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Guinea-pigs
Kinds of Guinea-pigs Terms modified by Guinea-pigs Selected AbstractsCentral Regulation of the Hypothalamic-Pituitary-Adrenal Axis During Fetal Development in the Guinea-PigJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2005D. Owen Abstract We have previously shown that the foetal guinea-pig hypothalamic-pituitary-adrenal (HPA) axis is activated near the time of parturition and that this is associated with changes in limbic glucocorticoid receptors (GR) and mineralocorticoid receptors. In the present study, we hypothesized that the foetal hypothalamic paraventricular nucleus (PVN) and pituitary contribute significantly to foetal HPA drive but that these areas remain sensitive to negative feedback by circulating glucocorticoids in late gestation. However, we observed decreased corticotrophin-releasing hormone mRNA expression in the PVN and decreased pro-opiomelanocortin (POMC) mRNA levels in the anterior pituitary with advanced gestational age. The reduction in POMC mRNA expression was likely the result of negative feedback via circulating glucocorticoids because GR mRNA was unchanged during development in the foetal pituitary. Furthermore, we found that maternally administered glucocorticoids significantly decreased foetal pituitary POMC mRNA expression in a dose-dependent manner at gestational day (gd) 62 with male foetuses being more sensitive to these effects. These findings show that the foetal HPA axis remains highly sensitive to glucocorticoid feedback even as plasma adrenocorticotropic hormone and cortisol levels are elevated at the end of gestation. [source] Neural Circuits Regulating Pulsatile Luteinizing Hormone Release in the Female Guinea-Pig: Opioid, Adrenergic and Serotonergic InteractionsJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2001A. C. Gore Abstract We studied three neurotransmitters involved in the regulation of pulsatile luteinizing hormone (LH) release: opioid peptides, serotonin and norepinephrine, using the ovariectomized guinea-pig. This is an attractive animal model due to the regularity of its LH pulses, enabling any disruptions to be clearly ascertained. In all experiments, a specific agonist or antagonist was administered, either alone or serially to enable detection of interactions, and effects on mean LH concentrations, pulse amplitude and interpulse interval were determined by PULSAR analysis. In the ovariectomized guinea-pig, catecholamines are stimulatory (acting through the ,1 and ,2 but not , receptors, unlike other species), opioids inhibitory and serotonin permissively stimulatory to pulsatile LH release. Stimulatory effects of the opiate antagonist were not blocked by pretreatment with an ,1 - or ,2 -adrenergic antagonist. Similarly, pretreatment with the opiate antagonist did not prevent the suppression of LH release by ,1 and ,2 antagonists. This suggests that, in the guinea-pig, effects of opiates and catecholamines on LH release are exerted by independent pathways to luteinizing hormone releasing hormone (LHRH) neurones. For the opiate,serotonin interactions, pretreatment with the serotonergic antagonist did not block the stimulatory effect of the opiate antagonist on LH release. However, pretreatment with the opiate agonist could not be overcome by the serotonergic agonist. This suggests that the effects of the serotonin system on LHRH release may be indirectly mediated by opioid neurones. Taken together, these studies demonstrate that the three neurotransmitter systems studied are critically involved in normal pulsatile LH release in the female guinea-pig, and demonstrate novel functional relationships between the opioid and the adrenergic and serotonergic systems. [source] Comparative Anatomy of the Male Guinea-Pig and Human Lower Urinary Tract: Histomorphology and Three-Dimensional ReconstructionANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2001Neuhaus The guinea-pig is often used for experimental studies in urology. However, the anatomy of the lower urinary tract of the guinea-pig is poorly described in the literature. The structure and function of the lower urinary tract, i.e. continence, micturition and sexual function, are closely related to the gross anatomy of the pelvis and the fine structure of the musculature. We investigated the anatomy and histomorphology of the lower urinary tract by serial sections in male guinea-pigs and compared it to that in humans. Immunohistochemical stainings for alpha-smooth muscle cell actin were used to differentiate between smooth and striated muscles. By using whole pelvic preparations, including all internal organs preserved in their in situ location for three-dimensional reconstruction, we developed three-dimensional models, which elucidate the spatial relationship of all muscular structures and can help to deduce functional aspects of lower urinary tract function. In the guinea-pig, most of the muscles found in humans can be demonstrated in comparable location and extension. However, the structure of the prostate and the existence of the so-called coagulation glands define a significant difference in the morphology of the prostatic urethra. [source] Maternal Effort is State Dependent: Energetic Limitation or Regulation?ETHOLOGY, Issue 4 2008Anke Rehling Many small altricial rodents have a postpartum oestrus and are often simultaneously pregnant and lactating. Negative influences of concurrent pregnancy and lactation on both lactational performance and the litter in utero are commonly observed and have been interpreted as resulting from high simultaneous energetic demands of gestation and lactation. We studied these effects in the precocial guinea-pig (Cavia aperea f. porcellus) that, like many altricial rodents, has a postpartum oestrus, but in which the peaks of energy expenditure on lactation and gestation are widely separated. This life history allowed to investigate whether physiological regulation other than by energetic limitations may be responsible for allocation conflicts arising when lactation and gestation overlap. By comparing simultaneously pregnant and lactating females with lactating non-pregnant females, we show that females in the former group nurse less and wean earlier than females of the latter group. In a comparison of litter size, litter mass, and pup mortality of females that had not been lactating during pregnancy with females that had been simultaneously pregnant and lactating, we show that the latter do not reduce investment in the following litter. In our study, energetic constraints on ad libitum fed females are unlikely and we therefore suggest that the results must be explained by regulatory constraints on lactational effort. We point out that this explanation has not been excluded for the effects observed in altricial small mammals. [source] Effects of ouabain on contractions induced by manganese ions in Ca2+ -free, isotonic solutions with varying concentrations of K+ in guinea-pig taenia coliFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2005Tetsuyuki Nasu Abstract The action of ouabain, a cell membrane Na+, K+ -ATPase blocker, on contractions induced by manganese ions (Mn2+) in Ca2+ -free, isotonic solutions with varying concentrations of K+ in the external medium were investigated in order to evaluate the underlying role of external Na+ in Mn2+ -induced contractions in isolated taenia coli of the guinea-pig. Mn2+ at 5 mm induced greater contractions as external isotonic K+ concentrations progressively increased from 10 to 100 mm. Ouabain (2 × 10,4 m) completely inhibited tension development stimulated by 5 mm Mn2+ in isotonic, 30 mm K+ (96 mm Na+) medium. Whereas, the tension inhibitory effects of ouabain became progressively weaker as isotonic, external K+ concentrations increased to 60 mm, which successively decreased external Na+ concentrations. Eventually, ouabain failed to affect contractions stimulated by Mn2+ in isotonic, 126 mm K+, Na+ -deficient medium. Ouabain caused progressively greater increase in cellular Na+ concentrations as the Na+ concentrations increased in the isotonic, K+ medium. While, pyruvate, which penetrates cell independently of external Na+, reversed the inhibition of tension by ouabain in isotonic, 30 mm K+, Na+ -sufficient (96 mm) medium containing 5 mm Mn2+. These results suggested that Mn2+ induced the contraction, which was maintained by glucose transport depending on external Na+, in the case of Na+ -sufficient medium in K+ -depolarized taenia coli. However, it induced the contraction independent of external Na+, in the case of Na+ -deficient, K+ medium. Ouabain might exhibit greater inhibition of the contraction induced by Mn2+ as the decrease in the Na+ gradient across the cell membranes continues. [source] A novel approach to assessing percutaneous VX poisoning in the conscious guinea-pig,JOURNAL OF APPLIED TOXICOLOGY, Issue 5 2008Helen Mumford Abstract Nerve agents like VX (S-2-diisopropylaminoethyl-O-ethyl-methylphosphonothiolate) are potent irreversible acetylcholinesterase (AChE) inhibitors. Following percutaneous nerve agent exposure there is a slower rate of absorption, later onset and longer duration of signs of poisoning. Relatively little is known about the physiological effects of percutaneously applied nerve agent in unanaesthetised laboratory animals. Heart rate (ECG), brain electrical activity (EEG), body temperature, locomotor activity and clinical signs were monitored following percutaneous application of VX to conscious guinea-pigs. A fall in heart rate (bradycardia) preceded incapacitation following the highest VX dose, and occurred in the absence of incapacitation at the lower doses. Following the highest dose of VX (0.592 mg kg,1) three out of four animals died within 24 h. The lower two doses of VX (0.296 and 0.148 mg kg,1), produced extended periods of bradycardia in the absence of observable signs of poisoning. Bradycardia preceded, or occurred in the absence of, a temperature decrease; seizure-like EEG changes were not observed at any of the VX doses tested. Acetylcholinesterase activity was significantly inhibited in the blood and most brain areas at 48 h. There were significant dose-related decreases in body weight at 24 and 48 h following VX. This preliminary study suggests that decreased heart rate may be an early sign of the toxic effects of VX, whereas temperature and observable clinical signs are not good early indicators of percutaneous VX poisoning in this animal model. Future studies will use this model to assess the benefit of administering medical countermeasures in response to a defined decrease in heart rate. © Crown Copyright 2007. Reproduced with the permission of the Controller of HMSO. Published by John Wiley & Sons, Ltd. This article was published online on 5 December 2007. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected [30 May 2008]. [source] Neural Circuits Regulating Pulsatile Luteinizing Hormone Release in the Female Guinea-Pig: Opioid, Adrenergic and Serotonergic InteractionsJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2001A. C. Gore Abstract We studied three neurotransmitters involved in the regulation of pulsatile luteinizing hormone (LH) release: opioid peptides, serotonin and norepinephrine, using the ovariectomized guinea-pig. This is an attractive animal model due to the regularity of its LH pulses, enabling any disruptions to be clearly ascertained. In all experiments, a specific agonist or antagonist was administered, either alone or serially to enable detection of interactions, and effects on mean LH concentrations, pulse amplitude and interpulse interval were determined by PULSAR analysis. In the ovariectomized guinea-pig, catecholamines are stimulatory (acting through the ,1 and ,2 but not , receptors, unlike other species), opioids inhibitory and serotonin permissively stimulatory to pulsatile LH release. Stimulatory effects of the opiate antagonist were not blocked by pretreatment with an ,1 - or ,2 -adrenergic antagonist. Similarly, pretreatment with the opiate antagonist did not prevent the suppression of LH release by ,1 and ,2 antagonists. This suggests that, in the guinea-pig, effects of opiates and catecholamines on LH release are exerted by independent pathways to luteinizing hormone releasing hormone (LHRH) neurones. For the opiate,serotonin interactions, pretreatment with the serotonergic antagonist did not block the stimulatory effect of the opiate antagonist on LH release. However, pretreatment with the opiate agonist could not be overcome by the serotonergic agonist. This suggests that the effects of the serotonin system on LHRH release may be indirectly mediated by opioid neurones. Taken together, these studies demonstrate that the three neurotransmitter systems studied are critically involved in normal pulsatile LH release in the female guinea-pig, and demonstrate novel functional relationships between the opioid and the adrenergic and serotonergic systems. [source] 1,8-Cineole induces relaxation in rat and guinea-pig airway smooth muscleJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2009Nilberto Robson Falcão Nascimento Abstract Objectives 1,8-Cineole is a monoterpene with anti-inflammatory, vascular and intestinal smooth muscle relaxant activity. We have evaluated the potential bronchodilatatory activity of this compound. Methods 1,8-Cineole was tested against carbachol, histamine, K+ 80 mM and ovalbumin-induced bronchial contractions in Wistar rat or guinea-pig tissues. Some of the guinea-pigs had been previously sensitized with an intramuscular injection of 5% (w/v) ovalbumin/saline solution. Control animals received 0.3 ml saline. In separate experimental groups the response to 1,8-cineole (1,30 mg/kg), phenoterol (0.05,5 mg/kg) or vehicle (0.3% Tween in saline) was studied. Key findings 1,8-Cineole decreased, in vivo, rat bronchial resistance with similar efficacy as phenoterol (66.7 ± 3.2% vs 72.1 ± 5.3%). On the other hand, the maximal relaxant response to 1,8-cineole in carbachol-precontracted rat tracheas was 85.5 ± 5.7% (IC50 = 408.9 (328,5196) ,g/ml) compared with 80.2 ± 4.8% (IC50 = 5.1 (4.3,6.1) ,g/ml) with phenoterol. The addition of 1,8-cineole to guinea-pig tracheal rings tonically contracted with K+ 80 mM induced a concentration-related relaxation. The maximal relaxation elicited by 1,8-cineole was 113.6 ± 11.7% (IC50 127.0 (115.9,139.2) ,g/ml) compared with 129.7 ± 14.6% (IC50 0.13 (0.12,0.14) ,g/ml) achieved after phenoterol administration. In addition, the incubation of tracheal rings with 1,8-cineole (100, 300 or 1000 ,g/ml), 15 min before inducing phasic contractions with K+ 80 mM, decreased the maximal amplitude of the contraction by 31.6 ± 4.6, 75.7 ± 2.7 and 92.2 ± 1.5%, respectively. In another set of experiments, neither the maximal response nor the IC50 for the 1,8-cineole-induced relaxation were different between normal and ovalbumin-sensitized tissues. Moreover, the relaxation of bronchial rings contracted after exposure to 1 ,g/ml ovalbumin occurred at a faster rate in rings pre-incubated with 1,8-cineole when compared with rings pre-incubated with vehicle only (Tween 0.3%). Therefore, in the first minute after the antigen challenge, the tracheal tissue relaxed after the peak contraction by 6.5, 21.4 (P < 0.05 vs control) and 66.9% (P < 0.05 vs control) in the presence of 100, 300 or 1000 ,g/ml 1,8-cineole, respectively. Conclusions 1,8-Cineole relaxed rat and guinea-pig (nonsensitized and ovalbumin-sensitized) airway smooth muscle by a nonspecific mechanism. [source] Plasticity and ambiguity of the electrophysiological phenotypes of enteric neuronsNEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2009K. Nurgali Abstract, Advances in knowledge of enteric neurons electrophysiological characteristics have led to the realisation that the properties of the neurons are dependent on the state of the intestine, the region, the method of recording and the species. Thus, under different experimental conditions, electrophysiological studies cannot provide a reliable signature that identifies the functional type of neuron. In the normal guinea-pig small intestine, taken as a model tissue, neurons can be separated into two electrophysiological groups, S and AH neurons. Combined morphological and physiological studies place several classes of motor and interneurons in the S group, and intrinsic primary afferent neurons in the AH group. There is some evidence for subgroups of S neurons, in which electrophysiological differences are correlated with functional subtypes, but these subgroups have been incompletely investigated. Morphologically characterized Dogiel type II (DII) neurons are recognisable in many species, from mouse to human, but their electrophysiological characteristics are only partly conserved across species or cannot be satisfactorily defined due to technical difficulties. There is a strong need for a comprehensive analysis of channels and currents of S/Dogiel type I neuron subtypes, similar to the comprehensive analysis of AH/DII neurons in the guinea-pig, and similar studies need to be conducted in human and other species. The purpose of this review is to highlight that criteria used for electrophysiological definition of enteric neurons might not be sufficient to distinguish between functional classes of neurons, due to intrinsic properties of neuronal subpopulations, plasticity in pathological conditions and differences in recording techniques. [source] The effect of mosapride citrate on proximal and distal colonic motor function in the guinea-pig in vitroNEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2008H. S. Kim Abstract, Mosapride citrate (mosapride), a substituted benzamide, is a selective 5-HT4 receptor agonist, and is known to have prokinetic properties on the stomach. However, it is unclear whether mosapride also has a prokinetic effect on the colon. We previously found that mosapride significantly shortened colonic transit time in the guinea-pig, an animal with a distribution of colonic 5-HT4 receptors similar to that of a human. So, we aimed to separately evaluate the effect of mosapride on proximal and distal colonic motor function in the guinea-pig. Proximal (approximately 8 cm from the ileocolic junction) and distal colon (approximately 8 cm from the anus) were removed. Both ends of the colon were connected to a chamber containing a Krebs-Henseleit solution. To measure colonic transit time, artificial faeces were inserted into the oral side of the lumen and moved towards the anal side by intraluminal perfusion via a peristaltic pump. A total of 6 cm of transit was observed and time was measured in 2 cm increments. A tissue bath study, using electrical stimulation, was performed to estimate the contractile activity of the circular musculature of the colon. Immunohistochemical staining for 5-HT4 receptors was performed in the myenteric plexus and circular muscle in both proximal and distal colon, and the stained area was measured using a microscope and computer software. Mosapride enhanced contraction at 10,9 to 10,7 mol L,1, coinciding with rapid transit both in proximal and distal colon. This pattern was more prominent in proximal colon. At the high dose (10,6 mol L,1) mosapride had little or no effect on colonic contraction. This stimulatory effect was attenuated by GR113808, atropine and tetrodotoxin. In the myenteric plexus, the density of 5-HT4 receptors was significantly greater in the proximal colon than in the distal colon, but in circular muscle the density was greater in the distal colon. Thus, mosapride accelerates transit through increased contraction in the proximal colon more than distal colon. The different distribution of neuronal and muscular 5-HT4 receptors may support these findings. Therefore, mosapride may be a useful alternative to tegaserod and cisapride for constipation. [source] The opioid system in the gastrointestinal tractNEUROGASTROENTEROLOGY & MOTILITY, Issue 2004C. Sternini Abstract µ-, ,- and ,-opioid receptors (ORs) mediate the effects of endogenous opioids and opiate drugs. Here we report (1) the distribution of µOR in the guinea-pig and human gastrointestinal tract in relation to endogenous ligands, to functionally distinct structures in the gut and to ,OR and ,OR; and (2) the ligand-induced µOR endocytosis in enteric neurones using in vitro and in vivo models. In the guinea pig, µOR immunoreactivity is confined mainly to the myenteric plexus. µOR myenteric neurones are most numerous in the small intestine, followed by the stomach and the proximal colon. µOR immunoreactive fibres are dense in the muscle layer and the deep muscular plexus, where they are in close association with interstitial cells of Cajal. This distribution closely matches the pattern of enkephalin. µOR enteric neurones comprise functionally distinct populations of neurones of the ascending and descending pathways of the peristaltic reflex. In human gut, µOR immunoreactivity is localized to myenteric and submucosal neurones and to immune cells of the lamina propria. ,OR immunoreactivity is located in both plexuses where it is predominantly in varicose fibres in the plexuses, muscle and mucosa, whereas ,OR immunoreactivity appears to be confined to the myenteric plexus and to bundles of fibres in the muscle. µOR undergoes endocytosis in a concentration-dependent manner, in vitro and in vivo. Pronounced µOR endocytosis is observed in neurones from animals that underwent abdominal surgery that has been shown to induce delay in gastrointestinal transit. We can conclude that all three ORs are localized to the enteric nervous system with differences among species, and that µOR endocytosis can be utilized as a means to visualize enteric neurones activated by opioids and sites of opioid release. [source] Synaptic facilitation and enhanced neuronal excitability in the submucosal plexus during experimental colitis in guinea-pigTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Alan E. Lomax Intestinal secretion is regulated by submucosal neurones of the enteric nervous system. Inflammation of the intestines leads to aberrant secretory activity; therefore we hypothesized that the synaptic and electrical behaviours of submucosal neurones are altered during colitis. To test this hypothesis, we used intracellular microelectrode recording to compare the excitability and synaptic properties of submucosal neurones from normal and trinitrobenzene sulphonic acid (TNBS)-inflamed guinea-pig colons. Inflammation differentially affected the electrophysiological characteristics of the two functional classes of submucosal neurones. AH neurones from inflamed colons were more excitable, had shorter action potential durations and reduced afterhyperpolarizations. Stimulus-evoked fast and slow excitatory postsynaptic potentials (EPSPs) in S neurones were larger during colitis, and the incidence of spontaneous fast EPSPs was increased. In control preparations, fast EPSPs were almost completely blocked by the nicotinic receptor antagonist hexamethonium, whereas fast EPSPs in inflamed S neurones were only partially inhibited by hexamethonium. In inflamed tissues, components of the fast EPSP in S neurones were sensitive to blockade of P2X and 5-HT3 receptors while these antagonists had little effect in control preparations. Control and inflamed S neurones were equally sensitive to brief application of acetylcholine, ATP and 5-HT, suggesting that synaptic facilitation was due to a presynaptic mechanism. Immunoreactivity for 5-HT in the submucosal plexus was unchanged by inflammation; this indicates that altered synaptic transmission was not due to anatomical remodelling of submucosal nerve terminals. This is the first demonstration of alterations in synaptic pharmacology in the enteric nervous system during inflammation. [source] Comparative Anatomy of the Male Guinea-Pig and Human Lower Urinary Tract: Histomorphology and Three-Dimensional ReconstructionANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2001Neuhaus The guinea-pig is often used for experimental studies in urology. However, the anatomy of the lower urinary tract of the guinea-pig is poorly described in the literature. The structure and function of the lower urinary tract, i.e. continence, micturition and sexual function, are closely related to the gross anatomy of the pelvis and the fine structure of the musculature. We investigated the anatomy and histomorphology of the lower urinary tract by serial sections in male guinea-pigs and compared it to that in humans. Immunohistochemical stainings for alpha-smooth muscle cell actin were used to differentiate between smooth and striated muscles. By using whole pelvic preparations, including all internal organs preserved in their in situ location for three-dimensional reconstruction, we developed three-dimensional models, which elucidate the spatial relationship of all muscular structures and can help to deduce functional aspects of lower urinary tract function. In the guinea-pig, most of the muscles found in humans can be demonstrated in comparable location and extension. However, the structure of the prostate and the existence of the so-called coagulation glands define a significant difference in the morphology of the prostatic urethra. [source] The effects of selective phosphodiesterase III and V inhibitors on adrenergic and non-adrenergic, non-cholinergic relaxation responses of guinea-pig pulmonary arteriesAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 2 2003A. Tasatargil Summary 1 The aim of the present study was to investigate the role of several possible neurotransmitters in mediating non-adrenergic, non-cholinergic (NANC) relaxation, and the effects of phosphodiesterase (PDE) III and V inhibitors on adrenergic and NANC relaxation in branch pulmonary artery (PA) of guinea-pig. 2 Under the NANC conditions, electrical field stimulation (EFS, 60 V, 0.2 ms, 20 Hz) induced a tetrodotoxin-sensitive relaxation of the histamine-precontracted PA rings. The nitric oxide (NO) synthase inhibitor NG -nitro- l -arginine methyl ester (l -NAME, 10,4 m) and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10,5 m) partially inhibited the EFS-induced relaxation. The inhibitory effect of l -NAME was reversed completely by l -arginine (10,3 m), but not d -arginine (10,3 m). 3 This NANC relaxation was attenuated by 8-phenyltheophylline (10,5 m), a P1 -purinoceptor antagonist. 4 The NANC response was potentiated by 10,6 m zaprinast, a type V PDE inhibitor, but was unaffected by 3 × 10,6 m milrinone, a type III PDE inhibitor. 5 Sodium nitroprusside (SNP) caused a concentration-dependent vasodilator effect which was potentiated by zaprinast, but unaffected by milrinone. Moreover, the effect of combination of zaprinast with milrinone was not significantly different from that observed with zaprinast alone. 6 Isoprenaline produced a concentration-dependent vasodilatation in branch PA of guinea-pig which was potentiated by both zaprinast and milrinone, the efficacy of milrinone being greater than zaprinast. 7 These results suggest that both nitrergic and purinergic pathways are involved in mediating the NANC relaxation in branch PA of guinea-pig. The combination of PDE III or V inhibitors with vasorelaxant drugs may be a hopeful approach for the treatment of pulmonary hypertension. [source] The relative importance of the time-course of receptor occupancy and response decay on apparent antagonist potency in dynamic assaysAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2000M. Corsi 1 The potency of the ,1 -adrenoceptor antagonist atenolol was measured as an inhibitor of responses to isoprenaline in guinea-pig left atria. Measurements were made in two ways, firstly, by pre-incubating the atria with a given concentration of atenolol followed by an isoprenaline dose,response curve and, secondly, by measuring the response to isoprenaline followed by addition of atenolol. 2 It was found that the estimation of atenolol potency as an antagonist of ,1 -adrenoceptors by these two methods gave divergent results. Specifically, it was found that the isoprenaline-induced increased rate of myocardial relaxation was resistant to receptor blockade. Thus, the rate-limiting step in the relaxation response was dissociated from receptor activation and therefore, could not be used for the measurement of receptor occupancy. 3 In contrast, the positive inotropic response was very responsive to receptor occupancy. However, when atenolol was used to block a steady-state isoprenaline response, there was a complicating depression of basal inotropy after receptor blockade that obfuscated measurement of receptor blockade. 4 In general, these data indicated that the blockade of a steady-state agonist response to measure the potency of an antagonist might in some cases yield erroneous results. These studies indicate some caution in the interpretation of blockade responses in pre-contracted or pre-stimulated pharmacological preparations. [source] Nitric oxide (NO) modulation of PAF-induced cardiopulmonary action: interaction between NO synthase and cyclo-oxygenase-2 pathwaysBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2001Fulvia Fabi To further investigate into the mechanisms of PAF-induced cardiopulmonary actions, we examined the effects of the nitric oxide synthase (NOS) inhibitor L -N, -nitro- L -arginine (L -NNA), of the specific cyclooxygenase-2 (COX-2) inhibitor NS 398, and of the combined presence of both COX and NOS inhibitors on the PAF responses in the heart lung preparation of guinea-pig (HLP). In HLPs perfused with homologous blood, dose-response curves for the haemodynamic and bronchial effects of PAF (1 , 32 ng) were carried out in the absence or presence of L -NNA (200 ,M). L -NNA caused an increase in the resting pulmonary arterial pressure (PAP) without affecting the other basal values, and strongly potentiated the bronchoconstriction and pulmonary hypertension elicited by PAF. An enhancement of the PAF-induced actions on right atrial pressure (RAP) and cardiac output (CO) was also observed. All the effects of L -NNA were antagonized by L -arginine (2 mM). The presence of L -NNA in the perfusing blood of HLPs failed to affect the pulmonary hypertensive and bronchoconstrictor responses induced by the thromboxane A2 mimetic U46619 (0.05 , 1.6 ,g), 5-hydroxytryptamine (0.1 , 1.6 ,g), and histamine (0.1 , 1.6 ,g), thus suggesting that these PAF secondary mediators are not responsible for the hyper-responsiveness to PAF induced by L -NNA. Blocking COX-2 pathway with NS 398 (15 , 30 ,M) did not alter the cardiopulmonary resting variables. However, a reduction of the PAF-mediated pulmonary hypertension, but not of bronchoconstriction, was observed. When L -NNA was added to the perfusing medium of HLPs pre-treated with NS 398 or with indomethacin (15 ,M), the basal PAP values were enhanced. However, in the combined presence of COX and NOS inhibitors, only a slight increase in the hypertensive responses to the highest doses of PAF was observed, whereas the PAF mediated actions at bronchial and cardiac level were unaffected. This study indicates that (i) the cardiopulmonary actions induced by PAF are specifically modulated by endogenous NO through the NOS pathway, and (ii) COX-2 isoform is involved in the pulmonary hypertensive, but not bronchoconstrictor, effects of PAF. Furthermore, an interaction between PAF stimulated COX, particularly COX-2, and NOS pathways appears to take a functional role at both bronchial and cardiovascular level. British Journal of Pharmacology (2001) 134, 777,788; doi:10.1038/sj.bjp.0704311 [source] Activity of corneal nociceptive nerve fibers during allergic challenge of the ocular surfaceACTA OPHTHALMOLOGICA, Issue 2009J GALLAR Purpose The aim of this work was to study in vitro the spontaneous and stimulus-evoked electrical activity of corneal nociceptive nerve fibers during acute allergic inflammation of the ocular surface induced in the guinea-pig. Methods Animals received i.p. 10% ovalbumin (OVA). 14 days later, a 10µl drop of OVA was applied topically to each eye. Blinking and scratching movements directed to the eye were measured during 10 min, and ocular symptoms (edema and hyperemia) and tear rate were measured. Animals were killed afterwards and both eyes were immediately excised and mounted in a superfused (32°C) recording chamber. Electrical activity of corneal sensory receptors was recorded from nerve filaments dissected from the ciliary nerves. Mechanical (calibrated von Frey hairs), thermal (bath solution temperature down to 20°C or up to 52°C), and chemical stimulation (30s-pulses of 98%CO2) were performed. Spontaneous (SA) and stimulus-evoked activity were analyzed. Results After the allergic challenge, eye-scratching behavior was present in 4 out of 15 animals and blinking movements increased from 1±0.05 to 26±5. Tearing also increased compared to control (33±3 vs. 5±1 mm). Compared to naive eyes, proportion of nociceptors with SA (17% vs. 5%) and spontaneous discharge rate (0.13±0.07 vs. 0.01±0.01 imp/s) were increased. Mechanical threshold of mechano-nociceptive units decreased significantly (0.37±0.05 vs. 0.89±0.13 mN). Chemosensitivity of polymodal nociceptors was slightly increased (1.87±0.42 vs. 1.34±0.23 imp/s). Conclusion Changes in corneal sensory nerve activity observed acutely after allergic challenge of the eye surface may constitute the basis of itching and discomfort sensations, and hypersensitivity observed in allergic patients. [source] Cochlear delays measured with distortion product otoacoustic emissionsCLINICAL OTOLARYNGOLOGY, Issue 4 2000S. Schneider Objective. To investigate the generation place and mechanism of distortion product otoacoustic emissions (DPOAEs) by measuring their delays. Materials and methods. Two tones with the frequencies f1 and f2 (f1 < f2) were presented to the ear canal of a guinea-pig by two telephones. The frequency of one of the tones was varied while the other was kept constant. The amplitude and phase of four DPOAEs (2f1,f2, 3f1,2f2, 4f1,3f2 and 2f2,f1) were measured as a function of frequency. From the phase vs. frequency relation of the DPOAE the cochlear delay is calculated, which is related to the place where the emission is generated. Results. Delays that were determined by varying the f1 frequency appear to be equal for all four distortion products. When the f2 frequency is varied, the delays of the DPOAEs with frequencies 2f1,f2, 3f1,2f2, 4f1,3f2 and 2f2,f1 are significantly larger than the delays of the DPOAE with frequency 2f2,f1. Conclusion. The DPOAEs 2f1,f2, 3f1,2f2 and 4f1,3f2 are generated at the same cochlear place, close to the characteristic place of the f2 frequency. The DPOAE with frequency 2f2,f1 comes from a more basal location in the cochlea. [source] Effects of repeated injections of fibroblast-stimulating lipopeptide-1 on fever, formation of cytokines, and on the responsiveness to endotoxin in guinea-pigsACTA PHYSIOLOGICA, Issue 1 2009A. Greis Abstract Aims:, We investigated, whether the Toll-like receptors (TLRs)-2/6-agonist fibroblast-stimulating lipopeptide-1 (FSL-1), like the TLR-4 agonist lipopolysaccharide (LPS), induces a state of tolerance. We further tested the influence of repeated pre-treatment with FSL-1 on the animals' responsiveness to LPS. Methods:, Abdominal temperature was recorded in unrestrained guinea-pigs with intra-abdominally implanted radiotransmitters. Circulating concentrations of tumour necrosis factor (TNF) and interleukin-6 (IL-6) were measured with specific bioassays. We tested the effects of intra-arterial (i.a.) or intraperitoneal (i.p.) injections of 100 ,g kg,1 FSL-1, repeated five times at intervals of 3 days. The animals' responses to i.a. or i.p. injections of 10 ,g kg,1 LPS were determined another 3 days later and compared to those of naïve guinea-pigs. Results:, The FSL-1-induced TNF peak was significantly attenuated starting with the third i.a. administration, while fever was unimpaired and the IL-6-peak just tended to decrease. Fever and IL-6 in response to i.a. injections of LPS were identical in both groups, while circulating TNF was higher in naïve compared to FSL-1 pre-treated animals. The effects of repeated i.p. injections of FSL-1 were more pronounced resulting in attenuation of fever as well as circulating TNF and IL-6, the strongest reduction observed after the third stimulation with FSL-1. Repeated i.p. pre-treatment with FSL-1 induced hyporesponsiveness to i.p. administration of LPS compared to naïve animals with regard to fever and especially with regard to LPS-induced formation of cytokines. Conclusions:, There is a development of tolerance to FSL-1 and cross-tolerance between FSL-1 and LPS depending on the route of administration of the respective TLR-2/6 and TLR-4 agonists. [source] Nerve growth factor increases airway responses and decreases levels of exhaled nitric oxide during histamine challenge in an in vivo guinea-pig modelACTA PHYSIOLOGICA, Issue 2 2001S. G. Friberg There is a growing body of evidence supporting the idea that nerve growth factor (NGF) may be involved in the development of asthma-associated symptoms, such as airway hyper-responsiveness. Increased levels of NGF have recently been described in serum and in the airways of asthmatics. We have examined whether exhaled nitric oxide (NO) levels might be altered during the increased airway responses upon NGF treatment in guinea-pigs in vivo. Intravenous (i.v.) administration of histamine normally elicits a rapid peak in insufflation pressure (IP) and in exhaled NO, followed by a period of decreased concentrations of exhaled NO. Anaesthetized guinea-pigs were pre-treated intravenously with either saline, 4 or 80 ng kg,1 NGF 30 min before i.v. challenge with 16 ,g kg,1 histamine. At 80 ng kg,1 NGF significantly enhanced the airway obstruction caused by histamine, whereas the peak acute increase in exhaled NO was not enhanced. Following the increase, came a rapid drop, an effect enforced in the NGF treated animals. Subsequently, the time to return to 90% of resting exhaled NO was increased, from 12 min in saline-treated animals to 48 min in NGF-treated animals. Our data confirm that NGF can enhance airway responses to histamine. Moreover, our study shows a decrease in exhaled NO following a histamine challenge, an effect enhanced by NGF. A reduced ability to release exhaled NO may be a mechanism for increased airway responses during elevated NGF levels. The interaction between NGF and airway NO formation, and its relation to airway responses, merit further investigation. [source] Enhancement of Ca2+ -regulated exocytosis by indomethacin in guinea-pig antral mucous cells: arachidonic acid accumulationEXPERIMENTAL PHYSIOLOGY, Issue 1 2006Shoko Fujiwara Ca2+ -regulated exocytosis is enhanced by an autocrine mechanism via the PGE2,cAMP pathway in antral mucous cells of guinea-pigs. The inhibition of the PGE2,cAMP pathway by H-89 (an inhibitor of protein kinase A, PKA) or aspirin (ASA, an inhibitor of cyclo-oxygenase, COX) decreased the frequency of ACh-stimulated exocytotic events by 60%. Indomethacin (IDM, an inhibitor of COX), however, decreased the frequency of ACh-stimulated exocytotic events only by 30%. Moreover, IDM increased the frequency of ACh-stimulated exocytotic events by 50% in H-89-treated or ASA-treated cells. IDM inhibits the synthesis of Prostaglandin (PGG/H) and (15R)-15-hydroxy-5,8,11 cis-13-trans-eicosatetraenoic acid (15R-HPETE), while ASA inhibits only the synthesis of PGG/H. Thus, IDM may accumulate arachidonic acid (AA). AACOCF3 or N -(p -amylcinnamoyl) anthranilic acid (ACA; both inhibitors of phospholipase A2, PLA2), which inhibits AA synthesis, decreased the frequency of ACh-stimulated exocytotic events by 60%. IDM, however, did not increase the frequency in AACOCF3 -treated cells. AA increased the frequency of ACh-stimulated exocytotic events in AACOCF3 - or ASA-treated cells, similar to IDM in ASA- and H-89-treated cells. Moreover, in the presence of AA, IDM did not increase the frequency of ACh-stimulated exocytotic events in ASA-treated cells. The PGE2 release from antral mucosa indicates that inhibition of PLA2 by ACA inhibits the AA accumulation in unstimulated and ACh-stimulated antral mucosa. The dose,response study of AA and IDM demonstrated that the concentration of intracellular AA accumulated by IDM is less than 100 nm. In conclusion, IDM modulates the ACh-stimulated exocytosis via AA accumulation in antral mucous cells. [source] Enhancement of protective humoral immune responses against Herpes simplex virus-2 in DNA-immunized guinea-pigs using protein boostingFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2008Fatemeh Fotouhi Abstract Genital Herpes is a common sexually transmitted disease that is caused mostly by Herpes simplex virus type 2 (HSV-2). Its prevalence has increased in developing countries in spite of the availability of valuable antiviral drug therapy. Considering the importance of HSV-2 infections, effective vaccines remain the most likely hope for controlling the spread of HSV diseases. In the present study, the complete HSV-2 glycoprotein D gene was isolated and cloned into different plasmid vectors to construct a DNA vaccine and prepare recombinant subunit vaccines using a baculovirus expression system. The vaccines were tested alone or in combination to evaluate their ability to induce protective immunity in guinea-pigs against genital HSV infections. Immunization elicited humoral responses as measured by neutralization tests and enzyme-linked immunosorbent assay, and immunized animals had less severe genital skin disease as well as reduced replication of the challenging virus in the genital tract during experimental infection. Our results further demonstrate that DNA priming-protein boosting induced a neutralizing antibody titer higher than that obtained with DNA,DNA vaccination. The massive increase of antibody titer following DNA priming-protein boosting might be attributed to a recall of B cell memory. [source] A comparative histological evaluation of the biocompatibility of materials used in apical surgeryINTERNATIONAL ENDODONTIC JOURNAL, Issue 11 2004C. J. A. Sousa Abstract Aim, To evaluate the biological properties of a variety of materials that could be used in apical surgery. Methodology, The intraosseous implant technique recommended by the FDI (1980) and ADA (1982) was used to test the following materials: zinc oxide-eugenol (ZOE), mineral trioxide aggregate (MTA), and Z-100 light-cured composite resin. Thirty guinea-pigs, 10 for each material, divided into experimental periods of 4 and 12 weeks, received one implant on each side of the lower jaw symphysis. The connective tissue response alongside the lateral wall outside the cup served as a negative control for the technique. At the end of the observation periods, the animals were killed and the specimens prepared for routine histological examination to evaluate their biocompatibility. Results, The reaction of the tissue to the materials diminished with time. The ZOE cement was highly toxic during the 4-week experimental period, but this profile changed significantly after 12 weeks, when it showed biocompatible characteristics. MTA and Z-100 showed biocompatibility in this test model at both time periods. Conclusions, MTA and Z-100 composite were biocompatible at 4 and 12 weeks in this experimental model. [source] A novel approach to assessing percutaneous VX poisoning in the conscious guinea-pig,JOURNAL OF APPLIED TOXICOLOGY, Issue 5 2008Helen Mumford Abstract Nerve agents like VX (S-2-diisopropylaminoethyl-O-ethyl-methylphosphonothiolate) are potent irreversible acetylcholinesterase (AChE) inhibitors. Following percutaneous nerve agent exposure there is a slower rate of absorption, later onset and longer duration of signs of poisoning. Relatively little is known about the physiological effects of percutaneously applied nerve agent in unanaesthetised laboratory animals. Heart rate (ECG), brain electrical activity (EEG), body temperature, locomotor activity and clinical signs were monitored following percutaneous application of VX to conscious guinea-pigs. A fall in heart rate (bradycardia) preceded incapacitation following the highest VX dose, and occurred in the absence of incapacitation at the lower doses. Following the highest dose of VX (0.592 mg kg,1) three out of four animals died within 24 h. The lower two doses of VX (0.296 and 0.148 mg kg,1), produced extended periods of bradycardia in the absence of observable signs of poisoning. Bradycardia preceded, or occurred in the absence of, a temperature decrease; seizure-like EEG changes were not observed at any of the VX doses tested. Acetylcholinesterase activity was significantly inhibited in the blood and most brain areas at 48 h. There were significant dose-related decreases in body weight at 24 and 48 h following VX. This preliminary study suggests that decreased heart rate may be an early sign of the toxic effects of VX, whereas temperature and observable clinical signs are not good early indicators of percutaneous VX poisoning in this animal model. Future studies will use this model to assess the benefit of administering medical countermeasures in response to a defined decrease in heart rate. © Crown Copyright 2007. Reproduced with the permission of the Controller of HMSO. Published by John Wiley & Sons, Ltd. This article was published online on 5 December 2007. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected [30 May 2008]. [source] 1,8-Cineole induces relaxation in rat and guinea-pig airway smooth muscleJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2009Nilberto Robson Falcão Nascimento Abstract Objectives 1,8-Cineole is a monoterpene with anti-inflammatory, vascular and intestinal smooth muscle relaxant activity. We have evaluated the potential bronchodilatatory activity of this compound. Methods 1,8-Cineole was tested against carbachol, histamine, K+ 80 mM and ovalbumin-induced bronchial contractions in Wistar rat or guinea-pig tissues. Some of the guinea-pigs had been previously sensitized with an intramuscular injection of 5% (w/v) ovalbumin/saline solution. Control animals received 0.3 ml saline. In separate experimental groups the response to 1,8-cineole (1,30 mg/kg), phenoterol (0.05,5 mg/kg) or vehicle (0.3% Tween in saline) was studied. Key findings 1,8-Cineole decreased, in vivo, rat bronchial resistance with similar efficacy as phenoterol (66.7 ± 3.2% vs 72.1 ± 5.3%). On the other hand, the maximal relaxant response to 1,8-cineole in carbachol-precontracted rat tracheas was 85.5 ± 5.7% (IC50 = 408.9 (328,5196) ,g/ml) compared with 80.2 ± 4.8% (IC50 = 5.1 (4.3,6.1) ,g/ml) with phenoterol. The addition of 1,8-cineole to guinea-pig tracheal rings tonically contracted with K+ 80 mM induced a concentration-related relaxation. The maximal relaxation elicited by 1,8-cineole was 113.6 ± 11.7% (IC50 127.0 (115.9,139.2) ,g/ml) compared with 129.7 ± 14.6% (IC50 0.13 (0.12,0.14) ,g/ml) achieved after phenoterol administration. In addition, the incubation of tracheal rings with 1,8-cineole (100, 300 or 1000 ,g/ml), 15 min before inducing phasic contractions with K+ 80 mM, decreased the maximal amplitude of the contraction by 31.6 ± 4.6, 75.7 ± 2.7 and 92.2 ± 1.5%, respectively. In another set of experiments, neither the maximal response nor the IC50 for the 1,8-cineole-induced relaxation were different between normal and ovalbumin-sensitized tissues. Moreover, the relaxation of bronchial rings contracted after exposure to 1 ,g/ml ovalbumin occurred at a faster rate in rings pre-incubated with 1,8-cineole when compared with rings pre-incubated with vehicle only (Tween 0.3%). Therefore, in the first minute after the antigen challenge, the tracheal tissue relaxed after the peak contraction by 6.5, 21.4 (P < 0.05 vs control) and 66.9% (P < 0.05 vs control) in the presence of 100, 300 or 1000 ,g/ml 1,8-cineole, respectively. Conclusions 1,8-Cineole relaxed rat and guinea-pig (nonsensitized and ovalbumin-sensitized) airway smooth muscle by a nonspecific mechanism. [source] Bronchodilatory effects of the aqueous extract of Gynostemma pentaphyllum and gypenosides III and VIII in anaesthetized guinea-pigsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2005Clara Circosta The bronchodilatory activity of the aqueous extract of Gynostemma pentaphyllum Makino leaves was investigated in anaesthetized guinea-pigs and compared with two of its isolated gypenosides (III and VIII). The results showed that the intravenous administration of the decoction of G. pentaphyllum (2.5, 5 or 10 mg kg,1) decreased bronchial resistance in basal conditions and significantly (P<0.01) reduced (68% inhibition) the bronchoconstrictor action of histamine. Furthermore, the extract antagonized (80% inhibition) the bronchoconstrictor response induced by the antigen in sensitized guinea-pigs. Gypenosides III (0.7 mg kg,1, i.v.) and VIII (0.3 mg kg,1, i.v.) caused a similar protective effect in both experimental models used; however, the duration and the intensity of the action was less than that of the extract containing corresponding quantities of gypenosides III and VIII. This study confirmed the validity of the traditional use of this plant in the treatment of asthma and other respiratory disorders. [source] Involvement of thromboxane A2 (TXA2) in the early stages of oleic acid-induced lung injury and the preventive effect of ozagrel, a TXA2 synthase inhibitor, in guinea-pigsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2004Yoichi Ishitsuka ABSTRACT An intravenous injection of oleic acid into animals can produce a lung injury with hypoxaemia and pulmonary vascular hyper-permeability. Although oleic acid lung injury is used as a model of acute respiratory distress syndrome (ARDS), the precise mechanisms of the lung injury are still unclear. We have investigated whether thromboxane A2 (TXA2) participated in the lung injury and have evaluated the efficacy of ozagrel, a TXA2 synthase inhibitor, on the lung injury in guinea-pigs. Oleic acid injection increased the plasma level of TXB2, a stable metabolite of TXA2, and the time-course of plasma TXB2 was similar to that of the decreased partial oxygen pressure of arterial blood (Pao2) induced with oleic acid. Ozagrel administered intravenously 30 min before oleic acid injection prevented the decrease in Pao2 and pulmonary vascular hyper-permeability. It also prevented increases in lactate dehydrogenase activity, a measure of lung cell injury, TXB2 and its weight ratio to 6-keto prostaglandin F1 , in bronchoalveolar lavage fluid. Although ozagrel administered simultaneously with oleic acid ameliorated the decrease in Pao2, post treatment showed little effect. We suggest that TXA2 participated in the oleic acid lung injury, as an "early phase" mediator, and rapidly-acting TXA2 synthase inhibitors were effective in the prevention of acute lung injury. [source] ,-Monoisostearyl glyceryl ether enhances percutaneous penetration of indometacin in-vivoJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2002Atsushi Suzuki ABSTRACT Molecules that reversibly remove the barrier resistance of skin enhance penetration. ,-Monoisostearyl glyceryl ether (GE-IS) is a novel compound that can be used as a non-ionic surfactant and increases percutaneous penetration of indometacin in rat abdominal skin in-vitro. The present study investigated GE-IS-induced enhancement of indometacin penetration in-vivo. When 1% GE-IS in propylene glycol was applied to rat abdominal skin, serum and muscle concentrations of indometacin increased markedly. Anti-inflammatory activities of test solutions containing both indometacin and GE-IS were investigated in experimental models of acute and chronic inflammation. Application of indometacin with GE-IS to the skin produced greater inhibitory effects on carrageenan-induced rat paw oedema, UV-induced erythema in guinea-pigs, and adjuvant arthritis in rats, compared with application of indometacin alone. The results suggest that GE-IS enhances penetration in-vivo and improves the anti-inflammatory effects of indometacin in animal models. Thus, GE-IS might contribute to the development of cosmetic or medical formulations to improve transfer of bioactive substances to hypodermal sites. [source] Body Distribution of Poly- DL -lactide-poly(ethylene glycol) Microspheres with Entrapped Leptospira interrogans Antigens Following Intravenous and Oral Administration to Guinea-pigsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2000XIAOHONG LI Poly- DL -lactide-poly(ethylene glycol) (PELA) microspheres with entrapped antigens were administered intravenously and orally into guinea-pigs to quantitatively determine the in-vivo distribution and release profiles. PELA microspheres containing 125I-labelled outer-membrane protein Leptospira interrogans antigens (125I-OMP) were prepared by double-emulsion solvent extraction procedure, and characterized with respect to size, morphology and in-vitro release profiles. The fractured sections of liver and spleen were inspected by scanning electron microscopy, which indicated that microspheres had successfully been entrapped within the above tissues after intravenous injection and oral administration. At predetermined intervals, the blood and such tissues as the liver, spleen, kidney, thyroid, small intestine and mesentery were collected, and the radioactivity was measured by gamma scintillation counting. Following intravenous administration, 56.7% of administered microspheres were accumulated in immunization-related tissues, and 40.1% of microspheres were located in the liver and spleen. However, there was limited uptake efficiency (8.33%) following oral administration, and 49.5% of the absorbed microspheres were located in the intestinal mucosa. Compared with in-vitro release, the in-vivo release profiles of 125I-OMP from PELA microspheres, determined from the decreasing radioactivity in the above tissues, were much faster and the burst effect was higher. Antigen-loaded PELA microspheres were efficiently entrapped within immunization-related tissues after intravenous administration, but orally administered PELA microspheres showed limited uptake efficiency. Further investigation is needed to improve intestinal absorption. [source] In Vivo Dysfunction of the Term Alveolar Macrophage After in Utero Ethanol ExposureALCOHOLISM, Issue 2 2007Xiao-Du Ping Background: The effects of in utero alcohol exposure on the immune function of the newborn remain under investigation. Fetal ethanol (ETOH) exposure increases oxidative stress in the developing lung, in part due to decreased availability of the antioxidant glutathione (GSH). We have previously shown that in utero ETOH impairs alveolar macrophage phagocytosis and viability in the premature pup, while maintaining GSH availability with maternal supplementation of S -adenosyl-methionine (SAM) during ETOH ingestion improves macrophage function and viability. We hypothesized that dysfunction of the neonatal alveolar macrophage exposed to ETOH in utero would persist at term gestation. Methods: Using a guinea-pig model of fetal ETOH exposure, timed-pregnant guinea-pigs were pair-fed ETOH±the GSH precursor SAM and the diet continued until spontaneous delivery. Term alveolar macrophages were evaluated using fluorescent microscopy for phagocytosis and apoptosis after in vitro incubation with Staphalococcus aureus. Using an in vivo model of intranasal Staph. aureus inoculation, the in vivo function of the term alveolar macrophage was also investigated using confocal fluorescent analysis. Results: In utero ETOH exposure increased oxidant stress in the alveolar macrophage and decreased phagocytosis and viability in vitro and in vivo. Confocal analysis of phagocytosis in vivo demonstrated a marked impairment of internalization of the bacteria by the ETOH-exposed alveolar macrophage. The addition of SAM during maternal ETOH ingestion prevented loss of alveolar macrophage function and viability in vitro and in vivo. Conclusions: In utero ETOH exposure impairs alveolar macrophage function and viability in vitro and in vivo even at term gestation. The ETOH-induced changes in macrophage function and viability can be ablated with maternal SAM supplementation. Further investigations are required to identify the mechanisms of ETOH-induced derangement of phagocytosis in the neonatal alveolar macrophage and the clinical ramifications of altered immune function after in utero alcohol exposure for the newborn. [source] | |||||||||||||