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  • 1
    Electronic Resource
    Electronic Resource
    Bioavailability and toxicity of sediment-bound lead to a filter-feeder bivalve Crassostrea gigas (Thunberg) (1995)
    Springer
    BioMetals 8 (1995), S. 280-289 
    Details
    ISSN: 1572-8773
    Keywords: lead ; suspended sediment ; oyster ; bioavailability ; cytopathology ; electron probe microanalysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Two different approaches were used to study the bioavailability of sediment-bound lead. In vitro techniques simulating the potential metal desorption under conditions prevailing in the digestive tract were assayed on a contaminated sediment. An experimental model of a food chain was designed to determine the retention of lead in the soft tissues of oysters according to the environmental source of the metal (water or sediment). Neither enzymatic action nor leaching at low pH (both aspects of digestion) induce the release of important lead amounts from particles. Therefore, after 3 weeks of exposure, the retention of lead from the trophic source is lower (1%) compared with direct contamination (5%). Lysosomes are the major intracellular structures responsible for lead storage in the gills, digestive tract and digestive gland. The abundance of lysosomes and their lead amount vary according to the gross concentrations in the soft tissues. The cytopathological data are in agreement with the results about lead accumulation: in oysters exposed to sediment-bound lead, impairments are not so marked as in individuals contaminated directly from water but the same organelles are concerned. Mitochondrial impairments may be related to the effect of lead on cellular respiration processes and changes involving the granular endoplasmic reticulum may have an effect on the level of protein synthesis. Cellular extrusions carrying away numerous lysosomes loaded with lead could account for the balancing of lead incorporation between 2 and 3 weeks of exposure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00141600
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  • 2
    Electronic Resource
    Electronic Resource
    Thrombospondin co-localises with TGFβ and IGF-I in the extracellular matrix of human osteoblast-like cells and is modulated by 17β estradiol (1995)
    Springer
    Cellular and molecular life sciences 51 (1995), S. 235-244 
    Details
    ISSN: 1420-9071
    Keywords: Human ; bone ; thrombospondin ; growth factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Thrombospondin (TSP) is a multifunctional glycoprotein which is synthesised by several cell types including osteoblasts, and incorporated into the extracellular matrix (ECM) of these cells. The function and regulation of TSP in bone is not clear. In this study, using a long term culture model of human osteoblast-like cells, we examined the distribution of TSP in the ECM and its modulation by added estradiol. In this model the osteoblast-like cells form a regular multilayer which continues to increase in depth up to 50 days post confluence. In the ECM of these cultures and in 19-week fetal bone, the bone markers osteocalcin and alkaline phosphatase were diffusely distributed in the matrix. In contrast, labelling for TSP was concentrated, confined to the banded collagen and its immediately adjacent ECM. This pattern of labelling resembled that of the growth factors transforming growth factorβ-I (TGFβ), and insulin-like growth factor-I (IGF-I), with which TSP label co-localised. Labelling intensities were comparable between fetal bone and the in vitro material for TSP, TGFβ and IGF-I. TSP label was present by 10 days post confluence, reached a maximum by 20 days, and declined slowly thereafter, a time course which was similar to that of IGF-I. Incubation of osteoblast-like cell cultures with 17β estradiol resulted in an increase in multilayer depth and a maximal 3-fold increase in TSP labeling at 30 days as well as approximately 2-fold increases for TGFβ and IGF-I. The dose-response relationship for these responses to estradiol treatment was biphasic with maximal increases at 10−10 M–10−11 M of added estradiol. Treatment with 17α estradiol produced labelling intensities that were not significantly different from controls. Studies with other cell types have suggested that TSP may be involved in modulation of growth factor activity. The similarities between TSP, TGFβ and IGF-I, in terms of their distribution and regulation by 17β estradiol treatment, may indicate a role for TSP in modulating bone cell proliferation and function through interaction with local growth factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01931104
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  • 3
    Electronic Resource
    Electronic Resource
    EDTA soluble protein of human mature normal enamel (1979)
    Springer
    Calcified tissue international 28 (1979), S. 227-231 
    Details
    ISSN: 1432-0827
    Keywords: Enamel ; Human ; Proteins ; Analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Pure human mature enamel was prepared using a careful microdissection technique. After EDTA dissolution, the soluble proteins were recovered representing a concentration of 0.035% in the initial enamel. When the samples were analyzed with polyacrylamide gel electrophoresis, Coomassie Brilliant Blue staining revealed only one sharp fast migrating band, whereas o-toluidine blue, methylene blue, Amido Black 10B, and pyronine red G showed a thin double band at the same migration distance. Ultracentrifugation studies suggested that the proteins were of low molecular weight or of weak density. Absorption spectra showed a strong absorbance at 260 nm. After hydrolysis, amino acid analyses yielded a composition of 25% Gly, 13.5% Glu, 11% Ser, and 11% Pro. Cysteine measured as cysteic acid was present at 2%, and 2% hydroxyproline was found. A carbohydrate content of 15% was estimated by the anthrone method. Glucose, galactose, mannose, and fucose, identified through gas chromatography, were in a molar ratio of 9:4:3:1. Thus the organic matrix of adult human enamel consists of one or possibly two acidic glycoproteins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441240
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  • 4
    Electronic Resource
    Electronic Resource
    Characterization of 12 microsatellite loci of the human MHC in a panel of reference cell lines (1997)
    Springer
    Immunogenetics 47 (1997), S. 131-138 
    Details
    ISSN: 1432-1211
    Keywords: Key words HLA ; Microsatellite loci ; Microsatellite typing ; Human ; MHC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The human genome contains a large number of interspersed microsatellite repeats which exhibit a high degree of polymorphism and are inherited in a Mendelian fashion, making them extremely useful genetic markers. Several microsatellites have been described in the HLA region, but allele nomenclature, a set of broadly distributed controls, and typing methods have not been standardized, which has resulted in discrepant microsatellite data between laboratories. In this report we present a detailed protocol for genotyping microsatellites using a semi-automated fluorescence-based method. Twelve microsatellites within or near the major histocompatibility complex (MHC) were typed in the 10th International Histocompatibility Workshop homozygous typing cell lines (HTCs) and alleles were designated based on size. All loci were sequenced in two HTCs providing some information on the level of complexity of the repeat sequence. A comparison of allele size obtained by genotyping versus that obtained by direct sequencing showed minor discrepancies in some cases, but these were not unexpected given the technical differences in the methodologies. Fluorescence-based typing of microsatellites in the MHC described herein is highly efficient, accurate, and reproducible, and will allow comparison of results between laboratories.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050338
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics, pharmacodynamics and bioavailability of the ACE inhibitor ramipril (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 513-518 
    Details
    ISSN: 1432-1041
    Keywords: Ramipril ; bioavailability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and pharmacodynamics of the prodrug ramipril and its active ACE-inhibiting metabolite ramiprilat were investigated in an open, randomised, three-way cross-over study in 12 healthy male volunteers. Subjects received 2.5 mg ramipril orally, 2.5 mg ramipril intravenously and 2.5 mg ramiprilat intravenously. The absolute bioavailability as judged by ramipril plasma AUC was 15 %, by ramiprilat plasma AUC, 44 %. Ramiprilat formation from intravenous ramipril was 53 % and from oral ramipril 28 %. Urinary recovery of oral ramipril was 23 %, i. v. ramipril 49 %, and i. v. ramiprilat 68 % of the given dose. Maximum ACE inhibition was highest (100 %) after i. v. ramiprilat; it was 99 % after i. v. ramipril and 84 % following oral ramipril. ACE inhibition over 24 h was highest after i. v. ramipril, 2 % less with i. v. ramiprilat and 34 % less with oral ramipril. Ramiprilat renal clearance was concentration dependent. The biological availability of ramipril can best be judged by ramiprilat AUC, urinary recovery of ramipril and metabolites, or ACE inhibition over 24 h. It is concluded that the bioavailability of oral ramipril seems to be in the range of 44–66 %.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193704
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  • 6
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and bioavailability of a sustained-release diltiazem formulation (Mono-Tildiem LP 300 mg) after repeated administration in healthy volunteers (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 259-264 
    Details
    ISSN: 1432-1041
    Keywords: Diltiazem ; sustained-release formulation ; pharmacokinetics ; bioavailability ; bioequivalence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The usual dosage regimen of diltiazem (Tildiem) is 60 mg 3–4 times a day. A sustained-release formulation has been developed (Mono-Tildiem LP 300 mg) in order to allow a single daily administration. Two repeated dosing studies were performed in healthy volunteers. The absolute bioavailability of sustained-release diltiazem LP 300 mg was investigated using concomitant i.v. administration of 13C-labelled drug: absolute bioavailability of the “once a day” formulation was 35%. The second study compared sustained-release diltiazem LP 300 mg with the standard formulation of diltiazem. The results showed that the diltiazem plasma concentrations obtained after the LP formulation remained stable between 2 and 14 h after administration and were compatible with a once a day administration. Relative bioavailability of sustained-release diltiazem LP 300 mg was 79.3% compared with diltiazem. Therefore, a unitary dose of sustained-release diltiazem LP 300 mg was chosen as the dose equivalent to the daily dose administered with the standard diltiazem formulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00198308
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  • 7
    Electronic Resource
    Electronic Resource
    Comparison of the bioavailability of dexibuprofen administered alone or as part of racemic ibuprofen (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 505-511 
    Details
    ISSN: 1432-1041
    Keywords: Ibuprofen ; Dexibuprofen ; enantiomer ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Two bioavailability studies of S(+)-ibuprofen (dexibuprofen) were conducted in healthy volunteers to define the relationship between the bioavailability of the drug after administration of dexibuprofen alone or as part of ibuprofen racemate. Enantioselective plasma drug analysis was used throughout. In the first study, the bioavailability of dexibuprofen from a 400 mg tablet formulation was compared with that from 400 mg in aqueous solution. The tablet formulation did not influence the bioavailability of the drug and dexibuprofen was well absorbed from the gastro-intestinal tract. The second study was divided into three identical parts. Bioavailability of dexibuprofen 200, 400 and 600 mg was compared with its bioavailability from ibuprofen racemate 400, 800 and 1200 mg. The second study showed that the mean relative bioavailability of dexibuprofen to ibuprofen racemate was 0.66, thus enabling the estimation of clinically useful dexibuprofen doses from the usual doses of the racemate. The 95% confidence interval limits did not include 0.5, leading to the conclusion that administering half of the racemate dose would not provide patients with an adequate amount of therapeutically active drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194342
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  • 8
    Electronic Resource
    Electronic Resource
    Temperature dependency of the release and bioavailability of nicotine from a nicotine vapour inhaler; in vitro/ in vivo correlation (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 495-500 
    Details
    ISSN: 1432-1041
    Keywords: Key words Nicotine ; vapour inhaler ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To investigate the temperature dependency of the dose released and the plasma levels of nicotine from a vapour inhaler. Methods: In an open, randomised, three-way cross-over pharmacokinetic study 18 healthy subjects inhaled nicotine for 20 min (80 inhalations) every hour for 10 h (11 administrations) at three different environmental temperatures: 20°, 30° and 40 °C. In the in vitroexperiment, 5, 10, 15 and 20 l air were forced through the inhaler. With a 15 l air volume, the average amount of nicotine released was 1.44, 3.49, 4.80 and 6.99 mg at 10 °C, 22 °C, 29 °C and 40 °C, respectively. The maximum dose released at the highest temperature (40 °C) and the largest air volume investigated (20 l) was approximately 7.5 mg. Results: In vivo peak plasma levels obtained at 30° and 40 °C were 29.7 and 34.0 ng · ml−1, compared with 22.5 ng · ml−1 at ambient room temperature (20 °C). At 20 °C, the area under the plasma concentration–time curve (AUC) of the last dosing interval was 20.5 ng · ml−1 · h. At 30 °C and 40 °C, the AUCs were 26.5 and 30.3 ng · ml−1 · h, respectively. The results thus showed a mean increase of the in vivo AUC by 29% at 30 °C and by 48% at 40 °C compared with the AUC at 20 °C. These increases should be compared to the in vitro results, showing a mean increase of 59% and 122%, respectively, at 30° and 40 °C. The in vitro results also showed that a relatively larger fraction of the dose was released into the first 5 l of air at the higher temperatures, at 40 °C, about 50% of the total amount released into 20 l. Conclusion: It was concluded that the in vitro/in vivo discrepancy was most probably due to increased aversive effects at elevated temperatures, causing the subjects to inhale smaller puff volumes. Further, the inhaler would not produce nicotine plasma levels exceeding those achieved following cigarette smoking, even in a hot climate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050324
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  • 9
    Electronic Resource
    Electronic Resource
    Bioavailability of a new effervescent tablet of ibuprofen in healthy volunteers (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 505-506 
    Details
    ISSN: 1432-1041
    Keywords: Key words Ibuprofen; effervescent tablets ; kinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050327
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  • 10
    Electronic Resource
    Electronic Resource
    Single dose pharmacokinetics of sumatriptan in healthy volunteers (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 543-548 
    Details
    ISSN: 1432-1041
    Keywords: Sumatriptan ; pharmacokinetics ; single dose ; bioavailability ; dose proportionality ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Sumatriptan is classified as a vascular 5HT1 receptor agonist and is effective in the acute treatment of migraine and cluster headache. Sumatriptan is available as an injection for subcutaneous administration and as a tablet for oral administration. The pharmacokinetics of sumatriptan differ depending on the route of administration. The mean subcutaneous bioavilability is 96% compared to 14% for the oral tablet. The lower bioavailability following oral administration is due mainly to presystemic metabolism. The inter-subject variability in plasma sumatriptan concentrations is greater following oral administration and a faster rate of absorption of drug into the systemic circulation is achieved following subcutaneous dosing. The pharmacokinetics of sumatriptan are linear up to a subcutaneous dose of 16 mg. Following oral dosing up to 400 mg, the pharmacokinetics are also linear, with the exception of rate of absorption, as indicated by a dose dependent increase in time to peak concentration. Sumatriptan is a highly cleared compound that is eliminated from the body primarily by metabolism to the pharmacologically inactive indoleacetic acid analogue. Both sumatriptan and its metabolite are excreted in the urine. Although the renal clearance of sumatriptan is only 20% of the total clearance, it exceeds the glomerular filtration rate, indicating that sumatriptan undergoes active renal tubular secretion. Sumatriptan has a large apparent volume of distribution (170 1) and an elimination half-life of 2 h. Oral doses of sumatriptan were administered as a solution of dispersible tablets and subcutaneous dosing was by injection into the arm. In clinical practice, sumatriptan is administered as a film coated tablet or by subcutaneous injection into the thigh.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193709
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  • 11
    Electronic Resource
    Electronic Resource
    Absolute bioavailability and pharmacokinetics of valsartan, an angiotensin II receptor antagonist, in man (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 115-120 
    Details
    ISSN: 1432-1041
    Keywords: Key words Valsartan; pharmacokinetics ; deconvolu‐tion ; healthy volunteers ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics of orally and intravenously administered valsartan were determined in two studies. In a first pilot study, three i.v. doses of valsartan were given in an ascending manner (5, 10 and 20 mg) to evaluate tolerability and basic pharmacokinetics of the i.v. formulation. In a second study, the absolute bioavailability of 80 mg valsartan from a capsule and a buffered solution was compared with a 20 mg i.v. dose. Methods: The concentrations of valsartan in plasma and urine were measured using HPLC. The disposition of valsartan after an i.v. dose was characterized by biphasic decay kinetics, with a distribution phase (half-life 1.0 h), followed by a longer elimination phase (half-life 9.5 h). The volume of distribution at steady state was 16.9 l, and the total body clearance 2.2 l · h−1. 29% of the i.v. dose was recovered unchanged in the urine. Results: Plasma levels peaked 2 h after oral administration of the 80 mg capsule. Thereafter, plasma levels declined biexponentially with a terminal t1/2 of 7.0 h. Cmax was reached 1 h after administration of the solution, and t1/2 was 7.5 h. On average 7.3% (capsule) and 12.6% (solution) of the dose was excreted in the urine as the unchanged drug. The fraction of dose absorbed and systemically available after oral administration was 0.23 for the capsule and 0.39 for the solution, based on AUC. Absorption appeared to follow two first-order processes. The first phase was rapid, with a half-life of 0.5 h and 0.9 h for solution and capsule, respectively. The slower absorption phase was characterized by a half-life of 6.5 h for the solution and 3.5 h for the capsule. Most of the drug was absorbed during the period 0.4 h to 3 h post-dosing, and 90% of the fraction absorbed from the capsule was absorbed within 5 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050259
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  • 12
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and bioavailability of oral and intramuscular artemether (1997)
    Springer
    European journal of clinical pharmacology 52 (1997), S. 307-310 
    Details
    ISSN: 1432-1041
    Keywords: Key words Artemether ; Thai males; malaria ; dihydroartemisinin ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The pharmacokinetics and bioavailability of artemether and dihydroartemisinin were investigated in eight Thai males following the administration of single oral and intramuscular doses of artemether (300 mg) in a randomized two-way cross-over study. Results: Both oral and intramuscular artemether were well-tolerated. In most cases, artemether and dihydroartemisinin were detected in plasma after 30 min and declined to levels below the limit of detection within 18–24 h. Compared with intramuscular administration, oral administration of artemether resulted in a relatively rapid but incomplete absorption [Cmax: 474 vs 540 ng · ml−1; t max: 2.0 vs 3.9 h; AUC: 2.17 vs 5.20 μg · h · ml−1]. Geographic means of lag-time and absorption half-life (t 1/2a) of oral vs intramuscular artemether were 0.28 and 1.1 h vs 0.30 and 2 h, respectively. t 1/2z was significantly shortened after the oral dose [2.8 vs 6.9 h]. Mean oral bioavailability relative to intramuscular administration was 43.2%. The ratio of the AUCs of artemether to dihydroartemisinin was significantly lower after the oral than after the intramuscular dose (geometric mean: 0.29 vs 0.60).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050295
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  • 13
    Electronic Resource
    Electronic Resource
    Influence of milk products on fluoride bioavailability in man (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 211-215 
    Details
    ISSN: 1432-1041
    Keywords: fluoride ; bioavailability ; calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of milk products on the gastrointestinal absorption of fluoride from sodium fluoride tablets was studied in five healthy subjects. Two different diets were tested: (1) 250 ml standardized milk (3% fat) and (2) 500 ml of milk, 3 pieces of white bread with cheese and 150 ml of yoghurt. The 100% bioavailability of sodium fluoride tablets during fasting was greatly decreased by coadministration of milk products: with Diet 1 the absolute bioavailability calculated from combined plasma and urine data was in the range 50–79% and with Diet 2 it ranged from 50–71%. It is suggested that the decreased bioavailability produced by dairy products should be taken into account when establishing fluoride dosage regimens for prophylaxis of caries.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562063
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  • 14
    Electronic Resource
    Electronic Resource
    Effect of lidocaine on the absorption, disposition and tolerance of intramuscularly administered cefoxitin (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 273-279 
    Details
    ISSN: 1432-1041
    Keywords: Cefoxitin ; lidocaine ; intramuscular ; bioavailability ; pain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The use of lidocaine HCl solution at concentrations of 0.5 and 1.0% to reconstitute sodium cefoxitin relieves the pain associated with intramuscular injections of the antibiotic. Cefoxitin absorption by the intramuscular route is initially rapid and is virtually complete. Peak serum concentrations, corresponding to about one-half those of a comparable intravenous infusion, are achieved in 30 min. Continuing absorption tends to maintain higher serum concentrations for longer times. Renal clearance and serum half-life of cefoxitin do not appear to be affected by lidocaine at its effective anaesthetic concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607426
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  • 15
    Electronic Resource
    Electronic Resource
    Bioavailability of p-chlorophenoxyisobutyric acid (clofibrinic acid) after repeated doses of its calcium salt to humans (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 49-53 
    Details
    ISSN: 1432-1041
    Keywords: p-Chlorophenoxyisobutyric acid ; clofibrate ; steady-state plasma concentrations ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations and bioavailability of clofibrinic acid have been estimated under conditions approaching the steady-state during a ten-day period of administration as clofibrate or as a calcium clofibrinate-carbonate combination (1:1 w/w) at a dosage interval of 12 h. Formulation — related differences in bioavailability were not significant, and the 95% confidence limits of these differences were within −2% to +8% of the mean for the reference formulation of clofibrate. The mean steadystate plasma concentrations of clofibrinic acid measured on the tenth day of dosing were 116 µg/ml±22 S.D. and 119 µg/ml±23 S.D. after administration of 885 mg as clofibrate and the calcium clofibrinate-carbonate combination respectively. The peaks of mean plasma concentrations were 70 µg/ml±15 S.D., 119 µg/ml±32 S.D. and 131 µg/ml±26 S.D. on the first, fifth and tenth day of dosing with clofibrate, and 62 µg/ml±13 S.D., 127 µg/ml±S.D. and 143 µg/ml±25 S.D. on the corresponding days of dosing with the calcium clofibrinate-carbonate combination. After the last dose on the tenth day of dosing, the mean apparent half-lives of elimination of clofibrinic acid from plasma were 24.2 h±4.4 S.D. and 25.5 h±3.2 S.D. after administration of clofibrate and the calcium clofibrinate-carbonate combination respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606682
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  • 16
    Electronic Resource
    Electronic Resource
    Gastrointestinal absorption of hydrochlorothiazide enhanced by concomitant intake of food (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 125-128 
    Details
    ISSN: 1432-1041
    Keywords: bioavailability ; diuretics ; gastrointestinal absorption ; hydrochlorothiazide ; thiazides ; food effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Hydrochlorothiazide (hct) 75 mg was administered orally to eight healthy volunteers without (Study I) or together with a standardized meal (Study II), and plasma and urine concentrations of hct were analyzed by GLC. The plasma levels of hct were higher initially when the tablets were taken on an empty stomach, but after 5 h they were higher in Study II. There was no difference between the two studies in the area under plasma concentration time curves. The urinary recovery of hct totalled 55.6±4.9 mg when the drug was given with food and 47.4±6.0 when it was taken on an empty stomach. The difference is significant (p〈0.01). As the urinary recovery represents the uptake of hct, it appears that the gastrointestinal absorption of hct is enhanced when the drug is given with food.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609756
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  • 17
    Electronic Resource
    Electronic Resource
    Evaluation of medigoxin in outpatients (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 251-258 
    Details
    ISSN: 1432-1041
    Keywords: medigoxin ; digoxin ; dissolution rate ; proportionality ; bioavailability ; prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We compared our ability to predict the dose of medigoxin and of digoxin required to achieve a fixed serum concentration (the dose requirement) in 33 outpatients. Preliminary work supported the assumptions that the steady state glycoside concentration achieved was proportional to the daily dose given to an individual, and that the bioavailability of the different tablet presentations was similar for either glycoside. We were not able to predict the dose requirement from patient characteristics with any more certainty for medigoxin than for digoxin. Not only the between-patient variability in dose requirement, but also the within-patient variability, was similar for the two glycosides. However the digoxin used had a dissolution rate of over 90% in 1 h. When comparing medigoxin with digoxin of lower, or more variable dissolution rate, medigoxin may be preferable.
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    URL: http://dx.doi.org/10.1007/BF00562801
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    Comparative bioavailability of a microcrystalline theophylline tablet and uncoated aminophylline tablets (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 417-421 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; aminophylline ; bioavailability ; rapidly dissolving tablet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of a rapidly dissolving tablet of theophylline and three brands of standard aminophylline tablets was estimated in a four way cross-over study involving 8 healthy adult volunteers. The relative extent of bioavailability as assessed by the measurement of the total area under the plasma concentration time curves showed no difference between the products (P〉0.05). Computed estimates of the rate of drug absorption were similar for all 4 products tested. The results indicate that the rapidly dissolving tablet offers no advantage in respect to rate and extent of absorption over conventional aminophylline tablets.
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    URL: http://dx.doi.org/10.1007/BF00568203
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  • 19
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    Bioavailability of metronidazole in fasting and non-fasting healthy subjects and in patients with Crohn's disease (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 69-72 
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    ISSN: 1432-1041
    Keywords: Metronidazole ; serum concentration ; bioavailability ; food intake ; healthy subjects ; Crohn's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The possible influence of food intake on the bioavailability of metronidazole was examined in ten healthy volunteers by administration of a single dose of metronidazole on an empty stomach, and with a standardized breakfast. Food intake did not significantly alter the bioavailability of metronidazole. The interindividual variation in bioavailability appeared to be slight. In nine patients with Crohn's disease, the absorption of metronidazole appeared to be reduced and to be more variable than in healthy subjects. In both groups there was a clear relationship between the amount absorbed and dose/kg body weight. Thus, from the pharmacokinetic point of view, metronidazole can safely be given either with or between meals. The dose should be related to body weight.
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    URL: http://dx.doi.org/10.1007/BF00561408
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  • 20
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    Bioavailability of three phenytoin preparations in healthy subjects and in epileptics (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 285-290 
    Details
    ISSN: 1432-1041
    Keywords: Phenytoin acid ; phenytoin calcium ; bioavailability ; inequivalence of generics ; normal subjects ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum phenytoin concentrations have been studied in epileptic patients and healthy subjects taking tablets of phenytoin calcium (Desitin), A, phenytoin acid (Desitin), B, and phenytoin acid (Nordmark), C. Retrospective data and prospective investigation of hospitalized patients on long-term phenytoin treatment showed that significantly higher serum concentrations of phenytoin were produced by the phenytoin acid preparations B and C than by the phenytoin calcium preparation A. In a cross over study six volunteers received 200 mg/day of preparations A, B, and C for three weeks. In this study, too, higher phenytoin serum concentrations were produced by B and C than by A, although the differences were not statistically significant. The reasons for the discrepancies between the studies in healthy and epileptic subjects are discussed.
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    URL: http://dx.doi.org/10.1007/BF00607428
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  • 21
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    Human pharmacokinetics and bioavailability of temazepam administered in soft gelatin capsules (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 383-386 
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    ISSN: 1432-1041
    Keywords: Benzodiazepine ; temazepam ; pharmacokinetics ; bioavailability ; hard and soft gelatine capsules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels of temazepam were determined in healthy subjects after single oral administration of soft and hard gelatin capsules, and after 7 consecutive night-time doses in soft capsules. Absorption from soft gelatin capsules was significantly faster and produced earlier and higher peak plasma levels. The two pharmaceutical forms did not show any significant difference in relative availability. The apparent half-life of temazepam after night-time administration was significantly shorter than after morning administration, but no change in half-life was observed between the first and seventh night-time doses.
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    URL: http://dx.doi.org/10.1007/BF00562455
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  • 22
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    Dose tolerance and pharmacokinetic studies of L (+) pseudoephedrine capsules in man (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 253-259 
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    ISSN: 1432-1041
    Keywords: Pseudoephedrine ; side effects ; bioavailability ; multiple oral dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Dose tolerance and pharmacokinetic studies of pseudoephedrine sustained action capsules were performed in thirty-three adult male subjects who received either 120 mg or 150 mg capsules every twelve hours for seven consecutive days in a double-blind parallel design study. Although only one subject in the 150 mg group was discontinued prematurely from this study, a large number of side effects typical of CNS stimulation were seen. A placebo effect might account for a portion of these complaints, however symtoms evaluated as being due to drug were significantly more severe and persistent in the 150 mg group. Pulse rates showed a persistent and significant increase while systolic and diastolic blood pressure fell from the baseline values in both groups. A pharmacokinetic analysis of the pseudoephedrine plasma concentration-time data provided estimates of half-life and the volume of distribution/availability ratio. The values obtained were in good agreement with values reported by others. Half-life was not influenced by urine pH probably as a result of the narrow range of urine pHs observed in the subjects. Calculations of relative bioavailability suggest that the 120 mg capsule formulation has a 30% greater bioavailability compared to the 150 mg capsule.
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    URL: http://dx.doi.org/10.1007/BF00560458
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  • 23
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    Absolute bioavailability of chlorthalidone in man: A cross-over study after intravenous and oral administration (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 35-50 
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    ISSN: 1432-1041
    Keywords: chlorthalidone ; pharmacokinetics ; oral and i.v. doses ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven normal human volunteers each received a constant-rate infusion of chlorthalidone for 2 h, and the same (commonly 50 mg) single oral dose on separate occasions. The concentration of unchanged chlorthalidone was analyzed over a 100 to 220 h period in plasma, red blood cells, urine and faeces after both dosage forms. A three compartment model was required to describe the intravenous plasma concentrations in five of the subjects. A two compartment model sufficed to account for the decay of the oral plasma concentrations in all seven subjects. The mean plasma t1/2 after i.v. dosing was 36.5 h (±10.5 SD), and the mean plasma t1/2 after oral doses was 44.1 h (±9.6 SD). The mean red blood cell concentration t1/2 after i.v. doses was 46.4 h (±9.9 SD), and the mean red blood cell t1/2 after the oral doses was 52.7 h (±9.0 SD). The shorter i.v. half-live was not equally manifest in all subjects, being mainly apparent in three of them. In all cases the urinary excretion rate plots were parallel to the plasma concentration curves. As the faster decay after i.v. administration was not accompanied by increased renal clearance, the difference must have been due to non-renal mechanism. The mean total of 65.4 (±8.6 SD) % of the intravenous dose was excreted in urine over infinite time, whereas the mean total excretion after the oral dose was 43.8 (±8.5 SD) %. Faecal excretion ranged from 1.3–8.5% of dose in the i.v. study to 17.5–31.2% of dose in the oral study. The sum of the amounts present in urine plus faeces pointed strongly to an important metabolic route of elimination of chlorthalidone. Bioavailability estimates (F) from three sets of data were — a mean F of 0.61 from plasma concentrations, 0.67 from urinary excretion measurements and 0.72 from the erythrocyte concentrations. Simulations with a non-linear model indicated lesser validity of the estimate from erythrocyte concentrations. It was concluded that the average of plasma and urine data, F=0.64, yielded the best estimate of the oral availability of chlorthalidone 50 mg in man.
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    URL: http://dx.doi.org/10.1007/BF00563556
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  • 24
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    Disposition pharmacokinetics of bezafibrate in man (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 31-38 
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    ISSN: 1432-1041
    Keywords: bezafibrate ; hyperlipoproteinemia ; bioavailability ; pharmacokinetics ; GC-MS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition kinetics of bezafibrate, a newly developed drug of great lipid-lowering potency, were investigated in normal male subjects. Five male volunteers received14C-labelled bezafibrate orally in solution, and a further 10 were given the same dose (300 mg) of un-labelled drug as tablets. The concentration of bezafibrate in serum and urine from the latter was determined by GC, and in the former total radioactivity in serum, urine and feces was followed for 48 h, and urinary excretion products were analysed by TLC and GC-MS. Rapid absorption from the gastrointestinal tract led to peak serum levels 30 min and 2 h after administration of solution and tablets, respectively. Since approximately 95% of the administered14C-bezafibrate was excreted in urine within 48 h, and almost all the remainder was detected in feces, absorption can be regarded as complete after administration in solution. The relative optimal bioavailability from the tablets was also complete, since in both cases approximately 50% of the administered dose was detected as unchanged bezafibrate in urine within 24 h by GC in the tablet study, and by TLC in the solution study. Of the decomposition products, more than 20% of the dose was present as glucuronides and the remainder consisted of several more polar compounds, one of which was identified as a hydroxyderivative of bezafibrate. Since the apparent halflife of bezafibrate in serum was 2.1 h, this new drug possesses favourable pharmacokinetic features: rapid and complete absorption, even from tablets, combined with a conveniently short half-life, and clearance which is half renal (56 ml/min) and half metabolic (43 ml/min), giving a total clearance of 99 ml/min.
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    URL: http://dx.doi.org/10.1007/BF00644963
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  • 25
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    Pharmacokinetic, bioavailability and pharmacodynamic study of indobufen (K 3920), an inhibitor of platelet aggregation, after a single dose in man (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 323-327 
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    ISSN: 1432-1041
    Keywords: indobufen ; platelet aggregation ; single dose ; bioavailability ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six healthy volunteers received single iv and oral doses of 2-[p-(1-oxo-2-isoindolinyl)phenyl] butyric acid 100 mg (indobufen; K 3920), an inhibitor of platelet aggregation. Plasma levels and urinary excretion of the drug were determined by GLC. Collagen-induced platelet aggregation was assessed turbidimetrically at various intervals after administration. The plasma half-life of the drug was 7–8 h and more than 70% of the administered dose was recovered within 48 h in urine, as unchanged drug and as the glucuronide of indobufen. After oral administration of tablets of two different formulations, the drug was completely absorbed, but one formulation showed faster absorption. The maximal inhibitory effect on platelet aggregation was observed 1 to 4 h after iv administration, and it had decreased by 8 h. After tablets, peak effect and the time of the peak were similar, but activity was significantly prolonged, in accordance with the higher plasma levels found at 8 h. The data suggest that the effect of indobufen on platelets is reversible, and that for this drug platelets behave as a compartment that slowly equilibrates with plasma.
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    URL: http://dx.doi.org/10.1007/BF00558435
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  • 26
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    Absolute bioavailability of quinidine in two sustained release preparations (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 45-48 
    Details
    ISSN: 1432-1041
    Keywords: quinidine ; slow release formulation ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of quinidine in two sustained release preparations A and B has been compared in three females and three males with i.v. administration of quinidine. The initial rate of oral absorption did not differ between the two drug preparations; the peak concentration was observed after 4 h both for A and B, but was significantly higher after B. A slower decrease in plasma concentration was observed after preparation A than B. Absolute bioavailability did not differ significantly between A (median value 78.4%) and B (median 87.1%). Drug absorption in vivo was in good agreement with the results of in vitro dissolution tests on both preparations. The slower decrease in plasma concentration found for the new sustained release form of quinidine should be of clinical advantage.
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    URL: http://dx.doi.org/10.1007/BF00644965
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  • 27
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    Effect of dose on bioavailability of oral digoxin (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 53-55 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; bioavailability ; dose-dependency ; urinary excretion ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine healthy volunteers received single 0.25, 0.5, 1.0, 1.5, and 2.0 mg doses of oral digoxin tablets in random sequence on five occasions separated by at least 4 weeks. Urinary excretion of immunoassayable digoxin was determined from 8 consecutive 24 h urine samples collected after each dose. Mean values of cumulative urinary excretion of digoxin at the 5 doses were: 40.9, 35.6, 36.4, 34.1, and 33.5% of the dose (F=0.64; d. f.=4.32; N. S.). Mean values of urinary excretion half-life were: 2.48, 2.03, 2.20, 2.07, and 1.87 days (F=2.87; d. f.=4.32;p=0.05). Thus, the bioavailability of orally administered digoxin tablets in healthy volunteers is dose-independent over an 8-fold range of doses.
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    URL: http://dx.doi.org/10.1007/BF00558384
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  • 28
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    Pharmacokinetics and bioavailability of diacetolol, the main metabolite of acebutolol (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 287-292 
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    ISSN: 1432-1041
    Keywords: diacetolol ; acebutolol ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of diacetolol, the principal metabolite of acebutolol, were studied in 6 healthy subjects. Plasma concentrations were determined following a single intravenous injection of diacetolol 100 mg and three oral doses of diacetolol 100, 400 and 800 mg, in random order. The average oral bioavailability of diacetolol was F: 0.302±0.052 (100 mg), 0.363±0.052 (400 mg) and 0.426±0.068 (800 mg); the differences are not significant. The mean plasma half-life of the terminal phase, 7.94±0.26 h after intravenous administration, was significantly higher than after oral administration 12.27±1.00 h (100 mg), 12.82±1.59 h (400 mg) and 13.05±1.22 h (800 mg) (p〈0.02 to 0.05); the mean urine half-lives of the terminal phase were not significantly different. Renal clearance of diacetolol 10.2±0.81·h−1 represented about two-thirds of total body clearance 15.9±1.21·h−1. The results suggest either a first-pass effect or incomplete absorption of diacetolol after oral administration.
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    URL: http://dx.doi.org/10.1007/BF00562806
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  • 29
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    Bioavailability of ketoprofen in man with and without concomitant administration of aluminium phosphate (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 305-307 
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    ISSN: 1432-1041
    Keywords: ketoprofen ; aluminium phosphate ; bioavailability ; antacid ; pharmacokinetics ; interaction study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The purpose of this study was to determine whether a concomitant single dose of antacid (aluminium phosphate), or multiple doses of this antacid, administered prior to and with ketoprofen would alter the bioavailability of this non steroidal anti-inflammatory agent. The possible effects of aluminium phosphate were evaluated following administration of ketoprofen alone (Phase I), co-administration of antacid and ketoprofen (Phase II), and antacid for four days before administration of ketoprofen with co-administration on the day of the study (Phase III). There were no significant differences between treatment means for peak plasma concentration, time to peak plasma concentration, and area under the plasma concentration-time curve. The observed differences were due only to individual effects. The results indicate a lack of interaction between ketoprofen and the antacid aluminium phosphate (Phosphalugel)
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  • 30
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    Human pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 359-365 
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    ISSN: 1432-1041
    Keywords: tolfenamic acid ; anti-inflammatory agent ; human pharmacokinetics ; bioavailability ; intravenous administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent was studied in six healthy volunteers after an intravenous dose of 100 mg and oral doses of 100, 200, 400 and 800 mg. The disposition of intravenous tolfenamic acid could be described by two-compartment open model, with a central compartment volume (Vdc) of 5.6±0.31 (mean±SE), volume during β-phase (Vdβ) of 31±21, and a total elimination rate constant (k10) 1.6±0.1 h−1. The terminal elimination half-life was 2.5±0.6 h and the total plasma clearance 155±15 ml/min. The elimination occured principally by extrarenal mechanisms, the recovery of unchanged drug together with is glucuronide in urine averaging only 8.8% of the intravenous dose. The binding of tolfenamic acid to plasma proteins averaged 99.7%. The gastrointestinal absorption had a mean half-life of 1.7±0.1 h. Based on comparison of areas under the plasma concentration time-curves after intravenous and oral administration, the biovailability of tolfenamic acid capsules averaged 60%. The rate and extent of absorption and the rate of elimination of tolfenamic acid were independent of dose.
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    Pharmacokinetics and bioavailability of tranexamic acid (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 65-72 
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    ISSN: 1432-1041
    Keywords: tranexamic acid ; pharmacokinetics ; bioavailability ; oral absorption ; influence of food ; plasma clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Tranexamic acid 1 g was given intravenously to three healthy volunteers. Plasma concentrations decayed in three monoexponential phases. Most elimination took place during the first eight hours, giving an apparent elimination half-life of approximately two hours. Plasma clearance ranged between 110–116 ml/min. The urinary recovery of tranexamic acid exceeded 95% of the dose. Ten healthy volunteers were given tranexamic acid 2 g orally on an empty stomach, and together with a meal. Food had no influence on the absorption of tranexamic acid, as judged by comparison of the peak plasma concentration, the time required to reach the peak, the AUC from zero to six hours, and the urinary excretion data. The oral bioavailability of tranexamic acid, calculated from 24 h urinary excretion after oral and intravenous administration, was 34% of the dose.
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  • 32
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    A comparison of the bioavailability and potency of dexamethasone phosphate and sulphate in man (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 277-282 
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    ISSN: 1432-1041
    Keywords: dexamethasone phosphate ; dexamethasone sulphate ; intravenous injection ; bioavailability ; pituitary-adreno-cortical suppression ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolic fate and ACTH-supressant activity of two injectable dexamethasone esters, 21-phosphate and 21-sulphate, were studied in healthy men. After i.v. injection of 20 mg free steroid alcohol, dexamethasone phosphate was efficiently hydrolyzed to free dexamethasone, reaching its peak plasma concentration within 5 min. About 9% of the administered dose appeared in the urine as free dexamethasone. By contrast, virtually no free dexamethasone was found in plasma and urine after injection of dexamethasone sulphate. Pharmacokinetic analysis showed that dexamethasone sulphate had a shorter plasma half-life and a higher metabolic clearance rate than free dexamethasone. A larger fraction (60%) of dexamethasone sulphate was rapidly excreted unmetabolized in urine. The plasma cortisol level was significantly suppressed for more than 24 h after dexamethasone phosphate, while the plasma cortisol profile after dexamethasone sulphate merely showed physiological circadian variations. When the steroid esters were injected after pretreatment with metyrapone, a definite suppression of plasma ACTH was noted after dexamethasone phosphate, but again, dexamethasone sulphate was ineffective. These results cast serious doubt on the clinical value of dexamethasone sulphate as an injectable glucocorticoid, and critical reevaluation of this preparation is needed.
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  • 33
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    Single-dose pharmacokinetics of metoclopramide (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 465-471 
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    ISSN: 1432-1041
    Keywords: metoclopramide ; pharmacokinetics ; bioavailability ; first-pass effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time courses of plasma metoclopramide concentrations were followed in six subjects after oral and intravenous single dose administration. Plasma concentration-time data following i.v. administration in each subject were found to fit a two compartment model with a mean terminal half-life of 4.55 h±0.80 h and a mean distribution half-time of 0.35 h±0.09 h. Volumes of distribution were high (3.43±1.181 · kg−1), and clearances (0.53±0.191 · kg−1h−1) approached liver plasma flow. This suggests that metoclopramide occurs at higher concentrations in tissues than in plasma, and that its clearance is probably limited by liver blood flow rather than liver metabolic capacity. The post-absorption decline in metoclopramide plasma levels after oral administration was also biexponential in each subject. The terminal half-life was 5.17 h±0.98 h. Mean volume of distribution and mean clearance were similar to intravenous values (after adjustment for bioavailability). Oral absorption was rapid with peak plasma concentrations being reached at a mean time of 0.93 h. A mean bioavailability of 0.77 was calculated for the six subjects, and it was postulated that this incomplete availability is due to a first-pass effect. The inter-individual variation in the degree of ‘first-pass’ was considerable (0.47–1.14).
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    URL: http://dx.doi.org/10.1007/BF00542101
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  • 34
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    Single dose pharmacokinetics and bioavailability of methadone in man studied with a stable isotope method (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 473-478 
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    ISSN: 1432-1041
    Keywords: methadone ; bioavailability ; pharmacokinetics ; single dose ; stable isotope technique ; two compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of methadone was studied in eight opiate dependent subjects during detoxification. Plasma concentrations were determined by mass fragmentography for 48 hours after administration of methadone 20 mg as tablets and simultaneous intravenous injection of deuterium-labelled methadone 20 mg. Pharmacokinetic parameters were calculated for the intravenous dose assuming a two compartment open model. Bioavailability was determined by comparing the areas under the plasma concentration versus time curves of unlabelled and labelled methadone. The beta-phase plasma half-lives varied five-fold, with a range from 8.5 to 47 h. The apparent volumes of distribution varied from 2.1 to 5.61/kg. Five patients had a bioavailability exceeding 90%, and three had lower bioavailabilities of between 41 and 76%. The unlabelled and labelled drug appeared to be pharmacokinetically equivalent. The data show that for a majority of these subjects the bioavailability was higher than 45%, the previously reported value. The marked individual variation in methadone pharmacodynamics and kinetics, and the possibilities both of cellular and methabolic tolerance, require an individually optimized dosage regimen.
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  • 35
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    Relative bioavailability of cyclosporin from conventional and microemulsion formulations in heart-lung transplant candidates with cystic fibrosis (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 285-289 
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    ISSN: 1432-1041
    Keywords: Cyclosporin ; Cystic fibrosis ; pharmacokinetics ; bioavailability ; formulation ; transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Patients with cystic fibrosis absorb cyclosporin poorly and erratically. We have compared the relative bioavailability of cyclosporin from conventional and microemulsion formulations in 5 adult heart-lung transplant candidates with cystic fibrosis. Relative bioavailability was compared at two dose levels (200 mg and 800 mg). A randomized 4-period cross-over study was performed with at least a 7 days washout period between each single dose pharmacokinetic study. Blood cyclosporin concentrations were measured by a selective monoclonal antibody-based radioimmunoassay. The bioavailability of cyclosporin from the microemulsion formulation was 1.84 (95% C.I. 1.05 to 3.22; P−0.04) and 2.09 (95% C.I. 0.95 to 4.61; P−0.06) times higher compared with the conventional formulation at 200 mg and 800 mg respectively. Cmax following the microemulsion formulation was 3.38 (C.I. 1.14 to 10.59; P−0.04) and 2.77 (C.I. 1.48 to 5.19; P−0.01) times higher compared with the conventional formulation at 200 mg and 800 mg respectively. The higher Cmax following the microemulsion formulation was accompanied by shorter tmax. An enhancement of cyclosporin absorption with the microemulsion formulation was demonstrated in each patient for at least one dose level. We conclude that rate and extent of cyclosporin absorption from the microemulsion formulation is greater compared with the conventional formulation in patients with cystic fibrosis. The potential therapeutic and economic benefits of the micro-emulsion formulation should be evaluated in cystic fibrosis patients following heart-lung transplantation.
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    URL: http://dx.doi.org/10.1007/BF00198313
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    Bioavailability and pharmacokinetics of cimetidine (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 335-340 
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    ISSN: 1432-1041
    Keywords: cimetidine ; enterohepatic circulation ; irregular absorption ; bioavailability ; pharmacokinetics ; volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability and pharmacokinetics of cimetidine have been studied in healthy volunteers after administration of single intravenous (100 mg) and oral doses (100, 400 and 800 mg). After i.v. administration, the kinetics of cimetidine could be described by a linear, two compartment open model. Substantial variation in half-life was observed between subjects, with a mean value of 2.1 h (range 0.9–4.7). Cimetidine had a low hepatic extraction ratio and a high total plasma clearance, due to extensive urinary excretion of unchanged drug. After oral administration, the plasma concentration vs time curves in most subjects exhibited two marked peaks, an observation that seemed to be constant within individuals and was independent of dose. Bioavailability, estimated as the area under the plasma concentration vs time curves (AUC), after oral doses as compared to the intravenous dose, in most cases exceeded 100%. There was no correlation between bioavailability estimated as AUC and as urinary excretion of unchanged drug. These observations may indicate an enterohepatic circulatory mechanism, predominantly after oral administration. Both unchanged drug and its sulphoxide metabolite appear to be excreted in bile. The latter was shown in vitro to be reduced to cimetidine by fecal bacteria.
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    Absorption of oral and intramuscular chlordiazepoxide (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 267-274 
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    ISSN: 1432-1041
    Keywords: Chlordiazepoxide ; benzodiazepines ; pharmacokinetics ; bioavailability ; intramuscular injection ; alcohol withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of oral and intramuscular (i. m.) chlordiazepoxide hydrochloride (CDX · HCl) was compared in two pharmacokinetic studies. In Study One, single 50-mg doses of CDX · HCl were administered orally and by i. m. injection to 14 healthy volunteers using a crossover design. Whole-blood concentrations of chlordiazepoxide (CDX) and its first active metabolite, desmethylchlordiazepoxide (DMCDX), were determined in multiple samples drawn after the dose. Mean pharmacokinetic variables for CDX following oral and i. m. administration, respectively, were: highest measured blood concentration, 1.65 vs 0.87 µg/ml (p〈0.001); time of highest concentration, 2.3 vs 7.6 h after dosing (p〈0.001); apparent absorption half-life, 0.71 vs 3.39 h (p〈0.001). Biphasic absorption after i. m. injection, consistent with precipitation at the injection site, was observed in 9 of 14 subjects. Based upon comparison with previous intravenous data, the completeness of absorption was 100% for oral vs 86% for i. m. CDX · HCl (p〈0.1). In Study Two, 28 male chronic alcoholics with clinical manifestations of the acute alcohol withdrawal syndrome were randomly assigned to one of four treatment conditions: 50 or 100 mg doses of CDX · HCl, by mouth or by i. m. injection. Concentrations of CDX and DMCDX, determined in plasma samples drawn every 20 min for 5 h following the dose, were significantly higher after oral administration of a given dose than at corresponding points in time after i.m. injection after the same dose. Thus absorption of oral CDX is reasonably rapid and complete, whereas the absorption rate of i. m. CDX is slow.
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    URL: http://dx.doi.org/10.1007/BF00716362
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    Simultaneous determination of the intravenous and oral pharmacokinetic parameters of D,L-verapamil using stable isotope-labelled verapamil (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 133-137 
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    ISSN: 1432-1041
    Keywords: verapamil ; pharmacokinetics ; bioavailability ; hepatic first-pass metabolism ; stable isotopes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Following i. v. administration, the plasma concentration-time curve of verapamil could best be described by either a mono- or biexponential equation. Total plasma clearance (1.26 l/min) approached liver blood flow (1.5 l/min), so it can be concluded that its clearance is liver blood flow-dependent. Although absorption was almost complete after oral administration, absolute bioavailability (20%) was low, due to extensive hepatic first-pass metabolism. The approach using stable isotope-labelled and unlabelled drug permits simultaneous administration by the intravascular and extravascular routes, thus allowing determination of absolute bioavailability in a single experiment.
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    URL: http://dx.doi.org/10.1007/BF00568400
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    Pharmacokinetics of proxyphylline in adults after intravenous and oral administration (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 149-155 
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    ISSN: 1432-1041
    Keywords: proxyphylline ; asthma ; pharmacokinetics ; bioavailability ; healthy adults ; theophylline derivative
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum concentrations and urinary excretion of proxyphylline have been measured in five healthy adults after intravenous (29 µmol/kg), single oral (21 µmol/kg) and multiple oral (21 µmol/kg three times a day) doses to produce steady state. The mean peak time after oral administration was 29 min. The mean fraction absorbed was 1.09 calculated from serum concentrations, and 1.05 calculated from urinary excretion of the drug. The apparent volume of distribution was 0.61 l/kg (0.53–0.72 l/kg), 26% higher in males than in females. A two-compartment open model was found to describe the decline in the serum concentrations, giving a mean distribution half-life of 6 min. The intersubject ranges of biological half-life were 8.1–12.1 h and 8.3–12.6 h calculated from serum and urine data, respectively. 24% (18–29%) of the dose was excreted unchanged in urine, which agreed with the relationship between the calculated total body clearance and the renal clearance of the drug.
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    Influence of phenobarbital treatment on cimetidine kinetics (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 343-347 
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    ISSN: 1432-1041
    Keywords: cimetidine ; phenobarbital ; gastro-intestinal absorption ; bioavailability ; renal clearance ; non-renal clearance ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of orally administered cimetidine was studied in 8 healthy subjects before and after 3 weeks of treatment with phenobarbital 100 mg daily, and in a separate study 4 subjects received cimetidine intravenously before and after the administration of phenobarbital. There was no change in the volume of distribution, but total plasma clearance was increased by a mean of 18%, mainly due to a 37% increase in nonrenal clearance. Renal clearance and half-life were not significantly altered. The area under the plasma concentration-time curve after oral administration was significantly (P≪0.05) reduced by a mean of 15% after phenobarbital treatment. The amount of cimetidine excreted in urine and its sulphoxide metabolite were significantly (P〈0.05) reduced, on average by 34% and 26%, respectively by phenobarbital treatment. The data indicate that an apparent 20% reduction in the absorption of cimetidine was due to induction of gastrointestinal metabolism of cimetidine, with some contribution also from hepatic metabolism. Reduced absorption per se could not be totally excluded. Although the magnitude of the change was small, the finding of an 11% decrease in the time to achieve an effective plasma level of cimetidine after phenobarbital treatment may contribute to the ineffectiveness of cimetidine in certain patients.
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  • 41
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    Influence of food on the absorption of phenytoin in man (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 269-274 
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    ISSN: 1432-1041
    Keywords: phenytoin ; food-intake ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of food intake on the absorption of phenytoin was examined in eight healthy volunteers, by study of single-dose kinetics following ingestion of phenytoin 300 mg either with a standardized breakfast or on an empty stomach. Blood samples were collected at regular intervals from 0 to 48 h, and serum concentrations of unmetabolized phenytoin were determined by gas chromatography. Serum concentrations of the major metabolite of phenytoin, 4-hydroxyphenytoin, were measured by mass fragmentography. Concurrent intake of food and phenytoin appeared to accelerate absorption of the drug from the formulation used, and the peak concentrations were significantly higher (mean increase 40%) in the postprandial than in the preprandial state. As reflected by the AUC (area under the curve), the amount of drug absorbed was increased during postprandial conditions, although the difference only reached borderline significance. It is suggested that phenytoin should always be taken in a defined relation to meals.
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    Absorption of quinidine from an enteric-coated preparation (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 107-112 
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    ISSN: 1432-1041
    Keywords: quinidine ; enteric-coated tablets ; bioavailability ; gastric emptying ; pH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of quinidine from single and multiple doses of an enteric-coated preparation (Systodin®) was studied in seven healthy subjects, and was compared with the pharmacokinetics of intravenously administered quinidine and the results of in vitro dissolution tests of the tablets. Absorption of quinidine began after a variable delay, 2–8 h (mean 4.8) after fasting and 3–10 h (mean 6.1) after food. The rate of absorption varied both in and between individuals. It appeared to be lower when the drug was administered after food. Multiple doses after food gave a pattern of plasma concentration-time curves similar to that found on administration of single doses after food. The delay prior to absorption was prolonged at night. The ratio between the maximum and minimum concentration of quinidine during a dose interval varied from 1.3 to 3.2 (mean 2.0). Bioavailability of quinidine in fasting subjects ranged from 69 to 95% (mean 83); variation was greater when doses were administered after food. The release of quinidine from the enteric-coated preparation was pH dependent and was sustained at low pHs as may be found in the intestines. The results indicate that the absorption of quinidine from the enteric-coated formulation was dependent on the highly variable rate of gastric emptying and the pH of intestinal fluid, and it varied greatly both within and between individuals.
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    Pharmacokinetics of prazepam in man (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 141-147 
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    ISSN: 1432-1041
    Keywords: prazepam ; N-desmethyldiazepam ; bioavailability ; pharmokinetics ; electron-capture gasliquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An original electron-capture gas chromatographic assay was developed for simultaneous measurement of plasma levels of the benzodiazepine derivative prazepam and of its principal unconjugated metabolite, N-desmethyldiazepam. The assay was used to study the pharmacokinetics of the drug and its comparative bioavailability from tablets and from a specially prepared solution. Nine healthy adult volunteers were studied. Each volunteer on one occasion took 30 mg of the drug in tablet form, and on another occasion 30 mg of the drug in solution. In all subjects, N-desmethyldiazepam appeared in plasma shortly after prazepam appeared and reached a peak within four hours of prazepam ingestion. Thereafter plasma N-desmethyldiazepam levels were much higher than plasma prazepam levels throughout. Prazepam became undetectable within six hours of intake, whereas its metabolite could still be measured in plasma fourteen days after dosage. Thus much of the pharmacological action of prazepam may be mediated through its metabolite, N-desmethyldiazepam. In five of the nine subjects, areas under the plasma level curves for the metabolite were not markedly different for the tablet and solution formulations studied. In the other four subjects the area under the curve for the tablets was 50% to 80% of the area under the curve for the solution. The time to reach peak plasma level for the metabolite was shorter after the solution formulation (mean 2.0±SD 1.2 h) than after the tablet formulation (mean 4.2±SD 1.7 h).
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    Serum theophylline levels after use of an anhydrous crystalline theophylline suppository (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 449-452 
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    ISSN: 1432-1041
    Keywords: theophylline ; ethylenediamine ; suppository ; serum concentration ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of theophylline from a suppository not containing ethylenediamine was tested in 9 healthy volunteers. AUC after rectal administration of anhydrous crystalline theophylline 250 mg (AUCrectal) was compared with the AUC after oral administration of microcrystalline theophylline 250 mg (Nuelin®; AUCoral) in a randomized, cross-over study. The ratio AUCrectal/AUCoral was 0.75 at 10 h, and the ratio AUCrectal×βrectal/AUCoral×βoral extrapolated to infinite time was 0.83. A mean concentration of 5.7 µg/ml was reached 3.7 h after a single rectal dose. The absorption studies were performed with suppositories stored for 15 weeks at 22 °C. No effect on the in vitro release rate of theophylline from the suppository was observed during storage at room temperature from 3 to 31 weeks after production. Since aminophylline suppositories are known to decompose upon storage, the results suggest that a formulation without ethylenediamine is preferable for the rectal administration of theophylline.
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    URL: http://dx.doi.org/10.1007/BF00542098
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    The clinical pharmacokinetics of buflomedil in normal subjects after intravenous and oral administration (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 459-463 
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    ISSN: 1432-1041
    Keywords: buflomedil ; vasodilatation ; pharmacokinetics ; bioavailability ; vasoactive drug
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A dose-ranging pharmacokinetic study of buflomedil was carried out in eight subjects to determine the pharmacokinetic parameters of the drug after oral and intravenous administration. Based on AUC∞ analyses, the pharmacokinetics of buflomedil were found to be linear within the dose ranges studied (50 to 200 mg for i. v. injection and 150 to 450 mg for oral administration). In the oral study, the mean biological half-life of the drug was 2.97 h, while after intravenous dose it was 3.25 h. The apparent volume of distribution after the pseudodistribution equilibrium (Fdβ) and volume of distribution at the steady state (Vdss) were 1.43±0.24 l/kg and 1.32±0.26 l/kg, respectively. The mean urinary recovery of intact drug and the metabolite, paradesmethyl buflomedil, after intravenous dosing, were 23.6% and 18.7%, respectively, while after oral dosing, they were 18% and 14.8%, respectively. On the average, 72% of the dose was obserbed into the systemic circulation after oral administration. This level of bioavailability was attributed to the hepatic first-pass effect.
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  • 46
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    Proscillaridin activity in portal and peripheral venous blood after oral administration to man (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 277-281 
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    ISSN: 1432-1041
    Keywords: Proscillaridin ; oral administration ; portal venous sample ; porto-peripheral concentration difference ; bioavailability ; 86Rb-uptake inhibition assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of proscillaridin A was studied in four patients undergoing catheterization of the portal vein for diagnostic purposes. Proscillaridin 1.5 mg was given as a single oral dose and plasma glycoside activity was analyzed by the86Rb-uptake inhibition technique. Proscillaridin appeared rapidly in the portal blood, peak activity being found after 15 min in three and after 30 min in one patient. In peripheral blood the peak activity occurred after approximately 35 min. Despite rapid passage across the gut wall, porto-peripheral differences in glycoside activity were small; they were zero after 4 h. The mean amount absorbed as active proscillaridin during the first 4 h after the dose was calculated to be only 7.1% of the given amount. Late porto-peripheral differences, probably due to enterohepatic recycling, appeared after 6 h in three patients. The results suggest that proscillaridin undergoes first pass inactivation in the gut wall. Enterohepatic recirculation may contribute to the amounts of active glycoside that reach the systemic circulation.
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    Plasma concentrations, bioavailability and dissolution of chlorpropamide (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 207-212 
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    ISSN: 1432-1041
    Keywords: Chlorpropamide ; hypoglycaemic agent ; bioavailability ; plasma concentrations ; bioequivalence ; dissolution tests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability of chlorpropamide from two new formulations (Melitase® tablets) has been compared to that from a reference formulation which is currently in clinical use as a hypoglycaemic agent. In both rate and extent of bioavailability, all three formulations may be considered equivalent, providing allowances are made for differences in drug content. With 95% confidence, the mean bioavailability of chlorpropamide from the new formulations was within about 16% of the mean from the reference formulation, and formulation-related differences were not statistically significant. Although all three formulations were shown to have similar dissolution profiles, dissolution of chlorpropamide was pH-dependent in vitro. Dissolution was almost complete during 30 min at pH 7.2, but only 40%–60% had dissolved during 90 min at pH 2.0. A peak mean concentration of 22.7 µg/ml was reached 3 h after administration of 2×100 mg tablets of the new formulation and peak mean concentrations of 26.8 µg/ml and 27.4 µg/ml were reached 3 h and 4 hours after administration of one 250 mg tablet of the new formulation and one 250 mg tablet of the reference formulation respectively. Formulation-related differences of mean plasma concentrations (after scaling for equal doses of 250 mg) were not significant and each formulation provided similar plasma concentrations at corresponding times after administration. Statistically significant subject-related differences in all the parameters of bioavailability were shown by analyses of variance.
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  • 48
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    Systemic availability of ergotamine tartrate after three successive doses and during continuous medication (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 355-360 
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    ISSN: 1432-1041
    Keywords: ergotamine ; migraine ; bioavailability ; radioimmunoassay ; plasma level ; CSF level ; continuous dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma ergotamine concentrations were determined by radioimmunoassay in 10 healthy subjects after a 2 mg oral dose of ergotamine, administered at 24 h intervals on three consecutive days. After the first dose the mean peak plasma level of 0.35±0.05 (SEM) ng/ml was found 1–2 h after administration. In the samples obtained 2 h after the second and third doses, plasma ergotamine levels did not exceed the first peak value. On the other hand, after the third and last dose the plasma ergotamine began to rise slowly, reaching maximum of 0.70± 0.10 ng/ml on the 6th day after administration. This supports the concept of accumulation of the drug or of immunoreactive metabolites. CSF ergotamine was determined in 4 patients, who underwent lumbar puncture for other diagnostic purposes, 1 to 2 h after the 2 mg oral dose. A concentration of 0.40± 0.03 ng/ml was observed. In seven out of 18 migraine patients who were taking ergotamine preparations daily (mean 11.7 mg/week), ergotamine could not be detected in plasma 1 h after administration of the dose. In the remaining migraine patients, the pattern of plasma ergotamine after both the daily and the test doses was similar to that of the 10 healthy subjects. The results in volunteers and migraine patients suggest notable variation in bioavailability of the drug. It seems that in most subjects there is accumulation or tissue redistribution of ergotamine or its immunoreactive metabolites, although in a significant number of migraine patients who use the drug daily, ergotamine does not appear to be biologically available.
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    The pharmacokinetics of diclofenac sodium following intravenous and oral administration (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 405-410 
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    ISSN: 1432-1041
    Keywords: diclofenac ; plasma levels ; intravenous bolus administration ; oral administration ; enteric coating ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of diclofenac were examined following single rapid intravenous injection and also following single oral doses to healthy female volunteers. After intravenous injection plasma levels of diclofenac fell rapidly and were below the limits of detection at 5.5 h postdosing. Individual drug profiles were described by a triexponential function and mean half-lives of the three exponential phases were 0.05, 0.26 and 1.1 h. After oral doses of enteric-coated tablets, the lag time between dosing and the appearance of drug in plasma varied between 1.0 and 4.5 h. However once drug absorption had commenced similar plasma drug profiles were obtained in different individuals. Peak plasma diclofenac levels ranged from 1.4 to 3.0 µg · ml−1. The mean terminal drug half-life in plasma was 1.8 h after oral doses. This value was not significantly greater than the value of 1.1 h following intravenous doses. Fifty percent of orally dosed diclofenac did not reach the systemic circulation due, predominantly, to first-pass metabolism.
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    First pass hydroxylation of nortriptyline: Concentrations of parent drug and major metabolites in plasma (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 219-224 
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    ISSN: 1432-1041
    Keywords: Nortriptyline ; 10-OH-nortriptyline ; bioavailability ; plasma metabolites ; first pass metabolism ; oral dose ; intramuscular dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nortriptyline was given orally and intramuscularly to six depressed patients. Plasma concentrations of parent drug and the unconjugated and conjugated principal metabolite, 10-hydroxynortriptyline, were determined by mass fragmentography. There was a significant decrease in the area under the nortriptyline plasma concentration — time curve after the oral route of administration, whilst the elimination rate was unchanged. With the oral dose, plasma concentrations of the metabolites were higher and peaked earlier than after intramuscular administration, whilst the opposite was true for the parent compound. This proves that the difference in bioavailability between the two routes of administration was due to first pass metabolism. As determined from the ratio between corresponding areas, the relative bioavailability of the oral dose was 66±21 S.D. per cent. This fraction is higher than that reported previously when intravenous nortriptyline was used as the reference dosage form.
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    Influence of nutritional status on plasma levels and relative bioavailability of tetracycline (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 281-284 
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    ISSN: 1432-1041
    Keywords: Tetracycline ; bioavailability ; plasma levels ; nutritional state ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Relative bioavailability after oral administration of a single dose and Cmin levels of tetracycline in plasma after multiple doses were determined in groups of well-nourished and undernourished subjects. The relative bioavailability of tetracycline, assessed by the area under serum concentration time-curves, did not differ in undernourished and well-nourished patients. The plasma levels were not different in the two groups after the conventional dose of tetracycline HCl 250 mg at 6 hour intervals. However, in these studies undernourished subjects received a higher dose per kg body weight, which could have compensated for any effect of a shortened half life of the drug. When the dose per kg body weight was reduced, the Cmin levels were lower. On the other hand, with the same dose per kg body weight at more frequent intervals, the plasma concentrations were similar to those in well-nourished subjects. These studies indicate that the dosage regimen should be based both on body weight and on the nutritional status of the individual.
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    The effect of an antacid on the bioavailability of indomethacin (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 65-68 
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    ISSN: 1432-1041
    Keywords: Indomethacin ; antacids ; drug-drug interactions ; bioavailability ; drug combinations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The biovailability of indomethacin from two indomethacin-antacid (aluminum hydroxide magnesium carbonate and magnesium hydroxide) combinations was compared with the bioavailability of oral indomethacin. Relative bioavailability was estimated by three methods: comparison of plasma concentrations at various times, comparison of areas under plasma concentration time curves, and comparison of the amount of drug excreted unchanged in the urine. A double blind three-way crossover study was conducted in twelve healthy volunteers. The combination with the slightly smaller amount of antacid (preparation A) showed significantly decreased bioavailability by all three methods in comparison with indomethacin alone (preparation C). The combination with the larger amount of antacid (preparation B) was also less bioavailable than preparation C. This effect was significant only for the comparison of areas under curves and not for plasma levels, although the mean plasma levels produced by preparation B at all times were lower than those for preparation C. These findings suggest that aluminum hydroxide magnesium carbonate and magnesium hydroxide decrease the bioavailability of indomethacin.
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    Pharmacokinetics of tolmetin with and without concomitant administration of antacid in man (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 421-428 
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    ISSN: 1432-1041
    Keywords: Tolmetin ; pharmacokinetics ; bioavailability ; antacid ; oral dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The purpose of this study was to determine whether a concomitant single dose of antacid or multiple doses of antacid administered prior to, and with tolmetin, alter the pharmacokinetics of tolmetin when the drug was administered as a commercially available tablet containing tolmetin sodium. The possible effects of the antacid on plasma concentrations and urinary excretion of tolmetin and its major metabolite were evaluated following administration of: (a) tolmetin sodium alone; (b) antacid four time a day for three days prior to a single dose of tolmetin sodium, with continuation of the antacid during the day tolmetin was given; and (c) co-administration of single doses of tolmetin sodium and antacid. The twenty-four subject study was of the crossover type. There were no significant differences among treatment means for: (i) peak plasma concentrations of both tolmetin and metabolite, (ii) AUC 0–8 h and AUC 0-∞ for both tolmetin and metabolite, (iii) time to peak plasma concentration for both tolmetin and metabolite, (iv) plasma concentrations of both tolmetin and the metabolite at all sampling times (except for tolmetin at 2 h), (v) renal clearance of both tolmetin and its metabolite, and (vi) the amount of metabolite excreted in the 0–24 h urine. There were small, but significant, differences among amounts of tolmetin excreted in the 0–24 h urine. Semilogarithmic plots of both tolmetin and metabolite plasma concentrations past the peak concentrations were curved over the entire 8-h observation period; although the elimination half-life of tolmetin has been reported to be about one hour, the half-life most probably exceeds 2.6 h in most subjects. The results of this study indicate a lack of a significant drug-drug interaction between the non-steroidal anti-inflammatory agent, tolmetin sodium, and a commonly used antacid, which is a mixture of magnesium and aluminium hydroxides.
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    Pharmacokinetics of coumarin and its 7-hydroxy-metabolites upon intravenous and peroral administration of coumarin in man (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 457-461 
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    ISSN: 1432-1041
    Keywords: Coumarin ; 7-Hydroxycoumarin ; drug disposition ; first-pass effect ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of coumarin (C) upon i.v. and p.o. administration and its metabolites 7-hydroxy-coumarin (7-HC) and 7-hydroxy-coumarin glucuronide (7-HCG) have been studied. Six healthy volunteers were involved in this investigation. Four of the volunteers participated in a crossover study. Coumarin was administered i.v. and p.o. in dose sizes of 0.25 mg/kg and 0.857 mg/kg, respectively. Coumarin is rapidly absorbed p.o., however the availability to systemic circulation is less than 4%. The rest of the dose appears quantitatively as 7-HC and 7-HCG in systemic circulation suggesting an extensive firstpass effect. Coumarin and 7-HCG are best fitted to an open two-compartment model, whereas 7-HC is best fitted to an open one-compartment model. The biological half-life of both C (0.80 vs. 1.02 h) and 7-HCG (1.47 vs. 1.15 h) was not significantly different for the two routes of administration. The large total clearance of C again suggests a first-pass effect; while that of 7-HCG, which is nearly exclusively eliminated into urine, indicates active tubular secretion of the glucuronide.
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    Bioavailability of norethindrone in human subjects (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 35-39 
    Details
    ISSN: 1432-1041
    Keywords: Norethindrone ; bioavailability ; man ; competitive protein binding ; sex differences ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A competitive protein binding assay for norethindrone was developed to measure plasma levels in human subjects. The plasma levels were considerably higher in women than in men, especially at low dose levels. The plasma levels were directly related to the dose in men; but greater variations in the plasma levels were observed in women. The plasma half-life was about 5 h in both sexes with single oral doses of 5 to 20 mg. A comparative bioavailability study with norethindrone from 2 different manufacturers, formulated in the same manner, showed no significant differences in absorption characteristics and provided sufficient data for pharmacokinetic analysis.
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    The pharmacokinetics of slow-release procainamide (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 261-265 
    Details
    ISSN: 1432-1041
    Keywords: Procainamide ; slow release formulations ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Procainamide was given to 20 patients with normal renal function as an i.v. bolus of 500 mg followed by 1.0 or 1.5 g eight-hourly by mouth in the form of a slow release preparation (Durules). 97.6±27.1 (SD)% of the oral procainamide was absorbed, the absorption half life being 1.54 h. The elimination half life following the oral formulation was 6.0±0.8 h, compared to a mean of 3.4±0.4 h following i.v. administration. Elimination half life following i.v. administration was slightly related to acetylator status, being 2.75±0.9 h in fast acetylators, and 4.4±2.4 h in slow acetylators. This dependence on acetylator status was not seen in half life following oral administration. Total body clearance, steady state plasma procainamide and N-acetylprocainamide were not significantly dependent on acetylator status, although a few patients who are slow acetylators had unexpectedly low clearance and high steady state procainamide concentrations when given the higher dose.
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    The comparative bioavailability of Lanoxin tablets and Lanoxicaps with and without sorbitol (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 357-360 
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    ISSN: 1432-1041
    Keywords: Lanoxin tablets ; Lanoxicaps ; sorbitol ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary (1) The mean cumulative urinary digoxin excretion over 8 days was compared in 8 healthy volunteers after single doses of digoxin administered as 3 Lanoxin tablets of 0.25 mg, 3 digoxin tablets of 0.2 mg, 12 Lanoxicaps without sorbitol of 0.05 mg, 6 Lanoxicaps without sorbitol of 0.1 mg digoxin, 3 Lanoxicaps without sorbitol of 0.2 mg and 3 Lanoxicaps with sorbitol of 0.2 mg. (2) There was no significant difference between the 8 day cumulative urinary excretion for any of the Lanoxicaps treatments. (3) Cumulative urinary excretion after 3 digoxin tablets of 0.2 mg was significantly (P〈0.05) lower than after all other treatments. (4) Cumulative urinary excretion after 3 Lanoxin tablets of 0.25 mg was not significantly different from that after any of the Lanoxicaps treatments except 0.1 mg Lanoxicaps without sorbitol, it was significantly (P〈0.05) lower after the latter. (5) Mean urinary excretion of digoxin was 60% of ingested dose for all Lanoxicaps treatments and was significantly (P〈0.05) higher than the mean value of 50% for both tablet treatments. (6) Enhanced absorption of digoxin from Lanoxicaps was confirmed and shown to be unrelated to the sorbitol content of the capsule shell.
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    In vitro release and in vivo serum fluoride levels and urinary excretion after different sodium fluoride tablets (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 225-230 
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    ISSN: 1432-1041
    Keywords: fluoride ; sustained release tablets ; serum concentration ; urinary excretion ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Various sodium fluoride tablets used for the treatment of osteoporosis were evaluated. The tablets were characterized in vitro by determining the release curves. The serum levels and urinary recovery of fluoride were determined after a single oral dose either of rapidly soluble (conventional), sustained release or enterocoated tablets. The in vivo study showed that administration of sustained release tablets eliminated high serum peaks and prolonged the duration of an elevated serum level as compared to conventional tablets. The biovailability of the fluoride was lower after intake of sustained release and enterocoated tablets, and there was an increase in the interindividual variance of biovailability.
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    Effect of food on the absorption of hydralazine in man (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 53-58 
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    ISSN: 1432-1041
    Keywords: hydralazine ; food ; absorption ; plasma level ; salivary level ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Single oral doses of hydralazine (Apresoline) 50 mg were administered on two occasions to eight healthy volunteers when fed and fasting. Blood and saliva samples were taken at intervals after dosing and analysed for drug. Heart rate and blood pressure were measured before and at intervals after dosing, at rest, after tilt and exercise. Plasma hydralazine levels showed wide inter-individual variation. The areas under the plasma concentration-time curve (0–8 h), the height of the peak plasma levels and the time to peak were not significantly different between the fed and fasting state. Salivary hydralazine levels were readily measurable but showed little correlation with plasma levels. The heart rate and pulse pressure were increased after drug both at rest, supine and erect, and after exercise for between 6 and 8 h.
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    Ketoprofen pharmacokinetics and bioavailability based on an improved sensitive and specific assay (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 127-133 
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    ISSN: 1432-1041
    Keywords: ketoprofen ; pharmacokinetics ; multipledose ; bioavailability ; assay ; modelling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A commercial capsule containing 50 mg of ketoprofen (Orudis), a simple capsule containing 50 mg of ketoprofen alone and 50 mg of ketoprofen in an aqueous solution were given as separate doses in a randomized sequence to 12 normal adult males. The areas under the resulting plasma concentration-time curves (AUC) were remarkably consistent for each volunteer. The bioavailability from the commerical capsule relative to that from the solution was 99.7%±10.5% and that from the simple capsule was 102%±10%. After 6 of the volunteers had taken the commercial capsule 6 hourly for thirteen doses, their AUC extrapolated to infinity was significantly higher (by 22%) than that after the single dose indicating, contrary to previous reports, accumulation upon multiple dosing. The interdose AUC after the thirteenth dose was, however, statistically indistinguishable from the AUC-to-infinity after the single dose as might be expected from linear kinetics. The ketoprofen solution generated peak plasma concentrations in only one-third the time (21±7 min) required for the capsules (commercial, 72±45; simple, 61±39 min). Despite plasma concentrations being tracked over a 200-fold range, log linearity was not established within 12 h in any of the 42 profiles obtained. A two-compartment open model was fitted to the solution data giving excellent prediction of the time-to-peak and clearance (Cl/F=5.2±1.1 l/h) as determined by eye and by log-trapezoidal rule, respectively.
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    URL: http://dx.doi.org/10.1007/BF00607149
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    Pharmacokinetics of zimelidine in humans — Plasma levels and urinary excretion of zimelidine and norzimelidine after intravenous and oral administration of zimelidine (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 135-139 
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    ISSN: 1432-1041
    Keywords: zimelidine ; norzimelidine ; antidepressant ; pharmacokinetics ; bioavailability ; urinary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five healthy adults were administered zimelidine orally (150 mg) and by intravenous infusion (20 mg) in a crossover design. Blood and urine samples were collected for a period of 28 hours after dosing and the concentrations of zimelidine and norzimelidine determined. There was no significant difference in terminal phase half-life of zimelidine after oral (4.7 h±1.3 SD) or intravenous dosing (5.1 h±0.7 SD). An average of 50% of the ingested oral dose reached the systemic circulation. Excretion of unchanged zimelidine in urine was on average 1.26% of the intravenous dose. In appears that zimelidine is completely absorbed from the gastrointestinal tract and “first-pass metabolism” in the liver reduces the bioavailability to 50%. The mean plasma half-life for norzimelidine was 22.8 h. The area under the plasma concentration time curve for norzimelidine after oral administration was 92% of that after intravenous administration. The plasma concentration of both zimelidine and norzimelidine are predicted to approach steady-state within 3–5 days.
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    Impaired cimetidine absorption due to antacids and metoclopramide (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 225-228 
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    ISSN: 1432-1041
    Keywords: cimetidine ; antacids ; metoclopramide ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 8 healthy subjects the absorption of cimetidine was investigated when given alone, together with 60 ml aluminium/magnesium hyroxyde containing antacid (neutralising capacity 26 mmol HCl/10 ml), and together with liquid metoclopramide 14 mg. The antacid significantly (P〈0.01) reduced the bioavailability (area under the plasma level-time curve) of cimetidine, on average by one third. Metoclopramide also reduced the bioavailability by an average of 22%. The reductions were associated with significantly reduced excretion of cimetidine in urine. There was no change in the half-life or renal clearance of cimetidine, supporting the hypothesis of reduced gastrointestinal absorption. The results indicate that cimetidine and antacids should not be given together, and that the dose of cimetidine may have to be increased if it is administered concomitantly with metoclopramide.
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    Cytoplasmic annulate lamellae in human spermatogenesis (1977)
    Springer
    Cell & tissue research 176 (1977), S. 235-242 
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    ISSN: 1432-0878
    Keywords: Annulate lamellae ; Spermatogenesis ; Ultrastructure ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Electron microscopic examination of normal human testicular tissue revealed annulate lamellae (AL) in the cytoplasm of primary spermatocytes and spermatids. AL of primary spermatocytes are encountered in the perinuclear region, parallel to the nuclear envelope and form single or multiple membranous profiles containing numerous annuli (500–600 Å in diameter) frequently associated with a fibrillar electron dense material. Spermatids contain numerous layers of AL either continuous with the nuclear envelope and caudal to the acrosome or peripherally positioned in the cytoplasm. Individual lamellae possess terminal dilations and display continuities with the endoplasmic reticulum. The interlamellar space in spermatid AL is entirely filled with a fine granular electron dense material. Additionally, the break-down of AL in spermatozoan residual bodies is indicated by a dilation of AL cisternae to form vacuoles following the dissolution of pore complexes.
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    The human rete testis (1978)
    Springer
    Cell & tissue research 189 (1978), S. 409-433 
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    ISSN: 1432-0878
    Keywords: Rete testis ; Human ; Histophysiology ; Chordae retis ; Scanning electron microscopy ; Transmission electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The human rete testis was examined with regard to 1) the number and distribution of entrances of seminiferous tubules, 2) the light microscopic topography and 3) details of the passages as revealed by scanning and transmission electron microscopy. In a newborn 1474 entrances were counted, approximately 50 % entering from the right and 50 % from the left of the central long axis. Three major subdivisions of the rete were distinguished and described: a septal (or interlobular) part represented by tubuli recti, a tunical (or mediastinal) part which is a true network of channels, and an extratesticular part characterized by dilatations (up to 3 mm wide) which we have called bullae retis. In SEM, cylindrical strands running from wall to wall in the tunical and extratesticular rete spaces are a prominent feature. We have called these chordae retis. They are covered by epithelium and are 5–40 μm wide and 15 to more than 100 μm long. They contain a peculiar tissue consisting of central myoid cells in a fibroelastic matrix. The smaller chordae are avascular. In the light of these findings the rete is interpreted as a highly complex myoelastic sponge. Its function is discussed.
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    URL: http://dx.doi.org/10.1007/BF00209130
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    Human microvascular endothelial cell-extracellular matrix interaction in cellular growth state determination (1995)
    Springer
    Cell & tissue research 279 (1995), S. 37-45 
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    ISSN: 1432-0878
    Keywords: Microvascular endothelial cells ; Cell growth ; Extracellular matrix ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We introduce two methods, both of which are based on cellular-extracellular matrix interaction, which will facilitate the study of human microvascular endothelial cells. One method describes the means to obtain a G1 population baseline in human microvasclular endothelial cells. Because of the contribution of the extracellular matrix in endothelial cell growth, synchronization in G1 was possible only after the incorporation of angiostatic levels of heparin and hydrocortisone into the extracellular matrix. In the second method, we demonstrate that selective perturbation of human microvascular endothelial cell-extracellular matrix interactions results in the induction of a transitional growth state, between proliferative and differentiated growth states, in human microvascular endothelial cells. In the functional, microtubule formation assays, transitional growth state endothelial cells display rates that are indermediate between those obtained from differentiated and proliferative endothelial cells. Our results demonstrate the importance of the human microvascular endothelial cell-extracellular matrix interaction in the determination of cellular growth state. Our findings also imply that responsiveness of microvascular endothelial cells to their cellular-extracellular matrix environs is highest during the differentiated growth state.
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    Immuno-electron-microscopic localization of types III pN-collagen and IV collagen, laminin and tenascin in developing and adult human spleen (1995)
    Springer
    Cell & tissue research 282 (1995), S. 117-127 
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    ISSN: 1432-0878
    Keywords: Spleen ; Fetus ; Development ; Extracellular matrix ; Immuno-electron microscopy ; Transmission electron microscopy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The distribution of the extracellular matrix proteins types III pN-collagen and IV collagen, laminin and tenascin was investigated in fetal, infant, and adult human spleens by using immuno-electron microscopy. The presence of type III pN-collagen was assessed by using an antibody against the aminoterminal propeptide of type III procollagen. All the proteins other than type III pN-collagen were found in reticular fibers throughout development. In the white pulp of the fetus aged 16 gestational weeks, only an occasional type III pN-collagen-containing fibril was present, although type III pN-collagen was abundant in the reticular fibers of the red pulp. Conversely, in adults, most of the reticular fibers of the white pulp, but not of the red pulp, were immunoreactive for type III pN-collagen. Ring fibers, the basement membranes of venous sinuses, were well developed in both infant and adult spleens. The first signs of their formation could be seen as a discontinuous basement membrane, which was immunoreactive for type IV collagen, laminin, and tenascin in the fetus aged 20 gestational weeks. Intracytoplasmic immunoreactivity for all the proteins studied was visible in the mesenchymal cells of the fetus aged 16 gestational weeks and in the reticular cells of the older fetuses, which also showed labeling for type IV collagen and laminin in the endothelial cells. The results suggest that proteins of the extracellular matrix are produced by these stationary cells.
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    The monoclonal antibody GB 42 – a useful marker for the differentiation of myofibroblasts (1995)
    Springer
    Cell & tissue research 281 (1995), S. 231-242 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Placenta ; Stem villi ; Actin isoforms ; Myofibroblasts ; Smooth muscle cells ; Immunohistochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The expression patterns of a variety of cytoskeletal antigens were studied in normal human tissues (placenta, umbilical cord, myometrium, colon, mammary gland, testis, skeletal muscle, myocardium) as well as in abnormal human tissues (palmar fibromatosis, fibrocystic disease of the mammary gland, mammary carcinoma). The immunohistochemical binding patterns of the monoclonal antibody GB 42 were compared to those of commercial antibodies directed against vimentin, desmin, smooth muscle myosin, pan actin, α-smooth muscle actin and γ-smooth muscle actin. Methods applied comprised immunohistochemistry on cryostat sections and paraffin sections. Immunogold immunocytochemistry was performed on Lowicryl sections. The patterns of GB 42-binding were confirmed biochemically by SDS-PAGE and Western-blotting, and quantitative amino acid analysis. Our data suggest that the monoclonal antibody GB 42 recognizes an actin isoform which is identical to, or closely related to, γ-smooth muscle actin. Unlike the commercially available antibody against γ-smooth muscle actin, GB 42 does not cross-react with α-skeletal or α-cardiac actins. The GB 42-antigen is expressed in smooth muscle cells, myoepithelial cells and in later stages of differentiation of myofibroblasts, in all the tissues investigated. Throughout the development of smooth muscle cells and myofibroblasts, the appearance of the GB 42-antigen occurs after the expression of vimentin, desmin and α-smooth muscle actin, but prior to the expression of smooth muscle myosin. GB 42 is a reliable marker for higher stages of differentiation of smooth muscle cells and myofibroblasts.
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    The monoclonal antibody GB 42 — a useful marker for the differentiation of myofibroblasts (1995)
    Springer
    Cell & tissue research 281 (1995), S. 231-242 
    Details
    ISSN: 1432-0878
    Keywords: Placenta ; Stem villi ; Actin isoforms ; Myofibroblasts ; Smooth muscle cells ; Immunohisto-chemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The expression patterns of a variety of cytoskeletal antigens were studied in normal human tissues (placenta, umbilical cord, myometrium, colon, mammary gland, testis, skeletal muscle, myocardium) as well as in abnormal human tissues (palmar fibromatosis, fibrocystic disease of the mammary gland, mammary carcinoma). The immunohistochemical binding patterns of the monoclonal antibody GB 42 were compared to those of commerical antibodies directed against vimentin, desmin, smooth muscle myosin, pan actin, α-smooth muscle actin and γ-smooth muscle actin. Methods applied comprised immunohistochemistry on cryostat sections and paraffin sections. Immunogold immunocytochemistry was performed on Lowicryl sections. The patterns of GB 42-binding were confirmed biochemically by SDS-PAGE and Western-blotting, and quantitative amino acid analysis. Our data suggest that the monoclonal antibody GB 42 recognizes an actin isoform which is identical to, or closely related to, γ-smooth muscle actin. Unlike the commercially available antibody against γ-smooth muscle actin, GB 42 does not cross-react with α-skeletal or α-cardiac actins. The GB 42-antigen is expressed in smooth muscle cells, myoepithelial cells and in later stages of differentiation of myofibroblasts, in all the tissues investigated. Throughout the development of smooth muscle cells and myofibroblasts, the appearance of the GB 42-antigen occurs after the expression of vimentin, desmin and α-smooth muscle actin, but prior to the expression of smooth muscle myosin. GB 42 is a reliable marker for higher stages of differentiation of smooth muscle cells and myofibroblasts.
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    Age-related differences in the temporal and spatial regulation of matrix metalloproteinases (MMPs) in normal skin and acute cutaneous wounds of healthy humans (1997)
    Springer
    Cell & tissue research 290 (1997), S. 581-591 
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    ISSN: 1432-0878
    Keywords: Key words: Ageing ; Skin ; Proteinase ; Wound ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Despite the association of increasing age with chronic wound-healing disorders and an impaired rate of healing of acute cutaneous wounds, the role of matrix metalloproteinases (MMPs) is unknown. To determine the spatial and temporal patterns and activities of MMP-1, -2, -3 and -9, 132 healthy humans aged between 19 and 96 years underwent 4-mm punch biopsies followed by wound excision between day 1 and day 180 post-wounding. Wounds showed an age-related increase in MMP-2 and MMP-9 immunostaining from day 3; this was associated with degradation of gelatin as shown by zymograms and with increased proteinase activity as shown by azocoll assays. Distinct spatial localisations for each MMP were observed: MMP-2 was found in epidermal structures; MMP-9 was observed in inflammatory cells up to day 21; MMP-1 was localised to keratinocytes at the wound margin. Normal old skin showed pro-MMP-2 bands on zymography and increased MMP-2 immunostaining. These results indicate that: (1) intrinsic ageing is associated with the up-regulation of MMPs previously associated with chronic wound healing; (2) wound-tissue proteinases are essentially active up to day 21 postwounding; and (3) intrinsic ageing may predispose to tissue breakdown disorders because of MMP-2 up-regulation in normal skin.
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    The fibroblast-specific MAb AS02: a novel tool for detection and elimination of human fibroblasts (1997)
    Springer
    Cell & tissue research 290 (1997), S. 593-599 
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    ISSN: 1432-0878
    Keywords: Key words: Fibroblast-specific antibody ; Fibroblast separation and elimination ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The unwelcome presence of fibroblasts in many cell cultures prevents the long term cultivation of various cell types and work with pure populations. Recently, we described a novel fibroblast-specific monoclonal antibody (MAb AS02) that recognises a membrane-bound antigen. We have now developed a method using the fibroblast-specific MAb AS02 immobilised on goat-anti-mouse-magnetic beads to separate contaminating fibroblasts. An endothelial cell line experimentally contaminated with 5%–50% fibroblasts was successfully purified. Additionally, an endothelial cell line with an initial fibroblast contamination of 1.5% was prepared. A proportion of each preparation was cultured with no separation step being performed, whereas the remainder was cultured after purification with MAb AS02 to exclude the presence of a minor number of fibroblasts (〈0.1%). The proportion of fibroblasts increased up to 38% in the fifth passage of culture without elimination of the low initial fibroblast contamination, whereas in the fraction with the separation step, no fibroblasts were detectable by flow cytometry, even after the fifth passage. We also used the antibody to detect the presence of naturally contaminating fibroblasts in thyrocyte cultures. After cultivation of thyrocyte cultures over five passages, the number of fibroblasts increased dramatically up to 50%–80% of the whole population. Subsequently, we successfully applied the method for complete elimination of naturally contaminating fibroblasts from freshly isolated thyrocyte cultures from enzymatically digested thyroid glands. Thus, MAb AS02 is a fibroblast-specific marker that is a useful tool for the detection and elimination of contaminating fibroblasts. The specificity of MAb AS02 permits the universal application of this antibody for human cell cultures of interest.
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    Light-microscopical investigation of the distribution of extracellular matrix molecules and calcifications in human dental pulps of various ages (1997)
    Springer
    Cell & tissue research 289 (1997), S. 145-154 
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    ISSN: 1432-0878
    Keywords: Key words: Teeth ; Dental pulp ; Immunohistology ; Extracellular matrix ; Collagen ; Aging ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The distribution of extracellular matrix molecules, especially collagen types I, III, V, and VI, in the extracellular matrix of the connective tissue of human dental pulp of various ages was studied by polarization and indirect immunofluorescence microscopy by using a conventional fluorescence microscope and a confocal laser scanning microscope. Polarization and immunofluorescence microscopy of paraffin sections showed thick fibers of collagen type I, which represented the main component of the connective tissue matrix of the dental pulp. By indirect immunofluorescence, thin fibers and small bundles of collagen type III were determined to be one of the main fibrillar elements present in the dental pulp matrix. Collagen type IV was detected by a clear intense staining of the basement membrane of blood vessels at all ages examined. Collagens type V and VI formed a dense meshwork of thin microfibrils throughout the stroma of the connective tissue of the dental pulp. These fibers were localized around blood vessels and appeared to be enriched in the subodontoblastic layer. Investigations by means of confocal laser scanning microscopy revealed fibers of collagen type VI spiralling between fully differentiated odontoblasts toward the predentin layer. With advancing age, the connective tissue matrix appeared to be condensed and aggregates of thick fiber bundles could be observed. Furthermore, the participation of various collagen types in the composition of pulp stones was shown. These calcifications and diffuse calcifications increased in frequency with advancing age in a statistically significant manner.
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    Immunohistochemical localization of the small proteoglycans decorin and biglycan in human intervertebral discs (1997)
    Springer
    Cell & tissue research 289 (1997), S. 185-190 
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    ISSN: 1432-0878
    Keywords: Key words: Small proteoglycans ; Intervertebral disc ; Decorin ; Biglycan ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Immunohistochemistry was used to study the presence and distribution of the core proteins of the small proteoglycans decorin and biglycan in the various compartments of human intervertebral discs. Both proteoglycans could be found in the outer tendon-like parts of the annulus fibrosus, indicating their potential role in collagen network formation and biomechanical stress resistance. The loss of both proteoglycans in the annulus of individuals older than 50 years reflects a normal age-related change. In the nucleus pulposus, decorin could be found in fibrillar areas of the interterritorial matrix, thereby indicating co-localization of decorin with fibrils containing type II collagen. Biglycan was present in the extracellular matrix of the nucleus pulposus of adults. The pericellular immunoreactive rims observed around nucleus pulposus cells and giant chondrones indicated local biosynthetic activity for these small proteoglycans. The staining patterns in cartilage endplates resembled those found in human hyaline articular cartilage.
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    Differential distribution of five members of the matrix metalloproteinase family and one inhibitor (TIMP-1) in human liver and skin (1997)
    Springer
    Cell & tissue research 289 (1997), S. 173-183 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Collagen ; Matrilysin (PUMP) ; Wound healing ; Tumors ; Fat-storing cells ; Peripheral nerve glial cells ; Fibrocytes ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Matrix metalloproteinases represent a family of zinc-dependent proteolytic enzymes thought to be involved in normal and disease-related tissue remodeling processes. Increasing information about these enzymes is becoming available concerning their primary sequences, regulation at the mRNA level, activation of proenzymes, and modulation of enzyme activity by tissue inhibitors. In contrast, their morphological distribution and biological functions in normal tissues are poorly understood. In the present report, the comparative distribution of five members (gelatinase-A, gelatinase-B, matrilysin, stromelysin-1, and stromelysin-3) of the matrix metalloproteinase family and of one inhibitor (TIMP-1) has been morphologically analyzed in human liver and skin with the aid of new monospecific antibodies. Because of their common designation as matrix proteinases, these enzymes might have been expected to be distributed throughout these tissues, or at least in the connective tissue. However, each member of the family produces a highly specific pattern, staining structures such as arteriolar smooth muscle cells, myoepithelial cells in secretory portions or the luminal lining in excretory ducts of dermal sweat glands, liver bile canaliculi, or structures surrounding peripheral nerve axons. No reactivity is detected in rat tissues.
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    GDNF improves survival and reduces apoptosis in human embryonic dopaminergic neurons in vitro (1997)
    Springer
    Cell & tissue research 289 (1997), S. 207-210 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Parkinson’s disease ; Programmed cell death ; Dopamine ; Growth factors ; Neurotransplantation ; Glia ; Human ; Bonnet monkey ; Macaca radiata (Primates)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Dopamine cell death is the primary problem limiting the value of neurotransplantation in human patients with Parkinson’s disease. To address this problem, we added glial cell line-derived neurotrophic factor (GDNF) to cultures of embryonic dopaminergic neurons obtained from human and from Bonnet monkey (Macaca radiata) in an effort to reduce apoptotic cell death and improve overall cell survival. Tissue from three human embryos, 7–8 weeks post-conception, and one 9-week post-conception monkey embryo were dissociated and cultured in F-12 media with 5% human placental serum. GDNF (10 ng/ml) in human cultures nearly doubled dopamine neuron survival and reduced the rate of apoptosis from 6% to 3%. In monkey cultures, GDNF also enhanced dopamine neuron survival and reduced the apoptotic rate. We conclude that GDNF improves the survival of primate embryonic dopamine neurons in culture by reducing apoptosis.
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    Coordinated change between complement C1s production and chondrocyte differentiation in vitro (1997)
    Springer
    Cell & tissue research 289 (1997), S. 299-305 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Complement C1s ; Sandwich ELISA ; Chondrocytes ; Cell culture ; Differentiation ; Ascorbic acid ; Syrian hamster ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. In vitro synthesis of the first component of complement C1s was examined by using hamster epiphyseal chondrocytes (HAC) and human chondrosarcoma cell line HCS-2/8. Hamster and human C1s produced by the cells were quantified by immunoblotting and sandwich enzyme-linked immunosorbent assay (ELISA), respectively. It was possible to measure active and inactive C1s by sandwich ELISA, when we used anti-human C1s monoclonal antibodies, M241 recognizing only active C1s, and M365 and M81 recognizing both active and inactive C1s. Approximately 40% of C1s secreted from HCS-2/8 was found to be activated in the culture medium, whereas C1s from HAC was not. C1s production increased in accordance with chondrocyte differentiation induced by ascorbic acid. In contrast, transforming growth factor-beta1 and basic fibroblast growth factor, which inhibited differentiation, suppressed C1s production. These results confirmed our previous observation showing that C1s synthesis increased with differentiation into hypertrophic chondrocytes in vivo.
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    Development of striated rootlets during ciliogenesis in the human oviduct epithelium (1997)
    Springer
    Cell & tissue research 290 (1997), S. 39-42 
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    ISSN: 1432-0878
    Keywords: Key words: Ciliogenesis ; Striated rootlets ; Oviduct ; Ciliated cells ; Ultrastructure ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Striated rootlets in ciliated cells are conical banded structures composed of longitudinally aligned filaments. The formation of striated rootlets during ciliognesis in the human oviduct epithelium was studied by electron microscopy. Primitive rootlets appeared at the proximal side of basal bodies before or at the same time as ciliary budding. After the formation of several striations, the tip of the rootlets extended deeply toward the interior of the cell and became differentiated into two distinct parts, viz., the proximal conical part connected to the basal body and the distal fibrillar part. The periodicity of the striations in the fibrillar part was 68.5±2.95 nm, about 5 nm longer than that of the conical part (63.9±2.25 nm). The dark band in the striation was thicker in the fibrillar part than in the conical part. Since the fibrillar part was not observed in the mature cilium, this part was considered as being either degraded or changed into the conical part during ciliogenesis.
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    Functional and structural interactions between osteoblastic and preosteoclastic cells in vitro (1995)
    Springer
    Cell & tissue research 281 (1995), S. 33-42 
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    ISSN: 1432-0878
    Keywords: Osteoblasts ; Preosteoclasts ; Cell differentiation ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Osteoblasts are involved in the bone resorption process by regulating osteoclast maturation and activity. In order to elucidate the mechanisms underlying osteoblast/preosteoclast cell interactions, we developed an in vitro model of co-cultured human clonal cell lines of osteoclast precursors (FLG 29.1) and osteoblastic cells (Saos-2), and evaluated the migratory, adhesive, cytochemical, morphological, and biochemical properties of the co-cultured cells. In Boyden chemotactic chambers, FLG 29.1 cells exhibited a marked migratory response toward the Saos-2 cells. Moreover, they preferentially adhered to the osteoblastic monolayer. Direct co-culture of the two cell types induced: (1) positive staining for tartrate-resistant acid phosphatase in FLG 29.1 cells; (2) a decrease of the alkaline phosphatase activity expressed by Saos-2 cells; (3) the appearance of typical ultrastructural features of mature osteoclasts in FLG 29.1 cells; (4) the release into the culture medium of granulocyte-macrophage colony stimulating factor. The addition of parathyroid hormone to the co-culture further potentiated the differentiation of the preosteoclasts, the cells tending to fuse into large multinucleated elements. These in vitro interactions between osteoblasts and osteoclast precursors offer a new model for studying the mechanisms that control osteoclastogenesis in bone tissue.
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    Immuno-electron-microscopic localization of types III pN-collagen and IV collagen, laminin and tenascin in developing and adult human spleen (1995)
    Springer
    Cell & tissue research 282 (1995), S. 117-127 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Spleen ; Fetus ; Development ; Extracellular matrix ; Immuno-electron microscopy ; Transmission electron microscopy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The distribution of the extracellular matrix proteins types III pN-collagen and IV collagen, laminin and tenascin was investigated in fetal, infant, and adult human spleens by using immuno-electron microscopy. The presence of type III pN-collagen was assessed by using an antibody against the aminoterminal propeptide of type III procollagen. All the proteins other than type III pN-collagen were found in reticular fibers throughout development. In the white pulp of the fetus aged 16 gestational weeks, only an occasional type III pN-collagen-containing fibril was present, although type III pN-collagen was abundant in the reticular fibers of the red pulp. Conversely, in adults, most of the reticular fibers of the white pulp, but not of the red pulp, were immunoreactive for type III pN-collagen. Ring fibers, the basement membranes of venous sinuses, were well developed in both infant and adult spleens. The first signs of their formation could be seen as a discontinuous basement membrane, which was immunoreactive for type IV collagen, laminin, and tenascin in the fetus aged 20 gestational weeks. Intracytoplasmic immunoreactivity for all the proteins studied was visible in the mesenchymal cells of the fetus aged 16 gestational weeks and in the reticular cells of the older fetuses, which also showed labeling for type IV collagen and laminin in the endothelial cells. The results suggest that proteins of the extracellular matrix are produced by these stationary cells.
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    Decreased adhesion of oxidized LDL-stimulated platelets caused by cytochalasin D (1995)
    Springer
    Cell & tissue research 280 (1995), S. 183-188 
    Details
    ISSN: 1432-0878
    Keywords: Blood platelets ; Oxidized LDL ; Cytochalasin D ; Reflection contrast microscopy ; Image analysis ; Electron microscopy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The adhesion of human blood platelets is studied with an in vitro model using reflection contrast microscopy and an image analysis system. The adhesive feature is promoted by oxidatively modified low density lipoprotein, which also induces functional morphological changes of platelets. However, when washed platelets are pretreated with 0.05 mM cytochalasin D, oxidized low density lipoprotein (100 μg/ml) causes a slower increase of the adhesion area (11.6 μm2/min) compared to untreated platelets (15.7 μm2/min) or platelets treated by oxidized low density lipoprotein alone (20.5 μm2/min, P〈0.01). These results are supported by light transmission analysis and by transmission electron microscopy. Our experiments suggest that cytochalasin D inhibits the change of platelets in shape induced by oxidized low density lipoprotein, hinders the adhesion, but does not prevent the adhesion entirely.
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    Expression of the endogenous 14-kDa β-galactoside-binding lectin galectin in normal human skin (1995)
    Springer
    Cell & tissue research 280 (1995), S. 1-10 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Galectin ; β-Galactoside-binding lectin ; Human ; Skin ; Immunocytochemistry ; Immunohistochemistry ; Hybridization ; in situ ; Langerhans cell ; Man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The localization of an endogenous 14-kDa β-galactoside-binding lectin (galectin) and its pattern of gene expression were examined in normal human skin by light- and electron microscopy. Under the light microscope, immunostaining of 14-kDa galectin was observed in the cell membrane of cells in the basal and spinous layers of the epidermis. Galectin was also found in the Langerhans cells, as shown by double labeling using anti-14-kDa galectin and anti-CD1a antibodi es. In the dermis, immunostaining for the 14-kDa galectin was positive in the extracellular matrix and fibroblasts. At the electron-microscopic level of resolution, galectin was located primarily along the plasma membrane of keratinocytes, and in both the cytoplasm and nucleus of Langerhans cells in the epidermis, whereas in the dermis it was detected in the extracellular matrix and in both the nucleus and cytoplasm of fibroblasts. The gene expression of 14-kDa galectin was visualized by the HRP-staining me thod following in situ hybridization techniques. The expression was detected in the cytoplasm of cells in the basal and spinous layers of the epidermis; whereas, in the dermis, it was detected in the cytoplasm of fibroblasts. Moreover, SDS-polyacrylamide gel electrophoresis and lectin-blot analysis revealed that this galectin bound to glycoproteins of approximately 17, 62, and 72 kDa in the epidermis and to those of 29, 54, and 220 kDa in the dermis. The present study indicates that 1) normal human skin produces the β-galactoside-binding 14-kDa galectin, and 2) this galectin is located in both the epidermis, particularly in the keratinocytes and Langerhans cells, and in the dermis. These results suggest that galectin is important for cell-cell contact and/or adhesion in the epidermis and for cell-extracellular matrix interaction in the dermis.
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    Expression of the endogenous 14-kDa β-galactoside-binding lectin galectin in normal human skin (1995)
    Springer
    Cell & tissue research 280 (1995), S. 1-10 
    Details
    ISSN: 1432-0878
    Keywords: Galectin ; β-Galactoside-binding lectin ; Human ; Skin ; Immunocytochemistry ; Immunohistochemistry ; Hybridization, in situ ; Langerhans cell ; Man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The localization of an endogenous 14-kDa β-galactoside-binding lectin (galectin) and its pattern of gene expression were examined in normal human skin by light- and electron microscopy. Under the light microscope, immunostaining of 14-kDa galectin was observed in the cell membrane of cells in the basal and spinous layers of the epidermis. Galectin was also found in the Langerhans cells, as shown by double labeling using anti-14-kDa galectin and anti-CD1a antibodies. In the dermis, immunostaining for the 14-kDa galectin was positive in the extracellular matrix and fibroblasts. At the electron-microscopic level of resolution, galectin was located primarily along the plasma membrane of keratinocytes, and in both the cytoplasm and nucleus of Langerhans cells in the epidermis, whereas in the dermis it was detected in the extracellular matrix and in both the nucleus and cytoplasm of fibroblasts. The gene expression of 14-kDa galectin was visualized by the HRP-staining method following in situ hybridization techniques. The expression was detected in the cytoplasm of cells in the basal and spinous layers of the epidermis; whereas, in the dermis, it was detected in the cytoplasm of fibroblasts. Moreover, SDS-polyacrylamide gel electrophoresis and lectin-blot analysis revealed that this galectin bound to glycoproteins of approximately 17, 62, and 72 kDa in the epidermis and to those of 29, 54, and 220 kDa in the dermis. The present study indicates that 1) normal human skin produces the β-galactoside-binding 14-kDa galectin, and 2) this galectin is located in both the epidermis, particularly in the keratinocytes and Langerhans cells, and in the dermis. These results suggest that galectin is important for cell-cell contact and/or adhesion in the epidermis and for cell-extracellular matrix interaction in the dermis.
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    Platelet/endothelial cell adhesion molecule-1 (PECAM-1) is localized over the entire plasma membrane of endothelial cells (1997)
    Springer
    Cell & tissue research 290 (1997), S. 623-631 
    Details
    ISSN: 1432-0878
    Keywords: Key words: PECAM-1 (platelet/endothelial cell adhesion molecule-1) ; Endothelium ; HUVEC (human umbilical vein endothelial cells) ; Myocardium ; Ultrastructure ; Human ; Rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The subcellular localization of PECAM-1 in endothelial cells was examined by using advanced morphological techniques, such as confocal scanning microscopy and immunolabeling procedures for electron microscopy. The localization of PECAM-1 was studied immunohistochemically with five specific monoclonal antibodies and one polyclonal antibody (all anti-human) in human and rabbit myocardium and in isolated endothelial cells. In vivo, PECAM-1 was localized uniformly on the plasma membrane of all vascular endothelial cells, predominantly on the luminal side of vessels. No specific increase in labeling was found at sites of cell-to-cell contact. In vitro, primary isolated cells (human umbilical vein endothelial cells) showed continuous labeling of the entire cell membrane. Cells of higher passages were labeled in a manner similar to freshly isolated cells. Our findings refute the commonly accepted hypothesis that PECAM-1 is localized only at cell-to-cell contacts. Further, we have not been able to confirm the hypothesis regarding the important mechanical role of PECAM-1 in stabilizing the endothelial monolayer. Since PECAM-1 is also expressed on platelets and is known to bind to itself, the way in which PECAM-1-positive endothelial cells are protected against binding of PECAM-1-positive platelets remains unclear. In view of these findings, the role of PECAM-1 in the leukocyte migration cascade needs to be re-evaluated.
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    Immuno-electron microscopy reveals that the excitotoxin quinolinate is associated with the plasma membrane in human peripheral blood monocytes/macrophages (1997)
    Springer
    Cell & tissue research 290 (1997), S. 633-639 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Quinolinic acid ; Interferon-γ ; Kynurenine ; Electron microscopy ; Immunocytochemistry ; Excitotoxicity ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract.  Quinolinate (QUIN), a tryptophan-derived excitotoxin, was localized ultrastructurally in human peripheral blood monocytes/macrophages (MØ) by immuno-electron microscopy. A combined carbodiimide/glutaraldehyde/paraformaldehyde-based fixation procedure was developed for optimal retention of QUIN in the cell as well as minimal loss of ultrastructure; a silver-enhanced colloidal gold detection system was used for electron-microscopic analysis. Gold particles representing QUIN immunoreactivity were associated with the inner side of the plasma membrane in normal MØ. The number of gold particles increased significantly when QUIN levels were elevated by treatment with its precursor kynurenine, but location of the gold particles remained essentially the same under this condition. Treatment with interferon-γ increased the number of Golgi bodies, vacuoles and pseudopodia, reflecting the activated state of the cell. Significantly increased numbers of gold particles representing QUIN were detectable in approximately the same location as in the case of kynurenine treatment. Combined treatment with kynurenine and interferon-γ maximally increased the number of gold particles at the periphery of the cell. The pseudopodia were intensely stained with gold particles, while they were not detectable in the inner part of the cytoplasm or in any other organelle even under this activated condition. The significance of the specific location of QUIN revealed in the present study and its relation to the release and subsequent actions of QUIN are discussed.
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    Immunohistochemistry of matrix metalloproteinases (MMP), their substrates, and their inhibitors (TIMP) during trophoblast invasion in the human placenta (1997)
    Springer
    Cell & tissue research 291 (1997), S. 133-148 
    Details
    ISSN: 1432-0878
    Keywords: Key words Placenta ; Extravillous trophoblast ; Matrix-type fibrinoid ; Extracellular matrix ; MMP ; TIMP ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The invasion of extravillous trophoblast cells into the maternal endometrium is one of the key events in human placentation. The ability of these cells to infiltrate the uterine wall and to anchor the placenta to it as well as their ability to infiltrate and to adjust utero-placental vessels to pregnancy depends, among other things, on their ability to secrete enzymes that degrade the extracellular matrix. Most of the latter enzymes belong to the family of matrix metalloproteinases. Their activity is regulated by the tissue inhibitors of matrix metalloproteinases. We have studied the distribution patterns of matrix metalloproteinases-1, -2, -3, and -9 and their inhibitors TIMP-1 and TIMP-2 as compared to the distribution of their substrates along the invasive pathway of extravillous trophoblast of 1st, 2nd, and 3rd trimester placentas by means of light microscopy on paraffin and cryostat sections as well as at the ultrastructural level (only 3rd trimester placenta). The comparison of different methods proved to be necessary, since the immunohistochemical distribution patterns of these soluble enzymes are considerably influenced by the pretreatment of tissues. All three methods revealed immunoreactivities of both, proteinases and their inhibitors, not only intracellularly in the extravillous trophoblast but also extracellularly in its surrounding matrix, the distribution patterns depending on the stage of pregnancy and on the degree of differentiation of trophoblast cells along their invasive pathway. Within the extracellular matrix, immunolocalization of matrix metalloproteinases as well as their inhibitors showed a specific relation to certain extracellular matrix molecules.
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    Distribution and subcellular localization of a lysosome-associated protein in human genital organs (1997)
    Springer
    Cell & tissue research 287 (1997), S. 335-342 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Lysosomal membrane antigen ; Immunohistochemistry ; Biosynthesis ; Prostate-membrane-specific antigen ; Apocrine secretion ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The tissue distribution, preferentially in the human male genital system, and the subcellular localization of the lysosome-associated membrane protein 2 (lamp 2) was studied immunohistochemically using a mouse monoclonal antibody, 2D5. Strong immunoreactivity was present in the tubular system of the kidney, in acinar cells of salivary glands and pancreas, prostate, mammary glands, placenta and in cutaneous sweat glands. Moderate immunoreactivity was observed in cerebral neuronal cells, epidermal cells, testis, epididymis, seminal vesicle and endometrium. Very low immunoreactivity was found in liver. In some of the tissues mentioned, the distribution pattern of immunoreactivity is smooth and homogeneous, while in others it is granular and concentrated in the supra- or perinuclear cytoplasm. The subcellular distribution was studied on ultracryosections and on pre-embedding-processed chopper sections of human prostate. In the latter gland, the protein is not restricted to epithelium, but is also present in stromal cells. Ultrastructurally, the immunoreactivity in secretory cells was localized in electron-translucent vacuoles and granules, including the secretory granules. A close association with cell membranes was not generally the case. Only part of the immunoreactive material was linked to the apical plasma membrane pointing to a biosynthesis independent from an association step with the apical plasma membrane. As shown by immunoelectron microscopy and Western blotting, a high amount of lamp 2 is secreted and is found in so-called prostasomes. The findings indicate that in the human prostate most of the membrane-bound lamp 2 is released from the secretory cells, presumably in an apocrine fashion.
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    Occurrence of enzymes of free radical metabolism suggests the possible cytotoxic capacity of the transitional epithelium of the human ureter (1997)
    Springer
    Cell & tissue research 287 (1997), S. 351-356 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Urothelium ; Tartrate-resistant acid phosphatase ; Nitric oxide synthase I ; Superoxide dismutase ; Immunocytochemistry ; Free radicals ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Three enzymes, viz., tartrate-resistant acid phosphatase (TRAP), nitric oxide synthase I (NOS-I), and superoxide dismutase (SOD), involved in the production and metabolism of free radicals or radical equivalents, were demonstrated by immunocytochemistry in the urothelium of the ureters of six patients of various ages. Two of these enzymes (TRAP and NOS-I) were colocalized in the most apical and lateral border of the superficial cells of the urothelium. In contrast, SOD showed a patchy or granular distribution within the supranuclear region of these cells. Intra- and subepithelial macrophages exhibited a weak TRAP, but no NOS-I or SOD, immune reaction. On the basis of the immunocytochemical findings, arguments in favor of a cytotoxic function of the superficial cells of the human urothelium are presented.
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    Number and size of epineurial blood vessels in normal and diseased human sural nerves (1997)
    Springer
    Cell & tissue research 290 (1997), S. 31-37 
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    ISSN: 1432-0878
    Keywords: Key words: Sural nerve ; Blood vessels ; Angiopathic neuropathy ; Vasculitis ; Peripheral neuropathy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The number and dimensions of epineurial blood vessels in normal human sural nerves have, thus far, not been determined using systematic, reproducible morphometric methods, although this nerve is most frequently used for diagnostic biopsies. Quantitative changes in epineurial blood vessels appear to be major parameters for identifying angiopathy and angiopathic peripheral neuropathy. Therefore, we examined the epineurial blood-vessel number in relation to the age of the patients and to the number and size of the nerve fascicles in each of 51 human sural nerve biopsies. The data from a control group were compared with pathological cases. We found that the number of epineurial blood vessels (normal mean: 57.7) increased significantly (up to 196) in biopsies where there were signs of angiopathy (P≤0.01) or vasculitis (P≤0.05). The increase in the number of epineurial blood vessels usually resulted from a proliferation of capillaries. The fascicular cross-sectional area did not appear to be related to the number of epineurial blood vessels, although it increased significantly in cases with vasculitis (P≤0.05) or an axonal type of neuropathy (P≤0.05). Thus, this study shows that the number of epineurial blood vessels is a helpful parameter in verifying angiopathy and angiopathic peripheral neuropathy.
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    A model system for long-term serum-free suspension organ culture of human fetal tissues: experiments on digits and skin from multiple body regions (1997)
    Springer
    Cell & tissue research 290 (1997), S. 51-60 
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    ISSN: 1432-0878
    Keywords: Key words: Serum-free culture medium ; Organ culture ; Fetal digits ; Fetal skin ; Nails ; Hair follicles ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. We have optimized a suspension organ culture (SOC) system previously used to study human fetal skin in vitro. Eleven types of media were used to culture fetal digits and skin samples (ranging from 59–91 days of estimated gestational age) for periods of 3 or 4 weeks. The cultures were supplemented with 0%–10% bovine calf serum and exposed to 5%–45% oxygen atmospheres. Optimal conditions, which were selected based upon the morphologic and histologic properties of the cultured tissues, were: DMEM-F12 medium in a serum-free environment with a 45% oxygen atmosphere. The refined SOC system supports the maintenance and/or continued development of the epidermis and dermis of trunk, back, scalp, and digital skin, developing hair follicles, nails, and glands. Overall, development and differentiation mimicked the in vivo state more closely than that observed when using other in vitro culture systems. The effects of bovine calf serum and oxygen levels are presented, and the potential for manipulating the environment of this system for studying mechanisms of cutaneous development is also discussed.
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    A further type of transient cytoplasmic organelle in human spermatids (1978)
    Springer
    Cell & tissue research 192 (1978), S. 359-361 
    Details
    ISSN: 1432-0878
    Keywords: Spermatids ; Human ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Osmiophilic granules with surrounding vesicles resembling flower-like structures occur transiently during the differentiation of human spermatids. These organelles are incorporated into the residual bodies when mature spermatids are released from the germinal epithelium.
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    URL: http://dx.doi.org/10.1007/BF00220752
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  • 90
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    Ultrastructural study of periodic lamellar granules in human neutrophils (1995)
    Springer
    Cell & tissue research 281 (1995), S. 69-76 
    Details
    ISSN: 1432-0878
    Keywords: Periodic lamellar granule ; Primary granule ; Chronic myeloproliferative disorder ; Neutrophils ; Electron microscopy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Granules consisting of periodically arranged membranous lamellae and amorphous electron-opaque material, i.e., periodic lamellar granules, are present in human neutrophils. To date, no extensive ultrastructural studies have been carried out on these granules because of their infrequent presence in neutrophils. The bone marrow of 18 cases of chronic myeloproliferative disorders, including one case of chronic neutrophilic leukemia in which periodic lamellar granules were frequently seen in neutrophils, was investigated by electron microscopy. Periodic lamellar granules were seen in neutrophils in 12 of the 18 cases at varying frequencies. They were preferentially seen in immature neutrophils. The transverse profiles of these granules revealed concentric complete/incomplete rings or periodic parallel straight lines, i.e., various patterns of lamellar arrangement were present. Periodic lamellar granules were positive for myeloperoxidase and lysozyme at the electron-microscopic level. These results suggest that these granules represent a primary neutrophil granule subtype. However, their functional and pathologic significance remains unknown.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00307959
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  • 91
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    Decreased adhesion of oxidized LDL-stimulated platelets caused by cytochalasin D (1995)
    Springer
    Cell & tissue research 280 (1995), S. 183-188 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Blood platelets ; Oxidized LDL ; Cytochalasin D ; Reflection contrast microscopy ; Image analysis ; Electron microscopy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The adhesion of human blood platelets is studied with an in vitro model using reflection contrast microscopy and an image analysis system. The adhesive feature is promoted by oxidatively modified low density lipoprotein, which also induces functional morphological changes of platelets. However, when washed platelets are pretreated with 0.05 mM cytochalasin D, oxidized low density lipoprotein (100 μg/ml) causes a slower increase of the adhesion area (11.6 μm2/min) compared to untreated platelets (15.7 μm2/min) or platelets treated by oxidized low density lipoprotein alone (20.5 μm2/min, P〈0.01). These results are supported by light transmission analysis and by transmission electron microscopy. Our experiments suggest that cytochalasin D inhibits the change of platelets in shape induced by oxidized low density lipoprotein, hinders the adhesion, but does not prevent the adhesion entirely.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00304523
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  • 92
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    Microgravity and hypergravity effects on collagen biosynthesis of human dermal fibroblasts (1995)
    Springer
    Cell & tissue research 282 (1995), S. 513-517 
    Details
    ISSN: 1432-0878
    Keywords: Microgravity ; Collagen ; Bone ; Dermal fibroblasts ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Astronauts experiencing long periods of space flight suffer from severe loss of bone tissue, particularly in those bones that carry the body weight under normal gravity. It is assumed that the lack of mechanical load decreases connective tissue biosynthesis in bone-forming cells. To test this assumption, quantitative and qualitative aspects of collagen synthesis under microgravity, normal gravity, and hypergravity conditions were investigated by incubating human fibroblast cultures with [3H]-proline for 4, 7, 10, and 20 h during the Spacelab D2-mission in 1993. Quantitative analysis revealed an increase of collagen synthesis under microgravity conditions, being up to 143% higher than in 1 g controls. In contrast, hypergravity samples showed a decrease in collagen synthesis with increasing g, being at the 13% level at 10 g. The relative proportion of collagen in total synthesized protein showed a slight decrease with increasing g. The secretion of collagen by the cells, proline hydroxylation of individual collagen α-chains, and the relative proportions of synthesized collagens I, III, and V were not affected under any of the applied conditions.
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    URL: http://dx.doi.org/10.1007/BF00318883
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  • 93
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    Elastic fibres are an essential component of human placental stem villous stroma and an integrated part of the perivascular contractile sheath (1995)
    Springer
    Cell & tissue research 283 (1995), S. 133-141 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Elastic fibres ; Placental stem villi ; Extravascular smooth muscle cells ; Adhesion plaques ; Talin immunoreactivity ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The stroma of human placental stem villi is believed to consist only of reticular and collagen fibres. In the present study we were able to show for the first time by light (orcein staining) and electron microscopy large amounts of elastic fibres in the stem villous stroma. Electron microscopically, homogeneous elastin was found alone or in association with microfibrils. In addition, microfibrils were observed forming long bands. These three structures, generally known to form elastic connective tissue, were seen in close connection with placental extravascular smooth muscle cells, which belong to the perivascular contractile sheath (PVCS) of stem villi. Elastin was associated with these smooth muscle cells and connected to collagen fibres via microfibrils. Collagen fibres were additionally interconnected by spike-like structures. Extravascular smooth muscle cells revealed numerous adhesion plaques which occupied conspicuously long cytoplasmic faces of the plasma membrane. In cryostat sections, immunoreactivity of talin, an attachment protein of adhesion plaques linking intracellular α-actin filaments with extracellular fibronectin, was detected in extravascular and vascular (media) smooth muscle cells. The arrangement of placental extravascular smooth muscle cells, elastic and collagen fibres suggests a functional myofibroelastic unit within the PVCS, which surrounds the large foetal blood vessels possibly contributing to elasticity and supporting tensile and/or contracting forces within the stem villi.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410050521
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  • 94
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    Expression of neural cell adhesion molecule (N-CAM) in perisinusoidal stellate cells of the human liver (1995)
    Springer
    Cell & tissue research 283 (1995), S. 159-165 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Cell adhesion molecules ; neuronal ; Stellate cells ; Liver ; Immunohistochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Neural cell adhesion molecule (N-CAM) is distributed in most nerve cells and some non-neural tissues. The present immunohistochemical study has revealed, for the first time, the expression of N-CAM in perisinusoidal stellate cells of the human liver. Liver specimens were stained with monoclonal antibody against human Leu19 (N-CAM) by a streptoavidin-biotin-peroxidase-complex method. Light- and electron-microscopic analyses have shown that N-CAM-positive nerve fibers are distributed in the periportal and intermediate zones of the liver lobule. Perisinusoidal stellate cells in these zones are also positive for N-CAM. N-CAM is expressed on the surface of the cell, including cytoplasmic projections. Close contact of N-CAM-positive nerve endings with N-CAM-positive stellate cells has been observed. On the other hand, stellate cells in the centrilobular zone exhibit weak or no reaction for N-CAM. Perivascular smooth muscle cells and fibroblasts in the portal area and myofibroblasts around the central veins are negative for N-CAM. The present results indicate that the perisinusoidal stellate cells in the periportal and intermediate zones of the liver lobule characteristically express N-CAM, unlike other related mesenchymal cells, and suggest that the intralobular heterogeneity of N-CAM expression by stellate cells is related to the different maturational stages of these cells.
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    URL: http://dx.doi.org/10.1007/s004410050524
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  • 95
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    Ultrastructural distribution of endogenous immunoglobulin-G in human term amniochorion (1995)
    Springer
    Cell & tissue research 281 (1995), S. 367-374 
    Details
    ISSN: 1432-0878
    Keywords: Placenta ; Amniochorion ; Cytotrophoblast cells ; Immunoglobulin G ; Immunocytochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Maternal immunoglobulin-G (IgG) is known to be transported across the placental syncytiotrophoblast during the period when the human fetus is incapable of manufacturing these defensive molecules. In this study we investigated the possible role of the amniochorion, that surrounds the amniotic cavity in which the fetus lies, in the transfer of immunoglobulin. Endogenous IgG was localised in the amniochorion by confocal immunofluorescence microscopy and by ultrastructural labelling of ultrathin frozen tissue sections using the protein A-gold technique. Immunoreactivity was identified in the extracellular matrix tissues and necrotic amniotic epithelial cells. Healthy amniotic epithelial cells and cytotrophoblast cells of the chorion laeve were devoid o endogenous IgG. These results suggest a possible non-specific paracellular transport pathway between cytotrophoblast cells, which may conceivably contribute to the acquisition of passive immunity by the fetus, and offer a rational explanation for the presence of small quantities of maternal IgG in the amniotic fluid.
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    URL: http://dx.doi.org/10.1007/BF00583405
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    Molecular anatomy of the perivascular sheath in human placental stem villi: the contractile apparatus and its association to the extracellular matrix (1997)
    Springer
    Cell & tissue research 290 (1997), S. 601-607 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Placental stem villi ; Perivascular contractile sheath ; Molecules of adhesion plaques ; Extracellular matrix molecules ; Immunocytochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. In previous studies, we have shown that smooth muscle cells and myofibroblast subpopulations of the perivascular stem villous sheath of the human placenta contain focal adhesion plaques and talin immunoreactivity. The close association of these cells to elastic and collagen fibres have led to the assumption of a functional myofibroelastic unit within the perivascular stem villous sheath. Interactions between the extracellular matrix and smooth muscle cells depend on a variety of structural protein assemblies. In the present study, we examined, by immunocytochemistry, whether the molecular assembly of extracellular matrix proteins and molecules of focal adhesions, known to be essential for signal transduction in smooth muscle cells, are also found in smooth muscle cells of the perivascular stem villous sheath of the human placenta. Vascular and extravascular smooth muscle cells were immunoreactive for α-actinin, vinculin, paxillin and tensin, the integrin chains α1 and β1, and the basement membrane components laminin and heparan/-chondroitin sulfate proteoglycan perlecan. pp125FAK did not react. In the extracellular matrix of blood vessel walls and the perivascular stem villous sheath, we found immunoreactivity of fibronectin and collagen types I, VI and undulin (collagen type XIV). From our data we conclude that within the perivascular stem villous sheath, there exists a system of signal transduction molecules, indicating a cross talk between the smooth muscle cells of this sheath and their surrounding extracellular matrix.
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    URL: http://dx.doi.org/10.1007/s004410050965
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    Human follicular dendritic cells in vitro and follicular dendritic-cell-like cells (1997)
    Springer
    Cell & tissue research 288 (1997), S. 381-389 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Germinal center ; Follicular dendritic cells ; Cell culture ; Adhesion and co-stimulatory molecules ; Emperipolesis ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Human follicular dendritic cell (FDC)-like cells (FLC) have been utilized for the in vitro analysis of germinal center reactions. However, there is no consensus whether FLC represent FDC in vitro. The purpose of the present study has therefore been to determine distinguishing features of FDC and FLC in vitro. The expression of CD40, CD54, CD49d, cytokine (γ-IFN and IL-4)-dependent MHC-class II, and CD106 was observed to be specific for the determination of FDC in long-term culture. The cytokine-dependent emperipolesis of germinal center B cells was establised as another discriminating property for FDC in vitro. In 2 out of 72 long-term cultures of FDC, we encountered dividing cells among the non-dividing population of FDC. The dividing cells expressed accessory molecules similar to those of FDC but showed emperipolesis only for the initial few days of their growth. FDC did not enhance the CD40-dependent proliferation of germinal center B cells; in contrast, FLC augumented it. Both types of cells produced a significant amount of cytokine-dependent IL-6. Further studies are needed to determine whether FLC originate from FDC in vitro.
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    URL: http://dx.doi.org/10.1007/s004410050824
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    Angioarchitecture of the human spermatic cord (1997)
    Springer
    Cell & tissue research 288 (1997), S. 391-398 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Spermatic cord ; Pampiniform plexus ; Arterio-venous anastomoses ; Casting preparations ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Human spermatic cords were investigated by means of cast preparations, light-microscopic examination and computer-aided 3-dimensional reconstructions from serial sections of paraffin-embedded material. After leaving the testis, the testicular veins formed two principal groups co-existing side by side. Numerous veno-venous anastomoses could be observed within each individual group, whereas only a few mutual intergroup anastomoses were found. The testicular artery ran within one group but showed no close topographical relationship to the other group. Light microscopy of the serial sections revealed that the group of veins with no close topographical relationship to the testicular artery ran at a distance of several centimeters embedded within fatty tissue. With the help of computer-aided 3-dimensional reconstructions, a spatial picture of the vascular organization was obtained. These results allowed the following classification of the veins of the pampiniform plexus. Group-I veins formed a tight plexus around the testicular artery by means of veno-venous anastomoses. Group-II veins formed veno-venous anastomoses between each other and ran over at a sizeable distance embedded in fatty tissue but showed no close topographical relationship to the testicular artery. Group-III vessels formed veno-venous anastomoses between group-I and group-II. Group IV veins formed arterio-venous anastomoses with the testicular artery. Based on the differences in wall structure and diameter, a subclassification in group-I and group-II was undertaken. This organization of the veins of the human pampiniform plexus should further the understanding of physiological processes, such as the transfer of hormones and other substances from the veins to the testicular artery and vice versa. It should also facilitate the tracing of the veins during antegrade sclerosing.
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    URL: http://dx.doi.org/10.1007/s004410050825
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    Distribution of heat-shock protein 60 immunoreactivity in testes of infertile men (1997)
    Springer
    Cell & tissue research 288 (1997), S. 539-544 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Testis ; hsp60 ; Infertility ; Spermatogonia ; Immunohistochemistry ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The immunohistochemical localization of heat-shock protein 60 (hsp60) was investigated in testicular biopsies obtained from 121 adult men with disturbed fertility. In normal unaffected tubules, hsp60 immunoreactivity was localized to spermatogonia, primary spermatocytes and Sertoli cells. In spermatogonia, cytosolic and mitochondrial labelling could be differentiated. In general, the number of stained spermatogonia decreased with the loss of spermatogenic function. A significant (P〈0.01) reduction of stained spermatogonia was observed in testes with maturation arrest of spermatogenesis at the level of primary spermatocytes (30.2±21.6%) compared with testes exhibiting normal spermatogenesis. In addition, the decrease in the score correlated significantly with the diminution of cytosolic hsp60 immmunolabelling (coefficient r=0.25, P=0.03). There was a significant difference (P〈0.01) in the percentage of cytosolic-stained spermatogonia in testes with a score equal to or greater than 5 (14.7±9.8%) and a score less than 5 (8.9±6.9%). These observations suggest that a low level of hsp60 expression in spermatogonia may lead to a different pattern of protection, which in turn could be involved in low spermatogenic efficiency.
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    URL: http://dx.doi.org/10.1007/s004410050839
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  • 100
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    Complement Cls, a classical enzyme with novel functions at the endochondral ossification center: immunohistochemical staining of activated Cls with a neoantigen-specific antibody (1997)
    Springer
    Cell & tissue research 288 (1997), S. 557-565 
    Details
    ISSN: 1432-0878
    Keywords: Key words: Complement Cls ; Neoantigen ; Cartilage ; Hypertrophic chondrocyte ; Immunohistochemistry ; Rheumatoid arthritis ; Decorin ; Syrian hamster ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The secondary ossification center of 14- to 16-day-old hamster tibiae was examined immunohistochemically with active and inactive Cls-specific antibodies, RK5 and RK4, respectively. At the ossification center, chondrocytes differentiate from proliferating and hypertrophic to degenerating stages, and their site is occupied by the bone marrow. Cls was strongly immunostained in hypertrophic chondrocytes. In order to discover whether Cls is activated at a particular site, the cartilage was immunostained with RK5 and RK4. RK5 mainly reacted with degrading matrix around invading vessels. In contrast, RK4 strongly stained hypertrophic chondrocytes. Immunoelectron microscopy revealed Cls on degrading fragments of chondrocytes and fibers of cartilage matrix. Decorin, one of the major matrix proteoglycans, was dose and time dependently degraded by Cls. Type II collagen and type I gelatin were also degraded. Articular cartilage from patients with rheumatoid arthritis was positively immunostained (11/12 cases) with an anti-Cls monoclonal antibody (mAb) PG11, whereas normal articular cartilage (5/5 cases) was negative, suggesting Cls participation in the etiology of rheumatoid arthritis.
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    URL: http://dx.doi.org/10.1007/s004410050841
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