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  • Column liquid chromatography  (124)
  • Immunohistochemistry  (65)
  • healthy volunteers  (55)
  • Springer  (244)
  • Cambridge University Press
  • Frontiers Media
  • 2020-2022
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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 41 (1985), S. 1173-1175 
    ISSN: 1420-9071
    Schlagwort(e): Immunohistochemistry ; immunologic deficiency syndromes ; lymph nodes ; protease inhibitors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary One of two cases of acquired immune deficiency syndrome-related persistent generalized lymphadenopathy revealed a profoundly altered pattern of dendritic reticulum cells as demonstrated by immunoreactive acid cysteine proteinase inhibitor. The alterations could be related to totally or partially destructed lymphoid secondary follicles.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1432-1041
    Schlagwort(e): BW443C ; enkephalin ; opioid peptide ; healthy volunteers ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied 16 healthy men to evaluate preliminary pharmacodynamics and kinetics of BW443C given by i.v. infusions. Four volunteers received escalating doses at weekly intervals, starting at 0.1 µg·kg−1 for 60 min and increasing to a maximum of 2.0 µg·kg−1·min−1 for 180 min. Subsequently 12 different subjects received single i.v. infusions of 10 µg·kg−1·min−1 for 20 min. Subjective effects were reported and objective measurements made of central nervous and cardiovascular effects. Blood was sampled at intervals on all occasions, plasma concentrations were determined by radioimmunoassay and pharmacokinetic profiles were analysed using NONLIN. Dry mouth and some nasal stuffiness were reported and postural hypotension occurred in 5/16 subjects at plasma concentrations 〉0.8 µg·ml−1. Supine blood pressure was well maintained in all subjects and hypotension resolved within 60–90 min of discontinuing the infusion. There was no evidence of sedation, mood change, nausea, vomiting, miosis, change in accomodation or respiratory depression. Rapid infusions produced transient feelings of warmth, heavy eyelids, heavy legs, and increased bowel sounds, which resolved despite increasing plasma concentrations. The disposition of the peptide was adequately described by a 2-compartment model with a mean ± SD plasma clearance of 123±18 ml·min−1 and a half-life of 2.0±0.4 h.
    Materialart: Digitale Medien
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 34 (1988), S. 263-266 
    ISSN: 1432-1041
    Schlagwort(e): tyramine ; propranolol ; pressure response ; blood pressure ; beta-adrenoceptor blockers ; healthy volunteers ; indenolol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect β-adrenoceptor blockade on the pressor response to tyramine has been investigated in 6 healthy volunteers, each submitted to an i.v. tyramine pressor test before and after 7 days of propranolol 40 mg b.d. or indenolol 60 mg o.d. Tyramine was given as i.v. boluses of 1–6 mg, alternating with saline, in a randomized, single blind fashion. Prior to treatment tyramine caused a temporary, dose-dependent increase in systolic and diastolic blood pressure, whilst the heart rate remained unaffected. Both propranolol and indenolol reduced the pressor response to tyramine, as shown by a significant increase in ED15, i.e. the dose of tyramine required to increase systolic blood pressure by 15%.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; controlled-release formulation ; pharmacokinetics ; pharmacodynamics ; exercise heart rate ; healthy volunteers ; efficacy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic and pharmacodynamic properties of a new multiple-unit, controlled-release (CR) formulation of metoprolol1 (metoprolol succinate, 95 mg once daily), which has almost constant (zero-order) release properties over most of a 24-h dose interval, have been compared with those of conventional metoprolol tablets (metoprolol tartrate, 100 mg once daily and 50 mg twice daily), in 12 healthy male volunteers. The steady-state plasma concentrations of metoprolol after five days of treatment varied less throughout the day with the CR than with the conventional formulation. This was associated with a considerably lower peak plasma concentration and the achievement of a significantly higher plasma concentration at the end of the dose interval. Similarly, the effect on exercise-induced tachycardia was maintained at a relatively constant level throughout the day after treatment with the CR formulation. A significantly greater effect 24 h after administration was achieved with the CR formulation, when compared with once-daily dosing with metoprolol tablets, 100 mg. Twice-daily dosing with metoprolol tablets, 50 mg, produced a similar β1-blocking effect at the end of the dose interval to that observed with metoprolol CR. Although the steady-state plasma concentrations indicated significantly lower systemic availability for the CR formulation, compared with both regimens of metoprolol tablets, the total effect over the dose interval, expressed as the area under the efficacy curve (AUEC), was similar for the three treatments. The relationship between steady-state plasma concentrations and the pharmacodynamic efficacy at corresponding times, indicated that plasma concentrations were more effectively utilized after the administration of the CR formulation than after the conventional tablet regimens. The results of this study clearly indicate the potential benefits offered by the new metoprolol CR formulation, under all circumstances where a constant degree of β1-selective blockade, without plasma peaks and troughs, is preferred.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 34 (1988), S. 283-289 
    ISSN: 1432-1041
    Schlagwort(e): piroxicam ; tenoxicam ; cholestyramine ; accelerated drug elimination ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied the influence of multiple oral doses of cholestyramine on the single dose pharmacokinetics of tenoxicam and piroxicam in eight healthy young volunteers. Each subject received on two occasions single intravenous injections of 20 mg tenoxicam and on another two occasions single oral doses of 20 mg piroxicam. Both medications were followed by multiple oral doses of either cholestyramine or plain water (placebo). Compared with placebo cholestyramine accelerated the elimination of both drugs. The average values of half-lives were reduced (tenoxicam: 31.9 h vs 67.4 h; piroxicam: 28.1 h vs 46.8 h) due to increases in clearance. Cholestyramine-mediated enhancement of drug elimination was most pronounced in the subjects with a comparatively low baseline drug clearance. Thus, intersubject variability in clearance was smaller when the drug administrations were followed by the anion-exchange resin. The twofold acceleration of tenoxicam elimination in the present study in man contrasts with a much larger effect (five-fold) seen in experiments with dogs. This points to a much easier access of unchanged tenoxicam to the intestinal lumen in the dogs than in man. Comparing the pharmacokinetics of tenoxicam and piroxicam in the same volunteers revealed a high degree of correlation in clearance and half-lives and similar intersubject variabilities in mean kinetic variables.
    Materialart: Digitale Medien
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 34 (1988), S. 595-599 
    ISSN: 1432-1041
    Schlagwort(e): rifampicin ; rifabutin ; microsomal enzyme induction ; healthy volunteers ; antimicrobial agent
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The comparative enzyme inducing effects of rifabutin and the chemically related drug rifampicin have been investigated in 8 normal subjects. Rifampicin 600 mg daily for 7 days caused considerable shortening of the antipyrine half-life and a marked increase in antipyrine clearance, associated with an increased rate of conversion to norantipyrine and, to a lesser extent, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine. The urinary excretion of 6-β-hydroxycortisol was also markedly increased, while plasma GGT activity showed only a slight albeit statistically significant elevation. In the same subjects, rifabutin in the proposed therapeutic dosage (300 mg daily) for 7 days also enhanced the metabolic elimination of antipyrine, with preferential stimulation of the demethylation pathway, and increased the excretion of 6-β-hydroxycortisol, but the magnitude of the effects was signifiantly less than after rifampicin. No significant change in plasma GGT was seen. The results indicate that, contrary to the findings in animals, rifabutin does have enzyme inducing properties in man, although at the dosages assessed they were considerably less than those of rifampicin.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 65-68 
    ISSN: 1432-1041
    Schlagwort(e): metronidazole ; cimetidine ; pharmacokinetics ; drug interaction ; drug metabolism ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The time course of the effect of cimetidine on the pharmacokinetics of metronidazole was investigated in 6 healthy volunteers. Cimetidine 1.0 g/day was administered for 9-days and metronidazole 500 mg was administered orally on the second and eighth days, and in a control experiment. During cimetidine treatment the plasma kinetics of metronidazole and its partial clearance by renal excretion of the unchanged compound, glucuronidation, hydroxylation and oxidation to its acetic acid metabolite were not significantly different from the control values. The results indicate that cimetidine does not influence the pharmacokinetics or metabolism of a single oral dose of metronidazole.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 69-75 
    ISSN: 1432-1041
    Schlagwort(e): L-carnitine ; pharmacokinetics ; intravenous and oral doses ; bioavailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of single intravenous and oral doses of L-carnitine 2 and 6 g was studied in 6 healthy subjects on a low-carnitine diet. Carnitine was more rapidly eliminated from plasma after the 6 g dose. Comparing the doses, the t1/2β of the elimination phase (β) was 6.5 h vs 3.9 h, the elimination constant 0.40 vs 0.50 h−1 and the plasma carnitine clearance was 5.4 vs 6.11 · h−1 for the 2 g and 6 g doses, respectively, showing dose-related elimination. Saturable kinetics were not found. The apparent volumes of distribution after the two doses were not significantly different and were of the same order as the total body water. Urinary recoveries of the 2 g and 6 g doses were 70% and 82%, respectively, during the first 24 h. Following the oral doses, there was no significant difference between the areas under the plasma carnitine concentration-time curves. Urinary recovery was 8% and 4% for the 2 g and 6 g doses during the first 24 h. Oral bioavailability was 16% for the 2 g dose and 5% for the 6 g dose. The results suggest that the mucosal absorption of carnitine was already saturated by the 2 g dose.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1432-1041
    Schlagwort(e): acetaminophen ; codeine ; clearance ; metabolite formation ; glucuronidation ; pharmacokinetics ; healthy volunteers ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In nine healthy volunteers, the clearance and metabolism of acetaminophen 1000 mg i.v. was evaluated with and without two concomitant oral doses of codeine in order to investigate a possible interaction. Plasma acetaminophen was followed for 720 min and urine was collected for 24 h after each dose for determination of metabolites. When codeine was coadministered, the average total clearance of acetaminophen and its clearance by glucuronidation, sulphation and mercapturate formation were 0.58 to 1.12-times the control values. It is concluded that therapeutic doses of codeine do not influence the clearance or metabolism of acetaminophen.
    Materialart: Digitale Medien
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 237-240 
    ISSN: 1432-1041
    Schlagwort(e): platelet activating factor (PAF) ; WEB 2086 ; platelet aggregation ; PAF-antagonist ; dose response ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary WEB 2086 is a novel PAF-acether antagonist, whose pharmacological action in man has only been preliminarily defined. Twelve healthy male volunteers received oral doses of 5, 30 and 90 mg and over the following 24 h inhibition of 5 × 10−8 M PAF-acether-induced platelet aggregation ex vivo was studied as an indicator of pharmacological activity. WEB 2086 inhibited PAF-acether-induced platelet aggregation in all the doses tested, with the maximum effect 1 to 2 h after administration. After 2 h 5- 30- and 90-mg doses caused, respectively, 87, 98 and 100% inhibition. The magnitude and duration of the inhibitory effect was dose-dependent, with a significant action still detectable 10 h after administration of all three doses, and 12 h after administration of the two highest doses (30 and 90 mg). The subjects did not complain of any significant adverse effect and all completed the study.
    Materialart: Digitale Medien
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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 371-377 
    ISSN: 1432-1041
    Schlagwort(e): ACTH 4-10 ; radioimmunoassay ; plasma extraction ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A specific radioimmunoassay for the quantitative measurement of ACTH 4-10 and a procedure for its extraction from plasma have been developed. Its pharmacokinetics was studied in eight healthy male volunteers given ACTH 4-10 125 µg/kg body weight as a bolus i.v. injection, by infusion and intranasally. Following the i.v. bolus, plasma levels rapidly declined biexponentially, with half-lives of 0.39±0.05 min for the α-phase and 3.84 ± 1.5 min for the β-phase (mean±SD). The constant rate i.v. infusion yielded steady-state levels between 0.74 and 5.06 ng/ml plasma. Administered as intranasal spray, absorption of intact ACTH 4-10 was low and variable (maximal bioavailability 7.6%). The results are discussed in relation to the dose-dependent effects of ACTH 4-10 on the auditory evoked potential.
    Materialart: Digitale Medien
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 413-417 
    ISSN: 1432-1041
    Schlagwort(e): antipyrine ; acetaminophen ; lidocaine ; drug interactions ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Pharmacokinetic interactions between antipyrine and acetaminophen were evaluated in 7 healthy volunteers. On 3 occasions subjects received:1, antipyrine 1.0 g intravenously (i.v.);2, acetaminophen 650 mg i.v.;3, antipyrine 1.0 g and acetaminophen 650 mg i.v. simultaneously. Between Trials 1 and 3, antipyrine elimination t1/2 (17.2 vs 17.4 h), clearance (0.44 vs 0.43 ml·min−1·kg−1) and 24-h recovery of antipyrine and metabolites (313 vs 293 mg) did not differ significantly. Between Trials 2 and 3, acetaminophen Vz was reduced (1.14 vs 1.00 l·kg−1), t1/2 prolonged (2.7 vs 3.3 h), clearance reduced (4.8 vs 3.6 ml·min−1·kg−1), and fractional urinary recovery of acetaminophen glucuronide reduced. Eight additional subjects received 50 mg of lidocaine hydrochloride i.v. in the control state, and on a second occasion immediately after antipyrine 1.0 g given i.v. The two trials did not differ significantly in lidocaine Vz (2.6 vs 2.7 l·kg−1), t1/2 (2.0 vs 2.4 h) or clearance (15.0 vs 13.5 ml·min−1·kg−1). Although acetaminophen does not alter antipyrine kinetics, acute administration of antipyrine appears to impair acetaminophen clearance, possibly via inhibition of glucuronide formation. However, antipyrine has no significant effect on the kinetics of a single i.v. dose of lidocaine.
    Materialart: Digitale Medien
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  • 13
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1988), S. 619-624 
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; isomers ; chronopharmacokinetics ; cardiovascular effects ; circadian changes ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Four subjects were synchronized with activity from 07 to 23 h and were given a single oral dose of 80 mg racemic propranolol at fixed times (08, 14, 20 and 02 h) at weekly intervals. ANOVA revealed significant circadian changes in the peak propranolol concentration (Cmax), with a maximum at 08 h and a minimum at 02 h after drug intake; tmax was not dependent on the circadian phase. The elimination half-life varied significantly with the time of day, being shortest at 08 h (3.3 h) and longest at 20 h (4.9 h). The stereospecificity of the propranolol pharmacokinetics was not dependent on the time of drug intake. No circadian variation was found in the maximum decrease in heart rate, but the time to peak effect was dependent on the time of drug intake; tmax was 2.3 h at 08 h and 7.0 h at 02 h. Thus, the time to peak drug concentration did not coincide with the time to peak effect on heart rate at different times of day. Circadian changes were also found in the systolic blood pressure and in the double product. The results show a significant daily variation in the pharmacokinetics and cardiovascular effects of propranolol. However, chronokinetics cannot explain the circadian changes in the effects of the drug. It is concluded that circadian variation in sympathetic tone and vascular reactivity is mainly responsible for the circadian changes in the effects of propranolol.
    Materialart: Digitale Medien
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  • 14
    ISSN: 1432-1041
    Schlagwort(e): flumazenil ; ethanol ; alcohol intoxication ; benzodiazepine antagonist ; interaction ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Flumazenil is a specific benzodiazepine antagonist. This study was designed to determine whether it also reverses CNS depression due to acute alcohol intoxication. Intoxication was experimentally induced in 6 healthy volunteers by intravenous infusion of ethanol. Individual constant ethanol plasma concentrations in the range 1.47±0.04 g · l−1 to 1.71±0.03 g · l−1 were maintained over 6 h. Two doses of flumazenil (0.1 or 0.2 mg · kg−1) and placebo were administered intravenously in a randomized, double-blind, two-way cross-over fashion. A battery of psychometric tests and subjective ratings of mood and performance were performed at baseline and at regular intervals during the study. Before the administration of flumazenil the characteristic symptoms and signs of ethanol intoxication were present in all subjects. Performance (measured by visual analogue scales), reaction time, digit symbol substitution test, and a tracing test, were markedly impaired by ethanol. After the injection of flumazenil three volunteers reported some subjective improvement in performance. However, in none of the subjects was there a difference between either dose of flumazenil and placebo in terms of an improvement in the objective psychometric variables.
    Materialart: Digitale Medien
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 563-566 
    ISSN: 1432-1041
    Schlagwort(e): tenoxicam ; pharmacokinetics ; elderly ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Fourteen elderly subjects (10 women, 4 men) with a mean age of 81 (SD 6.7) years and in need of anti-inflammatory drug treatment were given a single dose of 20 mg tenoxicam. After a drug-free interval of 5 weeks, multiple dose treatment with 20 mg tenoxicam once daily for 56 days was initiated. The single and multiple dose kinetics of tenoxicam were investigated after HPLC determination of tenoxicam in the plasma. The elimination half-life of tenoxicam ranged from 44 to 132 h (mean 71.9 h) with no significant difference between the single and multiple dosage regimens. Tenoxicam reached maximum plasma concentrations after 1.4 and 1.1 h, with values of 3.6 and 15.5 µg·ml−1, for the single and multiple dosage regimen respectively. The corresponding trough values (24-h values) were 1.8 and 11.7 µg·ml−1. A mean accumulation ratio of 5.1 was calculated. The mean increase in the area under the plasma concentration time curves at steady-state was 21% more than predicted from the initial single dose. This deviation from linearity was considered to be of minor clinical significance. The kinetics of tenoxicam in elderly were similar to that published for young healthy volunteers.
    Materialart: Digitale Medien
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  • 16
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 607-612 
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; atenolol ; baroreflex function ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The acute administration of the β-adrenoceptor antagonists propranolol (80 mg) and atenolol (50 mg) on baroreflex function were investigated in healthy volunteers. Two h after administration both propranolol and atenolol significantly prolonged the supine R-R interval (1126, 1128 ms respectively) compared to placebo (1012 ms); systolic arterial pressure also fell (102.9, 102.0 mm Hg respectively) compared to placebo (112.6 mm Hg). Baroreflex function, assessed using glyceryl trinitrate to deactivate the baroreceptors was unchanged by these drugs compared to placebo. Baroreflex sensitivity (slope of the linear regression line relating R-R interval to systolic blood pressure) using phenylephrine to activate the baroreceptors, was also unchanged (17.2, 17.9 ms/mm Hg respectively) compared to placebo (19.9 ms/mm Hg). However both regression lines were shifted (p〈0.05) to the left compared to placebo.
    Materialart: Digitale Medien
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  • 17
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 593-599 
    ISSN: 1432-1041
    Schlagwort(e): maprotiline ; nomifensine ; ethanol ; drug interaction ; echocardiography ; psychometry ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Eight healthy volunteers received low doses of maprotiline and nomifensine up to 50 mg b. d. for 15 days in a double-blind, cross-over, placebo controlled study, during which echocardiography and psychomotor testing were carried out before and after the intake of alcohol 1 g/kg. Maprotiline increased heart rate and cardiac output and reduced peripheral resistance compared to placebo and nomifensine. Nomifensine alone was associated with a slight decrease in heart rate. Alcohol alone caused a significant increase in diastolic blood pressure, but did not otherwise modify the cardiovascular measures. The antidepressants did not augment the effects of alcohol. Antidepressants alone had no effect on psychomotor skills, but alcohol always impaired performance. No additional effects of alcohol were produced by the antidepressants. It appears that practically important peripheral or central consequences are unlikely to follow drinking a moderate amount of alcohol during regular therapy with low therapeutic doses of catecholamine reuptake inhibiting antidepressants. Experimental studies of the interaction of antidepressants and alcohol in patients with chronic heart disease seem to be justified.
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  • 18
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 631-635 
    ISSN: 1432-1041
    Schlagwort(e): enoximone ; heart failure ; inotropic activity ; pharmacokinetics ; pharmacodynamics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The relationship between the pharmacokinetics and pharmacodynamics of enoximone, a new positive inotropic agent, was investigated in 6 healthy men. The volunteers received single oral and i.v. doses of 3 and 1 mg/kg, respectively, and placebo in a double-blind cross-over trial. Plasma concentrations of enoximone and its sulphoxide metabolite, effects on the corrected electromechanical systole (QS2c), the impedance cardiogram (dZ/dt)/RZ index, blood pressure and heart rate were determined over an 8-h period. Peak effects on QS2c and the (dZ/dt)/RZ index were obtained after approximately 1 h. During the first hour, the cardiac effects lagged behind the high plasma concentrations. Thereafter, the effects on QS2c were closely correlated with the plasma concentrations both of enoximone and its sulphoxide derivative (r≥0.90). The concentration-effect curves of both substances were parallel and were independent of the route of administration. The inotropic activity was not related to the drug level in hypothetical peripheral compartments. The results suggest that determination of plasma enoximone 1 h after administration and thereafter may be useful in assessing the haemodynamic activity of the drug. Should this observation also be present in a clinical situation, plasma enoximone measurements might be a valuable tool in management of patients suffering from heart failure.
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  • 19
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 367-370 
    ISSN: 1432-1041
    Schlagwort(e): captopril ; pharmacokinetics ; healthy volunteers ; i.v. application
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic characteristics of intravenously-administered captopril were investigated in 7 healthy men 20 to 33 years old. Capropril, labeled with14C, was given by injection over a 1 min period at mean doses of 2.78 mg (13.8 µCi), 5.67 mg (28.2 µCi) and 11.4 mg (56.8 µCi). Concentrations of unchanged captopril, captopril disulfide, and other metabolites (collectively) were determined in body fluids. Pharmacokinetic parameters were calculated for unchanged captopril, and it was shown that the disposition of intravenously-administered drug was linear with respect to dose over the dosage range studied.
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  • 20
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 385-389 
    ISSN: 1432-1041
    Schlagwort(e): oxazepam ; pharmacokinetics ; i.v.-/oral administration ; bioavailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Six healthy volunteers received oxazepam 15 mg i.v. and orally at an interval of at least one week. The kinetic variables of i.v. oxazepam were: elimination half-life (t1/2β) 6.7 h, total clearance (CL) 1.07 ml·min−1·kg−1, volume of distribution (Vc) 0.27 l·kg−1 (0.21–0.49) and volume of distribution at steady-state (Vss) 0.59 l·kg−1. The intravenous disposition of unbound oxazepam was characterized by a clearance of 22.5ml·min−1·kg−1 and a distribution volume of 12.3 l·kg−1. After oral oxazepam the peak plasma level was reached in 1.7 to 2.8 h. The plasma t1/2β at 5.8 h was not significantly different from the i.v. value. Absorption was almost complete, with a bioavailability of 92.8%. Urinary recovery was 80.0 and 71.4% of the dose after intravenous and oral administration, respectively. Renal clearance (CLR) of the glucuronide metabolite was 1.10 ml·min−1·kg−1 (0.98–1.52). Oxazepam was extensively bound to plasma protein with a free fraction of 4.5%.
    Materialart: Digitale Medien
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  • 21
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 33 (1988), S. 625-628 
    ISSN: 1432-1041
    Schlagwort(e): nadolol ; pharmacokinetics ; 14C-nadolol ; healthy volunteers ; i.v. administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary To support the increasing use of intravenous β-blockers during cardiovascular emergency and surgery, dose proportionality of pharmacokinetics of nadolol was evaluated after intravenous administration of 14C-nadolol at doses of 1, 2 and 4 mg to nine healthy volunteers. There were no observed differences in the excretion or the pharmacokinetics of nadolol with respect to the dose administered. Over a 72-h period after drug administration, an average of about 60% of the dose was excreted in the urine and about 15% was excreted in the feces. The range of values for total body clearance (219 to 250 ml·min−1), renal clearance (131 to 150 ml·min−1), mean residence time (10.5 to 11.3 h), half-life (8.8 to 9.4 h), and steady-state volume of distribution (Vss) (147 to 157 l) indicated that nadolol was extensively distributed and slowly cleared from the body. There was a linear correlation (r 2=0.97) between the area under the plasma concentration of nadolol versus time curve (AUC) and the dose. All pharmacokinetics parameters, except Vss, were slightly, but significantly, different at the 4 mg dose. Superposition of the dose-normalized average concentrations indicated that despite these minor differences in parameters, the pharmacokinetic behavior of nadolol was linear with respect to dose. Urinary excretion of nadolol was dose independent.
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  • 22
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 173-176 
    ISSN: 1432-1041
    Schlagwort(e): omeprazole ; pepsinogen ; serum pepsinogen A ; serum pepsinogen C ; gastric pepsin ; urinary pepsinogen A ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary To investigate the effect of omeprazole on serum and urinary pepsinogens and on gastric pepsin, 8 healthy male volunteers were studied before and after 9 days of treatment with omeprazole 60 mg/day p.o. Fasting serum samples and 24 h urine specimens were obtained, and gastric contents were aspirated at 15-min intervals, 4 prior to and 6 during pentagastrin 1.5 µg·kg−1·h−1 i.v. during intra-gastric perfusion with NaCl 0.9% and phenol red 3 mg·ml−1 as an inert recovery marker. Basal and pentagastrin-stimulated volume and acid secretion were significantly decreased. The basal and pentagastrin stimulated pepsin output remained unchanged but pepsin concentration in gastric secretion was increased. Administration of omeprazole resulted in a significant increase in the serum PGA and PGC levels. The 24-h urinary excretion of PGA increased, but that of PGC remained unchanged, and so did the renal clearances of creatinine and pepsinogen A. The renal clearance of pepsinogen C decreased. It was concluded that omeprazole did not affect gastric pepsin output, but, due to the decreased volume output, the concentration of pepsin in the gastric secretion was increased. Omeprazole increased the serum levels of pepsinogen A and C because more pepsinogen was released into the systemic circulation. This might be due to greater back-diffusion of pepsinogen from the gastric mucosa into the systemic circulation as a result of the higher pepsinogen concentration in gastric secretion.
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  • 23
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 221-223 
    ISSN: 1432-1041
    Schlagwort(e): sertraline ; antidepressants ; critical flicker fusion ; psychopharmacology ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A double-blind, placebo controlled, cross-over study was carried out in 10 normal healthy volunteers to investigate the effects of sertraline 25 mg, 50 mg, 75 mg and 100 mg on aspects of cognitive functioning. Changes with respect to placebo in objective tests of psychomotor function (critical flicker fusion and choice reaction time) showed that sertraline had an alerting effect. The changes were not consistent with subjective reports of drowsiness.
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  • 24
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 29 (1985), S. 221-224 
    ISSN: 1432-1041
    Schlagwort(e): fenfluramine ; norfenfluramine ; isomers ; pharmacokinetics ; healthy volunteers ; chronic treatment
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of accumulation and elimination of d- and l-fenfluramine (F) and norfenfluramine (NF) have been studied in 8 young healthy volunteers given daily doses of 60 mg of sugar-coated tablets of 20 mg dl-F hydrochloride (dl-F) t.i.d. and capsules of 15 mg d-F hydrochloride (d-F) b.i.d. for 15 days. Repeated doses of d-F plus l-F gave the same values for the parameters measured as did d-F administered alone. Steady-state concentrations of all compounds were achieved within 4–8 days. The predicted mean steady-state concentrations of d-F and elimination half-lives calculated from the results of a previous single dose study were similar to those measured at steady state in this study, confirming the lack of effect of the drug on hepatic microsomal enzymes and on kinetics after repeated dosing. d-NF concentrations were approximately half those of the parent drug and the half-life was almost twice as long. Steady state concentrations both of L-f and l-NF were consistently about 40–50% higher than of the d-isomers and there was a comparable in the half-life.
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  • 25
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 29 (1985), S. 331-336 
    ISSN: 1432-1041
    Schlagwort(e): nitroglycerin ; transdermal preparation ; blood viscosity ; plasma viscosity ; healthy volunteers ; haematocrit ; haemodilution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Transdermal nitroglycerin (Nitroderm TTS 5) and a placebo were applied to 10 healthy male volunteers for 10 days. Before the first application and 6, 24, 48, 96, and 240 h thereafter, the viscosity of plasma and whole blood was measured and the packed-cell volume determined. During nitroglycerin application, the viscosity of plasma and whole blood was significantly diminished, and after 10 days it averaged 5% below the initial value. The greater the initial viscosity, the more marked was the druginduced reduction: in 5 subjects with plasma and whole-blood viscosities near the lower limit of the normal range, there was only a temporary decrease and the values reverted to their initial levels after 4 days; in the other 5 subjects, whose whole-blood viscosities were near the upper limit of the normal range, a 10% reduction was still demonstrable after 10 days. In those subjects all values measured throughout the 10-day observation period were significantly below the initial values. The haematocrit readings followed the same pattern as the alterations in viscosity. It can be assumed, therefore, that the decrease in viscosity induced by nitroglycerin results from “internal haemodilution”. The clinical relevance of the changes observed is discussed. The improvement in the rheological properties of the blood may contribute to the anti-anginal effect of Nitroderm TTS.
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  • 26
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 113-117 
    ISSN: 1432-1041
    Schlagwort(e): nadolol ; nifedipine ; tachycardia ; cardiovascular response ; healthy volunteers ; pharmacokinetics ; exercise heart rate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a placebo controlled exercise protocol using healthy volunteers the effects of nadolol 80 mg and 160 mg orally and of nadolol 80 mg during treatment with nifedipine 20 mg 8 hourly were compared. Resting systolic and diastolic blood pressures were reduced by both nifedipine (p〈0.05) and nadolol (p〈0.01) acting alone. An unexpected finding was that nifedipine alone significantly inhibited exercise tachycardia (p〈0.01) (8 to 12 h post dose). Predictably both doses of nadolol produced significant reduction in exercise tachycardia which was still apparent at 24 h. There was a linear relationship between log10 plasma nadolol concentration and reduction in exercise heart rate. The combined inhibitory effects of nifedipine and nadolol 80 mg on exercise heart rate showed partial additivity but did not summate. There was no pharmacokinetic interaction between the 2 drugs. The inhibition of exercise tachycardia by nifedipine, not previously documented, is consistent with an effect of the drug on the sinus node, as has been reported in in-vitro studies, and may contribute to the drugs efficacy in angina.
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  • 27
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 155-158 
    ISSN: 1432-1041
    Schlagwort(e): digoxin ; digitoxin ; cardiac glycosides ; ventilation ; respiration ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Eight healthy volunteers were studied to ascertain the effect of digoxin and the relatively more lipophylic cardiac glycoside, acetyl-digitoxin on ventilation. Baseline ventilation as well as the response to the inspiration of 2.2% and 4.8% carbon dioxide were assessed. Digoxin produced a depression of minute volume and oxygen consumption whereas acetyl-digitoxin produced the opposite effect. This could be the result of a relatively greater vagomimetic effect with digoxin and a greater symphatomimetic effect with acetyl-digitoxin. These findings might have clinical implications in cardiac patients who have pulmonary disease.
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  • 28
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 143-148 
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; beta-adrenergic blockade ; maximal aerobic power ; acute and chronic administration ; exercise ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The acute and long-term effects of the beta1-adrenoceptor blocking agent metoprolol on blood pressure and maximal aerobic power (Wmax) were studied in 10 healthy subjects. Progressive maximal bicycle ergometer tests were performed after intravenous administration of placebo and metoprolol (0.15 mg×kg−1 and 0.30 mg×kg−1), and at the end of 4-week treatment periods with placebo, conventional metoprolol (C-M) and slow-release metoprolol (SR-M). The reduction in maximal exercise heart rate (HRmax) was correlated with the log plasma metoprolol concentration. Despite a reduction in HRmax of 23 beats/min after 0.15 mg×kg−1 metoprolol, Wmax was unaffected. After 0.30 mg×kg−1 HRmax was reduced by 40 beats/min and Wmax by 5.0%. During chronic treatment, the reductions in HRmax and Wmax were 48 beats/min and 7.5% (C-M) and 45 beats/min and 6.9% (SR-M), respectively. Resting systolic blood pressure was not changed after acute administration of metoprolol but it was reduced during chronic beta-blocker treatment. Resting diastolic blood pressure was not affected after acute or chronic treatment. Exercise systolic blood pressure remained unchanged after 0.15 mg×kg−1 metoprolol i.v. The fall in exercise systolic pressure after 0.30 mg×kg−1 metoprolol i.v. (18±5 mmHg) was significantly smaller than that during chronic treatment (30±6 mmHg C-M; 30±6 mmHg, SR-M). During chronic metoprolol treatment a certain % HRmax corresponded to a higher % Wmax than during placebo treatment, but the shift appeared to be of minor practical importance. The results show that the reduction in maximal aerobic power was comparable after acute i.v. administration and after 4 weeks oral treatment with metoprolol, if the degree of beta blockade (i.e. reduction in maximal exercise heart rate) was similar.
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  • 29
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 433-437 
    ISSN: 1432-1041
    Schlagwort(e): isofezolac ; probenecid ; pharmacokinetics ; anti-inflammatory drug ; drug interaction ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The interaction between isofezolac and probenecid has been studied with the aid of a specific HPLC assay for isofezolac in plasma and urine. 8 healthy adult volunteers received a single 40 mg oral dose of isofezolac before and after 3 days of loading with 0.5 g probenecid t.i.d. There was an increase in the maximum plasma isofezolac concentration from 2.44 to 3.38 µg · ml−1 when probenecid was given. The AUC of isofezolac in plasma increased from 6.73 to 11.28 µg · h · ml−1. After the last dose in a 7 day treatment with 40 mg isofezolac t.i.d., there was an increase in the maximum plasma isofezolac level from 2.84 to 4.96 µg · ml−1 when probenecid was given. The rate of absorption of isofezolac was not affected. An increase in the AUC of isofezolac in plasma was observed from 11.74 to 26.34 µg · h · ml−1. The major effect of probenecid on isofezolac metabolism was a 50% reduction in total isofezolac (free+conjugates) excreted inurine. Because of this interaction, patients given isofezolac combined with probenecid will have a higher steady-state plasma level of isofezolac than when probenecid is not administered.
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  • 30
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 659-664 
    ISSN: 1432-1041
    Schlagwort(e): BTS 49465 ; hypertension ; pharmacokinetics ; blood pressure effect ; heart rate effect ; side-effects ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic and haemodynamic effects of a 200 mg oral dose of BTS 49465 (7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) were investigated in a double-blind placebo controlled study. BTS 49465 was rapidly absorbed and cleared from the systemic circulation with a half-life of 1.6 h by oxidation to the sulphone metabolite. The metabolite was cleared with a half-life of 37.6 h. Saliva concentrations of both BTS 49465 and its metabolite correlated well with the plasma concentrations. Compared to placebo, BTS 49465 produced statistically significant reductions in blood pressure and increases in heart rate both supine and after a 60° head up tilt. The time course of the haemodynamic changes suggested that the sulphone metabolite contributed to the overall hypotensive response. Plasma Renin Activity was only marginally elevated and there was no evidence of acute fluid retention. BTS 49465 was well tolerated in terms of haematological and biochemical parameters and subjective side-effects.
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  • 31
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 671-675 
    ISSN: 1432-1041
    Schlagwort(e): famotidine ; histamine H2-receptor antagonist ; diazepam ; hepatic elimination ; tubular secretion ; drug interaction ; cytochrome P450 ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 8 healthy male volunteers the pharmacodynamic responses to a single dose of diazepam and a single dose of procainamide were assessed before and after pre-treatment with the H2-receptor antagonist famotidine in a randomized crossover study. The pharmacokinetics of diazepam and procainamide were also studied, and the binding of famotidine to human liver microsomes was also measured. Cimetidine induced binding changes with a spectral dissociation constant (Ks) of 0.87 mM, whereas famotidine produced no measurable spectral alteration in concentrations up to 4 mM. The elimination half-life (t1/2: 45.6 h) and total plasma clearance (CL: 0.28 ml/min/kg) of diazepam were not significantly altered by famotidine (t1/2=39.0±11.4 h; CL =0.31±0.08 ml/min/kg). Similarly, there was no enhancement of the sedative effect of diazepam by famotidine. The pharmacodynamics and pharmacokinetics of procainamide and N-acetylprocainamide (NAPA), too, were not significantly changed by famotidine: procainamide t1/2 2.9 vs 3.0 h under famotidine and renal clearance (CLR) 436 vs 443 ml/min; and NAPA CLR 195 vs 212 ml/min under famotidine. The data suggest that famotidine, in contrast to cimetidine, does not affect the pharmacokinetics of diazepam (hepatic elimination) or procainamide (tubular secretion). This new H2-receptor antagonist appears to be devoid of an interaction potential for either type of drug elimination.
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  • 32
    ISSN: 1432-1041
    Schlagwort(e): atenolol ; bopindolol ; metoprolol ; oxidation polymorphism ; debrisoquine ; bufuralol ; stereoselective metabolism ; pharmacological effect ; healthy volunteers ; beta-blocker
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Ten healthy subjects whose genetic oxidative phenotype had been determined (6 extensive and 4 poor metabolizers of the debrisoquine-sparteine type of polymorphism) received single oral doses of 3 beta-blockers: atenolol, bopindolol and metoprolol. The plasma concentrations and the extent of the decrease in exercise-induced tachycardia were determined. The oxidative polymorphism was only significant for substances that had a high hepatic first pass metabolism, such as metoprolol. The metabolic pathway under genetic control was highly stereoselective. This observation must be taken into account when assessing the relation between the plasma concentration and effect of these drugs, which are often administered as racemic mixtures.
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  • 33
    ISSN: 1432-1041
    Schlagwort(e): converting enzyme inhibitor ; CGS 14824A ; pharmacodynamics ; plasma renin ; plasma angiotensin ; aldosterone ; side-effects ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The converting enzyme inhibitor CGS 14824A was evaluated in 15 healthy male volunteers. First, the efficacy of a single 5 or 10 mg oral dose in antagonizing the pressor response to exogenous angiotensin I was tested in 2 subjects. Blood pressure and heart rate were monitored continuously through an intra-arterial catheter. CGS 14824A 5 mg reduced the response to angiotensin I within 75 min to 50%, and 10 mg within 1 h to less than 25%, and for a period of more than 4 h. Subsequently, plasma renin and converting enzyme activity, plasma angiotensin I, angiotensin II and aldosterone were measured serially before and up to 72 h following oral administration of 2, 5, 10 or 20 mg CGS 14824A to groups of 5 volunteers. Plasma converting enzyme activity fell to well below 10% of baseline within 1 h after administration of 5 mg or more CGS 14824 A. Within 2 h following 2 mg p.o., a similarly low level was reached. Twenty four hours following the 20 mg dose, plasma converting enzyme activity was still below 10%. As expected, plasma renin activity and angiotensin I rose while angiotensin II and aldosterone fell following the 2 mg dose. This pattern of effects was enhanced by increasing the dose. Nonetheless, 24 h after the 20 mg dose, plasma angiotensin II and aldosterone had returned to their baseline levels. No side-effects occurred. Thus, in normal volunteers, CGS 14824A was an effective, potent and long acting converting enzyme inhibitor.
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  • 34
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 273-277 
    ISSN: 1432-1041
    Schlagwort(e): ketanserin ; catecholamines ; renin activity ; norepinephrine ; epinephrine ; dopamine ; healthy volunteers ; plasma levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a placebo controlled, single blind, randomized cross over study catecholamines (CA) and renin activity (PRA) in plasma were measured in 2 female and 4 male healthy volunteers, at rest in the supine position, following a single intravenous injection of 0.15 mg/kg ketanserin (K) and placebo (P, 10 ml saline). K caused a significant increase in the area under the plasma norepinephrine (NE) time curve (AUCNE) from 13,200 to 18,100 ng × 1−1 × min for 1 hour after the injection. The area under the plasma epinephrine (E) time curve (AUCE) was also increased but to a lesser extent; it was significantly elevated from 54 to 68 ng × 1−1 × min for 1 minute after the injection. Dopamine (DA) and PRA did not show any significant response to ketanserin. Following the P injection, none of the four parameters showed any significant change.
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  • 35
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 229-230 
    ISSN: 1432-1041
    Schlagwort(e): diazepam ; dipotassiumchlorazepate ; benzodiazepines ; bioavailability ; administration ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Dipotassium chlorazepate (DPC) and diazepam (DZM) were given i.m. and i.v. to 6 healthy volunteers in doses of 20 mg (48.9 µmol) DPC and 15 mg (52.0 µmol) DZM. The interval between the injections was at least 1 week. Plasma samples were analyzed for DPC and DZM by HPLC. The bioavailability of DPC and DZM after i.m. administration, determined from computer calculated AUCs, was 1.04 and 0.85, respectively.
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 463-467 
    ISSN: 1432-1041
    Schlagwort(e): ceftizoxime ; cephalosporins ; renal excretion ; tubular reabsorption ; tubular secretion ; healthy volunteers ; biliary excretion ; clearance studies
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of ceftizoxime, a newly developed cephalosporin, were evaluated in 6 healthy subjects, with respect to its excretory pathways especially by the biliary route. Total, renal and biliary clearance were determined at two different steady states. Steady state was achieved by constant intravenous infusion (604.1 mg/h) over 6 h after an initial loading dose (750 mg); 1.5 h after discontinuation of that infusion, a further infusion was commenced at a lower rate (284 mg/h) over 3 h, the second steady state being reached 0.5 to 1.0 h later. The drug was mainly excreted by the kidneys (56.7 to 92.9% of the dose). Biliary excretion, measured by the duodenal perfusion and marker dilution technique, was low (0.2 to 7.8% of the dose). Urinary and biliary excretion as well as total clearance were not dose-dependent. However, there was pronounced interindividual variation in total (35.2 to 236 ml/min) and renal clearance (10.6 to 208 ml/min), which could both be explained by varying interindividual urinary flow rates (mean flow rate: 0.99 ml/min to 3.14 ml/min). Intraindividual variation in renal clearance was less pronounced, but in the same subject changes in renal clearance were correlated with changes in urinary flow rate. From the varying renal clearance, which exceeded the glomerular filtration rate at high urinary flow rates and was below it at low urinary flow rates, it can be concluded that, in addition to glomerular filtration, tubular secretion and tubular reabsorption are involved in the renal excretion of ceftizoxime. The half-life calculated from two point estimates after discontinuation of the infusion at the higher rate tended to be longer in subjects with high total clearance (e. g. 1.4 h, clearance 223 ml/min) and shorter in subjects with low total clearance (e.g. 0.85 h, clearance 35.2 ml/min). From this it is concluded that the true half-life was not observed after discontinuation of the infusion.
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  • 37
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 607-609 
    ISSN: 1432-1041
    Schlagwort(e): growth hormone ; valproate ; GABA ; stress ; exercise ; healthy volunteers ; GABAergic transmission
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of the GABAergic drug sodium valproate (SV) on the exercise-induced release of growth hormone (GH) was investigated in 10 healthy males. The exercise test consisted of using a stationary bicycle ergometer at 450 kg/min for 20 min. SV 600 mg blunted the increase in GH induced by the exercise, suggesting GABAergic regulation of GH secretion in man, at least under certain physiological conditions.
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  • 38
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 89-95 
    ISSN: 1432-1041
    Schlagwort(e): moclobemide ; Ro 11-1163 ; pharmacokinetics ; bioavailability ; MAO activity in platelets ; monoamine metabolites in urine ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentrations of the MAO-inhibitor moclobemide (Ro 11-1163) were determined in six healthy male subjects after oral (tablets) administration. Effects on MAO activity in platelets and excretion of monoamine metabolites in urine were investigated. The design of the study was a double-blind cross-over study with single oral doses of placebo, 50, 100 and 200 mg of moclobemide. The elimination profile of the drug showed that the half life of the unchanged drug ranged between 1 and 2 h except in one subject with a half-life of about 4 h. The mean bioavailability calculated using flow model concepts was F=0.43 after 50 mg, F=0.47 after 100 mg and F=0.59 after 200 mg. The outlier with a t1/2 of 4 h was found to have a bioavailability of more than 0.80 after all 3 doses. The slightly increasing bioavailability with higher doses was interpreted as evidence of saturable hepatic first-pass elimination of the drug. MAO activity in platelets was measured before and 2, 6 and 24 h after drug administration. No inhibition of platelet MAO was obtained at any point in time or dose level, as to be expected since moclobemide preferentially inhibits MAO A. Urine excretion of the monoamine metabolites homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxy-phenylglycol (MOPEG) and 5-hydroxyindoleacetic acid (5-HIAA) was followed during 48 h after placebo, 50 and 200 mg of moclobemide. Time but not dose contributed significantly to the variability in excretion of the monoamine metabolites. An apparent reduction of HVA and DOPAC levels was obtained in the early phase after the administration of 200 mg of moclobemide. In 1 subject with a mild drug reaction a pronounced decrease in the levels of all the metabolites was obtained. In the other 5 subjects, the compound was very well tolerated with a few reported side-effects like increased activity, somnolence or sweatings. There was a slight but significant increase in blood pressure following 50 and 100 mg but not 200 mg of moclobemide.
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  • 39
    ISSN: 1432-1041
    Schlagwort(e): sulphinpyrazone ; metabolism ; single dose ; chronic treatment ; pharmacokinetics ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of sulphinpyrazone and its major metabolites (sulfide, sulfone, p-hydroxysulfone and p-hydroxy-sulphinpyrazone) were investigated in 9 volunteers after a single oral dose as well as after chronic treatment for 23 days. Chronic administration of sulphinpyrazone, in comparison with a single oral dose, led to significant changes in plasma AUC (115.86 to 42.90 mg/l·h), in renal clearance (1.06 to 1.80l/h), in hepatic intrinsic clearance (319.0 to 598.0l/h), and in the unbound fraction in plasma 1.15 to 1.69%) and in tissue (2.73 to 1.31%). The volume of distribution changed from 20.24 to 52.041. The steady state concentrations predicted from the single dose were significantly higher than the values found after chronic treatment. The results suggest that sulphinpyrazone induces its own metabolism. The metabolism of the sulfone, p-hydroxysulfone and the p-hydroxy-sulphinpyrazone to further degradation products was also induced. Chronic treatment with sulphinpyrazone reduced the plasma AUC of the sulfide and caused a decrease in its elimination half-life (20.9 to 14.3 h). Since considerable amounts of the sulfide are formed in the G.I. tract, it is suggested that besides the induction of metabolism, bacteria which reduce sulphinpyrazone to the sulfide may also be responsible for the observed pharmacokinetic changes.
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  • 40
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 29 (1985), S. 67-71 
    ISSN: 1432-1041
    Schlagwort(e): dipyrone ; dipyrone metabolites ; human protein binding ; analgesic antipyretic drugs ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Four metabolites of dipyrone, 4-methyl-aminoantipyrine (MAA), 4-aminoantipyrine (AA), 4-formylaminoantipyrine (FAA) and 4-acetylamino-antipyrine (AAA) can be identified in human plasma after its oral administration. The plasma protein binding of the metabolites in samples from 20 healthy volunteers was determined by ultrafiltration. None of the metabolites were found to be extensively bound to plasma proteins. The binding of MAA and AA was relatively higher than of FAA and AAA, as expected from their chemical structure. The mean percentage plasma protein binding was 57.6% for MAA, 47.9 for AA, 17.8 for FAA and 14.2% for AAA. The correlation between the unbound concentration in plasma and the total concentrations of MAA, AA, FAA and AAA was linear. No association was evident between the total protein plasma concentration and the extent of binding. The possible therapeutic implications related to protein binding of several analgesic and non-steroidal anti-inflammatory drugs are discussed.
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  • 41
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 29 (1985), S. 91-95 
    ISSN: 1432-1041
    Schlagwort(e): midazolam ; 1-hydroxymethylmidazolam ; pharmacokinetics ; dose proportionality ; benzodiazepine ; healthy volunteers ; side-effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were investigated following oral administration of 7.5, 15 and 30 mg doses of midazolam in solution to 12 healthy subjects. Compared to the 7.5 mg dose, the Cmax and AUC parameters of both midazolam and 1-hydroxymethylmidazolam increased proportionally after the 15 mg dose and more than proportionally after the 30 mg dose. The t1/2 for midazolam remained relatively constant between the 7.5 and 15 mg doses whereas it increased slightly but significantly after the 30 mg dose. These data indicated that the pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were linear between the 7.5 and 15 mg oral dose range. However, after the 30 mg dose, the systemic availability of midazolam and the AUC for 1-hydroxymethylmidazolam appeared to be greater than that anticipated from the lower doses, possibly due to saturation of midazolam first-pass metabolism. This ist not expected to have any clinical significance under the conditions of therapeutic use.
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  • 42
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 29 (1985), S. 413-416 
    ISSN: 1432-1041
    Schlagwort(e): nifedipine ; indomethacin ; whole blood aggregometry ; 6-keto-prostaglandin F1α ; blood pressure ; platelet aggregation ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Pre-incubation of human platelets with nifedipine in vitro or treatment of normal volunteers with nifedipine, 30 mg daily for one week, did not alter ADP induced aggregation measured by whole blood aggregometry. 6-oxo-Prostaglandin F1α remained undetectable in plasma following oral administration of nifedipine to normal volunteers. The hypotensive response to intravenous nifedipine administration was similar in spontaneously hypertensive rats pretreated with indomethacin or placebo. These results conflict with previous reports that nifedipine alters platelet aggregation and prostaglandin metabolism.
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  • 43
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 221-222 
    ISSN: 1432-1041
    Schlagwort(e): calcium entry blockers ; bronchomotor tone ; ethanol ; nifedipine ; flunarizine ; diltiazem ; verapamil ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of various Calcium Entry Blockers (CEBs; nifedipine, flunarizine, diltiazem, verapamil) on ethanol-induced bronchoconstriction was studied in normal healthy volunteers. Nifedipine and diltiazem inhibited the bronchoconstriction and verapamil and flunarizine had no effect. The data favour the general hypothesis of differential tissue sensitivity to the various CEBs. The activity of CEBs on bronchomotor tone may be of therapeutic value in patients in whom bronchodilator activity is recommended in addition to the cardiovascular action.
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  • 44
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 411-417 
    ISSN: 1432-1041
    Schlagwort(e): ketanserin ; ketanserinol ; pharmacokinetics ; age ; healthy volunteers ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The bioavailability of ketanserin has been examined in a cross-over experiment in 21 elderly subjects (aged 59–72 years) by administration of tablets (40 mg), solution (40 mg) and injectable solution (10 mg). After two weeks of treatment with 40 mg ketanserin tablets further 18 blood samples for analysis were collected under steady-state conditions. Plasma levels were measured by HPLC. The absolute bioavailability of ketanserin tablets was 52.7%; their relative bioavailability compared to a solution containing an equal quantity of active compound was 85.5%. Therefore, the low absolute bioavailability of ketanserin cannot be attributed to the formulation. The active compound was rapidly liberated from the tablet, reaching a peak of 103.8 ng/ml after 0.97 h. Individual plasma level-time curves were fitted to an open three compartment model and a half-life of 17.7±7.26 h was calculated for the terminal elimination phase. An average terminal elimination half-life of 15.4±4.2 ng/ml was found after administration of the ketanserin solution. Multiple dosing with 40 mg tablets b.d.s. resulted in an AUC over one dosing interval at steady-state of 666±201 ng × h/ml. The AUC extrapolated to infinity was 1200±405 ng × h/ml for the last tablet. This is 1.8-times the AUC in one dosing interval, and 2.3-times the AUC of a single dose. Under steady-state conditions, the mean peak plasma level was 155.1 ng/ml (1.08 h after dosing) and the terminal half-life was 19.1±5.1 h. For the metabolite ketanserinol terminal half-lives of 21.4 h after a single tablet and 31.0 h after discontinuation of multiple dosing were calculated. Compared to the parent compound there was much more marked accumulation of ketanserinol. Despite moderate accumulation and prolongation of the terminal half-life of ketanserin under steady-state conditions, dosage adjustment is not required in elderly people. First-pass metabolism and bioavailability remained in the range found in previous studies of ketanserin in young subjects.
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  • 45
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 567-571 
    ISSN: 1432-1041
    Schlagwort(e): vinpocetine ; cognitive function ; information processing ; memory ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Twelve healthy female volunteers received pre-treatments with vinpocetine 10, 20, 40 mg and placebo (t.d.s.) for two days according to a randomised, double-blind crossover design. On the third day of treatment and 1 h following morning dosage, subjects completed a battery of psychological tests including Ciritcal Flicker Fusion (CFF), Choice Reaction Time (CRT), Subjective Ratings of Drug Effects (LARS) and a Sternberg Memory Scanning Test. No statistically significant changes from placebo were observed on CFF, CRT or subjective ratings of drug effects. However, memory as assessed using the Sternberg technique was found to be significantly improved following treatment with vinpocetine 40 mg when compared to placebo and results suggested a localised effect of the drug on the serial comparison stage of the reaction process.
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  • 46
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 631-636 
    ISSN: 1432-1041
    Schlagwort(e): salbutamol ; histamine plasma concentration ; bronchorelaxation ; healthy volunteers ; induced bronchoconstriction ; carbachol ; bronchoconstrictor mediators
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma histamine in 8 normal subjects was measured before and after inhalation of carbachol to induce a 50% fall in specific airway conductance (SGaw). The measurements were repeated 5 min after inhalation of salbutamol or placebo. No significant change in plasma histamine occurred after placebo or carbachol inhalation, despite the persistent induced bronchospasm after the latter treatment. In contrast, plasma histamine was significantly increased from 0.25 to 0.43 ng/ml after salbutamol inhalation. Simultaneously, induced bronchospasm was relieved, from 51% to 103% of baseline SGaw. Thus, the relief of carbachol-induced bronchospasm by salbutamol was associated with a rise in plasma histamine. Since salbutamol itself is a potent inhibitor of mast cell degranulation and histamine release, the present findings suggest that histamine may be released and sequestered within the lungs during carbachol-induced-bronchospasm, and also that desequestration of bronchoconstrictor mediators accumulated at the point of contact of bronchial smooth muscle may contribute to the relief of bronchospasm by salbutamol.
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  • 47
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 649-652 
    ISSN: 1432-1041
    Schlagwort(e): digitoxigenin ; monodigitoxoside ; bisdigitoxoside ; biovailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic behavior of digitoxigenin is affected by the number of glycosides present. This study was conducted to compare the bioavailabilities of the bis- and monodigitoxosides of digitoxigenin in man. Intravenous and oral doses of the two drugs were administered to six normal volunteers. Blood samples were collected up to 28 days after each dose, and assayed for the specific drug administered and for total radioassayable drug. Both drugs were virtually completely absorbed, based on serum concentrations of administered drug plus metabolites. However, the mean bioavailability of unchanged bisdigitoxoside was only 56.3% indicating that substantial metabolism occurred prior to entry into the systemic circulation. Monodigitoxoside was virtually completely metabolized prior to entry into the systemic circulation.
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  • 48
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 28 (1985), S. 685-688 
    ISSN: 1432-1041
    Schlagwort(e): prostaglandin analogue ; renal function ; vasodilator ; L-644,122 ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary L-644,122 is a chemically stable vasodilator prostaglandin analogue. It is a selective renal vasodilator in dogs. The object of the present study was to determine whether it increases effective renal plasma flow (ERPF) in man. L-644,122 was administered intravenously to 4 healthy volunteers and by mouth to 4 mild hypertensives. It did not increase ERPF. Instead it acted as a non-specific vasodilator, lowering diastolic blood pressure and increasing heart rate. An unexpected increase in glomerular filtration rate (19% greater than placebo) after low dose intravenous L-644,122 merits further study.
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 34 (1988), S. 363-368 
    ISSN: 1432-1041
    Schlagwort(e): bisoprolol ; propranolol ; beta-adrenergic blockade ; atropine ; exercise testing ; ethnic differences ; healthy volunteers ; autonomic tone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A randomized, double-blind, placebo-controlled study was performed in 8 white and 8 black volunteers matched for sex, age and mass. The effect of 3 intravenous doses of a new, cardiose-lective beta-adrenergic blocker, bisoprolol, on the heart rate increase after standardized exercise was compared to that of 3 doses of propranolol. As described previously for propranolol, black volunteers showed less response than whites to beta-blockade assessed in terms of the reduction in exercise-induced tachycardia. The effects of the two beta-blockers were similar and the apparent ethnic difference was seen with both drugs. It has previously been shown that black volunteers have a higher intrinsic heart rate (i.e. heart rate after parasympathetic and beta-adrenergic blockade of the heart) than whites, but their resting heart rates are similar because of greater parasympathetic tone in blacks. When exercise-load was calculated as increase in heart rate above that after atropinization, no ethnic differences were seen. It is suggested that in populations that are heterogenous in terms of the heart rate increase after atropine, work load should be standardized in terms of the increase in heart rate over the atropine heart rate rather than on absolute heart rate. The apparent ethnic difference represents a flaw in methodology as applied to a heterogenous volunteer population.
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  • 50
    ISSN: 1432-1041
    Schlagwort(e): oxprenolol ; beta-blockade ; concentration-effect relationship ; non-invasive monitoring ; exercise test ; blood pressure monitoring ; healthy volunteers ; predictive model
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The relationship between the plasma concentration of oxprenolol and its haemodynamic effects during physical exercise was studied in 6 healthy volunteers, in whom BP and heart rate (HR) were continuously monitored by non-invasive techniques (Fin-A-Press-Tonometer) during repeated three-minute exercise periods for 8 h after treatment. Using the fitted pharmacokinetic curve, the drug effect was related to its plasma concentration using the Emax model. The mean EC50 for the relationship between drug concentration and heart rate during exercise (HRex) was 73.1 ng/ml, and for systolic blood pressure during exercise (SBPex) it was 112.7 ng/ml. Emax was 29.0% for HRex, and 33.2% for SBPex. There were no consistent differences between the parameters for the effects on HRex and SPBex. Thus, using a new, non-invasive technique for continuous measurement of blood pressure, the effect of a beta-adrenoceptor blocking drug on SBPex was described with similar accuracy as its effect on HRex.
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  • 51
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 59-64 
    ISSN: 1432-1041
    Schlagwort(e): adinazolam ; cimetidine ; pharmacokinetics ; pharmacodynamics ; healthy volunteers ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Adinazolam is a new triazolobenzodiazepine bearing an alkyl-amino side chain. A cross-over double-blind placebo controlled study was carried out in 12 healthy volunteers, in order to check the possible interaction between cimetidine and adinazolam after repeated co-administration. Cimetidine or placebo were given during 17 days. Beginning on Day 8 of each treatment, adinazolam was given in the increasing doses following sequence of doses for 3 days: 10 mg b.i.d., 20 mg b.i.d. and 20 mg t.i.d. A pharmacokinetic and pharmacodynamic study was performed on the third day at each dose. A wash-out of three weeks was included between the two treatments. Cimetidine increased significantly the AUC values of both adinazolam and N-desmethyladinazolam, reduced the oral clearance of adinazolam, and prolonged adinazolam's half-life. The digit symbol substitution test was significantly affected at each dose level while the manual dexterity was marginally impaired by adinazolam plus cimetidine. Saftee-up interview and Clyde mood scale indicated an increased sedation under adinazolam plus cimetidine in four subjects.
    Materialart: Digitale Medien
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  • 52
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 85-88 
    ISSN: 1432-1041
    Schlagwort(e): ibuprofen ; nizatidine ; cimetidine ; drug interaction ; pharmacokinetics ; healthy volunteers ; H2-antagonists
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The potential for interaction between ibuprofen and two histamine H2-receptor blocking drugs — nizatidine and cimetidine — was investigated in six healthy male volunteers aged 20 to 25 years. Each subject received placebo, nizatidine 300 mg and cimetidine 800 mg orally at 9.00 p.m. daily for six doses in three randomised treatment periods separated by eight days. On the third day of each treatment period ibuprofen 400 mg was administered at the same time and venous blood samples were taken at intervals throughout the night and subsequently up to 84 h after administration. There was no difference in the area under the plasma concentration-time curve, rate of absorption or half-life of elimination of ibuprofen between the three treatments. The elimination half-life of ibuprofen on placebo was 2.04 h. The elimination half-life of nizatidine on ibuprofen was 1.72 h and that of cimetidine was 3.54 h. The latter is higher than previously reported in normal subjects. It is concluded that neither H2-blocker affects the kinetics of ibuprofen in man.
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  • 53
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 177-181 
    ISSN: 1432-1041
    Schlagwort(e): fluocortolone ; cortisol ; alternate day therapy ; plasma cortisol ACTH ; plasma level ; healthy volunteers ; circadian rhythm
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of fluocortolone and its effect on the circadian rhythm of plasma cortisol and ACTH have been studied during different schedules of oral administration. Groups of 6 healthy male adults were given a single daily dose of fluocortolone 5, 10 and 20 mg, and another group received 20 mg every second day. Administration to all groups was continued for 8 days. Pharmacokinetic parameters of fluocortolone (half lives of absorption- t1/2a and elimination t1/2e, volume of distribution V and oral clearance (CL/f) were independent of the duration of treatment and dose. Areas under the plasma level curves, AUC and Cmax values increased in proportion to the dose, indicating dose linearity of fluocortolone pharmacokinetics. A normal morning cortisol peak occurred during all treatment schedules, which indicates that circadian cortisol secretion was not seriously affected by the glucocorticoid treatment. On the other hand, when the level of circulating fluocortolone was high the 12.00 a.m. and 4.00 p.m. cortisol levels were diminished compared to the pre and posttreatment values. There was no definite correlation between the ACTH and cortisol levels, either on treatment or on control days. ACTH levels were suppressed by daily treatment with the 20 mg dose. Thus, even during administration of a high dose of a glucocorticoid, the circadian secretion of cortisol can be preserved if the treatment is adjusted according to the half-life of the drug.
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  • 54
    ISSN: 1432-1041
    Schlagwort(e): xamoterol ; partial agonist ; beta1-selective ; physical performance ; metabolism ; healthy volunteers ; hormone levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a double-blind, random, cross-over study, 14 healthy male volunteers received xamoterol 200 mg (Corwin; C) twice daily or placebo (P) for two seven-day medication periods to investigate effects on physical performance, cardiocirulatory parameters, metabolism and hormone levels during exercise. An oral glucose tolerance test (OGTT) was also done. C showed a positive inotropic effect up to an exercise intensity of 100 W, corresponding to a heart rate of about 100 beats · min−1. Chronotropic regulation of the heart remained unchanged, but the increase in systolic blood pressure was more pronounced and the catecholamines behaved as after P. From 150 W onwards, C exhibited beta-blocking properties; heart rate was reduced by up to 8 beats · min−1; systolic blood pressure remained unchanged; and the catecholamines showed a more pronounced increase than after P. Diastolic blood pressure behaved almost identically under all test conditions. With the exception of a slightly increased level of free fatty acids at rest, the parameters of physical performance, lipid and carbohydrate metabolism and the hormone levels under all conditions after C showed similar behaviour to that after as P. The findings indicate that physical performance capacity, cardiocirculatory system, metabolism and hormones were not negatively influenced by C.
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  • 55
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; ramixotidine ; prolactin ; testosterone ; 17 beta-estradiol ; H2-receptors ; CM 57755A ; gastrin ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Three groups of eight healthy male volunteers received placebo for 2 days, then daily morning doses either of cimetidine 800 mg, ramixotidine 750 mg (CM 57755A), or placebo, for 14 days, and then were all returned to placebo for one more day. Plasma levels of prolactin, testosterone and 17β-estradiol were measured on Days 2, 3, 16 and 17 in blood samples taken 30 and 15 min before and 0, 60, 120, 180, 240 and 300 min after treatment. Gastrin was assayed in blood collected on the same days 180 min after treatment. Mean pre- and post-treatment areas under the time-concentration curves of the first three hormones were not significantly different in the three groups on any test day, or within the same group throughout the four test days. Mean plasma gastrin levels ranged between 27 and 42 pg/ml, respectively, in the placebo and cimetidine treated groups on test day 3, and intermediate values were found in the group receiving CM 57755A. There was no statistically significant difference in gastrin level between the groups on any test day or within the same group throughout the four test days. No subjective side-effects attributable to the treatments were reported, and there were no abnormalities in blood pressure, heart rate or standard laboratory tests.
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  • 56
    ISSN: 1432-1041
    Schlagwort(e): acetylsalicylic acid ; infarct prevention ; platelet aggregation ; pharmacokinetics ; healthy volunteers ; secondary heart attack prevention ; AMIS ; PARIS ; German-Austrian trials
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a cross-over study 6 healthy male subjects were given for 9 days the acetylsalicylic acid (ASA) preparations used in the Aspirin Myocardial Infarction Study (AMIS), Persantine-Aspirin Reinfarction Study (PARIS) and German-Austrian secondary heart attack prevention trials, exactly according to the original study protocols. Plasma concentrations of ASA and its main metabolites salicylic acid (SA) and salicyluric acid (SUA), as well as platelet function (collagen-induced platelet aggregation; tissue extract-induced change in platelet shape) were studied repeatedly on the first day of each medication period and were again examined on the sixth and ninth days. Differences in the plasma concentrations of ASA and its metabolites were found only on the first day, probably as a result of different absorption rates. Collagen-induced platelet aggregation was more rapidly inhibited the faster the preparation was absorbed. Each ASA preparation inhibited tissue extract-induced platelet shape change from the first dose, although statistically significant inhibition was seen only with the AMIS preparation. It is concluded that differences in the antithrombotic efficiency of ASA cannot be explained by differences in the pharmacokinetic and antiplatelet profiles of the various ASA preparations tested.
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  • 57
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 239 (1985), S. 25-29 
    ISSN: 1432-0878
    Schlagwort(e): Frog skin ; Bombina orientalis ; Cutaneous gland ; Immunohistochemistry ; Fluorescence histochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Immunohistochemistry and fluorescence histochemistry were applied to the skin of the frog, Bombina orientalis, to detect the localization of bombesin and 5-hydroxytryptamine. The dermal layer contains three types (type 1, 2 and 3) of cutaneous glands but only the type-1 gland simultaneously contains bombesin and 5-hydroxytryptamine. This result suggests for the first time the coexistence of a bioactive peptide and monoamine in a cutaneous gland of the frog.
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  • 58
    ISSN: 1432-0878
    Schlagwort(e): Immunohistochemistry ; CRF ; Hypothalamus ; Coturnix quail ; Adrenalectomy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Immunohistochemical localization of corticotropin-releasing factor (CRF)-like immunoreactivity in the brain of the Japanese quail was studied by means of the peroxidase anti-peroxidase (PAP) method. CRF-immunopositive perikarya of parvocellular neurons were observed mainly in the nucleus praeopticus medialis and nucleus paraventricularis. Additional perikarya were also detected in the nucleus hypothalamicus posterior medialis in the hypothalamus and in the non-hypothalamic nucleus accumbens, nucleus septalis lateralis and nucleus dorsomedialis and dorsolateralis thalami. No CRF immunoreaction was found to coexist with the vasotocin (Vt)-containing system in comparative examination of consecutive sections treated with anti-vasopressin (Vp) serum. The CRF-immunoreactive fibers were detected mainly in the external layer of the anterior median eminence but not in its posterior division. Unilateral adrenalectomy induced the marked reduction in number of the CRF immunopositive fibers in the anterior median eminence.
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  • 59
    ISSN: 1432-0878
    Schlagwort(e): Gastrin cell ; Pyloric mucosa ; Ontogenesis ; Immunohistochemistry ; Mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Ontogenesis of gastrin cells was studied in the pyloroduodenal mucosa of the mouse using anti-human G17 serum, R-1301, and anti-human G34(1–15) serum, R-2703. R-1301-immunostained cells first appeared in the pyloric mucosa of 14-day-old fetuses. Cells stained with both R-1301 and R-2703 appeared immediately after birth, and gradually increased in number to the adult level. Most R-1301-reactive cells were also reactive to R-2703, whereas some cells that reacted with R-1301 exhibited very weak or no reaction with R-2703. The discrepancy between these two immunoreactivities is discussed. In the duodenum, a considerable number of R-1301-reactive cells were present from the perinatal stage and through out adult development. A few R-2703-reactive cells were seen in the duodenum of young mice but not of the adult.
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  • 60
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 239 (1985), S. 271-278 
    ISSN: 1432-0878
    Schlagwort(e): Brain macrophage ; Fetus ; Histogenesis ; Immunohistochemistry ; Monoclonal antibody ; Mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary A study on the localization of fetal and neonatal brain macrophages of mice from embryonic day 10 (E10) to postnatal day 21 (P21) was carried out immunohistochemically using a monoclonal antibody against a macrophage differentiation antigen (Mac-1) and the labeled avidin-biotin technique. In the central nervous system, the macrophages recognized first were mainly located in the choroid plexuses of the fourth and lateral ventricles at E14. Their number increased at E17–P3 and gradually decreased thereafter. In the cerebral parenchyma, a few macrophages appeared at E14 in the matrix cell layer. They were also detected in the migrating zone at E15, E17 and in the cortical plate at E19. Mapping of positive cells at the stage of neuroblast formation (E15, E17, E19) disclosed the precise distribution of cerebral macrophages. The macrophages that appeared first in the choroid plexuses at E15 may be derived from the subarachnoid vessels, which extend into the stroma of the choroid plexuses when the matrix cell layer invaginates into the lateral ventricle to form the choroid plexuses. Almost all of the macrophages recognized in the cerebral parenchyma disappeared at P9 when the cytoarchitecture seemed to be completed. In the cerebellum, which develops later than the cerebrum, macrophages appeared after birth and were located mainly in the internal granular layer. The brain macrophages always appeared in the regions where cell proliferation and brain remodeling are most active at each stage. These findings suggest that fetal and neonatal brain macrophages may play an important role in scavenging degenerated cells and cell debris during histogenesis of the central nervous system.
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  • 61
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 239 (1985), S. 395-404 
    ISSN: 1432-0878
    Schlagwort(e): Epididymis ; Innervation ; Neuropeptides ; Substance P ; Vasoactive intestine polypeptide (VIP) ; Immunohistochemistry ; Guinea pig
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The innervation of the ductuli efferentes and seven zones of the guinea-pig epididymis was investigated using immunohistochemical, histochemical and electron-micro-scopical techniques. Nerve fibers were localized by use of antibodies against substance P (SP-IR), vasoactive intestinal polypeptide (VIP-IR) and dopamine-beta-hydroxylase (DBH-IR). In the ductuli efferentes and all zones of the epididymal duct, SP-IR is consistently observed in the interstitial tissue and perivascular areas. Histochemistry reveals a significant amount of acetylcholinesterase-containing fibers in the interstitial, perivascular and periductal smooth muscles of the ductuli efferentes and zones V, VI and VII. In contrast to the homogeneous distribution of SP-IR within all zones of the epididymis, VIP-IR is seen only in zones VI and VII. Within these zones, VIP-IR is detected in large amounts in the subepithelial and muscular layers as is a sparse number of SP-IR varicosities. DBH-IR is also seen throughout all zones in the interstitial and perivascular regions with a tendency to increase in zones VI and VII. Transmission electron microscopy (TEM) reveals evidence of a cholinergic (agranular vesicles, AGV), adrenergic (small granular vesicles, SGV) and peptidergic (large granular vesicles, LGV) innervation throughout the interstitial connective tissue of the ductuli efferentes and all epididymal zones. Furthermore AGV are localized in the subepithelial layer, and also co-stored with LGV in the muscular layer of zones VI and VII. No nerve profiles were encountered within the epithelium. Correlation of immunohistochemical findings to TEM counterparts as well as their possible functional role are discussed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 62
    ISSN: 1432-0878
    Schlagwort(e): Juxtaglomerular cells ; Renin ; Immunohistochemistry ; Movat silver impregnation ; Bufo
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The cellular localization of renin was examined in the kidneys of some amphibians of the genus Bufo by immunoperoxidase and immunofluorescence techniques with an antiserum to renin isolated from the submandibular gland of the mouse. Immunoreactivity could be demonstrated in the media cells of the afferent arterioles (juxtaglomerular cells) close to as well as at great distance from the glomeruli. Occasionally, media cells of larger arterial vessels were also stained. The immunohistochemical data seem to be in accordance with earlier results obtained with a modified silver impregnation technique (Movat's staining procedure) used for the visualization of juxtaglomerular cells in non-mammalian vertebrates. Mouse kidney tissue, studied for purposes of comparison, showed renin-immunoreactivity as described by earlier investigators, i.e., immunoreactive staining in the afferent arterioles near the glomeruli and in the proximal tubule cells.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 63
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 239 (1985), S. 505-510 
    ISSN: 1432-0878
    Schlagwort(e): S-100 protein ; Immunohistochemistry ; Retina ; Ciliary body ; Iris ; Human fetus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The present study deals with the localization and development of S-100 protein-like immunoreactivity in the retina, ciliary body and iris of human fetuses. In the retina, numerous astrocytes, densely distributed in the nerve-fiber layer and ganglion-cell layer, were stained strongly with the S-100 antiserum. The first immunoreactive astrocytes occurred at the posterior pole of the retina and spread gradually outward and toward the ora serrata with increasing age. Müller cells were not immunoreactive for S-100 during development, except in the retina of the latest fetus examined. S-100 immunoreactivity was also found in the nonpigmented ciliary epithelium and posterior epithelium of the iris, both of which are developed from the inner wall of the optic cup. On the other hand, the pigmented epithelium extending from retina to iris, derived from the outer layer of the optic cup, was free of S-100 immunoreactivity.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 64
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 240 (1985), S. 323-332 
    ISSN: 1432-0878
    Schlagwort(e): Mammalian-like peptides ; Insect midgut ; Immunohistochemistry ; Endocrine-cell ultrastructure ; Peptidergic and serotoninergic innervation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The midgut of Blaberus craniifer is principally made up of columnar epithelial cells which are derived from small regenerative cells found grouped in nidi. Between them, small sparsely granulated cells with clear cytoplasm can be observed lying on the basal lamina. Mainly based on the size, shape and texture of their secretory granules, at least ten types of such endocrine cells have been identified. Five cell types contain a uniform population of dense granules: (1) medium-sized, round to oval granules; (2) small elongated granules; (3) large irregular granules; (4) oval granules with a highly osmiophilic core; (5) oval, haloed granules. Five others are characterized by a heterogeneous population of granules: (6) small, round to oval, variably electron-dense granules; (7) oval medium-sized granules of variable electron density; (8) large irregular granules of variable electron density; (9) small dense granules and large vesicles with filamentous material; (10) small dense granules and very large pale vesicles. In addition, near the regenerative cells, large cells characterized by very large, irregular, dense granules (up to 4 μm), lack contact with the lumen, and reach the basal lamina only by slender cytoplasmic processes. Several antisera raised against mammalian peptides and amine were used to reveal axonal fibers and endocrine cells. Serotonin-like immunoreactivity is localized in a profuse innervation of the muscle layers that surround the epithelium, whereas cholecystokinin and methionine-enkephalin antisera stain a more moderate number of axonal fibers. Cholecystokinin-, methionine-enkephalin-, substance P-, vasoactive intestinal peptide-, somatoliberin-, and gonadoliberin-like immunoreactivities were detected in endocrine cells of the epithelium. While most of the cells appear pyramidal, oval, fusiform or bowl-shaped, and seem to lack contact with the lumen, cells reaching it have been detected reacting with antisera to cholecystokinin, substance P, vasoactive intestinal peptide, somatoliberin and gonadoliberin.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 65
    ISSN: 1432-0878
    Schlagwort(e): Non-ciliated tracheal cell ; Smooth endoplasmic reticulum ; Ultrastructure ; Cytochrome P-450 ; Immunohistochemistry ; Mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Non-ciliated SER-rich cells of the tracheal epithelium of normal, phenobarbital-treated and 3-methylcholanthrene-treated mice were studied ultrastructurally and immunohistochemically. The apical portion of these cells protrudes into the tracheal lumen, especially in the mice treated with the two compounds, and the apical cytoplasm is filled with numerous tubular elements of SER. Besides, the non-ciliated cells of 3-methylcholanthrene-treated mice show a strong positive reaction to the antiserum against microsomal cytochrome P-450 of liver. These findings support the concept that the non-ciliated tracheal cell may be involved in the metabolism of endogeneous and exogeneous chemical compounds.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 66
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 240 (1985), S. 575-584 
    ISSN: 1432-0878
    Schlagwort(e): CRF neurons ; Neurosecretory neurons ; Hypothalamus ; Immunohistochemistry ; Colchicine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The immunoreactive CRF-neurons of the rat hypothalamus have been examined immunohistochemically employing anti-rat CRF serum. These neurons are confined to the paraventricular nucleus, dorsomedial-lateral hypothalamic area, and suprachiasmatic nucleus, and are, respectively, also immunoreactive to anti-Met-enk, -alpha-MSH, and -VIP sera. Intraventricular administration of colchicine (50 μg/5 μl/rat) induces a dramatic enhancement of the immunostainability of the cell somata, and also accelerates the development of immunoreactivity of other stored peptides, especially in the paraventricular nucleus. The CRF-neurons respond to adrenalectomy by showing increased immunoreactivity and an increase in the number of cell bodies; in the dorsomedial-lateral area and suprachiasmatic nucleus, there is also an enhanced immunoreactivity for alpha-MSH and VIP, respectively. CRF-cells in the paraventricular nucleus become markedly hypertrophied, but do not show any enhanced immunoreactivity for Met-enk. Since the axons of the paraventricular neurons run to the median eminence, it is probable that they are involved with the endocrine control of hypophysial ACTH release. It is concluded that the CRF-containing neurons in rat hypothalamus consist of three types which are functionally and morphologically different.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 67
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 241 (1985), S. 429-433 
    ISSN: 1432-0878
    Schlagwort(e): Thyroglobulin ; Immunohistochemistry ; Nervous system ; Annelids
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Immunohistochemical studies were performed by use of specific rabbit antisera and purified antibodies to human Tg on cephalic and body sections of Eisenia foetida and on cephalic sections of Lumbricus terrestris. Secondary antisera, either fluorescein- or peroxidase-conjugated, were used to identify the immunoreaction. Immunoreactive perikarya and some immunoreactive nerve fibres were detected in both the cerebral ganglion and the ventral nerve cord of E. foetida. From 8 to 19 Tg-like positive neurons per frontal section were observed in the brain, mainly in the dorsal zone. From 2 to 4 positive perikarya per ganglion were found in sagittal sections of the ventral nerve cord with a repetitive distribution. Numerous positive neurons were also found in the cephalic segments of L. terrestris. The present results indicate that a substance immunologically related to mammalian Tg is synthesized in earthworms. This suggests that some conservative sequences of Tg structure arose very early in evolution and supports the idea of a common evolutionary origin for endocrine and nervous systems.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 68
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 242 (1985), S. 391-398 
    ISSN: 1432-0878
    Schlagwort(e): Development, ontogenetic ; Lymph nodes ; Non-lymphoid cells ; Lymphocytes ; Immunohistochemistry ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The postnatal development of the various cell populations in the rat popliteal lymph node was investigated applying enzyme-histochemical and immunohistochemical techniques. From birth, T-lymphocytes and interdigitating cells were demonstrable. During the development of the young lymph node, T-lymphocytes of the helper phenotype outnumbered the T-cells with a suppressor phenotype; they account for approximately 70% and 30% of all T-lymphocytes, respectively. At the very first day of postnatal life, post-capillary venules were already present. B-lymphocytes occurred later than T-cells during ontogeny; they were found on the second day after birth, most of them being IgM- or IgG-bearing lymphocytes. The first primary follicles occurred at day 18 and contained principally membrane-stained IgM cells and, to a lesser extent, membrane-stained IgG cells. The appearance of follicular dendritic cells correlated with the formation of primary follicles. With respect to the macrophages, it appeared that the ED1- and ED3-positive subpopulations were present with a similar distributional pattern as seen in adults, but in considerably lower numbers. The expression of ED2, however, showed a sudden increase in the third week of life. Findings of the present study are discussed in relation to those obtained in other investigations dealing with the ontogenetic development of lymphoid organs.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 69
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 253 (1988), S. 677-681 
    ISSN: 1432-0878
    Schlagwort(e): Neurohypophysis ; Hypothalamo-neurohypophyseal system ; Vasopressin ; Oxytocin ; Immunohistochemistry ; Phodopus sungorus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The topography of oxytocin (OT)- and vasopressin (VP)-containing axons of the hypothalamo-neurohypophyseal system was studied in the neurohypophysis of the Djungarian hamster (Phodopus sungorus) by means of immunohistochemistry. Compared with other mammalian species, the neurohypophysis of Phodopus shows some peculiarities. Accumulations of OT-immunoreactivity around the distal vessels of the primary portal plexus can be observed in the distal median eminence and neural stem. This staining pattern indicates that OT is secreted into portal blood. In the neural lobe, OT- and VP-immunopositive fibers terminate in different areas. The vast majority of the OT-containing axons is distributed in the dorsal part of the neural lobe. In contrast, VP-containing axons are mainly found in the centre of the neural lobe up to the pars intermedia.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 70
    ISSN: 1432-0878
    Schlagwort(e): Immunohistochemistry ; Light microscopy ; Neuroendocrine regulation ; Neuropeptides ; Columba livia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution of VIP- and TRH-immunoreactivity in neurons and processes within the hypothalamus of the pigeon was investigated with light-microscopic immunocytochemical techniques. Most of the VIP-containing neurons are concentrated in the middle and caudal parts of the hypothalamus, with the greatest concentration of perikarya occurring in the medial and lateral part of the ventromedial hypothalamic nucleus and the infundibular nucleus. These cells give rise to axons that seem to extend into the median eminence. An extensive network of VIP-immunoreactive fibers and varicosities occupy the external layer of the median eminence. The majority of TRH-containing neurons is found in the anterior hypothalamus with the greatest concentration of cells in the magnocellular preoptic, medial preoptic, suprachiasmatic and paraventricular nuclei. TRH-immunoreactive fibers and varicosities form a dense arborization in the external layer of the median eminence. Lactation seems to induce substantial changes in VIP as well as in TRH-immunostaining in the median eminence and other hypothalamic regions as compared to control, sexually active animals. Furthermore, TRH-immunoreactivity decreased in the median eminence following 60-min exposure to cold. These results suggest that VIP- and TRH-containing pathways in the pigeon hypothalamus are involved in the mediation of neuroendocrine responses.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 71
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 252 (1988), S. 99-106 
    ISSN: 1432-0878
    Schlagwort(e): γ-Aminobutyric acid (GABA) ; Glutamic acid decarboxylase ; Immunohistochemistry ; Auditory system ; Chicken (White Leghorn)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution of presumed GABAergic neurons and axon terminals in nuclei of the higher auditory pathway of the chicken was investigated by immunocytochemical methods employing antisera to the rate-limiting enzyme of GABA synthesis, glutamic acid decarboxylase, and to GABA. In the mesencephalic auditory center (MLD) about 20% of the cells reveal immunoreactivity. In contrast, the thalamic relay station nucleus ovoidalis is devoid of immunostained somata. This nucleus contains a high density of punctate immunoreactive structures presumed to be GABAergic axon terminals. In the auditory forebrain center field L and the auditory portions of the hyperstriatum ventrale, up to 8% of the cells were immunopositive. These neurons were significantly smaller than estimated from measurements of the overall cell population in these nuclei. From the two-dimensional arrangement of immunopositive neurons it is suggested that the GABAergic system in the avian auditory telencephalon consists of two separate groups of neurons: one subgroup mediating local inhibitory interactions, the other responsible for lateral inhibition between different frequency representations.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 72
    ISSN: 1432-0878
    Schlagwort(e): Neuronal markers ; Neuropeptides ; Immunohistochemistry ; Heart innervation ; Atrial natriuretic peptide (ANP) ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The innervation and myocardial cells of the human atrial appendage were investigated by means of immunocytochemical and ultrastructural techniques using both tissue sections and whole mount preparations. A dense innervation of the myocardium, blood vessels and endocardium was revealed with antisera to general neuronal (protein gene product 9.5 and synaptophysin) and Schwann cell markers (S-100). The majority of nerve fibres possessed neuropeptide Y immunoreactivity and were found associated with myocardial cells, around small arteries and arterioles at the adventitial-medial border and forming a plexus in the endocardium. Subpopulations of nerve fibres displayed immunoreactivity for vasoactive intestinal polypeptide, somatostatin, substance P and calcitonin gene-related peptide. In whole-mount preparations of endocardium, substance P and calcitonin gene-related peptide immunoreactivities were found to coexist in the same varicose nerve terminals. Ultrastructural studies revealed the presence of numerous varicose terminals associated with myocardial, vascular smooth muscle and endothelial cells. Neuropeptide Y immunoreactivity was localised to large electron-dense secretory vesicles in nerve terminals which also contained numerous small vesicles. Atrial natriuretic peptide immunoreactivity occurred exclusively in myocardial cells where it was localised to large secretory vesicles. The human atrial appendage comprises a neuroendocrine complex of peptidecontaining nerves and myocardial cells producing ANP.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 73
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 254 (1988), S. 331-340 
    ISSN: 1432-0878
    Schlagwort(e): GABA ; Interneurons ; Flight ; Immunohistochemistry ; Locusta migratoria (Insecta)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The transmitter content of identified inhibitory interneurons in the flight system of the locust, Locusta migratoria, has been characterized using antibodies raised against protein-conjugated gamma aminobutyric acid. Identified flight neurons were filled with the fluorescent dye, Lucifer Yellow. Serial sections of dye-filled neurons were incubated with an antibody to gamma aminobutyric acid which was subsequently tagged with a fluorescent marker. Excitatory motoneurons to wing muscles and 13 flight interneurons (3 excitatory, 7 inhibitory, and 3 with unknown synaptic effect) were examined. Neither the moto-neurons nor any of the 3 excitatory interneurons contained immunoreactive material. Six of the 7 inhibitory interneurons did contain immunoreactive material. All the neurons which contained immunoreactive material and whose synaptic effect is known were inhibitory. We conclude that most of the inhibitory flight interneurons which have been described use gamma aminobutyric acid as their transmitter. Interestingly, at least 1 set of interneurons known to be inhibitory does not use gamma aminobutyric acid. We predict that the 2 interneurons which do contain immunoreactive material and whose synaptic effect is not yet known will be found to have inhibitory roles in the operation of the flight circuitry.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 74
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 254 (1988), S. 361-367 
    ISSN: 1432-0878
    Schlagwort(e): Entorhinal cortex ; Non-pyramidal neurons ; Interstitial neurons ; Somatostatin ; Immunohistochemistry ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution of somatostatin-immunoreactive cells and processes throughout the human entorhinal region and subjacent white matter was examined either by the unlabelled antibody-enzyme method or by the avidin-biotin method. The brain slices were obtained at autopsy with a short post-mortem delay. The majority of somatostatin immunoreactive nerve cells was found in the inner principal layer and subjacent white matter. In addition, individually scattered immunoreactive neurons were observed in both the outer principal layer and lamina dissecans. The immunoreactive perikarya varied in shape and ranged in size from 10 to 30 μm. Without exception the neurons could be classified as belonging to the group of non-pyramidal neurons. Each neuron gave rise to a few thick dendrites and a thin axon with a beaded appearance. In the adult human brain, the pattern formed by lipofuscin granules deposited in the nerve cells can be considered characteristic for the type of the neuron. Therefore, immunoreactive perikarya were documented, destained of chromogen and restained to demonstrate lipofuscin pigment and basophilic substance. It became evident from these studies that the previously immunoreactive cells were characterized by a large rounded and eccentrically located nucleus, sparse basophilic substance and, in most cases, a lack of lipofuscin granules. A few of the immunoreactive cells were laden with coarse pigment granules. The findings permit classification of entorhinal somatostatin-immunoreactive neurons as either non-pigmented or pigment-laden non-pyramidal neurons.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 75
    ISSN: 1432-0878
    Schlagwort(e): Substance P ; Cardiovascular system ; Central nervous system ; Immunohistochemistry ; Mapping ; Cat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution of substance P-immunoreactivity (SP-IR) in the brainstem and spinal cord of normal and colchicine-pretreated cats was analysed using the peroxidase-antiperoxidase (PAP) technique. Numerous SP-IR fibers are present in the nucleus solitarius, nucleus dorsalis nervi vagi and nucleus spinalis nervi trigemini, various parts of the formatio reticularis, substantia grisea centralis mesencephali, locus coeruleus and nucleus parabrachialis. SP-IR perikarya occur in the substantiae gelatinosa and intermedia of the spinal cord, the nucleus spinalis nervi trigemini-pars caudalis, the nucleus dorsalis nervi vagi, and the nucleus solitarius, as well as in the adjacent formatio reticularis and the medullary nuclei of the raphe. In addition, SP-IR cell bodies are located in the nuclei raphe magnus and incertus, ventral and dorsal to the nucleus tegmentalis dorsalis (Gudden), nucleus raphe dorsalis, substantia grisea centralis mensencephali, locus coeruleus, nucleus parabrachialis and colliculus superior. The results indicate that SP-IR neurons may be involved in the regulation of cardiovascular functions both at the central and peripheral level. A peripheral afferent portion seems to terminate in the nucleus solitarius and an efferent part is postulated to originate from the nucleus dorsalis nervi vagi and from the area of the nuclei retroambiguus, ambiguus and retrofacialis.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 76
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 241 (1985), S. 565-580 
    ISSN: 1432-0878
    Schlagwort(e): Neuropeptides ; Enteric nervous system ; Immunohistochemistry ; Gut motility ; Necturus maculosus (Urodele)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The presence and distribution of regulatory peptides in nerves and endocrine cells of the stomach, intestine and rectum of a urodele amphibian, the mudpuppy, Necturus maculosus, was studied immunohistochemically in sections or whole-mount preparations of the gut wall. The effect of the occurring peptides on gut motility was studied in isolated strip preparations of circular and longitudinal smooth muscle from different parts of the gut. Bombesin-, neurotensin-, substance P- and VIP-like immunoreactivity was present in abundant nerve fibres in the myenteric plexus of both stomach, intestine and rectum. Single fibres or bundles were present in the circular muscle layer and in a well-developed deep muscular plexus in the intestine and rectum. Immunoreactive nerve cells were found in the myenteric plexus of the stomach, intestine (neurotensin only) and rectum. Gastrin/CCK-like immunoreactivity was observed only in a few fibres in stomach and rectum. Endocrine cells containing bombesin-, met-enkephalin-, gastrin/CCK-, neurotensin-, somatostatin- or substance P- like immunoreactivity were present in the mucosa. The effect of bombesin was an inhibition of the rhythmic activity in circular muscle preparations and in longitudinal muscle from the rectum, while longitudinal muscle from the stomach usually responded with a weak increase in tonus. Neurotensin, like bombesin, was inhibitory on the spontaneous rhythmic activity of circular muscle throughout the gut, while the effect on longitudinal muscle was an increase in tonus. Met-enkephalin and substance P increased the tonus of all types of preparations, and often, in addition, initiated a rhythmic activity superimposed on this maintained tonus. VIP had a general inhibitory effect on the preparations, decreasing tonus and/or abolishing rhythmic activity. It is concluded that bombesin-, neurotensin-, substance P- and VIP-like peptides are present in nerves throughout the urodele gut and may have physiological functions in regulating the motility of the gut. The gastrin/CCK-like peptide present in nerves of the stomach and rectum may affect the function of these parts of the gut. The regulatory peptides present in endocrine cells may, perhaps with the exception of the somatostatin-like peptide, affect the motility humorally.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 77
    ISSN: 1432-0878
    Schlagwort(e): Female reproductive tract ; Immunohistochemistry ; Neuropeptide tyrosine ; Vasoactive intestinal polypeptide ; Substance P ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Location, distribution and density of nerve fibers immunoreactive to neuropeptide tyrosine, vasoactive intestinal polypeptide and substance P were studied in the reproductive tract of the female rat and compared with acetylcholinesterase-positive (“cholinergic”) and noradrenergic nerves. Plexuses of all types of fibers were present in the vagina, uterine cervix, uterine horn and oviduct. In the tubular reproductive organs all of these types of nerve fibers appeared to innervate vascular and non-vascular smooth muscle and nearly all types of fibers formed plexuses subjacent to the epithelium lining the organs. Individual fibers of all classes appeared to innervate fascicles of smooth muscle in the mesometrium of the uterine horn. A few acetylcholinesterase-positive and substance P-immunoreactive fibers were present in the ovary but no vasoactive intestinal polypeptide-immunoreactive nerves were observed. Noradrenergic and neuropeptide tyrosine-immunoreactive nerves were numerous in the ovary where they were seen in the interstitial gland tissue and associated with follicles and blood vessels. It is suggested that these nerves may influence hemodynamic events and non-vascular smooth muscle in such functions as transport of sperm and ova and parturition. Substance P-immunoreactive nerve fibers are likely to be sensory fibers that could have roles in neurohormonal reflexes.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 78
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 254 (1988), S. 341-346 
    ISSN: 1432-0878
    Schlagwort(e): Odontoblast ; Calbindin ; Immunohistochemistry ; Electron microscopy ; Teeth ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The presence of 28 kDa calbindin in human odontoblasts was studied by use of specific antibodies raised against chick duodenal 28 kDa calbindin, in immunofluorescence, immuno-peroxidase, and electron-microscopic labelling experiments. The calbindin-like protein was detected mainly in the cytoplasm of odontoblast cell bodies, in their processes and occasionally in their nuclei. Correspondingly, at the ultrastructural level, immunoreactive material was associated with the cytosol, microfilaments and cilia. These findings suggest that human odontoblasts express a 28 kDa vitamin D-dependent calcium-binding protein, unlike those of rats and mice in which ameloblasts are the only cells immunoreactive for the protein.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 79
    ISSN: 1432-0878
    Schlagwort(e): Photoperiod ; Pituitary gland, Pars tuberalis ; TSH ; Immunohistochemistry ; Phodopus sungorus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Certain secretory cells in the hypophysial pars tuberalis of the Djungarian hamster display marked circannual structural alterations. The present investigation deals with the immunohistochemical properties of this cell group. A distinct TSH-like immunoreactivity was found in secretory cells of this type in the pars tuberalis of animals exposed to long photoperiods, whereas under short photoperiods the TSH-like immunoreactivity was nearly absent. In the pars distalis, the number and distribution of TSH-positive cells did not differ significantly between animals maintained under long and under short photoperiods. LH-and FSH-positive cells could not be detected in the pars tuberalis, but they are clearly present in the pars distalis of both groups of hamsters. Our immunocytochemical results suggest that photoperiodic stimuli influence the secretory activity of TSH-like immunoreactive cells in the pars tuberalis. A connection with the neuroendrocrine-thyroid axis is discussed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 80
    ISSN: 1432-0878
    Schlagwort(e): Pituitary allografts ; Immunohistochemistry ; Hamster ; Mesocricetus auratus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary We used immunohistochemistry to identify cells present in pituitary allografts in the hamster. Hypophyses removed from neonatal hamsters or adenohypophyses removed from adult females were placed beneath renal capsules of hypophysectomized adult females. Serum PRL, LH, and GH concentrations were measured at two, five, and eight weeks after placement of allografts. Allografts were removed after eight weeks and stained for cells containing PRL, LH, FSH, GH, or ACTH. Allografts did not release LH or GH. Those of adult adenohypophyseal tissue released significantly more PRL. The morphology of allografts of neonatal hypophyseal tissue resembled that of the adult adenohypophysis in situ. Lactotrophs, corticotrophs, somatotrophs and LH-cells were observed; very few FSH-cells were present. Allografts of adult adenohypophyseal tissue contained pituitary cells, numerous cavities, often enclosing lymphoid cells, and fibrous tissue. Atypical lactotrophs were the numerically dominant cells in these allografts; all other cells were present. The LH-cells outnumbered FSH-cells. These observations suggest that: (a) development of normal adenohypophyseal morphology can occur in an ectopic position; (b) intracellular hormones are present in cells in an ectopic site; (c) development and retention of intracellular FSH is more dependent on occupation of the normal position of the adenohypophysis than is retention of intracellular LH; and (d) release of PRL occurs from atypical cells in allografts of adult adenohypophyseal tissue.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 81
    ISSN: 1432-0878
    Schlagwort(e): Fine structure ; Immunohistochemistry ; Anterior pituitary gland ; Snell dwarf mice
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Snell dwarf mice display remarkable retardation of growth after birth and are known to lack prolactin (PRL), thyroid stimulating hormone (TSH) and growth hormone (GH). The aim of this study was to determine the reason for these hormonal deficiencies. We examined the fine structure of the gland and its immunohistochemical staining pattern with respect to antisera raised against PRL, TSH, GH, adrenocorticotrophic hormone (ACTH) and luteinizing hormone (LH). The gland of control mice reacted immunohistochemically against all antisera used, whereas only ACTH-producing cells (ACTH cells) and LH-producing cells (LH cells) were distinguished in the dwarf mice. ACTH cells in dwarf mice varied in cell shape, although they were similar in size to those of controls. The distribution of secretory granules in the cytoplasm varied from cell to cell. LH cells in the dwarf mice showed immature features, having poorly developed rough endoplasmic reticulum and Golgi apparatus. The cells were about half the size of controls, and secretory granules were smaller. In dwarf mice, non-granulated cells were encountered in addition to granulated ACTH and LH cells. Some of them formed small clusters, characteristic cell junctions being found between the cells; they thus appeared to be follicular cells. The above results suggest that hormone deficiency in Snell dwarf mice is a result of a defect in the hormoneproducing cells in the gland.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 82
    ISSN: 1432-0878
    Schlagwort(e): Neurokinin A ; Substance P ; Dental pulp ; Immunohistochemistry ; Cat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution and origin of neurokinin A (NKA)-like immunoreactivity were investigated in feline dental pulp by an indirect immunofluorescence method. NKA-containing nerve fibres with varicosities, which entered the dental pulp via apical foramen, were distributed throughout this tissue. Many NKA-containing nerve fibres were localized around blood vessels, but some were observed apart therefrom. At the odontoblastic layer, thin NKA-containing nerve fibres were observed running straight toward the pulp-predentinal border between odontoblasts. After inferior alveolar nerve section, all NKA-containing nerve fibres disappeared in the dental pulp, while the removal of the superior cervial ganglion resulted in no change in the distribution of these fibres. The correlation of NKA-like immunoreactivity and substance P (SP)-like immunoreactivity was also investigated by double-immunofluorescence technique. The distribution of NKA-containing nerve fibres was very similar to that of SP-containing nerve fibres; it appeared that all NKA-containing nerve fibres contained SP.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 83
    ISSN: 1432-0878
    Schlagwort(e): Periodontal ligament ; Incisor ; Neurofilament protein ; S-100 protein ; Immunohistochemistry ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Nervous elements in the periodontal ligament and dental pulp of rat incisors were investigated by means of immunohistochemistry for neurofilament protein (NFP) and glia-specific S-100 protein. The periodontal ligament in the incisors was densely innervated by NFP-immunoreactive nerve fibers; the distribution of the nerve fibers and their terminations differed markedly from those in molars. NFP-positive, thick nerve bundles entered the lingual periodontal ligament through slits located in the mid-region of the alveolar socket, and immediately formed numerous Ruffini-like corpuscles. In the labial periodontal ligament, all of the NFP-immunoreactive nerve fibers terminated in free endings. The restricted location of the stretch receptor, Ruffini-like corpuscle, in the lingual periodontal ligament appears to be an essential element, because this region is regularly extended during mastication. The nervous elements were restricted to the alveolar half of the periodontal ligament in every region; they avoided the dental half of the periodontal ligament, which presumably moves continuously with the tooth. Pulpal nerve fibers in incisors also showed a characteristic distribution different from those in molars; individual nerve fibers with beaded structures ran in the center of the pulp toward the incisai edge, and did not form the subodontoblastic nerve plexus of Raschkow. Immunostaining for S-100 protein revealed a distribution pattern of nervous elements similar to that for NFP, suggesting that the nerves supplying the periodontal ligament and dental pulp were mostly covered by a Schwann sheath.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 84
    ISSN: 1432-0878
    Schlagwort(e): Skeletal muscle ; Chronic stimulation ; Fiber transformation ; Myosin heavy chain isoforms ; Immunohistochemistry ; Histochemistry ; Rabbit
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Chronically stimulated fast-twitch muscles of the rabbit were histochemically and immunohistochemically analyzed in serial cross sections (1) for percentages of fiber types, and (2) for the presence of myosin heavy chain isoforms during fast-to-slow transformation. By four weeks of stimulation the number of type-I fibers had increased more than fourfold, while only about 6% of the original IIB fibers remained. Type-IC and -IIC fibers transiently rose to 20% of the total fiber population. After 16 weeks, the number of type-I fibers had increased to 42%. With prolonged stimulation fewer fibers reacted with antibodies against embryonic and neonatal myosins and more with the antibody against slow myosin. The reaction for embryonic myosin was most often detected in the C fibers (IC, IIC). Immunohistochemical subtypes were observed for each fiber type in the stimulated muscles. The greatest number was seen in type-IIC fibers, which, in addition to their reaction for fast/neonatal and slow myosins, might also react with the antibodies against neonatal/embryonic and embryonic myosins. These findings indicated that the transforming fibers temporarily expressed myosin heavy chain isoforms normally not detectable in adult skeletal muscle. Myotubes reacted strongly with the antibodies against fast/neonatal and embryonic myosins, and some of them also with the antibody against slow myosin. Thus, it appears that under the influence of the low frequency stimulus pattern some of the newly formed myotubes developed into type-I fibers.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 85
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 240 (1985), S. 361-365 
    ISSN: 1432-0878
    Schlagwort(e): Gastrin cells ; Gastrin variants ; Enkephalin variants ; Immunohistochemistry ; Pig
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Region-specific antisera to three enkephalins: met-enkephalin, met-enkephalin-Arg6-Phe7 and met-enkephalin-Arg6-Gly7-Leu8, together with four region specific antisera to progastrin: C-terminal G17 specific, N-terminal G34 specific, cryptic peptides A- and B-specific, were used in immunohistochemical studies of hog antral mucosa. A sub-population (6–10%) of the gastrin-containing endocrine cells (G-cells) was found to react with antisera to met-enkephalin, met-enkephalin-Arg6-Phe7 and met-enkephalin-Arg6-Gly7-Leu8. About 30% of all the enkephalin-containing cells were identified as G-cells. The results indicate that a fraction of G-cells produces both enkephalin-like peptides and gastrin.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 86
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 240 (1985), S. 711-721 
    ISSN: 1432-0878
    Schlagwort(e): Serotonin ; Immunohistochemistry ; Hypothalamus ; Mesencephalon ; Guinea-pig
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution of serotonin in the hypothalamus and the mesencephalon of guinea-pigs pretreated with both pargyline and L-tryptophan was investigated immunohistochemically using monoclonal antibodies to 5-HT. 5-HT-positive fibers and varicosities appeared distributed throughout the hypothalamus. Some areas showed a greater density of immunoreactivity: the suprachiasmatic nucleus, the region of the supraoptic crest, the area of the medial forebrain bundle, the ventral part of the nucleus ventromedialis, the median eminence and the ventral part of the mammillary bodies. 5-HT nerve fibers were also scattered in the posterior lobe of the pituitary. An extensive supraependymal plexus of immunoreactive axons was observed in most ventricular regions. No 5-HT positive cell bodies were present in the hypothalamus of the guinea-pig under our experimental conditions, whereas an intense serotonin immunoreactivity was detected in perikarya of the brain stem. 5-HT cell bodies were found predominantly in the raphe region including the nucleus raphe dorsalis and raphe medianus, nucleus interpeduncularis, reticular formation and dorsal area of the medial lemniscus.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 87
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 241 (1985), S. 17-24 
    ISSN: 1432-0878
    Schlagwort(e): Retina ; Amacrine cells ; Neuropeptides ; Immunohistochemistry ; Enkephalins ; Glucagon ; Neuropeptide Y (NPY) ; Substance P ; Skates (Elasmobranchii)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution of immunoreactive neuropeptides was investigated in the retina of three species of skates (Raja clavata, R. radiata, R. oscellata), elasmobranch fish often used in electrophysiological work on the retina. Enkephalins, neuropeptide Y (NPY), substance P and glucagon were found in different types of amacrine cells. All four peptides appeared in cell bodies in the innermost part of the inner nuclear layer. Processes from the cells containing enkephalins were numerous and ramified throughout the inner plexiform layer. Processes from the cells containing glucagon were thick and rare, and were found throughout the inner plexiform layer, at times with a predominance in sublaminae 1 and 4. NPY-immunoreactive fibres appeared mainly in sublamina 1 but also in 2 or 3, and substance-P-immunoreactive fibres in sublaminae 1,4 and 5. Antisera against somatostatin, VIP or neurotensin did not show any immunoreactivity in the skate retina.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 88
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 253 (1988), S. 647-656 
    ISSN: 1432-0878
    Schlagwort(e): Neuropeptides ; Vascular innervation ; Immunohistochemistry ; Small intestine ; Guinea pig
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The neuropeptide content of nerve fibers associated with submucosal arteries in the small intestine of guinea pigs was studied in whole-mount preparations using immunohistochemical methods. Tissues were obtained from normal animals or animals in which the small intestine had been extrinsically denervated. In normal animals, submucosal arteries are innervated by extrinsic sensory nerve fibers which contain both substance P and calcitonin gene-related peptide, and by sympathetic noradrenergic nerve fibers. In preparations obtained from animals 5–9 days after denervation, nerve fibers which contained substance P without detectable calcitonin gene-related peptide were associated with a few submucosal arteries. Nerve fibers which contained vasoactive intestinal peptide were also associated with some arteries. By 42–48 days after extrinsic denervation, substance P-containing fibers (without calcitonin gene-related peptide) and vasoactive intestinal peptide-containing fibers were associated with nearly every blood vessel. The extrinsic sympathetic nerve fibers did not regenerate during the course of this study. The nerve fibers associated with submucosal arteries in denervated tissues were not sensitive to capsaicin treatment. The alteration in the innervation of submucosal arterioles that follows extrinsic denervation of the gut may reflect either an increase in the neuropeptide content of the fibers, synthesis of a new peptide, or an increase in the number of fibers as a result of axonal sprouting.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 89
    ISSN: 1432-0878
    Schlagwort(e): Enterochromaffin cells ; Immunohistochemistry ; Intestine ; Neurons ; Serotonin ; Anguilla australis, Platycephalus bassensis, Tetractenos glaber (Teleostei)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The formaldehyde-induced fluorescence technique had shown 5-hydroxytryptamine-containing enteric neurons in the intestine of the teleost Platycephalus bassensis, but did not reveal such neurons in the intestine of Tetractenos glaber or Anguilla australis. Re-examination of these animals with 5-hydroxytryptamine immunohistochemistry showed immunoreactive enteric neurons in the intestine of all three teleost species. The 5-hydroxytryptamine-containing enteric neurons showed essentially the same morphology in all species examined: the somata were situated in the myenteric plexus, extending down into the circular muscle layer, but none were found in the submucosa; processes were found in the myenteric plexus, the circular muscle layer and the lamina propria. It was concluded that the neurons may innervate the muscle layers or the mucosal epithelium, but were unlikely to be interneurons. In a range of teleosts, enterochromaffin cells were found in the intestine of only those species in which the formaldehyde technique did not visualize neuronal 5-hydroxytryptamine. Available evidence suggests that, in vertebrates, 5-HT-containing enterochromaffin cells are lacking only where there is an innervation of the gut mucosa by nerve fibres containing high concentrations of 5-HT.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 90
    ISSN: 1432-0878
    Schlagwort(e): Calbindin-D 28K (CaBP28K) ; Immunohistochemistry ; Motoneurons ; Spinal cord ; Apteronotus leptorhynchus, Carrassius auratus, Pollimyrus isidori (Teleostei)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution and localization of the calciumbinding protein, calbindin-D 28K (CaBP28K), in the spinal cord motoneurons of larvae of the teleost fish, Apteronotus leptorhynchus (Gymnotidae) and Pollimyrus isidori (Mormyridae), and in the adult goldfish, Carassius auratus (Cyprinidae), were determined by means of immunohistochemistry. Sections of whole larvae and goldfish spinal cord were reacted with a polyclonal antibody to rat renal CaBP28K. CaBP28K was located by the PAP technique (Sternberger). It was found in the soma, dendrites, axons and axon terminals of spinal motoneurons but not in those of electromotoneurons of Apteronotus leptorhynchus, whereas it occurred in both motoneurons and electromotoneurons of the larval electric organ of Pollimyrus isidori. In these species CaBP28K was also present in the electromotoneuron axon terminals that make synaptic contacts with the pedicles of the electrocytes. In adult Carassius auratus, CaBP28K was found in the soma, dendrites and axons of certain spinal motoneurons. The results indicate that, in teleosts, the motoneurons containing CaBP28K may represent a well-defined population within the spinal cord; the role of this protein in these cells remains to be determined.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 91
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 252 (1988), S. 219-222 
    ISSN: 1432-0878
    Schlagwort(e): Somatostatin (SRIF) ; Striatum ; Neuropeptides ; Caudate-putamen ; Immunohistochemistry ; Guinea pig
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Two populations of neurons displaying somatostatin-like immunoreactivity were detected immunohistochemically in the guinea pig striatum using a monoclonal antibody. Sparse, well-stained neurons similar to those described in other species were observed throughout the guinea pig caudate-putamen. These neurons contained both neuropeptide Y and NADPH-diaphorase in addition to somatostatin. A second large population of somatostatin immunoreactive neurons in which these other substances did not coexist was found within the putamen.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 92
    ISSN: 1432-0878
    Schlagwort(e): Lingual filiform papilla ; Sensory apparatus ; Immunohistochemistry ; Neurofilament protein ; S-100 protein ; Cattle ; Rat (Wistar)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Nervous elements supplying the filiform papillae of the tongue of cattle and rats were investigated using immunohistochemistry against neurofilament protein (NFP) and glia-specific S-100 protein. The rod-shaped bovine filiform papillae were heavily keratinized along their entire length and lacked the connective tissue core that occurs in other mammals. Instead, the core was located posterior to the filiform papilla. The base of the bovine filiform papillae was invaded vertically by laminar connective tissue papillae. The core contained a large number of NFP-positive nerve fibers, most of them terminating as free endings in its anterior margin. NFP-positive nerves gathered around the anterior ridge of the epithelium at the base of the core and occasionally penetrated into the epithelium. The laminar connective tissue papillae at the base of the filiform papilla also contained NFP-positive nerve fibers. The core contained S-100-immunoreactive lamellated corpuscles, which were identified as “simple corpuscles” in electron micrographs. The structure and innervation of the bovine filiform papilla suggest that they represent a specialized sensory apparatus. The pyramidal filiform papillae of the rat were smaller, each containing a simple connective tissue core. Few NFP-positive nerve fibers from the nerve plexus entered the core. Filiform papillae are thus less specialized in rats than in cattle.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 93
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 253 (1988), S. 129-135 
    ISSN: 1432-0878
    Schlagwort(e): Glutamate decarboxylase (GAD) ; Nervous system ; Immunohistochemistry ; Cereal-giant interneuron system ; Insects ; Cockroach, Periplaneta americana
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary An antiserum against glutamate decarboxylase (GAD) of the rat brain was used to locate GAD activity in sections of the nervous system of the cockroach, Periplaneta americana. The sixth abdominal ganglion was chosen because electrophysiological evidence suggests the presence of GABAergic inhibitory synapses in the cereal-giant interneuron system. Groups of somata and numerous fibres and tracts were positively labelled by the GAD antiserum. A posterior group of labelled somata could be identified close to the entry of the cereal nerves. A line of somata clusters lay along a ventro-lateral furrow. Another discrete row of GAD-like cells was located dorso-laterally. Some small cells among the dorsal unpaired neurons were labelled. A small central group appeared under these cells. An abundance of GAD-like processes and transversal tracts were found within the neuropile. The different systems of GABAergic inhibitors in the ganglion are discussed; in particular we show that the fibres of cereal nerve X are not labelled. This demonstrates that the latter act on the giant fibres via interneurons. We suggest that the group that sends axons into the overlapping region between the cereal nerve and the giant fibre could be the inhibitory interneurons involved in this system.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 94
    ISSN: 1432-0878
    Schlagwort(e): Calcitonin gene-related peptide ; Biliary pathway ; Liver ; Immunohistochemistry ; Substance P ; Albino guinea-pigs
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Calcitonin gene-related peptide immunoreactivity was localized immunohistochemically in nerve fibers innervating the biliary pathway and liver of the guinea-pig. Immunoreactive fibers are present in all layers of the gallbladder and biliary tract and are particularly numerous around blood vessels. In the liver, immunoreactive processes are usually restricted to the interlobular space and porta hepatis, and only a few, very thin, beaded processes were observed in the hepatic parenchyma. A rich innervation is also associated with the vena portae. Positive ganglion cell bodies were not visualized within the ganglionated plexus of the biliary system, whereas they were found in the myenteric and submucosal plexus in the cranial portion of the duodenum corresponding to the sphincter of Oddi. The vast majority, if not all, of calcitonin gene-related peptide-immunoreactive fibers contain substance P immunoreactivity; however, there are some substance P-containing fibers lacking calcitonin gene-related peptide immunoreactivity. The lack of co-occurrence of calcitonin gene-related peptide and substance P immunoreactivities in intrinsic ganglion cells suggests that these two peptides are coexpressed in the extrinsic component of the innervation of the hepatobiliary system.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 95
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 253 (1988), S. 173-179 
    ISSN: 1432-0878
    Schlagwort(e): Opioid peptides ; Serotonin ; Enterochromaffin cells ; Immunohistochemistry ; Dog ; Guinea-pig ; Man
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary It has long been disputed whether mammalian enterochromaffin (EC-) cells contain a peptide in addition to serotonin. Previous immunohistochemical studies have provided evidence for the presence of enkephalins in EC-cells. These findings, however, are equivocal. Therefore, the problem of opioid peptides in EC-cells has been re-examined in the gastro-intestinal mucosa of dog, guinea-pig and man. A battery of antisera against derivatives of pro-opiomelanocortin, pro-enkephalin and pro-dynorphin have been applied to semithin serial sections of the tissues, in combination with fluorescence histochemistry and serotonin immunocytochemistry. Our findings indicate that EC-cells of the investigated species contain pro-dynorphin-related peptides, i.e. dynorphin A and α-neo-endorphin, but no derivatives from pro-opiomelanocortin or pro-enkephalin. Since remarkable interspecies variations occur with respect to the number and staining characteristics of opioid immunoreactive EC-cells, it is concluded that pro-dynorphin shows specific routes of post-translational processing depending upon the species and the gastro-intestinal segment investigated. Future studies should focus on the mutual relationships between serotonin and dynorphins and on the physiological significance of these peptides in the gastrointestinal tract.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 96
    ISSN: 1432-0878
    Schlagwort(e): Immunohistochemistry ; Neurons ; Substance P ; Enkephalin ; Spinal dorsal horn ; Rat (Sprague-Dawley)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The topographical localization of substance P (SP) and methionine-enkephalin-octapeptide (Enk-8) was examined immunohistochemically in the surface layer of the dorsal horn of rat cervical spinal cord. Although a few neurons were immunoreactive for Enk-8 in the intact animals, after an intracisternal administration of colchicine, immunoreactive Enk-8 neurons were numerous, and half of them indicated immunoreactivity also for SP. Some immunoreactive SP neurons appeared to show no immunoreactivity for Enk-8. Immuno-reactive nerve fibers, on the other hand, were numerous, and many of them contained both peptides. Electron-microscopic examination of the nerve fibers in tissue prepared by a freeze-drying procedure and stained by a postembedding procedure, revealed the costoring of both peptides in the same cored vesicles. The physiological significance of this costoring is discussed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 97
    ISSN: 1432-0878
    Schlagwort(e): Immunohistochemistry ; Mammary gland ; Epithelial transport ; Milk secretion ; Lactation ; Bovine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Immunoperoxidase methods were used to localize secretory component, immunoglobulin A and immunoglobulin G1 in mammary tissue from dairy cows. In lactating tissue, immunostaining for immunoglobulin A and secretory component was observed primarily in the luminal contents of alveoli. By day 2 of involution, alveolar epithelial cells stained for both immunoglobulin A and secretory component. Staining of alveolar epithelial cells for immunoglobulin A and secretory component continued throughout the period of mammary involution. No staining for secretory component was observed in the interalveolar stromal area. Immunoglobulin G1 immunostaining was localized primarily in the interalveolar areas in lactating tissue, but was localized at the apical and basolateral surface of alveolar cells on day 2 of involution. In contrast to immunoglobulin A, immunoglobulin G1 staining of epithelial cells did not persist and was primarily in the interalveolar areas by day 4. These results suggest that an increased localization of immunoglobulin G1 in bovine mammary epithelial cells may occur transiently in early involution, while an increase in immunoglobulin A and secretory component localization in epithelial cells persists throughout involution.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 98
    ISSN: 1432-0878
    Schlagwort(e): Corticotropin-releasing factor (CRF) ; Medulla oblongata ; Inferior olive ; Immunohistochemistry ; Cat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Corticotropin releasing factor (CRF)-immunoreactive (IR) perikarya, visualized by the indirect immunoperoxidase method in colchicine-pretreated cats, were localized in many discrete regions of the medulla oblongata. They were found mainly in the dorsal aspect and midline of the medulla oblongata, and more rostrally in the ventrolateral portion. Our results also demonstrated CRF-IR neurons in the rostrocaudal extent of the inferior olive, probably projecting to the cerebellar cortex via thick axons visualized along the lateral edge of the medulla. CRF-IR olivary cells were also found in the pontine cat from which the forebrain was removed, but neither in hypophysectomized nor adrenalectomized cats.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 99
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 253 (1988), S. 539-546 
    ISSN: 1432-0878
    Schlagwort(e): Kidney ; Renal innervation ; Catecholamine-synthesizing enzymes ; Dopamine ; Immunohistochemistry ; Dog
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Two cytochemical techniques were used at the ultrastructural level to study the distribution of specific axon types to different intrarenal structures in the dog. Using the chromaffin reaction to distinguish catecholaminergic fibres from other axon populations, it was found that the renal cortex of the dog is supplied only by catecholaminergic nerves. Immunostaining for tyrosine hydroxylase (TH) labelled all of the intracortical nerves, and 20% to 25% of these profiles also contained dopa decarboxylase (DDC)-immunoreactivity, indicating they were dopaminergic rather than noradrenergic. Both DDC-positive and DDC-negative axons were seen in close association (∼80 nm) with blood vessels and juxtaglomerular cells as well as tubular epithelial cells. The distribution of TH- and DDC-immunoreactive nerves in the renal cortex is compatible with existing functional evidence indicating that both dopaminergic and noradrenergic nerves are involved in the regulation of renal blood flow, tubular reabsorption and renin release.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 100
    ISSN: 1432-0878
    Schlagwort(e): Heart ; Atrial-specific granules ; Atrial natriuretic polypeptide (ANP) ; Purkinje fiber ; Immunohistochemistry ; Impulse-conducting system ; Swine (Sus scrofa domestica)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The ultrastructure of porcine ventricular tissue was studied by electron microscopy and immunocytochemical techniques. Electron-dense specific granules were found in both Purkinje fibers and transitional cells in the ventricular walls, and were positively stained by the immunogold staining method using an antiserum against atrial natriuretic polypeptide (ANP). This suggests that both the Purkinje fibers and transitional cells display the same specific granules as atrial cardiocytes containing ANP. These results demonstrate that Purkinje fibers and two types of transitional cells, in addition to the ordinary ventricular cardiocytes, can be identified in porcine ventricular wall tissue.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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