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Biomedical subjects

W Krause

Publications and source records attributed to W Krause.

At least 181 records · Page 10Linked to original sources
PubMed1990

Pharmacokinetics of (+)-rolipram and (-)-rolipram in healthy volunteers.

Plasma levels of S-(+)-rolipram and R-(-)-rolipram in six healthy male volunteers were measured by radioimmunoassay after intravenous injection of 0.1 mg and oral administration of 1.0 mg of the pure enantiomers. Following i.v. treatment, plasma levels of both isomers declined in three phases, with half-lives of 0.2 h, 0.6-0.9 h and 6-8 h. Total clearance was 6 ml.min-1.kg-1. Oral administration of 1.0 mg gave a peak concentration of 16 ng.ml-1 after 0.5 h. Bioavailability of (+)-rolipram was 77% and of the (-) enantiomer it was 74%. There was no significant difference in Cmax, half-life, total clearance or bioavailability between the two enantiomers.

Administration, Oral↗
PubMed1990

Synthesis of a deuterated analogue and development of antibody/GC/MS for the determination of nocloprost in plasma.

An analytical method for the determination of the PGE derivative nocloprost in plasma was developed combining the features of both radioimmunoassay and GC/MS. The antibody usually employed in nocloprost radioimmunoassay was coupled to Sepharose 4B and used as a stationary phase for the extraction of the drug. After appropriate derivatisation, nocloprost was determined by GC/MS in the negative ion-chemical ionisation mode. As an internal standard deuterated nocloprost was synthesized and added to the plasma samples before extraction. The extraction recovery was 94% and the limit of detection was 5 pg/ml. Intra- and interassay precision at 100 pg/ml was calculated as 3.3 and 4.0%, respectively.

Calibration↗
PubMed1990

Ultrastructure and quantitative composition of isolated endothelial cells of rat liver.

Isolated endothelial cells (n 110; 350-540 microns3 in volume) of the sinusoid of rat liver were found to differ from in situ endothelial cells by their rounded shape with the nucleus usually in the centre and fenestrae of the sieve plates across the entire cytoplasm. Their volume density is 0.2814 (SE 0.0085). Some of them tend to form complex, ramified structures as well as clefts and vacuoles up to 1 micron in size. Dense bodies are other structures quite often seen in endothelial cells (Vv 0.0189, SE 0.0085). Mitochondria, on the other hand, are extremely rare (Vv 0.0023, SE 0.0009). Both the preservation and relocation of sieve structure after isolation may probably be due to the cytoskeleton which in vivo causes changes of size and number of endothelial cell fenestrae under physiological and pathological conditions.

Animals↗
PubMed1990

Monoclonal antibodies against antigens expressed by human sperm.

The production and characterization of 21 mouse monoclonal antibodies (TüS1-TüS21) with specificity predominantly for human spermatozoa antigens is described. Reactivity of cells from human ejaculates, peripheral blood and several organs was determined using the alkaline phosphatase-anti-alkaline phosphatase (APAAP)-technique as well as the indirect immunofluorescence test. 15 of the monoclonal antibodies reacted with various regions of human sperm and often also with their precursor cells in the testis. Cross-reactivity with animal spermatozoa was frequently observed.

Acrosome↗
PubMed1990

Pharmacokinetics of iloprost in patients with severe peripheral arterial occlusive disease.

The pharmacokinetics of iloprost were studied in 12 hospitalized patients suffering from severe peripheral arterial occlusive disease (PAOD) stages III or IV according to Fontaine. The patients were 8 males and 4 females aged from 49 to 83 years. Apart from PAOD, several other concomitant diseases were present, e.g. myocardial and/or renal insufficiency, diabetes and hypertension. Patients were treated daily with i.v. infusions of iloprost at dosages of 1.0-3.3 ng/kg/min over a period of 4 to 6 h. Dose-normalized steady-state plasma levels ranged from 39 to 100 pg/ml (65 +/- 20 pg/ml). The total clearance accounted for 16 +/- 5 ml/min/kg. Post-infusion disposition in the plasma was biphasic with half-lives of 4 +/- 2 min and 37 +/- 8 min. The plasma level profiles obtained on days 4 and 14 of treatment in 3 patients were similar. Sex specific kinetic differences were not observed. In comparison to healthy volunteers, studied in an earlier trial, total clearance was slightly lower and consequently steady state levels were increased (p less than 0.05) in PAOD patients. Half-lives in the plasma were not significantly different.

Aged↗
PubMed1990

Development, validation and practical use of a sensitive and specific radioimmunoassay for the determination of iloprost.

Iloprost is a potent, clinically effective PGI2-mimetic. Therapeutic plasma levels are in the low pg-range and currently analyses of biological samples are performed by GC/MS after antiserum-column extraction. Although this method exhibits high sensitivity and specificity it permits only limited numbers of samples to be analyzed owing to time-consuming work-up. The present report describes the development of a novel highly selective antiserum and its use for the RIA determination of iloprost in biological samples. An antiserum was raised against "iloprost-9-pentynyl"-BSA in rabbits. Iloprost-[3H]-methylester with a specific activity of 66.9 Ci/mmol was used as a tracer. RIA-analyses were carried out with 0.05-0.5 ml plasma adjusted to pH2 with 1 N HCl and extracted with 2.5 ml diethylether. Separation of antiserum bound and unbound iloprost was achieved by the charcoal method. Extraction recovery of iloprost was approximately 90% at pH less than or equal to 4. The detection limit of the novel assay was 1-2 pg/tube corresponding to 5-10 pg/ml plasma (if 0.1-0.2 ml plasma was used). Coefficients of variations were 8% and 2% (within-day, n = 3) and 17% and 12% (day-to-day, n = 5) at 50 and 100 pg/ml. RIA- and GC/MS-levels of iloprost measured in human samples were similar (p less than 0.001). Cross-reactivity HPLC-chromatograms of plasma extracts did not reveal any peak apart from iloprost. The RIA-method exhibits both a similar specificity and detection limit to GC/MS and will be used for further analyses.

Animals↗
PubMed1990

Pharmacokinetics of iloprost in patients with hepatic dysfunction.

In the present experiment the pharmacokinetics of iloprost was studied in eight hospitalized patients suffering from liver cirrhosis (mean age: 56 years, 3 females, 5 males, child-classification: A [n = 1], B [n = 5], C [n = 2]/mean 14C-aminopyrine breath test: 3.9% dose/2 h). Iloprost was administered as a 1 h-i.v. infusion with 1 ng/kg/min to all the test subjects. Steady state plasma levels of 93 +/- 31 pg/ml were observed at the end of infusion. The terminal half-life of iloprost was 28 +/- 24 min. From AUC values of 126 +/- 60 pg.h/ml a total clearance of 10 +/- 5 ml/min/kg was calculated. The study demonstrated that iloprost clearance was reduced by a factor of 2 in patients suffering from hepatic dysfunction compared with healthy subjects. Individual dose titration is the recommended dose regimen for iloprost therapy in all patients. Therefore, apart from a reduction of the starting dose (of approximately 50%) for titration, special recommendations are not necessary for patients with impaired liver function.

Adult↗
PubMed1990

Pharmacokinetics of iloprost in patients with chronic renal failure and on maintenance haemodialysis.

Iloprost is a potent, chemically stable prostacyclin-mimetic for which therapeutic efficacy has been proven in patients with peripheral arterial occlusive disease (PAOD) and in those suffering from Raynaud's phenomenon. In volunteers and PAOD-patients the pharmacokinetics of iloprost after intravenous (i.v.) infusion treatment was characterized by dose-dependent steady-state plasma levels, a terminal half-life of approximately 20-30 min, and a total clearance of 15-20 ml/min/kg. Bioinactivation was mainly due to beta-oxidation. In the present study the pharmacokinetics of iloprost was investigated in 21 patients suffering from renal insufficiency, which either required haemodialysis or not. They were treated by one hour i.v. infusion with 1 ng/kg/min and blood samples were taken during and after the end of infusion. Due to technical sampling problems iloprost pharmacokinetics could only be calculated for seven dialysis and eight non-dialysis patients. In the dialysis patients steady-state levels were 114 to 320 pg/ml as compared to 36 to 70 pg/ml in the non-dialysis group. Half-lives were similar in both groups: alpha-phase: 0.05 h and beta-phase: 0.5 h. The total clearance was 2.6 to 8.0 ml/min/kg (dialysis patients) and 13.2 to 25.8 ml/min/kg (non-dialysis patients). The present study demonstrated that the pharmacokinetic profile of iloprost in patients with renal failure (not subject to haemodialysis) was similar to that observed in PAOD-patients and volunteers. In patients on maintenance haemodialysis, iloprost clearance was reduced by a factor of four. The iloprost dose regimen required in general (due to interindividual variability in response) a careful dose titration.

Adult↗
PubMed1990

Pharmacokinetics of the anxiolytic beta-carboline derivative abecarnil in the mouse, rat, rabbit, dog, cynomolgus monkey and baboon. Studies on species differences.

The pharmacokinetics of abecarnil (isopropyl 6-(benzyloxy)-4-(methoxymethyl)-9H-pyrido [3,4-b] indole-3-carboxylate, ZK 112 119) were studied in the mouse, rat, rabbit, dog, cynomolgus monkey and baboon using 14C-labeled drug and HPLC with fluorescence detection for measurement of unchanged drug. Abecarnil was rapidly and completely absorbed after oral doses of 10 mg/kg. At higher doses, absorption was prolonged and incomplete in the cynomolgus monkey. The bioavailability of abecarnil was 20-30% in all the species investigated. The terminal half-life of the unchanged drug in plasma was relatively similar in all species (0.6-1.7 h). Abecarnil was able to pass the blood-brain barrier achieving concentrations in the brain similar to those in plasma. Tissue distribution of labeled compounds was rapid with highest concentrations in the liver, adrenals, kidneys and pancreas followed by the bone marrow, lungs, heart, fat, spleen, ovaries and thyroid gland. Excretion of radiolabeled compounds proceeded predominantly in the feces of the rat, the rabbit and the cynomolgus monkey.

Animals↗
PubMed1990

Pharmacokinetics and acute toleration of the beta-carboline derivative abecarnil in man.

Plasma levels of the beta-carboline, abecarnil (isopropyl 6-(benzyloxy)-4-(methoxymethyl)-9H-pyrido [3,4-b]indole-3- carboxylate, ZK112119) which is presently under development as an anxiolytic, were measured by HPLC with fluorescence detection in six healthy male volunteers given 30 micrograms/kg i.v. and 5 and 10 mg p.o. Following i.v. injection, plasma levels declined biphasically with half-lives of 6 min and 3.4 h. The total clearance was 13 ml/min/kg. After oral administration, maximum concentrations were reached after 2 h. The bioavailability was approximately 60%. The terminal half-life after p.o. administration was 7 h. No clinically relevant changes in ECG, vital signs or standard laboratory measurements occurred. Eight different adverse reactions were noted by the subjects. The most frequently reported side-effects were tiredness, dizziness, unsteady gait and lack of concentration.

Adult↗
PubMed1990

In-vitro and in-vivo characterisation of two sustained release formulations for the antidepressant rolipram.

Using the pellet technology two sustained release formulations for (dl)-rolipram (ZK 62 711; CAS 61413-54-5) were developed and characterised by in-vitro dissolution tests and in a cross-over study in healthy male volunteers. In-vitro, 50% release was achieved within 2.5 h for formulation A and within 4 h for B. In-vivo, Cmax values of 4.4 +/- 0.9 ng/ml (A) and 2.1 +/- 0.8 ng/ml (B) were observed 2.8 +/- 0.8 h or 10.3 +/- 3.7 h after oral intake of 3 mg (dl)-rolipram. The terminal disposition half-life in the plasma was similar for both formulations (12 +/- 13 h and 11 +/- 2 h). Expectedly, the relative bioavailability of formulation B was lower compared to A (72%). Using the pellet technology, formulations with an intended release profile can be tailored to suit by mixing pellets with different release characteristics within one dosage form.

Adult↗
PubMed1990

[Use of sperm cryopreservation by tumor patients].

Impairment of spermatogenesis can be expected after cytostatic treatment or radiation for cancer. To improve fertility prognosis, semen samples are usually deep-frozen and stored in liquid nitrogen prior to such a therapy. However, after therapy this deep-frozen sperm is seldom used. Of 47 patients for whom we started cryopreservation of semen during the years 1983-1988, 20 men were no longer interested in further storage within 2 years, so that the deposits were destroyed. Up to now, none of the 27 samples still existing has been used for artificial insemination or in vitro fertilization (IVF). Possible reasons for this are discussed.

Adolescent↗
PubMed1990

Morphometrical characterization of isolated rat hepatocytes.

Mononuclear hepatocytes account for 81% of all isolated hepatocytes of adult rats and are 3800 +/- 209 microns3 in volume with a surface of 1191 +/- 44 microns2, while the other 19% are binuclear cells, 4735 +/- 688 microns3 in volume and 1347 +/- 72 microns2 in surface. The plasma membrane contains few microvilli and different amounts of blebs. The organelle-free ectoplasmic zone beneath the plasma membrane is 1-6 microns in width. The cell organelles are centralized around the cell nucleus. The mitochondrial volume density (Vv) is 0.402 +/- 0.028; this is twice as high as that of hepatocytes in situ of adult rats. This result together with an about 50% volume decrease of isolated versus hepatocytes in situ supports the interpretation that unstructured ground plasma in the form of cytopheres is emitted into the surrounding space, probably by shedding of cytoplasmic protrusions, leading to a rise in relative mitochondrial volume levels. To avoid misinterpretation of results obtained from studies directed onto the metabolism of isolated hepatocytes, due consideration should be given to these findings.

Animals↗
PubMed1990

Growth hormone secretion in children after therapy for acute lymphoblastic leukaemia.

In eight children, after the termination of therapy for acute lymphoblastic leukaemia (ALL) the secretion of growth hormone (GH) was determined by the stimulation test with clonidine. The children were treated in the period from 1983 till 1988 and they were administered chemotherapy, intrathecal methotrexate therapy and cranial irradiation 60CO in a dose of 1800 rads. In one case a complete GH deficiency was found, in three cases there was a partial deficiency and in the remaining cases the secretion was regular. No correlation was found between the biochemical values of GH and the clinical stature. There was also no interrelation between the duration of therapy (chemotherapy) and the degree of pituitary gland failure. We have compared the results of GH output in children treated for ALL with those of 44 children in whom short stature was diagnosed. The age in both groups was similar.

Child↗
PubMed1990

Quantitative ultrastructure of isolated Kupffer cells of rat liver.

The average volume of isolated Kupffer cells of rat liver is 821 +/- 64 microns 3, the average surface being 423 +/- 24 microns 2 (599 microns 2, with cell processes included). The surface structure (pseudopodia, lamellipodia, filopodia, microvilli) of isolated cells is much less developed than that of Kupffer cells in situ. By morphometric characterization volume densities are 0.1264 +/- 0.0077 (SE) for mitochondria and 0.3591 +/- 0.0169 for lysosomal structures. The volume of mitochondria amount to 0.79 +/- 0.04 microns 3.

Animals↗
PubMed1989

[Sexually transmitted diseases as causes of disorders of male fertility].

Infections with sexually transmitted germs may affect the male fertility in different ways. Possible consequences are impairment of the spermatogenesis, induction of auto-immune mechanisms, spermatodysfunction, and inflammatory occlusion of the ejaculatory duct. Only in high concentrations, bacteria (e.g. E. coli) may result in reducing the motility of spermatozoa. The germ counts observed under clinical conditions, however, do not come up with these high levels. The same is true for mycoplasmas. As a whole, sexually transmitted infections only play a minor role with regard to male infertility.

Humans↗