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Biomedical subjects

W Krause

Publications and source records attributed to W Krause.

At least 217 records · Page 12Linked to original sources

Circulatory activity of dopamine-dipeptide compounds.

Three newly synthesized dopamine-dipeptide compounds (Gly-Pro-dopamide, Lys-Pro-dopamide, Z-Lys-Pro-dopamide) which should be cleft in vivo by the enzyme dipeptidyl peptidase IV (EC 3.4.14.5) were investigated as to their protective activity against hemorrhagic shock in rats. All three compounds increased significantly the survival times of animals, subjected to hemorrhage, in nearly the same manner as dopamine did. They also relaxed the blood vessels of isolated perfused rat kidneys pretreated with phenoxybenzamine. This activity demonstrates a vasodilation via dopaminergic receptors. Regarding the blood pressure increasing activity, mediated by excitation of alpha-receptors, Gly-Pro-dopamide was less potent than dopamine but affected blood pressure about four times longer than dopamine did. Lys-Pro-dopamide and Z-Lys-Pro-dopamide were nearly equieffective to dopamine.

Animals↗

In vitro inhibition of lens epithelial cell proliferation and migration.

Delayed opacification of the posterior capsule is the most common cause of decreased visual acuity after extracapsular cataract extraction. In humans, this has been shown to result from migration and possibly proliferation of residual lens epithelial cells onto the central posterior capsule. We studied a group of pharmacologic agents to determine their ability to inhibit lens epithelial cell proliferation and migration in vitro. A drug capable of inhibiting lens epithelial cell growth and/or migration, if free of unacceptable toxic effects on other cell populations, might be used to prevent lens capsule opacification. Anti-proliferative activity was exhibited by several agents, with 50% inhibition of growth occurring at the following concentrations: 5-fluorouracil, 30 micrograms/ml; daunomycin, 10 ng/ml; colchicine, 15 ng/ml; doxorubicin, 5 ng/ml; dexamethasone, 100 micrograms/ml; and cytosine arabinoside, 100 ng/ml. Colchicine inhibited lens epithelial cell migration by 50% at 20 ng/ml.

Animals↗

[Long-term experiences with autoinjection therapy of papaverine in erectile dysfunction].

Long-term experience with intracavernous self-injection of papaverine in 36 patients with erectile failure is reported. The average required dose of papaverine in 2037 documented injections was 31.5 mg. The rate of complications was low with a mean follow-up of 6.9 months. Prolonged erections occurred four times. Two patients reported the development of tolerance. In one man circumscribed induration of the tunica albuginea was observed, which disappeared spontaneously after change of the injection site. No infections of the corpora cavernosa, circulatory disturbances or signs of hepatotoxicity were observed.

Adult↗

[Hormone studies in andrology].

Investigation of endocrine function is mainly performed by measuring plasma levels of the hormones concerned. Their evaluation must take into account the spontaneous alterations of hormonal plasma levels. With regard to gonadotrophins, the short-term episodic peaks of LH are significant. Testosterone levels, as well, show extensive short-term variations; in addition we find a marked circadian rhythm. Seasonal variations of longer duration are possibly superposed. Regarding the evaluation of testosterone levels, we must consider its protein-binding. Only the free fraction of the hormone is biologically active. Concerning the function and secretory capacity of endocrine organs, stimulation tests often provide us with better results than the determination of basal plasma levels. The gonadotropic function of the hypophysis can be stimulated by intravenous application of 100 micrograms GnRH leading to increased blood levels of LH and FSH. The stimulation of the testosterone biosynthesis is achieved by application of hCG. The testosterone plasma levels rise within a few hours; a second peak follows after about 48 hours. Functional tests are also significant regarding the therapeutical prognosis of spermatogenetic disorders treated with gonadotrophins. Their outcome is even better if the secretory capacity of the hypophysis and the Leydig's cell apparatus has been proved sufficient before treatment.

Chorionic Gonadotropin↗

Human studies on the benzodiazepine receptor antagonist beta-carboline ZK 93,426: preliminary observations on psychotropic activity.

The beta-carboline ZK 93,426, a benzodiazepine receptor antagonist, was administered intravenously to human volunteers at two different doses (0.01 mg/kg, 0.04 mg/kg) according to a double-blind, placebo controlled design. Vital functions (i.e. blood pressure, heart rate, ECG, EEG), peripheral (finger) skin temperature and performance in psychometric tests for psychotropic and cognitive effects were evaluated. Blood samples were collected in addition and certain pharmacokinetic parameters were estimated. ZK 93,426 in both doses was well tolerated and exhibited no side effects. A decrease in peripheral skin temperature and heart rate was observed. In a general estimation of behavioural changes, volunteers experienced a stimulant and activating effect of the drug. An improvement in performance was observed in two cognitive tasks, the "logical reasoning task" and "pictures differences task" which estimated concentration and attention, respectively. No effects were found in time estimation. Plasma levels 5 min after intravenous administration of ZK 93 426 were 16 +/- 10 ng/ml and 52 +/- 31 ng/ml for 0.01 mg/kg and 0.04 mg/kg, respectively. Total clearance was calculated as 46 +/- 22 ml/min/kg (0.04 mg/kg).

Adolescent↗

Pharmacokinetics and pharmacodynamics of radio-labeled iloprost in elderly volunteers.

The plasma levels and excretion of tritium-labeled iloprost in healthy elderly male and female volunteers have been measured after i.v. infusion of 2 ng X kg-1 X min-1 for 4 h and oral administration of 0.1 and 0.48 microgram/kg. During infusion, a steady-state of labeled compounds in the plasma was not achieved. Total radioactivity declined from a mean of 408 pg equiv/ml in three phases, with half-lives of 24 min, 1.7 h and 5.0 h, respectively. A steady-state of unchanged iloprost was reached rapidly with a peak of 81 pg/ml. Plasma levels declined biphasically with half-lives of 6 min and 31 min. Total clearance was 24 ml X min-1 X kg-1. Maximum concentrations of labeled substances after oral administration were 307 and 1,051 pg equiv/ml after 29 and 39 min, respectively. The peak of unchanged iloprost (116 pg/ml) was observed 7.5 min after an oral dose of 0.48 microgram/kg. Bioavailability was 16%. Iloprost was totally metabolized and the metabolites were mainly excreted in urine. The main biotransformation products in plasma and urine were tentatively identified by cochromatography as dinor- and tetranoriloprost and their glucuronides. ADP-induced platelet aggregation was reduced by 60% during the i.v. infusion and 15 min after oral administration of 0.48 microgram/kg. Heart rate and blood pressure were virtually unaffected. Common side-effects were facial flush, headache and nausea.

Aged↗

Glycosphingolipid composition of human semen.

Glycosphingolipids were extracted from human semen and purified. Based on the fluorometric assay of sphingosine, in spermatozoa a content of 4.4 +/- 0.9 nmol/10(8) cells of gangliosides and 22.1 +/- 1.7 nmol/10(8) cells of neutral glycosphingolipids was determined. Seminal plasma contained 4.1 +/- 0.6 nmol gangliosides and 29.3 +/- 1.5 nmol neutral glycosphingolipids per milliliter. The glycosphingolipid component patterns of human spermatozoa and seminal plasma were determined by thin-layer chromatography. Four neutral glycolipids were isolated and their carbohydrate moieties were characterized. All of these glycolipid components belonged to the globo-series. Gas chromatography, combined gas chromatography/mass fragmentography, and exoglycosidase treatments revealed the following structures for the glycosphingolipids of human semen: Glc1-Cer, Gal beta 1-4Glc1-Cer, Gal alpha 1-4Gal beta 1-4Glc1-Cer, and Gal-NAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc1-Cer. In addition, the occurrence of trace amounts of lactoneotetraosyl- and lactoneohexaosylceramide was detected by immunostaining after thin-layer chromatographic separation. Human spermatozoa, as well as seminal plasma, contained the gangliosides Glac1,Glac2, a sialolactoneotetraosylceramide, and a sialolactoneohexaosylceramide. The gangliosides were identified on the basis of their running characteristics by high-performance thin-layer chromatography, exoglycosidase treatment, and immunostaining after thin-layer chromatography. The ceramide composition of the glycolipids in human spermatozoa, as well as in seminal plasma, was dominated by C22:0-behenic acid and the saturated sphingoid d18:0, sphinganine.

Chromatography, Ion Exchange↗

[Resorption of progesterone through the intact skin of the breast in comparison with other body regions].

In healthy female volunteers the percutaneous absorption of progesterone from an ointment is studied comparing the absorption in the breast skin and that of other regions (thigh, abdomen). Before and certain times after the application progesterone serum levels are measured. A significant increase of mean serum levels (1 to 1.9 ng/ml) ist observed after application to the breast, while it is missing after application to other sites. Individual values of progesterone levels show a distinct peak after 30-120 min following application to the breast, while it lacks in three cases following other application. Serum peaks do not depend on the skin thickness as determined by ultrasound measurement. Percutaneous treatment with progesterone obviously is easier to perform using the breast skin than that of other regions.

Administration, Topical↗

Estimation of organelle water fractions from frozen-dried cryosections.

Local dry mass or water fractions can be measured on frozen-dried cryosections assuming constant section thickness in the hydrated state and no net water movements and no differential shrinkage during freezing and drying. These assumptions have been tested on a model consisting of isolated rat liver mitochondria in an albumin matrix with a concentration similar to the dry mass concentration of the cytoplasm. The dry mass concentrations of mitochondria before freezing as measured by interference microscopy and after freezing and freeze-drying of the sections as measured by X-ray microanalysis and scanning microdensitometry are shown to be equal as long as the ice crystals in the medium are smaller than about 100 nm. It is concluded, therefore, that the above-mentioned assumptions could also hold for the cryopreparation of cells and tissues.

Animals↗

Environmental risk factors in the history of male patients of an infertility clinic.

93 consecutive patients attending our andrologic department for marital infertility were asked for possible environmental risk factors including traumata, heat, noise, smoking, radiation, micro waves, pesticides, and plastics. The data were correlated to the mean seminal parameters. No significant differences were found between patients being positive for a certain risk factor and those being negative.

Adult↗

Pharmacokinetics and metabolism of mespirenone, a new aldosterone antagonist, in rat and cynomolgus monkey.

The pharmacokinetics and metabolism of mespirenone were examined in rat and cynomolgus monkey using the tritiated drug. Following i.v. administration, mespirenone exhibited a short half-life and a high plasma clearance; after oral administration the unchanged compound was not detectable. Thus, mespirenone has to be considered a pro-drug. From rat urine three metabolites were isolated by h.p.l.c. and identified by mass spectra and 1H n.m.r., all having retained the 7 alpha-sulphur substituent as a thiomethyl or a sulphinylmethyl group. The 7 alpha-thiomethyl metabolite had a half-life of six hours in rat plasma and its AUC value was 35% of that for total 3H. As this metabolite has marked anti-aldosterone activity, it is an active metabolite that contributes to the pharmacological effect of mespirenone.

Administration, Oral↗

[Immotile cilia syndrome].

The case of a patient with immotile cilia is reported. This syndrome is characterized by infertility caused by immotile spermatozoa and by bronchiectases owing to inadequate function of ciliated cells. Electron microscope studies showed gross abnormalities of the axial threads in the flagella of the spermatozoa examined.

Adult↗

[Percutaneous resorption of testosterone, androstenedione and estradiol and their effect on serum steroid levels].

2.5 mg/m2 body surface of testosterone, 0.5 mg/m2 estradiol and 1.25 mg/m2 androstenedione were applied to the skin of healthy young men. The steroids were dissolved in a mixture of ethanol, water, and propylenglycol and applied to 10% of the body surface. Thus the amount given was equivalent to about one fifth of the amount in mg/m2. Serum levels of testosterone, androstenedione, and estradiol were measured by means of radioimmunology, both before the application as well as 2, 4, 8, and 24 h afterwards. Pregneolone and androstenedione did not alter the serum levels of the hormones determined. Testosterone and estradiol lead to a short peak of their serum concentration. Our results indicate that precursor steroids, pregnenolone and androstenedione, are rapidly metabolized to other compounds before they reach the blood in measurable amounts.

Administration, Topical↗

[Decreased incidence of postgonococcal urethritis following minocycline treatment compared to penicillin/spectinomycin].

Two groups of 30 patients each suffering from gonococcal urethritis were treated either with minocyclin for 7 days or with a single administration of penicillin or spectinomycin, respectively. 30% of them revealed an additional infection with C. trachomatis or U. urealyticum. On the 8th day, we observed remaining symptoms in only 20% of the patients treated with minocyclin, but in 40% of the group treated with penicillin/spectinomycin.

Adult↗