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  • pharmacokinetics  (96)
  • Immunohistochemistry  (36)
  • Springer  (132)
  • Annual Reviews
  • Blackwell Publishing Ltd
  • 2005-2009
  • 1990-1994  (132)
  • 1980-1984
  • 1991  (132)
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  • 2005-2009
  • 1990-1994  (132)
  • 1980-1984
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  • 1
    Digitale Medien
    Digitale Medien
    Immunohistochemical study of temporal variations in cytochrome P-450 isozymes in rat testis and their modifications by the inductive effects of cadinenes (1991)
    Springer
    International journal of biometeorology 35 (1991), S. 234-238 
    Details
    ISSN: 1432-1254
    Schlagwort(e): Temporal variation ; Cytochrome P-450 isozyme ; Testis ; Immunohistochemistry ; Cadinenes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Geographie , Physik
    Notizen: Abstract Temporal variations in cytochrome P-450 isozymes of rat testis, PB-P-450 (forms of cytochrome P-450 strongly induced by phenobarbital) and MC-P-448 (forms of cytochrome P-450 strongly induced by 3-methylcholanthrene), were investigated immunohistochemically by the avidin-biotin-complex method using specific antibodies against PB-P-450 and MC-P-448 isozymes. Immunoreactivity to both PB-P-450 and MC-P-448 isozymes was observed in Leydig cells. The number of PB-P-450 positive Leydig cells was found to undergo significant time-of-day variation with a peak time of 0000 hours (light phase from 0800 to 2000 hours). Injection of cadinenes (300 mg/kg per day intraperitoneally at 48 and 96 h before sacrifice) induced PB-P-450 isozyme but did not induce MC-P-448 isozyme. The induction of PB-P-450 isozyme by cadinenes was time dependent, and the early dark phase (2000 and 0000 hours) was most sensitive. These results suggest that temporal variation of cytochrome P-450 isozymes is one of the important physiological variations in detoxification and activation of various xenobiotics and chemicals in the testis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01047291
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  • 2
    Digitale Medien
    Digitale Medien
    Clinical pharmacokinetics and tolerability of alpidem in healthy subjects given increasing single doses (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 369-374 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Alpidem ; Anxiolytics ; pharmacokinetics ; tolerance ; metabolites ; sedation ; adverse events
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a double-blind, placebo-controlled, crossover experiment in 21 healthy male volunteers, aged 19 to 27 y, the pharmacokinetics and tolerance of the new anxiolytic drug alpidem (SL80.0342) and its three major metabolites were studied after single doses of 25, 50, 100 and 200 mg. Plasma concentrations of alpidem (in 20 subjects) and metabolites (in 6 subjects) were measured by HPLC over a period of 54 h after dosing. Cmax, tmax and AUC(0–54) and, when possible, t1/2 were determined for alpidem and metabolites and the dose linearity of the parameters was investigated. The time to peak of alpidem was dose independent in most subjects and was short (1–4 h); the mean values at the four dosing levels were 1.9, 1.7, 1.6 and 1.8 h. The peak concentration increased with the dose, the mean values being 17, 34, 88 and 115 ng · ml−1, respectively. In 50% of the subjects cmax tended to stabilize between the 100 and 200 mg dose. Dose linearity was also present for the AUC, which plateaued between the 100 and 200 mg dose in only 3 out of 20 subjects; the mean AUC was 119, 281, 669 and 1117 ng · ml−1 · h, respectively. The apparent half-life of elimination appeared to be dose independent, mean values at the increasing dosing levels being 18.7, 19.9, 18,1 and 17.9 h. A similar relationship between the kinetics parameters and dose of the alpidem was observed for the metabolites SL83.0912, SL80.0522 and SL83.0725. The formation of metabolites was not saturated as their AUCs relative to corresponding alpidem AUCs were not dose related. Thus the kinetics of alpidem and its three major metabolites were linear after doses of 25 to 200 mg. The drug was well tolerated by most of the subjects. Sedation and dizziness occurred mainly after the 100 and 200 mg doses.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314970
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  • 3
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of caffeine in patients with decompensated type I and type II diabetes mellitus (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 449-452 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Diabetes mellitus ; Caffeine ; pharmacokinetics ; P-450 mono-oxygenase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Diabetes may alter the pharmacokinetics of aminopyrine and antipyrine, which are used to assess liver function. Caffeine has recently been used to test liver function, but the effect of diabetes on caffeine kinetics is not known. The kinetics of caffeine has been examined in patients with decompensated Type I and Type II diabetes and in two age- and sex-matched control groups. In both types of diabetes the apparent caffeine clearance, half-life, and apparent volume of distribution were similar to controls. It is concluded that decompensated diabetes does not influence the cytochrome P-448 mono-oxygenase system responsible for caffeine metabolism.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00626367
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  • 4
    Digitale Medien
    Digitale Medien
    Dopamine pharmacokinetics in critically ill newborn infants (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 593-597 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Dopamine ; Newborns ; critically ill patients ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Dopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5–20 μg · kg−1 · min−1, for presumed or proven sepsis and hypotensive shock. Steady-state concentrations of dopamine ranged from 0.013–0.3 μg/ml. Total body clearance averaged 115 ml · kg−1 · min−1. The apparent volume of distribution and elimination half life averaged 1.8 1 · kg−1 and 6.9 min, respectively. No relationship was observed between dopamine pharmacokinetics and gestational age, postnatal age or birthweight. Substantial interindividual variation was seen in dopamine pharmacokinetics in seriously ill infants, and plasma concentrations could not be predicted accurately from its infusion rate. Marked variation in clearance explains in part, the wide dose requirements of dopamine needed to elicit clinical response in critically ill newborn infants.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00279976
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  • 5
    Digitale Medien
    Digitale Medien
    The concentration-dependent disposition and kinetics of inulin (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 619-624 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Inulin ; pharmacokinetics ; half life ; distribution ; concentration-dependent clearance ; healthy subjects ; chronic renal failure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of inulin was studied in 30 healthy male and 10 healthy female volunteers, and 10 patients with stable chronic renal failure (mean creatinine clearance 45 ml·min−1) following intravenous infusion of 70 mg·kg−1 over 5 min. Plasma concentrations fell rapidly initially but the rate of decline decreased continuously over 8 h and a linear terminal elimination phase could not be identified. Inulin was excreted rapidly by the subjects with normal renal function and 97.3% of the dose was recovered in the urine in 8 h. There was a progressive highly significant fall in the renal clearance of inulin after 2 h as plasma concentrations fell below about 150 mg·l−1. Six to 8 h after administration the clearance was less than 50% of the initial value in the healthy volunteers and the corresponding fall in the renal patients was 33%. The concentration-dependent renal clearance of inulin was confirmed in “step-up” and “step-down” constant infusion studies in which clearances were measured at mean plasma concentrations ranging from 35.2 to 186.7 mg·l−1. These studies virtually excluded time, changes in posture and urine flow rate as important factors. There was no statistically significant fall in clearance during the first 2 h and kinetic analysis was based on data obtained over this time. Under these conditions the mean plasma half life, volume of distribution (Vss) and total body clearance of inulin in the healthy males, healthy females and patients with chronic renal failure were 73.2, 65.5 and 172.4 min, 10.5, 9.6 and 8.81·70 kg−1 and 113.3, 111.5 and 43.3 ml·min−1·70 kg−1 respectively. There were no sex differences in any of the kinetic variables. The mechanism of the concentration-dependent clearance of inulin is unknown but the findings are consistent with saturable renal tubular reabsorption. Care is required with the use of inulin for measurement of the glomerular filtration rate by the single injection technique.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00279982
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  • 6
    Digitale Medien
    Digitale Medien
    Effect of ampicillin on mefloquine pharmacokinetics in thai males (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 631-633 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Mefloquine ; ampicillin ; Thai subjects ; pharmacokinetics ; enterohepatic recycling ; drug interaction ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of a single oral dose of mefloquine given either alone or with ampicillin has been studied in 8 healthy Thai male volunteers. There was a significantly higher maximum whole blood mefloquine concentration after coadministration with ampicillin (1648 vs 1228 ng·ml−1), as well as a significantly reduced terminal half life (15.3 vs 17.7 days), mean residence time (20.1 vs 23.4 days) and volume of distribution at steady state (14.1 vs 19.4 l·kg−1). Although there was no significant change in the AUC from zero time to infinity, the AUC from zero time to 5 days was significantly increased by ampicillin (4.86 vs 3.27 μg·ml−1 day). These changes in mefloquine disposition after antibiotic treatment may be due both to an increase in fractional bioavailability and a reduction in the enterohepatic recycling of mefloquine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00279985
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  • 7
    Digitale Medien
    Digitale Medien
    Lack of effect of multiple dose sucralfate on the pharmacokinetics of roxatidine acetate (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 637-638 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Roxatidine acetate ; sucraflate ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00279987
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  • 8
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of halofantrine and n-desbutylhalofantrine in patients with falciparum malaria following a multiple dose regimen of halofantrine (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 161-164 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Halofantrine ; Malaria falciparum ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Halofantrine is a new blood schizontocidal drug used for the treatment of multidrug-resistant falciparum malaria. The pharmacokinetics of halofantrine (HAL) and its principal metabolite, N-desbutylhalofantrine (BHAL), was investigated in 6 adult male patients of Melanesian origin with uncomplicated falciparum malaria. The patients received 500 mg of halofantrine hydrochloride at times 0, 6 and 12 h (total 1.5 g). All patients responded to treatment with a mean parasite clearance time of 52.7 h and a mean fever clearance time of 33.8 h. The following kinetic parameters (mean values) were determined for HAL and BHAL, respectively: maximum plasma concentration (Cmax)=896 and 491 ng·ml−1; time to reach the Cmax (tmax)=15 and 56 h; elimination half-life (t1/2)=91 and 79 h and the mean residence time (MRT)=71 and 102 h. Based on the clinical response the plasma concentrations of HAL and BHAL were adequate for the treatment of uncomplicated falciparum malaria in the 6 patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265910
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  • 9
    Digitale Medien
    Digitale Medien
    Fosinopril pharmacokinetics and pharmacodynamics in chronic ambulatory peritoneal dialysis patients (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 165-169 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Fosinopril ; fosinoprilat ; CAPD ; ACE-inhibitor ; pharmacokinetics ; pharmacodynamics ; peritoneal dialysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and pharmacodynamics of fosinoprilat, the diacid of fosinopril sodium, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated after the oral administration of 10 mg of fosinopril sodium to 6 chronic ambulatory peritoneal dialysis (CAPD) patients. The results from 1 patient are reported separately because of the presence of concomitant liver dysfunction. The mean t1/2, Cmax, tmax, and AUC values for 5 of the CAPD patients were 19.5 h, 202 ng·ml−1, 4.8 h, and 3.19 μg·h·ml−1, respectively. Values for 1 CAPD patient with liver dysfunction were t1/2 of 65.4 h, Cmax of 182 ng·ml−1, tmax of 9 h, and AUC of 18.1 μg·h·ml−1. Peritoneal clearance of fosinoprilat was negligible, ranging from 0.07 to 0.23 ml·min−1. Serum ACE activity remained significantly suppressed at 24 and 48 h after fosinopril sodium administration with mean decreases from baseline of 94.2% and 70.6%, respectively. ACE activity was suppressed to an even greater degree in the patient with liver dysfunction, remaining 97% inhibited 72 h after drug administration. Plasma renin activity (PRA) increased and plasma aldosterone concentrations decreased following drug administration. Mean arterial pressure did not change appreciably throughout the study. Dosage reductions may not be necessary in the majority of dialysis patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265911
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  • 10
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of intravenous bisoprolol in obese and non-obese volunteers (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 171-174 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Bisoprolol ; pharmacokinetics ; obesity ; blood flow
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of a single i. v. dose of dlbisoprolol 0.16 mg·kg−1 ideal body weight has been studied in 8 obese women (mean weight 91 kg; 161% of ideal body weight) and 8 non-obese women (51 kg; 94% of ideal body weight). Compared to the controls, the obese subjects showed an increase in the total apparent volume of distribution (Vz) (182 vs 135 1) and a decrease in Vz per kg body weight (2 vs 2.7 l·kg−1). There was a negative correlation between Vz l·kg−1 and the percentage of ideal body weight (r=−0.672). Total body clearance was increased, but t1/2 and renal clearance was unchanged. It is concluded that tissue diffusion of bisoprolol in obese subjects is limited, despite its lipophilicity, possibly because of alteration in the blood flow to adipose tissue produced by bisoprolol.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265912
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  • 11
    Digitale Medien
    Digitale Medien
    Steady state pharmacokinetics of hydrolysed bopindolol in young and elderly men (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 175-178 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Bopindolol ; pharmacokinetics ; beta-adrenoceptor blocker ; age ; hydrolysed bopindolol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Steady-state pharmacokinetic parameters of the new, long-acting beta-adrenoceptor blocker bopindolol have been measured in 17 young and 20 elderly healthy men. The t1/2β and the AUC(0→24 h) of hydrolysed bopindolol (the active metabolite) were both increased (40% and 26%, respectively) in the elderly subjects but tmax, Cmax and CL/f were not altered. However, after adjusting the parameters to allow for the different average body weights of the two groups, Cmax and CL/f became significantly different (+29% and −30%, respectively). AUC(0→24 h) was increased by 41%. The changes of up to 41% in pharmacokinetic parameters were smaller than the alterations of 50–100% usually seen when titrating doses of antihypertensive drugs. The clinical relevance of the effects was not examined, but similar changes have been reported for other beta-blockers which did not appear to be clinically relevant and did not affect the dosage required to treat hypertension.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265913
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  • 12
    Digitale Medien
    Digitale Medien
    Dose-dependent absorption and elimination of cefadroxil in man (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 179-183 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cefadroxil ; saturable absorption ; saturable renal tubular reabsorption ; cephalexin ; competitive inhibition ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic behaviour of cefadroxil was dose-dependent in healthy male volunteers following the oral administration of single doses of 5, 15, and 30 mg · kg−1. As the dose of cefadroxil increased from 5 to 15 and 30 mg · kg−1, the peak plasma concentrations, normalized to 5 mg · kg−1, decreased significantly from 15.1 to 10.7 and 7.6 mg·l−1, while the corresponding normalized areas under the plasma concentration-time curves from 0 to 2 h decreased significantly from 1258 to 946 and 801 min·mg·l−1. When the same subjects were given 5 mg·kg−1 of cefadroxil together with 45 mg·kg−1 of cephalexin, the absorption of cefadroxil was slowed to a similar or greater extent than with the high dose of cefadroxil. Although the absorption rate decreased as the dose increased, the systemic availability of cefadroxil was essentially complete at all doses, as judged by the 24 h urinary recoveries of the antibiotic. Kinetic analysis of the plasma concentration-time curves gave the best fit with a zero-order followed by a first-order absorption process, consistent with saturable intestinal absorption of cefadroxil. The elimination rate of cefadroxil was directly related to dose and plasma concentrations, and the clearance at the dose of 5 mg·kg−1 was significantly increased by the simultaneous administration of high-dose cephalexin. The renal clearance of cefadroxil ranged from 98 ml·min·l−1 at total plasma cephalosporin (cefadroxil + cephalexin) concentrations less than 2.5 mg·l−1 to 156 mg·l−1 at concentrations greater than 40 mg·l−1. These findings are consistent with saturable active gastrointestinal absorption and renal tubular reabsorption of cefadroxil, with competitive inhibition of both processes by cephalexin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265914
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  • 13
    Digitale Medien
    Digitale Medien
    Interaction of ORG 10172, a low molecular weight heparinoid, and digoxin in healthy volunteers (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 245-250 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Org 10172 ; Digoxin ; heparinoid ; pharmacokinetics ; pharmacodynamics ; drug interactions
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Potential pharmacokinetic and pharmacodynamic interactions between a new low molecular weight heparinoid Org 10172 (bolus injection of 3250 anti-Xa units) and digoxin (0.25 mg once daily for 8 days) were studied in 6 healthy male volunteers using an open, randomised three-way cross-over design. Digoxin produced a slight increase in clearance of anti-Xa activity from 4.3 to 4.8 ml·min−1, while plasma anti-thrombin and thrombin generation inhibiting (TGI) activity remained unchanged. Digoxin did not affect the actions of Org 10172 on the clotting tests. In the presence of Org 10172 there was a reduction in the AUC of digoxin during one dosing interval after the seventh digoxin tablet from 20 to 17 ng·ml−1·h, and a significant reduction in the average serum digoxin conentration. Since renal digoxin clearance was not significantly changed this probably might be due to a change in the non-renal clearance of digoxin. Atrio-ventricular node conduction, as measured by PR-time intervals, remained unchanged during all three treatments. In conclusion, although the pharmacokinetics of Org 10172 and digoxin were slightly changed by the combination, it is probably safe to administer Org 10172 and digoxin simultaneously. The clinical relevance of the slight decrease in plasma anti-Xa activity levels cannot yet be defined.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315437
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  • 14
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of tiaprofenic acid in children after a single oral dose (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 251-253 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Tiaprofenic acid ; children ; pharmacokinetics ; NSAID
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary. Twelve healthy children in three age groups anaesthetized for minor surgery were given a single oral dose of tiaprofenic acid (3 mg · kg−1) (TA). Seven blood samples and zero to 8 and 8 to 24 h urines were collected. TA concentrations in plasma and urine were measured by HPLC. No significant difference was found between the age groups in the kinetic parameters of TA and no correlation was found between these parameters and age; tmax=2.12h, Cmax=8.78mg · l−1, AUC(0→8 h) 33.9mg · h · l−1, AUC=39.3 mg · h · l−1, t1/2=2.35 h, Vz=0.319 l · kg−1, CL=0.094 l · h−1 · kg−1. Renal clearance was 14 ml · h−1. kg−1. 33% of the TA dose was recovered in the 24 h urine, 48% of which was conjugated, whereas in adults, TA is only found in urine as conjugates. The apparent plasma clearance was significantly higher (56%) than in 12 healthy adults given 1.5 mg · kg−1 TA. Volume of distribution and t1/2 did not significantly differ between children and adults. Since no relationship has been established between plasma TA and either efficacy or toxicity, a different dose regimen cannot be recommended in 3–11 year-old children from that in adults.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315438
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  • 15
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of midazolam in children: comparative study of intranasal and intravenous administration (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 355-357 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Midazolam ; pharmacokinetics ; intranasal ; intravenous ; children ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Twelve children 1–5 y old were randomly assigned to receive midazolam 0.2 mg·kg−1 either by the intravenous (IV) or intranasal (IN) routes. After IN administration the rapid onset of absorption was observed (tmax 12 min). After both routes of administration the half-life was similar (2.2 h IN and 2.4 h IV). After IN administration the apparent plasma clearance and volume of distribution were about twice as high as after IV administration. The results are consistent with an estimated mean bioavailability of 55%.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314967
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  • 16
    Digitale Medien
    Digitale Medien
    Antipyrine kinetics in undernourished diabetics (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 359-361 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Diabetes ; Antipyrine ; undernutrition ; drug metabolism ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In developing countries diabetics frequently suffer from varying grades of malnutrition. The combined effect of malnutrition and non-insulin dependent diabetes (NIDDM) on the drug metabolising enzyme system has been evaluated using antipyrine as a protodrug. All the patients were under treatment and their plasma glucose values were within normal limits. The AUC of antipyrine was similar in all the groups. Although none of the kinetic parameters was altered in normal diabetics, the clearance of antipyrine was decreased and its half life was prolonged, with an increase in volume of distribution, in undernourished diabetics compared to undernourished controls. The results indicate that diabetes per se may not influence antipyrine kinetics when the blood glucose is well under control, but in the presence of undernutrition, it significantly alters the disposition of the drug.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314968
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  • 17
    Digitale Medien
    Digitale Medien
    Lack of effect of paracetamol on the pharmacokinetics and metabolism of codeine in man (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 379-382 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Codeine ; paracetamol ; codeine-6-glucuronide ; pharmacokinetics ; metabolism ; partial clearance ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma and urine concentrations of codeine and its measurable metabolites were determined by HPLC in six healthy subjects after a single 30 mg oral dose of codeine either alone or after 7 doses of 1 g paracetamol 8 hourly. After codeine alone, the t1/2 (h), AUC (μmol·l−1·h) and CLR (ml·min−1) for codeine were 2.2, 0.81, and 252 respectively. These were not significantly altered by paracetamol: 2.2, 0.84, and 291 respectively. For codeine-6-glucuronide the values were 2.4, 22.0, and 29.7 respectively. These were not significantly different from those after codeine plus paracetamol: 2.4, 21.9, and 39.6. There were no significant differences between the two treatments in the apparent partial clearances (ml·min−1) of codeine to morphine (88 codeine alone, 70 codeine plus paracetamol), to norcodeine (71 codeine alone, 88 codeine plus paracetamol), and to codeine-6-glucoronide (820 codeine alone, 1022 codeine plus paracetamol). The urinary excretion of codeine-6-glucuronide, morphine, norcodeine, and codeine were not significantly different between the two treatments.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314972
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  • 18
    Digitale Medien
    Digitale Medien
    Relationship between renal function and disposition of oral cefixime (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 579-583 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cefixime ; renal failure ; pharmacokinetics ; volunteers ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of cefixime following a single oral dose of 200 mg have been investigated in 6 normal subjects and in 22 patients with various degrees of renal insufficiency. Serum and urine samples were collected between 0 and 72 h and were subjected to two methods of analysis: bioassay and HPLC. There was a linear relationship between the two sets of results from 228 samples. This result suggests that none of the metabolites, which may accumulte in uraemic patients, has antibacterial activity. In normal subjects, the peak serum level (Cmax) was 2.50 μg·ml−1 at 2.83 h (tmax); the apparent elimination half-life (t1/2) was 3.73 h; the apparent total body clearance (CL·f−1) was 154 ml·min−1, the mean renal clearance (CLR) was 39.1 ml·min−1 and the apparent fraction of the dose recovered in 24 h urine was 0.22. In uraemic patients, Cmax and tmax were slightly increased and t1/2 was increased to 12–14 h in patients with an endogenous creatinine clearance below 20 ml·min−1. The apparent volume of distribution was decreased. Apparent total and renal clearances were lower in proportion to the degree of renal insufficiency. Linear relationships were found between CL/f, CLR and creatinine clearance (CLCR). The findings suggest that the dose of cefixime needs to be reduced only in patients with severe renal failure.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314988
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  • 19
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of chlormezanone in elderly patients (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 603-607 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Chlormezanone ; pharmacokinetics ; elderly
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of Chlormezanone (CM) has been determined after a single oral dose of 400 mg CM in 5 young volunteers (28 y) and in 8 elderly patients (79 y). In the young subjects, CM was rapidly absorbed and distributed, and was slowly eliminated with a half-life of 38 h major metabolites were not detected in plasma or urine. Only 3% of CM was excreted unchanged in urine. In elderly patients absorption was delayed but not reduced; the Cmax and AUC did not differ from those in younger subjects, the elimination rate was reduced compared to the younger subjects (mean 54 h). The increase was in part related to the reduction in renal function and metabolism observed in aging. However, the change in pharmacokinetics was moderate and no adjustment in dosage seems necessary for treatments of limited duration in elderly patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314993
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  • 20
    Digitale Medien
    Digitale Medien
    Clinical chronopharmacology of oral sustained-release isosorbide-5-mononitrate in healthy subjects (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 71-75 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Isosorbide-5-mononitrate ; sustained-release formulation ; pharmacokinetics ; cardiovascular effects ; chronopharmacology ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 10 healthy male subjects the pharmacokinetics and haemodynamic effects of sustained-release isosorbide-5-mononitrate 60 mg (IS-5-MN) were studied after oral administration at two different times in the day (08.00 h and 20.00 h). Effects on blood pressure and heart rate after 3 min standing upright were measured in relation to the individual circadian control values. The pharmacokinetic parameters (Cmax, tmax, AUC, t1/2) did not differ after morning and after evening dosing, tmax being 5.2 h and 4.9 h, respectively. In contrast, the cardiovascular effects of IS-5-MN were clearly circadian phase-dependent. The maximum decrease in blood pressure decrease and increase in heart rate occurred significantly earlier after the evening (BPsys 2.8 h; BPdia 2.9 h; HR 3.8 h) than after the morning dose (BPsys 5.0 h; BPdia 6.0 h; HR 5.2 h). Thus, the peak haemodynamic effects coincided with the peak drug concentration after the morning dose, whereas the peak effect was in advance of the peak drug concentration after the evening dose of IS-5-MN. The data provide evidence of circadian phase-dependency in the dose-response relationship of oral IS-5-MN.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315142
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  • 21
    Digitale Medien
    Digitale Medien
    Pitfalls of pharmacokinetic dosage guidelines in renal insufficiency (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 87-93 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Pharmacotherapy ; renal insufficiency ; pharmacokinetics ; renal drug elimination ; drug monitoring ; dosage guidelines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary As the renal elimination of most drugs is closely correlated with the endogenous creatinine clearance, it is possible to use this parameter of kidney function to adjust drug dosage in renal failure. However, this simple procedure neglects possible changes in the volume of distribution, plasma protein binding, drug metabolism, intestinal absorption, and pharmacodynamics in renal insufficiency, as well as the occurrence of biologically active drug metabolities. Because of these uncertainties in critical cases the validity of the dosage calculated using the creatinine clearance should be checked by clinical surveillance and measurements of drug blood concentrations. Further, pharmacokinetic dosage guidelines based on the individual creatinine clearance may not be applicable to diuretics and drugs which have markedly differing kinetics of pharmacodynamic effects and blood levels.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315145
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  • 22
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of the anti-inflammatory drug ximoprofen in healthy subjects and in disease states (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 101-106 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Ximoprofen ; pharmacokinetics ; normal subjects ; hepatic disease ; renal disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of ximoprofen, a potent new non-steroidal anti-inflammatory agent, has been investigated in normal healthy subjects and in patients with hepatic or renal disease. After intravenous infusion of 22.8 mg to healthy subjects, plasma ximoprofen concentrations declined in a polyexponential manner with a terminal phase half-life of 1.9 h. The systemic clearance of ximoprofen was 115 ml·min−1 and the volumes of distribution were 18.0 l Vz and 13.8 l Vss. Ximoprofen was 80–90% bound to plasma proteins. The systemic availabilities (f) of orally and rectally administered doses of 30 mg of ximoprofen were 98% and 56% respectively and, in the case of the rectal dose, absorption appeared to be prolonged leading to “flip-flop” kinetics. After single oral doses of 30 mg of ximoprofen to patients with hepatic disease, half-life (2.2 h), peak plasma concentrations (1.55 μg·ml−1 cf 1.04 μg·ml−1 in healthy subjects) and areas under the curve (6.12 μg·h·ml−1 cf 3.54 μg·h·ml−1 in healthy subjects) were significantly different from those in healthy subjects. After single oral doses of 30 mg of ximoprofen to patients with renal disease, pharmacokinetic parameters of half-life (4.0 h), mean residence time (6.0 h) and area under the curve (9.2 μg·h·ml−1) were significantly different from those in healthy subjects. There were no significant differences in pharmacokinetic parameters between patients having differing degrees of renal disease. These data nevertheless suggest that accumulation of ximoprofen in hepatic or renal disease would be of slight or negligible clinical relevance and that no alteration of the dose regimen (up to 15 mg twice daily) may be required when ximoprofen is administered in these disease states.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315147
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  • 23
    Digitale Medien
    Digitale Medien
    CSF Baclofen levels after intrathecal administration in severe spasticity (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 363-365 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Baclofen ; severe spasticity ; pharmacokinetics ; CSF ; intrathecal injection
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetic parameters in the CSF of baclofen given to 4 patients as an intrathecal bolus are reported. Considerable inter-individual variability in the parameters was observed. The elimination half-life ranged from 0.9 to 5 h and the clearance from 0.013 to 0.08 l·h−1. In order to optimize treatment, it is suggested that CSF baclofen levels be matched to changes in Hoffman's monosynaptic reflex (H reflex).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265844
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  • 24
    Digitale Medien
    Digitale Medien
    Evaluation of proposed sulphoxidation pathways of carbocysteine in man by HPLC quantification (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 387-392 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Carbocysteine ; pharmacogenetics ; drug metabolism ; sulphoxidation ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A quantitative study has been made of the metabolism of S-carboxymethyl-L-cysteine (CMC) and its sulphoxides in volunteers by HPLC. Precolumn derivatization was applied prior to gradient reversed phase HPLC separation and fluorescence detection. For CMC and its metabolites containing a primary amino group the reagent 9-fluorenylmethylchloroformate was used. The other metabolites of CMC were derivatized at their carboxylic group with 1-pyrenyldiazomethane to give stable fluorescent products. Urine samples were collected for 8 h after oral administration of 1.125 g CMC to 33 healthy volunteers. Elimination of CMC in urine as sulphoxides did not account for more than 1% of the dose in any of the volunteers. Thus, CMC-sulphoxide metabolites are not quantitatively important. Recovery of the original substance in 8-hour urines ranged from 10 to 30% and a further 2 to 20% was recovered as the metabolite thiodiglycolic acid. Oral doses of 0.19, 1.125, and 2.25 g CMC in a second group of 12 healthy volunteers did not reveal dose dependence of the urinary excretion of the sulphoxides or of thiodiglycolic acid. Serum concentration-time-curves of CMC, (S)- and (R)-CMC sulphoxide were measured in a group of 9 healthy volunteers. The CMC sulphoxides in serum reached 1.5% of the parent substance after 4 hours. The ratio of CMC to its sulphoxide metabolites was similar in serum and urine. Pharmacogenetic polymorphism of sulphoxidation was not confirmed by the specific HPLC methods used.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265849
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  • 25
    Digitale Medien
    Digitale Medien
    Interaction of metoprolol with lorazepam and bromazepam (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 405-409 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Metoprolol ; lorazepam ; bromazepam ; interaction ; psychomotor tests ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The interaction between metoprolol and bromazepam and lorazepam was studied in 12 healthy male volunteers aged 21–37 years. Metoprolol had no significant effect on the pharmacokinetics of bromazepam or lorazepam. However, bromazepam AUC was 35% higher in the presence of metoprolol. Bromazepam enhanced the effect of metoprolol on systolic blood pressure but not on diastolic blood pressure or pulse rate. Lorazepam had no effect on either blood pressure or pulse. Metoprolol did not enhance the effect of bromazepam on the psychomotor tests used in this study. Metoprolol caused a small increase in critical flicker fusion threshold with lorazepam but had no effect on the other tests. Lorazepam (2 mg) was more potent than bromazepam (6 mg) in the doses used in this study. The interaction of metoprolol with bromazepam and lorazepam is unlikely to be of clinical significance. No change in dose is necessary when using these drugs together.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265852
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  • 26
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of ibuprofen in febrile children (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 427-428 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Ibuprofen ; children ; fever ; pharmacokinetics ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Ibuprofen may be an alternative to acetaminophen to control fever in children but little is known about its pharmacokinetics in pediatric patients. We studied 17 patients (age 3–10 yr) with fever; the most prevalent diagnoses were streptococcal pharyngitis and otitis media. Ibuprofen liquid was given as a single dose, 5 mg/kg (9 patients) or 10 mg/kg (8 patients). Multiple blood samples were collected over 8 hours and analyzed by HPLC. The maximum observed serum concentrations of ibuprofen ranged from 17–42 μm·ml−1 at 5 mg·kg−1 and 25–53 μm·ml−1 at 10 mg·kg−1 doses. Pharmacokinetics did not appear to be affected by ibuprofen dose. Mean tmax, oral clearance and elimination half life were 1.1 h, 1.2 ml·min−1·kg−1, and 1.6 h, respectively in patients at 5 mg·kg−1 doses; the corresponding values were 1.2 h, 1.4 ml·min−1·kg−1, and 1.6 h in those receiving 10 mg·kg−1 doses. There was no relationship between age and ibuprofen kinetics. No adverse effects occurred in any patients. These data suggest that ibuprofen pharmacokinetics may not be affected by dose between 5 and 10 mg/kg or age between 3 and 10 years.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265858
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  • 27
    Digitale Medien
    Digitale Medien
    Disposition of epirubicin and metabolites with repeated courses to cancer patients (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 481-487 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Epirubicin ; pharmacokinetics ; plasma concentrations ; cancer patients
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Thirteen cancer patients were studied following a total of 41 courses of epirubicin (EPI) (38–50 mg·m−2, mean 49.2 mg·m−2, administered by a 60 min infusion), together with other cancer chemotherapeutic agents. The aim was to consider the disposition of EPI and metabolites following subsequent courses as it has been reported that doxorubicin (the 4′-epimer parent of EPI) clearance is increased following the first administration. We have observed that EPI-glucuronide accounted for a mean 78.0%, epirubicinol 0.2% and epirubicinol-glucuronide 19.3% and that parent EPI accounted for only 2.4% of the EPI-compounds measured (mean of all patients and courses) for the 3 h period immediately following the infusion. These data confirm the rapid metabolism of EPI and the dominance of the glucuronidation metabolite pathway (which is not available to doxorubicin) and are compared with the metabolite profile observed in other reports. Large inter- and intra-individual variability in area under the plasma concentration/time curve were observed with no clear evidence of any consistent directional trend for such fluctuations, suggesting that factors contributing to EPI disposition are multivariate.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315227
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  • 28
    Digitale Medien
    Digitale Medien
    Polymorphic flecainide disposition under conditions of uncontrolled urine flow and pH (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 155-162 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Flecainide ; sparteine/debrisoquine polymorphism ; metabolism ; enantiomers ; pharmacokinetics ; stereoselectivity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of R- and S-flecainide have been determined in five poor (PM) and five extensive (EM) metabolisers of sparteine/debrisoquine under conditions of uncontrolled urine flow and pH. The half-lives of R- and S-flecainide in PMs (R 19.3 h; S 16.1 h) were approximately twice those observed in EMs (R 8.8 h; S 9.1 h). The apparent oral clearances of R- and S-flecainide were lower in PMs (R 313 ml·min−1; S 379 ml·min−1) than in EMs (R 783 ml·min−1; S 828 ml·min−1). The renal clearance, however, was comparable for both enantiomers in both EMs and PMs, and therefore the phenotypic differences in flecainide disposition observed must be due to differences in metabolic clearance. The nonrenal clearance of both enantiomers was significantly lower in poor (R 123 ml·min−1; S 201 ml·min−1) relative to extensive metabolisers (R 533 ml·min−1; S 586 ml·min−1). The partial clearance to the two major metabolites meta-O-dealkylated flecainide (MODF) and the meta-O-dealkylated lactam of flecainide (MODLF) was significantly lower in poor (62 ml·min−1) than extensive (267 ml·min−1) metabolisers. The impairment in flecainide metabolism in poor metabolisers of sparteine/debrisoquine has therefore been confirmed. Under conditions reflecting the clinical situation the difference in disposition between EMs and PMs would be considerable. However, it may be predicted that at standard doses concentrations greater than 1000 ng·ml−1 would not be attained in the PMs studied. The serum protein binding of R- and S-flecainide was studied in each subject and no differences between the enantiomers or the phenotypes were observed (Free fraction EM: R 0.43; S 0.42; PM R: 0.46; S: 0.46). Enantioselective disposition was noted in all PMs studied, due to a significantly lower nonrenal clearance of the R-enantiomer. In extensive metaboliser subjects, considerable interindividual variation in the enantioselective disposition of flecainide was noted, ranging from metabolism favouring either enantiomer to the absence of any selectivity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00280070
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  • 29
    Digitale Medien
    Digitale Medien
    The relationships between dose and concentration of tolbutamide and insulin and glucose responses in patients with non-insulin-dependent diabetes (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 163-168 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Tolbutamide ; diabetes mellitus ; non-insulin dependent ; pharmacokinetics ; pharmacodynamics ; glucose ; insulin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary It is uncertain how the hypoglycaemic effect of sulphonylureas varies with drug concentration in patients with non-insulin-dependent diabetes mellitus. The interrelationship of tolbutamide dosage and concentration, and glucose and insulin concentrations were therefore examined in 54 out-patients (the observational group) and in 20 patients studied under controlled conditions (the experimental group). In the observational group, tolbutamide concentration depended significantly on the daily dose, time from dose to sampling, body weight, and age. Blood glucose and insulin concentration were related, but were independent of tolbutamide concentration. In the experimental group, peak, but not pre-dose, tolbutamide concentration, depended on dose and on body mass index. Fasting and maximum post-prandial blood glucose concentration were positively correlated with maximum tolbutamide concentration, probably because tolbutamide dosage was highest in those with the poorest response. In the subset with a fasting blood glucose concentration of less than 8 mmol·l−1, neither glucose nor insulin concentrations depended significantly on tolbutamide concentrations. Tolbutamide concentration does not directly determine hypoglycaemic response in outpatients, and therapeutic monitoring of drug concentrations would not improve the management of such patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00280071
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  • 30
    Digitale Medien
    Digitale Medien
    Effect of duration of levodopa/decarboxylase inhibitor therapy on the pharmacokinetic handling of levodopa in elderly patients with idiopathic Parkinson's disease (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 459-462 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Levodopa/decarboxylase inhibitor ; Parkinson's Disease ; pharmacokinetics ; duration of therapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We address, from a pharmacokinetic viewpoint, the important question of why some patients with clinical idiopathic Parkinson's disease experience a fall off in benefit from levodopa maintenance therapy. Thirteen such patients, of mean age 78 y, without overt fluctuations in motor control in temporal relation to dosing with a levodopa/decarboxylase inhibitor combination, were studied. Levodopa (currently 400 to 800 mg daily) had been started at between 61 and 81 y of age, the mean duration of therapy being 54 months. Plasma concentrations of levodopa and its peripheral metabolite, 3-0-methyldopa, were measured before a morning dose of levodopa (100 mg)/carbidopa (25 mg) and at hourly intervals for 6 h after. There was a significant negative regression between duration of levodopa therapy (but not age or severity of disease) and the area under the plasma concentration/time curve (AUC) for levodopa attributed to the test dose. A significant negative regression was also seen of duration of therapy on the dose absorbed per unit distribution volume, but not on the elimination rate constant, indicating a decrease in bioavailability and/or an increase in distribution volume with duration. There was a tendency for the plasma 3-0-methyldopa concentration, standardised for daily dose, [30MD], to increase with duration of therapy. Although, the regression of duration on [30MD] did not reach statistical significance, that on the ratio, [30MD]/AUC, did so at the 0.01 level. The amount by, and time for which, the plasma levodopa concentration exceeds any critical threshold for the competitive active uptake process into the brain may thus decrease with duration of therapy. This may explain in part the limited reversal of the neurological deficit, which is more typical of later onset Parkinsonism, and, possibly, the decrement in biological half time with duration of therapy, typical of early onset disease. 3-0-Methyldopa is known to compete for active uptake with levodopa; the ratio, [30MD]/AUC, may be a measure of this competition. Intrinsic activity of neuronal uptake mechanisms, capacity of the basal ganglia for storage of dopamine, and post synaptic neuronal activity may, of course, also be determinants of clinical outcome.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00626369
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  • 31
    Digitale Medien
    Digitale Medien
    Elimination of flecainide as a function of urinary flow rate and pH (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 61-63 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Flecainide ; dose adjustment ; urinary pH ; urinary flow rate ; renal elimination ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In order to evaluate the influence of urinary flow rate at different pH values on the pharmacokinetics of the basic antiarrhythmic drug flecainide 7 healthy men received 50 mg flecainide under 4 different conditions: 1. acidic urine (pH 5) and a high fluid load (125 ml · h−1) 2. acidic urine (pH 5) and a low fluid load (25 ml · h−1) 3. alkaline urine (pH 8) and a high fluid load (125 ml · h−1) 4. alkaline urine (pH 8) and a low fluid load (25 ml · h−1) At acidic pH the half-life, the amount of unchanged drug in the urine (Ae), renal clearance (CLR) and area under the curve (AUC) were independent of the fluid load. At alkaline pH Ae (5.8 vs 2.6 mg) and CLR (73 vs 33 ml · min−1) were significantly affected by fluid load (high vs low), whereas half-life and AUC were not different (15.7 vs 16.0 h, 1480 vs 1540 ng · ml−1 · h). When comparing acidic and alkaline urinary pH conditions, half-life, Ae, CLR, and AUC were different. For a high fluid load the values at acidic vs alkaline pH were half-life 10.0 vs 15.7 h; Ae 15.9 vs 5.8 mg; CLR 288 vs 73 ml · min−1; AUC 976 vs 1480 ng · ml−1 · h. For a low fluid load the corresponding values at acidic vs alkaline pH were half-life 10.1 vs 16.0 h; Ae 15.9 vs 2.6 mg; CLR 267 vs 33 ml · min−1; AUC 1045 vs 1540 ng · ml−1 · h. It is concluded that urinary pH affects flecainide pharmacokinetics independently of urinary flow rate, and that a high flow enhances the elimination of flecainide only with an alkaline urine. This effect of flow rate does not appear to be of clinical relevance.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00280108
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  • 32
    Digitale Medien
    Digitale Medien
    Kinetics of cholinesterase inhibition by eptastigmine in man (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 83-84 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Eptastigmine ; cholinesterase inhibitor ; Alzheimer's disease ; pharmacokinetics ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00280116
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  • 33
    Digitale Medien
    Digitale Medien
    Pharmacokinetic investigation of oral and IV dihydroergotamine in healthy subjects (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 597-602 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Dihydroergotamine mesilate ; pharmacokinetics ; urinary excretion ; prolonged half-life ; deep compartment ; RIA ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A new radioimmunoassay (RIA) for the specific measurement of dihydroergotamine (DHE), sufficiently sensitive for the determination of low plasma concentrations, has been used to investigate the pharmacokinetics of unchanged DHE. In a randomized crossover trial, eight healthy male volunteers received single doses of DHE 5 mg, 10 mg and 20 mg orally and 0.1 mg and 0.5 mg intravenously. It was possible to determine plasma concentrations and urinary excretion of DHE over the following 48 h. A long terminal plasma elimination phase of unchanged DHE (half-life 15 h) was found. A similar terminal elimination half-life was also calculated from urine data. The multi-exponential decline in plasma DHE with a long terminal half-life suggests that distribution into a deep compartment contributes to the long-lasting effect of the drug. Plasma protein binding was 93%. Despite extensive tissue distribution (Vz=33 l/kg) and a high plasma clearance (CLP=2l/min), dose-independent linear pharmacokinetics was observed. The present assay was at least 20-times more specific than the polyvalent RIA used previously and appears suitable to explore the pharmacokinetics of unchanged DHE in patients on low-dose therapy. The long terminal elimination half-life of DHE only reported previously in studies using 3H-labelled drug, and considered to be due to metabolites, was also true for the parent compound. This, in addition to the sustained pharmacological activity of the 8′-hydroxy metabolite already shown, provides a further explanation for the long duration of action of DHE in animals and man.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314992
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  • 34
    Digitale Medien
    Digitale Medien
    Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 615-617 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Piperine ; Propranolol ; Theophylline ; pharmacokinetics ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of piperine on the bioavailability and pharmacokinetics of propranolol and theophylline has been examined in a crossover study. Six subjects in each group received a single oral dose of propranolol 40 mg or theophylline (150 mg) alone or in combination with piperine 20 mg daily for 7 days. An earlier tmax and a higher Cmax and AUC were observed in the subjects who received piperine and propranolol. It produced a higher Cmax, longer elimination half-life and a higher AUC with theophylline. In clinical practice, the enhanced systemic availability of oral propranolol and theophylline could be exploited to achieve better therapeutic control and improved patient compliance.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314996
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  • 35
    Digitale Medien
    Digitale Medien
    Inhibition of ex-vivo PAF-induced platelet aggregation by the PAF-antagonist RP 48740: relationship to plasma concentrations in healthy volunteers (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 141-145 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Platelet activating ; Factor RP 48740 ; platelet aggregation ; PAF-antagonist ; dose-response relationship ; adverse effects ; pharmacokinetics ; dose-response relationship
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary RP 48740, 3-(3-pyridyl)-1H,3H-pyrrolo [1,2-c] thiazole-7-carboxamide, a specific competitive PAF-receptor antagonist in vitro, was given to 29 healthy male volunteers for 7 days. Plasma drug concentrations and exvivo PAF-induced platelet aggregation were assessed on Days 1, 4, and 7. RP 48740 had linear pharmacokinetics after single and repeated doses. It caused stable inhibition of PAF-induced platelet aggregation in a dose-dependent manner. The effect disappeared within 24 h, even after 7 days of repeated doses. The effect of RP 48740 displayed a sigmoidal relation to the plasma drug concentration; I50 2.3 (0.3) mg·l−1. There were no clinical or biological adverse reactions to RP 48740 during the study.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265907
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  • 36
    Digitale Medien
    Digitale Medien
    Enantioselective steady-state kinetics of unbound disopyramide and its dealkylated metabolite in man (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 481-484 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Disopyramide ; pharmacokinetics ; protein binding ; enantiomers ; metabolism ; metabolite kinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Disopyramide is provided as a racemic mixture of R and S enantiomers, which have different pharmacodynamic and pharmacokinetic characteristics. Five volunteers were given racemic disopyramide 100 mg and 200 mg t.d.s. in a cross-over design. Plasma and urine concentrations of disopyramide and its active metabolite monodesisopropyl-disopyramide (MND) were determined at steady state by an enantioselective HPLC method. Unbound drug in plasma was measured after ultrafiltration. There was enantioselective clearance of unbound disopyramide (0.39 l.h−1.kg−1 for R-disopyramide and 0.58 l.h−1.kg−1 for S-disopyramide after 100 mg t.d.s.). The enantioselectivity was due to differences in the metabolism of disopyramide to MND and in further non-renal clearance, and the renal clearance of disopyramide was not enantioselective. The in vivo protein binding of disopyramide, which was saturable for both enantiomers, was also enantioselective. The difference in binding of the two enantiomers was explained by a difference in apparent binding capacity rather than in apparent binding affinity. The renal clearance of S-MND was significantly higher than R-MND (0.29 and 0.19 l.h−1.kg−1, respectively, after 100 mg t.d.s.). The renal clearance of MND also showed a tendency to saturation at higher concentrations.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00626374
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  • 37
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of oral salbutamol controlled-release in Asian patients with asthma (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 495-496 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Asthma ; Salbutamol ; Asians ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Using a double blind, double dummy crossover design, single dose and steady state pharmacokinetics of oral controlled release (SCR) salbutamol 4 mg and 8 mg tablets b. d. has been studied in 8 Asian patients. Plasma salbutamol was measured over 12 h. In 8 patients the single dose mean Cmax was 4.2 ng·ml−1 and 7.7 ng·ml−1 after 4 and 8 mg, respectively. In 5 patients the steady state mean Cmax, Cmin and tmax were 8.1 ng·ml−1 and 4.7 ng·ml−1 and 6 h for the 4 mg tablets and 14.1 ng·ml−1 and 7.1 ng·ml−1 and 4 h for the 8 mg tablets. It is concluded that both doses of SCR show features of controlled release and that they produced a relatively constant plasma level of salbutamol in Asian patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00626378
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  • 38
    Digitale Medien
    Digitale Medien
    Relation between plasma concentration and clinical efficacy after sublingual single dose apomorphine in Parkinson's disease (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 493-494 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Parkinson's disease ; Apomorphine ; pharmacokinetics ; adverse effect ; on-off effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five patients with Parkinson's disease were given a single sublingual dose of apomorphine in 3 mg tablets (2 patients received 18 mg and 3 patients took 39 mg). The therapeutic effect appeared within 33.0 min and lasted 137 min. There was a significant correlation between peak concentration, area under the curve, dose (mg/kg) and the duration of the therapeutic effect.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00626377
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  • 39
    Digitale Medien
    Digitale Medien
    Therapeutic monitoring of cyclosporin — an update (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 273-283 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cyclosporin A ; therapeutic monitoring ; assay techniques ; pharmacokinetics ; dose-response relationships
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The success of organ transplantation is closely related to clinical use of the immunosuppressive drug cyclosporin (CsA). The dosage of CsA is complicated by the large intra- and interindividual variability in its pharmacokinetics, as well as by the narrow concentration range between insufficient immunosuppression and toxicity. Potential sources of error in the sampling procedure and the advantages and disadvantages of the available analytical methods are discussed. Traditionally, 12 or 24 hour trough concentrations of CsA are monitored. Recently, peak concentrations or estimation of AUCs by a limited sampling strategy have been tried to improve the relatively weak concentration-effect and concentration-toxicity relationships found with trough CsA concentration monitoring. Studies of the CsA concentration-effect relationships for various treatment indications are reviewed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314952
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  • 40
    Digitale Medien
    Digitale Medien
    Verapamil in the prophylaxis of bronchial asthma (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 317-319 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Asthma ; Verapamil ; histamine-induced bronchoconstriction ; calcium antagonists ; plasma levels ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A single oral dose of verapamil 80 mg was shown significantly to inhibit histamine-induced bronchoconstriction in 8 out of 16 asthmatic subjects (maximum increase in PD20FEVHi 416%). There was still significant protection (Δ PD20FEV1Hi〉100%) in the responders 5 h after the oral dose. The relationship of the bronchoprotective effect to the plasma level of verapamil was also examined. Responders and non-responders did not differ significantly in the peak plasma level or the time course of the plasma verapamil concentration. The protective effect was not correlated with the peak plasma level of verapamil or with the baseline bronchial hyperreactivity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314959
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  • 41
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of paroxetine in patients with cirrhosis (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 351-354 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Paroxetine ; Cirrhosis ; pharmacokinetics ; multiple-dose study ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a 14-day multiple-dose study the pharmacokinetics of paroxetine was investigated in 12 patients with alcoholic cirrhosis and in 6 subjects without liver disease. The dose of 20–30 mg paroxetine daily was adjusted to the reduction in liver function, as assessed by the galactose elimination capacity. Accordingly, all but two of the cirrhotic patients received 20 mg, while all six control subjects received 30 mg. Dose-corrected, trough drug concentration at steady state (CSS min) and dose-corrected AUC24h were significantly higher in the patients with liver diseases than in the control subjects [3.4 vs 1.5 ng · ml−1 per mg paroxetine and 89 vs 43 h (ng) · ml−1 per mg paroxetine]. The elimination t1/2 was prolonged [83 vs 36 h], but the difference was not statistically significant, and the cirrhotic patients were still able to clear almost all the paroxetine by metabolism. All but two patients with cirrhosis experienced nausea during the first two or three days after the first dose, while none of the controls had this symptom. The study showed slower elimination of paroxetine and consequently higher plasma levels in patients with cirrhosis, suggesting that in the latter the dose of paroxetine should be in the lower end of the therapeutic range.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314966
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  • 42
    Digitale Medien
    Digitale Medien
    Dose-dependent pharmacokinetics of benzoic acid following oral administration of sodium benzoate to humans (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 363-368 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Benzoic acid ; hippuric acid ; pharmacokinetics ; hyperammonaemia ; ureagenesis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma concentration-time data for benzoic and hippuric acids and urinary excretion-time data for hippuric acid were analyzed simultaneously after oral doses of 40, 80 or 160 mg/kg sodium benzoate administered at least one week apart to 6 healthy subjects. The mean AUCs of benzoic acid after the doses of 80 and 160 mg/kg of sodium benzoate were 3.7- and 12.0-times greater, respectively, than after 40 mg/kg. However, the mean AUC of hippuric acid was roughly proportional to the benzoate doses. The observed data were explained by a one-compartment model with first-order rate absorption and Michaelis-Menten elimination of benzoic acid, together with a one-compartment model with first-order elimination for hippuric acid. Although the maximum rate of biotransformation of benzoic acid to hippuric acid varied between 17.2 and 28.8 mg·kg−1·h−1 among the six individuals, the mean value (23.0 mg·kg−1·h−1) was fairly close to that provided by daily maximum dose (0.5 g·kg−1·day−1) recommended in the treatment of hyperammonaemia in patients with inborn errors of ureagenesis. The individual maximum rate of metabolism can be estimated from the urinary excretion rate of hippuric acid 1.5 to 3 h after the single oral dose of 80 to 160 mg·kg−1 sodium benzoate. The justification of this concept requires further studies in patients with inborn errors of urea synthesis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314969
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  • 43
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of intramuscular nicomorphine and its metabolites in man (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 375-378 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Nicomorphine ; 6-nicotinoylmorphine ; morphine ; intramuscular administration ; metabolism ; absorption ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary After i.m. injection nicomorphine is relatively slowly absorbed from the muscular depot and is found in the serum for approximately 1 h. The rate of absorption differs between patients and governs the overall pharmacokinetic profile of the compound. The relative AUCs were nicomorphine 18%, 6-nicotinoylmorphine 17%, and morphine 65%. Nicomorphine and 6-nicotinoylmorphine have significantly higher AUCs after i.m. injection than after i.v. injection, while the AUC of morphine and the total AUC show no difference between the two modes of administration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00314971
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  • 44
    Digitale Medien
    Digitale Medien
    Decreased and variable systemic availability of zidovudine in patients with AIDS if administered with a meal (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 305-308 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Zidovudine ; acquired immunodeficiency syndrome (AIDS) ; pharmacokinetics ; bioavailability ; food intake
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The systemic availability of oral zidovudine has been studied in 13 patients with the acquired immunodeficiency syndrome (AIDS) dosed either fasting or with breakfast. The mean peak plasma concentration and AUC of zidovudine were significantly 2.8- and 1.4-times higher in fasting patients than in those treated during meal. In both conditions the mean half-life was about 1.5 h and the period of plasma zidovudine concentrations 〉1 μmol · l−1 was 2 h (NS). It is concluded that if zidovudine is taken on an empty stomach, high peak plasma concentrations and decreased variation in pharmacological parameters may be expected. Whether or not this will influence toxicity and efficacy remains to be shown.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315215
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  • 45
    Digitale Medien
    Digitale Medien
    Absorption of theophylline from a new theophylline controlled-release capsule (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 319-320 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Theophylline ; controlled-release formulation ; absorption ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315219
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  • 46
    Digitale Medien
    Digitale Medien
    Diuretic effect and disposition of furosemide in cystic fibrosis (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 333-341 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Furosemide ; cystic fibrosis ; pharmacokinetics ; diuretic effect ; baseline urine flow
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacodynamics and kinetics of single oral and intravenous doses of furosemide were studied in 9 patients (mean age 18.5 y) with cystic fibrosis. The diuretic effect of furosemide lasted for 6 h after oral administration and 2 h following intravenous injection of the drug. The patients with cystic fibrosis had a more pronounced diuretic response both to the oral and intravenous treatments than that reported in normals. Furosemide caused a marked decrease in urine pH for 5 h following the oral dose and between the 2nd and 3rd h after i.v. injection. The baseline nocturnal urine flow rate in 7 of the 9 patients given furosemide orally was increased by 30.6% compared to that reported in healthy subjects. The bioavailability of furosemide, its mean absorption rate and the mean plasma and urinary elimination half-lives both of the oral and the intravenous drug were similar to those reported in normal subjects. The patients with cystic fibrosis showed, however, about double normal mean total clearance after both the oral and i.v. treatments, and its renal clearance was almost half the plasma clearance. Nonrenal clearance was markedly increased in the patients, which agreed with a considerable decrease in the renal excretion of the drug. The mean apparent volume of distribution was also markedly increased compared to data in the literature. Oral furosemide resulted in a moderate increase in haematocrit and haemoglobin levels in 7 of 9 patients with cystic fibrosis and marked hypokalemia developed in 6 of the 9 patients 6 h after dosing. Pulmonary function tests performed at that time were changed in an inconsistent manner. The sweat test was significantly perturbed in those subjects, although the concentration of chloride in sweat did not fall below 60 mEq/l in any of the sweat samples tested.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265840
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  • 47
    Digitale Medien
    Digitale Medien
    The pharmacokinetics and pharmacodynamics of lisuride in healthy volunteers after intravenous, intramuscular, and subcutaneous injection (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 399-403 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Lisuride ; pharmacokinetics ; prolactin concentrations ; healthy volunteers ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentration of lisuride and prolactin have been measured in twelve healthy male volunteers after IV, IM or SC injection of 25 μg lisuride hydrogen maleate as an aqueous solution. After IV administration the plasma lisuride fell in two phases with half-lives of 14 min and 1.5 h. Total clearance was 13 ml·min−1·kg−1. After IM and SC injection the plasma concentrations peaked at 12 to 15 min and the profiles were similar to that found after IV administration. The systemic availabilities were 90% and 94%, respectively. Prolactin concentrations were reduced by a maximum of 60% relative to the normal circadian rhythm after all three routes of administration. The treatments were well tolerated, the only adverse reactions reported by some of the volunteers being mild, transient dizziness, tiredness, and nausea.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265851
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  • 48
    Digitale Medien
    Digitale Medien
    Disposition of oral quinine in acute falciparum malaria (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 49-52 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Quinine ; pharmacokinetics ; falciparum malaria
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma quinine concentrations following oral quinine sulphate 10 mg salt/kg have been measured by HPLC in 15 adult Thai patients with uncomplicated falciparum malaria. In 10 of the same patients the study was repeated in convalescence. In acute malaria plasma concentrations were approximately 50% higher than in convalescence; the mean acute peak plasma quinine concentration was 8.4 mg·l−1 compared to 5.7 mg·l−1 in convalescence. There was considerable variation in the rate of drug absorption, particularly in acute malaria. The mean time to peak plasma concentration was 5.9 h in acute malaria and 3.2 h in convalescence. The apparent clearance of oral quinine (CL/f) during the illness was 1.51 ml·kg−1·min−1, which was significantly lower than in convalescence — 2.67 ml·kg−·min−1. Estimated free quinine clearance was also lower in the acute phase: 30.6 compared to 49.0 ml·kg−1·min−1 in convalescence. Mean (SD) plasma protein binding of quinine was 94.7% in acute malaria and 92.8% in convalescence. Binding was significantly correlated with the plasma concentration of α1 acid glycoprotein (r=0.5), which was significantly higher in the acute phase; 1.48 g·l−1 compared to 1.05 g·l−1 during convalescence. Oral quinine sulphate was well absorbed in uncomplicated falciparum malaria. High blood concentrations following the administration of oral quinine in acute malaria are probably related to increased plasma protein binding, lower apparent volume of distribution, and a reduction in its systemic clearance.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315138
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  • 49
    Digitale Medien
    Digitale Medien
    Lack of effect of omeprazole treatment on steady-state plasma levels of metoprolol (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 61-65 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Omeprazole ; substituted benzimidazole ; metoprolol ; interaction ; cytochrome P450 ; debrisoquine hydroxylase ; pharmacokinetics ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a randomised double-blind crossover study, seven healthy males were concomitantly given metoprolol 100 mg o. d. as a controlled release formulation, and omeprazole 40 mg o. d. or placebo, for 8 days. Plasma levels of the R- and S-enantiomers of metoprolol were determined on the 8th day of each treatment. The subjects were also characterised by their metabolic capacity to hydroxylate debrisoquine. Concomitant omeprazole treatment had no significant influence on the steady-state plasma levels of the two enantiomers of metoprolol. All subjects were characterised by extensive debrisoquine hydroxylation, i.e. extensive metoprolol metabolism. As metoprolol is metabolised to a great extent by debrisoquine hydroxylase (IID6), it is concluded that concomitant omeprazole treatment will probably have a negligible influence on the metabolism of the relatively large number of drugs mainly metabolised by this isoenzyme of the cytochrome P450 family.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315140
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  • 50
    Digitale Medien
    Digitale Medien
    Is there a need for more precise definitions of bioavailability? (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 123-126 
    Details
    ISSN: 1432-1041
    Schlagwort(e): bioavailability definition ; health authorities ; pharmacokinetics ; drug registration Participants: L. P. Balant (Geneva, Switzerland), L. Z. Benet (San Francisco, USA), H. Blume (Eschborn, FRG), G. Bozler (Biberach, FRG), D. D. Breimer (Leiden, The Netherlands), M. Eichelbaum (Stuttgart, FRG), U. Gundert-Remy (Berlin, FRG), J. L. Hirtz (Paris, France), E. Mutschler (Frankfurt, FRG), K. K. Midha (Saskatoon, Canada), A. G. Rauws (Bilthoven, The Netherlands), W. A. Ritschel (Cincinnati, USA), L. N. Sansom (Adelaide, Australia), J. P. Skelly (Rockville, USA), and K.-O. Vollmer (Freiburg, FRG)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary After evaluation of the present definitions in a set of particular cases, it was agreed that there was no need for “more precise” definitions and that the current ones were adequate in the majority of cases. However, it was felt that the present definitions might be improved, in particular in view of the existence of non-systemically acting drugs and future “targeted drugs”. Thus, the FDA definition might be modified as follows: “Bioavailability means the rate and extent to which the active drug ingredient or therapeutic moiety from a drug product becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action”.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00280064
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  • 51
    Digitale Medien
    Digitale Medien
    Changes in gentamicin pharmacokinetic profiles induced by mechanical ventilation (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 297-302 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Gentamicin ; pharmacokinetics ; mechanical ventilation ; therapeutic dose range
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of controlled mechanical ventilation (CMV) on the pharmacokinetic profile of gentamicin has been examined in 23 patients after elective open heart surgery. A parallel design was adopted in two groups of patients: 13 patients requiring CMV for at least 32 h after surgery, all of whom were able to breath spontaneously (SB) after 72 h (study group), and 10 patients who required CMV for only a brief period and who showed SB at 32 h postsurgery. Haemodynamic parameters remained stable throughout the study. Apparent volume of distribution (Vz), half-life (t1/2), total clearance (CL), peak (C max ss ) and trough (C min ss ) plasma levels at steady-state for target levels (6–8 μg/ml), were measured. In the study group significant differences between CMV and SB conditions were found in Vz (mean 0.36 and 0.25 l/kg), t1/2 (mean 3.63 and 2.90 h) and C max ss (mean 4.30 and 5.53 μg/ml) while C min ss (mean 1.06 μg·ml−1 and 0.92 μg·ml−1) did not change significantly. In contrast, the pharmacokinetics in the control group showed no differences. It appears that CMV leads to an increase in gentamicin Vz, which accounts for the fall in C max ss below the therapeutic dose range (〈5 μg/ml) recommended for gentamicin. It seems advisable to use a larger dose of gentamicin in patients receiving CMV, even before the level is assessed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315213
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  • 52
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of intravenous and oral chlordesmethyldiazepam in patients on regular haemodialysis (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 65-68 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Chlordesmethyldiazepam ; pharmacokinetics ; i.v./p.o. administration ; renal failure ; protein binding ; pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of a single 2 mg IV dose of chlordesmethyldiazepam has been studied in 11 patients with renal failure on regular haemodialysis and in 11 age-matched healthy controls. The kinetics was also examined after a single 2 mg oral dose in 6 of the 11 renal failure patients. After intravenous administration the kinetics of total chlordesmethyldiazepam in renal patients and controls were the same. The unbound fraction of the drug in renal patients was higher (5.5%) than in controls (2.9%). Correction for differences in protein binding revealed a reduced apparent volume of distribution (47 vs. 140 l · kg−1) and a reduced clearance (5.0 vs. 10.5 ml · min−1 · kg−1) in the patients. The systemic availability of oral chlordesmethyldiazepam was good (82%) despite a relatively slow absorption rate.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00280109
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  • 53
    Digitale Medien
    Digitale Medien
    Response to furosemide during dehydration with and without naproxen pretreatment of kidney donors and renal transplant recipients (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 209-214 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Furosemide ; renal transplant recipients ; kidney donors ; naproxen ; dehydration ; pharmacokinetics ; salt-regulation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The response to 40 mg furosemide p.o. in 6 healthy kidney donors and 6 renal transplant recipients with and without naproxen pretreatment has been studied. No volume replacement was given in order to study the development of tolerance. The subjects showed an average dehydration of 1.5 kg · 6 h−1. While mean creatinine clearance was equal in patients and donors (76 vs 80 ml/min), renal furosemide clearance was significantly lower in the patients (47 vs 81 ml/min; P〈0.05). The patients also excreted a smaller fraction of the dose in the urine (5.7 vs 7.8 mg/6 h; P〈0.05). As the overall renal sensitivity was similar in the two groups, the natriuretic response was correspondingly smaller in transplant recipients as compared to donors. Within the observation period of 6 h after dosing, acute tolerance developed in the donors and in 4 of the 6 patients, as shown by clockwise hysteresis in the dose (urine furosemide excretion rate)-response (natriuresis) curves. Pretreatment with naproxen reduced renal sensitivity to furosemide (right shift of the dose response curve) in all the donors but in only 2 of the patients. In both groups acute tolerance was less pronounced after naproxen, which may indicate involvement of the prostaglandin system in the development of acute tolerance. The results may also indicate regeneration of sympathetic nerves with functional capacity in at least some renal transplants, or that other mechanisms of salt regulation compensate for loss of sympathetic nerve activity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315197
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  • 54
    Digitale Medien
    Digitale Medien
    Monitoring of the free concentration of cyclosporine in plasma in man (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 571-575 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cyclosporine ; free drug in plasma ; therapeutic drug monitoring ; renal transplantation ; plasma binding ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The free fraction of cyclosporine A (CsA) and its total plasma concentration as determined by HPLC(CsAT) were prospectively monitored in 66 recipients of renal transplants. The free CsA levels (CsAu) were calculated. The variability in free CsA levels was no less than for total CsAT levels. The correlation between CsAu and CsAT was high (r=0.90). Both CsAT and CsAu covaried with serum triglycerides and apolipoprotein A1. Fourty-four of the 66 patients suffered acute rejection episodes on 69 occasions. CsAT and CSAu both decreased and to a similar extent at the occurrence of acute rejection (42% and 59% decrease, respectively; significant vs baseline. Notsignificant difference in decrease in CsATvsCsAu). Acute nephrotoxicity occurred on 11 occasions in 10 patients. Both CsAT and CSAu were approximately twice as high at the time of acute nephrotoxicity as compared to one week previously. Both CsAT and CsAu were higher during the first month after transplantation in patients with than in patients without systemic infection. Thus, plasma CsAu gave no additional clinical information or guidance compared to CsAT in renal transplant recipients. Due to the complexity of its assay, which requires two consecutive analyses, there does not appear to be any need for routine monitoring of CsAu in renal transplant recipients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00279972
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  • 55
    Digitale Medien
    Digitale Medien
    Flecainide: evidence of non-linear kinetics (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 57-59 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Flecainide ; pharmacokinetics ; ventricular arrhythmias
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of flecainide has been studied in 12 patients with ventricular arrhythmias, both after single administration and during chronic treatment. Both the half-life and the AUC were significantly increased during chronic treatment. This suggests that the kinetics of flecainide might be non-linear also in patients with normal kidney and liver function. The increase in plasma flecainide levels during chronic treatment could not be predicted, so close monitoring of its plasma levels is advisable.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00280107
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  • 56
    Digitale Medien
    Digitale Medien
    Pharmacokinetic profile and tolerability of pimobendan in patients with terminal renal insufficiency (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 107-111 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Pimobendan ; pharmacokinetics ; tolerability ; renal impairment ; adverse effects ; haemodynamic actions
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of an i.v. bolus of pimobendan (P) 2.5 mg and 5.0 mg, its tolerability and the effect on heart rate and blood pressure have been studied in 12 subjects (42–70 y) suffering from severe terminal renal impairment. Plasma level data were compared with those obtained in a previous investigation in healthy volunteers. Pharmacokinetics were dose linear and were comparable to those in healthy subjects. No adjustment of the dose of P is necessary in patients with severe renal impairment. Tolerability of P, observed by means of blood pressure monitoring, clinical chemistry tests, electrocardiography and subjective judgement resulted in 4 complaints out of 12 patients: three suffered from orthostatic problems and vomiting, and one patient had nausea. Mean heart rate was elevated by 19% (2.5 mg) and 16% (5.0 mg). Blood pressure was significantly reduced after 2.5 mg P (23% systolic and 26% diastolic pressure), and after 5.0 mg P by 25% systolic and 23% diastolic pressure.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315148
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  • 57
    Digitale Medien
    Digitale Medien
    Clinical pharmacokinetics of 3-day continuous infusion cisplatin and daily bolus 5-Fluorouracil (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 115-117 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cisplatin ; 5-Fluorouracil ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315150
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  • 58
    Digitale Medien
    Digitale Medien
    Continuous infusion of high-dose metoclopramide: comparison of pharmacokinetically adjusted and standard doses for the control of cisplatin-induced acute emesis (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 283-286 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Metoclopramide cancer chemotherapy ; emesis ; continuous infusion ; pharmacokinetics ; cisplatin ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Metoclopramide was administered by continuous infusion to two groups each of 14 patients on chemotherapy, randomized to receive either doses adjusted to individual pharmacokinetic parameters or doses adjusted as usual to body weight. The mean plasma concentration at the end of the infusion in the adjusted group was 1.01 mg · 1−1, close to that aimed for (1.20 mg · 1−1). It was significantly different from that in the other group, v0.54 mg · 1−1. Antiemetic efficacy, defined as ⩽2 emetic events in the 24 h following cisplatin, was similar in both groups (being found in 12/14 (86%) and 10/14 patients (71%), respectively). Analysis of the cumulative percentage of responders according to plasma concentration showed a clear plasma concentration-effect relationship. Routine MCP pharmacokinetic dosage adjustment is not indicated, but this therapeutic approach can be used to optimize antiemetic therapy in poor responder patients.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315210
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  • 59
    Digitale Medien
    Digitale Medien
    Cyclosporine pharmacokinetics in liver transplant recipients: evaluation of results using both polyclonal radioimmunoassay and liquid chromatographic analysis (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 513-519 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Cyclosporine ; liver transplant recipients ; radioimmunoassay ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Pharmacokinetic variables were derived from cyclosporine measurements using liquid chromatography (HPLC) and radioimmunoassay with a non-selective polyclonal antibody (PARIA) in 11 orthotopic liver transplant recipients studied in paired oral and intravenous studies both before and after permanent clamping of the biliary T-tube. After oral drug administration, mean areas under blood cyclosporine concentration versus time curves before clamping were around 5.2-fold greater by PARIA than HPLC but 2.9-fold greater after clamping and closer to comparable values after intravenous cyclosporine (2.5 and 2.3-fold, respectively). Cyclosporine clearance was smaller by PARIA than HPLC (mean 7.3 versus 3.3 ml · min−1 · kg−1, respectively, before clamping). Both values decreased by 25% after clamping (to 5.5 and 2.4 ml · min−1 · kg−1, respectively), although there was no significant change in distribution or elimination half-lives (around 0.5 and 8 h, respectively). The mean bioavailability of oral cyclosporine increased significantly after clamping in 9 patients (from 10.6% to 28.1% by HPLC and from 14.8 to 35.1% by PARIA) but in two patients who developed the vanishing bile duct syndrome values fell to 〈 10% and the proportional overestimation of cyclosporine concentrations by PARIA increased. Clamping had no significant effect on the mean apparent volumes of distribution but values of Vz were approximately twice those of Vss (around 2.6 and 1.3 l · kg−1 by PARIA and HPLC respectively). Mean half lives after clamping were shorter following oral than intravenous cyclosporine (t1/2λ2 around 15 h enterally versus 8 h parenterally). These data suggest delays in cyclosporine absorption and significant first pass metabolism which may contribute to higher PARIA:HPLC ratios after oral dosing and to reduced bioavailability before clamping.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315232
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  • 60
    Digitale Medien
    Digitale Medien
    Single-dose and steady-state kinetics of morphine and its metabolites in cancer patients — a comparison of two oral formulations (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 585-591 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Morphine ; metabolites ; clinical trial ; pharmacokinetics ; controlled release formulation ; cancer patients ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The single-dose and steady state kinetics of morphine given as controlled-release tablets (30 mg every 12 h) and as a solution (15 mg every 6 h) have been compared in 11 cancer patients with chronic pain. The concentrations of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) were analyzed by HPLC. There were no significant differences between the tablets and solution in the mean steady state concentrations of morphine, M3G or M6G. The tmax was 3.3 h for the tablets compared to 1.1 h for the solution. After giving the controlled-release tablets every 12 h there was a significantly higher fluctuation index of the morphine concentrations than after the solution. Urinary recovery at steady state was comparable between the two preparations, with averages of 57% and 47%, respectively. Thus, no major differences were found in the pharmacokinetics of morphine and its glucuronidated metabolites after 30 mg morphine as controlled-release tablets every 12 h or 15 mg of morphine solution every 6 h, except for a significantly longer tmax and greater fluctuation in morphine concentrations after the controlled-release tablets.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00279975
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  • 61
    Digitale Medien
    Digitale Medien
    Sublingual captopril — a pharmacokinetic and pharmacodynamic evaluation (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 393-398 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Captopril ; sublingual ; pharmacokinetics ; pharmacodynamics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In this study we compared the pharmacokinetics and pharmacodynamics of captopril after sublingual and peroral administration. Single 25 mg doses of captopril were administered sublingually and perorally on two different occasions in a randomised cross-over fashion to eight healthy volunteers aged 22–35 years. The kinetics of unchanged captopril, plasma renin activity (PRA), BP and heart rate were studied over three hours after both peroral and sublingual administration of captopril. Mean pharmacokinetic parameters for unchanged captopril after sublingual administration were: Cmax, 234 ng·ml−1; tmax, 45 min; AUC (0–3 h), 15.1 μg·ml−1. min. Mean pharmacokinetic parameters for unchanged captopril after peroral administration were: Cmax, 228 ng·ml−1; tmax, 75 min; AUC (0–3 h), 17.0 μg·ml−1. min. tmax was significantly shorter when captopril was administered sublingually; all other pharmacokinetic parameters were equivalent. The plasma captopril concentrations achieved post drug administration led to increases in PRA and reductions in BP. tmax for PRA was 86 min for sublingual captopril and 113 min for perorally administered drug. Peak PRA values were, however, not significantly different. BP, as expected, was not reduced dramatically in these healthy volunteer subjects, however, in systolic BP vs time profiles, BP was significantly lower after volunteers received sublingual captopril. Heart rate increased slightly after captopril administration; there were no differences between the two routes of administration. Administration of captopril sublingually, therefore led to a more rapid attainment of plasma captopril concentrations and had a more rapid onset of pharmacological effect when compared with peroral administration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265850
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  • 62
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of SUN 1165, a new antiarrhythmic agent, in renal dysfunction (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 411-414 
    Details
    ISSN: 1432-1041
    Schlagwort(e): SUN 1165 ; renal failure ; antiarrhythmic agent ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of a new Class I antiarrhythmic agent, SUN 1165, has been studied in 32 patients with varying degrees of renal impairment following a single oral dose of 50 mg. The apparent volume of distribution at steady state was 1.48 1 · kg−1, the absorption rate constant was 2.2 h−1, and plasma protein binding was 26.8% in subjects with normal renal function. These variables were not altered with renal impairment. More than 60% of SUN 1165 given orally was excreted unchanged via the kidney, both by tubular secretion and glomerular filtration. The elimination rate constant, the apparent total body clearance and the apparent renal clearance were linearly correlated with the endogenous creatinine clearance. The half-time of elimination was 3.4 h in normal subjects and it was prolonged to 23.7 h in severe renal failure (creatinine clearance below 20 ml · min−1 · 1.48 m−2). Dosage adjustment of SUN 1165 is necessary in renal failure.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00265853
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  • 63
    Digitale Medien
    Digitale Medien
    Phylogenetic study of serotonin-immunoreactive structures in the pancreas of various vertebrates (1991)
    Springer
    Cell & tissue research 263 (1991), S. 237-243 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Serotonin ; Pancreas ; Phylogenic study ; Immunohistochemistry ; Teleosts ; Chicken ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution pattern of serotonin (5HT) in the pancreas was studied immunohistochemically by using a 5HT monoclonal antibody in various vertebrates including the eel, bullfrog, South African clawed toad, turtle, chicken, mouse, rat, guinea-pig, cat, dog and human. In all species examined, except the bullfrog, 5HT-like immunoreactivity was observed in nerve fibers, in endocrine cells, or in both. Positive nerve fibers were found in the eel, turtle, mouse, rat and guinea-pig. These fibers ran mainly along the blood vessels and partly through the gap between the exocrine glands. In the eel and guinea-pig, positive fibers invaded the pancreatic islet. Occasionally, these positive fibers were found adjacent to the surface of both exocrine and endocrine cells, suggesting a regulatory role of 5HT in pancreatic function. 5HT-positive endocrine cells were observed in the pancreas of all species except for the bullfrog and rat. In the eel and in mammals such as the mouse, guinea-pig, cat, dog and human, 5HT-positive cells were mainly observed within the pancreatic islet. In the South African clawed toad, turtle and chicken, the positive cells were mainly in the exocrine region. The present study indicates that the distribution patterns of 5HT in the pancreas varies considerably among different species.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318765
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  • 64
    Digitale Medien
    Digitale Medien
    Pentosome — a new connective tissue component —is a subunit of amyloid P (1991)
    Springer
    Cell & tissue research 263 (1991), S. 431-438 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Connective tissue ; EHS tumor ; Basement membrane ; Amyloid P component ; Immunohistochemistry ; Mouse (C57BL/6)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary A new minute connective tissue structure, referred to as “pentosome”, has been investigated by electron microscopy and its nature has been examined by immunoperoxidase tests. Pentosomes are 3.5-nm wide, particulate structures that have been observed in the posterior chamber of the eye, the connective tissue spaces of the mouse foot-pad and the matrix of the mouse EHS tumor. They are usually found in the vicinity of microfibrils whether they are free or associated with elastic fibers. They tend to be organized into groups forming a three-dimensional semi-crystalline lattice at 10-nm intervals, but are connected by fine filaments. At high magnification, pentosomes appear as hollow structures composed of two parallel pentagons, which respectively measure 2.7 and 3.5 nm, and are held together by a cross-bar. A series of immunoperoxidase tests has only shown antigenicity against a serum protein, the amyloid P component. However, pentosomes are only about one-third the size of the 8.5-nm wide, disk-like segments of the amyloid P molecule. Since they could be subunits of these molecules, such subunits were prepared and compared with pentosomes; they appeared to be identical. It is concluded that the pentosomes found in connective tissue are AP subunits.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00327277
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  • 65
    Digitale Medien
    Digitale Medien
    Action and immunoreactivity of neuropeptides in the buccal neuromuscular system of a prosobranch mollusc, Rapana thomasiana (1991)
    Springer
    Cell & tissue research 264 (1991), S. 57-62 
    Details
    ISSN: 1432-0878
    Schlagwort(e): FMRFamide ; Catch-relaxing peptide (CARP) ; Radula muscle ; Immunohistochemistry ; Rapana thomasiana (Mollusca)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary In a prosobranch mollusc, Rapana thomasiana, the catch-relaxing peptide H-Ala-Met-Pro-Met-Leu-Arg-Leu-NH2 (CARP) was found to depress the contraction of the radula protractor and retractor elicited by electrical stimulations. The action of CARP was in contrast to that of other neuropeptides, H-Phe-Met-Arg-Phe-NH2 (FMRFamide) and H-Phe-Leu-Arg-Phe-NH2 (FLRFamide), which enhanced the contraction of the radula protractor and retractor, respectively. By immunohistochemical examinations, FMRFamide-like immunoreactive neurons were found on the rostral side of the right buccal ganglion and the caudal side of the left ganglion, where some CARP-like immunoreactive neurons were also distributed, indicating a possible coexistence of FMRFamide and CARP. FMRFamide- and CARP-like immunoreactivities were also detected in the neuropile of buccal ganglia, radula nerves arising from the ganglia, and nerve fibers in the radula muscles. The present results suggest that FMRFamide- and CARP-like peptides are involved in the regulation of the contraction of the radula muscles.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00305722
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  • 66
    Digitale Medien
    Digitale Medien
    Distribution of calbindinlike immunoreactive structures in the optic tectum of normal and eye-enucleated cyprinid fish (1991)
    Springer
    Cell & tissue research 265 (1991), S. 511-516 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Calbindin ; Immunohistochemistry ; Teleosts ; Visual system ; Entreleation ; Cyprinus carpio ; Tinca tinca (Teleostei)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Using the ABC immunohistochemical method, we investigated the distribution of calbindinlike immunoreactive structures in the optic tectum of normal fish, Tinca tinca, and from normal and unilaterally eye-enucleated fish, Cyprinus carpio. In nonoperated individuals of both species the optic tectum contained numerous immunoreactive neurons with strongly positive somata located in the stratum periventriculare and a thick immunolabeled dendritic shaft ascending radially toward the stratum fibrosum et griseum superficiale. The retinorecipient layers contained many fibrous immunoreactive structures. Some varicose fibers, isolated or in small bundles, were localized to the stratum album centrale, especially in the dorsal tectal half. Unilateral eye removal produced the disappearance of the immunoreactive fibrous structures located in the retinorecipient layers of the tectum contralateral to the enucleation. The present work shows that calbindinlike immunoreactive substances are localized in specific neural circuits of the fish optic tectum and suggests that the calbindin-like immunoreactive fibers in the retinorecipient strata are of retinal origin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00340874
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  • 67
    Digitale Medien
    Digitale Medien
    Expression of carbohydrate epitopes L2/HNK-1 and L3 in the larva and imago of Drosophila melanogaster and Calliphora vicina (1991)
    Springer
    Cell & tissue research 265 (1991), S. 589-600 
    Details
    ISSN: 1432-0878
    Schlagwort(e): L2/HNK-1 carbohydrate epitope ; L3 carbohydrate epitope ; Immunohistochemistry ; Extracellular matrix ; Calliphora vicina (Insecta) ; Drosophila melanogaster (Insecta)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The carbohydrate epitopes L2/HNK-1 and L3 belong to two overlapping families of adhesion molecules in the vertebrate, and probably the invertebrate nervous systems. To investigate their pattern of expression during the development of insects, cryosections of late third instar larvae and imagoes of Drosophila melanogaster and Calliphora vicina were studied by indirect immunofluorescence using several monoclonal antibodies to the L2/HNK-1 and one monoclonal antibody to the L3 epitope. Each monoclonal antibody to the L2/HNK-1 epitope showed a different immunohistological staining pattern, which differed from that of the L3 monoclonal antibody. In both insect species the immunohistological staining patterns for the two carbohydrate epitopes were similar at the two developmental stages, with immunoreactivity not confined to the nervous system. In larvae, immunoreactivities of the monoclonal antibodies L2.334 and L3.492 were predominantly associated with the extracellular matrix as indicated by co-localization with laminin, particularly in the imaginal discs, while L2.349 revealed a more cell surface-associated distribution. In imagoes, immunoreactivities were detectable in most organs studied.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00340883
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  • 68
    Digitale Medien
    Digitale Medien
    Transient expression of a calcium-binding protein (spot 35-calbindin) and its mRNA in the immature pituicytes of embryonic rats (1991)
    Springer
    Cell & tissue research 266 (1991), S. 325-330 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Calbindin ; Neurohypophysis ; Development, ontogenetic ; Immunohistochemistry ; In-situ hybridization ; Electron microscopy ; Rat (Wistar)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Spot 35 protein is a Ca-binding protein originating from the rat cerebellum; it is now referred to spot 35-calbindin. This protein is expressed in immature pituicytes of the neurohypophyseal anlage in the E11–E18 rat embryo. The gene expression of spot 35-calbindin was detected by in-situ hybridization analysis only at stage E11–E12. Profiles of spot 35-positive nerve fibers of a neurosecretory nature were found in anlage at stage E16. At this stage, some immature pituicytes are partially immunopositive for spot 35-calbindin only in their peripheral cytoplasm; others are immunonegative. At birth and thereafter through adulthood, abundant nerve fibers are the sole structures immunoreactive for spot 35-calbindin; all the pituicytes are immunonegative, resulting in a light-microscopic appearance of numerous immunonegative round profiles, corresponding to pituicytes, and capillaries embedded in the granularly immunostained neurohypophysis. The present findings suggest that, during specific embryonic stages, immature pituicytes exert some as yet unidentified roles related to Ca-mediated functions involving the expression of spot 35-calbindin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318188
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  • 69
    Digitale Medien
    Digitale Medien
    Histamine-like immunoreactivity in the visual system and brain of Drosophila melanogaster (1991)
    Springer
    Cell & tissue research 266 (1991), S. 391-398 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Photoreceptor cells ; Nervous system central ; Visual system ; Histamine ; Transmitter ; Immunohistochemistry ; Drosophila melanogaster (Insecta)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary In this study, immunohistochemistry on cryostat sections is used to demonstrate anti-histamine immunoreactivity in the Drosophila brain. The results support earlier findings that histamine is probably a transmitter of insect photoreceptors. It is further shown that, in Drosophila, all imaginal photoreceptors including receptor type R7 are anti-histamine immunoreactive, whereas the larval photoreceptors do not seem to contain histamine. In addition to the photoreceptors, fibres in the antennal nerve and approximately 12 neurons in each brain hemisphere show strong histamine-like immunoreactivity. These cells arborize extensively in large parts of the central brain.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318195
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  • 70
    Digitale Medien
    Digitale Medien
    Developmental expression of glial markers in ependymocytes of the rat subcommissural organ: role of the environment (1991)
    Springer
    Cell & tissue research 266 (1991), S. 553-561 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Subcommissural organ ; Differentiation ; Transplantation ; Immunohistochemistry ; GFAP ; S100 protein ; Serotonin ; Rat (Sprague-Dawley)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The rat subcommissural organ (SCO), principally composed of modified ependymocytes (a type of glial cell), is a suitable model for the in vivo study of glial differentiation. An immunohistochemical study of the ontogenesis of rat SCO-ependymocytes from embryonic day 13 to postnatal day 10 shows that these cells express transitory glial fibrillary acidic protein (GFAP) from embryonic day 19 until postnatal day 3. However, S100 protein (S100) is never expressed in the SCO-cells, contrasting with the ventricle-lining cells of the third ventricle, which contain S100 as early as embryonic day 17. Environmental factors could be responsible for the repression of GFAP and S100 in adult rats, because GFAP and S100 are observed in ependymocytes of SCO 3 months after being grafted from newborn rat into the fourth ventricle of an adult rat. Neuronal factors might be involved in the control of the expression of S100, since after the destruction of serotonin innervation by neurotoxin at birth, S100 can be observed in some SCO-ependymocytes of adult rats. On the other hand, GFAP expression is apparently not affected by serotomin denervation, suggesting the existence of several factors involved in the differentiation of SCO-cells.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318597
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  • 71
    Digitale Medien
    Digitale Medien
    Distribution of the 3-fucosyl-N-acetyl-lactosamine (FAL) epitope in the adult mouse brain (1991)
    Springer
    Cell & tissue research 263 (1991), S. 353-366 
    Details
    ISSN: 1432-0878
    Schlagwort(e): 3-Fucosyl-N-acetyl-lactosamine (FAL) ; Leu-M1 ; CD-15 marker ; Brain mapping ; Immunohistochemistry ; Mouse (NMRI)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution of the 3-fucosyl-N-acetyl-lactosamine (FAL) epitope within the adult mouse brain was studied by immunohistochemistry using the monoclonal antibody Leu-M1. Leu-M1-positive elements comprised astrocytes and neurons. FAL-positive astrocytes were particularly abundant in barrier structures of the brain, but were also prominent at the periphery of most medullated fiber tracts. Their intracerebral distribution led to a distinct pattern of organization, which in some locations, including the cerebral cortex, could be used for an extended regional architectonic description. Since only some FAL-positive astrocytes were also positive for glial fibrillary acid protein (GFAP), the emerging topography of the FAL-positive astrocytes often differed from the GFAP-distribution. In the cerebellum, Bergmann glia cells expressed the FAL epitope and, in the vermis, their arrangement had a band-like appearance. Positive oligodendrocytes could not be identified. The common ependymal cells were negative, whereas tanycytes were highly immunoreactive. The Leu-M1 antibody also stained some neurons. These occurred in selected neocortical regions, within the dorsal and ventral striatum, in the globus pallidus, the nucleus basalis of Meynert, the nucleus diagonalis and some hypothalamic areas. In some instances, their morphology and location indicated an association with neurochemically specified cell groups.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318777
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  • 72
    Digitale Medien
    Digitale Medien
    Immunohistochemical localization of porcine diazepam-binding inhibitor (DBI) to rat endocrine pancreas (1991)
    Springer
    Cell & tissue research 263 (1991), S. 395-398 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Diazepam-binding inhibitor (DBI) ; DBI-like immunoreactivity ; Pancreas, endocrine ; Immunohistochemistry ; Peptides ; Rat (Sprague-Dawley)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The occurrence of diazepam-binding inhibitor (DBI), isolated and characterized from porcine upper intestine, was examined in the pancreas of Sprague-Dawley albino rats using indirect immunofluorescence. The polypeptide was found in the endocrine Langerhans islets and, utilizing double-labelling controls, it was shown to be present within the peripherally located glucagon-containing cells. Regulation of islet hormone production may therefore be under DBI control.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318781
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  • 73
    Digitale Medien
    Digitale Medien
    Immunoreactivities for chromogranin A and B, and secretogranin II in the guinea pig entero-endocrine system: cellular distributions and intercellular heterogeneities (1991)
    Springer
    Cell & tissue research 264 (1991), S. 231-241 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Chromogranin ; Secretogranin ; Enteroendocrine cells ; Immunohistochemistry ; Guinea pig
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The family of the chromogranin/secretogranin proteins consists of three major subtypes: chromogranin A (CgA), chromogranin B (CgB) and secretogranin II (SgII). These proteins are present in various endocrine cells and organs. Using immunohistochemistry on serial semithin sections, we have investigated ten endocrine cell types of the guinea pig gastro-intestinal tract for their content of chromogranin/secretogranin proteins. The gastrin cell was the only cell type containing immunoreactivities for all three chromogranin subtypes. The majority of entero-endocrine cells showed immunoreactivities for CgA and SgII. Somatostatin cells lacked immunoreactivities for any of the chromogranins. Moreover, the densities of the corresponding immunoreactivities varied among the different endocrine cell types or even among endocrine cells of a given population. Aminergic endocrine cells (e.g., enterochromaffin and enterochromaffin-like cells) regularly exhibited strong immunoreactivities for CgA but failed to react for SgII. In peptidergic endocrine cells, the immunoreactivities for both CgA and SgII ranged from dense to faint. This was also true for CgB in gastrin cells. Hence, only CgA and SgII can be considered as regular constituents of entero-endocrine cells. The intercellular differences in immunoreactivities for all three chromogranin subtypes indicate that every endocrine cell has its own composition of chromogranin/secretogranin proteins. This may be due to differences in the regulation of biosynthesis or processing of the chromogranins in individual endocrine cells; this in turn might be related to the functional states of endocrine cells.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00313960
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  • 74
    Digitale Medien
    Digitale Medien
    Synaptophysin immunoreactivity in the mammalian endocrine pancreas (1991)
    Springer
    Cell & tissue research 264 (1991), S. 461-467 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Synaptophysin ; P38 ; Membrane proteins ; Endocrine pancreas ; Islet cells ; Immunohistochemistry ; Human ; Dog ; Gerbil
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Synaptophysin, a major membrane glycoprotein of small presynaptic vesicles in neurons, has also been found in microvesicles of endocrine cells, e.g., of the endocrine pancreas. In the present study, the endocrine pancreas in 9 mammalian species (man, dog, mink, bovine, rabbit, guinea pig, rat, mouse, gerbil) has been investigated immunohistochemically for synaptophysin immunoreactivity. Synaptophysin-positive cells have been identified and localized on semithin plastic sections. Our study demonstrates that, in all species examined, all pancreatic endocrine cell types are consistently synaptophysin-positive independent of their location within the tissue, or the conditions of tissue processing. In addition, a few cells that cannot be hormonally identified show synaptophysin immunoreactivity. Hence, synaptophysin appears to be a regular constituent of all pancreatic endocrine cells in mammals. In several species, a subpopulation of endocrine cells, consisting of glucagon-containing and/or pancreatic-polypeptide-containing cells, exhibits a significantly higher degree of synaptophysin immunoreactivity. In the gerbil, this heterogeneity can readily be detected from the day of birth onwards. Our findings indicate that closely related endocrine cell types may differ with respect to the content of synaptophysin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00319036
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  • 75
    Digitale Medien
    Digitale Medien
    Tyrosine hydroxylase- and neuropeptide Y-immunoreactive nerve fibers in the pineal complex of untreated rats and rats following removal of the superior cervical ganglia (1991)
    Springer
    Cell & tissue research 265 (1991), S. 63-71 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Neuropeptide Y ; Tyrosine hydroxylase ; Extrasympathetic innervation ; Pineal gland ; Deep pineal ; Immunohistochemistry ; Rat (Wistar)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution of tyrosine hydroxylase (TH)- and neuropeptide Y (NPY)-immunoreactive(IR) nerve fibers in the pineal complex was investigated in untreated rats and rats following bilateral removal of the superior cervical ganglia. In normal animals, a large number of TH- and NPY-IR nerve fibers were present in the pineal capsule, the perivascular spaces, and intraparenchymally between the pinealocytes throughout the superficial pineal and deep pineal gland. A small number of TH-IR and NPY-IR nerve fibers were found in the posterior and habenular commissures, a few fibers penetrating from the commissures into the deep pineal gland. To elucidate the origin of these fibers, the superior cervical ganglion was removed bilaterally in 10 animals, and the pineal complex was examined immunohistochemically. Two weeks after the ganglionectomy, the TH-IR and NPY-IR nerve fibers in the superficial pineal gland had almost completely disappeared. On the other hand, in the deep pineal and the pineal stalk, the TH-IR and NPY-IR fibers were still present after ganglionectomy. These data show that the deep pineal gland and the pineal stalk possess an extrasympathetic innervation by TH-IR and NPY-IR fibers. It is suggested that the extrasympathetic TH-IR and NPY-IR nerve fibers innervating the deep pineal and the pineal stalk originate from the brain.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318140
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  • 76
    Digitale Medien
    Digitale Medien
    The catecholaminergic system of an annelid (Ophryotrocha puerilis, Polychaeta) (1991)
    Springer
    Cell & tissue research 265 (1991), S. 175-184 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Nervous system ; Nervous system, peripheral ; Catecholamines ; Immunohistochemistry ; Glyoxylic acid fluorescence ; Ophryotrocha puerilis (Annelida)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The complex catecholaminergic (CA) nervous system of the polychaete Ophryotrocha puerilis is documented using glyoxylic acid induced fluorescence (GIF) and immunohistochemistry. CA-neurons are found both in the central and peripheral nervous system. In the brain, about 50 CA-neurons are present in the perikaryal layer together with numerous CA fibres. Two pairs of CA perikarya are characteristic for each ganglion of the ventral nerve cord. CA-neurites in the ventral nerve cord are mainly arranged in 4 strands paralleling the longitudinal axis of the worm. Fluorescent neurons with receptive ciliary structures are present in body appendages (antennae, palps, urites, parapodial cirri), in the body-wall, and within the oesophageal wall. Furthermore, a subepidermal nerve net of free CA nerve endings has been found. After incubation of specimens with dopamine prior to the development of GIF more fluorescent perikarya could be observed; the fluorescence was also intensified. Pre-incubation with reserpine reduced the intensity of GIF. Results of high pressure liquid chromatography and immunostaining with a polyclonal antibody against a dopamine-glutaraldehyde-complex suggest that dopamine is the major CA transmitter. It is thought that dopaminergic neurons together with ciliary receptive structures act as mechano- and/or chemoreceptors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318152
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  • 77
    Digitale Medien
    Digitale Medien
    The endocrine pancreas of glucagon-and somatostatin-immunized rabbits (1991)
    Springer
    Cell & tissue research 265 (1991), S. 251-260 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Endocrine pancreas ; Immunization ; Glucagon ; Somatostatin ; Immunohistochemistry ; Rabbit (Chinchilla, Ch:b:Ch)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Peptide antibodies raised in rabbits are widely used in biology and medicine. During immunization of the animals, the respective antibodies may affect the endocrine cells physiologically responsible for the synthesis of peptides used as antigens. Since corresponding morphological data are still sparse, the rabbit endocrine pancreas was systematically investigated by light microscopy and immunocytochemistry after long-term immunization against glucagon and somatostatin. Both immunizations led to an increase in the number of islets (nesidioblastosis), to the development of giant islets (macronesia), and to changes in the relative proportions of the major types of endocrine cells or their hormonal content. The latter changes differed after either immunization: glucagon immunization resulted in hypertrophy and hyperplasia of glucagon cells and a decrease in their hormonal content; somatostatin immunization led to an increased proportion of somatostatin cells and a lowered hormonal content of insulin cells. The various alterations were expressed differently according to islet type; islets of the rabbit pancreas differ in size or angioarchitecture, and in the proportion and distribution of endocrine cells. The present findings point to autocrine or paracrine effects of the respective peptides. These effects, however, are obviously of differing significance in morphologically heterogeneous islets.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00398073
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  • 78
    Digitale Medien
    Digitale Medien
    Morphological alteration of gut-associated lymphoid tissue after long-term total parenteral nutrition in rats (1991)
    Springer
    Cell & tissue research 266 (1991), S. 29-36 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Parenteral feeding ; Gut-associated lymphoid tissue ; Peyer's patches ; Immunoglobulin A ; Immunohistochemistry ; Rat (Wistar)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The morphological alteration of gut-associated lymphoid tissue (GALT) induced by long-term absence of dietary stimulation was investigated. Male Wistar rats weighing ∼230 g were maintained with total parenteral nutrition (TPN). Control rats were allowed to have the same amount of the solution orally. After two weeks, the morphological alteration of GALT was examined. Although no significant difference in weight gain was noted between the two groups, the area comprised by Peyer's patches was decreased in TPN rats. The number of transported lymphocytes and the ratio of helper T (Th) cells to suppressor/cytotoxic T (Ts/c) cells in intestinal lymph were lowered after TPN treatment. In an immunohistochemical study of the rat ileum, the number of T cells and the Th/Ts/c ratio were decreased both in the intraepithelial spaces and in the lamina propria of TPN rats. The percentage of interleukin-2 receptor-positive cells and the number of IgA-containing cells in the lamina propria were significantly reduced in TPN rats. These results suggest that dietary stimulation might play a role in the maintenance of GALT function and morphology.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00678708
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  • 79
    Digitale Medien
    Digitale Medien
    Distribution of 5-HT (serotonin) immunoreactivity in the central nervous system of the inshore hagfish,Eptatretus burgeri (1991)
    Springer
    Cell & tissue research 266 (1991), S. 107-116 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Serotonin ; Immunohistochemistry ; CSF-contacting neurons ; Raphe ; Hagfish (Eptatretus burgeri)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Immunohistochemical techniques were used to study the distribution of serotonin in the central nervous system of the hagfish,Eptatretus burgeri, in order to produce a detailed map of serotonin-containing structures. In the hypothalamus, many serotonin-containing neurons contacted the cerebrospinal fluid. Most of the serotonin-containing cell bodies were located in the raphe region, where they were compactly distributed at the level of the nucleus motorius tegmenti pars anterior but more diffusely distributed at the level of the nucleus motorius tegmenti pars posterior. Serotonin-containing cell bodies and varicose fibers were widely distributed throughout the brain and upper spinal cord segments, but the distribution density was not even. On the basis of its abundance, serotonin can be judged to have an important function in the control of the hagfish central nervous system. From a phylogenetic point of view, serotonin-containing neurons in the raphe region appear to be a common property of all classes of vertebrates studied except the lampreys, whereas serotonin-containing cerebrospinal fluid-contacting neurons may be considered to be a primitive condition in all nonmammalian vertebrates.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00678717
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  • 80
    Digitale Medien
    Digitale Medien
    Constancies in the neuronal architecture of the suboesophageal ganglion at metamorphosis in the beetleTenebrio molitor L. (1991)
    Springer
    Cell & tissue research 266 (1991), S. 173-190 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Neuroanatomy ; Identified neurons ; Immunohistochemistry ; Suboesophageal ganglion ; Tenebrio molitor (Insecta)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Topological organization of identified neurons has been characterized for the larval, pupal and imaginal suboeosphageal neuropil of the meal-worm beetleTenebrio molitor. Neuronal fate mapping allows identification of individually persisting neurons in the metamorphosing suboesophageal ganglion ofTenebrio. Analysis was performed on interneurons characterized by serotonin and CCAP (crustacean cardioactive peptide) immunohistochemistry, on motoneurons that innervate the dorsal and ventral longitudinal muscles, and on suboesophageal descending neurons. All these different populations of neurons show topologically invariant features throughout metamorphosis. Motoneurons, interneurons, and descending suboesophageal neurons of the imaginal suboeosphageal ganglion embody individually persisting larval interneurons. Impacts for a functional interpretation of the neuronal architecture of the suboesophageal ganglion are discussed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00678723
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  • 81
    Digitale Medien
    Digitale Medien
    Target-specific innervation by autonomic and sensory nerve fibers in hairy fetal skin transplanted into the anterior eye chamber of adult rat (1991)
    Springer
    Cell & tissue research 266 (1991), S. 259-263 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Hairy skin tissue fetal ; Transplantation ; Anterior eye chamber ; Immunohistochemistry ; Rat (Wistar)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Pieces of hairy skin tissue of fetal rat were transplanted into the anterior eye chamber of adult rats. The ability of autonomic and sensory nerve fibers from the host iris to innervate the grafted skin tissue was immunohistochemically and enzyme-histochemically examined using antisera against tyrosine hydroxylase (TH), substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP), and a reaction medium for acetylcholinesterase (AchE). The grafted tissue was successfully implanted and connected with the host iris. Epidermis, dermis, subcutaneous tissue, hairs, hair follicles, sebaceous glands, and piloerector muscles developed in the graft. Two weeks after transplantation, TH-, SP-, and CGRP-immunoreactive fibers were observed in association with the blood vessels in the graft. Four weeks after transplantation, TH-immunoreactive fibers were distributed in the piloerector muscles, whereas SP-and CGRP-immunoreactive fibers were present around the hair follicles. VIP-immunoreactive and AchE-positive fibers were restricted to the host iris at all survival times. These results suggest that the outgrowth of autonomic and sensory nerve fibers from the host iris show target specificity for the grafted skin tissue.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318181
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  • 82
    Digitale Medien
    Digitale Medien
    Mating alters topography and content of oxytocin immunoreactivity in male mouse brain (1991)
    Springer
    Cell & tissue research 266 (1991), S. 399-403 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Oxytocin ; Mating ; Oxytocinergic systems ; Radioimmunoassay ; Immunohistochemistry ; Functional activation ; Mouse (Holtzman CD, C. River)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Sexual stimulation of males has been reported to affect hypothalamic oxytocinergic systems. In the present study we used radioimmunoassays of micro-dissected forebrain regions and immunocytochemical analysis of Vibratome sections to study the oxytocin systems of naive males, males killed after one mating, and males mated daily with different receptive females for 3 weeks. In males that had mated once, less oxytocin-immunoreactive neurons were observed in the paraventricular (PVN), supraoptic (SON) and periventricular (NPE) nuclei than in naive males. However, after repeated matings, the number of immunoreactive neurons and their staining intensity was increased in these regions. Furthermore, additional oxytocinergic neurons could be found in the lateral subcommissural nucleus, the zona incerta and the ansa lenticularis of repeatedly mated males. Oxytocin-immunoreactive neurons were only occasionally seen in these areas in unmated males or in animals that had been killed after initial mating. Radio-immunoassays of microdissected PVN, SON, NPE and the lateral hypothalamus confirmed the reduction in oxytocin-immunoreactive levels after a first mating by a male and the increase after repeated matings. It is likely that oxytocin secretion into peripheral and portal circulation is stimulated by the endocrine conditions associated with initial mating. These immediate effects may be followed by the activation of synthesis in oxytocin neurons in several sites of the basal forebrain.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318196
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  • 83
    Digitale Medien
    Digitale Medien
    Postnatal development of the brush cells in the common bile duct of the rat (1991)
    Springer
    Cell & tissue research 266 (1991), S. 507-510 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Brush cells ; Billiary system ; Development, ontogenetic ; Immunohistochemistry ; Liver fatty-acid-binding protein ; Rat (Wistar)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The postnatal development of brush cells in the distal segment of the common bile duct of the rat was examined with respect to cell number and immuno-reactivity for liver fatty acid-binding protein (L-FABP). The brush cells, distinguishable from the principal cells by scanning electron microscopy, first appeared in the common bile duct 4 weeks after birth. They showed a remarkable increase in number, with a sex difference in time, i.e., between 8 and 12 weeks in the male and between 10 and 14 weeks in the female. In both sexes, the frequency of brush cells reached approximately 30% of total epithelial cells by 16 weeks and remained constant until 40 weeks of age. Cells with positive immuno-reactivity for L-FABP first appeared in small numbers at 8 weeks. Immuno-electron microscopy revealed that all immunoreactive cells were brush cells. They increased in number gradually from 16 to 40 weeks with no sex difference. At 40 weeks, the immunoreactive cells reached approximately 7.5% of total epithelial cells, corresponding to one-fourth of the number of brush cells. These results indicate that the occurrence of the brush cell population in the common bile duct is a late event in the postnatal development of the rat and that its functional maturation progresses with aging.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318592
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  • 84
    Digitale Medien
    Digitale Medien
    Neurons with histaminelike immunoreactivity in the segmental and stomatogastric nervous systems of the crayfishPacifastacus leniusculus and the lobsterHomarus americanus (1991)
    Springer
    Cell & tissue research 266 (1991), S. 197-207 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Stomatogastric ganglion ; Interneuron ; Crustacea ; Histamine ; Immunohistochemistry ; Pacifastacus leniusculus (Crustacea) ; Homarus americanus (Crustacea)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary We used a polyclonal antiserum against histamine to map histaminelike immunoreactivity (HLI) in whole mounts of the segmental ganglia and stomatogastric ganglion of crayfish and lobster. Carbodiimide fixation permitted both HRP-conjugated and FITC-conjugated secondary antibodies to be used effectively to visualize HLI in these whole mounts. Two interneurons that send axons through the inferior ventricular nerve (ivn) and the stomatogastric nerve to the stomatogastric ganglion had strong HLI, both in crayfish and in lobster. These ivn interneurons were known from other evidence to be histaminergic. The neuropil of the stomatogastric ganglion in both crayfish and lobster contained brightly labeled terminals of axons that entered the ganglion from the stomatogastric nerve. No neuronal cell bodies in this ganglion had HLI. Each segmental ganglion contained at least one pair of neurons with HLI. Some neurons in the subesophageal ganglion and in each thoracic ganglion labeled very brightly. Axons of projection interneurons with strong HLI occurred in the dorsal lateral tracts of each segmental ganglion, and sent branches to the lateral neuropils and tract neuropils of each ganglion. All the labeled neurons were interneurons; no HLI was observed in peripheral nerves.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00678725
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  • 85
    Digitale Medien
    Digitale Medien
    Antigenic heterogeneity of the reticular meshwork in the white pulp of mouse spleen (1991)
    Springer
    Cell & tissue research 266 (1991), S. 223-229 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Reticulum cells ; Monoclonal antibodies ; Splenic white pulp ; Immunohistochemistry ; Mouse (C3H/He)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Monoclonal antibodies against cellular components of reticular meshworks were produced by immunizing rats with heterogeneous stromal-cell population of mouse spleen. Immunohistochemical screening selected two antibodies, WP-1 and RPSC-2. WP-1 proved to immunostain the meshwork of the B area densely, leaving the marginal zone unstained; it also reacted sparsely with the meshwork of the T-cell region. In contrast, RPSC-2 selectively immunostained the meshwork of the T region. Immuno-electron microscopy clearly visualized, for both antibodies, reaction products being deposited along the cytomembrane of the fibroblastic reticulum cells, along their abundant cytoplasmic processes that were densely intertwined with lymphocytes. Double immunostaining with RPSC-2 followed by WP-1 clearly divided the white pulp into the T and the B domains. The meshwork in the T-cell region proved to be immunostainable with both WP-1 and RPSC-2. Thus, the fibroblastic reticulum cells of the T-and the B-cell areas, while indistinguishable by routine microscopy, are at least partially heterogeneous.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318177
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  • 86
    Digitale Medien
    Digitale Medien
    Centrin- and α-actinin-like immunoreactivity in the ciliary rootlets of insect sensilla (1991)
    Springer
    Cell & tissue research 266 (1991), S. 231-238 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Ciliary rootlets ; Sensilla ; Mechanoreceptors ; α-Actinin ; Centrin ; Cryofixation ; Immunohistochemistry ; Periplaneta americana, Schedorhinotermes lamanianus (Insecta)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Long ciliary rootlets are a characteristic feature of the dendritic inner segments of the sensory cells in insect sensilla. These rootlets are composed of highly ordered filaments and are regularly cross-striated. Collagenase digestion and immunohistochemistry reveal that the rootlets are probably not composed of collagen fibers. However, double-labeling experiments with phalloidin and anti-α-actinins show that antibodies to α-actinin react with the ciliary rootlets of the sensilla, but do not stain the scolopale, which is composed of actin filaments as visualized by phalloidin. Antibodies to centrin, a contractile protein isolated from flagellar rootlets of green algae, also stain the ciliary rootlets. Within the ciliary rootlets of insect sensilla, α-actinin may be associated with filaments other than actin filaments. The immunohistochemical localization of a centrin-like protein suggests that contractions probably occur within the rootlets. The centrin-like protein may play a role during the mechanical transduction or adaptation of the sensilla.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318178
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  • 87
    Digitale Medien
    Digitale Medien
    Basal cells in the mouse olfactory epithelium after axotomy: immunohistochemical and electron-microscopic studies (1991)
    Springer
    Cell & tissue research 266 (1991), S. 239-245 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Basal cells ; Olfactory epithelium ; Axotomy ; Immunohistochemistry ; Mouse (dd)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The olfactory epithelium of mice after axotomy was investigated to clarify the stem cells of olfactory cells by double immunostaining using antikeratin (MA903) and anti-bromodeoxyuridine (BrdU) antibodies and by conventional electron microscopy. When a single dose of BrdU was given to mice 9 days after axotomy, immunostaining for BrdU was found in the globose basal cells which were negative for MA903, but not in the basal cells proper which were positive for MA903. The BrdU-immunoreactive cells increased 3-to 6-fold over the number of these cells in the controls, indicating active cell proliferation. At other postoperative days (4 and 14 days), fewer BrdU-immunoreactive cells were found. Furthermore, three pulses of BrdU resulted in numerous BrdU-immunolabelings in the globose basal cells and a few in the basal cells proper. There was no detectable difference in the number of labeled basal cells proper in operated and unoperated mice. In the electron micrographs 9 days after axotomy, the basal cells proper, flat-shaped in unoperated mice, appeared cylindrical or pyramidal in shape and the globose basal cells often lay between the basal cells proper. In unoperated controls, the globose basal cells were located above the flat-shaped basal cells proper. The results suggest that the stem cells of the olfactory cells are globose basal cells and not basal cells proper, and that the shape of basal cells proper changes in relation to the active proliferation of stem cells.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318179
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  • 88
    Digitale Medien
    Digitale Medien
    Immunohistochemical colocalization of insulin, aromatic L-amino acid decarboxylase and dopamine beta-hydroxylase in islet B cells of chicken pancreas (1991)
    Springer
    Cell & tissue research 263 (1991), S. 131-136 
    Details
    ISSN: 1432-0878
    Schlagwort(e): B cells ; Insulin ; Catecholamine ; synthesizing enzymes ; Immunohistochemistry ; Chicken
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The identity of the monoamine which produces a very weak formaldehyde-induced fluorescence in some pancreatic islet cells was studied by fluorescence microscopy and immunohistochemistry either on the same tissue section or on serial tissue sections of tissue from male chickens. Pancreatic islet cells showing this very weak formaldehyde-induced fluorescence react immunohistochemically with antisera directed against insulin, aromatic L-amino acid decarboxylase and dopamine beta-hydroxylase and therefore appear to be islet B cells producing insulin and noradrenaline.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318408
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  • 89
    Digitale Medien
    Digitale Medien
    Immunoreactive Tamm-Horsfall protein in the kidney and skin of the frog Rana temporaria (1991)
    Springer
    Cell & tissue research 263 (1991), S. 585-587 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Kidney ; Skin ; Tamm-Horsfall protein ; Immunohistochemistry ; Rana temporaria (Anura), Rat (Wistar), Rabbit
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Tamm-Horsfall protein (THP) is the main protein in normal human urine, and is found in the thick limb of the Loop of Henle in human kidney, and in other mammalian species. The skin of the frog, Rana temporaria, has similar physiological properties to this mammalian kidney tissue. In the present study, an immunohistological method involving an antibody to human THP was used to investigate the distribution of this distinctive protein in frog kidney and skin, and to compare its distribution with that found in the kidney tubules of rat and rabbit. THP-positive material was detected in the distal renal tubules and nephric duct of frogs, and was also located in the superificial epidermis of skin. It is suggested that its presence in amphibian skin is consistent with the hypothesis that THP is an important component of tissues that absorb sodium and chloride ions, but remain impermeable to water.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00327292
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  • 90
    Digitale Medien
    Digitale Medien
    Met5-enkephalin-Arg6-Gly7-Leu8-immunoreactive nerve fibers in the major salivary glands of the rat: evidence for both sympathetic and parasympathetic origin (1991)
    Springer
    Cell & tissue research 264 (1991), S. 15-22 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Salivary glands ; Innervation ; Immunohistochemistry ; Met5-enkephalin-Arg6-Gly7-Leu8 ; Tyrosine hydroxylase ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The localization of the proenkephalin A-derived octapeptide, Met5-enkephalin-Arg6-Gly7-Leu8 (MEAGL), was studied in the major salivary glands of Sprague-Dawley and Wistar rats with the indirect immunofluorescence method. MEAGL-immunoreactive nerve fibers were found around the acini, along intra-and interlobular salivary ducts and in close contact with blood vessels. In the parotid and submandibular glands tyrosine hydroxylase (TH) immunoreactivity was observed in nerve fibers around the acini, in association with intra- and interlobular salivary ducts and around blood vessels, while in the sublingual gland TH-immunoreactive nerve fibers were only seen around blood vessels. Parasympathetic neurons in submandibular ganglia contained MEAGL immunoreactivity. Moderate TH immunoreactivity was seen in some neurons of the submandibular ganglia. A subpopulation of sympathetic principal neurons in the superior cervical ganglion were immunoreactive for both MEAGL and TH. In the trigeminal ganglion, no MEAGL-immunoreactive sensory neurons or nerve fibers were observed. Superior cervical ganglionectomies resulted in a complete disappearance of TH-immunoreactive nerve fibers, while MEAGL-immunoreative nerve fibers were still present in the glands. The presence of MEAGL immunoreactivity in neurons of both sympathetic superior cervical ganglia and parasympathetic submandibular ganglia and the results of superior cervical ganglionectomies suggest, that MEAGL-immunoreactive nerve fibers in the major salivary glands of the rat have both sympathetic and parasympathetic origin.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00305718
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  • 91
    Digitale Medien
    Digitale Medien
    Cell types in the fetal pars tuberalis of the human adenohypophysis at mid-gestation (1991)
    Springer
    Cell & tissue research 264 (1991), S. 161-165 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Adenohypophysis ; Pars tuberalis ; Ultrastructure ; Immunohistochemistry ; Fetal ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The pars tuberalis of the adenohypophysis was investigated in three human fetuses at mid-gestation by electron microscopy or immunohistochemistry. In addition to gonadotrophs and thyrotrophs, identified by immunohistochemistry and ultrastructural morphology, electron microscopy revealed the existence of an additional differentiated cell type closely resembling “pars tuberalis-specific” cells known from other species. The role of this cell type in the human endocrine regulation remains to be elucidated.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00305734
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  • 92
    Digitale Medien
    Digitale Medien
    Cytophysiology of neurosecretory axon terminals in the brain of an annelid (Ophryotrocha puerilis, Polychaeta) (1991)
    Springer
    Cell & tissue research 264 (1991), S. 339-345 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Neurosecretion ; Catecholamines ; HPLC ; Immunohistochemistry ; Glyoxylic acid fluorescence ; Ophryotrocha puerilis (Annelida)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary In the posterior part of the brain of the protandric polychaete Ophryotrocha puerilis neurosecretory cells form prominent axon terminals. The terminals are arranged in two complexes. The perikarya of these presumably monopolar neurons are scattered in the anterior part of the cerebral perikaryal layer. In females the terminals store large amounts of neurosecretory material. It has been suggested earlier that neurosecretions of the terminals may play a role during sex reversal from females to males. Application of histamine caused the release of neurosecretory material from the respective terminals in females. However, this discharge was not followed by sex reversal. Application of reserpine had no influence on the terminals. Neither by in vivo observation nor by ultrastructural analysis any effect of reserpine on the terminal complexes could be observed. In isolated terminals filled with neurosecretory material from females, catecholamines could not be detected by HPLC. Also, polyclonal antibodies against dopamine did not stain the terminal complexes. Furthermore, the complexes did not develop any fluorescence after glyoxylic acid treatment. Therefore, the present results contradict the hypothesis that the neurosecretory material of the respective axon terminals is catecholaminergic and that it is involved in sex differentiation. The function of the secretory neurons studied here remains unclear.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00313972
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  • 93
    Digitale Medien
    Digitale Medien
    Cellular subsets of the milky spots in the human greater omentum (1991)
    Springer
    Cell & tissue research 264 (1991), S. 599-601 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Milky spots ; Greater omentum ; Immunohistochemistry ; Macrophages ; B-lymphocytes ; Tlymphocytes ; Mast cells ; Human
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The cellular composition of the human milky spots was investigated on surgically removed specimens of the greater omentum of three 8-month-old infants operated on for neuroblastoma. Monoclonal antibodies and immunohistochemical methods for recognition of macrophages, B-lymphocytes and T-lymphocytes and toluidine-blue staining for mast cells were used. The mean number of cells in one milky spot amounted to 570±33. This cell population was composed of 47.5% macrophages, 29.1% B-lymphocytes, 11.7% T-lymphocytes and 6.1% mast cells. Since inflammation was absent in the material investigated, the numerical data found in the present paper could be regarded as representative cell levels of normal milky spots.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00319049
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  • 94
    Digitale Medien
    Digitale Medien
    Distribution of gonadotropin-releasing hormone-like peptides in the brain during development of juvenile male Rana esculenta (1991)
    Springer
    Cell & tissue research 265 (1991), S. 51-55 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Brain ; Gonadotropin-releasing hormone ; Spermatogenesis ; Reproductive cycle ; Immunohistochemistry ; Development, ontogenetic ; Rana esculenta (Anura)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The distribution and density of cell bodies and fibers immunoreactive to GnRH-like peptides were investigated in the brain of male juvenile frogs (Rana esculenta) during postmetamorphic development. An immunohistochemical technique was used, involving antisera raised against 4 variants of GnRH: mammalian GnRH, chicken GnRH-I, chicken GnRH-II and salmon GnRH. A comparison of the immunohistochemical distribution at 8 different developmental stages shows that the maximum density of immunoreactive-GnRH elements, and the full distributional complexity of this system, is attained at the completion of spermatogenesis. Immunoreactive-GnRH cell bodies first appear in the anterior preoptic area during the metamorphic climax, and then appear sequentially in the medial septal area, tegmentum and, lastly, in the retrochiasmatic area and olfactory bulb when immunoreactive-fibers also reach the cerebellum. The GnRH system reacts positively to antisera for all 4 GnRH variants, but immunoreactivity for chicken GnRH-I is the weakest.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318138
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  • 95
    Digitale Medien
    Digitale Medien
    Tropomyosin is co-localized with the actin filaments of the scolopale in insect sensilla (1991)
    Springer
    Cell & tissue research 265 (1991), S. 11-17 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Sensilla ; Mechanoreceptors ; Scolopidia ; Actin filaments ; Tropomyosin ; Cryofixation ; Immunohistochemistry ; Immunogold ultrahistochemistry ; Periplaneta americana, Schedorhinotermes lamanianus (Insecta)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Immuno-electron microscopy confirms that the scolopale, a characteristically prominent cytoskeletal element of insect scolopidia, is composed mainly of actin filaments. Immunohistochemistry reveals that these filaments are co-localized with tropomyosin. Myosin S1-decoration shows that their polarity is unidirectional. Antibodies to α-actinin do not bind within the scolopale. The association of these actin filaments with tropomyosin in the absence of myosin, together with their uniform polarity, strongly suggests that, in the scolopale, they have a stabilizing rather than contractile function. Filament elasticity would appear to be important for stimulation. The degree of elasticity may well be governed by the extent of tropomyosin binding.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318134
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  • 96
    Digitale Medien
    Digitale Medien
    Morphological evidence for a close interaction of chromaffin cells with cortical cells within the adrenal gland (1991)
    Springer
    Cell & tissue research 265 (1991), S. 1-9 
    Details
    ISSN: 1432-0878
    Schlagwort(e): Chromaffin cells ; Adrenal cortex ; Steroid production ; Immunohistochemistry ; Rat (SIV, Ivanovas, FRG)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The adrenal medulla appears to exert a regulatory influence on adrenocortical steroidogenesis. We have therefore studied the morphology of rat, porcine and bovine adrenals in order to characterize the contact zones of adrenomedullary and adrenocortical tissues. The distribution of chromaffin cells located within the adrenal cortex and of cortical cells located within the adrenal medulla was investigated. Chromaffin cells were characterized by immunostaining for synaptophysin and chromogranin A, both being considered specific for neuroendocrine cells. Cortical cells were characterized by immunostaining for 17α-hydroxylase, an enzyme of the steroid pathway. Cellular contacts of chromaffin cells and cortical cells were examined at the electron microscopical level. In rat and porcine adrenals, rays of chromaffin cells, small cell clusters and single chromaffin cells or small invaginations from the medulla could be detected in all three zones of the cortex. Chromaffin cells often spread in the subcapsular space of the zona glomerulosa. In porcine and bovine adrenals, 17α-hydroxylase immunoreactive cells were localized within the medulla. Single cortical cells and small accumulations of cells were spread throughout this region. At the ultrastructural level, the chromaffin cells located within the cortex in pig and rat adrenals formed close cellular contacts with cortical cells in all three zones. Our morphological data provide evidence for a possible paracrine role of chromaffin cells; this may be important for the neuroregulation of the adrenal cortex.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318133
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  • 97
    Digitale Medien
    Digitale Medien
    Differential distribution of β-pigment-dispersing hormone (β-PDH)-like immunoreactivity in the stomatogastric nervous system of five species of decapod crustaceans (1991)
    Springer
    Cell & tissue research 265 (1991), S. 19-33 
    Details
    ISSN: 1432-0878
    Schlagwort(e): β-Pigment-dispersing hormone (β-PDH) ; Ganglia, invertebrate ; Immunohistochemistry ; Antibody staining ; Peptide localization ; Cancer antennarius, Procambarus clarkii, Panulirus interruptus (Crustacea)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Pigment-dispersing hormone (PDH) acts to disperse pigments within the chromatophores of crustaceans. Using an antibody raised against β-PDH from the fiddler crab Uca pugilator, we characterized the distribution of β-PDH-like immunoreactivity in the stomatogastric nervous system of five decapod crustaceans: the crabs, Cancer borealis and Cancer antennarius, the lobsters, Panulirus interruptus and Homarus americanus, and the crayfish, Procambarus clarkii. No somata were stained in the stomatogastric ganglion (STG) or the esophageal ganglion in any of these species. Intense PDH-like staining was seen in the neuropil of the STG in P. interruptus only. In all 5 species, cell bodies, processes, and neuropil within the paired circumesophageal ganglia (CGs) showed PDH-like staining; the pattern of this staining was unique for each species. In each CG, the β-PDH antibody stained: 1 large cell in C. borealis; 3 small to large cells in C. antennarius; 3–8 medium cells in P. clarkii; 1–4 small cells in H. americanus; and 13–17 small cells in P. interruptus. The smallest cell in each CG in C. antennarius sends its axon, via the inferior esophageal nerves, into the opposite CG; this pair of cells, not labeled in the other species studied, may act as bilateral coordinators of sensory or motor function. These diverse staining patterns imply some degree of evolutionary diversity among these crustaceans. A β-PDH-like peptide may act as a neuromodulator of the rhythms produced by the stomatogastric nervous system of decapod crustaceans.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00318135
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  • 98
    Digitale Medien
    Digitale Medien
    Cyclopentenyl cytosine: Interspecies predictions based on rodent plasma and urine kinetics (1991)
    Springer
    Investigational new drugs 9 (1991), S. 9-17 
    Details
    ISSN: 1573-0646
    Schlagwort(e): cyclopentenyl cytosine ; interspecies ; pharmacokinetics ; toxicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A hybrid compartmental-physiological model for cyclopentenyl cytosine (CPE-C) is designed on the basis of early limited rodent pharmacokinetic data. Application of model independent pharmacokinetics and biochemical knowledge was first used to conceptualize such a model. The approach was to scale the physiological parameters of the model (compartmental clearances) and keep constant the anatomic parameters of the model (compartment volumes). Scaling of physiological mechanisms was based on body weight/surface area ratios. Using these principles, simulations with the model can reasonably anticipate the in vivo behavior of (CPE-C) in several species (mouse, rat, dog). The model is useful in understanding species differences in pharmacokinetic behavior of CPE-C.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00194539
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  • 99
    Digitale Medien
    Digitale Medien
    Ifosfamide pharmacokinetics (1991)
    Springer
    Investigational new drugs 9 (1991), S. 305-311 
    Details
    ISSN: 1573-0646
    Schlagwort(e): ifosfamide ; pharmacokinetics ; review
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract This review examines and details the pharmacokinetics of ifosfamide (a congener of cyclophosphamide) when administered by a number of commonly used chemotherapeutic regimes. The influence of route of administration, schedule of administration and dose on the pharmacokinetics of ifosfamide and its metabolites are discussed. Oral fractionated ifosfamide therapy, which causes an excessively high incidence of neurotoxicity, is similar to intravenous fractionated therapy in that it exhibits a time dependent increase in ifosfamide metabolic clearance. Five g/m2 ifosfamide given intravenously as a short (half hour) or long (24 hr) infusion does not exhibit dose dependent (zero-order) pharmacokinetics. In patients who develop ifosfamide/mesna associated CNS toxicity the pharmacokinetics of parent ifosfamide are not aberrant. This implies that ifosfamide metabolites are more likely to be responsible for the neurotoxicity rather than the parent drug. The development of simple and more specific analytical methodology, will allow further studies of the pharmacokinetics of the active ifosfamide metabolite(s). This may lead to further optimisation of the therapeutic index of ifosfamide treatment.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00183570
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  • 100
    Digitale Medien
    Digitale Medien
    The pharmacokinetics of aspirin in rats and the effect of buffer (1991)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 19 (1991), S. 157-173 
    Details
    ISSN: 1573-8744
    Schlagwort(e): aspirin ; rat ; pharmacokinetics ; effect of buffer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Aspirin (acetylsalicyclic add) was administered to rats intravenously, orally, and intraintestinally at different doses or in different dosage forms. The distribution and elimination kinetics of aspirin in rats following intravenous administration were best described by a two-compartmental open system and were dose independent up to 15 mg/kg. The terminal elimination half-life following intravenous dosing (10 mg/kg) was 3.36±0.85min (n=15) with the clearance being 8.40±1.24 L/(kg.hr). Intravenous distribution and elimination kinetics of aspirin in rats were not influenced by an orally administered buffered solution with a buffer capacity of 0.933 mEq ANC (acid neutralizing capacity) per kg of body weight. However, this orally buffered solution did change the gastrointestinal absorption kinetics of aspirin in rats. The absolute bioavailable dose of aspirin was 56.6±10.4% (n=6)following its administration in an unbuffered solution while it was only 31.8±8.0% (n=6)following administration in the buffered solution. The corresponding values of the absolute bioavailable doses were 43.4±3.7% and 25.5±1.8% following intraintestinal administration. The lower systemic availability of aspirin in the presence of buffer is attributed to a greater fraction of the administered dose becoming available for absorption from the intestine where the extraction efficiency is higher than that in the stomach.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01073867
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