[Fertility and adnexitis in the male].
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Bacterial Infections↗
Biomedical subjects
W Krause
Publications and source records attributed to W Krause.
[The possibilities of separating spermatozoa].
Some methods for the separation of spermatozoa are described, with the aim of: 1. Increasing the "quality" of seminal parameters in subfertile men 2. Separating spermatozoa containing X and Y chromosomes 3. Deleting spermatozoa containing certain genetic information. Mainly gravimetric methods were used and concentration of motile spermatozoa was obtained, but the sperm density was always diminished. None of the methods used so far has been able to increase the fertility index or change the sex proportion of children born after artificial insemination.
Cell Separation↗
Reticulocyte lipoxygenase changes the passive electrical properties of bovine heart submitochondrial particles.
Purified reticulocyte lipoxygenase oxygenates the polyunsaturated phospholipids of sonified submitochondrial particles from bovine heart as measured by a burst of oxygen uptake. Over the frequency range of 0.5 to 100 MHz, the complex impedance of the submitochondrial particles as a function of the frequency before and after lipoxygenase attack was measured. From these data, the membrane capacity, the conductivity of the membrane and the conductivity inside the particles were calculated. Lipoxygenase action causes a 4-fold increase in the membrane capacity and a 2-fold increase in the membrane conductivity. Using the method of deformation of electric pulses, kinetic measurements were performed. In parallel to the changes of the passive electric properties, a partial inhibition of NADH oxidase and succinate oxidase was caused by the lipoxygenase attack. Oxygen uptake, changes of the passive electric properties and the inhibition of respiratory enzymes were prevented by lipoxygenase inhibitors. Owing to the high oxygen consumption produced by the lipoxygenase reaction, anaerobiosis was reached within the first 30 s in the closed chamber. Therefore, it must be concluded that the changes in passive electric properties and the inhibition of the respiratory enzymes are due to secondary anaerobic processes such as the hydroperoxidase reaction catalyzed by the lipoxygenase or a slow redistribution of peroxidized membrane lipids. The results are discussed in relation to the breakdown of mitochondria during the maturation process of red cells.
Animals↗
Determination of canrenone, the major metabolite of spironolactone, in plasma and urine by high-performance liquid chromatography.
An assay procedure for measuring plasma and urine levels of canrenone is described. The drug is extracted with n-hexane-toluene (1:1, v/v) after adding spirorenone as internal standard, and is then separated from plasma constituents and metabolites by high-performance liquid chromatography followed by UV detection at 285 nm. The limit of detection is less than 5 ng/ml. Interference with a series of spironolactone and canrenone metabolites was not observed. Plasma levels and renal excretion of canrenone after oral administration of 200 mg of spironolactone and intravenous injection of 200 mg of potassium canrenoate to a healthy male volunteer were measured.
Administration, Oral↗
[The diagnosis of sexual function disorders. Screening studies of angiological factors in disorders of sexual function].
106 outpatients, visiting our department because of sexual disturbances, underwent a standardized examination program. The following anamnestic data and clinical and laboratory findings were recorded: Details of the vita sexualis, evidences for genital and vascular diseases, endocrine abnormalities including diabetes mellitus, drug consumption. Genital organs were judged by clinical examination, blood-pressure, oscillography and penis-flow-index were measured, hormones, sugar and lipids in blood serum were determined, with respect to a special indication, cavernosography and pelvic angiography were performed, and prostatic inflammation was excluded. None of the anamnestic data differ in its frequency from that of the total population. Mean blood pressure, oscillographic indices, hormone levels, and lipids were found within the normal range. Only a high rate of diabetes mellitus (6%) in all patients and a high rate of pathologic penis-flow-index in men between 40 and 60 years of age were found. We conclude from our results, that medical history and laboratory findings in general will indicate no pathogenetic mechanism in impotence. Just the recording of penile blood flow will give positive correlations.
Adult↗
[Differential diagnosis and therapy of male urethritis].
The infectious male urethritis is characterized by the urethral discharge, which is clear or purulent due to the number of leucocytes. Infection occurs mostly in sexual intercourse. Neisseria gonorrhoeae today causes only about 20-30% of the infections. Gramnegative bacteria are demonstrable by microscopic examination of the urethral discharge, otherwise by cultivation. Ureaplasma and chlamydia trachomatis, an intracellular growing bacterium, are the most frequent agents in infectious urethritis. They are often found together, the cultivation requires special laboratory conditions. They are common saprophytis bacteria within the urethra (u. urealyticum in up to 50%), their number of colony forming units of urethritis, like yeasts, viruses, trichomonas are rare. The treatment of gonorrhoic urethritis is done by penicillin or spectinomycin. Infections by u. urealyticum and c. trachomatis are treated with tetracyclin. Although spontaneous healing is not uncommon, therapy should be performed with respect to the high risk of following prostatitis and epididymitis.
Anti-Bacterial Agents↗
Pharmacokinetics of canrenone after oral administration of spironolactone and intravenous injection of canrenoate-K in healthy man.
Five healthy male volunteers received canrenoate-K 200 mg (Sincomen pro injectione) by intravenous injection and one week later spironolactone 200 mg (Sincomen-100) orally. Plasma levels and urinary excretion of unchanged canrenone were determined up to 24 h by a specific HPLC method. Following intravenous administration, the maximum plasma level of 2066 +/- 876 ng/ml was found after 29 +/- 15 min and thereafter the concentration declined with a half-life of 3.7 +/- 1.2 h. Total clearance was 4.2 +/- 1.7 ml/min . kg. After oral ingestion, the maximum concentration of 177 +/- 33 ng/ml was observed at 4.4 +/- 0.9 h. The absolute bioavailability of canrenone was 25 +/- 9%. Within 24 h, respectively 0.4 and 0.6 mg, canrenone were excreted by the kidney after intravenous and oral administration. The half-life of elimination was 4.9 +/- 1.8 h (i.v.) and 3.9 +/- 1.2 h (p.o.).
Administration, Oral↗
Pharmacokinetics of the new aldosterone antagonist, spirorenone, in healthy volunteers after single and repeated daily doses.
The plasma concentrations of spirorenone in two groups of male volunteers have been determined after single and 14 daily doses of spirorenone 10 and 40 mg. Independent of the dose and pretreatment, spirorenone was absorbed with a half-life of 20-30 min, achieving maximum concentrations of about 100 ng/ml (10 mg) and 260 ng/ml (40 mg) after 1-2 h. Disposition of the parent drug was biphasic with half-lives of 50-60 min (distribution) and 5-6 h (elimination). Neither significant accumulation nor enzyme induction were observed after prolonged treatment. In one test subject given spirorenone 40 mg, the concentration of an active metabolite, 1,2-dihydrospirorenone, was measured. This compound accumulated considerably after multiple dosing and the area under the plasma concentration-time curve increased from 16 to 52% relative to that of spirorenone itself.
Adult↗
Pharmacokinetics and biotransformation of the prostacyclin analogue, ZK 36 374. III. Development of a radioimmunoassay and its application to the pharmacokinetics of ZK 36 374 in the rat.
The development of a radioimmunoassay for ZK 36 374, a chemically stable prostacyclin analogue, and its application to the pharmacokinetics of the drug in the rat is described. Antiserum against ZK 36 374 was raised in rabbits by immunization with ZK 36 374 coupled to bovine serum albumin via the carboxylic group. ZK 36 374 is extracted from plasma samples and purified from matrix constituents by means of octadecyl silyl cartridges. At a plasma concentration of 2.5 ng/ml intra- and interassay variations are 6 and 7%, respectively. The limit of detection is 0.5 ng/ml. After intravenous administration of 200 micrograms/kg to female Wistar rats a biphasic decline of the drug concentration in the plasma was observed with half-lives of 5 min and 3 h. Oral doses of 200 and 2000 micrograms/kg were very rapidly absorbed reaching maximum plasma levels of 3 and 32 ng/ml as early as 10-15 min p.admin.. Bioavailability at the two dose levels was calculated to be 8 and 13% of dose. Disposition was biphasic, as well, with a somewhat prolonged beta-phase after the highest dose.
Administration, Oral↗
Pharmacokinetics of the stable prostacyclin analogue, nileprost, in the rat.
The synthesis of radioactive nileprost, tritium-labelled at positions 18 and 19, and its application to the pharmacokinetics and biotransformation of this chemically stable prostacyclin derivative in the rat is described. 3H-Nileprost was absorbed after oral administration with a half-life of 23 min reaching maximum concentrations in the plasma 90 min after treatment. After intravenous injection there was a threephasic decline in plasma levels with half-lives of 15 min, 0.9 h and 11 h, respectively. Unchanged drug was eliminated with t 1/2 = 14 min. Brain levels of drug or metabolites were less than 5% of corresponding plasma concentrations. In autoradiographs after i.v. and oral administration a very low volume of distribution was found with maximum levels in the liver, the kidney and the stomach mucosa. Nileprost was very rapidly excreted, mainly by biliary elimination. Ten metabolites were detected in urine and bile, one of them being formed exclusively in the gut wall. The main fraction of 3H-activity in urine and bile, however, was due to unchanged drug.
Animals↗
Pharmacokinetics and biotransformation of the prostacyclin analogue, ZK 36 374, in the monkey (Macaca fascicularis).
The pharmacokinetics of ZK 36 374 after intravenous, oral and topical administrations to female monkeys has been investigated using tritium-labelled drug. Following intravenous injection of 2 and 200 microgram/kg a triphasic decline in the plasma levels of labelled compounds was observed with half-lives of 45 min, 4.3 h and 1.7 d. The half-life of the unchanged drug was 13 min. Almost 10% of an oral dose of 200 microgram/kg were bioavailable exhibiting maximum plasma levels of 5.7 +/- 3.6 ng/ml. The drug was totally metabolized and excreted mainly with the urine in the form of more than 10 metabolites. Following topical application of 1 mg, 5.5 +/- 2.2% of the dose was percutaneously absorbed using a TRIS-buffered solution of ZK 36 374 and 1.3 +/- 0.2% was absorbed applying an ethanolic solution of the drug. The plasma levels of labelled compounds were practically constant during the whole observation period of 36 hours.
Administration, Oral↗
Pharmacokinetics and biotransformation of methane sulphonanilides with anti-inflammatory activity in the rat and monkey--comparison with piroxicam.
The biotransformation of N-(6-phenoxyindan-5-yl)methansulphonamide (PMS) and of its 2',4'-difluoro derivative (DF-PMS) were studied in vitro using rat-liver homogenate followed by h.p.l.c. separation and mass-spectrometric identification of metabolites. Both sulphonamides were rapidly oxidized at positions 1 and 3. The pharmacokinetics of DF-PMS and of piroxicam were examined in the rat and monkey (Macaca fascicularis). Considerable concentrations were achieved in the plasma only by the 1-oxo metabolite of DF-PMS but not by the unchanged drug, indicating that the administered compound was a pro-drug of the active principle. 1-Oxo DF-PMS exhibited shorter half-lives, larger volumes of distribution and higher total clearance rates than piroxicam in the animal model studied.
Animals↗
[Effect of drugs and environmental pollutants on human spermatogenesis].
Following a short description of the dynamics of spermatogenesis possible pharmacological effects are discussed. These are: 1st a directly cytotoxic effect, 2nd a peripheral endocrine effect (androgen inhibition), and 3rd a central endocrin eff (gonadotrophin inhibition). Cytostatic drugs are the substances most dangerous to the seminiferous epithelium. If the treatment period takes more than 6 months, the damage is irreversible. After shorter periods the risk of chromosomal disarrangements is enhanced in the phase of regeneration. The widespread environmental pesticides act in a similar manner. Also retinoids, sulfasalazine and heavy metals have predominantly cytotoxic effects. Hormones administered in pharmacological doses will exert endocrine effects. The clinical symptoms are mainly those of disturbed sexual function, as the lack of testosterone is visible at first in peripheral organs. Estrogens, gestagens and antiandrogens act in a similar manner, but even exogenous testosterone will inhibit the spermatogenesis.
Androgens↗
[Labor monitoring using microcomputers].
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Computers↗
Plasma levels of mepindolol in healthy volunteers after oral doses of mepindolol sulphate.
Three groups of healthy volunteers were given oral doses of 5, 10 and 20 mg, respectively, of the beta-receptor blocking drug mepindolol sulphate (Corindolan). Plasma levels of the active compound mepindolol were measured by means of a sensitive and specific HPLC method. Mepindolol was rapidly absorbed reaching maximum concentrations of 21 +/- 7 ng/ml (5 mg), 47 +/- 23 ng/ml (10 mg) and 54 +/- 29 ng/ml (20 mg) 1--3 h after administration. The AUC ratio of the three doses studied was 1 : 1.9 : 3.0 suggesting incomplete absorption in the 20 mg group. The biological half-life of the drug was calculated to be 3--4 h, independently of the dose administered.
Administration, Oral↗
[HLA system and disorders of spermatogenesis].
Concerning the question of associations between HLA-antigens and idiopathic disturbancies of the spermatogenesis the HLA-ABC and DR-antigens were determined in 65 patients. All patients had less than 5 mio/ml spermatozoa in at least two semen samples. Significantly higher frequencies of certain HLA antigens were not found within the group of patients, when compared with unrelated healthy control individuals. Suggestions from other authors, that a part of idiopathic spermatogenetic disorders are associated with HLA-antigens, are not confirmed by our results. One family in which three brothers suffered from azoospermia was also HLA-typed. None of the four parental haplotypes was shared by all of the three brothers.
HLA Antigens↗
Determination of plasma levels of spirorenone, a new aldosterone antagonist, and one of its metabolites by high-performance liquid chromatography.
A method for the determination of plasma concentrations of spirorenone, a new aldosterone antagonist, and one of its metabolites, chromatographically characterized as 1,2-dihydro-spirorenone, is described. The assay utilizes high-performance liquid chromatography with UV detection. Reproducible results can be obtained with standard deviations of about 5% and the limit of detection is less than 5 ng/ml. Plasma levels of drug and metabolite have been measured after oral doses of 10 and 40 mg, respectively, administered to two male volunteers.
Adult↗
Transfer of mepindolol to newborns by breast-feeding mothers after single and repeated daily doses.
The concentrations of mepindolol in plasma and milk of five breastfeeding mothers were determined after 1 and 5 daily doses of mepindolol sulphate 20 mg. In the newborns plasma levels were measured once on the first and fifth days of the study. The mean maternal plasma concentration of mepindolol 2 h after administration was 52 ng/ml both after 1 and 5 doses; in the milk 18 and 22 ng/ml the corresponding concentrations were. The average plasma/milk drug concentration ratio was 2.6 +/- 1.6. Plasma levels in the newborn were below the detection limit of 1 ng/ml, except for one baby in whom 2 and 5 ng/ml, respectively, were found 4 h after one and five maternal doses.
Adult↗