Aeroallergen‐induced dyspnea in freely moving guinea pigs: quantitative measurement by bias flow ventilated whole body plethysmography

Chand, N.; Nolan, K.; Pillar, J.; Lomask, M.; Diamantis, W.; Sofia, R. D.

doi:10.1111/j.1398-9995.1993.tb00721.x

Cited by 38 publications

(23 citation statements)

References 9 publications

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“…Therefore, in this study the Penh is considered as a total lung resistance index (iRL), as has been proposed by others and us (Allen et al 1995;Chand et al 1993;Hamelmann et al 1997;Sommer et al 1998).…”

Section: Penh=((te-rt)/rt)(pep/pip)mentioning

confidence: 98%

“…The plethysmographic system has been previously described in detail (Chand et al 1993;Hamelmann et al 1997). Briefly, the pressure inside the chamber was measured by a differential pressure transducer (SCXL004DN; Sensym, Milpitas, Calif., USA) connected to a preamplifier, and continuously monitored through a software (Buxco Biosystem XA v1.1) in a microcomputer.…”

Section: General Proceduresmentioning

confidence: 99%

See 1 more Smart Citation

Identification of mechanisms involved in the acute airway toxicity induced by parathion

Segura

Chávez

Montaño

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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Organophosphates are still widely used worldwide and cause thousands of intoxications every year. In this work we investigated the mechanisms of parathion (Pth) airway toxicity, using biochemical and functional approaches. A plethysmographic technique for unrestrained guinea pigs was used to analyze Pth-induced modifications of airway mechanics and responsiveness to acetylcholine (ACh: 0.1-3.2 mg/ml, 2-min inhalation each dose). The isolated perfused rabbit lung preparation was used to study the acute effects of Pth on airway responsiveness to ACh (10(-8)-10(-3) M), histamine (10(-8)-10(-3) M) and substance P (10(-10)-10(-6) M), pulmonary acetylcholinesterase inhibition and cytochrome P450 (P450) activity, and their modifications with previous administration of Pth (1 mg/kg s.c. daily, 7 days). We found that: (1) In guinea pigs Pth (3.2-17 mg/kg i.p.) produced a dose-dependent increase in a lung resistance index (iRL), which was greatly reverted (approximately 50%) by salbutamol (2 mg/ml, 2-min inhalation, or 10 microg/kg i.p.). This salbutamol effect was transient (5-10 min), suggesting that this bronchodilator triggered additional obstructive mechanisms. (2) Pth increased the water content in lung parenchyma samples, but not in trachea or bronchi, and augmented the respiratory secretions measured through monosaccharide content in bronchoalveolar lavage. (3) The increase in iRL was greater in female animals, probably due to a higher P450 basal activity, and completely blocked by pharmacological inhibition of P450 with piperonyl butoxide (500 mg/kg i.p.). (4) In male guinea pigs a subclinical dose of Pth (10 mg/kg i.p.) induced airway hyperresponsiveness to ACh. In isolated perfused rabbit lung Pth (10(-6) M) produced airway hyperresponsiveness to ACh and histamine, the latter prevented by atropine (10(-5) M). (5) Repetitive exposure to subclinical doses (1 mg/kg s.c.) of Pth during 1 week caused approximately 80% inhibition of P450 activity in rabbits, which was not enough, however, to prevent the functional manifestation of Pth toxicity in the airways.

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Section: Penh=((te-rt)/rt)(pep/pip)mentioning

confidence: 98%

Section: General Proceduresmentioning

confidence: 99%

Identification of mechanisms involved in the acute airway toxicity induced by parathion

Segura

Chávez

Montaño

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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“…In 'f .,C, .ir a first one, 5-HT was administered i.v. to anesthetized mice (5,18), and in the second, methacholine was administered by aerosol to awake animals (19). This is important since bronchoconstrictor responses may differ according to the route of administration of the agonists, which determines the first line cell species that is encountered.…”

mentioning

confidence: 99%

“…Indeed, IL-5 was present in the BALF and serum of the BP2 mice after antigen challenge and the anti-IL-5 antibody TRFK-5 suppressed altogether eosinophilia in airways and tissues and BHR. In allergen-challenged guinea pigs, anti-IL-5 antibody also suppressed airway eosinophilia (26) and BHR (27,28). CD4+ T lymphocytes that migrate into the lungs after antigen challenge (29) are responsible for the local production of IL-4 and IL-5, which are important in B-and T-lymphocyte development and function and in eosinophil activation and differentiation (30).…”

mentioning

confidence: 99%

Eosinophil recruitment into the respiratory epithelium following antigenic challenge in hyper-IgE mice is accompanied by interleukin 5-dependent bronchial hyperresponsiveness.

Eum

Hailé

Lefort

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

185

132

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A murine model for antigen-induced bronchial hyperreactivity (BHR) and airway eosinophilia, two hallmarks of asthma, was developed using ovalbuminimmunized mice, which produce large amounts of IgE (named BP2, "Bons Producteurs 2," for High Line of Selection 2). A single intranasal ovalbumin challenge failed to modify the bronchial responses, despite the intense eosinophil recruitment into the bronchoalveolar lavage fluid and airways. When mice were challenged twice a day for 2 days or once a day for 10 days, BHR in response to i.v. 5-hydroxytryptamine or to inhaled methacholine was induced in BP2 mice but not in BALB/c mice. Histological examination showed that eosinophils reached the respiratory epithelium after multiple ovalbumin challenges in BP2 mice but remained in the bronchial submucosa in BALB/c mice. Total IgE titers in serum were augmented significantly with immunization in both strains, but much more so in BP2 mice. Interleukin 5 (IL-5) titers in serum and bronchoalveolar lavage fluid of BP2 mice were augmented by the antigenic provocation, and a specific anti-IL-5 neutralizing antibody suppressed altogether airway eosinophilia and BHR, indicating a participation of IL-5 in its development. Our results indicate that the recruitment of eosinophils to the airways alone does not induce BHR in mice and that the selective effect on BP2 mice is related to their increased IgE titers associated with antigen-driven eosinophil migration to the epithelium, following formation and secretion of IL-5.Bronchial hyperreactivity (BHR) Evaluation of Bronchoconstriction. In a first procedure, mice were prepared as described (5), using the computerized pulmonary analyzer (Mumed PR800 system, UK) adapted to mice. To evaluate the effect of antigenic challenge on airway responsiveness, 5-hydroxytryptamine (5-HT; Sigma) was injected into the cannulated jugular vein at 10, 20, 40, 80, 160, and 320 jig/kg in a volume of 100 ,ul during 10 sec at 5-min intervals. The results were expressed as PD30, PD60, and PD90 (the amount of 5-HT needed to augment the bronchial resistance by 30%, 60%, and 90%). In a second procedure, unrestrained conscious mice were placed in a whole body plethysmographic chamber (Buxco Electronics, Sharon, CT) to analyze the respiratory waveforms. After a few minutes for stabilization, an aerosol of methacholine (3 x 10-2 M in the aerosolator; Aldrich) was delivered during 20 and 60 sec, at a 10-min interval. The airway resistance was expressed as Penh = [Te (expiratory time)/40% of Tr (relaxation time) -1] x Pef (peak expiratory flow)/Pif (peak inspiratory flow) x 0.67, according to the recommendations of the manufacturer. To calculate the APenh (difference between the basal and maximal value), the average of five maximal values was used.

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“…The potential for adverse effects on respiration or motor activity/sedation were assessed using whole-body plethysmography and rotarod test in rats. 119,120 Effects on respiration were quantified by the measurement of respiratory rate, tidal volume, peak inspiratory flow, peak expiratory flow, inspiration time and expiration time. At the maximum test dose tested of 16 lg/kg IV, which was 3Á2-fold the analgesic ED50 dose in the tail-flick test, cebranopadol did not produce any significant changes in the measured respiratory parameters or on In vitro human binding assay results motor coordination.…”

Section: Potential For Aesmentioning

confidence: 99%

Cebranopadol: novel dual opioid/NOP receptor agonist analgesic

et al. 2016

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SUMMARYWhat is known and objective: Chronic pain presents a difficult clinical challenge because of the limited efficacy, the limiting adverse-effect profile or the abuse potential of current analgesic options. Cebranopadol is a novel new agent in clinical trials that combines dual agonist action at opioid and nociceptin/orphanin FQ peptide (NOP) receptors. It is the first truly unique, centrally acting analgesic in several years. We here review the basic and clinical pharmacology of cebranopadol. Methods: Published literature and Internet sources were searched to identify information related to the basic science (pharmacology and medicinal chemistry) and development (clinical trial) information on the mechanism of dual opioid and NOP receptor pharmacologic action in general, and for cebranopadol in particular. The identified sources were reviewed and the information synthesized. Results: The preclinical testing of cebranopadol has characterized it as a dual opioid and NOP receptor agonist that displays antinociceptive and antihyperalgesic action in a variety of acute and chronic pain models in animals. Unlike most current traditional opioids, it is generally more potent against neuropathic than nociceptive pain. Several phase 2 clinical trials have been completed. What is new and conclusion: Despite the medical need, a truly novel centrally acting analgesic has not been developed in many years. Cebranopadol represents a truly novel mechanistic approach. Its actual place in pain pharmacotherapy awaits the results of phase 3 clinical trials.

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Aeroallergen‐induced dyspnea in freely moving guinea pigs: quantitative measurement by bias flow ventilated whole body plethysmography

Cited by 38 publications

References 9 publications

Identification of mechanisms involved in the acute airway toxicity induced by parathion

Identification of mechanisms involved in the acute airway toxicity induced by parathion

Eosinophil recruitment into the respiratory epithelium following antigenic challenge in hyper-IgE mice is accompanied by interleukin 5-dependent bronchial hyperresponsiveness.

Cebranopadol: novel dual opioid/NOP receptor agonist analgesic

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