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Kinds of Pigs Selected AbstractsThe Defibrillation Efficacy of High Frequency Alternating Current Sinusoidal Waveforms in Guinea PigsPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 2p1 2003SCOTT J. ROBERTS ROBERTS, S.J., et al.: The Defibrillation Efficacy of High Frequency Alternating Current Sinusoidal Waveforms in Guinea Pigs. There have been few basic studies of alternating current (AC) defibrillation, despite growing interest in the ability of AC to terminate or alter ongoing fibrillation. Based on fibrillation threshold testing, it has been suggested that cardiac tissue is most sensitive to long duration, low strength AC stimulation at around 50 Hz. This has not been directly tested for defibrillation. Two subcutaneous electrodes were placed 40 mm apart on opposing aspects of the guinea pig thorax. Seven seconds were allowed to elapse between fibrillation initiation and defibrillation. The tested waveforms were at 50, 100, 200, 500, and 1000 Hz with 2, 4, 8, 16, and 32-cycles. The efficacy of every waveform was measured using a single stimulus in a large population of animals. Forty-one guinea pigs were used in the fixed energy group. Thirty-three guinea pigs were used in the fixed amplitude group with additional 1-cycle waveforms tested. The 200-Hz and the 2-cycle waveforms were significantly more efficacious than those at other frequencies(P < 0.02)and other durations(P < 0.001). The 50-Hz waveforms were the least successful. Amplitude, not duration or energy, was the determinate of efficacy for 2-cycle (the most efficacious) waveforms. Unlike low strength stimulation, defibrillation strength stimuli are most effective with high frequency (200 Hz) pulses (2 cycles). (PACE 2003; 26[Pt. I]:599,604) [source] Short-Term Antiandrogen Flutamide Treatment Causes Structural Alterations in Somatic Cells Associated with Premature Detachment of Spermatids in the Testis of Pubertal and Adult Guinea PigsREPRODUCTION IN DOMESTIC ANIMALS, Issue 3 2010LR Maschio Contents In spite of widespread application of flutamide in the endocrine therapies of young and adult patients, the side effects of this antiandrogen on spermatogenesis and germ-cell morphology remain unclear. This study evaluates the short-term androgen blockage effect induced by the administration of flutamide to the testes of pubertal (30-day old) and adult (65- and 135-day old) guinea pigs, with an emphasis on ultrastructural alterations of main cell types. The testes removed after 10 days of treatment with either a non-steroidal antiandrogen, flutamide (10 mg/kg of body weight) or a pharmacological vehicle alone were processed for histological, quantitative and ultrastructural analysis. In pubertal animals, flutamide androgenic blockage induces spermatogonial differentiation and accelerates testes maturation, causing degeneration and detachment of primary spermatocytes and round spermatids, which are subsequently found in great quantities in the epididymis caput. In post-pubertal and adult guinea pigs, in addition to causing germ-cell degeneration, especially in primary spermatocytes, and leading to the premature detachment of spherical spermatids, the antiandrogen treatment increased the relative volume of Leydig cells. In addition, ultrastructural evaluation indicated that irrespective of age antiandrogen treatment causes an increase in frequency of organelles involved with steroid hormone synthesis in the Leydig cells and a dramatic accumulation of myelin figures in their cytoplasm and, to a larger degree, in Sertoli cells. In conclusion, the transient exposition of the guinea pigs to flutamide, at all postnatal ages causes some degenerative lesions including severe premature detachment of spermatids and accumulation of myelin bodies in Leydig and Sertoli cells, compromising, at least temporarily, the spermatogenesis. [source] Upregulation of Group 1 CD1 Antigen Presenting Molecules in Guinea Pigs with Experimental Autoimmune Encephalomyelitis: An Immunohistochemical StudyBRAIN PATHOLOGY, Issue 1 2003Barbara Cipriani In humans, group 1 CD1 glycoproteins present foreign and self lipid and glycolipid antigens to Tcells. Homologues of these molecules are not found in mice or rats but are present in guinea pigs (GPs). We examined CD1 and MHC class II expression in the central nervous system (CNS) of GPs sensitized for experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. In normal GPs and the uninflamed CNS, low-level MHC class II (MHC II) immunoreactivity occurred on vascular elements, meningeal macrophages and parenchymal microglial cells, whereas immunoreactivity for CD1 was absent. In the inflamed CNS, the majority of infiltrating cells were MHC II+ and microglia showed increased expression. CD1 immunoreactivity was detected on astrocytes and subsets of inflammatory cells including B cells and macrophages. Minimal CD1 and MHC II co-expression was noted on inflammatory cells or glia. We conclude that group 1 CD1 molecules are strongly upregulated in the inflamed CNS on subsets of cells distinct from the majority of MHC II bearing cells. The expression of CD1 proteins in such lesions broadens the potential repertoire of antigens recognized at these sites and highlights the value of the GP as a model for studies of the relevance of CD1 molecules in host defense and autoimmune diseases. [source] Brief exposure to the biological mother "potentiates" the isolation behavior of precocial Guinea pig pupsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 8 2006Michael B. Hennessy Abstract When isolated rat pups are briefly reunited with a lactating female, her subsequent removal leads to a dramatic increase in the emission of ultrasonic vocalizations, but not other behaviors. Whether this socially induced augmentation of isolation behavior (i.e., "potentiation") is characteristic only of altricial rodents is not known. Therefore, we examined precocial guinea pig pups in a potentiation paradigm. Ten-day-old guinea pigs were isolated in a test cage for 10 min, at which time they were then placed into a second cage for 5 min that either contained a companion or, for controls, was empty. Pups were then isolated again in the test cage for a second 10-min period. Control pups showed a significant reduction in vocalizing and locomotor activity from the first to second isolation period. Exposure to the biological mother prevented the decline in both behaviors (Experiment 1), whereas exposure to a familiar littermate (Experiment 2) had no effect, and exposure to an unfamiliar lactating female (Experiment 3) had only a minimal effect on locomotor activity. The results show that potentiation of isolation behaviors is not limited to altricial rodents, and suggest that specific characteristics of the effect (i.e., its magnitude, the specific behaviors affected, and the selectivity of the response to particular social partners) varies with the abilities and requirements of the young, as well as the behavioral ecology of the species in question. © 2006 Wiley Periodicals, Inc. Dev Psychobiol 48: 653,659, 2006. [source] An immunogold investigation of the distribution of GABA and glycine in nerve terminals on the somata of spherical bushy cells in the anteroventral cochlear nucleus of guinea pigEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2004S. Mahendrasingam Abstract Spherical bushy neurons in the anteroventral cochlear nucleus receive glutamatergic primary terminals from the cochlear nerve and terminals of noncochlear (i.e. nonprimary) origin, many of which colocalize gamma-aminobutyric acid (GABA) and glycine. Here the relationship between GABA and glycine in these terminals has been investigated using postembedding immunogold labelling. A significant negative correlation was found between the density of terminal labelling for GABA and for glycine in four guinea pigs. Terminals could be divided into three categories, GABA-only, glycine-only, or colocalizing depending on whether they had a significantly higher labelling density for either amino acid than the primary terminals. The overall labelling density in all four animals was significantly greater for GABA in GABA-only terminals than colocalizing ones but similar for glycine in both. Within the terminals, the labelling density over synaptic vesicles, nonvesicular regions of cytoplasm and mitochondria was also investigated. No significant difference was detected in the labelling density of vesicles compared with nonvesicular regions for either amino acid. However, a significant difference was found between the overall labelling density over mitochondria and nonvesicular regions for both. There was also significantly more mitochondrial GABA labelling in GABA-only terminals compared to colocalizing terminals but mitochondrial glycine labelling was similar in glycine-only and colocalizing terminals. Thus the level of GABA is higher in single than in colocalizing terminals, particularly in the mitochondria, but similar for glycine in both. It is possible therefore that the presence of glycine affects the level of GABA in the nonprimary terminals but that the presence of GABA does not affect the level of glycine. [source] Trace eyeblink conditioning in decerebrate guinea pigsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2003Sadaharu Kotani Abstract We investigated the trace eyeblink conditioning in decerebrate guinea pigs to elucidate the possible role of the cerebellum and brainstem in this hippocampus-dependent task. A 350-ms tone conditioned stimulus was paired with a 100-ms periorbital shock unconditioned stimulus with a trace interval of either 0, 100, 250 or 500 ms. Decerebrate animals readily acquired the conditioned response with a trace interval of 0 or 100 ms. Even in the paradigm with a 500-ms trace interval, which is known to depend critically on the hippocampus in all animal species examined, the decerebrate guinea pigs acquired the conditioned response, which had adaptive timing as well as in the other paradigms with a shorter trace interval. However, it took many more trials to learn in the 500-ms trace paradigm than in the shorter trace interval paradigms, and the conditioned response expression was unstable from trial to trial. When decerebrate animals were conditioned step by step with a trace interval of 100, 250 and 500 ms, sequentially, they easily acquired the adaptive conditioned response to a 500-ms trace interval. However, the frequency of conditioned responses decreased after the trace interval was shifted from 250 ms to 500 ms, which was not observed after the shift from 100 ms to 250 ms. These results suggest that the cerebellum and brainstem could maintain the ,trace' of the conditioned stimulus and associate it with the unconditioned stimulus even in the 500-ms trace paradigm, but that the forebrain might be required for facilitating and stabilizing the association. [source] On the origin of intrinsic matrix of acellular extrinsic fiber cementum: Studies on growing cementum pearls of normal and bisphosphonate-affected guinea pig molarsEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 3 2002Chantha K. Jayawardena Cementum pearls (CPs) belong to a type of acellular extrinsic fiber cementum (AEFC) that form on the maturing enamel of guinea pig molars. This study aimed to elucidate the forming process of intrinsic matrix of AEFC using the CPs of normal and bisphosphonate-affected guinea pig molars as experimental models. A group of guinea pigs were subjected to continuous administration of 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) for 2 wk to inhibit mineralization of growing CPs. Fenestration of the enamel organ and migration of periodontal cells on to the exposed surface of maturing enamel appeared to be unaffected by HEBP, whereas de novo formation as well as growth of pre-existing CPs did not proceed under the same conditions. Immunoreactions for osteopontin were located exclusively on the mineralized matrix of preformed CPs, implying the absence of additional deposition or accumulation of putative intrinsic cementum matrix on the affected CPs, where the propagation of mineral phase had been arrested. In both normal and HEBP-treated groups, distinct enzymatic reactions for alkaline phosphatase appeared on the cells of the periodontal ligament associated closely with the sites of CP formation, and along the mineralization front of CPs. These observations suggest that the mineralization process per se plays a central role in the deposition of AEFC matrix and that alkaline phosphatase of periodontal cells penetrating through the enamel organ to the maturing enamel surface plays a key role in the mineralization process of CPs. [source] N -acetylcysteine inhibits chromium hypersensitivity in coadjuvant chromium-sensitized albino guinea pigs by suppressing the effects of reactive oxygen speciesEXPERIMENTAL DERMATOLOGY, Issue 8 2010Bour-Jr Wang Please cite this paper as: N -acetylcysteine inhibits chromium hypersensitivity in coadjuvant chromium-sensitized albino guinea pigs by suppressing the effects of reactive oxygen species. Experimental Dermatology 2010; 19: e191,e200. Abstract Background:, Chromium hypersensitivity is an important issue in occupational skin disease. When hexavalent chromium enters the cell, it can be reduced to trivalent chromium, resulting in the formation of reactive oxygen species (ROS). ROS are considered to play an important role in the progression of allergic contact dermatitis. N -acetylcysteine (NAC) could increase glutathione levels in the skin and act as an antioxidant. Aims:, We attempted to demonstrate that NAC could inhibit chromium hypersensitivity in a coadjuvant chromium-sensitized albino guinea pig model by counteracting the formation of ROS. Methods:, We utilized a coadjuvant chromium-sensitized albino guinea pig model to evaluate both the severity of the skin reaction by intradermal and epicutaneous elicitation tests and the sensitization rate of chromium hypersensitivity in NAC-treated and NAC-untreated albino guinea pigs (GP). Furthermore, three ROS parameters, including H2O2, malondialdehyde (MDA) levels in the skin and the oxygen radical absorbance capacity (ORAC) in plasma, were analyzed in NAC-treated and NAC-untreated coadjuvant chromium-sensitized albino GP. Results:, The severity of the skin reaction in the intradermal and epicutaneous elicitation test significantly diminished when the albino GP were treated with a dose of 1200 mg/kg/day of NAC. This dose also significantly decreased the sensitization rate of chromium hypersensitivity. In addition, treatment with 1200 mg/kg/day of NAC significantly reduced the H2O2 and MDA levels in the skin and significantly increased the ORAC in the plasma of albino GP. Therefore, NAC could be a potential chemopreventative agent to prevent the progression of chromium hypersensitivity. [source] Mycobacterium tuberculosis possesses a functional enzyme for the synthesis of vitamin C, L -gulono-1,4-lactone dehydrogenaseFEBS JOURNAL, Issue 19 2006Beata A. Wolucka The last step of the biosynthesis of l -ascorbic acid (vitamin C) in plants and animals is catalyzed by l -gulono-1,4-lactone oxidoreductases, which use both l -gulono-1,4-lactone and l -galactono-1,4-lactone as substrates. l -Gulono-1,4-lactone oxidase is missing in scurvy-prone, vitamin C-deficient animals, such as humans and guinea pigs, which are also highly susceptible to tuberculosis. A blast search using the rat l -gulono-1,4-lactone oxidase sequence revealed the presence of closely related orthologs in a limited number of bacterial species, including several pathogens of human lungs, such as Mycobacterium tuberculosis, Pseudomonas aeruginosa, Burkholderia cepacia and Bacillus anthracis. The genome of M. tuberculosis, the etiologic agent of tuberculosis, encodes a protein (Rv1771) that shows 32% identity with the rat l -gulono-1,4-lactone oxidase protein. The Rv1771 gene was cloned and expressed in Escherichia coli, and the corresponding protein was affinity-purified and characterized. The FAD-binding motif-containing Rv1771 protein is a metalloenzyme that oxidizes l -gulono-1,4-lactone (Km 5.5 mm) but not l -galactono-1,4-lactone. The enzyme has a dehydrogenase activity and can use both cytochrome c (Km 4.7 µm) and phenazine methosulfate as exogenous electron acceptors. Molecular oxygen does not serve as a substrate for the Rv1771 protein. Dehydrogenase activity was measured in cellular extracts of a Mycobacterium bovis BCG strain. In conclusion, M. tuberculosis produces a novel, highly specific l -gulono-1,4-lactone dehydrogenase (Rv1771) and has the capacity to synthesize vitamin C. [source] Neurochemical regulation of swallowing reflex in guinea pigsGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1-2 2001Yu X Jia Background: Most peripheral afferent fibers involved in swallowing travel through the glossopharyngeal and vagus nerves and terminate in the nucleus of the tractus solitarius (NTS) and nodose ganglion (NG). Sensory neurons within the NTS and NG contain several neurotransmitters, including acetylcholine, histamine, serotonin and dopamine. The roles of these four neurotransmitters were investigated. Methods: The effects of atropine (muscarinic cholinergic receptor antagonist); pyrilamine maleate (PM, histamine H1 receptor antagonist); cimetidine (histamine H2 receptor antagonist); 8-hydroxy-2-(di- n -propylamino)-tetralin (8-OH-DPAT, specific 5-HT1A receptor agonist); and selective dopamine D1 receptor antagonist (Sch-23390) on the number of swallows elicited by distilled water in anesthetized guinea pigs were investigated. Results: Atropine (0.2 mg/kg) inhibited swallowing by approximately 70%; PM (30 mg/kg) inhibited swallowing by approximately 60%; cimetidine (30 mg/kg) inhibited swallowing by approximately 52.9% and Sch-23390 (chronic treatment) inhibited swallowing by approximately 40%. In contrast, 8-OH-DPAT did not alter the number of swallows. Chronic pretreatment of Sch-23390 markedly decreased the substance P (SP) content in the pharyngeal mucosa and the esophagus. Conclusion: These findings indicate that acetylcholine, histamine and dopamine are involved in the regulation of the swallowing reflex, whereas it is unlikely that serotonin is involved. [source] Parallel activation of field CA2 and dentate gyrus by synaptically elicited perforant path volleysHIPPOCAMPUS, Issue 8 2004Renata Bartesaghi Abstract Previous studies showed that dorsal psalterium (PSD) volleys to the entorhinal cortex (ENT) activated in layer II perforant path neurons projecting to the dentate gyrus. The discharge of layer II neurons was followed by the sequential activation of the dentate gyrus (DG), field CA3, field CA1. The aim of the present study was to ascertain whether in this experimental model field, CA2, a largely ignored sector, is activated either directly by perforant path volleys and/or indirectly by recurrent hippocampal projections. Field potentials evoked by single-shock PSD stimulation were recorded in anesthetized guinea pigs from ENT, DG, fields CA2, CA1, and CA3. Current source-density (CSD) analysis was used to localize the input/s to field CA2. The results showed the presence in field CA2 of an early population spike superimposed on a slow wave (early response) and of a late and smaller population spike, superimposed on a slow wave (late response). CSD analysis during the early CA2 response showed a current sink in stratum lacunosum-moleculare, followed by a sink moving from stratum radiatum to stratum pyramidale, suggesting that this response represented the activation and discharge of CA2 pyramidal neurons, mediated by perforant path fibers to this field. CSD analysis during the late response showed a current sink in middle stratum radiatum of CA2 followed by a sink moving from inner stratum radiatum to stratum pyramidale, suggesting that this response was mediated by Schaffer collaterals from field CA3. No early population spike was evoked in CA3. However, an early current sink of small magnitude was evoked in stratum lacunosum-moleculare of CA3, suggesting the presence of synaptic currents mediated by perforant path fibers to this field. The results provide novel information about the perforant path system, by showing that dorsal psalterium volleys to the entorhinal cortex activate perforant path neurons that evoke the parallel discharge of granule cells and CA2 pyramidal neurons and depolarization, but no discharge of CA3 pyramidal neurons. Consequently, field CA2 may mediate the direct transfer of ENT signals to hippocampal and extrahippocampal structures in parallel with the DG-CA3-CA1 system and may provide a security factor in situations in which the latter is disrupted. © 2004 Wiley-Liss, Inc. [source] Evaluation of a magnetic resonance biomarker of osteoarthritis disease progression: doxycycline slows tibial cartilage loss in the Dunkin Hartley guinea pigINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2009Jonathan Bowyer Summary The objective was to assess the effect of doxycycline treatment on a magnetic resonance imaging (MRI) biomarker of cartilage volume loss, and on matrix metalloproteinase (MMP) activity in a guinea pig osteoarthritis model. Guinea pigs (9 months old) were dosed with vehicle or doxycycline, 0.6, 3.0 mg/kg/day for 66 days. Fat-suppressed 3D gradient-echo MRI of the left knee was acquired pre- and post dosing. Change in medial tibial plateau (MTP) cartilage volume (MT.VC) was determined using image analysis. At termination, MTP cartilage was removed from knees and proteolytic MMP activity determined using a fluorescent peptide substrate assay. Vehicle-treated animals lost 20.5% (95% CI mean 25.6,15.1) MT.VC. The doxycycline (0.6 mg/kg/day) group lost 8.6% (P < 0.05, 95% CI 20.6 to ,5.3) whilst the 3.0 mg/kg/day group lost 10.0% (P < 0.05, 95% CI 13.9,6.0%). Endogenous levels of active MMPs were below limits of detection in all samples. However, doxycycline treatment ablated amino phenyl mercuric acid activated MMP-13 and MMP-8 levels, reduced MMP-9 levels by 65% and MMP-1 levels by 24%. Doxycycline treatment resulted in partial protection from MT.VC loss and was associated with complete reduction in MMP-13 and MMP-8, and partial reduction in MMP-9 activity. These data imply a role of MMPs in cartilage degeneration but incomplete protection suggests that additional doxycycline insensitive mechanisms are important in this model. The protective effect of doxycycline correlates with the clinical finding of lessened joint space narrowing, strengthens the utility of this animal model in identifying disease-modifying osteoarthritic drugs and supports the use of MRI biomarkers of cartilage loss. [source] Eine erweiterte Evaluation der Neurolept-Anästhesie für Meerschweinchen mit einer Analyse gemischt-exspiratorischer Gase während Spontanatmung.JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2004Wirkung des Fastens auf das kardiorespiratorische System und den Metabolismus Zusammenfassung Das beatmete Meerschweinchen wurde oft für neurophysiologische und respiratorische Studien eingesetzt. Diese Spezies ist auch für eine Evaluation künstlicher Sauerstoffträger, entwickelt aus Hämoglobin, geeignet, weil seine Sauerstoff-Hämoglobin-Bindung der des Menschen sehr ähnlich ist. Andererseits ist eine Narkose dieser Tiere wegen kardio-respiratorischer Depression mit herkömmlichen Verfahren schwierig. Bewährt hat sich die folgende intraperitoneal zu verabreichende Neurolept-Anästhesie: 0,2 mg Fentanyl (Janssen/D), 10 mg Droperidol (Janssen/D) sowie 400 mg Urethan in 10 ml isotonischer Natriumchlorid-Lösung pro kg Körpergewicht. Unser neues Tier-Modell ermöglicht, mit einem speziellen Ventilsystem den Gasaustausch unter Spontanatmung, kardiovaskuläre wie auch Blutgaswerte und damit den Säure-Basen-Status zu messen. Die vitalen Parameter der Tiere, blieben über mehr als 6 Stunden stabil und nahe bei Werten wacher Tiere, insbesondere der mittlere arterielle Blutdruck. Deswegen ist diese etablierte Neurolept-Anästhesie des Meerschweinchens für Forschungszweck zu bevorzugen. Nüchterne Tiere zeigten signifikant erniedrigte Blut-pH- (7,345 bzw. 7,401) sowie Herzfrequenz- (244 bzw. 277 min,1) und Ventilationswerte (167 bzw. 205 ml/min) im Vergleich zu nicht nüchternen Tieren. Summary An Extended Evaluation of a Neuroleptanesthesia for the Guinea Pig with Analysis of Mixed Expiratory Gases during Spontaneous Breathing. Effects of Fasting on the Cardiorespiratory System and Metabolism The artificially ventilated guinea pig was frequently used for neurophysiological and respiratory studies. This species is also preferable for an evaluation of hemoglobin based artificial oxygen carriers, because its oxygen hemoglobin binding is very similar to that of man. But the narcosis of this animal-species is very difficult, because of cardiorespiratory depression induced by conventional procedures. The following intraperitoneal administered neuroleptanesthesia was proved in guinea pigs: 0,2 mg Fentanyl (Janssen/D), 10 mg Droperidol (Janssen/D) and 400 mg Urethan in 10 ml isotonic sodium chloride solution per kg body weight. Our new animal model with a special valve system enables to assess the gas exchange under spontaneous breathing, cardiovascular and the acid-base parameters. The vital parameters of animals were stable over 6 hours and very close to those of awake animals, especially the arterial average blood pressure. For that reason, this established neuroleptanesthesia of guinea pigs is preferable for research purpose. The fasted animals show significantly decreased values of arterial blood pH (7,345 vs. 7,401), of heart frequency (244 vs. 277 min,1), and of ventilation value (167 vs. 205 ml/min) compared to non-fasted animals. [source] The safety of Bacillus subtilis and Bacillus indicus as food probioticsJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2008H.A. Hong Abstract Aims:, To conduct in vitro and in vivo assessments of the safety of two species of Bacillus, one of which, Bacillus subtilis, is in current use as a food supplement. Methods and Results:, Cultured cell lines, Caco-2, HEp-2 and the mucus-producing HT29-16E cell line, were used to evaluate adhesion, invasion and cytotoxicity. The Natto strain of B. subtilis was shown to be able to invade and lyse cells. Neither species was able to adhere significantly to any cell line. The Natto strain was also shown to form biofilms. No strain produced any of the known Bacillus enterotoxins. Disc-diffusion assays using a panel of antibiotics listed by the European Food Safety Authority (EFSA) showed that only Bacillus indicus carried resistance to clindamycin at a level above the minimum inhibitory concentration breakpoints set by the EFSA. In vivo assessments of acute and chronic dosing in guinea pigs and rabbits were made. No toxicity was observed in animals under these conditions. Conclusions:,Bacillus indicus and B. subtilis should be considered safe for oral use although the resistance of B. indicus to clindamycin requires further study. Significance and Impact of the Study:, The results support the use of B. subtilis and B. indicus strains as food supplements. [source] Allergenicity testing of supermethrin, phenoxyacetic acid and DNCB using in vivo and in vitro modifications of the local lymph node assays, maximization and epicutaneous testingJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2001M. Kuricova Abstract The purpose of this study was to compare two methods of testing for allergenicity: in vivo and in vitro modifications of local lymph node assays (LLNA) in mice and the maximization and epicutaneous skin tests in guinea pigs as per the Organization for Economic Cooperation and Development (1981). Two pesticides,the synthetic pyrethroid insecticide supermethrin (SM) and the herbicide phenoxyacetic acid (PAA),were evaluated using this testing battery. 1-Chloro-2,4-dinitrobenzene (DNCB) was selected as a reference allergen for the local lymph node assay. In vitro modification of LLNA proliferative response per standard cell count in lymphocyte cultures derived from treated Balb/c mice did not differ from control mice. Results of the in vivo modification showed that treatment with 50% PAA and 50% SM resulted in a lower proliferation response of lymphocytes in lymph nodes compared with control animals. The vigour of the proliferative response varied more in in vivo modification of LLNA. Stimulation indices were <3, so PAA and SM did not indicate classification as allergens. Lymphocyte proliferation in 1% DNCB-activated lymph nodes was approximately fivefold higher than in those derived from control mice. Proliferation response in vitro calculated as stimulation index was higher in DNCB-treated mice than those observed in vivo, but differences were not dramatic. Auricular lymph node weight and cellularity in mice treated with PAA and SM were similar to controls. The DNCB stimulation index for lymph node cellularity was 5.5. Lymph node weight was three times higher in comparison with controls. In the maximization test in guinea pigs SM and PAA acid resulted in 40% and 50% of animals demonstrating sensitization, respectively. Epicutaneous administration resulted in weaker reaction. Both SM and PAA are mildly strong sensitizers by this battery. Copyright © 2001 John Wiley & Sons, Ltd. [source] Effect of octanol:water partition coefficients of organophosphorus compounds on biodistribution and percutaneous toxicity,,JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 5 2006Steven E. Czerwinski Abstract Knowledge of partition coefficient (log P) data can play a critical role in understanding the pharmacokinetic and pharmacodistributive properties of toxic organophosphorus (OP) compounds. Using a recently published gas chromatographic method, the octanol:water log P values for the compounds tabun (GA), sarin (GB), cyclosarin (GF), and O -ethyl- S -(2-diisopropylaminoethyl) methylphosphonothiolate (VX) were determined to be 0.384 ± 0.033, 0.299 ± 0.016, 1.038 ± 0.055, and 0.675 ± 0.070, respectively. Based on these data, the log P value of the fluorophosphonate fragment, common to GB, soman (GD), and GF, was determined to be ,2.256 ± 0.273. The predictive value for absorption and distribution of the determined log P values was compared to measured values. The time to onset of local fasciculations (47.3, 29.0, 8.8, 8.5, and 6.3 min, respectively) in guinea pigs exposed percutaneously to equilethal doses of GA, VX, GF, GB, or GD was used as an indicator of dermal penetration. There was a good correlation (r = 0.95) between the measured log P value and the rate of onset of local fasciculations. Assuming a direct correspondence, equilibrium tissue:blood log P may be estimated from octanol:water log P. Comparison of the estimated and directly measured tissue:blood log P revealed a correlation of 0.8 for GD in liver, muscle, and adipose tissue. Our results demonstrate the use of log P data to both predict absorption and determine the distribution of OP compounds in tissues. This facilitates further estimates of in vivo OP effects from in vitro experiments. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:241,246, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20140 [source] Analysis of the Defibrillation Efficacy for 5-ms WaveformsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2004DONGXU GUAN Ph.D. Introduction: Empirical studies have shown that biphasic defibrillation waveforms are more efficacious than monophasic waveforms. However, a more systematic approach to waveform development might be more productive. This study tested 147 multiphasic waveforms uniformly sampled from all possible 5-ms waveforms. Methods and Results: One hundred ninety-eight guinea pigs (850,1,050 g) received 30 episodes of ventricular fibrillation followed by transthoracic defibrillation. The first 10 shocks were used to determine the ED50 for a biphasic control. Then, 20 waveforms including 2 controls were tested once at the ED50. Of the 147 waveforms tested here, 21 waveforms showed equivalent or greater efficacies than the biphasic control, with one being statistically more efficacious (P < 0.05). Two fundamental assumptions were addressed: (1) similarly efficacious waveforms are analytically similar, and (2) a single optimal waveform can be described. The mean percentage of similarly efficacious waveforms with similar shapes was greater than zero in the most efficacious 21 waveforms (P = 0.023), but less efficacious waveforms showed randomly distributed shapes. Cluster analysis revealed that the best waveforms share a major phase containing most of the defibrillation energy. The optimal waveform shape extrapolated from the sample waveforms was a 2.5/1-ms biphasic-type waveform (highest correlation r = 0.701, P < 0.001). Conclusion: This work supports the assumption that efficacious waveforms are similarly shaped and the notion that one single optimum exists. (J Cardiovasc Electrophysiol, Vol. 15, pp. 447-454, April 2004) [source] Use of a rodent model to show that varicella-zoster virus ORF61 is dispensable for establishment of latency,JOURNAL OF MEDICAL VIROLOGY, Issue S1 2003Hitoshi Sato Abstract Varicella-zoster virus (VZV) results in a latent infection in humans after primary infection. Latency has also been established in guinea pigs and rats after inoculation with the virus. It was found that infection of cotton rats with the Oka vaccine strain of VZV results in a latent infection. To begin to identify which genes are required for latency, we infected cotton rats with VZV strain Oka that is deleted for ORF61. ORF61 protein transactivates certain VZV promoters and enhances the infectivity of viral DNA in transient transfections. Deletion of ORF61 results in abnormal syncytia and impairs the growth of VZV in vitro. Inoculation of cotton rats with ORF61-deleted Oka virus resulted in latent VZV infection in the nervous system similar to that seen for animals infected with parental virus. Thus, the cotton rat can be used to study the ability of mutants in the Oka vaccine strain of VZV to establish latent infection. J. Med. Virol. 70:S79,S81, 2003. © 2003 Wiley-Liss, Inc. [source] Experimental hepatitis A virus infection in guinea pigsJOURNAL OF MEDICAL VIROLOGY, Issue 4 2001Britt Hornei Abstract Although many of the properties of hepatitis A virus (HAV) are known, several aspects of HAV pathogenesis are still not understood, such as the mechanism underlying the hepatotropism or HAV replication in extrahepatic sites. Detailed studies of these aspects were hampered mostly by the lack of accessible animal models, since only nonhuman primates are susceptible to experimental infections. An alternative animal model would also be of interest to assess the primary replication site and for the evaluation of the safety and efficacy of vaccines. A study was undertaken to determine whether HAV can infect guinea pigs and whether they are useful as a model for studying aspects of HAV pathogenesis and for the evaluation of vaccines. HAV variants adapted to primate or guinea pig tissue culture were used to inoculate guinea pigs intraperitoneally and by the oral route. The animals were observed for clinical disease, shedding of HAV in stools, viremia, seroconversion, evidence for liver damage by biochemical liver function tests, virus presence in the liver, development of hepatic histopathological changes, and occurrence of HAV in extrahepatic organs. The animals developed an active, clinically inapparent infection with specific histopathological changes in the liver. Although virus replication occurred, as shown by RT-PCR and isolation of infectious virus from feces and serum, it seems unlikely that guinea pigs are suitable for studying the clinical features of hepatitis A, because the clinical and laboratory parameters remained normal. However, guinea pigs appear useful for studying some aspects of HAV pathogenesis and for testing the safety of vaccines. J. Med. Virol. 64:402,409, 2001. © 2001 Wiley-Liss, Inc. [source] Tibolone Rapidly Attenuates the GABAB Response in Hypothalamic NeuronesJOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2008J. Qiu Tibolone is primarily used for the treatment of climacteric symptoms. Tibolone is rapidly converted into three major metabolites: 3,- and 3,-hydroxy (OH)-tibolone, which have oestrogenic effects, and the ,4-isomer (,4-tibolone), which has progestogenic and androgenic effects. Because tibolone is effective in treating climacteric symptoms, the effects on the brain may be explained by the oestrogenic activity of tibolone. Using whole-cell patch clamp recording, we found previously that 17,-oestradiol (E2) rapidly altered ,-aminobutyric acid (GABA) neurotransmission in hypothalamic neurones through a membrane oestrogen receptor (mER). E2 reduced the potency of the GABAB receptor agonist baclofen to activate G-protein-coupled, inwardly rectifying K+ (GIRK) channels in hypothalamic neurones. Therefore, we hypothesised that tibolone may have some rapid effects through the mER and sought to elucidate the signalling pathway of tibolone's action using selective inhibitors and whole cell recording in ovariectomised female guinea pigs and mice. A sub-population of neurones was identified post hoc as pro-opiomelanocortin (POMC) neurones by immunocytochemical staining. Similar to E2, we have found that tibolone and its active metabolite 3,OH-tibolone rapidly reduced the potency of the GABAB receptor agonist baclofen to activate GIRK channels in POMC neurones. The effects were blocked by the ER antagonist ICI 182 780. Other metabolites of tibolone (3,OH-tibolone and ,4-tibolone) had no effect. Furthermore, tibolone (and 3,OH-tibolone) was fully efficacious in ER, knockout (KO) and ER,KO mice to attenuate GABAB responses. The effects of tibolone were blocked by phospholipase C inhibitor U73122. However, in contrast to E2, the effects of tibolone were not blocked by protein kinase C inhibitors or protein kinase A inhibitors. It appears that tibolone (and 3,OH-tibolone) activates phospholipase C leading to phosphatidylinositol bisphosphate metabolism and direct alteration of GIRK channel function. Therefore, tibolone may enhance synaptic efficacy through the Gq signalling pathways of mER in brain circuits that are critical for maintaining homeostatic functions. [source] Chronic Prenatal Ethanol Exposure Increases Glucocorticoid-Induced Glutamate Release in the Hippocampus of the Near-Term Foetal Guinea PigJOURNAL OF NEUROENDOCRINOLOGY, Issue 11 2006U. Iqbal Exposure to high cortisol concentration can injure the developing brain, possibly via an excitotoxic mechanism involving glutamate (Glu). The present study tested the hypothesis that chronic prenatal ethanol exposure (CPEE) activates the foetal hypothalamic-pituitary-adrenal axis to produce high cortisol exposure in the foetal compartment and alters sensitivity to glucocorticoid-induced Glu release in the foetal hippocampus. Pregnant guinea pigs received daily oral administration of ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding from gestational day (GD) 2 until GD 63 (term, approximately GD 68) at which time they were euthanised, 1 h after their final treatment. Adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined in foetal plasma. Basal and electrically stimulated Glu and ,-aminobutyric acid (GABA) efflux in the presence or absence of dexamethasone (DEX), a selective glucocorticoid-receptor agonist, were determined ex vivo in foetal hippocampal slices. Glucocorticoid receptor (GR), mineralocorticoid receptor (MR) and N -methyl- d -aspartate (NMDA) receptor NR1 subunit mRNA expression were determined in situ in the hippocampus and dentate gyrus. In the near-term foetus, CPEE increased foetal plasma ACTH and cortisol concentrations. Electrically stimulated glutamate, but not GABA, release was increased in CPEE foetal hippocampal slices. Low DEX concentration (0.3 µM) decreased stimulated glutamate, but not GABA, release in both CPEE and control foetal hippocampal slices. High DEX concentration (3.0 µM) increased basal release of Glu, but not GABA, in CPEE foetal hippocampal slices. GR, but not MR, mRNA expression was elevated in the hippocampus and dentate gyrus, whereas NR1 mRNA expression was increased in the CA1 and CA3 fields of the foetal hippocampus. These data demonstrate that CPEE increases high glucocorticoid concentration-induced Glu release in the foetal hippocampus, presumably as a consequence of increased GR expression. These effects of CPEE, coupled with increased glutamate release and increased NMDA receptor expression, may predispose the near-term foetal hippocampus to GR and Glu-NMDA receptor-mediated neurodevelopmental toxicity. [source] Comparative Analysis of Immunoreactive Cells for Androgen Receptors and Oestrogen Receptor , in Copulating and Non-Copulating Male RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2006W. Portillo Abstract In some species, including gerbils, guinea pigs, mice, rams and rats, some apparently normal males fail to mate. These kinds of animals have been named ,noncopulating (NC)'. The cause of this behavioural deficit is unknown. The present study aimed to determine whether NC male rats have alterations in the amount of androgen (AR) and oestrogen receptor , (ER,) in a neuronal circuit important for the control of male sexual behaviour; the vomeronasal projection pathway. We evaluated the number of AR and ER, immunoreactive (AR-IR and ER,-IR) cells in the accessory olfactory bulb (AOB), the bed nucleus of the stria terminalis (BNST), the anterior-dorsal medial amygdala (MeAD), the posterior dorsal amygdala (MePD) and the medial preoptic area (MPOA). The results demonstrate that the number of AR-IR cells in NC males was significantly higher compared to copulating (C) males in the MePD, but no significant differences were found in any of the other structures analysed. ER,-IR cells were more abundant in NC than in C males in the MeAD and the MePD. However, in the MPOA the number of ER,-IR cells was significantly reduced in NC males. No significant differences were found in the AOB or in the BNST. A similar pattern of results was observed when regions within these structures that are activated by Fos expression, on mating or exposure to sexually relevant cues were analysed. The differences in the number of AR and ER in particular brain areas could be associated with alterations in sexual behaviour as well as partner and olfactory preference for receptive females seen in NC male rats. [source] Characterization of Gonadotrophin-Releasing Hormone Precursor cDNA in the Old World Mole-Rat Cryptomys Hottentotus Pretoriae: High Degree of Identity with the New World Guinea Pig SequenceJOURNAL OF NEUROENDOCRINOLOGY, Issue 5 2005T. Kalamatianos Abstract Regulation of pituitary gonadotrophins by the decapeptide gonadotrophin-releasing hormone 1 (GnRH1) is crucial for the development and maintenance of reproductive functions. A common amino acid sequence for this decapeptide, designated as ,mammalian' GnRH, has been identified in all mammals thus far investigated with the exception of the guinea pig, in which there are two amino acid substitutions. Among hystricognath rodents, the members of the family Bathyergidae regulate reproduction in response to diverse cues. Thus, highveld mole-rats (Cryptomys hottentotus pretoriae) are social bathyergids in which breeding is restricted to a particular season in the dominant female, but continuously suppressed in subordinate colony members. Elucidation of reproductive control in these animals will be facilitated by characterization of their GnRH1 gene. A partial sequence of GnRH1 precursor cDNA was isolated and characterized. Comparative analysis revealed the highest degree of identity (86%) to guinea pig GnRH1 precursor mRNA. Nevertheless, the deduced amino acid sequence of the mole-rat decapeptide is identical to the ,mammalian' sequence rather than that of guinea pigs. Successful detection of GnRH1-synthesizing neurones using either a guinea pig GnRH1 riboprobe or an antibody against the ,mammalian' decapeptide is consistent with the guinea pig-like sequence for the precursor and the classic ,mammalian' form for the decapeptide. The high degree of identity in the GnRH1 precursor sequence between this Old World mole-rat and the New World guinea pig is consistent with the theory that caviomorphs and phiomorphs originated from a common ancestral line in the Palaeocene to mid Eocene, some 63,45 million years ago. [source] Macrophage contribution to the response of the rat organ of Corti to amikacinJOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2007Sabine Ladrech Abstract Transdifferentiation of nonsensory supporting cells into sensory hair cells occurs naturally in the damaged avian inner ear. Such transdifferentiation was achieved experimentally in the cochlea of deaf guinea pigs through Atoh 1 gene transfection. Supporting cells may therefore serve as targets for transdifferentiation therapy. Supporting cells rapidly degenerate after hair cell disappearance, however, limiting the therapeutic window for gene transfer. We studied the time course of ultrastructural and phenotypical changes occurring in Deiters cells (hair cell supporting cells) after ototoxic treatment in the rat. The presence of macrophages in the cochlea was also investigated, to study any deleterious effects they may have on pathologic tissues. One week after treatment most hair cells had disappeared. Deiters cells no longer expressed the glial marker vimentin but instead displayed typical hair cell markers, the calcium binding proteins calbindin and parvalbumin. This suggests that a process of transdifferentiation of Deiters cells into hair cells was activated. By 3 weeks post-treatment, however, the Deiters cells began to degenerate and by 10 weeks post-treatment the organ of Corti was degraded fully. Interestingly, a marked increase in macrophage density was seen after the end of amikacin treatment to 10 weeks post-treatment. This suggests chronic inflammation is involved in epithelium degeneration. Consequently, early treatments with anti-inflammatory factors might promote supporting cell survival, thus improving the efficacy of more specific strategies aimed to regenerate hair cells from nonsensory cells. © 2007 Wiley-Liss, Inc. [source] Connexin 43 gap junction proteins are up-regulated in remyelinating spinal cordJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2007W.A. Roscoe Abstract Alterations in the expression of gap junction proteins have previously been observed in several diseases affecting the central nervous system; however, the status of connexin 43 (Cx43) has not yet been reported in spinal cord remyelination. We studied Cx43 expression in demyelination and remyelination by using a chronic guinea pig model of experimental allergic encephalomyelitis (EAE). Hartley guinea pigs were immunized with homogenized whole CNS and complete Freund's adjuvant. Animals became chronically ill by day 40 postimmunization, and animals with paralysis were entered into the study. Animals were treated on days 40,60 postimmunization with either saline or drugs that promote remyelination: an adenosine amine congener (100 ,g/kg), an anti-,4-integrin blocker (CT301; ELN 69299; 30 mg/kg), or a combination of both drugs. Remyelination was induced in all drug-treated groups. Cx43 expression was virtually absent in demyelinated lesions of saline-treated controls compared with healthy tissue and normal appearing white matter (P < 0.001), whereas Cx43 was considerably increased (300,500%) in remyelinating lesions of all treatment groups (P < 0.001), most notably in CT301-treated animals. These changes in Cx43 expression indicate that Cx43 may beimportant for recovery from neuroinflammation. © 2007 Wiley-Liss, Inc. [source] Enhanced expression of vascular endothelial growth factor by periodontal pathogens in gingival fibroblastsJOURNAL OF PERIODONTAL RESEARCH, Issue 1 2003Kanyarat Suthin Vascular endothelial growth factor (VEGF) has recently attracted attention as a potent inducer of vascular permeability and angiogenesis. Aberrant angiogenesis is often associated with lesion formation in chronic periodontitis. The aim of the present study was to investigate the properties of VEGF expression in human gingival fibroblasts (HGF) culture. HGF were stimulated with lipopolysaccharide (LPS), vesicle (Ve) and outer membrane protein (OMP) from Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. HGF constitutively produced VEGF and levels were significantly enhanced (P < 0.01) by stimulation with Ve and OMP from A. actinomycetemcomitans and P. gingivalis at concentrations of 10 µg/ml or higher. On the other hand, VEGF levels were not increased by LPS stimulation. VEGF mRNA expression was also observed in Ve- and OMP-stimulated HGF. A vascular permeability enhancement (VPE) assay was performed using guinea pigs to ascertain whether supernatant from cultures of Ve- and OMP-stimulated HGF enhance vascular permeability in vivo. Supernatant from cultures of Ve- and OMP-stimulated HGF strongly induced VPE. This was markedly suppressed upon simultaneous injection of anti-VEGF polyclonal antibodies with the supernatant. Heating and protease treatment of the stimulants reduced the VEGF enhancing levels in Ve and OMP in vitro. These results suggest that Ve and OMP may be crucial heat-labile and protease-sensitive components of periodontal pathogens that enhance VEGF expression. In addition, VEGF might be associated with the etiology of periodontitis in its early stages according to neovascularization stimulated by periodontal pathogens causing swelling and edema. [source] Cyamemazine metabolites: effects on human cardiac ion channels in-vitro and on the QTc interval in guinea pigsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2008William Crumb Monodesmethyl cyamemazine and cyamemazine sulfoxide, the two main metabolites of the antipsychotic and anxiolytic phenothiazine cyamemazine, were investigated for their effects on the human ether-à-go-go related gene (hERG) channel expressed in HEK 293 cells and on native INa, ICa, Ito, Isus or IK1 of human atrial myocytes. Additionally, cyamemazine metabolites were compared with terfenadine for their effects on the QT interval in anaesthetized guinea pigs. Monodesmethyl cyamemazine and cyamemazine sulfoxide reduced hERG current amplitude, with IC50 values of 0.70 and 1.53 ,M, respectively. By contrast, at a concentration of 1 ,M, cyamemazine metabolites failed to significantly affect INa, Ito, Isus or IK1 current amplitudes. Cyamemazine sulfoxide had no effect on ICa at 1 ,M, while at this concentration, monodesmethyl cyamemazine only slightly (17%), albeit significantly, inhibited ICa current. Finally, cyamemazine metabolites (5 mg kg,1 i.v.) were unable to significantly prolong QTc values in the guinea pig. Conversely, terfenadine (5 mg kg,1 i.v.) significantly increased QTc values. In conclusion, cyamemazine metabolite concentrations required to inhibit hERG current substantially exceed those necessary to achieve therapeutic activity of the parent compound in humans. Moreover, cyamemazine metabolites, in contrast to terfenadine, do not delay cardiac repolarization in the anaesthetized guinea pig. These non-clinical findings explain the excellent cardiac safety records of cyamemazine during its 30 years of extensive therapeutic use. [source] Red wine polyphenolic compounds inhibit tracheal smooth muscle contraction during allergen-induced hyperreactivity of the airwaysJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2007Sona Franova The aims of the study were to investigate the short and long-term effects of Provinol (red wine polyphenolic compounds) on tracheal smooth muscle reactivity using an in-vitro model of ovalbumin-induced airway inflammation in guinea-pig trachea, and to evaluate the role of nitric oxide (NO) in the bronchodilatory effect of Provinol. The amplitude of tracheal smooth muscle contraction in response to mediators of bronchoconstriction ,histamine (10 nM-1 mM), acetylcholine (10 nM-1 mM) and to allergen (ovalbumin 10,5 -10,3 g mL,1) was used as a parameter of tracheal smooth muscle reactivity. To test the short-term effects of Provinol, isolated tracheal strips were pre-treated for 30 min with Provinol (10,4mg mL,1) alone or in combination with N, -nitro-L-arginine methyl ester (L-NAME; 10,6mol L,1). To test the long-term effects of Provinol, isolated tracheal strips were prepared from guinea pigs that had been treated for 14 days with Provinol (20mg kg,1 per day) alone or in combination with L-NAME (40 mg kg,1 per day). Incubation of tracheal smooth muscle with Provinol decreased the amplitude of contraction in response to ovalbumin, histamine and acetylcholine. The non-selective NO synthase inhibitor L-NAME partially abolished the effect of Provinol on acetylcholine and ovalbumin-induced but not histamine-induced bronchoconstriction. A similar profile was observed after 14 days' oral administration of Provinol. In conclusion, Provinol inhibited the allergen- and spasmogen-induced contraction of tracheal smooth muscle in ovalbumin-sensitized guinea pigs via a mechanism that was mediated at least partially through the metabolism of NO. [source] Nasal administration of albuterol: an alternative route of deliveryJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2004Anwar A. Hussain The use of metered-dose inhalers for the delivery of albuterol, a ,2 -selective adrenergic agonist, is associated with drawbacks, especially in children and the elderly. This investigation was designed to assess the effectiveness of albuterol delivered intranasally and to compare this delivery route with intratracheal and intravenous delivery. Three parameters of pulmonary function (peak maximal expiratory flow, maximal expiratory flow at 50% vital capacity, and total lung capacity) in anaesthetized, artificially ventilated guinea pigs were used to determine the degree of protection produced by albuterol against bronchoconstrictor responses provoked by acetylcholine. The heart rate was also measured. Although intranasal albuterol induced a slower protective action during the very initial phase of absorption, the drug was shown to be equally effective when administered either intranasally or intratracheally. In contrast, despite a significant effect initially in the case of intravenous albuterol, its ability to influence pulmonary function faded rather rapidly. No statistically significant differences in heart rate could be detected among the different treatment groups. In conclusion, intranasal albuterol may offer an alternative to metered-dose inhalers for the treatment of acute bronchospasm and for prevention of exercise-induced asthma, especially for children and the elderly. [source] In Utero Ethanol Exposure Impairs Defenses Against Experimental Group B Streptococcus in the Term Guinea Pig LungALCOHOLISM, Issue 2 2009Theresa W. Gauthier Background:, The effects of fetal alcohol exposure on the risks of neonatal lung injury and infection remain under investigation. The resident alveolar macrophage (AM) is the first line of immune defense against pulmonary infections. In utero ethanol (ETOH) exposure deranges the function of both premature and term guinea pig AM. We hypothesized that fetal ETOH exposure would increase the risk of pulmonary infection in vivo. Methods:, We developed a novel in vivo model of group B Streptococcus (GBS) pneumonia using our established guinea pig model of fetal ETOH exposure. Timed-pregnant guinea pigs were pair fed ±ETOH and some were supplemented with the glutathione (GSH) precursor S -adenosyl-methionine (SAM-e). Term pups were given GBS intratracheally while some were pretreated with inhaled GSH prior to the experimental GBS. Neonatal lung and whole blood were evaluated for GBS while isolated AM were evaluated using fluorescent microscopy for GBS phagocytosis. Results:, Ethanol-exposed pups demonstrated increased lung infection and sepsis while AM phagocytosis of GBS was deficient compared with control. When SAM-e was added to the maternal diet containing ETOH, neonatal lung and systemic infection from GBS was attenuated and AM phagocytosis was improved. Inhaled GSH therapy prior to GBS similarly protected the ETOH-exposed pup from lung and systemic infection. Conclusions:, In utero ETOH exposure impaired the neonatal lung's defense against experimental GBS, while maintaining GSH availability protected the ETOH-exposed lung. This study suggested that fetal alcohol exposure deranges the neonatal lung's defense against bacterial infection, and support further investigations into the potential therapeutic role for exogenous GSH to augment neonatal AM function. [source] | ||||||||||||||||||||||||||||||||||||||||