The aim of this study was to isolate and characterize highly enriched membrane proteins by two-dimensional (2-D) electrophoresis and to identify surface antigens binding sperm autoantibodies (SpAb). The presence of SpAb may reduce fertility by affecting sperm motility and acrosome reaction. The presence of the SpAb was shown to prevent sperm penetration of cervical mucus, to inhibit sperm-zona pellucida interaction, and to interfere with the sperm-egg fusion. The swim-up method was used to separate mature and motile sperm. Sperm membranes were obtained by hypoosmotic swelling, homogenization and sonication. Membranes were further isolated by differential centrifugation steps. The highly purified human sperm membrane proteins were separated by two-dimensional gel electrophoresis and electrotransferred to polyvinylidene difluoride (PVDF) membrane. The antigens were identified by bound SpAb, the sources of which were seminal plasma samples of infertile patients or of patients following vasectomy. Fourteen surface antigens were detected. Their identification may be (i) important for understanding the mechanism by which SpAb impair sperm fertilization capacity, (ii) suitable as a basis of new methods of fertility regulation, and (iii) helpful in developing reproducible and reliable methods for determinations of SpAb.

Antigens, Surface↗

PubMedDate not supplied

Pharmacokinetics of mepindolol administered alone and in combination with hydrochlorothiazide--a bioequivalence study.

The bioavailability and pharmacokinetics of 10 mg of mepindolol sulphate and of 25 mg of hydrochlorothiazide were compared in a cross-over design in five healthy volunteers after the administration of either the single drugs (Corindolan and Esidrix) or in combination (Tenesor). Maximum concentrations of mepindolol in the plasma of 25 ng ml-1 were achieved 1.6 h after both treatments and the half-life of disposition was calculated to be 4-5 h, being somewhat longer after the combination tablet. The amount of hydrochlorothiazide renally eliminated up to 48 h after drug intake was about 60 per cent of the dose. The half-life of renal excretion was 3 h. The two formulations of mepindolol sulphate and hydrochlorothiazide proved to be bioequivalent with a tendency to better mepindolol bioavailability in the combination form.

Adult↗

PubMedDate not supplied

The pharmacokinetics and biotransformation of 14C-lisuride hydrogen maleate in rhesus monkey and in man.

14C-labelled lisuride hydrogen maleate was administered intravenously (25 micrograms) and orally (200 micrograms) to three male and three female elderly volunteers. Following i.v. injection radioimmunologically determined plasma levels of unchanged lisuride showed a three-phasic decline with half-lives of 3 minutes, 16 minutes and 2.9 hours. The total clearance was 16 +/- 9 ml/min/kg. Bioavailability was estimated to be 14% of oral dose. Determination of 14C-radioactivity did not show any specific enrichment of lisuride metabolites in cellular components of blood. The drug was almost totally metabolized and its degradation products were eliminated equally via the kidney and liver. Total recovery was about 90% of dose. The elimination half-life was 10 hours. Small parts of the dose administered were renally excreted with a half-life of 23 hours. Lisuride is metabolized extensively. HPLC radiochromatograms of freely extractable metabolites from urine did not show marked differences between both routes of administration. More than 15 compounds were freely extractable, only one of them represented more than 5% of dose. Phase II reactions were quantitatively unimportant. From rhesus monkey urine 6 metabolites were isolated. Chemical structures were proposed for 5 of them. They were assigned to the pattern of freely extractable human urinary metabolites and covered about 50% of radiolabel corresponding to about 13% of dose. The main freely extractable urinary metabolite was thought to be the 2-keto-3-hydroxy-lisuride derivative. Structures of the other four metabolites and earlier observations on the stability of the N'-ethyl-3H label led to the interpretation of independent changes of lisuride by different enzymatic processes such as oxidative N-deethylation, hydroxylation of the benzene system, monooxygenation at C2 and C9, and oxidation of double bonds at C2/C3 and C9/C10.

Animals↗

PubMedDate not supplied

Pharmacokinetics of pirazolac--a new anti-inflammatory drug--in human volunteers. I. Absorption, disposition, biotransformation and excretion.

The absorption, disposition, biotransformation and excretion of the nonsteroidal anti-inflammatory drug pirazolac were investigated in 6 volunteers (3 males, 3 females, age 50 greater than years) after intravenous and oral administration of 50 mg 14C-pirazolac as an aqueous solution of the sodium salt. Pirazolac was very rapidly and completely absorbed and bioavailable when orally administered in a dose of 50 mg in solution. Maximum pirazolac levels in plasma of 6 micrograms/ml (30% of dose in total plasma volume) were already reached after approx. 20 minutes. No metabolites were detectable in the plasma. Pirazolac was eliminated from the plasma in two phases with half-lives of 3 hours and 16 hours, respectively, regardless of administration route. After intravenous and oral administration approximately 80% of the dose was excreted with the urine and approximately 15% with the feces within 7 days, indicating a complete excretion of 14C-radioactivity. In urine, approximately 10% of the dose was identified as unchanged pirazolac and 70% as pirazolac ester glucuronide.

Administration, Oral↗

PubMedDate not supplied

Pharmacokinetics of bromerguride, a new dopamine-antagonistic ergot derivative in rat and dog.

Bromerguride is a novel dopamine antagonistic ergot derivative in which a complete reversed pharmacodynamic profile has been obtained by bromine substitution at position 2 as compared to dopamine agonistic lisuride. The pharmacokinetics of the new drug has been investigated following i.v. and i.g. administration of the 14C-labelled compound to rat (R) and beagle dog (D) with regard to drug registration requirements and to serve other preclinical disciplines (toxicology, pharmacology). Because of incomplete absorption the oral bioavailability was approx. 40% at dose levels of 0.25 mg/kg (R, D) and 4 mg/kg (D) and 20% after i.g. dosing of 5 mg/kg (R). Most of the 14C-label in plasma consisted of unchanged bromerguride apart from small amounts of the N-monodesethyl metabolite, which was also obtained as a biodegradation product in a rat liver perfusion experiment. Bromerguride plasma levels declined with half-lives of 0.7 h and 9 h (R) and 0.2 h and 2.7 h (D) after i.v. treatment. Peak levels in rat brain and plasma were observed within 1-2 h after oral dosing; brain levels accounting for 1/10 of bromerguride plasma levels. Whole body autoradiographs in rat demonstrated that the 14C-label was rapidly distributed into tissues and organs, readily passed the blood-brain and the placental barrier. Bromerguride was excreted to less than 10% unchanged with urine. Excretion was mainly biliary. Most of the 14C-label was recovered in the excreta within 24 h postdose.

Animals↗

PubMedDate not supplied

Pharmacokinetics of the dopamine partial agonist, terguride, in the rat and rhesus monkey.

3H-labelled terguride was rapidly and completely absorbed in the rat after oral administration of up to 50 mg/kg. In the rhesus monkey, absorption was prolonged. The bioavailability of terguride was 79% in the rat and 15% in the monkey. Plasma levels of the unchanged drug declined with a half-life of 50 min (rat) or 20 min (monkey). Tissue distribution as studied by autoradiography in pregnant rats showed highest concentrations of labelled compounds in the liver, the cervical gland and the kidney. Lower levels were found in the thymus, the spinal cord, the placenta and the heart muscle followed by the fetal tissue, the muscles and the brain. Radioactivity was excreted mainly in the faeces when administered to the rat and to a higher extent in the urine after treatment of rhesus monkeys.

Administration, Oral↗

PubMedDate not supplied

Relevance of male accessory gland infection for subsequent fertility with special focus on prostatitis.

Infections of the male genitourinary tract may contribute to infertility to a various extent depending on the site of inflammation. Especially in prostatitis, the exact classification of the infection contributes to its impact on changes in the ejaculate. Similarly, in urethritis, epididymitis and orchitis, only a clear clinical diagnosis allows a rational approach to altered sperm parameters. Several inflammatory and reactive alterations of sperm quality seem to be proven; nevertheless, the impact of these findings on male fertility remains in many cases unclear. Even therapeutic trials do not provide more insights into the association of male genital infections and impaired fertility, although the efficacy of antibiotic trials seems to be proven. For the future, it may be decisive to evaluate inflammatory changes in the ejaculate not only on the basis of standard but also on functional parameters, thus providing new definitions of the interactions between male urogenital tract infection and disturbances of male fertility.

Anti-Bacterial Agents↗

PubMedDate not supplied

Concentration of immunreactive FSH, LH and prolactin in seminal fluid following i.v. application of LH-RH and TRH.

Immunreactive FSH, LH and Prolactin are measured in seminal fluid and serum following i.v. injection of LH-RH and TRH. Levels of hormone levels in serum and seminal fluid are not correlated. Only LH levels, but not those of FSH and PRL depend on the interval between injection of releasing factors and ejaculation. Dilution curves and column chromatography of seminal fluid LH point that it might not be identical to serum LH. Since in the testis a HCG immunreactive substance has been described it is likely that it forms part of the LH concentrations measured in seminal fluid.

Follicle Stimulating Hormone↗

PubMedDate not supplied

The occurrence of carcino-embryonic antigen-like immunoreactivity in human semen.

A substance reacting in a radioimmunoassay for carcino-embryonic antigen (CEA) was found in normal human seminal fluid. It has a mean concentration of 118 ng/ml, it is independent from sperm count and even demonstrable in obstructive azoospermia. Parallelity of dilution curves shows immunologic similarity to the tumor CEA from colon carcinoma. From a gel chromatographic system it is eluted within the same molecular range as iodinated CEA.

Adult↗

PubMedDate not supplied

Carcinoembryonic antigen-like substance is a marker of prostatic secretory function.

Specimens of pre- and postpubertal and adult prostatic tissue and seminal vesicles were examined for the presence of carcinoembryonic antigen-like immunoreactivity. A positive immunoreaction of the epithelium of the prostate was observed after the onset of puberty and was comparable to that of secretory acid phosphatase. It was absent from the epithelium of the seminal vesicles. The CEA-like substance of the prostate may therefore be used as a marker of prostatic secretory activity.

Acid Phosphatase↗

PubMedDate not supplied

Long-term variations of seminal parameters.

57 outpatients visited our department for the first time 1975-1978 and a second time four years later (1979-1982). Both semen analyses were compared with respect to the year of the first examination. Significant variations of seminal parameters with increasing age were not found, but sperm count and rate of abnormal sperms was significantly higher in the years 1975-1978 than in 1979-1982 at the second visit. Individual patients showed, despite the fairly constant mean values, marked variations of sperm count from one analysis to the next.

Adult↗

PubMedDate not supplied

On the teratogenesis of round-headed spermatozoa: investigations with antibodies against acrosin, an intraacrosomally located acrosin-inhibitor, and the outer acrosomal membrane.

Acrosin, the outer acrosomal membrane (OAM) and an acrosin inhibitor were studied in testicular cells and ejaculated spermatozoa of fertile men and in those of an infertile patient with exclusively round-headed spermatozoa in his ejaculates. The investigations were performed with the aid of immunohistochemical techniques using specific antibodies against the three acrosomal markers isolated from boar spermatozoa. The spermatozoa of fertile men exhibit staining for acrosin, the OAM and the acrosin inhibitor in the cap region while the round-headed spermatozoa of the patient are totally negative for the three markers, clearly supporting the conclusions of other authors that round-headed spermatozoa lack acrosomes. The lack of the acrosin system was further substantiated by the gelatin substrate film technique. In the course of normal human spermatogenesis acrosin, the OAM and the acrosin inhibitor we first demonstrable in early round spermatids, namely in identical compartments adjacent to the cell nucleus. During spermatid differentiation the staining for the three markers becomes flattened over the nucleus, resulting in a cap-like structure in testicular spermatozoa. In contrast to the ejaculated round-headed spermatozoa, the early round spermatids in the testis of the infertile patient exhibit fluorescent staining for the three markers in the region adjacent to the nuclear membrane. In the course of further spermiogenesis, the staining did not extend over the nuclear membrane, as was observed during normal spermiogenesis, but became separated from the nuclear membrane, as was observed during normal spermiogenesis, but became separated from the nuclear membrane, was translocated at various locations in the cytoplasm and was finally eliminated with the loss of the cytoplasm. These results are in accordance with the results of electron microscopically investigations on the teratogenesis of round-headed spermatozoa. Furthermore, the developmental pattern of the acrosin inhibitor during normal and abnormal spermiogenesis supports the intraacrosomal location of the acrosin inhibitor recently described by Tschesche et al. (1982).

Acrosin↗