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M M Cloutier

Publications and source records attributed to M M Cloutier.

36 records · Page 2Linked to original sources
PubMed1990

Duramycin enhances chloride secretion in airway epithelium.

The effect of duramycin, a polypeptide antibiotic, on Cl- transport in canine tracheal epithelium mounted in Ussing chambers was studied. Over a narrow concentration range, duramycin increased short-circuit current (Isc) and net Cl- secretion and had no effect on mannitol flux when added to the mucosal bathing solution. The maximum increase in Isc was observed at a duramycin concentration of 2 X 10(-6) M and was associated with an increase in both unidirectional Cl- fluxes. Higher duramycin concentrations produced a decrease in Isc. Submucosal addition of duramycin had no effect on Isc except at high concentrations. Pretreatment of tissues with mucosal amiloride (10(-4) M) to reduce basal Na+ transport had no effect on the subsequent response to duamycin. In other tissues pretreated with 10(-3) M dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP), duramycin produced a further increase in Isc and net Cl- secretion similar to its effect in nonpretreated tissues. In all instances the increase in Isc was entirely accounted for by an increase in net Cl- secretion. We conclude that duramycin increases Isc and Cl- secretion in airway epithelium. Although the mechanism of activation is not known, these data demonstrate that duramycin increases Cl- secretion by a pathway other than cAMP. An understanding of the mechanism of action of duramycin may further our understanding of Cl- secretion regulation in airway epithelium.

Animals↗
PubMed1989

Respiratory syncytial virus alters electrophysiologic properties in cotton rat airway epithelium.

The effect of respiratory syncytial virus (RSV) infection on the electrophysiologic properties of the airway epithelium was studied in tracheas obtained from cotton rats, after in vivo exposure to the virus. RSV infection was documented by tissue culture infectivity and immunofluorescent antibody techniques. Light microscopic studies of the tracheas 72 hours after exposure to RSV revealed normal epithelial morphology. RSV infection produced a 28% decrease in short-circuit current (Isc) and an almost 100% increase in tissue resistance. The decrease in Isc was partially attributed to a decrease in Cl secretion, while the increase in tissue resistance was associated with significant restriction to sodium and chloride movement through the paracellular pathway in RSV-infected tracheas. We conclude from these studies that RSV infection in the cotton rat trachea produces significant changes in active and passive ion flows. Alterations in ion transport across the airway epithelium may result in changes in secondary water transport across the airways and may contribute to the pathophysiology of RSV bronchiolitis and other locally invasive mucosal viral infections in children.

Airway Resistance↗
PubMed1989

Effects of tannins from different sources on airway epithelial and platelet function.

The uniqueness of tannin isolated from aqueous extracts of cotton bracts (CBE) on the electrophysiological and ion transport properties of the canine tracheal epithelium and on 5-hydroxytryptamine (5-HT) release from platelets was investigated. The effect of CBE from Deltapine 41 cotton picked before (green, containing high-concentration, high-molecular-weight tannin) and after (brown, containing low-concentration, low-molecular-weight tannin) senescence and Darjeeling tea extracts and tannin isolated from Darjeeling tea were compared to the effects of Acala SJ-2 CBE and Acala SJ-2 tannin. Green Deltapine 41 CBE was similar to Acala SJ-2 CBE in decreasing short-circuit current (Isc) and net chloride secretion and in producing a dose-response release of 5-HT from platelets. Both Green and Brown Deltapine 41 CBE altered the paracellular pathway, but were less potent than Acala SJ-2 CBE. Brown Deltapine 41 CBE stimulated chloride transport in the airway epithelium and did not produce 5-HT release from human platelets. Darjeeling tea and tea tannin increased Isc and net chloride secretion and caused 5-HT release from platelets only at high concentrations. These studies demonstrate that all tannins are not alike; they suggest that molecular weight and concentration may be important for tannin activity and that the tannin in cotton bracts extract may be unique to cotton in its effect on the airway epithelium and on platelets.

Airway Resistance↗
PubMed1989

p-aminohippurate transport in the airways: role of Na+ and HCO3-.

The role of Na+ and HCO3- in the transport of p-aminohippurate (PAH) across the canine tracheal epithelium was investigated using Ussing chamber techniques and radiolabeled PAH. Under control conditions, net PAH absorption or a tendency toward net PAH absorption was observed. Neither amiloride (10(-4) M), furosemide (10(-3) M), ouabain (2 x 10(-4) M), nor Na+ substitution of the Ringer solution with choline had any effect on unidirectional PAH fluxes. When the Ringer solution was replaced with a HCO3(-)-free solution, net PAH absorption was consistently observed. In HCO3(-)-free experiments, unidirectional PAH absorptive fluxes were inhibited by mucosal addition of either of the stilbene derivatives, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, 10(-4) M) or 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS, 10(-4) M). DIDS was more effective than SITS and was also effective in inhibiting PAH absorption in tissues bathed in Ringer solution. Submucosal DIDS or SITS had no effect on PAH fluxes either in HCO3(-)-free or Ringer experiments. We conclude that PAH transport in canine tracheal epithelium occurs by a HCO3(-)-PAH exchange process located on the luminal membrane. PAH transport is not Na+ dependent but is inhibited by both DIDS and SITS.

Amiloride↗
PubMed1987

Probenecid affects chloride secretion in canine tracheal epithelium.

The effects of probenecid on the electrophysiology, ion transport properties, and permeability characteristics of the canine tracheal epithelium mounted in Ussing chambers were studied. Mucosal addition of probenecid had 2 effects: at low concentrations (0.1 to 0.5 mM), probenecid increased short-circuit current (Isc) and net Cl secretion, whereas higher concentrations (5 and 10 mM) decreased Isc and net Cl secretion; 1 mM probenecid had no effect. The change in Isc was accounted for entirely by the change in the net Cl secretion. The effects were rapidly reversible and even after prolonged exposure were not associated with any change in the paracellular pathway as evidenced by mannitol fluxes. Submucosal addition of probenecid produced a significant decrease in Isc and net Cl secretion only at 10 mM, and the effect was delayed, suggesting movement of some of the probenecid into the mucosal bath. We conclude from these experiments that probenecid at concentrations greater than 1 mM inhibits Cl secretion in canine tracheal epithelium; the effect is primarily from the mucosal side and is reversible. Because probenecid is structurally related to a group of analogs of benzoic acid that inhibit the Cl conductance at the apical membrane, we suggest that probenecid might also block the electrically conductive Cl exit pathway in the apical cell membrane.

Animals↗
PubMed1986

Effects of endotoxin and tannin isolated from cotton bracts on the airway epithelium.

The effects of increasing concentrations of tannin isolated from cotton bracts and endotoxin prepared from Enterobacter agglomerans on the electrophysiologic and ion transport properties of the canine tracheal epithelium mounted in Ussing chambers were examined. Results were compared with those obtained using cotton bracts extract (CBE). Tannin concentrations in the isolated tannin and in the cotton bracts were analyzed spectrophotometrically. When added to the mucosal bathing solution, tannin produced a significant decrease in transepithelial potential difference and short-circuit current (lsc) with a maximal response at 25 microliter. The decrease in lsc was accounted for entirely by a decrease in net chloride secretion. The effects were reversible and specific for the mucosal bathing solution. In contrast to CBE, tannin had no effect on mannitol flux, suggesting no effect on the paracellular pathway. Endotoxin at a concentration of 10 micrograms/ml had no effect on the electrophysiologic properties of the canine trachea. We conclude that tannin in CBE is responsible for the decrease in lsc observed with aqueous extracts of CBE but is not responsible for the changes in the paracellular pathway. We also conclude that endotoxin alone has no effect on the airway epithelium.

Animals↗
PubMed1985

p-Aminohippurate transport in canine tracheal epithelium.

The unidirectional fluxes of 20, 100, 500, and 2,000 microM rho-aminohippurate (PAH) were measured under open- and short-circuit conditions in canine tracheal epithelium mounted as flat sheets in Ussing chambers. In tissues pretreated with mucosal indomethacin (10(-6) M) and amiloride (10(-4) M), unidirectional PAH fluxes under short-circuit conditions increased with increasing bath concentrations but there was no significant net PAH transport. After stimulation of chloride secretion by mucosal cyclic adenosine 3',5' -cyclic monophosphate (cAMP 10(-3) M), there was a significant increase in the secretory flux of PAH and a significant decrease in the absorptive flux of PAH. This resulted in net PAH secretion that demonstrated saturation kinetics with an apparent Michaelis-Menten constant of 754 microM by Lineweaver-Burk analysis. Intracellular concentrations of PAH were 0.4-1.2 times bath concentrations after pretreatment with indomethacin and amiloride and increased to 2.6-3.3 times bath concentrations after cAMP. Under open-circuit conditions, secretory PAH flux decreased and absorptive flux increased resulting in net PAH absorption. We conclude from these early studies that the canine tracheal epithelium possesses a specialized system for the transport of organic anions in the airways and that this transport system may share many similarities with organic anion transport in the kidney.

Amiloride↗
PubMed1984

Effect of cotton bracts extract on canine tracheal epithelium and shunt pathway.

The effects of increasing concentrations (5 to 100 microliters) of an aqueous extract of cotton bracts (CBE) on the electrophysiologic properties and paracellular pathway of the canine trachea mounted in Ussing chambers were examined. The CBE produced a 50% decrease in short-circuit current and a dose-dependent decrease in transepithelial potential difference and tissue resistance when added to the mucosal bathing solution. The decrease in tissue resistance after exposure to 25 and 100 microliters was followed by an increase in mannitol flux, suggesting an effect on the paracellular pathway. No significant effect on mannitol flux was seen after 5 microliters CBE, when results were compared with control tissues from the same dog. The effects of 5 microliters CBE but not higher concentrations were reversible. Submucosal CBE had no effect on the electrophysiologic properties of the canine trachea or on mannitol flux. We conclude that in the canine tracheal epithelium, CBE inhibits active ion transport, alters the paracellular pathway, and acts only from the luminal surface.

Animals↗
PubMed1984

Effects of cAMP, furosemide, and ouabain on transtracheal tetracycline and chloramphenicol influx in the rat.

Using an in vitro perfusion model of the rat trachea, we studied the effects of dibutyryl cAMP (10(-3)M), terbutaline sulfate (1.7 X 10(-4)M), furosemide (10(-3)M), and ouabain (10(-3)M) on net transtracheal tetracycline and chloramphenicol influx. Submucosal cAMP and terbutaline increased transepithelial potential difference and short-circuit current and net tetracycline influx from control values of 0.496 +/- 0.066 (mean +/- SEM, n = 9) and 0.451 +/- 0.077 nM/cm2 h (n = 7) by 51 and 29%, respectively. Submucosal furosemide and ouabain decreased transepithelial potential difference, short-circuit current, and net tetracycline influx from control values by 22 and 29%, respectively. Neither cAMP, terbutaline, furosemide, nor ouabain had any effect on net chloramphenicol influx. These data suggest that drugs used in conjunction with antibiotics in patients with obstructive pulmonary disease may alter delivery of certain antibiotics into the airway lumen.

Animals↗
PubMed1982

Significance of roentgenographic abnormalities in children hospitalized for asthma.

The relatively high incidence of roentgenographic abnormalities in patients hospitalized for acute asthma has led some to recommend that all such patients receive chest x-ray examination upon admission to the hospital. We studied the incidence and clinical predictability of the roentgenographic findings by asking the admitting physician to indicate, prior to obtaining a roentgenogram, whether he thought pneumonia, pneumothorax, pneumomediastinum or other significant abnormality was present. A treatment plan was also outlined at that time. Seven of 128 patients (5.5 percent) had roentgenograms suggestive of pneumonia or pneumothorax; three of these were suspected clinically. In 14 cases the clinical suspicion of pneumonia or pneumothorax was not borne out roentgenographically. The initial treatment plan was altered in only three cases. The low incidence of roentgenographic abnormalities and the failure of these minor abnormalities to substantially influence treatment suggest that routine chest roentgenograms may not have to be performed on all children hospitalized for acute asthma.

Adolescent↗
PubMed1981

Effects of hyperoxia on transtracheal chloramphenicol influx.

Effects of exposure to high partial pressures of oxygen on transtracheal influx of chloramphenicol (Chlor) were examined using in vitro perfusion of the rat trachea. Net Chlor influx decreased with increasing duration of exposure to 100% O2 from control levels of 37.0 +/- 2.4 ng.min-1.trachea-1 to 30.0 +/- 1.0 ng.min-1.trachea-1 after 36 h of exposure to 100% O2 and was further depressed after 48 h of exposure to 100% O2 60 23.0 +/- 0.9 ng.min-1.trachea-1. Examination of the O2-exposed tracheas by light microscopy showed normal morphology. In contrast, net Chlor influx was not affected by exposure to 50% O2 for 48 h. In a separate group of rats recovery from the effects of hyperoxia was studied. Within 24 h after removal from the hyperoxic environment, net Chlor influx had returned to control levels. We conclude that high partial pressures of oxygen inhibit net Chlor influx in the rat trachea at a time when tracheal histology is normal. This inhibition is a function of the partial pressure of oxygen and the duration of exposure and it is reversible after removal from the hyperoxic environment.

Animals↗
PubMed1981

Studies of chloramphenicol and tetracycline influx in the rat trachea.

A tracheal tissue perfusion system capable of determining net fluxes of drugs into the lumen of the airways in vitro and in vivo was used to study the characteristics of chloramphenicol and tetracycline influx in the rat trachea. For both antibiotics, the rate of net influx did not vary with the rate of tracheal perfusion at flow rates between 0.7 and 4.2 microliter/min. At 37 degrees C when the concentration of the antibiotic in the bath surrounding the trachea was increased, the net influx of the antibiotic into the tracheal lumen initially increased linearly. The rate of increase was 1.15 ng/min.trachea per microgram/ml for chloramphenicol at chloramphenicol concentrations in the bath between 12 and 108 microgram/ml and 0.61 ng/min.trachea per microgram/ml for tetracycline at bath concentrations between 4 and 24 microgram/ml. At chloramphenicol concentrations in the bath between 108 and 168 microgram/ml and at bath tetracycline concentrations between 24 and 96 microgram/ml, a maximum rate of influx was observed. At 6 degrees C, net influx for both antibiotics was less than the influx observed at 37 degrees C. Net influx again increased with increasing antibiotic concentrations in the bath but at a slower rate (0.29 ng/min.trachea per microgram/ml for chloramphenicol and 0.25 ng/min.trachea per microgram/ml for tetracycline). At 24 degrees C, net influx and the increase in influx with increasing bath concentrations were intermediate between the influx and the rate of increase in influx observed for chloramphenicol at 37 and 6 degrees C (0.5 ng/min.trachea per microgram/ml). There was no difference in net influx between the in vitro and in vivo experiments for either chloramphenicol or tetracycline at comparable bath or plasma concentrations. This study demonstrates that antibiotic transport in the airways can be studied in vitro using this perfusion system. Tetracycline and chloramphenicol influx demonstrate concentration and temperature dependence and saturability in the rat trachea.

Animals↗
PubMed1981

Chronic cough in children: a manifestation of airway hyperreactivity.

Fifteen children who presented with chronic cough as an isolated manifestation of respiratory disease were evaluated for the presence of exercise-induced airway hyperreactivity. Pulmonary function tests using air and a helium/oxygen gas mixture were performed before exercise. Eight subjects were also evaluated by spirometry and maximum expiratory flow volume curves before and after isoproterenol inhalation on a separate day. Ten subjects had normal pulmonary function tests at rest and five had isolated minor abnormalities. No significant changes in pulmonary function tests were recorded after inhalation of isoproterenol in the eight subjects studied. Following exercise, all 15 subjects demonstrated changes in pulmonary function tests which were similar to those seen in children with mild exercise-induced bronchospasm. After institution of theophylline, exercise-induced decreases in flow rates low in the vital capacity were blocked in all subjects; however, several subjects had persistent mild decreases in peak flow. Within six months of discontinuing the theophylline, cough recurred in 11 of the 15 subjects. Nine subjects were restudied after return of their cough. Exercise again resulted in decreased lung function. Reinstitution of theophylline eliminated the cough in these nine subjects. This study demonstrates that chronic cough in some children may be a manifestation of airway hyperreactivity. Both the cough and the reactivity can be blocked with theophylline.

Adolescent↗
PubMedDate not supplied

Eprazinone alters lung lavage lipid levels and transtracheal ion transport.

Eprazinone therapy improves pulmonary function and arterial pO2 in patients with chronic bronchitis; however, the mechanism of action is unknown. The purpose of this study was to determine if eprazinone alters either lung surfactant levels in bronchoalveolar lavage fluid (BAL) of normal rats, or ion transport across canine tracheal epithelium mounted in Ussing chambers. In the surfactant studies, normal rats were force fed three doses (50, 100, and 200 mg/kg) of eprazinone for 4 days. Eprazinone at a dose of 200 mg/kg significantly increased total and individual (with the exception of phosphatidylinositol) phospholipid levels and decreased total neutral lipids. Lower doses of eprazinone significantly decreased neutral lipid levels without affecting the phospholipids. There was no change in BAL levels of protein or cells and no abnormal histology. In airway epithelial studies, mucosal addition of eprazinone produced a dose-dependent partially reversible decrease in short-circuit current (Isc). The decrease in Isc at lower eprazinone concentrations was accounted for entirely by a decrease in net chloride secretion while at higher concentrations both sodium and chloride transport were affected. Submucosal eprazinone had no affect on ion transport. These studies suggest that eprazinone influences both BAL lipid levels and ion transport, either of which could lead to a beneficial therapeutic effect.

Absorption↗
PubMedDate not supplied

Duramycin increases intracellular calcium in airway epithelium.

Duramycin increases short-circuit current (Isc) and net Cl- secretion in tracheal epithelium. We measured the intracellular free calcium ([Ca2+]i) response to duramycin using Indo-1 and bovine and canine tracheal cell suspensions, and the effect of an intracellular calcium chelator, BAPTA, and the protein kinase C inhibitor, staurosporine, on the Isc and [Ca2+]i response to duramycin. [Ca2+]i increased in a dose-dependent manner from basal levels of 34 +/- 5 to 949 +/- 136 nM at 5 x 10(-6) M duramycin. Both BAPTA (50 microM) and staurosporine (5-50 nM) pretreatment blunted the increase in Isc and net Cl- secretion produced by duramycin. BAPTA also blunted the rise in [Ca2+]i produced by duramycin (5 x 10(-6) M) in the presence of extracellular calcium (499 +/- 122 nM). In the absence of extracellular calcium, the duramycin-induced (5 x 10(-6) M) rise in [Ca2+]i was blunted from 949 +/- 136 nM (stimulation in the presence of Ca2+) to 621 +/- 122 nM, and was further decreased in the presence of BAPTA to 197 +/- 42 nM. In contrast, staurosporine (50 nM) pretreatment had no effect on the rise in [Ca2+]i produced by duramycin (basal 90 +/- 27 to 861 +/- 110 nM at 5 x 10(-6) M). Duramycin had no effect on [Ca2+]i in human neutrophils. These data demonstrate that duramycin releases calcium from intracellular stores and stimulates the influx of calcium in airway epithelial cells. These data also demonstrate that, in the presence of protein kinase C pathway blockade, an increase in intracellular free calcium is not sufficient for chloride secretion; thus, duramycin-stimulated chloride secretion may depend upon protein kinase C.

Alkaloids↗