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  • 1
    Electronic Resource
    Electronic Resource
    Blood-nerve barrier in the Vater-Pacini corpuscle of cat mesentery (1984)
    Springer
    Anatomy and embryology 169 (1984), S. 237-247 
    Details
    ISSN: 1432-0568
    Keywords: Vater-Pacini corpuscle ; Cat mesentery ; Freeze-fracture ; Tracer experiments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Correlated thin-section, freeze-fracture and tracer examinations were used to examine the blood-nerve barrier of the Vater-Pacini corpuscles in cat mesentery. A laminar inner core and a multilayered outer core enfolded the terminal nerve fiber of the corpuscle. The lamellar cells of both cores were characterized by numerous vesicular membrane invaginations. Freeze-fracture images and tracer experiments employing lanthanum nitrate proved that these invaginations are static structures mediating in neither active pinocytosis nor the transcellular transport of metabolites. In both inner and outer cores, lamellar cells were connected to one another by tight junctions of either the zonula or the fascia type, that occurred between lamellar-cell processes within the lamella and between the cells of adjacent lamellae. Intravascularly applied lanthanum lay at the out-ermost regions of the corpuscles without entering their internal zones, apparently because lamellar-cell tight junctions hindered further penetration. The results of our investigations suggest strongly that the Vater-Pacini corpuscle lamellae enfolding the nerve terminal form an effective diffusion barrier against the permeation of tissue fluids, thus preserving the corpuscle internal circumference.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315629
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  • 2
    Electronic Resource
    Electronic Resource
    Antipyrine clearance in patients with Gilbert's syndrome (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 297-302 
    Details
    ISSN: 1432-1041
    Keywords: Gilbert's syndrome ; antipyrine clearance ; drug oxidizing capacity ; smoking habit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic parameters of antipyrine (AP) were examined in 45 normal healthy subjects (18 heavy smokers, 5 mild smokers, and 22 nonsmokers) and in 12 patients with Gilbert's syndrome (GS), amongst whom 2 mild and 1 heavy smokers were included. Heavy smokers were defined as persons smoking more than 20 cigarettes/day and mild smokers as those smoking less than 10 cigarettes/day. Significant differences (unpaired Student's t-test) in the elimination t1/2 of AP among the study groups and in its total plasma clearance (CL) were observed without any change in the apparent volume of distribution. The individual CL values varied within the same study groups, but the mean±SD (0.026±0.004 l/h/kg) in the GS patients did not significantly differ from that in normal nonsmokers (0.025±0.006 l/h/kg) or in normal mild smokers (0.028±0.001 l/h/kg). When the 3 patients with GS who smoked were excluded, the mean CL of the group (0.025 l/h/kg) was again comparable to that of the normal nonsmokers and mild smokers. The mean (±SD) CL in normal heavy smokers (0.040±0.012 l/h/kg) was significantly greater than in normal mild smokers (p〈0.05), in normal nonsmokers (p〈0.001) and in patients with GS (p〈0.001). The results suggest that drug oxidation capacity estimated from the total plasma CL of AP appears unimpaired in GS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542163
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ketoprofen following single oral, intramuscular and rectal doses and after repeated oral administration (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 407-414 
    Details
    ISSN: 1432-1041
    Keywords: ketoprofen ; pharmacokinetics ; relative bioavailability ; single doses ; repeated doses ; prediction of kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ketoprofen was studied in the same healthy subjects after single oral, intramuscular and rectal doses, and after repeated oral administration. No significant difference in the mean t1/2 (1.13–1.27 h) was observed after the different modes of administration. The mean [AUC] 0 ∞ after rectal administration of a suppository showed the minimum significant difference (p〈0.05) from that after oral administration of the capsule. The apparent volume of distribution (Vd/F) was approximately 10–15% of body weight. The renal contribution (mean, 0.10–0.15 ml/min/kg) to the plasma clearance of free ketoprofen was assumed to be, at most, 8.3–12.9%. The projected cumulative excretion of total (free plus conjugated) ketoprofen via urine exceeded 63–75% of the dose, of which approximately 90% was ketoprofen glucuronide. A mean of 71–96% and 73–93% of the oral capsule was estimated to be systemically available after administration of the intramuscular preparation and rectal suppository, respectively. In four of seven subjects, CPK concentration was elevated after the intramuscular injection. The mean steady-state concentration of ketoprofen in plasma ranged from 0.43 to 5.62 µg/ml after the final dose of a 50 mg q.i.d. regimen. The disposition data and plasma levels observed at steady-state were in agreement with those predicted from the single oral dose study. The accumulation ratio was 1.08±0.08. The results suggest that the rectal suppository can be recommended as an extravascular mode of administration of this drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00636794
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  • 4
    Electronic Resource
    Electronic Resource
    Bioavailability and pharmacokinetics of theophylline following plain uncoated and sustained-release dosage forms in relation to smoking habit (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 361-369 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; smoking ; sustained release formulation ; dosage forms ; multidose pharmacokinetics ; bioavailability ; circadian variation in kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of theophylline following 10 days of multiple doses of a plain uncoated (640 mg, q.i.d.) and a sustained-release tablet formulation (600 mg, b.i.d.) were related to habitual smoking in 11 healthy adult male volunteers, who had previously taken part in a single-dose study of an intravenous preparation of theophylline and of the same oral dosage form. There were significant differences (p〈0.05 to 0.01) in the steady-state mean and minimum theophylline concentration and AUC between the groups (6 smokers versus 5 nonsmokers), but not between other variables. A difference (p〈0.05) in peak time was also found between the dosage forms. The mean elimination t1/2 was significantly (p〈0.05) shorter in smokers than in nonsmokers. The intersubject variability in plasma theophylline concentration observed on the final trial day in the smoking group was larger and diverged more from simulation curves generated from the mean pharmacokinetic parameters of the single-dose study of the same formulations as compared to that of the nonsmoking group. There was no significant difference between the two groups in the mean accumulation ratio and absolute bioavailability of the two dosage forms. The mean morning (7 a.m.) trough theophylline concentrations after both formulations were significantly (p〈0.05 to 0.01) greater than the evening (7 p.m.) values within the same group. The average number of reported side-effects was significantly (p〈0.001) greater during the earlier period (Days 1 to 3) than the later period of the trial. A trend was observed suggesting that the incidence of side-effects was less in smokers than in nonsmokers. The results indicate that smoking is a determinant not only of enhanced elimination of theophylline but that it also produces more variability in the plasma level, irrespective of the dosage form administered or the dosing scheme employed. There may be circadian variation in theophylline kinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610056
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  • 5
    Electronic Resource
    Electronic Resource
    Bioavailability and pharmacokinetics of theophylline in plain uncoated and sustained-release dosage forms in relation to smoking habit I. Single dose study (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 79-87 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; smoking habit ; absolute bioavailability ; pharmacokinetics ; sustained release preparation ; plain tablet preparation ; antipyrine pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability and pharmacokinetics of theophylline from a plain uncoated and 2 newly designed, sustained-release tablet formulations, as compared to intravenous aminophylline, were studied in 12 healthy adult male volunteers. The subjects were divided into two groups (n=6) with respect to smoking habit and on 4 separate occasions each received, on a randomized cross-over basis, a single dose of 400 mg equivalent of theophylline from every dosage form. The intravenous aminophylline study showed that habitual smoking had a significant (p〈0.05) effect on plasma theophylline clearance (0.051±0.006 vs 0.035±0.004 l/kg/h). Smoking significantly reduced the raw AUC from the 4 dosage forms (p〈0.05), but did not change the characteristics of absorption of each formulation. There was a non-significant trend towards reduced absolute bioavailability of theophylline from sustained-release formulations in smokers (percentage mean difference — 16% for one formulation and 13% for another). The trend was not observed for the plain uncoated tablet, which was rapidly absorbed (p〈0.01 to 0.05 in Ka, tmax and Cmax compared to sustained-release tablets). Similarity of the in vitro dissolution profiles of the two sustained-release formulations did not imply similarity of the in vivo absorption characteristics. Plasma clearances of theophylline and antipyrine were significantly correlated (p〈0.05,r=0.693,n=10). Thus, smoking enhanced the elimination of theophylline regardless of the dosage form administered. However, the extent to which habitual smoking may affect the hepatic first-pass effect on theophylline from sustained-release formulations requires further study. The results also suggest that theophylline and antipyrine may share a similar or common and presumably polycyclic hydrocarbon-inducible form(s) of microsomal drugmetabolizing enzyme.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613931
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  • 6
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and absolute bioavailability of carteolol, a new β-adrenergic receptor blocking agent (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 95-101 
    Details
    ISSN: 1432-1041
    Keywords: carteolol ; pharmacokinetics ; beta-adrenoreceptor blocking drug ; absolute bioavailability ; plasma levels ; urinary excretion ; renal handling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and absolute bioavailability of a new nonselective β-adrenoreceptor blocking agent, carteolol, were investigated after administration of single intravenous and oral doses to eight normal volunteers. Plasma and urine drug concentrations were measured by an HPLC method. The pharmacokinetic parameters after intravenous dosing were obtained by a two-compartment analysis: elimination or β-phase t1/2 4.7±0.3 h; Vc, 0.74±0.101/kg; Vd, 4.05±0.48 l/kg; Cl, 10.13±0.94 ml/min/kg; ClR, 6.56±0.58 ml/min/kg; and ClNR, 3.57±0.40 ml/min/kg. The absolute bioavailability obtained from plasma data was 83.7±8.0%, which was consistent with that derived from analysis of urine of 82.7±4.2%. The amounts excreted unchanged in urine up to 48 h after the intravenous and oral doses were 65.0±1.5% and 53.8±3.2% of the administered doses, respectively. The t1/2 for removal of the drug derived from plasma and urine findings after intravenous and oral dosing were similar, which indicates that the main route of elimination of carteolol is via the kidneys. As the ClR of carteolol exceeded the Cl of creatinine there may be renal tubular secretion of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544023
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  • 7
    Electronic Resource
    Electronic Resource
    Concentration-effect and time-effect relationships of carteolol (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 749-757 
    Details
    ISSN: 1432-1041
    Keywords: carteolol ; beta-blockade ; dose-response relation ; duration of action ; plasma level-effect relation ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concentration-beta blocking effect and time-effect relationships of carteolol were examined in eight normal adults given 15 mg i.v. and 20 mg orally on separate occasions. Resting and post-exercise blood pressures and heart rates were assessed before and at various times up to 48 h after each dose. Carteolol, a β-blocker with some partial agonist activity, produced an insignificant, transient increase in heart rate 2 to 6 h after both doses, and a fall (p〈0.05) in diastolic blood pressure 4 and 6 h after the intravenous dose and 6 h after the oral dose in the resting supine position, as compared to the corresponding baseline values. All values of the post-exercise heart rate and the double product after each of the doses were significantly (p〈0.001) below the baseline values for the entire period (48 h) of observation. A significant correlation between the log plasma carteolol concentration (log C) and its beta-blocking effect (E: p〈0.001, r=0.508 i.v.; p〈0.001, r=0.626, p.o.) was found. The r-values for individuals were higher (0.852 to 0.977, intravenous; 0.817 to 0.981, oral) than for the group as a whole. The slope (m) of the relationship, E=m·log C+r, showed a certain variance within and between individuals. When the absolute reduction in exercise-induced heart rate was plotted against time and the rate of decline of effect (Rd) and duration of action were estimated from the time-effect relationship, the mean Rd values were 0.655 and 0.462 beats/min per h, and for the duration of action they were 83.8 and 123.9 h after the intravenous and oral doses, respectively. The effect declined at a slower rate (p〈0.02) and the duration of beta-blockade was longer (p〈0.01) after the oral dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542514
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  • 8
    Electronic Resource
    Electronic Resource
    Individualized aminophylline therapy in patients with obstructive airway disease: Oral dosage prediction from an intravenous test dose (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 111-121 
    Details
    ISSN: 1432-1041
    Keywords: aminophylline ; asthma ; individual aminophylline dose ; theophylline disposition ; intravenous test dose ; oral dosage prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Theophylline disposition after an intravenous test dose of aminophylline was determined in 83 subjects: 7 patients with and 58 without congestive heart failure (CHF), and 18 healthy controls. Based on the pharmacokinetics of theophylline in the individual, the oral dosage of aminophylline was scheduled to attain steady-state trough theophylline concentrations (Cpred) near the therapeutic margin. Significant differences in theophylline clearance with a relatively constant volume of distribution were observed between various groups divided by age, smoking habit and CHF; the significantly different (p〈0.001) mean clearance values were: 0.042±0.0161/h/kg (mean ± SD) in patients without CHF (n=58) as opposed to 0.016±0.001 l/h/kg in patients with CHF(n=7), 0.038±0.013 l/h/kg in non-smokers (n=59) versus 0.054±0.015 l/h/kg in smoking subjects (n=17), and 0.030±0.010 l/h/kg in elderly (〉60 years) non-smoking patients (n=7) versus 0.057±0.017 l/h/kg in smoking patients (n=5) aged 40 to 59 years. No gender-related difference was detected in theophylline disposition. For all subjects together (n=83), there was no significant correlation between age and clearance (r=-0.111, p〉0.1). The multivariate analysis indicated that the overall variability in theophylline clearance was affected first by the smoking habit (t=4.960; p〈0.001) and second by CHF (t=-3.052; p〈0.001), but not by age (t=1.140) or by sex (t=0.069). 78% of the patients who did not have CHF required a daily dose of aminophylline of 600 to 900 mg, whereas a dose of 300 to 450 mg was the rule in patients with CHF. The measured steady-state minimum concentration (Cmeas) ranged from 5.4 to 14.6 µg/ml (9.0±2.2 µg/ml: mean ± SD) which was in good agreement with the Cpred (5.6 to 13.6, 9.0±1.6 µg/ml) in all patients (n=60) who received the oral dose of aminophylline calculated from the test dose. The overall prediction error was -0.08±1.83 µg/ml (−1.42±19.90%); only 3 of 60 measurements were found to be outside±2 SD. It is concluded that using a test dose to individualize aminophylline therapy is likely to remain the most reliable means to assure the maximum therapeutic benefit in patients with airway obstruction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00545964
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  • 9
    Electronic Resource
    Electronic Resource
    Statistical consideration of using colony diameter as a measure of mycoplasmal growth (1983)
    Oxford, UK : Blackwell Publishing Ltd
    FEMS microbiology letters 19 (1983), S. 0 
    Details
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1574-6968.1983.tb00500.x
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  • 10
    Electronic Resource
    Electronic Resource
    Induction of Immunological Tolerance to Single-stranded and Double-stranded DNA (1982)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 16 (1982), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Single-stranded (ss) and double-stranded (ds) DNA were conjugated with the copolymers of d-glutamic acid and d-lysin (d-GL). Administration of ss-DNA-d-GL conjugates to C3H/He and NZB/W F1 mice could render the mice tolerant to both direct and indirect anti-ss-DNA antibody-forming cell responses, irrespective of their immune status. Repeated administration of ss-DNA- or ds-DNA-d-GL conjugates decreased the levels of anti-ss-DNA and anti-ds-DNA antibody titres and reduced the occurrence of ss-DNA and ds-DNA antibody-forming cells even in old female NZB/W F1 mice that had already developed an autoimmune state with lupus nephritis. The unresponsiveness was DNA-specific, and the state of tolerance was stable in vitro at the cellular level after the removal of the tolerogen. This tolerance model would be useful in analysing the regulatory mechanisms in anti-ss-DNA and anti-ds-DNA antibody production, and application of this kind of therapy in the treatment of systemic lupus erythematosus is suggested.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1982.tb00714.x
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