In vivo, in vitro correlation of acetylcholine airway responsiveness in sensitized guinea pigs. The role of modified epithelial functions.

1994 ◽  
Vol 149 (6) ◽  
pp. 1494-1498 ◽  
Author(s):  
Y Masaki ◽  
M Munakata ◽  
M Amishima ◽  
Y Homma ◽  
Y Kawakami
Keyword(s):  
Guinea Pigs ◽  
Airway Responsiveness

Paradoxical effect of salbutamol in a model of acute organophosphates intoxication in guinea pigs: role of substance P release

2007 ◽  
Vol 292 (4) ◽  
pp. L915-L923 ◽  
Author(s):  
Jaime Chávez ◽  
Patricia Segura ◽  
Mario H. Vargas ◽  
José Luis Arreola ◽  
Edgar Flores-Soto ◽  
...  
Keyword(s):  
Substance P ◽  
Guinea Pigs ◽  
Smooth Muscle Contraction ◽  
In Vivo Experiments ◽  
Intracellular Ca ◽  
Neurokinin 1 ◽  
Substance P Release

Organophosphates induce bronchoobstruction in guinea pigs, and salbutamol only transiently reverses this effect, suggesting that it triggers additional obstructive mechanisms. To further explore this phenomenon, in vivo (barometric plethysmography) and in vitro (organ baths, including ACh and substance P concentration measurement by HPLC and immunoassay, respectively; intracellular Ca2+ measurement in single myocytes) experiments were performed. In in vivo experiments, parathion caused a progressive bronchoobstruction until a plateau was reached. Administration of salbutamol during this plateau decreased bronchoobstruction up to 22% in the first 5 min, but thereafter airway obstruction rose again as to reach the same intensity as before salbutamol. Aminophylline caused a sustained decrement (71%) of the parathion-induced bronchoobstruction. In in vitro studies, paraoxon produced a sustained contraction of tracheal rings, which was fully blocked by atropine but not by TTX, ω-conotoxin (CTX), or epithelium removal. During the paraoxon-induced contraction, salbutamol caused a temporary relaxation of ∼50%, followed by a partial recontraction. This paradoxical recontraction was avoided by the M2- or neurokinin-1 (NK1)-receptor antagonists (methoctramine or AF-DX 116, and L-732138, respectively), accompanied by a long-lasting relaxation. Forskolin caused full relaxation of the paraoxon response. Substance P and, to a lesser extent, ACh released from tracheal rings during 60-min incubation with paraoxon or physostigmine, respectively, were significantly increased when salbutamol was administered in the second half of this period. In myocytes, paraoxon did not produce any change in the intracellular Ca2+ basal levels. Our results suggested that: 1) organophosphates caused smooth muscle contraction by accumulation of ACh released through a TTX- and CTX-resistant mechanism; 2) during such contraction, salbutamol relaxation is functionally antagonized by the stimulation of M2 receptors; and 3) after this transient salbutamol-induced relaxation, a paradoxical contraction ensues due to the subsequent release of substance P.

THE ROLE OF TESTOSTERONE AND ANDROSTENEDIONE AS PRECURSORS OF EPITESTOSTERONE IN GUINEA PIGS (IN VIVO AND IN VITRO STUDIES)

1971 ◽  
Vol 67 (1) ◽  
pp. 187-196 ◽  
Author(s):  
Marian Szamatowicz ◽  
Michel Drosdowsky ◽  
Max F. Jayle
Keyword(s):  
Sex Differences ◽  
Guinea Pigs ◽  
In Vitro Studies ◽  
Male And Female ◽  
Testosterone Production ◽  
Liver Slices

ABSTRACT After injection of [7α-3H] androstenedione and [4-14C] testosterone into male and female guinea pigs, doubly labelled aetiocholanolone, 5α-androstanedione and epiandrosterone were identified in the urine. No epitestosterone was detected. Ovaries, testes, adrenals and liver slices were incubated with the same precursors. Epitestosterone production was observed in all organs except in the adrenals. According to the epitestosterone 3H/14C ratio, it can be concluded that in guinea pigs an interconversion of testosterone, androstenedione and epitestosterone takes place. In liver, androstenedione is preferentially converted to epitestosterone without sex differences, whereas in ovary and testis epitestosterone derives preferentially from testosterone.

O3-induced airway hyperresponsiveness to noncholinergic system and other stimuli

1992 ◽  
Vol 73 (1) ◽  
pp. 354-361 ◽  
Author(s):  
M. G. Campos ◽  
P. Segura ◽  
M. H. Vargas ◽  
B. Vanda ◽  
H. Ponce-Monter ◽  
...  
Keyword(s):  
Substance P ◽  
Bronchoalveolar Lavage ◽  
Guinea Pigs ◽  
Airway Hyperresponsiveness ◽  
Airway Responsiveness ◽  
Insufflation Pressure

The effect of O3 exposure (3 ppm, 1 h) on the in vivo and in vitro airway responsiveness, as well as the changes in cell contents in bronchoalveolar lavage (BAL) fluid, were evaluated 16–18 h after O3 exposure in sensitized and nonsensitized male guinea pigs. The sensitization procedure was performed through repeated inhalation of ovalbumin for 3 wk. Increase in pulmonary insufflation pressure produced by the excitatory nonadrenergic noncholinergic (eNANC) system, histamine, and antigen were assessed in in vivo conditions, whereas airway responsiveness to histamine and substance P was evaluated in in vitro conditions by use of tracheal chains with or without epithelium and lung parenchymal strips. We found that O3 exposure 1) increased the neutrophil content in BAL fluids in both sensitized and nonsensitized guinea pigs, 2) caused hyperresponsiveness to eNANC stimulation in nonsensitized guinea pigs (although combination of sensitization and O3 exposure paradoxically abolished the hyperresponsiveness to eNANC stimulation), 3) increased the in vivo bronchoconstrictor responses to histamine and antigen, 4) caused hyperresponsiveness to substance P in nonsensitized tracheae with or without epithelium and in sensitized tracheae with epithelium, 5) did not modify the responsiveness to histamine in tracheae with or without epithelium (and in addition, epithelium removal caused hyperresponsiveness to histamine even in those tracheae exposed to O3), and 6) produced hyperresponsiveness to histamine in lung parenchymal strips either from sensitized or nonsensitized guinea pigs.

Ozone-induced airway hyperresponsiveness: role of superoxide anions, NEP, and BK receptors

1995 ◽  
Vol 78 (3) ◽  
pp. 1015-1022 ◽  
Author(s):  
H. Tsukagoshi ◽  
E. B. Haddad ◽  
J. Sun ◽  
P. J. Barnes ◽  
K. F. Chung
Keyword(s):  
Airway Hyperresponsiveness ◽  
Lavage Fluid ◽  
Airway Responsiveness ◽  
Ozone Exposure ◽  
Brown Norway ◽  
Superoxide Anions ◽  
Norway Rat

We investigated the role of reactive oxygen species in ozone-induced airway hyperresponsiveness (AHR) in Brown Norway rats. Airway responsiveness to inhaled acetylcholine (ACh) and bradykinin (BK) and inflammatory cell recruitment in bronchoalveolar lavage fluid (BALF) were measured in vivo. Neutral endopeptidase (NEP) activity assay and measurement of BK-receptor binding sites in Brown Norway rat lungs were carried out in vitro. Apocynin (5 mg/kg), an inhibitor of superoxide anion-generating NADPH oxidase, was administered perorally 30 min before a 3- or 6-h exposure to 3 ppm of ozone, and the animals were studied 18–24 h postexposure. Ozone induced increases in airway responsiveness to ACh and BK and in neutrophil counts in BALF. Apocynin inhibited the increase in airway responsiveness to BK but not to ACh without affecting the neutrophil counts in BALF. The antioxidants allopurinol and deferoxamine prevented ozone-induced AHR to both ACh and BK but did not reduce neutrophil counts. To further examine the mechanisms of ozone-induced AHR to BK, we measured NEP activity and the density of BK receptors in vitro after ozone exposure. Ozone exposure had no significant effect either on NEP activity or on the affinity and the number of BK receptors in lungs from rats treated with or without apocynin. We conclude that superoxide anions released from inflammatory cells in the airway may be involved in ozone-induced AHR. Inactivation of NEP or upregulation of BK receptors do not appear to be involved, but the possibility of localized changes cannot be excluded.

scholarly journals In Vitro and In Vivo Activities of Levofloxacin against Biofilm-Producing Pseudomonas aeruginosa

1998 ◽  
Vol 42 (7) ◽  
pp. 1641-1645 ◽  
Author(s):  
Hiroko Ishida ◽  
Yoshihisa Ishida ◽  
Yuichi Kurosaka ◽  
Tsuyoshi Otani ◽  
Kenichi Sato ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Standard Method ◽  
Phosphate Buffer ◽  
Guinea Pigs ◽  
Therapeutic Efficacy ◽  
Killing Activity ◽  
Biofilm Bacteria

ABSTRACT Interactions between biofilm cells of Pseudomonas aeruginosa and levofloxacin were studied. P. aeruginosa incubated for 6 days with Teflon sheets formed a biofilm on its surface. Against the biofilm bacteria, levofloxacin at an MIC determined by the standard method for the strain was highly bactericidal whereas gentamicin, ceftazidime, and ciprofloxacin showed no significant killing activity. Levofloxacin, ciprofloxacin, and gentamicin, but not ceftazidime, exhibited killing activity against nongrowing cells of the strain incubated in phosphate buffer. In addition, levofloxacin, ciprofloxacin, and ceftazidime, but not gentamicin, showed the ability to penetrate an agar containing alginate. These findings may explain the efficacy of levofloxacin and the ineffectiveness of gentamicin and ceftazidime against biofilm bacteria; however, the cause of the ineffectiveness of ciprofloxacin still remains to be determined. In experimental pneumonia in guinea pigs, in which the biofilm mode of growth of the strain was observed in the lung, only levofloxacin exhibited substantial therapeutic efficacy. These findings suggest the significant role of levofloxacin in therapy of biofilm bacterium-associated infectious diseases.

Role of thromboxane receptors in Forssman shock in guinea pigs

1989 ◽  
Vol 67 (1) ◽  
pp. 44-51 ◽  
Author(s):  
W. A. Schumacher ◽  
T. E. Steinbacher ◽  
G. T. Allen ◽  
M. L. Ogletree
Keyword(s):  
Guinea Pigs ◽  
Dynamic Compliance ◽  
Receptor Stimulation ◽  
Thromboxane Receptor ◽  
Pulmonary Manifestations ◽  
Airways Resistance ◽  
Thromboxane Receptors

Forssman shock is a bronchospastic reaction mounted in guinea pigs on intravenous administration of an antiserum obtained from rabbits immunized against sheep erythrocytes. The involvement of thromboxane receptors in Forssman shock was determined with SQ 30,741, which was characterized as a selective antagonist of these receptors in guinea pig airways in vitro and in vivo. A volume of antiserum producing consistent, sublethal bronchoconstriction was given either alone (control) or 3 min after SQ 30,741 (0.03, 0.3, or 1.0 mg/kg iv) to urethan-anesthetized guinea pigs. In controls, maximum reductions in dynamic compliance (-59 +/- 6%, P less than 0.01) and increases in airways resistance (383 +/- 97%, P less than 0.01) were detected 1 min after antiserum. Both responses were significantly inhibited by SQ 30,741, either partially at 0.03 mg/kg or completely at 0.3 mg/kg. An accompanying thrombocytopenia was not abated by SQ 30,741. In separate experiments, bronchospasm was reduced by aerosol administration of 0.1% SQ 30,741 and completely prevented by aspirin (10 mg/kg iv). When Forssman antiserum was injected in lethal quantities to other guinea pigs, SQ 30,741 (1 mg/kg iv) attentuated only the resistance component of bronchospasm and did not prevent death. These data demonstrate that thromboxane receptor stimulation is a pivotal step in the pulmonary manifestations of sublethal Forssman shock but is less crucial in more severe forms of the reaction.

scholarly journals Airway Responsiveness to Acetylcholine in Congenitally Bronchial-Hypersensitive(BHS) and Bronchial-Hyposensitive(BHR) Guinea Pigs in Vivo and in Vitro.

1998 ◽  
Vol 47 (3) ◽  
pp. 173-181 ◽  
Author(s):  
Yukihiro YAGI ◽  
Masayoshi KUWAHARA ◽  
Masashi MAEDA ◽  
Hiromi KADOTA ◽  
Shizue SAEGUSA ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Airway Responsiveness

Evidence for the existence of a C25-sesterterpene pathway of steroidogenesis not involving cholesterol as an obligatory intermediate

1983 ◽  
Vol 61 (7) ◽  
pp. 714-721 ◽  
Author(s):  
Bhagu R. Bhavnani ◽  
Tony Wong
Keyword(s):  
Isotope Dilution ◽  
Guinea Pigs ◽  
Radiochemical Purity ◽  
Specific Activity ◽  
Dilution Technique ◽  
Isotope Dilution Technique ◽  
Alternate Pathway

Previous in vitro studies had indicated the possibility of steroidogenesis through a C25-sesterterpene pathway in which squalene and cholesterol are not required as obligatory intermediates. To investigate whether such a pathway exists in vivo, the precursor role of [7-3H]23,24-dinor-5-cholene-3β,20-diol in the in vivo formation of cortisol by the guinea pigs was studied. The [3H]23,24-dinor-5-cholene-3β,20-diol was synthesized by reacting [3H]pregnenolone acetate with a Grignard reagent. The product was purified by chromatography and its radiochemical purity was established by the isotope dilution technique. In the first experiment a total of 134 × 106 dpm of [3H]23,24-dinor-5-cholene-3β,20-diol was injected subcutaneously into three guinea pigs. Urine was collected for 8 days and was pooled. Only 12% of the administered dose was excreted in the urine. The urine was extracted and a neutral extract (3 × 106 dpm) was obtained. From this extract 2.3 mg of cortisol containing 2.9 × 104 dpm was isolated. Radiochemical purity of the isolated cortisol was established by the isotope dilution technique. Radiochemical purity was further confirmed by conversion to cortisol 21-acetate and subsequently to 11β-hydroxyandrost-4-ene-3,17-dione and recrystallization to constant specific activity. The results of this experiment were confirmed by repeating the experiment with a higher specific activity [3H]23,24-dinor-5-cholene-3β,20-diol. These results indicate that the C25-sesterterpene pathway is a possible in vivo alternate pathway of steroidogenesis, not involving either squalene or cholesterol as obligatory intermediates.

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