Pharmacological studies on supersensitization. III. Effect of potentiators on isolated tracheal preparation of guinea pig (author''s transl)

A living vaccine, the bacille Calmette Guérin (BCG) strain of Mycobacterium tuberculosis bovis, has been administered in a single postoperative intrapleural dose as a controlled equivalent of postoperative empyema in 38 patients following pulmonary resection for lung cancer. This form of regional immunotherapy is reasonably well tolerated if the vaccine is given in a limited dose and if a follow-up course of isoniazid (INH) is administered. In this report, the technical details of this new therapeutic program are reviewed. The preliminary findings in a randomized prospective clinical train of the technique indicate that patients with Stage I lung cancer are significantly benefitted by the treatment. Patients with more advanced disease are unimproved by this form of therapy.     

A comparative study of guinea pig and rat tracheal reactivity

Species differences in behavior and responses of guinea pig (GPT) and rat (RT) tracheal smooth muscle to electrical field stimulation (EFS) and chemicals were investigated under semi-isometric conditions. Indomethacin augmented and papaverine reduced the contractions elicited by EFS in both tissues. They relaxed the GPT and did not affect the tone decline in the RT. Experiments with different load, cartilage content, thread and rubber strips suggest the role of elastic elements in passive elongation of the RT. This was independent of muscarinic, adrenergic, histaminergic and serotoninergic receptors, nitric oxide, eicosanoids and metabolic processes. The second response on repeated administration of acetylcholine was augmented and that of serotonin attenuated in both GPT and RT. Upon repeated elevation of [K+]o the tissues responded in an opposite manner. Further data are provided on similarities (modulation of cholinergic transmission by prostaglandins, sensitization to acetylcholine and desensitization to serotonin) and differences (innervation, responses to repeated elevation of [K+]o, presence/absence of prostaglandin-regulated basal tone and spontaneous activity) in reactivity of GPT and RT.     

Roles of histamine receptor in a guinea pig asthma model

A case of parotidomegaly associated with anorexia is described, and the psychoneurological and etiopathogenetic theories of main feed disorders (anorexia/bulimia) are discussed. Particularly, a rare pathology of maxillofacial interest is presented: parotidomegaly associated with anorexia. The diagnosis and differential diagnosis of this pathology is discussed.     

Potentiation of purinergic neurotransmission in guinea pig urinary bladder by histamine

Patients suffering from the inflammatory condition of interstitial cystitis frequently exhibit an increased number of mast cells in the bladder. To determine whether mast cell mediators have the potential to influence the neurogenic contraction of the bladder smooth muscle and thereby possibly contribute to the symptoms of interstitial cystitis, we examined the effects of histamine, a major inflammatory mediator of mast cell origin, on nerve- and agonist-induced contractions of in vitro strips of guinea pig urinary bladder. Histamine (10 microM.) potentiated by more than 50% the nerve-induced contraction of bladder strips evoked by field stimulation with 0.5 msec. pulses at 4 Hz. Because the neurogenic contraction of the bladder is mediated by at least two neurotransmitters, acetylcholine (ACh) and ATP, we examined the effects of histamine on each of these transmitters. Histamine potentiated responses to the purinergic component of the neurogenic response (that part of the neurogenic response that remains after treatment with atropine) and potentiated responses to exogenously applied ATP. Histamine did not potentiate the response to the cholinergic component of the neurogenic response (that part of the neurogenic response that remains after desensitization of purinoceptors with alpha, beta-methylene ATP) nor responses to carbachol, a cholinergic agonist. These results indicate that histamine potentiates the neurogenic response of the bladder by influencing the purinergic component, apparently at postjunctional sites.     

Effect of antigen challenge on sensitized guinea pig trachea

Leiomyosarcomas of the small intestine were found in dogs during experimental induction of gastric carcinoma by oral administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Leiomyosarcomas were found most frequenly in the duodenum and jejunum, and occasionally in the stomach but never in the ileum, colon, or rectum. The leiomyosarcomas developed in all the dogs given 50 mug/ml of MNNG in deionized water to drink but not in dogs fed on porridge food made from standard pellet diet mashed with MNNG at the same concentration in tap water. Intestinal sarcomas developed in 3 months to 5 years after the end of MNNG administration, and frequently metastasized to the liver and/or the peritoneum.     

The action of histamine on the slow-wave and spike activities of the cat and guinea pig ureter

Histamine increased the oscillation frequency of the slow-wave activity in the cat ureter and changed the characteristics of the AP plateau phase. A specific and sensitive to histamine electrogenic Na/Ca agent seems to take part in generation of the ureter spontaneous activity.     

Effect of cetirizine on antigen-induced tracheal contraction of passively sensitized guinea pigs

BACKGROUND: Cetirizine dihydrochloride (cetirizine), a potent histamine H1-receptor antagonist, has been developed as an anti-allergy drug. OBJECT: The anti-allergic effects and mechanism of cetirizine were studied using in vitro assay systems. METHODS: We investigated the effect of cetirizine on antigen-induced contractions of isolated tracheal strips and on chemical mediator release from antigen-stimulated lung chips taken from passively sensitized guinea pigs. We examined the antigen-induced mobilization of Ca2+ in MC/9 mast cells sensitized with IgE. RESULTS: Cetirizine inhibited the antigen-induced contraction of isolated guinea-pig trachea concentration dependently. Pyrilamine, another histamine H1-receptor antagonist, delayed the response but did not change the maximum amplitude. Cetirizine at the concentration of 3 microM also inhibited the antigen-induced release of histamine, leukotriene D4, and leukotriene E4 from guinea pig lung chips. Furthermore, it inhibited the antigen-induced Ca2+ increase in MC/9 mast cells, whereas pyrilamine did not. CONCLUSION: These findings suggest that one anti-allergic mechanism of cetirizine may inhibit mediator release which is, at least partially, mediated by a decrease in the transient Ca2+ influx in mast cells.     

Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust

OBJECTIVES: Diesel exhaust is a common air pollutant made up of several gases, hydrocarbons, and particles. An experimental study was carried out which was designed to evaluate if a particle trap on the tail pipe of an idling diesel engine would reduce effects on symptoms and lung function caused by the diesel exhaust, compared with exposure to unfiltered exhaust. METHODS: Twelve healthy non-smoking volunteers (aged 20-37) were investigated in an exposure chamber for one hour during light work on a bicycle ergometer at 75 W. Each subject underwent three separate double blind exposures in a randomised sequence: to air and to diesel exhaust with the particle trap at the tail pipe and to unfiltered diesel exhaust. Symptoms were recorded according to the Borg scale before, every 10 minutes during, and 30 minutes after the exposure. Lung function was measured with a computerised whole body plethysmograph. RESULTS: The ceramic wall flow particle trap reduced the number of particles by 46%, whereas other compounds were relatively constant. It was shown that the most prominent symptoms during exposure to diesel exhaust were irritation of the eyes and nose and an unpleasant smell increasing during exposure. Both airway resistance (R(aw)) and specific airway resistance (SR(aw)) increased significantly during the exposures to diesel exhaust. Despite the 46% reduction in particle numbers by the trap effects on symptoms and lung function were not significantly attenuated. CONCLUSION: Exposure to diesel exhaust caused symptoms and bronchoconstriction which were not significantly reduced by a particle trap.     

Paracrine endothelin signaling in the control of basal cell proliferation in guinea pig tracheal epithelium

Immunofluorescent analyses revealed distinct cellular/subcellular localization of endothelin (ET) receptors and ET-1 in the epithelial cell layer of guinea pig trachea. ETA was expressed predominantly in the basal cells. ETB was expressed predominantly in the ciliated columnar cells and was polarized at the apical side of the cell body within the cells. Anti-ET-1-immunoreactive cytoplasmic granules were contained in the secretory cells that were scattered throughout the epithelial layer. Cell proliferation assays with immersion cultures of differentially plated cells (basal cell-enriched, non-basal cell-enriched and mixed cell cultures) indicated the presence of paracrine ET-1 signaling pathways that transmit both positive and negative effects on the basal cell proliferation. Direct activation of ETA expressed on the basal cells caused enhancement of their growth, whereas that of ETB expressed on the ciliated columnar cells caused suppression of the basal cell growth. The latter effect was transmitted by nitric oxide whose production was stimulated by ETB activation. Furthermore, blockade of either ETA or ETB compromised the epithelial cell layer formation under the air-interphase culture, which indicates the dependence of tracheal epithelial remodeling on a balance between the positive and negative effects of ET-1 on the basal cell growth.     

H1- and H2-receptors for histamine in the ileum of the guinea pig

Clark's equation used in its inverted form (double reciprocal plots) was shown to be valid regarding the interaction of histamine with its receptors in the guinea-pig ileum. Burimamide, a typical H2-receptor antagonist potentiated the stimulating effect of small concentrations of histamine (10(-6) M) on the intestinal smooth muscle, probably, by blocking H2-receptors which may show the opposite effect. The calculated parameters of affinity (pKn) remained constant under different conditions. A linear correlation between length of the preparation and maximal contractions has been found.     

Effect of exposure of guinea pigs to cigarette smoke on elastolytic activity of pulmonary macrophages

STUDY OBJECTIVE: To determine the effect of exposure to cigarette smoke on the elastolytic activity of guinea pigs' alveolar macrophages (AMs), and to compare elastolytic activity of AMs obtained by BAL with that of lung macrophages (LMs) obtained from minced lung tissue. METHODS: AMs were obtained by BAL from seven adult guinea pigs exposed to cigarette smoke for 5 d/wk during 6 weeks, as well as from age-matched control guinea pigs. From each animal, one lung was used to obtain LMs by mincing and teasing the lung, followed by enzymatic digestion and isolation of mononuclear cells by Hypaque-Ficoll separation. The other lung was inflated and fixed to quantitate emphysema by the destructive index (DI). Elastolytic activity (microgram of elastin degraded by 10(6) macrophages) was determined at 24, 48, and 72 h, by culturing AMs and LMs (1 x 10(6) cells in 1 mL of medium) in 3H-elastin-coated wells. RESULTS: In animals exposed to cigarette smoke, the total number of BAL cells (8.6+/-2.1 x 10(6)) and DI (21.8+/-8.1) were significantly higher than in nonexposed animals (6.4+/-1.8 x 10(6), p<0.05 for cells, and 12.1+/-4.1, p<0.01 for DI). Elastolytic activity of AMs from smoke-exposed guinea pigs was significantly higher at 24, 48, and 72 h than elastolytic activity of AMs from control animals (19.0+/-9.4 vs 10.0+/-5.3, p<0.05 at 72 h). Likewise, elastolytic activity of LMs was significantly higher in exposed than nonexposed guinea pigs (11.8+/-7.7 vs 7.4+/-5.0 at 72 h, p<0.05). Elastolytic activity of LMs was not significantly different from elastolytic activity of AMs, both in exposed guinea pigs (11.8+/-7.7 vs 19.0+/-9.4 at 72 h) and nonexposed animals (7.4+/-5.0 vs 10.0+/-5.3 at 72 h). CONCLUSIONS: These results indicate that elastolytic activity of both AMs and LMs of guinea pigs increases significantly after exposure to cigarette smoke and that AMs and LMs have similar elastolytic activities.     

Effect of perilymphatic fistulas on evoked otoacoustic emissions in the guinea pig

Round window perilymphatic fistulas were surgically created in 20 guinea pigs. Distortion product otoacoustic emissions (DPOAEs) at 2fl - f2 were recorded prior to and immediately following laceration of the round window. The stimuli were equal level sinusoids (f1 < f2) with f2 ranging from 2 to 10 kHz, a fixed f2:f1 ratio of 1.25, and stimulus levels (L2 = L1) ranging from 20 to 80 dB SPL. After an 18-day survival period, emission measurements were repeated, and fluorescein was infused into the cerebrospinal fluid to verify patency or closure of the fistula. Nine animals demonstrated patent fistulas, whereas 11 had closed fistulas. There was a statistically significant reduction in DPOAE amplitude after an acute fistula across all stimulus levels (p < .001). At 18 days the DPOAE amplitudes in animals with healed fistulas could not be differentiated from controls, whereas DPOAE amplitudes in animals with patent fistulas were statistically different from controls (p < .05). The results suggest that evoked otoacoustic emissions may be useful in detecting perilymphatic fistulas.     

The influence of (+/-)-kavain on population spikes and long-term potentiation in guinea pig hippocampal slices

The judicious use of perioperative antibiotic prophylaxis reduces the infectious complications of surgery. However, increased bacterial resistance within hospitals may make antibiotic prophylaxis less effective in the future and alternative strategies are needed. New immunomodulatory agents might prevent wound infections by stimulation of the host immune system. To test this hypothesis, we administered poly-[1-6]-beta-D-glucopyranosyl- [1-3] -beta-D-glucopyranose glucan (PGG glucan), which enhances neutrophil microbicidal activity, intravenously to guinea pigs in doses ranging from 0.015 to 4 mg/kg of body weight on the day before, on the day of, and on the day after intermuscular inoculation with methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis. Abscesses were identified at 72 h, and median infective doses (ID50) and statistical significance were determined by logistic regression. Guinea pigs receiving PGG glucan and inoculated with methicillin-resistant S. aureus and S. epidermidis exhibited ID50 of as much as 2.5- and 60-fold higher, respectively, than those of control guinea pigs not receiving PGG glucan. Maximal protection was observed with a dose of 1 mg of PGG glucan per kg, and efficacy was reduced at higher as well as at lower PGG glucan doses. Furthermore, a single dose of PGG glucan given 24 h following bacterial inoculation was found to be effective in preventing infection. We conclude that PGG glucan reduces the risk of staphylococcal abscess formation. Neutrophil-activating agents are a novel means of prophylaxis against surgical infection and may be less likely than antibiotics to be affected adversely by the increasing antibiotic resistance of nosocomial pathogens.     

矿井环境中柴油机尾气颗粒的净化研究

在金属矿山中生产运行的采矿、运输等设备部分是柴油机动力系统,其排放的尾气给工作人员和机器设备带来诸多的危害。对柴油机尾气中的细微颗粒进行分析,并结合前人的研究成果,提出了采用可控循环通风方法解决通风不足,采用尾气引射器将柴油机尾气导出独头巷道,采用文丘里除尘器净化井下环境中柴油机尾气颗粒的综合有效措施。     

Effect of otologic drill noise on ABR thresholds in a guinea pig model

The noise generated by the otologic drill has been implicated as a cause of sensorineural hearing loss after ear surgery. However, clinical studies on this subject are contradictory and difficult to interpret. Therefore a guinea pig model was used to study whether the level of noise generated by the otologic drill can cause threshold shifts in the auditory brainstem response (ABR). The source noise was a recording obtained during a human cadaver mastoidectomy using a microphone and an accelerometer. Ten female Topeka-strain guinea pigs were exposed to the recorded drill noise for a period of 55 minutes. Exposure included both air-conducted energy from a speaker and bone-conducted energy from a bone vibrator applied directly to the skull. ABR threshold measurements were taken pre-exposure (baseline), immediately after exposure, and at weekly intervals thereafter for 3 weeks. Three control animals were subjected to the same procedure without the sound exposure. A significant threshold shift (p < 0.0001) was seen for each frequency tested (2, 4, 8, 16, 20, and 32 kHz) immediately after exposure to noise in all experimental animals. Thresholds returned to baseline within 3 weeks. We conclude that the level of noise generated by the otologic drill in mastoid surgery can cause a temporary threshold shift in this guinea pig model.     

Direct evidence for histamine H3 receptor-mediated inhibition of norepinephrine release from sympathetic terminals of guinea pig myocardium

AIM: To study the histamine H3 receptors mediated inhibition of norepinephrine (NE) release from cardiac sympathetic terminals of guinea pig isolated atria. METHODS: Release of NE induced by electric field stimulation (50 mA, 5 ms) in the bath solution was measured by HPLC-ECD. RESULTS: The release of NE caused by field stimulation was attenuated by (R)-alpha-methyl-histamine (alpha-MeHA, 0.1 nmol.L-1(-10) mumol.L-1) in a concentration-dependent manner. Thioperamide concentration-dependently antagonized the inhibition of alpha-MeHA. Blockade of H1, H2, alpha 2, beta 2-receptors failed to prevent the inhibitory effect of alpha-MeHA. Thioperamide (1 nmol.L-1(-10) mumol.L-1), when used alone, concentration-dependently facilitated the release of NE evoked by field stimulation. CONCLUSION: The presynaptic histamine H3-receptors inhibited the NE release from cardiac sympathetic terminals.