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  • 1
    Electronic Resource
    Electronic Resource
    The effect of terbutaline (PINN) 1-(3.5-dihydroxyphenyl)-2-(t-butylamino)-ethanol on the choledochoduodenal sphincter (1970)
    Springer
    Cellular and molecular life sciences 26 (1970), S. 388-389 
    Details
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Dieβ- Rezeptoren vom Sphinkter von Oddi werden durch Terbutalin selektiv stimuliert.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01896904
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of enprofylline, a xanthine lacking adenosine receptor antagonism, in patients with chronic obstructive lung disease (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 395-402 
    Details
    ISSN: 1432-1041
    Keywords: enprofylline ; theophylline ; obstructive lung disease ; adenosine ; antagonism ; bronchodilatation ; plasma levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Enprofylline, a xanthine-derivative shown experimentally to lack universal adenosine receptor antagonism, has been examined in patients with partly reversible, chronic, obstructive lung disease. Significant bronchodilation was produced by enprofylline 2 mg/kg, giving a peak plasma concentration of 3.0±0.6 µg/ml (mean ± SD). A dose of 2+4 mg/kg dilated the bronchi at least to the same extent as theophylline 9.2±0.9 mg/kg (plasma level 18.5±4.7 µg/ml). Neither at the low nor at the high dosage (2+4 mg/kg), giving plasma concentrations of 8.5±1.4 µg/ml, did enprofylline produce theophylline-like CNS effects, such as restlessness and tremor, but it did exhibit some of the innocuous side effects expected with xanthine derivatives, such as epigastric discomfort and headache. The comparison with theophylline was limited because different dosage forms had to be used (solution and tablets), which for example, resulted in different absorption rates. Nevertheless, the present findings indicate enprofylline to be a potent bronchodilator in patients with obstructive lung disease, suggesting that adenosine-receptor antagonism is not involved in the bronchodilator effects of xanthines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542541
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  • 3
    Electronic Resource
    Electronic Resource
    Increase in plasma free fatty acids and natriuresis by xanthines may reflect adenosine antagonism (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 33-38 
    Details
    ISSN: 1432-1041
    Keywords: adenosine antagonism ; xanthines ; theophylline ; enprofylline ; free fatty acids ; natriuresis ; catecholamines ; renin ; insulin ; glucagons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The hypothesis has been examined that adenosine is involved in the diuretic and free fatty acid (FFA) — releasing action of xanthines. The effects of theophylline (T), a potent adenosine antagonist, were compared with those of enprofylline (3-propyl xanthine, E), which exerts negligible antagonism of adenosine. Eight healthy male volunteers were given E 1.5 mg/kg, T 5.0mg/kg or placebo 0.9% saline (P) intravenously in a double-blind, randomized, cross-over investigation. Blood samples were analyzed for E, T, catecholamines (CA: adrenaline, noradrenaline and dopamine), FFA, renin, glucose, glucagon and insulin, and urine was collected at 2-h intervals. T (plasma concentration 53±8 µmol/l) but not E (11±2 µmol/l) caused an increase in FFA from 0.42 to 0.86 mmol/l after 90 min. Without affecting the urinary excretion of potassium, T doubled natriuresis and the urine volume as compared to E and P. Neither T nor E had any effect on plasma CA, or on any other of the metabolic parameters studied. E, but not T, produced a small but statistically significant decrease in diastolic blood pressure (5 mmHg) and an increase in heart rate (3 beats/min). It is suggested that the difference between E and T in terms of stimulation of FFA-release and natriuresis may be related to their different ability to antagonize adenosine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546705
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  • 4
    Electronic Resource
    Electronic Resource
    Histamine-induced airway mucosal exudation of bulk plasma and plasma-derived mediators is not inhibited by intravenous bronchodilators (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 59-65 
    Details
    ISSN: 1432-1041
    Keywords: Nasal airways ; Plasma exudation ; Xanthine derivatives ; fibrinogen ; bradykinins ; terbutaline ; theophylline ; nasal mucosa ; nasal lavage ; histamine provocation test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Experimental data suggest the possibility that common bronchodilators, such as the xanthines and β2-adrenoceptor agonists, may produce microvascular anti-permeability effects in the subepithelial microcirculation of the airways. In this study, we have examined the effect of bronchodilators given intravenously on exudation of differentsized plasma proteins (albumin and fibrinogen) and the generation of plasma-derived peptides (bradykinins) in human nasal airways challenged with histamine. In a double-blind, crossover, placebo-controlled and randomised trial, 12 normal volunteers were given IV infusions of terbutaline sulphate, theophylline and enprofylline to produce therapeutic drug levels. The effect of topical nasal provocation with histamine was closely followed by frequently nasal lavage with saline. The lavage fluid levels of albumin, fibrinogen and bradykinins increased significantly after each histamine provocation. The ratio of albumin-to-fibrinogen in plasma and the lavage fluid was 24 and 56, respectively, indicating that topical histamine provocation induced a largely non-sieved flux of macromolecules across the endothelial-epithelial barriers. The systemically administered drugs did not affect the nasal symptoms (sneezing, secretion and blockage), nor did they significantly reduce the levels of plasma proteins and plasma-derived mediators in the nasal lavage fluids. The present data suggest that systemic xanthines and β2-adrenoceptor agonists, at clinically employed plasma levels, may not affect the microvascular (and epithelial) exudative permeability and the bradykinin forming capacity of human airways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195917
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  • 5
    Electronic Resource
    Electronic Resource
    Absorption of enprofylline from the gastrointestinal tract in healthy subjects (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 329-333 
    Details
    ISSN: 1432-1041
    Keywords: enprofylline ; healthy subjects ; absorption ; pharmacokinetics ; oral- ; duodenal- ; colonic administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Enprofylline, a new potent bronchodilator xanthine drug, was given orally as an aqueous solution to 6 healthy subjects in single doses of 2, 4 and 6 mg/kg. The two lower doses produced plasma concentrations in the range 1–4 mg/l, i.e. in the assumed “therapeutic interval” according to previous animal studies. A high 24 h urine recovery of unchanged drug, with mean values for the three dose levels ranging from 85 to 91% of the given dose, indicated good absorption and little metabolism. The dose-corrected area under the plasma concentration-time curve rose with dose as the latter was increased from 2 to 6 mg/kg. This indicates that the elimination of enprofylline is capacity-limited at high doses. Double peaks in the plasma concentration-time curves at the higher dose levels suggested intermittent and delayed gastric emptying as a possible explanation. This hypothesis was confirmed by studies in 6 other healthy subjects, who received the drug solution by three different routes; by mouth, via a catheter in the duodenum, and rectally via a catheter in the colon. The corresponding time to peak values (mean±SEM) were 32.5±8.7, 13.3±2.5, and 157±23 min.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542170
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  • 6
    Electronic Resource
    Electronic Resource
    Epithelial pathways for luminal entry of bulk plasma (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 25 (1995), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Inflammatory challenges of the airway mucosa cause luminal entry of bulk plasma. Extravasation of plasma is well described but the routes for epithelial passage of plasma are largely unknown. Using colloidal gold (5 nm) as tracer we have now examined the fate of extravasated plasma in the airways. The tracer was given intravenously to anaesthetized, ovalbumin-sensitized guinea-pigs 2min prior to airway mucosal challenge with 12pmol ovalbumin (the dose was selected from a separate dose-response study). Tissue specimens were collected 30s, 3 and 6 min after end of challenge (separate time course experiments suggested that the peak rate of entry of plasma occurred at about 5 min). The colloidal gold particles were visualized by autometallographic silver intensification. The gold produced no circulatory disturbance and had a uniform vascular distribution with negligible adherence to vascular endothelium. After challenge gold was first widely distributed in the lamina propria. At 3 and 6 min the tracer was also in the epithelium and airway lumen. It appeared that plasma was moved distinctly between and all around each epithelial cell. Bright field-, scanning-, and transmission electron-microscopy indicated that the luminal entry of plasma did not affect the integrity of the epithelial lining. This study demonstrates that the plasma exudate moves across an intact epithelial layer through ubiquitous paracellular pathways. Even at a pronounced acute plasma exudation response exceedingly small amounts of plasma may pass around a single cell explaining the non-injurious nature of mucosal exudation of bulk plasma in health and disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1995.tb01025.x
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  • 7
    Electronic Resource
    Electronic Resource
    Asymmetrical effects of increases in hydrostatic pressure on macromolecular movement across the airway mucosa. A study in guinea-pig tracheal tube preparations (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 21 (1991), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This study employed isolated guinea-pig tracheal tube preparations in order to examine effects of increases in hydrostatic pressure on the movement of macromolecular solutes (fluorescein isothiocyanate-conjugated dextran; FITC-D, MW 70 kD; kept either in serosal or mucosal bathing fluids) across the mucosa. An asymmetry of the mucosal barrier was demonstrated by the finding that under baseline zero-pressure difference conditions luminal entry of serosal FITC-D was greater than serosal entry of luminal FITC-D. Furthermore, an increased serosal pressure (5 cm H2O) moved significant amounts of serosal FITC-D into the lumen, whereas a corresponding pressure applied on the luminal side only marginally increased mucosal crossing of luminal FITC-D. By raising the luminal pressure to 10 and 20 cm H2O (which may be used as positive end-expiratory pressures (PEEP) in vivo in patients) mucosal penetration of luminal FITC-D was as marked as that induced in the opposite direction by the low (5 cm H2O) serosal pressure increase. Another aspect of the asymmetry of the airway mucosal barrier was evident from experiments examining the effect of a serosal pressure increase on mucosal penetration of luminal FITC-D. Neither during nor after the period of sustained serosal pressure increase was luminal FITC-D crossing the mucosa to a greater extent than under baseline zero-pressure conditions. This finding agrees with in-vivo data demonstrating that plasma exudation into the airway lumen may not be associated with an increased absorption of luminal solutes. The present results support the possibility that a plasma exudate itself creates pathways for its luminal entry by the following mechanism: by increasing the subepithelial hydrostatic pressure slightly a lateral compressive effect on epithelial cells is achieved, whereby apical tight junctions also separate to let through a bulk flow of different-sized plasma solutes; this is a distinct increase in outward permeability on the epithelium and when the pressure is reduced the tight junctions reassemble; hence, both during and after the exudation process the mucosa maintains its integrity as a barrier to luminal solutes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1991.tb00813.x
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  • 8
    Electronic Resource
    Electronic Resource
    Toluene diisocyanate produces an increase in airway tone that outlasts the inflammatory exudation phase (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 21 (1991), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Toluene diisocyanate (TDI) is a causative agent in occupational asthma. Through an oral catheter TDI, 0·03 μl, dissolved in 0·02 ml olive oil. was superfused on the tracheobronchial mucosa of anaesthetized guinea-pigs. TDI induced plasma exudation into both airway tissue and lumen (peak effect: 5 hr; duration ∼ 17 hr). Light microscopy examinations demonstrated that the epithelium was not disrupted by this process (and that microvessels are abundant just beneath the epithelium). At days 6 and 21 after exposure to TDI PAS-positive cells were increased, but no other histological alterations were found. Also, the occurrence of peptide-containing nerve fibres was not altered by TDI. After TDI-exposure the airway smooth muscle tone was elevated as examined in vitro at base-line and at concentration-response to carbachol. The largest increases in tone were recorded 21 days after exposure to TDI. The abnormally large tone was not associated with an increased thickness of the smooth muscle layer nor was it associated with reduced effects of either β2-agonist (terbutaline) or xanthine- (theophylline) relaxants. It is concluded that TDI-induced plasma exudation into guinea-pig airways occurs for 17 hr without disrupting the epithehal lining and without causing major changes in the airway peptidergic innervation. Both the airway tone, and the number of mucous cells, are increased for at least 3 weeks after exposure to TDI.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1991.tb03201.x
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  • 9
    Electronic Resource
    Electronic Resource
    Topical vasoconstrictor (oxymetazoline) does not affect histamine-induced mucosal exudation of plasma in human nasal airways (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 22 (1992), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Mucosal exudation of almost unfiltered plasma proteins, plasma-derived mediators and fluid has recently been advanced as a major respiratory defence mechanism. Oxymetazoline chloride is a commonly used decongestant agent. By reducing blood flow it may reduce mucosal exudation and thus compromise the mucosal defence capacity. This study examines the effect of topically applied oxymetazoline on histamine-induced plasma exudation into human nasal airways. Twelve normal volunteers participated in a double-blind, randomized, cross-over and placebo-controlled study with pretreatment with a single dose oxymetazoline chloride (5 μg or 50 μg; a dose previously known to reduce nasal mucosal blood flow by almost 50%) prior to the histamine challenge sequence. Nasal lavages were performed every 10 min for 140 min, and three histamine challenges were performed at 30-min intervals during this period. The concentrations of two exudative indices, N-alpha-tosyl-l-arginine methyl ester (TAME)-esterase activity and albumin, were measured in the nasal lavage fluids. Nasal symptoms (sneezing, nasal secretion and blockage) were assessed by a scoring technique.Histamine induced all three symptoms with correlatively raised levels of the biochemical markers for plasma exudation. Oxymetazoline chloride caused a significant decrease in nasal stuffiness, but did not influence the other nasal symptoms or the histamine-induced plasma exudation. It is concluded that histamine-induced plasma exudation is not influenced by topical oxymetazoline. Thus, an important airway defence reaction such as plasma exudation may be little affected by topical α-adrenoreceptor-mediated vasoconstriction. It is further suggested that the antiblockage effect of oxymetazoline can be utilized in nasal research without interfering with the exudative indices which appear on the mucosal surface as a quantitative reflection of the airway tisue involvement in inflammatory processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1992.tb03103.x
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  • 10
    Electronic Resource
    Electronic Resource
    Allergen, bradykinin, and capsaicin increase outward but not inward macromolecular permeability of guinea-pig tracheobronchial mucosa (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 21 (1991), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: When inflammatory stimuli are applied on the airway mucosa, plasma is promptly extravasated from the subepithelial microvessels. The plasma exudate distributes in the lamina propria and much of it is soon transmitted across the epithelial lining. The rapid luminal entry of large plasma solutes must reflect a dramatic change in mucosal permeability. Previously it has been thought that such a perviousness of the mucosal barrier would be bidirectional in nature. This study in anaesthetized guinea-pigs examines whether absorption across the mucosa is increased (above control) during, and immediately after, the plasma exudation process. An oral catheter, introduced into the tracheal lumen, was used to superfuse the lower airways with 0.04 ml of a solution containing the absorption tracer 131I-albumin and a selected dose of a provocating agent: allergen, 3 pmol (ovalbumin in IgE-sensitized animals); bradykinin. 5 nmol; capsaicin, 0.4 nmol; or carbachol, 8 nmol. The superfusate had a desired distribution on the tracheobronchial mucosa so that specific airway and not bronchoalveolar exudation: absorption ratios could be determined. In separate experiments it was confirmed that the present provocations, except carbachol (P 〉 0.05), moved significant amounts of plasma into the airway lumen (P 〈 0.001). This was distinctly an increase in the outward mucosal permeability because the absorption of luminal 131I-albumin into circulating plasma was not significantly different from control with any of the provocations (P 〉 0.05). The present data support our notion that unfiltered plasma exudates can operate on the mucosal surface, in first-line defence reactions, without compromising the integrity of the epithelial lining as a barrier to luminal material.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1991.tb00833.x
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