic permeability changes under a well-defined in vitro system, and suggests that vascular permeability changes in the streptozotocin-diabetic guinea pig may be associated with an ascorbic acid deficit.

  6. Hydrogen sulphide inhibits carbachol-induced contractile responses in β-escin permeabilized guinea-pig taenia caecum.

    PubMed

    Denizalti, Merve; Durlu-Kandilci, N Tugba; Bozkurt, T Emrah; Sahin-Erdemli, Inci

    2011-05-11

    Hydrogen sulphide (H(2)S) is an endogenous mediator producing a potent relaxation response in vascular and non-vascular smooth muscles. While ATP-sensitive potassium channels are mainly involved in this relaxant effect in vascular smooth muscle, the mechanism in other smooth muscles has not been revealed yet. In the present study, we investigated how H(2)S relaxes non-vascular smooth muscle by using intact and β-escin permeabilized guinea-pig taenia caecum. In intact tissues, concentration-dependent relaxation response to H(2)S donor NaHS in carbachol-precontracted preparations did not change in the presence of a K(ATP) channel blocker glibenclamide, adenylate cyclase inhibitor SQ-22536, guanylate cyclase inhibitor ODQ, protein kinase A inhibitor KT-5720, protein kinase C inhibitor H-7, tetrodotoxin, apamin/charybdotoxin, NOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin. We then studied how H(2)S affected carbachol- or Ca(2+)-induced contractions in permeabilized tissues. When Ca(2+) was clamped to a constant value (pCa6), a further contraction could be elicited by carbachol that was decreased by NaHS. This decrease in contraction was reversed by catalase but not by superoxide dismutase or N-acetyl cysteine. The sarcoplasmic reticulum Ca(2+)-ATPase pump inhibitor, cyclopiazonic acid, also decreased the carbachol-induced contraction that was further inhibited by NaHS. Mitochondrial proton pump inhibitor carbonyl cyanide p-trifluromethoxyphenylhydrazone also decreased the carbachol-induced contraction but this was not additionally changed by NaHS. The carbachol-induced Ca(2+) sensitization, calcium concentration-response curves, IP(3)- and caffeine-induced contractions were not affected by NaHS. In conclusion, we propose that hydrogen peroxide and mitochondria may have a role in H(2)S-induced relaxation response in taenia caecum. PMID:21371473

  7. 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.

  8. 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.

  9. "Human guinea pigs"--a history.

    PubMed

    Pappworth, M H

    In 1967, Pappworth expanded a 1962 journal article on unethical experiments with human subjects into a book, Human Guinea Pigs: Experimentation on Man (Routledge). Here Pappworth describes the impetus behind his controversial article and book, and the reaction to both from the British media, the British medical establishment, the Ministry of Health, and Parliament. He discusses the effectiveness of ethical codes, editorial policies, and research ethics committees in safeguarding human subjects from overzealous or unethical researchers. He warns of the need for all those involved in human experimentation -- researchers, their units, ethics committees, editors of medical journals -- to tighten the self regulatory mechanisms in place lest public reaction to unethical research bring on legal sanctions. PMID:2279175

  10. Generation of DPOAEs in the guinea pig.

    PubMed

    Withnell, Robert H; Shaffer, Lauren A; Talmadge, Carrick L

    2003-04-01

    In humans, distortion product otoacoustic emissions (DPOAEs) at frequencies lower than the f(2) stimulus frequency are a composite of two separate sources, these two sources involving two distinctly different mechanisms for their production: non-linear distortion and linear coherent reflection [Talmadge et al., J. Acoust. Soc. Am. 104 (1998) 1517-1543; Talmadge et al., J. Acoust. Soc. Am. 105 (1999) 275-292; Shera and Guinan, J. Acoust. Soc. Am. 105 (1999) 332-348; Kalluri and Shera, J. Acoust. Soc. Am. 109 (2001) 662-637]. In rodents, DPOAEs are larger, consistent with broader filters; however the evidence for two separate mechanisms of DPOAE production as seen in humans is limited. In this study, we report DPOAE amplitude and phase fine structure from the guinea pig with f(2)/f(1) held constant at 1.2 and f(2) swept over a range of frequencies. Inverse Fast Fourier Transform analysis and time-domain windowing were used to separate the two components. Both the 2f(1)-f(2) DPOAE and the 2f(2)-f(1) DPOAE were examined. It was found that, commensurate with human data, the guinea pig DPOAE is a composite of two components arising from different mechanisms. It would appear that the 2f(1)-f(2) emission measured in the ear canal is usually dominated by non-linear distortion, at least for a stimulus frequency ratio of 1.2. The 2f(2)-f(1) DPOAE exhibits amplitude fine structure that, for the animals examined, is predominantly due to the variation in amplitude of the place-fixed component. Cochlear delay times appear consistent with a linear coherent reflection mechanism from the distortion product place for both the 2f(1)-f(2) and 2f(2)-f(1) place-fixed components. PMID:12684183

  11. Guinea-pig productivity under traditional management.

    PubMed

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

    1998-04-01

    Results of a 12 month study of traditional guinea-pig production in the western highlands of Cameroon are reported. The mean age of guinea-pigs (Cavia porcellus L.) at first parturition, kidding interval and litter size at birth were 126.30 +/- 10.40 d, 64.8 +/- 1.70 d and 1.63 +/- 0.26 kids respectively. The annual reproductive rate was 9.18 kids/breeding doe while the doe post-partum weight was 530 g. Mean body weights at birth, presumed weaning (21 d) and 15 weeks of age were 78.36 +/- 3.20, 147.51 +/- 8.10 and 418.88 +/- 32 g respectively. Type of birth and sex had a significant effect on body weight at all ages. Birth weight dropped significantly from 83.88 +/- 2.87 g for singles to 81.57 +/- 3.40 g for twins, 74.25 +/- 2.39 g for triplets and 73.75 +/- 4.12 g for quadruplets. These differences were maintained to maturity (15 weeks). Males were generally heavier than females. Mortality rates were relatively high among kids: 24% at birth, 39% at 3 weeks and 40% at 15 weeks. Productivity indices were 0.827 kg of young weaned per doe per year, 1560 g of young weaned per kg of doe per year and 2.52 kg of young weaned per kg metabolic weight (kg 0.75) of female per year. PMID:9719838

  12. Antitussive Effects of Memantine in Guinea Pigs

    PubMed Central

    Smith, Jaclyn A.; Hilton, Emma C. Y.; Saulsberry, Loren

    2012-01-01

    Background: 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. Methods: 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. Results: 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. Conclusions: 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. PMID:22016492

  13. Absence of pork-like insulin in guinea pig tissues.

    PubMed Central

    Eng, J; Yalow, R S

    1982-01-01

    By using a technique for concentrating insulin 100-fold from tissue extracts with 75-95% recoveries, we earlier failed to detect pork-like insulin in guinea pig tissues and thus were unable to confirm reports from the National Institutes of Health that these tissues contain a pork-like insulin at concentrations averaging 1 ng/g. This difference could have been due to differences in strains of guinea pigs studied or in the species specificities of the antisera used for radioimmunoassay. In the current study, tissue extracts from both NIH and Hartley guinea pigs were assayed with three antisera routinely used in our laboratory and one antiserum that had been used in the National Institutes of Health laboratory. We observed that pork-like insulin in tissues from both strains of guinea pigs as determined with the four antisera is less than 0.02 ng/g. We therefore conclude that is is unlikely that nonpancreatic guinea pig tissues contain or synthesize a peptide resembling pork or other non-guinea pig mammalian insulin. PMID:7045868

  14. Receptors involved in the modulation of guinea pig urinary bladder motility by prostaglandin D2

    PubMed Central

    Guan, Na N; Svennersten, Karl; de Verdier, Petra J; Wiklund, N Peter; Gustafsson, Lars E

    2015-01-01

    Background and Purpose We have described a urothelium-dependent release of PGD2-like activity which had inhibitory effects on the motility of guinea pig urinary bladder. Here, we have pharmacologically characterized the receptors involved and localized the sites of PGD2 formation and of its receptors. Experimental Approach In the presence of selective DP and TP receptor antagonists alone or combined, PGD2 was applied to urothelium-denuded diclofenac-treated urinary bladder strips mounted in organ baths. Antibodies against PGD2 synthase and DP1 receptors were used with Western blots and for histochemistry. Key Results PGD2 inhibited nerve stimulation -induced contractions in strips of guinea pig urinary bladder with estimated pIC50 of 7.55 ± 0.15 (n = 13), an effect blocked by the DP1 receptor antagonist BW-A868C. After blockade of DP1 receptors, PGD2 enhanced the contractions, an effect abolished by the TP receptor antagonist SQ-29548. Histochemistry revealed strong immunoreactivity for PGD synthase in the urothelium/suburothelium with strongest reaction in the suburothelium. Immunoreactive DP1 receptors were found in the smooth muscle of the bladder wall with a dominant localization to smooth muscle membranes. Conclusions and Implications In guinea pig urinary bladder, the main effect of PGD2 is an inhibitory action via DP1 receptors localized to the smooth muscle, but an excitatory effect via TP receptors can also be evoked. The urothelium with its suburothelium might signal to the smooth muscle which is rich in PGD2 receptors of the DP1 type. The results are important for our understanding of regulation of bladder motility. PMID:25917171

  15. Gene Targeting to the Uteroplacental Circulation of Pregnant Guinea Pigs.

    PubMed

    Mehta, Vedanta; Ofir, Keren; Swanson, Anna; Kloczko, Ewa; Boyd, Michael; Barker, Hannah; Avdic-Belltheus, Adnan; Martin, John; Zachary, Ian; Peebles, Donald; David, Anna L

    2016-08-01

    Our study aimed to target adenoviral gene therapy to the uteroplacental circulation of pregnant guinea pigs in order to develop a novel therapy for fetal growth restriction. Four methods of delivery of an adenovirus encoding β-galactosidase (Ad.LacZ) were evaluated: intravascular injection using phosphate-buffered saline (PBS) into (1) uterine artery (UtA) or (2) internal iliac artery or external administration in (3) PBS or (4) pluronic F-127 gel (Sigma Aldrich). Postmortem examination was performed 4 to 7 days after gene transfer. Tissue transduction was assessed by X-gal histochemistry and enzyme-linked immunosorbent assay. External vascular application of the adenovirus vector in combination with pluronic gel had 91.7% success rate in terms of administration (85% maternal survival) and gave the best results for maternal/fetal survival and local transduction efficiency without any spread to maternal or fetal tissues. This study suggests an optimal method of gene delivery to the UtAs of a small rodent for preclinical studies. PMID:26865541

  16. 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

  17. 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. PMID:25871402

  18. Absorption Kinetics of Subcutaneously Administered Ceftazidime in Hypoperfused Guinea Pigs

    PubMed Central

    Ebihara, Tsuyoshi; Oshima, Shinji; Okita, Mitsuyoshi; Shiina, Sayumi; Negishi, Akio; Ohara, Kousuke; Ohshima, Shigeru; Iwasaki, Hiroyuki; Yoneyama, Akira; Kitazumi, Eiji; Kobayashi, Daisuke

    2014-01-01

    Background Pneumonia is the most common cause of death in patients with severe motor and intellectual disabilities (SMID), and intravenous ceftazidime (CAZ) is a widely used treatment for such infections. However, intravenous administration in patients with SMID may be difficult because of insufficient vascular development. Objectives The aim of our study was to determine the feasibility of subcutaneous drug administration by mentholated warm compresses (WMCs) as an alternative delivery method for ceftazidime in patients with SMID. Methods CAZ was subcutaneously administered to the abdominal region of naphazoline-treated hypoperfused guinea pigs, which were used as a hemodynamic model of patients with SMID. MWCs or warm compresses (WCs) were applied to the injection site to increase blood flow. We calculated the cumulative CAZ absorption over time by using the deconvolution method. Results Application of MWCs or WCs increased blood flow at the administration site and increased CAZ plasma levels. Application of MWCs or WCs after subcutaneous CAZ injection led to higher CAZ plasma levels than the mutant prevention concentration for a longer period than was observed for CAZ administration without the application of MWCs or WCs. Conclusions The application of MWCs or WCs enhanced subcutaneous CAZ absorption by increasing blood flow. MWCs and WCs are considered to be safe and routine methods to induce defecation after surgery on the digestive system; thus, the combination of these methods and subcutaneous CAZ administration is a potential method for treating pneumonia in patients with SMID. PMID:26649076

  19. Involvement of 5-HT1B receptors in triptan-induced contractile responses in guinea-pig isolated iliac artery.

    PubMed

    Jähnichen, S; Radtke, O A; Pertz, H H

    2004-07-01

    Using a series of triptans we characterized in vitro the 5-hydroxytryptamine (5-HT) receptor that mediates the contraction in guinea-pig iliac arteries moderately precontracted by prostaglandin F2alpha (PGF2alpha). Additionally, we investigated by reverse-transcriptase polymerase chain reaction (RT-PCR) which triptan-sensitive receptor is present in this tissue. Frovatriptan, zolmitriptan, rizatriptan, naratriptan, sumatriptan, and almotriptan contracted guinea-pig iliac arteries with pD2 values of 7.52+/-0.04, 6.72+/-0.03, 6.38+/-0.06, 6.22+/-0.05, 5.86+/-0.05 and 5.26+/-0.04 respectively. For comparison, the pD2 values for 5-HT and 5-carboxamidotryptamine (5-CT) were 7.52+/-0.02 and 7.55+/-0.03 respectively. In contrast to all other triptans tested, the concentration-response curve for eletriptan was biphasic (first phase: 0.01-3 microM, pD2 approximately 6.6; second phase: > or = 10 microM). Contractions to 5-HT, 5-CT, frovatriptan, zolmitriptan, rizatriptan, naratriptan, sumatriptan, almotriptan, and eletriptan (first phase) were antagonized by the 5-HT1B/1D receptor antagonist GR127935 (10 nM) and the 5-HT1B receptor antagonist SB216641 (10 nM). RT-PCR studies in guinea-pig iliac arteries showed a strong signal for the 5-HT1B receptor while expression of 5-HT1D and 5-HT1F receptors was not detected in any sample. The present results demonstrate that triptan-induced contraction in guinea-pig iliac arteries is mediated by the 5-HT1B receptor. The guinea-pig iliac artery may be used as a convenient in vitro model to study the (cardio)vascular side-effect potential of anti-migraine drugs of the triptan family. PMID:15185063

  20. Pathogenesis of Lassa virus infection in guinea pigs.

    PubMed Central

    Jahrling, P B; Smith, S; Hesse, R A; Rhoderick, J B

    1982-01-01

    A rodent model for human Lassa fever was developed which uses inbred (strain 13) and outbred (Hartley) guinea pigs. Strain 13 guinea pigs were uniformly susceptible to lethal infection by 2 or more PFU of Lassa virus strain Josiah. In contrast, no more than 30% of the Hartley guinea pigs died regardless of the virus dose. In lethally infected strain 13 guinea pigs, peak titers of virus (10(7) to 10(8) 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 14 to 16 days. Virus reached low titers (10(4) PFU) in the plasma and brain and intermediate titers in the liver, adrenal glands, kidney, pancreas, and heart. In moribund animals, the most consistent and severe histological lesion as an interstitial pneumonia. In contrast, the brain was only minimally involved. The immune response of lethally infected strain 13 guinea pigs, as measured by the indirect fluorescent antibody test, was detectable within 10 days of infection and was similar in timing and intensity to the fluorescent antibody test response of both lethally infected and surviving outbred animals. In contrast to the fluorescent antibody response, neutralizing antibody developed late in convalescence and was thus detected only in surviving outbred guinea pigs. The availability of a rodent model for human Lassa fever in uniformly susceptible strain 13 guinea pigs should facilitate detailed pathophysiological studies and efficacy testing of antiviral drugs, candidate vaccines, and immunotherapy regimens to develop control methods for this life-threatening disease in humans. Images PMID:6749685

  1. [Effects of thromboxane A2 synthetase inhibitor, DP-1904 on the action of vasoactive substances in guinea pig trachea and lung tissue strips].

    PubMed

    Shimizu, K; Kobayashi, J; Iwanaga, T; Kuratomi, Y; Kitamura, S

    1989-03-01

    Thromboxane A2 (TxA2) is a potent platelet aggregator and vascular or bronchial constrictor. DP-1904, a newly synthesized imidazol TxA2 synthetase inhibitor, is a potent and long-acting agent. The present investigation was conducted to explore the effect of DP-1904 on the contractile or relaxing responses in guinea pig trachea and lung tissue strips induced by various vasoactive substances. Fourteen guinea pigs, weighing 300-350 g, were sacrificed. Trachea and lungs were removed, cut spirally, set up in bioassay glass jackets and superfused with Krebs-Henseleit solution at 37 degrees C, saturated with oxygen and carbon dioxide. Contraction of tissues was detected by an isotonic transducer and displayed on a polyrecorder. Arachidonic acid-induced relaxing responses in guinea pig trachea strips were attenuated significantly by the continuous infusion of DP-1904 in a dose-dependent fashion. Arachidonic acid-induced contractile responses in guinea pig lung strips were attenuated significantly by the continuous infusion of DP-1904, dose-dependently. Acetylcholine-, histamine- and prostaglandin F2 alpha-induced contractile responses in guinea pig lung and trachea strips were attenuated significantly by the continuous infusion of DP-1904, dose-dependently. The above results suggest that DP-1904 might be a useful therapeutic agent for the treatment of chronic obstructive lung diseases. PMID:2615088

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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...

  7. 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...

  8. 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...

  9. O3-induced mucosa-linked airway muscle hyperresponsiveness in the guinea pig

    SciTech Connect

    Murlas, C.G.; Murphy, T.P.; Chodimella, V. )

    1990-07-01

    We investigated the effects of ozone exposure (3.0 ppm, 2 h) on the responsiveness of guinea pig airway muscle in vitro from animals developing bronchial hyperreactivity. Muscarinic reactivity in vivo was determined by measuring specific airway resistance (sRaw) in response to increasing concentrations of aerosolized acetylcholine (ACh) administered before and 30 min after exposure. Immediately after reactivity testing, multiple tracheal rings from ozone- and air-exposed animals were prepared and the contractile responses to increasing concentrations of substance P, ACh, or KCl were assessed in the presence of 10 microM indomethacin with or without 1 microM phosphoramidon, an inhibitor of neutral endopeptidase. Isometric force generation in vitro was measured on stimulation by cumulative concentrations of the agonists, and force generation (in g/cm2) was calculated after determination of muscle cross-sectional area. The smooth muscle of mucosa-intact airways from guinea pigs with ozone-induced bronchial hyper-reactivity proved to be hyperresponsive in vitro to substance P and ACh but not to KCl. Pretreatment with phosphoramidon abolished the increase in substance P responsiveness but had no effect on muscarinic hyperresponsiveness after ozone exposure. Furthermore, substance P responsiveness was not augmented in ozone-exposed airways in which the mucosa had been removed before testing in vitro. Likewise, muscarinic hyperresponsiveness was not present in ozone-exposed airways without mucosa. Our data indicate that airway smooth muscle responsiveness is increased in guinea pigs with ozone-induced bronchial hyperreactivity and suggest that this hyperresponsiveness may be linked to non-cyclooxygenase mucosa-derived factors.

  10. Comparison of guinea pig cytomegalovirus and guinea pig herpes-like virus: pathogenesis and persistence in experimentally infected animals.

    PubMed Central

    Tenser, R B; Hsiung, G D

    1976-01-01

    The pathogenesis of guinea pig cytomegalovirus (GPCMV) and guinea pig herpes-like virus (GPHLV) in guinea pigs was compared. Animals were inoculated with the two viruses by different routes and sacrificed after varying periods of time. GPCMV was consistently isolated from salivary gland 2 weeks postinoculation and thereafter following intraperitoneal or subcutaneous incoulaton. Virus was less frequently found in other tissues including blood, spleen, and kidney. Intranuclear inclusions were seen in tissue sections of salivary gland after inoculation with GPCMV- infected tissue suspension, but were only rarely found after inoculation with tissue culture virus. In GPHLV-infected guinea pigs, consistent latent infection of leukocytes and other tissues was detected by cocultivation techniques. Intranuclear inclusions were not found in the spleen, salivary gland, or other infected tissues after GPHLV infection with either tissue culture virus or infected tissue suspension. Guinea pigs inoculated with GPCMV produced high titers of specific neutralizing antibody to the homologous virus; those inoculated with GPHLV developed long-term viremia accompanied by minimal neutralizing antibody levels to the virus. Images PMID:178599

  11. Parainfluenza 3-Induced Cough Hypersensitivity in the Guinea Pig Airways.

    PubMed

    Zaccone, Eric J; Lieu, TinaMarie; Muroi, Yukiko; Potenzieri, Carl; Undem, Blair E; Gao, Peisong; Han, Liang; Canning, Brendan J; Undem, Bradley J

    2016-01-01

    The effect of respiratory tract viral infection on evoked cough in guinea pigs was evaluated. Guinea pigs were inoculated intranasally with either parainfluenza type 3 (PIV3) and cough was quantified in conscious animals. The guinea pigs infected with PIV3 (day 4) coughed nearly three times more than those treated with the viral growth medium in response to capsaicin, citric acid, and bradykinin. Since capsaicin, citric acid, and bradykinin evoked coughing in guinea pigs can be inhibited by drugs that antagonize the transient receptor potential cation channel, subfamily V, member 1 (TRPV1), it was reasoned that the virally-induced hypertussive state may involve alterations in TPRV1 activity. PIV3 infection caused a phenotypic switch in tracheal nodose Aδ "cough receptors" such that nearly 50% of neurons began to express, de novo, TRPV1 mRNA. There was also an increase TRPV1 expression in jugular C-fiber neurons as determined by qPCR. It has previously been reported that tracheal-specific nodose neurons express the BDNF receptor TrkB and jugular neurons express the NGF receptor TrkA. Jugular neurons also express the artemin receptor GFRα3. All these neurotrophic factors have been associated with increases in TRPV1 expression. In an ex vivo perfused guinea pig tracheal preparation, we demonstrated that within 8 h of PIV3 infusion there was no change in NGF mRNA expression, but there was nearly a 10-fold increase in BDNF mRNA in the tissue, and a small but significant elevation in the expression of artemin mRNA. In summary, PIV3 infection leads to elevations in TRPV1 expression in the two key cough evoking nerve subtypes in the guinea pig trachea, and this is associated with a hypertussive state with respect to various TRPV1 activating stimuli. PMID:27213574

  12. Parainfluenza 3-Induced Cough Hypersensitivity in the Guinea Pig Airways

    PubMed Central

    Lieu, TinaMarie; Muroi, Yukiko; Potenzieri, Carl; Undem, Blair E.; Gao, Peisong; Han, Liang; Canning, Brendan J.

    2016-01-01

    The effect of respiratory tract viral infection on evoked cough in guinea pigs was evaluated. Guinea pigs were inoculated intranasally with either parainfluenza type 3 (PIV3) and cough was quantified in conscious animals. The guinea pigs infected with PIV3 (day 4) coughed nearly three times more than those treated with the viral growth medium in response to capsaicin, citric acid, and bradykinin. Since capsaicin, citric acid, and bradykinin evoked coughing in guinea pigs can be inhibited by drugs that antagonize the transient receptor potential cation channel, subfamily V, member 1 (TRPV1), it was reasoned that the virally-induced hypertussive state may involve alterations in TPRV1 activity. PIV3 infection caused a phenotypic switch in tracheal nodose Aδ “cough receptors” such that nearly 50% of neurons began to express, de novo, TRPV1 mRNA. There was also an increase TRPV1 expression in jugular C-fiber neurons as determined by qPCR. It has previously been reported that tracheal-specific nodose neurons express the BDNF receptor TrkB and jugular neurons express the NGF receptor TrkA. Jugular neurons also express the artemin receptor GFRα3. All these neurotrophic factors have been associated with increases in TRPV1 expression. In an ex vivo perfused guinea pig tracheal preparation, we demonstrated that within 8 h of PIV3 infusion there was no change in NGF mRNA expression, but there was nearly a 10-fold increase in BDNF mRNA in the tissue, and a small but significant elevation in the expression of artemin mRNA. In summary, PIV3 infection leads to elevations in TRPV1 expression in the two key cough evoking nerve subtypes in the guinea pig trachea, and this is associated with a hypertussive state with respect to various TRPV1 activating stimuli. PMID:27213574

  13. Experimental congenital syphilis: guinea pig model.

    PubMed Central

    Wicher, K; Baughn, R E; Wicher, V; Nakeeb, S

    1992-01-01

    Neonates born to female guinea pigs of either a highly susceptible (C4D) or a resistant (Albany) strain, infected prior to or during pregnancy with a single dose of Treponema pallidum, showed in their sera from the first day of life immunoglobulin M (IgM) antibodies to T. pallidum, circulating immune complexes consisting of IgM antibodies and treponemal antigens, and IgM rheumatoid factor. Although the animals were asymptomatic for a 6-month observation period, several lines of evidence indicated that they were infected in utero. Molecular analysis of whole sera, purified serum IgM fraction, or dissociated immune complexes demonstrated IgM reactivity against one (47 kDa) or more of several T. pallidum peptides (15, 17, 37, 42, 45, and 87 kDa) recognized as integral membrane components. Sequential analysis of the neonates' sera by immunoblot and enzyme-linked immunosorbent assay, using alcohol-treated T. pallidum, T. phagedenis biotype Reiter, and T. vincentii, demonstrated early IgM antibodies followed 3 to 4 months later by IgG2- and IgG1-specific antibodies to T. pallidum. Moreover, an infectivity test done in five rabbits with pooled tissue extracts prepared from liveborn or stillborn animals evoked a seroconversion in two rabbits (reactive Venereal Disease Research Laboratory and fluorescent treponemal antibody tests), suggesting the presence of T. pallidum in the organs. Sera from neonates born to either T. phagedenis biotype Reiter-injected mothers or three normal pregnant females were all serologically negative. The model offers new possibilities for exploration of factors responsible for asymptomatic infection often observed in human congenital syphilis. Images PMID:1729190

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

    NASA Astrophysics Data System (ADS)

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

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

  15. The role of TRPM8 in the Guinea-pig bladder-cooling reflex investigated using a novel TRPM8 antagonist.

    PubMed

    Gardiner, Jennifer C; Kirkup, Anthony J; Curry, John; Humphreys, Sian; O'Regan, Paul; Postlethwaite, Michael; Young, Kimberley C; Kitching, Linda; Ethell, Brian T; Winpenny, David; McMurray, Gordon

    2014-10-01

    Patients with overactive bladder often exhibit abnormal bladder contractions in response to intravesical cold saline (positive ice-water test). The molecular entity involved in cold sensation within the urinary bladder is unknown, but a potential candidate is the ion channel, transient receptor potential (melastatin)-8 (TRPM8). The objective of the present study was to investigate the role of TRPM8 in a bladder-cooling reflex evoked in anaesthetised guinea-pigs that is comparable to the positive ice-water test seen in patients. Guinea-pig TRPM8 was cloned from L6 dorsal root ganglia (DRG) and expressed in HEK293 cells. Functional agonist- and cold-induced Ca2+ influx and electrophysiology assays were performed in these cells, and for comparison in HEK293 cells expressing human TRPM8, using a novel TRPM8 antagonist, the S-enantiomer of 1-phenylethyl 4-(benzyloxy)-3-methoxybenzyl (2-aminoethyl) carbamate hydrochloride (PBMC). Potency data from these assays was used to calculate intravenous infusion protocols for targeted plasma concentrations of PBMC in studies on micturition reflexes evoked by intravesical infusion of menthol or cold saline in anaesthetised guinea-pigs. Tissue expression of TRPM8 in guinea-pig bladder, urethra and in dorsal root ganglia neurones traced from the bladder was also investigated. TRPM8 mRNA and protein were detected in L6 dorsal root ganglia, bladder urothelium and smooth muscle. PBMC antagonised in vitro activation of human and guinea-pig TRPM8 and reversed menthol and cold-induced facilitation of the micturition reflex at plasma concentrations consistent with in vitro potencies. The present data suggest that the bladder-cooling reflex in the guinea-pig involves TRPM8. The potential significance of TRPM8 in bladder disease states deserves future investigation. PMID:25058909

  16. Prevention of antigen-induced bronchial hyperreactivity and airway inflammation in sensitized guinea-pigs by tacrolimus.

    PubMed Central

    Lapa e Silva, J R; Ruffié, C; Lefort, J; Nahori, M A; Vargaftig, B B; Pretolani, M

    1999-01-01

    We examined the effect of the immunosuppressive agent, tacrolimus (FK506), on antigen-induced bronchial hyperreactivity to acetylcholine and leukocyte infiltration into the airways of ovalbumin-challenged guinea-pigs. Subcutaneous injection of 0.5 mg/kg of FK506, 1 h before and 5 h after intra-nasal antigen challenge prevented bronchial hyperreactivity to aerosolized acetylcholine, eosinophilia in bronchoalveolar lavage (BAL) fluid and bronchial tissue and the invasion of the bronchial wall by CD4+ T-lymphocytes. FK506 also suppressed ovalbumin-induced increase in the number of leukocytes adhering to the pulmonary vascular endothelium and expressing alpha4-integrins. Inhibition by FK506 of antigen-induced bronchial hyperreactivity in sensitized guinea-pigs may thus relate to its ability to prevent the emergence of important inflammatory components of airway inflammation, such as eosinophil accumulation, as well as CD4+ T-lymphocyte infiltration into the bronchial tissue. PMID:10704085

  17. Effect of Rb+ on cromakalim-induced relaxation and ion fluxes in guinea pig trachea.

    PubMed

    Foster, K A; Arch, J R; Newson, P N; Shaw, D; Taylor, S G

    1992-11-01

    The effects of cromakalim, verapamil and salbutamol have been examined in guinea pig trachealis smooth muscle in both Krebs physiological salt solution and Krebs solution where K+ has been replaced by Rb+. Cromakalim-induced relaxation in the presence of Rb+ was reduced in extent and became transient, whilst the relaxation response to verapamil was enhanced and that to salbutamol unaffected. The transient relaxation occurring in Rb+ was blocked by quinidine and glibenclamide. The presence of extracellular Rb+ also prevented cromakalim-stimulated efflux of both 86Rb+ and 42/43K+. There was, however, no effect on cromakalim-stimulated 86Rb+ uptake. It is proposed that cromakalim is opening two populations of potassium channel in guinea pig tracheal smooth muscle, one of which is susceptible to blockade by Rb+ and one of which is not. The latter channel appears to play the dominant role in cromakalim-stimulated uptake, and is responsible for the transient relaxation response in the presence of rubidium, whilst the former is responsible for the maintained relaxation. PMID:1468491

  18. Long-acting progestin-only contraceptives impair endometrial vasculature by inhibiting uterine vascular smooth muscle cell survival

    PubMed Central

    Kayisli, Umit A.; Basar, Murat; Guzeloglu-Kayisli, Ozlem; Semerci, Nihan; Atkinson, Helen C.; Shapiro, John; Summerfield, Taryn; Huang, S. Joseph; Prelle, Katja; Schatz, Frederick; Lockwood, Charles J.

    2015-01-01

    Molecular mechanisms responsible for abnormal endometrial vasculature in women receiving long-acting progestin-only contraceptives (LAPCs) are unknown. We hypothesize that LAPCs impair vascular smooth muscle cell (VSMC) and pericyte proliferation and migration producing thin-walled hyperdilated fragile microvessels prone to bleeding. Proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (αSMA) double-immunostaining assessed VSMC differentiation and proliferation in endometria from women before and after DepoProvera (Depo) treatment and from oophorectomized guinea pigs (OVX-GPs) treated with vehicle, estradiol (E2), medroxyprogesterone acetate (MPA), or E2+MPA. Whole-genome profiling, proliferation, and migration assays were performed on cultured VSMCs treated with MPA or etonogestrel (ETO). Endometrial vessels of Depo-administered women displayed reduced αSMA immunoreactivity and fewer PCNA (+) nuclei among αSMA (+) cells (P < 0.008). Microarray analysis of VSMCs identified several MPA- and ETO-altered transcripts regulated by STAT1 signaling (P < 2.22 × 10−6), including chemokine (C-C motif) ligand 2 (CCL2). Both MPA and ETO reduce VSMC proliferation and migration (P < 0.001). Recombinant CCL2 reversed this progestin-mediated inhibition, whereas a STAT1 inhibitor abolished the CCL2 effect. Similarly, the endometria of MPA treated OVX-GPs displayed decreased αSMA staining and fewer PCNA (+) nuclei in VSMC (P < 0.005). In conclusion, LAPCs promote abnormal endometrial vessel formation by inhibiting VSMC proliferation and migration. PMID:25847994

  19. 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 113.38 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD...

  20. 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. PMID:20015469

  1. 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 113.38 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD...

  2. 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.

  3. 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)

  4. NASAL LAVAGE ANTIOXIDANTS IN GUINEA PIGS, RATS AND MICE

    EPA Science Inventory

    A new nasal lavage technique was used to compare the washout curves and total lavagable amounts (per kg body wt) of protein, ascorbate, glutathione and uric acid in guinea pigs, rats and mice. Washout curves were usually observed with sequential lavage volumes of saline of 1.0 ml...

  5. Alpha1-adrenoceptors in the guinea pig thoracic aorta.

    PubMed

    Yamamoto, Y; Koike, K

    1999-01-01

    In the present study, we tried to determine which alpha1-adrenoceptor subtypes are involved in the guinea pig thoracic aorta by using in vitro functional analysis. In first, we tried to estimate the pA2 values of some key alpha1-adrenoceptor antagonists (prazosin, 5-methylurapidil, WB4101, BMY7378 and tamsulosin) against responses to norepinephrine in the thoracic aorta of guinea pigs. The concentration-response curves of norepinephrine were rightward shifted by the presence of prazosin, 5 methylurapidil, WB4101, BMY7378 and tamsulosin. The pA2 values for these antagonists against norepinephrine were 7.83, 7.78, 8.20, 5.73 and 9.57, respectively. In second, we tried to compare the estimated pA2 values obtained in the present study with reported pKi and pA2 values for cloned and native alpha1-adrenoceptor subtypes. In rabbit mesenteric artery, trigone, urethra, prostate and human lower urinary tract which were proposed to contain the putative alpha1L-adenoceptor, we obtained the good correlation for the pA2 values reported in these tissues with pA2 values estimated in guinea pig thoracic aorta. Moreover, regression lines were close to the line of identity. These results suggest that the alpha1-adenoceptors mediating contraction of guinea pig thoracic aorta are similar pharmacologically to the putative alpha1L-adenoceptor subtype in rabbit mesenteric artery, trigone, urethra, prostate and human lower urinary tract. As a final point, guinea pig thoracic aorta may be able to use as a tool to develop the new alpha1-adrenoceptor antagonist which is therapeutically advantageous in the treatment of urinary tract obstruction (e. g., in benign prostatic hyperplasia). PMID:10733154

  6. Course of coccidioidomycosis in intratracheally infected guinea pigs.

    PubMed Central

    Cox, R A; Pavey, E F; Mead, C G

    1981-01-01

    Two hundred Hartley-inbred guinea pigs were infected intratracheally with 50 viable arthrospores of Coccidioides immitis. At weeks 1 through 10 postinfection, groups of 20 guinea pigs were assayed for skin test, macrophage migration inhibitory factor (MIF), and lymphocyte transformation (LT) responses to coccidioidin. Forty-eight hours after skin testing and just before MIF and LT assays, blood was obtained for complement-fixing (CF) antibody titers and the animals were autopsied to assess the extent of fungal dissemination. Immunological assays established that skin tests and MIF responses converted within 3 weeks of infection. LT responses were not demonstrable until week 5. Dissemination of C. immitis to the liver or spleen was an early event, with 21% of guinea pigs positive by week 2 and 70% positive by week 5. CF antibody titers were demonstrable at week 5, increased logarithmically through week 7, then increased at a slower rate thereafter. Concomitant with the decreased rate of antibody production, guinea pigs began to clear C. immitis from their extrapulmonary tissues. Skin test responses peaked at 6 weeks postinfection when CF antibody titers were less than or equal to 1:16 and then plateaued with increased CF titers. Although this overall immunological profile is consistent with the disease in humans, there was not a direct correlation between CF antibody titer and dissemination to the liver or spleen, nor was there an inverse correlation between CF antibody titers and skin test or MIF responses. Rather, CF antibody titers and cell-mediated immune responses were equally demonstrable in guinea pigs with disseminated or nondisseminated disease. PMID:7216468

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

    PubMed

    Kline, Loren; Karpinski, Edward

    2016-06-01

    Progesterone (P), 17β-estradiol (E2), and dihydrotestosterone (DHT) affect gallbladder motility. When gallbladders were taken from women and men, women had more estrogen and P receptors than men. Both P and E2 had an inhibitory effect upon gallbladder contractility in men and premenopausal and postmenopausal women. Similar findings have been reported in gallbladder strips from male and female guinea pigs. In the present study, there was no significant difference in the amount of E2-, P-, or DHT-induced relaxation of CCK-induced tension when the responses in gallbladder strips from male and female guinea pigs were compared. Three metabolites of P were used: 17-hydroxyprogesterone (17-P), 20α-hydroxyprogesterone (20-P), and 21-hydroxyprogesterone (21-P). There was no significant difference in the responses from strips from male and female guinea pigs. In order to determine if the effects of E2 and P were additive, strips from male animals were exposed to either E2 or P and the amount of relaxation recorded. After recovery, the strips were exposed to E2 or P in reverse order to ensure the order of treatment had no effect. Then, the strips were treated with both E2 and P simultaneously and the relaxation recorded. This procedure was repeated with strips from female guinea pigs. The effect of E2 and P was found to be additive; however, the response of the strips from each sex were not significantly different. It is concluded that the sex of the guinea pig has no significant effect on the response to the sex hormones used. PMID:27354545

  8. Influence of resting tension on protease-activated receptor-mediated relaxation in guinea-pig tracheas.

    PubMed

    Franchi-Micheli, Sergio; Mazzetti, Luca; Cantore, Mirian; Ciuffi, Mario; Zilletti, Lucilla; Failli, Paola

    2005-01-01

    We investigate the role of resting tension on thrombin (THR) induced relaxation of guinea-pig tracheas precontracted with acetylcholine (ACh). Isometric contractions of isolated guinea-pig tracheas were recorded at 4 and 6 g resting tension; and ACh dose-response curves were performed. THR relaxed ACh-precontracted tracheas and this effect was mimicked by the type 2 protease activating receptor agonist peptide (PAR-2 AP) and trypsin. The relaxant effect of 3 U ml(-1) THR and 100 nmol ml(-1) PAR-2 AP was prevented at 4 g by preincubation with the nitric oxide synthase (NOS) inhibitor l-NAME and at 6g resting tension by ibuprofen and diclofenac. However, adenosine trisphospahate (ATP) relaxation was totally prevented by cyclooxygenase (COX) inhibitors but not by NOS inhibitors at both resting tensions. Resting tension influenced the effect of PGE2 on contractile tone of isolated guinea-pig tracheas, the maximal relaxation being -11.1+/-2.97 and -2.0+/-0.4 6 mg mg(-1) tissue wet weight at 6 and 4 g, respectively. Moreover, 30 nmol ml(-1) PGE2 can relax ACh-precontracted tracheas, being the effect up to 91 and 30% at 6 and 4 g, respectively. These data demonstrate that trachea responsiveness is highly dependent on the smooth muscle length, revealing new aspects of stretch-activated receptors that can influence trachea responsiveness in vivo. PMID:15649856

  9. Effects of aqueous leaf extract of Bryophyllum pinnatum on guinea pig tracheal ring contractility.

    PubMed

    Ozolua, Raymond I; Eboka, Chuks J; Duru, Comfort N; Uwaya, Dickson O

    2010-01-01

    Aqueous leaf extract of Bryophyllum pinnatum Lam (Crassulaceae) is used as a cough remedy and for the prophylaxis of asthma. Since drugs used for the prophylaxis of asthma may be acting on airway smooth muscles, we investigated the effects of aqueous leaf extract of the plant on the contractile responses of isolated tracheal rings. Guinea pigs were grouped into non-sensitized, ovalbumin (OA)-sensitized, OA-sensitized but 200 mg/kg/day x 21 extract-treated, and OA-sensitized but 400 mg/kg/day x 21 extract-treated. The extract was administered orally. Tracheal rings obtained from the four groups were mounted in organ baths and used to test spasmolytic and antispasmodic effects of the extract on histamine or carbachol-induced contractions. Concentrations of 0.125-1.0 mg/ml of the extract did not relax histamine or carbachol-induced precontractions. The presence of 0.25-1.0 mg/ml of the extract in organ baths significantly reduced the maximal contractile responses (Emax) to cumulative concentrations of histamine or carbachol irrespective of the experimental group. pD2 values were significantly reduced for histamine and carbachol in rings obtained from 400 mg/kg/day x 21 extract-treated group. It is concluded that aqueous leaf extract of B. pinnatum possesses antispasmodic effects on the guinea pig tracheal rings. The results lend credence to the use of the extract for the prophylaxis of asthma in ethnomedicine. PMID:22314954

  10. Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD.

    PubMed

    Pera, T; Zuidhof, A; Valadas, J; Smit, M; Schoemaker, R G; Gosens, R; Maarsingh, H; Zaagsma, J; Meurs, H

    2011-10-01

    Airway remodelling and emphysema are major structural abnormalities in chronic obstructive pulmonary disease (COPD). In addition, pulmonary vascular remodelling may occur and contribute to pulmonary hypertension, a comorbidity of COPD. Increased cholinergic activity in COPD contributes to airflow limitation and, possibly, to inflammation and airway remodelling. This study aimed to investigate the role of acetylcholine in pulmonary inflammation and remodelling using an animal model of COPD. To this aim, guinea pigs were instilled intranasally with lipopolysaccharide (LPS) twice weekly for 12 weeks and were treated, by inhalation, with the long-acting muscarinic receptor antagonist tiotropium. Repeated LPS exposure induced airway and parenchymal neutrophilia, and increased goblet cell numbers, lung hydroxyproline content, airway wall collagen and airspace size. Furthermore, LPS increased the number of muscularised microvessels in the adventitia of cartilaginous airways. Tiotropium abrogated the LPS-induced increase in neutrophils, goblet cells, collagen deposition and muscularised microvessels, but had no effect on emphysema. In conclusion, tiotropium inhibits remodelling of the airways as well as pulmonary inflammation in a guinea pig model of COPD, suggesting that endogenous acetylcholine plays a major role in the pathogenesis of this disease. PMID:21349917

  11. Scanning electron microscopy of terminal airways of guinea pigs chronically inhaling diesel exhaust

    SciTech Connect

    Kucukcelebi, A.; Mohamed, F.; Barnhart, M.I.

    1983-01-01

    The structural physiology of airways from 80 guinea pigs was examined for changes induced by diesel exhaust (DE) exposure. Acute, subacute and chronic studies contrasted inhalation effects of 250, 750, 1500 and 6000 micrograms DE/m3 with ''clean air'' breathing of age-matched controls. Nonciliated epithelial (Clara) cells, epithelial type 2 cells and alveolar macrophages were increased in a DE dose dependent fashion. Also, eosinophils, were recruited. Epithelial type 1 cells of the distal airways internalized DEP. The relative dustiness (particulate density) of airways was assessed from coded specimens. Some 86% of DE exposed animals were correctly identified. Scanning Electron Microscopy (SEM) resolved surface located DE particulates (DEP). Single particles, loose clusters, low density agglomerates occurred. While SEM visual clues are insufficient for absolute identification of DE particles, there was supporting evidence from transmission electron microscopy (TEM) and from SEM studies comparing vascular with intratracheally fixed specimens. Presumptive DEP were notable on bifurcation bridges in respiratory bronchioles and alveolar ducts while alveolar outpockets had heavy dust burdens. Clumps of macrophages in such alveoli almost occluded the airspace. We conclude that normal guinea pigs appear to adapt to a chronic DE stress environment. But, the ultrastructural basis (cellular protrusions, DEP agglomerates and secretional debris) exists in peripheral airways for airflow instability and increased airflow resistance.

  12. Propagation of pacemaker activity in the guinea-pig antrum

    PubMed Central

    Hennig, G W; Hirst, G D S; Park, K J; Smith, C B; Sanders, K M; Ward, S M; Smith, T K

    2004-01-01

    Cyclical periods of depolarization (slow waves) underlie peristaltic contractions involved in mixing and emptying of contents in the gastric antrum. Slow waves originate from a myenteric network of interstitial cells of Cajal (ICC-MY). In this study we have visualized the sequence and propagation of Ca2+ transients associated with pacemaker potentials in the ICC network and longitudinal (LM) and circular muscle (CM) layers of the isolated guinea-pig gastric antrum. Gastric antrum was dissected to reveal the ICC-MY network, loaded with Fluo-4 AM and activity was monitored at 37°C. Ca2+ waves propagated throughout the ICC-MY network at an average velocity of 3.24 ± 0.12 mm s−1 at a frequency of 4.87 ± 0.16 cycles min−1 (n = 4). The propagation of the Ca2+ wave often appeared ‘step-like’, with separate regions of the network being activated after variable delays. The direction of propagation was highly variable (Δ angle of propagation 44.3 ± 10.9 deg per cycle) and was not confined to the axes of the longitudinal or circular muscle. Ca2+ waves appeared to spread out radially from the site of initiation. The initiating Ca2+ wave in ICC-MY was correlated to secondary Ca2+ waves in intramuscular interstial cells of Cajal, ICC-IM, and smooth muscle cells, and the local distortion (contraction) in a field of view. TTX (1 μm) had little effect on slow wave or pacemaker potential activity, but 2-APB (50 μm) blocked all Ca2+ waves, indicating a pivotal role for intracellular Ca2+ stores. Nicardipine (2 μm) eliminated the Ca2+ transient generated by smooth muscle, but did not affect the fast upstroke associated with ICC-MY. These results indicate that slow waves follow a sequence of activation, beginning with the ICC-MY and ICC-IM network, followed later by a sustained Ca2+ transient in the muscle layers that is responsible for contraction. PMID:14754999

  13. Pharmacological characteristics of liriodenine, isolated from Fissistigma glaucescens, a novel muscarinic receptor antagonist in guinea-pigs.

    PubMed Central

    Lin, C H; Chang, G J; Su, M J; Wu, Y C; Teng, C M; Ko, F N

    1994-01-01

    1. The pharmacological activities of liriodenine, isolated from Fissistigma glaucescens, were determined in isolated trachea, ileum and cardiac tissues of guinea-pigs. 2. Liriodenine was found to be a muscarinic receptor antagonist in guinea-pig trachea as revealed by its competitive antagonism of carbachol (pA2 = 6.22 +/- 0.08)-induced smooth muscle contraction. It was slightly more potent than methoctramine (pA2 = 5.92 +/- 0.05), but was less potent than atropine (pA2 = 8.93 +/- 0.07), pirenzepine (pA2 = 7.02 +/- 0.09) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, pA2 = 8.72 +/- 0.07). 3. Liriodenine was also a muscarinic antagonist in guinea-pig ileum (pA2 = 6.36 +/- 0.10) with a pA2 value that closely resembled that obtained in the trachea. 4. Liriodenine was 10 fold less potent in atrial preparations (left atria, pA2 = 5.24 +/- 0.04; right atria, pA2 = 5.35 +/- 0.09 and 5.28 +/- 0.07 for inotropic and chronotropic effects, respectively) than in smooth muscle preparations. 5. High concentration of liriodenine (300 microM) partially depressed the contractions induced by U-46619, histamine, prostaglandin F2 alpha, neurokinin A, leukotriene C4 and high K+ in the guinea-pig trachea. The inhibitions were characterized by a rightward shift in the concentration-response curves with suppression of their maximal contraction. 6. High concentration of liriodenine (300 microM) did not affect U-46619- or neurokinin A-induced tracheal contraction in the presence of nifedipine (1 microM) or in Ca(2+)-free (containing 0.2 mM EGTA) medium. 7. Neither cyclic AMP nor cyclic GMP content of guinea-pig trachealis was changed by liriodenine (30-300 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7812621

  14. 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.

  15. 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.

  16. Diffuse Infiltrative Gastrointestinal Lipomatosis in a Guinea Pig (Cavia porcellus)

    PubMed Central

    Beninson, Jennifer A; Keller, Jill M; Hoenerhoff, Mark J

    2015-01-01

    An intact adult male guinea pig (Cavia porcellus) went into cardiopulmonary arrest during a surgical procedure, and efforts at resuscitation were unsuccessful. Gross examination revealed a gastric rupture along the greater curvature of the stomach, which was associated with free blood and ingesta in the abdominal cavity, and a 2-cm nodular, partially circumferential, soft-to-firm mass within the pyloric region. Histologically, the pyloric mass was composed of sheets of infiltrative adipocytes expanding the muscular wall. Similar infiltrative sheets of adipocytes were present adjacent to the rupture site and within the small intestine, cecum, and colon. These findings are consistent with diffuse infiltrative lipomatosis, an exceedingly rare condition in human and veterinary species. This report is the first description of this rare disease in guinea pigs, and the concurrent involvement of both the stomach and intestines has not been reported in any veterinary species. PMID:26473346

  17. 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.

  18. 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. PMID:25592147

  19. 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. PMID:19222441

  20. The purinoceptors of the guinea-pig isolated taenia caeci.

    PubMed

    Piper, A S; Hollingsworth, M

    1995-07-01

    The guinea-pig taenia caeci contains both P1 and P2 purinoceptors mediating relaxation. The P2 purinoceptors have been further characterized using an experimental approach designed to minimise complicating factors. In the presence of the adenosine uptake inhibitor S-(4-nitrobenzyl)-6-thioinosine (NBTI, 300 nM) and a pA100 concentration of the P1 purinoceptor antagonist 8-sulphophenyltheophylline (140 microM), the potency order of agonists was: 2-methylthio-ATP > adenosine 5'-triphosphate (ATP) = alpha, beta-methylene ATP > beta, gamma-methylene ATP > uridine 5'-triphosphate. Suramin antagonized ATP (pA2 = 5.52 +/- 0.17, Schild plot slope = 0.67 +/- 0.08) and 2-methylthio-ATP (pA2 = 5.78 +/- 0.30, Schild plot slope = 1.37 +/- 0.39) while responses to 5'-N-ethylcarboxamidoadenosine (NECA) were unaffected. The findings suggest that suramin, while it is selective for P2 relative to P1 purinoceptors, is not a true competitive antagonist. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) antagonized ATP in isolated guinea-pig vas deferens, but had no effect on responses to ATP in guinea-pig taenia caeci indicating it is selective for P2X relative to P2Y purinoceptors. PMID:7589176

  1. Establishment, Culture, and Characterization of Guinea Pig Fetal Fibroblast Cell

    PubMed Central

    Mahboobi, Reza; Dianatpour, Mehdi; Zare, Shahrokh; Hosseini, Seyed Ebrahim

    2014-01-01

    Establishment of Guinea pig fetal fibroblast cells and their biological evaluation before and after cryopreservation were the main purposes of this study. After determination of the proper age of pregnancy by ultrasonography, 30 days old fetuses of Guinea pigs were recovered. Their skins were cut into small pieces (1 mm2) and were cultured. When reaching 80–90% confluence, the cells were passaged. Cells of the second and eighth passages were cultured in 24-well plates (4 × 104 cells/well) for 6 days and three wells per day were counted. The average cell counts at each time point were then plotted against time and the population doubling time (PDT) was determined. Then, vials of cells (2 × 106 cells/mL) were cryopreserved for 1 month and after thawing, the cell viability was evaluated. The PDT of the second passage was about 23 h and for the eighth passage was about 30 h. The viability of the cultures was 95% in the second passage and 74.5% in the eighth passage. It was shown that the Guinea pig fetal fibroblast cell culture can be established using the adherent culture method while, after freezing, the viability indices of these cells were favorable. PMID:24790770

  2. 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. PMID:26139838

  3. Antigen-binding small lymphocytes in the guinea-pig

    PubMed Central

    Donald, D.; Beck, J. Swanson

    1974-01-01

    The time course of the relative distribution of small lymphocytes binding 125I-labelled human thyroglobulin (HTg) in cell suspensions from the peripheral blood and various lymphoid organs was studied in guinea-pigs at progressive intervals up to 28 days after immunization with an emulsion of HTg and BCG in Freund's incomplete adjuvant (FIA). Small lymphocytes binding 125I-labelled HTg were first detected in peripheral blood, popliteal (draining) lymph node, spleen and bone marrow preparations on the 10th day, and in mesenteric (distant) lymph node and thymus preparations on the 14th day after primary immunization. In general, the percentage of these cells increased progressively thereafter until the end of the period of study. Blocking experiments with unlabelled antigens indicated that the binding of 125I-labelled HTg by small lymphocytes was specific. An anti-HTg antibody cytophilic for guinea-pig small lymphocytes was demonstrated by the passive transfer of antigen-binding capacity to lymphocytes of unimmunized animals with hyperimmune guinea-pig serum. It is proposed that, in these experiments, anti-HTg cytophilic antibody was bound first to small lymphocytes in the tissues participating actively in the immune response (popliteal node, spleen and bone marrow) before spilling over into the general circulation to coat lymphocytes at other sites (mesenteric node and thymus). PMID:4604111

  4. Acute effects of aflatoxins on guinea pig isolated ileum.

    PubMed

    Luzi, A; Cometa, M F; Palmery, M

    2002-10-01

    Previous studies on the aflatoxins have focused mainly on their chronic toxic effects. In this study we investigated the acute gastrointestinal effects of four common aflatoxins on isolated guinea pig ileum. AFB(1) (EC(50) 4.6+/-0.4 microM) and AFB(2) (EC(50)17+/-4.4 microM) contracted isolated guinea pig ileum in a dose-dependent manner, whereas AFG(1) and AFG(2) evoked no contractions. Atropine (5.9 nM 11.8 and 23.6 nM) antagonized AFB(1)-induced contractions in a dose-dependent manner. Pretreatment with the nicotinic ganglionic blocker, hexamethonium (up to 55 microM), left AFB(1)-induced contractions unchanged. In contrast, tetrodotoxin (0.3 microM), blocked AFB(1) contractile activity. The two inhibitors of ACh release, morphine (0.3 microM) and clonidine (0.4 microM), antagonized EC(50) AFB(1)-induced contractions, and apamin, a drug that increases neuronal excitability, facilitated the EC(50) AFB(1)-induced contractile effect. The choline uptake blocker, hemicholinium (17.4 microM) markedly reduced AFB(1)-induced contractions. These results suggest that aflatoxins induce their contractile effect indirectly through the cholinergic system by stimulating acetylcholine release from the postganglionic parasympathetic nerve endings. The acute actions of aflatoxins on isolated guinea pig ileum could explain their acute gastrointestinal effects in humans and animals. PMID:12206819

  5. 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.

  6. Organophosphorus Inhibition and Characterization of Recombinant Guinea Pig Acetylcholinesterase.

    PubMed

    Ruark, Christopher D; Chapleau, Richard R; Mahle, Deirdre A; Gearhart, Jeffery M

    2015-01-01

    Organophosphorus (OP) pesticides and nerve agents have been designed to inhibit the hydrolysis of the neurotransmitter acetylcholine by covalently binding to the active site serine of acetylcholinesterase while Alzheimer drugs and prophylactics, such as tacrine, are characterized by reversible binding. Historically, the guinea pig has been believed to be the best non-primate model for OP toxicology and medical countermeasure development because, similarly to humans, guinea pigs have low amounts of circulating OP metabolizing carboxylesterase. To explore the hypothesis that guinea pigs are the appropriate responder species for OP toxicology and medical countermeasure development, guinea pig acetylcholinesterase (gpAChE) was cloned into pENTR/D-TOPO, recombined into pT-Rex-DEST30 and expressed in Human Embryonic Kidney 293 cells. Recombinant gpAChE was purified to a specific activity of 800 U/mg using size exclusion and immobilized nickel affinity chromatography, with purity confirmed by gel electrophoresis. Ellman's assay was used to enzymatically characterize gpAChE, identifying a K(M) of 154±18.7 µmol L(-1) and a k(cat) of 4.79x10(4)±5.26x10(2) /sec. Apparent gpAChE IC50's for diisopropylfluorophosphate, dicrotophos, paraoxon, and an Alzheimer's drug, tacrine, were found to be 10.1±1.98, 337±108, 1.02±0.29 and 0.30±0.01 µmol L(-1), respectively. Apparent gpAChE inhibition constants for diisopropylfluorophosphate, dicrotophos, paraoxon, and tacrine were found to be 8.40±0.60, 4.50±0.30, 0.29±0.01 and 0.42±0.07 µmol L(-1), respectively. Lineweaver-Burk plots confirmed tacrine as a mixed inhibitor and paraoxon, dicrotophos and diisopropylfluorophosphate as irreversible non-competitive inhibitors. gpAChE bimolecular rate constants for diisopropylfluorophosphate, dicrotophos and paraoxon were found to be 1.44±0.33x10(4), 1.56±0.12x10(3) and 4.57± 0.23x10(5) L µmol(-1) min(-1), respectively. Although the blood levels of OP metabolizing carboxylesterases

  7. TRANSPORT OF SALT AND WATER IN RABBIT AND GUINEA PIG GALL BLADDER.

    PubMed

    DIAMOND, J M

    1964-09-01

    A simple and reproducible method has been developed for following fluid transport by an in vitro preparation of mammalian gall bladder, based upon weighing the organ at 5 minute intervals. Both guinea pig and rabbit gall bladders transport NaCl and water in isotonic proportions from lumen to serosa. In the rabbit bicarbonate stimulates transport, but there is no need for exogenous glucose. The transport rate is not affected by removal of potassium from the bathing solutions. Albumin causes a transient weight loss from the gall bladder wall, apparently by making the serosal smooth muscle fibers contract. Active NaCl transport can carry water against osmotic gradients of up to two atmospheres. Under passive conditions water may also move against its activity gradient in the presence of a permeating solute. The significance of water movement against osmotic gradients during active solute transport is discussed. PMID:14212148

  8. Effects of inhaled municipal refuse incinerator fly ash in the guinea pig

    SciTech Connect

    Alarie, Y.; Iwasaki, M.; Stock, M.F.; Pearson, R.C.; Shane, B.S.; Lisk, D.J. )

    1989-01-01

    Fly ash was collected from two municipal refuse incinerators. It was analyzed for heavy metals, elements, and a wide range of toxic organics. It was resuspended in air for inhalation exposure of guinea pigs. These animals were exposed at high concentrations of each ash 6 h/d for 5 d, and tissues were taken 45 d after the exposure. Following the first exposure and after each daily exposure the ventilatory response of these animals upon challenge with CO{sub 2} was found to be depressed. Recovery occurred following exposure. Heavy metals, cadmium, lead, zinc, and mercury were elevated in the lungs of these animals. Histologic evaluation of pulmonary tissue revealed multifocal pneumoconiosis. Interstitial infiltration by macrophages and smooth muscle hypertrophy of blood vessels and bronchioles were also observed. There was no evidence of a dioxin-like toxic effect following inhalation of these ashes.

  9. In oculo transplants of myometrium from postpartum guinea pigs fail to support sympathetic reinnervation

    PubMed Central

    BRAUER, M. MONICA; BURNSTOCK, GEOFFREY; THRASIVOULOU, CHRISTOPHER; COWEN, TIMOTHY

    1998-01-01

    Sympathetic nerves to the enlarged fetus-containing region of the uterus undergo degenerative changes during late pregnancy and show slow regrowth after parturition. It is not known whether this unusual response of sympathetic nerves to smooth muscle hypertrophy is due to the sensitivity of short adrenergic neurons to hormonal changes, or whether the nerves respond to changes in the neurotrophic capacity of the target. We have investigated this question using in oculo transplantation. Small pieces of myometrium from the uterine horn of virgin guinea pigs, or from the region previously occupied by the placenta and fetus in postpartum guinea pigs, were transplanted into the anterior eye chamber. After 3 wk in oculo, the pattern of reinnervation of the transplants was assessed on whole mount stretch preparations stained for tyrosine hydroxylase. The histology of the transplants was examined in toluidine blue-stained semithin sections. Myometrial transplants from virgin donors and uterine artery transplants from both virgin and postpartum donors became organotypically reinnervated by sympathetic fibres from the host iris. In contrast, sympathetic nerves did not reinnervate myometrial transplants from postpartum donors, although they approached the transplants and became distributed in the surrounding connective tissue. All transplanted tissues showed a normal histological appearance. Both the myometrium and uterine artery from postpartum donors retained a hypertrophic appearance after 3 wk in oculo. We interpret these results to indicate that the degeneration of sympathetic nerves in late pregnancy, as well as their slow regrowth to the uterus after delivery, may be due to changes in uterine smooth muscle rather than a particular sensitivity of short adrenergic neurons to hormonal changes. PMID:10029184

  10. 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

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Primary enclosures used to transport... enclosures used to transport live guinea pigs and hamsters. No person subject to the Animal Welfare regulations shall offer for transportation, or transport, in commerce any live guinea pig or hamster in...

  12. Infection of Guinea Pigs with Vesicular Stomatitis New Jersey Virus Transmitted by Culicoides sonorensis (Diptera: Ceratopogonidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Interpretive Biting midges,Culicoides sonorensis were shown to be capable of transmitting vesicular stomatitis New Jersey virus (VSNJV) to guinea pigs. Despite seroconversion for VSNJV, none of the guinea pigs developed clinical signs when infected in the abdomen by either infected insects or by nee...

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

    PubMed Central

    FENG, RUI; LIU, YAN; SUN, XUEFEI; WANG, YAN; HU, HUIYUAN; GUO, FENG; ZHAO, JINSHENG; HAO, LIYING

    2015-01-01

    The aim of the present study was to isolate and characterize a complementary DNA (cDNA) clone encoding the calmodulin (CaM; GenBank accession no. FJ012165) gene from guinea pig hearts. The CaM gene was amplified from cDNA collected from guinea pig hearts and inserted into a pGEM®-T Easy vector. Subsequently, CaM nucleotide and protein sequence similarity analysis was conducted between guinea pigs and other species. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to investigate the CaM 3 expression patterns in different guinea pig tissues. Sequence analysis revealed that the CaM gene isolated from the guinea pig heart had ∼90% sequence identity with the CaM 3 genes in humans, mice and rats. Furthermore, the deduced peptide sequences of CaM 3 in the guinea pig showed 100% homology to the CaM proteins from other species. In addition, the RT-PCR results indicated that CaM 3 was widely and differentially expressed in guinea pigs. In conclusion, the current study provided valuable information with regard to the cloning and expression of CaM 3 in guinea pig hearts. These findings may be helpful for understanding the function of CaM3 and the possible role of CaM3 in cardiovascular diseases. PMID:26136979

  14. 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... pigs or hamsters contained therein; (3) the inner surfaces of corrugated fiberboard, cardboard,...

  15. 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.

  16. Multielement residues in tissues of guinea pigs fed sweet clover grown on fly ash.

    PubMed

    Furr, K; Stoewsand, G S; Bache, C A; Gutenmann, W A

    1975-05-01

    Yellow sweet clover (Melilotus officinalis) was harvested from fly ash dumped in a landfill site at Lansing, NY. This clover was chopped, dried, and formulated at 45% into an otherwise purified diet and fed to six guinea pigs for 90 days. Control sweet clover was harvested from gravelly subsoil and processed and fed to another group of guinea pigs for the same period. Samples of fly ash, gravelly subsoil, sweet clover, liver, kidneys, and left-rear gastrocnemius muscle of all guinea pigs were freeze-dried and analyzed for 35 elements by neutron activation analysis. The fly ash contained 28 elements at higher levels than the gravelly subsoil, while the clover harvested from fly ash contained 19 elements in increased amounts over those in the clover harvested from the gravel soil. Growth rate of both groups of guinea pigs was similar. Rubidium and selenium were present at higher levels in the tissues of guinea pigs fed the fly ash clover. PMID:1130838

  17. Effects of ONO-6950, a novel dual cysteinyl leukotriene 1 and 2 receptors antagonist, in a guinea pig model of asthma.

    PubMed

    Yonetomi, Yasuo; Sekioka, Tomohiko; Kadode, Michiaki; Kitamine, Tetsuya; Kamiya, Akihiro; inoue, Atsuto; Nakao, Takafumi; Nomura, Hiroaki; Murata, Masayuki; Nakao, Shintaro; Nambu, Fumio; Fujita, Manabu; Nakade, Shinji; Kawabata, Kazuhito

    2015-10-15

    We assessed in this study the anti-asthmatic effects of ONO-6950, a novel cysteinyl leukotriene 1 (CysLT1) and 2 (CysLT2) receptors dual antagonist, in normal and S-hexyl glutathione (S-hexyl GSH)-treated guinea pigs, and compared these effects to those of montelukast, a CysLT1 selective receptor antagonist. Treatment with S-hexyl GSH reduced animals LTC4 metabolism, allowing practical evaluation of CysLT2 receptor-mediated airway response. ONO-6950 antagonized intracellular calcium signaling via human and guinea pig CysLT1 and CysLT2 receptors with IC50 values of 1.7 and 25 nM, respectively (human receptors) and 6.3 and 8.2 nM, respectively (guinea pig receptors). In normal guinea pigs, both ONO-6950 (1 or 0.3 mg/kg, p.o.) and the CysLT1 receptor antagonist montelukast (0.3 or 0.1 mg/kg, p.o.) fully attenuated CysLT1-mediated bronchoconstriction and airway vascular hyperpermeability induced by LTD4. On the other hand, in S-hexyl GSH-treated guinea pigs ONO-6950 at 3 mg/kg, p.o. or more almost completely inhibited bronchoconstriction and airway vascular hyperpermeability elicited by LTC4, while montelukast showed only partial or negligible inhibition of these airway responses. In ovalbumin sensitized guinea pigs, treatment with S-hexyl GSH on top of pyrilamine and indomethacin rendered antigen-induced bronchoconstriction sensitive to both CysLT1 and CysLT2 receptor antagonists. ONO-6950 strongly inhibited this asthmatic response to the level attained by combination therapy with montelukast and BayCysLT2RA, a selective CysLT2 receptor antagonist. These results clearly demonstrate that ONO-6950 is an orally active dual CysLT1/LT2 receptor antagonist that may provide a novel therapeutic option for patients with asthma. PMID:26318198

  18. Effects of cigarette smoke and hypoxia on pulmonary circulation in the guinea pig.

    PubMed

    Ferrer, E; Peinado, V I; Castañeda, J; Prieto-Lloret, J; Olea, E; González-Martín, M C; Vega-Agapito, M V; Díez, M; Domínguez-Fandos, D; Obeso, A; González, C; Barberà, J A

    2011-09-01

    Cigarette smoke (CS) and chronic hypoxia (CH) can produce pulmonary hypertension. Similarities and differences between both exposures and their interaction have not been explored. The aim of the present study was to investigate the effects of CS and CH, as single factors or in combination, on the pulmonary circulation in the guinea pig. 51 guinea pigs were exposed to CS for 12 weeks and 32 were sham-exposed. 50% of the animals in each group were additionally exposed to CH for the final 2 weeks. We measured pulmonary artery pressure (P(pa)), and the weight ratio between the right ventricle (RV) and left ventricle plus the septum. Pulmonary artery contractility in response to noradrenaline (NA), endothelium-dependent vasodilatation and distensibility were evaluated in organ bath chambers. The number of small intrapulmonary vessels showing immunoreactivity to smooth muscle (SM) α-actin and double elastic laminas was assessed microscopically. CS and CH induced similar increases of P(pa) and RV hypertrophy (p<0.05 for both), effects that were further enhanced when both factors were combined. CH increased the contractility to NA (p<0.01) and reduced the distensibility (p<0.05) of pulmonary arteries. Animals exposed to CS showed an increased number of small vessels with positive immunoreactivity to SM α-actin (p<0.01) and those exposed to CH a greater proportion of vessels with double elastic laminas (p<0.05). We conclude that CH amplifies the detrimental effects of CS on the pulmonary circulation by altering the mechanical properties of pulmonary arteries and enhancing the remodelling of pulmonary arterioles. PMID:21310874

  19. The effect of ozone on inflammatory cell infiltration and airway hyperresponsiveness in the guinea pig lung

    SciTech Connect

    Schultheis, A.J.H.

    1993-01-01

    Inflammatory cells may contribute to the development of exaggerated bronchoconstrictor responses since a persistent link has been noted between pulmonary inflammation and airway hyperresponsiveness. In these studies guinea pigs were exposed to 2.0 ppm ozone for 4 hours, then immediately sacrificed or allowed to breathe filtered air for up to 14 days. Following ozone exposure there was an immediate massive neutrophil infiltration into the lung. Neutrophils in lung digest dropped to control values within 3-12 hours post-ozone but remained elevated in BAL fluid for 3 days. There was probable eosinophil degranulation within the first 24 hours post-ozone. Guinea pigs were hyperresponsive to vigal stimulation through 3 days post-ozone. Although they were also hyperresponsive to ACh, responses to MCh were unchanged. Neuronal M[sub 2] receptors were dysfunctional through 3 days post-ozone. There was resolution of inflammation, airway responsiveness, and neuronal M[sub 2] receptor function by 14 days post-exposure. This investigation has (1) confirmed an immediate lung inflammation following acute ozone exposure; (2) established that cells in BAL give a distorted reflection of inflammatory events in lung digest; (3) demonstrated that ozone-induced hyperresponsiveness is at least partially due to efferent cholinergic mechanisms without functional changes of muscarinic receptors on airway smooth muscle; (4) shown that ACh may not be an appropriate agent to test ozone-induced airway hyperresponsiveness; and (5) demonstrated that inhibitory neuronal M[sub 2] receptors are dysfunctional following ozone exposure. There was close linkage between these events, suggesting that they may be causally related. This investigation proposes a specific mechanism, dysfunction of neuronal M[sub 2] receptors, by which inflammatory cells could cause airway hyperresponsiveness following acute ozone exposure.

  20. 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

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

    PubMed

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

    2015-01-01

    The domesticated guinea pig, Cavia porcellus (Hystricomorpha, Rodentia), is an important laboratory species and a model for a number of human diseases. Nevertheless, genomic tools for this species are lacking; even its karyotype is poorly characterized. The guinea pig belongs to Hystricomorpha, a widespread and important group of rodents; so far the chromosomes of guinea pigs have not been compared with that of other hystricomorph species or with any other mammals. We generated full sets of chromosome-specific painting probes for the guinea pig by flow sorting and microdissection, and for the first time, mapped the chromosomal homologies between guinea pig and human by reciprocal chromosome painting. Our data demonstrate that the guinea pig karyotype has undergone extensive rearrangements: 78 synteny-conserved human autosomal segments were delimited in the guinea pig genome. The high rate of genome evolution in the guinea pig may explain why the HSA7/16 and HSA16/19 associations presumed ancestral for eutherians and the three syntenic associations (HSA1/10, 3/19, and 9/11) considered ancestral for rodents were not found in C. porcellus. The comparative chromosome map presented here is a starting point for further development of physical and genetic maps of the guinea pig as well as an aid for genome assembly assignment to specific chromosomes. Furthermore, the comparative mapping will allow a transfer of gene map data from other species. The probes developed here provide a genomic toolkit, which will make the guinea pig a key species to unravel the evolutionary biology of the Hystricomorph rodents. PMID:26010445

  2. Vaccination against bovine herpes mammillitis virus infections in guinea pigs.

    PubMed

    Smee, D F; Leonhardt, J A

    1994-01-01

    Bovine herpes mammillitis virus or bovine herpesvirus type 2 (BHV-2) causes ulcerative lesions on the teats and udders of infected cows. Since no commercial vaccine is available for this disease, we investigated certain experimental BHV-2 vaccines against this virus in infected guinea pigs. Vaginally infected guinea pigs get severe, self-limiting vaginal infections characterized by erythema and swelling and the production of measurable vaginal virus titers. Two vaccine approaches were investigated: vaccination with wild-type (WT) virus by the subcutaneous route, and vaccination either subcutaneously or intravaginally with a thymidine kinase (TK) deficient (TK-) virus. The TK- strain was prepared by passage of BHV-2 in the presence of the potent TK-dependent antiviral agent 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methyluracil (FMAU). The antiviral activity of FMAU against the virus in plaque reduction assays changed from 0.05 to 2 microM at the same time that the TK activity of the mutant virus decrease to 7% of WT virus TK activity. Subcutaneous vaccination of guinea pigs with WT and TK- viruses did not induce vaginal infection. Primary vaginal infection (vaccination) with the TK- virus led to greatly reduced lesion severity compared to vaginal infection with the WT virus. However, the amount of vaginal virus titers recovered during these primary infections was similar for both TK- and WT viruses, indicating that both viruses had equal infecting potential. Thirty days after vaccination the animals were re-infected intravaginally with WT virus. The vaccinated animals showed dramatically reduced lesion severity and low recoverable virus titers compared to age-matched nonvaccinated animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7928285

  3. 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. PMID:26837703

  4. 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

  5. Photoaffinity labeling of mammalian. cap alpha. /sub 1/-adrenergic receptors: identification of the ligand binding subunit with a high affinity radioiodinated probe. [Rats, guinea pigs, rabbits

    SciTech Connect

    Leeb-Lundberg, L.M.F.; Dickinson, K.E.J.; Heald, S.L.; Wikberg, J.E.S.; Hagen, P.O.; DeBernardis, J.F.; Winn, M.; Arendsen, D.L.; Lefkowitz, R.J.; Caron, M.G.

    1984-02-01

    A description is given of the synthesised and characterization of a novel high affinity radioiodinated ..cap alpha../sub 1/-adrenergic receptor photoaffinity probe, 4-amino-6,7-dimethoxy-2-(4-(5-(4-azido-3-(/sup 125/I)iodophenyl)pentanoyl)-1-piperazinyl) quinazoline. In the absence of light, this ligand binds with high affinity (K/sub d/ = 130 pm) in a reverisble and saturable manner to sites in rat hepatic plasma membranes. The binding is stereoselective and competitively inhibited by adrenergic agonists and antagonists with an ..cap alpha../sub 1/-adrenergic specificity. Upon photolysis, this ligand incorporates irreversibly into plasma membranes prepared from several mammalian tissues including rat liver, rat, guinea pig, and rabbit spleen, rabbit lung, and rabbit aorta vascular smooth muscle cells, also with typical ..cap alpha../sub 1/-adrenergic specificity. Autoradiograms of such membrane samples subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveal a major specifically labeled polypeptide at M/sub 4/ = 78,000-85,000, depending on the tissue used, in addition to some lower molecular weight peptides. Protease inhibitors, in particular EDTA, a metalloprotease inhibitor, dramatically increases the predominance of the M/sub r/ = 78,000-85,000 polypeptide while attenuating the labeling of the lower molecular weight bands. This new high affinity radioiodinated photoaffinity probe should be of great value for the molecular characterization of the ..cap alpha../sub 1/-adrenergic receptor.

  6. Formation of slow-reacting substance by guinea pig immunoglobulins.

    PubMed Central

    Jancar, S.; Akimura, O. K.; Dias da Silva, W.

    1976-01-01

    The capacity of guinea pig antibodies to mediate the antigen-induced release of slow-reacting substance (SRS) in the rat peritoneal cavity is restricted to IgG2 and, to a lesser extent, to IgG1 populations of immunoglobulin. IgM and homocytotropic antibody of the reaginic type lacked this activity. The process was partially blocked by previous decomplementation of the rats, was not affected by previous reduction of the circulating leukocytes, and was partially suppressed by previous depletion of circulating platelets with an antiserum to rat platelets. PMID:11696

  7. 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. PMID:26948264

  8. Anatomy and Disorders of the Oral Cavity of Guinea Pigs.

    PubMed

    Legendre, Loic

    2016-09-01

    Acquired dental disease represents the most common oral disorder of guinea pigs. Most patients are presented with nonspecific clinical signs and symptoms, such as weight loss, reduced food intake, difficulty chewing and/or swallowing. The physical examination must be followed by standard radiography and/or computed tomography, and thorough inspection under general anesthesia. Several complications may follow, including periodontal disease, subluxation of the temporomandibular joint, periapical infection, and abscessation. The dental treatment is aimed to restore the proper length and shape of both the incisor and cheek teeth, associated with medical and supportive treatment. Abscesses should be surgically addressed by complete excision. PMID:27497208

  9. Regulation of vascular tone and arterial blood pressure: role of chloride transport in vascular smooth muscle.

    PubMed

    Hübner, Christian A; Schroeder, Björn C; Ehmke, Heimo

    2015-03-01

    Recent studies suggest that primary changes in vascular resistance can cause sustained changes in arterial blood pressure. In this review, we summarize current knowledge about Cl(-) homeostasis in vascular smooth muscle cells. Within vascular smooth muscle cells, Cl(-) is accumulated above the electrochemical equilibrium, causing Cl(-) efflux, membrane depolarization, and increased contractile force when Cl(-) channels are opened. At least two different transport mechanisms contribute to raise [Cl(-)] i in vascular smooth muscle cells, anion exchange, and cation-chloride cotransport. Recent work suggests that TMEM16A-associated Ca(2+)-activated Cl(-) currents mediate Cl(-) efflux in vascular smooth muscle cells leading to vasoconstriction. Additional proteins associated with Cl(-) flux in vascular smooth muscle are bestrophins, which modulate vasomotion, the volume-activated LRRC8, and the cystic fibrosis transmembrane conductance regulator (CFTR). Cl(-) transporters and Cl(-) channels in vascular smooth muscle cells (VSMCs) significantly contribute to the physiological regulation of vascular tone and arterial blood pressure. PMID:25588975

  10. Effects of marmin, a compound isolated from Aegle marmelos Correa, on contraction of the guinea pig-isolated trachea.

    PubMed

    Nugroho, Agung Endro; Anas, Yance; Arsito, Puguh Novi; Wibowo, Joko Tri; Riyanto, Sugeng; Sukari, Mohamad Aspollah

    2011-10-01

    Marmin or 7-(6',7'-dihydroxygeranyl-oxy)coumarin is a compound isolated from Aegle marmelos Correa. In the study, we examined the effects of marmin on the contraction of guinea pig-isolated trachea stimulated by several inducers, namely histamine, metacholine, compound 48/80. We also evaluated its action against contraction induced by extracellular or intracellular calcium ion. The possibility of marmin to potentiate the relaxation effect of isoprenaline was also studied. Marmin added in the organ bath at 10 min prior to the agonist inhibited the contraction elicited by histamine and metacholine in a concentration-dependent manner. Moreover, marmin antagonized the histamine-induced contraction in competitive manner. Marmin mildly potentiated the relaxation effect of isoprenaline. In the study, marmin abrogated the contraction of tracheal smooth muscle induced by compound 48/80, an inducer of histamine release. Besides, marmin successfully inhibited CaCl(2)-induced contraction in Ca(2+)-free Krebs solution. Marmin also inhibited two phases of contraction which were consecutively induced by metacholine and CaCl(2) in Ca(2+)-free Krebs solution. Based on the results we concluded that marmin could inhibit contraction of the guinea-pig tracheal smooth muscle, especially by interfering histamine receptor, inhibiting the histamine release from mast, inhibiting intracellular Ca(2+) release from the intracellular store and the Ca(2+) influx through voltage-dependent Ca(2+) channels. PMID:21959801

  11. 1,2-Naphthoquinone activates vanilloid receptor 1 through increased protein tyrosine phosphorylation, leading to contraction of guinea pig trachea

    SciTech Connect

    Kikuno, Shota; Taguchi, Keiko; Iwamoto, Noriko; Yamano, Shigeru; Cho, Arthur K.; Froines, John R.; Kumagai, Yoshito . E-mail: yk-em-tu@md.tsukuba.ac.jp

    2006-01-15

    1,2-Naphthoquinone (1,2-NQ) has recently been identified as an environmental quinone in diesel exhaust particles (DEP) and atmospheric PM{sub 2.5}. We have found that this quinone is capable of causing a concentration-dependent contraction of tracheal smooth muscle in guinea pigs with EC{sub 5} value of 18.7 {mu}M. The contraction required extracellular calcium and was suppressed by L-type calcium channel blockers nifedipine and diltiazem. It was found that 1,2-NQ activated phospholipase A2 (PLA2)/lipoxygenase (LO)/vanilloid receptor (VR1) signaling. Additionally, 1,2-NQ was capable of transactivating protein tyrosine kinases (PTKs) such as epidermal growth factor receptor (EGFR) in guinea pig trachea, suggesting that phosphorylation of PTKs contributes to 1,2-NQ-induced tracheal contraction. Consistent with this notion, this action was blocked by the PTKs inhibitor genistein and the EGFR antagonist PD153035, indicating that contraction was, at least in part, attributable to PTKs phosphorylation that activates VR1, resulting in increased intracellular calcium content in the smooth muscle cells.

  12. Differential regulation by a peroxisome proliferator of the different multifunctional proteins in guinea pig: cDNA cloning of the guinea pig D-specific multifunctional protein 2.

    PubMed Central

    Caira, F; Clémencet, M C; Cherkaoui-Malki, M; Dieuaide-Noubhani, M; Pacot, C; Van Veldhoven, P P; Latruffe, N

    1998-01-01

    After our previous report on the cloning of two cDNA species in guinea pig, both encoding the same hepatic 79 kDa multifunctional protein 1 (MFP-1) [Caira, Cherkaoui-Malki, Hoefler and Latruffe (1996) FEBS Lett. 378, 57-60], here we report the cloning of a cDNA encoding a second multifunctional peroxisomal protein (MFP-2) in guinea-pig liver. This 2356 nt cDNA encodes a protein of 735 residues (79.7 kDa) whose sequence shows 83% identity with rat MFP-2 [Dieuaide-Noubhani, Novikov, Baumgart, Vanhooren, Fransen, Goethals, Vandekerckhove, Van Veldhoven and Mannaerts (1996) Eur. J. Biochem. 240, 660-666]. In parallel, we studied the effect of ciprofibrate, a hypolipaemic agent also known as peroxisome proliferator in rodent, on the expression of MFP-1 and MFP-2 (2.6 kb) in rats and guinea pigs. By Northern blotting analysis we demonstrated that three MFP-1-related mRNA species are expressed in the guinea-pig liver. The expression of two of them (3.5 and 2.6 kb) is slightly increased by ciprofibrate, whereas the 3.0 kb MFP-1 mRNA is, unlike the rat one, strongly down-regulated in guinea pigs treated with ciprofibrate. In a similar way, the hepatic expression of the guinea-pig 2.6 kb MFP-2 mRNA is also down-regulated in guinea pigs treated with ciprofibrate. These results demonstrate (1) that in contrast with the unique 3.0 kb MFP-1 rat mRNA, at least three hepatic MFP-1-related mRNA species are co-expressed in guinea pig; and (2) that, opposed to the accepted idea of non-responsiveness of the guinea pig to ciprofibrate, this drug affects MFP-1 and MFP-2 gene expression in this species. Also, the mRNA species for acyl-CoA oxidase and thiolase, two other enzymes of the peroxisomal beta-oxidation pathway that are induced severalfold in responsive species are down-regulated in guinea pig. This paper is the first, to our knowledge, reporting the down-regulation of the expression of genes encoding enzymes involved in the peroxisomal beta-oxidation of fatty acids (MFP-1) and

  13. 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.

  14. 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. PMID:9840262

  15. Molecular basis of complement C3 deficiency in guinea pigs.

    PubMed Central

    Auerbach, H S; Burger, R; Dodds, A; Colten, H R

    1990-01-01

    In experiments to ascertain the biochemical basis of a genetically determined deficiency of the third component of complement (C3) in guinea pigs, we found that C3-deficient liver and peritoneal macrophages contain C3 messenger RNA of normal size (approximately 5 kb) and amounts, that this mRNA programs synthesis of pro-C3 in oocytes primed with liver RNA and in primary macrophage cultures. In each instance, heterodimeric native C3 protein was secreted with normal kinetics but the C3 protein product of the deficient cells failed to undergo autolytic cleavage and was unusually susceptible to proteolysis. These data and a selective failure of C3 in plasma of deficient animals to incorporate [14C]methylamine suggested either a mutation in primary structure of the C3 protein or a selective defect in co- or postsynthetic processing affecting the thiolester bridge, a structure important for C3 function. A mutation in the primary structure of C3 was ruled out by comparison of direct sequence analysis of C3 cDNA generated from two C3 deficient and two C3 sufficient guinea pig liver libraries. Three base pair differences, none resulting in derived amino acid sequence differences were identified. Finally, restriction fragment length polymorphisms were identified in the C3 gene that are independent of the deficiency phenotype. This marker of the C3 gene permits testing of these hypotheses using molecular biological and classical genetic methods. Images PMID:1973176

  16. [Studies on coccidiosis in guinea pigs. 2. Epizootiological survey].

    PubMed

    Muto, T; Yusa, T; Sugisaki, M; Tanaka, K; Noguchi, Y; Taguchi, K

    1985-01-01

    An epizootiological survey has been carried out on naturally occurring coccidiosis in Hartley guinea pigs (weight, 250g) purchased by the National Institute of Health, Tokyo during the period 1964 to 1982. Coccidial infections in breeding colonies of guinea pigs were observed very frequently in weaned animals but scarcely in adult and suckling animals. Oocysts of Eimeria caviae were detected in 53.8% of the 7,162 fecal samples collected from transportation boxes and coccidiosis occurred in 39% of the 1,461 dead or culled animals obtained during the routine one week quarantine period. In the period 1964 to 1971, particularly high rates of prevalence of oocysts, between 55-86%, and incidence of coccidiosis, between 55-76%, were observed. These rates were clearly reduced in the period 1972 to 1982, with a lower rate of isolation of oocysts ranging from 14-48% and les than 20% incidence of coccidiosis (except in 1981 and 1982). The monthly fluctuation of occurrence rates of oocysts and clinical coccidiosis differed over the period of study. From 1964 to 1971, the high prevalence of oocysts was consistently observed accompanied by a bimodal pattern of incidence of coccidiosis in April (85%) and October (78%). In the period 1972 to 1982, both parameters showed a single peak, for prevalence of oocysts in June (60.7%) and for incidence of coccidiosis in May (45%). Oocysts in feces disappeared in February and March and coccidiosis occurred irregularly in 1981 and 1982.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3987821

  17. 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.

  18. Distribution of cholinergic cells in guinea pig brainstem

    PubMed Central

    Motts, S.D.; Slusarczyk, A.S.; Sowick, C.S.; Schofield, B.R.

    2008-01-01

    We used an antibody to choline acetyltransferase (ChAT) to label cholinergic cells in guinea pig brainstem. ChAT-immunoreactive (ChAT-IR) cells comprise several prominent groups, including the pedunculopontine tegmental nucleus, laterodorsal tegmental nucleus, and parabigeminal nucleus, as well as the cranial nerve somatic motor and parasympathetic nuclei. Additional concentrations are present in the parabrachial nuclei and superior colliculus. Among auditory nuclei, the majority of ChAT-IR cells are in the superior olive, particularly in and around the lateral superior olive, the ventral nucleus of the trapezoid body and the superior paraolivary nucleus. A discrete group of ChAT-IR cells is located in the sagulum, and additional cells are scattered in the nucleus of the brachium of the inferior colliculus. A group of ChAT-IR cells lies dorsal to the dorsal nucleus of the lateral lemniscus. A few ChAT-IR cells are found in the cochlear nucleus and the ventral nucleus of the lateral lemniscus. The distribution of cholinergic cells in guinea pigs is largely similar to that of other species; differences occur mainly in cell groups that have few ChAT-IR cells. The results provide a basis for further studies to characterize the connections of these cholinergic groups. PMID:18222049

  19. Pharmacology of Bradykinin-Evoked Coughing in Guinea Pigs.

    PubMed

    Hewitt, Matthew M; Adams, Gregory; Mazzone, Stuart B; Mori, Nanako; Yu, Li; Canning, Brendan J

    2016-06-01

    Bradykinin has been implicated as a mediator of the acute pathophysiological and inflammatory consequences of respiratory tract infections and in exacerbations of chronic diseases such as asthma. Bradykinin may also be a trigger for the coughing associated with these and other conditions. We have thus set out to evaluate the pharmacology of bradykinin-evoked coughing in guinea pigs. When inhaled, bradykinin induced paroxysmal coughing that was abolished by the bradykinin B2 receptor antagonist HOE 140. These cough responses rapidly desensitized, consistent with reports of B2 receptor desensitization. Bradykinin-evoked cough was potentiated by inhibition of both neutral endopeptidase and angiotensin-converting enzyme (with thiorphan and captopril, respectively), but was largely unaffected by muscarinic or thromboxane receptor blockade (atropine and ICI 192605), cyclooxygenase, or nitric oxide synthase inhibition (meclofenamic acid and N(G)-nitro-L-arginine). Calcium influx studies in bronchopulmonary vagal afferent neurons dissociated from vagal sensory ganglia indicated that the tachykinin-containing C-fibers arising from the jugular ganglia mediate bradykinin-evoked coughing. Also implicating the jugular C-fibers was the observation that simultaneous blockade of neurokinin2 (NK2; SR48968) and NK3 (SR142801 or SB223412) receptors nearly abolished the bradykinin-evoked cough responses. The data suggest that bradykinin induces coughing in guinea pigs by activating B2 receptors on bronchopulmonary C-fibers. We speculate that therapeutics targeting the actions of bradykinin may prove useful in the treatment of cough. PMID:27000801

  20. 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.

  1. Biochemical studies on the toxicity of hematite dust. [Guinea pigs

    SciTech Connect

    Das, B.; Khatoon, N.; Srivastava, R.C.; Viswanathan, P.N.; Rahman, Q.

    1983-12-01

    Biochemical alterations in guinea pig lungs caused by hematite dust were followed at 150 days after intratracheal administration of the dust. In vivo dust exposure caused a significant increase in mitochondrial protein content and cytochrome c oxidase activity whereas diaphorase activity remained unaltered. Mitochondria from the exposed animals were apparently in a swollen state and their contraction profile upon the addition of ATP reflected permeability changes. However, in vitro dust caused no significant alterations. Significant increases in glycogen content along with an insignificant decrease in glycogen phosphorylase activity were also observed in hematite-treated guinea pig lungs. Decrease in drug-metabolizing enzymes such as aniline hydroxylase and tyrosine aminotransferase activities were also evident in the post mitochondrial fraction of the siderotic lungs. (/sup 3/H)Leucine-incorporation studies showed increased protein synthesis in the postmitochondrial fraction. Increase in protein synthesis in mitochondria was only marginal whereas in whole homogenate it decreased considerably. Experiments employing dust tagged with radioactive iron indicated the rapid mobilization of iron from lung and its distribution to various organs. The presence of iron-binding protein was confirmed by employing Sephadex gel-filtration techniques.

  2. 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

  3. Evidence for independent evolution of functional progesterone withdrawal in primates and guinea pigs

    PubMed Central

    Nnamani, Mauris C.; Plaza, Silvia; Romero, Roberto; Wagner, Günter P.

    2013-01-01

    Background and objectives: Cervix remodeling (CRM) is a critical process in preparation for parturition. Early cervix shortening is a powerful clinical predictor of preterm birth, and thus understanding how CRM is regulated is important for the prevention of prematurity. Humans and other primates differ from most other mammals by the maintenance of high levels of systemic progesterone concentrations. Humans have been hypothesized to perform functional progesterone withdrawal (FPW). Guinea pigs are similar to humans in maintaining high-progesterone concentrations through parturition, thus making them a prime model for studying CRM. Here, we analyze the phylogenetic history of FPW and document gene expression in the guinea pig uterine cervix. Methodology: Data on progesterone withdrawal were collected from the literature, and character evolution was analyzed. Uterine cervix samples were collected from non-pregnant, mid-pregnant and late pregnant guinea pigs. RNA was extracted and sequenced. Relative transcript levels were estimated and compared among sample groups. Results: The phylogenetic analysis shows that FPW evolved independently in primates and guinea pigs. The transcriptome data confirms that guinea pigs down-regulate progesterone receptor toward parturition, in contrast to humans. Some of the similarities between human and guinea pig are: down-regulation of estrogen receptor, up-regulation of VCAN and IGFBP4 as well as likely involvement of prostaglandins. Conclusions and implications: (i) FPW in guinea pigs evolved independently from that in primates. (ii) A small set of conserved gene regulatory changes has been detected. PMID:24481205

  4. 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. PMID:26963642

  5. 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

  6. Vascular Smooth Muscle Cells in Atherosclerosis.

    PubMed

    Bennett, Martin R; Sinha, Sanjay; Owens, Gary K

    2016-02-19

    The historical view of vascular smooth muscle cells (VSMCs) in atherosclerosis is that aberrant proliferation of VSMCs promotes plaque formation, but that VSMCs in advanced plaques are entirely beneficial, for example preventing rupture of the fibrous cap. However, this view has been based on ideas that there is a homogenous population of VSMCs within the plaque, that can be identified separate from other plaque cells (particularly macrophages) using standard VSMC and macrophage immunohistochemical markers. More recent genetic lineage tracing studies have shown that VSMC phenotypic switching results in less-differentiated forms that lack VSMC markers including macrophage-like cells, and this switching directly promotes atherosclerosis. In addition, VSMC proliferation may be beneficial throughout atherogenesis, and not just in advanced lesions, whereas VSMC apoptosis, cell senescence, and VSMC-derived macrophage-like cells may promote inflammation. We review the effect of embryological origin on VSMC behavior in atherosclerosis, the role, regulation and consequences of phenotypic switching, the evidence for different origins of VSMCs, and the role of individual processes that VSMCs undergo in atherosclerosis in regard to plaque formation and the structure of advanced lesions. We think there is now compelling evidence that a full understanding of VSMC behavior in atherosclerosis is critical to identify therapeutic targets to both prevent and treat atherosclerosis. PMID:26892967

  7. Glucose oxidation and oxygen consumption of isolated guinea pig and muskrat hearts.

    PubMed

    McKean, T A

    1987-01-01

    Glucose in Krebs-Henseleit buffer was presented to isolated Langendorff perfused muskrat and guinea pig hearts that were paced at 240 beats/min. Glucose uptake (amount removed from the perfusion fluid) was 3 times greater in the muskrat hearts than in the guinea pig heart. Glucose oxidation (amount converted to CO2) and oxygen consumption did not differ in the hearts of the two species. When glucose is the only exogenous substrate, isolated muskrat hearts extract more glucose than guinea pig hearts but oxidize similar amounts of glucose and have a similar myocardial oxygen consumption. PMID:2881679

  8. 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. PMID:25421024

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

    PubMed

    Mao, Junfeng; Liu, Shuangzhen; Fu, Chunyan

    2016-06-01

    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

  10. 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.

  11. Elastic fibres in the vesicourethral junction and urethra of the guinea pig: quantification with computerised image analysis

    PubMed Central

    DASS, NARINDER; McMURRAY, GORDON; BRADING, ALISON F.

    1999-01-01

    Elastic fibres, which are intimately associated with collagen, a major component of the urethra, have been assumed to contribute to the resting urethral closure pressure. The Miller stain for elastin was used to demonstrate elastic fibres in cryostat sections of guinea pig bladder base, vesicourethral junction (VUJ) and urethra. Computerised image analysis was employed to objectively quantify these fibres. Both male and female guinea pigs showed significantly greater amounts of circularly disposed elastic fibres in the VUJ than in the other 2 regions examined. This particular disposition of fibres may be responsible for imparting resiliency and plasticity to the VUJ, allowing it to distend and recoil repeatedly in response to urine outflow. Furthermore, the elastic fibres may be partly responsible for the passive occlusive force in this region. Elastic fibres in the distal urethra were not quantified because of their relative paucity. Sagittal sections of the urethra revealed a mass of longitudinally arranged elastic fibres localised almost exclusively within the mucosa, submucosa and longitudinal smooth muscle layer. Functionally, this arrangement may exist to facilitate urethral length changes that occur in micturition. PMID:10580860

  12. Vinpocetine Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells.

    PubMed

    Ma, Yun-Yun; Sun, Lin; Chen, Xiu-Juan; Wang, Na; Yi, Peng-Fei; Song, Min; Zhang, Bo; Wang, Yu-Zhong; Liang, Qiu-Hua

    2016-01-01

    Vascular calcification is an active process of osteoblastic differentiation of vascular smooth muscle cells; however, its definite mechanism remains unknown. Vinpocetine, a derivative of the alkaloid vincamine, has been demonstrated to inhibit the high glucose-induced proliferation of vascular smooth muscle cells; however, it remains unknown whether vinpocetine can affect the osteoblastic differentiation of vascular smooth muscle cells. We hereby investigated the effect of vinpocetine on vascular calcification using a beta-glycerophosphate-induced cell model. Our results showed that vinpocetine significantly reduced the osteoblast-like phenotypes of vascular smooth muscle cells including ALP activity, osteocalcin, collagen type I, Runx2 and BMP-2 expression as well as the formation of mineralized nodule. Vinpocetine, binding to translocation protein, induced phosphorylation of extracellular signal-related kinase and Akt and thus inhibited the translocation of nuclear factor-kappa B into the nucleus. Silencing of translocator protein significantly attenuated the inhibitory effect of vinpocetine on osteoblastic differentiation of vascular smooth muscle cells. Taken together, vinpocetine may be a promising candidate for the clinical therapy of vascular calcification. PMID:27589055

  13. Audiometric effects of simulated sonic booms in guinea pigs

    NASA Astrophysics Data System (ADS)

    Reinis, S.; Weiss, D. S.; Featherstone, J. W.; Tsaros, C.

    1987-03-01

    Changes of hearing thresholds have been studied in guinea pigs following exposure to 100 simulated sonic booms. Simulated sonic booms increased the hearing thresholds at frequencies above 30 kHz. The only early structural change observed was an appearance of a small blood clot in the scala tympani of the basal turn of the cochlea. Although these changes may be specific for small laboratory animals only, they indicate that caution is necessary in exposing people to repeated or intense sonic booms. Also, the data indicate that, following the exposure to the sonic booms, the high frequency hearing is influenced first. Therefore, audiometric testing following the sonic boom exposure should not be limited to the routine audiometric curve ending at 8 kHz.

  14. 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

  15. 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.

  16. Interactions of trimebutine with guinea-pig opioid receptors.

    PubMed

    Roman, F; Pascaud, X; Taylor, J E; Junien, J L

    1987-05-01

    Affinities of trimebutine (TMB) and N-desmethyl trimebutine (NDTMB) for mu, delta and kappa opioid receptor subtypes have been examined using specific 3H-ligands and guinea-pig membrane. TMB and NDTMB showed a relative higher affinity for the mu receptor subtype although they were, respectively, 30- and 48-fold less active than morphine. The receptor selectivity index for mu, delta and kappa were 100:12:14.4 for TMB, 100:32:25 for NDTMB and 100:5:5 for morphine. The sodium shift ratio was 14 for TMB, 10 for NDTMB and 37 for morphine. These data show that (unlike morphine, a pure mu agonist) TMB and NDTMB can be classified as weak opioid agonists and confirm that peripheral opioid receptors mediate their gastrointestinal motility effects. PMID:2886594

  17. Assay of contact photosensitivity to musk ambrette in guinea pigs.

    PubMed

    Kochever, I E; Zalar, G L; Einbinder, J; Harber, L C

    1979-08-01

    This study reports the induction of contact photodermatitis to musk ambrette, 2-methoxy-3,5-dinitro-4-methyl-t-butylbenzene, in guinea pigs. Photoallergic contact dermatitis was assayed using 2 alternative induction methods. Successful photosensitization was achieved only when the nuchal skin was stripped with scotch tape before application of musk ambrette and ultraviolet radiation. Induction methods utilizing nonstripped nuchal skin which induce photosensitivity to potent photoallergens were ineffective for musk ambrette. Phtotoxicity tests to musk ambrette at concentrations between 1 and 50% and a dose of 10.2 joules/cm2 from "Black Light" fluorescent tubes were all negative. Under identical irradiation conditions, anthracene at 0.9% and 8-methoxypsoralen at 1% were consistently positive. The mechanism of photosensitivity to musk ambrette appears to be photoallergic rather than phototoxic. The requirement for skin abrasion to induce photosensitization parallels the clinical reports of photosensitivity to musk ambrette in man. PMID:458189

  18. [Scanning electron microscopy study of experimental chorioretinitis in guinea pigs].

    PubMed

    Renard, G; Usui, M; De Kozak, Y; Faure, J P

    1976-04-01

    Retinal lesions are described with the scanning electron microscope in the uveo retinitis induced in guinea pigs by immunization with rod outer segments of bovine retina. The two surfaces in contact of the pigment epithelium and the photoreceptors are separated from each other and observed on flat preparations. On the epithelial side, the evolution of the degenerescence of epithelial cells is observed, from the early disappearance of villosities until the total destruction of the cells. Through lacks in the epithelial layer where the choroid appears, inflammatory cells migrate towards the retina. The impairement of the visual cells is characterized by progressive destruction of outer then inner segments, with preservation of the external limiting membrane. In some areas the degenerative process reaches the layer of visual cells nuclei. Macrophages, and local clusters of lymphocytes are seen in contact with the retinal surface. PMID:135548

  19. Transmission of Influenza B Viruses in the Guinea Pig

    PubMed Central

    Pica, Natalie; Chou, Yi-Ying; Bouvier, Nicole M.

    2012-01-01

    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. PMID:22301149

  20. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  2. Normal behavior and the clinical implications of abnormal behavior in guinea pigs.

    PubMed

    Bradley, T A

    2001-09-01

    Cavies are becoming more popular as pets because they are relatively easy to care for and provide never-ending love and entertainment with their curious but gentle nature. As with other species, the best way to learn about guinea pig behavior is to own guinea pigs. Understanding normal behavior provides the practitioner with the ability to more easily recognize pathology and abnormal behavior. This allows the veterinarian to provide necessary supportive care and pain management more quickly while performing diagnostics and determining the need for therapeutics. Understanding the behavior of cavies allows the clinician to better educate guinea pig-owning clients and to better and more quickly serve the needs of their guinea pig patients. PMID:11601108

  3. Use of guinea pig embryo cell cultures for isolation and propagation of group A coxsackieviruses.

    PubMed Central

    Landry, M L; Madore, H P; Fong, C K; Hsiung, G D

    1981-01-01

    The isolation of group A coxsackieviruses from clinical specimens generally requires the use of suckling mice. By using guinea pig embryo cells, the following coxsackieviruses were isolated from throat swabs and stool samples obtained from patients with a variety of illnesses: two of type A2, one each of types A6 and A8, and four of type 10. Distinct cytopathic effects were produced in 3 to 5 days in the guinea pig embryo cells inoculated with the clinical specimens. In addition, a number of prototype group A coxsackieviruses, including types 2--6, 8, 10, and 12, were readily propagated in guinea pig embryo cell cultures. Thus, guinea pig embryo cells appeared to be a sensitive alternative cell culture system for the isolation and propagation of certain types of group A coxsackieviruses. Images PMID:6263943

  4. 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

  5. Postnatal development of substance P in the inner ear of the guinea pig.

    PubMed

    Nowak, R; Zelck, U; Rathsack, R; Oehme, P; Scholtz, H J; Koitschev, A; Beleites, B

    1990-01-01

    Appreciable amounts of substance P (SP) were found in guinea pig cochleas. The highest values were found in the postnatal period. Data presented favor the assumption of SP acting as a neuromodulator or neurotransmitter in the inner ear. PMID:1693520

  6. SULFAMETHOXAZOLE-TRIMETHOPRIM TREATMENT OF GUINEA PIGS INFECTED WITH 'LEGIONELLA PNEUMPOPHILA'

    EPA Science Inventory

    Legionnaires' disease is a bacterial pneumonia caused by Legionella pneumophila. Many antibiotics inhibit the growth of L. pneumophila in vitro, but only erythromycin and rifampin have been clinically effective. Parallel results have been observed in guinea pigs infected ip with ...

  7. Chronic estrogen exposure maintains elevated levels of progesterone receptor mRNA in guinea pig hypothalamus.

    PubMed

    Bayliss, D A; Millhorn, D E

    1991-05-01

    We performed in situ hybridization on hypothalamic sections from ovariectomized guinea pig using a cocktail of three 35S-labeled oligonucleotides complementary to mammalian progesterone receptor (PR) cDNA. PR mRNA was readily detected in hypothalamic neurons from guinea pigs pretreated with 17 beta-estradiol benzoate (E2B), but not from animals which did not receive supplemental E2B. The distribution of PR mRNA-containing cells corresponded well with previous localizations of PR in guinea pig. In contrast to earlier reports of E2B regulation of PR mRNA in rat hypothalamus, however, we found that PR mRNA remained elevated during chronic exposure to E2B (up to 10 days) in guinea pig. PMID:2072827

  8. Immunolocalization of a guinea pig sperm surface antigen recognized by a monoclonal antibody E74.

    PubMed Central

    Ilayperuma, Isurani

    2002-01-01

    E74 is a mouse monoclonal antibody raised against the acrosome-reacted guinea pig spermatozoa. This study describes immunolocalization of the E74 antigen in guinea pig spermatozoa. Immunoelectron microscopy of guinea pig spermatozoa shows that the E74 antigen is localized on the equatorial segment plasma membrane following the acrosome reaction but not associated with the surface of the acrosome-intact spermatozoa. Immunoblot analysis of Triton X-100 extract of cauda epididymal guinea pig spermatozoa following one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis shows that E74 antibody recognizes a protein with an apparent molecular weight of 45,000 dalton. Immunoblot of sperm extracts separated by two dimensional gel electrophoresis indicates a broad spot of 45,000 dalton in the 5 to 7.5 isoelectric focusing range. Images Figure 1 Figure 2 PMID:12074481

  9. Biochemical properties of the bromodeoxyuridine-induced guinea pig virus.

    PubMed

    Michalides, R; Schlom, J; Dahlberg, J; Perk, K

    1975-10-01

    The biophysical and biochemical properties of the virus particles released by guinea pig embryo cells treated with 5-bromo-2'-deoxyuridine (BUdR) have been compared to those of the B-type mouse mammary tumor virus (MMTV) and the C-type Rauscher murine leukemia virus. The high-molecular-weight (60 to 70S) RNA of the BUdR-induced guinea pig virus (GPV) has a molecular weight of 8 X 106 when measred by mixed agarose polyacylamide gel electrophoresis. The virus particles isolated from the tissue culture medium of BUdR-induced guniea pig cells have the following properties in common with MMTV: (i) a buoyant density of 1.18 g/ml in sucrose and 1.21 g/ml in CsCl, and (ii) a DNA polymerase that prefers Mg2+ over Mn2+ in an assay using the synthetic template poly(rC):oligo(dG). No nucleic acid sequence homology between GPV RNA and the viral RNAs of the MMTV, murine leukemia virus, hamster sarcoma virus, or Mason-Pfizer monkey virus could be observed in a competition hybridization assay using the radioactive-labeled GPV 60 to 70S RNA. By this same competition by hybridization assay the frequency of GPV proviral sequences was estimated to be at least 83 per haploid cellular genome of guniea pig cells. No nucleic acid sequences related to be GPV RNA were detected in the DNA of normal tissues of mice, rats, cats, dogs, baboons, or humans by direct RNA-DNA hybridization using radioactive GPV60 to 70S RNA. PMID:51933

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

    PubMed Central

    Korani, M; Rezayat, SM; Gilani, K; Bidgoli, S Arbabi; 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. PMID:21720498

  11. Guinea Pig Lung Lavage Cells After Intranasal BCG Sensitization

    PubMed Central

    Terai, T.; Ganguly, Rama; Waldman, Robert H.

    1979-01-01

    Recent studies have suggested that intranasal administration of antigen can induce local cell-mediated immunity in lung lavage cells. The present study was designed to examine the changes in composition of lung lavage cells and their capacity to produce the lymphokine migration inhibitory factor after intranasal immunization with BCG in guinea pigs. Results indicate that guinea pigs responded to respiratory tract BCG infection with an increase in immunocompetent cells in the bronchoalveolar tract and with production of migration inhibitory factor. After local pulmonary BCG administration, the total number of cells increased as compared with that of the uninfected animals, the increase being statistically significant within 2 weeks. This marked increase in the total cell population is due to a more than doubling of the number of macrophages in the lavage fluid. Animals also developed at this time positive delayed hypersensitivity to intradermally administered purified protein derivative. A significant increase in the total lymphoid cells and macrophage population was observed again at 6 weeks after sensitization, suggesting that the response is biphasic in nature. At 6 weeks, however, there was also a significant rise in total lymphocytes and T cell population in addition to macrophage numbers. This increase in T cells correlated with an increase in production of migration inhibitory factor in the presence of purified protein derivative. These data suggest that the immune response of the respiratory tract after BCG challenge involves increased recruitment of immunocompetent cells locally at the site of infection and that these cells are capable of producing effector molecules in terms of the elaboration of migration inhibitory factor. PMID:387595

  12. Pharmacokinetics of activated protein C in guinea pigs

    SciTech Connect

    Berger, H. Jr.; Kirstein, C.G.; Orthner, C.L. )

    1991-05-15

    Protein C is a vitamin K-dependent zymogen of the serine protease, activated protein C (APC), an important regulatory enzyme in hemostasis. In view of the potential of human APC as an anticoagulant and profibrinolytic agent, the pharmacokinetics and tissue distribution of APC were studied in guinea pigs. The plasma elimination of a trace dose of {sup 125}I-APC was biphasic following an initial rapid elimination of approximately 15% of the injected dose within 1 to 2 minutes. This rapid removal of {sup 125}I-APC from the circulation was found to be a result of an association with the liver regardless of the route of injection. Essentially identical results were obtained with active site-blocked forms of APC generated with either diisopropylfluorophosphate or D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone, which indicates that the active site was not essential for the liver association. Accumulation of all three forms of APC in the liver peaked at 30 minutes and then declined as increasing amounts of degraded radiolabeled material appeared in the gastrointestinal tract and urine. Removal of the gamma-carboxyglutamic acid (gla) domain of diisopropylphosphoryl-APC resulted in a 50% reduction in the association with liver and an accumulation in the kidneys. Protein C and protein S were cleared from the circulation at rates approximately one-half and one-fourth, respectively, that of APC. Both in vitro and in vivo, APC was found to form complexes with protease inhibitors present in guinea pig plasma. Complex formation resulted in a more rapid disappearance of the enzymatic activity of APC than elimination of the protein moiety. These findings indicate two distinct mechanisms for the elimination of APC. One mechanism involves reaction with plasma protease inhibitors and subsequent elimination by specific hepatic receptors. (Abstract Truncated)

  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. [Effects of trimebutine maleate (TM-906) on the spontaneous contraction of the isolated guinea pig stomach].

    PubMed

    Takenaga, H; Magaribuchi, T; Tamaki, H

    1982-08-01

    Effects of trimebutine maleate (TM-906) on the spontaneous contraction were investigated in the isolated circular smooth muscle of the antrum region of the guinea pig stomach. TM-906 dose-dependently reduced the amplitude of the regular spontaneous contraction without any marked change in its frequency and basal tension. This effect of TM-906 was also observed in the presence of phentolamine, propranolol, atropine, and tetrodotoxin. However, the inhibitory effect of TM-906 was overcome by increasing the extracellular concentration of CaCl2. On the other hand, in preparations which exhibited irregular spontaneous contraction, TM-906 regularized it, and spontaneous contraction with regular frequency and amplitude was elicited. In addition, this regularizing effect of TM-906 was also observed in the presence of atropine and tetrodotoxin. It was concluded that TM-906 has dual effects on the spontaneous contraction, reducing the amplitude of regular contraction and regularizing the irregular contraction. These effects of TM-906 may be attributed to the direct action on the smooth muscle. PMID:7173739

  15. Bitter avoidance in Guinea Pigs (Cavia porcellus) and Mice (Mus musculus and Peromyscus leucopus)

    PubMed Central

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

    2010-01-01

    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 non-herbivorous mouse species (Mus musculus and Peromyscus leucopus). Guinea pigs did show weaker avoidance of QHCl 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. PMID:21090891

  16. Tachykinin NK(3) receptor agonists induced microvascular leakage hypersensitivity in the guinea-pig airways.

    PubMed

    Daoui, S; Ahnaou, A; Naline, E; Emonds-Alt, X; Lagente, V; Advenier, C

    2001-12-21

    Microvascular leakage hypersensitivity is a main component of neurogenic inflammation and of tachykinin effects. The aim of this study was to examine the ability of neurokinin B and of the tachykinin NK(3) receptor agonists, [MePhe(7)]neurokinin B or senktide, to potentiate when given by aerosol the microvascular leakage induced by histamine in guinea-pig airways and to compare their effects to those of tachykinin NK(1) (substance P, [Sar(9),Met(O(2))(11)]substance P) or tachykinin NK(2) (neurokinin A, [betaAla(8)]neurokinin A (4-10)) receptor agonists. Guinea-pigs were pretreated successively for 10 min with aerolized salbutamol and phosphoramidon; 15 min later, they were exposed for 30 min to an aerosolized solution of tachykinin receptor agonists; 24 h later, the animals were anaesthetized and vascular permeability was quantified by extravasation of Evans blue dye. Neurokinin B, [MePhe(7)]neurokinin B and senktide (3 x 10(-6)-3 x 10(-5)M) induced a potentiation of the effects of histamine on the vascular permeability in the trachea and main bronchi. Compared to other tachykinin NK(1) and NK(2) receptor agonists, the order of potency was: senktide>neurokinin B=[Sar(9),Met(O(2))(11)]substance P=[betaAla(8)]neurokinin A (4-10)=[MePhe(7)]neurokinin B>neurokinin A>substance P. The potentiation by [MePhe(7)]neurokinin B of histamine-induced microvascular leakage was abolished by the tachykinin NK(1) receptor antagonist SR140333 ([(S)1-(2-[3-(3,4-dichlorophenyl)-1-(3-iso-propoxyphenylacetyl)piperidin-3-yl]etyl)-4-phenyl-1-azoniabicyclo[2.2.2]octane, chloride]) or the tachykinin NK(3) receptor antagonists SR 142801 ([(R)-(N)-(1-(3-(l-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl) propyl)-4-phenylpiperidin-4-yl)-N-methylacetamide]) and SB 223412 ([(S)-(-)-N-(alpha-ethylbenzyl)-3-hydroxy-2-phenylquinoline-4-carboxamide]). In conclusion, these results suggest that tachykinin NK(3) receptors might be involved in the potentiation of histamine-induced increase in microvascular

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

    PubMed Central

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

    2015-01-01

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

  18. 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.

  19. 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.

  20. Functional preservation of vascular smooth muscle tissue

    NASA Technical Reports Server (NTRS)

    Alexander, W. C.; Hutchins, P. M.; Kimzey, S. L.

    1973-01-01

    The ionic and cellular feedback relationships operating to effect the vascular decompensatory modifications were examined to reveal procedures for implementing protective measures guarding against vascular collapse when returning from a weightless environment to that of the earth's gravity. The surgical procedures for preparing the rat cremaster, and the fixation methods are described. Abstracts of publications resulting from this research are included.

  1. Mebendazole Reduces Vascular Smooth Muscle Cell Proliferation and Neointimal Formation Following Vascular Injury in Mice

    PubMed Central

    Wang, Jintao; Wang, Hui; Guo, Chiao; Luo, Wei; Lawler, Alyssa; Reddy, Aswin; Wang, Julia; Sun, Eddy B.; Eitzman, Daniel T.

    2014-01-01

    Mebendazole is an antihelminthic drug that exerts its effects via interference with microtubule function in parasites. To determine the utility of mebendazole as a potential treatment for vascular diseases involving proliferation of vascular smooth muscle cells, the effects of mebendazole on vascular smooth muscle cell proliferation were tested in vitro and in a mouse model of arterial injury. In vitro, mebendazole inhibited proliferation and migration of murine vascular smooth muscle cells and this was associated with altered intracellular microtubule organization. To determine in vivo effects of mebendazole following vascular injury, femoral arterial wire injury was induced in wild-type mice treated with either mebendazole or placebo control. Compared with placebo-treated mice, mebendazole-treated mice formed less neointima at the site of injury. Mebendazole is effective at inhibiting vascular smooth muscle cell proliferation and migration, and neointimal formation following arterial injury in mice. PMID:24587248

  2. Piperine Congeners as Inhibitors of Vascular Smooth Muscle Cell Proliferation.

    PubMed

    Mair, Christina E; Liu, Rongxia; Atanasov, Atanas G; Wimmer, Laurin; Nemetz-Fiedler, Daniel; Sider, Nadine; Heiss, Elke H; Mihovilovic, Marko D; Dirsch, Verena M; Rollinger, Judith M

    2015-08-01

    Successful vascular healing after percutaneous coronary interventions is related to the inhibition of abnormal vascular smooth muscle cell proliferation and efficient re-endothelialization. In the search for vascular smooth muscle cell anti-proliferative agents from natural sources we identified piperine (1), the main pungent constituent of the fruits from Piper nigrum (black pepper). Piperine inhibited vascular smooth muscle cell proliferation with an IC50 of 21.6 µM, as quantified by a resazurin conversion assay. Investigations of ten piperamides isolated from black pepper fruits and 15 synthesized piperine derivatives resulted in the identification of three potent vascular smooth muscle cell proliferation inhibitors: the natural alkaloid pipertipine (4), and the two synthetic derivatives (2E,4E)-N,N-dibutyl-5-(3,5-dimethoxyphenyl)penta-2,4-dienamide (14) and (E)-N,N-dibutyl-3-(naphtho[2,3-d][1,3]dioxol-5-yl)acrylamide (20). They showed IC50 values of 3.38, 6.00, and 7.85 µM, respectively. Furthermore, the synthetic compound (2E,4E)-5-(4-fluorophenyl)-1-(piperidin-1-yl)penta-2,4-dien-1-one (12) was found to be cell type selective, by inhibiting vascular smooth muscle cell proliferation with an IC50 of 11.8 µM without influencing the growth of human endothelial cells. PMID:26132851

  3. Neurotrophin and Neurotrophin Receptors in Vascular Smooth Muscle Cells

    PubMed Central

    Donovan, Michael J.; Miranda, Rajesh C.; Kraemer, Rosemary; McCaffrey, Timothy A.; Tessarollo, Lino; Mahadeo, Debbie; Sharif, Setareh; Kaplan, David R.; Tsoulfas, Pantelis; Parada, Luis; Toran-Allerand, C. Dominique; Hajjar, David P.; Hempstead, Barbara L.

    1995-01-01

    The neurotrophins, a family of related polypeptide growth factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3 and NT-4/5 promote the survival and differentiation of distinctive sets of embryonic neurons. Here we define a new functional role for neurotrophins, as autocrine or local paracrine mediators of vascular smooth muscle cell migration. We have identified neurotrophins, and their cognate receptors, the trk tyrosine kinases, in human and rat vascular smooth muscle cells in vivo. In vitro, cultured human smooth muscle cells express BDNF; NT-3; and trk A, B, and C Similarly, rat smooth muscle cells expressed all three trk receptors as well as all four neurotrophins. Moreover, NGF induces cultured human smooth muscle cell migration at subnanomolar concentrations. In the rat aortic balloon deendothelialization model of vascular injury, the expression of NGF, BDNF, and their receptors trk A and trk B increased dramatically in the area of injury within 3 days and persisted during the formation of the neointima. In human coronary atherosclerotic lesions, BDNF, NT-3, and NT-4/5, and the trk B and trk C receptors could be demonstrated in smooth muscle cells. These findings suggest that neurotrophins play an important role in regulating the response of vascular smooth muscle cells to injury. ImagesFigure 1Figure 2Figure 3Figure 5Figure 6Figure 7Figure 8 PMID:7639328

  4. The effect of a lipid-rich diet on the properties and composition of lipoprotein particles from the Golgi apparatus of guinea-pig liver.

    PubMed

    Chapman, M J; Mills, G L; Taylaur, C E

    1973-02-01

    phospholipid. We conclude that the Golgi LD particle is normally present in the Golgi-apparatus cell fraction from guinea-pig liver, and may represent the end product of lipoprotein biosynthesis in the smooth endoplasmic reticulum. 7. The serum LD lipoproteins and Golgi LD particles were quite distinct in chemical composition. However, these two lipoprotein species were immunochemically identical and exhibited a similar range of flotation rate. It appears unlikely that the Golgi LD particles are secreted as the precursors of the serum LD lipoproteins. PMID:4352903

  5. Sphingosylphosphorylcholine inhibits macrophage adhesion to vascular smooth muscle cells.

    PubMed

    Wirrig, Christiane; McKean, Jenny S; Wilson, Heather M; Nixon, Graeme F

    2016-09-01

    Inflammation in de-endothelialised arteries contributes to the development of cardiovascular diseases. The process that initiates this inflammatory response is the adhesion of monocytes/macrophages to exposed vascular smooth muscle cells, typically stimulated by cytokines such as tumour necrosis factor-α (TNF). The aim of this study was to determine the effect of the sphingolipid sphingosylphosphorylcholine (SPC) on the interaction of monocytes/macrophages with vascular smooth muscle cells. Rat aortic smooth muscle cells and rat bone marrow-derived macrophages were co-cultured using an in vitro assay following incubation with sphingolipids to assess inter-cellular adhesion. We reveal that SPC inhibits the TNF-induced adhesion of macrophages to smooth muscle cells. This anti-adhesive effect was the result of SPC-induced changes to the smooth muscle cells (but not the macrophages) and was mediated, at least partly, via the sphingosine 1-phosphate receptor subtype 2. Lipid raft domains were also required. Although SPC did not alter expression or membrane distribution of the adhesion proteins intercellular adhesion molecule-1 and vascular cellular adhesion protein-1 in smooth muscle cells, SPC preincubation inhibited the TNF-induced increase in inducible nitric oxide synthase (NOS2) resulting in a subsequent decrease in nitric oxide production. Inhibiting NOS2 activation in smooth muscle cells led to a decrease in the adhesion of macrophages to smooth muscle cells. This study has therefore delineated a novel pathway which can inhibit the interaction between macrophages and vascular smooth muscle cells via SPC-induced repression of NOS2 expression. This mechanism could represent a potential drug target in vascular disease. PMID:27402344

  6. Effects of trimebutine maleate (TM-906) on the spontaneous contraction of isolated guinea pig colon.

    PubMed

    Takenaga, H; Magaribuchi, T; Tamaki, H

    1984-02-01

    Effects of trimebutine maleate (TM-906) on the spontaneous contraction of isolated guinea pig colon were investigated. TM-906 in the concentrations of 10(-6) g/ml and 10(-5) g/ml increased the tone without affecting the amplitude of the spontaneous contraction in the preparations with low tone, whereas it decreased the tone and the amplitude of the spontaneous contraction in the preparations with high tone. At the higher concentration (10(-4) g/ml). TM-906 decreased the tone and finally abolished the spontaneous contraction in any preparation. The increase in tone induced by TM-906 was prevented by diltiazem and exposure to Ca++-free solution, but not by tetrodotoxin, atropine, phentolamine or propranolol, and depended on the extracellular concentration of CaCl2. On the other hand, the decrease in tone and amplitude of the spontaneous contraction produced by TM-906 were not prevented by tetrodotoxin, phentolamine or propranolol. TM-906 further increased the tone increased by 10 mM KCl, while it decreased the tone increased by 30 mM KCl. From results described above, it is suggested that TM-906 possesses both a relaxing effect and an excitatory effect which seem to be due to its direct action on the smooth muscle. PMID:6748369

  7. Evaluation of the pulmonary effects of wood smoke in guinea pigs by repeated CO2 challenges

    SciTech Connect

    Wong, K.L.; Stock, M.F.; Malek, D.E.; Alarie, Y.

    1984-08-01

    Male, English smooth haired guinea pigs were exposed to thermal decomposition products, i.e., smoke, generated by heating Douglas fir in an open system. Various amounts of Douglas fir were placed in a furnace, at room temperature, and heated at a rate of 11 degrees C/min until completely decomposed. Major decomposition occurred between 160 and 490 degrees C, and the animals were exposed during this time for a period of 30 min. Immediately before exposure and at various times after exposure, each animal was evaluated by whole-body plethysmography to measure tidal volume and respiratory frequency during air breathing as well as during challenge with 10% CO2. Exposure to smoke from Douglas fir resulted in a diminished ventilatory response to 10% CO2. Comparing the effect of wood smoke to the effect of smoke from polyvinylchloride from previous experiments wood smoke was found to be 10 times less potent than smoke from polyvinylchloride and animals recovered much more rapidly than with smoke from polyvinylchloride.

  8. Mechanisms of Vascular Smooth Muscle Contraction and the Basis for Pharmacologic Treatment of Smooth Muscle Disorders

    PubMed Central

    Brozovich, F.V.; Nicholson, C.J.; Degen, C.V.; Gao, Yuan Z.; Aggarwal, M.

    2016-01-01

    The smooth muscle cell directly drives the contraction of the vascular wall and hence regulates the size of the blood vessel lumen. We review here the current understanding of the molecular mechanisms by which agonists, therapeutics, and diseases regulate contractility of the vascular smooth muscle cell and we place this within the context of whole body function. We also discuss the implications for personalized medicine and highlight specific potential target molecules that may provide opportunities for the future development of new therapeutics to regulate vascular function. PMID:27037223

  9. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

    PubMed

    Kurabayashi, Masahiko

    2015-05-01

    Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area. PMID:25926569

  10. 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.

  11. Antitussive activity of iodo-resiniferatoxin in guinea pigs

    PubMed Central

    Trevisani, M; Milan, A; Gatti, R; Zanasi, A; Harrison, S; Fontana, G; Morice, A; Geppetti, P

    2004-01-01

    Background: Iodo-resiniferatoxin (I-RTX) has recently been described as an ultra potent antagonist of the transient receptor potential vanilloid-1 (TRPV1). Methods: The ability of I-RTX to inhibit cough induced by inhalation of two putative TRPV1 stimulants (capsaicin and citric acid) was tested in non-anaesthetised guinea pigs. Results: Pretreatment with I-RTX either intraperitoneally (0.03–0.3 µmol/kg) or by aerosol (0.1–3 µM) reduced the number of coughs produced by inhalation of citric acid (0.25 M) and capsaicin (30 µM) in a dose dependent manner. Capsazepine (CPZ) also reduced citric acid and capsaicin induced cough, but the activity of I-RTX was 10–100 times more potent than CPZ in all the experimental conditions tested. Conclusions: I-RTX is a novel and potent antitussive drug which inhibits cough mediated by agents possibly acting via TRPV1 activation. PMID:15333853

  12. Interaction between titanium and cadmium in various guinea pig organs.

    PubMed

    Takano, Takashi; Kaneda, Takeharu; Kaneshige, Masaki; Tsutsumi, Tomoko; Ochiai, Yoshitsugu; Shimizu, Kazumasa; Hondo, Ryo; Mochizuki, Mariko; Ueda, Fukiko

    2013-02-01

    Titanium (Ti) is used in many fields, while cadmium (Cd) is known to cause the itai-itai disease. In the present study, possible interactions between titanium and cadmium were investigated. Aorta, taenia coli, and liver were removed from male guinea pigs. Muscle tension was measured using intact aorta and taenia coli and using β-escin-permeabilized taenia coli in a physiological salt solution and a hyperpotassium solution containing Cd and/or Ti. Cellular Cd contents were determined using all tissues after washout with EDTA solution. Cadmium-induced relaxation in the hyperpotassium solution recovered significantly (P < 0.01) following Ti treatment in taenia coli, but not in the aorta. In β-escin-permeabilized taenia coli, the percentage recoveries after Cd treatment and after Ti plus Cd treatment were 67.3 ± 8.7 % (n = 4) and 87.7 ± 3.8 % (n = 4), respectively, compared with Ca-induced control contraction. Cellular Cd contents in taenia coli decreased significantly following treatment with Ti 10(-4) M. Although similar results were obtained using the aorta and the liver, there were no significant differences between the control and Ti 10(-5) M. High concentrations of Ti may reduce cellular Cd content. PMID:23238609

  13. Biosynthesis of glucagon in isolated pancreatic islets of guinea pigs

    PubMed Central

    Hellerström, Claes; Howell, Simon L.; Edwards, John C.; Andersson, Arne; Östenson, Claes-Göran

    1974-01-01

    1. The biosynthesis of glucagon in guinea-pig A2 cells was investigated by incubation of isolated islets of Langerhans in the presence of [3H]tryptophan for periods of up to 14 days. Proteins were extracted from islets and incubation media and analysed by gel filtration. 2. In addition to very-high-molecular-weight (100000) proteins, the principal tryptophan-containing biosynthetic product after incubation for up to 17h was a protein of minimum mol.wt. 9000, which co-eluted on gel filtration with a peak of glucagon-like immunoreactivity, but was apparently devoid of biological activity in a fat-cell assay. A discrete peak of labelled glucagon was only recovered after incubation for at least 6 days. Losses of glucagon during the extraction and rapid secretion of newly synthesized glucagon into incubation media were excluded as reasons for the lack of recovery of labelled hormone from islets after shorter incubations. 3. The 9000-mol.wt. protein was localized to A2 cells in experiments using B-cell-depleted islets, and to A2-cell granules by subcellular fractionation and electron-microscopic radioautography. Only glucagon was secreted into the incubation medium. 4. Possible relationships between the 9000-mol.wt. protein and glucagon are discussed in the light of postulated mechanisms of glucagon biosynthesis. PMID:4615708

  14. Particle size influences aerosol deposition in guinea pigs during bronchoconstriction

    SciTech Connect

    Praud, J.P.; Macquin-Mavier, I.; Wirquin, V.; Meignan, M.; Harf, A.

    1986-03-01

    The role of two factors determining the deposition of aerosols in the respiratory tract was investigated: the particle size and the nature of the airflow in the airways. An aerosol of Tc99 m-DTPA was generated, with a mass median aerodynamic diameter of either 3 ..mu..m (Bird nebulizer) or 0.5 ..mu..m (Jouan nebulizer). The vehicle was either saline (S) or histamine (H) at a concentration which was previously shown to induce a 50% decrease of specific airway conductance. Spontaneously breathing guinea pigs were exposed during 2 minutes to the aerosol, then killed and the radioactivity in the pharynx, the trachea, the large bronchi and the remaining parenchyma was measured. Results are evaluated as the percentage of total radioactivity in the respiratory tract (mean +/- SEM). Analysis of variance showed that there was a significant difference in the pattern of deposition for large particles (3 ..mu..m) during bronchoconstriction: the more proximal deposition can be ascribed to inertial impaction. Particle size should be clearly defined during histamine challenge in experimental animals.

  15. 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.

  16. Respiratory response of guinea pigs to zinc oxide fume

    SciTech Connect

    Amdur, M.O.; McCarthy, J.F.; Gill, M.W.

    1983-02-01

    Zinc has been found enriched in the fine particle fraction of atmospheric aerosols and in the surface layer of fly ash. Experimental combustion studies of coal have demonstrated that zinc is vaporized and recondensed into the submicrometer fraction of the combustion aerosols. This size fraction may contain as much as 1.5% zinc when a coal of high zinc content (Illinois No. 6) is used. Zinc sulfate and zinc ammonium sulfate are among the sulfates with demonstrable irritant potency. Zinc oxide was thus chosen as the initial aerosol for studies of biological and chemical interaction of high temperature generated submicrometer metal oxides with sulfur dioxide. This paper reports the respiratory response of guinea pigs to short term exposure to freshly formed zinc oxide fume. These studies of zinc oxide alone have relevance to industrial exposure. The recommended TLV for zinc oxide is 5 mg/m/sup 3/ and the recommended STEL is 10 mg/m/sup 3/. Concentrations used in our studies were below these recommended levels.

  17. Observations on chloralose-induced myoclonus in guinea-pigs.

    PubMed Central

    Chadwick, D.; Hallett, M.; Jenner, P.; Marsden, C. D.

    1980-01-01

    1 The physiological, biochemical and pharmacological features of alpha-chloralose-induced myoclonus in the guinea-pig have been studied. 2 EMG bursts in muscles jerking in chloralose-induced myoclonus are long, and are not time-locked to any cortical event recorded in the EEG, although they are evoked by auditory or peripheral nerve stimuli. 3 The efferent conduction velocity down the spinal cord of the signals generating the EMG bursts is fast but the afferent conduction velocity up the cord for stimulus-evoked jerks is slow, in distinction to the reverse characteristics of the spino-bulbo-spinal relfex arc. 4 alpha-Choralose did not cause any consistent change in 5-hydroxytryptamine (5-HT) or 5-hydroxyindoleacetic acid levels in any brain area, nor did it alter 5-HT turnover as judged by the depletion of 5-HT after p-chlorophenylalanine pretreatment. 5 Pretreatment of animals with drugs that increase brain 5-HT action (L-tryptophan with a monoamine oxidase inhibitor, or 5-hydroxytryptophan), or antagonize the action of 5-HT (cyproheptadine) did not abolish or obviously increase chloralose-induced myoclonus. 6 Chloralose-induced myoclonus is not similar to 5-HT-sensitive reticular reflex myoclonus in man. PMID:6156735

  18. Ouabain uptake by endocytosis in isolated guinea pig atria

    SciTech Connect

    Nunez-Duran, H.; Riboni, L.; Ubaldo, E.; Kabela, E.; Barcenas-Ruiz, L. Instituto Nacional de Cardiologia, Mexico DF )

    1988-10-01

    Mammalian cells specifically internalize some molecular species through receptor-mediated endocytosis (RME). The authors have used four different experimental protocols to investigate whether ouabain enters cardiac cells of guinea pig atrium through this pathway. First, by electron microscope morphometry the authors found that ouabain increased endocytic vesicles in atrial cells. Second, by scintillation counting they found that ({sup 3}H)ouabain uptake by the tissue is decreased by three treatments that decrease RME, i.e., NH{sub 4}Cl, trifluoperazine, and 16 mM (K{sup +}){sub 0}. Third, by radioautography at the electron microscope level, they checked that in preceding experiments ({sup 3}H)ouabain was washed out of plasma membrane after 60-min rinse and interiorized into the cardiac cells. Fourth, isometric tension recordings showed that the positive inotropic effect of ouabain was diminished in the presence of inhibitors, whereas that of a hydrophobic analogue, ouabagenin, was not affected. These results suggest that ouabain enters cardiac cells through RME and also that an intracellular site may, at least in part, be responsible for its inotropic effect.

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

    PubMed Central

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

    2010-01-01

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

  20. 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.

  1. Natural antibodies to treponemal antigens in four strains of guinea-pigs.

    PubMed Central

    Jakubowski, A; Wicher, V; Gruhn, R; Wicher, K

    1987-01-01

    A total of 185 serum samples obtained from healthy male and female guinea-pigs of inbred strains 2 and 13 and outbred strains C4D and Hartley A were examined for natural antibodies to treponemal antigens by ELISA using Treponema pallidum (TP), T. phagedenis biotype Reiter (TR) and T. vincentii (TV) antigens and by the FTA test. The prevalence and titres of natural antibodies depended on the age and strain of guinea-pig and the treponemal antigen used. One- and 7-day-old guinea-pigs contained significantly (P less than 0.001) higher levels of natural antibodies than did animals 1 or 3-6 months old. The similar high levels of natural antibodies in newborn guinea-pigs and their mothers (12-30 months old) and the sharp drop observed at the age of 1 month suggested maternal transfer as the mechanism of acquisition. In young adults 3-6 months old, the age group most susceptible to TP infection, antibodies to TP and TR were at their lowest levels, but antibodies reacting to TV had already begun to rise. Natural antibodies were of the IgG1 and IgG2 but not of the IgM class. The highest levels of natural antibodies were in the C4D guinea-pigs; the lowest were in the Hartley A strain. Natural antibody activity was inhibited or adsorbed by TR antigens. PMID:3546103

  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. PMID:26363291

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

    PubMed

    Skjönsberg, Åsa; Mannström, Paula

    2015-07-01

    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. PMID:26053702

  4. 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.

  5. Characterization of a thromboxane A2/prostaglandin H2 receptor in guinea pig lung membranes using a radioiodinated thromboxane mimetic

    SciTech Connect

    Saussy, D.L. Jr.; Mais, D.E.; Dube, G.P.; Magee, D.E.; Brune, K.A.; Kurtz, W.L.; Williams, C.M. )

    1991-01-01

    Thromboxane A2 (TXA2) and prostaglandin H2 (PGH2) are potent constrictors of airway smooth muscle and may mediate some of the pulmonary effects of leukotrienes. To date, the TXA2/PGH2 receptor in lung has not been well characterized. In this report, we describe the evaluation of the TXA2/PGH2 receptor in guinea pig lung membranes using the new radiolabeled TXA2 mimetic (1S(1 alpha,2 beta(5Z),3 alpha(1E,3S*),4 alpha))-7-(3-(3-hydroxy-4-(4'- iodophenoxy)-1-butenyl)-7-oxabicyclo-(2.2.1)heptan-2-yl)-5-h eptenoic acid (IBOP). IBOP elicited a dose-dependent contraction of guinea pig lung parenchymal strips (EC50 = 3.03 +/- 0.97 nM, three experiments), which was blocked by the TXA2/PGH2 antagonists SQ29548 (pKB = 7.44 +/- 0.2, three experiments), BM13505 (pKB = 6.29 +/- 0.26, three experiments), and I-PTA-OH (pKB = 5.82 +/- 0.36, three experiments). In radioligand binding studies, the binding of (125I)IBOP to guinea pig lung membranes prepared from perfused lungs was saturable, displaceable, and dependent upon protein concentration. Binding was optimal at pH 6.5 and was enhanced by the addition of mono- and divalent cations. The standard assay buffer was 25 mM 3-(N-morpholino)propanesulfonic acid, pH 6.5, 100 mM NaCl, 5 mM MgCl2. Binding was inhibited by pretreatment with dithiothreitol, N-ethylmaleimide, or beta-mercaptoethanol. Binding was unaffected by the addition of guanine nucleotide analogs at concentrations up to 300 microM. Analysis of the time course of binding of (125)IBOP at 30 degrees yielded k-1 = 0.0447 min-1, k1 = 2.49 x 10(8) M-1 min-1, and Kd = k-1/k1 = 180 pM. Computer analysis of equilibrium binding studies using nonlinear methods (LUNDON-1) revealed a single class of noninteracting binding sites with a Kd of 86.9 +/- 11.9 pM and a Bmax of 81.8 +/- 7.7 fmol/mg of protein (three experiments).

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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....

  7. β-Nicotinamide adenine dinucleotide acts at prejunctional adenosine A1 receptors to suppress inhibitory musculomotor neurotransmission in guinea pig colon and human jejunum.

    PubMed

    Wang, Guo-Du; Wang, Xi-Yu; Liu, Sumei; Xia, Yun; Zou, Fei; Qu, Meihua; Needleman, Bradley J; Mikami, Dean J; Wood, Jackie D

    2015-06-01

    Intracellular microelectrodes were used to record neurogenic inhibitory junction potentials in the intestinal circular muscle coat. Electrical field stimulation was used to stimulate intramural neurons and evoke contraction of the smooth musculature. Exposure to β-nicotinamide adenine dinucleotide (β-NAD) did not alter smooth muscle membrane potential in guinea pig colon or human jejunum. ATP, ADP, β-NAD, and adenosine, as well as the purinergic P2Y1 receptor antagonists MRS 2179 and MRS 2500 and the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine, each suppressed inhibitory junction potentials in guinea pig and human preparations. β-NAD suppressed contractile force of twitch-like contractions evoked by electrical field stimulation in guinea pig and human preparations. P2Y1 receptor antagonists did not reverse this action. Stimulation of adenosine A1 receptors with 2-chloro-N6-cyclopentyladenosine suppressed the force of twitch contractions evoked by electrical field stimulation in like manner to the action of β-NAD. Blockade of adenosine A1 receptors with 8-cyclopentyl-1,3-dipropylxanthine suppressed the inhibitory action of β-NAD on the force of electrically evoked contractions. The results do not support an inhibitory neurotransmitter role for β-NAD at intestinal neuromuscular junctions. The data suggest that β-NAD is a ligand for the adenosine A1 receptor subtype expressed by neurons in the enteric nervous system. The influence of β-NAD on intestinal motility emerges from adenosine A1 receptor-mediated suppression of neurotransmitter release at inhibitory neuromuscular junctions. PMID:25813057

  8. β-Nicotinamide adenine dinucleotide acts at prejunctional adenosine A1 receptors to suppress inhibitory musculomotor neurotransmission in guinea pig colon and human jejunum

    PubMed Central

    Wang, Guo-Du; Wang, Xi-Yu; Liu, Sumei; Xia, Yun; Zou, Fei; Qu, Meihua; Needleman, Bradley J.; Mikami, Dean J.

    2015-01-01

    Intracellular microelectrodes were used to record neurogenic inhibitory junction potentials in the intestinal circular muscle coat. Electrical field stimulation was used to stimulate intramural neurons and evoke contraction of the smooth musculature. Exposure to β-nicotinamide adenine dinucleotide (β-NAD) did not alter smooth muscle membrane potential in guinea pig colon or human jejunum. ATP, ADP, β-NAD, and adenosine, as well as the purinergic P2Y1 receptor antagonists MRS 2179 and MRS 2500 and the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine, each suppressed inhibitory junction potentials in guinea pig and human preparations. β-NAD suppressed contractile force of twitch-like contractions evoked by electrical field stimulation in guinea pig and human preparations. P2Y1 receptor antagonists did not reverse this action. Stimulation of adenosine A1 receptors with 2-chloro-N6-cyclopentyladenosine suppressed the force of twitch contractions evoked by electrical field stimulation in like manner to the action of β-NAD. Blockade of adenosine A1 receptors with 8-cyclopentyl-1,3-dipropylxanthine suppressed the inhibitory action of β-NAD on the force of electrically evoked contractions. The results do not support an inhibitory neurotransmitter role for β-NAD at intestinal neuromuscular junctions. The data suggest that β-NAD is a ligand for the adenosine A1 receptor subtype expressed by neurons in the enteric nervous system. The influence of β-NAD on intestinal motility emerges from adenosine A1 receptor-mediated suppression of neurotransmitter release at inhibitory neuromuscular junctions. PMID:25813057

  9. Dual effect of trimebutine on contractility of the guinea pig ileum via the opioid receptors.

    PubMed

    Taniyama, K; Sano, I; Nakayama, S; Matsuyama, S; Takeda, K; Yoshihara, C; Tanaka, C

    1991-12-01

    Preparations of longitudinal muscle attached to myenteric plexus from guinea pig ileum were used to observe the effect of trimebutine on intestinal motility. Electrical stimulation at 0.2 Hz and 5 Hz produced contraction mediated by the release of acetylcholine in the preparations. The response to low-frequency stimulation (0.2 Hz) was inhibited by trimebutine (10(-8)-10(-5) mol/L), and the response to high-frequency stimulation (5 Hz) was enhanced by the drug at low concentrations (10(-8)-10(-7) mol/L) and inhibited by high concentrations (10(-6)-10(-5) mol/L). This enhancement was mimicked by [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin, and was antagonized by naloxone but not by MR2266. Enhancement by trimebutine was inhibited by yohimbine. Trimebutine (greater than or equal to 10(-8) mol/L) inhibited stimulation (5 Hz)-evoked release of norepinephrine, and the trimebutine effect was antagonized by naloxone but not by MR2266. Low concentrations of trimebutine inhibit norepinephrine release via the mu-opioid receptor and enhance intestinal motility by preventing the adrenergic inhibition of acetylcholine release. Inhibition by trimebutine was antagonized either by naloxone or MR2266. High concentrations of trimebutine may inhibit acetylcholine release via the mu- and kappa-opioid receptors, after which the intestinal motility is inhibited. Trimebutine at further high concentrations (greater than 10(-5) mol/L) contracted single smooth muscle cells from the circular muscle layers but not from the longitudinal muscle layers. The usual dose of trimebutine may exert dual effect on the intestinal motility indirectly through cholinergic and adrenergic neurons without direct effect on the smooth muscle. PMID:1659547

  10. Different ontogeny of rate of force generation and shortening velocity in guinea pig trachealis.

    PubMed

    Chitano, P; Wang, J; Cox, C M; Stephens, N L; Murphy, T M

    2000-04-01

    Juveniles of many species, including humans, display greater airway responsiveness than do adults. This may involve changes in airway smooth muscle function. In the present work we studied force production and shortening velocity in trachealis from 1-wk-old (1 wk), 3-wk-old (3 wk), and 3-mo-old (adult) guinea pigs. Strips were electrically stimulated (60 Hz, 18 V) at their optimal length (l(o)) to obtain maximum active stress (P(o)) and rate of stress generation. Then, force-velocity curves were elicited at 2.5 s from the onset of the stimulus. By applying a recently developed modification of Hill's equation for airway smooth muscle, the maximum shortening velocity at zero load (V(o)) and the value alpha. gamma/beta, an index of internal resistance to shortening (Rsi), were calculated (alpha, beta, and gamma are the constants of the equation). P(o) increased little with maturation, whereas the rate of stress generation increased significantly (0.40 +/- 0.03, 0.45 +/- 0.03, 0. 51 +/- 0.03 P(o)/s for 1 wk, 3 wk, and adult animals). V(o) slightly increased early with maturation to decrease significantly later (1. 79 +/- 0.67, 2.45 +/- 0.92, and 0.55 +/- 0.09 l(o)/s for 1 wk, 3 wk, and adult animals), whereas the Rsi showed an opposite trend (14.98 +/- 5.19, 8.99 +/- 3.01, and 32.07 +/- 5.54 mN. mm(-2). l(o)(-1). s for 1 wk, 3 wk, and adult animals). This early increase of force generation in combination with late increase of Rsi may explain the changes of V(o) with age. An elevated V(o) may contribute to the incidence of airway hyperresponsiveness in healthy juveniles. PMID:10749828

  11. Localised calcium release events in cells from the muscle of guinea-pig gastric fundus

    PubMed Central

    Parsons, S P; Bolton, T B

    2004-01-01

    After enzymatic dispersion of the muscle of the guinea-pig gastric fundus, single elongated cells were observed which differed from archetypal smooth muscle cells due to their knurled, tuberose or otherwise irregular surface morphology. These, but not archetypal smooth muscle cells, consistently displayed spontaneous localized (i.e. non-propagating) intracellular calcium ([Ca2+]i) release events. Such calcium events were novel in their magnitude and kinetic profiles. They included short transient events, plateau events and events which coalesced spatially or temporally (compound events). Quantitative analysis of the events with an automatic detection programme showed that their spatio-temporal characteristics (full width and full duration at half-maximum amplitude) were approximately exponentially distributed. Their amplitude distribution suggested the presence of two release modes. Carbachol application caused an initial cell-wide calcium transient followed by an increase in localized calcium release events. Pharmacological analysis suggested that localized calcium release was largely dependent on external calcium entry acting on both inositol trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) to release stored calcium. Nominally calcium-free external solution immediately and reversibly abolished all localized calcium release without blocking the initial transient calcium release response to carbachol. This was inhibited by 2-APB (100 μm), ryanodine (10 or 50 μm) or U-73122 (1 μm). 2-APB (100 μm), xestospongin C (XeC, 10 μm) or U-73122 (1 μm) blocked both spontaneous localized calcium release and localized release stimulated by 10 μm carbachol. Ryanodine (50 μm) also inhibited spontaneous release, but enhanced localized release in response to carbachol. This study represents the first characterization of localized calcium release events in cells from the gastric fundus. PMID:14608011

  12. 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

  13. Differences in susceptibility to infection with Treponema pallidum (Nichols) between five strains of guinea pig.

    PubMed

    Wicher, K; Wicher, V; Gruhn, R F

    1985-02-01

    Groups of 10 young male guinea pigs of inbred strains 2 and 13 and outbred strains Hartley A, Hartley B, and one deficient in the fourth component of complement (C4D) were infected intradermally with 80 X 10(6) Treponema pallidum (Nichols). The course of infection and production of antitreponemal antibody were examined. Strain C4D guinea pigs were the most susceptible to infection (100%); inbred strains 2 and 13 and outbred strain Hartley B showed 80-90% symptomatic infection; and the Hartley A strain was the least susceptible to infection (10%). Strain 13 animals responded with the highest antitreponemal antibody activity, and the Hartley A strain with the lowest. The results suggest that genetic factors or complement, or both, may influence the degree of susceptibility to infection with T pallidum in guinea pigs. PMID:3910539

  14. The release of histamine by parasympathetic stimulation in guinea-pig auricle and rat ileum.

    PubMed Central

    Bani-Sacchi, T; Barattini, M; Bianchi, S; Blandina, P; Brunelleschi, S; Fantozzi, R; Mannaioni, P F; Masini, E

    1986-01-01

    Two preparations, a segment of rat ileum and the vagally innerved guinea-pig auricles, have been used in an analysis of the responses to vagal or to electrical field stimulation. The responses to parasympathetic stimulation were depressed by atropine and by tetrodotoxin, and potentiated by eserine. Supramaximal stimulation (10-20 Hz) resulted in increased release of acetylcholine and histamine, both in rat ileum and guinea-pig auricles. The release of histamine after parasympathetic stimulation did not exhibit tachyphylaxis, and it was not reproduced by non-parasympathetic stimuli. In both preparations, atropine produced a significant, dose-related reduction of histamine measured in the bath fluid after stimulation, while eserine increased histamine output. A significant diminution of mast cell granules metachromasia was observed in guinea-pig auricles and in rat intestine after parasympathetic stimulation. The possibility is discussed that acetylcholine released by parasympathetic stimulation would in turn evoke the secretion of histamine from tissue mast cells. PMID:2422351

  15. 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

  16. 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.

  17. Effects of a potassium channel opener (SDZ PCO 400) on guinea-pig and human pulmonary airways.

    PubMed Central

    Chapman, I. D.; Kristersson, A.; Mathelin, G.; Schaeublin, E.; Mazzoni, L.; Boubekeur, K.; Murphy, N.; Morley, J.

    1992-01-01

    1. SDZ PCO 400 evoked dose-related relaxation of isolated airway smooth muscle. For human bronchus precontracted by endogenous tone or addition of carbachol (10(-5) M), IC50 values were 1.74 microM and 1.82 microM respectively. With guinea-pig trachea contracted by endogenous tone, a comparable IC50 (1.79 microM) was observed, but no IC50 (less than 100 microM) could be determined following contraction by carbachol (10(-6) M). 2. Airway obstruction induced by intravenous bombesin in the anaesthetized ventilated guinea-pig was diminished by intravenous injection of SDZ PCO 400 (ID50 54 micrograms kg-1) or by introduction into the duodenum (ID50 1.0 mg kg-1). Inhalation of nebulized SDZ PCO 400 (0.1 mg kg-1) diminished airway obstruction due to intravenous injection of histamine (3.2-5.6 micrograms kg-1) for up to 20 min. 3. Increased bronchoconstrictor responses to bombesin (180-240 ng kg-1) following intravenous infusion of platelet activating factor (PAF) or (+/-)-isoprenaline, or to histamine (1.0-3.2 micrograms kg-1) following intravenous injections of immune complexes, were suppressed following concomitant intravenous infusion of SDZ PCO 400 (ID50 0.3 mg kg-1 h-1, 1.0 mg kg-1 h-1 and 0.1 mg kg-1 h-1 respectively). 4. Intravenous injection of SDZ PCO 400 (0.1 mg kg-1) effected transient (less than 10 min) inhibition of histamine-induced bronchospasm, yet diminished, for prolonged periods [up to 40 min] the enhanced bronchoconstrictor responses to histamine that followed intravenous injections of immune complexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1382782

  18. 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

  19. 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. PMID:27101759

  20. 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.

  1. 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.

  2. Apparent lack of beta 3-adrenoceptors and of insulin regulation of glucose transport in brown adipose tissue of guinea pigs.

    PubMed

    Himms-Hagen, J; Triandafillou, J; Begin-Heick, N; Ghorbani, M; Kates, A L

    1995-01-01

    Norepinephrine-induced thermogenesis was substantial in adipocytes from brown adipose tissue (BAT) of cold-acclimated guinea pigs but absent in adipocytes from BAT of warm-acclimated guinea pigs. There was no thermogenic response to any beta 3-adrenergic agonist (CL-316,243, ZD-7114, BRL-28410, CGP-12177). The receptor was characterized as a beta 1-adrenoceptor. Adrenergic agonists stimulated adenylate cyclase in membranes from BAT of both warm- and cold-acclimated guinea pigs also via a beta 1-adrenoceptor; beta 3-adrenergic agonists had no effect. Glucose transport by brown adipocytes from warm-acclimated guinea pigs was not stimulated by either norepinephrine or insulin. Cold acclimation induced the appearance of stimulation of glucose transport by norepinephrine in association with the appearance of a large capacity for thermogenesis, but there was little improvement in response to insulin. GLUT4 was present in membranes from BAT of both warm- and cold-acclimated guinea pigs. Insulin is known to have an antilipolytic effect on both BAT and white adipose tissue of guinea pigs. Thus there is a selective lack of insulin-regulated glucose transport that is not improved by cold acclimation. Guinea pigs may have a mutated component of the translocation mechanism for GLUT4. beta 3-Adrenoceptors appear to be absent in brown adipocytes of adult guinea pigs, as in white adipocytes of guinea pigs, yet are known to be present in the gut. Tissue-specific expression of beta 3-adrenergic receptors in guinea pigs may differ from that in rats, in which receptors are expressed in the adipose tissues and gut. PMID:7840345

  3. Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

    SciTech Connect

    Buehler, Paul W.; Butt, Omer I.; D'Agnillo, Felice

    2011-06-10

    Highlights: {yields} Toxicological implications associated with the use of NaNO{sub 2} therapy to treat systemic cell-free Hb exposure are not well-defined. {yields} Systemic Hb exposure followed by NaNO{sub 2} infusion induces acute CNS toxicities in guinea pigs. {yields} These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO{sub 2} alone. {yields} NaNO{sub 2}-mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO{sub 2}) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO{sub 2} with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO{sub 2} on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO{sub 2}, at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO{sub 2} alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

  4. Differential responses of pulmonary arteries and veins to histamine and 5-HT in lung explants of guinea-pigs

    PubMed Central

    Shi, Weibin; Wang, Chong-Gang; Dandurand, Ron J; Eidelman, David H; Michel, René P

    1998-01-01

    The mechanisms by which histamine and 5-HT differentially contract pulmonary arteries and veins are unclear. In lung explants from 26 guinea-pigs, we compared responses of pulmonary arteries and vein to histamine, 5-HT and KCl, and examined potential determinants for the differential responses. Lungs were filled with agarose, sectioned into ∼1 mm thick slices, and vascular luminal areas measured by image analysis.Histamine and 5-HT produced a concentration-dependent constriction in arteries and veins, greater in the latter. KCl constricted arteries and veins equally.The histamine H1 antagonist chlorpheniramine (10−4 M) abolished contractions to histamine; the H2 antagonist cimetidine enhanced maximal responses and sensitivity of arteries and veins to histamine, and diminished the differences between their maximal responses; the NO synthase inhibitor Nω-nitro-L-arginine (L-NOARG) increased the maximal responses of arteries and veins, and the differences between their responses; indomethacin had no effect.Contractions to 5-HT were abolished in arteries and markedly reduced in veins by the 5-HT2 antagonist ketanserin (10−4 M); L-NOARG potentiated the maximal responses of arteries but not of veins; indomethacin increased the maximal responses of arteries but reduced them in veins.By morphometry, arteries had a greater medial thickness and luminal diameter than veins.The data suggest that in guinea-pigs, H2 receptors are responsible for the differential contractile responses of pulmonary arteries and veins to histamine, whereas endothelium-derived vasoactive substances are responsible for their differential contractile responses to 5-HT. PMID:9605557

  5. 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

  6. The sensitizing capacity of multifunctional acrylates in the guinea pig.

    PubMed

    Björkner, B

    1984-10-01

    The multifunctional acrylates used in ultraviolet (UV) curable resins act as cross-linkers and "diluents". They are usually based on di(meth)acrylate esters of dialcohols or tri- and tetra-acrylate esters of polyalcohols. In UV-curable coatings, the most commonly used are pentaerythritol triacrylate (PETA), trimethylolpropane triacrylate (TMPTA) and 1,6-hexanediol diacrylate (HDDA). In other uses, such as dental composite resin materials, the dimethacrylic monomers based on n-ethylene glycol are the most useful. The sensitizing capacity of various multifunctional acrylates and their cross-reactivity pattern have been investigated with the guinea pig maximization test. The tests show that BUDA (1,4-butanediol diacrylate) and HDDA are moderate to strong sensitizers and that they probably cross-react with each other. The n-ethylene glycol diacrylates and methacrylates tested are weak or non-sensitizers. Tripropylene glycol diacrylate (TPGDA) is a moderate and neopentyl glycol diacrylate (NPGDA) a strong sensitizer, whereas neopentyl glycol dimethacrylate is a non-sensitizer. The commercial PETA is a mixture of pentaerythritol tri- and tetra-acrylate (PETA-3 and PETA-4). PETA-3 is a much stronger sensitizer than PETA-4. Simultaneous reactions were seen between PETA-3, PETA-4 and TMPTA. The oligotriacrylate OTA 480 is a moderate sensitizer, but no concomitant reactions were seen with PETA-3, PETA-4 or TMPTA. Of the multifunctional acrylates tested, the di- and triacrylic compounds should be regarded as potent sensitizers. The methacrylated multifunctional acrylic compounds are weak or non-sensitizers. PMID:6499426

  7. Purification and characterization of guinea pig liver morphine 6-dehydrogenase.

    PubMed

    Yamano, S; Kageura, E; Ishida, T; Toki, S

    1985-05-10

    Morphine 6-dehydrogenase, which catalyzes the dehydrogenation of morphine to morphinone, has been purified about 440-fold from the soluble fraction of guinea pig liver with a yield of 38%. The purified enzyme was a homogeneous protein on polyacrylamide gel disc electrophoresis and isoelectric focusing. The molecular weight and isoelectric point of the enzyme were 29,000 and 7.6, respectively. The enzyme utilizes both NAD and NADP as a cofactor, and the Km values were 0.12 mM for NAD and 0.42 mM for NADP. The Vmax values for morphine were 588 milliunits/mg of protein (with NAD) and 1600 milliunits/mg of protein (with NADP). The Km values for morphine were 0.12 mM (with NAD) and 0.49 mM (with NADP). The enzyme also exhibited activity for morphine-related compounds: nalorphine, normorphine, codeine, and ethylmorphine; however, 7,8-saturated congeners such as dihydromorphine and dihydrocodeine were poor substrates. The enzyme was inactivated by removal of 2-mercaptoethanol from the enzyme solution. The inactivated enzyme was rapidly recovered by the addition of 2-mercaptoethanol. Phenylarsine oxide and CdCl2 (dithiol modifiers) inhibited competitively toward cofactor binding and noncompetitively toward morphine binding. These results suggest that the enzyme possesses the essential thiol groups, probably vicinal dithiol, at or near the cofactor-binding site. Using the partially purified enzyme, 8-(2-hydroxyethylthio)dihydromorphinone was isolated as the product and identified by UV, mass, and NMR spectra. It was confirmed that morphinone proposed as the dehydrogenation product was nonenzymatically and covalently bound to 2-mercaptoethanol. Accordingly, the isolated morphinone-2-mercaptoethanol conjugate must be formed by two steps: enzymatic production of morphinone from morphine and then nonenzymatic binding of 2-mercaptoethanol to morphinone. PMID:2580834

  8. Bradykinin-induced contraction of guinea pig lung in vitro.

    PubMed

    Lach, E; Trifilieff, A; Mousli, M; Landry, Y; Gies, J P

    1994-08-01

    We have investigated the contractile effect of bradykinin (BK) in guinea pig lung in vitro. BK induces a dose-related contraction of lung parenchymal strips which is increased significantly in the presence of 10(-5) M captopril (an angiotensin converting enzyme inhibitor) or 10(-5) M DL-thiorphan (a neutral endopeptidase inhibitor). The kininase I inhibitor, DL-2-mercaptomethyl-3-guanidino-ethylthiopropionic acid (MGTPA), has no effect on the BK-induced contraction. BK is more potent in contracting parenchymal lung strips than other contractile agents (histamine, carbachol and substance P), however the BK-induced maximal contraction is lower than those obtained with histamine and carbachol. The B1 agonist, des-Arg9-BK, does not contract lung parenchymal strips. The new BK B2 receptor antagonists (Hoe 140, NPC 17731 and NPC 17761), which possess binding affinities in the nanomolar range, inhibit the BK-induced contractile response in a dose-dependent manner. The BK-induced contraction was unaffected by propranolol, atropine, tetrodotoxin, capsaicin pre-treatment, triprolidine, methysergide, Ro 19-3704 and N omega-nitro-L-arginine-methyl-ester (L-NAME), excluding the involvement of nervous pathways, preformed mast cell mediators, platelet-activating factor and nitric oxide. However, indomethacin, a cyclooxygenase inhibitor, AA-861, a 5-lipoxygenase inhibitor, and furegrelate, a thromboxane A2 synthase inhibitor, decreased the contractile response to BK, suggesting that both cyclooxygenase and 5-lipoxygenase products are involved in this contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7990978

  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. Effect of cinitapride in isolated ileum obtained from guinea-pigs treated with morphine.

    PubMed

    Colado, M I; Alfaro, M J; del Val, V L; Martín, M I

    1991-01-01

    1. Cinitapride enhanced the contractile response induced by electrical stimulation in the guinea-pig myenteric plexus-longitudinal muscle strip preparations. 2. The contractile force was significantly increased in strips pretreated with morphine "in vitro" and in tolerant strips. 3. However when tissues were obtained from tolerant guinea-pigs and morphine was not added to the organ bath (morphine-abstinence), the cinitapride effect was significantly decreased. 4. Although further work is required to explain the changes in the effect of cinitapride after acute morphine treatment and in morphine tolerant tissues, the changes observed suggest that some of the cinitapride effects could be linked with the peripheral opioid system. PMID:1662171

  11. 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.

  12. Stimulation of anti-tumour immunity in guinea-pigs by methanol extraction residue of BCG.

    PubMed Central

    Wainberg, M. A.; Deutsch, V.; Weiss, D. W.

    1976-01-01

    The immunoprophylactic effects of the methanol extraction residue (MER) of BCG were investigated in Strain 2 guinea-pigs injected with cells of the transplantable, diethylnitrosamine-induced, Line 10 hepatocarcinoma. Pretreatment with MER at times ranging from 18 to 182 days prior to tumour implantation protected approximately 40% of guinea-pigs from progressive neoplastic disease. In addition, MER-treated animals developed specific cell-mediated anti-tumour immunity both more rapidly and at higher levels than did non-MER-treated tumour-bearing controls. It was not possible, however, to prognosticate from the results of such laboratory studies to the outcome of immunoprophylaxis. PMID:187207

  13. Digesta retention and fibre digestion in maras (Dolichotis patagonum) and guinea-pigs.

    PubMed

    Sakaguchi, E; Nippashi, K; Endoh, G

    1992-04-01

    1. Digestibilities of feed and turnover time (1/k), transit time (TT) and mean retention time (MRT: 1/k+TT) of fluid and particle markers were measured in maras (Dolichotis patagonum) and guinea-pigs (Cavia procellus) fed a diet containing 50% alfalfa. 2. The digestibility of fibre was similar in both animals, however, the digestibilities of crude protein (nitrogen x 6.25) and crude ash were lower in the mara than in the guinea-pig. 3. 1/k of the digesta markers were similar in both animals, suggesting that the two animals possess similar dilution and retention time of digesta in their caecum and proximal colon. PMID:1351463

  14. The vertebrobasilar arterial system in guinea pig as compared with dog and human.

    PubMed

    Majewska-Michalska, E

    1998-01-01

    The arterial system formed by branches of the vertebral and basilar arteries in guinea pig was compared to that of dog and human. The vertebrobasilar arterial system in particular species shows similarities and differences, considering its structure and arising branches. The differences are mainly due to the length of the basilar artery. In guinea pig the vertebrobasilar system distribute blood to the 2/3 of the brain. The same distribution is in dog. In human the carotid system predominates in the supply of the brain. PMID:9835170

  15. Interaction of glutathione and ascorbic acid in guinea pig lungs exposed to nitrogen dioxide

    SciTech Connect

    Leung, H.-W.; Morrow, P.E.

    1981-01-01

    The interaction of two important water-soluble antioxidants, glutathione and ascorbic acid, was studied. The perfused guinea pig lung was found to contain about twice as much reduced glutathione as ascorbic acid. Nitrogen dioxide exposure decreased the levels of the two antioxidants both in vitro and in vivo. Ascorbic acid concentration was lowered to a greater extent than glutathione. The pulmonary ascorbic acid level was identical in both control and glutathione-deficient guinea pigs exposed to nitrogen dioxide, suggesting that there was little interaction between the two antioxidants in the lungs during oxidant stress.

  16. The relationship between contraction and intracellular sodium in rat and guinea-pig ventricular myocytes.

    PubMed Central

    Harrison, S M; McCall, E; Boyett, M R

    1992-01-01

    1. The contraction, measured optically, and the intracellular Na+ activity (aNai), measured with the Na(+)-sensitive fluorescent dye SBFI, have been recorded simultaneously in rat and guinea-pig ventricular myocytes. 2. In rat and guinea-pig ventricular myocytes at rest, aNai was 7.8 +/- 0.3 mM (n = 4) and 5.1 +/- 0.3 mM (n = 16), respectively. 3. When both rat and guinea-pig ventricular myocytes were stimulated at 1 Hz after a rest there was usually a gradual increase in twitch shortening (referred to as a 'staircase') over several minutes accompanied by an increase in aNai over a similar time course. Twitch shortening increased by 21 +/- 3% (n = 6) and 20 +/- 4% (n = 16) (of steady-state twitch shortening during 1 Hz stimulation) per millimolar rise in aNai in rat and guinea-pig ventricular myocytes, respectively. 4. When rat and guinea-pig ventricular myocytes were exposed to strophanthidin to block the Na(+)-K+ pump, there were increases in twitch shortening and aNai over similar time courses. Twitch shortening increased by 24 +/- 4% (n = 5) and 20 +/- 3% (n = 10) (of control twitch shortening) per millimolar rise in aNai in rat and guinea-pig ventricular myocytes respectively. 5. The inotropic effect of cardiac glycosides, such as strophanthidin, is widely regarded to be principally the result of the rise in aNai. The similarity of the relation between twitch shortening and aNai during the staircase and on application of strophanthidin suggests that the progressive increase in the strength of contraction during the staircase was also linked to the rise in aNai. 6. In guinea-pig, but not rat, ventricular myocytes there was hysteresis in the relation between twitch shortening and aNai on application and wash-off of strophanthidin. This indicates that strophanthidin has another inotropic action in guinea-pig ventricular myocytes. 7. A computer model of excitation-contraction coupling has been developed to simulate the staircase and the action of cardiac glycoside

  17. 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

  18. Effects of Schisandra chinensis extracts on cough and pulmonary inflammation in a cough hypersensitivity guinea pig model induced by cigarette smoke exposure.

    PubMed

    Zhong, Shan; Nie, Yi-chu; Gan, Zhen-yong; Liu, Xiao-dong; Fang, Zhang-fu; Zhong, Bo-nian; Tian, Jin; Huang, Chu-qin; Lai, Ke-fang; Zhong, Nan-shan

    2015-05-13

    Schisandra chinensis (S. chinensis) is a traditional Chinese medicine commonly used in prescription medications for the treatment of chronic cough. However, the material basis of S. chinensis in relieving cough has not been completely elucidated yet. This study established a guinea pig model of cough hypersensitivity induced by 14 days of cigarette smoke (CS) exposure, to evaluate the antitussive, antioxidant, and anti-inflammatory effects of three S. chinensis extracts. And then the function of four lignans in reducing expression of TRPV1 and TRPA1 was examined using A549 cells induced by cigarette smoke extract (CSE). The results demonstrated that both ethanol extract (EE) and ethanol-water extract (EWE) of S. chinensis, but not water extract (WE), significantly reduced the cough frequency enhanced by 0.4M citric acid solution in these cough hypersensitivity guinea pigs. Meanwhile, pretreatment with EE and EWE both significantly attenuated the CS-induced increase in infiltration of pulmonary neutrophils and total inflammatory cells, as well as pulmonary MDA, TNF-α, and IL-8, while remarkably increased activities of pulmonary SOD and GSH. According to H&E and immunofluorescence staining assays, airway epithelium hyperplasia, smooth muscle thickening, inflammatory cells infiltration, as well as expression of TRPV1 and TRPA1, were significantly attenuated in animals pretreatment with 1g/kg EE. Moreover, four lignans of EE, including schizandrin, schisantherin A, deoxyschizandrin and γ-schisandrin, significantly inhibited CSE-induced expression of TRPV1, TRPA1 and NOS3, as well as NO release in A549 cells. In conclusion, S. chinensis reduces cough frequency and pulmonary inflammation in the CS-induced cough hypersensitivity guinea pigs. Lignans may be the active components. PMID:25681545

  19. Relaxation of evoked contractile activity of isolated guinea-pig ileum by (+/-)-kavain.

    PubMed

    Seitz, U; Ameri, A; Pelzer, H; Gleitz, J; Peters, T

    1997-08-01

    Kava pyrones are the pharmacologically active compounds of Piper methysticum Forst. In the present study, the effect of the synthetic kava pyrone (+/-)-kavain was investigated on evoked contractile activity of isolated guinea-pig ileum. (+/-)-Kavain (1 microM-1 mM) dose-dependently reduced contractions of ileum evoked by carbachol (10 microM), by BAY K 8644 (0.3 microM), or by substance P (0.05 microM). (+/-)-Kavain also inhibited the contractile responses induced by raising the extracellular K+ concentration from 4 to 20 mM and by blocking the K+ channel by barium chloride (1 mM) or 4-aminopyridine (0.3 mM). After pre-incubation with 1 microM nifedipine, carbachol (1 microM) evoked 18.2 +/- 14.3% of contraction at control (i.e. prior pre-incubation with nifedipine). This remaining response was completely abolished by high concentrations of (+/-)-kavain (400 microM). After treatment of the longitudinal ileum strips with pertussis toxin (PTX), carbachol (1 microM) evoked 27.0 +/- 6.2% of the control response in untreated ileum. These contractions were also blocked by (+/-)-kavain (400 microM). However, (+/-)-kavain had no effect on the caffeine-induced (20 mM) contractions of ileum strips, which were permeabilized with digitonin or beta-escin. Moreover, it failed to affect Ca(2+)-evoked contractions of skinned muscles. These results suggest that the kava pyrone (+/-)-kavain may act in a non-specific musculotropic way on the smooth muscle membrane. PMID:9270372

  20. Mechanism of cadmium-induced contraction in ileal longitudinal muscle of guinea-pig.

    PubMed Central

    Asai, F.; Nishimura, M.; Satoh, E.; Urakawa, N.

    1982-01-01

    1 The mechanism of cadmium (Cd2+)-induced contraction was studied in isolated ileal longitudinal muscle of guinea-pig. 2 CdCl2 (1x10(-8) to 1x10-4M)) caused a transient contraction which subsided within approximately 6 min of application. The contraction was reproducible and dependent on the concentration. The dose-response curve was bell-shaped. A maximal response was observed at concentrations of 5x10(-6) to 1x10(-5) M. 3 The contractile effect was inhibited to some degree at 20 degree C or by tetrodotoxin (0.1 microgram/ml), hyoscine (o.1 microgram/ml), but completely inhibited by Ca2+ -removal from the medium. 4 Cd2+ increased the output of [14C]-acetylcholine biosynthesized from [14C] by the preparation depending on the concentration. The increase terminated within the first 6 min and was reduced by tetrodotoxin (0.1 microgram/ml) or by removal of Ca2+ from the medium. 5 Both the contractile and transmitter releasing effects of Cd2+ were dependent on the concentration of external Ca2+. Strontium ions were able to replace Ca2+ -induced transmitter release. 6 It is suggested that Cd2+ contracts ileal longitudinal muscle through a release of cholinergic transmitter from the parasympathetic nerve terminals, which is dependent on external Ca2+. It also has a smaller hyoscine-resistant contractile effect, presumably due to a direct action on smooth muscle cells. PMID:7066605

  1. Effect of ozone treatment on airway reactivity and epithelium-derived relaxing factor in guinea pigs.

    PubMed

    Fedan, J S; Millecchia, L L; Johnston, R A; Rengasamy, A; Hubbs, A; Dey, R D; Yuan, L X; Watson, D; Goldsmith, W T; Reynolds, J S; Orsini, L; Dortch-Carnes, J; Cutler, D; Frazer, D G

    2000-06-01

    Ozone (O(3)) is toxic to respiratory epithelium and causes airway inflammation and hyperreactivity. To evaluate the role of the epithelium in the development of hyperreactivity, we examined in guinea pigs the effects of inhaled O(3) (3 ppm for 1 h; 0-24 h after exposure) on 1) reactivity to inhaled methacholine (MCh), 2) reactivity of the isolated, perfused trachea (IPT) to MCh, 3) epithelium-derived relaxing factor (EpDRF)-mediated relaxations of IPT induced by mucosal hyperosmolar solutions, 4) neurogenic contraction and relaxation responses, 5) transepithelial potential difference, and 6) microscopic analysis of nitrotyrosine immunofluorescence, substance P fiber density, and tracheal morphology. At 0 h, O(3) caused hyperreactivity to inhaled MCh and mucosally but not serosally applied MCh in IPT (only in the presence of the epithelium) and a decrease in transepithelial potential difference. Inhibition of EpDRF-induced relaxation responses occurred at 2 h. All of these changes returned to control by 12 to 18 h. O(3) had no effect on neurogenic responses. Nitrotyrosine immunofluorescence appeared in the trachea at 0 h in detached epithelial cell ghosts and in intrapulmonary airways by 6 h. Substance P fiber density was elevated in smooth muscle at 0 and 18 h but not in epithelium or lamina propria of intrapulmonary and extrapulmonary bronchi. Loss of cilia and mucosubstances in the mucosa occurred at 0 h; the epithelium became markedly attenuated over 12 to 24 h. A reversible increase in epithelial permeability and a decrease in EpDRF production may contribute to O(3)-induced hyperreactivity to MCh. PMID:10869370

  2. The passive membrane properties and excitatory junction potentials of the guinea pig deferens.

    PubMed Central

    Bywater, R A; Taylor, G S

    1980-01-01

    1. Electrotonic potentials were recorded from the superficial smooth muscle cells of the guinea-pig vas deferens using the method of Abe & Tomita (1968), in response to low-amplitude, long-duration (greater than or equal to 2 sec) pulses. 2. Averaging techniques were used to increase the signal/noise ratio, and the intracellularly recorded electrotonic potentials were corrected for extracellular voltage drop across the bath series resistance. 3. Since the length of tissue in the stimulating and recording compartments affects the time course of electrotonic potentials (see Appendix and Bywater & Redman, 1978) the passive membrane properties were measured with known amounts of tissue in these two compartments. 4. The length constant (lambda) was 0.86 mm and the membrane time constant (tau m) 270 msec. 5. Excitatory junction potentials (e.j.p.s) were recorded and averaged in response to field stimulation of intact branches of the hypogastric nerve. The mean time constant of the exponential decay phase of the e.j.p. (288 msec) was similar to the membrane time constant (tau m = 270 msec). 6. As the e.j.p.s showed little change in amplitude or time constant of decay when recorded up to several millimetres from the stimulating electrode it was assumed that the tissue was isopotential during the e.j.p., and an estimate was made of the time course of the underlying junctional current. 7. The estimated time course of the junctional current during an e.j.p. was similar to the observed time course of a spontaneous junction potential (s.e.j.p.). 8. As the time course of the junctional current during an s.e.j.p.is similar to the time course of the potential change it is likely that the factors which determine the time current underlying the s.e.j.p. also determine the time course of the e.j.p. current. PMID:7381788

  3. Identification of the tracheal and laryngeal afferent neurones mediating cough in anaesthetized guinea-pigs

    PubMed Central

    Canning, Brendan J; Mazzone, Stuart B; Meeker, Sonya N; Mori, Nanako; Reynolds, Sandra M; Undem, Bradley J

    2004-01-01

    We have identified the tracheal and laryngeal afferent nerves regulating cough in anaesthetized guinea-pigs. Cough was evoked by electrical or mechanical stimulation of the tracheal or laryngeal mucosa, or by citric acid applied topically to the trachea or larynx. By contrast, neither capsaicin nor bradykinin challenges to the trachea or larynx evoked cough. Bradykinin and histamine administered intravenously also failed to evoke cough. Electrophysiological studies revealed that the majority of capsaicin-sensitive afferent neurones (both Aδ- and C-fibres) innervating the rostral trachea and larynx have their cell bodies in the jugular ganglia and project to the airways via the superior laryngeal nerves. Capsaicin-insensitive afferent neurones with cell bodies in the nodose ganglia projected to the rostral trachea and larynx via the recurrent laryngeal nerves. Severing the recurrent nerves abolished coughing evoked from the trachea and larynx whereas severing the superior laryngeal nerves was without effect on coughing. The data indicate that the tracheal and laryngeal afferent neurones regulating cough are polymodal Aδ-fibres that arise from the nodose ganglia. These afferent neurones are activated by punctate mechanical stimulation and acid but are unresponsive to capsaicin, bradykinin, smooth muscle contraction, longitudinal or transverse stretching of the airways, or distension. Comparing these physiological properties with those of intrapulmonary mechanoreceptors indicates that the afferent neurones mediating cough are quite distinct from the well-defined rapidly and slowly adapting stretch receptors innervating the airways and lungs. We propose that these airway afferent neurones represent a distinct subtype and that their primary function is regulation of the cough reflex. PMID:15004208

  4. Interstitial adenosine concentration during norepinephrine infusion in isolated guinea pig hearts

    PubMed Central

    GORMAN, MARK W.; WANGLER, ROGER D.; BASSINGTHWAIGHTE, JAMES B.; MOHRMAN, DAVID E.; WANG, C. Y.; SPARKS, HARVEY V.

    2010-01-01

    This study determined the effect of norepinephrine (NE) on cardiac interstitial fluid adenosine concentration ([ADO]isf). Isolated guinea pig hearts were perfused with a Krebs-Henseleit buffer solution. Radiolabeled albumin, sucrose, and adenosine were injected under control conditions and after 3 and 20 min of NE infusion to obtain multiple indicator dilution curves that were used to determine capillary transport parameters for adenosine. These parameters together with venous adenosine concentrations were used in a mathematical model to calculate [ADO]isf. Capillary transport parameters were not changed significantly by NE infusion. Because of uncertainty regarding two model parameters, two sets of [ADO]isf values were calculated. One set used best-fit values obtained from indicator dilution curves, and a second set used parameters chosen to provide the highest [ADO]isf values consistent with indicator dilution curves. Venous adenosine concentrations were 1.9 ± 0.4 nM under control conditions and 243 ± 110 and 45 ± 25 nM after 3 and 20 min of NE infusion, respectively. Calculated [ADO]isf was 2.6–9.4, 591–1,288, and 166–324 nM, respectively, under these same conditions. We conclude that NE infusion greatly increases [ADO]isf, and adenosine is responsible for most of the vasodilation at 3 min. The subsequent fall in venous concentration is due to a fall in [ADO]isf rather than to decreased capillary permeability. Vascular resistance remained low while [ADO]isf fell, which suggests that additional vasodilators are important during maintained NE infusion. PMID:1887934

  5. Synthesis, docking study and relaxant effect of 2-alkyl and 2-naphthylchromones on rat aorta and guinea-pig trachea through phosphodiesterase inhibition.

    PubMed

    Rodríguez-Ramos, Fernando; Navarrete, Andrés; González-Andrade, Martín; Alarcón, Carlos; Aguilera-Cruz, Alejandro; Reyes-Ramírez, Adelfo

    2013-10-01

    Chromone (4), which form the base structure of various flavonoids isolated as natural products, is capable of relaxing smooth muscle. This is relevant to the treatment of high blood pressure, asthma and chronic obstructive pulmonary disease. The former disorder involves the contraction of vascular smooth muscle (VSM), and the latter two bronchoconstriction of airway smooth muscle (ASM). One of the principal mechanisms by which flavonoids relax muscle tissue is the inhibition of phosphodiesterases (PDEs), present in both VSM and ASM. Therefore, a study was designed to analyze the structure-activity relationship of chromone derivatives in vaso- and bronchorelaxation through the inhibition of PDE. Docking studies showed that these chromones bind at the catalytic site of PDEs. Consequently, we synthesized analogs of chromones substituted at position C-2 with alkyl and naphthyl groups. These compounds were synthesized from 2-hydroxyacetophenone and acyl chlorides in the presence of DBU and pyridine, modifying the methodology reported for the synthesis of 3-acylchromones by changing the reaction temperature from 80 to 30°C and using methylene chloride as solvent, yielding the corresponding phenolic esters 10a-10h. These compounds were cyclized with an equivalent of DBU, pyridine as solvent, and heated at reflux temperature, yielding the chromones 11a-11h. Evaluation of the vasorelaxant effect of 4, 11a-11h on rat aorta demonstrated that potency decreases with branched alkyl groups. Whereas the EC50 of compound 11d (substituted by an n-hexyl group) was 8.64±0.39 μM, that of 11f (substituted by an isobutyl group) was 14.58±0.64 μM. Contrarily, the effectiveness of the compound is directly proportional to the length of the alkyl chain, as evidenced by the increase in maximal effect of compound 11c versus 11d (66% versus 100%) and 11e versus 11f (60% versus 96%). With an aromatic group like naphthyl as the C-2 substituent, the effectiveness was only 43%. All compounds

  6. Recognition of Modified Conditioning Sounds by Competitively Trained Guinea Pigs

    PubMed Central

    Ojima, Hisayuki; Horikawa, Junsei

    2016-01-01

    The guinea pig (GP) is an often-used species in hearing research. However, behavioral studies are rare, especially in the context of sound recognition, because of difficulties in training these animals. We examined sound recognition in a social competitive setting in order to examine whether this setting could be used as an easy model. Two starved GPs were placed in the same training arena and compelled to compete for food after hearing a conditioning sound (CS), which was a repeat of almost identical sound segments. Through a 2-week intensive training, animals were trained to demonstrate a set of distinct behaviors solely to the CS. Then, each of them was subjected to generalization tests for recognition of sounds that had been modified from the CS in spectral, fine temporal and tempo (i.e., intersegment interval, ISI) dimensions. Results showed that they discriminated between the CS and band-rejected test sounds but had no preference for a particular frequency range for the recognition. In contrast, sounds modified in the fine temporal domain were largely perceived to be in the same category as the CS, except for the test sound generated by fully reversing the CS in time. Animals also discriminated sounds played at different tempos. Test sounds with ISIs shorter than that of the multi-segment CS were discriminated from the CS, while test sounds with ISIs longer than that of the CS segments were not. For the shorter ISIs, most animals initiated apparently positive food-access behavior as they did in response to the CS, but discontinued it during the sound-on period probably because of later recognition of tempo. Interestingly, the population range and mean of the delay time before animals initiated the food-access behavior were very similar among different ISI test sounds. This study, for the first time, demonstrates a wide aspect of sound discrimination abilities of the GP and will provide a way to examine tempo perception mechanisms using this animal species

  7. 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 ...

  8. Papular Dermatitis Induced in Guinea Pig by Biting Midge Culicoides Sonorensis (Diptera: Ceratopogonidaie)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 h...

  9. The influence of starvation upon hepatic drug metabolism in rats, mice, and guinea pigs.

    NASA Technical Reports Server (NTRS)

    Furner, R. L.; Feller, D. D.

    1971-01-01

    Male rats, mice, and guinea pigs were starved for 1, 2, or 3 days, and the metabolism of ethylmorphine, p-nitroanisole, and aniline was studied. Results suggest that the oxidative enzyme systems studied are not interdependent, and the pathways studied appear to be species dependent.

  10. 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.

  11. ALTERED FUNCTION AND HISTOLOGY IN GUINEA PIGS AFTER INHALATION OF DIESEL EXHAUST

    EPA Science Inventory

    Health effects of inhaled diesel engine exhaust were evaluated in infant guinea pigs following 4 and 8 weeks of exposure. Animals were exposed to 1 part exhaust diluted by 13 parts clean air for 20 hr/day, 7 days/week. Lung function, electrocardiogram, growth rate, and histopatho...

  12. Pancreatic lesions induced in rabbits and guinea-pigs with pancreatic antigens.

    PubMed Central

    Wright, P H; Gingerich, R L; King, S; Lacy, P E

    1976-01-01

    Rabbits and guinea-pigs were immunized with various pancreatic antigens in Freund's adjuvant. Rabbits received unfractionated bovine insulin and the "A" component and "single peak" insulin separated from it by gel-filtration. All produced antibodies capable of reacting with porcine insulin but none were found to have pancreatic lesions when killed up to 6 weeks after initial injection. Guinea-pigs immunized with bovine "A" component developed pancreatic peri-ductulitis which appeared most frequently (10/20) in animals killed 30 days after a single injection and less frequently in animals killed after 60 (4/10) and 90(1/10) days. Similar lesions were found in only a small proportion of control animals (2/23) or of guinea-pigs immunized with single peak bovine insulin (3/22). Guinea-pigs immunized with homogenates of homologous and heterologous islets of Langerhans developed signs of peri-ductulitis in a high proportion of animals killed up to about 60 days after first injection (18/26). None of these animals exhibited clearly defined signs of diabetes mellitus and the incidence of induced lesions could not be correlated with levels of circulating insulin-binding antibodies. Images Fig. 2 PMID:821683

  13. 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

  14. Protection of guinea pigs against Leptospira interrogans serovar Lai by LipL21 DNA vaccine.

    PubMed

    He, Han Jiang; Wang, Wen Yu; Wu, Zhong Dao; Lv, Zhi Yue; Li, Jun; Tan, Li Zhi

    2008-10-01

    In this study, the full lipL21 gene fragment encoding outer membrane protein LipL21 was cloned from L. interrogans serovar Lai and inserted into eukaryotic expression vector pcDNA3.1(+). The guinea pigs were immunized with pcDNA3.1(+)-lipL21, pcDNA3.1(+) or PBS. Six weeks after the second immunization, the splenocytes were isolated to detect their proliferative ability by lymphocyte transformation experiments. In addition, microscopic agglutination test was used for quantitative detection of specific antibodies. The rest guinea pigs were challenged intraperitoneally with L. interogans sorevar Lai. Then, protective effect was evaluated on the basis of survival and histopathological lesions in the kidneys, lungs, and liver. The lipL21 gene was successfully expressed in COS-7 cells through recombinant pcDNA3.1(+)-lipL21. The titer of specific antibodies substantially increased, and the stimulation index of splenocytes increased significantly. Hence, the pcDNA3.1(+)-lipL21 could protect the immunized guinea pigs from homotypic Leptospira infection. Furthermore, no obvious pathologic changes were observed in the pcDNA3.1(+)-lipL21 immunized guinea pigs. The results showed that the protective effect with pathogenic strains of Leptospira was shared by LipL21 mediated through a plasmid vector. Consequently, these results indicated that the lipL21 DNA vaccine was a promising candidate for the prevention of leptospirosis. PMID:18954563

  15. Use of a Far-Infrared Active Warming Device in Guinea Pigs (Cavia porcellus)

    PubMed Central

    Zarndt, Bethany S; Buchta, Jessica N; Garver, Lindsey S; Davidson, Silas A; Rowton, Edgar D; Despain, Kenneth E

    2015-01-01

    Small mammals have difficulty maintaining body temperature under anesthesia. This hypothermia is a potential detriment not only to the health and comfort of the animal but also to the integrity of any treatment given or data gathered during the anesthetic period. Using an external warming device to assist with temperature regulation can mitigate these effects. In this study, we investigated the ability of an advanced warming device that uses far-infrared (FIR) heating and responds to real-time core temperature monitoring to maintain a normothermic core temperature in guinea pigs. Body temperatures were measured during 30 min of ketamine–xylazine general anesthesia with and without application of the heating device. The loss of core body heat from anesthetized guinea pigs under typical (unwarmed) conditions was significant, and this loss was almost completely mitigated by application of the FIR heating pad. The significant difference between the temperatures of the actively warmed guinea pigs as compared with the control group began as early as 14 min after anesthetic administration, leading to a 2.6 °C difference at 30 min. Loss of core body temperature was not correlated with animals’ body weight; however, weight influences the efficiency of FIR warming slightly. These study results show that the FIR heating device accurately controls core body temperature in guinea pigs, therefore potentially alleviating the effects of body heat loss on animal physiology. PMID:26632788

  16. Specific activities of antioxidative enzymes in the cochlea of guinea pigs at different stages of development.

    PubMed

    Zelck, U; Nowak, R; Karnstedt, U; Koitschev, A; Käcker, N

    1993-01-01

    Significant activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were found in the cochleas of guinea pigs of different ages. The specific activities of SOD and GSH-Px (expressed as units/mg protein) increased significantly from fetal animals to animals 2 days old and then to 6-month-old animals. PMID:8369116

  17. PLACENTAL TRANSFER AND FETAL DEPOSITION OF HEXACHLOROBENZENE IN THE HAMSTER AND GUINEA PIG

    EPA Science Inventory

    Hexachlorobenzene (HCB) was administered at dose levels of 0, 1.0, 10.0, or 50.0 mg HCB/kg body wt by gavage to pregnant hamsters and guinea pigs for 6 days up to the time of liver development in the fetus. Samples of maternal fat, thymus, skin, liver, lung, brain, spleen, urinar...

  18. Use of a Far-Infrared Active Warming Device in Guinea Pigs (Cavia porcellus).

    PubMed

    Zarndt, Bethany S; Buchta, Jessica N; Garver, Lindsey S; Davidson, Silas A; Rowton, Edgar D; Despain, Kenneth E

    2015-11-01

    Small mammals have difficulty maintaining body temperature under anesthesia. This hypothermia is a potential detriment not only to the health and comfort of the animal but also to the integrity of any treatment given or data gathered during the anesthetic period. Using an external warming device to assist with temperature regulation can mitigate these effects. In this study, we investigated the ability of an advanced warming device that uses far-infrared (FIR) heating and responds to real-time core temperature monitoring to maintain a normothermic core temperature in guinea pigs. Body temperatures were measured during 30 min of ketamine-xylazine general anesthesia with and without application of the heating device. The loss of core body heat from anesthetized guinea pigs under typical (unwarmed) conditions was significant, and this loss was almost completely mitigated by application of the FIR heating pad. The significant difference between the temperatures of the actively warmed guinea pigs as compared with the control group began as early as 14 min after anesthetic administration, leading to a 2.6 °C difference at 30 min. Loss of core body temperature was not correlated with animals' body weight; however, weight influences the efficiency of FIR warming slightly. These study results show that the FIR heating device accurately controls core body temperature in guinea pigs, therefore potentially alleviating the effects of body heat loss on animal physiology. PMID:26632788

  19. 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

  20. NITROGEN DIOXIDE EXPOSURE AND LUNG ANTIOXIDANTS IN ASCORBIC ACID-DEFICIENT GUINEA PIGS

    EPA Science Inventory

    The authors have previously found that ascorbic acid (AA) deficiency in guinea pigs enhances the pulmonary toxicity of nitrogen dioxide (NO2). The present study showed that exposure to NO2 (4.8 ppm, 3 hr) significantly increased lung lavage fluid protein (a sensitive indicator of...

  1. 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.

  2. 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.

  3. Human vascular smooth muscle cells express a urate transporter.

    PubMed

    Price, Karen L; Sautin, Yuri Y; Long, David A; Zhang, Li; Miyazaki, Hiroki; Mu, Wei; Endou, Hitoshi; Johnson, Richard J

    2006-07-01

    An elevated serum uric acid is associated with the development of hypertension and renal disease. Renal regulation of urate excretion is largely controlled by URAT1 (SLC22A12), a member of the organic anion transporter superfamily. This study reports the specific expression of URAT1 on human aortic vascular smooth muscle cells, as assessed by reverse transcription-PCR and Western blot analysis. Expression of URAT1 was localized to the cell membrane. Evidence that the URAT1 transporter was functional was provided by the finding that uptake of 14C-urate was significantly inhibited in the presence of probenecid, an organic anion transporter inhibitor. It is proposed that URAT1 may provide a mechanism by which uric acid enters the human vascular smooth muscle cell, a finding that may be relevant to the role of uric acid in cardiovascular disease. PMID:16775029

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

    PubMed Central

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

    2014-01-01

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

  5. Origin and differentiation of vascular smooth muscle cells

    PubMed Central

    Wang, Gang; Jacquet, Laureen; Karamariti, Eirini; Xu, Qingbo

    2015-01-01

    Vascular smooth muscle cells (SMCs), a major structural component of the vessel wall, not only play a key role in maintaining vascular structure but also perform various functions. During embryogenesis, SMC recruitment from their progenitors is an important step in the formation of the embryonic vascular system. SMCs in the arterial wall are mostly quiescent but can display a contractile phenotype in adults. Under pathophysiological conditions, i.e. vascular remodelling after endothelial dysfunction or damage, contractile SMCs found in the media switch to a secretory type, which will facilitate their ability to migrate to the intima and proliferate to contribute to neointimal lesions. However, recent evidence suggests that the mobilization and recruitment of abundant stem/progenitor cells present in the vessel wall are largely responsible for SMC accumulation in the intima during vascular remodelling such as neointimal hyperplasia and arteriosclerosis. Therefore, understanding the regulatory mechanisms that control SMC differentiation from vascular progenitors is essential for exploring therapeutic targets for potential clinical applications. In this article, we review the origin and differentiation of SMCs from stem/progenitor cells during cardiovascular development and in the adult, highlighting the environmental cues and signalling pathways that control phenotypic modulation within the vasculature. PMID:25952975

  6. Structural and Kinetic Characterization of Guinea Pig l-Asparaginase Type III

    PubMed Central

    2015-01-01

    We investigated whether an uncharacterized protein from guinea pig could be the enzyme behind Kidd’s serendipitous discovery, made over 60 years ago, that guinea pig serum has cell killing ability. It has been long known that an enzyme with l-asparaginase activity is responsible for cell killing, although astonishingly, its identity remains unclear. Bacterial asparaginases with similar cell killing properties have since become a mainstay therapy of certain cancers such as acute lymphoblastic leukemia. By hydrolyzing asparagine to aspartate and ammonia, these drugs deplete the asparagine present in the blood, killing cancer cells that rely on extracellular asparagine uptake for survival. However, bacterial asparaginases can elicit an adverse immune response. We propose that replacement of bacterial enzymes with the guinea pig asparaginase responsible for serum activity, by its virtue of being more closely related to human enzymes, will be less immunogenic. To this goal, we investigated whether an uncharacterized protein from guinea pig with putative asparaginase activity, which we call gpASNase3, could be that enzyme. We examined its self-activation process (gpASNase3 requires autocleavage to become active), kinetically characterized it for asparaginase and β-aspartyl dipeptidase activity, and elucidated its crystal structure in both the uncleaved and cleaved states. This work reveals that gpASNase3 is not the enzyme responsible for the antitumor effects of guinea pig serum. It exhibits a low affinity for asparagine as measured by a high Michaelis constant, KM, in the millimolar range, in contrast to the low KM (micromolar range) required for asparaginase to be effective as an anticancer agent. PMID:24669941

  7. Effects of 900 MHz electromagnetic field emitted by cellular phones on electrocardiograms of guinea pigs.

    PubMed

    Meral, I; Tekintangac, Y; Demir, H

    2014-02-01

    This study was carried out to determine the effects of electromagnetic field (EMF) emitted by cellular phones (CPs) on electrocardiograms (ECGs) of guinea pigs. A total of 30 healthy guinea pigs weighing 500-800 g were used. After 1 week of adaptation period, animals were randomly divided into two groups: control group (n = 10) and EMF-exposed group (n = 20). Control guinea pigs were housed in a separate room without exposing them to EMFs of CPs. Animals in second group were exposed to 890-915 MHz EMF (217 Hz of pulse rate, 2 W of maximum peak power and 0.95 wt kg(-1) of specific absorption rate) for 12 h day(-1) (11 h 45 min stand-by and 15 min speaking mode) for 30 days. ECGs of guinea pigs in both the groups were recorded by a direct writing electrocardiograph at the beginning and 10th, 20th and 30th days of the experiment. All ECGs were standardized at 1 mV = 10 mm and with a chart speed of 50 mm sec(-1). Leads I, II, III, lead augmented vector right (aVR), lead augmented vector left (aVL) and lead augmented vector foot (aVF) were recorded. The durations and amplitudes of waves on the trace were measured in lead II. The data were expressed as mean with SEM. It was found that 12 h day(-1) EMF exposure for 30 days did not have any significant effects on ECG findings of guinea pigs. However, this issue needed to be further investigated in a variety of perspectives, such as longer duration of exposure to be able to elucidate the effects of mobile phone-induced EMFs on cardiovascular functions. PMID:24220873

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

    PubMed Central

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

    2013-01-01

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

  9. Sp8 expression in putative neural progenitor cells in guinea pig and human cerebrum.

    PubMed

    Zhang, Xue-Mei; Cai, Yan; Wang, Fang; Wu, Jun; Mo, Lin; Zhang, Feng; Patrylo, Peter R; Pan, Aihua; Ma, Chao; Fu, Jin; Yan, Xiao-Xin

    2016-09-01

    Neural stem/progenitor cells have been characterized at neurogenic sites in adult mammalian brain with various molecular markers. Here it has been demonstrated that Sp8, a transcription factor typically expressed among mature GABAergic interneurons, also labels putative neural precursors in adult guinea pig and human cerebrum. In guinea pigs, Sp8 immunoreactive (Sp8+) cells were localized largely in the superficial layers of the cortex including layer I, as well as the subventricular zone (SVZ) and subgranular zone (SGZ). Sp8+ cells at the SGZ showed little colocalization with mature and immature neuronal markers, but co-expressed neural stem cell markers including Sox2. Some layer I Sp8+ cells also co-expressed Sox2. The amount of Sp8+ cells in the dentate gyrus was maintained 2 weeks after X-ray irradiation, while that of doublecortin (DCX+) cells was greatly reduced. Mild ischemic insult caused a transient increase of Sp8+ cells in the SGZ and layer I, with the subgranular Sp8+ cells exhibited an increased colabeling for the mitotic marker Ki67 and pulse-chased bromodeoxyuridine (BrdU). Sp8+ cells in the dentate gyrus showed an age-related decline in guinea pigs, in parallel with the loss of DCX+ cells in the same region. In adult humans, Sp8+ cells exhibited comparable morphological features as seen in guinea pigs, with those at the SGZ and some in cortical layer I co-expressed Sox2. Together, these results suggested that Sp8 may label putative neural progenitors in guinea pig and human cerebrum, with the labeled cells in the SGZ appeared largely not mitotically active under normal conditions. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 939-955, 2016. PMID:26585436

  10. Characterization and distribution of putative 5-ht7 receptors in guinea-pig brain.

    PubMed Central

    To, Z. P.; Bonhaus, D. W.; Eglen, R. M.; Jakeman, L. B.

    1995-01-01

    1. In the presence of (-)-cyanopindolol (1.0 microM) and sumatriptan (1.0 microM), 0.5 nM [3H]-carboxamidotrytamine ([3H]-5-CT) labelled a single population of receptors in guinea-pig cerebral cortex membranes. 2. 5-HT-displaceable binding was rapid, saturable and reversible. A high affinity binding site was characterized both by equilibrium saturation (Kd = 0.76 +/- 0.28 nM; Bmax = 68.1 +/- 26.7 fmol mg-1 protein) and kinetic (Kd = 0.18 +/- 0.05 nM) analysis. The pharmacological profile of this site was similar to the profile obtained in transfected CHO-K1 cells expressing guinea-pig 5-ht7 receptors. 3. Autoradiographic analysis revealed a discrete localization of binding sites in guinea-pig brain, with the highest density of sites in the medial thalamic nuclei and related limbic and cortical regions. Moderate levels of binding were detected in sensory relay nuclei, substantia nigra, hypothalamus, central grey and dorsal raphe nuclei. This distribution corresponded to that observed using in situ hybridization with [35S]-UTP labelled riboprobes complementary to mRNA encoding the guinea-pig 5-ht7 receptor. 4. In conclusion, under appropriate conditions, [3H]-5-CT labelled a single population of saturable binding sites that corresponded to an endogenous 5-ht7 receptor in guinea-pig brain. The distribution of 5-ht7 receptors in thalamocortical and limbic brain regions suggests a role for these receptors in sensory and affective behaviours. Images Figure 5 Figure 6 PMID:7647964

  11. Pulmonary effects of inhaled zinc oxide in human subjects, guinea pigs, rats, and rabbits

    SciTech Connect

    Gordon, T.; Chen, L.C.; Fine, J.M.; Schlesinger, R.B.; Su, W.Y.; Kimmel, T.A.; Amdur, M.O. )

    1992-08-01

    Occupational exposure to freshly formed zinc oxide (ZnO) particles (less than 1.0 micron aerodynamic diameter) produces a well-characterized response known as metal fume fever. An 8-hr threshold limit value (TLV) of 5 mg/m3 has been established to prevent adverse health effects because of exposure to ZnO fumes. Because animal toxicity studies have demonstrated pulmonary effects near the current TLV, the present study examined the time course and dose-response of the pulmonary injury produced by inhaled ZnO in guinea pigs, rats, rabbits, and human volunteers. The test animals were exposed to 0, 2.5, or 5.0 mg/m3 ZnO for up to 3 hr and their lungs lavaged. Both the lavage fluid and recovered cells were examined for evidence of inflammation or altered cell function. The lavage fluid from guinea pigs and rats exposed to 5 mg/m3 had significant increases in total cells, lactate dehydrogenase, beta-glucuronidase, and protein content. These changes were greatest 24 hr after exposure. Guinea pig alveolar macrophage function was depressed as evidenced by in vitro phagocytosis of opsonized latex beads. Significant changes in lavage fluid parameters were also observed in guinea pigs and rats exposed to 2.5 mg/m3 ZnO. In contrast, rabbits showed no increase in biochemical or cellular parameters following a 2-hr exposure to 5 mg/m3 ZnO. Differences in total lung burden of ZnO, as determined in additional animals by atomic absorption spectroscopy, appeared to account for the observed differences in species responses. Although the lungs of guinea pigs and rats retained approximately 20% and 12% of the inhaled dose, respectively, rabbits retained only 5%.

  12. In vivo formation of nitrosocarbamates in the stomach of rats and guinea pigs

    SciTech Connect

    Rickard, R.W.; Dorough, H.W.

    1984-01-01

    The N-nitrosocarbamates are potent mutagens and carcinogens and have been synthesized under acid conditions that prevail in the human stomach. However, it has never been documented that nitrosocarbamates are actually formed in vivo in the stomach of any mammalian species. Using /sup 14/C-labeled carbaryl and carbofuran, attempts were made to isolate the nitroso derivatives from the stomach contents of rats and guinea pigs treated orally with the carbamate and sodium nitrite. Only trace quantities of nitrocarbamate were recovered from the rat stomach, whereas 0.5 to 2.0% of the carbamate doses were isolated as the nitroso derivative from the contents of the guinea pig stomach. The rather low apparent yields resulted in part from the instability of the nitrosocarbamates and from absorption of the carbamate and/or nitrosocarbamate from the stomach. Higher rates of synthesis were indicated by incubating the carbamates with sodium nitrite in the presence of the stomach contents at 37/sup 0/C for 15 min. About 30% nitrosation occurred with the guinea pig and about 0.5% with the rat. The difference was attributed to the pH of the gastric contents. For the rat, the pH ranged from 3 to 5; gastric contents of the guinea pig had a pH between 1 and 2. Since the pH of the human stomach is also in the pH 1-2 range, it is likely that nitrosation of carbamates in humans would be very similar to that in the guinea pig. 21 references, 3 figures, 3 tables.

  13. Metabolism and disposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin in guinea pigs

    SciTech Connect

    Olson, J.R.

    1986-09-15

    Marked interspecies variability exists in the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with the guinea pig being the mammalian species most sensitive to the acute toxicity of TCDD. The metabolism and disposition of TCDD was investigated in guinea pigs for 45 days following a single exposure to purified (/sup 3/H)TCDD (0.56 microgram/kg, ip). Guinea pigs included in the toxicokinetic study gained body weight, maintained a normal relative body composition, and exhibited no gross signs of toxicity during the 45-day study. Approximately 36% of the dose of TCDD-derived /sup 3/H remained in the adipose tissue at 45 days following exposure to (/sup 3/H)TCDD, while the liver, pelt, and skeletal muscle and carcass each contained about 7% of the administered dose. Although most of the TCDD-derived radioactivity in liver, kidney, perirenal adipose tissue, and skeletal muscle represented unchanged TCDD, from 4 to 28% of the /sup 3/H was associated with metabolites of TCDD. This unexpected finding suggests that TCDD metabolites are not efficiently excreted from guinea pigs. The urinary and fecal excretion of TCDD-derived radioactivity followed apparent first-order kinetics, with an elimination half-life of 93.7 +/- 15.5 days (mean +/- SD). HPLC analysis of urine and bile from (/sup 3/H)TCDD-treated guinea pigs showed that all of the radioactivity represented metabolites of TCDD, indicating that these routes of elimination are dependent on prior metabolism of TCDD. However, 70 to 90% of the radioactivity in fecal samples was found to represent unmetabolized TCDD throughout the 45-day excretion study. The presence of TCDD in feces and its absence in bile suggest that the fecal excretion of unchanged TCDD resulted from the direct intestinal elimination of the lipophilic toxin.

  14. Myorelaxant activity of 2-t-butyl-4-methoxyphenol (BHA) in guinea pig gastric fundus.

    PubMed

    Fusi, F; Valoti, M; Petkov, G V; Boev, K K; Sgaragli, G P

    1998-10-30

    This study investigates the mechanism whereby the antioxidant 2-t-butyl-4-methoxyphenol (BHA) relaxes guinea pig gastric fundus smooth muscle. In circular smooth muscle strips, 10 microM cyclopiazonic acid, a specific inhibitor of sarcoplasmic reticulum Ca2+-ATPase, induced a prolonged rise in tension which depended on the presence of extracellular Ca2+. BHA (pIC50 = 5.83), sodium nitroprusside (6.85), isoproterenol (7.69) and nifedipine (8.02), but not 2,6-di-t-butyl-4-methoxyphenol (DTBHA) (up to 30 microM), relaxed muscle strips contracted with cyclopiazonic acid. Methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyri dine-5-carboxylate (Bay K 8644) (1 microM) antagonised the nifedipine- but not the BHA-induced relaxation. Nifedipine and isoproterenol (10 microM) caused a decrease in spontaneous tone, but did not counteract the subsequent rise in tension elicited by 10 microM cyclopiazonic acid. Conversely, 100 microM BHA and 100 microM sodium nitroprusside not only significantly reduced spontaneous tone but also markedly impaired the response of the muscles to cyclopiazonic acid. DTBHA failed to show either effect. When added to preparations completely relaxed by 100 microM BHA, 10 mM tetraethylammonium still elicited nifedipine-sensitive tonic and phasic contractions in the presence or absence of 10 microM cyclopiazonic acid. BHA and DTBHA inhibited, in a concentration-dependent manner, the Ca2+-promoted contraction of strips depolarised by 10 mM tetraethylammonium. The BHA antagonism showed a non-competitive profile while that of DTBHA was competitive. In muscle strips at rest, 10 microM BHA caused a significant increase in tissue cAMP concentration, leaving cGMP unmodified. To conclude, the myorelaxant action of BHA on gastric fundus smooth muscle appears to be mediated partly by an increase in cAMP levels and partly by inhibition of Ca2+ influx from the extracellular space. PMID:9845271

  15. A comparison of the stimulatory effects of metoclopramide and cinitapride in the guinea-pig isolated ileum.

    PubMed

    Massingham, R; Bou, J; Roberts, D J

    1985-03-01

    The pharmacological effects of a new benzamide derivative cinitapride, have been compared to those of metoclopramide in guinea-pig isolated ileum and longitudinal smooth muscle-myenteric plexus preparations treated with propranolol (3 microM). Cinitapride (EC50 = 0.74 microM) was 6 times more potent than metoclopramide (EC50 = 4.69 microM) in enhancing the twitch response of co-axially stimulated preparations and 11 times more potent in eliciting contractions in non-stimulated tissues, their respective EC50 values being 0.58 microM and 6.52 microM. These contractile effects of cinitapride and metoclopramide amounted to approximately 25% of the maximum response of the tissues to acetylcholine (1 microM). Neither cinitapride nor metoclopramide, in concentrations up to 10 microM, significantly affected concentration-response curves to exogenous acetylcholine or 5-hydroxytryptamine but both drugs elicited a concentration-dependent potentiation of the ileum responses to a fixed concentration (10 microM) of the ganglion stimulant dimethylphenylpiperazinium (DMPP). Analysis of the twitch-enhancing and contractile effects of cinitapride using a variety of drugs suggested that a common, prejunctional locus of action upon the cell bodies or axons of postganglionic, parasympathetic neurones of the myenteric plexus is involved in both of these responses. In hexamethonium (100 microM) and methysergide (0.1 microM)-treated longitudinal smooth muscle preparations desensitization or blockade of 5-hydroxytryptamine receptors using high concentrations of the same agonist (30 microM) or quipazine (10 microM) or the putative antagonists cocaine (30 microM) or tubocurarine (10 microM) produced small inhibitions (congruent to 20%) of the contractile responses to metoclopramide and cinitapride but did not affect twitch responses to these drugs. It is concluded that cinitapride is a more potent stimulant of guinea-pig intestinal smooth muscle than metoclopramide in vitro although the

  16. P2-purinoceptors mediating spasm of the isolated uterus of the non-pregnant guinea-pig.

    PubMed

    Piper, A S; Hollingsworth, M

    1996-04-01

    1. The isolated uterus of the non-pregnant guinea-pig has been suggested to contain P1-, and possibly P2-purinoceptors mediating spasm. The presence of P1-purinoceptors has been confirmed and these receptors have been further characterized. 2. In the presence of the adenosine uptake inhibitor, S-(4-nitrobenzyl)-6-thioinosine (NBTI, 300 nM) and a pA100 concentration of the P1-purinoceptor antagonist 8-sulphophenyltheophylline (140 microM), the potency order of agonists as spasmogens was: 2 methylthio ATP > alpha,beta methylene ATP = UTP = ATP > beta,gamma methylene ATP. This order is not consistent with any single recognised P2-purinoceptor subtype. 3. Indomethacin (1 microM) treatment abolished responses to 2 methylthio ATP, alpha,beta methylene ATP and UTP, while spasm to ATP was significantly inhibited. When the endometrial and circular smooth muscle cell layers were removed, spasmogenic responses to ATP, 2 methylthio ATP, alpha,beta methylene ATP and UTP were significantly reduced. 4. 2-methylthio ATP was able to cause desensitization to itself, but not to UTP, indicating that these agonists act at different receptor sites. 5. The P2-purinoceptor antagonist, suramin antagonized 2 methylthio ATP with a PA2 of 5.9 +/- 0.3. Suramin was also an antagonist of ATP and UTP. In the case of ATP, the antagonism was not dependent on suramin concentration, while for UTP the interaction appeared to be non-equilibrium. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 microM) had no effect on spasm to ATP, UTP or 2 methythio ATP. 6. In the presence of indomethacin, responses to ATP were unaffected by 8-sulphophenyltheophylline (140 microM) or by suramin (100 microM), but PPADS (10 microM) antagonized ATP. 7. These results suggest that the isolated uterus of the non-pregnant guinea-pig contains a mixture of P2-purinoceptors. P2U- (or UTP-selective pyrimidinoceptors) and P2Y-purinoceptors appear to be present, probably mainly located on the endometrial or

  17. Effects of Selective Inhibition of PDE4 by YM976 on Airway Reactivity and Cough in Ovalbumin-Sensitized Guinea Pigs.

    PubMed

    Mokrý, J; Urbanová, A; Medvedová, I; Kertys, M; Mikolka, P; Kosutová, P; Mokrá, D

    2016-01-01

    Phosphodiesterases (PDEs) are enzymes involved in the degradation of cAMP and cGMP. Selective PDE4 inhibitors (e.g., roflumilast) are effective in therapy of chronic obstructive pulmonary disease associated with neutrophil inflammation. The aim of this study was to evaluate the effects of a selective PDE4 inhibitor, YM976, on citric acid-induced cough, in vivo and in vitro airway smooth muscle reactivity to histamine, and on inflammatory mediators in ovalbumin-sensitized guinea pigs, with experimentally induced eosinophil inflammation. The YM976 was administered intraperitoneally at a dose of 1.0 mg/kg once daily for 7 days. Sensitization with ovalbumin led to a significant increase in the number of coughs, and in vivo and in vitro airway reactivity. Also, increased plasma levels of IL-4, IL-5, and PAF were observed, with a significant increase in the differential count of eosinophils in both blood and bronchoalveolar lavage fluid. The YM976 suppressed the number of coughs, the airway reactivity in tracheal tissue strips, and the IL-4 level. The findings indicate that PDE4 inhibition by YM976 exerts antitussive and anti-inflammatory effects in guinea pigs with ovalbumin-induced eosinophilic inflammation. PMID:27130219

  18. Comparison of guinea-pig, bovine and rat alpha 1-adrenoceptor subtypes.

    PubMed Central

    Büscher, R.; Heeks, C.; Taguchi, K.; Michel, M. C.

    1996-01-01

    1. To elucidate a possible role of species differences in the classification of alpha 1-adrenoceptor subtypes, we have characterized the alpha 1-adrenoceptors in guinea-pig spleen, kidney and cerebral cortex and in bovine cerebral cortex using concentration-dependent alkylation by chloroethylclonidine and competitive binding with 5-methlurapidil, methoxamine, (+)-niguldipine, noradrenaline, oxymetazoline, phentolamine, SDZ NVI-085, tamsulosin and (+)-tamsulosin. Rat liver alpha 1B-adrenoceptors were studied for comparison. Chloroethylclonidine-sensitivity and (+)-niguldipine affinity were also compared at cloned rat and bovine alpha 1a-adrenoceptors. 2. Chloroethylclonidine concentration-dependently inactivated alpha 1-adrenoceptors in all five tissues. While chloroethylclonidine inactivated almost all alpha 1-adrenoceptors in rat liver and guinea-pig kidney and brain, 20-30% of alpha 1-adrenoceptors in guinea-pig spleen and bovine brain were resistant to alkylation by 10 microM chloroethylclonidine. With regard to concentration-dependency guinea-pig kidney and brain were approximately 10 fold less sensitive than guinea-pig spleen or rat liver. 3. In rat liver, all drugs tested competed for [3H]-prazosin binding with steep and monophasic curves. Drug affinities were relatively low and resembled most closely those of cloned rat alpha 1b-adrenoceptors. 4. In guinea-pig spleen, all drugs tested competed for [3H]-prazosin binding with steep and monophasic curves. Drug affinities were relatively low and resembled most closely those of cloned rat alpha 1b-adrenoceptors. 5. In guinea-pig kidney most drugs tested competed for [3H]-prazosin binding with steep and monophasic curves and had relatively low drug affinities close to those of cloned rat alpha 1b- and alpha 1d-adrenoceptors. However, noradrenaline and tamsulosin had consistently biphasic competition curves recognizing 36-39% high and 61-64% low affinity sites. 6. In guinea-pig cerebral cortex, all drugs tested

  19. Interaction of antibody-aggregated C4 and guinea-pig red cells: coagglutination phenomenon of Bordet and Gengou.

    PubMed Central

    Davies, K; Wilson, A B; Coombs, R R

    1981-01-01

    The component of bovine serum (coagglutinogen) responsible for coagglutination of guinea-pig red cells has been shown to be c4, as anticipated from our previously reported findings on human serum. To effect coagglutination, the C4 needs to be aggregated by antibody; thereby probably increasing the avidity of the C4 for the receptors on guinea-pig red cells. The coagglutinating activity is lost if univalent Fab anti-C4 is used, but it can be restored by adding IgG antibody to the Fab. A procedure is described for producing antibody reagents to human or bovine C4 by injecting guinea-pigs with well-washed coagglutinated guinea-pig red cells. PMID:7275174

  20. [Effect produced by the alkaloid fraction of Mimosa tenuiflora (tepescohuite) on the peristaltic reflex of the guinea pig ileum].

    PubMed

    Meckes-Lozoya, M; Lozoya, X; González, J L; Martínez, M

    1990-01-01

    An alkaloidal fraction was obtained from Mimosa tenuiflora (Willd.) Poir (tepescohuite) trunk bark. The product contained mainly an indolealkylamine and three minor alkaloids. This fraction inhibited the peristaltic reflex in the guinea-pig isolated ileum in vitro. PMID:2103706

  1. Macrophages are stimulated by muramyl dipeptide to induce polymorphonuclear leukocyte accumulation in the peritoneal cavities of guinea pigs.

    PubMed

    Nagao, S; Nakanishi, M; Kutsukake, H; Yagawa, K; Kusumoto, S; Shiba, T; Tanaka, A; Kotani, S

    1990-02-01

    N-Acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide [MDP]) injected intraperitoneally significantly increased the number of cells entering the peritoneal cavity of guinea pigs primed with liquid paraffin or thioglycollate. There was a close relationship between peritoneal polymorphonuclear leukocyte (PMN) accumulation and the uptake of glucosamine by macrophages in guinea pigs treated with a variety of bacterial cell surface components such as cell wall peptidoglycan subunits and bacterial or synthetic lipid A. The PMN accumulation was also facilitated by the intraperitoneal transfer of the peritoneal macrophages that had been stimulated by MDP in vitro. Furthermore, cell-free lavage fluids taken from the peritoneum of MDP-treated guinea pigs also initiated the influx of PMNs when introduced into the peritoneal cavities of liquid paraffin-pretreated guinea pigs. These results suggest that a soluble factor which attracts neutrophils is produced by MDP-treated macrophages. Partial characterization of the factor is described. PMID:2298491

  2. Inhibition of the effects of thrombin on guinea pig platelets by the diacylglycerol lipase inhibitor RHC 80267

    SciTech Connect

    Amin, D.; Sutherland, C.A.; Khandwala, A.S.; Jamall, I.S.; Kapoor, A.L.

    1986-10-01

    Phospholipase C (PLC) and diacylglycerol lipase (DGL) activities were found in guinea pig platelet microsome preparations. No phospholipase A2 (PLA2) activity was detected. RHC 80267 (1,6-di (0-(carbamoyl) cyclohexanone oxime)hexane) inhibited DGL activity (IC50 = 4 uM) from guinea pig platelet microsomes but had no effect on PLC. RHC 80267 inhibited platelet aggregation (IC50 = 11 uM), release of arachidonic acid (AA), its metabolites, and ATP (IC50 = 4.5 uM) when guinea pig platelets were challenged with a low concentration of thrombin. We propose that PLC-DGL is an important enzymatic pathway for the release of AA in guinea pig platelets.

  3. Pacemaker phase shift in the absence of neural activity in guinea-pig stomach: a microelectrode array study

    PubMed Central

    Nakayama, Shinsuke; Shimono, Ken; Liu, Hong-Nian; Jiko, Hideyasu; Katayama, Noburu; Tomita, Tadao; Goto, Kazunori

    2006-01-01

    Gastrointestinal (GI) motility is well organized. GI muscles act as a functional syncytium to achieve physiological functions under the control of neurones and pacemaker cells, which generate basal spontaneous pacemaker electrical activity. To date, it is unclear how spontaneous electrical activities are coupled, especially within a micrometre range. Here, using a microelectrode array, we show a spatio-temporal analysis of GI spontaneous electrical activity. The muscle preparations were isolated from guinea-pig stomach, and fixed in a chamber with an array of 8 × 8 planar multielectrodes (with 300 μm in interpolar distance). The electrical activities (field potentials) were simultaneously recorded through a multichannel amplifier system after high-pass filtering at 0.1 Hz. Dihydropyridine Ca2+ channel antagonists are known to differentiate the electrical pacemaker activity of interstitial cells of Cajal (ICCs) by suppressing smooth muscle activity. In the presence of nifedipine, we observed spontaneous electrical activities that were well synchronized over the array area, but had a clear phase shift depending on the distance. The additional application of tetrodotoxin (TTX) had little effect on the properties of the electrical activity. Furthermore, by constructing field potential images, we visualized the synchronization of pacemaker electrical activities resolving phase shifts that were measurable over several hundred micrometres. The results imply a phase modulation mechanism other than neural activity, and we postulate that this mechanism enables smooth GI motility. In addition, some preparations clearly showed plasticity of the pacemaker phase shift. PMID:16990400

  4. Extraneuronal Monoamine Transporter Mediates the Permissive Action of Cortisol in the Guinea Pig Trachea: Possible Involvement of Tracheal Chondrocytes

    PubMed Central

    Wang, Chen; Qiu, Wenying; Zheng, Yiqing; Li, Hui; Li, Yijia; Feng, Bing; Guo, Shu; Yan, Li; Cao, Ji-Min

    2013-01-01

    Cortisol, a member of glucocorticoids, could potentiate the action of catecholamine by a non-genomic mechanism. Although this permissive effect has been well appreciated in the anti-asthmatic medication, the underlying signaling pathway has remained mysterious. Here, we show that extraneuronal monoamine transporter (EMT), a membraneous reuptake transporter for circulating catecholamine clearance, is the direct target of cortisol in its permissive effect. We found that BSA-conjugated cortisol, which functions as a cortisol but cannot penetrate cell membrane, enhanced the spasmolytic effect of β-adrenoceptor agonist (isoprenaline) in histamine-sensitized tracheal spirals of guinea pigs, and pharmacological inhibition of EMT with famotidine was powerful enough to imitate the permissive action of cortisol. To our surprise, EMT protein expression was high in the chondrocytes of tracheal cartilage, but was undetectable in tracheal smooth muscle cells. The functionality of EMT was further confirmed with measurement of catecholamine uptake by tracheal chondrocytes. Moreover, cortisol-initiated membrane signaling could activate protein kinase C (PKC), which phosphorylates EMT and induces its internalization via a lipid raft-dependent pathway. Both of the mechanisms slow down the reuptake process by chondrocytes, leading to extracellular catecholamine accumulation and results in a more profound adrenergic signaling activation in tracheal smooth muscle cells. Thus, an EMT-centered pathway was proposed to explain the permissive action of cortisol. Collectively, our results highlight the role of EMT in the crosstalk between glucocorticoid and catecholamine. EMT may represent a promising target for adrenergic signaling modulation. PMID:24098439

  5. Improved facility and sensitivity in the use of guinea pigs for the isolation of Legionella pneumophila from cooling tower water

    SciTech Connect

    Leinbach, E.D.; Winkler, H.H.; Wood, D.O.; Coggin, J.H. Jr.

    1983-03-01

    The established criteria for the determination of the optimum time for the sacrifice of guinea pigs inoculated with samples of cooling tower water were found to be inadequate for the detection of low levels of Legionella pneumophila. By ignoring the requirement for fever and by sequentially sacrificing the infected guinea pigs on days 3 through 5 postinoculation, we simplified the procedure, and the sensitivity of detection was improved a great deal.

  6. Morpho-functional patterns of kidney injury in the experimental leptospirosis of the guinea-pig (L. icterohaemorrhagiae).

    PubMed

    Dávila de Arriaga, A J; Rocha, A S; Yasuda, P H; De Brito, T

    1982-10-01

    Thirty-seven guinea-pigs experimentally infected with a virulent strain of L. icterohaemorrhagiae, were submitted to a renal function study as evaluated through the maximal urinary concentration (MUC) test, blood urea nitrogen (BUN) and afterwards had their kidneys examined by light and electron microscopy. Vascular changes were also studied after the administration of colloidal carbon as a marker. Through the MUC test and BUN determination, two groups of tubulo-interstitial lesions can be visualised, one in animals without renal sufficiency, manifested chiefly by cell edema with RE dilation and another, in animals with renal insufficiency, characterised not only by marked cell edema and mitochondrial changes, but also by proximal tubule regenerative aspects without overt tubular necrosis. Interstitial edema and focal nephritis was prominent in both groups, a finding which minimises their role in the pathogenesis of renal failure in experimental leptospirosis. Vascular injury, affecting the vessels of the renal microcirculation chiefly at the cortico-medular junction, was observed in both groups. Its severity and extension ran parallel to the intensity of the tubular injury. This suggests a simultaneous action of a noxious agent liberated by the leptospires over both structures, tubular damage being accentuated by the local circulatory changes. PMID:7131130

  7. Activation of the alternative complement pathway by natural antibody to glycolipids in guinea-pig serum.

    PubMed Central

    Okada, N; Yasuda, T; Tsumita, T; Okada, H

    1983-01-01

    Liposomes containing paragloboside (PG) on their membrane were readily lysed by C4-deficient guinea-pig serum (C4D-GPS) through activation of the alternative complement pathway (ACP). Therefore we examined the reactivity of several types of guinea-pig serum (GPS) on PG-liposomes and determined that all GPS except that from specific pathogen-free (SPF) Hartley guinea-pigs had lytic capacity in Mg-EGTA-GVB (gelatin veronal-buffered saline containing Mg++ and ethyleneglycol-bis(beta-aminoethyl ether)N,N'-tetraacetate). This lytic capacity of GPS corresponded with the amount of natural antibody to PG in those sera. Although GPS of SPF guinea-pigs (SPF-GPS) could not lyse PG-liposomes in Mg-EGTA-GVB, it could lyse the liposomes when heated C4D-GPS or Hartley GPS was added. Natural antibody to PG in the heated sera was regarded to have sensitized PG-liposomes to lysis by SPF-GPS via ACP activation. Since the antibody to PG-liposomes was removed by lacto-N-nor-hexaosylceramide which has the same chemical structure in the terminal oligosaccharide, the antibody to PG in GPS was suggested to have a specificity to the terminal structure of oligosaccharide shared by lacto-N-nor-hexaosylceramide. Furthermore, the IgM fraction, which had been prepared by gel filtration of heated C4D-GPS on a Sephadex G200 column, could also sensitize PG-liposomes to lytic reaction of SPF-GPS in Mg-EGTA-GVB. This sensitizing capacity of heated C4D-GPS was suppressed by absorption of the serum or its IgM fraction with anti-guinea-pig mu-chain antibody coupled to Sepharose. Therefore, it was concluded that the lysis of PG-liposomes by GPS in Mg-EGTA-GVB was a result of ACP activation mediated by natural antibodies to PG of the IgM type which are present in usual GPS. This conclusion indicated that natural antibodies of the IgM type might play a role with ACP in host defence, especially in C4-deficient guinea-pigs where the classical complement pathway is impaired. PMID:6193057

  8. Effect of dexamethasone on antigen-induced high molecular weight glycoconjugate secretion in allergic guinea pigs.

    PubMed

    Savoie, C; Plant, M; Zwikker, M; van Staden, C J; Boulet, L; Chan, C C; Rodger, I W; Pon, D J

    1995-08-01

    The ovalbumin-sensitized guinea pig is commonly used as a small animal model of allergic asthma. This animal model exhibits many of the hallmark characteristics observed in patients afflicted with asthma including nonspecific airway hyperreactivity, airway eosinophilia, early and late phase bronchoconstriction, and plasma extravasation into the airways. In addition, mucous hypersecretion in the airways of asthmatic patients is thought to be responsible for the plugging of distal airways and to contribute to the morbidity and mortality associated with the disease process. In this study we examined whether the allergic guinea pig model exhibits an increase in airway high molecular weight glycoconjugate (HMWG) secretion in response to an antigen challenge and whether dexamethasone exerts any modulatory effects upon the response. Ovalbumin (OVA) -sensitized guinea pigs were challenged with OVA 2 wk following the initial exposure. Trachobronchoalveolar lavages (TBAL) were performed, and the samples were assayed for total eosinophil cell number, eosinophil peroxidase activity (EPO), and both acidic and neutral HMWG content. Morphometric analysis of mucous-containing cells was also performed on tissue sections prepared from the trachea, mainstem bronchus, and three lobes of the left lung. Within 24 h of an antigen challenge, TBAL samples obtained from the allergic guinea pigs exhibited increases in eosinophil cell number, measured EPO enzyme activity, and acidic HMWG content compared to TBAL samples prepared from vehicle-exposed animals. These antigen-induced changes were dependent on the concentration of aerosolized OVA administered. Exposing the animals to 0.3% OVA provoked a 6.23-fold increase in airway eosinophils, 15-fold elevation in TBAL EPO enzyme activity, and 175% increase in TBAL acidic HMWG. No significant changes in TBAL neutral HMWG were measured. The changes in measured EPO activity correlated with the levels of acidic HMWG found in the TBAL samples (r = 0

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

    SciTech Connect

    Dissanayake, V.U.; Hughes, J.; Hunter, J.C. )

    1991-07-01

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

  10. The involvement of platelet activating factor in endotoxin-induced pulmonary platelet recruitment in the guinea-pig.

    PubMed Central

    Beijer, L.; Botting, J.; Crook, P.; Oyekan, A. O.; Page, C. P.; Rylander, R.

    1987-01-01

    1 Exposure of conscious guinea-pigs to an aerosol of endotoxin (25-100 micrograms ml-1) resulted in a dose-related, progressive accumulation of platelets in the thoracic region. Accumulation of 111indium oxine labelled erythrocytes was not observed following exposure to an aerosol of endotoxin (50 micrograms ml-1). 2 Pretreatment of guinea-pigs with the selective platelet activating factor (Paf)-antagonists. CV-3988 or brotizolam resulted in a dose-related inhibition of endotoxin-induced pulmonary platelet recruitment. Pretreatment of guinea-pigs with the selective Paf-antagonist BN 52021 resulted in significant inhibition of endotoxin-induced pulmonary platelet recruitment, although the effects of BN 52021 were not dose-related. 3 Pretreatment of guinea-pigs with indomethacin at doses known to inhibit cyclo-oxygenase did not inhibit endotoxin-induced pulmonary platelet recruitment, whereas higher doses of indomethacin produced a reduction in platelet recruitment in the lung. 4 Pretreatment of guinea-pigs with the anticoagulant heparin and the prostacyclin analogue ZK 36374 inhibited endotoxin-induced platelet recruitment. 5 These observations suggest that endotoxin-induced pulmonary platelet recruitment in the guinea-pig is secondary to the release of platelet activating factor, but not to cyclo-oxygenase products of arachidonic acid and may also involve activation of the coagulation cascade. PMID:2447993

  11. Effects of sulfuric acid mist inhalation on mucous clearance and on airway fluids of rats and guinea pigs

    SciTech Connect

    Wolff, R.K.; Henderson, R.F.; Gray, R.H.; Carpenter, R.L.; Hahn, F.F.

    1986-01-01

    The responses of guinea pigs and rats to inhaled sulfuric acid aerosols were compared to define species differences and to determine the small-animal model most relevant to human exposures. Rats were exposed for 6 hr to 1, 10, and 100 mg H/sub 2/SO/sub 4//m/sup 3/. Guinea pigs were exposed for 6 h to 1, 10, and 27 mg H/sub 2/SO/sub 4//m/sup 3/. Tracheal mucous clearance of guinea pigs was slowed 1 d after exposures to 1 mg H/sub 2/SO/sub 4//m/sup 3/. A tendency toward faster clearance was observed at high concentrations of H/sub 2/SO/sub 4/ for both guinea pigs and rats (statistically significant only for the rats). The speeding of mucous clearance was correlated with increases in airway sialic acid and also with the appearance of excess tracheal secretions, detected using scanning electron microscopy in both rats and guinea pigs. The responses of guinea pigs to sulfuric acid exposures were more similar to those reported for humans than were those of rats.

  12. Interaction of Vascular Smooth Muscle Cells Under Low Shear Stress

    NASA Technical Reports Server (NTRS)

    Seidel, Charles L.

    1998-01-01

    The blood vessel wall consists of three cellular layers, an outer adventitial, a middle medial and an inner intimal layer. When the blood vessel forms in the embryo it begins as a tube composed of a single cell type called endothelial cells. Over time, other cells are recruited from the surrounding tissue to form additional layers on the outer surface of the endothelial tube. The cells that are recruited are called mesenchymal cells. Mesenchymal cells are responsible for the production of connective tissue that holds the blood vessel together and for developing into vascular smooth muscle cells that are responsible for regulating the diameter of the vessel (1) and therefore, blood flow. In a fully developed blood vessel, the endothelial cells make- up the majority of cells in the intimal layer while the mesenchymal cells make-up the majority of cells in the medial and adventitial layers. Within the medial layer of a mature vessel, cells are organized into multiple circular layers of alternating bands of connective tissue and cells. The cell layer is composed of a mixture of mesenchymal cells that have not developed into smooth muscle cells and fully developed smooth muscle cells (2). The assembly and organization of complex tissues is directed in part by a signaling system composed of proteins on the cell surface called adhesion molecules. Adhesion molecules enable cells to recognize each other as well as the composition of the connective tissue in which they reside (3). It was hypothesized that the different cell types that compose the vascular wall possess different adhesion molecules that enable them to recognize each other and through this recognition system, form the complex layered organization of the vascular wall. In other words, the layered organization is an intrinsic property of the cells. If this hypothesis is correct then the different cells that make up the vessel wall, when mixed together, should organize themselves into a layered structure

  13. In vitro differentiation of porcine aortic vascular precursor cells to endothelial and vascular smooth muscle cells.

    PubMed

    Zaniboni, Andrea; Bernardini, Chiara; Bertocchi, Martina; Zannoni, Augusta; Bianchi, Francesca; Avallone, Giancarlo; Mangano, Chiara; Sarli, Giuseppe; Calzà, Laura; Bacci, Maria Laura; Forni, Monica

    2015-09-01

    Recent findings suggest that progenitor and multipotent mesenchymal stromal cells (MSCs) are associated with vascular niches. Cells displaying mesenchymal properties and differentiating to whole components of a functional blood vessel, including endothelial and smooth muscle cells, can be defined as vascular stem cells (VSCs). Recently, we isolated a population of porcine aortic vascular precursor cells (pAVPCs), which have MSC- and pericyte-like properties. The aim of the present work was to investigate whether pAVPCs possess VSC-like properties and assess their differentiation potential toward endothelial and smooth muscle lineages. pAVPCs, maintained in a specific pericyte growth medium, were cultured in high-glucose DMEM + 10% FBS (long-term medium, LTM) or in human endothelial serum-free medium + 5% FBS and 50 ng/ml of hVEGF (endothelial differentiation medium, EDM). After 21 days of culture in LTM, pAVPCs showed an elongated fibroblast-like morphology, and they seem to organize in cord-like structures. qPCR analysis of smooth muscle markers [α-smooth muscle actin (α-SMA), calponin, and smooth muscle myosin (SMM) heavy chain] showed a significant increment of the transcripts, and immunofluorescence analysis confirmed the presence of α-SMA and SMM proteins. After 21 days of culture in EDM, pAVPCs displayed an endothelial cell-like morphology and revealed the upregulation of the expression of endothelial markers (CD31, vascular endothelial-cadherin, von Willebrand factor, and endothelial nitric oxide synthase) showing the CD31-typical pattern. In conclusion, pAVPCs could be defined as a VSC-like population considering that, if they are maintained in a specific pericyte medium, they express MSC markers, and they have, in addition to the classical mesenchymal trilineage differentiation potential, the capacity to differentiate in vitro toward the smooth muscle and the endothelial cell phenotypes. PMID:26135800

  14. Upregulation of decorin by FXR in vascular smooth muscle cells

    SciTech Connect

    He Fengtian; Zhang Qiuhong; Kuruba, Ramalinga; Gao Xiang; Li Jiang; Li Yong; Gong Wei; Jiang, Yu; Xie Wen; Li Song

    2008-08-08

    Decorin is a member of the family of small leucine-rich proteoglycans that are present in blood vessels and synthesized by vascular smooth muscle cells (VSMCs). Decorin plays complex roles in both normal vascular physiology and the pathogenesis of various types of vascular disorders. However, the mechanisms of regulation of decorin expression in vasculature are not clearly understood. Particularly little information is available about a role of nuclear receptors in the regulation of decorin expression. In the present study, we report that activation of vascular FXR by a specific ligand resulted in upregulation of decorin at the levels of both mRNA and protein. FXR appears to induce decorin expression at a transcriptional level because (1) upregulation of decorin mRNA expression was abolished by the treatment of a transcription inhibitor, actinomycin D; and (2) decorin promoter activity was significantly increased by activation of FXR. Functional analysis of human decorin promoter identified an imperfect inverted repeat DNA motif, IR8 (-2313TGGTCAtagtgtcaTGACCT-2294), as a likely FXR-responsive element that is involved in decorin regulation.

  15. Cartilage oligomeric matrix protein prevents vascular aging and vascular smooth muscle cells senescence.

    PubMed

    Wang, Meili; Fu, Yi; Gao, Cheng; Jia, Yiting; Huang, Yaqian; Liu, Limei; Wang, Xian; Wang, Wengong; Kong, Wei

    2016-09-16

    Aging-related vascular dysfunction contributes to cardiovascular morbidity and mortality. Cartilage oligomeric matrix protein (COMP), a vascular extracellular matrix protein, has been described as a negative regulatory factor for the vascular aging-related processes including atherosclerosis and vascular calcification. However, whether COMP is implicated in the process of vascular aging remains unclear. Here, we identified a novel function of COMP in preventing vascular aging and vascular smooth muscle cells (VSMCs) senescence. Firstly, vascular COMP expression was decreased in three different senescence-accelerated mouse models and was also declining with age. COMP(-/-) mice displayed elevated senescence-associated markers expression, including p53, p21 and p16, in the aortas compared with their wild type (WT) littermates. In accordance, COMP deficiency induced aging-related vascular dysfunction as evidenced by the significantly reduced phenylephrine-induced contraction and increased vascular stiffness as evaluated by pulse wave velocity. The aortic wall of COMP(-/-) mice was susceptible to senescence by displaying senescence-associated β-galactosidase (SA β-gal) activity induced by periadventitial application of CaCl2 to the abdominal aorta. In vitro, COMP knockdown by small interfering (si) RNA led to the elevation of p53, p21 and p16 as well as SA β-gal activity in VSMCs after H2O2 stimulation. VSMCs isolated from COMP(-/-) mice showed elevated senescence-associated markers expression and supplement of COMP adenovirus to COMP-deficient VSMCs greatly rescued cellular senescence. Taken together, these findings revealed the essential role of COMP in retarding the development of vascular aging and VSMC senescence. PMID:27498005

  16. Protein A suppresses immune responses during Staphylococcus aureus bloodstream infection in guinea pigs

    DOE PAGESBeta

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

    2015-01-06

    Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links 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 Bmore » cell responses. Immunization with SpAKKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity.« less

  17. Pulpal uptake of mercury from lined amalgam restorations in guinea pigs.

    PubMed

    Akyüz, Serap; Caglar, Esber

    2002-12-01

    The aim of the present study was to examine pulp in amalgam-restored teeth of guinea pigs with respect to the presence of mercury, and to evaluate whether lining of cavities with resin modified glass ionomer cements had any effect on the penetration of mercury. Class V cavities were prepared in 63 incisor teeth of 21 guinea pigs. Three amalgam restorations were placed per animal, one without base liner and two with different resin-modified glass ionomer cements (GC Lining LC and Ionoseal). Following observation periods of 1, 7 or 30 d, teeth were extracted and the mercury concentration in the pulp tissue was evaluated using atomic absorption spectrophotometry. It was found that resin-modified glass ionomer cements significantly diminished the transport of mercury into the pulp between day 7 and day 30 after amalgam insertion. PMID:12507220

  18. In vivo cystometrogram studies in urethane-anesthetized and conscious guinea pigs.

    PubMed

    Peterson, J S; Hanson, R C; Noronha-Blob, L

    1989-05-01

    Urinary bladder cystometry using urethral catheters is described in vivo in a urethane-anesthetized guinea pig preparation and compared to an awake-animal preparation in which surgically implanted catheters were used. Anticholinergic drugs dose-dependently inhibited the peak intravesical pressure (PvesP) to a maximum of approximately 80% but had no effect on other cystometrogram (CMG) parameters (threshold pressure, bladder capacity). Stereoselectivity was evident; dexetimide but not levetimide potently depressed PvesP. Oxybutynin was equipotent (ID50 approximately 0.15 mg/kg) in both preparations and showed a similar duration of action (t1/2 = 48-53 min). The data suggests that CMG parameters and the effects of oxybutynin were not affected by urethane anesthesia, making the in vivo urethane-anesthetized guinea pig preparation a valuable tool to evaluate both the filling and voiding phases of cystometry. PMID:2724992

  19. Semicarbazide-sensitive amine oxidase activity of guinea pig dorsal skin.

    PubMed

    Buffoni, F; Cambi, S; Banchelli, G; Ignesti, G; Pirisino, R; Raimondi, L

    1994-01-01

    A semicarbazide-sensitive amine oxidase activity with a high affinity for benzylamine (Bz.SSAO) (E.C. 1.4.3.6) is present in guinea pig dorsal skin. This enzymic activity oxidized benzylamine, histamine, 1,4-methylhistamine and acetylputrescine and was inhibited by semicarbazide and by B24 (3,5-diethoxy-4-aminomethylpyridine), a selective inhibitor of Bz.SSAO enzymes. It cross reacted with the antibodies raised against pure pig plasma benzylamine oxidase. Immunohistochemistry showed that it was localized in fibroblasts. Bz.SSAO activity of guinea pig dorsal skin increased during the process of skin healing. A treatment of the wounds with 3 micrograms of b-FGF significantly accelerated the process of skin healing and the increase of Bz.SSAO activity. PMID:7931260

  20. Adapted Lethality: What We Can Learn from Guinea Pig-Adapted Ebola Virus Infection Model

    PubMed Central

    Cheresiz, S. V.; Semenova, E. A.; Chepurnov, A. A.

    2016-01-01

    Establishment of small animal models of Ebola virus (EBOV) infection is important both for the study of genetic determinants involved in the complex pathology of EBOV disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. Since the wild-type EBOV is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. Here, we provide an overview of our several adaptation series in guinea pigs, which resulted in the establishment of guinea pig-adapted EBOV (GPA-EBOV) variants different in their characteristics, while uniformly lethal for the infected animals, and compare the virologic, genetic, pathomorphologic, and immunologic findings with those obtained in the adaptation experiments of the other research groups. PMID:26989413

  1. Adapted Lethality: What We Can Learn from Guinea Pig-Adapted Ebola Virus Infection Model.

    PubMed

    Cheresiz, S V; Semenova, E A; Chepurnov, A A

    2016-01-01

    Establishment of small animal models of Ebola virus (EBOV) infection is important both for the study of genetic determinants involved in the complex pathology of EBOV disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. Since the wild-type EBOV is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. Here, we provide an overview of our several adaptation series in guinea pigs, which resulted in the establishment of guinea pig-adapted EBOV (GPA-EBOV) variants different in their characteristics, while uniformly lethal for the infected animals, and compare the virologic, genetic, pathomorphologic, and immunologic findings with those obtained in the adaptation experiments of the other research groups. PMID:26989413

  2. Schistosoma mansoni: migration potential of normal and radiation attenuated parasites in naive guinea pigs

    SciTech Connect

    Kamiya, H.; McLaren, D.J.

    1987-02-01

    Compressed tissue autoradiography using (75Se)selenomethionine labelled parasites has been used to investigate the migration potential of normal and radiation attenuated cercariae of Schistosoma mansoni in naive guinea pigs. By Day 14 after infection. 44% of normal parasites were detected as reduced silver foci in the liver; this value corresponded well with the number of liver parasites recovered by retrograde perfusion of the hepatic portal system on Day 42 (42% of the challenge). In contrast, cercariae subjected to 50 krad of gamma irradiation failed to migrate out of the skin. The migration capacity of 20 krad irradiated parasites was less severely affected in that about half of the challenge parasites reached the lungs, but virtually none moved to the liver. These data are discussed in relation to the kinetics of immunity induced in guinea pigs by infection or vaccination with normal or radiation attenuated parasites.

  3. Effect of somatostatin on 45Ca fluxes in guinea-pig isolated atria.

    PubMed Central

    Díez, J.; Tamargo, J.

    1987-01-01

    The effect of somatostatin (SS, 10(-6) M and 5 X 10(-6) M) was studied on 45Ca fluxes in guinea-pig isolated atria. SS produced a dose-dependent decrease in 45Ca uptake, this effect being dependent on the stimulation rate and Ca concentration in the bathing media. The decrease in 45Ca uptake was more evident at faster (60 and 180 beats min-1) than at slower frequencies (15 beats min-1) and was less evident in high Ca (5.4 mM). SS had no effect on 45Ca efflux. These results suggest that SS inhibits the slow inward Ca current in guinea-pig atrial fibres. PMID:2435352

  4. [Effects of endothelin on electrophysiological and contractile activity of guinea pig papillary muscles].

    PubMed

    Zhang, Z; Li, Y L; He, R R

    1997-04-01

    Effects of endothelin on electrophysiological activity and contractility were examined in guinea pig papillary muscle using intracellular microelectrode and contractile tension recording technique. The results indicated that ET-1 prolonged APD, especially PPD and increased the contractile tension in a dose-dependent manner. The ET-induced effects were not influenced by K+ channel blocker TEA, but inhibited by L-type Ca2+ channel blocker nifedipine, ETA receptor selective antagonist BQ-123 and atriopeptin III in a concentration-dependent manner. It is suggested that the changes in electrophysiological activity and the positive inotropic effect induced by ET-1 in guinea pig muscles are due to the elevation of intracellular calcium, which may be mediated by ETA receptor. PMID:9812849

  5. The pathogenesis of leptospirosis I. Hemorrhages in experimental leptospirosis in guinea pigs.

    PubMed

    Higgins, R; Cousineau, G

    1977-04-01

    In experimental infections of guinea pigs with a virulent strain of Leptospira icterohaemorrhagiae widespread hemorrhages were observed. Thrombocytopenia, prolongation of prothrombin, thrombin, partial thromboplastin and coagulation times, decrease of plasma fibrinogen, factor V, factor VIII and the presence of fibrinogen degradation products were demonstrated. Treatment of infected guinea pigs with heparin prolonged life for two to three days. The histological observations revealed that the main lesion is a severe injury of the vasculature, mainly arteries, arterioles and capillaries. Most of the endothelial cells are affected or destroyed and the muscular fibers of arteries and arterioles are injured. With Martius-Scarlet-Blue, Weigert or Picro-Mallory stains it was demonstrated that the organization seen in the vessels is not all made of fibrin. The conclusion reached was that the hemorrhages observed in experimental leptospirosis in guines pigs are due to disseminated intravascular coagulation. PMID:861835

  6. Gentamicin iontophoresis in the treatment of bacterial otitis externa in the guinea pig model.

    PubMed

    King, D M; Estrem, S A

    1990-10-01

    Pseudomonas otitis externa is one of the most common infections treated by otolaryngologists. Infections induced in 30 guinea pigs appeared similar to that seen in humans. The ears were then placed into four treatment groups: group A, which received a single cleaning; group B, which received a single cleaning followed by gentamicin drops 4 times daily; group C, which received a single cleaning followed by a single gentamicin iontophoresis treatment; and group D, the control group, which received no treatment. Infections were analyzed by grading edema, purulence, and erythema. An average of 10.2 days was required for control group to return to normal appearance. Groups A, B, and C had mean resolution times of 5.9, 4.7, and 4.3 days, respectively. Gentamicin iontophoresis appears to be promising, with results as good as drop therapy in otitis externa in the guinea pig model. PMID:2215045

  7. SOME BIOCHEMICAL CHANGES IN THE GUINEA PIG DURING INFECTION WITH COXIELLA BURNETII

    PubMed Central

    Paretsky, D.; Downs, C. M.; Salmon, C. W.

    1964-01-01

    Paretsky, D. (University of Kansas, Lawrence), C. M. Downs, and C. W. Salmon. Some biochemical changes in the guinea pig during infection with Coxiella burnetii. J. Bacteriol. 88:137–142. 1964.—Guinea pigs infected with Coxiella burnetii, the rickettsial agent of Q fever, were studied for 11 days postinfection. Maximal changes in liver lipids, liver phosphorylase, and uridine diphosphate glucose (UDPG)-glycogen glucosyl-transferase activities occurred 3 to 4 days post-infection. In this period, total liver lipids increased from 1.26 to 5.46 mg/mg of N, with the largest increment in the glyceride fraction. Liver glycogen virtually disappeared by the second day, with no chemically detectable restoration until the eleventh day. A pattern of altered phosphorylase and UDPG-glycogen transglucosylase activities was observed, with maximal phosphorylase and minimal glucosyltransferase activities at the third and fourth days. Histochemical observations confirmed chemical analyses for lipids and glycogen. PMID:14197878

  8. SOME BIOCHEMICAL CHANGES IN THE GUINEA PIG DURING INFECTION WITH COXIELLA BURNETII.

    PubMed

    PARETSKY, D; DOWNS, C M; SALMON, C W

    1964-07-01

    Paretsky, D. (University of Kansas, Lawrence), C. M. Downs, and C. W. Salmon. Some biochemical changes in the guinea pig during infection with Coxiella burnetii. J. Bacteriol. 88:137-142. 1964.-Guinea pigs infected with Coxiella burnetii, the rickettsial agent of Q fever, were studied for 11 days postinfection. Maximal changes in liver lipids, liver phosphorylase, and uridine diphosphate glucose (UDPG)-glycogen glucosyl-transferase activities occurred 3 to 4 days post-infection. In this period, total liver lipids increased from 1.26 to 5.46 mg/mg of N, with the largest increment in the glyceride fraction. Liver glycogen virtually disappeared by the second day, with no chemically detectable restoration until the eleventh day. A pattern of altered phosphorylase and UDPG-glycogen transglucosylase activities was observed, with maximal phosphorylase and minimal glucosyltransferase activities at the third and fourth days. Histochemical observations confirmed chemical analyses for lipids and glycogen. PMID:14197878

  9. Fully effective contraception in male and female guinea pigs immunized with the sperm protein PH-20.

    PubMed

    Primakoff, P; Lathrop, W; Woolman, L; Cowan, A; Myles, D

    1988-10-01

    Immunization of male and female animals with extracts of whole sperm cells is known to cause infertility. Also, men and women who spontaneously produce antisperm antibodies are infertile but otherwise healthy. Although the critical sperm antigens are unknown, these observations have led to the proposal that sperm proteins might be useful in the development of a contraceptive vaccine. The guinea pig sperm surface protein PH-20 is essential in sperm adhesion to the extracellular coat (zona pellucida) of the egg, a necessary initial step in fertilization. Here, we report that 100% effective contraception was obtained in male and female guinea pigs immunized with PH-20. Antisera from immunized females had high titres, specifically recognized PH-20 in sperm extracts, and blocked sperm adhesion to the egg zona pellucida in vitro. The contraceptive effect was long-lasting and reversible: immunized females, mated at intervals of six to fifteen months after immunization, progressively regained fertility. PMID:3419530

  10. Induction of contact dermatitis in guinea pigs by quaternary ammonium compounds: the mechanism of antigen formation.

    PubMed Central

    Schallreuter, K U; Schulz, K H; Wood, J M

    1986-01-01

    Eight quaternary ammonium compounds were tested for their ability to induce contact dermatitis in guinea pigs by using a modified Freund's complete adjuvant test together with the guinea pig maximization test. Only two quaternary ammonium salts of the eight tested could be designated as strong allergens. These two active substances were shown to be capable of stable association with membrane lipids in forming immunogenic complexes. This surface complexation phenomenon was confirmed by using a spin-labeled quaternary ammonium salt which competed for binding sites at the surface of epidermal cells in vivo. Electron spin resonance was used to demonstrate that stable "ion-pairs" are formed between binding sites and the two allergenic preservatives. Furthermore, information was obtained on the kinetics of immunogenic complex formation as well as on the position and orientation of the quaternary ammonium ion at the cell surface. PMID:3830108

  11. Extraction of an incisor embedded within the nasal cavity in two guinea pigs

    PubMed Central

    KIDO, Nobuhide; ONO, Kaori; OMIYA, Tomoko; OGUCHI, Yukio; SETOGAWA, Moemi; MACHIDA, Yuuki

    2015-01-01

    Oral examination of two guinea pigs revealed that the unilateral incisor was absent. On radiographic examination, the incisor was identified within the nasal cavity in both patients. Under anesthesia in both patients, the skin was incised from the nostril to 1.5 cm proximal, and the premaxilla and part of the maxilla were exposed. The bone was removed using a surgical drill, and the incisor was exposed in the nasal cavity. The root was grasped with forceps and carefully extracted as it was degraded and very fragile. Diagnosis was easy using oral and radiographic examination. In guinea pig patients where an incisor is absent on oral examination, this condition should be considered. PMID:26118492

  12. Induction of contact drematitis in guinea pigs by quaternary ammonium compounds: the mechanisms of antigen formation

    SciTech Connect

    Schallreuter, K.R.; Schulz, K.H.; Wood, J.M.

    1986-12-01

    Eight quaternary ammonium compounds were tested for their ability to induce contact dermatitis in guinea pigs by using a modified Freund's complete adjuvant test together with the guinea pig maximization test. Only two quaternary ammonium salts of eight tested could be designated as strong allergens. These two active substances were shown to be capable of stable association with membrane lipids in forming immunogenic complexes. This surface complexation phenomenon was confirmed by using a spin-labeled quaternary ammonium salt which competed for binding sites to the surface of epidermal cells in vivo. Electron spin resonance was used to demonstrate that stable ion-pairs are formed between binding sites and the two allergenic preservatives. Furthermore, information was obtained on the kinetics of immunogenic complex formation as well as on the position and orientation of the quaternary ammonium ion at the cell surface.

  13. Comparison of the bronchoconstrictor and cardiovascular effects of some tachykinins in guinea pigs.

    PubMed

    Goel, V; Biggs, D F

    1987-03-01

    The effects of three tachykinins [substance P (SP), physalaemin (PH), and eledoisin-related peptide (ERP)] were investigated in anesthetized paralyzed guinea pigs. We measured airway resistance (R) and dynamic thoracic elastance (E) with a computerized technique, and blood pressure via a carotid artery. Tachykinins injected iv or intra-aortically (ia) induced dose-dependent increases in R and E, 4 times greater on iv than ia injection. They did not give rise to tachyphylaxis. As a bronchoconstrictor, PH was 5.0X and ERP 1.8X more potent than SP; time to peak response was longer for PH than for ERP and SP; and hypotensive responses, which were of similar magnitude for all three substances, lasted longest after PH. Bronchoconstrictor responses were unaltered by bilateral vagotomy, atropine, mecamylamine, and mepyramine. Morphine reduced PH-induced increases in R (P less than 0.01) and E (P less than 0.05), which were not reversed by naloxone, and capsaicin treatment 1 week before the experiments reduced both SP- and PH-induced increases in E (P less than 0.05). [D-Pro2,D-Trp7,9]-SP reduced ERP-induced increases in R and E, and [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP reduced both SP- and PH-induced increases in R and E. We conclude that PH is the most potent bronchoconstrictor of the tachykinins tested. Tachykinin-induced bronchospasm is 'non-reflex' arising via a direct effect on airway smooth muscle; the release of histamine, acetylcholine, or other tachykinins is not involved in the responses. [D-Pro2,D-Trp7,9]-SP is more effective at SP-E receptors, and [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP at SP-P receptors; both types of receptor are located all along the airways. PMID:2434817

  14. The relaxant action of osthole isolated from Angelica pubescens in guinea-pig trachea.

    PubMed

    Teng, C M; Lin, C H; Ko, F N; Wu, T S; Huang, T F

    1994-02-01

    The effect of osthole, isolated from Angelica pubescens, on the contraction of guinea-pig trachea was studied. Osthole (25-100 mumol/l), theophylline (10-1000 mumol/l) and higher concentrations of nifedipine (0.1-100 mumol/l) suppressed the contraction response curves of tracheal smooth muscle caused by carbachol, prostaglandin F2 alpha (PGF2 alpha), U46619 (thromboxane A2 analogue) and leukotriene C4 (LTC4) in a concentration-dependent manner. The contraction caused by high K+ (120 mmol/l) and cumulative concentrations of CaCl2 (0.03-3 mmol/l) was also inhibited concentration-dependently by osthole (25-100 mumol/l), theophylline (10-1000 mumol/l) and lower concentrations of nifedipine (0.01-0.1 mumol/l). The relaxant actions of osthole were not affected by propranolol (1 mumol/l), glibenclamide (10 mumol/l) or removal of tracheal epithelium. Osthole (100 mumol/l) was still effective in causing tracheal relaxation in the presence of nifedipine (1 mumol/l). In Ca(2+)-free- and EGTA (0.2 mmol/l)-containing medium, the relaxing effect of osthole was more potent than in normal Krebs solution. Osthole (25 and 50 mumol/l) caused 2.9 and 6.5, or 3.0 and 5.6 fold, respectively, increase in potency of forskolin or sodium nitroprusside in causing tracheal relaxation but did not affect that by cromakalim. Osthole (50 mumol/l) enhanced the increase in tissue cAMP and cGMP levels induced by forskolin and sodium nitroprusside, respectively, and in higher concentrations (100 and 250 mumol/l), itself increased markedly tissue cAMP and cGMP contents. Osthole (10-250 mol/l) inhibited the activity of cAMP and cGMP phosphodiesterases in a concentration-dependent manner. It is concluded that osthole exerts a non-specific relaxant effect on the trachealis by inhibiting the cAMP and cGMP phosphodiesterases. PMID:8170504

  15. Evidence that antidromically stimulated vagal afferents activate inhibitory neurones innervating guinea-pig trachealis.

    PubMed Central

    Canning, B J; Undem, B J

    1994-01-01

    1. We recently described a capsaicin-sensitive vagal pathway mediating non-adrenergic, non-cholinergic (NANC) relaxations of an isolated, innervated rostral guinea-pig tracheal preparation. These afferent fibres are carried by the superior laryngeal nerves and relaxations elicited by their activation are insensitive to autonomic ganglion blockers such as hexamethonium. In the present study this vagal relaxant pathway was further characterized. 2. Relaxations of the trachealis elicited by electrical stimulation of capsaicin-sensitive vagal afferents were mimicked by bath application of capsaicin. Relaxations elicited by both methods were abolished when the tissue between the trachea and the adjacent oesophagus was disrupted. Indeed, separating the trachea from the oesophagus uncovered a contractile effect of capsaicin administration on the trachealis. 3. Capsaicin-induced, oesophagus-dependent relaxations of the trachealis were blocked by pretreatment with the fast sodium channel blocker tetrodotoxin (TTX). By contrast, capsaicin-induced contractions of the trachealis (obtained in the absence of the oesophagus) were unaffected by tetrodotoxin. 4. Substance P, neurokinin A (NKA) and neurokinin B (NKB) also elicited NANC relaxations of precontracted trachealis that were abolished by separating the trachea from the oesophagus or by TTX pretreatment. Like capsaicin, the tachykinins elicited only contractions of the trachealis following TTX pretreatment or separation of the trachea from the adjacent oesophagus. 5. Relaxations elicited by stimulation of the capsaicin-sensitive nerves were unaffected by a concentration of the tachykinin NK2 receptor-selective antagonist, SR 48968, that is selective for NK2 receptor blockade and were not mimicked by the NK2 receptor-selective agonist [beta-Ala8]-NKA(4-10). This suggests that NK2 receptors are not responsible for these relaxations. By contrast, the NK3 receptor-selective agonist, senktide analogue, and the NK1 receptor

  16. Hypoxic vasodilatation in isolated, perfused guinea-pig heart: an analysis of the underlying mechanisms.

    PubMed Central

    von Beckerath, N; Cyrys, S; Dischner, A; Daut, J

    1991-01-01

    1. The mechanisms underlying hypoxic dilatation of coronary arteries were studied in isolated guinea-pig hearts perfused with physiological salt solution at 37 degrees C. The hearts were perfused at a constant rate of 3-10 ml min-1; coronary perfusion pressure (CPP) and isovolumetric left ventricular pressure (LVP) were measured with piezoresistive transducers. 2. Addition of the K+ channel opener cromakalim (500 nM) to the perfusate caused a maximal vasodilatation in beating hearts, i.e. a decrease in CPP of about 50%. Switching from normal perfusate (partial pressure of O2 (PO2), 650-700 mmHg) to hypoxic perfusate (PO2, 9-10 mmHg) caused a similar vasodilatation. Both of these effects were prevented by 2 microM-glibenclamide, a blocker of ATP-sensitive potassium channels. Hypoxic vasodilatation was accompanied by a marked decrease in LVP, which was reduced by 56 +/- 22% (mean +/- S.D.) in the presence of glibenclamide. 3. In hearts arrested by increasing the K+ concentration of the perfusate to 15 mM, the addition of the adenosine-uptake inhibitor dipyridamole evoked a maximal vasodilatation and this was inhibited by 76 +/- 7% in the presence of glibenclamide. 4. The adenosine antagonist 8-phenyltheophylline (8-PT; 5 microM) inhibited the vasodilatation induced by dipyridamole by 88 +/- 10%. In contrast, hypoxic vasodilatation was unaffected by 5 microM 8-PT. This suggests that hypoxic dilatation of coronary arteries is not mediated by release of adenosine from cardiomyocytes. 5. In order to test whether release of endothelium-derived relaxing factor (EDRF) contributed to hypoxic vasodilatation we blocked EDRF synthesis with N omega-nitro-L-arginine (NNA). When applied at a perfusion rate of 10 ml min-1 to arrested hearts, 10 microM-NNA increased CPP by 35% and prolonged the delay between application of hypoxic solution and half-maximal vasodilatation from 52 +/- 9 to 129 +/- 29 s. 6. Under control conditions the relation between perfusion rate and the CPP

  17. Mast cell expression of the serotonin1A receptor in guinea pig and human intestine.

    PubMed

    Wang, Guo-Du; Wang, Xi-Yu; Zou, Fei; Qu, Meihua; Liu, Sumei; Fei, Guijun; Xia, Yun; Needleman, Bradley J; Mikami, Dean J; Wood, Jackie D

    2013-05-15

    Serotonin [5-hydroxytryptamine (5-HT)] is released from enterochromaffin cells in the mucosa of the small intestine. We tested a hypothesis that elevation of 5-HT in the environment of enteric mast cells might degranulate the mast cells and release mediators that become paracrine signals to the enteric nervous system, spinal afferents, and secretory glands. Western blotting, immunofluorescence, ELISA, and pharmacological analysis were used to study expression of 5-HT receptors by mast cells in the small intestine and action of 5-HT to degranulate the mast cells and release histamine in guinea pig small intestine and segments of human jejunum discarded during Roux-en-Y gastric bypass surgeries. Mast cells in human and guinea pig preparations expressed the 5-HT1A receptor. ELISA detected spontaneous release of histamine in guinea pig and human preparations. The selective 5-HT1A receptor agonist 8-hydroxy-PIPAT evoked release of histamine. A selective 5-HT1A receptor antagonist, WAY-100135, suppressed stimulation of histamine release by 5-HT or 8-hydroxy-PIPAT. Mast cell-stabilizing drugs, doxantrazole and cromolyn sodium, suppressed the release of histamine evoked by 5-HT or 8-hydroxy-PIPAT in guinea pig and human preparations. Our results support the hypothesis that serotonergic degranulation of enteric mast cells and release of preformed mediators, including histamine, are mediated by the 5-HT1A serotonergic receptor. Association of 5-HT with the pathophysiology of functional gastrointestinal disorders (e.g., irritable bowel syndrome) underlies a question of whether selective 5-HT1A receptor antagonists might have therapeutic application in disorders of this nature. PMID:23518679

  18. Effects of intravitreal ropivacaine on retinal thickness and integrity in the guinea pig

    PubMed Central

    Olmez, Gonul; Soker Cakmak, Sevin; Ipek Soker, Sevda; Nergiz, Yusuf; Yildiz, Fethin

    2005-01-01

    Background: Retrobulbar anesthesia is widely used for ocular surgery.Ocular complications are possible when retrobulbar anesthesia is accidentally injected intravitreally. Objective: The aim of this study was to determine the relative retinal toxicitiesof ropivacaine hydrochloride, a local anesthetic, using various concentrations in guinea pigs. Methods: This randomized, investigator-masked, experimental study wasconducted at the Department of Anesthesiology, Dicle University, Diyarbakir, Turkey. The right eyes of 18 guinea pigs were assigned to 1 of 3 treatment groups: 1%, 0.75%, or 0.5% ropivacaine. The right eye of each animal was injected intravitreally with 0.1 mL of 1%, 0.75%, or 0.5% ropivacaine. The left eye of each animal was injected with a balanced saline solution (control). The guinea pigs were euthanized 7 days after injection, and the retinal structures were examined using light microscopy. The total thickness of each retina was measured using an ocular micrometer. Results: No histologic abnormalities were observed in the control eyes.Retinal damage of most of the retinal section was seen in the eyes receiving study drug. The eyes injected with 0.5% ropivacaine had a generally intact appearance, with the exception of some atrophy and disorganization. Overall, the eyes injected with 1% ropivacaine had significantly more extensive retinal thinning compared with the eyes injected with 0.75% or 0.5% ropivacaine (both, P < 0.01). In the eyes injected with 0.75% or 1% ropivacaine, disorganization of the structure of the retinal layers and atrophy were noted on histopathology. The mean total thicknesses of the retina were significantly less in all ropivacaine-treated eyes compared with that in the controls (P < 0.001) Conclusions: In this small experimental study, ropivacaine had concentration-dependent toxic effects on guinea pig retinas. PMID:24672138

  19. Mast cell expression of the serotonin1A receptor in guinea pig and human intestine

    PubMed Central

    Wang, Guo-Du; Wang, Xi-Yu; Zou, Fei; Qu, Meihua; Liu, Sumei; Fei, Guijun; Xia, Yun; Needleman, Bradley J.; Mikami, Dean J.

    2013-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] is released from enterochromaffin cells in the mucosa of the small intestine. We tested a hypothesis that elevation of 5-HT in the environment of enteric mast cells might degranulate the mast cells and release mediators that become paracrine signals to the enteric nervous system, spinal afferents, and secretory glands. Western blotting, immunofluorescence, ELISA, and pharmacological analysis were used to study expression of 5-HT receptors by mast cells in the small intestine and action of 5-HT to degranulate the mast cells and release histamine in guinea pig small intestine and segments of human jejunum discarded during Roux-en-Y gastric bypass surgeries. Mast cells in human and guinea pig preparations expressed the 5-HT1A receptor. ELISA detected spontaneous release of histamine in guinea pig and human preparations. The selective 5-HT1A receptor agonist 8-hydroxy-PIPAT evoked release of histamine. A selective 5-HT1A receptor antagonist, WAY-100135, suppressed stimulation of histamine release by 5-HT or 8-hydroxy-PIPAT. Mast cell-stabilizing drugs, doxantrazole and cromolyn sodium, suppressed the release of histamine evoked by 5-HT or 8-hydroxy-PIPAT in guinea pig and human preparations. Our results support the hypothesis that serotonergic degranulation of enteric mast cells and release of preformed mediators, including histamine, are mediated by the 5-HT1A serotonergic receptor. Association of 5-HT with the pathophysiology of functional gastrointestinal disorders (e.g., irritable bowel syndrome) underlies a question of whether selective 5-HT1A receptor antagonists might have therapeutic application in disorders of this nature. PMID:23518679

  20. Metabolism of [14C]methamphetamine in man, the guinea pig and the rat

    PubMed Central

    Caldwell, J.; Dring, L. G.; Williams, R. T.

    1972-01-01

    1. The metabolites of (±)-2-methylamino-1-phenyl[1-14C]propane ([14C]methamphetamine) in urine were examined in man, rat and guinea pig. 2. In two male human subjects receiving the drug orally (20mg per person) about 90% of the 14C was excreted in the urine in 4 days. The urine of the first day was examined for metabolites, and the main metabolites were the unchanged drug (22% of the dose) and 4-hydroxymethamphetamine (15%). Minor metabolites were hippuric acid, norephedrine, 4-hydroxyamphetamine, 4-hydroxynorephedrine and an acid-labile precursor of benzyl methyl ketone. 3. In the rat some 82% of the dose of 14C (45mg/kg) was excreted in the urine and 2–3% in the faeces in 3–4 days. In 2 days the main metabolites in the urine were 4-hydroxymethamphetamine (31% of dose), 4-hydroxynorephedrine (16%) and unchanged drug (11%). Minor metabolites were amphetamine, 4-hydroxyamphetamine and benzoic acid. 4. The guinea pig was injected intraperitoneally with the drug at two doses, 10 and 45mg/kg. In both cases nearly 90% of the 14C was excreted, mainly in the urine after the lower dose, but in the urine (69%) and faeces (18%) after the higher dose. The main metabolites in the guinea pig were benzoic acid and its conjugates. Minor metabolites were unchanged drug, amphetamine, norephedrine, an acid-labile precursor of benzyl methyl ketone and an unknown weakly acidic metabolite. The output of norephedrine was dose-dependent, being about 19% on the higher dose and about 1% on the lower dose. 5. Marked species differences in the metabolism of methamphetamine were observed. The main reaction in the rat was aromatic hydroxylation, in the guinea pig demethylation and deamination, whereas in man much of the drug, possibly one-half, was excreted unchanged. PMID:4646771

  1. Validation of a Behavioral Ethogram for Assessing Postoperative Pain in Guinea Pigs (Cavia porcellus)

    PubMed Central

    Dunbar, Misha L; David, Emily M; Aline, Marian R; Lofgren, Jennifer L

    2016-01-01

    Although guinea pigs (Cavia porcellus) have been used in research for more than a century and remain the most prevalent USDA-covered species, little has been elucidated regarding the recognition of clinical pain or analgesic efficacy in this species. We sought to assess pain in guinea pigs by using newer, clinically relevant methods that have been validated in other rodent species: the behavioral ethogram and cageside proxy indicator. In this study, 10 male guinea pigs underwent electronic von Frey testing of nociception, remote videorecording of behavior, and cageside assessment by using time-to-consumption (TTC) of a preferred treat test. These assessments were performed across 2 conditions (anesthesia only and castration surgery under anesthesia) at 3 time points (2, 8, and 24 h after the event). The anesthesia only condition served to control for the nonpainful but potentially distressing components of the surgical experience. Compared with those after anesthesia only conditions, subtle body movements were increased and nociceptive thresholds were decreased at 2 and 8 h after surgery. At 24 h, neither subtle body movement behaviors nor nociceptive thresholds differed between the 2 conditions. In contrast, TTC scores did not differ between the anesthesia only and surgery conditions at any time point, underscoring the challenge of identifying pain in this species through cageside evaluation. By comparing ethogram scores with measures of nociception, we validated select behaviors as pain-specific. Therefore, our novel ethogram allowed us to assess postoperative pain and may further serve as a platform for future analgesia efficacy studies in guinea pigs. PMID:26817977

  2. The effect of some new antihistamines on the anaphylactic microshock of the guinea-pig

    PubMed Central

    Herxheimer, H.; Stresemann, E.

    1963-01-01

    The dose/response curves for the protective effects of the new antihistamine compounds trimeprazine, 10-(3-diethylamino-2-methylpropyl)phenothiazine 1,1-dioxide hydrochloride (oxomemazine hydrochloride), cyproheptadine, homochlorcyclizine and methotrimeprazine against the anaphylactic microshock of the guinea-pig were similar to that of promethazine. The first three compounds, however, protected at lower doses than promethazine (5 to 10 μg/kg). The protective effect of cyproheptadine lasted longer than 24 hr. PMID:14110740

  3. THE EFFECT OF SOME NEW ANTIHISTAMINES ON THE ANAPHYLACTIC MICROSHOCK OF THE GUINEA-PIG.

    PubMed

    HERXHEIMER, H; STRESEMANN, E

    1963-12-01

    The dose/response curves for the protective effects of the new antihistamine compounds trimeprazine, 10-(3-diethylamino-2-methylpropyl)phenothiazine 1,1-dioxide hydrochloride (oxomemazine hydrochloride), cyproheptadine, homochlorcyclizine and methotrimeprazine against the anaphylactic microshock of the guinea-pig were similar to that of promethazine. The first three compounds, however, protected at lower doses than promethazine (5 to 10 mug/kg). The protective effect of cyproheptadine lasted longer than 24 hr. PMID:14110740

  4. Frictional Properties of Hartley Guinea Pig Knees With and Without Proteolytic Disruption of the Articular Surfaces

    PubMed Central

    Teeple, Erin; Fleming, Braden C.; Mechrefe, Anthony P.; Crisco, Joseph J.; Brady, Mark F.; Jay, Gregory D.

    2007-01-01

    Summary Objective To apply a pendulum technique to detect changes in the coefficient of friction of the articular cartilage of the intact guinea pig tibiofemoral joint after proteolytic disruption. Design 22 hind limbs were obtained from eleven 3-month old Hartley Guinea pigs. 20 knees were block randomized to one of two treatment groups receiving injections of: 1) α-chymotrypsin (to disrupt the superficial layer of the articular surface) or 2) saline (sham; to control for the effects of the intra-articular injection). The legs were mounted in a pendulum where the knee served as the fulcrum. The decay in pendulum amplitude as a function of oscillation number was first recorded and the coefficient of friction of the joint was determined from these data before injection. 10 μL of either isotonic saline or 1 Unit/μL α-chymotrypsin was then injected into the intra-articular joint space and incubated for two hours. The pendulum test was repeated. Changes in the coefficient of friction between the sham and α-chymotrypsin joints were compared. One additional pair of knees was used for histological study of the effects of the injections. Results Treatment with α-chymotrypsin significantly increased the coefficient of friction of the guinea pig knee by 74% while sham treatment decreased it by 8%. Histological sections using Gomori trichrome stain verified that the lamina splendens was damaged following treatment with α-chymotrypsin and not following saline treatment. Conclusions Treatment with α-chymotrypsin induces mild cartilage surface damage and increases the coefficient of friction in the Hartley guinea pig knee. PMID:17010648

  5. Behavioral recovery induced by applied electric fields after spinal cord hemisection in guinea pig

    SciTech Connect

    Borgens, R.B.; Blight, A.R.; McGinnis, M.E.

    1987-10-16

    Applied electric fields were used to promote axonal regeneration in spinal cords of adult guinea pigs. A propriospinal intersegmental reflex (the cutaneous trunci muscle reflex) was used to test lateral tract function after hemisection of the thoracic spinal cord. An electrical field (200 microvolts per millimeter, cathode rostral) applied across the lesion led to functional recovery of the cutaneous trunci muscle reflex in 25 percent of experimental animals, whereas the functional deficit remained in control animals, which were implanted with inactive stimulators.

  6. Cellular immune responses to amoebic liver abcess in the guinea-pig.

    PubMed Central

    Bray, R S; Harris, W G

    1977-01-01

    Guinea-pigs infected in the liver with the Biswas strain of Entamoeba histolytica showed no dermal hypersensitivity but showed positive lymphocyte transformation and macrophage-migration inhibition. The time sequence showed an activated response at 4 days after infection, a full response at 8 days when the liver abscesses were resolving and a waning response at 12 days when the abscesses had healed. PMID:891028

  7. Fetal guinea pig brain 15-hydroxyprostaglandin dehydrogenase: Ontogeny and effect of ethanol

    SciTech Connect

    Treissman, D.; Brien, J.F. )

    1991-03-01

    The objectives of this study were to determine the ontogeny of 15-hydroxyprostaglandin dehydrogenase (15-OH-PGDH) activity in the brain of the fetal guinea pig and to test the hypothesis that acute in vitro ethanol exposure produces concentration-dependent inhibition of fetal brain 15-OH-PGDH activity. Enzyme activity was determined in vitro by measuring the rate of oxidation of PGE2 to 15-keto-PGE2 using an optimized radiometric procedure. The study was conducted utilizing the whole brain of the fetal guinea pig at mean gestational ages of 34, 43 and 62 days (term, about 66 days) and the brain stem (pons and medulla) of the fetal guinea pig at mean gestational ages of 43 and 62 days. The direct effect of acute in vitro exposure to ethanol was assessed by incubating 15-OH-PGDH with ethanol in the concentration range of 10 to 80 mM. 15-OH-PGDH was measurable in the whole brain and brain stem, and the enzyme activity was similar for the gestational ages examined. There was no significant ethanol-induced inhibition of 15-OH-PGDH activity in the whole brain or brain stem. The data demonstrate that the whole brain and brain stem of the fetal guinea pig have the capacity to metabolize PGE2 to 15-keto-PGE2, an inactive metabolite, during the second half of gestation. The data apparently are not consistent with the hypothesis that acute in vitro exposure to ethanol directly inhibits 15-OH-PGDH activity in fetal brain.

  8. Validation of a Behavioral Ethogram for Assessing Postoperative Pain in Guinea Pigs (Cavia porcellus).

    PubMed

    Dunbar, Misha L; David, Emily M; Aline, Marian R; Lofgren, Jennifer L

    2016-01-01

    Although guinea pigs (Cavia porcellus) have been used in research for more than a century and remain the most prevalent USDA-covered species, little has been elucidated regarding the recognition of clinical pain or analgesic efficacy in this species. We sought to assess pain in guinea pigs by using newer, clinically relevant methods that have been validated in other rodent species: the behavioral ethogram and cageside proxy indicator. In this study, 10 male guinea pigs underwent electronic von Frey testing of nociception, remote videorecording of behavior, and cageside assessment by using time-to-consumption (TTC) of a preferred treat test. These assessments were performed across 2 conditions (anesthesia only and castration surgery under anesthesia) at 3 time points (2, 8, and 24 h after the event). The anesthesia only condition served to control for the nonpainful but potentially distressing components of the surgical experience. Compared with those after anesthesia only conditions, subtle body movements were increased and nociceptive thresholds were decreased at 2 and 8 h after surgery. At 24 h, neither subtle body movement behaviors nor nociceptive thresholds differed between the 2 conditions. In contrast, TTC scores did not differ between the anesthesia only and surgery conditions at any time point, underscoring the challenge of identifying pain in this species through cageside evaluation. By comparing ethogram scores with measures of nociception, we validated select behaviors as pain-specific. Therefore, our novel ethogram allowed us to assess postoperative pain and may further serve as a platform for future analgesia efficacy studies in guinea pigs. PMID:26817977

  9. Synergistic effects of LTB4 and LTD4 on leukocyte emigration into the guinea pig conjunctiva.

    PubMed

    Spada, C S; Woodward, D F; Hawley, S B; Nieves, A L; Williams, L S; Feldmann, B J

    1988-02-01

    Leukotrienes (LT) B4 and D4, alone and in combination, were topically applied to the eyes of guinea pigs, and their effects on conjunctival leukocyte infiltration studied. LTD4 potentiated the neutrophil response to LTB4, even though no neutrophil emigration was evoked by LTD4 itself over a dose range of 10-1000 ng. LTB4 alone at the 1-ng and 10-ng doses failed to evoke any leukocyte emigration, but significant numbers of neutrophils were observed at these concentrations when LTD4 (1-1000 ng) was present. Although a dose-dependent increase in neutrophil infiltration was observed for the 100-ng and 1000-ng doses of LTB4, cell counts were substantially higher with these doses in the presence of LTD4. Eosinophil numbers increased in a dose-related manner in response to LTB4 and LTD4 alone, with a greater response to LTD4. The addition of either 10 ng or 100 ng of LTB4 to graded doses of LTD4 (10-1000 ng) caused increased eosinophil numbers, the lower dose of LTB4 potentiating the response to LTD4 and the higher LTB4 dose showing no significant effect. The effects on leukocyte infiltration that were evoked by the LT combinations could not be explained simply on the basis of an increase in vascular permeability. Bradykinin (BK), a potent conjunctival microvascular permeability factor that does not elicit any leukocyte infiltration, did not significantly potentiate LTB4-induced eosinophil or neutrophil emigration. The synergistic effects of LTs on leukocyte emigration are also difficult to ascribe to hyperemia (ie, increased blood volume in the conjunctiva), because both LTB4 and LTD4 caused only very modest increases in conjunctival blood content, and BK, which did not potentiate the leukocytic responses to LTB4, caused marked increases in tissue blood content. High-dose LT combinations caused eosinophils, but not neutrophils, to migrate into the conjunctival epithelium and fragment, resulting in overt tissue damage. These results further suggest a synergistic

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

    PubMed Central

    Feng, Hua; Wang, Fang; Wang, Changmiao

    2016-01-01

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

  11. Single treatment of VX poisoned guinea pigs with the phosphotriesterase mutant C23AL: Intraosseous versus intravenous injection.

    PubMed

    Wille, Timo; Neumaier, Katharina; Koller, Marianne; Ehinger, Christina; Aggarwal, Nidhi; Ashani, Yacov; Goldsmith, Moshe; Sussman, Joel L; Tawfik, Dan S; Thiermann, Horst; Worek, Franz

    2016-09-01

    The recent attacks with the nerve agent sarin in Syria reveal the necessity of effective countermeasures against highly toxic organophosphorus compounds. Multiple studies provide evidence that a rapid onset of antidotal therapy might be life-saving but current standard antidotal protocols comprising reactivators and competitive muscarinic antagonists show a limited efficacy for several nerve agents. We here set out to test the newly developed phosphotriesterase (PTE) mutant C23AL by intravenous (i.v.), intramuscular (i.m.; model for autoinjector) and intraosseous (i.o.; model for intraosseous insertion device) application in an in vivo guinea pig model after VX challenge (∼2LD50). C23AL showed a Cmax of 0.63μmolL(-1) after i.o. and i.v. administration of 2mgkg(-1) providing a stable plasma profile up to 180min experimental duration with 0.41 and 0.37μmolL(-1) respectively. The i.m. application of C23AL did not result in detectable plasma levels. All animals challenged with VX and subsequent i.o. or i.v. C23AL therapy survived although an in part substantial inhibition of erythrocyte, brain and diaphragm AChE was detected. Theoretical calculation of the time required to hydrolyze in vivo 96.75% of the toxic VX enantiomer is consistent with previous studies wherein similar activity of plasma containing catalytic scavengers of OPs resulted in non-lethal protection although accompanied with a variable severity of cholinergic symptoms. The relatively low C23AL plasma level observed immediately after its i.v. or i.o load, point at a possible volume of distribution greater than the guinea pig plasma content, and thus underlines the necessity of in vivo experiments in antidote research. In conclusion the i.o. application of PTE is efficient and resulted in comparable plasma levels to the i.v. application at a given time. Thus, i.o. vascular access systems could improve the post-exposure PTE therapy of nerve agent poisoning. PMID:27397758

  12. The Guinea pig as a preclinical model for demonstrating the efficacy and safety of statins.

    PubMed

    Madsen, Cort S; Janovitz, Evan; Zhang, Rongan; Nguyen-Tran, Van; Ryan, Carol S; Yin, Xiaohong; Monshizadegan, Hossain; Chang, Ming; D'Arienzo, Celia; Scheer, Susan; Setters, Robert; Search, Debra; Chen, Xing; Zhuang, Shaobin; Kunselman, Lori; Peters, Andrew; Harrity, Thomas; Apedo, Atsu; Huang, Christine; Cuff, Carolyn A; Kowala, Mark C; Blanar, Michael A; Sun, Chong-Qing; Robl, Jeffrey A; Stein, Philip D

    2008-02-01

    Statins, because of their excellent efficacy and manageable safety profile, represent a key component in the current armamentarium for the treatment of hypercholesterolemia. Nonetheless, myopathy remains a safety concern for this important drug class. Cerivastatin was withdrawn from the market for myotoxicity safety concerns. BMS-423526 [{(3R,5S)-7-[4-(4-fluorophenyl)-6,7-dihydro-2-(1-methylethyl)-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-3-yl]-3,5-dihydroxy-heptenoic acid} sodium salt], similar to cerivastatin in potency and lipophilicity, was terminated in early clinical development due to an unacceptable myotoxicity profile. In this report, we describe the guinea pig as a model of statin-induced cholesterol lowering and myotoxicity and show that this model can distinguish statins with unacceptable myotoxicity profiles from statins with acceptable safety profiles. In our guinea pig model, both cerivastatin and BMS-423526 induced myotoxicity at doses near the ED(50) for total cholesterol (TC) lowering in plasma. In contrast, wide differences between myotoxic and TC-lowering doses were established for the currently marketed, more hydrophilic statins, pravastatin, rosuvastatin, and atorvastatin. This in vivo model compared favorably to an in vitro model, which used statin inhibition of cholesterol synthesis in rat hepatocytes and L6 myoblasts as surrogates of potential efficacy and toxicity, respectively. Our conclusion is that the guinea pig is a useful preclinical in vivo model for demonstrating whether a statin is likely to have an acceptable therapeutic safety margin. PMID:17986646

  13. Spontaneous Healing of Mycobacterium ulcerans Lesions in the Guinea Pig Model

    PubMed Central

    Silva-Gomes, Rita; Marcq, Elly; Trigo, Gabriela; Gonçalves, Carine M.; Longatto-Filho, Adhemar; Castro, António G.; Pedrosa, Jorge; Fraga, Alexandra G.

    2015-01-01

    Buruli Ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans infection. BU is characterized by a wide range of clinical forms, including non-ulcerative cutaneous lesions that can evolve into severe ulcers if left untreated. Nevertheless, spontaneous healing has been reported to occur, although knowledge on this process is scarce both in naturally infected humans and experimental models of infection. Animal models are useful since they mimic different spectrums of human BU disease and have the potential to elucidate the pathogenic/protective pathway(s) involved in disease/healing. In this time-lapsed study, we characterized the guinea pig, an animal model of resistance to M. ulcerans, focusing on the macroscopic, microbiological and histological evolution throughout the entire experimental infectious process. Subcutaneous infection of guinea pigs with a virulent strain of M. ulcerans led to early localized swelling, which evolved into small well defined ulcers. These macroscopic observations correlated with the presence of necrosis, acute inflammatory infiltrate and an abundant bacterial load. By the end of the infectious process when ulcerative lesions healed, M. ulcerans viability decreased and the subcutaneous tissue organization returned to its normal state after a process of continuous healing characterized by tissue granulation and reepethelialization. In conclusion, we show that the experimental M. ulcerans infection of the guinea pig mimics the process of spontaneous healing described in BU patients, displaying the potential to uncover correlates of protection against BU, which can ultimately contribute to the development of new prophylactic and therapeutic strategies. PMID:26625302

  14. Captain America, Tuskegee, Belmont, and Righteous Guinea Pigs: Considering Scientific Ethics through Official and Subaltern Perspectives

    NASA Astrophysics Data System (ADS)

    Weinstein, Matthew

    2008-09-01

    With an eye towards a potential scientific ethics curriculum, this paper examines four contrasting discourses regarding the ethics of using human subjects in science. The first two represent official statements regarding ethics. These include the U.S.’s National Science Education Standards, that identify ethics with a professional code, and the Belmont Report, that conceptualizes ethics in three principles to guide research oversight boards. Contrasting this view of ethics as decorum and practice in line with a priori principles is the conception of ethics from unofficial sources representing populations who have been human subjects. The first counter-discourse examined comes from Guinea Pig Zero, an underground magazine for professional human subjects. Here ethics emerges as a question of politics over principle. The good behavior of the doctors and researchers is an effect of the politics and agency of the communities that supply science with subjects. The second counter-discourse is a comic book called Truth, which tells the story of Black soldiers who were used as guinea pigs in World War II. Ethics is both more political and more uncertain in this narrative. Science is portrayed as complicit with the racism of NAZI Germany; at the same time, and in contrast to the professional guinea pigs, neither agency nor politics are presented as effective tools for forcing the ethical conduct of the scientific establishment. The conclusion examines the value of presenting all of these views of scientific ethics in science education.

  15. Drinking preferences in chinchillas (Chinchilla laniger), degus (Octodon degu) and guinea pigs (Cavia porcellus).

    PubMed

    Hagen, K; Clauss, M; Hatt, J-M

    2014-10-01

    Chinchilla (Chinchilla laniger), degus (Octodon degus) and guinea pigs (Cavia porcellus) are South American rodents living in a semi-arid habitat with varying, species-specific adaptations to water deprivation. Nonetheless, several diseases have been linked to insufficient water intake when these species are kept as pets, such as urolithiasis or obstipation. This study evaluated preferences for drinking systems. Six animals of each species were given a choice between an open dish and a nipple drinker. Food intake and water intake were measured daily for 13 days. Chinchillas in this study had significantly lower water intakes than the other two species, indicating particular species-specific adaptations to aridity. All chinchillas favoured open dishes, whereas the degus and guinea pigs had variable individual preferences. Water intake of chinchillas was similar or higher in this study than in previous studies where nipple drinkers were used. The results indicate that degus and guinea pigs can meet their drinking water needs with nipple drinkers; for chinchillas, other drinking systems may be more adequate. PMID:24405017

  16. Comparison of effects of glass fibre and glass powder on guinea-pig lungs

    PubMed Central

    Botham, Susan K.; Holt, P. F.

    1973-01-01

    Botham, Susan K., and Holt, P. F. (1973).British Journal of Industrial Medicine,30, 232-236. Comparison of effects of glass fibre and glass powder on guinea-pig lungs. Following 24 hours inhalation by guinea-pigs of powdered glass dust, the pulmonary effects over the succeeding month differed from those previously observed to follow inhalation of glass fibre in that (1) fewer erythrocytes escaped from the capillaries, (2) very few giant cells were produced, (3) erythrocytes and intracellular glass particles were cleared more readily because junctions between respiratory and terminal bronchioles were not blocked by giant cells, (4) intracellular granules containing Perls-positive material did not appreciably increase in number or intensity of staining during the month, and (5) particles were not coated with Perls-positive material during the time that pseudo-asbestos bodies would be formed from glass fibres. The difference between the effects of chemically similar glass powder and fibre during a month in a guinea-pig lung is considered to be due to the morphology of the inhaled particle. Images PMID:4124978

  17. Use of the Albino Guinea-pig to Detect the Skin-sensitizing Ability of Chemicals

    PubMed Central

    Stevens, M. A.

    1967-01-01

    The guinea-pig has been used for over 20 years to demonstrate skin-sensitizing ability in chemical compounds. Correlation between the results of workers in this field is difficult because of the wide range of conditions under which tests for sensitizing potential have been performed. This has made difficult any attempt to compare the relative abilities of various chemical compounds to produce skin sensitization. In a routine test for skin-sensitizing potential, solutions of suspected sensitizing substance have been applied over three days to the ears of guinea-pigs, and the flanks have been challenged one week later with a range of concentrations of suspected sensitizing substance. The erythematous reaction produced 24 hours after challenge was rated and compared with that in unsensitized controls. Various alternative methods of skin testing have been compared with this ear-flank test. The ear-flank test gives good, reproducible results with many classes of chemical compound, including types of compound not previously described as giving rise to sensitization in the guinea-pig or in man, and including some compounds which are known to have carcinogenic potential. It is also demonstrated that sensitizing potential is found more frequently among aromatic (aryl) than aliphatic (alkyl) compounds. Particularly strong sensitization reactions are produced by certain aryl halides, aryl isocyanates, aryl hydrazines, N-nitroso compounds, and aromatic nitroso-compounds. An attempt is made to relate the results of animal tests to reported cases of human skin sensitization. PMID:6028714

  18. Blocking Dopaminergic Signaling Soon after Learning Impairs Memory Consolidation in Guinea Pigs

    PubMed Central

    Lee, Kiera-Nicole; Chirwa, Sanika

    2015-01-01

    Formation of episodic memories (i.e. remembered experiences) requires a process called consolidation which involves communication between the neocortex and hippocampus. However, the neuromodulatory mechanisms underlying this neocortico-hippocampal communication are poorly understood. Here, we examined the involvement of dopamine D1 receptors (D1R) and D2 receptors (D2R) mediated signaling on memory consolidation using the Novel Object Recognition (NOR) test. We conducted the tests in male Hartley guinea pigs and cognitive behaviors were assessed in customized Phenotyper home cages utilizing Ethovision XT software from Noldus enabled for the 3-point detection system (nose, center of the body, and rear). We found that acute intraperitoneal injections of either 0.25 mg/kg SCH23390 to block D1Rs or 1.0 mg/kg sulpiride to block D2Rs soon after acquisition (which involved familiarization to two similar objects) attenuated subsequent discrimination for novel objects when tested after 5-hours in the NOR test. By contrast guinea pigs treated with saline showed robust discrimination for novel objects indicating normal operational processes undergirding memory consolidation. The data suggests that involvement of dopaminergic signaling is a key post-acquisition factor in modulating memory consolidation in guinea pigs. PMID:26275140

  19. Effect of intratympanic application of efinaconazole 10 % solution in the guinea pig.

    PubMed

    Arakawa, Kazuya; Nomura, Kazuhiro; Oshima, Hidetoshi; Honkura, Yohei; Ikeda, Ryoukichi; Hidaka, Hiroshi; Kawase, Tetsuaki; Katori, Yukio

    2016-05-01

    Efinaconazole 10 % solution is a new triazole antifungal agent developed for the topical treatment of fungal infections of the nails. The current study examined the effect of intratympanic application of efinaconazole 10 % solution in the guinea pig ear. Sixteen male Hartley guinea pigs (weight 501-620 g) were divided into 3 groups to be treated with efinaconazole 10 % solution, gentamicin (50 mg/mL), or saline solution. Topical solutions of 0.2 mL were applied through a small hole made at the tympanic bulla once daily for 7 consecutive days. Post-intervention auditory brainstem responses were obtained 7 days after the last treatment. The extent of middle ear damage and hair cell loss was investigated. The efinaconazole- and gentamicin-treated groups showed severe deterioration in auditory brainstem response threshold. Middle ear examination revealed extensive changes in the efinaconazole-treated group and medium changes in the gentamicin-treated group. Hair cells were preserved in the efinaconazole- and saline-treated groups, but severe damage was seen in the gentamicin group. In conclusion, efinaconazole 10 % solution applied intratympanically to the guinea pig middle ear caused significant middle ear inflammation and hearing impairment. PMID:26024697

  20. Primary structure of the cytosolic beta-glucosidase of guinea pig liver.

    PubMed Central

    Hays, W S; Jenison, S A; Yamada, T; Pastuszyn, A; Glew, R H

    1996-01-01

    The cytosolic beta-glucosidase (EC 3.2.1.21) present in the livers of mammalian species is distinguished by its broad specificity for sugars and its preference for hydrophobic aglycones. We purified the cytosolic beta-glucosidase from guinea pig liver and sequenced 142 amino acid residues contained within 12 trypsin digest fragments. Using degenerate oligonucleotide primers deduced from the peptide sequences, a 622 bp cytosolic beta-glucosidase cDNA was amplified by reverse-transcriptase PCR, using total guinea pig liver RNA as template. The 'rapid amplification of cDNA ends (RACE)' method [Frohman (1993) Methods Enzymol. 218, 340-356] was used to synthesize the remaining segments of the full-length cDNA. The complete cDNA contained 1671 nucleotides with an open reading frame coding for 469 amino acid residues. The amino acid sequence deduced from the cDNA sequence included the amino acid sequences of all 12 trypsin digest fragments derived from the purified enzyme. Amino acid sequence analysis indicates that the guinea pig liver cytosolic beta-glucosidase is a Family 1 beta-glycosidase and that it is most closely related to mammalian lactase-phlorizin hydrolase. These results suggest that the cytosolic beta-glucosidase and lactase-phlorizin hydrolase diverged from a common evolutionary precursor. PMID:8920987

  1. Spontaneous Healing of Mycobacterium ulcerans Lesions in the Guinea Pig Model.

    PubMed

    Silva-Gomes, Rita; Marcq, Elly; Trigo, Gabriela; Gonçalves, Carine M; Longatto-Filho, Adhemar; Castro, António G; Pedrosa, Jorge; Fraga, Alexandra G

    2015-12-01

    Buruli Ulcer (BU) is a necrotizing skin disease caused by Mycobacterium ulcerans infection. BU is characterized by a wide range of clinical forms, including non-ulcerative cutaneous lesions that can evolve into severe ulcers if left untreated. Nevertheless, spontaneous healing has been reported to occur, although knowledge on this process is scarce both in naturally infected humans and experimental models of infection. Animal models are useful since they mimic different spectrums of human BU disease and have the potential to elucidate the pathogenic/protective pathway(s) involved in disease/healing. In this time-lapsed study, we characterized the guinea pig, an animal model of resistance to M. ulcerans, focusing on the macroscopic, microbiological and histological evolution throughout the entire experimental infectious process. Subcutaneous infection of guinea pigs with a virulent strain of M. ulcerans led to early localized swelling, which evolved into small well defined ulcers. These macroscopic observations correlated with the presence of necrosis, acute inflammatory infiltrate and an abundant bacterial load. By the end of the infectious process when ulcerative lesions healed, M. ulcerans viability decreased and the subcutaneous tissue organization returned to its normal state after a process of continuous healing characterized by tissue granulation and reepethelialization. In conclusion, we show that the experimental M. ulcerans infection of the guinea pig mimics the process of spontaneous healing described in BU patients, displaying the potential to uncover correlates of protection against BU, which can ultimately contribute to the development of new prophylactic and therapeutic strategies. PMID:26625302

  2. Production of experimental ulcerative colitis in gnotobiotic guinea pigs with simplified microflora.

    PubMed Central

    Onderdonk, A B; Franklin, M L; Cisneros, R L

    1981-01-01

    Conventional guinea pigs provided with a solution of 5% (wt/vol) degraded carrageenan as the sole source of oral fluids developed ulcerations of their ceca and large intestines within 30 days. Similar lesions were not detected in germfree guinea pigs treated in an identical manner, suggesting that an intestinal microflora was necessary for development of intestinal lesions. To simplify the bacterial flora required for production of cecal ulcerations, 10 pools consisting of 10 bacterial strains each were isolated from the cecal microflora of carrageenan-treated animals. Groups of germfree guinea pigs were associated with 2 of the 10 pools by orogastric intubation and observed for development of disease. One-half of each group was treated with carrageenan. The two bacterial pools were characterized by the presence of cytopathic effects for WI-38 and Vero cells, increased chemotactic activity, and increased concentrations of long-chain fatty acids. The results indicated that animals associated with those two pools developed cecal ulcerations during carrageenan treatment. Preliminary results also indicated that cecal ulcerations developed in germfree animals mono-associated with a strain of Bacteroides vulgatus isolated from one of the pools, regardless of whether carrageenan was administered, suggesting a bacterial involvement in disease development in the absence of carrageenan treatment. PMID:7216487

  3. Pulmonary dendritic cell distribution and prevalence in guinea pig airways: effect of ovalbumin sensitization and challenge.

    PubMed

    Lawrence, T E; Millecchia, L L; Frazer, D G; Fedan, J S

    1997-08-01

    We characterized the localization and prevalence of dendritic cells (DC) in guinea pig airways before and after s.c. sensitization and aerosol challenge with ovalbumin (OVA). DC, eosinophils, macrophages, T cells and B cells in lung and trachea were identified and quantified in frozen sections using monoclonal antibodies and computer-assisted image analysis. Airway reactivity of conscious animals to inhaled methacholine was examined. In unsensitized animals, DC were localized primarily within the lamina propria of the trachea and bronchi, in the submucosa of the trachea and in the adventitia of the bronchi. In contrast to reported studies on rats, few DC were noted in the epithelium. After OVA challenge, sensitized animals demonstrated an early obstructive response and a late-phase response that was well developed by 18 hr. Challenge with OVA increased DC prevalence in the lamina propria and submucosa of the trachea and in the lamina propria and adventitia of the bronchi. There was widespread eosinophilia throughout the airways, but no changes in B cells or T cells were evident. Macrophages were increased in the epithelium of both OVA-treated and saline-treated animals. At 18 hr after challenge, sensitized guinea pigs but not saline-treated controls were hyperreactive to inhaled methacholine. Except for macrophages, none of these effects were observed after saline treatment. Our findings indicate that inflammation in the airways of OVA-sensitized guinea pigs involves infiltration of DC, which is seen at the time animals are hyperreactive to inhaled methacholine. PMID:9262368

  4. A randomized controlled trial of trypsin to treat brown recluse spider bites in Guinea pigs.

    PubMed

    Cabaniss, Wyman W; Bush, Sean; O'Rourke, Dorcas P; Fletcher, Paul F; Brewer, Kori L; Lertpiriyapong, Kvin; Punja, Mohan; Miller, Susan N; Meggs, William J

    2014-09-01

    Brown recluse spider bites result in necrotic skin lesions for which there is no known antidote. Since venom toxins are proteins, a proteolytic enzyme like trypsin might be effective in reducing toxicity. The aim of this study was to conduct a randomized controlled trial of trypsin to treat brown recluse spider bites in guinea pigs. Subjects were 18 female guinea pigs. Anesthesia for injections was inhaled isoflurane. Analgesia was 0.05 mg/kg of buprenorphine twice a day as needed. Intervention was intradermal injection of 30 μg of brown recluse venom (Spider Pharm, Yarnell, AZ). Immediately after envenomation, subjects were randomized to two groups of nine: trypsin 10 μg in 1 mL normal saline and 1 mL of normal saline. The primary outcome was lesion area over a 10-day time period. Statistical analysis was performed with repeated measures ANOVA. Mean lesion area was smaller but not statistically different in the placebo group. Maximum lesion size occurred at day 4 in both groups, when lesion area was 76.1 ± 108.2 mm(2) in the placebo group and 149.7 ± 127.3 mm(2) in the treatment group. P value was 0.15 for placebo vs. treatment. This study did not establish a role for trypsin as a treatment for brown recluse spider bites in a guinea pig model. PMID:24849803

  5. A unique localization of mechanoreceptors in the periodontal tissue of guinea pig teeth.

    PubMed

    Jayawardena, Chantha K; Takahashi, Nobuyuki; Takano, Yoshiro

    2002-08-01

    This study describes the unique distribution of Ruffini endings (RE) in the periodontal tissues of the guinea pig teeth with special references to their presence in the enamel-related aspects of the continuously growing incisors and molars. In guinea pig incisors, immunohistochemistry for PGP 9.5 and glia specific S-100 protein revealed a condensed distribution of well-developed RE in the bone-related part of the lingual periodontal ligament as has been reported in many other rodents. In most cases, some RE-like nerve elements characterized by dendritic ramification and rounded terminal Schwann cells were found to be located in the labial, enamel-related regions, where no periodontal ligament-like fiber arrangement was established. In the molar periodontal ligament, well-developed RE-like nerve elements were also distributed in the enamel-related part, but in intimate relation to thick periodontal fiber bundles inserted in the cementum pearls grown on the enamel surface. In some cases, few RE were located in the apical region of the alveolar socket, where no periodontal fiber bundles could be identified. Our data provide the first morphological evidence of the presence of RE-like nerve elements in the enamel-related, fibrous connective tissue of continuously erupting rodent incisors. These data indicate that RE in guinea pig periodontal tissues have variable spatial correlation to the surrounding fibers, implicating their diverse mechanoreceptive properties depending on the anatomical location. PMID:12389662

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

    PubMed

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

    2010-01-01

    A 21-year-old male presented at the emergency room with jaundice, itching, dry cough, malaise and weight loss of 10 kg during the preceding four weeks. Eighteen months earlier, the patient had suffered an automobile accident leading to polytrauma. Serological markers for viral or other causes of hepatitis were absent. For suspected secondary sclerosing cholangitis, ultrasound and ERCP were performed but failed to reveal pathological findings. A liver biopsy showed cholestatic liver disease without signs of portal field-associated hepatitis. Hepato-biliary scintigraphy demonstrated hepatocellular dysfunction. The patient finally mentioned his guinea pig farm with around 50 animals, 20 of which had recently died for unknown reasons. The patient and three of his guinea pigs were subsequently tested for serological evidence of leptospirosis. IgG and IgM antibodies reacting with Leptospira interrogans were detected in the patient's serum, and all 3 guinea pigs were serologically positive for serovar Bratislava. Bacterial culture was not successful, and also PCR tests remained negative. The clinical symptoms quickly resolved after the initiation of antibiotic therapy with amoxicillin. PMID:20072994

  7. Twenty-four-Hour Measurement of Intraocular Pressure in Guinea Pigs (Cavia porcellus).

    PubMed

    Ansari-Mood, Maneli; Mehdi-Rajaei, Seyed; Sadjadi, Reza; Selk-Ghaffari, Masoud; Williams, David L

    2016-01-01

    The objective of this study was to measure intraocular pressure (IOP) in intact, healthy guinea pigs (15 male, 15 female) every 2 h for a 24-h period. First, IOP was measured by using rebound tonometry (RBT). After a 1-min rest period, 0.5% proparacaine ophthalmic solution, a topical anesthetic, was applied to both eyes; 4 min after anesthetic instillation, IOP was measured by using applanation tonometry (APT). The IOP was lower during the light period (0700 to 1900) than during the dark phase (2000 to 0600). The lowest IOP by both RBT and APT (3.68 and 13.37 mm Hg, respectively) occurred at 0700, whereas maximal IOP occurred at 2300 for RBT (8.12 mm Hg) but at 2100 for APT (20.62 mm Hg). No significant differences in IOP between the left and right eyes or between RBT and APT were noted. In addition, daily variations in the IOP of guinea pigs seem to be independent of sex and body weight. The results of this study may be beneficial in the diagnosis and observation of glaucoma in guinea pigs. PMID:26817986

  8. Neuronal release of endogenous dopamine from corpus of guinea pig stomach.

    PubMed

    Shichijo, K; Sakurai-Yamashita, Y; Sekine, I; Taniyama, K

    1997-11-01

    Neuronal release of endogenous dopamine was identified in mucosa-free preparations (muscle layer including intramural plexus) from guinea pig stomach corpus by measuring tissue dopamine content and dopamine release and by immunohistochemical methods using a dopamine antiserum. Dopamine content in mucosa-free preparations of guinea pig gastric corpus was one-tenth of norepinephrine content. Electrical transmural stimulation of mucosa-free preparations of gastric corpus increased the release of endogenous dopamine in a frequency-dependent (3-20 Hz) manner. The stimulated release of dopamine was prevented by either removal of external Ca2+ or treatment with tetrodotoxin. Dopamine-immunopositive nerve fibers surrounding choline acetyltransferase-immunopositive ganglion cells were seen in the myenteric plexus of whole mount preparations of gastric corpus even after bilateral transection of the splanchnic nerve proximal to the junction with the vagal nerve (section of nerves between the celiac ganglion and stomach). Domperidone and sulpiride potentiated the stimulated release of acetylcholine and reversed the dopamine-induced inhibition of acetylcholine release from mucosa-free preparations. These results indicate that dopamine is physiologically released from neurons and from possible dopaminergic nerve terminals and regulates cholinergic neuronal activity in the corpus of guinea pig stomach. PMID:9374701

  9. Neurogenic airway inflammation induced by repeated intra-esophageal instillation of HCl in guinea pigs.

    PubMed

    Liu, Chunli; Chen, Ruchong; Luo, Wei; Lai, Kefang; Zhong, Nanshan

    2013-04-01

    This study was conducted to investigate if repeated intra-esophageal acid administrations may induce neurogenic inflammation in the airways and nodose ganglion in a guinea pig model. Guinea pigs were sedated and perfused with 0.1 N HCl in the distal esophagus via a nasoesophageal catheter for 14 consecutive days. Substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and calcitonin gene-related peptide concentration were measured by ELISA or radioimmunoassay. Neuropeptide expression in the airways and nodose ganglion was detected by immunohistochemistry and assessed semi-quantitatively. Inflammation was found in the trachea and bronchi. There was a threefold increase in substance P concentration in the trachea, main bronchi, and lung homogenate and a twofold increase in NKA and NKB concentration in the main bronchi, lung homogenate, and bronchial alveolus lavage fluid, respectively. The SP and NKA expressions in the airways and nodose ganglion were also significantly increased. Chronic intra-esophageal acid instillation induces significant neurogenic inflammation in the airways and nodose ganglion in the vagus nerve in guinea pigs. PMID:23225164

  10. Effects of novel bile salts on cholesterol metabolism in rats and guinea-pigs.

    PubMed

    Fears, R; Brown, R; Ferres, H; Grenier, F; Tyrrell, A W

    1990-11-01

    Novel bile salts (quaternary ammonium conjugates) inhibited cholic acid binding and transport in everted ileal sacs in vitro. The cationic piperazine conjugate of lithocholic acid (di-iodide salt, compound 8, BRL 39924A) appeared most active, inhibiting binding by 29% and transport by 59% in guinea-pig ileum (200 microM). BRL 39924A also inhibited taurocholate uptake into guinea-pig ileal sacs and cholate uptake into rat ileal sacs and was selected for further study in vivo. In hyperlipidaemic rats, BRL 39924A significantly raised cholesterol 7 alpha-hydroxylase activity and decreased hepatic accumulation of exogenous cholic acid. HDL cholesterol concentration in the serum increased and the level of VLDL plus LDL cholesterol decreased. In hyperlipidaemic guinea-pigs. BRL 39924A lowered serum total cholesterol and triglyceride levels. Although metabolic changes were less than those achieved with the bile acid sequestrant, cholestyramine, the doses of BRL 39924A used were much lower (100-500 mg/kg body wt). Selective inhibition of receptor mediated bile acid uptake may be associated with local side-effects but these novel bile salts are useful pharmacological tools to examine the effects of receptor blockade on lipoprotein metabolism. PMID:2242032

  11. Chemoinvestigatory and sexual behavior of male guinea pigs following vomeronasal organ removal.

    PubMed

    Beauchamp, G K; Martin, I G; Wysocki, C J; Wellington, J L

    1982-08-01

    The vomeronasal organs of male guinea pigs were removed (VNX; n = 10) or males experienced sham surgery (Sham; n = 10). Subsequently a battery of chemosensory tests of investigatory responsiveness to conspecific urine was conducted. Additionally, male subjects were paired with female conspecifics for short and long periods and social and sexual behaviors were monitored. VNX males exhibited a depression in urine investigation and this depression became more profound following repeated testing and/or the passage of time. By 6.3 months following surgery, investigatory responsiveness to urine was practically eliminated. Maintenance of responsiveness to urine odors may require reinforcing input through the accessory olfactory system. In contrast to these effects on responsiveness to odors, VNX and Sham males were indistinguishable in their social and sexual behavior. These data indicate that male guinea pigs without a VNO: (1) Exhibit a depression of investigation of urine odors which is time dependent and which may involve an extinction-like process; (2) continue to discriminate classes of urine (e.g., urine from male vs urine from female conspecifics); and (3) exhibit normal sexual behavior. The vomeronasal organ in the male domestic guinea pig is apparently critical for the maintenance of normal responsiveness to sex odors but, in its absence, other sensory systems are capable of maintaining normal sexual behavior under conditions of laboratory testing. PMID:7146138

  12. Endogenous leukotriene D4 formation during anaphylactic shock in the guinea pig.

    PubMed Central

    Keppler, A; Orning, L; Bernström, K; Hammarström, S

    1987-01-01

    Experiments on the metabolism and excretion of i.v. administered selectively labeled [3H8]leukotriene C4 in bile duct-cannulated guinea pigs indicated predominantly biliary excretion of tritium. The major leukotriene metabolite in bile was identified as leukotriene D4. By monitoring leukotriene excretion radioimmunochromatographically, it was shown that guinea pigs suffering from anaphylactic shock produce leukotriene D4 endogenously. Immunological challenge of animals sensitized to ovalbumin was accompanied by an increase of biliary leukotriene D4 concentrations from 10 +/- 1 to 86 +/- 10 nM (mean +/- SEM, n = 5, P less than 0.001). When considering that bile flow was decreased to about half after challenge, the excretion rate of leukotriene D4 in bile increased from 0.88 +/- 0.16 before to 3.18 +/- 0.38 pmol X min-1 X kg-1 after challenge (mean +/- SEM, n = 5, P less than 0.002). It is concluded that systemic anaphylaxis in the guinea pig is associated with endogenous generation of leukotriene C4 (up to 1 nmol/kg during a 30-min period after the challenge. PMID:3039514

  13. Instituting Dark-Colored Cover to Improve Central Space Use Within Guinea Pig Enclosure.

    PubMed

    Byrd, Charles P; Winnicker, Christina; Gaskill, Brianna N

    2016-01-01

    Domestic guinea pigs (Cavia aperea f. porcellus) in laboratories have been shown to actively avoid the centers of their cages. This experiment tested a novel, dark-colored "shader" placed over the central portion of a cage. Based on the observed behavior of wild guinea pig species, it was hypothesized that utilization of the central portion of the cage would increase when the shader was present. Eleven male and 11 female albino, 3-week-old Hartley guinea pigs (Crl:HA) experienced the control and treatment conditions in a crossover study design. They spent more time in central cage sections when the shader was present and spent more time in and around the food hopper when the shader was absent (p < .001). Differences between sexes included increased inactivity in males versus females (p < .05) and a difference in time spent in a corner section of the cage (p < .001), likely associated with location in the room. We concluded that the presence of a shader increased utilization of cage space, which appeared to provide a similar increase in space utilization as structural enrichments. PMID:27223319

  14. Twenty-four–Hour Measurement of Intraocular Pressure in Guinea Pigs (Cavia porcellus)

    PubMed Central

    Ansari-Mood, Maneli; Mehdi-Rajaei, Seyed; Sadjadi, Reza; Selk-Ghaffari, Masoud; Williams, David L

    2016-01-01

    The objective of this study was to measure intraocular pressure (IOP) in intact, healthy guinea pigs (15 male, 15 female) every 2 h for a 24-h period. First, IOP was measured by using rebound tonometry (RBT). After a 1-min rest period, 0.5% proparacaine ophthalmic solution, a topical anesthetic, was applied to both eyes; 4 min after anesthetic instillation, IOP was measured by using applanation tonometry (APT). The IOP was lower during the light period (0700 to 1900) than during the dark phase (2000 to 0600). The lowest IOP by both RBT and APT (3.68 and 13.37 mm Hg, respectively) occurred at 0700, whereas maximal IOP occurred at 2300 for RBT (8.12 mm Hg) but at 2100 for APT (20.62 mm Hg). No significant differences in IOP between the left and right eyes or between RBT and APT were noted. In addition, daily variations in the IOP of guinea pigs seem to be independent of sex and body weight. The results of this study may be beneficial in the diagnosis and observation of glaucoma in guinea pigs. PMID:26817986

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

    SciTech Connect

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

    1987-09-01

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

  16. Macrophage TNF-α mediates parathion-induced airway hyperreactivity in guinea pigs

    PubMed Central

    Bruun, Donald A.; Jacoby, David B.; van Rooijen, Nico; Lein, Pamela J.; Fryer, Allison D.

    2013-01-01

    Organophosphorus pesticides (OPs) are implicated in human asthma. We previously demonstrated that, at concentrations that do not inhibit acetylcholinesterase activity, the OP parathion causes airway hyperreactivity in guinea pigs as a result of functional loss of inhibitory M2 muscarinic receptors on parasympathetic nerves. Because macrophages are associated with asthma, we investigated whether macrophages mediate parathion-induced M2 receptor dysfunction and airway hyperreactivity. Airway physiology was measured in guinea pigs 24 h after a subcutaneous injection of parathion. Pretreatment with liposome-encapsulated clodronate induced alveolar macrophage apoptosis and prevented parathion-induced airway hyperreactivity in response to electrical stimulation of the vagus nerves. As determined by qPCR, TNF-α and IL-1β mRNA levels were increased in alveolar macrophages isolated from parathion-treated guinea pigs. Parathion treatment of alveolar macrophages ex vivo did not significantly increase IL-1β and TNF-α mRNA but did significantly increase TNF-α protein release. Consistent with these data, pretreatment with the TNF-α inhibitor etanercept but not the IL-1β receptor inhibitor anakinra prevented parathion-induced airway hyperreactivity and protected M2 receptor function. These data suggest a novel mechanism of OP-induced airway hyperreactivity in which low-level parathion activates macrophages to release TNF-α-causing M2 receptor dysfunction and airway hyperreactivity. These observations have important implications regarding therapeutic approaches for treating respiratory disease associated with OP exposures. PMID:23377347

  17. A search for functional histamine H4 receptors in the human, guinea pig and mouse brain.

    PubMed

    Feliszek, Monika; Speckmann, Valerie; Schacht, Daniel; von Lehe, Marec; Stark, Holger; Schlicker, Eberhard

    2015-01-01

    Histamine H4 receptors are expressed in immune cells, but their potential role in the brain is less clear. Although H4 transcripts have been identified in human and rat brain, the presence of H4 receptors on the protein level has so far not been proven since appropriate antibodies fulfilling the strict criteria for G protein-coupled receptors are missing. Here, we searched for functional H4 receptors in human, guinea pig and mouse cortex. We studied whether H4 receptor activation is associated with increased GTPγS binding and reduced noradrenaline release. The latter two effects have been previously shown for H3 receptors, which, like the H4 receptors, are coupled to G i/o protein. G protein activation was studied using (35)S-GTPγS binding in cortical membranes. The electrically induced (3)H-noradrenaline release was determined in superfused cortical slices. The H4 agonist 4-methylhistamine failed to affect (35)S-GTPγS binding and/or noradrenaline release in human, guinea pig and mouse cortex although an H 3 receptor-mediated increase in (35)S-GTPγS binding and inhibition of noradrenaline release occurred in parallel experiments. In conclusion, functional H4 receptors increasing (35)S-GTPγS binding and/or decreasing noradrenaline release are not found in human, guinea pig and mouse cortex. PMID:25300787

  18. Multipotent stromal cells for autologous cell therapy approaches in the guinea pig model.

    PubMed

    Frölich, Katrin; Scherzed, Agmal; Mlynski, Robert; Technau, Antje; Hagen, Rudolf; Kleinsasser, Norbert; Radeloff, Andreas

    2011-01-01

    Multipotent stromal cells have become of increasing interest due to their potential to provide therapeutic approaches for autologous tissue repair. However, these cells are not well defined in the guinea pig, which represents an important model in hearing research. Adipose-tissue-derived stem cells (ADSC) and bone-marrow-derived stem cells (BMSC) were isolated from different donor sites, and growth curves were generated to judge the proliferation potential. Adipogenic, chondrogenic and osteogenic differentiation was induced and confirmed histologically. Finally, the capability of guinea pig ADSC to differentiate into neuron-like cells was investigated. With regard to the expansion potential, total cell number and doubling time, ADSC from the neck were the most suitable cells of the tested donor sites. Both ADSC and BMSC showed nearly identical behaviour and ability to undergo multilineage differentiation. Thus, we identified ADSC from the neck as a promising cell source for autologous cell-based approaches in hearing research using the guinea pig model. PMID:20975314

  19. Effect of ultrasound on transdermal drug delivery to rats and guinea pigs.

    PubMed Central

    Levy, D; Kost, J; Meshulam, Y; Langer, R

    1989-01-01

    The effect of therapeutic range ultrasound (1 MHz) on skin permeation of D-mannitol, a highly polar sugar alcohol, inulin, a high molecular weight polysaccharide and physostigmine, a lipophilic anticholinesterase drug was studied in rats and guinea pigs. D-Mannitol and inulin are totally and rapidly excreted, once they have penetrated through the skin into the blood stream, permitting direct in vivo monitoring. For evaluating skin penetration of physostigmine the decrease of whole blood cholinesterase was measured. Ultrasound nearly completely eliminated the lag time usually associated with transdermal delivery of drugs. 3-5 min of ultrasound irradiation (1.5 W/cm2 continuous wave or 3 W/cm2 pulsed wave) increased the transdermal permeation of inulin and mannitol in rats by 5-20-fold within 1-2 h following ultrasound application. Ultrasound treatment also significantly increased (P less than 0.05) the inhibition of cholinesterase during the first hour after application in both physostigmine treated rats and guinea pigs: while in control guinea pigs no significant inhibition of cholinesterase could be detected during the first 2 h after application of physostigmine, the ultrasound treated group showed a 15 +/- 5% (mean +/- SEM) decrease in blood cholinesterase 1 h after ultrasound application. For physostigmine-treated rats the level of cholinesterase inhibition 1 h after ultrasound application was 53 +/- 5% in the ultrasound-treated group and 35 +/- 5% in the controls. PMID:2498396

  20. Anatomical study of the arterial blood supply to the thoracolumbar spinal cord in guinea pig.

    PubMed

    Mazensky, David; Danko, Jan; Petrovova, Eva; Supuka, Peter; Supukova, Anna

    2015-09-01

    Guinea pigs are frequently used as experimental models in studies of ischemic spinal cord injury. The aim of this study was to describe the arterial blood supply to the thoracolumbar spinal cord in 20 adult English self guinea pigs using the corrosion and dissection techniques. The dorsal intercostal arteries arising from the dorsal surface of the thoracic aorta were found as follows: in eight pairs in 70% of cases, in seven pairs in 20% of cases and in nine pairs in 10% of cases. Paired lumbar arteries were present as seven pairs in all the cases. The occurrence of the ventral and dorsal branches of the spinal rami observed in the thoracic and lumbar region was higher on the left than on the right. The artery of Adamkiewicz was present in 60% of cases as a single vessel and in 40% of cases as a double vessel. On the dorsal surface of the spinal cord, we found two dorsal spinal arteries in 60% of cases and three in 40% of cases. The presence of the artery of Adamkiewicz and nearly regular segmental blood supplying the thoracolumbar part of the spinal cord in all our studied animals is the reason for using guinea pigs as a simple model of ischemic damage to the thoracolumbar part of the spinal cord. PMID:24966109

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

    PubMed

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

    2016-01-01

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

  2. U-60,257 inhibits O3-induced bronchial hyperreactivity in the guinea pig

    SciTech Connect

    Murlas, C.; Lee, H.K.

    1985-10-01

    We studied the effects on ozone-induced airway hyperreactivity of U-60,257, a pyrroloprostacyclin shown to inhibit leukotriene C/D biosynthesis in vitro. A group of 5 guinea pigs were pretreated with U-60,257 (5 mg/kg IV), and studied before and 30 min after a 15 min exposure to 3.0 ppm ozone. These animals were compared to a similarly exposed group that was untreated (n = 10). Reactivity was determined by measuring specific airway resistance (SRaw) upon intravenous acetylcholine infusion in unanesthetized, spontaneously breathing animals. Prior to ozone exposure, we found that U-60,257 treatment did not affect either SRaw or muscarinic reactivity. After exposure to 3.0 ppm, all untreated guinea pigs showed substantial muscarinic hyperreactivity. In contrast, no significant change in SRaw or muscarinic reactivity occurred after ozone in any animal pretreated with U-60,257. We conclude that ozone-induced bronchial hyperreactivity in the guinea pig rapidly develops after a brief, high level exposure. This effect may be mediated, in part, by leukotrienes generated upon ozone exposure.

  3. Endogenous leukotriene D/sub 4/ formation during anaphylactic shock in the guinea pig

    SciTech Connect

    Keppler, A.; Oerning, L.; Bernstroem, K.; Hammarstroem, S.

    1987-08-01

    Experiments on the metabolism and excretion of i.v. administered selectively labeled (/sup 3/H/sub 8/)leukotriene C/sub 4/ in bile duct-cannulated guinea pigs indicated predominantly biliary excretion of tritium. The major leukotriene metabolite in bile was identified as leukotriene D/sub 4/. By monitoring leukotriene excretion radioimmunochromatographically, it was shown that guinea pigs suffering from anaphylactic shock produce leukotriene D/sub 4/ endogenously. Immunological challenge of animals sensitized to ovalbumin was accompanied by an increase of biliary leukotriene D/sub 4/ concentrations from 10 +/- 1 to 86 +/- 10 nM. When considering that bile flow was decreased to about half after challenge, the excretion rate of leukotriene D/sub 4/ in bile increased from 0.88 +/- 0.16 before 3.18 +/- 0.38 pmol x min/sup -1/ x kg/sup -1/ after challenge. It is concluded that systemic anaphylaxis in the guinea pig is associated with endogenous generation of leukotriene C/sub 4/.

  4. Prostaglandins in the perilymph of guinea pig with type II collagen induced ear diseases

    SciTech Connect

    Takeda, T.; Chiang, T.; Kitano, H.; Sudo, N.; Kim, S.Y.; Ha, S.; Woo, V.; Wolf, B.; Floyd, R.; Yoo, T.J.

    1986-03-01

    The authors have studied the prostaglandins (PGs) in the perilymph from guinea pig with type II collagen induced autoimmune ear disease. Hartly guinea pigs were immunized with type II collagen in CFA and auditory brain stem responses (ABR) were measured at 2, 3, 4, and 6 months after initial immunization perilymph was obtained and the levels of PGE2 and 6 keto-PGFl..cap alpha.. were measured by radioimmunoassays. Temporal bones were examined for the histopathologic changes. Immunized guinea pigs showed the evidence of hearing loss by ABR. The temporal bones showed the following changes: spiral ganglia degeneration, mild to moderate degree of degeneration in organ of Corti, infrequent very mild endolymphatic hydrops and labrynthitis. The perilymph from immunized animals contained about 5 times more PGE2 and about 3 times more 6 keto-PGFl..cap alpha.. than control animals. However, between these two groups, there was no difference in the CSF and sera levels of PGE2 and 6 keto-PGFl..cap alpha... Thus, this study suggests that these inflammatory mediators might be involved in the pathogenesis of collagen induced autoimmune inner ear disease.

  5. Role of smooth muscle cell mineralocorticoid receptor in vascular tone.

    PubMed

    Tarjus, Antoine; Belozertseva, Ekaterina; Louis, Huguette; El Moghrabi, Soumaya; Labat, Carlos; Lacolley, Patrick; Jaisser, Frédéric; Galmiche, Guillaume

    2015-08-01

    Identification of the mineralocorticoid receptor (MR) in the vasculature (i.e., endothelial and smooth muscle cells) raised the question of its role in vascular function and blood pressure control. Using a mouse model with conditional inactivation of MR in vascular smooth muscle cell (VSMC) (MR(SMKO)), we have recently shown that the VSMC MR is crucial for aldosterone-salt-induced carotid stiffening. In the present study, we have investigated the specific contribution of the VSMC MR in the regulation of vascular tone in large vessels. In MR(SMKO) mice, contractions induced by potassium chloride and calcium (Ca(2+)) are decreased in the aorta, whereas contraction is normal in response to phenylephrine and caffeine. The difference in response to Ca(2+) suggests that the VSMC-specific deficiency of the MR modifies VSM Ca(2+) signaling but without altering the intracellular Ca(2+) store handling. The relaxation induced by acetylcholine is not affected by the absence of MR. However, the relaxation induced by Ach in the presence of indomethacin and the relaxation induced by sodium nitroprussiate are significantly reduced in MR(SMKO) mice compared to controls. Since endothelial nitric oxide synthase (eNOS) activity is increased in mutant mice, their altered relaxation reflects impairment of the nitric oxide (NO) signaling pathway. In addition to altered NO and Ca(2+) signaling, the activity of myosin light chain and its regulators, myosin light chain kinase (MLCK) and myosin phosphatase (MLCP), is reduced. In conclusion, MR expressed in VSMC is required for NO and Ca(2+) signaling pathways and contractile protein activity leading to an altered contraction/relaxation coupling. PMID:25262754

  6. Effects of histamine on the contractile and electrical activity in isolated lymphatic vessels of the guinea-pig mesentery

    PubMed Central

    Fox, James L R; von der Weid, Pierre-Yves

    2002-01-01

    The effect of histamine on the rate of lymphatic vessel constrictions and lymphatic smooth muscle membrane potential was examined in the guinea-pig mesentery. Histamine (0.01–5 μM) increased the frequency and decreased the amplitude of constrictions in lymphatic vessels under intraluminal perfusion. This response was accompanied by a depolarization of the smooth muscle membrane potential, an increase in the activity of spontaneous transient depolarizations (STDs), the proposed pacemaker for constrictions in these vessels, and an increase in the occurrence of action potentials. Responses to histamine were inhibited by the H1 receptor antagonist pyrilamine (0.2 μM), but unaffected by NO synthase inhibition with NG-nitro L-arginine (L-NOARG, 100 μM) and lysis of the endothelium. In about 50% of the vessels, a decrease in constriction frequency, STD activity and a smooth muscle hyperpolarization were observed in response to dimaprit (10 μM), suggesting the presence of H2 receptors. These vessels had also a significantly lower basal contractile rate. Lymphatic vessel pumping was not affected by R-α-methylhistamine (10–50 μM), ruling out a role for H3 receptor stimulation in the histamine response. The present results suggest a direct action of histamine on the lymphatic smooth muscle via stimulation of H1 (and in some vessels H2) receptors. H1 receptors enhance and H2 receptors slow down lymphatic pumping, the dominant effect being an increased contractile activity. Correlation of these effects with histamine-induced changes in membrane potential and STD activity suggests the involvement of these electrical changes in the initiation of the contractile response. PMID:12163355

  7. [Effects of histamine on the pressure-volume curve of the respiratory system in the guinea pig].

    PubMed

    Clerici, C; Macquin, I; Lhoste, F; Atlan, G; Harf, A

    1985-01-01

    Intravenous infusion of histamine has been shown to constrict smooth muscle of alveolar ducts. In this study, we have assessed the effects of a prolonged infusion of histamine to obtain a steady state response on quasistatic pressure-volume curves (P-V curves) together with the changes in dynamic compliance (Cdyn) and conductance (G) of the respiratory system. Increasing doses of histamine were given in order to obtain the dose-response characteristics of the changes in Cdyn, G and P-V curves. In nine anesthetized guinea-pigs under mechanical ventilation, administration of histamine resulted in a fall in Cdyn and G with a decrease of 50% of initial value approximately for 150 ng X kg-1 X s-1 of histamine. Modifications of the P-V curves were characterized by a decrease in the maximal volume, and an increase in the hysteresis of the P-V loop due to the downward displacement of the inflation limb. With infusion of histamine, there was a large decrease of quasi-static compliance which appeared to account for most of the decrease in dynamic compliance. Such changes in P-V curves can be related both to a closure of alveolar ducts and to an alteration of lung distensibility. Comparison of the dose-response curves for the different parameters indicated that Cdyn and G reflect, at least in part, events occurring in the periphery of the lung. PMID:4041662

  8. Characterization of the guinea pig animal model and subsequent comparison of the behavioral effects of selective dopaminergic drugs and methamphetamine

    PubMed Central

    Lee, Kiera-Nicole; Pellom, Samuel T.; Oliver, Ericka; Chirwa, Sanika

    2014-01-01

    Though not commonly used in behavior tests guinea pigs may offer subtle behavior repertoires that better mimic human activity and warrant study. To test this, 31 Hartley guinea pigs (male, 200–250 g) were evaluated in PhenoTyper cages using the video-tracking EthoVision XT 7.0 software. Results showed that guinea pigs spent more time in the hidden zone (small box in corner of cage) than the food/water zone, or arena zone. Guinea pigs exhibited thigmotaxis (a wall following strategy) and were active throughout the light and dark phases. Eating and drinking occurred throughout the light and dark phases. An injection of 0.25 mg/kg SCH23390, the dopamine D1 receptors (D1R) antagonist, produced significant decreases in time spent in the hidden zone. There were insignificant changes in time spent in the hidden zone for guinea pigs treated with 7.5 mg SKF38393 (D1R agonist), 1.0 mg/kg sulpiride (D2R antagonist), and 1.0 or 10.0 mg/kg methamphetamine. Locomotor activity profiles were unchanged after injections of saline, SKF38393, SCH23390 and sulpiride. By contrast, a single injection or repeated administration for 7 days of low-dose methamphetamine induced transient hyperactivity but this declined to baseline levels over the 22-hour observation period. Guinea pigs treated with high-dose methamphetamine displayed sustained hyperactivity and travelled significantly greater distances over the circadian cycle. Subsequent 7-day treatment with high-dose methamphetamine induced motor sensitization and significant increases in total distances moved relative to single drug injections or saline controls. These results highlight the versatility and unique features of the guinea pig for studying brain-behavior interactions. PMID:24436154

  9. Covalent binding of nitroso-sulfonamides to glutathione S-transferase in guinea pigs with delayed type hypersensitivity.

    PubMed

    Eyanagi, Reiko; Toda, Akihisa; Imoto, Masumi; Uchiyama, Hidemori; Ishii, Yuji; Kuroki, Hiroaki; Kuramoto, Yukako; Soeda, Shinji; Shimeno, Hiroshi

    2012-04-01

    Drug induced allergies are believed to be induced by conjugates consisting of biological macromolecules and active metabolites. The present study investigated whether guinea pig glutathione S-transferase (gpGST), a protein that binds with sulfanilamide (SA) and sulfamethoxazole (SMX), could be detected in the liver cytosol fraction of guinea pigs that intraperitoneally received SA or SMX, and whether gpGST is a carrier protein. We synthesized three nitroso compounds, i.e., 4-nitroso-sulfanilamide (SA-NO), 4-nitrososulfamethoxazole (SMX-NO) and fluorescent-labeled nitroso compound (DNSBA-NO), and examined binding quantities of nitroso compounds to gpGST purified from untreated female guinea pigs. Furthermore, the concentrations of IgG in serum antibody for nitroso compounds were estimated using ELISA. When guinea pigs were sensitized using the three nitroso compounds, the dose dependent skin reactions were confirmed with each compound. In addition, sensitized guinea pigs using each nitroso compound showed positive skin reactions at an elicitation test performed using gpGST alone. The results confirmed synthesis of antibody against gpGST due to hapten sensitization. Therefore, when a nitroso compound binds with gpGST in the body of guinea pigs, nitroso-gpGST acts as a neoantigen, which induces synthesis of autoantibody. Thus, gpGST appears to be one of the carrier proteins that induce sulfa drug-induced allergies. Immunization of guinea pigs with active metabolite of drugs may give information for predicting the occurrence of delayed type hypersensitivity in human. PMID:22342371

  10. Passive sensitization of skin and lung by guinea-pig immunoglobulins

    PubMed Central

    Colquhoun, D.; Brocklehurst, W. E.

    1965-01-01

    Guinea-pig γ1- and γ2-globulins have been purified by preparative electrophoresis followed by chromatography. No γ1-globulin was detectable in purified γ2-globulin, but purified γ1-globulin always contained fast γ2-globulin. Normal guinea-pig serum contained much less γ1-globulin than immune serum. Antisera prepared against normal guinea-pig serum did not contain useful amounts of antibody specific for γ1-globulin. Guinea-pig lung tissue was sensitized by very low concentrations of guinea-pig γ1-globulin (of the order of 6×10-10 molar) but γ2-globulin antibodies were almost inactive. No evidence was found that the trace of activity in γ2-globulin was not due to very slight contamination with γ1-globulin antibodies. The finding that γ1-globulin antibodies are far more potent than γ2-globulin antibodies in sensitizing skin has been confirmed, but several lines of evidence suggest that γ2-globulin antibodies may also have weak activity. Thus quantitative passive cutaneous anaphylaxis (PCA) tests showed that whenever the γ2-globulin fraction contained antibody it appeared far more potent relative to γ1-globulin than when the same proteins were tested on lung tissue. The PCA activity of moderate amounts of purified γ2-globulin antibodies disappeared faster than the skin sensitization produced by small amounts of γ1-globulin antibodies, and the γ2-globulin preparations did not contain enough γ1-globulin impurity to account for their PCA activity. No inhibition of skin responses was observed with the largest doses of antigen tested. The most plausible explanation of these results is that, under the conditions of our experiments, γ2-globulin antibody had weak PCA activity. Objections to this hypothesis are discussed. The PCA activity of γ2-globulin antibody probably involves a mechanism different from that of the sensitization produced by the highly potent γ1-globulin antibody. ImagesFIG. 4FIG. 5FIG. 6FIG. 7FIG. 8FIG. 9 PMID:4159033

  11. Simulated Hypergravity Alters Vascular Smooth Muscle Cell Proliferation and Motility

    NASA Technical Reports Server (NTRS)

    Hunt, Shameka; Bettis, Barika; Harris-Hooker, Sandra; Sanford, Gary L.

    1997-01-01

    The cellular effects of gravity are poorly understood due to its constancy and nonavailability of altered gravitational models. Such an understanding is crucial for prolonged space flights. In these studies, we assessed the influence of centrifugation at 6G (HGrav) on vascular smooth muscle (SMC) mobility and proliferation. Cells were: (a) plated at low density and subjected to HGrav for 24-72 hr for proliferation studies, or (b) grown to confluency, subjected to HGrav, mechanically denuded and monitored for cell movement into the denuded area. Controls were maintained under normogravity. SMC showed a 50% inhibition of growth under HGrav and 10% serum; HGrav and low serum resulted in greater growth inhibition. The rate of movement of SMC into the denuded area was 2-3-fold higher under HGrav in low serum compared to controls, but similar in 10% serum. These studies show that HGrav has significant effects on SMC growth and mobility, which are dependent on serum levels.

  12. Neostigmine-induced contraction and nitric oxide-induced relaxation of isolated ileum from STZ diabetic guinea pigs

    PubMed Central

    Cellini, Joseph; Jukic, Anne Marie Zaura; LePard, Kathy J.

    2011-01-01

    Both delayed gastrointestinal transit and autonomic neuropathy have been documented in patients with diabetes mellitus. The mechanism of neostigmine, an agent that mimics release of acetylcholine from autonomic neurons by prokinetic agents, to contract smooth muscle, despite dysfunctional enteric neural pathways, was determined using isolated ilea from STZ-treated and control guinea pigs. Both bethanechol- and neostigmine-induced contractions were stronger in diabetic ileum. Bethanechol-induced contractions of control but not diabetic ileum were increased by low dose scopolamine suggesting reduced activation of presynaptic muscarinic autoreceptors in diabetic ileum. The muscarinic receptor antagonist 4-DAMP strongly, but the nicotinic receptor antagonist hexamethonium only weakly, reduced neostigmine-induced contractions of control and diabetic ilea. The amount of acetylcholine, inferred from tissue choline content, was increased in diabetic ileum. Nicotinic neural and noncholinergic postjunctional smooth muscle receptors contributed more strongly to neostigmine-induced contractions in diabetic than control ileum. Relaxation of diabetic ileum by exogenous nitric oxide generated from sodium nitroprusside was comparable to control ileum, but smooth muscle relaxation by L-arginine using neuronal nitric oxide synthase to generate nitric oxide was weaker in diabetic ileum with evidence for a role for inducible nitric oxide synthase. Despite autonomic neuropathy, neostigmine strongly contracted ileum from diabetic animals but by a different mechanism including stronger activation of postjunctional muscarinic receptors, greater synaptic acetylcholine, stronger activation of noncholinergic excitatory pathways, and weaker activation of inhibitory pathways. A selective medication targeting a specific neural pathway may more effectively treat disordered gastrointestinal transit in patients with diabetes mellitus. PMID:21880552

  13. A Factor Capable of Increasing Vascular Permeability Present in Lymph Node Cells

    PubMed Central

    Willoughby, D. A.; Boughton, Barbara; Schild, H. O.

    1963-01-01

    A soluble extract from guinea-pig lymph node cells (LPF) has been found to increase vascular permeability in the skin of the rat. The active substance has been differentiated from histamine, 5-hydroxytryptamine, bradykinin, substance P, kallikrein and the globulin permeability factors from rat and guinea-pig serum by means of parallel quantitative assays. LPF was present in both sensitized and non-sensitized guinea-pig lymph node cells and in lymph node cells from rats and mice. LPF also increased vascular permeability in the skin of guinea-pigs, mice and rabbits. The possible importance of this factor in the mechanism of the delayed reactions is discussed. ImagesFIG. 1FIG. 3 PMID:14069726

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

    PubMed

    Ueno, Shunji; Kashimoto, Takashige; Susa, Nobuyuki; Ishii, Masamitsu; Chiba, Toshikazu; Mutoh, Ken-ichiro; Hoshi, Fumio; Suzuki, Takashi; Sugiyama, Masayasu

    2003-03-01

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

  15. Calcium oscillations in human mesenteric vascular smooth muscle.

    PubMed

    Navarro-Dorado, Jorge; Garcia-Alonso, Mauricio; van Breemen, Cornelis; Tejerina, Teresa; Fameli, Nicola

    2014-02-28

    Phenylephrine (PE)-induced oscillatory fluctuations in intracellular Ca(2+) concentration ([Ca(2+)]i) of vascular smooth muscle have been observed in many blood vessels isolated from a wide variety of mammals. Paradoxically, until recently similar observations in humans have proven elusive. In this study, we report for the first time observations of adrenergically-stimulated [Ca(2+)]i oscillations in human mesenteric artery smooth muscle. In arterial segments preloaded with Fluo-4 AM and mounted on a myograph on the stage of a confocal microscope, we observed PE-induced oscillations in [Ca(2+)]i, which initiated and maintained vasoconstriction. These oscillations present some variability, possibly due to compromised health of the tissue. This view is corroborated by our ultrastructural analysis of the cells, in which we found only (5 ± 2)% plasma membrane-sarcoplasmic reticulum apposition, markedly less than measured in healthy tissue from laboratory animals. We also partially characterized the oscillations by using the inhibitory drugs 2-aminoethoxydiphenyl borate (2-APB), cyclopiazonic acid (CPA) and nifedipine. After PE contraction, all drugs provoked relaxation of the vessel segments, sometimes only partial, and reduced or inhibited oscillations, except CPA, which rarely caused relaxation. These preliminary results point to a potential involvement of the sarcoplasmic reticulum Ca(2+) and inositol 1,4,5-trisphosphate receptor (IP3R) in the maintenance of the Ca(2+) oscillations observed in human blood vessels. PMID:24508261

  16. Arteriolar vascular smooth muscle cells: mechanotransducers in a complex environment.

    PubMed

    Hill, Michael A; Meininger, Gerald A

    2012-09-01

    Contraction of small artery (diameters typically less than 250 μm) vascular smooth muscle cells (VSMCs) plays a critical role in local control of blood flow and arterial pressure through its affect on vascular caliber. Specifically, contraction of small arteries in response to increased intraluminal pressure is referred to as the myogenic response and represents an important role for mechanotransduction. Critical questions remain as to how changes in pressure are sensed by VSMCs and transduced across the cell membrane to tune the contractile state of the cell. Recent studies suggest a pivotal role for interactions between VSMCs and extracellular matrix (ECM) proteins. Thus, pressure-induced deformation of ECM proteins and their cell surface receptors (for example, integrins) may initiate contraction and cytoskeletal remodeling through modulation of ion channels, membrane depolarization, increased intracellular Ca(2+) and actomyosin crossbridge cycling. Importantly, it is argued that the contractile properties of small artery VSMCs reflect an intimate and integrated interaction with their extracellular environment and the three-dimensional structure of the vessel wall. PMID:22677491

  17. The effects of compensated cardiac hypertrophy on dihydropyridine and ryanodine receptors in rat, ferret and guinea-pig hearts.

    PubMed

    Rannou, F; Sainte-Beuve, C; Oliviero, P; Do, E; Trouvé, P; Charlemagne, D

    1995-05-01

    The number of dihydropyridine and ryanodine receptors (DHP-R and RyR) has been measured in control and hypertrophied ventricles from rats, guinea pigs and ferrets to determine whether these two channels contribute to the alterations in excitation-contraction coupling (ECC), and in Ca2+ transient during compensated cardiac hypertrophy. We found that ventricular hypertrophy did not change the density of DHP-R. Mild hypertrophy did not alter the density of RyR in the rat but decreased it in the guinea-pig and in the ferret (30% and 36%, respectively). Severe hypertrophy decreased the density of RyR by 20% in the rat and by 34% in the guinea-pig. Therefore, the decrease is greater in ferret and guinea-pig hearts than in rat heart. We conclude that the sarcoplasmic reticulum (SR) Ca2+ release channels but not the L-type Ca2+ channels could contribute to the slowing of intracellular Ca2+ movements and to the reduced velocity of shortening of the hypertrophied hearts. We suggest that, in the guinea pig and ferret hearts which express only the beta myosin heavy chain (MHC) isoform, the reduced velocity of shortening during hypertrophy is related to the decrease in RyR density, whereas in the rat, it is regulated primarily via a shift in the MHC isoform, except in severe hypertrophy in which the moderate decrease in RyR would also be involved. PMID:7473781

  18. High-fat diet-dependent modulation of the delayed rectifier K(+) current in adult guinea pig atrial myocytes.

    PubMed

    Aromolaran, Ademuyiwa S; Colecraft, Henry M; Boutjdir, Mohamed

    2016-06-01

    Obesity is associated with hyperlipidemia, electrical remodeling of the heart, and increased risk of supraventricular arrhythmias in both male and female patients. The delayed rectifier K(+) current (IK), is an important regulator of atrial repolarization. There is a paucity of studies on the functional role of IK in response to obesity. Here, we assessed the obesity-mediated functional modulation of IK in low-fat diet (LFD), and high-fat diet (HFD) fed adult guinea pigs. Guinea pigs were randomly divided into control and obese groups fed, ad libitum, with a LFD (10 kcal% fat) or a HFD (45 kcal% fat) respectively. Action potential duration (APD), and IK were studied in atrial myocytes and IKr and IKs in HEK293 cells using whole-cell patch clamp electrophysiology. HFD guinea pigs displayed a significant increase in body weight, total cholesterol and total triglycerides within 50 days. Atrial APD at 30% (APD30) and 90% (APD90) repolarization were shorter, while atrial IK density was significantly increased in HFD guinea pigs. Exposure to palmitic acid (PA) increased heterologously expressed IKr and IKs densities, while oleic acid (OA), severely reduced IKr and had no effect on IKs. The data are first to show that in obese guinea pigs abbreviated APD is due to increased IK density likely through elevations of PA. Our findings may have crucial implications for targeted treatment options for obesity-related arrhythmias. PMID:27130822

  19. Effect of ouabain on mechanical and electrical properties of rat and guinea pig hearts at 180 C.

    PubMed

    Diacono, J; Dietrich, J

    1977-04-01

    The effects of ouabain 10(-6) M on rat and guinea pig hearts have been studied at 18 degrees C, in order to reduce almost fully both the Na+, K+-dependent ATPase activity and the ouabain induced inhibition of this enzyme. In isolated guinea pig hearts the positive inotropic response to ouabain obtained at 32 degrees C disappeared at 18 degrees C. On the contrary, the contractile strength of rat hearts was slightly reduced by ouabain and in the same manner at both temperatures. Current and voltage clamp experiments carried out at 18 degrees C in ventricular fibres revealed that ouabain 10(-6) M decreased both the action potential overshoot and the fast sodium current in rat and guinea pig, by reduction of the membrane sodium conductance. Ouabain did not change the calcium current in guinea pig preparations, whereas in rat heart muscle this current was reduced. The effects of ouabain on both the action potential plateau and outward repolarizing current indicated some inconsistencies from preparation to preparation and cannot therefore be considered as significant. The persistence of the ouabain induced alterations of g Na (in rat and guinea pig) and calcium current (in rat) at 18 degrees C supports the hypothesis of two ouabain cell receptors in heart muscle. PMID:141917

  20. Identification and properties of pathways for K+ transport in guinea-pig and rat alveolar epithelial type II cells.

    PubMed Central

    Kemp, P J; Roberts, G C; Boyd, C A

    1994-01-01

    86Rb+ was used to study potassium uptake and efflux in type II pneumocytes freshly isolated from adult guinea-pig and rat lung. Both species exhibited a substantial ouabain-sensitive component of potassium influx. In rats, most of the ouabain-resistant influx was abolished by bumetanide and removal of extracellular chloride elicited no further effect. In contrast, only a proportion of the ouabain-insensitive uptake was inhibitable by bumetanide in guinea-pigs and this species showed an additional component of influx, which was chloride dependent and which was reduced by either the K(+)-H(+)-ATPase inhibitor, omeprazole, or by the stilbene derivative, 4,4'-diisothiocyanostilbene-2,2'-disulphonate (DIDS). The chloride-dependent component was also apparent in efflux experiments in guinea-pigs, but was absent in rats. Ouabain-insensitive ATPase activity was assayed in highly purified apical membranes from guinea-pig type II pneumocytes. This activity was inhibitable by omeprazole (apparent inhibition constant, Ki, was approximately 40 microM), was potassium dependent (apparent activation constant, Ka, was approximately 200 microM) and was doubled by the addition of nigericin. While potassium transport in rat type II cells is adequately accounted for by Na(+)-K(+)-ATPase and Na(+)-K(+)-2Cl- cotransport, our data suggest the additional presence of K(+)-Cl- cotransport and K(+)-H(+)-ATPase in guinea-pig type II pneumocytes. A model of how alveolar subphase acidification may occur is proposed. PMID:8046636

  1. Changes in pulmonary lavage fluid of guinea pigs exposed to ultrafine zinc oxide with adsorbed sulfuric acid

    SciTech Connect

    Conner, M.W.; Flood, W.H.; Rogers, A.E.; Amdur, M.O.

    1989-01-01

    Ultrafine metal oxide particles (diameters less than 0.1 microns) and sulfur dioxide are important products of coal combustion. Interaction of these products in the effluent stream results in formation of ultrafine particles with adsorbed sulfur compounds, including sulfuric acid. The toxicity of ultrafine zinc oxide particles with adsorbed sulfuric acid was evaluated by comparing pulmonary lavage fluid from guinea pigs exposed for 1, 2, 3, 4, or 5 consecutive daily 3-h periods to ultrafine zinc oxide generated in the presence of sulfur dioxide (ZnO + SO/sub 2/) to pulmonary lavage fluid from guinea pigs exposed to an equivalent concentration of ultrafine ZnO. Two groups of guinea pigs exposed either to SO/sub 2/ or to particle-free furnace gas served as additional controls. Cells, protein, and activities of lactate dehydrogenase, acid phosphatase, and alkaline phosphatase were increased in lavage fluid obtained from guinea pigs exposed to ZnO + SO/sub 2/ as compared to guinea pigs exposed to ZnO. These results demonstrate the potential importance of ultrafine metal oxides as carries of sulfuric acid derived from fossil fuel combustion.

  2. Caveolin-3 Promotes a Vascular Smooth Muscle Contractile Phenotype

    PubMed Central

    Gutierrez-Pajares, Jorge L.; Iturrieta, Jeannette; Dulam, Vipin; Wang, Yu; Pavlides, Stephanos; Malacari, Gabriella; Lisanti, Michael P.; Frank, Philippe G.

    2015-01-01

    Epidemiological studies have demonstrated the importance of cardiovascular diseases in Western countries. Among the cell types associated with a dysfunctional vasculature, smooth muscle (SM) cells are believed to play an essential role in the development of these illnesses. Vascular SM cells are key regulators of the vascular tone and also have an important function in the development of atherosclerosis and restenosis. While in the normal vasculature, contractile SM cells are predominant, in atherosclerotic vascular lesions, synthetic cells migrate toward the neointima, proliferate, and synthetize extracellular matrix proteins. In the present study, we have examined the role of caveolin-3 in the regulation of SM cell phenotype. Caveolin-3 is expressed in vivo in normal arterial SM cells, but its expression appears to be lost in cultured SM cells. Our data show that caveolin-3 expression in the A7r5 SM cell line is associated with increased expression of contractility markers such as SM α-actin, SM myosin heavy chain but decreased expression of the synthetic phenotype markers such as p-Elk and Klf4. Moreover, we also show that caveolin-3 expression can reduce proliferation upon treatment with LDL or PDGF. Finally, we show that caveolin-3-expressing SM cells are less sensitive to apoptosis than control cells upon treatment with oxidized LDL. Taken together, our data suggest that caveolin-3 can regulate the phenotypic switch between contractile and synthetic SM cells. A better understanding of the factors regulating caveolin-3 expression and function in this cell type will permit the development of a better comprehension of the factors regulating SM function in atherosclerosis and restenosis. PMID:26664898

  3. Drug modulation of antigen-induced paw oedema in guinea-pigs: effects of lipopolysaccharide, tumour necrosis factor and leucocyte depletion.

    PubMed

    da Motta, J I; Cunha, F Q; Vargaftig, B B; Ferreira, S H

    1994-05-01

    -oedematogenic effects of LPS and/or TNF alpha are possibly associated with their capacity to inhibit leucocyte emigration. Accordingly, guinea-pigs rendered leucopenic with vinblastine exhibited less intense oedema after ovalbumin. Vinblastine did not affect oedema induced by PAF or bradykinin,indicating that vascular responsiveness was not involved. PMID:8032630

  4. The effects of chrysin and pinostrobin, two flavonoids isolated from Teloxys graveolens leaves, on isolated guinea-pig ileum.

    PubMed

    Meckes, M; Paz, D; Acosta, J; Mata, R

    1998-12-01

    The pharmacological effects of pinostrobin and chrysin obtained from the aerial parts of Teloxys graveolens (Chenopodiaceae) were evaluated using isolated in vitro guinea-pig ileal smooth muscle. Both flavonoids inhibited the contractions evoked by high concentrations of potassium. The potency of the relaxant effect was determined by measuring the capacity of each product in reducing the phasic and the slower sustained tonic contractile responses induced by depolarization with 60 mM K(+). Concentrations up to 5 × 10(-7) M of pinostrobin and 1 × 10(-7) M of chrysin induced a non-competitive depression of responses to Ca(2+) in ileum preparations bathed in a Ca(2+)-free, high K(+) medium. Both compounds produced a rightward displacement of the concentration-response curves to Ca(2+) with a concentration-dependant increase of EC(50) and a decrease of the maximal response. Examination of the inhibitory effect produced by these flavonoids on the phasic component of contractile response evoked with K(+) and on the contraction induced with caffeine, led to propose a different intracellular mechanism of action used by these compounds. The results obtained led us to conclude that the previously detected relaxant effect of Teloxys graveolens crude extract is due in part, to the presence of chrysin and pinostrobin, which inhibit intestinal smooth muscle contractions by means of a calcium-mediated mechanism. Since the modulation of calcium fluxes in the mucosal epithelium may play a role in antidiarrheal drug action, the observed effects in vitro could in the same way explain the popular use of the plant for the treatment of diarrhea. PMID:23196029

  5. Characterization of Guinea Pig Antibody Responses to Salivary Proteins of Triatoma infestans for the Development of a Triatomine Exposure Marker

    PubMed Central

    Dorňáková, Veronika; Salazar-Sanchez, Renzo; Borrini-Mayori, Katty; Carrion-Navarro, Oscar; Levy, Michael Z.; Schaub, Günter A.; Schwarz, Alexandra

    2014-01-01

    Background Salivary proteins of Triatoma infestans elicit humoral immune responses in their vertebrate hosts. These immune responses indicate exposure to triatomines and thus can be a useful epidemiological tool to estimate triatomine infestation. In the present study, we analyzed antibody responses of guinea pigs to salivary antigens of different developmental stages of four T. infestans strains originating from domestic and/or peridomestic habitats in Argentina, Bolivia, Chile and Peru. We aimed to identify developmental stage- and strain-specific salivary antigens as potential markers of T. infestans exposure. Methodology and Principal Findings In SDS-PAGE analysis of salivary proteins of T. infestans the banding pattern differed between developmental stages and strains of triatomines. Phenograms constructed from the salivary profiles separated nymphal instars, especially the 5th instar, from adults. To analyze the influence of stage- and strain-specific differences in T. infestans saliva on the antibody response of guinea pigs, twenty-one guinea pigs were exposed to 5th instar nymphs and/or adults of different T. infestans strains. Western blot analyses using sera of exposed guinea pigs revealed stage- and strain-specific variations in the humoral response of animals. In total, 27 and 17 different salivary proteins reacted with guinea pig sera using IgG and IgM antibodies, respectively. Despite all variations of recognized salivary antigens, an antigen of 35 kDa reacted with sera of almost all challenged guinea pigs. Conclusion Salivary antigens are increasingly considered as an epidemiological tool to measure exposure to hematophagous arthropods, but developmental stage- and strain-specific variations in the saliva composition and the respective differences of immunogenicity are often neglected. Thus, the development of a triatomine exposure marker for surveillance studies after triatomine control campaigns requires detailed investigations. Our study resulted

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

    PubMed

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

    2016-04-01

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

  7. Luteolin Ameliorates Hypertensive Vascular Remodeling through Inhibiting the Proliferation and Migration of Vascular Smooth Muscle Cells

    PubMed Central

    Su, Jie; Xu, Han-Ting; Yu, Jing-Jing; Gao, Jian-Li; Lei, Jing; Yin, Qiao-Shan; Li, Bo; Pang, Min-Xia; Su, Min-Xia; Mi, Wen-Jia; Chen, Su-Hong; Lv, Gui-Yuan

    2015-01-01

    Objectives. Preliminary researches showed that luteolin was used to treat hypertension. However, it is still unclear whether luteolin has effect on the hypertensive complication such as vascular remodeling. The present study was designed to investigate the effect of luteolin on the hypertensive vascular remodeling and its molecular mechanism. Method and Results. We evaluated the effect of luteolin on aorta thickening of hypertension in spontaneous hypertensive rats (SHRs) and found that luteolin could significantly decrease the blood pressure and media thickness of aorta in vivo. Luteolin could inhibit angiotensin II- (Ang II-) induced proliferation and migration of vascular smooth muscle cells (VSMCs). Dichlorofluorescein diacetate (DCFH-DA) staining result showed that luteolin reduced Ang II-stimulated ROS production in VSMCs. Furthermore, western blot and gelatin zymography results showed that luteolin treatment leaded to a decrease in ERK1/2, p-ERK1/2, p-p38, MMP2, and proliferating cell nuclear antigen (PCNA) protein level. Conclusion. These data support that luteolin can ameliorate hypertensive vascular remodeling by inhibiting the proliferation and migration of Ang II-induced VSMCs. Its mechanism is mediated by the regulation of MAPK signaling pathway and the production of ROS. PMID:26495010

  8. Endothelial-dependent relaxant actions of carbachol and substance P in arterial smooth muscle.

    PubMed

    Bolton, T B; Clapp, L H

    1986-04-01

    In helical strips cut from the small mesenteric artery of guinea-pig (GPSMA) (0.3-0.6 mm o.d.) relaxations induced by substance P were more susceptible to damage of the endothelium by rubbing than were relaxations evoked by carbachol. Relaxations induced by 2-nicotin-amidoethyl nitrate (SG75) were unaffected by this procedure. Relaxations evoked by the calcium ionophore A23187 persisted when those to substance P had been abolished by rubbing the endothelium in GPSMA, rabbit mesenteric and rabbit ear arteries. In guinea-pig pulmonary artery and aorta relaxations to A23187 were lost after this treatment. Carbachol and SG75 were more effective in inhibiting phasic than tonic tension induced by noradrenaline in GPSMA, but substance P was more effective against tonic tension. In the GPSMA, carbachol and substance P inhibited tension produced by noradrenaline to similar extents. However, carbachol was less, and substance P much less effective in inhibiting tension evoked by high-potassium solution than by noradrenaline. Susceptibility of relaxations to blockade by haemoglobin in GPSMA was: substance P greater than carbachol greater than ATP greater than SG75. The membrane potential of smooth muscle cells in the media of the GPSMA was recorded by microelectrode. Carbachol, but not substance P, hyperpolarized the cells both in the presence and absence of noradrenaline at concentrations which relaxed the muscle. These results suggest a heterogeneity in the mechanisms of endothelial-dependent relaxations induced by various vascular relaxants. PMID:2423170

  9. Immunocytochemical evidence for SNARE protein-dependent transmitter release from guinea pig horizontal cells

    PubMed Central

    Lee, Helen; Brecha, Nicholas C.

    2013-01-01

    Horizontal cells are lateral interneurons that participate in visual processing in the outer retina but the cellular mechanisms underlying transmitter release from these cells are not fully understood. In non-mammalian horizontal cells, GABA release has been shown to occur by a non-vesicular mechanism. However, recent evidence in mammalian horizontal cells favors a vesicular mechanism as they lack plasmalemmal GABA transporters and some soluble NSF attachment protein receptor (SNARE) core proteins have been identified in rodent horizontal cells. Moreover, immunoreactivity for GABA and the molecular machinery to synthesize GABA have been found in guinea pig horizontal cells, suggesting that if components of the SNARE complex are expressed they could contribute to the vesicular release of GABA. In this study we investigated whether these vesicular and synaptic proteins are expressed by guinea pig horizontal cells using immunohistochemistry with well-characterized antibodies to evaluate their cellular distribution. Components of synaptic vesicles including vesicular GABA transporter, synapsin I and synaptic vesicle protein 2A were localized to horizontal cell processes and endings, along with the SNARE core complex proteins, syntaxin-1a, syntaxin-4 and synaptosomal-associated protein 25 (SNAP-25). Complexin I/II, a cytosolic protein that stabilizes the activated SNARE fusion core, strongly immunostained horizontal cell soma and processes. In addition, the vesicular Ca2+-sensor, synaptotagmin-2, which is essential for Ca2+-mediated vesicular release, was also localized to horizontal cell processes and somata. These morphological findings from guinea pig horizontal cells suggest that mammalian horizontal cells have the capacity to utilize a regulated Ca2+-dependent vesicular pathway to release neurotransmitter, and that this mechanism may be shared among many mammalian species. PMID:20384779

  10. Mechanisms underlying nutrient-induced segmentation in isolated guinea pig small intestine.

    PubMed

    Gwynne, R M; Bornstein, J C

    2007-04-01

    Mechanisms underlying nutrient-induced segmentation within the gut are not well understood. We have shown that decanoic acid and some amino acids induce neurally dependent segmentation in guinea pig small intestine in vitro. This study examined the neural mechanisms underlying segmentation in the circular muscle and whether the timing of segmentation contractions also depends on slow waves. Decanoic acid (1 mM) was infused into the lumen of guinea pig duodenum and jejunum. Video imaging was used to monitor intestinal diameter as a function of both longitudinal position and time. Circular muscle electrical activity was recorded by using suction electrodes. Recordings from sites of segmenting contractions showed they are always associated with excitatory junction potentials leading to action potentials. Recordings from sites oral and anal to segmenting contractions revealed inhibitory junction potentials that were time locked to those contractions. Slow waves were never observed underlying segmenting contractions. In paralyzed preparations, intracellular recording revealed that slow-wave frequency was highly consistent at 19.5 (SD 1.4) cycles per minute (c/min) in duodenum and 16.6 (SD 1.1) c/min in jejunum. By contrast, the frequencies of segmenting contractions varied widely (duodenum: 3.6-28.8 c/min, median 10.8 c/min; jejunum: 3.0-27.0 c/min, median 7.8 c/min) and sometimes exceeded slow-wave frequencies for that region. Thus nutrient-induced segmentation contractions in guinea pig small intestine do not depend on slow-wave activity. Rather they result from a neural circuit producing rhythmic localized activity in excitatory motor neurons, while simultaneously activating surrounding inhibitory motor neurons. PMID:17218474

  11. Effects of Eszopiclone and Zolpidem on Sleep and Waking States in the Adult Guinea Pig

    PubMed Central

    Xi, Mingchu; Chase, Michael H.

    2008-01-01

    Study Objective: The present study was designed to compare and contrast the effects of eszopiclone and zolpidem on the states of sleep and wakefulness in chronically instrumented, unanesthetized adult guinea pigs. Design: Adult guinea pigs were implanted with electrodes to record sleep and waking states and to perform a frequency analysis of the EEG. Eszopiclone (1 and 3 mg/kg) and zolpidem (1 and 3 mg/kg) were administered intraperitoneally. Measurements and Results: The administration of eszopiclone (1 and 3 mg/kg) resulted in a significant dose-dependent increase in NREM sleep. Zolpidem produced a significant increase in NREM sleep, but only at a dose of 3 mg/kg. The following changes in NREM and REM sleep, as well as in the power spectra, were all significant when the effects of 1 and 3 mg/kg of eszopiclone were compared with responses induced with 1 and 3 mg/kg of zolpidem, respectively: The increase in NREM sleep produced by eszopiclone was greater than that following the administration of zolpidem. The mean latency to NREM sleep following the administration of eszopiclone was significantly shorter than zolpidem. Eszopiclone significantly increased the latency to REM sleep. The mean duration of episodes of NREM sleep was increased by eszopiclone, but not by zolpidem. The EEG power increased in the delta band and decreased in the theta band during NREM sleep following the administration of eszopiclone. No significant changes occurred in any of the frequency bands analyzed following zolpidem administration. Conclusions: The differences in the effects of eszopiclone and zolpidem on sleep and waking states and the power spectra of the EEG likely reflect the fact that eszopiclone and zolpidem bind to different subunits of the GABAA receptor complex. Citation: Xi M; Chase MH. Effects of eszopiclone and zolpidem on sleep and waking states in the adult guinea pig. SLEEP 2008;31(7):1043-1051. PMID:18652100

  12. The Effect of DA-9701 in Opioid-induced Bowel Dysfunction of Guinea Pig

    PubMed Central

    Hussain, Zahid; Rhee, Kwang Won; Lee, Young Ju; Park, Hyojin

    2016-01-01

    Background/Aims Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics. DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber has promising effects on GI motor function. Therefore, we aim to evaluate the prokinetic effects of DA-9701 in an OIBD model of guinea pig. Methods The ileal and distal colon muscle contraction in presence of different doses of DA-9701, morphine, and combination (morphine + DA-9701) was measured by tissue bath study. The prokinetic effect of DA-9701 was assessed by charcoal transit and fecal pellet output assay in an OIBD model of guinea pig. Results DA-9701 significantly increased the amplitude and area under the curve of ileal muscle contraction, while there was insignificant effect on the distal colon compared to the control. The maximal amplitude of ileal muscle contraction was acquired at a concentration of 10 μg/mL of DA-9701. In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control. Morphine delayed both upper (P < 0.01) and lower (P < 0.05) GI transit, and delayed GI transit was restored by the administration of DA-9701. Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles. Conclusions DA-9701 significantly increased the amplitude of contraction of the ileal muscle, however the distal colon muscle contraction was insignificant. Additionally, it restored delayed upper and lower GI transit in an OIBD model of guinea pig, and it might prove to be a useful candidate drug in a clinical trial for OIBD. PMID:26932898

  13. Antitussive activity of sigma-1 receptor agonists in the guinea-pig

    PubMed Central

    Brown, Claire; Fezoui, Malika; Selig, William M; Schwartz, Carl E; Ellis, James L

    2003-01-01

    Current antitussive medications have limited efficacy and often contain the opiate-like agent dextromethorphan (DEX). The mechanism whereby DEX inhibits cough is ill defined. DEX displays affinity at both NMDA and sigma receptors, suggesting that the antitussive activity may involve central or peripheral activity at either of these receptors. This study examined and compared the antitussive activity of DEX and various putative sigma receptor agonists in the guinea-pig citric-acid cough model. Intraperitoneal (i.p.) administration of DEX (30 mg kg−1) and the sigma-1 agonists SKF-10,047 (1–5 mg kg−1), Pre-084 (5 mg kg−1), and carbetapentane (1–5 mg kg−1) inhibited citric-acid-induced cough in guinea-pigs. Intraperitoneal administration of a sigma-1 antagonist, BD 1047 (1–5 mg kg−1), reversed the inhibition of cough elicited by SKF-10,047. In addition, two structurally dissimilar sigma agonists SKF-10,047 (1 mg ml−1) and Pre-084 (1 mg ml−1) inhibited cough when administered by aerosol. Aerosolized BD 1047 (1 mg ml−1, 30 min) prevented the antitussive action of SKF-10,047 (5 mg kg−1) or DEX (30 mg kg−1) given by i.p. administration and, likewise, i.p. administration of BD 1047 (5 mg kg−1) prevented the antitussive action of SKF-10,047 given by aerosol (1 mg ml−1). These results therefore support the argument that antitussive effects of DEX may be mediated via sigma receptors, since both systemic and aerosol administration of sigma-1 receptor agonists inhibit citric-acid-induced cough in guinea-pigs. While significant systemic exposure is possible with aerosol administration, the very low doses administered (estimated <0.3 mg kg−1) suggest that there may be a peripheral component to the antitussive effect. PMID:14691051

  14. The Effect of Natural Adjuvants on Pathological Changes in Sensitized Guinea Pig Lungs

    PubMed Central

    Neamati, Ali; Boskabady, Mohammad Hossein; Tabatabaei, Abass; Mohaghegh Hazrati, Saleh

    2014-01-01

    Background: Anti-inflammatory effect of natural adjuvants has been reported. Lung inflammation is the most characterized pathological feature in asthma. Objectives: The effects of three natural adjuvants (PC, G2, and G2F registered as a patent in the Iranian Patent Office) on sensitized guinea pigs lungs were examined in the present study. Materials and Methods: Lung pathological changes were examined in control and five groups of randomly divided guinea pigs including: sensitized animals (S, receiving normal saline, 0.5 ml i.p.); sensitized animals treated with adjuvant PC; G2F (0.1 ml i.p. for both cases); G2 (0.4 ml i.p.); and PC + G2 (receiving both PC and G) adjuvants (twice a week for 4 weeks for all groups). Sensitization of animals was done by injection and inhalation of ovalbumin (OA). Results: All pathological changes in S group including the eosinophil infiltration (scoring 3.28 ± 0.28), lymphocyte infiltration (2.82 ± 0.26), local epithelial necrosis (2.71 ± 0.47) and mucosal plug (2.75 ± 0.37) were significantly higher than control group (0.64 ± 0.18, 1.36 ± 0.24, 0.36 ± 0.18 and 0.28 ± 0.18 for eosinophil infiltration, lymphocyte infiltration, epithelial necrosis and mucosal plug respectively, P < 0.001 for all cases). Treatment with all adjuvants improved all pathological changes significantly (P < 0.05 to P < 0.001). Conclusions: These results indicate preventive effects of all natural adjuvants (especially G2) on pathological changes of the lung in sensitized guinea pigs. PMID:24719739

  15. Determination of oxidative stress and activities of antioxidant enzymes in guinea pigs treated with haloperidol

    PubMed Central

    GUMULEC, JAROMIR; RAUDENSKA, MARTINA; HLAVNA, MARIAN; STRACINA, TIBOR; SZTALMACHOVA, MARKETA; TANHAUSEROVA, VERONIKA; PACAL, LUKAS; RUTTKAY-NEDECKY, BRANISLAV; SOCHOR, JIRI; ZITKA, ONDREJ; BABULA, PETR; ADAM, VOJTECH; KIZEK, RENE; NOVAKOVA, MARIE; MASARIK, MICHAL

    2013-01-01

    Guinea pigs (Cavia porcellus) were treated with haloperidol (HP), and free radical (FR) and ferric reducing antioxidant power (FRAP) assays were used to determine oxidative stress levels. Furthermore, the superoxide dismutase (SOD), glutathione reductase (GR) and glutathione-S-transferase (GST) activity levels were detected and glucose levels and the reduced and oxidized glutathione (GSH/GSSG) ratio were measured in HP-treated and untreated guinea pigs. The present study demonstrated that the administration of HP causes significant oxidative stress in guinea pigs (P=0.022). In animals treated with HP, the activity of GST was significantly increased compared with a placebo (P= 0.007). The elevation of SOD and GR activity levels and increase in the levels of glutathione (GSH) in HP-treated animals were not statistically significant. In the HP-untreated animals, a significant positive correlation was observed between oxidative stress detected by the FR method and GST (r=0.88, P=0.008) and SOD (r=0.86, P= 0.01) activity levels, respectively. A significant negative correlation between the levels of plasma glucose and oxidative stress detected by the FRAP method was observed (r=−0.78, P=0.04). Notably, no significant correlations were observed in the treated animals. In the HP-treated group, two subgroups of animals were identified according to their responses to oxidative stress. The group with higher levels of plasma HP had higher enzyme activity and reactive oxygen species production compared with the group with lower plasma levels of HP. The greatest difference in activity (U/μl) between the two groups of animals was for GR. PMID:23403848

  16. Tonic eye movements induced by bilateral and unilateral galvanic vestibular stimulation (GVS) in guinea pigs.

    PubMed

    Kim, Juno

    2013-01-01

    Galvanic vestibular stimulation (GVS) stimulates primary vestibular afferents innervating the semicircular canals (SCCs) and otoliths found in the inner ear of humans and other mammals, including guinea pigs. To determine which pathways contribute to eye movements generated by this artificial vestibular stimulation in guinea pigs, low current intensities of GVS were passed either bilaterally between the tensor-tympani muscles of the two ears (up to 30 μA) or unilaterally between one tensor-tympani electrode and an indifferent on the back of the neck (up to 60 μA). Both forms of GVS were found to selectively generate tonic eye movements without nystagmus, characteristic of the otolith-ocular reflex; the axis of eye rotation did not align with any semicircular canal plane, but was oriented close to the expected axis of eye rotation that would occur in response to the net stimulation of otolith afferents. The induced eye rotation was predominantly vertical with a smaller horizontal deviation and very little torsion. Consistent with the results of previous human studies, the tonic eye movements were found to exhibit bilateral gain enhancement, whereby bilateral GVS generated twice the amplitude of eye rotation as unilateral anodal or cathodal stimulation alone. Eye movement responses to unilateral GVS were symmetrical in amplitude during equivalent intensities of anodal and cathodal stimulation, consistent with the known responses of more regularly and intermediately discharging primary vestibular afferents to GVS. These results together suggest that more regularly discharging otolith-ocular projections may mediate the tonic changes in eye position induced during maintained, low-intensity GVS in guinea pigs. PMID:23022577

  17. Diet-induced dyslipidemia leads to nonalcoholic fatty liver disease and oxidative stress in guinea pigs.

    PubMed

    Tveden-Nyborg, Pernille; Birck, Malene M; Ipsen, David H; Thiessen, Tina; Feldmann, Linda de Bie; Lindblad, Maiken M; Jensen, Henrik E; Lykkesfeldt, Jens

    2016-02-01

    Chronic dyslipidemia imposed by a high-fat and high-caloric dietary regime leads to debilitating disorders such as obesity, nonalcoholic fatty liver disease (NAFLD), and insulin resistance. As disease rates surge, so does the need for high validity animal models to effectively study the causal relationship between diet and disease progression. The dyslipidemic guinea pig displays a high similarity with the human lipoprotein profile and may in this aspect be superior to other rodent models. This study investigated the effects of 2 long-term Westernized diets (0.35% cholesterol, 18.5% vegetable oil and either 15% or 20% sucrose) compared with isocaloric standard chow in adult guinea pigs. Biochemical markers confirmed dyslipidemia in agreement with dietary regimens; however, both high-fat groups displayed a decreased tissue fat percentage compared with controls. Macroscopic appearance, histopathologic evaluation, and plasma markers of liver function confirmed NAFLD in high-fat groups, supported by liver redox imbalance and markers suggesting hepatic endothelial dysfunction. Plasma markers indicated endothelial dysfunction in response to a high-fat diet, although atherosclerotic lesions were not evident. Evaluation of glucose tolerance showed no indication of insulin resistance. The 5% increase in sucrose between the 2 high-fat diets did not lead to significant differences between groups. In conclusion, we find the dyslipidemic guinea pig to be a valid model of diet imposed dyslipidemia, particularly with regards to hepatic steatosis and endothelial dysfunction. Furthermore, the absence of obesity supports the present study setup as targeting NAFLD in nonobese individuals. PMID:26518991

  18. Effect of memantine on cough reflex sensitivity: translational studies in guinea pigs and humans.

    PubMed

    Dicpinigaitis, Peter V; Canning, Brendan J; Garner, Rachel; Paterson, Blake

    2015-03-01

    Cough is the most common complaint for which outpatients in the United States seek medical attention, and yet available therapeutic options for cough lack proven efficacy and are further limited by safety and abuse liabilities. Thus, safe and effective cough suppressants are needed. Recent preclinical studies described the antitussive effects of memantine, an N-methyl-d-aspartate receptor channel blocker used in the treatment of Alzheimer's disease. The goals of the present study were to compare the antitussive effects of memantine, dextromethorphan, and codeine in guinea pigs; to relate the dose-dependent actions of memantine in these studies to peak plasma concentrations achieved following oral administration; and to provide the first ever evaluation of the antitussive effect of memantine in humans. In guinea pigs, memantine and codeine were comparable in efficacy and potency but both were superior to dextromethorphan in the citric acid cough challenge model. The pharmacokinetic analyses suggest that memantine was active in guinea pigs at micromolar plasma concentrations. Subsequently, 14 healthy volunteers as well as 14 otherwise healthy adults with acute viral upper respiratory tract infection (URI) underwent capsaicin cough challenges 6 hours after ingestion of 20 mg memantine and matched placebo in a randomized, double-blind, crossover fashion. In healthy volunteers, memantine significantly inhibited cough reflex sensitivity (P = 0.034). In subjects with URI, responsiveness to capsaicin was markedly increased, and in these patients, the inhibition of cough reflex sensitivity by memantine relative to placebo did not reach statistical significance (P = 0.088). These data support further research to investigate the potential of memantine as a clinically useful antitussive. PMID:25525191

  19. Modification of Osteoarthritis in the Guinea Pig with Pulsed Low-Intensity Ultrasound Treatment

    PubMed Central

    Gurkan, Ilksen; Ranganathan, Archana; Yang, Xu; Horton, Walter E.; Todman, Martin; Huckle, James; Pleshko, Nancy; Spencer, Richard G.

    2010-01-01

    Objective The Hartley guinea pig develops articular cartilage degeneration similar to that seen in idiopathic human osteoarthritis. We investigated whether the application of pulsed low-intensity ultrasound (PLIUS) to the Hartley guinea pig joint would prevent or attenuate the progression of this degenerative process. Methods Treatment of male Hartley guinea pigs was initiated at the onset of degeneration (8 weeks of age) to assess the ability of PLIUS to prevent osteoarthritis, or at a later age (12 months) to assess the degree to which PLIUS acted to attenuate the progression of established disease. PLIUS (30 mW/cm2) was applied to stifle joints for 20 minutes per day over periods ranging from three to ten months, with contralateral limbs serving as controls. Joint cartilage histology was graded according to a modified Mankin scale to evaluate treatment effect. Immunohistochemical staining for IL-1 receptor antagonist (IL-1ra), MMP-3, MMP-13, and TGF-β1 was performed on the cartilage to evaluate patterns of expression of these proteins. Results PLIUS did not fully prevent cartilage degeneration in the prevention groups, but diminished the severity of the disease, with the treated joints showing markedly decreased surface irregularities and a much smaller degree of loss of matrix staining as compared to controls. PLIUS also attenuated disease progression in the groups with established disease, although to a somewhat lesser extent as compared to the prevention groups. Immunohistochemical staining demonstrated a markedly decreased degree of TGF-β1 production in the PLIUS-treated joints. This indicates less active endogenous repair, consistent with the marked reduction in cartilage degradation. Conclusions PLIUS exhibits the ability to attenuate the progression of cartilage degeneration in an animal model of idiopathic human OA. The effect was greater in the treatment of early, rather than established, degeneration. PMID:20175971

  20. Vigilance states, EEG spectra, and cortical temperature in the guinea pig.

    PubMed

    Tobler, I; Franken, P; Jaggi, K

    1993-06-01

    Vigilance states, electroencephalogram (EEG) power spectra (0.25-25.0 Hz), and cortical temperature (TCRT) were obtained in nine guinea pigs for 24 h in a 12:12-h light-dark (LD 12:12) schedule. Sleep was markedly polyphasic and fragmented and amounted to 32% of recording time, which is a low value compared with sleep in other rodents. There was 6.8% more sleep in the light period than in the dark period. EEG power density in non-rapid eye movement (NREM) sleep showed no significant temporal trend within the light or the dark period. The homeostatic aspects of sleep regulation, as proposed in the two-process model, can account for the slow-wave activity (SWA) pattern also in the guinea pig: The small 24-h amplitude of the sleep-wakefulness pattern resulted in a small, 12% decline of SWA within the light period. In contrast to more distinctly nocturnal rodents, SWA in the dark period was not higher than in the light period. TCRT showed no difference between the light and the dark period. TCRT in REM sleep and waking was higher than TCRT in NREM sleep. TCRT increased after the transition from NREM sleep to either REM sleep or waking, and decreased in the last minute before the transition and after the transition from waking to NREM sleep. Motor activity measured in six animals for 11 days in constant darkness showed no apparent rhythm in three animals and a significant circadian rhythm in three others. Our data support the notion that guinea pigs exhibit only a weak circadian rest-activity rhythm. PMID:8322965

  1. Target organs of infection in guinea pigs with acquired congenital syphilis.

    PubMed Central

    Wicher, K; Abbruscato, F; Wicher, V; Baughn, R; Noordhoek, G T

    1996-01-01

    The target organs of infection in guinea pigs with asymptomatic acquired or congenital syphilis were identified by PCR and in some cases by rabbit infectivity test (RIT). The prevalence of Treponema pallidum DNA was examined in the following seven organs: the inguinal and mesenteric lymph nodes, spleen, liver, kidney, heart, and brain. Test samples consisted of 95 organs from two genetically different strains of female guinea pigs (C4-deficient and Albany) with different susceptibilities to cutaneous infection by T. pallidum and 195 organs from their asymptomatic offspring. Twenty organs from dams of both strains injected with heat-killed T. pallidum and 19 organs from their progeny served as negative controls. The infections of mothers and neonates were documented by PCR, RIT, and serology. Though any of the organs tested could be infected, there was a spirochetal predilection for some anatomical locations, such as the lymph nodes, heart, and brain, regardless of the strain, route of maternal infection, and age. None of the 49 organs collected from control animals were positive by PCR. In infected C4-deficient dams, one to four organs were positive by PCR, whereas the organs of 7 of their 27 (25%) asymptomatic offspring were treponemal DNA negative, despite evidence of immunoglobulin M treponemal antibodies. Comparative analysis done by both PCR and RIT on a limited number of samples showed 90% agreement between results. An examination of multiple samples obtained from single organs demonstrated that even within 24 h of spirochetemia, when most organs appeared to be infected, not all samples from an individual organ were positive by PCR. A specific immunological response in guinea pigs with congenital syphilis was a more consistent parameter of vertical transmission than was an analysis of T. pallidum DNA. PMID:8757850

  2. Efficacy of the investigational echinocandin ASP9726 in a guinea pig model of invasive pulmonary aspergillosis.

    PubMed

    Wiederhold, Nathan P; Najvar, Laura K; Matsumoto, Satoru; Bocanegra, Rosie A; Herrera, Monica L; Wickes, Brian L; Kirkpatrick, William R; Patterson, Thomas F

    2015-05-01

    ASP9726 is an investigational echinocandin with in vitro activity against Aspergillus species. We evaluated the pharmacokinetics and efficacy of this agent in an established guinea pig model of invasive pulmonary aspergillosis. ASP9726 plasma concentrations were measured in guinea pigs administered either a single dose or multiple doses of this agent at 2.5, 5, and 10 mg/kg of body weight/day by subcutaneous injection. Immunosuppressed guinea pigs were inoculated with A. fumigatus AF293, and ASP9726 (2.5, 5, and 10 mg/kg/day), voriconazole (10 mg/kg by oral gavage twice daily), or caspofungin (3 mg/kg/day by intraperitoneal injection) was administered for 8 days. Changes in fungal burden were measured by enumerating CFU and by quantitative PCR of specimens from within the lungs, as well as by analysis of serum (1 → 3)-β-D-glucan and galactomannan. Lung histopathology was also evaluated. ASP9726 plasma concentrations increased in a dose-proportional manner, and the drug was well tolerated at each dose. Each dose of ASP9726, voriconazole, and caspofungin significantly reduced pulmonary fungal burden as measured by quantitative PCR and by determining (1 → 3)-β-D-glucan and galactomannan levels, but only voriconazole significantly reduced numbers of CFU. ASP9726 at 5 mg/kg also significantly improved survival. Histopathology demonstrated morphological changes in hyphae in animals exposed to ASP9726 and caspofungin, consistent with the activities of the echinocandins. These results suggest that ASP9726 may be efficacious for the treatment of invasive pulmonary aspergillosis. PMID:25753643

  3. Human umbilical cord mesenchymal stem cells alleviate nasal mucosa radiation damage in a guinea pig model.

    PubMed

    Duan, Hong-Gang; Ji, Fang; Zheng, Chun-Quan; Wang, Chun-Hua; Li, Jing

    2015-02-01

    Nasal complications after radiotherapy severely affect the quality of life of nasopharyngeal carcinoma patients, and there is a compelling need to find novel therapies for nasal epithelial cell radiation damage. Therefore, we investigated the therapeutic effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) in guinea pig model of nasal mucosa radiation damage and explored its therapeutic mechanism. Cultured hUC-MSCs were injected intravenously immediately after radiation in the nasal mucosa-radiation-damage guinea pig model. Migration of hUC-MSCs into the nasal mucosa and the potential for differentiation into nasal epithelial cells were evaluated by immunofluorescence. The therapeutic effects of hUC-MSCs were evaluated by mucus clearance time (MCT), degree of nasal mucosa edema, and the nasal mucosa cilia form and coverage ratio. Results indicate that the hUC-MSCs migrated to the nasal mucosa lamina propria and did not differentiate into nasal epithelial cells in this model. The MCT and degree of mucosal edema were improved at 1 week and 1 month after radiation, respectively, but no difference was found at 3 months and 6 months after radiation. The nasal mucosa cilia form and coverage ratio was not improved 6 months after radiation. Thus, hUC-MSCs can migrate to the nasal mucosa lamina propria and improve MCT and mucosa edema within a short time period, but these cells are unable to differentiate into nasal epithelial cells and improve nasal epithelial regeneration in the nasal mucosa radiation damage guinea pig model. PMID:25209829

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

    PubMed

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

    2016-01-01

    Chemical warfare nerve agents (CWNAs) are known to cause behavioral abnormalities in cases of human exposures and in animal models. The behavioral consequences of single exposures to CWNAs that cause observable toxic signs are particularly well characterized in animals; however, less is known regarding repeated smaller exposures that may or may not cause observable toxic signs. In the current study, guinea pigs were exposed to fractions (0.1, 0.2, or 0.4) of a medial lethal dose (LD50) of sarin, soman, or VX for two weeks. On each exposure day, and for a post-exposure period, acoustic startle response (ASR) was measured in each animal. Although relatively few studies use guinea pigs to measure behavior, this species is ideal for CWNA-related experiments because their levels of carboxylesterases closely mimic those of humans, unlike rats or mice. Results showed that the 0.4 LD50 doses of soman and VX transiently increased peak startle amplitude by the second week of injections, with amplitude returning to baseline by the second week post-exposure. Sarin also increased peak startle amplitude independent of week. Latencies to peak startle and PPI were affected by agent exposure but not consistently among the three agents. Most of the changes in startle responses returned to baseline following the cessation of exposures. These data suggest that doses of CWNAs not known to produce observable toxic signs in guinea pigs can affect behavior in the ASR paradigm. Further, these deficits are transient and usually return to baseline shortly after the end of a two-week exposure period. PMID:26829110

  5. Acrylamide-induced prenatal programming of intestine structure in guinea pig.

    PubMed

    Tomaszewska, E; Dobrowolski, P; Puzio, I; Prost, L; Kurlak, P; Sawczuk, P; Badzian, B; Hulas-Stasiak, M; Kostro, K

    2014-02-01

    Potential effects of prenatal administration of acrylamide (ACR) on postnatal development of the small intestine were not examined experimentally yet. The aim of this study was to establish changes of morphological parameters of the small intestine damaged by prenatal action of ACR in guinea pigs. The 3 mg/kg body weight of ACR was given in drinking water every day during the last 35 days of the pregnancy in guinea pigs. The histomorphometry of the duodenum and jejunum was determined. Immunohistochemical staining with anti cadherin antibody was performed. Maternal treatment with ACR led to the decrease of the expression of cadherin in the epithelium. Maternal ACR treatment increased the number of total, divided and inactive crypt, and the number of damaged villi in the duodenum and jejunum of newborn guinea pigs. The thickness of myenteron and submucosa, mucosa fractal dimension and the depth of crypts in the duodenum were increased by ACR. Additionally, in offspring born by mothers administered with ACR the decrease of villi epithelium thickness and active crypt number was observed. Moreover, ACR decreased goblet cells and inact villi number in the duodenum, mucosa thickness and crypts width in the jejunum. Intestine absorptive surface was affected by ACR in the jejunum as well. Results of measurements showed that maternal ACR treatment had negative influence on small intestine histomorphometry. ACR acting prenatally influenced small intestine nervous plexuses that became enlarged by 2.5 times compared with the control group. In conclusion, our results showed the negative impact of maternal ACR treatment on histological structure, integrity and innervation of small intestine wall as well as on absorptive function of small intestine mucosa. PMID:24622835

  6. Potent Rifamycin-Sparing Regimen Cures Guinea Pig Tuberculosis as Rapidly as the Standard Regimen

    PubMed Central

    Dutta, Noton K.; Alsultan, Abdullah; Gniadek, Thomas J.; Belchis, Deborah A.; Pinn, Michael L.; Mdluli, Khisimuzi E.; Nuermberger, Eric L.; Peloquin, Charles A.

    2013-01-01

    Strategies involving new drug combinations, as well as new uses of existing drugs, are urgently needed to reduce the time required to cure patients with drug-sensitive or multidrug-resistant (MDR) tuberculosis (TB). We compared the sterilizing activity of the standard first-line antitubercular regimen, rifampin-isoniazid-pyrazinamide (RHZ), with that of the novel regimen PA-824–moxifloxacin–pyrazinamide (PaMZ), which is currently being studied in clinical trials (NCT01498419), in the guinea pig model of chronic TB infection, in which animals develop necrotic granulomas histologically resembling their human counterparts. Guinea pigs were aerosol infected with ∼2 log10 bacilli of wild-type Mycobacterium tuberculosis H37Rv, and antibiotic treatment was initiated 6 weeks after infection. Separate groups of animals received RHZ, PaMZ, or single or two-drug components of the latter regimen administered at human-equivalent doses 5 days/week for a total of 8 weeks. Relapse rates were assessed 3 months after discontinuation of treatment to determine the sterilizing activity of each combination regimen. PaMZ given at human-equivalent doses was safe and well tolerated for the entire treatment period and rendered guinea pig lungs culture negative more rapidly than RHZ did. After 1 month of treatment, 80% and 50% of animals in the RHZ and PaMZ groups, respectively, had lung culture-positive relapse. Both combination regimens prevented microbiological relapse when administered for a total of 2 months. Our data support the use of PaMZ as a novel isoniazid- and rifamycin-sparing regimen suitable for treatment of both drug-sensitive TB and MDR-TB. PMID:23733473

  7. Maternal Vitamin C Deficiency during Pregnancy Persistently Impairs Hippocampal Neurogenesis in Offspring of Guinea Pigs

    PubMed Central

    Tveden-Nyborg, Pernille; Vogt, Lucile; Schjoldager, Janne G.; Jeannet, Natalie; Hasselholt, Stine; Paidi, Maya D.

    2012-01-01

    While having the highest vitamin C (VitC) concentrations in the body, specific functions of VitC in the brain have only recently been acknowledged. We have shown that postnatal VitC deficiency in guinea pigs causes impairment of hippocampal memory function and leads to 30% less neurons. This study investigates how prenatal VitC deficiency affects postnatal hippocampal development and if any such effect can be reversed by postnatal VitC repletion. Eighty pregnant Dunkin Hartley guinea pig dams were randomized into weight stratified groups receiving High (900 mg) or Low (100 mg) VitC per kg diet. Newborn pups (n = 157) were randomized into a total of four postnatal feeding regimens: High/High (Control); High/Low (Depleted), Low/Low (Deficient); and Low/High (Repleted). Proliferation and migration of newborn cells in the dentate gyrus was assessed by BrdU labeling and hippocampal volumes were determined by stereology. Prenatal VitC deficiency resulted in a significant reduction in postnatal hippocampal volume (P<0.001) which was not reversed by postnatal repletion. There was no difference in postnatal cellular proliferation and survival rates in the hippocampus between dietary groups, however, migration of newborn cells into the granular layer of the hippocampus dentate gyrus was significantly reduced in prenatally deficient animals (P<0.01). We conclude that a prenatal VitC deficiency in guinea pigs leads to persistent impairment of postnatal hippocampal development which is not alleviated by postnatal repletion. Our findings place attention on a yet unrecognized consequence of marginal VitC deficiency during pregnancy. PMID:23119033

  8. Mast cell mediators in citric acid-induced airway constriction of guinea pigs

    SciTech Connect

    Lin, C.-H.; Lai, Y.-L. . E-mail: tiger@ha.mc.ntu.edu.tw

    2005-08-15

    We demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. In this study, we further investigated the underlying mediator(s) for this type of airway constriction. At first, to examine effects caused by blocking agents, 67 young Hartley guinea pigs were divided into 7 groups: saline + CA; methysergide (serotonin receptor antagonist) + CA; MK-886 (leukotriene synthesis inhibitor) + CA; mepyramine (histamine H{sub 1} receptor antagonist) + CA; indomethacin (cyclooxygenase inhibitor) + CA; cromolyn sodium (mast cell stabilizer) + CA; and compound 48/80 (mast cell degranulating agent) + CA. Then, we tested whether leukotriene C{sub 4} (LTC{sub 4}) or histamine enhances CA-induced airway constriction in compound 48/80-pretreated guinea pigs. We measured dynamic respiratory compliance (Crs) and forced expiratory volume in 0.1 s (FEV{sub 0.1}) during either baseline or recovery period. In addition, we detected histamine level, an index of pulmonary mast cell degranulation, in bronchoalveolar lavage (BAL) samples. Citric acid aerosol inhalation caused decreases in Crs and FEV{sub 0.1}, indicating airway constriction in the control group. This airway constriction was significantly attenuated by MK-886, mepyramine, cromolyn sodium, and compound 48/80, but not by either methysergide or indomethacin. Both LTC{sub 4} and histamine infusion significantly increased the magnitude of CA-induced airway constriction in compound 48/80-pretreated guinea pigs. Citric acid inhalation caused significant increase in histamine level in the BAL sample, which was significantly suppressed by compound 48/80. These results suggest that leukotrienes and histamine originating from mast cells play an important role in CA inhalation-induced noncholinergic airway constriction.

  9. Immediate post-dosing paralysis following severe soman and VX toxicosis in guinea pigs.

    PubMed

    Bide, R W; Schofield, L; Risk, D J

    2005-01-01

    There have been numerous studies of the central nervous system (CNS) involvement in organophosphate (OP) poisoning showing status epilepticus and/or 'electrographic seizures'. Brain damage has been demonstrated as 'neuronal necrosis' primarily in the cortex, thalamus and hippocampus. To the authors' knowledge there have been no reports of partial/total paralysis following close upon OP exposure although delayed paralysis has been reported. This report summarizes the immediate, OP induced paralytic events recorded in guinea pigs during development of the Canadian reactive skin decontaminant lotion (RSDL). As part of the development work, supra-lethal cutaneous doses of OP were applied to large numbers of guinea pigs followed by decontamination with the RSDL or predecessor lotions and solvents. Soman (pinacolyl methylphosphonofluoridate; GD) challenges were applied to 1277 animals and S-(2-diisopropyl-aminoethyl) methylphosphorothiolate (VX) challenges to 108. The classic sequence of clinical signs--ptyalism, tremors, fasciculations, convulsions, apnea and flaccid paralysis before death--was seen in the 658 animals that died and in many of the survivors. Eighty-four of 688 survivors of GD and 4 of 39 survivors of VX showed random paralysis of various distal regions following recovery from an insult which produced convulsions and/or flaccid paralysis. Because the experiments were designed to assess the decontamination procedures, there were no apparent relationships between the amounts of OP applied and the sequellae recorded. The observations of paralysis were also incidental to the prime focus of the experiments. Because of this, only ten animals paralysed following GD exposure were examined for histological effects. The pathologist diagnosed 'encephalomalacia' and 'focal necrotic lesions' in the cerebral cortex and 'focal necrotic lesions' in one spinal cord. Of the 84 guinea pigs paralysed after GD challenge, one was not decontaminated and the decontaminants used

  10. Efficacy of the Investigational Echinocandin ASP9726 in a Guinea Pig Model of Invasive Pulmonary Aspergillosis

    PubMed Central

    Najvar, Laura K.; Matsumoto, Satoru; Bocanegra, Rosie A.; Herrera, Monica L.; Wickes, Brian L.; Kirkpatrick, William R.; Patterson, Thomas F.

    2015-01-01

    ASP9726 is an investigational echinocandin with in vitro activity against Aspergillus species. We evaluated the pharmacokinetics and efficacy of this agent in an established guinea pig model of invasive pulmonary aspergillosis. ASP9726 plasma concentrations were measured in guinea pigs administered either a single dose or multiple doses of this agent at 2.5, 5, and 10 mg/kg of body weight/day by subcutaneous injection. Immunosuppressed guinea pigs were inoculated with A. fumigatus AF293, and ASP9726 (2.5, 5, and 10 mg/kg/day), voriconazole (10 mg/kg by oral gavage twice daily), or caspofungin (3 mg/kg/day by intraperitoneal injection) was administered for 8 days. Changes in fungal burden were measured by enumerating CFU and by quantitative PCR of specimens from within the lungs, as well as by analysis of serum (1→3)-β-d-glucan and galactomannan. Lung histopathology was also evaluated. ASP9726 plasma concentrations increased in a dose-proportional manner, and the drug was well tolerated at each dose. Each dose of ASP9726, voriconazole, and caspofungin significantly reduced pulmonary fungal burden as measured by quantitative PCR and by determining (1→3)-β-d-glucan and galactomannan levels, but only voriconazole significantly reduced numbers of CFU. ASP9726 at 5 mg/kg also significantly improved survival. Histopathology demonstrated morphological changes in hyphae in animals exposed to ASP9726 and caspofungin, consistent with the activities of the echinocandins. These results suggest that ASP9726 may be efficacious for the treatment of invasive pulmonary aspergillosis. PMID:25753643

  11. Acute respiratory toxicity following inhalation exposure to soman in guinea pigs

    SciTech Connect

    Perkins, Michael W.; Pierre, Zdenka; Rezk, Peter; Sabnekar, Praveena; Sciuto, Alfred M.; Nambiar, Madhusoodana P.

    2010-06-01

    Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m{sup 3} concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m{sup 3} soman survived, while animals exposed to 841, and 1121 mg/m{sup 3} resulted in 38% and 13% survival, respectively. The microinstillation inhalation exposure LCt{sub 50} for soman determined by probit analysis was 827.2 mg/m{sup 3}. A majority of the animals that died at 1121 mg/m{sup 3} developed seizures and died within 15-30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5-6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24 h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs.

  12. Arachidonic acid metabolites do not mediate toluene diisocyanate-induced airway hyperresponsiveness in guinea pigs

    SciTech Connect

    Gordon, T.; Thompson, J.E.; Sheppard, D.

    1988-05-01

    Arachidonic acid metabolites have previously been demonstrated to mediate the airway hyperresponsiveness observed in guinea pigs and dogs after exposure to ozone. Guinea pigs were treated with indomethacin (a cyclooxygenase inhibitor), U-60,257 (piriprost, a 5-lipoxygenase inhibitor), or BW775c (a lipoxygenase and cyclooxygenase inhibitor) and exposed to air or 3 ppm TDI. Airway responsiveness to acetylcholine aerosol was examined 2 h after exposure. In control animals, the provocative concentration of acetylcholine which caused a 200% increase in pulmonary resistance over baseline (PC200) was significantly less (p less than 0.05) after exposure to TDI (8.6 +/- 2.0 mg/ml, geometric mean + geometric SE, n = 10) than after exposure to air (23.9 + 2.5 mg/ml, n = 14). The airway responsiveness to acetylcholine in animals treated with indomethacin or piriprost and exposed to TDI was not different from that of control animals exposed to TDI. Treatment with BW755c enhanced the airway hyperresponsiveness observed in animals exposed to TDI without altering the PC200 of animals exposed to air. The PC200 of animals treated with BW755c and exposed to TDI (2.3 + 0.8 mg/ml, n = 8) was significantly lower than the PC200 of control animals exposed to TDI (p less than 0.025). These results suggest that products of arachidonic acid metabolism are not responsible for TDI-induced airway hyperresponsiveness in guinea pigs. BW755c, however, appears to potentiate the TDI-induced airway hyperresponsiveness to acetylcholine by an as yet unidentified mechanism.

  13. Role of transient receptor potential ankyrin 1 in gastric accommodation in conscious guinea pigs.

    PubMed

    Koseki, Junichi; Oshima, Tadayuki; Kondo, Takashi; Tomita, Toshihiko; Fukui, Hirokazu; Watari, Jiro; Hattori, Tomohisa; Kase, Yoshio; Miwa, Hiroto

    2012-04-01

    We report the establishment of a new model for measuring gastric tone and liquid meal-induced accommodation in conscious guinea pigs and the role played by transient receptor potential ankyrin 1 (TRPA1). An indwelling polyethylene bag was placed in proximal stomachs of 5-week-old male Hartley guinea pigs. Gastric tone was measured by distending the bag and recording changes in intrabag pressure at various volumes. Gastric accommodation was measured by administering liquid meals and recording intrabag pressure over time. N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME) (a nitric-oxide synthase inhibitor), atropine sulfate (atropine) (a muscarinic receptor antagonist), allyl isothiocyanate (AITC) (a TRPA1 agonist), or theophylline-7-(N-4-isopropylphenyl) acetamide (HC-030031) (a selective TRPA1 antagonist) was administered 15 to 60 min before measurement. Gastric tone was increased by stepwise distension of the bag and was further significantly increased by L-NAME and significantly decreased by atropine. A liquid meal (15% w/v; 1.7 kcal) significantly decreased intrabag pressure 5 to 20 min after administration, indicating gastric accommodation; this was completely suppressed by L-NAME and further enhanced by atropine. AITC significantly increased gastric tone; this increase was decreased by HC-030031 and atropine. A combination of AITC and L-NAME significantly increased gastric tone compared with L-NAME alone. HC-030031 alone significantly decreased gastric tone. Liquid meal-induced gastric accommodation was significantly suppressed by pretreatment with AITC. We established a new model for measuring gastric tone and accommodation in conscious guinea pigs. TRPA1 activation suppresses gastric accommodation by increasing gastric tone through cholinergic neuronal pathways. PMID:22262922

  14. Immediate inhibitory effect of methylprednisolone suleptanate (U-67590A) on antigen-induced cutaneous and airway anaphylactic responses in guinea-pigs.

    PubMed Central

    Hashimoto, M.; Shinozaki, Y.; Katori, M.

    1993-01-01

    1. Inhibitory effects of water-soluble glucocorticoids administered intravenously were examined on skin and airway reactions caused by antigen challenge or chemical mediators in guinea-pigs. 2. Methylprednisolone suleptanate (U-67590A) which is an analogue of methylprednisolone, produced immediate inhibition of 3-h and 7-day homologous passive cutaneous anaphylaxis (PCA) reactions, but not of histamine- or bradykinin-induced cutaneous vascular permeability, when administered 10 min before antigen challenge. In contrast, methylprednisolone succinate (MP) or dexamethasone (DXM) administered 10 min before antigen challenge failed to show an immediate inhibitory effect on the PCA or mediator-induced reactions. When administered 1 to 5 h before antigen challenge, all the steroids used in this study reduced both PCA and mediator-induced reactions. 3. Pretreatment with cycloheximide almost completely abolished the late inhibition of 3-h PCA and histamine reactions produced by U-67590A or MP, but it did not affect the immediate inhibition of 3-h PCA produced by U-67590A. 4. U-67590A also demonstrated immediate inhibitory effects on antigen-induced bronchoconstriction in guinea-pigs actively sensitized with ovalbumin even when administered 10 min before antigen challenge, whereas MP and DXM failed to show the immediate inhibitory effect. When administered 3 h before antigen challenge, all the steroids used in this study reduced the response to antigen. 5. The late inhibitory effect of U-67590A administered 3 h before antigen challenge was almost completely abolished by treatment with cycloheximide or 17 alpha-methyltestosterone, whereas the immediate inhibition produced by U-67590A administered 10 min before challenge was not affected by this treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7682130

  15. Identification of both NK1 and NK2 receptors in guinea-pig airways.

    PubMed Central

    McKee, K. T.; Millar, L.; Rodger, I. W.; Metters, K. M.

    1993-01-01

    1. NK1 and NK2 receptors have been characterized in guinea-pig lung membrane preparations by use of [125I-Tyr8]-substance P and [125I]-neurokinin A binding assays in conjunction with tachykinin-receptor selective agonists ([Sar9Met(O2)11]substance P for NK1 and [beta Ala8]neurokinin A (4-10) for NK2) and antagonists (CP-99,994 for NK1 and SR48968 for NK2). 2. The presence of high affinity, G-protein-coupled NK1 receptors in guinea-pig lung parenchymal membranes has been confirmed. The rank order of affinity for competing tachykinins was as predicted for an NK1 receptor: substance P = [Sar9Met(O2)11]substance P > substance P-methyl ester = physalaemin > neurokinin A = neurokinin B >> [beta Ala8]neurokinin A (4-10). The novel NK1 antagonist CP-99,994 has a Ki of 0.4 nM at this NK1 site. 3. In order to characterize [125I]-neurokinin A binding to guinea-pig lung, the number of [125I]-neurokinin A specific binding sites was increased 3-4 fold by purification of the parenchymal membranes over discontinuous sucrose gradients. The rank order of affinity determined for NK1- and NK2-receptor agonists and antagonists in competition for these sites showed that the majority (80%) of [125I]-neurokinin A specific binding was also to the NK1 receptor. 4. Under conditions where the guinea-pig lung parenchymal NK1 receptor was fully occupied by a saturating concentration of either [Sar9Met(O2)11]substance P (1 microM) or CP-99,994 (2.7 microM), residual [125I]-neurokinin A specific binding was inhibited in a concentration-dependent manner by both [beta Ala8]neurokinin A and SR48968. This result shows that the NK2 receptor is also present in these preparations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7694756

  16. Experimental joint immobilization in guinea pigs. Effects on the knee joint

    NASA Technical Reports Server (NTRS)

    Marcondesdesouza, J. P.; Machado, F. F.; Sesso, A.; Valeri, V.

    1980-01-01

    In young and adult guinea pigs, the aftermath experimentally induced by the immobilization of the knee joint in hyperextended forced position was studied. Joint immobilization which varied from one to nine weeks was attained by plaster. Eighty knee joints were examined macro and microscopically. Findings included: (1) muscular hypotrophy and joint stiffness in all animals, directly proportional to the length of immobilization; (2) haemoarthrosis in the first week; (3) intra-articular fibrous tissue proliferation ending up with fibrous ankylosis; (4) hyaline articular cartilage erosions; (5) various degrees of destructive menisci changes. A tentative explanation of the fibrous tissue proliferation and of the cartilage changes is offered.

  17. Effect of calcitonin pretreatment on naturally occurring intervertebral disc degeneration in guinea pig

    PubMed Central

    Jiang, Xiaohua; Tian, Faming; Wang, Wenya; Yan, Jinyin; Liu, Huanjiang; Liu, Binbin; Song, Huiping; Zhang, Yingze; Shen, Yong; Zhang, Liu

    2015-01-01

    Introduction: Our previous study suggested protective effects of calcitonin (CT) on experimental osteoarthritis. The aim of the present study was to provide evidence of whether CT pretreatment could prevent naturally occurring intervertebral disc degeneration in guinea pigs. Methods: Forty-two 3 months old female guinea pigs were randomly assigned into 2 groups as follows: Twenty-four were treated by normal saline as control group and sacrificed at 3, 6, 9 and 12 months of age (6 animals at each time point), the other 18 were received salmon CT (8 ug/kg/day, everyday) treatment at 3 months of age and sacrificed at the age of 6, 9 and 12 months respectively. Van Gieson stain and the histological score were used to identify the histological changes of the lumbar intervertebral discs. The disc height and vertebral body height were measured. Immunohistochemistry measurements for glycosaminoglycan, type II collagen, and matrix metalloprotease (MMP)-1 expressions were performed. Bone quality and microstructural changes in the L3-6 lumbar vertebral bodies were assessed by bone mineral density (BMD), micro-CT analysis and biomechanical testing. Results: Histological analysis indicated significantly higher disc degeneration scores in 9-month-old guinea pigs in comparison with younger animals, and grew higher with increasing age. CT treatment significantly reduced the histological score, and increased the disc height and the ratio to vertebral body height in 12 months old animals, as well as upregulated the glycosaminoglycan, type II collagen and inhibited the MMP-1 expression. Micro-CT analysis showed decreased percent bone volume (BV/TV) and increased trabecular separation (Tb.Sp), structural model index (SMI) in 12 months old animals in comparison with the younger animals. Markedly increased BV/TV and decreased Tb.Sp were observed in CT treated animals when compared with control animals. The biomechanical properties including maximum load, maximum stress, yield stress and

  18. Carrageenan-induced ulceration of the large intestine in the guinea pig.

    PubMed

    Watt, J; Marcus, R

    1971-02-01

    A 5% aqueous solution of degraded carrageenan derived from the red seaweed Eucheuma spinosum was fed to guinea pigs in their drinking water over a period of 20-45 days. Occult blood in the faeces and multiple ulcers in the caecum, colon and rectum occurred in 100% of animals by the 30th day. The clinical and pathological features bear a close resemblance to human ulcerative colitis. The method provides a simple experimental model for the study of various aspects of the pathology of ulcerative lesions in the large intestine as well as the effects of therapeutic agents. PMID:5548564

  19. Regulation of apolipoprotein B-containing lipoproteins by dietary soluble fiber in guinea pigs.

    PubMed

    Fernandez, M L; Vergara-Jimenez, M; Conde, K; Behr, T; Abdel-Fattah, G

    1997-03-01

    Dietary soluble-fiber sources such as pectin, guar gum, or psyllium decrease plasma concentrations of low-density-lipoprotein (LDL) cholesterol in guinea pigs by distinct mechanisms, including increases in LDL apolipoprotein (apo) B turnover and/or decreases in LDL apo B flux (J Lipid Res 1995; 36:2394-404). The present studies were undertaken to test whether changes in the rates of very-low-density lipoprotein (VLDL) apo B secretion, VLDL conversion to LDL, and hepatic uptake of VLDL were related to the cholesterol-lowering actions of these soluble fibers. Guinea pigs were fed (by wt) 12.5% pectin, 12.5% guar gum, 7.5% psyllium, or a control diet containing cellulose as the fiber source. Plasma cholesterol concentrations were significantly lower in guinea pigs fed pectin, guar gum, and psyllium by 42%, 46%, and 35%, respectively (P < 0.001), compared with those animals fed the control diet, whereas plasma triacylglycerol concentrations were lower only with guar gum intake. The secretion rate of triacylglycerol, determined after Triton was injected to block VLDL catabolism, was not different among dietary treatment groups whereas the secretion rate of apo B was lower with pectin, guar gum, and psyllium intakes (P < 0.01). In addition, pectin, guar gum, and psyllium significantly altered the composition of newly secreted VLDLs by increasing the number of triacylglycerol and phospholipid molecules in the secreted lipoprotein, indicating the presence of larger nascent VLDLs. In contrast, the average particle diameter of mature VLDLs as determined by electron microscopy was smaller in the dietary soluble-fiber groups in the following order: pectin < psyllium < guar gum. Plasma lecithin-cholesteryl acyltransferase and cholesteryl ester transfer protein activities were lower with intake of pectin, guar gum, and psyllium (P < 0.01). Injection of radiolabeled lipoproteins indicated that pectin, guar gum, and psyllium intakes resulted in more rapid VLDL and LDL apo B

  20. Electron microscopic study on the interaction between normal guinea pig peritoneal macrophages and Coxiella burnetii.

    PubMed Central

    Kishimoto, R A; Veltri, B J; Canonico, P G; Shirey, F G; Walker, J S

    1976-01-01

    An electron microscopic study was conducted to explore the interaction between normal guinea pig peritoneal macrophages and phase I and II Coxeilla burnetii previously treated with either normal or immune serum. A comparison was made on the efficiency of phagocytosis and subsequent killing of rickettsiae by macrophages. Both phases of rickettsiae previously treated with normal serum multiplied within phagosomes after phagocytosis with resultant destruction of macrophages. In contrast, suspending rickettsiae in immune serum rendered them more susceptible to phagocytosis and potentiated their destruction within macrophages. Images PMID:825466

  1. Effects of butenafine hydrochloride, a new benzylamine derivative, on experimental tinea pedis in guinea pigs.

    PubMed Central

    Arika, T; Yokoo, M; Maeda, T; Amemiya, K; Yamaguchi, H

    1990-01-01

    Butenafine is a new antifungal benzylamine. The efficacy of butenafine was investigated in an experimental tinea pedis model in guinea pigs, which is pathologically similar to natural infections in humans. Butenafine (0.1 ml) in 0.2 to 1.0% solutions was applied to the site of infection. Treatment was started on day 10 postinfection and was continued for 20 days. Butenafine applied once daily exhibited excellent dose-related therapeutic efficacy. The efficacy of butenafine was significantly superior to those tolnaftate, clotrimazole, and bifonazole. PMID:2073117

  2. Effects of butenafine hydrochloride, a new benzylamine derivative, on experimental tinea pedis in guinea pigs.

    PubMed

    Arika, T; Yokoo, M; Maeda, T; Amemiya, K; Yamaguchi, H

    1990-11-01

    Butenafine is a new antifungal benzylamine. The efficacy of butenafine was investigated in an experimental tinea pedis model in guinea pigs, which is pathologically similar to natural infections in humans. Butenafine (0.1 ml) in 0.2 to 1.0% solutions was applied to the site of infection. Treatment was started on day 10 postinfection and was continued for 20 days. Butenafine applied once daily exhibited excellent dose-related therapeutic efficacy. The efficacy of butenafine was significantly superior to those tolnaftate, clotrimazole, and bifonazole. PMID:2073117

  3. Effects of acute ozone exposure on the electrophysiological properties of guinea pig trachea

    SciTech Connect

    Croxton, T.L.; Takahashi, Masahiko; Kokia, Ira

    1994-12-31

    Acute ozone (O{sub 3}) exposures produce an increase in the apparent permeability of the tracheal epithelium, but the mechanism of this response is poorly understood. Comparison of previous studies suggests that qualitative differences may exist between measurements made in vivo or in vitro. To test this possibility we used both in vitro and in vivo electrophysiological techniques to investigate the effects of O{sub 3} exposure on guinea pig tracheal epithelium. Male Hartley guinea pigs were exposed to either 1 or 2 ppm O{sub 3} or to filtered air for 3 h and were studied 0, 6, or 24 h after exposure. Air-exposed animals had in vitro mean tracheal potential (V{sub T}) -32.0 {+-} 1.5 mV, conductance (G{sub T}{sup L}) 2.18 {+-} 0.22 mS/cm, short-circuit current (I{sub SC}{sup L}) 62.6 {+-} 3.7 {mu}A/cm, and diameter (D) 2.44 {+-} 0.10 mm. In vitro properties after 1 ppm O{sub 3} exposure did not differ at any time point from control. Two parts per million O{sub 3} increased I{sub SC}{sup L}, but only at 6 h postexposure. The effect of O{sub 3} on I{sub SC}{sup L} was abolished by amiloride. There were no significant changes in V{sub T}, G{sub T}{sup L}, or D. In vivo tracheal potential under pentobarbital anesthesia was -19.7 {+-} 1.7 mV. At 6 h postexposure to 2 ppm O{sub 3}, but not at 0 or 24 h, in vivo V{sub I} was increased. Thus, acute exposure of guinea pigs to a high concentration of O{sub 3} caused a delayed increase in Na{sup +} absorption by the trachea with no change in conductance. This indicates that paracellular permeability of guinea pig tracheal epithelium was not substantially increased by acute O{sub 3} and suggests that enhanced macromolecular uptake in this species probably occurs transcellularly. 24 refs., 1 fig., 2 tabs.

  4. The interaction of triethyltin with a component of guinea-pig liver supernatant. Evidence for histidine in the binding sites

    PubMed Central

    Rose, M. S.; Lock, E. A.

    1970-01-01

    A protein fraction was isolated from guinea-pig liver that binds triethyltin with an affinity of approx. 2×106m−1 at pH8.0. It was shown that the protein responsible for binding 70% of the triethyltin found in guinea-pig liver after injection of radioactively labelled triethyltin is at most a few per cent of the total liver protein. Evidence is presented from the kinetics of loss of binding and loss of certain amino acids on photo-oxidation with either Methylene Blue or Rose Bengal that each binding site consists of two histidine residues. PMID:5494221

  5. Comparison of Serum Protection Tests in Guinea-pigs and Mice for Foot-and-Mouth Disease Antibody Evaluation

    PubMed Central

    Cunha, Raymundo G.

    1963-01-01

    A comparison of serum protection tests carried out in guinea-pigs, young adult mice and suckling mice for evaluation of foot-and-mouth disease antibody is described in this paper. The results indicate that the test performed in young adult mice is the most accurate and consistent. The dose of serum giving the 50 per cent lesion score end-point in guinea-pigs is about 45 and 170 times larger than that giving 50 per cent protection to suckling mice and to young adult mice, respectively. PMID:17649423

  6. Identification of beta 2-adrenoceptors on guinea pig alveolar macrophages using (-)-3-( sup 125 I)iodocyanopindolol

    SciTech Connect

    Leurs, R.; Beusenberg, F.D.; Bast, A.; Van Amsterdam, J.G.; Timmerman, H. )

    1990-08-01

    The beta-adrenoceptor antagonist (-)-3-({sup 125}I)iodocyanopindolol (({sup 125}I)ICYP) binds with high affinity and in saturable way to membranes of guinea pig alveolar macrophages. The equilibrium dissociation constant for ({sup 125}I)ICYP is 24.3 +/- 1.2 pM, and the number of binding sites is 166.3 +/- 13.7 fmol/mg protein (N = 4, +/- SEM). Displacement studies with selective antagonists showed that ({sup 125}I)ICYP labels beta 2-adrenoceptors on guinea pig alveolar macrophages.

  7. PDMS Elastic Micropost Arrays for Studying Vascular Smooth Muscle Cells

    PubMed Central

    Cheng, Qi; Sun, Zhe; Meininger, Gerald; Almasri, Mahmoud

    2015-01-01

    This paper describes the design, modeling, fabrication and characterization of a micromachined array of high-density 3-dimensional microposts (100×100) made of flexible material (silicone elastomers) for use to measure quantitatively the cellular traction force and contractile events in isolated vascular smooth muscle cells (VSMCs). The micropost array was fabricated with diameters ranged from 3 to 10 μm, with edge to edge spacing of 5, 7 and 10 μm, and with a height to diameter aspect ratio up to 10. VSMCs exerted larger basal traction forces when they were grown on stiffer micropost arrays. These basal traction forces were 80% larger in control VSMCs than in VSMCs in which integrin linked kinase (ILK) was knocked down using shRNA. The addition of Angiotensin II (ANGII) led to VSMC contraction as evidenced by an increased traction force exerted on the microposts under the cell. This ANGII induced contractile response and change in traction force on the microposts was not observed in VSMCs lacking ILK. Following treatment of VSMCs with Cytochalasin D to depolymerize the actin cytoskeleton, the VSMCs exhibited relaxation that was apparent as a significant reduction in the measured traction force exerted on microposts under the cell. Overall, this study demonstrates the usefulness of micropost arrays for study of the contractile responsiveness of VSMC and the results indicate that ILK plays a critical role in the signaling pathways leading to the generation of substrate traction force in VSMC. PMID:26451074

  8. Tensile Properties of Contractile and Synthetic Vascular Smooth Muscle Cells

    NASA Astrophysics Data System (ADS)

    Miyazaki, Hiroshi; Hasegawa, Yoshitaka; Hayashi, Kozaburo

    Tensile properties of vascular smooth muscle cells (VSMCs) of synthetic and contractile phenotypes were determined using a newly developed tensile test system. Synthetic and contractile VSMCs were isolated from the rabbit thoracic aorta with an explant and an enzymatic digestion method, respectively. Each cell floated in Hanks' balanced salt solution of 37°C was attached to the fine tips of a pair of micropipettes with a cell adhesive and, then, stretched at the rate of 6µm/sec by moving one of the micropipettes with a linear actuator. Load applied to the cell was measured with a cantilever-type load cell; its elongation was determined from the distance between the micropipette tips using a video dimension analyzer. The synthetic and contractile VSMCs were not broken even at the tensile force of 2.4µN and 3.4µN, respectively. Their stiffness was significantly higher in contractile phenotype (0.17N/m) than in synthetic one (0.09N/m). The different tensile properties between synthetic and contractile cells are attributable to the differences in cytoskeletal structures and contractile apparatus.

  9. Molecular mechanisms of increased vascular smooth muscle contraction in SHR

    SciTech Connect

    Sharma, R.V.; Aqel, M.B.; Butters, C.; McEldoon, J.; Bhalla, R.C.

    1986-03-01

    The isometric tension development and /sup 45/Ca influx in response to NE and methoxamine stimulation were significantly (P < .05) increased in SHR caudal arteries as compared to WKY. Estimation of /sup 3/H-prazosin binding to the membranes isolated from caudal artery of WKY and SHR showed a single class of high affinity binding sites with Kd values: SHR, 128 +/- 14 pM; WKY, 141 +/- 19 pM and the Bmax values; SHR, 108 +/- 14 fmoles/mg protein; WKY, 113 +/- 21 fmoles/mg protein. Nifedipine inhibition of caudal artery contractions in response to NE stimulation was significantly greater (P < .05) in SHR as compared to WKY. On the other hand, there were no differences between WKY and SHR caudal artery rings either in the isometric tension development, /sup 45/Ca influx or nifedipine inhibition in response to K/sup +/-depolarization. Their results indicate that the increased vascular smooth muscle contraction in SHR in response to NE-stimulation may be due to increased Ca/sup 2 +/ influx through the receptor operated Ca/sup 2 +/ channels.

  10. Extracellular calcium sensing in rat aortic vascular smooth muscle cells

    SciTech Connect

    Smajilovic, Sanela; Hansen, Jakob Lerche; Christoffersen, Tue E.H.

    2006-10-06

    Extracellular calcium (Ca2+o) can act as a first messenger in many cell types through a G protein-coupled receptor, calcium-sensing receptor (CaR). It is still debated whether the CaR is expressed in vascular smooth muscle cells (VSMCs). Here, we report the expression of CaR mRNA and protein in rat aortic VSMCs and show that Ca2+o stimulates proliferation of the cells. The effects of Ca2+o were attenuated by pre-treatment with MAPK kinase 1 (MEK1) inhibitor, as well as an allosteric modulator, NPS 2390. Furthermore, stimulation of the VSMCs with Ca2+o-induced phosphorylation of ERK1/2, but surprisingly did not cause inositol phosphate accumulation. We were not able to conclusively state that the CaR mediates Ca2+o-induced cell proliferation. Rather, an additional calcium-sensing mechanism may exist. Our findings may be of importance with regard to atherosclerosis, an inflammatory disease characterized by abnormal proliferation of VSMCs and high local levels of calcium.

  11. Identification of possible adenosine receptors in vascular smooth muscle

    SciTech Connect

    Doctrow, S.R.

    1985-01-01

    Adenosine is a vasodilator and has been implicated in increased blood flow in tissues that undergo energy deficiency. During conditions such as hypoxia and ischemia, adenosine is produced and is said to increase blood flow by relaxing the vascular smooth muscle (VSM) lining the resistance vessels. The goal of this research was to identify receptors that might be responsible for adenosine-mediated VSM relaxation. When an insoluble fraction from calf aortic VSM was incubated with /sup 32/P-ATP, two components were phosphorylated. One was identified as myosin light chain by MW, pl, and immunoprecipitation. The other product was identified as phosphatidylinositol-4-phosphate (DPI) by tic. Both phosphorylations were inhibited by adenosine and by 5'-chloro-5'-deoxyadenosine (Cl-Ado). DPI production was much more sensitive to the nucleosides than was myosin phosphorylation. Neither inhibition involved change in cAMP production. Phosphatidylinositol (Pl) kinase in the VSM membranes required magnesium, was activated and solubilized by Triton X-100, and phosphorylated both endogenous and exogenous Pl. Cl-Ado inhibited Pl kinase in a manner competitive with respect to ATP and noncompetitive with respect to Pl. Adenosine and adenosine analogs modified in the ribose ring were inhibitors with potencies comparable to that of Cl-Ado. Adenine nucleotides and purine-modified adenosine analogs were weaker inhibitors than Cl-Ado.

  12. Vinpocetine suppresses pathological vascular remodeling by inhibiting vascular smooth muscle cell proliferation and migration.

    PubMed

    Cai, Yujun; Knight, Walter E; Guo, Shujie; Li, Jian-Dong; Knight, Peter A; Yan, Chen

    2012-11-01

    Abnormal vascular smooth muscle cell (SMC) activation is associated with various vascular disorders such as atherosclerosis, in-stent restenosis, vein graft disease, and transplantation-associated vasculopathy. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. However, its role in pathological vascular remodeling remains unexplored. Herein, we show that systemic administration of vinpocetine significantly reduced neointimal formation in carotid arteries after ligation injury. Vinpocetine also markedly decreased spontaneous remodeling of human saphenous vein explants in ex vivo culture. In cultured SMCs, vinpocetine dose-dependently suppressed cell proliferation and caused G1-phase cell cycle arrest, which is associated with a decrease in cyclin D1 and an increase in p27Kip1 levels. In addition, vinpocetine dose-dependently inhibited platelet-derived growth factor (PDGF)-stimulated SMC migration as determined by the two-dimensional migration assays and three-dimensional aortic medial explant invasive assay. Moreover, vinpocetine significantly reduced PDGF-induced type I collagen and fibronectin expression. It is noteworthy that PDGF-stimulated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), but not protein kinase B, was specifically inhibited by vinpocetine. Vinpocetine powerfully attenuated intracellular reactive oxidative species (ROS) production, which largely mediates the inhibitory effects of vinpocetine on ERK1/2 activation and SMC growth. Taken together, our results reveal a novel function of vinpocetine in attenuating neointimal hyperplasia and pathological vascular remodeling, at least partially through suppressing ROS production and ERK1/2 activation in SMCs. Given the safety profile of vinpocetine, this study provides insight into the therapeutic potential of vinpocetine in proliferative vascular disorders. PMID:22915768

  13. Vinpocetine Suppresses Pathological Vascular Remodeling by Inhibiting Vascular Smooth Muscle Cell Proliferation and Migration

    PubMed Central

    Cai, Yujun; Knight, Walter E.; Guo, Shujie; Li, Jian-Dong; Knight, Peter A.

    2012-01-01

    Abnormal vascular smooth muscle cell (SMC) activation is associated with various vascular disorders such as atherosclerosis, in-stent restenosis, vein graft disease, and transplantation-associated vasculopathy. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. However, its role in pathological vascular remodeling remains unexplored. Herein, we show that systemic administration of vinpocetine significantly reduced neointimal formation in carotid arteries after ligation injury. Vinpocetine also markedly decreased spontaneous remodeling of human saphenous vein explants in ex vivo culture. In cultured SMCs, vinpocetine dose-dependently suppressed cell proliferation and caused G1-phase cell cycle arrest, which is associated with a decrease in cyclin D1 and an increase in p27Kip1 levels. In addition, vinpocetine dose-dependently inhibited platelet-derived growth factor (PDGF)-stimulated SMC migration as determined by the two-dimensional migration assays and three-dimensional aortic medial explant invasive assay. Moreover, vinpocetine significantly reduced PDGF-induced type I collagen and fibronectin expression. It is noteworthy that PDGF-stimulated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), but not protein kinase B, was specifically inhibited by vinpocetine. Vinpocetine powerfully attenuated intracellular reactive oxidative species (ROS) production, which largely mediates the inhibitory effects of vinpocetine on ERK1/2 activation and SMC growth. Taken together, our results reveal a novel function of vinpocetine in attenuating neointimal hyperplasia and pathological vascular remodeling, at least partially through suppressing ROS production and ERK1/2 activation in SMCs. Given the safety profile of vinpocetine, this study provides insight into the therapeutic potential of vinpocetine in proliferative vascular disorders. PMID:22915768

  14. VPAC1 receptors regulate intestinal secretion and muscle contractility by activating cholinergic neurons in guinea pig jejunum.

    PubMed

    Fung, Candice; Unterweger, Petra; Parry, Laura J; Bornstein, Joel C; Foong, Jaime P P

    2014-05-01

    In the gastrointestinal tract, vasoactive intestinal peptide (VIP) is found exclusively within neurons. VIP regulates intestinal motility via neurally mediated and direct actions on smooth muscle and secretion by a direct mucosal action, and via actions on submucosal neurons. VIP acts via VPAC1 and VPAC2 receptors; however, the subtype involved in its neural actions is unclear. The neural roles of VIP and VPAC1 receptors (VPAC1R) were investigated in intestinal motility and secretion in guinea pig jejunum. Expression of VIP receptors across the jejunal layers was examined using RT-PCR. Submucosal and myenteric neurons expressing VIP receptor subtype VPAC1 and/or various neurochemical markers were identified immunohistochemically. Isotonic muscle contraction was measured in longitudinal muscle-myenteric plexus preparations. Electrogenic secretion across mucosa-submucosa preparations was measured in Ussing chambers by monitoring short-circuit current. Calretinin(+) excitatory longitudinal muscle motor neurons expressed VPAC1R. Most cholinergic submucosal neurons, notably NPY(+) secretomotor neurons, expressed VPAC1R. VIP (100 nM) induced longitudinal muscle contraction that was inhibited by TTX (1 μM), PG97-269 (VPAC1 antagonist; 1 μM), and hyoscine (10 μM), but not by hexamethonium (200 μM). VIP (50 nM)-evoked secretion was depressed by hyoscine or PG97-269 and involved a small TTX-sensitive component. PG97-269 and TTX combined did not further depress the VIP response observed in the presence of PG97-269 alone. We conclude that VIP stimulates ACh-mediated longitudinal muscle contraction via VPAC1R on cholinergic motor neurons. VIP induces Cl(-) secretion directly via epithelial VPAC1R and indirectly via VPAC1R on cholinergic secretomotor neurons. No evidence was obtained for involvement of other neural VIP receptors. PMID:24578344

  15. Functional coupling of TRPV4 channels and BK channels in regulating spontaneous contractions of the guinea pig urinary bladder.

    PubMed

    Isogai, Ayu; Lee, Ken; Mitsui, Retsu; Hashitani, Hikaru

    2016-09-01

    We investigated the role of TRPV4 channels (TRPV4) in regulating the contractility of detrusor smooth muscle (DSM) and muscularis mucosae (MM) of the urinary bladder. Distribution of TRPV4 in DSM and MM of guinea-pig bladders was examined by fluorescence immunohistochemistry. Changes in the contractility of DSM and MM bundles were measured using isometric tension recording. Intracellular Ca(2+) dynamics were visualized by Cal-520 fluorescent Ca(2+) imaging, while membrane potential changes were recorded using intracellular microelectrode technique. DSM and MM expressed TRPV4 immunoreactivity. GSK1016790A (GSK, 1 nM), a TRPV4 agonist, evoked a sustained contraction in both DSM and MM associated with a cessation of spontaneous phasic contractions in a manner sensitive to HC-067047 (10 μM), a TRPV4 antagonist. Iberiotoxin (100 nM) and paxilline (1 μM), large conductance Ca(2+)-activated K(+) (BK) channel blockers restored the spontaneous contractions in GSK. The sustained contractions in DSM and MM were reduced by nifedipine (10 μM), a blocker of L-type voltage-dependent Ca(2+) channels (LVDCCs) by about 40 % and by nominally Ca(2+)-free solution by some 90 %. GSK (1 nM) abolished spontaneous Ca(2+) transients, increased basal Ca(2+) levels and also prevented spontaneous action potential discharge associated with DSM membrane hyperpolarization. In conclusion, Ca(2+) influx through TRPV4 appears to activate BK channels to suppress spontaneous contractions and thus a functional coupling of TRPV4 with BK channels may act as a self-limiting mechanism for bladder contractility during its storage phase. Despite the membrane hyperpolarization in GSK, Ca(2+) entry mainly through TRPV4 develops the tonic contraction. PMID:27497848

  16. Effects of histamine, ethanol, and a detergent on exudation and absorption across guinea pig airway mucosa in vivo.

    PubMed Central

    Greiff, L; Erjefält, I; Wollmer, P; Pipkorn, U; Persson, C G

    1991-01-01

    This study examined effects of three substances that cause mucosal provocation (histamine, ethanol, and the detergent dioctylsodium sulphosuccinate (DOSS] on the flux of solutes across airway vascular mucosal barriers in anaesthetised guinea pigs. The inward flux was assessed as absorption of iodine-131 labelled albumin (MW 69,000) from the tracheobronchial surface into the circulation and the outward flux as the exudation of two intravenously administered plasma tracers--125I albumin (MW 69,000) and fluorescein isothiocyanate conjugated (FITC) dextran (MW 70,000)--into the airway. The absorption of technetium-99m labelled DTPA (MW 492) from the tracheobronchial airways was determined in separate experiments. Histamine (5.0 nmol) dissolved in 40 microliters saline and superfused on the tracheobronchial mucosal surface caused significant and similar entry of 125I albumin and FITC dextran into the airway lumen. This dose of histamine did not, however, alter the absorption of small (99mTc DTPA) or large (131I albumin) solutes across the airway mucosa. Ethanol (0.17 mumol), superfused in the same way, also caused significant exudation of the plasma tracers into the airway lumen. In addition, ethanol increased the absorption of 131I albumin without causing change in the disappearance rate of 99mTc DTPA. The detergent, DOSS (0.28 nmol), dissolved in ethanol (0.17 mumol), caused a pronounced increase in exudation and much increased absorption of small and large tracer solutes. Thus three patterns of change in airway mucosal barriers were found. The agents that are toxic to membranes, ethanol and DOSS, caused a bidirectional increase in permeability across the mucosa, whereas histamine caused only an outward exudative flux. The results obtained with histamine are similar to those seen previously with bradykinin, capsaicin, and allergen, suggesting that endogenous inflammatory mediators have a role in mucosal defence, producing entry of plasma exudates into the airway lumen

  17. Adenosine 5'-triphosphate release evoked by electrical nerve stimulation from the guinea-pig gallbladder.

    PubMed

    Takahashi, T; Kusunoki, M; Ishikawa, Y; Kantoh, M; Yamamura, T; Utsunomiya, J

    1987-01-28

    The endogenous release of adenosine 5'-triphosphate (ATP) from strips of guinea-pig gallbladder during transmural stimulation (TS) was measured with a firefly luciferine-luciferase reaction. TS (15V, 1 ms, 0.5-5 Hz, for 1 min) caused a rapid and marked increase of ATP release in a frequency-dependent manner. Both ATP release and contractions evoked by TS (15 V, 5 Hz, 1 ms) were completely abolished in Ca-free medium. BaCl2 (3 X 10(-3) M), a direct muscle stimulant, produced almost the same degree of contractile tension as TS (15 V, 5 Hz, 1 ms) while the ATP release induced by BaCl2 was significantly reduced to about 60 percent of that induced by TS. Atropine (10(-6) M) significantly reduced TS-evoked contraction without affecting ATP release. It was suggested, therefore, that some of the ATP release induced by TS was of neural origin. Theophylline (a P1-purinoreceptor antagonist) 10(-6) M, quinidine (a non-specific P2-purinoreceptor antagonist) 10(-6) M and apamin (a potassium channel blocking agent) 10(-8) M had no effects on TS-evoked contraction and ATP release, suggesting the absence of a presynaptic autoregulatory mechanism of ATP release in the guinea-pig gallbladder. PMID:3556400

  18. Toxicological scoring of Alzheimer's disease drug huperzine in a guinea pig model.

    PubMed

    Pohanka, Miroslav; Zemek, Filip; Bandouchova, Hana; Pikula, Jiri

    2012-04-01