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Sample records for guinea-pig vascular smooth

  1. Na+,K+-ATPase activity and responsiveness of vascular smooth muscle to norepinephrine, angiotensin II and calcium ionophore A23187 in guinea pig aortic strips.

    PubMed

    Sekine, K; Yamakawa, K; Ogata, E

    1984-01-01

    The functional significance of the Na+,K+-ATPase activity in defining the sensitivity of vascular smooth muscle response to pressor stimuli was studied in guinea pig aortic strips. Subthreshold doses of ouabain (10(-8), 10(-7), 10(-6)M), potentiated the norepinephrine- and angiotensin II-induced contractile responses, dose-dependently. Furthermore, in the presence of subthreshold dose of ouabain (10(-6)M), tension developments were observed with subthreshold doses of norepinephrine and angiotensin II. The mechanism by which subthreshold dose of ouabain potentiated the norepinephrine-induced contractile response was revealed to involve the enhancement both of sensitivity and contractile activity. Ouabain (10(-6)M) potentiated the norepinephrine- and A23187-induced contractile responses, even in the presence of verapamil. These facts indicate that suppression of the vascular Na+,K+-ATPase activity could favor the development of hypertension through potentiating contractile responses to various stimuli and that the potentiation could be a reflection, at least partly, of the decrease in Ca2+-efflux.

  2. Contractile reactions of guinea pig airway smooth muscles in the presence of stannum oxide nanosized particles.

    PubMed

    Kapilevich, L V; Zaytseva, T N; Nosarev, A V; Agev, B G; Dyakova, E Yu; Ogorodova, L M; Magaeva, A A; Terecova, O G; Itin, V I

    2012-05-01

    Contractile reactions of the guinea pig airway smooth muscles in the presence of stannum dioxide nanosized particles were studied. Contractile reactions to cholinergic and histaminergic stimulation were potentiated by inhalations of nanoparticle aerosol and by exposure of isolated smooth muscle segments to nanoparticle suspension.

  3. Cholinergic facilitation of neurotransmission to the smooth muscle of the guinea-pig prostate gland.

    PubMed

    Lau, W A; Pennefather, J N; Mitchelson, F J

    2000-07-01

    1. Functional experiments have been conducted to assess the effects of acetylcholine and carbachol, and the receptors on which they act to facilitate neurotransmission to the stromal smooth muscle of the prostate gland of the guinea-pig. 2. Acetylcholine and carbachol (0.1 microM - 0.1 mM) enhanced contractions evoked by trains of electrical field stimulation (20 pulses of 0.5 ms at 10 Hz every 50 s with a dial setting of 60 V) of nerve terminals within the guinea-pig isolated prostate. In these concentrations they had negligible effects on prostatic smooth muscle tone. 3. The facilitatory effects of acetylcholine, but not those of carbachol, were further enhanced in the presence of physostigmine (10 microM). 3. The facilitatory effects of carbachol were unaffected by the neuropeptide Y Y(1) receptor antagonist BIBP 3226 ((R)-N(2)-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-arginina mide) (0.3 microM, n=3) or suramin (100 microM, n=5). Prazosin (0.1 microM, n=5) and guanethidine (10 microM, n=5) alone and in combination (n=4), reduced responses to field stimulation and produced rightward shifts of the log concentration-response curves to carbachol. 4. The rank orders of potency of subtype-preferring muscarinic receptor antagonists in inhibiting the facilitatory actions of acetylcholine and carbachol were: pirenzepine > HHSiD (hexahydrosiladifenidol) > pF-HHSiD (para-fluoro-hexahydrosiladifenidol)>/= 5 himbacine, and pirenzepine > HHSiD > himbacine>/= 5 pF-HHSiD, respectively. These profiles suggest that muscarinic receptors of the M(1)-subtype mediate the facilitatory effects of acetylcholine and carbachol on neurotransmission to the smooth muscle of the guinea-pig prostate.

  4. Wood creosote inhibits calcium mobilization in Guinea pig colonic smooth muscle.

    PubMed

    Morino, Hirofumi; Ataka, Koji; Ito, Masafumi; Kuge, Tomoo

    2004-07-01

    Wood creosote, a mixture of simple phenolic compounds, has long been used as an herbal antidiarrheal medicine. Previous studies have shown that wood creosote has antimotility activity on the gastrointestinal (GI) tract, although its mechanism of action is not completely understood. The in vitro efficacy of wood creosote on calcium mobilization in guinea pig colonic smooth muscle was evaluated using a digital video camera system mounted on an inverted fluorescence microscope. The effects of wood creosote on spontaneous periodic increases in the free cytosolic calcium concentration ([Ca(2+)](i)), acetylcholine (ACh)-enhanced periodic increases in [Ca(2+)](i), and tetrodotoxin- or nifedipine-resistant spontaneous periodic increases in [Ca(2+)](i) were evaluated. Wood creosote decreased the amplitude of spontaneous (IC(50)=21 microg/ml) and ACh-enhanced (IC(50)=40 microg/ml) periodic increases in [Ca(2+)](i) in guinea pig colonic smooth muscle. Wood creosote also decreased the amplitude of both tetrodotoxin- and nifedipine-resistant spontaneous periodic increases in [Ca(2+)](i). These results suggest that antimotility activity through inhibition of Ca(2+) mobilization in the GI tract is at least partially responsible for the antidiarrheal activity of wood creosote. Wood creosote may exert its antimotility effect, at least in part, on network regions of interstitial cells of Cajal, which act as pacemaker cells and mediators of neurotransmission in the GI tract.

  5. 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.

  6. Effects of gymnodinium breve toxin on the smooth muscle preparation of guinea-pig ileum

    PubMed Central

    Grunfeld, Y.; Spiegelstein, M.Y.

    1974-01-01

    1 The effects of Gymnodinium breve neurotoxin (GT) on smooth muscles were studied using the guinea-pig isolated ileum. 2 The toxin caused strong spasmogenic effects at 1-4 μg/ml, characterized by prolonged tonic contraction with superimposed pronounced pendular movements. Tachyphylaxis was observed upon administration of successive doses. 3 Atropine blocked the contractile response elicited by GT, whereas mepyramine and hexamethonium failed to do so. These findings tentatively suggested a cholinergic involvement at a post-ganglionic site of action. 4 In the presence of tetrodotoxin the effects of GT were abolished, excluding direct action of the toxin on the smooth muscle. 5 It is concluded that GT exerts its spasmogenic effects through stimulation of the post-ganglionic cholinergic nerve fibres. PMID:4152867

  7. Effects of Gymnodinium breve toxin on the smooth muscle preparation of guinea-pig ileum

    PubMed Central

    Grunfeld, Y.; Spiegelstein, M.Y.

    1974-01-01

    1 The effects of Gymnodinium breve neurotoxin (GT) on smooth muscles were studied using the guinea-pig isolated ileum. 2 The toxin caused strong spasmogenic effects at 1-4 μg/ml, characterized by prolonged tonic contraction with superimposed pronounced pendular movements. Tachyphylaxis was observed upon administration of successive doses. 3 Atropine blocked the contractile response elicited by GT, whereas mepyramine and hexamethonium failed to do so. These findings tentatively suggested a cholinergic involvement at a post-ganglionic site of action. 4 In the presence of tetrodotoxin the effects of GT were abolished, excluding direct action of the toxin on the smooth muscle. 5 It is concluded that GT exerts its spasmogenic effects through stimulation of the post-ganglionic cholinergic nerve fibres. PMID:4155337

  8. Unique properties of muscularis mucosae smooth muscle in guinea pig urinary bladder

    PubMed Central

    Layne, Jeffrey J.; Pearson, Jessica M.; Sarkissian, Hagop; Nelson, Mark T.

    2011-01-01

    The muscularis mucosae, a type of smooth muscle located between the urothelium and the urinary bladder detrusor, has been described, although its properties and role in bladder function have not been characterized. Here, using mucosal tissue strips isolated from guinea pig urinary bladders, we identified spontaneous phasic contractions (SPCs) that appear to originate in the muscularis mucosae. This smooth muscle layer exhibited Ca2+ waves and flashes, but localized Ca2+ events (Ca2+ sparks, purinergic receptor-mediated transients) were not detected. Ca2+ flashes, often in bursts, occurred with a frequency (∼5.7/min) similar to that of SPCs (∼4/min), suggesting that SPCs are triggered by bursts of Ca2+ flashes. The force generated by a single mucosal SPC represented the maximal force of the strip, whereas a single detrusor SPC was ∼3% of maximal force of the detrusor strip. Electrical field stimulation (0.5–50 Hz) evoked force transients in isolated detrusor and mucosal strips. Inhibition of cholinergic receptors significantly decreased force in detrusor and mucosal strips (at higher frequencies). Concurrent inhibition of purinergic and cholinergic receptors nearly abolished evoked responses in detrusor and mucosae. Mucosal SPCs were unaffected by blocking small-conductance Ca2+-activated K+ (SK) channels with apamin and were unchanged by blocking large-conductance Ca2+-activated K+ (BK) channels with iberiotoxin (IbTX), indicating that SK and BK channels play a much smaller role in regulating muscularis mucosae SPCs than they do in regulating detrusor SPCs. Consistent with this, BK channel current density in myocytes from muscularis mucosae was ∼20% of that in detrusor myocytes. These findings indicate that the muscularis mucosae in guinea pig represents a second smooth muscle compartment that is physiologically and pharmacologically distinct from the detrusor and may contribute to the overall contractile properties of the urinary bladder. PMID:21632849

  9. The effect of cromakalim on the smooth muscle of the guinea-pig urinary bladder.

    PubMed Central

    Foster, C. D.; Fujii, K.; Kingdon, J.; Brading, A. F.

    1989-01-01

    1. The actions of cromakalim were studied on the detrusor muscle from guinea-pig urinary bladder. Cromakalim reduced the frequency and amplitude of spontaneous contractile activity of the smooth muscle of the guinea-pig urinary bladder at 5 x 10(-8)M and abolished the activity at concentrations above 5 x 10(-7)M. 2. Electrophysiological experiments demonstrated that cromakalim increased membrane conductance, caused a dose-dependent hyperpolarization of the cell membrane and loss of spike activity. These events are consistent with the opening of K+ channels. 3. The effects of 10(-6)M and 10(-5)M cromakalim on the contractile responses to carbachol, potassium and transmural nerve stimulation were studied. Cromakalim did not prevent the detrusor from responding to these agents, although it significantly reduced the contractile response to K+ at concentrations below 70 mM. 4. Uptake and efflux experiments using 86Rb+ were unable to demonstrate any significant effect on transmembrane movement produced by cromakalim (10(-5)M). 5. 43K+ efflux showed a dose-dependent increase in the rate constant on addition of cromakalim. The difference in the selectivity for K+ over Rb+ was confirmed in dual label uptake experiments. 6. Substitution experiments in which the K+ ions in the tissue were gradually replaced by Rb+ demonstrated that cromakalim had a progressively decreasing effect on spontaneous activity as internal K+ was lowered. When all the K+ was replaced by Rb+, cromakalim no longer inhibited spontaneous activity, confirming that the channel opened by cromakalim appears relatively impermeant to Rb+. PMID:2720312

  10. Electrical properties of smooth muscle in the guinea-pig urinary bladder.

    PubMed Central

    Bramich, N J; Brading, A F

    1996-01-01

    1. The effects of transmural nerve stimulation were examined on preparations of detrusor smooth muscle from guinea-pig urinary bladder using intracellular recording techniques. Most recordings were made from preparations in which spontaneous and evoked action potentials had been inhibited by nifedipine (10 microM), a dihydropyridine that blocks L-type Ca2+ channels. 2. Supramaximal stimuli evoked excitatory junction potentials (EJPs) which could be divided into three basic types. Type 1 EJPs had short latencies (< 30 ms) and fast rise times (< 60 ms). Type 2 EJPs consisted of two components: a small depolarization that was followed by a second depolarization with a faster rise time. In a third type of cell, at high strengths of stimulation, EJPs resembled type 1 EJPs but at lower strengths of stimulation were similar in time course to type 2 EJPs. 3. All EJPs were abolished by tetrodotoxin (1 microM) and reduced by omega-conotoxin (0.1 microM), but were unaffected by hexamethonium (0.1 mM), suggesting that they result from the release of transmitter from post-ganglionic nerve fibres. All responses persisted in the presence of atropine (1 microM) but were abolished following the desensitization of P2-purinoceptors with alpha, beta-methylene ATP (m-ATP; 10 microM). 4. Spontaneous excitatory junction potentials (SEJPs) were also recorded from most cells. SEJPs were similar in appearance to fast single-component EJPs; however, in general they had a briefer time course. SEJPs persisted in the presence of tetrodotoxin (1 microM). 5. The electrical properties of urinary bladder smooth muscle were also examined. Voltage changes induced by point current injection into cells had fast rates of rise and decay (time constant, 5-20 ms). The input resistance of cells ranged between 12 and 108 M omega. When recordings were taken from cells near the point of current injection, resultant electrotonic potentials could be detected in only a small proportions of cells. 6. The results

  11. 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.

  12. Oxygen consumption by the isolated smooth muscle of guinea-pig taenia coli

    PubMed Central

    Bülbring, Edith; Golenhofen, K.

    1967-01-01

    1. An apparatus is described for simultaneous measurement of oxygen consumption and electrical and mechanical activity of isolated smooth muscle preparations. 2. The mean oxygen uptake by the isolated taenia coli of the guinea-pig was 10-20 μl./g/min. 3. In spontaneously active preparations, adrenaline (10-8-10-7 g/ml.) caused, with the inhibition of electrical and mechanical activity, a reduction in oxygen uptake. 4. After prolonged exposure to substrate free solution spontaneous activity ceased periodically. Adrenaline, when applied during a silent period, had no detectable effect on resting oxygen consumption, while readmission of substrate, either glucose or β-hydroxybutyrate, increased oxygen uptake. 5. Adrenaline did not modify the increased oxygen uptake during the initial recovery period when it was given simultaneously with the substrate. However, adrenaline shortened the time interval which elapsed from the addition of substrate until spontaneous activity was resumed, indicating an acceleration of the recovery process. ImagesFig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7 PMID:16992285

  13. Co-axial bioassay of a smooth muscle relaxant factor released from guinea-pig tracheal epithelium.

    PubMed

    Fernandes, L B; Paterson, J W; Goldie, R G

    1989-01-01

    1. The ability of guinea-pig trachea to release an epithelium-derived relaxant factor (EpDRF) was assessed in a co-axial bioassay system. 2. Histamine (100 microM) and methacholine (25 microM) caused endothelium-dependent relaxation of rat isolated aorta, presumably via the release of endothelium-derived relaxant factor (EDRF). In contrast, endothelium-denuded rat aorta did not relax in response to these agents. 3. EDRF release was detected in response to methacholine in a co-axial bioassay system, consisting of intact rabbit aorta tube (EDRF donor) and endothelium-denuded rat aorta strip (assay preparation). These results indicated the transfer of EDRF from a donor to an assay preparation, thereby validating the co-axial bioassay method. 4. Substitution of endothelium-intact rabbit aorta tube by epithelium-intact guinea-pig tracheal tube tissue in co-axial assemblies, still allowed the assay preparation to relax in response to histamine or methacholine. Removal of the intact tracheal tube from the system, or removal of the epithelium from the donor tracheal tube in co-axial preparations, abolished such relaxant responses. These observations are consistent with histamine- or methacholine-induced release of an epithelium-derived relaxant factor (EpDRF) from the trachea. 5. In the co-axial assembly comprising intact guinea-pig trachea and endothelium-denuded rat aorta, histamine and methacholine produced concentration-dependent, EpDRF-induced aortic relaxation. Mean concentrations of histamine and methacholine producing 50% of the maximum relaxation (EC50) were 39.8 microM and 2.7 microM respectively. Histamine-induced relaxation was inhibited in the presence of mepyramine (2 microM) and responses to methacholine were inhibited by atropine (0.1 microM). 6. Methylene blue (50 microM) had no effect on such relaxant responses, indicating that EpDRF does not activate guanylate cyclase. Furthermore, the cyclo-oxygenase inhibitor indomethacin (5 microM), the cyclo

  14. AlF4- induces Ca2+ oscillations in guinea-pig ileal smooth muscle.

    PubMed

    Himpens, B; Missiaen, L; Droogmans, G; Casteels, R

    1991-02-01

    The effects of different compounds that inhibit the isolated plasma-membrane Ca2+/Mg2(+)-ATPase on the cytosolic free Ca2+ concentration ([Ca2+]i) and on the corresponding force development have been examined in smooth muscle of the longitudinal layer of the guinea-pig ileum. F-, in the presence of Al3+, induced an increase of the resting force and of the amplitude of the superimposed phasic contractions. The increase of resting force was associated with an increased level of basal [Ca2+]i while the phasic contractions were accompanied by concomitant oscillations in [Ca2+]i. Comparable contractions could be induced by vanadate and the calmodulin antagonist calmidazolium. The oscillations of [Ca2+]i and of force elicited by AlF4- were not modified by adrenergic or cholinergic blocking agents but were inhibited by verapamil. These phasic contractions were not affected by depleting the intracellular Ca2+ stores with ryanodine. This finding excludes a cytosolic origin of these oscillations. However, hyperpolarization and complete depolarization of the cells inhibited the oscillations. It is concluded that AlF4-, vanadate and calmidazolium induce cytoplasmic Ca2+ oscillations possibly by acting at the plasma membrane. Indeed all these substances affect by different mechanisms the isolated plasma-membrane Ca2+/Mg2(+)-ATPase. The generation of membrane-linked Ca2+ oscillations could therefore be related to an inhibition of the plasma-membrane Ca2+ pump resulting in an increase of [Ca2+]i. This change in [Ca2+]i could be responsible for the pronounced changes of the electrical and mechanical activity of this tissue.

  15. The calcium content of the smooth muscle of the guinea-pig taenia coli

    PubMed Central

    Goodford, P. J.

    1967-01-01

    1. The in vitro calcium content of the smooth muscle of the guinea-pig taenia coli was 3·0 m-mole Ca/kg wet wt. when phosphate was omitted from the bathing medium, and was almost independent of pH changes in the range 6·7-7·6. 2. The calcium content was not changed when 1 mM phosphate was included in the medium, if the pH was 6·7 or 7·0. However, when the pH was 7·6, the calcium content increased by 1·5 m-mole Ca/kg wet wt. in the presence of phosphate. 3. The calcium content rose by 1·1 m-mole Ca/kg wet wt. when NaCl in the bathing medium was replaced by isotonic sucrose, and rose by 0·7 m-mole Ca/kg wet wt. when MgCl2 in the bathing medium was replaced. These increases may reflect a competition between Ca2+ and other cations for fixed negative sites in the tissue. 4. The initial rapid phase of 42K exchange corresponded to an `extra-cellular 42K-space' of 470 ml./kg fresh wt. in normal solution, rising to 560 ml./kg. fresh wt. in low-sodium solution and to 760 ml./kg fresh wt. in calcium-free low-sodium solution. In this last medium the extra-cellular [14C]sorbitol space was only 390 ml./kg fresh wt., so that there was a large excess of rapidly-exchanging potassium which may have been competing at fixed negative sites. PMID:6051800

  16. Heat production in chemically skinned smooth muscle of guinea-pig taenia coli.

    PubMed Central

    Lönnbro, P; Hellstrand, P

    1991-01-01

    1. The rate of heat production of chemically skinned guinea-pig taenia coli smooth muscle at 25 degrees C was measured using microcalorimetric techniques. 2. Muscle strips were mounted isometrically and incubated in solutions containing MgATP (3.2 mM) and phosphocreatine (PCr, 12 mM), pH 6.9. Activation was obtained by the injection of Ca2+ into the sample compartment of the calorimeter. 3. The heat production rate of the resting preparation (pCa 9) was 0.40 +/- 0.03 mW g-1 wet weight (n = 23). During maximal activation (pCa 4.8) the heat rate increased to 1.12 +/- 0.07 mW g-1 (mean +/- S.E.M., n = 15). With stepwise increase in [Ca2+] from pCa 9 to 4.8 the energetic cost of force maintenance tended to increase at higher [Ca2+]. 4. After activation by Ca2+, the heat production rate reached its maximum while force was still increasing. 5. Changing ionic strength from 90 to 150 mM had no effect on either basal or activated heat rate. Oligomycin, amphotericin B and the adenylate kinase inhibitor Ap5A had no effect on the basal heat rate. 6. Exchanging ATP in the incubation medium for inosine triphosphate (ITP) reduced the force and heat production after injection of Ca2+. The basal heat production was not lowered when ATP was exchanged for ITP. 7. The observed enthalpy change for PCr splitting at 25 degrees C (pH 6.9, ionic strength 90 mM) was -28 +/- 3 kJ mol-1 (mean +/- S.E.M., n = 9). After correction for the phosphate equilibrium, buffer reactions, and Mg2+ binding to PCr and HPO42-, the net enthalpy change is calculated to be -39 +/- 3 kJ mol-1. 8. Heat production in the skinned smooth muscle consists of one basal component present in relaxed muscle, and one component associated with contraction. The nature of the basal heat production is unclear but does not seem to involve turnover of phosphate on the myosin light chains. The increase in the energetic tension cost with increasing activation by Ca2+ has implications for the understanding of the contractile

  17. Functional expression of KCNQ (Kv7) channels in guinea pig bladder smooth muscle and their contribution to spontaneous activity

    PubMed Central

    Anderson, U A; Carson, C; Johnston, L; Joshi, S; Gurney, A M; McCloskey, K D

    2013-01-01

    Background and Purpose The aim of the study was to determine whether KCNQ channels are functionally expressed in bladder smooth muscle cells (SMC) and to investigate their physiological significance in bladder contractility. Experimental Approach KCNQ channels were examined at the genetic, protein, cellular and tissue level in guinea pig bladder smooth muscle using RT-PCR, immunofluorescence, patch-clamp electrophysiology, calcium imaging, detrusor strip myography, and a panel of KCNQ activators and inhibitors. Key Results KCNQ subtypes 1–5 are expressed in bladder detrusor smooth muscle. Detrusor strips typically displayed TTX-insensitive myogenic spontaneous contractions that were increased in amplitude by the KCNQ channel inhibitors XE991, linopirdine or chromanol 293B. Contractility was inhibited by the KCNQ channel activators flupirtine or meclofenamic acid (MFA). The frequency of Ca2+-oscillations in SMC contained within bladder tissue sheets was increased by XE991. Outward currents in dispersed bladder SMC, recorded under conditions where BK and KATP currents were minimal, were significantly reduced by XE991, linopirdine, or chromanol, and enhanced by flupirtine or MFA. XE991 depolarized the cell membrane and could evoke transient depolarizations in quiescent cells. Flupirtine (20 μM) hyperpolarized the cell membrane with a simultaneous cessation of any spontaneous electrical activity. Conclusions and Implications These novel findings reveal the role of KCNQ currents in the regulation of the resting membrane potential of detrusor SMC and their important physiological function in the control of spontaneous contractility in the guinea pig bladder. PMID:23586426

  18. Mechanism of vanadate-induced contraction of airways smooth muscle of the guinea-pig.

    PubMed Central

    Nayler, R. A.; Sparrow, M. P.

    1983-01-01

    The characteristics of vanadate-induced contraction of airways smooth muscle are described in isolated preparations of guinea-pig central and peripheral airways. Vanadate (1-1000 microM) induced sustained contractions of trachea and lung parenchymal strips within 1 min of challenge. It was more potent (P less than 0.001) on the lung strip (EC50 = 63 microM) than on the trachea (EC50 = 123 microM). The lung strip also developed greater maximum isometric tension (P less than 0.001) than the trachea. The efficacy on the lung strip was 2 and the trachea 0.6, relative to the response to acetylcholine (efficacy = 1). Vanadate-induced contractions of the trachea were not inhibited by atropine, mepyramine, phentolamine or indomethacin, nor after mast cell depletion by compound 48/80, showing that contractions were not mediated via specific receptors or by release of endogenous mediators of tone. Inorganic phosphate specifically inhibited vanadate responses in a dose-dependent and reversible manner, suggesting a common site of action. Contractions could be elicited in depolarized muscle and after treatment with ouabain plus propranolol, showing that membrane depolarization and inhibition of the Na, K-ATPase system were not involved in the contractile action of vanadate. Pretreatment of tracheal smooth muscle with verapamil had no influence on contractions elicited by vanadate. After removal of extracellular calcium, vanadate-induced contractions declined slowly with time, indicating that influx of extracellular calcium was not giving rise to contractions elicited by vanadate. Vanadate markedly increased the rate of calcium efflux from trachealis muscle loaded with 45Ca into both Ca2+-free and normal Krebs solutions; this is compatible with vanadate mobilizing an intracellular store of Ca2+. Such a store involving sites with Ca-ATPase activity would be consistent with the action of vanadate in isolated membrane preparations. Membrane-skinned tracheal fibres contracted by

  19. Production by R-alpha-methylhistamine of a histamine H3 receptor-mediated decrease in basal vascular resistance in guinea-pigs.

    PubMed

    McLeod, R L; Gertner, S B; Hey, J A

    1993-10-01

    1. The effect of the selective histamine H3 receptor agonist, R-alpha-methylhistamine given intravenously (10-100 micrograms kg-1) was examined on baseline total peripheral resistance (TPR), and cardiovascular haemodynamics in bilaterally vagotomized, anaesthetized guinea-pigs. 2. R-alpha-methylhistamine produced a dose-dependent hypotension and fall in TPR at 30 and 100 micrograms kg-1. A decrease in heart rate (HR) was observed at a dose of 100 micrograms kg-1. R-alpha-methylhistamine (10-100 micrograms kg-1) also produced a dose-dependent fall in rate pressure product (RPP). There was no effect on cardiac output (CO) or stroke volume (SV) at these doses. 3. Histamine H1 and H2 blockade in animals pretreated with a combination of chlorpheniramine (0.3 mg kg-1) and cimetidine (3.0 mg kg-1) did not alter the haemodynamic actions of R-alpha-methyl-histamine (100 micrograms kg-1, i.v.). Pretreatment with the selective H3 antagonist, thioperamide (1 mg kg-1), completely blocked the action of R-alpha-methylhistamine on haemodynamic parameters. 4. To study the mechanism of action of R-alpha-methylhistamine, the vasodilator hydralazine (1 mg kg-1, i.v.) was used. Hydralazine lowered BP, TRP and RPP in guinea-pigs pretreated with ipratropium (50 micrograms kg-1, i.v.). Hydralazine had no effect on HR, SV or CO. 5. R-alpha-methylhistamine (100 micrograms kg-1) did not affect the vasopressor action and increases in TPR produced by adrenaline (1 and 3 micrograms kg-1). On the other hand, the vasodilator hydralazine (1 mg kg-1, i.v.) inhibited the effects of adrenaline (3 micrograms kg-1) on TPR and RPP. The effect of both doses of adrenaline on BP were attenuated by hydralazine. Therefore, the inhibitory effects of R-alpha-methylhistamine are not mediated through a direct action on vascular smooth muscle.6. In adrenalectomized guinea-pigs, R-alpha-methylhistamine (100 microg kg-1) produced a drop in BP and HR.There was no difference between the effects of R

  20. 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

  1. Na+ gradient-dependent Mg2+ transport in smooth muscle cells of guinea pig tenia cecum.

    PubMed Central

    Tashiro, M; Konishi, M

    1997-01-01

    Thin strips of guinea pig tenia cecum were loaded with the Mg2+ indicator furaptra, and the indicator fluorescence signals measured in Ca2+-free condition were converted to cytoplasmic-free Mg2+ concentration ([Mg2+]i). Lowering the extracellular Na+ concentration ([Na+]o) caused a reversible increase in [Mg2+]i, consistent with the inhibition of Na+ gradient-dependent extrusion of cellular Mg2+ (Na+-Mg2+ exchange). Curve-fitting analysis indicated that the relation between [Na+]o and the rate of rise in [Mg2+], had a Hill coefficient of approximately 3, a [Na+]o at the half-maximal rate of rise of approximately 30 mM, and a maximal rate of 0.16 +/- 0.01 microM/s (mean +/- SE, n = 6). Depolarization with 56 mM K+ shifted the curve slightly toward higher [Na+]o without significantly changing the maximal rate, suggesting that the Na+-Mg2+ exchange was inhibited by depolarization. The maximal rate would correspond to a flux of 0.15-0.4 pmol/cm2/s, if cytoplasmic Mg2+ buffering power (defined as the ratio of the changes in total Mg2+ and free Mg2+ concentrations) is assumed to be 2-5. Ouabain (1-5 microM) increased the intracellular Na+ concentration, as assessed with fluorescence of SBFI (sodium-binding benzofuran isophthalate, a Na+ indicator), and elevated [Mg2+]i. In ouabain-treated preparations, removal of extracellular Na+ rapidly increased [Mg2+]i, with an initial rate of rise roughly proportional to the degree of the Mg2+ load, and, probably, to the Na+ load caused by ouabain. The enhanced rate of rise in [Mg2+]i (up to approximately 1 microM/s) could be attributed to the Mg2+ influx as a result of the reversed Na+-Mg2+ exchange. Our results support the presence of a reversible and possibly electrogenic Na+-Mg2+ exchange in the smooth muscle cells of tenia cecum. PMID:9414247

  2. Electrophysiological study of the intestinal smooth muscle of the guinea-pig

    PubMed Central

    Kuriyama, H.; Osa, T.; Toida, N.

    1967-01-01

    The membrane properties of single cells of intestinal smooth muscle of duodenum, jejunum, ileum, caecum and rectum of guinea-pig have been studied. 1. The membrane potentials of longitudinal muscles of the duodenum, jejunum, ileum, caecum and rectum varied from 54 to 56 mV and those of circular muscles of jejunum, ileum, caecum and rectum varied from 57 to 60 mV. The ablated longitudinal muscle had a slightly lower value (50 mV) than the intact one. 2. The longitudinal muscle generated spontaneous discharges but these were rare in the circular muscles of the intestine except for the caecum. Overshoot potentials could be observed in all regions of the intestine. The maximum rate of rise of the spontaneously discharging longitudinal muscles varied from 11 to 18 V/sec. 3. Not all of the slow potential changes (but at least some) were generated by the nervous elements distributed between the muscle layers and in them. 4. The conduction velocities measured from the longitudinal muscles of jejunum and rectum in the presence of tetrodotoxin were 2·1 cm/sec and 4·0 cm/sec respectively. 5. Chronaxies of the longitudinal muscles of jejunum and rectum were 2-5 msec and 5-18 msec respectively. 6. Intracellular stimulation of the single cells of the duodenum and caecum could trigger a spike, similar to that observed in the taenia coli. The spikes were mostly graded ones; a spike of full size was rarely elicited. When the spikes were triggered, the after-hyperpolarization appeared consistently presumably caused by the increased potassium conductance. 7. The effective membrane resistance and the time constant were measured for the longitudinal muscles of the jejunum and rectum. When spikes were generated by intracellular stimulation the observed values were 40-50 MΩ and 3-5 msec in both tissues. These values were the same as those observed in the taenia coli. 8. When the time constant of the membrane was measured by the extracellular polarizing method, the longitudinal muscles

  3. Comparison of /sup 45/Ca binding and mobilization in cartilage and smooth muscle of guinea pig trachea

    SciTech Connect

    Goodman, F.R.; Weiss, G.B.; Sturm, B.

    1986-03-01

    In guinea pig trachea, separation of smooth muscle from cartilage permits measurement of /sup 45/Ca fluxes in more homogeneous preparations. The role of cartilage Ca/sup + +/ as a source for smooth muscle Ca/sup + +/ mobilization can be assessed by similar experiments with the two dissociated preparations. Equilibration of /sup 45/Ca into cartilage occurred over 2 hr; plotting of /sup 45/Ca uptake on Scatchard coordinates yields high and low affinity Ca/sup + +/ uptake components similar to those in tracheal and other smooth muscles. Washout of /sup 45/Ca from cartilage demonstrated two components with the more rapid including the extracellular (/sup 14/C-sucrose) compartment. Washout of higher affinity /sup 45/Ca (after incubation in 0.03 mM Ca/sup + +/) was increased in cartilage by Sr/sup + +/, added Ca/sup + +/, La/sup + + +/ and EGTA. Comparison with tracheal smooth muscle /sup 45/Ca washouts indicates that those Ca/sup + +/ components previously identified as of intracellular origin were not present in cartilage. Exposure to 60 mM (added) K/sup +/ during /sup 45/Ca washout increased /sup 45/Ca efflux in cartilage but not in smooth muscle. This release of /sup 45/Ca by K/sup +/ may indicate that Ca/sup + +/ can be mobilized from cartilage sites by K/sup +/ to support smooth muscle contractile responses. Thus, cartilage Ca/sup + +/ could be an important source of Ca/sup + +/ for excitation-contraction coupling in guinea pig tracheal smooth muscle.

  4. The Immunization of Guinea-pigs and Mice with a Whole-Culture Extract of a Smooth and a Rough Strain of Brucella abortus

    PubMed Central

    Keppie, J.; Witt, K.; Smith, H.

    1972-01-01

    A purified killed Br. abortus vaccine developed for use in man from the smooth strain 544 and previously tested in mice (Keppie, Witt and Smith, 1971) has now been shown to immunize guinea-pigs without the addition of adjuvant. A similar vaccine prepared from the rough strain 45/20 also immunized guinea-pigs but to a slightly lesser degree. The activity of both vaccines in the guinea-pig was markedly enhanced by the use of water-in-oil emulsions. A commercially available killed vaccine, “Duphavac”, prepared from strain 45/20 for use in cattle, was slightly more active in guinea-pigs than the emulsified whole-culture extract of “544” possibly because its oily adjuvant was different. In mice, all the “45/20” vaccines were only feebly protective even when given with oily adjuvant, in sharp contrast to the “544” vaccines which were highly active in this animal, with or without adjuvant. As expected, the “45/20” vaccines were much less agglutinogenic than the “544” vaccines but both produced a similar degree of delayed hypersensitivity in guinea-pigs. It is suggested that the whole-extract vaccine from strain 544 is suitable for a trial in man. PMID:4628447

  5. 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

  6. Muscarinic activity modulated by C-type natriuretic peptide in gastric smooth muscles of guinea-pig stomach.

    PubMed

    Xing, De-gang; Huang, Xu; Li, Chun-hui; Li, Xiang-lan; Piao, Lian-hua; Gao, Ling; Zhang, Yang; Kim, Yong-chul; Xu, Wen-xie

    2007-10-04

    Natriuretic peptides (NPs) are a cyclic guanosine monophosphate (cGMP) generation system like nitric oxide (NO) and play an inhibitory regulation in gastrointestinal motility but the effect of NPs on muscarinic activity is still unclear. This study was designed to investigate effect of C-type natriuretic peptide (CNP) on muscarinic control of gastric motility and its ion channel mechanism. The spontaneous contraction of gastric smooth muscle strip was recorded by using physiograph in guinea-pig. Membrane currents and potential were recorded by using whole-cell patch-clamp technique. CNP significantly inhibited muscarinic M receptor agonist carbachol (Cch)-induced contractions of gastric smooth muscle strips and dramatically hyperpolarized Cch-induced depolarization of membrane potential in gastric single smooth muscle cell. Muscarinic currents induced by both Cch and GTPgammaS, a G-protein agonist were significantly suppressed by CNP. 8-Br-cGMP mimicked the effect of CNP on Cch-induced muscarinic currents, and the peak holding current was decreased from -200.66+/-54.35 pA of control to -67.35+/-24.82 pA. LY83583, a guanylate cyclase nonspecific inhibitor, significantly weakened the inhibitory effect of CNP on muscarinic current while zaprinast, a cGMP sensitive phosphoesterase inhibitor, potentiated the inhibitory effect of CNP on muscarinic current. cGMP production was dramatically enhanced by CNP and this effect was suppressed by LY83583 in gastric smooth muscle. These results suggest that CNP modulates muscarinic activity via CNP-NPR-particulate guanylate cyclase (pGC)-cGMP pathway in guinea-pig.

  7. Relaxant effect of ethanol extract of Carum carvi on dispersed intestinal smooth muscle cells of the guinea pig.

    PubMed

    Al-Essa, Mohammed K; Shafagoj, Yanal A; Mohammed, Faysal I; Afifi, Fatma U

    2010-01-01

    The present study investigates the direct effects of Carum carvi L. (Apiaceae) ethanol extract on dispersed intestinal smooth muscle cells (SMC) of guinea pigs. Effects of the plant extract on SMC and of acetylcholine (Ach) on extract pretreated SMC were measured by micrometric scanning technique. Three different extract concentrations (2.5 mg/mL, 250 mug/mL, and 25 mug/mL) were used. Ethanol extract of C. carvi reduced significantly the response of dispersed SMC to Ach. Pretreatment of SMC with the highest concentration of C. carvi ethanol extract (2.5 mg/mL) has significantly inhibited the response of SMC to Ach. The data obtained indicate a dose-dependent inhibition of the contraction induced by Ach. This response may explain, in part, the beneficial effect of caraway in relieving gastrointestinal symptoms associated with dyspepsia.

  8. Evaluation of vascular clearance as a marker for virulence of alphaviruses: disassociation of rapid clearance with low virulence of venezuelan encephalitis virus strains in guinea pigs.

    PubMed Central

    Jahrling, P B; Heisey, G B; Hesse, R A

    1977-01-01

    The concept that relates low virulence of certain alphaviruses to low viremia and efficient vascular clearance of virus was tested in guinea pigs. Previously published studies with hamsters suggested that virulent strains maintain high viremias primarily because they are cleared inefficiently from the blood. In the present study, with guinea pigs, six of six virulent strains of Venezuelan encephalitis virus were cleared inefficiently, whereas three of six nonlethal or benign virus strains were cleared rapidly. However, three other guinea pig-benign Venezuelan encephalitis virus strains cleared slowly, to produce a high viremia was correlated with inefficient growth in primary viral replication sites. Thus, the potential of some alphaviruses to produce destructive lesions may be restricted by efficient clearance of virus from the blood, whereas the growth of other benign alphavirus strains may be restricted after the virus is presented to target cells. PMID:892910

  9. Fetal Growth Restriction Induces Heterogeneous Effects on Vascular Biomechanical and Functional Properties in Guinea Pigs (Cavia porcellus)

    PubMed Central

    Cañas, Daniel; Herrera, Emilio A.; García-Herrera, Claudio; Celentano, Diego; Krause, Bernardo J.

    2017-01-01

    Aim: Fetal growth restriction (FGR) is associated with a variety of cardiometabolic diseases in adulthood which could involve remodeling processes of the vascular walls that could start in the fetal period. However, there is no consensus whether this remodeling affects in a similar way the whole vascular system. We aimed to determine the effects of FGR on the vasoactive and biomechanical properties of umbilical and systemic vessels in fetal guinea pigs. Methods: FGR was induced by implanting ameroid occluders at mid-gestation in uterine arteries of pregnant guinea pigs, whilst the control group was exposed to simulated surgery. At the term of gestation, systemic arteries (aorta, carotid and femoral) and umbilical vessels were isolated to determine ex vivo contractile and biomechanical responses (stretch-stress until rupture) on a wire myograph, as well as opening angle and residual stresses. Histological characteristics in tissue samples were measured by van Gieson staining. Results: Aorta and femoral arteries from FGR showed an increased in biomechanical markers of stiffness (p < 0.01), contractile capacity (p < 0.05) and relative media thickness (p < 0.01), but a reduced internal diameter (p < 0.001), compared with controls. There were no differences in the biomechanical properties of carotid and umbilical from control and FGR fetuses, but FGR umbilical arteries had a decreased contractile response to KCl (p < 0.05) along with a reduced relative media thickness (p < 0.05). Conclusion: Altogether, these changes in functional, mechanical and morphological properties suggest that FGR is associated with a heterogeneous pro-constrictive vascular remodeling affecting mainly the lower body fetal arteries. These effects would be set during a pathologic pregnancy in order to sustain the fetal blood redistribution in the FGR and may persist up to adulthood increasing the risk of a cardiovascular disease. PMID:28344561

  10. Fetal Growth Restriction Induces Heterogeneous Effects on Vascular Biomechanical and Functional Properties in Guinea Pigs (Cavia porcellus).

    PubMed

    Cañas, Daniel; Herrera, Emilio A; García-Herrera, Claudio; Celentano, Diego; Krause, Bernardo J

    2017-01-01

    Aim: Fetal growth restriction (FGR) is associated with a variety of cardiometabolic diseases in adulthood which could involve remodeling processes of the vascular walls that could start in the fetal period. However, there is no consensus whether this remodeling affects in a similar way the whole vascular system. We aimed to determine the effects of FGR on the vasoactive and biomechanical properties of umbilical and systemic vessels in fetal guinea pigs. Methods: FGR was induced by implanting ameroid occluders at mid-gestation in uterine arteries of pregnant guinea pigs, whilst the control group was exposed to simulated surgery. At the term of gestation, systemic arteries (aorta, carotid and femoral) and umbilical vessels were isolated to determine ex vivo contractile and biomechanical responses (stretch-stress until rupture) on a wire myograph, as well as opening angle and residual stresses. Histological characteristics in tissue samples were measured by van Gieson staining. Results: Aorta and femoral arteries from FGR showed an increased in biomechanical markers of stiffness (p < 0.01), contractile capacity (p < 0.05) and relative media thickness (p < 0.01), but a reduced internal diameter (p < 0.001), compared with controls. There were no differences in the biomechanical properties of carotid and umbilical from control and FGR fetuses, but FGR umbilical arteries had a decreased contractile response to KCl (p < 0.05) along with a reduced relative media thickness (p < 0.05). Conclusion: Altogether, these changes in functional, mechanical and morphological properties suggest that FGR is associated with a heterogeneous pro-constrictive vascular remodeling affecting mainly the lower body fetal arteries. These effects would be set during a pathologic pregnancy in order to sustain the fetal blood redistribution in the FGR and may persist up to adulthood increasing the risk of a cardiovascular disease.

  11. Some effects of nicorandil on the smooth muscles of the rat and guinea pig

    SciTech Connect

    Weston, A.H.

    1987-01-01

    In rat isolated portal vein, nicorandil (0.1-500 microM) abolished spontaneous tension waves and inhibited mechanical responses to norepinephrine (0.1-100 microM) and KCl (5-80 mM). Intracellular electrical recording showed that nicorandil (0.1-1 microM) abolished spontaneous multispike complexes and at higher concentrations (up to 500 microM) raised the membrane potential to approximately -90 mV. Using /sup 86/Rb as a K+-marker, nicorandil (5-500 microM) increased the /sup 86/Rb efflux rate coefficient. In rat isolated aorta, nicorandil (8-32 microM) inhibited mechanical responses to norepinephrine (0.125-100 microM) and KCl (5-80 mM), but had no effect on /sup 86/Rb exchange. In guinea pig isolated taenia caeci, nicorandil (4-64 microM) relaxed spontaneous mechanical tone and increased /sup 86/Rb efflux in the absence and presence of apamin, 100 nM. It is concluded that the inhibitory effects of nicorandil in portal vein and taenia caeci are mediated at least in part by a mechanism which involves the opening of apamin-insensitive, /sup 86/Rb-permeable K+ channels. In aorta, however, the opening of such channels was not detected, and the inhibitory effects of nicorandil in this tissue are associated with an, as yet, undefined mechanism.

  12. ATP release and contraction mediated by different P2-receptor subtypes in guinea-pig ileal smooth muscle

    PubMed Central

    Matsuo, Katsuichi; Katsuragi, Takeshi; Fujiki, Sono; Sato, Chiemi; Furukawa, Tatsuo

    1997-01-01

    The present study was addressed to clarify the subtypes of P2-purinoceptor involved in ATP release and contraction evoked by α,β-methylene ATP (α,β-mATP) and other P2-agonists in guinea-pig ileum.α,β-mATP 100 μM produced a transient and steep contraction followed by ATP release from tissue segments. These maximum responses appeared with different time-courses and their ED50 values were 5 and 25 μM, respectively. The maximum release of ATP by α,β-mATP was markedly reduced by 250 μM suramin, 30 μM pyridoxal-phosphate-6-azophenyl-2′,5′-disulphonic acid (PPADS) and 30 μM reactive blue 2 (RB-2), P2-receptor antagonists. However, the contractile response was inhibited by suramin, tetrodotoxin and atropine, but not by PPADS and RB-2.Although the contraction caused by α,β-mATP was strongly diminished by Ca2+-removal and nifedipine, and also by tetrodotoxin and atropine at 0.3 μM, the release of ATP was virtually unaffected by these procedures.UTP, β,γ-methylene ATP (β,γ-mATP) and ADP at 100 μM elicited a moderate release of ATP. The release caused by UTP was virtually unaffected by RB-2. However, these P2-agonists failed to elicit a contraction of the segment.The potency order of all the agonists tested for the release of ATP was α,β-mATP>UTP>β,γ-mATP>ADP.In superfusion experiments with cultured smooth muscle cells from the ileum, α,β-mATP (100 μM) enhanced the release of ATP 5 fold above the basal value. This evoked release was inhibited by RB-2.These findings suggest that ATP release and contraction induced by P2-agonists such as α,β-mATP in the guinea-pig ileum result mainly from stimulation of different P2-purinoceptors, P2Y-like purinoceptors on the smooth muscles and, probably, P2X-purinoceptors on cholinergic nerve terminals, respectively. However, the ATP release may also be mediated, in part, by P2U-receptors, because UTP caused RB-2-insensitive ATP release. PMID:9283712

  13. Membrane properties of the smooth muscle of guinea-pig ureter

    PubMed Central

    Kuriyama, H.; Osa, T.; Toida, N.

    1967-01-01

    1. The membrane properties of the guinea-pig ureter were studied in physiological Krebs solution by intra- and extracellular stimulating methods. 2. The mean membrane potential was 50 mV. Action potentials triggered by external stimulation were composed of repetitive spikes and a plateau phase. 3. The effects of intracellular polarization on the membrane activity elicited by extracellular stimulation were observed. Anodal polarization enhanced the amplitude and the maximum rate of rise of the spike while cathodal polarization reduced them. The number of the spikes, the duration and amplitude of the plateau phase were not changed by polarization of any direction. 4. The spikes triggered by intracellular stimulation were mostly graded, but repetitive spikes sometimes continued even after cessation of the stimulation. The effective membrane resistance was 15-23 MΩ and the time constant was 2-3 msec. 5. Conduction velocity (V), chronaxie, time constant (τ) and space constant (λ) of the tissue were measured by extracellular stimulation. These values were as follows: V, 3-6 cm/sec; chronaxie, 20-40 msec; τ, 200-300 msec; λ, 2·5-3 mm. The conduction of excitation might be related to the cable properties of the tissue. 6. The relative refractory period measured by extracellular stimulation was as long as 30 sec. During the relative refractory period dissociation of the slow depolarization and the spikes was observed by successive stimuli. 7. The plateau phase was prolonged and the frequency of the spontaneous discharges was increased by treatment with Ba2+. Tetrodotoxin had no effect on spike activity nor on the plateau phase, but Mn2+ blocked the membrane activity. PMID:6050102

  14. Effects of various osmotic solutions on membrane properties of smooth muscle cells of the guinea pig ureter.

    PubMed

    Ohshima, K

    1981-09-01

    Effects of various osmotic solutions on membrane properties of smooth muscle cells of the guinea pig ureter were investigated using the microelectrode and double sucrose gap methods. In Krebs solution, the mean membrane potential was -53 mV, chronaxie was 104 msec, length constant of the tissue was 1.03 mm, time constant of the membrane was 65.8 msec, and conduction velocity of excitation was 19.2 mm per sec. Hyperosmotic solution (1.5, 2.0, or 2.5 times the normal osmolarity) depolarized the membrane, generated the spike activity, reduced the length constant of the tissue, increased the time constant of the membrane, prolonged the chronaxie, and reduced the conduction velocity. Hyposmotic solutions (0.85 and 0.67 times the normal osmolarity) produced opposite changes on the passive and active characteristics of the membrane compared to findings in hyperosmotic solution except that the time constant of the membrane was increased in both hyper- and hyposmolar solutions. Increase in the time constant of the membrane and reduced length constant of the tissue in hyperosmotic solution can be explained by an increase in the internal resistance, including the cell to cell junctional resistance and shrinkage of the cell diameter (from 6.2 to 3.0 micrometer).

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

    PubMed

    Mallows, R S; Bolton, T B

    1987-06-15

    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.

  16. Interaction of 28Mg with Ca and K in the smooth muscle of guinea-pig taenia coli

    PubMed Central

    Sparrow, M. P.

    1969-01-01

    1. The uptake of 28Mg, and the total tissue content of Mg, Ca, Na and K have been determined in the smooth muscle of the guinea-pig taenia coli. The Mg content was 6·56 m-mole/kg fresh wt. immediately after dissection, falling slowly to 5·11 after 6 hr immersion in Krebs solution at 37° C. 2. The Mg content rose to 15·4 m-mole/kg fresh wt. during immersion in isotonic sucrose containing only MgCl2. It was independent of the Mg2+ concentration in this solution, but was depressed when K+ or Ca2+ ions were added. 3. 28Mg uptake showed three separate phases, extracellular, intermediate and slow. The size of the extracellular phase was proportional to the Mg2+ concentration in the solution, but the size of the slow phase was constant. The size of the intermediate phase, exchanging with a half-time of a few minutes, was depressed when K+ or Ca2+ ions were added. 4. The results are compatible with a competition between Mg in the intermediate phase of tracer exchange, and K+ or Ca2+ ions for fixed anionic sites in the tissue. PMID:5347717

  17. Deciduoma growth in the ovariectomized guinea pig: steroid hormone-mediated vascular support of endometrial differentiation.

    PubMed

    Garris, D R

    1988-05-01

    The ability of ovarian steroid hormones to modulate experimentally induced decidual tissue (DT) growth and the associated changes in uterine blood flow rates (UBF) was examined in ovariectomized guinea pigs after uterine trauma (designated day 0 of the studies). Uteri that were exposed, but not manipulated, served as controls. Uterine and DT weights as well as UBF, rates, were subsequently recorded on either day 5 or 10 posttrauma. Oil treatment failed to induce an increase in either control or traumatized uterine weights between days 5 and 10, and trauma had no effect on UBF rates in either group. Daily progesterone (P; 2 mg) treatment induced a significant elevation in DT weight by day 10 and elevated UBF rates between days 5 and 10 relative to control values. Daily P treatment augmented by estradiol (E2; 1 microgram) therapy on days 0 and 1 induced a significant increase in DT weights and UBF rates between days 5 and 10 in both control and DT groups relative to those in oil-treated animals. Combined P and E2 (P/E2) treatment induced a moderate increase in DT weight by day 10 posttrauma and elevated UBF rates in both control and DT groups. Acute treatment (i.e. days -3 to 0) with these steroid regimens indicated that neither P nor P/E2 treatment maintained DT growth. However, day -3 to 0 treatment with P in combination with a single day 0 injection of E2 allowed for maximal DT growth by day 10 and maintained elevated UBF rates relative to control values. P/E2 treatment between days -3 and 0 also induced an increase in UBF rates in both control and DT uteri relative to those in oil-treated animals. These results indicate that E2 is essential for supporting the P-directed differentiation and proliferation of stimulated guinea pig endometrium into DT. The ability of decidualization to occur in the absence of chronic steroid support indicates that uterine sensitization for cellular differentiation in this species only requires that the endometrium be initially primed

  18. Effects of K(+) channel openers on spontaneous action potentials in detrusor smooth muscle of the guinea-pig urinary bladder.

    PubMed

    Takagi, Hiroaki; Hashitani, Hikaru

    2016-10-15

    The modulation of spontaneous excitability in detrusor smooth muscle (DSM) upon the pharmacological activation of different populations of K(+) channels was investigated. Effects of distinct K(+) channel openers on spontaneous action potentials in DSM of the guinea-pig bladder were examined using intracellular microelectrode techniques. NS1619 (10μM), a large conductance Ca(2+)-activated K(+) (BK) channel opener, transiently increased action potential frequency and then prevented their generation without hyperpolarizing the membrane in a manner sensitive to iberiotoxin (IbTX, 100nM). A higher concentration of NS1619 (30μM) hyperpolarized the membrane and abolished action potential firing. NS309 (10μM) and SKA31 (100μM), small conductance Ca(2+)-activated K(+) (SK) channel openers, dramatically increased the duration of the after-hyperpolarization and then abolished action potential firing in an apamin (100nM)-sensitive manner. Flupirtine (10μM), a Kv7 channel opener, inhibited action potential firing without hyperpolarizing the membrane in a manner sensitive to XE991 (10μM), a Kv7 channel blocker. BRL37344 (10μM), a β3-adrenceptor agonist, or rolipram (10nM), a phosphodiesterase 4 inhibitor, also inhibited action potential firing. A higher concentration of rolipram (100nM) hyperpolarized the DSM and abolished the action potentials. IbTX (100nM) prevented the rolipram-induced blockade of action potentials but not the hyperpolarization. BK and Kv7 channels appear to predominantly contribute to the stabilization of DSM excitability. Spare SK channels could be pharmacologically activated to suppress DSM excitability. BK channels appear to be involved in the cyclic AMP-induced inhibition of action potentials but not the membrane hyperpolarization.

  19. Regional differences in the frequency of slow waves in smooth muscle of the guinea-pig stomach.

    PubMed

    Domae, Kazumasa; Hashitani, Hikaru; Suzuki, Hikaru

    2008-12-01

    The frequency of slow waves recorded from circular muscle bundles with attached longitudinal muscle (intact muscle) was compared with that of slow potentials recorded from isolated circular muscle bundles (isolated muscle) from the guinea-pig stomach. In intact muscle preparations, slow waves were generated in the corpus, antrum and pylorus with a higher frequency in the corpus (about 5 min(-1)) than the other regions (about 2 min(-1) in antrum, about 1.5 min(-1) in pylorus). The resting potential amplitude was graded across the stomach, at about -50 mV in the fundus, -60 mV in the corpus, -65 mV in the antrum and -70 mV in the pylorus. A similar distribution of resting membrane potential and slow potential frequency was also observed in isolated muscle bundles from the different regions. Caffeine (1 mM) abolished slow waves in some corpus preparations and inhibited the 2nd component of slow waves in the antrum and pylorus, and also abolished slow potentials in isolated muscle preparations from any region of the stomach. This suggests that myenteric interstitial cells of Cajal (ICC-MY) are heterogeneously distributed in the stomach (pylorus, antrum and part of the corpus regions), with a homogeneous distribution of muscular interstitial cells of Cajal (ICC-IM) within the circular muscle bundles. The frequency of slow potentials in smooth muscle isolated from any region of the stomach changed linearly in response to membrane potential changes produced by either current injection or high potassium solutions. The frequency of slow potentials after setting the membrane potential at -60 mV was larger in the corpus than the antrum, suggesting that the high frequency discharge of corpus muscle is produced by the low membrane potential and additional unidentified factors. We suggest that the regional difference in slow wave discharge is produced mainly by ICC-IM, and the role of ICC-MY may be little, if any.

  20. Nitric oxide inhibits smooth muscle responses evoked by cholinergic nerve stimulation in the guinea pig gastric fundus.

    PubMed

    Yoneda, S; Suzuki, H

    2001-12-01

    In circular smooth muscle tissues of the guinea pig gastric fundus, transmural nerve stimulation (TNS) evoked an atropine-sensitive cholinergic excitatory junction potential (e.j.p.) and, after inhibiting the e.j.p. with atropine, an apamin-sensitive nonadrenergic noncholinergic (NANC) inhibitory junction potential (i.j.p.). The amplitude of e.j.p.s was similar when the frequency of TNS was low (<0.5 Hz), but it decreased successively (depression phenomenon) when the frequency was high (>1 Hz). The depression phenomenon was attenuated after inhibiting the production of nitric oxide (NO) with N(omega)-nitro-L-arginine (NOLA), but was not altered by inhibiting the i.j.p. with apamin. The e.j.p.s were increased in amplitude by the inhibition of cholinesterase activity, but they were decreased by NO produced from SNP with no alteration of their depression phenomenon. Isometric twitch contractions were depressed during high-frequency TNS. NOLA caused an increase in the amplitude of twitch contractions and the attenuation of their depression that changed the transient contraction produced by high-frequency TNS (1 Hz) to a tetanic one. SNP reduced the amplitude of twitch contractions, with no alteration of the depression phenomena. Contractions produced by low concentrations of acetylcholine, but not by high concentrations, were attenuated by SNP, with no alteration of the membrane depolarization. The results suggest that NO produced during TNS has inhibitory actions on cholinergic transmission; the depression of e.j.p.s is mainly prejunctional events, and the depression of mechanical responses is mainly postjunctional events.

  1. [The characteristics and oxidative modulation of large-conductance calcium-activated potassium channels in guinea-pig colon smooth muscle cells.].

    PubMed

    Huang, Wei-Feng; Ouyang, Shou; Zhang, Hui

    2009-06-25

    To investigate the characteristics of large-conductance calcium-activated potassium channels (BK(Ca)) and the effect of hydrogen peroxide (H2O2) on BK(Ca) in guinea-pig proximal colon smooth muscle cells, single smooth muscle cells of guinea-pig colon were enzymatically isolated in low calcium solution containing papain (3 mg/mL), DTT (2 mg/mL), and bovine serum albumin (BSA, 2 mg/mL). Tissues were incubated at 36 degrees C in enzyme solution for 15 min and were then suspended in enzyme-free low calcium solution. Inside-out single channel recording technique was used to record BK(Ca) current. The intracellular (bath) and microelectrode solution both contained symmetrical high potassium. The BK(Ca) in guinea-pig colon smooth muscle cell possesses: 1) voltage-dependence, 2) high selectivity for potassium ion, 3) large conductance (223.7 pS+/-9.2 pS), 4) dependence of [Ca(2+)](i). Intracellular application of H2O2 decreased the open probability (P(o)) of BK(Ca) at low concentration (

  2. Carbon dioxide-induced inhibition of mechanical activity in gastrointestinal smooth muscle preparations isolated from the guinea-pig.

    PubMed

    Fujimoto, Hiroyuki; Shigemasa, Yuhsuke; Suzuki, Hikaru

    2011-01-01

    Mechanical responses of smooth muscle elicited by application of CO2-gas bubbled physiological salt solution (CO2-gas solution) were investigated in isolated stomach antrum and colon preparations of the guinea-pig. Circular smooth muscle preparations of both colon and stomach were spontaneously active with periodic generation of phasic contractions. In colonic preparations, the CO2-gas solution produced a biphasic response, with an initial small transient contraction followed by a sustained inhibition of phasic contractions. Removal of the CO2-gas solution allowed a slow recovery of the spontaneous contractions over a period of about 40 min. The recovery developed with a similar time course irrespective of the length of time exposed to CO2-gas solution. The inhibitory responses elicited by CO2-gas solution were not modulated by atropine, Nω-nitro-L-arginine or neostigmine. Atropine-sensitive excitatory responses of smooth muscle elicited by transmural nerve stimulation or exogenously applied acetylcholine were attenuated or abolished in the presence of CO2-gas solution. In stomach preparations, the CO2-gas solution elicited a tri-phasic response, with an initial transient relaxation followed by a transient contraction and then a sustained inhibition of the rhythmic contractions. The peak amplitude of the transient contraction was about 2.5 times larger than the spontaneous phasic contractions. The pH of the CO2-gas solution was reduced to about 6. Application of pH 6 solution again produced a tri-phasic response, as was the case for the CO2-gas solution, however the amplitude of the transient contraction was only about 0.4 times that of the spontaneous contractions. The re-appearance of the abolished phasic contraction was quicker with the pH 6 solution (about 1.8 min) than it was for the CO2-gas solution (about 6 min). The inhibitory responses elicited by the CO2-gas solution could be simulated only partly by the acidified solution, and a possible involvement of

  3. Changes in guinea pig gallbladder smooth muscle Ca2+ homeostasis by acute acalculous cholecystitis.

    PubMed

    Gomez-Pinilla, Pedro J; Morales, Sara; Camello-Almaraz, Cristina; Moreno, Rosario; Pozo, María J; Camello, Pedro J

    2006-01-01

    Impaired smooth muscle contractility is a hallmark of acute acalculous cholecystitis. Although free cytosolic Ca2+ ([Ca2+]i) is a critical step in smooth muscle contraction, possible alterations in Ca2+ homeostasis by cholecystitis have not been elucidated. Our aim was to elucidate changes in the Ca2+ signaling pathways induced by this gallbladder dysfunction. [Ca2+]i was determined by epifluorescence microscopy in fura 2-loaded isolated gallbladder smooth muscle cells, and isometric tension was recorded from gallbladder muscle strips. F-actin content was quantified by confocal microscopy. Ca2+ responses to the inositol trisphosphate (InsP3) mobilizing agonist CCK and to caffeine, an activator of the ryanodine receptors, were impaired in cholecystitic cells. This impairment was not the result of a decrease in the size of the releasable pool. Inflammation also inhibited Ca2+ influx through L-type Ca2+ channels and capacitative Ca2+ entry induced by depletion of intracellular Ca2+ pools. In addition, the pharmacological phenotype of these channels was altered in cholecystitic cells. Inflammation impaired contractility further than Ca2+ signal attenuation, which could be related to the decrease in F-actin that was detected in cholecystitic smooth muscle cells. These findings indicate that cholecystitis decreases both Ca2+ release and Ca2+ influx in gallbladder smooth muscle, but a loss in the sensitivity of the contractile machinery to Ca2+ may also be responsible for the impairment in gallbladder contractility.

  4. 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.

  5. 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

  6. Transmission from intramural inhibitory nerves to the smooth muscle of the guinea-pig taenia coli.

    PubMed

    Bennett, M R; Burnstock, G; Holman, M

    1966-02-01

    1. Membrane potential changes of smooth muscle cells were recorded during stimulation of the intramural inhibitory nerves to the taenia coli.2. Stimulation across the taenia coli with single pulses of 200 musec duration excites the intramural nerves and not the muscle directly.3. The membrane potential changes due to stimulation of the intramural inhibitory nerves were different from those produced by perivascular inhibitory nerve stimulation in the following ways: hyperpolarizations (i.j.p.'s) of up to 25 mV were produced in response to single pulses; the latency, i.e. the time taken for the membrane to hyperpolarize after a stimulus of maximal strength, was as short as 80 msec; when the nerves were stimulated repetitively the membrane was hyperpolarized by up to 35 mV and all spontaneous activity was abolished; the mean hyperpolarization due to repetitive stimulation increased with the frequency of stimulation up to 10 pulses/sec and then remained constant; the hyperpolarization due to stimulation at frequencies greater than 5 pulses/sec was not maintained but decreased after 3-5 sec of stimulation; and finally when stimulation had ceased action potentials commenced firing at frequencies greater than normal.4. The amplitude and rate of hyperpolarization of the i.j.p. increased with increasing strength of stimulation until a maximum amplitude and rate of hyperpolarization was reached. The recovery or depolarizing phase of the i.j.p. was exponential with a time constant which varied from about 250 msec to 500 msec and could not therefore be due to the discharge of the membrane capacitance. In some cases there was an inflexion on this depolarizing phase and in these cases recovery led directly into an action potential.5. Spontaneous hyperpolarizations of the membrane were seen in some cells, and these hyperpolarizations were similar to those recorded on submaximal stimulation of the intramural nerves.6. There were no changes in the characteristics of the i.j.p. in

  7. Evidence for the primary role for 4-aminopyridine-sensitive K(v) channels in beta(3)-adrenoceptor-mediated, cyclic AMP-independent relaxations of guinea-pig gastrointestinal smooth muscles.

    PubMed

    Horinouchi, Takahiro; Tanaka, Yoshio; Koike, Katsuo

    2003-02-01

    contribute to cyclic AMP-independent vascular smooth muscle relaxations induced through activation of G(s) protein-coupled receptors, did not apparently show any inhibitory effects on SQ-22536-resistant, beta(3)-adrenoceptor-mediated relaxations in these gastrointestinal smooth muscles. The present results indicate that 4-AP-sensitive K(v) channels play a primary role in beta(3)-adrenoceptor-mediated, cyclic AMP-independent relaxations of guinea-pig gastrointestinal smooth muscles. In these smooth muscles, BK(Ca) channels seem to apparently contribute insignificantly to cyclic AMP-independent relaxations following stimulation of beta(3)-type of adrenoceptors.

  8. Assessment of in vivo fetal growth and placental vascular function in a novel intrauterine growth restriction model of progressive uterine artery occlusion in guinea pigs

    PubMed Central

    Herrera, Emilio A.; Alegría, René; Farias, Marcelo; Díaz‐López, Farah; Hernández, Cherie; Uauy, Ricardo; Regnault, Timothy R. H.; Casanello, Paola

    2016-01-01

    Key points Intrauterine growth restriction (IUGR) is associated with short‐ and long‐term detrimental cardiometabolic effects.Mice and rats are commonly used to assess IUGR, but differences in placental and fetal developmental physiology relative to those in humans highlight the need for alternative small animal IUGR models.We developed a guinea pig IUGR model by gradual occlusion of uterine arteries by ameroid constrictor implantation. In this model, reduced uterine blood flow was associated with IUGR, allowing in vivo assessment of fetal growth trajectory and umbilico‐placental vascular function in conscious animals.The intervention induces placental vascular dysfunction and remodelling, as well as altered fetal abdominal growth resulting in an asymmetric IUGR and preserved brain growth. Abstract Intra‐uterine growth restriction (IUGR) is associated with short and long‐term metabolic and cardiovascular alterations. Mice and rats have been extensively used to study the effects of IUGR, but there are notable differences in fetal and placental physiology relative to those of humans that argue for alternative animal models. This study proposes that gradual occlusion of uterine arteries from mid‐gestation in pregnant guinea pigs produces a novel model to better assess human IUGR. Fetal biometry and in vivo placental vascular function were followed by sonography and Doppler of control pregnant guinea pigs and sows submitted to surgical placement of ameroid constrictors in both uterine arteries (IUGR) at mid‐gestation (35 days). The ameroid constrictors induced a reduction in the fetal abdominal circumference growth rate (0.205 cm day−1) compared to control (0.241 cm day−1, P < 0.001) without affecting biparietal diameter growth. Umbilical artery pulsatility and resistance indexes at 10 and 20 days after surgery were significantly higher in IUGR animals than controls (P < 0.01). These effects were associated with a decrease in the relative

  9. Regulation of intracellular pH in the smooth muscle of guinea-pig ureter: Na+ dependence.

    PubMed Central

    Aickin, C C

    1994-01-01

    1. Mechanisms involved in the regulation of intracellular pH (pHi) in smooth muscle cells of guinea-pig ureter have been investigated using double-barrelled pH-sensitive microelectrodes in isolated strips of tissue. 2. Removal of CO2-HCO3- from the superfusing solution caused a fall in the steady-state pHi except in a few cells which had been excised from the animal for many hours (usually > 24 h). The pHi value was 7.22 +/- 0.09 (n = 89; mean +/- S.D. of an observation) in solution buffered with 5% CO2-21 mM HCO3-, compared with 6.92 +/- 0.24 (n = 67) in the nominal absence of CO2-HCO3-. Recovery from experimentally induced acidosis was faster in the presence, rather than nominal absence, of CO2-HCO3- (mean half-times of 2.7 +/- 0.7 min, n = 41, and 4.6 +/- 1.3 min, n = 12, respectively). These results suggest the presence of both HCO(3-)-dependent and -independent mechanisms for the effective extrusion of acid equivalents. 3. Recovery from acidosis was dependent on external Na+ (Na+o) in both the presence and nominal absence of CO2-HCO3-, with an apparent half-maximal activation at approximately 4 and 20 mM Na+o, respectively. Removal of Na+o in the steady state caused a fall in pHi which proceeded at a faster rate in the presence rather than in the nominal absence of CO2-HCO3-. 4. Amiloride (100 microM-1 mM) reversibly inhibited the recovery from acidosis and caused a fall in the steady-state pHi when applied in the nominal absence of CO2-HCO3-, but had no measurable effect on either the recovery from acidosis or steady-state pHi in the presence of CO2-HCO3-. These results suggest that Na(+)-H+ exchange was responsible for extrusion of acid equivalents in the nominal absence of CO2 and HCO3-, but that it played little part under more physiological conditions. 5. Although Na(+)-H+ exchange appeared to be activated below a pHi of about 7.2, it was incapable of maintaining a 'normal' pHi in the nominal absence of CO2-HCO3- in freshly excised cells, where values

  10. gamma-Aminobutyric acid-A receptor-mediated suppression of 5-hydroxytryptamine-induced guinea-pig basilar artery smooth muscle contractility.

    PubMed

    Shirakawa, J; Hosoda, K; Taniyama, K; Matsumoto, S; Tanaka, C

    1989-01-01

    The mechanism of gamma-aminobutyric acid (GABA)-induced suppression of 5-hydroxytryptamine (5HT)-induced contractility of cerebral blood vessels was studied in single smooth muscle cells isolated from the guinea-pig basilar artery. GABA reduced 5HT-induced contraction of single smooth muscle cells, and the effect of GABA was mimicked by muscimol, but not baclofen. The response of muscimol was antagonized by bicuculline, thereby indicating that GABAA receptors exist on the smooth muscle of the basilar artery. Since GABA did not change the contraction induced by the addition of Ca2+ to the Ca2+-free medium in the presence of high K+, it is unlikely that GABA inhibits the influx of extracellular Ca2+. The caffeine-induced contraction in the Ca2+-free medium was reduced by GABA, and the effect of GABA was not obtained by treatment with furosemide and in the Cl- -free medium. These results indicate that GABA acts on the GABAA receptor located on smooth muscle cells and reduces the contractility of the basilar artery by suppression of the mobilization of intracellular Ca2+.

  11. 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

  12. Functional differences of Na+/Ca2+ exchanger expression in Ca2+ transport system of smooth muscle of guinea pig stomach.

    PubMed

    Sakai, Yasushi; Kinoshita, Hiroki; Saitou, Keiichirou; Homma, Ikuo; Nobe, Koji; Iwamoto, Takahiro

    2005-01-01

    The plasma membrane ATP-dependent Ca2+ pump and the Na+/Ca2+ exchanger (NCX) are the major means of Ca2+ extrusion in smooth muscle. However, little is known regarding distribution and function of the NCX in guinea pig gastric smooth muscle. The expression pattern and distribution of NCX isoforms suggest a role as a regulator of Ca2+ transport in cells. Na+ pump inhibition and the consequent to removal of K+ caused gradual contraction in fundus. In contrast, the response was significantly less in antrum. Western blotting analysis revealed that NCX1 and NCX2 are the predominant NCX isoforms expressed in stomach, the former was expressed strongly in antrum, whereas the latter displayed greater expression in fundus. Isolated plasma membrane fractions derived from gastric fundus smooth muscle were also investigated to clarify the relationship between NCX protein expression and function. Na+-dependent Ca2+ uptake increased directly with Ca2+ concentration. Ca2+ uptake in Na+-loaded vesicles was markedly elevated in comparison with K+-loaded vesicles. Additionally, Ca2+ uptake by the Na+- or K+-loaded vesicles was substantially higher in the presence of A23187 than in its absence. The result can be explained based on the assumption that Na+ gradients facilitate downhill movement of Ca2+. Na+-dependent Ca2+ uptake was abolished by the monovalent cationic ionophore, monensin. NaCl enhanced Ca2+ efflux from vesicles, and this efflux was significantly inhibited by gramicidin. Results documented evidence that NCX2 isoform functionally contributes to Ca2+ extrusion and maintenance of contraction-relaxation cycle in gastric fundus smooth muscle.

  13. Mechanisms for monovalent cation-dependent depletion of intracellular Mg2+:Na+-independent Mg2+ pathways in guinea-pig smooth muscle

    PubMed Central

    Nakayama, Shinsuke; Nomura, Hideki; Smith, Lorraine M; Clark, Joseph F; Uetani, Tadayuki; Matsubara, Tatsuaki

    2003-01-01

    It has been suggested that magnesium deficiency is correlated with many diseases. 31P NMR experiments were carried out in order to investigate the effects of Na+ substitution on Mg2+ depletion in smooth muscle under divalent cation-free conditions. In the taenia of guinea-pig caeci, the intracellular free Mg2+ concentration ([Mg2+]i) was estimated from the chemical shifts of (1) the β-ATP peak alone and (2) β- and γ-ATP peaks. Both estimations indicated that [Mg2+]i decreased only very slowly in Mg2+-free, Ca2+-free solutions in which Na+ was substituted with large cations such as NMDG (N-methyl-D-glucamine) and choline. Furthermore, the measurements of tension development supported the suggestion of preservation of intracellular Mg2+ with NMDG substitution. Substituting extracellular Na+ with the small cation, Li+, also shifted the β-ATP peak towards a lower frequency, but the frequency shift was significantly less than that seen upon Na+ substitution with K+. The estimated [Mg2+]i depletion was, however, comparable with that seen after Na+ substitution with K+ using the titration curves of metal-free and Mg2+-bound ATP obtained in Li+-based model solutions. It was concluded that Mg2+ rapidly decreases only when small cations were the major electrolyte of the extracellular medium. Na+ substitutions with NMDG, choline or Li+ had little effect on intracellular ATP concentration after 100 min treatment. PMID:12844514

  14. Large-conductance voltage- and Ca2+-activated K+ channel regulation by protein kinase C in guinea pig urinary bladder smooth muscle.

    PubMed

    Hristov, Kiril L; Smith, Amy C; Parajuli, Shankar P; Malysz, John; Petkov, Georgi V

    2014-03-01

    Large-conductance voltage- and Ca(2+)-activated K(+) (BK) channels are critical regulators of detrusor smooth muscle (DSM) excitability and contractility. PKC modulates the contraction of DSM and BK channel activity in non-DSM cells; however, the cellular mechanism regulating the PKC-BK channel interaction in DSM remains unknown. We provide a novel mechanistic insight into BK channel regulation by PKC in DSM. We used patch-clamp electrophysiology, live-cell Ca(2+) imaging, and functional studies of DSM contractility to elucidate BK channel regulation by PKC at cellular and tissue levels. Voltage-clamp experiments showed that pharmacological activation of PKC with PMA inhibited the spontaneous transient BK currents in native freshly isolated guinea pig DSM cells. Current-clamp recordings revealed that PMA significantly depolarized DSM membrane potential and inhibited the spontaneous transient hyperpolarizations in DSM cells. The PMA inhibitory effects on DSM membrane potential were completely abolished by the selective BK channel inhibitor paxilline. Activation of PKC with PMA did not affect the amplitude of the voltage-step-induced whole cell steady-state BK current or the single BK channel open probability (recorded in cell-attached mode) upon inhibition of all major Ca(2+) sources for BK channel activation with thapsigargin, ryanodine, and nifedipine. PKC activation with PMA elevated intracellular Ca(2+) levels in DSM cells and increased spontaneous phasic and nerve-evoked contractions of DSM isolated strips. Our results support the concept that PKC activation leads to a reduction of BK channel activity in DSM via a Ca(2+)-dependent mechanism, thus increasing DSM contractility.

  15. Regulation of Guinea Pig Detrusor Smooth Muscle Excitability by 17β-Estradiol: The Role of the Large Conductance Voltage- and Ca2+-Activated K+ Channels.

    PubMed

    Provence, Aaron; Hristov, Kiril L; Parajuli, Shankar P; Petkov, Georgi V

    2015-01-01

    Estrogen replacement therapies have been suggested to be beneficial in alleviating symptoms of overactive bladder. However, the precise regulatory mechanisms of estrogen in urinary bladder smooth muscle (UBSM) at the cellular level remain unknown. Large conductance voltage- and Ca2+-activated K+ (BK) channels, which are key regulators of UBSM function, are suggested to be non-genomic targets of estrogens. This study provides an electrophysiological investigation into the role of UBSM BK channels as direct targets for 17β-estradiol, the principle estrogen in human circulation. Single BK channel recordings on inside-out excised membrane patches and perforated whole cell patch-clamp were applied in combination with the BK channel selective inhibitor paxilline to elucidate the mechanism of regulation of BK channel activity by 17β-estradiol in freshly-isolated guinea pig UBSM cells. 17β-Estradiol (100 nM) significantly increased the amplitude of depolarization-induced whole cell steady-state BK currents and the frequency of spontaneous transient BK currents in freshly-isolated UBSM cells. The increase in whole cell BK currents by 17β-estradiol was eliminated upon blocking BK channels with paxilline. 17β-Estradiol (100 nM) significantly increased (~3-fold) the single BK channel open probability, indicating direct 17β-estradiol-BK channel interactions. 17β-Estradiol (100 nM) caused a significant hyperpolarization of the membrane potential of UBSM cells, and this hyperpolarization was reversed by blocking the BK channels with paxilline. 17β-Estradiol (100 nM) had no effects on L-type voltage-gated Ca2+ channel currents recorded under perforated patch-clamp conditions. This study reveals a new regulatory mechanism in the urinary bladder whereby BK channels are directly activated by 17β-estradiol to reduce UBSM cell excitability.

  16. Inhibitory action of insulin-sensitizing agents on calcium channels in smooth muscle cells from resistance arteries of guinea-pig

    PubMed Central

    Nakamura, Yoshito; Ohya, Yusuke; Onaka, Uran; Fujii, Koji; Abe, Isao; Fujishima, Masatoshi

    1998-01-01

    The actions of troglitazone, pioglitazone, metformin and bezafibrate, agents that improve insulin-resistance, on voltage-dependent Ca2+ channels in arterial smooth muscle cells were examined by use of the conventional and nystatin-perforated whole-cell clamp methods. Single cells were freshly isolated from resistance mesenteric arteries of guinea-pigs. The actions of these agents on 77 mM K+-induced contraction of the isolated arteries were also examined with the use of isometric tension recording. The thiazolidinedione derivatives, troglitazone and pioglitazone, inhibited whole-cell Ca2+ currents in a dose-dependent manner with dissociation constants of 3.0 μM and 44.9 μM and Hill coefficients of 0.61 and 0.68, respectively. These two agents inhibited the 77 mM K+-induced contraction with similar potencies as those inhibiting the Ca2+ currents. Metformin and bezafibrate had no apparent effects on the Ca2+ current or high K+-induced contraction. The inhibitory action of troglitazone on Ca2+ currents was not affected by the command potential, the holding potential, or the stimulation frequency, suggesting that its mode of the action differs from that of known organic Ca2+ channel antagonists. The inhibitory action of troglitazone on Ca2+ currents was not affected by the addition of insulin to, or the removal of glucose from, the solutions. In conclusion, the thiazolidinedione derivatives directly inhibited the voltage-dependent Ca2+ channels in a different manner from that of organic Ca2+ channel antagonists. This inhibitory action on Ca2+ channels was not a common feature of insulin-sensitizing agents. PMID:9517387

  17. Modulation of slow waves by transmural nerve stimulation of smooth muscle tissue isolated from the corpus of the guinea-pig stomach.

    PubMed

    Tanaka, Chiharu; Domae, Kazumasa; Hashitani, Hikaru; Suzuki, Hikaru

    2009-06-01

    Modulation of slow waves in response to transmural nerve stimulation (TNS) was investigated in smooth muscle preparations isolated from the corpus of the guinea-pig stomach. Single TNS evoked an inhibitory junction potential (i.j.p.) and enhanced the amplitude of the following slow wave. Effects of atropine, N(omega)-nitro-L-arginine (L-NA) and apamin revealed that corpus smooth muscle was innervated by cholinergic excitatory, nitrergic inhibitory and apamin-sensitive inhibitory nerves. In preparations isolated from the upper corpus which generated slow waves of 5-15 mV amplitude, a 1 min train of TNS (0.5 or 1 Hz frequency) increased the amplitude, with further enhancement by L-NA, but inhibition by atropine. In the lower corpus, larger amplitude (20-30 mV) slow waves were generated but these were not altered by a TNS train. However, application of L-NA and neostigmine, or often L-NA alone, resulted in increased frequency and decreased amplitude of slow waves during TNS, with an associated depolarization of the membrane. These changes were inhibited by atropine. In the presence of atropine, TNS reduced slow wave amplitude in an L-NA-sensitive manner. Acetylcholine (ACh) at 1 nM increased the amplitude of slow waves in the upper corpus. In the lower corpus, while low concentrations of ACh (<10 nM) did not increase the frequency and decrease the amplitude of slow waves with an associated depolarization of the membrane, this occurred at high concentrations of ACh (>10 nM). Application of the NO donor, sodium nitroprusside (SNP, 10 nM-1 microM), reduced the amplitude of slow waves. The changes in amplitude of slow waves elicited by ACh or SNP were not associated with a significant change in frequency. These results indicate that in the corpus circular smooth muscle, neural modulation of slow waves appeared to be exerted mainly on the amplitude, but not on the frequency.

  18. Effects of endogenous and exogenous nitric oxide on electrical responses of circular smooth muscle isolated from the guinea-pig stomach antrum.

    PubMed

    Nakamura, Eri; Lee, Kyu Pil; So, Insuk; Kim, Ki Whan; Suzuki, Hikaru

    2004-10-01

    The effects of endogenous and exogenous nitric oxide (NO) on electrical activity were investigated in circular smooth muscle preparations isolated from the guinea-pig stomach antrum. The actions of endogenous NO were evaluated from the effects of inhibition of NO synthesis by N(omega)-nitro-L-arginine (nitroarginine), while those of exogenous NO were assessed from the effects of SIN-1, an NO donor. Antral circular smooth muscle generated slow potentials periodically at a frequency of about 1 cycle per min (cpm), and unitary potentials were also generated in a random fashion in the interval between slow potentials. Application of nitroarginine (10(-5) M) increased the frequency of slow potentials, with no significant alteration of the resting membrane potential and amplitude of slow potentials. Frequency analysis of unitary potentials revealed that nitroarginine also increased the spectral density at 0.01-1 Hz frequency. The refractory period for the generation of slow potentials evoked by depolarizing pulses was about 10 s, but was decreased to 6 s by nitroarginine. In the presence of nitroarginine, SIN-1 (10(-9)-10(-7) M) reduced the amplitude and frequency of slow potentials: low concentrations (<10(-8) M) reduced only the frequency of slow potentials, while higher concentrations (10(-8)-10(-7) M) reduced both the amplitude and frequency of slow potentials, in a concentration-dependent manner, before abolishing the slow potentials. The power spectrum of the unitary potentials indicated that SIN-1 (>10(-8) M) reduced the spectral density at 0.01-1 Hz frequency. The refractory period for the generation of slow potentials was increased again to about 10 s by SIN-1. Thus, the excitatory effects of nitroarginine could be antagonized by SIN-1, suggesting that the inhibitory effects of endogenous NO are comparable to those of exogenous NO produced by SIN-1. The results also suggested that the effects of NO on smooth muscle are insignificant and NO selectively inhibits

  19. Cardio-vascular safety beyond hERG: in silico modelling of a guinea pig right atrium assay

    NASA Astrophysics Data System (ADS)

    Fenu, Luca A.; Teisman, Ard; De Buck, Stefan S.; Sinha, Vikash K.; Gilissen, Ron A. H. J.; Nijsen, Marjoleen J. M. A.; Mackie, Claire E.; Sanderson, Wendy E.

    2009-12-01

    As chemists can easily produce large numbers of new potential drug candidates, there is growing demand for high capacity models that can help in driving the chemistry towards efficacious and safe candidates before progressing towards more complex models. Traditionally, the cardiovascular (CV) safety domain plays an important role in this process, as many preclinical CV biomarkers seem to have high prognostic value for the clinical outcome. Throughout the industry, traditional ion channel binding data are generated to drive the early selection process. Although this assay can generate data at high capacity, it has the disadvantage of producing high numbers of false negatives. Therefore, our company applies the isolated guinea pig right atrium (GPRA) assay early-on in discovery. This functional multi-channel/multi-receptor model seems much more predictive in identifying potential CV liabilities. Unfortunately however, its capacity is limited, and there is no room for full automation. We assessed the correlation between ion channel binding and the GPRA's Rate of Contraction (RC), Contractile Force (CF), and effective refractory frequency (ERF) measures assay using over six thousand different data points. Furthermore, the existing experimental knowledge base was used to develop a set of in silico classification models attempting to mimic the GPRA inhibitory activity. The Naïve Bayesian classifier was used to built several models, using the ion channel binding data or in silico computed properties and structural fingerprints as descriptors. The models were validated on an independent and diverse test set of 200 reference compounds. Performances were assessed on the bases of their overall accuracy, sensitivity and specificity in detecting both active and inactive molecules. Our data show that all in silico models are highly predictive of actual GPRA data, at a level equivalent or superior to the ion channel binding assays. Furthermore, the models were interpreted in

  20. Hydro-ethanolic Extract of Portulaca oleracea Affects Beta-adrenoceptors of Guinea Pig Tracheal Smooth Muscle

    PubMed Central

    Boskabady, Mohammad Hossein; Hashemzehi, Milad; Khazdair, Mohammad Reza; Askari, Vahid Reza

    2016-01-01

    Thestimulatory effect of the extract of Portulaca oleracea (P. olerace) on β-adrenoceptor of tracheal smooth muscle was examined.To examine β-adrenoceptor stimulatory effect, concentration response curve to isoprenaline was obtained in pre-contracted tracheal smooth muscle in the presence of three concentrations of aqueous-ethanolic extract, propranolol, and saline. Values of EC50 (the effective concentration of isoprenaline, causing 50% of maximum response) and dose ratio-1(CR-1) were measured. This effect was tested innon-incubated tracheal smooth muscle (group 1) and incubated tissues with chlorpheniramine (group 2). Concentration-response curves to isoprenaline in the presence of two higher concentrations of the extract in group 1 and all three concentrations in group 2 showed leftward shifts compared to isoprenaline curves produced in the presence of saline in both groups. EC50 obtained in the presence of propranolol was significantly higher than that of saline in both groups of experiments (p<0.05 for both cases). However, the EC50 obtained in the presence of two higher concentrations of the extract in group 1 and lower concentration in group 2 were non-significantly but those obtained of medium and high extract concentrations in the group 2 were significantly (p<0.05 for both cases)lower than those of saline. The values of (CR-1) obtained in the presence of all concentrations of the extract in groups1 and 2 were significantly lower than that of propranolol (p<0.05 to p<0.001).The results indicated a stimulatory effect of the P. olerace extract on ß 2-adrenoceptors of tracheal smooth muscle. PMID:28243284

  1. Spontaneous reproductive pathology in female guinea pigs.

    PubMed

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

    2016-11-01

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

  2. 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.

  3. Heme oxygenase-2 products activate IKCa: role of CO and iron in guinea pig portal vein smooth muscle cells.

    PubMed

    Hristov, Kiril L; Gagov, Hristo S; Itzev, Dimitar; Duridanova, Dessislava B

    2004-01-01

    Hemin (10 microM) and carbon monoxide (CO) increased iberiotoxin-blockable IKCa in portal vein smooth muscle cells. CO-induced IKCa activation was abolished by 10 microM ODQ, 10 microM cyclopiazonic acid and 1 microM KT5823. The hemin-induced effect on IKCa was abolished by pretreatment with Sn-protoporphyrin IX, a heme oxygenase inhibitor and Fe2+ chelator but was insensitive to inhibitors of soluble guanylate cyclase (GC) and cGMP-dependent protein kinase (PKG). There was no effect of hemin on IKCa in the presence of 3 microM dithiotreitol into the bath or 3 mM glutathione into the pipette solution. Superoxide dismutase (1000 U/ml) or catalase (3000 U/ml) added into the pipette solution also abolished the effect of hemin on IKCa in this tissue. Additionally, 10 microM hemin could not influence IKCa in Ca2+-free external solution or in the presence of 30 microM SKF 95356. It was concluded that CO increases IKCa via its "conventional" signaling pathway, which involves soluble GC and PKG activation and subsequent stimulation of sarcoplasmic reticulum Ca2+ pump activity resulting in Ca2+-dependent activation of IKCa due to the accumulation of Ca2+ into the space near the plasma membrane. On the other hand, internally produced CO could not yield the same IKCa increase, while Fe2+ derived from heme oxygenase 2-dependent degradation of hemin in portal vein smooth muscle cells gives rise to reactive oxygen species namely hydroxyl and superoxide radicals. Both radicals are responsible for the SKF 95356-sensitive non-selective cation channel activation, the Ca2+ influx and the subsequent increase of Ca2+ concentration near the plasma membrane that augments the KCa channel activity.

  4. Omental torsion in a guinea pig (Cavia porcellus)

    PubMed Central

    Shrubsole-Cockwill, Alana N.; Cockwill, Ken R.N.; Parker, Dennilyn L.

    2008-01-01

    An adult intact male guinea pig (Cavia porcellus) was presented with gastrointestinal stasis. Radiographic findings demonstrated a gas- and fluid-filled cecum. Treatment was initiated but the animal died shortly after presentation. Gross postmortem revealed omental torsion with vascular thrombosis and necrosis. This is the first report of omental torsion with vascular thrombosis in a domestic animal. PMID:19043488

  5. Ca2+ inhibition of inositol trisphosphate-induced Ca2+ release in single smooth muscle cells of guinea-pig small intestine.

    PubMed Central

    Zholos, A V; Komori, S; Ohashi, H; Bolton, T B

    1994-01-01

    1. Single smooth muscle cells from the longitudinal muscle layer of guinea-pig small intestine were voltage clamped using patch pipettes in the whole-cell mode. 2. When D-myo-inositol 1,4,5-trisphosphate (InsP3) was released at intervals, by photolysis of 'caged' InsP3 within the cell, increases in [Ca2+]i in many cells, as judged from Ca(2+)-activated K(+)-current, were all-or-none; release of InsP3 before a critical interval had elapsed, which was quite stable for an individual cell, resulted in no response. After Ca(2+)-induced Ca2+ release had been evoked by depolarization, the InsP3 response was inhibited. Oscillations in [Ca2+]i evoked by muscarinic receptor activation were unaffected by Ruthenium Red; during these oscillations exogenous InsP3 was not effective close to, or shortly after, peak [Ca2+]i but was effective at other times. 3. Reproducible release of Ca2+ and elevation of [Ca2+]i could be produced by brief (up to 0.5 s) pressure applications of 10 mM caffeine at intervals of 10 s or greater but caffeine itself rarely evoked oscillations in [Ca2+]i. Responses to flash release of InsP3 were reduced after caffeine-induced responses and recovery of caffeine-induced Ca2+ release was faster than recovery of InsP3-induced Ca2+ release. 4. The results support the idea that InsP3-induced Ca(2+)-store release can be inhibited by a certain level of [Ca2+]i at a time when Ca2+ stores have refilled and can be released by caffeine; they also support the suggestion that during oscillations of [Ca2+]i evoked by muscarinic receptor activation, Ca2+ inhibition of InsP3-induced Ca2+ release at some critical level of [Ca2+]i allows Ca2+ stores to refill and leads to a fall in [Ca2+]i so contributing to the oscillations which are observed. PMID:7531770

  6. Insulinoma in 2 guinea pigs (Cavia porcellus)

    PubMed Central

    2005-01-01

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

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

    PubMed

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

    2015-01-01

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

  8. Relaxant effects of NKH477, a new water-soluble forskolin derivative, on guinea-pig tracheal smooth muscle: the role of Ca2+-activated K+ channels

    PubMed Central

    Satake, K; Takagi, K; Kodama, I; Honjo, H; Toyama, J; Shibata, S

    1998-01-01

    Mechanisms underlying the bronchorelaxant action of NKH477, a newly developed water-soluble forskolin derivative, were investigated in guinea-pig isolated tracheal smooth muscle. In muscles precontracted with 3 μM histamine, NKH477 (1 nM–1 μM) caused a concentration-dependent decrease of isometric tension, resulting in a complete relaxation at 300 nM. The EC50 for the relaxation was 32.6±4.3 nM (n=6). In the presence of 30 or 90 nM iberiotoxin (IbTX), a selective blocker of the large-conductance Ca2+-activated K+ (BKCa) channel, the relaxing action of NKH477 on the histamine-induced contraction was inhibited, giving rise to a parallel shift of the concentration-response curves; the EC50 of NKH477 was increased to 131.4±20.4 nM at 30 nM IbTX (n=4), and 125.3±12.2 nM at 90 nM IbTX (n=4). Pretreatment of muscles with 30 mM tetraethylammonium (TEA) caused a similar rightward shift of the concentration-response curve to NKH477 with an increase of the EC50 to 139.8±18.4 nM (n=5). In contrast, the relaxing action of NKH477 was unaffected by 10 μM glibenclamide, an ATP-sensitive K+ channel blocker, or by 100 nM apamin, a blocker of small conductance Ca2+-activated K+ channels. In muscles pretreated with 1 μM nifedipine, a blocker of the voltage-dependent Ca2+ channel (VDC), 30–90 nM IbTX did not affect the relaxant effects of NKH477 on the histamine-induced contraction. In muscles precontracted by a K+-rich (40 mM) solution, NKH477 caused only minimal relaxation (19.8±1.7%, n=4) even at the highest concentration (1 μM). In experiments to measure the ratio of fura-2 fluorescence signals (R340/380) as an index of the intracellular Ca2+ concentration ([Ca2+]i), the application of 100 nM NKH477 or 200 nM isoprenaline to the preparation precontracted by 3 μM histamine resulted in a decrease in [Ca2+]i in association with a decrease in tension. The reduction of [Ca2+]i and tension by NKH477 was 47.0±5.6% and 62.8±7

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

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

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

  10. Guinea-pig reaginic antibody

    PubMed Central

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

    1973-01-01

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

  11. Guinea-pig reaginic antibody

    PubMed Central

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

    1973-01-01

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

  12. 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

  13. Effects of (-)-desmethoxyverapamil on heart and vascular smooth muscle

    SciTech Connect

    Nawrath, H.; Raschack, M.

    1987-09-01

    (-)-Desmethoxyverapamil (also known as (-)-devapamil or (-)-D888) has been developed as a verapamil type radioligand for the study of calcium channels. In the present investigation, the effects of (-)-desmethoxyverapamil on action potential (AP) and force of contraction in heart muscle preparations and on tension and /sup 45/Ca influx in vascular smooth muscle are described. In part, the effects were compared with the (+)-isomer of desmethoxyverapamil and the isomers of both verapamil and methoxyverapamil. In atrial and/or ventricular heart muscle preparations from guinea pigs, cats and man, (-)-desmethoxyverapamil decreased the force of contraction and shortened the AP duration. Slow response APs were depressed, whereas dV/dtmax of phase 0 of the AP remained unchanged. The rank order of potency of the (-)-isomers was as follows: desmethoxyverapamil greater than methoxyverapamil greater than verapamil. Potassium-induced contractures and /sup 45/Ca influx were depressed by the (-)-isomers of desmethoxyverapamil, methoxyverapamil and verapamil in the same potency rank order as observed in heart muscle. The (+)-isomers exerted qualitatively similar effects at about 10 to 200 times higher concentrations. Correspondingly, the increase in potency of the racemic mixtures of the drugs was accompanied by increases in stereoselectivity. It is concluded that (-)-desmethoxyverapamil is the most potent stereoselective calcium antagonist of the verapamil type with respect to its effects on heart and vascular smooth muscle.

  14. 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)

  15. Creep after loading in relaxed and contracted (KC1 or K2SO4 depolarized) smooth muscle (taenia coli of the guinea pig).

    PubMed

    Greven, K; Hohorst, B

    1975-08-29

    1. The time course of creep in the taenia coli of the guinea pig was recorded during 2000 sec (33 min 20 sec) in the relaxed (Ca2+-free bath solution with verapamil) and contracted (KCl or K2SO4 depolarized) states. 2. The variations in initial length before loading (l0), immediate elastic extension after loading (lE), and creep (N) were standardized with respoect to volume (cm/cm3) and compared among the different states. 3. Immediate elastic extension (lE) and particularly creep after 2000 sec (N2000) are minimal in the relaxed and maximal in the K2SO4-contracted state. The values in the KCl-contracted state are probably affected by intracellular swelling. Statistically, there is a significant difference between the overall length (l0 + lE + N2000) in the relaxed and in the K2SO4-contracted state when creep ends. 4. The hyperbolic relation of N to dN/dt representing the time course of creep mentioned in an earlier paper is reconfirmed for the relaxed as well as for the contracted state. 5. The parameters of the equation giving this relation are calculated from the experimental data. They characterize elastic properties and inner friction during creep. It is shown that the parameters of inner friction diminish more than those characterizing the elastic properties if the preparation is changed from the relaxed into the contracted state by K2SO4-depolarization. 6. In the discussion further evidence is given that not only changes in the diameter of the preparation but also changes of the intracellular elements must be responsible for the altered time course of creep during contraction.

  16. 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.

  17. 9 CFR 113.38 - Guinea pig safety test.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  18. 9 CFR 113.38 - Guinea pig safety test.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Guinea pig safety test. 113.38 Section... Standard Procedures § 113.38 Guinea pig safety test. The guinea pig safety test provided in this section... be injected either intramuscularly or subcutaneously into each of two guinea pigs and the...

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

    PubMed

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

    2014-11-01

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

  20. 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

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

    PubMed Central

    Yamamoto, T.; Cochrane, C. G.

    1982-01-01

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

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

    PubMed

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

    2012-07-01

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

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

    PubMed

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

    2006-06-01

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

  4. Skin toxicity of propranolol in guinea pigs.

    PubMed

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

    1999-05-01

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

  5. Prolactin Family of the Guinea Pig, Cavia porcellus

    PubMed Central

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

    2010-01-01

    Prolactin (PRL) is a multifunctional hormone with prominent roles in regulating growth and reproduction. The guinea pig (Cavia porcellus) has been extensively used in endocrine and reproduction research. Thus far, the PRL cDNA and protein have not been isolated from the guinea pig. In the present study, we used information derived from the public guinea pig genome database as a tool for identifying guinea pig PRL and PRL-related proteins. Guinea pig PRL exhibits prominent nucleotide and amino acid sequence differences when compared with PRLs of other eutherian mammals. In contrast, guinea pig GH is highly conserved. Expression of PRL and GH in the guinea pig is prominent in the anterior pituitary, similar to known expression patterns of PRL and GH for other species. Two additional guinea pig cDNAs were identified and termed PRL-related proteins (PRLRP1, PRLRP2). They exhibited a more distant relationship to PRL and their expression was restricted to the placenta. Recombinant guinea pig PRL protein was generated and shown to be biologically active in the PRL-responsive Nb2 lymphoma cell bioassay. In contrast, recombinant guinea pig PRLRP1 protein did not exhibit PRL-like bioactivity. In summary, we have developed a new set of research tools for investigating the biology of the PRL family in an important animal model, the guinea pig. PMID:20534723

  6. Arrangement of Renal Arteries in Guinea Pig.

    PubMed

    Mazensky, David; Flesarova, Slavka

    2017-03-01

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

  7. Watch out guinea pigs, here I come.

    PubMed

    Norton, T

    2001-04-01

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

  8. New guinea pig model of Cryptococcal meningitis.

    PubMed

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

    2007-08-01

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

  9. 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.

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

    PubMed

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

    1977-10-01

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

  11. Cyclic nucleotide phosphodiesterase isoenzymes in guinea-pig tracheal muscle and bronchorelaxation by alkylxanthines.

    PubMed

    Miyamoto, K; Kurita, M; Sakai, R; Sanae, F; Wakusawa, S; Takagi, K

    1994-09-15

    In this study the phosphodiesterase (PDE) isoenzymes in guinea-pig trachealis smooth muscle were separated by DEAE-Sepharose anion exchange chromatography, identified, and characterized. Furthermore the effect of theophylline and 1-n-butyl-3-n-propylxanthine (BPX) on the isolated PDE isoenzymes and on their tracheal relaxant effect were investigated and compared with the nonxanthine PDE inhibitors amrinone and Ro 20-1724. We identified five distinct isoenzymes in guinea-pig tracheal muscle; calcium/calmodulin-stimulated cyclic AMP PDE (PDE I), cyclic GMP-stimulated cyclic AMP PDE (PDE II), cyclic GMP-inhibited and amrinone-sensitive cyclic AMP PDE (PDE III), cyclic AMP-specific and Ro 20-1724-sensitive PDE (PDE IV), and cyclic GMP-specific PDE (PDE V). BPX strongly inhibited the PDE IV isoenzyme with high selectivity, while the inhibitory effect of theophylline was weak. The PDE IV inhibitors BPX and Ro 20-1724 synergistically increased the relaxant effect of the beta 2-adrenoceptor agonist salbutamol in carbachol-contracted trachea much more strongly than theophylline. In contrast, amrinone, a PDE III inhibitor, hardly influenced the relaxant effect of salbutamol, suggesting that the PDE IV isoenzyme is functionally associated with beta 2-adrenoceptors in guinea-pig trachea and that inhibition of this enzyme potentiates the ability of salbutamol to increase the intracellular cyclic AMP content. These results indicate that the PDE IV isoenzyme plays a significant role in alkylxanthine-mediated relaxation of guinea-pig trachea.

  12. Mechanics of Vascular Smooth Muscle.

    PubMed

    Ratz, Paul H

    2015-12-15

    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.

  13. Etilefrine and amezinium reduce uterine blood flow of pregnant guinea pigs.

    PubMed

    Hohmann, M; Künzel, W

    1989-02-01

    Etilefrine and Amezinium are used during pregnancy to prevent hypotension and fetal growth retardation. The effect of these drugs on uterine blood flow (UBF), uterine vascular resistance (UVR) and fetal growth are, however, unknown. 31 guinea pigs were injected daily with Etilefrine (3 X 0.14 mg/kg) and Amezinium (0.14 mg/kg) from day 30 to day 60. Uterine blood flow was measured with radioactive-labeled microspheres. Uterine vascular resistance was calculated from arterial blood pressure and uterine blood flow. 10 guinea pigs treated with 0.9% sodium chloride served as controls. As a response to Etilefrine and Amezinium, UBF fell by 68 and 48%, respectively, accompanied by an increase in UVR. The fetal weight decreased only slightly. It is concluded that long-term application of anti-hypotensive drugs may be hazardous to uterine blood flow and fetal growth.

  14. Autoradiographic visualization of muscarinic receptor subtypes in human and guinea pig lung

    SciTech Connect

    Mak, J.C.; Barnes, P.J. )

    1990-06-01

    Muscarinic receptor subtypes have been localized in human and guinea pig lung sections by an autoradiographic technique, using (3H)(-)quinuclidinyl benzilate (( 3H)QNB) and selective muscarinic antagonists. (3H)QNB was incubated with tissue sections for 90 min at 25 degrees C, and nonspecific binding was determined by incubating adjacent serial sections in the presence of 1 microM atropine. Binding to lung sections had the characterization expected for muscarinic receptors. Autoradiography revealed that muscarinic receptors were widely distributed in human lung, with dense labeling over submucosal glands and airway ganglia, and moderate labeling over nerves in intrapulmonary bronchi and of airway smooth muscle of large and small airways. In addition, alveolar walls were uniformly labeled. In guinea pig lung, labeling of airway smooth muscle was similar, but in contrast to human airways, epithelium was labeled but alveolar walls were not. The muscarinic receptors of human airway smooth muscle from large to small airways were entirely of the M3-subtype, whereas in guinea pig airway smooth muscle, the majority were the M3-subtype with a very small population of the M2-subtype present. In human bronchial submucosal glands, M1- and M3-subtypes appeared to coexist in the proportions of 36 and 64%, respectively. In human alveolar walls the muscarinic receptors were entirely of the M1-subtype, which is absent from the guinea pig lung. No M2-receptors were demonstrated in human lung. The localization of M1-receptors was confirmed by direct labeling with (3H)pirenzepine. With the exception of the alveolar walls in human lung, the localization of muscarinic receptor subtypes on structures in the lung is consistent with known functional studies.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-02-01

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

  17. 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…

  18. 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...

  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. Aerosolized polymerized type I collagen reduces airway inflammation and remodelling in a guinea pig model of allergic asthma.

    PubMed

    Moreno-Alvarez, Paola; Sánchez-Guerrero, Edgar; Martínez-Cordero, Erasmo; Hernández-Pando, Rogelio; Campos, María G; Cetina, Lucely; Bazán-Perkins, Blanca

    2010-04-01

    Collagen-polyvinylpyrrolidone (Collagen-PVP) has been demonstrated to elicit immunomodulatory properties in different chronic inflammatory diseases. Nevertheless, its effects on asthma are still unknown. We have evaluated whether collagen-PVP could modulate airway inflammation and remodelling in a guinea pig model of allergic asthma. Sensitized guinea pigs were challenged with the allergen (ovalbumin) six times (at 10-day intervals). From the third challenge on, animals were treated every 5 days with saline aerosols containing 0.16, 0.33, or 0.66 mg/ml of collagen-PVP (n = 5, respectively). Some guinea pigs, sensitized and challenged with saline as well as treated with 0 or 0.66 mg/ml collagen-PVP, were included in the study as control (n = 7) and sham groups (n = 5), respectively. From the first challenge on, ovalbumin induced a transient airway obstruction, measured by barometric plethysmography, which was not modified by collagen-PVP treatments. After the last allergen challenge, guinea pigs were anesthetized to obtain bronchoalveolar lavage (BAL) and the left lung caudal lobe. As expected, BAL cell count from allergen-challenged guinea pigs showed abundant neutrophils and eosinophils, as well as numerous tumor necrosis factor (TNF)-alpha-expressing granulocytes and macrophages in airway wall (determined by immunohistochemical assay). Neutrophilia and TNF-alpha-expressing leukocytes, from collagen-PVP treated animals, diminished from 0.16 mg/ml, and eosinophilia from 0.66 mg/ml of collagen-PVP doses. Histological changes induced by allergen challenges include thickening of connective tissue below airway epithelium and vascular wall widening of airway adjacent vessels; these changes were reduced by collagen-PVP treatment. Collagen-PVP seems to have anti-inflammatory and antifibrotic properties in this guinea pig asthma model.

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

    PubMed

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

    2016-01-01

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

  2. Vascular smooth muscle phenotypic diversity and function

    PubMed Central

    2010-01-01

    The control of force production in vascular smooth muscle is critical to the normal regulation of blood flow and pressure, and altered regulation is common to diseases such as hypertension, heart failure, and ischemia. A great deal has been learned about imbalances in vasoconstrictor and vasodilator signals, e.g., angiotensin, endothelin, norepinephrine, and nitric oxide, that regulate vascular tone in normal and disease contexts. In contrast there has been limited study of how the phenotypic state of the vascular smooth muscle cell may influence the contractile response to these signaling pathways dependent upon the developmental, tissue-specific (vascular bed) or disease context. Smooth, skeletal, and cardiac muscle lineages are traditionally classified into fast or slow sublineages based on rates of contraction and relaxation, recognizing that this simple dichotomy vastly underrepresents muscle phenotypic diversity. A great deal has been learned about developmental specification of the striated muscle sublineages and their phenotypic interconversions in the mature animal under the control of mechanical load, neural input, and hormones. In contrast there has been relatively limited study of smooth muscle contractile phenotypic diversity. This is surprising given the number of diseases in which smooth muscle contractile dysfunction plays a key role. This review focuses on smooth muscle contractile phenotypic diversity in the vascular system, how it is generated, and how it may determine vascular function in developmental and disease contexts. PMID:20736412

  3. PEROXISOMES IN INNER ADRENOCORTICAL CELLS OF FETAL AND ADULT GUINEA PIGS

    PubMed Central

    Black, Virginia H.; Bogart, Bruce I.

    1973-01-01

    Abundant membrane-bounded granules, 0.1–0.45 µm in diameter, occur among the elements of the smooth-surfaced endoplasmic reticulum in zona fasciculata and zona reticularis adrenocortical cells of guinea pigs. Acid phosphatase cannot be cytochemically demonstrated in them, and they are therefore distinct from lysosomes. Incubation in medium containing 3,3'-diaminobenzidine results in dense staining of the granules, identifying them as peroxisomes. These small peroxisomes increase in number as fetal adrenocortical cells differentiate, and they appear to arise from dilated regions of endoplasmic reticulum. They maintain interconnections with the smooth endoplasmic reticulum and with one another. PMID:4633170

  4. 9 CFR 113.38 - Guinea pig safety test.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... observed for 7 days. (b) If unfavorable reactions attributable to the product occur in either of the guinea pigs during the observation period, the serial or subserial is unsatisfactory. If unfavorable...

  5. 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.

  6. 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.

  7. Reversing the objective: Adding guinea pig pedagogies

    NASA Astrophysics Data System (ADS)

    Weinstein, Matthew

    2004-03-01

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

  8. Transglutaminase from Hair Follicle of Guinea Pig

    PubMed Central

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

    1972-01-01

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

  9. Electrocardiographic toxicity in the guinea pig.

    PubMed

    Lacroix, Pierre

    2002-11-01

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

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

    PubMed

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

    1992-03-01

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

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

    PubMed

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

    2002-07-01

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

  12. Notch Signaling in Vascular Smooth Muscle Cells.

    PubMed

    Baeten, J T; Lilly, B

    2017-01-01

    The Notch signaling pathway is a highly conserved pathway involved in cell fate determination in embryonic development and also functions in the regulation of physiological processes in several systems. It plays an especially important role in vascular development and physiology by influencing angiogenesis, vessel patterning, arterial/venous specification, and vascular smooth muscle biology. Aberrant or dysregulated Notch signaling is the cause of or a contributing factor to many vascular disorders, including inherited vascular diseases, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, associated with degeneration of the smooth muscle layer in cerebral arteries. Like most signaling pathways, the Notch signaling axis is influenced by complex interactions with mediators of other signaling pathways. This complexity is also compounded by different members of the Notch family having both overlapping and unique functions. Thus, it is vital to fully understand the roles and interactions of each Notch family member in order to effectively and specifically target their exact contributions to vascular disease. In this chapter, we will review the Notch signaling pathway in vascular smooth muscle cells as it relates to vascular development and human disease.

  13. Relative contributions of direct and indirect mechanisms mediating endothelin-induced contraction of guinea-pig trachea.

    PubMed Central

    Hay, D. W.; Hubbard, W. C.; Undem, B. J.

    1993-01-01

    1. The present study was undertaken to determine the mechanism of action of endothelin-1 (ET-1)-induced contraction of the guinea-pig isolated trachea. 2. ET-1 (1 nM-0.3 microM) produces a concentration-dependent contraction of guinea-pig trachea with an EC50 of approximately 25 nM. The combination of the peptidoleukotriene receptor antagonist, SK&F 104353 (10 microM) and the H1-histamine receptor antagonist, mepyramine (10 microM), which abolishes antigen-induced contraction in guinea-pig trachea, was without effect on ET-1 concentration-response curves. Furthermore, the platelet-activating factor (PAF) receptor antagonist, WEB 2086, (1 or 10 microM) did not inhibit ET-induced contraction. 3. ET-1 (0.3 microM) did not stimulate histamine or immunoreactive peptidoleukotriene release from guinea-pig isolated trachea. 4. The release of various prostanoids from guinea-pig trachea was increased significantly by ET-1 (0.3 microM); the profile of release was prostaglandin D2 (PGD2) = PGE2 = 6-keto PGF1 alpha (PGI2 metabolite) > thromboxane B2 = PGF2 alpha >> 9 alpha, 11 beta PGF2 (PGD2 metabolite). ET-1-induced release of prostaglandins, which was about 30% of that elicited by antigen in sensitized tissues, was not affected by epithelium removal and was observed in tissues from which the smooth muscle had been removed. Previous studies in our laboratory indicated that indomethacin potentiated contraction produced by high concentrations of ET-1, whereas a thromboxane receptor antagonist was without appreciable effect on ET-1 concentration-response curves. 5. Pretreatment of tissues for 1 h with capsaicin (10 microM), which depletes different sensory neurones, produced a small, but significant, inhibitory effect on ET-1 concentration-response curves in the presence but not the absence of the epithelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7507780

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

    PubMed

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

    2015-05-10

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

  15. Interstitial cells of Cajal mediate excitatory sympathetic neurotransmission in guinea pig prostate.

    PubMed

    Wang, Jiang-ping; Ding, Guo-fu; Wang, Qin-zhang

    2013-06-01

    Morphological and functional studies have confirmed that interstitial cells of Cajal (ICCs) are involved in many enteric motor neurotransmission pathways. Recent investigations have demonstrated that human and guinea pig prostate glands possess a distinct cell type with morphological and immunological similarities to ICCs. These prostate ICCs have a close relationship with nerve bundles and smooth muscle cells. Prostate smooth muscle tone is largely induced by stimulation from the sympathetic nervous system, which releases excitatory norepinephrine (NE) to act on the α1-adrenoceptor. We have performed morphological and functional experiments to determine the role of ICCs in sympathetic neurotransmission in the guinea pig prostate based on the hypothesis that prostate ICCs act as mediators of sympathetic neurotransmission. Immunohistochemistry revealed many close points of contact between ICCs and sympathetic nerve bundles and smooth muscle cells. Double-labeled sections revealed that α1-adrenoceptor and the gap junction protein connexin 43 were expressed in prostate ICCs. Surprisingly, prostate ICCs co-expressed tyrosine hydroxylase and dopamine β-hydroxylase, two markers of sympathetic neurons. Functionally, the application of NE evoked a large single inward current in isolated prostate ICCs in a dose-dependent manner. The inward current evoked by NE was mediated via the activation of α1-adrenoceptors, because it was abolished by the non-specific α-adrenoceptor antagonist, phentolamine and the specific α1-adrenoceptor antagonist, prazosin. Thus, ICCs in the guinea pig prostate are target cells for prostate sympathetic nerves and possess the morphological and functional characteristics required to mediate sympathetic signals.

  16. Vascular Calcification: Mechanisms of Vascular Smooth Muscle Cell Calcification

    PubMed Central

    Leopold, Jane A.

    2014-01-01

    Vascular calcification is highly prevalent and, when present, is associated with major adverse cardiovascular events. Vascular smooth muscle cells play an integral role in mediating vessel calcification by undergoing differentiation to osteoblast-like cells and generating matrix vesicles that serve as a nidus for calcium-phosphate deposition in the vessel wall. Once believed to be a passive process, it is now recognized that vascular calcification is a complex and highly regulated process that involves activation of cellular signaling pathways, circulating inhibitors of calcification, genetic factors, and hormones. This review will examine several of the key mechanisms linking vascular smooth muscle cells to vessel calcification that may be targeted to reduce vessel wall mineralization and, thereby, reduce cardiovascular risk. PMID:25435520

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

    PubMed

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

    1979-01-01

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

  18. 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

  19. 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

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

    PubMed

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

    2014-10-11

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

  1. 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

  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. 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...

  4. 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...

  5. 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...

  6. 9 CFR 3.36 - Primary enclosures used to transport live guinea pigs and hamsters.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

  7. 9 CFR 3.36 - Primary enclosures used to transport live guinea pigs and hamsters.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

    Rivers, T M; Berry, G P

    1931-06-30

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

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

    PubMed

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

    1995-01-01

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

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

    PubMed

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

    2012-08-01

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

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

    PubMed

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

    2014-10-05

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

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

    PubMed

    Tiritilli, A

    2001-10-01

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

  14. Modulation of sympathetic neurotransmission by neuropeptide Y Y2 receptors in rats and guinea pigs.

    PubMed

    Potter, Erica K; Tripovic, Diana

    2006-08-01

    We have investigated the effect of the Y2 receptor agonist (Y2 agonist; N-acetyl [Leu28,31] NPY 24-36), on contractions evoked by transmural electrical stimulation of sympathetic nerves of isolated arteries from a range of vascular beds in rats and guinea pigs. Contractions evoked by transmural stimulation of the rat renal, mesenteric and femoral arteries were significantly attenuated in the presence of the Y2 agonist. In these arteries, contractions were significantly inhibited in the presence of an alpha-adrenoceptor antagonist (76-97%). So we conclude that these responses were primarily mediated by noradrenaline and that the Y2 agonist attenuates the release of noradrenaline via presynaptic Y2 receptors. Contractions of the rat carotid artery were not attenuated by the Y2 agonist but were completely abolished in the presence of an alpha-adrenoceptor antagonist suggesting that in this artery the Y2 agonist has no effect on release of noradrenaline. In the guinea pig, carotid arteries contractions evoked by transmural nerve stimulation were attenuated in the presence of the Y2 agonist and inhibited by an alpha-adrenoceptor antagonist 75-87% suggesting that the Y2 agonist attenuates the release of noradrenaline via presynaptic Y2 receptors in this vessel. In the guinea pig femoral artery contractions evoked by transmural stimulation were not modified in the presence of the Y2 agonist but were completely abolished in the presence of an alpha-adrenoceptor antagonist. This suggests that the Y2 agonist does not modify noradrenaline release in this vessel. Contractions of the guinea pig mesenteric artery were significantly potentiated by the Y2 agonist, possibly by potentiation of neuropeptide Y (NPY) at the Y1 receptor. The Y1 antagonist inhibited more than 70 % of the response, indicating that the majority of the contraction was mediated by NPY. The current study demonstrates heterogeneity of neurotransmitter substances in sympathetic nerves supplying vascular beds

  15. Jasmine absolute (Jasminum grandiflora L.) and its mode of action on guinea-pig ileum in vitro.

    PubMed

    Lis-Balchin, M; Hart, S; Wan Hang Lo, B

    2002-08-01

    Jasmine (Jasminum grandiflorum L.) is used in aromatherapy as a holistic treatment for apathy, hysteria, uterine disorders and childbirth, muscle relaxation and coughs. Its stimulant nature, on inhalation, has been shown both in animals and man. Jasmine has a spasmolytic activity on guinea-pig ileum and rat uterus in vitro. The mechanism of action of the spasmolytic activity, studied in vitro using a guinea-pig ileum smooth muscle preparation, was postsynaptic and not atropine-like. The spasmolytic effect of jasmine absolute was most likely to be mediated through cAMP, and not through cGMP. The mode of action in vitro resembled that of geranium, lavender and peppermint oils. The contradictory effect in vitro and in vivo is probably due to the solely physiological effects of jasmine absolute in vitro (producing a relaxation) compared with that in vivo, where it has a strong psychological input, producing a stimulant effect in man and enhanced movement in animals.

  16. Increased airway responsiveness and decreased alveolar attachment points following in utero smoke exposure in the guinea pig.

    PubMed

    Elliot, J; Carroll, N; Bosco, M; McCrohan, M; Robinson, P

    2001-01-01

    Maternal smoking during pregnancy has been shown to result in abnormalities in lung function in newborn infants, including reduced expiratory flow and increased airway responsiveness to inhaled agonists. The mechanisms by which this occurs remain unclear. Using a guinea pig model of in utero smoke exposure, we measured airway responsiveness and lung morphology in a group of neonatal guinea pigs 21 d after delivery. Pregnant guinea pigs were exposed to cigarette smoke from Day 28 to term (Day 68 of gestation). After delivery newborn animals did not receive any smoke exposure. Airway wall thickness, smooth muscle area, and the number of points where the alveoli attached to the airway adventitia were measured. Airway responsiveness was increased (p < 0.05) and the mean distance between alveolar attachment points was increased (mean 0.052 +/- SE 0.001 mm versus 0.046 +/- 0.001, p = 0.001) in animals exposed to cigarette smoke in utero compared with nonexposed animals. Although not statistically significant, both the inner and outer airway wall and the smooth muscle area were greater in exposed animals compared with nonexposed animals. The increased mean distance between alveolar attachments in the smoke-exposed group was the result of a reduction in the number of attachments and an increase in the outer airway wall perimeter. These findings suggest that the increased airway responsiveness observed in postnatal animals, subsequent to in utero cigarette smoke exposure, may be the result of decreased alveolar attachment points to the airways and changes in airway dimensions.

  17. Biological effects of diesel exhaust particles (DEP) on tissues and cells isolated from respiratory tracts of guinea pigs.

    PubMed

    Hirafuji, M; Sakakibara, M; Endo, T; Murakami, S; Mori, Y; Sagai, M; Minami, M

    1995-11-01

    Diesel engine-powered vehicles emit some 30 to 100 times more particles than do gasoline engine cars. We previously reported that diesel exhaust particles (DEP) instilled intratracheally into mouse caused lung edema accompanying endothelial cell damage. In order to clarify further the biological effects of DEP on the respiratory system, the primary target of DEP instillation, we examined the direct action of DEP on isolated tissues and the cytotoxicity of DEP on cultured cells of respiratory tracts in guinea pigs. DEP were collected on glass fiber filters from a light-duty (2730 cc), four cylinder diesel engine. DEP induced a dose-dependent relaxation in tracheal smooth muscle and lung parenchymal preparations from guinea pigs. Neither propranolol nor ranitidine inhibited the relaxing effect of DEP on tracheal preparations. DEP also exhibited concentration- and time-dependent cytotoxicity on cultured tracheal smooth muscle cells and lung fibroblasts from guinea pigs, as assessed by specific [51Cr] release. These cytotoxicities induced by DEP were significantly inhibited by catalase, deferoxamine and MK-447, whereas SOD and mannitol had little effect. These inhibitory effects were blunted by the higher concentration of DEP. These results suggest that the cytotoxicity of DEP may cause dysfunction of respiratory tissues, which are mediated via oxygen radicals, probably hydroxyl radicals or hydrogen peroxides.

  18. Nongenomic bronchodilating action elicited by dehydroepiandrosterone (DHEA) in a guinea pig asthma model.

    PubMed

    Espinoza, Julia; Montaño, Luis M; Perusquía, Mercedes

    2013-11-01

    Primates secrete large amounts of the precursor steroid dehydroepiandrosterone (DHEA); in humans, its levels are low during childhood and start declining after the fourth decade. It has been postulated that the progressive decline in DHEA levels may be related with the severity of asthma associated with age. To determine whether DHEA may regulate the airway smooth muscle (ASM) activity, isolated tracheal rings with and without epithelium from male guinea pigs were isometrically recorded to characterize the response of ASM to DHEA at different concentrations on KCl- and carbachol (CCh)-induced contraction as well as on ovalbumin (OVA)-induced contraction in sensitized guinea pigs. Additionally, we used barometric plethysmography in sensitized guinea pigs in order to compare changes of the lung resistance increased by the antigen challenge to OVA in the absence and presence of different doses of DHEA. DHEA concentration-dependently abolished the contraction to KCl, CCh and OVA, and no differences were found in preparations with and without epithelium. DHEA-induced relaxation was not modified by the suppression of protein synthesis or transcription, pharmacological inhibition of nitric oxide (NO) synthase, nor by antagonist of β2-adrenergic receptors or an inhibitor of the 3β-HSD enzyme. Likewise, Ca(2+)-induced contraction in Ca(2+)-free depolarized tissues was antagonized by DHEA, and the contraction to the L-type voltage-dependent calcium channel activator (Bay K 8644) was inhibited by DHEA. Furthermore, DHEA prevented OVA-induced increases in lung resistance. These results indicate that DHEA-induced relaxation in ASM is a nongenomic (membrane) action and is not produced after its bioconversion. The data suggest that DHEA-induced relaxation is an epithelium- and NO-independent mechanism that involves a blockade of voltage-dependent calcium channels and possible non-selective cation channels.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  1. Calcitonin gene-related peptide (CGRP) regulates excitability and refractory period of the guinea pig ureter.

    PubMed

    Maggi, C A; Giuliani, S

    1994-08-01

    Previous studies have indicated that calcitonin gene-related peptide (CGRP), released from the peripheral endings of capsaicin-sensitive primary afferent neurons, may play a role as an inhibitory transmitter in the guinea pig ureter. The aim of this study was to compare the effect of capsaicin desensitization and administration of a CGRP receptor antagonist on the excitability and refractory period of the guinea pig ureter to electrical field stimulation. Electrical field stimulation using a long (5 msec.) pulse width produced phasic contractions of the ureter which were unaffected by tetrodotoxin, that is, were produced through direct excitation of ureteral smooth muscle. Human alpha CGRP (1 to 10 nM.) produced a concentration-dependent transient suppression of the evoked contractions, and its effect was prevented by the CGRP receptor antagonist human alpha CGRP(8-37) (1 microM.). In vitro capsaicin pretreatment (10 microM. for 15 minutes) to block neuropeptide release from peripheral endings of sensory nerves or administration of the CGRP receptor antagonist enhanced the responsiveness of the guinea pig ureter to electrical stimulation. In control ureters, the application of two trains of electrical stimuli failed to produce a second contraction at intertrain intervals greater than 20 seconds. The intertrain interval required to obtain a second contraction averaging 50% of the amplitude of the first response (ITI50) of control ureters was about 50 seconds. In vitro capsaicin pretreatment or administration of the CGRP receptor antagonist reduced the refractory period of the ureter to electrical field stimulation: ITI50 averaged 8.8 and 9.1 seconds after capsaicin or CGRP antagonist pretreatment, respectively. These findings demonstrate that capsaicin pretreatment or blockade of CGRP receptors produced qualitatively and quantitatively similar excitatory effects on ureteral excitability and refractory period and are in general agreement with the idea that CGRP is a

  2. Pathogenesis of Lassa Virus Infection in Guinea Pigs

    DTIC Science & Technology

    1982-08-01

    virus , an arenavirus distantly related to Lassa Lassa fever ...other arenaviruses in animal models (5. 6). In VOL. 37, 1982 LASSA VIRUS INFECTION IN GUINEA PIGS 777S[ iU FIG. 6. (A) Lassa viral antigens in...resem- ent with the hemoconcentration associated with bles human and primate Lassa virus infection other human hemorrhagic fever virus infections. than

  3. 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.

  4. EFFECTS OF METHYLNALTREXONE ON GUINEA PIG GASTROINTESTINAL MOTILITY

    PubMed Central

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

    2013-01-01

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

  5. Development of a Guinea Pig Lung Deposition Model

    DTIC Science & Technology

    2016-01-01

    Toxicology Letters 41:159-173. Brewer NR, Cruise LJ. (1997). The Respiratory System of the Guinea Pig: Emphasis on Species Differences. Contemp Top...3 3.1. MODELING DEPOSITION EFFICIENCY IN THE UPPER RESPIRATORY TRACT ............. 3 3.2. LUNG GEOMETRY...15 iv LIST OF FIGURES Figure 1. Compartmental representation of the respiratory tract

  6. The Guinea Pig as a Model of Infectious Diseases

    PubMed Central

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

    2008-01-01

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

  7. 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)

  8. 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.

  9. Further evidence for the heterogeneity of functional muscarinic receptors in guinea pig gallbladder.

    PubMed

    Akici, A; Karaalp, A; Iskender, E; Christopoulos, A; El-Fakahany, E E; Oktay, S

    2000-01-24

    Previous studies have suggested the presence of multiple muscarinic receptor subtypes in guinea pig gallbladder smooth muscle, although the relative abundance and functional role of these subtypes remains an area of significant research efforts. The present study utilized both radioligand kinetic and functional experiments to further probe the nature of the muscarinic receptors in gallbladder smooth muscle and their mode of coupling to intra- and extra-cellular Ca(2+) sources. Dissociation kinetic studies using [3H]N-methylscopolamine ([3H]NMS) indicated that the binding profile in guinea pig gallbladder smooth muscle could not be reconciled with that expected for a single muscarinic receptor subtype, the latter determined in parallel experiments conducted on the cloned muscarinic M(1)-M(5) subtypes in Chinese hamster ovary (CHO) cells. Furthermore, comparison of the gallbladder data with the dissociation characteristics of [3H]NMS in guinea pig urinary bladder revealed a significantly different kinetic profile, with the urinary bladder, but not the gallbladder, demonstrating biphasic radioligand dissociation kinetics. In functional experiments, carbachol caused a concentration-dependent contraction of guinea pig gallbladder smooth muscle strips in Ca(2+)-free or 5 mM Sr(2+)-substituted physiological salt solutions (PSS) with amplitudes of the maximal contractions corresponding to 45.8+/-8.0% and 33.2+/-6.6% of control responses in normal PSS, respectively. Furthermore, the stimulus-response characteristics of carbachol-mediated contraction appeared significantly altered in Ca(2+)-free PSS relative to normal or Sr(2+)-substituted PSS. The antagonist, methoctramine (1x10(-7)-3x10(-5) M), exerted only a slight inhibition of carbachol (10(-5) M)-induced contractions in 5 mM Sr(2+)-substituted medium, whereas it was significantly more potent in antagonizing gallbladder contractions in response to 10(-5) M carbachol in the absence of extracellular Ca(2+). Both atropine

  10. Purinergic regulation of guinea pig suburothelial myofibroblasts

    PubMed Central

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

    2004-01-01

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

  11. Control of Neurotransmission by NaV1.7 in Human, Guinea Pig, and Mouse Airway Parasympathetic Nerves.

    PubMed

    Kocmalova, Michaela; Kollarik, Marian; Canning, Brendan J; Ru, Fei; Adam Herbstsomer, R; Meeker, Sonya; Fonquerna, Silvia; Aparici, Monica; Miralpeix, Montserrat; Chi, Xian Xuan; Li, Baolin; Wilenkin, Ben; McDermott, Jeff; Nisenbaum, Eric; Krajewski, Jeffrey L; Undem, Bradley J

    2017-04-01

    Little is known about the neuronal voltage-gated sodium channels (NaVs) that control neurotransmission in the parasympathetic nervous system. We evaluated the expression of the α subunits of each of the nine NaVs in human, guinea pig, and mouse airway parasympathetic ganglia. We combined this information with a pharmacological analysis of selective NaV blockers on parasympathetic contractions of isolated airway smooth muscle. As would be expected from previous studies, tetrodotoxin potently blocked the parasympathetic responses in the airways of each species. Gene expression analysis showed that that NaV 1.7 was virtually the only tetrodotoxin-sensitive NaV1 gene expressed in guinea pig and human airway parasympathetic ganglia, where mouse ganglia expressed NaV1.1, 1.3, and 1.7. Using selective pharmacological blockers supported the gene expression results, showing that blocking NaV1.7 alone can abolish the responses in guinea pig and human bronchi, but not in mouse airways. To block the responses in mouse airways requires that NaV1.7 along with NaV1.1 and/or NaV1.3 is blocked. These results may suggest novel indications for NaV1.7-blocking drugs, in which there is an overactive parasympathetic drive, such as in asthma. The data also raise the potential concern of antiparasympathetic side effects for systemic NaV1.7 blockers.

  12. Relaxant effect of Thymus vulgaris on guinea-pig tracheal chains and its possible mechanism(s).

    PubMed

    Boskabady, M H; Aslani, M R; Kiani, S

    2006-01-01

    Thymus vulgaris for the treatment of respiratory diseases is indicated widely, and relaxant effects on smooth muscle have been shown previously. In the present study, the relaxant effects of macerated and aqueous extracts of Thymus vulgaris on tracheal chains of guinea-pigs were examined using cumulative concentrations of macerated and aqueous extracts in comparison with saline (as the negative control) and theophylline (as the positive control). The relaxant effects of four cumulative concentrations of macerated and aqueous extracts (0.25, 0.5, 0.75 and 1.0 g %) in comparison with saline (as the negative control) and four cumulative concentrations of theophylline (0.25, 0.5, 0.75 and 1.0 mm; as the positive control) were examined for their relaxant effects on precontracted tracheal chains of guinea-pig by 60 mm KCl and 10 microm methacholine in two different conditions: non-incubated tissues and incubated tissues with 1 microm propranolol and 1 microm chlorphenamine. There were significant correlations between the relaxant effects and the concentrations for both extracts and theophylline in all experimental groups (p < 0.01 to p < 0.001). These results demonstrated a potent relaxant effect of Thymus vulgaris on guinea-pig tracheal chains that was comparable to theophylline at the concentrations used.

  13. Isolation and culture of highly enriched populations of Leydig cells from guinea-pig (Cavia porcellus) testes.

    PubMed

    Kukucka, M A; Misra, H P

    1994-01-01

    Leydig cells were isolated from adult male guinea-pig testes using a multi-step procedure involving enzymatic dissociation and Percoll-gradient centrifugation. The following description is the first account of a successful isolation of adolescent guinea-pig Leydig cells. The enriched Leydig-cell preparation routinely isolated from six intact testicles yielded approximately 5.0 x 10(6) +/- 0.7 x 10(6) (+/- SEM) Leydig cells with a viability of 98.0 +/- 0.4% as determined using the trypan-blue exclusion method. The purity of the isolated cell population as assessed by 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) staining averaged 82.5 +/- 0.8%. Under light microscopy, guinea-pig Leydig cells were polyhedral in shape with a large prominent nucleus and a distinct nucleolus. The acidophilic cytoplasm contained numerous lipid-filled vesicles. Ultrastructurally, guinea-pig Leydig cells displayed an eccentrically located ovoid nucleus with dark-staining peripheral heterochromatin. Large quantities of mitochondria, smooth endoplasmic reticulum and particulate-laden lipid droplets were also evident. The steroidogenic potential of the isolated Leydig cells was verified using a maximally stimulating dose of ovine LH (100 ng ml-1) and human CG (200 mIU ml-1). Leydig cells incubated in a shaking (120 cycles min-1) water bath for 3 h at 37 degrees C in capped polypropylene microcentrifuge tubes produced 233 +/- 21 ng and 223 +/- 18 ng testosterone per 1 x 10(6) cells when maximally stimulated with oLH or hCG, respectively. The inclusion of low (1-5 microM) levels of sodium ascorbate during culture enhanced significantly Leydig-cell viability vs. control values.

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

    PubMed Central

    Hekman, Annemarie; Shulman, S.

    1971-01-01

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

  15. The GABAA agonist muscimol attenuates induced airway constriction in guinea pigs in vivo.

    PubMed

    Gleason, Neil R; Gallos, George; Zhang, Yi; Emala, Charles W

    2009-04-01

    GABA(A) channels are ubiquitously expressed on neuronal cells and act via an inward chloride current to hyperpolarize the cell membrane of mature neurons. Expression and function of GABA(A) channels on airway smooth muscle cells has been demonstrated in vitro. Airway smooth muscle cell membrane hyperpolarization contributes to relaxation. We hypothesized that muscimol, a selective GABA(A) agonist, could act on endogenous GABA(A) channels expressed on airway smooth muscle to attenuate induced increases in airway pressures in anesthetized guinea pigs in vivo. In an effort to localize muscimol's effect to GABA(A) channels expressed on airway smooth muscle, we pretreated guinea pigs with a selective GABA(A) antagonist (gabazine) or eliminated lung neural control from central parasympathetic, sympathetic, and nonadrenergic, noncholinergic (NANC) nerves before muscimol treatment. Pretreatment with intravenous muscimol alone attenuated intravenous histamine-, intravenous acetylcholine-, or vagal nerve-stimulated increases in peak pulmonary inflation pressure. Pretreatment with the GABA(A) antagonist gabazine blocked muscimol's effect. After the elimination of neural input to airway tone by central parasympathetic nerves, peripheral sympathetic nerves, and NANC nerves, intravenous muscimol retained its ability to block intravenous acetylcholine-induced increases in peak pulmonary inflation pressures. These findings demonstrate that the GABA(A) agonist muscimol acting specifically via GABA(A) channel activation attenuates airway constriction independently of neural contributions. These findings suggest that therapeutics directed at the airway smooth muscle GABA(A) channel may be a novel therapy for airway constriction following airway irritation and possibly more broadly in diseases such as asthma and chronic obstructive pulmonary disease.

  16. Effect of cinnarizine on IgE antibody-mediated experimental allergic reactions in guinea pigs.

    PubMed

    Nagai, H; Yamada, H; Yakuo, I; Inagaki, N; Choi, S H; Koda, A; Daikoku, M

    1987-02-01

    The anti-allergic activity and mechanism of cinnarizine was investigated in guinea pigs. Nifedipine, a calcium antagonist, and tranilast, a potent, orally active anti-allergic agent, were used as comparative drugs. Cinnarizine protected against fatal systemic anaphylactic shock in guinea pigs passively sensitized with IgE antibody. Cinnarizine reduced many of the features of severe respiratory disorders. Nifedipine and tranilast showed similar effects. Cinnarizine and nifedipine inhibited the contractile response to antigen of sensitized tracheal smooth muscle when the challenge was carried out at low antigen concentrations. Tranilast showed a tendency to inhibit the antigen-induced contraction of tracheal smooth muscle. Cinnarizine and nifedipine inhibited Ca-induced contraction in potassium-depolarized tracheal smooth muscle, tranilast had no effect. Cinnarizine showed antagonistic action to the contraction by histamine or leukotriene D4 (LTD4) of tracheal muscle. Nifedipine showed similar antagonistic action, although its potency is lower than cinnarizine. Tranilast showed slight antagonistic action to LTD4. Antigen-induced release of histamine and slow reacting substance of anaphylaxis (SRS-A) from sensitized lung tissues was inhibited by nifedipine and tranilast but not by cinnarizine. The release of histamine and SRS-A from lung tissues by calcium ionophore A23187 was inhibited by nifedipine and tranilast but not by cinnarizine. These results suggest that the anti-allergic action of cinnarizine is mainly due to the antagonistic action to allergic mediators and not by interfering with the release of mediators. Cinnarizine's mechanism seems to be related to its antagonistic action to Ca in smooth muscle, but not to the transport of Ca in releasing the anaphylactic chemical mediators in mast cells and other target cells.

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

    PubMed

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

    2003-01-01

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

  18. 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.

  19. Pharmacological characterisation of the smooth muscle antispasmodic agent tiropramide.

    PubMed

    Setnikar, I; Cereda, R; Pacini, M A; Revel, L; Makovec, F

    1989-09-01

    (+/-) Tiropramide hydrochloride, its D and L optical isomers and some of its metabolites were characterized in a number of in vitro pharmacological tests. Tiropramide showed broad spectrum antispasmodic activities on the isolated stomach of guinea pig electrically stimulated; on the longitudinal muscles of the ileum of guinea pig stimulated by electrical impulses, BaCl2, acetylcholine, histamine, serotonin, substance P and cholecystokinin octapeptide (CCK-8); on the spontaneous contractions and on the electrical inhibition of the jejunum of rabbit; on the spontaneous contractions and on the contractions provoked by BaCl2 and acetylcholine of the ascending colon of the rat; on the contractions provoked by BaCl2, acetylcholine, histamine and cerulein of the circular muscles of the gall bladder of the guinea pig; on the spontaneous contractions of the pyel-ureter preparation of the guinea pig; on the contractions of the uterus of the rat provoked by oxitocin, serotonin, acetylcholine, PGF2; on the spontaneous contraction of the portal vein of the rat; on the constriction of the tail artery of the rat provoked by electrical stimulation, epinephrine and ergotamine; on the contractions of the aortic strip of the rabbit stimulated by norepinephrine; on the contractions of the strip of bovine coronary artery depolarized by HCl. In general tiropramide had antispasmodic effect at 5-60 mumol/l concentration. It was more potent than papaverine on contractions provoked by electrical or chemical stimuli, and was less potent or ineffective on spontaneous and "physiological" contractions of the different smooth muscle preparations. Tiropramide had small effects on vascular smooth muscles and showed very small calcium channel blocking activity.

  20. Spontaneous Ameloblastic Fibroma in a Young Guinea Pig

    PubMed Central

    Tanaka, Makoto; Sawamoto, Osamu

    2013-01-01

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

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

    PubMed Central

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

    1993-01-01

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

  2. 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.

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

    PubMed

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

    2013-03-01

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

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

    PubMed Central

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

    2013-01-01

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

  5. Cobalt contraction of vascular smooth muscle

    SciTech Connect

    Dominiczak, A.; Clyde, E.; Bohr, D. )

    1991-03-11

    Although it has been reported that cobalt causes contraction of vascular smooth muscle, the mechanism responsible for this contraction has not been defined. The authors studied these contractions in rat aortic rings. Concentration-response studies indicated that the threshold for contraction was 10{sup {minus}8}M, maximum contraction occurred at 3 {times} 10{sup 7}M and relaxation began at 10{sup {minus}6}M. No contraction occurred in a calcium-free physiological salt solution and the contraction was not inhibited by H-7, a protein kinase C inhibitor. The authors conclude the cobalt in low concentrations causes contraction by activating calcium channels and that in high concentrations it causes relaxation by inactivating these same channels.

  6. CysLT2 receptor activation is involved in LTC4-induced lung air-trapping in guinea pigs.

    PubMed

    Sekioka, Tomohiko; Kadode, Michiaki; Yonetomi, Yasuo; Kamiya, Akihiro; Fujita, Manabu; Nabe, Takeshi; Kawabata, Kazuhito

    2017-01-05

    CysLT1 receptors are known to be involved in the pathogenesis of asthma. However, the functional roles of CysLT2 receptors in this condition have not been determined. The purpose of this study is to develop an experimental model of CysLT2 receptor-mediated LTC4-induced lung air-trapping in guinea pigs and use this model to clarify the mechanism underlying response to such trapping. Because LTC4 is rapidly converted to LTD4 by γ-glutamyltranspeptidase (γ-GTP) under physiological conditions, S-hexyl GSH was used as a γ-GTP inhibitor. In anesthetized artificially ventilated guinea pigs with no S-hexyl GSH treatment, i.v. LTC4-induced bronchoconstriction was almost completely inhibited by montelukast, a CysLT1 receptor antagonist, but not by BayCysLT2RA, a CysLT2 receptor antagonist. The inhibitory effect of montelukast was diminished by treatment with S-hexyl GSH, whereas the effect of BayCysLT2RA was enhanced with increasing dose of S-hexyl GSH. Macroscopic and histological examination of lung tissue isolated from LTC4-/S-hexyl-GSH-treated guinea pigs revealed air-trapping expansion, particularly at the alveolar site. Inhaled LTC4 in conscious guinea pigs treated with S-hexyl GSH increased both airway resistance and airway hyperinflation. On the other hand, LTC4-induced air-trapping was only partially suppressed by treatment with the bronchodilator salmeterol. Although montelukast inhibition of LTC4-induced air-trapping was weak, treatment with BayCysLT2RA resulted in complete suppression of this air-trapping. Furthermore, BayCysLT2RA completely suppressed LTC4-induced airway vascular hyperpermeability. In conclusion, we found in this study that CysLT2 receptors mediate LTC4-induced bronchoconstriction and air-trapping in S-hexyl GSH-treated guinea pigs. It is therefore believed that CysLT2 receptors contribute to asthmatic response involving air-trapping.

  7. Effects of Sarin on the Operant Behavior of Guinea Pigs

    DTIC Science & Technology

    2005-07-19

    concentration time profile of an OP compound in located beneath the house light. Reinforcement contingen- guinea pig resembles that of the marmoset monkey...resembles that of the marmoset monkey more cies and data collection were accomplished with 0.01 s closely than that of the rat [2]. resolution using a Pentium...serum AChE activity was inhibited by exposures may be due to behavioral tolerance, since this 80-90% [4,5,8,33]. In marmosets , the acute

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

    PubMed

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

    2013-12-01

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

  9. 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.

  10. Sympathetic innervation promotes vascular smooth muscle differentiation.

    PubMed

    Damon, Deborah H

    2005-06-01

    The sympathetic nervous system (SNS) is an important modulator of vascular smooth muscle (VSM) growth and function. Several lines of evidence suggest that the SNS also promotes VSM differentiation. The present study tests this hypothesis. Expression of smooth muscle myosin (SM2) and alpha-actin were assessed by Western analysis as indexes of VSM differentiation. SM2 expression (normalized to alpha-actin) in adult innervated rat femoral and tail arteries was 479 +/- 115% of that in noninnervated carotid arteries. Expression of alpha-actin (normalized to GAPDH or total protein) in 30-day-innervated rat femoral arteries was greater than in corresponding noninnervated femoral arteries from guanethidine-sympathectomized rats. SM2 expression (normalized to alpha-actin) in neonatal femoral arteries grown in vitro for 7 days in the presence of sympathetic ganglia was greater than SM2 expression in corresponding arteries grown in the absence of sympathetic ganglia. In VSM-endothelial cell cultures grown in the presence of dissociated sympathetic neurons, alpha-actin (normalized to GAPDH) was 300 +/- 66% of that in corresponding cultures grown in the absence of neurons. This effect was inhibited by an antibody that neutralized the activity of transforming growth factor-beta2. All of these data indicate that sympathetic innervation increased VSM contractile protein expression and thereby suggest that the SNS promotes and/or maintains VSM differentiation.

  11. 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.

  12. 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.

  13. A guinea pig model of bovine pneumonic pasteurellosis.

    PubMed Central

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

    1990-01-01

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

  14. Fluctuation analysis of nonselective cation currents induced by AIF complex in guinea-pig chromaffin cells.

    PubMed

    Inoue, M; Imanaga, I

    1996-11-11

    Properties of aluminium fluoride (AIF) complex-activated nonselective cation (NS) channels in guinea-pig chromaffin cells were investigated using the patch clamp technique. As the membrane potential was hyperpolarized from the holding potential of -55 mV, the AIF-induced nonselective cation current (INS) diminished progressively. With hyperpolarizations to -100 mV or more negative potentials, the AIF.INS almost instantaneously disappeared. The apparent unit conductance of AIF INS was estimated to be 3 pS by fluctuation analysis. The open state probability of AIF-activated NS channels became large with a decrease in concentration of free Mg2+ ions inside the cell and was less than 0.5 at 12 microM Mg2+. It is concluded that NS channels in the chromaffin cell apparently differ from those in smooth muscle cells.

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

    PubMed

    Jahrling, P B

    1983-01-01

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

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

    PubMed

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

    1996-01-01

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

  17. Plasticity of interstitial cells of cajal: a study in the small intestine of adult Guinea pigs.

    PubMed

    Mei, Feng; Han, Juan; Huang, Yue; Jiang, Zhong-Yong; Xiong, Cheng-Jie; Zhou, De-Shan

    2009-07-01

    Although it is well known that the reduction of interstitial cells of Cajal (ICCs) is associated with several gastrointestinal motility disorders in clinic, it is unknown whether the mature ICCs still have an active plasticity in adult mammals. This study focused on the issues of the reduction of ICCs during Imatinib administration and the recovery of ICCs following drug withdrawal in the small intestine of adult guinea pigs. ICCs were revealed by immunofluorescence on whole mount preparations with anti-Kit, alpha-smooth muscle actin, (alpha-SMA), and 5-bromo-2'-deoxyuridine (BrdU) antibodies. Moreover, the occurrence of apoptosis was also assayed. Imatinib treatment led to a gradual reduction of ICCs in number around the myenteric plexus and deep muscular plexus, which was dependent on the time but no apoptosis of ICCs was detected with the TUNEL method. During Imatinib treatment, some ICC-like cells were double labeled for Kit and alpha-SMA and a few ICC-like cells were only stained with alpha-SMA. When Imatinib was discontinued, the number of ICCs recovered to normal within 32 days. During this time, some proliferating ICCs were demonstrated by double labeling with Kit and BrdU antibodies. Our results indicated that Kit signaling was essential for the maintenance of survival and proliferation of the mature ICCs in the small intestine of adult guinea pigs. Moreover, ICCs might transdifferentiate to a type of alpha-SMA(+) cells, perhaps a phenotype of smooth muscle cells, when there is a loss-of-function of Kit.

  18. 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

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

    PubMed Central

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

    1985-01-01

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

  20. 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

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

    PubMed Central

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

    2004-01-01

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

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

    PubMed

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

    2004-11-01

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

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

    DTIC Science & Technology

    1984-01-01

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

  4. Enhanced nerve-stimulated muscarinic and neurokinin contractions of ileum from streptozotocin guinea-pigs.

    PubMed

    Cellini, J; Pommier, R; Porter, R; LePard, K J

    2012-10-01

    Diabetes mellitus can lead to neuropathy of enteric neurons, resulting in abnormal gut motility. These studies investigated voltage-dependent contributions of muscarinic M₃ receptor activation by acetylcholine and neurokinin NK₁ receptor activation by neurokinins to nerve-stimulated contractions of longitudinal ileal strips from STZ guinea-pigs, a type 1 diabetic model with insulin deficiency, but mild hyperglycaemia. Contractions to bethanechol, substance P methyl ester, and nerve stimulation were greater in diabetic as compared to control ileum. The muscarinic M₃ receptor antagonist 4-DAMP at lower voltages and the neurokinin NK₁ receptor antagonist SR140333 at higher voltages, but not the neurokinin NK₁ receptor antagonist CP-96,345, were more effective at inhibiting nerve-stimulated immediate peak contractions and total areas of contraction of ileum from diabetic as compared to control animals. For diabetic ileum, voltage-dependent increases in the areas of nerve-stimulated contraction were observed in the presence of 4-DAMP and CP-96,345 but not SR140333. At low voltages only, nerve-stimulated release of acetylcholine was greater from diabetic as compared to control ileum. Fluorescence intensity of tachykinin-like immunoreactivity was increased in ileal myenteric ganglia from diabetic as compared to control animals. In diabetic guinea-pigs, stronger ileal nerve-stimulated contractions reflected increased release of acetylcholine at lower voltages and tachykinins at higher voltages, as well as increased sensitivity of smooth muscle M₃ and NK₁ receptors to acetylcholine and tachykinins. Hypoinsulinaemia may be a primary contributor to intestinal motility dysfunction in type 1 diabetes mellitus.

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

    DTIC Science & Technology

    2014-12-11

    2008) Guinea pig model of Mycobacterium tuberculosis latent/dormant infection . Microbes and Infection 10: 1469–1476. 54. Smith DW, Balasubramanian V...RESEARCH ARTICLE Use of a Guinea Pig-Specific Transcriptome Array for Evaluation of Protective Immunity against Genital Chlamydial Infection ...Center for Emerging Infectious Diseases and Center of Excellence in Infection Genomics, University of Texas at San Antonio, One UTSA Circle, San Antonio

  6. 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

  7. 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

  8. Ciliary Muscle Cell Changes During Guinea Pig Development

    PubMed Central

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

    2015-01-01

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

  9. 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.

  10. Guinea-pig interpubic joint (symphysis pubica) relaxation at parturition: Underlying cellular processes that resemble an inflammatory response

    PubMed Central

    Rodríguez, Horacio A; Ortega, Hugo H; Ramos, Jorge G; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2003-01-01

    Background At term, cervical ripening in coordination with uterine contractions becomes a prerequisite for a normal vaginal delivery. Currently, cervical ripening is considered to occur independently from uterine contractions. Many evidences suggest that cervical ripening resembles an inflammatory process. Comparatively little attention has been paid to the increased flexibility of the pelvic symphysis that occurs in many species to enable safe delivery. The aim of this study was to investigate whether the guinea-pig interpubic joint relaxation process observed during late pregnancy and parturition resembles an inflammatory process. Methods Samples of pubic symphysis were taken from pregnant guinea-pigs sacrificed along gestation, parturition and postpartum. Serial sections of paraffin-embedded tissues were used to measure the interpubic distance on digitalized images, stained with Giemsa to quantify leukocyte infiltration and to describe the vascular area changes, or studied by the picrosirius-polarization method to evaluate collagen remodeling. P4 and E2 serum levels were measured by a sequential immunometric assay. Results Data showed that the pubic relaxation is associated with an increase in collagen remodeling. In addition, a positive correlation between E2 serum levels and the increase in the interpubic distance was found. On the other hand, a leukocyte infiltration in the interpubic tissue around parturition was described, with the presence of almost all inflammatory cells types. At the same time, histological images show an increase in vascular area (angiogenesis). Eosinophils reached their highest level immediately before parturition; whereas for the neutrophilic and mononuclear infiltration higher values were recorded one day after parturition. Correlation analysis showed that eosinophils and mononuclear cells were positively correlated with E2 levels, but only eosinophilic infiltration was associated with collagen remodeling. Additionally, we observed

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

    PubMed

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

    2000-06-01

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

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

    PubMed

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

    1993-01-01

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

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

    PubMed Central

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

    1980-01-01

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

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

    PubMed

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

    2016-10-01

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

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

    PubMed Central

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

    1985-01-01

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

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

    PubMed

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

    2012-04-25

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

  17. Physiological dilation of uteroplacental arteries in the guinea pig depends on nitric oxide synthase activity of extravillous trophoblast.

    PubMed

    Nanaev, A; Chwalisz, K; Frank, H G; Kohnen, G; Hegele-Hartung, C; Kaufmann, P

    1995-12-01

    The trophoblast invasion of uteroplacental arteries in the guinea pig has been studied by means of electron microscopy and immunohistochemisty. To identify trophoblast cells, smooth muscle cells, and endothelial cells, antibodies against cytokeratins, smooth muscle myosin, desmin, and vimentin were employed. Furthermore, the immunohistochemical expression patterns of nitric oxide synthase isoforms (eNOS, mNOS and bNOS) were studied and were compared with the enzyme histochemical staining for NADPH-diaphorase. Dilation of uteroplacental arteries begins prior to day 30, when trophoblast cells that coexpress endothelial and macrophage nitric oxide synthase can be found in the vicinity of the vessels and replace the surrounding peritoneal mesothelium. Trophoblast invasion of the arterial walls and the subsequent wall destruction are only secondary effects. Starting around day 50, the final steps of pregnancy-dependent vessel modifications involve intraarterial trophoblast adhesion to the endothelium and subsequent replacement of the endothelium by the trophoblast cells. These may centrifugally invade the vessel media eventually forming intraluminal plugs. These findings led us to the conclusion that in the guinea pig pregnancy-induced physiological dilation of the uteroplacental arteries is due to the effect of nitric oxide rather than being caused by trophoblast-induced media destruction.

  18. 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.

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

    PubMed Central

    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

  20. 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.

  1. 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.

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

    PubMed Central

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

    1992-01-01

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

  3. Chlamydial salpingitis in female guinea pigs receiving oral contraceptives.

    PubMed

    Barron, A L; Pasley, J N; Rank, R G; White, H J; Mrak, R E

    1988-01-01

    Female guinea pigs were given daily doses of a combination of oral contraceptive (OC) agents, consisting of mestranol and norethynodrel suspended in sesame oil or distilled H2O, and were infected in the genital tract with the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC). Counts of chlamydial inclusions in cells of vaginal smears collected during infection, showed prolongation and enhancement of infection in OC-treated animals as compared with controls. Appearance of IgG and IgA antibodies to GPIC in genital secretions, as determined by enzyme-linked immunosorbent assay (ELISA), was also delayed in OC-treated animals as compared with controls. OC-treated infected animals were killed on days 15 and 43, and gross pathological evidence for ascending infection culminating in salpingitis was found in all of five and four of five animals, respectively. On the other hand, among untreated infected controls on each sacrifice day, only one of five animals had any evidence for ascending infection. Chlamydiae were detected by light and electron microscopy in fallopian tube tissue collected on day 15 following OC-treatment but not in tissue from control animals.

  4. 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.

  5. 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.

  6. ACTION OF DIPHTHERIA TOXIN IN THE GUINEA PIG

    PubMed Central

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

    1970-01-01

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

  7. 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

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

    PubMed Central

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

    2012-01-01

    The Guinea pig (Cavia porcellus) is an excellent animal model for studying human tuberculosis (TB) and also for a number of other infectious and non-infectious diseases. One of the major roadblocks in effective utilization of this animal model is the lack of readily available immunological reagents. In order to address this issue, guinea pig interleukin 1 beta (IL-1β) and monocyte chemo attractant protein-1 (MCP-1) were efficiently cloned and expressed in a prokaryotic expression vector (pET-30a) and the expressed proteins in soluble form from both the genes were confirmed by N-terminal sequencing. The biological activity of recombinant guinea pig IL-1β was demonstrated by its ability to drive proliferation in thymocytes and the recombinant guinea pig MCP-1 exhibited chemotactic activity for guinea pig resident peritoneal macrophages. These biologically active recombinant guinea pig proteins will facilitate an in-depth understanding of the role they play in the immune responses of the guinea pig to TB and other diseases. PMID:22744745

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

    PubMed

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

    2016-10-01

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

  10. 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.

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

    PubMed

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

    2013-03-01

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

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

    PubMed

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

    2015-08-22

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

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

    PubMed

    Kleven, Gale A; Joshi, Prianca

    2016-03-01

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

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

    PubMed Central

    Kleven, Gale A; Joshi, Prianca

    2016-01-01

    The Hairless strain of guinea pigs (Cavia porcellus) is the result of a spontaneous recessive mutation first identified at the Institute Armand Frappier (IAF) in 1978. Despite the longstanding availability of this strain, little is known about its thermoregulatory behavior. The aim of this study was to determine temperature preference in Hartley and Hairless guinea pigs by observing each strain in a ring-shaped apparatus containing a nonlinear temperature gradient. Temperatures were maintained by separately controlled heating mats lining the apparatus. Set point temperatures ranged from 24 to 38 °C. Guinea pigs (Hartley female, Hairless female, and Hairless male guinea pigs; n = 8 each group) were placed either singly or in pairs at 1 of the 8 randomized starting points within the apparatus. Subjects were observed for 30 min and coded for location within the temperature gradient by both frequency and duration. When placed singly in the apparatus, all 3 groups spent more time in the 30 °C zones. However, when placed as pairs with a cagemate, Hartley female guinea pigs spent more time in the cooler range of temperatures from 24 to 30 °C, whereas Hairless guinea pigs preferred a range of 30 to 38 °C. These results confirm a temperature preference of 30 ± 2 °C for both Hartley and Hairless guinea pigs when singly housed. However, data from the paired housing condition suggest that context plays an important role in thermoregulatory behavior. PMID:27025807

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

    PubMed Central

    Dharmadhikari, Ashwin S.; Basaraba, Randall J.; Van Der Walt, Martie L.; Weyer, Karin; Mphahlele, Matsie; Venter, Kobus; Jensen, Paul A.; First, Melvin W.; Parsons, Sydney; McMurray, David N.; Orme, Ian M.; Nardell, Edward A.

    2012-01-01

    A natural TB infection model using guinea pigs may provide useful information for investigating differences in transmission efficiency and establishment of active disease by clinical TB strains in a highly susceptible host under controlled environmental conditions. We sought to examine the capacity of naturally transmitted multidrug-resistant M. tuberculosis to establish infection and produce active disease in guinea pigs. Guinea pigs were continuously exposed for 4 months to the exhaust air of a 6-bed multidrug-resistant tuberculosis inpatient hospital ward in South Africa. Serial tuberculin skin test reactions were measured to determine infection. All animals were subsequently evaluated for histologic disease progression at necropsy. Although 75% of the 362 exposed guinea pigs had positive skin test reactions [≥6mm], only 12% had histopathologic evidence of active disease. Reversions (≥ 6 mm change) in skin test reactivity were seen in 22% of animals, exclusively among those with reactions of 6 to 13 mm. Only two of 86 guinea pigs with reversion had histological evidence of disease compared to 47% (31/66) of guinea pigs with large, non-reverting reactions. Immunosuppression of half the guinea pigs across all skin test categories did not significantly accelerate disease progression. In guinea pigs that reverted a skin test, a second positive reaction in 27 (33%) of them strongly suggested re-infection due to ongoing exposure. These results show that a large majority of guinea pigs naturally exposed to human-source strains of multidrug-resistant tuberculosis became infected, but that many resolved their infection and a large majority failed to progress to detectable disease. PMID:21478054

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

    PubMed

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

    2014-12-01

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

  17. 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.

  18. Melatonin treatment reverts age-related changes in Guinea pig gallbladder neuromuscular transmission and contractility.

    PubMed

    Gomez-Pinilla, Pedro J; Camello-Almaraz, Cristina; Moreno, Rosario; Camello, Pedro J; Pozo, María J

    2006-11-01

    The incidence of gallbladder illness increases with age, but the altered mechanisms leading to gallbladder dysfunction are poorly understood. Here we determine the age-related alterations in gallbladder contractility and the impact of melatonin treatment. Isometric tension changes in response to electrical field stimulation and to agonists were recorded from guinea pig gallbladder muscle strips. [Ca(2+)](i) was determined by epifluorescence microscopy in fura-2 loaded isolated gallbladder smooth muscle cells, and F-actin content was quantified by confocal microscopy. Aging reduced neurogenic contractions, which was associated with the impairment of nitrergic innervation and with increased responsiveness of capsaicin-sensitive relaxant nerves, possibly involving calcitonin gene-related peptide. Melatonin treatment for 4 weeks restored neurogenic responses to normal values, with an associated recovery of nitrergic function and the disappearance of the capsaicin-sensitive component. Aging also reduced the contractile responses to cholecystokinin and Ca(2+) influx. The impaired contractility only correlated with diminished Ca(2+) mobilization in response to activation of Ca(2+) influx. Melatonin improved contractility and increased smooth muscle F-actin content without changing Ca(2+) homeostasis. In conclusion, aging impairs gallbladder function as the result of changes in the inhibitory neuromodulation of smooth muscle contractility and the reduction in the myogenic response to contractile agonists. Impaired contractility seems to be related to decreased Ca(2+) influx and damage of contractile proteins. Melatonin significantly ameliorated these age-related changes.

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

    PubMed Central

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

    1967-01-01

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

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

    PubMed

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

    2015-09-01

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

  1. 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.

  2. Activation of sensory nerves in guinea-pig isolated basilar artery by nicotine: evidence for inhibition of trigeminal sensory neurotransmission by sumatriptan.

    PubMed

    O'Shaughnessy, C T; Connor, H E

    1994-06-23

    Nicotine (100 microM), but not electrical field stimulation or potassium chloride (0.1-3 microM), caused capsaicin (1 microM)- and tetrodotoxin (1 microM)-sensitive relaxations of guinea-pig isolated basilar artery precontracted with prostaglandin F2 alpha. Nicotine-induced responses were blocked by the neurokinin NK1 receptor antagonist, GR82334 (10 microM), but were unaffected by the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP-(8-37) (1 microM). This suggests that nicotine activates capsaicin-sensitive sensory nerves in guinea-pig basilar artery to cause relaxation predominantly via substance P release. The vascular 5-HT1 receptor agonist, sumatriptan (0.3 and 3 microM), inhibited nicotine-induced relaxation (by 50 and 80% respectively); the inhibitory effect of sumatriptan (0.3 microM) was attenuated in the presence of the non-selective 5-HT1 receptor antagonist, methiothepin (0.1 microM). These data suggest that sumatriptan can inhibit sensory neurotransmission in guinea-pig basilar artery via activation of inhibitory prejunctional 5-HT1 receptors on sensory nerve terminals.

  3. 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

  4. H1-histamine receptors may mediate the contractile response of guinea-pig ileum to 'histamine-free' splenic extracts.

    PubMed Central

    Ainz, L. F.; Casis, E.; de Gandarias, J. M.; Gil-Rodrigo, C. E.; Goiriena de Gandarias, J. J.

    1983-01-01

    A water-soluble splenic factor, which produces a contractile response of the guinea-pig ileum, that is resistant to cholinoceptor and adrenoceptor antagonists is described. The ileal contractions elicited by the splenic extract showed some significant differences from those elicited by 5-hydroxytryptamine. The responses to splenic extract were not affected by the D-tryptamine-receptor antagonist, methysergide. The effect of the splenic extract on the guinea-pig ileum was similar to that of histamine. The H1-histamine antagonists, (+)-chloropheniramine and diphenhydramine, caused a parallel shift to the right of the splenic extract dose-response curve without suppression of the maximum response. A pA2 value of 8.97 +/- 0.03 for (+)-chloropheniramine and 7.55 +/- 0.1 for diphenhydramine was calculated. Significant histamine levels, as determined by fluorometric methods, could not be detected in the splenic extract. Likewise, the splenic factor did not release histamine from the intestinal preparation. These results support the view that: (i) the splenic factor acts through H1-histamine receptors; (ii) it is not histamine; (iii) it does not have any histamine releasing effect on the ileal smooth muscle. PMID:6652334

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

    PubMed

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

    2017-01-01

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

  6. Ontogeny of fetal movements in the guinea pig.

    PubMed

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

    2009-09-07

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

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

    PubMed Central

    Liu, Shuangzhen; Fu, Chunyan

    2016-01-01

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

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

    PubMed Central

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

    1977-01-01

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

  9. Programmable transdermal delivery of nicotine in hairless guinea pigs using carbon nanotube membrane pumps.

    PubMed

    Paudel, Kalpana S; Wu, Ji; Hinds, Bruce J; Stinchcomb, Audra L

    2012-10-01

    A compact switchable transdermal nicotine patch device was demonstrated to be effective in vivo in a hairless guinea pig animal model. This required the development and validation of a quantitative method for the simultaneous determination of cotinine and nicotine in hairless guinea pig plasma by liquid chromatography-mass spectrometry. Nicotine metabolism in hairless guinea pigs is rapid and cotinine was found to be the viable nicotine marker. The portable carbon nanotube membrane device, powered by a 1.5 V watch battery, was demonstrated to be a power efficient method to pump nicotine at levels six to eight times that of passive diffusion. Cotinine blood plasma levels in hairless guinea pigs were seen to increase from 6 to 12 ng/mL when the patch was turned from passive diffusion to an active pumping state. These nicotine patch devices are highly promising for potential clinical applications, with programmed delivery based on remote counseling, in order to improve smoking cessation treatments.

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

    PubMed

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

    2008-01-01

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

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

    PubMed

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

    1975-02-01

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

  12. 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.

  13. 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 ...

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2008-08-01

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

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

    PubMed

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

    2002-12-01

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

  17. Mechanism of vasodilation induced by alpha-human atrial natriuretic polypeptide in rabbit and guinea-pig renal arteries.

    PubMed Central

    Fujii, K; Ishimatsu, T; Kuriyama, H

    1986-01-01

    Effects of alpha-human atrial natriuretic polypeptide (alpha-HANP) on electrical and mechanical properties of smooth muscle cells of the guinea-pig and rabbit renal arteries and of the guinea-pig mesenteric artery were investigated. alpha-HANP (up to 10 nM) modified neither the membrane potential nor resistance of smooth muscle cells of the guinea-pig and rabbit renal arteries. In the guinea-pig mesenteric and renal arteries, alpha-HANP (up to 10 nM) had no effect on the amplitude and facilitation (mesenteric artery) or depression (renal artery) of excitatory junction potentials nor on action potentials. In the guinea-pig renal artery, alpha-HANP (up to 10 nM) had no effect on the depolarization induced by noradrenaline (NA) (up to 10 microM) but markedly inhibited NA-induced contraction. alpha-HANP (10 nM) slightly inhibited the K-induced contraction. In the rabbit renal artery, alpha-HANP (10 nM) inhibited the NA-induced contraction and to a lesser extent the K-induced contraction. In the rabbit renal artery, the effects of alpha-HANP on the release of Ca from the cellular storage by two applications of NA, and its re-storage, were investigated in Ca-free solution containing 2 mM-EGTA. When 5 nM-alpha-HANP was applied before and during the first application of 0.5 microM-NA, the contraction was markedly inhibited but the contraction to a second application of 10 microM-NA was potentiated. If the first dose of NA was 10 microM the effect was very small. Under the same experimental procedures, nitroglycerine (10 microM) showed almost the same effects as alpha-HANP on the NA-induced contractions. When both the first (3 mM) and second (10 mM) contractions were evoked by caffeine in Ca-free solution, alpha-HANP (5 nM) and nitroglycerine (10 microM) inhibited both contractions to the same extent. In the rabbit renal artery, applications of alpha-HANP or nitroglycerine increased the amount of guanosine 3',5'-phosphate (cyclic GMP) in a dose-dependent manner. However, a

  18. 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.

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

    PubMed

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

    2012-04-01

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

  20. 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

  1. Effects of Pentobarbital on Respiratory Functional Dynamics in Chronically Instrumented Guinea Pigs

    DTIC Science & Technology

    1991-01-01

    reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP 06 15 sodium pentobarbital; respiration; chronic single unit 06 04 recording...on redpirasrfuncsiond ’ namics in chronically instrumented guinea pigs. BRAIN RES BULL 26(l) 123-132. 1991.-Respiratory effects of sodium ...in chronicall’ instrumented guinea pigs. BRAIN RES BULL 26(1) 123-132, 1991.-Respiratory effects of sodium pentobarbital (35 mg/kg; IP) were studied in

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

    DTIC Science & Technology

    1991-11-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

    Agterberg, Martijn J H; Versnel, Huib

    2014-07-01

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

  5. 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)

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

    PubMed

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

    2001-01-01

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

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

    PubMed

    Zagorodnyuk, V P; Brookes, S J

    2000-08-15

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed

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

    2013-08-01

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

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

    PubMed

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

    2007-12-01

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

  11. 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

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

    PubMed

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

    2011-09-01

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

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

    PubMed

    Yamini, B; Sleight, S D

    1984-07-01

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

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

    PubMed

    Jensen, L A; Schwartz, B D

    1988-02-15

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

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

    PubMed

    Basso, B; Moretti, E; Fretes, R

    2014-01-15

    Chagas' disease, endemic in Latin America, is spread in natural environments through animal reservoirs, including marsupials, mice and guinea pigs. Farms breeding guinea pigs for food are located in some Latin-American countries with consequent risk of digestive infection. The aim of this work was to study the effect of vaccination with Trypanosoma rangeli in guinea pigs challenged with Trypanosoma cruzi. Animals were vaccinated with fixated epimastigotes of T. rangeli, emulsified with saponin. Controls received only PBS. Before being challenged with T. cruzi, parasitemia, survival rates and histological studies were performed. The vaccinated guinea pigs revealed significantly lower parasitemia than controls (p<0.0001-0.01) and a discrete lymphomonocytic infiltrate in cardiac and skeletal muscles was present. In the chronic phase, the histological view was normal. In contrast, control group revealed amastigote nests and typical histopathological alterations compatible with chagasic myocarditis, endocarditis and pericarditis. These results, together with previous works in our laboratory, show that T. rangeli induces immunoprotection in three species of animals: mice, guinea pigs and dogs. The development of vaccines for use in animals, like domestic dogs and guinea pigs in captivity, opens up new opportunities for preventive tools, and could reduce the risk of infection with T. cruzi in the community.

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

    PubMed

    Bergren, Dale R; Valentine, Jimmie L

    2016-12-01

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

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

    PubMed

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

    2013-04-01

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

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

    PubMed

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

    2013-10-01

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

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

    PubMed Central

    Choughule, Kanika V.; Barr, John T.

    2013-01-01

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

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

    PubMed 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

  1. [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.

  2. Effects of sodium selenite on vascular smooth muscle reactivity.

    PubMed

    Togna, G; Russo, P; Pierconti, F; Caprino, L

    2000-02-01

    The effects of sodium selenite (Na(2)SeO(3)) on the vascular smooth muscle reactivity of rabbit aorta were studied. In isolated rabbit aorta, Na(2)SeO(3) inhibited contractile response to phenylephrine and developed a lasting contracture in the vascular tissue. Relaxation in phenylephrine-precontracted aortic rings induced by sodium nitroprusside and 8-bromo-guanosine 3':5'-cyclic-monophosphate was also inhibited. Preliminary data obtained with ascorbic acid suggested a partial involvement of an oxidative mechanism. Excluding the possibility that Se damages actin or modifies its distribution (immunohistochemical evaluation), results indicate that Se alters vascular smooth muscle reactivity by inhibiting both its contracting and relaxing properties. Calcium-dependent mechanisms appear to be primarily involved and an interference with calcium re-uptake by sarcoplasmic reticulum as a possible site of Se vascular action could be hypothesized.

  3. Confocal Raman Microspectroscopy: The Measurement of VX Depth Profiles in Hairless Guinea Pig Skin and the Evaluation of RSDL

    DTIC Science & Technology

    2015-02-01

    USAMRICD-TR-15-01 Confocal Raman Microspectroscopy: The Measurement of VX Depth Profiles in Hairless Guinea Pig Skin and the Evaluation...5a. CONTRACT NUMBER guinea pig skin and the evaluation of RSDL 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Braue, EH...upper skin layers of hairless guinea pigs and to determine the ability of Reactive Skin Decontamination Lotion (RSDL) to remove or degrade VX from

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

    PubMed

    Daniel, T M

    1975-06-01

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

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

    PubMed Central

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

    2008-01-01

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

  6. Some pharmacological properties of the cremaster muscle of the guinea-pig.

    PubMed Central

    Ninomiya, J G

    1975-01-01

    1 The tension developed in the guinea-pig cremaster was recorded during spontaneous activity and electrical stimulation. Spontaneous rhythmic contraction was observed in many preparations, particularly in the tip of the cremaster. These contractions were very slow, lasting about 20 s and occuring at about 2 min intervals, but different preparations varied greatly. Twitches produced by electrical stimulation were similar to those in other skeletal muscles, being reduced by (+)-tubocurarine and abolished by tetrodotoxin. 2 A slow contraction could be initiated by electrical stimulation using a pulse longer than 10 ms in spontaneously active preparations and in some quiescent preparations. Spontaneous and evoked slow contractions were not suppressed by tetrodotoxin, but were selectively abolished by verapamil. Histamine increased the basal tension and generated spontaneous contractions in quiescent preparations. Hypertonic solutions also had excitatory effects. 3 Contractions produced by acetylcholine and carbachol were blocked by atropine. Those produced by adrenaline and noradrenaline were stronger than those due to histamine, acetylcholine and carbachol and were abolished by an alpha-adrenoceptor blocking agent, phentolamine. In the preparations in which the slow contraction was not observed, histamine, acetylcholine or adrenaline had very little effect. 4 It is suggested that the cremaster muscle consists of striated muscle together with some smooth muscle having properties similar to that in the vas deferens. PMID:1212560

  7. Biologic activity of purified cotton bract extracts in man and guinea pig.

    PubMed Central

    Buck, M G; Schachter, E N; Fick, R B; Merrill, W W; Cooper, J A; Keirns, J J; Oliver, J; Wall, J H

    1986-01-01

    Purified aqueous extracts of cotton bract induce acute airway constriction in healthy volunteers never before exposed to cotton bract. The response is similar to that of textile workers who inhale cotton dust. Approximately 60% of volunteers respond to bract extract with significant decreases in lung function, and these volunteers show an increased number of lymphocytes present in their lungs. Following inhalation of bract, the percent of polymorphonuclear leukocytes increases. Macrophages obtained by bronchoalveolar lavage from volunteers pre-challenged with bract extract release increased amounts of chemotactic factor and superoxide anion. Efforts to detect release of histamine and leukotrienes in volunteers following challenge with bract show no increase in urinary histamine and no significant release of leukotrienes in lung lavage fluid. Purified extracts exhibit chemotactic activity in vitro. They also contract guinea pig ileal longitudinal muscle in vitro. This preparation contains mast cells but no basophils, and the H-1 blocker, mepyramine blocks the contraction. Purified bract extracts contain no histamine or endotoxin but other contractors of smooth muscle may be present. The purified extract exhibits spectral, fluorescent, and radioimmune assay properties similar to a leukotriene B-like component. Cotton bract appears to have direct as well as cell-mediated activities. PMID:3011395

  8. Capsaicin-induced, capsazepine-insensitive relaxation of the guinea-pig ileum.

    PubMed

    Fujimoto, Seigo; Mori, Mayumi; Tsushima, Hiromi; Kunimatsu, Mitoshi

    2006-01-13

    The mechanisms underlying transient receptor potential vanilloid receptor type 1 (TRPV1)-independent relaxation elicited by capsaicin were studied by measuring isometric force and phosphorylation of 20-kDa regulatory light chain subunit of myosin (MLC(20)) in ileum longitudinal smooth muscles of guinea-pigs. In acetylcholine-stimulated tissues, capsaicin (1-100 microM) and resiniferatoxin (10 nM-1 microM) produced a concentration-dependent relaxation. The relaxant response was attenuated by 4-aminopyridine and high-KCl solution, but not by capsazepine, tetraethylammonium, Ba(2+), glibenclamide, charybdotoxin plus apamin nor antagonists of cannabinoid receptor type 1 and calcitonin-gene related peptide. A RhoA kinase inhibitor reduced the relaxant effect of capsaicin at 30 microM. Capsaicin and resiniferatoxin reduced acetylcholine- and caffeine-induced transient contractions in a Ca(2+)-free, EGTA solution. Capsaicin at 30 microM for 20 min did not alter basal levels of MLC(20) phosphorylation, but abolished an increase by acetylcholine in MLC(20) phosphorylation. It is suggested that the relaxant effect of capsaicin at concentrations used is not mediated by TRPV1, but by 4-aminopyridine-sensitive K(+) channels, and that capsaicin inhibits contractile mechanisms involving Ca(2+) release from intracellular storage sites. The relaxation could be explained by a decrease in phosphorylation of MLC(20).

  9. Sildenafil in a cigarette smoke-induced model of COPD in the guinea-pig.

    PubMed

    Domínguez-Fandos, David; Valdés, César; Ferrer, Elisabet; Puig-Pey, Raquel; Blanco, Isabel; Tura-Ceide, Olga; Paul, Tanja; Peinado, Víctor I; Barberà, Joan A

    2015-08-01

    Sildenafil, a phosphodiesterase-5 inhibitor used to treat pulmonary hypertension, may have effects on pulmonary vessel structure and function. We evaluated the effects of sildenafil in a cigarette smoke (CS)-exposed model of chronic obstructive pulmonary disease (COPD).42 guinea-pigs were exposed to cigarette smoke or sham-exposed and treated with sildenafil or vehicle for 12 weeks, divided into four groups. Assessments included respiratory resistance, pulmonary artery pressure (PAP), right ventricle (RV) hypertrophy, endothelial function of the pulmonary artery and lung vessel and parenchymal morphometry.CS-exposed animals showed increased PAP, RV hypertrophy, raised respiratory resistance, airspace enlargement and intrapulmonary vessel remodelling. CS exposure also produced wall thickening, increased contractility and endothelial dysfunction in the main pulmonary artery. CS-exposed animals treated with sildenafil showed lower PAP and a trend to less RV hypertrophy than CS-exposed only animals. Furthermore, sildenafil preserved the intrapulmonary vessel density and attenuated the airspace enlargement induced by CS. No differences in gas exchange, respiratory resistance, endothelial function and vessel remodelling were observed.We conclude that in this experimental model of COPD, sildenafil prevents the development of pulmonary hypertension and contributes to preserve the parenchymal and vascular integrity, reinforcing the notion that the nitric oxide-cyclic guanosine monophosphate axis is perturbed by CS exposure.

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

    PubMed

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

    2012-05-15

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

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

    PubMed

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

    2009-05-01

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

  12. KW-4679-induced inhibition of tachykininergic contraction in the guinea-pig bronchi by prejunctional inhibition of peripheral sensory nerves.

    PubMed Central

    Ikemura, T.; Okarmura, K.; Sasaki, Y.; Ishi, H.; Ohmori, K.

    1996-01-01

    1. Sensory mechanisms play an important role in the vagal regulation of tracheobronchial smooth muscle tone. We examined the effect of KW-4679, an anti-allergic drug, on guinea-pig tachykinin-mediated contractile responses induced by electrical field stimulation (EFS) in guinea-pig bronchial muscles. 2. EFS (8 Hz, 0.5 ms, 15 V, for 15 s) evoked biphasic contractile responses in the guinea-pig isolated main bronchus in the presence of 5 microM indomethacin. The contractions consisted of a fast phase of an atropine-sensitive transient contraction and a slow phase of a sustained contraction which was inhibited by a combination of the tachykinin NK1 receptor antagonist, (+/-)-CP-96,345 (1 microM) and the NK2 receptor antagonist, SR 48969 (0.1 microM). 3. KW-4679 preferentially inhibited the slow phase in a concentration-dependent manner by 43.2 +/- 7.7% at 10 microM, whereas the drug had no effect on the fast phase at concentrations up to 10 microM. KW-4679, at a concentration of 100 microM, inhibited not only the slow phase by 49.2 +/- 11.4%, but also the fast phase by 36.8 +/- 9.3% [corrected]. 4. KW-4679 (10 microM and 100 microM) did not affect the substance P-induced or neurokinin A-induced contraction. Against the acetylcholine-induced contractile responses, 100 microM KW-4679 had a marked effect producing a 10.2 fold shift to the right in the curve. 5. The inhibitory effect of KW-4679 (10 microM) on the slow phase contraction was not influenced by treatment with naloxone (100 nM), propranolol (1 microM), thioperamide (1 microM), saclofen (50 microM), yohimbine (1 microM), methiothepin (1 microM) or methysergide (1 microM). 6. The inhibitory effect of KW-4679 (10 microM) on the slow phase contraction was not influenced by treatment with intermediate or large conductance Ca(2+)-activated K+ channel blockers (charybdotoxin (10 nM) or iberiotoxin (10 nM)), but suppressed by treatment with small conductance Ca(2+)-activated K+ channel blockers, apamin (500 nM) or

  13. Caveolin-1 regulates contractility in differentiated vascular smooth muscle.

    PubMed

    Je, Hyun-Dong; Gallant, Cynthia; Leavis, Paul C; Morgan, Kathleen G

    2004-01-01

    Caveolin is a principal component of caveolar membranes. In the present study, we utilized a decoy peptide approach to define the degree of involvement of caveolin in PKC-dependent regulation of contractility of differentiated vascular smooth muscle. The primary isoform of caveolin in ferret aorta vascular smooth muscle is caveolin-1. Chemical loading of contractile vascular smooth muscle tissue with a synthetic caveolin-1 scaffolding domain peptide inhibited PKC-dependent increases in contractility induced by a phorbol ester or an alpha agonist. Peptide loading also resulted in a significant inhibition of phorbol ester-induced adducin Ser662 phosphorylation, an intracellular monitor of PKC kinase activity, ERK1/2 activation, and Ser789 phosphorylation of the actin binding protein caldesmon. alpha-Agonist-induced ERK1-1/2 activation was also inhibited by the caveolin-1 peptide. Scrambled peptide-loaded tissues or sham-loaded tissues were unaffected with respect to both contractility and signaling. Depolarization-induced activation of contraction was not affected by caveolin peptide loading. Similar results with respect to contractility and ERK1/2 activation during exposure to the phorbol ester or the alpha-agonist were obtained with the cholesterol-depleting agent methyl-beta-cyclodextrin. These results are consistent with a role for caveolin-1 in the coordination of signaling leading to the regulation of contractility of smooth muscle.

  14. Nuclear reprogramming and its role in vascular smooth muscle cells.

    PubMed

    Zaina, Silvio; del Pilar Valencia-Morales, Maria; Tristán-Flores, Fabiola E; Lund, Gertrud

    2013-09-01

    In general terms, "nuclear reprogramming" refers to a change in gene expression profile that results in a significant switch in cellular phenotype. Nuclear reprogramming was first addressed by pioneering studies of cell differentiation during embryonic development. In recent years, nuclear reprogramming has been studied in great detail in the context of experimentally controlled dedifferentiation and transdifferentiation of mammalian cells for therapeutic purposes. In this review, we present a perspective on nuclear reprogramming in the context of spontaneous, pathophysiological phenotypic switch of vascular cells occurring in the atherosclerotic lesion. In particular, we focus on the current knowledge of epigenetic mechanisms participating in the extraordinary flexibility of the gene expression profile of vascular smooth muscle cells and other cell types participating in atherogenesis. Understanding how epigenetic changes participate in vascular cell plasticity may lead to effective therapies based on the remodelling of the vascular architecture.

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

    PubMed

    Skjönsberg, Åsa; Mannström, Paula

    2015-07-08

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

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

    PubMed

    Shlyakhov, E; Rubinstein, E

    1994-01-01

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

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

    PubMed Central

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

    1990-01-01

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

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

    PubMed Central

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

    1986-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  20. 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.

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    1989-01-01

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

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

    PubMed Central

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

    1986-01-01

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

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

    PubMed

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

    2013-03-01

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

  6. Superoxide Production by Digitonin-Stimulated Guinea Pig Granulocytes

    PubMed Central

    Cohen, Harvey J.; Chovaniec, Margaret E.

    1978-01-01

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

  7. Surface immunoglobulin of guinea-pig leukaemic lymphocytes.

    PubMed Central

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

    1975-01-01

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

  8. Antitussive effect of Carum copticum in guinea pigs.

    PubMed

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

    2005-02-10

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

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

    PubMed

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

    1991-01-01

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

  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. Acquired chemotactic inhibitors during infection with guinea pig cytomegalovirus.

    PubMed Central

    Tannous, R; Myers, M G

    1983-01-01

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

  12. Sulfur Mustard Induces Immune Sensitization in Hairless Guinea Pigs

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2010-02-01

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

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

    PubMed

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

    2012-10-01

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

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

    PubMed

    Anderson, R R; Sheffield, L G

    1988-02-01

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

  16. 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

  17. 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....

  18. Smooth muscle-selective CPI-17 expression increases vascular smooth muscle contraction and blood pressure

    PubMed Central

    Su, Wen; Xie, Zhongwen; Liu, Shu; Calderon, Lindsay E.; Guo, Zhenheng

    2013-01-01

    Recent data revealed that protein kinase C-potentiated myosin phosphatase inhibitor of 17 kDa (CPI-17), a myosin phosphatase inhibitory protein preferentially expressed in smooth muscle, is upregulated/activated in several diseases but whether this CPI-17 increase plays a causal role in pathologically enhanced vascular smooth muscle contractility and blood pressure remains unclear. To address this possibility, we generated a smooth muscle-specific CPI-17 transgenic mouse model (CPI-17-Tg) and demonstrated that the CPI-17 transgene was selectively expressed in smooth muscle-enriched tissues, including mesenteric arteries. The isometric contractions in the isolated second-order branch of mesenteric artery helical strips from CPI-17-Tg mice were significantly enhanced compared with controls in response to phenylephrine, U-46619, serotonin, ANG II, high potassium, and calcium. The perfusion pressure increases in isolated perfused mesenteric vascular beds in response to norepinephrine were also enhanced in CPI-17-Tg mice. The hypercontractility was associated with increased phosphorylation of CPI-17 and 20-kDa myosin light chain under basal and stimulated conditions. Surprisingly, the protein levels of rho kinase 2 and protein kinase Cα/δ were significantly increased in CPI-17-Tg mouse mesenteric arteries. Radiotelemetry measurements demonstrated that blood pressure was significantly increased in CPI-17-Tg mice. However, no vascular remodeling was detected by morphometric analysis. Taken together, our results demonstrate that increased CPI-17 expression in smooth muscle promotes vascular smooth muscle contractility and increases blood pressure, implicating a pathological significant role of CPI-17 upregulation. PMID:23604714

  19. 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

  20. Real-time measurement of serotonin release and motility in guinea pig ileum

    PubMed Central

    Bertrand, Paul P

    2006-01-01

    Enterochromaffin (EC) cells are sensors that detect chemical or mechanical stimuli and respond with release of serotonin (5-HT). 5-HT activates local motor reflexes, but whether local motor reflexes also evoke 5-HT release is unknown. The aim of the present study was to establish the relationship between the release of 5-HT and the enteric neural circuits controlling the movements of the intestine. Recordings were made from full-thickness preparations of guinea pig ileum using electrochemical techniques with carbon fibre electrodes to measure local concentrations of 5-HT. The tension in the circular muscle (CM) and longitudinal muscle (LM) was recorded with force transducers. The release of 5-HT from the EC cells was detected selectively and the timing of the events quantified. Pressure-evoked peristalsis caused detectable 5-HT release only when the recording site was invaded by a ring of CM contraction. Spontaneous and stretch-evoked reflex contraction of the CM and LM occurred simultaneously with 5-HT release. Paralysis of the smooth muscle significantly reduced the stretch-evoked release. Muscarinic agonists evoked reflexes that were associated with increases in tension in CM and LM simultaneous with 5-HT release. Tetrodotoxin abolished the coordination between the CM contraction and 5-HT release but not the direct activation of the CM and EC cells by the agonists. In conclusion, the correlation between local motor reflexes and 5-HT release observed in the present study is caused primarily by the contraction of the smooth muscle and subsequent deformation of the mucosa. The EC cell is, thus, a site of convergence for mechanical forces that contribute to the release of 5-HT during motor reflexes. PMID:16959854

  1. Real-time measurement of serotonin release and motility in guinea pig ileum.

    PubMed

    Bertrand, Paul P

    2006-12-01

    Enterochromaffin (EC) cells are sensors that detect chemical or mechanical stimuli and respond with release of serotonin (5-HT). 5-HT activates local motor reflexes, but whether local motor reflexes also evoke 5-HT release is unknown. The aim of the present study was to establish the relationship between the release of 5-HT and the enteric neural circuits controlling the movements of the intestine. Recordings were made from full-thickness preparations of guinea pig ileum using electrochemical techniques with carbon fibre electrodes to measure local concentrations of 5-HT. The tension in the circular muscle (CM) and longitudinal muscle (LM) was recorded with force transducers. The release of 5-HT from the EC cells was detected selectively and the timing of the events quantified. Pressure-evoked peristalsis caused detectable 5-HT release only when the recording site was invaded by a ring of CM contraction. Spontaneous and stretch-evoked reflex contraction of the CM and LM occurred simultaneously with 5-HT release. Paralysis of the smooth muscle significantly reduced the stretch-evoked release. Muscarinic agonists evoked reflexes that were associated with increases in tension in CM and LM simultaneous with 5-HT release. Tetrodotoxin abolished the coordination between the CM contraction and 5-HT release but not the direct activation of the CM and EC cells by the agonists. In conclusion, the correlation between local motor reflexes and 5-HT release observed in the present study is caused primarily by the contraction of the smooth muscle and subsequent deformation of the mucosa. The EC cell is, thus, a site of convergence for mechanical forces that contribute to the release of 5-HT during motor reflexes.

  2. Activation of enteric nerve pathways in the guinea-pig duodenum by cholecystokinin octapeptide and pentagastrin.

    PubMed Central

    Ngu, M C

    1985-01-01

    The action and mechanism of action of cholecystokinin octapeptide (CCK-8) and pentagastrin on isolated segments of guinea-pig duodenum were examined using contractility studies and by intracellular recordings made from smooth muscle cells. Both CCK-8 and pentagastrin caused an excitatory contractile response. The threshold concentration ranged from 5 X 10(-11) to 10(-9) M for CCK-8 and 5 X 10(-10) to 10(-8) M for pentagastrin. The excitatory response was abolished by tetrodotoxin (3.1 X 10(-6) M) and atropine (1.5 X 10(-6) M) and inhibited by d-tubocurarine (up to 2.9 X 10(-5) M). In the presence of atropine a proportion of preparations relaxed in response to CCK-8 (nineteen of thirty-one) and pentagastrin (thirteen of seventeen). This response was only seen at high concentrations of the peptides (10(-8)-10(-7) M) and was abolished by tetrodotoxin (3 X 10(-6) M). Intracellular recordings from duodenal smooth muscle revealed multiple excitatory junction potentials (e.j.p.s) in response to CCK-8 and to pentagastrin. These e.j.p.s were identical to those evoked by transmural nerve stimulation and were abolished by atropine (1.5 X 10(-7) M) and by tetrodotoxin (3 X 10(-6) M). Inhibitory junction potentials (i.j.p.s) were not recorded in response to the peptides except on one occasion. It is suggested that CCK-8 and pentagastrin cause an increase in duodenal motility by the selective activation of excitatory pathways in the enteric nervous system. PMID:4032301

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

    PubMed Central

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

    1980-01-01

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

  4. Pathological and virological features of arenavirus disease in guinea pigs. Comparison of two Pichinde virus strains.

    PubMed

    Aronson, J F; Herzog, N K; Jerrells, T R

    1994-07-01

    A guinea pig passage-adapted strain of the arena-virus Pichinde (adPIC) is highly virulent in inbred guinea pigs, whereas the related strain PIC3739 is attenuated. Both viruses were macrophage tropic and infected peritoneal, splenic, liver, and alveolar macrophages during experimental Pichinde virus infection. Infection with the virulent strain was associated with unlimited viral replication in the face of exaggerated delayed-type hypersensitivity response, manifested by the macrophage disappearance reaction. Histopathological lesions unique to adPIC-infected guinea pigs included intestinal villus blunting with mucosal infiltration by pyknotic debris-laden macrophages and apoptosis of crypt epithelial cells. Splenic red pulp necrosis was also significantly associated with adPIC infection but not PIC3739 infection. These findings may provide clues to the pathogenesis of a group of poorly understood human viral hemorrhagic fevers.

  5. 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

  6. Inhibition of gastric secretion in guinea pig by relatively low dose ionizing radiation

    SciTech Connect

    Batzri, S.; Catravas, G.

    1988-11-01

    We evaluated the effect of a single dose of ionizing radiation on gastric secretion in awake guinea pigs equipped with a permanent gastric cannula. Changes in gastric secretion were measured using a dye dilution technique. Infusion of histamine increased acid and fluid output and there was a positive correlation (r = 0.93) between the two. Total body irradiation with 400 cGy, like cimetidine, suppressed acid and fluid secretion under basal conditions and during histamine stimulation by 50-90%. Recovery from the radiation damage was only partial after one week. Irradiation inhibited the rise in gastric juice volume during histamine stimulation and also reduced the normal gain in body weight of the guinea pig. These results demonstrate that ionizing radiations have an immediate and long lasting effects on the gastric mucosal function of the guinea pig.

  7. Naturally occurring Parelaphostrongylus tenuis-associated choriomeningitis in a guinea pig with neurologic signs.

    PubMed

    Southard, T; Bender, H; Wade, S E; Grunenwald, C; Gerhold, R W

    2013-05-01

    An adult male guinea pig (Cavia porcellus) with a 1-month history of hind limb paresis, torticollis, and seizures was euthanized and submitted for necropsy. Gross examination was unremarkable, but histologic examination revealed multifocal eosinophilic and lymphoplasmacytic choriomeningitis and cross sections of nematode parasites within the leptomeninges of the midbrain and diencephalon. Morphologic features of the nematode were consistent with a metastrongyle, and the parasite was identified as Parelaphostrongylus tenuis by polymerase chain reaction testing and nucleotide sequencing. Further questioning of the owner revealed that the guinea pig was fed grass from a yard often grazed by white-tailed deer (Odocoileus virginianus). To the authors' knowledge, this is the first report of a naturally occurring P. tenuis infection in a guinea pig.

  8. 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

  9. [Occurrence and distribution of ectoparasites in guinea pigs (Cavia spp.) in Peru, South America].

    PubMed

    de la Cruz, Katharina Dittmar; Ribbeck, Regine; Daugschies, Arwio

    2003-01-01

    Studies on the prevalence and distribution of ectoparasites in Peru were carried out during a period of 2 1/2 years. The survey included 17,421 domesticated guinea pigs (Cavia aperea f. porcellus) from 14 departments in all bioregions and altitude levels and 143 wild guinea pigs (Cavia aperea) from three areas (El Paramo, Junin and La Raya) in the Andes and the Cordillera. The guinea pig is an important source of food, especially for the rural population, the infestation with ectoparasites, such as fleas, lice or mites greatly contributes to a decrease in production and low performance. Ectoparasites can be vectors for a variety of pathogens, which is particularly problematic due to the close association of this animal with humans. Twenty one ectoparasite species have been recovered. New knowledge about host associations and distributions could be obtained. The results of the studies are presented under faunistic and ecological aspects.

  10. Spasmolytic activity of a herbal drug isolated from Tephrosia purpurea in guinea pigs.

    PubMed

    Soni, Kapil K; Khare, M L; Saxena, R C

    2004-04-01

    We investigated the spasmolytic activity of herbal drugs isolated from Tephrosia purpurea on guinea pigs for the treatment of asthma in India. For this investigation, the herbal drug was extracted with 70% ethanol in soxhlet apparatus. After purification and isolution, the drug was used in experimental animals to observe prophylactic activity. For anaphylactic activity, horse serum 0.5 ml along with triple antigen (0.5 ml) was induced in guinea pigs. To observe prophylactic activity, male guinea pigs weighing about 250-450 gms were killed by cervical dislocation and the trachea was isolated. Each trachea was cut in to six segments. Each segment consists of three cartilage rings. Each end of tracheal muscles was attached to the bronchospasm transducers for isometric recording of the tension charges on a polygraph. The results of experiments clearly showed the spasmolytic activity of the drug. The preliminary phytochemical investigation, however shows the presence of glycoside saponins.

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

    PubMed

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

    1998-12-01

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

  12. Novel triple neurokinin receptor antagonist CS-003 inhibits respiratory disease models in guinea pigs.

    PubMed

    Tsuchida, Hiroshi; Takahashi, Sakiko; Nosaka, Emi; Kuraya, Takako; Yamashita, Makoto; Morimoto, Kiyoshi

    2008-10-31

    Neurokinins are known to induce neurogenic inflammation related to respiratory diseases. The effects of CS-003 ([1-{2-[(2R)-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethyl}spiro[benzo[c]thiophene-1(3H),4'-piperidine]-(2S)-oxide hydrochloride]), a novel triple neurokinin receptor antagonist, on several respiratory disease models were evaluated in guinea pigs. As we have already shown that CS-003 is intravenously effective, we first determined if CS-003 was orally effective. CS-003 dose-dependently inhibited substance P-induced tracheal vascular hyperpermeability, neurokinin A- and neurokinin B-induced bronchoconstriction with ID(50) values of 3.6, 1.3 and 0.89 mg/kg (p.o.), respectively. CS-003 (10 mg/kg, p.o.) inhibited the number of coughs induced by capsaicin aerosol (P<0.01) and the antitussive effect was comparable to that of codeine. CS-003 (10 mg/kg, p.o.) also inhibited airway hyperresponsiveness to methacholine chloride in ovalbumin-induced asthma models (P<0.01), a milder one and a severer one. On the other hand, montelukast (10 mg/kg, p.o.), a leukotriene receptor antagonist, significantly inhibited the hyperresponsiveness only in the milder model (P<0.05). In an ovalbumin-induced rhinitis model, oral administration of CS-003 inhibited nasal blockade in a dose-dependent manner and the inhibitory effect was comparable to that of dexamethasone (10 mg/kg, p.o.). CS-003 (i.v.) also dose-dependently inhibited cigarette smoke-induced bronchoconstriction, tracheal vascular hyperpermeability and mucus secretion. These data show that CS-003, a potent orally active triple neurokinin receptor antagonist, may be useful for the treatment of respiratory diseases associated with neurokinins, such as allergic asthma, allergic rhinitis, chronic obstructive pulmonary disease and cough.

  13. Presynaptic histamine H1- and H3-receptors modulate sympathetic neurotransmission in isolated guinea pig vas deferens.

    PubMed

    Luo, X X; Tan, Y H

    1994-01-01

    The action of (R)-alpha-methylhistamine (alpha-MeHA), a selective H3-receptor agonist, on field stimulation induced contraction of guinea pig vas deferens was composed of 2 components: the "inhibition" (0.1-100 nmon.L-1) and the "enhancement" (1-10 mumol.L-1). In the presence of histamine H1 antagonist, chlorpheniramine (1 mumol.L-1), alpha-MeHA (0.1 nmol.L-1-10 mumol.L-1) showed only a concentration-dependent inhibition. Selective histamine H3-receptor antagonist, thioperamide (1 nmol.L-1-10 mumol.L-1) antagonized the inhibitory effect of alpha-MeHA and increased the contractile amplitude of vas deferens elicited by field pulses when thioperamide was used alone. alpha-MeHA 10 mumol.L-1 enhanced the contractile amplitude, which was reversed by chlorpheniramine 1 mumol.L-1, but not by ranitidine (1 mumol.L-1). Pyridelethylamine, an H1-receptor agonist, facilitated concentration-dependently the contractile response of vas deferens. The effect was antagonized by chlorpheniramine, but not by ranitidine. Dimaprit, an H2-receptor agonist had no effect on the field stimulation induced sympathetic response. Both alpha-MeHA and pyridelethylamine failed to influence the contraction of vas deferens elicited by direct field stimulation in smooth muscle or by exogenously applied norepinephrine. It was concluded that histamine H1- and H3-receptors existed in sympathetic terminals of guinea pig vas deferens and facilitated or inhibited the sympathetic neurotransmission.

  14. Effect of enhanced red blood cell aggregation on blood flow resistance in an isolated-perfused guinea pig heart preparation.

    PubMed

    Yalcin, Ozlem; Meiselman, Herbert J; Armstrong, Jonathan K; Baskurt, Oguz K

    2005-01-01

    The role of red blood cell (RBC) aggregation as a determinant of in vivo blood flow is still unclear. This study was designed to investigate the influence of a well-controlled enhancement of RBC aggregation on blood flow resistance in an isolated-perfused heart preparation. Guinea pig hearts were perfused through a catheter inserted into the root of the aorta using a pressure servo-controlled pump system that maintained perfusion pressures of 30 to 100 mmHg. The hearts were beating at their intrinsic rates and pumping against the perfusion pressure. RBC aggregation was increased by Pluronic (F98) coating of RBC at a concentration 0.025 mg/ml, corresponding to about a 100% increment in RBC aggregation as measured by erythrocyte sedimentation rate. Isolated heart preparations were perfused with 0.40 l/l hematocrit unmodified guinea pig blood and with Pluronic-coated RBC suspensions in autologous plasma. At high perfusion pressures there were no significant differences between the flow resistance values for the two perfusates, with differences in flow resistance only becoming significant at lower perfusion pressures. These results can be interpreted to reflect the shear dependence of RBC aggregation: higher shear forces associated with higher perfusion pressures should have dispersed RBC aggregates resulting in blood flow resistances similar to control values. Experiments repeated in preparations in which the smooth muscle tone was inhibited by pre-treatment with papaverine indicated that significant effects of enhanced RBC aggregation could be detected at higher perfusion pressures, underlining the compensatory role of vasomotor control mechanisms.

  15. 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.

  16. Airway epithelial-derived factor relaxes pulmonary vascular smooth muscle.

    PubMed

    Farah, Omar R; Li, Dongge; McIntyre, Brendan A S; Pan, Jingyi; Belik, Jaques

    2009-01-01

    The factors controlling the pulmonary vascular resistance under physiological conditions are poorly understood. We have previously reported on an apparent cross talk between the airway and adjacent pulmonary arterial bed where a factor likely derived from the bronchial epithelial cells reduced the magnitude of agonist-stimulated force in the vascular smooth muscle. The main purpose of this investigation was to evaluate whether bronchial epithelial cells release a pulmonary arterial smooth muscle relaxant factor. Conditioned media from SPOC-1 or BEAS-2B, a rat- and a human-derived bronchial epithelial cell line, respectively, were utilized. This media significantly relaxed precontracted adult but not fetal pulmonary arterial muscle in an oxygen tension-dependent manner. This response was mediated via soluble guanylate cyclase, involving AKT/PI3-kinase and neuronal nitric oxide synthase. Airway epithelial cell-conditioned media increased AKT phosphorylation in pulmonary smooth muscle cells (SMC) and reduced intracellular calcium change following ATP stimulation to a significantly greater extent than observed for bronchial SMC. The present data strongly support the evidence for bronchial epithelial cells releasing a stable and soluble factor capable of inducing pulmonary arterial SMC relaxation. We speculate that under physiological conditions, the maintenance of a low pulmonary vascular resistance, postnatally, is in part modulated by the airway epithelium.

  17. 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.

  18. Rifapentine is not more active than rifampin against chronic tuberculosis in guinea pigs.

    PubMed

    Dutta, Noton K; Illei, Peter B; Peloquin, Charles A; Pinn, Michael L; Mdluli, Khisimuzi E; Nuermberger, Eric L; Grosset, Jacques H; Karakousis, Petros C

    2012-07-01

    Rifamycins are key sterilizing drugs in the current treatment of active tuberculosis (TB). Daily dosing of rifapentine (P), a potent rifamycin with high intracellular accumulation, in place of rifampin (R) in the standard antitubercular regimen significantly shortens the duration of treatment needed to prevent relapse in a murine model of active TB. We undertook the current study to compare directly the activities of human-equivalent doses of P and R in a guinea pig model of chronic TB, in which bacilli are predominantly extracellular within human-like necrotic granulomas. Hartley strain guinea pigs were aerosol infected with ~200 bacilli of Mycobacterium tuberculosis H37Rv, and treatment given 5 days/week was initiated 6 weeks later. R at 100 mg/kg of body weight and P at 100 mg/kg were given orally alone or in combination with isoniazid (H) at 60 mg/kg and pyrazinamide (Z) at 300 mg/kg. Culture-positive relapse was assessed in subgroups of guinea pigs after completion of 1 and 2 months of treatment. Human-equivalent doses of R and P showed equivalent bactericidal activity when used alone and in combination therapy. In guinea pigs treated with rifampin, isoniazid, and pyrazinamide (RHZ) or PHZ, microbiological relapse occurred in the lungs of 8/10 animals treated for 1 month and in 0/10 animals treated for 2 months. Substitution of P for R in the standard antitubercular regimen did not shorten the time to cure in this guinea pig model of chronic TB. Data from ongoing clinical trials comparing the activity of these two drugs are awaited to determine the relevance of the guinea pig TB model in preclinical drug screening.

  19. 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

  20. The protective effect of Nigella sativa on lung injury of sulfur mustard-exposed Guinea pigs.

    PubMed

    Hossein, Boskabady Mohammad; Nasim, Vahedi; Sediqa, Amery

    2008-05-01

    The lung is one of the most exposable organs to chemical warfare agents such as sulfur mustard (SM) gas. Airway hyperresponsiveness and lung inflammation are reported in chemical warfare victims. There is no definite treatment for respiratory disorders induced by SM exposure. However, the protective effect of Nigella sativa on inflammatory process was shown. In the present study, the protective effect of Nigella sativa on tracheal responsiveness and lung inflammation of SM exposed guinea pigs was examined. Guinea pigs were exposed to diluent's solution (ethanol, control group), 100 mg/m(3) inhaled sulfur mustard (SME group), and SME treated with Nigella sativa, 0.08 g daily (SME+N), n = 6 for each group. Tracheal responsiveness (TR) to methacholine, total white blood cell (WBC) count of lung lavage, and differential WBC were done 14 days post exposure. The weigh of animal were measured at the beginning, middle (day 7), and the end (day 14) of the study. The TR of SM-exposed guinea pigs was significantly (P < .001) and WBC nonsignificantly higher than those of controls. In SME guinea pigs, there was a weight loss but in the case of SME+N guinea pigs, no obvious weight change thought the study was seen. The eosinophl, monocyte, and lympocytes in SME animals were significantly changed compared to control group (P < .001 for all cases). Monocyte, lymphocyte, and neutrophil number were decreased in SME+N group compared to SME animals, which was significant only for neutrophil (P < .05). These results showed a preventive effect of Nigella sativa on TR of SM-exposed guinea pigs.

  1. Role of interleukin-5 in enhanced migration of eosinophils from airways of immunized guinea-pigs.

    PubMed Central

    Coëffier, E; Joseph, D; Vargaftig, B B

    1994-01-01

    1. Platelet activating factor (PAF), leukotriene B4 (LTB4) and interleukin-5 (IL-5) are potent chemoattractants for guinea-pig eosinophils, which may be involved in eosinophil recruitment and up-regulation in allergic diseases. Eosinophils from the bronchoalveolar lavage fluid (BALF) of ovalbumin-sensitized guinea-pigs were collected 24 h after antigen provocation and migration induced by PAF, LTB4 and rhIL-5 was studied. 2. Total BALF content and distribution of eosinophils were greater in immunized, ovalbumin-challenged guinea-pigs (5.0 +/- 0.8 x 10(6)/guinea-pig; 12 +/- 1%) than in immunized, saline-challenged animals (3.0 +/- 0.7 x 10(6)/guinea-pig; 7 +/- 1%). 3. The chemoattraction of eosinophils isolated on a metrizamide gradient was studied in micro-Boyden chambers, results being expressed as the number of migrating cells (mean +/- s.e. mean). PAF and LTB4-induced migration of eosinophils from immunized and OA-challenged guinea-pigs were significantly enhanced, as compared to immunized and saline-challenged animals (170 +/- 36 vs 35 +/- 9 migrating eosinophils for 10 nM PAF; 271 +/- 60 vs 110 +/- 19 for 1 nM LTB4). 4. The IL-5 antibody TRFK-5, in vivo, reduced eosinophil recruitment in BALF of antigen-challenged immunized animals as well as the enhanced responsiveness of eosinophils from the challenged animals, suggesting a role for IL-5 in the priming of eosinophils in vivo. 5. In contrast to TRFK-5, nedocromil sodium reduced to a similar extent eosinophil, macrophage and lymphocyte recruitment into the BALF of antigen-challenged, but failed to down-regulate the enhanced responsiveness of eosinophils from the challenged animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7858864

  2. 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.

  3. Onset and duration of immunity in guinea pigs and mice induced with different Q fever vaccines.

    PubMed

    Kazár, J; Votruba, D; Propper, P; Schramek, S

    1986-11-01

    Protective effects of different types of Q fever vaccines, namely untreated Coxiella burnetii phase I cells (Cb I) or Cb I cells treated with chloroform-methanol (CM) mixture (Cb I-CM) and of a Q fever chemovaccine obtained by trichloroacetic acid extraction (TCAE) from intact Cb I cells, were compared in mice and guinea pigs at different intervals after intraperitoneal (i.p.) or subcutaneous (s.c.) immunizations. The highest degree of protection at all intervals studied was achieved with Cb I cells, irrespective of the route of immunization and i.p. or aerosol challenge. This vaccine exerted a protective effect in guinea pigs and mice as early as after one or two weeks post-immunization, the effect lasting for at least 40 weeks in mice (i.p. challenge) and 12 months in guinea pigs (aerosol challenge). Addition of small amount of Cb I cells to TCAE increased resistance of guinea pigs to aerosol challenge. Degree, onset and duration of protection to either type of virulent challenge afforded by Cb I-CM cells and TCAE was similar, but when compared with that of Cb I cells it was lower, started later (from the 2nd week in guinea pigs and the 3rd week in mice), and in mice it lasted for a shorter period (20 weeks only). The resistance to virulent challenge in guinea pigs did not depend on the levels of microagglutination (MA) antibodies and in mice it was reflected by delayed type hypersensitivity (DTH) reaction and adoptively transferred splenocytes, rather than by MA antibody titres and passive transfer of immune sera to recipient mice.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. The role of pheromones in the regulation of estrous cycle duration in the guinea pig.

    PubMed

    Jesel, L; Aron, C L

    1976-01-01

    A decrease in estrous cycle duration, due to shortening of the period of vaginal closure (VC), has been observed in female guinea pigs exposed to the odor of urine from males of the same species. VC shortening was also observed in females exposed to the odor of female urine collected during the period of vaginal opening (VO). No alteration in VC duration occurred, however, in females exposed to urine collected in the 1st 7 days of VC. Also VC shortening did not occur in bulbectomized females exposed to the odor of male urine. Therefore, it was concluded that guinea pig urine, when highly concentrated, contains pheromones capable of shortening estrous cycle VC.

  5. BCG vaccination enhances resistance to M. tuberculosis infection in guinea pigs fed a low casein diet.

    PubMed

    Sugawara, Isamu; Yamada, Hiroyuki; Mizuno, Satoru

    2007-03-01

    In order to examine the relationship between malnutrition and tuberculosis development in vivo, a malnourished guinea pig model fed with a low casein (5%) diet was developed. After being fed with the low casein diet, the guinea pigs were infected with Mycobacterium (M.) tuberculosis Kurono strain by aerosol infection, and seven weeks later were subjected to histopathologic examination, colony-forming unit (CFU) assay, fluorescence-activated cell sorter (FACS) analysis and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12 and inducible nitric oxide synthase (iNOS) mRNA. Another group of guinea pigs were vaccinated subcutaneously with 10(6) CFU BCG Tokyo for three weeks and then similarly infected by aerosol. Eighty-eight% (7/8) of the malnourished guinea pigs succumbed to mycobacterial infection within 85 days after infection, while the malnourished guinea pigs vaccinated with BCG Tokyo survived. CFU assay showed that lung and splenic CFUs were higher in the low casein diet-fed groups than in the control diet (20% casein)-fed groups, although both groups had significantly lower CFUs after vaccination with BCG Tokyo (p<0.01). Examination of lung histopathology revealed that pulmonary granulomas were large and disorganized in the groups fed the low casein diet. The number of visible lesions on the surfaces of the fixed lungs in guinea pigs fed control diet+BCG and low casein diet+BCG was low significantly. Pan T-, CD4-, CD8- and Mac antigen-positive cells were also recognized in the infected lung tissues of low casein-fed guinea pigs and Pan T-, CD4- and Mac antigen-positive cells increased after vaccination with BCG Tokyo. Expression of IFN-gamma, TNF-alpha, IL-12 and iNOS mRNA was also recognized in the infected lung tissues of low casein-fed guinea pigs and IFN-gamma and TNF-alpha mRNA expression was enhanced with BCG vaccination. These results indicate that

  6. 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

  7. 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.

  8. Opioid receptors on guinea-pig intestinal crypt epithelial cells.

    PubMed Central

    Lang, M E; Davison, J S; Bates, S L; Meddings, J B

    1996-01-01

    1. Opioid peptides promote net intestinal absorption via two mechanisms: stimulation of Na+ and Cl- absorption and inhibition of Cl- secretion. Although these transport changes are predominantly mediated by submucosal neurones, it is currently unclear whether opioid peptides can regulate enterocyte function directly. We therefore tested the hypothesis that enterocytes have specific opioid receptors. 2. Villus and crypt jejunal epithelial cells were isolated by the distended sac method from anaesthetized guinea-pigs. Flow cytometry was used to resolve enterocytes from other cell types and to determine whether binding of a fluorescently labelled opioid antagonist, naltrexone-FITC, could be prevented by unlabelled mu- and delta-opioid receptor agonists. A population of crypt enterocytes (approximately 21%) exhibited high-affinity naltrexone-FITC binding to both mu- and delta-type binding sites that was stereoselective and sodium dependent. Villus enterocytes did not exhibit any of these characteristics. 3. Basal cAMP production was elevated in both villus and crypt cells treated with IBMX (3-isobutyl-1-methylxanthine). Villus cells did not respond to 100 nM vasoactive intestinal peptide (VIP), nor were they affected by opioid peptides. In contrast, 100 nM VIP significantly increased cAMP production in crypt epithelial cells, which was significantly reduced by both morphiceptin and D-Ser2-Leu-Enk-Thr. This opioid-mediated effect was stereoselective and blocked by the opioid receptor antagonist naltrexone. 4. These experiments suggest that enterocytes isolated from the crypt epithelium of guineapigs have both mu- and delta-types of opioid receptors. It is possible that these cells participate in opioid-mediated regulation of intestinal secretion. Images Figure 12 PMID:8951719

  9. Macroscopic electrical propagation in the guinea pig urinary bladder.

    PubMed

    Hammad, F T; Stephen, B; Lubbad, L; Morrison, J F B; Lammers, W J

    2014-07-15

    There is little knowledge about macroscopic electrical propagation in the wall of the urinary bladder. Recording simultaneously from a large number of extracellular electrodes is one technology that could be used to study the patterns of macroscopic electrical propagations. The urinary bladders from 14 guinea pigs were isolated and placed in an organ bath. A 16 × 4-electrode array was positioned at various sites on the serosal bladder surface, and recordings were performed at different intravesical volumes. In four experiments, carbachol (CCH; 10(-6) M), nifedipine (10 mM), or tetrodotoxin (TTX; 10(-6) M) was added to the superfusing fluid. After the experiments, the extracellular signals were analyzed and propagation maps were constructed. Electrical waves were detected at all sites on the bladder surface and propagated for a limited distance before terminating spontaneously. The majority of waves (>90%) propagated in the axial direction (i.e., from dome to base or vice versa). An increase in vesicle volume significantly decreased the conduction velocity (from 4.9 ± 1.5 to 2.7 ± 0.7 cm/s; P < 0.05). CCH increased, nifedipine decreased, while TTX had little effect on electrical activities. In addition, a new electrical phenomenon, termed a "patch," was discovered whereby a simultaneous electrical deflection was detected across an area of the bladder surface. Two types of electrical activities were detected on the bladder surface: 1) electrical waves propagating preferentially in the axial direction and 2) electrical patches. The propagating electrical waves could form the basis for local spontaneous contractions in the bladder during the filling phase.

  10. 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.

  11. Angiotensin receptors and actions in guinea pig enteric nervous system.

    PubMed

    Wang, Guo-Du; Wang, Xi-Yu; Hu, Hong-Zhen; Fang, Xiu-Cai; Liu, Sumei; Gao, Na; Xia, Yun; Wood, Jackie D

    2005-09-01

    Actions of ANG II on electrical and synaptic behavior of enteric neurons in the guinea pig small intestine were studied. Exposure to ANG II depolarized the membrane potential and elevated neuronal excitability. The number of responding neurons was small, with responses to ANG II in 32% of submucosal neurons and 25% of myenteric neurons. Hyperpolarizing responses were evoked by ANG II in 45% of the neurons. The hyperpolarizing responses were suppressed by alpha2-noradrenergic receptor antagonists, which suggested that the hyperpolarizing responses reflected stimulation of norepinephrine release from sympathetic neurons. Exposure to ANG II enhanced the amplitude and prolonged the duration of noradrenergic inhibitory postsynaptic potentials and suppressed the amplitude of both fast and slow excitatory postsynaptic potentials. The selective ANG II(1) receptor (AT1R) antagonists, ZD-7115 and losartan, but not a selective AT2R antagonist (PD-123319), suppressed the actions of ANG II. Western blot analysis and RT-PCR confirmed expression of AT1R protein and the mRNA transcript for the AT1R in the enteric nervous system. No expression of AT2R protein or mRNA was found. Immunoreactivity for AT1R was expressed by the majority of neurons in the gastric antrum and small and large intestine. AT1R immunoreactivity was coexpressed with calbindin, choline acetyltransferase, calretinin, neuropeptide Y, and nitric oxide synthase in subpopulations of neurons. The results suggest that formation of ANG II might have paracrine-like actions in the enteric nervous system, which include alterations in neuronal excitability and facilitated release of norepinephrine from sympathetic postganglionic axons. The enhanced presence of norepinephrine is expected to suppress fast and slow excitatory neurotransmission in the enteric microcircuits and to suppress neurogenic mucosal secretion.

  12. [+]-Huperzine A protects against soman toxicity in guinea pigs.

    PubMed

    Wang, Ying; Wei, Yanling; Oguntayo, Samuel; Jensen, Neil; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2011-12-01

    The chemical warfare nerve agent (CWNA) soman irreversibly inhibits acetylcholinesterase (AChE) causing seizure, neuropathology and neurobehavioral deficits. Pyridostigmine bromide (PB), the currently approved pretreatment for soman, is a reversible AChE inhibitor that does not cross the blood-brain barrier (BBB) to protect against central nervous system damage. [-]-Huperzine A, a natural reversible AChE inhibitor, rapidly passes through the BBB and has numerous neuroprotective properties that are beneficial for protection against soman. However, [-]-Huperzine A is toxic at higher doses due to potent AChE inhibition which limits the utilization of its neuroprotective properties. [+]-Huperzine A, a synthetic stereoisomer of [-]-Huperzine A and a weak inhibitor of AChE, is non-toxic. In this study, we evaluated the efficacy of [+]-Huperzine A for protection against soman toxicity in guinea pigs. Pretreatments with [+]-Huperzine A, i.m., significantly increased the survival rate in a dose-dependent manner against 1.2× LD(50) soman exposures. Behavioral signs of soman toxicity were significantly reduced in 20 and 40 mg/kg [+]-Huperzine A treated animals at 4 and 24 h compared to vehicle and PB controls. Electroencephalogram (EEG) power spectral analysis showed that [+]-Huperzine A significantly reduces soman-induced seizure compared to PB. [+]-Huperzine A (40 mg/kg) preserved higher blood and brain AChE activity compared to PB in soman exposed animals. These data suggest that [+]-Huperzine A protects against soman toxicity stronger than PB and warrant further development as a potent medical countermeasure against CWNA poisoning.

  13. Biomechanical analysis of fracture healing in guinea-pigs.

    PubMed

    Kdolsky, Richard; Reihsner, Roland; Beer, Rudolf

    2008-01-01

    To validate the hypothesis that healing of fractures can be accelerated by oral administered L-arginine a guinea-pig model was chosen. A diaphyseal defect fracture was established in the right femur of each of the 32 small animals and stabilized. According to randomization groups the oral administration was realized (2 or 4 weeks medication / solvent). The following biomechanical variables were measured after 4 weeeks in 32 right femora and the corresponding uninjured left femora. The measurement for the healed femur was individually compared with that of the uninjured femur in each animal; bending, force (necessary for refracture) and energy (necessary for refracture). To apply the bending moment in a measurable and reproducible way each end of the femur was secured using a special device. For each femur a strain/momentum graph of the measurements and the essential parameters were drawn (stiffness, end of the linear range, and failure-point). The bending moment was always applied with the same loading rate. The following three variables were used for the biomechanical evaluation; bending stiffness, force until failure and energy necessary for refracture. The bending stiffness reached 73% by the control group and 88% by the 4-week treatment group. The force necessary for refracture was 52% in the control compared with 65% in the 4-week treatment group. The energy necessary for refracture was 36% in the control compared with 73% in the group treated for 4 weeks. The 2 week treatment group showed no statistical significant differences to the control, but the femora from the 4 week treatment group required statistically significant higher energy for refracture than the femora from the control.

  14. Stability of the guinea pigs personality - cognition - linkage over time.

    PubMed

    Brust, Vera; Guenther, Anja

    2017-01-01

    In human psychological research, personality traits as well as cognitive traits are usually validated for both, their stability over time and contexts. While stability over time gives an estimate on how genetically fixated a trait can be, correlations across traits have the power to reveal linkages or trade - offs. In animals, these validations have widely been done for personality but not for cognitive traits. We tested guinea pigs in four consecutive discrimination tasks using four unique pairs of objects with two objects of the same form but different size in each pair. The same animals were tested twice each for three personality traits, i.e. boldness, aggression and sociopositive behaviour. The animals did not learn to "always choose the larger item" in the cognitive task but learned to discriminate the two objects of each stimulus pair anew, so that we did test for learning speed in four slightly different task setups. Performance over the four tasks was significantly repeatable as well as all tested personality traits. A stable linkage over time was found between sociopositive behaviour and learning performance, probably indicating an ecological relevance for a correlation between these two traits. Still, not all traits seem to be connected amongst each other, as in our case boldness and aggression are both not linked to individual learning performance. Future studies will hopefully further investigate the repeatability of various cognitive traits in several species and thus lead to a better understanding of the interdependence of personality and cognition. This will help to unravel which suites of traits facilitate individual life histories and hence improve our understanding of the emergence and maintenance of individual differences.

  15. 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

  16. 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.

  17. Adenosine induces a cholinergic tracheal reflex contraction in guinea pigs in vivo via an adenosine A1 receptor-dependent mechanism.

    PubMed

    Reynolds, Sandra M; Docherty, Reginald; Robbins, Jon; Spina, Domenico; Page, Clive P

    2008-07-01

    Adenosine induces dyspnea, cough, and airways obstruction in asthma, a phenomenon that also occurs in various sensitized animal models in which a neuronal involvement has been implicated. Although adenosine has been suggested to activate cholinergic nerves, the precise mechanism has not been established. In the present study, the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA) induced a cholinergic reflex, causing tracheal smooth muscle contraction that was significantly inhibited by the adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 100 microg/kg) (P < 0.05) in anesthetized animals. Furthermore, the adenosine A(2) agonist 2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680) induced a small reflex, whereas the A(3) selective agonist N(6)-(3-iodobenzyl)-5'-N-methylcarbamoyladenosine (IB-MECA) was without effect. The tracheal reflex induced by CPA was also inhibited by recurrent nerve ligation or muscarinic receptor blockade (P < 0.001), indicating that a cholinergic neuronal mechanism of action accounted for this response. The cholinergic reflex in response to aerosolized CPA was significantly greater in passively sensitized compared with naive guinea pigs (P < 0.01). Chronic capsaicin treatment, which inhibited sensory nerve function, failed to inhibit CPA-induced reflex tracheal contractions in passively sensitized guinea pigs, although the local anesthetic lidocaine inhibited CPA-induced tracheal contractions. The effects of CPA on the reflex response was not dependent on the release of histamine from tissue mast cells or endogenous prostaglandins as shown by the lack of effect of the histamine H(1) receptor antagonist pyrilamine (1 mg/kg) or the cyclooxygenase inhibitor meclofenamic acid (3 mg/kg), respectively. In conclusion, activation of pulmonary adenosine A(1) receptors can stimulate cholinergic reflexes, and these reflexes are increased in allergic guinea pigs.

  18. Effect of the nonpeptide neurotensin antagonist, SR 48692, and two enantiomeric analogs, SR 48527 and SR 49711, on neurotensin binding and contractile responses in guinea pig ileum and colon.

    PubMed

    Labbé-Jullié, C; Deschaintres, S; Gully, D; Le Fur, G; Kitabgi, P

    1994-10-01

    The tridecapeptide neurotensin (NT) contracts the guinea pig ileum through a neurogenic process that is mediated in part by acetylcholine and substance P and relaxes the guinea pig colon through a direct action on smooth muscle cells involving the opening of Ca(++)-dependent K+ channels. The non-peptide NT antagonist, SR 48692 (2-[1-(7-chloro-4-quinolinyl)-5-(2,6- dimethoxyphenyl)pyrazol-3-yl)carbonylamino]tricyclo-(3.3.1.1 .3.7)decan-2- carboxylic acid), potently inhibited NT binding to membranes prepared from the guinea pig ileum and colon with Ki values of approximately 3 nM. SR 48527 ((S)-(+)-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazol-3- yl)carbonylamino]cyclohexylacetic acid) and SR 49711 ((R)-(-)-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazol- 3-yl)carbonylamino]cyclohexylacetic acid), two enantiomers structurally related to SR 48692, were respectively equipotent with and a 100-fold less potent than SR 48692 in inhibiting NT binding in both tissues. In both membrane preparations, NT binding was increased by Mg++ and decreased by Na+ and guanosine 5'-[gamma-thio]triphosphate, whereas SR 48692 binding was not significantly affected by these agents. SR 48692 inhibited NT-induced contraction and relaxation in guinea pig ileum and colon preparations, respectively, with Ki values between 4 and 5 nM. As in binding studies, SR 48527 was as potent, whereas SR 49711 was 100-fold less potent than SR 48692 in antagonizing NT responses in both the guinea pig ileum and colon. Altogether, our results show that NT receptors in the guinea pig ileum and colon, although functionally distinct, are coupled to G-proteins and display similar biochemical and pharmacological properties, in particular with regard to their sensitivity and stereoselectivity toward nonpeptide antagonists related to SR 48692. Because of their high potency to antagonize NT actions in intestinal preparations, SR 48692 and SR 48527 represent useful tools to study the physiological

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

    PubMed

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

    2014-06-30

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

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

    PubMed Central

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

    2014-01-01

    The guinea pig (Cavia porcellus) provides a useful animal model for studying the pathogenesis of many infectious diseases, and for preclinical evaluation of vaccines. However, guinea pig models are limited by the lack of immunological reagents required for characterization and quantification of antigen-specific T cell responses. To address this deficiency, an enzyme-linked immunospot (ELISPOT) assay for guinea pig interferon (IFN)-γ was developed to measure antigen/epitope-specific T cell responses to guinea pig cytomegalovirus (GPCMV) vaccines. Using splenocytes harvested from animals vaccinated with a modified vaccinia virus Ankara (MVA) vector encoding the GPCMV GP83 (homolog of human CMV pp65 [gpUL83]) protein, we were able to enumerate and map antigen-specific responses, both in vaccinated as well as GPCMV-infected animals, using a panel of GP83-specific peptides. Several potential immunodominant GP83-specific peptides were identified, including one epitope, LGIVHFFDN, that was noted in all guinea pigs that had a detectable CD8+ response to GP83. Development of a guinea pig IFN-γ ELISPOT should be useful in characterization of additional T cell-specific responses to GPCMV, as well as other pathogens. This information in turn can help focus future experimental evaluation of immunization strategies, both for GPCMV as well as for other vaccine-preventable illnesses studied in the guinea pig model. PMID:24856783

  1. Estrogen alters remodeling of the vaginal wall after surgical injury in guinea pigs.

    PubMed

    Balgobin, Sunil; Montoya, T Ignacio; Shi, Haolin; Acevedo, Jesus F; Keller, Patrick W; Riegel, Matthew; Wai, Clifford Y; Word, Ruth Ann

    2013-12-01

    Loss of pelvic organ support (i.e., pelvic organ prolapse) is common in menopausal women. Surgical reconstruction of pelvic organ prolapse is plagued with high failure rates. The objective of this study was to determine the effects of estrogen on biomechanical properties, lysyl oxidase (LOX), collagen content, and histomorphology of the vagina with or without surgical injury. Nulliparous ovariectomized guinea pigs were treated systemically with either 50 μg/kg/day estradiol (E2,) or vehicle. After 2 wk, vaginal surgery was performed, and animals were treated with either beta-aminopropionitrile (BAPN, an irreversible LOX inhibitor), or vehicle to determine the role of LOX in recovery of the vaginal wall from injury with or without E2. Estradiol resulted in (i) significant growth, increased smooth muscle, and increased thickness of the vagina, (ii) increased distensibility without compromise of maximal force at failure, and (iii) increased total and cross-linked collagen. In the absence of E2, BAPN resulted in decreased collagen and vaginal wall strength in the area of the injury. In contrast, in E2-treated animals, increased distensibility, maximal forces, and total collagen were maintained despite BAPN. Interestingly, LOX mRNA was induced dramatically (9.5-fold) in the injured vagina with or without E2 at 4 days. By 21 days, however, LOX levels declined to near baseline in E2-deprived animals. LOX mRNA levels remained strikingly elevated (12-fold) at 21 days in the estrogenized vagina. The results suggest that prolonged E2 induced increases in LOX, and collagen cross-links may act to sustain a matrix environment that optimizes long-term surgical wound healing in the vagina.

  2. Bradykinin stimulation of phosphoinositide hydrolysis in guinea-pig ileum longitudinal muscle.

    PubMed Central

    Ransom, R. W.; Goodman, C. B.; Young, G. S.

    1992-01-01

    1. Bradykinin (BK)-induced contraction of ileal smooth muscle is assumed to be due to phosphoinositide hydrolysis but this has never been reported. We have investigated whether BK receptors are linked to this transduction mechanism in guinea-pig ileum longitudinal muscle and determined whether these receptors are equivalent to those labelled in [3H]-BK binding assays. 2. In membranes prepared from longitudinal muscle, [3H]-BK bound to a single class of sites with high affinity. Characterization of the binding with BK analogues indicated that the radioligand selectivity labelled a B2 type receptor. 3. BK significantly elevated tissue levels of [3H]-inositol phosphates in longitudinal muscle slices preincubated with [3H]-myo-inositol. The agonists potencies of BK, Lys-BK, Met-Lys-BK, Tyr5-BK and Tyr8-BK were in agreement with their relative potencies in the binding assay. The B1 receptor agonist des-Arg9-BK, did not stimulate inositol phosphate production. The response to BK was blocked by known B2 receptor antagonists but not by the B1 antagonist des-Arg9, Leu8-BK. 4. BK-induced phosphoinositide hydrolysis was unaffected by exposure of muscle slices to either atropine or indomethacin. 5. The results indicate that the B2 receptors linked to phosphoinositide turnover in ileal longitudinal muscle exhibit properties similar to those involved in contractile responses. Also, the receptor mediating the phosphoinositide response is likely to be that labelled in the [3H]-BK binding studies. PMID:1324057

  3. Calcium responses induced by acetylcholine in submucosal arterioles of the guinea-pig small intestine

    PubMed Central

    Fukuta, Hiroyasu; Hashitani, Hikaru; Yamamoto, Yoshimichi; Suzuki, Hikaru

    1999-01-01

    Calcium responses induced by brief stimulation with acetylcholine (ACh) were assessed from the fluorescence changes in fura-2 loaded submucosal arterioles of the guinea-pig small intestine. Initially, 1–1.5 h after loading with fura-2 (fresh tissues), ACh increased [Ca2+]i in a concentration-dependent manner. This response diminished with time, and finally disappeared in 2–3 h (old tissues). Ba2+ elevated [Ca2+]i to a similar extent in both fresh and old tissues. ACh further increased the Ba2+-elevated [Ca2+]i in fresh tissues, but reduced it in old tissues. Responses were not affected by either indomethacin or nitroarginine. In fresh mesenteric arteries, mechanical removal of endothelial cells abolished the ACh-induced increase in [Ca2+]i, with no alteration of [Ca2+]i at rest and during elevation with Ba2+. In the presence of indomethacin and nitroarginine, high-K+ solution elevated [Ca2+]i in both fresh and old tissues. Subsequent addition of ACh further increased [Ca2+]i in fresh tissues without changing it in old tissues. Proadifen, an inhibitor of the enzyme cytochrome P450 mono-oxygenase, inhibited the ACh-induced changes in [Ca2+]i in both fresh and Ba2+-stimulated old tissues. It also inhibited the ACh-induced hyperpolarization. In fresh tissues, the ACh-induced Ca2+ response was not changed by apamin, charybdotoxin (CTX), 4-aminopyridine (4-AP) or glibenclamide. In old tissues in which [Ca2+]i had previously been elevated with Ba2+, the ACh-induced Ca2+ response was inhibited by CTX but not by apamin, 4-AP or glibenclamide. It is concluded that in submucosal arterioles, ACh elevates endothelial [Ca2+]i and reduces muscular [Ca2+]i, probably through the hyperpolarization of endothelial or smooth muscle membrane by activating CTX-sensitive K+ channels. PMID:10050015

  4. Toward an Integrative Computational Model of the Guinea Pig Cardiac Myocyte

    PubMed Central

    Gauthier, Laura Doyle; Greenstein, Joseph L.; Winslow, Raimond L.

    2012-01-01

    The local control theory of excitation-contraction (EC) coupling asserts that regulation of calcium (Ca2+) release occurs at the nanodomain level, where openings of single L-type Ca2+ channels (LCCs) trigger openings of small clusters of ryanodine receptors (RyRs) co-localized within the dyad. A consequence of local control is that the whole-cell Ca2+ transient is a smooth continuous function of influx of Ca2+ through LCCs. While this so-called graded release property has been known for some time, its functional importance to the integrated behavior of the cardiac ventricular myocyte has not been fully appreciated. We previously formulated a biophysically based model, in which LCCs and RyRs interact via a coarse-grained representation of the dyadic space. The model captures key features of local control using a low-dimensional system of ordinary differential equations. Voltage-dependent gain and graded Ca2+ release are emergent properties of this model by virtue of the fact that model formulation is closely based on the sub-cellular basis of local control. In this current work, we have incorporated this graded release model into a prior model of guinea pig ventricular myocyte electrophysiology, metabolism, and isometric force production. The resulting integrative model predicts the experimentally observed causal relationship between action potential (AP) shape and timing of Ca2+ and force transients, a relationship that is not explained by models lacking the graded release property. Model results suggest that even relatively subtle changes in AP morphology that may result, for example, from remodeling of membrane transporter expression in disease or spatial variation in cell properties, may have major impact on the temporal waveform of Ca2+ transients, thus influencing tissue level electromechanical function. PMID:22783206

  5. IP3 receptors regulate vascular smooth muscle contractility and hypertension

    PubMed Central

    Lin, Qingsong; Zhao, Guiling; Fang, Xi; Peng, Xiaohong; Tang, Huayuan; Wang, Hong; Jing, Ran; Liu, Jie; Ouyang, Kunfu

    2016-01-01

    Inositol 1, 4, 5-trisphosphate receptor–mediated (IP3R-mediated) calcium (Ca2+) release has been proposed to play an important role in regulating vascular smooth muscle cell (VSMC) contraction for decades. However, whether and how IP3R regulates blood pressure in vivo remains unclear. To address these questions, we have generated a smooth muscle–specific IP3R triple-knockout (smTKO) mouse model using a tamoxifen-inducible system. In this study, the role of IP3R-mediated Ca2+ release in adult VSMCs on aortic vascular contractility and blood pressure was assessed following tamoxifen induction. We demonstrated that deletion of IP3Rs significantly reduced aortic contractile responses to vasoconstrictors, including phenylephrine, U46619, serotonin, and endothelin 1. Deletion of IP3Rs also dramatically reduced the phosphorylation of MLC20 and MYPT1 induced by U46619. Furthermore, although the basal blood pressure of smTKO mice remained similar to that of wild-type controls, the increase in systolic blood pressure upon chronic infusion of angiotensin II was significantly attenuated in smTKO mice. Taken together, our results demonstrate an important role for IP3R-mediated Ca2+ release in VSMCs in regulating vascular contractility and hypertension. PMID:27777977

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2013-06-01

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

  8. [3H]-Mesulergine labels 5-HT7 sites in rat brain and guinea-pig ileum but not rat jejunum

    PubMed Central

    Hemedah, Maggie; Coupar, Ian M; Mitchelson, Fred J

    1999-01-01

    The primary aim of this investigation was to determine whether binding sites corresponding to the 5-HT7 receptor could be detected in smooth muscle of the rat jejunum. Binding studies in rat brain (whole brain minus cerebellum) and guinea-pig ileal longitudinal muscle were also undertaken in order to compare the binding characteristics of these tissues. Studies were performed using [3H]-mesulergine, as it has a high affinity for 5-HT7 receptors.In the rat brain and guinea-pig ileum, pKD values for [3H]-mesulergine of 8.0±0.04 and 7.9±0.11 (n=3) and Bmax values of 9.9±0.3 and 21.5±4.9 fmol mg−1 protein were obtained respectively, but no binding was detected in the rat jejunum. [3H]-mesulergine binding in the rat brain and guinea-pig ileum was displaced with the agonists 5-carboxamidotryptamine (5-CT)>5-hydroxytryptamine (5-HT)⩾5-methoxytryptamine (5-MeOT)>sumatriptan and the antagonists risperidone⩾LSD⩾metergoline>ritanserin>>pindolol.Despite the lack of [3H]-mesulergine binding in the rat jejunum, functional studies undertaken revealed a biphasic contractile response to 5-HT which was partly blocked by ondansetron (1 μM). The residual response was present in over 50% of tissues studied and was found to be inhibited by risperidone>LSD>metergoline>mesulergine=ritanserin>pindolol, but was unaffected by RS 102221 (3 μM), cinanserin (30 nM), yohimbine (0.1 μM) and GR 113808 (1 μM). In addition, the agonist order of potency was 5-CT>5-HT>5-MeOT>sumatriptan.In conclusion, binding studies performed with [3H]-mesulergine were able to detect 5-HT7 sites in rat brain and guinea-pig ileum, but not in rat jejunum, where a functional 5-HT7-like receptor was present. PMID:10051134

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

    PubMed

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

    2007-08-01

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

  10. Synthesis by guinea pig megakaryocytes of platelet glycoprotein receptors for fibrinogen and von Willebrand factor.

    PubMed

    Kupinski, J M; Miller, J L

    1986-08-01

    In the preceding paper, we described two monoclonal antibodies, PG-1 and PG-2, that selectively blocked the binding of von Willebrand factor (PG-1) or of fibrinogen (PG-2) to guinea pig platelets. In this study we examine the structures and site of synthesis of these receptors. NP-40 lysates of radiolabeled guinea pig platelets were immunoprecipitated with monoclonal antibodies PG-1 or PG-2, and the precipitates analyzed by SDS-PAGE. PG-1 recognized a single polypeptide with reduced Mr of 143,000 daltons, while PG-2 precipitated two chains with reduced Mr of 121,000 and 93,000 daltons. Periodate-[3H]borohydride labeling of platelets, in conjunction with two-dimensional SDS-PAGE, showed that all three of the polypeptides are glycoproteins and that the 143,000 and 121,000 dalton chains are linked by disulfide bond(s) to smaller, approximately 25,000 dalton polypeptides. Guinea pig megakaryocytes synthesized polypeptides immunoprecipitable by PG-1 and PG-2, with molecular weights similar to polypeptides found associated with platelet membranes. These studies demonstrate that guinea pig platelets have functional receptors for fibrinogen and von Willebrand factor that are structurally homologous to human platelet glycoproteins Ib, IIb and IIIa, and that these glycoproteins are synthesized by megakaryocytes.

  11. Experimental Chagas' disease in complement-deficient mice and guinea pigs.

    PubMed Central

    Dalmasso, A P; Jarvinen, J A

    1980-01-01

    The course of infection with trypomastigotes of Trypanosoma cruzi (House 510 strain) in mice and guinea pigs with genetic complement deficiencies was compared with that in normocomplementemic animals. Parasitemias in a mouse strain (B10.D2/old) genetically deficient in C5 and therefore unable to sustain lysis were similar to or lower than in a congenic normocomplementemic strain (B10.D2/new). The levels of C3 measured immunochemically were generally unaffected. There were no significant differences in mortality rates. These results indicate that, in mice, complement-mediated lysis does not play a significant role in the control of T. cruzi (House 510) infections. Studies were also performed in normocomplementemic guinea pigs and in guinea pigs genetically deficient in the fourth component of complement and thus unable to support functions mediated by the classical pathway of complement activation. No significant differences were noted between the two strains in the course of infection, persistence of subpatent infection, or rate of mortality, indicating that if the classical complement pathway plays a role in resistance to T. cruzi (House 510) in guinea pigs, this role must be a small one. PMID:6772558

  12. Olfactory experience modulates immature neuron development in postnatal and adult guinea pig piriform cortex.

    PubMed

    He, X; Zhang, X-M; Wu, J; Fu, J; Mou, L; Lu, D-H; Cai, Y; Luo, X-G; Pan, A; Yan, X-X

    2014-02-14

    Immature neurons expressing doublecortin (DCX+) are present around cortical layer II in various mammals including guinea pigs and humans, especially enriched in the paleocortex. However, little is known whether and how functional experience affects the development of this population of neurons. We attempted to explore a modulation by experience to layer II DCX+ cells in the primary olfactory cortex in postnatal and adult guinea pigs. Neonatal and 1-year-old guinea pigs were subjected to unilateral naris-occlusion, followed 1 and 2months later by morphometry of DCX+ cells in the piriform cortex. DCX+ somata and processes were reduced in the deprived relative to the non-deprived piriform cortex in both age groups at the two surviving time points. The number of DCX+ cells was decreased in the deprived side relative to internal control at 1 and 2months in the youths and at 2months in the adults post-occlusion. The mean somal area of DCX+ cells showed a trend of decrease in the deprived side relative to the internal control in the youths. In addition, DCX+ cells in the deprived side exhibited a lower frequency of colocalization with the neuron-specific nuclear antigen (NeuN) relative to counterparts. These results suggest that normal olfactory experience is required for the maintenance and development of DCX+ immature neurons in postnatal and adult guinea pig piriform cortex.

  13. 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.

  14. 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.

  15. 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.

  16. The role of cyclic nucleotides in guinea-pig bladder contractility

    PubMed Central

    Longhurst, Penelope A; Briscoe, Janice A K; Rosenberg, David J; Leggett, Robert E

    1997-01-01

    The effects of phosphodiesterase (PDE) inhibition and forskolin pretreatment on the contractile responses of guinea-pig urinary bladder strips to electrical field stimulation, carbachol, ATP and KCl were studied. Inhibition of cyclic AMP-specific PDE4 isozymes by rolipram significantly reduced the contractile response of bladder strips to field stimulation. Rolipram also suppressed the contractile response to low concentrations of carbachol, but potentiated the response to high concentrations. The contractile response to ATP was significantly reduced by rolipram treatment, but that to KCl was unaltered. Inhibition of cyclic GMP-specific PDE5 isozymes by zaprinast had no effects on the contractile response of bladder strips to field stimulation, ATP or KCl. Zaprinast suppressed the contractile responses to 1 μM carbachol and potentiated the response to high concentrations. Contractile responses to field stimulation and to carbachol after pretreatment with the adenylyl cyclase activator, forskolin, were qualitatively similar to those caused by rolipram treatment. β-Adrenoceptor blockade with propranolol partially reversed the inhibitory effects of rolipram on the response to field stimulation. Rolipram significantly reduced the contractile response of bladder strips from sensitized guinea-pigs to ovalbumin challenge, but zaprinast was ineffective. PDE inhibition had similar effects on the responsiveness of control and of sensitized guinea-pig bladder strips to field stimulation, carbachol, ATP and KCl. The data suggest that the contractile response of guinea-pig bladder strips can be modified by increases in cyclic AMP levels. PMID:9283701

  17. Human mast cell mediator cocktail excites neurons in human and guinea-pig enteric nervous system.

    PubMed

    Schemann, M; Michel, K; Ceregrzyn, M; Zeller, F; Seidl, S; Bischoff, S C

    2005-04-01

    Neuroimmune interactions are an integral part of gut physiology and involved in the pathogenesis of inflammatory and functional bowel disorders. Mast cells and their mediators are important conveyors in the communication from the innate enteric immune system to the enteric nervous system (ENS). However, it is not known whether a mediator cocktail released from activated human mast cells affects neural activity in the ENS. We used the Multi-Site Optical Recording Technique to image single cell activity in guinea-pig and human ENS after application of a mast cell mediator cocktail (MCMC) that was released from isolated human intestinal mucosa mast cells stimulated by IgE-receptor cross-linking. Local application of MCMC onto individual ganglia evoked an excitatory response consisting of action potential discharge. This excitatory response occurred in 31%, 38% or 11% neurons of guinea-pig submucous plexus, human submucous plexus, or guinea-pig myenteric plexus, respectively. Compound action potentials from nerve fibres or fast excitatory synaptic inputs were not affected by MCMC. This study demonstrates immunoneural signalling in the human gut and revealed for the first time that an MCMC released from stimulated human intestinal mast cells induces excitatory actions in the human and guinea-pig ENS.

  18. [Gallbladder contractility in early stages of lithogenesis in the lithogenic fed guinea pig].

    PubMed

    Lange, K; Gottschalk, M

    1995-07-01

    The main aim of our study was the investigation of gallbladder motility prior to gallstone formation in vivo in guinea pigs fed a lithogenic diet. In a first experiment guinea pigs were fed a lithogenic diet for 5, 15, 30 and 45 days. First gallstones (pigment calculi) appeared after 30 days diet application. The in vitro contractility after lithogenic diet remained unchanged. In a second experimental part the in vivo gallbladder contractility was measured in two experimental animal groups (control group and 21 days lithogenic fed guinea pigs). The isovolumetric pressure rise inside the gallbladder following the intravenous injection of 10(-9) mol/kg body weight ceruletid was the essential contractility parameter (intraluminal basal pressure 5 mm hg). Due to lithogenic feeding of 21 days--that means prior to gallstone formation--the isovolumetric pressure rise was significantly elevated (p < 0.01). Moreover we observed passive distensibility changes of gallbladder muscle due to muscular hyperplasia. The main result of this investigation is the fact that gallbladder muscle in guinea pigs fed a lithogenic diet response to ceruletid application with hypercontractility prior to provable pigment gallstone formation. However gallbladder hypomotility--believed to be a causal factor in cholelithogenesis--was not observed in our experimental conditions.

  19. Cutaneous Uptake of 14C-HD Vapor by the Hairless Guinea Pig.

    DTIC Science & Technology

    1996-10-01

    The hairless guinea pig ( HGP ) is used by our laboratory to model the human cutaneous response to sulfur mustard (HD) exposure. We have determined the...other aspects of the experimental model. These results contribute to a better understanding of the cutaneous response to HD in the HGP model.

  20. THE IMPACT OF ULTRAVIOLET IRRADIATION ON MORPHO-FUNCTIONAL STATE OF SKIN IN GUINEA PIGS.

    PubMed

    Myronchenko, S; Naumova, O; Zvyagintseva, T

    2016-11-01

    The purpose of this study was to assess the impact of ultraviolet irradiation (UV) on morphological and functional condition of the skin in guinea pigs. The study involved 30 albino guinea pigs weighing 400-500 g subjected to local exposure to UV irradiation. Control group consisted of intact guinea pigs. Histological studies of the skin were carried out at different stages of the trial (2 hours, 4 hours, 3 days, 8 days following the exposure). Microscopic examination showed morphological signs of acute inflammation in the skin of animals within the first three days following the exposure to UV irradiation. Within 2 hours following the exposure to UV irradiation these changes were minimal with signs of mild exudative changes. In 4 hours after the exposure histological changes increased. The specimens were also found to contain altered apoptotic keratinocytes (sunburn cells). Histopathological changes persisted and reached maximum severity by the 3rd day. Within post-erythema period (the 8th day) proliferative, hyperplastic, degenerative and dystrophic changes in the skin persisted. The prolonged nature of the changes in the skin is suggestive of the development of chronic inflammation in the skin of guinea pigs subjected to local exposure to UV irradiation.

  1. 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...

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

    PubMed

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

    2017-03-01

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

  3. Hypervitaminosis D and Metastatic Calcification in a Colony of Inbred Strain 13 Guinea Pigs, Cavia porcellus.

    PubMed

    Holcombe, H; Parry, N M; Rick, M; Brown, D E; Albers, T M; Refsal, K R; Morris, J; Kelly, R; Marko, S T

    2015-07-01

    A commercial diet fed to a colony of inbred strain 13 guinea pigs for approximately 6 weeks was subsequently recalled for excessive levels of vitamin D. Twenty-one of 62 animals exhibited clinical signs, including anorexia, lethargy, and poor body condition. Nine affected and 4 clinically normal animals were euthanized for further evaluation, including serum chemistry, urinalysis, and gross and/or histopathology. Macroscopic findings included white discoloration in multiple organs in 8 animals, and microscopic evaluation confirmed multiorgan mineralization in tissues from 7 animals. Serum 25-hydroxyvitamin D levels were elevated in 10 animals. Serum inorganic phosphorus and alkaline phosphatase levels were increased in all exposed animals; however, total calcium and ionized calcium levels were not significantly higher in exposed animals than in control strain 13 guinea pigs from a different institution. The data support a diagnosis of hypervitaminosis D with metastatic calcification. Following the diet recall, the remaining guinea pigs increased their food intake and regained body condition. Diagnostic testing of 8 animals euthanized approximately 3 months after returning to a normal diet demonstrated that serum parathyroid hormone remained significantly lower, and ionized calcium and ionized magnesium were significantly higher, in recovered animals compared to controls and exposed animals. These results indicate that diagnostic tests other than serum calcium are necessary for a diagnosis of hypervitaminosis D in guinea pigs.

  4. 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 ...

  5. Induction of renal and hepatic mixed function oxidases in the hamster and guinea pig.

    PubMed

    Smith, J H; Rush, G F; Hook, J B

    1986-02-01

    A marked species difference exists in the induction of renal and hepatic mixed function oxidase (MFO) activity between rats and rabbits. However, little is known about MFO induction in these organs from other laboratory animals. Male Golden Syrian hamsters and male Hartley guinea pigs were administered phenobarbital (PB) or beta-napthoflavone (BNF) at 70 and 40 mg/kg, respectively, as daily i.p. injections for 4 days. Polybrominated biphenyl (PBB) (Firemaster BP-6) was given as a single i.p. injection (50 mg/kg). Hamster hepatic microsomal ethoxyresorufin-O-deethylase (EROD) and benzphetamine-N-demethylase (BPND) were selectively induced by BNF and PB, respectively. PBB administration induced both hamster hepatic EROD and BPND. In contrast, hepatic microsomal MFO activity from the guinea pig was inducible by PB, PBB and BNF. Renal microsomal MFO activity in both species was inducible by BNF and PBB as arylhydrocarbon hydroxylase and EROD were induced approximately 10-fold. On the other hand, hamster BPND was induced by PB whereas guinea pig MFO activity was unaffected. Total renal cytochrome P-450 content was not affected by any of these inducers in either species. These data demonstrate selective patterns of induction in both hamster and guinea pig liver and kidney suggesting the involvement of multiple forms of cytochrome P-450.

  6. 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.

  7. Effect of estradiol on chlamydial genital infection of female guinea pigs.

    PubMed

    Rank, R G; White, H J; Hough, A J; Pasley, J N; Barron, A L

    1982-11-01

    Female guinea pigs were treated daily with 1 mg of beta-estradiol-3-benzoate intramuscularly beginning 14 days before intravaginal inoculation with the chlamydial agent of guinea pig inclusion conjunctivitis and continuing during the course of the infection. Treatment with estradiol was found to markedly influence the course of genital infection with the chlamydial agent of guinea pig inclusion conjunctivitis, producing infections of greater intensity and longer duration than those in control animals. Moreover, pathogenesis was altered in that ascending infection was observed, resulting in endometritis, cystic salpingitis, and cystitis. Infection in the controls was limited to the cervix and vagina. Estradiol treatment increased the apparent number of infected cells in the cervix and vagina as detected by histopathology and immunofluorescent staining. Humoral and cell-mediated immune responses to the chlamydial agent of guinea pig inclusion conjunctivitis were comparable in estradiol-treated and untreated animals. These data indicate that hormonal manipulation may have profound effects on the course of chlamydial genital infections.

  8. THE PREPARATION OF SECTIONS OF GUINEA PIG LIVER FOR ELECTRON MICROSCOPY

    PubMed Central

    Claude, Albert; Fullam, Ernest F.

    1946-01-01

    1. A method is described whereby sections of guinea pig liver cells can be prepared for electron microscopy after fixation. 2. The high resolving powerof the electron microscope reveals the presence of two components, one particulate, the other apparently of fibrous texture, in the ground substance of the cells. PMID:19871546

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

    PubMed

    Meza, Graciela; Aguilar-Maldonado, Beatriz

    2007-01-01

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

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

    PubMed

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

    2013-01-01

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

  11. Possible formation of nitrosamine in guinea pigs following exposure to nitrogen dioxide and dimethylamine

    SciTech Connect

    Chaudhari, A.; Dutta, S.

    1981-05-01

    The possibility of formation of nitrosamine was investigated in animals exposed to a combination of dimethylamine (DMA) and NO/sub 2/. First, the distribution and covalent binding of DMA and dimethylnitrosamine (DMN) in rats and guinea pigs were determined. The apparent volume of distribution and biological half-life for (/sup 14/C)-DMA or (/sup 14/C) DMN did not reveal any species difference. In general, there were no marked differences in accumulation of radioactivity in tissues of guinea pigs and rats 4 h after the administration of DMA, while the guinea pig tissues showed higher accumulation after DMN administration. Nucleic acid fractions prepared from liver and lungs of both species following administration of DMN or DMA in vivo showed much higher covalent binding with DMN than with DMA. Since guinea pig liver showed a higher degree of covalent binding than rat liver, this species was used to investigate the possible increase in covalent binding in the presence of NO/sub 2/ and DMA as a reflection of DMN formation. There was no evidence of enhancement of covalent binding when animals pretreated with (/sup 14/C)-DMA were exposed for vaious lengths of time to different concentrations of NO/sub 2/.

  12. The Interference of Stress on Physostigmine Pretreatment Against Soman Intoxication in Guinea Pigs

    DTIC Science & Technology

    2002-01-01

    1 THE INTERFERENCE OF STRESS ON PHYSOSTIGMINE PRETREATMENT AGAINST SOMAN INTOXICATION IN GUINEA PIGS Ingrid H.C.H.M. Philippens , Marloes J.A...1985) Fund. Appl. Toxicol. 5: S225-S231. 6 Harris, L.W. et al. (1984) Drug Chem. Toxicol. 7: 605-624. 7 Solana , R.P. et al. (1990) Fundam. Appl

  13. Pulmonary effects of the cocaine pyrolysis product, methylecgonidine, in guinea pigs.

    PubMed

    Chen, L C; Graefe, J F; Shojaie, J; Willetts, J; Wood, R W

    1995-01-01

    The pulmonary effects of the cocaine pyrolysis product, methylecgonidine (MEG; anhydroecgonine methyl ester), were assessed in guinea pigs. Specific airway conductance (SGaw), which decreases during bronchoconstriction, was measured in guinea pigs exposed to atmospheres containing a condensation aerosol of MEG free base (13 +/- 1 mg/liter of air), nebulized MEG fumarate (3 and 12% in phosphate buffered saline) or nebulized acetylcholine chloride (0.2 and 0.4% in phosphate buffered saline). A decrease in SGaw to 24.0 +/- 4.2% (mean +/- 2 S.E.M.) of baseline levels was observed in guinea pigs breathing MEG free base. A decrease to 28.4 +/- 4.5% of baseline was observed following administration of 0.4% acetylcholine. No change in SGaw was measured in guinea pigs exposed to 3% MEG fumarate but SGaw was reduced to 69.3 +/- 5.3% of baseline after exposure to 12% MEG fumarate. MEG free base poses an alkaline challenge to the lung, 3% MEG fumarate is neutral (pH approximately 7.4) and 12% MEG fumarate is acidic (pH approximately 4.3); thus, MEG free-base and 12% MEG fumarate might provoke a reflex bronchoconstriction due to direct pulmonary irritant effects. These results suggest that MEG free base produced during crack pyrolysis may play a role in bronchoconstriction observed in crack smokers.

  14. 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

  15. Vascular smooth muscle cell culture in microfluidic devices

    PubMed Central

    Wei, Y. C.; Chen, F.; Zhang, T.; Chen, D. Y.; Jia, X.; Wang, J. B.; Guo, W.; Chen, J.

    2014-01-01

    This paper presents a microfluidic device enabling culture of vascular smooth muscle cells (VSMCs) where extracellular matrix coating, VSMC seeding, culture, and immunostaining are demonstrated in a tubing-free manner. By optimizing droplet volume differences between inlets and outlets of micro channels, VSMCs were evenly seeded into microfluidic devices. Furthermore, the effects of extracellular matrix (e.g., collagen, poly-l-Lysine (PLL), and fibronectin) on VSMC proliferation and phenotype expression were explored. As a platform technology, this microfluidic device may function as a new VSMC culture model enabling VSMC studies. PMID:25379109

  16. 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

  17. 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

  18. 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.

  19. Nifurtimox-induced alterations in the cell-mediated immune response to PPD tin guinea-pigs.

    PubMed Central

    Lelchuk, R; Cardoni, R L; Levis, S

    1977-01-01

    Positive skin reactions to PPD in guinea-pigs immunized with Freund's complete adjuvant (FCA) were reversed after treatment with 10 mg/kg/day nifurtimox for 12 days. The in vitro migration of peripheral blood leucocytes from FCA-immunized guinea-pigs was inhibited with PPD, but it returned to normal values after nifurtimox treatment. Furthermore, the cell-free supernatant from PPD-stimulated lymphocytes from FCA-immunized nifurtimox-treated guinea-pigs did not inhibit the migration of normal cells. Thus the administration of nifurtimox impaired the specific cell-mediated immune response to PPD both in vivo and in vitro. PMID:414870

  20. Comparative metabolism of codeine in man, rat, dog, guinea-pig and rabbit: identification of four new metabolites.

    PubMed

    Cone, E J; Darwin, W D; Gorodetzky, C W

    1979-05-01

    The metabolism and excretion of codeine and its metabolites in untreated urine of man, rat, dog, guinea-pig and rabbit have been examined. Metabolites were identified by gas chromatography mass spectrometry operated in the chemical ionization mode (methane). Concentrations of codeine and metabolites were measured by selected ion monitoring. Both codeine and norcodeine were detected in the urine of all species but a new metabolite, hydrocodone, was found only in the urine from man, guinea-pig and dog. Additional metabolites (presumably resulting from the metabolism of hydrocodone) were also detected in man and guinea-pig. Overall recoveries of drug and metabolites from untreated urine were low for all species.

  1. 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

  2. Involvement of inflammatory mediators in the airway responses to trimellitic anhydride in sensitized guinea-pigs.

    PubMed Central

    Hayes, J. P.; Lotvall, J. O.; Barnes, P. J.; Newman Taylor, A. J.; Chung, K. F.

    1992-01-01

    1. We examined the effect of various pharmacological agents on the acute bronchoconstrictor response and airway microvascular leakage in a model of guinea-pig sensitization to trimellitic anhydride (TMA) a cause of low molecular weight occupational asthma in man. 2. Guinea-pigs were given intradermal injections of 0.1 ml of 0.3% TMA in corn oil; 21-28 days later, anaesthetized guinea-pigs were challenged with TMA conjugated to guinea-pig albumin by tracheal instillation. Changes in lung resistance were measured and airway microvascular leakage was quantified by measuring the extravasation of Evans blue dye into the airway tissue. 3. Sensitized guinea-pig (n = 9 in each group) were pretreated with chlorpheniramine (2.5 mg kg-1, i.v.), WEB 2086 (10 micrograms kg-1, i.v.), BW 4AC (50 mg kg-1, i.p.), nedocromil sodium (2% aerosol for 60 s) or vehicle alone. 4. Pretreatment with chlorpheniramine inhibited both the acute bronchoconstrictor response and the increase in airway microvascular leakage. WEB 2086 and nedocromil sodium partially inhibited the bronchoconstrictor response but had no significant effect on airway microvascular leakage. BW 4AC caused a non-significant reduction of the bronchoconstrictor response and airway microvascular leakage. 5. These results indicate that both the bronchoconstrictor response and the airway microvascular response in this model of sensitization is mediated to a large extent by histamine. PAF but not 5-lipoxygenase products also partially mediates the bronchoconstrictor response but not the airway microvascular leakage. Nedocromil sodium partially inhibits the bronchoconstrictor response only. PMID:1382788

  3. 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.

  4. 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.

  5. Developmental expression of Toll-like receptors in the guinea pig lung

    PubMed Central

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

    2017-01-01

    The guinea pig is a useful model for investigating infectious and non-infectious lung diseases due to the sensitivity of its respiratory system and susceptibility to infectious agents. Toll-like receptors (TLRs) are important components of the innate immune response and are critical for lung immune function. In the present study, the differentiation of epithelial cells in the guinea pig lung was examined during gestation by studying anatomic morphology and the major epithelial cell types using cell type-specific markers. The developmental expression of all 9 TLRs and the TLR signaling adaptors myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor associated factor 6 (TRAF-6) were investigated by reverse transcription-quantitative polymerase chain reaction and western blotting analysis. The formation of lung lobes in guinea pigs was observed at 45 days of gestation (dGA), along with the expression of the basal cell marker keratin 14 and the alveolar type II cell marker pro-surfactant protein. However, the cube cell marker secretoglobin family1A member 1 and ciliated cell marker b-tubulin IV were only detected in the lungs from 52 dGA onward. The expression levels of all TLRs, MyD88 and TRAF-6 were determined in lung tissues harvested from embryos, newborn, postnatal and adult animals. The expression levels of all TLR signaling components displayed similar dynamic expression patterns with gestation age and postnatal maturation time, except for TLR-4 and TLR-7. mRNA expression levels of TLR components were significantly increased in the lungs at 45 and 52 dGA, compared with later developmental stages. These results suggest that TLR expression in the guinea pig lung is developmentally regulated, enhancing the understanding of lung biology in guinea pig models. PMID:28098883

  6. Structural and kinetic characterization of guinea pig L-asparaginase type III.

    PubMed

    Schalk, Amanda M; Lavie, Arnon

    2014-04-15

    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.

  7. Hexamethonium-induced augmentation of the electrical twitch response in the guinea-pig ileum longitudinal muscle-myenteric plexus strip.

    PubMed

    Donnerer, Josef; Liebmann, Ingrid; Holzer-Petsche, Ulrike

    2014-08-08

    Longitudinal muscle-myenteric plexus strips of the guinea-pig ileum were used to investigate the nature of the hexamethonium-induced augmentation of the twitch response. All preparations were set up in Tyrode solution and intermittent longitudinal twitch contractions were evoked by single pulse electrical field stimulation. Hexamethonium, a blocker of nicotinic ganglionic transmission, at 300 μmol/l and 1 mmol/l augmented the twitch contractions by 21% and 35%, respectively. First we tested for a possible nicotinic drive onto an inhibitory neuronal component to the longitudinal smooth muscle cells. However, guanethidine (5 μmol/l), naloxone (1 μmol/l), or l-NAME (300 μmol/l) were without effect on the hexamethonium-induced augmentation. The P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS), 25-100 μmol/l, without altering the control twitch responses, dose-dependently reduced the hexamethonium-induced augmentation; at 100 μmol/l a statistically significantly inhibition was observed. Based on these functional experiments we found no evidence that blocking nicotinic transmission removed a tonic adrenergic, opioidergic or nitrergic inhibitory input to the longitudinal muscle. However, we provide evidence for a hexamethonium-induced augmentation of the P2 purinergic input to cholinergic motoneurons of the guinea-pig ileum longitudinal muscle. The P2-nicotinic receptor interaction presents a novel modulatory mechanism to cholinergic myenteric motor neurons.

  8. Effects of the benzodiazepine receptor agonist midazolam and antagonist flumazenil on 5-hydroxytryptamine release from guinea-pig intestine in vitro. Indirect support for a "natural" benzodiazepine-like substance in the intestine.

    PubMed

    Racké, K; Schwörer, H; Kilbinger, H

    1990-01-01

    Isolated segments of the guinea-pig small intestine and the guinea-pig stomach were vascularly perfused and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid into the portal venous effluent determined by high pressure liquid chromatography with electrochemical detection. Test substances were applied intraarterially. The benzodiazepine receptor agonist, midazolam, concentration-dependently increased (by 58%, at 1 nmol/l) and decreased (by 32%, at 100 nmol/l) the release of 5-HT from small intestine preparations. Both effects were blocked by the benzodiazepine receptor antagonist flumazenil (10 nmol/l) The stimulatory effect of midazolam was also abolished in the presence of tetrodotoxin (1 mumol/l) or scopolamine (100 nmol/l). In the absence of tetrodotoxin, flumazenil (10 nmol/l) alone decreased the release of 5-HT from the small intestine by 41%, but it increased the release of 5-HT by 50% in the presence of tetrodotoxin. Both effects of flumazenil were abolished in the presence of bicuculline (50 mumol/l). In the absence of tetrodotoxin, flumazenil (10 nmol/l) decreased also the release of 5-HT and its metabolite from the perfused stomach by about 40%, whereas midazolam (1 nmol/l) caused an increase by about 60%. In conclusion, benzodiazepine receptors modulate the previously described intrinsic GABAergic regulation of 5-HT release from enterochromaffin cells in the guinea-pig intestine. It is suggested that an endogenous benzodiazepine-like substance of non-neuronal origin is present in the small intestine and stomach of the guinea-pig.

  9. Biophysical Induction of Vascular Smooth Muscle Cell Podosomes

    PubMed Central

    Kim, Na Young; Kohn, Julie C.; Huynh, John; Carey, Shawn P.; Mason, Brooke N.; Vouyouka, Ageliki G.; Reinhart-King, Cynthia A.

    2015-01-01

    Vascular smooth muscle cell (VSMC) migration and matrix degradation occurs with intimal hyperplasia associated with atherosclerosis, vascular injury, and restenosis. One proposed mechanism by which VSMCs degrade matrix is through the use of podosomes, transient actin-based structures that are thought to play a role in extracellular matrix degradation by creating localized sites of matrix metalloproteinase (MMP) secretion. To date, podosomes in VSMCs have largely been studied by stimulating cells with phorbol esters, such as phorbol 12,13-dibutyrate (PDBu), however little is known about the physiological cues that drive podosome formation. We present the first evidence that physiological, physical stimuli mimicking cues present within the microenvironment of diseased arteries can induce podosome formation in VSMCs. Both microtopographical cues and imposed pressure mimicking stage II hypertension induce podosome formation in A7R5 rat aortic smooth muscle cells. Moreover, wounding using a scratch assay induces podosomes at the leading edge of VSMCs. Notably the effect of each of these biophysical stimuli on podosome stimulation can be inhibited using a Src inhibitor. Together, these data indicate that physical cues can induce podosome formation in VSMCs. PMID:25785437

  10. The daily pattern of heart rate, body temperature, locomotor activity, and autonomic nervous activity in congenitally bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs.

    PubMed

    Akita, Megumi; Kuwahara, Masayoshi; Nishibata, Ryoji; Mikami, Hiroki; Tsubone, Hirokazu

    2004-04-01

    We studied the characteristics of the rhythmicity of heart rate (HR), body temperature (BT), locomotor activity (LA) and autonomic nervous activity in bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs. For this purpose, HR, BT, LA, and electrocardiogram (ECG) were recorded from conscious and unrestrained guinea pigs using a telemetry system. Autonomic nervous activity was analyzed by power spectral analysis of heart rate variability. Nocturnal patterns, in which the values in the dark phase (20:00-06:00) were higher than those in the light phase (06:00-20:00), were observed in HR, BT and LA in both strains of guinea pigs. The autonomic nervous activity in BHS guinea pigs showed a daily pattern, although BHR guinea pigs did not show such a rhythmicity. The high frequency (HF) power in BHS guinea pigs was higher than that in BHR guinea pigs throughout the day. Moreover, the low frequency/high frequency (LF/HF) ratio in BHS guinea pigs was lower than that in BHR guinea pigs throughout the day. These results suggest that parasympathetic nervous activity may be predominant in BHS guinea pigs.

  11. [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.

  12. 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

  13. The relationship between dose-dependent antitussive and bronchodilatory effects of Opilia celtidifolia polysaccharide and nitric oxide in guinea pigs.

    PubMed

    Sutovská, M; Franová, S; Sadlonová, V; Grønhaug, T E; Diallo, D; Paulsen, B S; Capek, P

    2010-11-01

    A crude polysaccharide composed of uronic acids (32%), arabinose (26%), glucose (15%), galactose (11%), rhamnose (7%), mannose (5%), xylose (4%) and small amount of fucose residues has been isolated from the leaves of Opilia celtidifolia by boiled water extraction. Chemical analyses of Opilia polysaccharide revealed the prevalence of a pectin material with high arabinose and galacturonic acid contents. Opilia polysaccharide showed significant biological effects on chemically induced cough reflex and reactivity of airways smooth muscle in vitro and in vivo conditions in guinea pigs test system. Tests confirmed the dose-dependent cough-suppressive effect of Opilia polysaccharide comparable with activity of centrally acting codeine. Further, the bronchodilatory tests resulted in significant decrease in the values of specific airway resistance, which is very sensitive predictor of airway smooth muscle reactivity in vivo conditions regardless of bronchoconstricting mechanism. The results of in vitro experiments confirmed not only the bronchodilatory effect Opilia polysaccharide but revealed that its bronchodilatory mechanism is partially accompanied with enhanced NO production.

  14. Pharmacological reactivity of isolated guinea pig ileum to ethanol leaf extracts of Amaranthus caudatus and Solanum melongena.

    PubMed

    Saba, A B; Oridupa, O A

    2012-06-07

    The pharmacological reactivity of guinea pig ileum to ethanol leaf extract of Amaranthus caudatus and Solanum melongena were determined in vitro. Parameters evaluated include the threshold value and the concentration ratio (CR). The potency of the plant extracts as expressed by EC50, the Emax (maximum response) and its corresponding concentration were determined from the concentration response curve in the absence or presence of 2X10-7 M atropine or 2X10-7 M mepyramine. The study showed that the extract of Amaranthus caudatus or Solanum melongena produced a dose-dependent contraction of the smooth muscle of the guinea pig ileum with threshold values at 80 or 100mg/ml respectively. 2X10-7 M atropine or 2X10-7 M mepyramine individually caused a right shift on the cumulative concentration-response curve for each plant extract. The potencies of the plant extracts were significantly decreased, and the concentration producing Emax was significantly increased in the presence of the antagonists. The ileal contraction produced by A. caudatus was more sensitive to mepyramine antagonism. The EC50 (373.80±51.56mg/ml) and the concentration producing Emax (855.00±75.00mg/ml) for A. caudatus extract increased significantly to 849.00±29.16 mg/ml and 875.00±25 respectively in the presence of atropine, indicating that the extract interacted with muscarinic receptors. The mean EC50 and the concentration eliciting the Emax for S. melongena extract increased significantly from 288.91±32.46mg/ml and 600.00±22.00mg/ml to 385.21±19.20mg/ml and 800±0.00 mg/ml respectively in the presence of mepyramine thus indicating stimulation of the histaminergic H1 receptors of the gastrointestinal tract. Taken together, this study demonstrated that A. caudatus predominantly stimulates muscarinic receptors to produce contraction of the gastrointestinal smooth muscle, while S. melongena predominantly stimulates histaminergic H1 receptors.

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

    PubMed Central

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

    2017-01-01

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

  16. Monovalent Virus-Like Particle Vaccine Protects Guinea Pigs and Nonhuman Primates Against Infection with Multiple Marburg Viruses

    DTIC Science & Technology

    2008-05-01

    complete protection in guinea pigs against viremia, viral replication and pathological changes in tissues, and lethal disease following challenge...genes [6]. A recombinant vesicular stoma- titis virus vaccine encoding MARV GP protects NHPs against multiple isolates of MARV [7,8]. A replication ...viral replication and pathological changes in tissues, and lethal disease following challenge with MARV-Musoke, -Ravn, or Ci67. Guinea pigs vaccinated

  17. Development of a Novel Oligonucleotide Array for Genomic Screening of Chemical Warfare Agent Exposure in Guinea Pigs and Swine

    DTIC Science & Technology

    2004-04-01

    respectively. To address this gap in research tools, we have developed an oligonucleotide microarray that contains representative genes from guinea pig...To address this gap in research tools, we have developed an oligonucleotide microarray that contains representative genes from guinea pig...toxicogenomics. Toxicogenomics is focused on identifying changes in gene expression in response to a toxic chemical and then using that information to

  18. 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.

  19. Coagulation and fibrinolysis in capybara (Hydrochaeris hydrochaeris), a close relative of the guinea-pig (Cavia porcellus).

    PubMed

    Leitão, D P; Polizello, A C; Rothschild, Z

    2000-01-01

    Fibrinolytic and coagulation properties of capybara (Hydrochaeris hydrochaeris, LINNAEUS, 1766) plasma were analysed and the results compared to the guinea-pig (Cavia porcellus), a close relative. Capybara fibrinogen was isolated and fibrinolysis of its plasma was carried out in a homologous system and with bovine fibrin. Undiluted plasma did not have fibrinolytic activity on fibrin plates; euglobulins gave a dose-related response. Zymography of capybara and guinea-pig plasma gave the same patterns of activity as human or bovine plasma. Human urokinase (UK) and tissue plasminogen activator (t-PA) produced lysis in capybara fibrin plates. Streptokinase (SK) (500 IU/ml) did not activate capybara or guinea-pig plasma. In this system, human plasma was extensively activated. Coagulation tests for both species of rodent were prolonged. The capybara showed values for prothrombin time (PT) shorter than activated thromboplastin time (APTT). The guinea-pig, as already shown, had longer PT values. Factors X and VII were very low for capybara and guinea-pig when tested using reference curves and diagnostic kits for human plasma. It is suggested that the capybara could be a valuable laboratory animal considering its size and closeness to the guinea-pig, and this could allow for the provision of materials from one single animal when convenient or necessary.

  20. Influence of lipid profile and fatty acid composition on the oxidation behavior of rat and guinea pig low density lipoprotein.

    PubMed

    Vázquez, M; Merlos, M; Adzet, T; Laguna, J C

    1998-02-01

    Low density lipoprotein (LDL) oxidation is one of the first steps proposed for the development of atherosclerosis. Since lipid profile and fatty acid composition may affect this process, we studied the influence of these factors on the oxidation behavior of rat and guinea pig LDL. Marked compositional differences were observed. Thus, the main lipid carried by rat LDL was triglyceride (TG) (35.8 +/- 5.8%, w/w) whereas total cholesterol (TC) represented 23.8 +/- 3.0%. In contrast, guinea pig LDL contained 13.2 +/- 2% of TG and 44.8 +/- 4.5% of TC. Rat LDL contained higher 20:4(n-6) molar percentages than guinea pig LDL. Thiobarbituric acid reactive substances (TBARS) production (255 +/- 26 and 137 +/- 13 nmol malondialdehyde/mg prot. for rat and guinea pig LDL, respectively) and the maximum rate of conjugated dienes (CD) formation (485 +/- 93 and 77 +/- 11 nmol CD/min/mg protein for rat and guinea pig LDL, respectively) showed that rat LDL are less resistant to oxidation in vitro than guinea pig LDL. The higher oxidation rate of rat LDL seems to be related to its lipid profile, mainly to the high proportion of TG, and to the high content of 20:4(n-6), which is one of the fatty acids most prone to oxidation.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Schultheis, Katherine; Schaefer, Hubert; Yung, Bryan S; Oh, Janet; Muthumani, Karuppiah; Humeau, Laurent; Broderick, Kate E; Smith, Trevor R F

    2017-01-03

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

  3. Retinal and choroidal expression of BMP-2 in lens-induced myopia and recovery from myopia in guinea pigs.

    PubMed

    Li, Honghui; Wu, Juan; Cui, Dongmei; Zeng, Junwen

    2016-03-01

    The present study investigated the retinal and choroidal expression of bone morphogenetic protein-2 (BMP-2) in myopia and in myopia recovery in a guinea pig model. For this investigation, two groups of guinea pigs, lens‑induced myopia and recovery from myopia, were used, and defocused myopia was induced the guinea pigs wearing ‑4.00 D lenses on the right eyes for 3 weeks, with the left eyes serving as the contralateral. In the following week, the lenses of the guinea pigs in the recovery group were removed, and the refractive power and axial length were measured. The expression of BMP‑2 in the eyeballs was observed using immunohistochemistry and analyzed using Western blot analysis. After 3 weeks, the eyes acquired relative myopia and longer axial lengths in the two groups of guinea pigs. After 1 week without lenses in the recovery group, the myopia and axial lengths regressed. Immunofluorescence staining showed that BMP‑2 was expressed in the posterior retina, RPE, choroid and sclera. The expression of BMP‑2 decreased in the myopic retina of the guinea pigs. Following the regression of myopia in the recovery group, no difference in the expression of BMP‑2 was observed between the recovered treated eyes and the contralateral eyes. The choroidal expression level of BMP‑2 in the treated eyes showed no significant changes in either group. Therefore, BMP‑2 may be involved in the development of myopia, however, it does not have a primary role in the retinal and choroidal signals regulating scleral remodeling.

  4. Increased severity of tuberculosis in Guinea pigs with type 2 diabetes: a model of diabetes-tuberculosis comorbidity.

    PubMed

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

    2014-04-01

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

  5. 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.

  6. Vascular smooth muscle cell response on thin films of collagen.

    PubMed

    Elliott, John T; Woodward, John T; Langenbach, Kurt J; Tona, Alex; Jones, Peter L; Plant, Anne L

    2005-10-01

    Vascular smooth muscle cells (vSMC) cultured on gels of fibrillar type I collagen or denatured collagen (gelatin) comprise a model system that has been widely used for studying the role of the extracellular matrix in vascular diseases such as hypertension, restenosis and athrosclerosis. Despite the wide use of this model system, there are several disadvantages to using collagen gels for cellular studies. These include poor optical characteristics for microscopy, difficulty in verifying that the properties of the preparations are identical from experiment to experiment, heterogeneity within the gels, and difficulty in handling the gels because they are fragile. Previously, we developed an alternative collagen matrix by forming thin films of native fibrillar collagen or denatured collagen on self-assembled monolayers of alkanethiols [Elliott, J.T., Tona, A., Woodward, J., Jones,P., Plant, A., 2003a. Thin films of collagen affect smooth muscle cell morphology. Langmuir 19, 1506-1514.]. These substrates are robust and can be characterized by surface analytical techniques that allow both verification of the reproducibility of the preparation and high-resolution analysis of collagen structure. In addition, they have excellent optical properties that allow more details of the cell-matrix interactions to be observed by microscopy. In this study, we performed a side-by-side structural and functional comparison of collagen gels with thin films of collagen. Our results indicate that vSMC on thin films of collagen are nearly identical to vSMC on thick gels as determined by morphology, proliferation rate, integrin ligation, tenascin-C expression and intracellular signaling events. These results suggest that the features of collagen gels that direct the observed vSMC responses are adequately reconstituted in the thin films of collagen. These thin films will be useful for elucidating the features of the collagen matrix that regulate vSMC response and may be applicable to high

  7. Scanning electron microscopy of experimental Trichophyton mentagrophytes infections in guinea pig skin.

    PubMed Central

    Hutton, R D; Kerbs, S; Yee, K

    1978-01-01

    Trichophyton mentagrophytes invasion of guinea pig skin was examined by scanning electron microscopy. Biopsies were obtained daily for 12 days from experimental infection sites. Dermatophyte invasion, examined in detail by scanning electron microscopy of cross-sectioned, prefixed skin was evidenced by: the appearance of hyphae within the stratum corneum; follicular invasion by hyphae, which remained initially within the follicle wall; emergence of the hyphae from the wall into the follicular canal; proliferation of the fungus down the follicle, with furrowing of the follicle wall and hair shaft cuticle; penetration of hyphae into the hair shaft by subcuticular and transcuticular routes; and massive peripilar hyphal proliferation with arthrosporogenesis. A three-dimensional perception of the invasion sequence of a dermatophyte in guinea pig skin was obtained by scanning electron microscopy. Images PMID:711318

  8. External detection of pulmonary accumulation of indium-113m labelled transferrin in the guinea pig.

    PubMed Central

    Hultkvist-Bengtsson, U; Mårtensson, L

    1990-01-01

    Accumulation of radioisotope labelled transferrin in the lungs of guinea pigs was determined with an external detection system. The method is based on the intravascular and extravascular distribution of indium-113m labelled transferrin compared with the intravascular distribution of technetium-99m labelled red blood cells. Guinea pigs were given iloprost, a prostacyclin analogue and potent pulmonary vasodilator, and noradrenaline, a pulmonary vasoconstrictor, in an attempt to increase and decrease respectively the blood volume in the lungs. Neither agent altered transferrin accumulation in the lung by comparison with a saline infusion. Iloprost infused before and after oleic acid infusion reduced macro-molecular leakage when compared with oleic acid alone. These data suggest that the double isotope method can distinguish between hydrostatic and injury induced pulmonary oedema. PMID:1699294

  9. Isolation induced changes in Guinea Pig Cavia porcellus pup distress whistles.

    PubMed

    Monticelli, Patrícia F; Tokumaru, Rosana S; Ades, César

    2004-06-01

    Guinea Pig Cavia porcellus pups emit high-pitched distress whistles when separated from their mother. In order to assess the influence of the duration of a brief isolation period on whistle acoustic structure, we recorded the distress whistles of six 8-day old pups separated for 15 min from their group in a novel environment and compared the mean values of the first and last 30 whistle notes. Acoustic analysis revealed, throughout the session, a significant decrease in whistle duration, an increase in mean frequency and a tendency for a decrease in number of harmonics in the first part of the note. Results demonstrate that, throughout a brief isolation period, the vocal response of Guinea Pig pups to isolation undergoes structural changes possibly related to time-dependent changes in motivational state.

  10. Number of glomeruli in normal and hypertrophied kidneys of mice and guinea-pigs.

    PubMed Central

    Bonvalet, J P; Champion, M; Courtalon, A; Farman, N; Vandewalle, A; Wanstok, F

    1977-01-01

    1. In mice and guinea-pigs, the number of glomeruli was counted in kidneys during normal growth and in hypertrophy induced by unilateral nephrectomy. 2. In mice, the number of glomeruli increased sharply during the first 2 weeks in life, and more slowly afterwards. Unilateral nephrectomy, when performed during this period of natural increase, induced the formation of supplementary nephrons in the contralateral kidney. 3. In guinea-pigs, the number of glomeruli was almost complete at birth. No evidence of a supplementary increase in the number of nephrons was found in hypertrophied kidneys following unilateral nephrectomy. 4. These results, together wit previous data obtained in the rat, suggest that the ability to induce new nephrons after unilateral nephrectomy in different species would depend more on the state of kidney maturity at birth than on differences in the renal mechanisms which lead to hypertrophy. PMID:894607

  11. [Research progress of acute kanamycin sulfate-induced deafness in guinea pig].

    PubMed

    Yin, Zedeng; Kng, Weijia

    2012-05-01

    To present a summary of current knowledge regarding acute kanamycin sulfate-induced deafness in guinea pig, by reviewing the published literature. Animal model of acute deafness induced by a single dose of kanamycin sulfate in combination with ethacrynic acid or furosemide in guinea pig was usually used to investigate the mechanism of cochlear cell degeneration. There were different time sequences of cell degeneration of spiral ganglion cell and hair cell in different studies. The findings may result from different doses, order of two drugs administration or time point chosen. There remains scope for further research in chronic kanamycin-induced deafness, which more replicates the type of exposure to people than acute deafness.

  12. 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.

  13. [Presynaptic histamine H3-receptors exist on cardiac sympathetic terminals of guinea pig].

    PubMed

    Luo, X X

    1995-07-01

    This is the first time to report the existence of new presynaptic inhibitory autoreceptors--histamine H3-receptors in guinea pig myocardium. We found that (R)-alpha-methylhistamine (alpha-MeHA), a selective histamine H3-receptor agonist, attenuates the sympathetic inotropic response of isolated guinea pig atria elicited by electrical field stimulation. This inhibition was associated with a marked reduction in endogenous norepinephrine release. The above phenomenon was antagonised by selective histamine H3-receptor antagonists, and inhibited by pretreatment with N ethylmeleimide. The cardiac sympathetic response could be attenuated or facilitated by increase or decrease of endogenous histamine. Our findings indicate that the endogenous histamine might be involved in the modulation of cardiac sympathetic neurotransmission by interacting with histamine H3-receptors and the receptors are probably coupled to a G(o)/Gi protein.

  14. Effects of 5 alpha-dihydrotestosterone and methandrostenolone in male guinea pigs.

    PubMed

    Kinson, G A; Lubek, B M

    1981-02-01

    Young adult guinea pigs were studied 6 and 9 weeks after silastic capsules containing 5 alpha-hydrotestosterone (5 alpha-DHT) and methandrostenolone (Dianabol) were implanted. DHT was more effective in causing testicular atrophy and was apparently more androgenically potent in sustaining the size of the seminal vesicles. Both steroids led to hypertrophy of the masseter muscle and increase in gastrocnemius protein concentration. Cardiac tissue was sensitive to the effects of these steroids, particularly to the larger amounts of absorbed Dianabol, in terms of increases in DNA concentration and transient loss of tissue sodium, potassium, and calcium. All alterations in muscle composition occurred in the total absence of change in tissue water. Hypernatremia and hyperkalemia was present in steroid-treated animals with significant loss of urinary potassium in DHT-treated guinea pigs. Adrenal atrophy and the lowering of circulating cortisol was further indicative of effects upon adrenocortical function and the regulation of electrolyte balance.

  15. REGRESSION OF TRANSPLANTED LYMPHOMAS INDUCED IN VIVO BY MEANS OF NORMAL GUINEA PIG SERUM

    PubMed Central

    Kidd, John G.

    1953-01-01

    In the experiments here described transplanted lymphomas of two kinds regularly regressed following repeated injections of normal guinea pig serum intraperitoneally into mice carrying them, the animals meanwhile remaining lively and devoid of signs of illness or wasting. The lymphomas of untreated control mice, by contrast, usually grew progressively and killed their hosts within 20 to 30 days, and the same was true of the growth of other mice given repeated injections of horse serum or rabbit serum. In similar experiments, the cells of a transplanted lymphosarcoma of rats were temporarily kept from proliferating by repeated intraperitoneal injections of guinea pig serum, though the cells of two transplanted mammary carcinomas of mice, and those of fibrosarcoma, grew unimpeded in hosts likewise treated. Additional experiments related to the phenomenon here described, and a discussion of the findings as a whole, are given in an associated paper. PMID:13109110

  16. "Rickettsia amblyommii" induces cross protection against lethal Rocky Mountain spotted fever in a guinea pig model.

    PubMed

    Blanton, Lucas S; Mendell, Nicole L; Walker, David H; Bouyer, Donald H

    2014-08-01

    Rocky Mountain spotted fever (RMSF) is a severe illness caused by Rickettsia rickettsii for which there is no available vaccine. We hypothesize that exposure to the highly prevalent, relatively nonpathogenic "Rickettsia amblyommii" protects against R. rickettsii challenge. To test this hypothesis, guinea pigs were inoculated with "R. amblyommii." After inoculation, the animals showed no signs of illness. When later challenged with lethal doses of R. rickettsii, those previously exposed to "R. amblyommii" remained well, whereas unimmunized controls developed severe illness and died. We conclude that "R. amblyommii" induces an immune response that protects from illness and death in the guinea pig model of RMSF. These results provide a basis for exploring the use of low-virulence rickettsiae as a platform to develop live attenuated vaccine candidates to prevent severe rickettsioses.

  17. 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

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

    DOE PAGES

    Kim, Hwan Keun; Falugi, Fabiana; Thomer, Lena; ...

    2015-01-06

    Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links 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

  19. Clinical chemical responses to experimental airborne legionellosis in the guinea-pig.

    PubMed Central

    Hambleton, P.; Bailey, N. E.; Fitzgeorge, R. B.; Baskerville, A.

    1985-01-01

    Legionella pneumophila infection of guinea-pigs by the aerosol route with either of two strains, one (serogroup I) giving an acute the other (serogroup 3) giving a protracted illness, induced a pyrexia and similar pneumonic lesions. With both strains there was a bacteraemia with early decreases in serum iron and zinc and increases in serum copper concentrations. Marked changes in other serum components were evident only in those animals which had protracted illness (serogroup 3-infected animals). These included transient increases in aminotransferase, creatine kinase and sorbitol dehydrogenase activities and triglyceride levels, together with gradual decreases in alkaline phosphatase and leucine aminopeptidase activities. Serum lysozyme activity and acute-phase protein synthesis increased, as did the ratio of phenylalanine to tyrosine. The findings confirm the relevance of the aerosol-infected guinea-pig model for the investigation of the disease processes and evaluation of therapeutic measures for use in man. PMID:2580546

  20. Impaired T-cell functions in aged guinea-pigs restored by thymostimulin (TS).

    PubMed

    Falchetti, R; Cafiero, C; Caprino, L

    1982-01-01

    The age-related changes of different T-cell activities in guinea pigs and the effect of Thymostimulin (TS), a thymus extract, on the immunocompetence of these cells was studied. Mitogen-induced proliferation of peripheral blood lymphocytes was increased by TS in vitro. The intraperitoneal administration of TS (5 mg/kg) to aged animals restored the helper function of T lymphocytes and enhanced the reactivity to mitogens of both peripheral blood lymphocytes and spleen lymphocytes. The data obtained suggest that as in other species, there is an age-associated decline of immunological response, in guinea pigs too, probably due to a deficiency of thymic hormone(s) and that TS could correct this deficiency.

  1. 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.

  2. 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. PMID:27635195

  3. Bioconversion of C-6 sulfidopeptide leukotrienes by the responding guinea pig ileum determines the time course of its contraction.

    PubMed

    Krilis, S; Lewis, R A; Corey, E J; Austen, K F

    1983-04-01

    The naturally occurring sulfidopeptide leukotrienes, leukotriene (LT) C(4) (LTC(4)) [5(S)-hydroxy - 6(R) - S - glutathionyl - 7,9 - trans, 11,14 - cis - eicosatetraenoic acid] and its cysteinylglycine (LTD(4)) and cysteinyl (LTE(4)) analogs, which are derived by peptide cleavage, differ in the concentrations required to elicit comparable contractions of the guinea pig ileum, with respective potencies of 1.2:5:1. The effect of the ongoing bioconversion of LTC(4) and LTD(4) on the contractile response of the guinea pig ileum to each was determined by recording the pattern of the contraction and quantitating the initial agonist and its metabolic products. The contraction was elicited by radiolabeled agonist, and its conversion products were sampled at defined intervals and resolved by their retention times on reverse-phase high performance liquid chromatography. After a latent period of 60 s. LTC(4) initiated a linear response, followed by a slower, progressive response to a maximum level that was maintained without relaxation. The metabolic conversion of LTC(4) was <5% during the linear phase of contraction and complete inhibition of bioconversion of LTC(4) to LTD(4) by the presence of serine-borate complex did not alter the pattern of the spasmogenic response. As the maximum response in the presence of serine-borate complex was three-quarters of that obtained without the inhibitor of bioconversion, the predominant response was to LTC(4) itself. The spasmogenic response of the ileum to LTD(4) was immediate, linear to a maximum level, and immediately followed by a marked relaxation. That the failure of LTD(4) to sustain a contraction was due to its immediate, rapid, and quantitative conversion to the less potent LTE(4) was established by pharmacologically inhibiting and anatomically deleting the converting activity. In the presence of L-cysteine the conversion of LTD(4) to LTE(4) was largely inhibited and the maximum contractile response was well maintained. After

  4. Physiology, morphology and detailed passive models of guinea-pig cerebellar Purkinje cells.

    PubMed Central

    Rapp, M; Segev, I; Yarom, Y

    1994-01-01

    1. Purkinje cells (PCs) from guinea-pig cerebellar slices were physiologically characterized using intracellular techniques. Extracellular caesium ions were used to linearize the membrane properties of PCs near the resting potential. Under these conditions the average input resistance, RN, was 29 M omega, the average system time constant, tau 0, was 82 ms and the average cable length, LN, was 0.59. 2. Three PCs were fully reconstructed following physiological measurements and staining with horseradish peroxidase. Assuming that each spine has an area of 1 micron 2 and that the spine density over the spiny dendrites is ten spines per micrometre length, the total membrane area of each PC is approximately 150,000 microns 2, of which approximately 100,000 microns 2 is in the spines. 3. Detailed passive cable and compartmental models were built for each of the three reconstructed PCs. Computational methods were devised to incorporate globally the huge number of spines into these models. In all three cells the models predict that the specific membrane resistivity, Rm, of the soma is much lower than the dendritic Rm (approximately 500 and approximately 100,000 omega cm2 respectively). The specific membrane capacitance, Cm, is estimated to be 1.5-2 muF cm-2 and the specific cytoplasm resistivity, Ri, is 250 omega cm. 4. The average cable length of the dendrites according to the model is 0.13 lambda, suggesting that under caesium conditions PCs are electrically very compact. Brief somatic spikes, however, are expected to attenuate 30-fold when spreading passively into the dendritic terminals. A simulated 200 Hz train of fast, 90 mV somatic spikes produced a smooth 12 mV steady depolarization at the dendritic terminals. 5. A transient synaptic conductance increase, with a 1 nS peak at 0.5 ms and a driving force of 60 mV, is expected to produce approximately 20 mV peak depolarization at the spine head membrane. This EPSP then attenuates between 200- and 900-fold into the soma

  5. Innervation of the gallbladder: structure, neurochemical coding, and physiological properties of guinea pig gallbladder ganglia.

    PubMed

    Mawe, G M; Talmage, E K; Cornbrooks, E B; Gokin, A P; Zhang, L; Jennings, L J

    1997-10-01

    The muscle and epithelial tissues of the gallbladder are regulated by a ganglionated plexus that lies within the wall of the organ. Although these ganglia are derived from the same set of precursor neural crest cells that colonize the gut, they exhibit structural, neurochemical and physiological characteristics that are distinct from the myenteric and submucous plexuses of the enteric nervous system. Structurally, the ganglionated plexus of the guinea pig gallbladder is comprised of small clusters of neurons that are located in the outer wall of the organ, between the serosa and underlying smooth muscle. The ganglia are encapsulated by a shell of fibroblasts and a basal lamina, and are devoid of collagen. Gallbladder neurons are rather simple in structure, consisting of a soma, a few short dendritic processes and one or two long axons. Results reported here indicate that all gallbladder neurons are probably cholinergic since they all express immunoreactivity for choline acetyltransferase. The majority of these neurons also express substance P, neuropeptide Y, and somatostatin, and a small remaining population of neurons express vasoactive intestinal peptide (VIP) immunoreactivity and NADPH-diaphorase enzymatic activity. We report here that NADPH-diaphorase activity, nitric oxide synthase immunoreactivity, and VIP immunoreactivity are expressed by the same neurons in the gallbladder. Physiological studies indicate that the ganglia of the gallbladder are the site of action of the following neurohumoral inputs: 1) all neurons receive nicotinic input from vagal preganglionic fibers; 2) norepinephrine released from sympathetic postganglionic fibers acts presynaptically on vagal terminals within gallbladder ganglia to decrease the release of acetylcholine from vagal terminals; 3) substance P and calcitonin gene-related peptide, which are co-expressed in sensory fibers, cause prolonged depolarizations of gallbladder neurons that resemble slow EPSPs; and 4) cholecystokinin

  6. 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

  7. 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

  8. 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

    2016-09-06

    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.

  9. Histamine receptor type coupled to nitric oxide-induced relaxation of guinea-pig nasal mucosa.

    PubMed

    Bockman, C S; Zeng, W

    2002-01-01

    1 The aim of this study was to characterize the histamine receptor type mediating relaxation of the vascular bed of the nasal mucosa from the guinea-pig, and to determine the role of cyclo-oxygenase products and nitric oxide in this relaxant response to histamine. These studies were performed in isolated nasal mucosae examined in vitro to obtain potencies of histamine receptor-type selective agonists in causing vasorelaxation and to determine affinities of histamine receptor antagonists for inhibiting histamine-induced relaxation. 2 After contraction of nasal mucosae with noradrenaline, histamine caused a maximal relaxation response that was 75 +/- 6% of the contraction caused by noradrenaline with a mean EC50 value of 4.3 +/- 0.5 microM. Neither dimaprit (H2-receptor selective) nor R-alpha-methylhistamine (H3-receptor selective) caused significant relaxation of nasal mucosae. In contrast, betahistine (H1-receptor selective) caused an 81 +/- 7% relaxation of noradrenaline-induced tone with an EC50 value of 15 +/- 1 microM. 3 pA2 experiments were performed to obtain KB values of chlorpheniramine (H1-receptor selective) and diphenhydramine (H1-receptor selective) for blocking histamine-stimulated relaxation of nasal mucosae. KB values for chlorpheniramine (0.87 nM) and diphenhydramine (7.4 nM) were consistent with their interaction at the H1-receptor type. Additionally, neither 10 microM cimetidine (H2-receptor selective) nor 1 microM thioperamide (H3-receptor selective) had any effect on the relaxation curve for histamine. 4 In the presence of 10 microM indomethacin (cyclo-oxygenase inhibitor), histamine caused a maximal relaxation response of 73 +/- 5% of the noradrenaline-induced tone with an EC50 value of 2.9 +/- 0.2 microM, which was not different from control values (EC50 = 5.0 +/- 0.4 microM; maximal relaxation = 71 +/- 6%). In contrast, 200 microM NG-nitro-L-arginine (nitric oxide synthase inhibitor) completely inhibited histamine-induced relaxation of nasal

  10. 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

  11. 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.

  12. Long-term low ascorbic acid intake reduces bone mass in guinea pigs.

    PubMed

    Kipp, D E; Grey, C E; McElvain, M E; Kimmel, D B; Robinson, R G; Lukert, B P

    1996-08-01

    The effect of long-term (1 y) low to excess ascorbic acid (AA) intake on bone mass was evaluated using guinea pigs that were 12-14 d old at the start of the experiment. Dietary AA was low (0.15 g/ kg diet) (n = 7), normal (0.50 g/kg) (n = 8) or excess (10 g/kg) (n = 8). After 12 mo, total body bone mineral density (BMD, mg/cm2) and bone mineral content (BMC, g) were determined by dual energy X-ray absorptiometry. Histomorphometric analysis of the cancellous bone of the proximal tibial metaphysis was completed after in vivo dual fluorochrome labeling. Total body BMD of the low AA group was 4.9% lower (P < 0.05), and total body BMC was 12.4% lower (P < 0.05) than in the normal AA group. Total body BMD and BMC were similar in normal and excess AA groups and in the low and excess AA groups. Histomorphometric analysis indicated significantly greater (P < 0.05) double-labeled bone surface, mineralizing surface, and bone formation rate in the low AA guinea pigs compared with the normal AA animals. Thus, there was greater bone turnover in the low AA group than in the normal AA guinea pigs. No differences in histomorphometric endpoints existed between the normal AA and excess AA groups. Long-term AA deficiency, during the period of rapid growth and slower phases of skeletal maturation, resulted in bone abnormalities in adult guinea pig skeletons. Long-term dietary AA excess caused no such abnormalities.

  13. Pharmacokinetic Studies of Intramuscular Midazolam in Guinea Pigs Challenged With Soman

    DTIC Science & Technology

    2004-01-01

    diazepam and biperiden studied in this laboratory in a similar model (Capacio et al., 2001, 2003). This apparent volume of distribution reflects the...for the anticonvulsant biperiden determined under similar conditions (Capacio et al., 2003). In those studies biperiden demonstrated extensive... biperiden in guinea pigs challenged with soman. Drug Chem. Toxicol. 26(1):1-13. Dirnhuber, P., French, M. C., Green, D. M., Leadbeater, L., Stratton, J. A

  14. Advanced diagnostic imaging and surgical treatment of an odontogenic retromasseteric abscess in a guinea pig.

    PubMed

    Capello, V; Lennox, A

    2015-02-01

    A two-year-old guinea pig presented for difficulty chewing. Examination and diagnostic imaging, including computed tomography and magnetic resonance, revealed an odontogenic retromasseteric abscess associated with a mandibular cheek tooth. Treatment included removal of the abscess and marsupialisation of the surgical site for repeated debridement and healing by second intention. Unique features of this case included the use of advanced diagnostic imaging and utilisation of marsupialisation for surgical correction.

  15. Dual effect of GABA on the contractile activity of the guinea-pig isolated urinary bladder.

    PubMed

    Maggi, C A; Santicioli, P; Meli, A

    1985-06-01

    The effects of GABA and related substances were examined in isolated detrusor strips from the dome of the guinea-pig urinary bladder. GABA (0.01-1 mM) produced concentration-related phasic contractions of isolated strips from the guinea-pig urinary bladder dome. This effect of GABA was mimicked by homotaurine and muscimol, selective GABAA receptor agonists but not by (+/-)-baclofen, a selective GABAB receptor agonist. A specific cross desensitization was observed between GABA, homotaurine and muscimol but not between (+/-)-baclofen and GABA. GABA (1 mM)-induced contractions were antagonized by picrotoxin, a selective GABAA receptor antagonist. GABA-induced contractions were almost abolished by tetrodotoxin (0.5 microM, TTX) thus indicating their neurogenic origin. In addition GABA-induced contractions were partially antagonized by atropine (to about the same extent as those produced by dimethylphenylpiperazinium (DMPP), a ganglionic stimulant), but were unaffected by hexamethonium (10 microM), phentolamine (0.2 microM) or indomethacin (5 microM). In the presence of GABA the contractile effect of both DMPP (TTX-sensitive) and acetylcholine (ACh, TTX-insensitive) were significantly reduced. Similar findings were obtained with DMPP, i.e. in preparations exposed to this ganglionic stimulant both GABA- and ACh-induced contractions were depressed. Homotaurine but not (+/-)-baclofen mimicked the depressant effect of GABA on DMPP-induced contractions. The depressant effect of GABA on ACh-induced contractions of the guinea-pig urinary bladder was neurogenic in origin, i.e., was not observed in preparations exposed to TTX. These experiments indicate that GABA has a dual effect on the contractile behaviour of the guinea-pig isolated urinary bladder. Recently it has been proposed that endogenous GABA plays a neuromodulatory role in this organ. Our data suggest that in the early phase of neurogenic activation of detrusor muscle (micturition reflex) GABA might transiently

  16. Differential effects of R-isovaline and the GABAB agonist, baclofen, in the guinea pig ileum.

    PubMed

    Fung, Timothy; Asseri, Khalid A; Asiri, Yahya I; Wall, Richard A; Schwarz, Stephan K W; Puil, Ernest; MacLeod, Bernard A

    2016-11-15

    R-isovaline is a non-proteinogenic amino acid which produces analgesia in a range of nociceptive assays. Mediation of this effect by metabotropic receptors for γ-aminobutyric acid (GABA) and glutamate, demonstrated by previous work, may depend on the type of tissue or receptor system. The objective of this study was to assess the activity of R-isovaline acting at GABAB and group II metabotropic glutamate receptors in guinea pig ileum, which is known to exhibit well-defined responses to GABAB agonists such as baclofen. The effects of bath-applied R-isovaline and RS-baclofen were examined on electrically evoked contractions of guinea pig ileum and during GABAB antagonism by CGP52432. In separate experiments, the group II metabotropic glutamate receptor agonist, LY354740 was applied to determine the functional presence of these receptors. R-isovaline (1-100mM) decreased the amplitude of ileal muscle contractions and increased tension. RS-baclofen reduced contraction amplitude, but decreased tension. CGP52432 did not prevent the effects of R-isovaline on contraction amplitude, but antagonized effects of RS-baclofen on contraction amplitude. The group II metabotropic glutamate receptor agonist, LY354740, produced no detectable effects on evoked contractions. R-isovaline differed significantly from RS-baclofen in its actions in the guinea pig ileum, indicated in particular by the finding that CGP52432 blocked only the effects of RS-baclofen. The ileal tissue did not respond to a group II metabotropic glutamate receptor agonist, previously shown to co-mediate R-isovaline analgesia. These findings raise the possibility of a novel therapeutic target at unknown receptors for R-isovaline-like compounds in the guinea pig ileum.

  17. 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

  18. [Mechanisms operating in the action of pheromones on the estrous cycle of the guinea-pig].

    PubMed

    Jesel, L; Plas-Roser, S

    1976-01-01

    An increase in follicular growth was observed on the 6th and 8th days of the period of vaginal closure (PVC) in adult cyclic female guinea-pigs exposed to the odor of male urine from the beginning of this period. No statistically significant decrease in peripheral blood progesterone level occured on the same days of the PVC following exposure to the odor of male urine.

  19. Histamine protection in guinea-pigs produced by plant tumour extracts

    PubMed Central

    Broome, J.; Callow, R. K.; Feldberg, W.; Kovacs, B. A.

    1962-01-01

    Stable extracts were obtained from plant tumours, such as Hungarian oak galls and crown galls of infected tomato plants, which, injected intraperitoneally into guinea-pigs, protected the animals against a subsequent histamine aerosol. The protection produced by the oak gall extracts lasted for a few days and that produced by the crown gall extracts, if injected in sufficient amounts, sometimes for a few weeks. ImagesFig. 1Fig. 2 PMID:13873490

  20. [Deafness, induced by sodium ethacrynate in guinea pigs, alleviated by microwave treatment].

    PubMed

    Chen, X M; Din, D L; Luo, D F; Huangfu, M S; Jin, X M

    1992-01-01

    Microwave is used to treat temporal hearing loss caused by intravenous injection of the ethacrynic acid in guinea pigs. The recovery of hearing is much faster in the treated groups than in the control group. The article proposes possible mechanism of the effects against the ethacrynic acid induced deafness and assume that the result of this research can provide an experimental basis for treatment of some perceptive deafness due to ischemia of stria vascularis of the cochlea.

  1. Interaction of Pyridostigmine with the 5-HT(3) Receptor Antagonist Ondansetron in Guinea Pigs

    DTIC Science & Technology

    1993-05-13

    5 - HT3 RECEPTOR - ANTAGONIST .ONDANSETRON IN GUINEA PIGS BR. Capacio, CE. Byers...apart. REFERENCES 1. Fozard JR. 5 -HT; The Enigma Variations. =JE, 8, 501-506 (December 1987). 2. Watling KJ. 5 - HT3 Receptor Agonists and Antagonists . In... 5 -HT receptor subtype three antagonists (5HT 3 ) such as the compound ondansetron (OND) have been identified as useful in the treatment of

  2. Constitutive and allergen-induced expression of eotaxin mRNA in the guinea pig lung

    PubMed Central

    1995-01-01

    Eotaxin is a member of the C-C family of chemokines and is related during antigen challenge in a guinea pig model of allergic airway inflammation (asthma). Consistent with its putative role in eosinophilic inflammation, eotaxin induces the selective infiltration of eosinophils when injected into the lung and skin. Using a guinea pig lung cDNA library, we have cloned full-length eotaxin cDNA. The cDNA encodes a protein of 96 amino acids, including a putative 23-amino acid hydrophobic leader sequence, followed by 73 amino acids composing the mature active eotaxin protein. The protein-coding region of this cDNA is 73, 71, 50, and 48% identical in nucleic acid sequence to those of human macrophage chemoattractant protein (MCP) 3, MCP-1, macrophage inflammatory protein (MIP) 1 alpha, and RANTES, respectively. Analysis of genomic DNA suggested that there is a single eotaxin gene in guinea pig which is apparently conserved in mice. High constitutive levels of eotaxin mRNA expression were observed in the lung, while the intestines, stomach, spleen, liver, heart, thymus, testes, and kidney expressed lower levels. To determine if eotaxin mRNA levels are elevated during allergen-induced eosinophilic airway inflammation, ovalbumin (OVA)-sensitized guinea pigs were challenged with aerosolized antigen. Compared with the lungs from saline-challenged animals, eotaxin mRNA levels increased sixfold within 3 h and returned to baseline by 6 h. Thus, eotaxin mRNA levels are increased in response to allergen challenge during the late phase response. The identification of constitutive eotaxin mRNA expression in multiple tissues suggests that in addition to regulating airway eosinophilia, eotaxin is likely to be involved in eosinophil recruitment into other tissues as well as in baseline tissue homing. PMID:7869037

  3. 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.

  4. 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

  5. Intraocular pressure with rebound tonometry and effects of topical intraocular pressure reducing medications in guinea pigs

    PubMed Central

    Di, Yue; Luo, Xiu-Mei; Qiao, Tong; Lu, Na

    2017-01-01

    AIM To investigate the intraocular pressure (IOP) of adult guinea pig eyes with rebound tonometry (RBT), and assess the effects of four distinctive topical IOP reducing medications including Carteolol, Brimonidine, Brinzolamide and Latanoprost. METHODS The IOPs of twenty-four 12-week-old guinea pigs (48 eyes) were measured every two hours in one day with RBT as baselines. All the animals were then divided into four groups (Carteolol, Brimonidine, Brinzolamide and Latanaprost groups, n=6). The IOPs were measured and compared to the baseline 1, 2, 3, 5, 7, 9, 15 and 24h after treatment. RESULTS The mean baseline IOP of 24 guinea pigs (48 eyes) was 10.3±0.36 mm Hg (6-13 mm Hg) and no binocular significant differences of IOPs were observed (t=1.76, P>0.05). No significant difference of IOP in Carteolol group at each time point was observed before and after treatment (t=1.48, P>0.05). In Brimonidine group, IOP was 2.2±1.9 mm Hg lower than the baseline after one hour (t=3.856, P=0.003) and lasted for one hour. In Brinzolamide group, IOP was 1.4±1.1 mm Hg lower than the baseline after one hour (t=4.53, P=0.001) and lasted for 7h and the IOP declined most at 3h. In Latanaprost group, IOP was 2.1±1.3 mm Hg lower than the baseline after one hour (t=6.11, P=0.001) and lasted for one hour. CONCLUSION The IOP of guinea pig eyes is relatively stable compared to human eyes. In four reducing IOP medications, no significant effect of Carteolol is observed. Brinzolamide has the longest duration, while the Brimonidine has the shortest duration and the maximum level of treatment. PMID:28251075

  6. Transdermal delivery of isoniazid and rifampin in guinea pigs by electro-phonophoresis.

    PubMed

    Chen, Suting; Han, Yi; Yu, Daping; Huo, Fengmin; Wang, Fen; Li, Yunxu; Dong, Lingling; Liu, Zhidong; Huang, Hairong

    2017-11-01

    Electro-phonophoresis (EP) has been used as a drug delivery approach in clinical fields. The objective of the present study is to evaluate the skin permeability of isoniazid and rifampin in guinea pigs by EP to provide reference basis for clinical applications of such transdermal delivery system in the treatment of patients with superficial tuberculosis. Isoniazid and rifampin solutions were delivered transdermally with or without EP in health guinea pigs for 0.5 h. Local skin and blood samples were collected serially at 0, 1/2, 1, 2, 4, 6 and 24 h after dosing. Drug concentrations in local skin and blood were evaluated by high-performance liquid chromatography. Isoniazid concentrations in local skin of guinea pigs receiving isoniazid through EP transdermal delivery were significantly higher than in animals receiving only isoniazid with transdermal patch. However, for rifampin, patches alone group presented almost uniform concentration versus time curve with that of EP group, and both groups had concentrations much higher than the therapeutic concentration of the drug over sustainable time. After EP transdermal delivery, the mean peak concentrations of isoniazid and rifampin in skin were 771.0 ± 163.4 μg/mL and 81.2 ± 17.3 μg/mL respectively. Neither isoniazid nor rifampin concentration in blood could be detected (below the lower detection limit of 1 μg/mL) at any time point. The present study showed that application of EP significantly enhanced INH penetration through skin in guinea pigs, while RIF patch alone obtained therapeutic concentration in local skin. Our work suggests several possible medication approaches for efficient treatment of superficial tuberculosis.

  7. 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.

  8. Recombinant IgA is sufficient to prevent influenza virus transmission in guinea pigs.

    PubMed

    Seibert, Christopher W; Rahmat, Saad; Krause, Jens C; Eggink, Dirk; Albrecht, Randy A; Goff, Peter H; Krammer, Florian; Duty, J Andrew; Bouvier, Nicole M; García-Sastre, Adolfo; Palese, Peter

    2013-07-01

    A serum hemagglutination inhibition (HAI) titer of 40 or greater is thought to be associated with reduced influenza virus pathogenesis in humans and is often used as a correlate of protection in influenza vaccine studies. We have previously demonstrated that intramuscular vaccination of guinea pigs with inactivated influenza virus generates HAI titers greater than 300 but does not protect vaccinated animals from becoming infected with influenza virus by transmission from an infected cage mate. Only guinea pigs intranasally inoculated with a live influenza virus or a live attenuated virus vaccine, prior to challenge, were protected from transmission (A. C. Lowen et al., J. Virol. 83:2803-2818, 2009.). Because the serum HAI titer is mostly determined by IgG content, these results led us to speculate that prevention of viral transmission may require IgA antibodies or cellular immune responses. To evaluate this hypothesis, guinea pigs and ferrets were administered a potent, neutralizing mouse IgG monoclonal antibody, 30D1 (Ms 30D1 IgG), against the A/California/04/2009 (H1N1) virus hemagglutinin and exposed to respiratory droplets from animals infected with this virus. Even though HAI titers were greater than 160 1 day postadministration, Ms 30D1 IgG did not prevent airborne transmission to passively immunized recipient animals. In contrast, intramuscular administration of recombinant 30D1 IgA (Ms 30D1 IgA) prevented transmission to 88% of recipient guinea pigs, and Ms 30D1 IgA was detected in animal nasal washes. Ms 30D1 IgG administered intranasally also prevented transmission, suggesting the importance of mucosal immunity in preventing influenza virus transmission. Collectively, our data indicate that IgG antibodies may prevent pathogenesis associated with influenza virus infection but do not protect from virus infection by airborne transmission, while IgA antibodies are more important for preventing transmission of influenza viruses.

  9. Passive transfer of experimental autoimmune myasthenia by lymph node cells in inbred guinea pigs

    PubMed Central

    1975-01-01

    Passive transfer of experimental autoimmune myasthenia (EAM) was performed with lymph node cells from donor guinea pigs immunized with purified acetylcholine receptor (AChR) from Torpedo californica. Recipient animals revealed the same clinical signs and electromyographic patterns as observed in actively challenged animals. These phenomena are parallel to the clinical manifestations of the human disease myasthenia gravis, in which cellular response to AChR was recently demonstrated. PMID:1165476

  10. 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.

  11. 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.

  12. Guinea pig hippocampal 5-HT(1E) receptors: a tool for selective drug development.

    PubMed

    Klein, Michael T; Teitler, Milt

    2009-04-01

    Recent studies have indicated that the serotonin [5-hydroxytryptamine (5-HT)] 1E receptor, originally discovered in human brain tissue, is not expressed in rat or mouse brain. Thus, there have been few reports on 5-HT(1E) receptor drug development. However, expression of 5-HT(1E) receptor mRNA has been shown in guinea pig brain. To establish this species as an animal model for 5-HT(1E) drug development, we identified brain regions that exhibit 5-carboxyamidotryptamine, ritanserin, and LY344864 - insensitive [(3)H]5-HT binding (characteristic of the 5-HT(1E) receptor). In hippocampal homogenates, where 5-HT(1E) receptor density was sufficiently high for radioligand binding analysis, 100 nM 5-carboxyamidotryptamine, 30 nM ritanserin, and 100 nM LY344864 were used to mask [(3)H]5-HT binding at non-5-HT(1E) receptors. The K(d) of [(3)H]5-HT was 5.7 +/- 0.7 nM and is indistinguishable from the cloned receptor K(d) of 6.5 +/- 0.6 nM. The affinities of 16 drugs for the cloned and hippocampal-expressed guinea pig 5-HT(1E) receptors are essentially identical (R(2) = 0.97). These findings indicate that using these conditions autoradiographical distribution and signal transduction studies of the 5-HT(1E) receptor in guinea pig brain are feasible. Using the guinea pig as an animal model should provide important insights into possible functions of this receptor and the therapeutic potential of selective human 5-HT(1E) drugs.

  13. Minimal In Vivo Efficacy of Iminosugars in a Lethal Ebola Virus Guinea Pig Model

    PubMed Central

    Dowall, Stuart D.; Taylor, Irene; Rule, Antony; Alonzi, Dominic S.; Sayce, Andrew C.; Wright, Edward; Bentley, Emma M.; Thom, Ruth; Hall, Graham; Dwek, Raymond A.; Hewson, Roger; Zitzmann, Nicole

    2016-01-01

    The antiviral properties of iminosugars have been reported previously in vitro and in small animal models against Ebola virus (EBOV); however, their effects have not been tested in larger animal models such as guinea pigs. We tested the iminosugars N-butyl-deoxynojirimycin (NB-DNJ) and N-(9-methoxynonyl)-1deoxynojirimycin (MON-DNJ) for safety in uninfected animals, and for antiviral efficacy in animals infected with a lethal dose of guinea pig adapted EBOV. 1850 mg/kg/day NB-DNJ and 120 mg/kg/day MON-DNJ administered intravenously, three times daily, caused no adverse effects and were well tolerated. A pilot study treating infected animals three times within an 8 hour period was promising with 1 of 4 infected NB-DNJ treated animals surviving and the remaining three showing improved clinical signs. MON-DNJ showed no protective effects when EBOV-infected guinea pigs were treated. On histopathological examination, animals treated with NB-DNJ had reduced lesion severity in liver and spleen. However, a second study, in which NB-DNJ was administered at equally-spaced 8 hour intervals, could not confirm drug-associated benefits. Neither was any antiviral effect of iminosugars detected in an EBOV glycoprotein pseudotyped virus assay. Overall, this study provides evidence that NB-DNJ and MON-DNJ do not protect guinea pigs from a lethal EBOV-infection at the dose levels and regimens tested. However, the one surviving animal and signs of improvements in three animals of the NB-DNJ treated cohort could indicate that NB-DNJ at these levels may have a marginal beneficial effect. Future work could be focused on the development of more potent iminosugars. PMID:27880800

  14. Enzymatic oxidation of phthalazine with guinea pig liver aldehyde oxidase and liver slices: inhibition by isovanillin.

    PubMed

    Panoutsopoulos, Georgios I; Beedham, Christine

    2004-01-01

    The enzymes aldehyde oxidase and xanthine oxidase catalyze the oxidation of a wide range of N-heterocycles and aldehydes. These enzymes are widely known for their role in the metabolism of N-heterocyclic xenobiotics where they provide a protective barrier by aiding in the detoxification of ingested nitrogen-containing heterocycles. Isovanillin has been shown to inhibit the metabolism of aromatic aldehydes by aldehyde oxidase, but its inhibition towards the heterocyclic compounds has not been studied. The present investigation examines the oxidation of phthalazine in the absence and in the presence of the inhibitor isovanillin by partially purified aldehyde oxidase from guinea pig liver. In addition, the interaction of phthalazine with freshly prepared guinea pig liver slices, both in the absence and presence of specific inhibitors of several liver oxidizing enzymes, was investigated. ldehyde oxidase rapidly converted phthalazine into 1-phthalazinone, which was completely inhibited in the presence of isovanillin (a specific inhibitor of aldehyde oxidase). In freshly prepared liver slices, phthalazine was also rapidly converted to 1-phthalazinone. The formation of 1-phthalazinone was completely inhibited by isovanillin, whereas disulfiram (a specific inhibitor of aldehyde dehydrogenase) only inhibited 1-phthalazinone formation by 24% and allopurinol (a specific inhibitor of xanthine oxidase) had little effect. Therefore, isovanillin has been proved as an inhibitor of the metabolism of heterocyclic substrates, such as phthalazine, by guinea pig liver aldehyde oxidase, since it had not been tested before. Thus it would appear from the inhibitor results that aldehyde oxidase is the predominant enzyme in the oxidation of phthalazine to 1-phthalazinone in freshly prepared guinea pig liver slices, whereas xanthine oxidase only contributes to a small extent and aldehyde dehydrogenase does not take any part.

  15. A small animal model study of perlite and fir bark dust on guinea pig lungs.

    PubMed

    McMichael, R F; DiPalma, J R; Blumenstein, R; Amenta, P S; Freedman, A P; Barbieri, E J

    1983-05-01

    Fir bark (Abies) and perlite (noncrystalline silicate) dusts have been reported to cause pulmonary disease in humans. Guinea pigs were exposed to either fir bark or perlite dust in a special chamber. Severe pathologic changes occurred in the lungs, consisting of lymphoid aggregated and a perivascular inflammatory response. Both dusts caused similar changes although one was vegetable (fir bark) and the other mineral (perlite). Fir bark and perlite dust appeared to be more than just nuisance dusts.

  16. Guinea pig (Cavia porcellus) drinking preferences: do nipple drinkers compensate for behaviourally deficient diets?

    PubMed

    Balsiger, A; Clauss, M; Liesegang, A; Dobenecker, B; Hatt, J-M

    2016-07-23

    When offered diets with hay ad libitum, rabbits (Oryctolagus cuniculus) clearly prefer open dishes over nipple drinkers, but whether this preference also applies in guinea pigs (Cavia porcellus) is unsure. We tested the drinker preference of 10 guinea pigs when offered open dishes (OD) and nipple drinkers (ND) simultaneously and measured the amount of water consumed by each animal on four different diets (grass hay 100%, or as 10% of intake on diets of fresh parsley, seed mix or pelleted complete feed, respectively) on either of the drinking systems. All animals ingested the hay portion of the combined diets first. The amount of water consumed differed significantly between individual animals. Animals drank less water on parsley than on the other diets. Nine of 10 animals clearly preferred ND when having a choice, and eight of these drank more when on ND only. The difference between the drinking systems was not consistent across all diets: on hay, similar amounts of water were drunk when on OD or ND only. Differences in water intake were reflected in urine production. Because drinking from ND in guinea pigs involves jaw movements similar to those in chewing, the results could suggest that when motivation for oral processing behaviour is not satisfied by a diet, animals may respond in using ND beyond physiological water necessity. Whereas physiological water requirements are probably better investigated with other drinking systems due to a possible overestimation when using ND, offering ND to pet guinea pigs most likely offers a form of behavioural enrichment that at the same time may increase water intake and hence act as prophylaxis against urolithiasis.

  17. Synthetic detergents induced-biochemical and histological changes in skin of guinea pigs.

    PubMed

    Agarwal, C; Mathur, A K; Gupta, B N; Singh, A; Shanker, R

    1990-06-01

    The linear alkylbenzene sulphonate (LAS) based synthetic detergents-induced decrease in lipid peroxydation and increase in histamine content in exposed skin of guinea pigs in a dose-dependent manner. Histopathological alterations of exposed skin included moderate degree of hyperkeratinization at lower concentration but necrosis, scarring, sloughing as well as discontinuity of epidermis at higher concentrations. The results shows that the contact of skin with detergents causes dermal toxicity.

  18. Myocardial KChIP2 Expression in Guinea Pig Resolves an Expanded Electrophysiologic Role

    PubMed Central

    Nassal, Drew M.; Wan, Xiaoping; Liu, Haiyan; Deschênes, Isabelle

    2016-01-01

    Cardiac ion channels and their respective accessory subunits are critical in maintaining proper electrical activity of the heart. Studies have indicated that the K+ channel interacting protein 2 (KChIP2), originally identified as an auxiliary subunit for the channel Kv4, a component of the transient outward K+ channel (Ito), is a Ca2+ binding protein whose regulatory function does not appear restricted to Kv4 modulation. Indeed, the guinea pig myocardium does not express Kv4, yet we show that it still maintains expression of KChIP2, suggesting roles for KChIP2 beyond this canonical auxiliary interaction with Kv4 to modulate Ito. In this study, we capitalize on the guinea pig as a system for investigating how KChIP2 influences the cardiac action potential, independent of effects otherwise attributed to Ito, given the endogenous absence of the current in this species. By performing whole cell patch clamp recordings on isolated adult guinea pig myocytes, we observe that knock down of KChIP2 significantly prolongs the cardiac action potential. This prolongation was not attributed to compromised repolarizing currents, as IKr and IKs were unchanged, but was the result of enhanced L-type Ca2+ current due to an increase in Cav1.2 protein. In addition, cells with reduced KChIP2 also displayed lowered INa from reduced Nav1.5 protein. Historically, rodent models have been used to investigate the role of KChIP2, where dramatic changes to the primary repolarizing current Ito may mask more subtle effects of KChIP2. Evaluation in the guinea pig where Ito is absent, has unveiled additional functions for KChIP2 beyond its canonical regulation of Ito, which defines KChIP2 as a master regulator of cardiac repolarization and depolarization. PMID:26764482

  19. Vascular smooth muscle cell functional contractility depends on extracellular mechanical properties

    PubMed Central

    Steucke, Kerianne E.; Tracy, Paige V.; Hald, Eric S.; Hall, Jennifer L.; Alford, Patrick W.

    2015-01-01

    Vascular smooth muscle cells’ primary function is to maintain vascular homeostasis through active contraction and relaxation. In diseases such as hypertension and atherosclerosis, this function is inhibited concurrent to changes in the mechanical environment surrounding vascular smooth muscle cells. It is well established that cell function and extracellular mechanics are interconnected; variations in substrate modulus affect cell migration, proliferation, and differentiation. To date, it is unknown how the evolving extracellular mechanical environment of vascular smooth muscle cells affects their contractile function. Here, we have built upon previous vascular muscular thin film technology to develop a variable-modulus vascular muscular thin film that measures vascular tissue functional contractility on substrates with a range of pathological and physiological moduli. Using this modified vascular muscular thin film, we found that vascular smooth muscle cells generated greater stress on substrates with higher moduli compared to substrates with lower moduli. We then measured protein markers typically thought to indicate a contractile phenotype in vascular smooth muscle cells and found that phenotype is unaffected by substrate modulus. These data suggest that mechanical properties of vascular smooth muscle cells’ extracellular environment directly influence their functional behavior and do so without inducing phenotype switching. PMID:26283412

  20. 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 cholest