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Biomedical subjects

M Bygdeman

Publications and source records attributed to M Bygdeman.

At least 127 records · Page 7Linked to original sources
PubMed1987

Human fetal tissues grafted to rodent hosts: structural and functional observations of brain, adrenal and heart tissues in oculo.

The potential for growth and development of human tissue grafts was explored by transplantation to the anterior chamber of the eye of rats and mice. Tissues were obtained from therapeutic abortions, performed in the eighth to twelfth week of gestation, using a slight modification of routine vacuum aspirations. Recipients were either adult rats immunosuppressed with cyclosporin A and protected with antibiotics, or nude immunodeficient Balb C mice. Catecholamine-rich tissues such as chromaffin cells from the adrenal medulla, sympathetic ganglia, central dopamine neuroblasts from the substantia nigra, and noradrenaline neuroblasts from the locus coeruleus all survived grafting, and in many cases formed nerve fibers that invaded the host iris. Similarly, central serotonin neurons from developing raphe nuclei grafts were able to innervate host irides. Human fetal cerebellar and cerebral cortical transplants continued their development in rat host eyes. Extracellular recordings from such cerebellar and cortical grafts revealed spontaneously active cells with immature action potential waveforms. Spinal cord grafts also survived and contained substance P-immunoreactive neurons. Dorsal root ganglia were able to form nerve fibers invading the host iris, as evidenced by neurofilament immunohistochemistry. Heart tissue survived and manifested spontaneous rhythmic contractions in oculo. Both human cortex cerebri and heart tissue grafts became innervated by sympathetic adrenergic nerve fibers from the rat host iris. Thus both graft-to-host and host-to-graft neuronal connections may be established between man and rat. Taken together, these data suggest that transplantation of human fetal nervous tissues to the anterior chamber of immunosuppressed or immunodeficient rodent hosts yields a unique model system for studies of human brain development, developmental disturbances, connectivity, and the action of drugs.

Action Potentials↗
PubMed1987

Human fetal cerebellar and cortical tissue transplanted to the anterior eye chamber of athymic rats: electrophysiological and structural studies.

Human fetal tissue fragments from cortex cerebri and cerebellum were grafted to the anterior chamber of the eye of adult athymic nude rats. The grafts were obtained from tissue fragments recovered after elective routine abortions, performed in weeks 8-11 of gestation. Both cerebellar and cortex cerebri grafts survived and developed in the anterior chamber of the eye for 1-4 months. The transplants slowly became vascularized from the host iris. The grafts developed blood vessels with laminin-immunoreactive walls and contained relatively high amounts of glial fibrillary acidic protein- and neurofilament-immunoreactivity in the neuropil after 4 months in oculo. Recordings of extracellular action potentials from the grafts revealed spontaneously active neurons with action-potential waveforms similar to those observed in immature rodents. Morphologically, the grafts showed no signs of rejection. Clusters and bands of large neurons resembling Purkinje cells and dense aggregates of smaller granule-like cells could be found in the cerebellar grafts. Large neurons were also seen in the cortex grafts. Taken together, these data suggest that the athymic rat may serve as a useful tool for studies of central nervous system tissue from otherwise immunologically incompatible species.

Action Potentials↗
PubMed1987

Concentration of prostaglandins in seminal fluid of fertile men.

Semen samples from 31 men, all of whom had fathered a child within the preceding year, were analysed for sperm characteristics and for the content of prostaglandins (PGs). Mean concentrations (mg/l) for the four main groups of PGs were 67.1 for PGE, 3.2 for PGF, 245.7 for 19-hydroxy-PGE and 13.3 for 19-hydroxy-PGF. The individual values were distributed over a relatively wide range but the extremely wide ranges reported by previous authors were not confirmed. Information is also presented concerning the relative proportions of the four isomers of PGF, as well as those of 19-hydroxy-PGF. Only sperm density was related to PG concentration in fertile men. Polyzoospermia was associated with a low PGE concentration.

Dinoprost↗
PubMed1987

Role of prostaglandins in human reproduction: recent advances.

Our knowledge of the importance of PGs for the physiological regulation of male and female reproductive organs is rapidly increasing. In this presentation two examples have been described in detail. Data are accumulating indicating that PGs in semen are of major importance for sperm motility and the functional capacity of sperms. Recording of intrauterine pressure in early pregnant patients has shown that treatment with an antiprogestin depriving the myometrium from progesterone influence, will induce regular uterine contractions. The data support the hypothesis that the uterine activity is regulated by the balance between PGF2 alpha and progesterone.

Female↗
PubMed1987

Adenosine triphosphate in human semen: a study on conditions for a bioluminescence assay.

A comparison of different procedures for adenosinetriphosphate (ATP) determination in whole ejaculates showed that it is advantageous to treat the specimens with trichloroacetic acid (TCA before quantification of ATP by bioluminescence). Semen samples from different men were found to cause varying degrees of inhibition of the luciferin-luciferase reaction. Hence, internal ATP standard had to be added to each sample to allow calculation of endogenous ATP. Mean recovery of ATP was 98.5%. The intrassay and interassay coefficients of variation were 3.0% and 3.9%, respectively. A correlation between the number of progressively motile spermatozoa and the ATP concentration was found (r = 0.89, P = 0.0005, n = 22). The mean level of ATP was 0.49 nmol/living sperm X 10(6) in semen with normal sperm motility and sperm density obtained from 22 men attending our fertility clinic. Seminal ATP was detected only in the spermatozoa.

Adenosine Triphosphate↗
PubMed1986

Human fetal substantia nigra grafted to the dopamine-denervated striatum of immunosuppressed rats: evidence for functional reinnervation.

Human fetal substantia nigra tissue, obtained following therapeutic termination of first trimester pregnancies, was grafted to cavities overlying the striatum in ciclosporin-treated rats whose nigrostriatal dopamine system had been removed unilaterally by 6-hydroxydopamine. Tyrosine hydroxylase (TH) immunocytochemistry revealed large numbers of surviving human substantia nigra neurons that matured and formed TH-positive nerve fibers reinnervating the host rat striatum. Apomorphine-induced rotational behavior in grafted animals was reduced by 70-80% in optimal cases 3-5 months after grafting. Thus human fetal dopamine neurons can correct functional deficits in dopamine-denervated rat hosts.

Animals↗
PubMed1986

Randomized comparison of different prostaglandin analogues and laminaria tent for preoperative cervical dilatation. World Health Organization Special Programme of Research, Development and Research Training in Human Reproduction: Task Force on Prostaglandins for Fertility Regulation.

In an eleven-centre study, 627 nulliparous subjects in the 8th to 12th week of gestation admitted for termination of pregnancy were allocated to one of five treatments to induce pre-operative cervical dilatation. The treatments were: 0.5 mg PGE2 methyl sulphonylamide; 1.0 mg PGE1 methyl ester; 30 mg 9-methylene PGE2 free acid, 0.5 mg 15-methyl PGF2 alpha; a single medium-sized laminaria tent. The results indicate that the three PGE analogues are at least equally effective as one medium sized laminaria tent and more effective than 0.5 mg 15-methyl PGF2 alpha in producing adequate pre-operative cervical dilatation prior to vacuum aspiration. It is concluded that both pre-treatment with prostaglandin analogues and laminaria tent are effective methods for preoperative cervical dilatation and both types of treatment are associated with a low incidence of side effects. Prostaglandin analogue treatment can be administered by paramedical personnel but laminaria tent insertion has to be performed by medical staff.

16,16-Dimethylprostaglandin E2↗
PubMed1986

Plasma levels of antiprogestin RU 486 following oral administration to non-pregnant and early pregnant women.

RU 486 is a synthetic steroid which acts as an antiprogestin at the receptor level. The clinical usefulness of the compound for menstrual regulation and termination of early pregnancy is currently being evaluated. The aim of the present study was to determine the plasma levels of RU 486 following the oral administration of the compound to 42 pregnant and 10 non-pregnant women. The levels of RU 486 were measured by a radioimmunoassay method which uses chromatography on Sephadex LH 20 columns. The identity of the compound assayed as RU 486 was confirmed, but the presence of small amounts of two highly cross-reacting metabolites (monodemethyl and didemethyl RU 486) in the analyzed fractions could not be excluded. Following the ingestion of a single tablet containing 25 and 50 mg of the compound, a peak plasma value of approximately 3.5 to 4.0 mumol/l in both the pregnant and non-pregnant subjects was reached one to two hours later. The half-lives of elimination were about 20 hours in both the pregnant and the non-pregnant women. Following the repeated oral administration of 50, 100 or 200 mg of RU 486 daily for four days, maximum plasma levels of 2.9, 4.5 and 5.4 mumol/l, respectively, were found. Thus, the increase in plasma levels was not directly proportional to the increase in the dose. No accumulation of RU 486 in the plasma was found, even when the duration of treatment was prolonged to six days. The data partly explain the reported lack of relation between ingested dose and frequency of induced abortion and they may be useful for designing future studies on the use of compound to prevent implantation, induce menstruation or terminate an early pregnancy.

Abortifacient Agents↗
PubMed1985

Intracervical versus intravaginal PGE2 for induction of labor at term in patients with an unfavorable cervix.

In a randomized double-blind study we evaluated the effects on cervical ripening and labor induction of 0.5 mg PGE2 in gel given intracervically and 2.0 mg PGE2 given as a vaginal suppository. All patients were at term with unfavorable cervical scores. The indications for induction were toxemia, diabetes mellitus, Rh-immunization, or intrauterine growth retardation. Significantly better results for both cervical priming and labor induction were obtained after intracervical PGE2-gel application than after treatment with placebo or vaginal suppositories. Eleven out of 19 patients (58%) were delivered within 24 h after intracervical PGE2-gel compared to two out of 19 patients given placebo (p less than 0.01). In patients not delivered 24 h after the start of treatment, the mean cervical score had changed from 3.7 to 6.0 (p less than 0.05) after PGE2-gel application compared to a change from 3.9 to 4.3 after placebo treatment (n.s.). The outcome after treatment with PGE2 suppositories did not differ significantly from that with placebo treatment. In a subsequent study 25 patients were given 0.5 mg PGE2-gel intracervically. The results were consistent with those obtained in patients receiving PGE2-gel intracervically in the double-blind study. Few side effects were noted. No patient complained of gastro-intestinal discomfort but increased myometrial activity was observed in two patients; one after placebo and the other after active intracervical PGE2-gel treatment. The hyperactivity was readily countered with the beta 2-agonist, terbutaline. All infants were born in good condition with Apgar scores of 7 or more within 5 min. At pediatric examinations at 1 week and at 6 months of age all children seemed healthy.

Administration, Topical↗
PubMed1985

Progesterone receptor blockage. Effect on uterine contractility and early pregnancy.

RU 486 is an antiprogestin which acts at the receptor level. In the present study the effect of this compound on uterine contractility and sensitivity during early pregnancy was evaluated in 10 patients. Five patients in the 6th to 7th week of pregnancy received 25 mg RU 486 twice daily for four days. On the fourth day of treatment, uterine contractility was recorded. The remaining five early pregnant patients were untreated and served as control. Withdrawal of progesterone locally by RU 486 treatment resulted in the development of a regular uterine activity which was in sharp contrast to the low level contractility pattern found in the untreated control patients. Also the sensitivity to prostaglandin increased following RU 486 treatment. The efficacy of a sequential therapy of RU 486 and the PGE analogue 16-phenoxy-tetranor-PGE2 methyl sulfonylamide for termination of early pregnancy was also studied. Thirty-four early pregnant women (duration of amenorrhea for up to 49 days) admitted to the hospital for termination of their pregnancy volunteered for the study. The patients received 25 mg RU 486 twice or four times daily for four days. In the morning of the fourth day of RU 486 treatment, a small dose (0.25 mg) of the PGE analogue was given as a single intramuscular injection. The combined treatment resulted in complete abortion in 32 patients (94%). One patient experienced an incomplete abortion and in one patient the pregnancy continued unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortifacient Agents, Nonsteroidal↗
PubMed1985

The effect of prostaglandins on the bioconversion of arachidonic acid in cervical tissue in early human pregnancy.

The aim of the present study was to investigate in late first trimester and early second trimester patients whether whole cell homogenates of cervical tissue incubated with 14C-arachidonic acid was affected by pretreatment for 12 to 14 hours with PGE2 and 9-deoxo- 16,16-dimethyl-9-methylene PGE2 (9-methylene PGE2). After extraction, purification and separation, identification of the compounds found during incubation was achieved using radio-gas liquid chromatography and gas-liquid chromatography-mass spectrometry. Treatment with 9-methylene PGE2 accomplished a reduced production of 14C-labelled PGF2 alpha, -PGE2 and TxB2, while pretreatment with PGE2 induced increase in the production of 14C-6-keto-PGF1 alpha when cervical tissue homogenates were compared with specimens obtained from non-pretreated patients. Recently we reported a significantly increased formation of so far unidentified metabolite(s) in homogenates of human cervical tissue specimens obtained at or near term when compared with corresponding specimens obtained during early pregnancy. With both types of prostaglandin pretreatment there was a tendency of increased formation of these metabolites. It seems possible that the influence on the biochemistry of cervical tissue induced by PGE2 and 9-methylene PGE2 is mediated via the endogenous arachidonic acid cascade towards non-prostaglandin compound(s).

16,16-Dimethylprostaglandin E2↗
PubMed1985

The effect of naproxen on the concentration of prostaglandins in human seminal fluid.

Whole ejaculates were examined for their content of prostaglandins (PGs) during medication with 250 mg naproxen three times daily for 2 weeks. Six volunteers delivered semen samples before, periodically during, and after the period of medication. During treatment with naproxen, the concentration of PGE, PGF, 19-hydroxy-PGE, and 19-hydroxy-PGF significantly decreased. One week after cessation of medication the PG concentration had returned almost to that found before treatment. The four 19-hydroxy-PGF compounds could be determined separately and the relation between them estimated. The proportion of 8 alpha-19-hydroxy-PGF2 alpha increased, whereas that of 8 beta-19-hydroxy-PGF1 alpha decreased significantly during the medication period. No significant influence of the treatment on sperm density or motility could be observed. It is concluded that treatment with naproxen, a potent inhibitor of PG synthesis, significantly reduces the concentration of all PGs present in human seminal fluid. The implication of the effect on human fertility is discussed.

Alprostadil↗
PubMed1985

On the origin of prostaglandins in human seminal fluid.

To evaluate the origin of seminal prostaglandins, genital tract fluids were analysed for prostaglandin content in two clinical situations. Six patients delivered semen samples before and after vasectomy. In these patients the prostaglandin concentration remained essentially unchanged although sperm density decreased to zero. In another patient secretory products from the testis and epididymis, and the ejaculate representing mainly the secretion of the seminal vesicles and the prostate gland, were collected separately. Secretions obtained from the testis and epididymis did not contain detectable amounts of prostaglandins, whilst in the ejaculate from the same patient the concentration was within normal limits. The results of the study show that the testis and epididymis do not contribute significantly to the prostaglandin content of human seminal fluid. The previous assumption that the seminal vesicles are the main source of seminal prostaglandins is thus supported.

Epididymis↗
PubMed1985

Bioconversion of arachidonic acid in human pregnant uterine cervix.

The in vitro conversion of [14C]arachidonic acid by endocervical mucosa and cervical tissue specimens obtained in first trimester (9-12 w) and term pregnant patients (37-39 w) was studied in whole-cell homogenates. All radiolabelled products of the arachidonic acid cascade were extracted, purified and separated utilizing silicic acid chromatography, thin-layer chromatography and reversed phase partition chromatography and identified with radio-gas chromatography and gas chromatography-mass spectometry. Both types of tissue produced PGF2 alpha and PGE2, as well as TxB2. In cervical tissue specimens there was a significant increase in the production of all these three prostaglandins as the pregnancy progressed, whereas no such difference was seen in homogenates of endocervical mucosa. In both endocervical mucosa and cervical tissue specimens there was a highly significant increase in the production of a so-far unknown compound(s), in samples from term patients as compared with samples from first-trimester patients. The possible participation of this metabolite of [14C]arachidonic acid in the regulation of cervical ripening is discussed.

Arachidonic Acids↗
PubMed1985

Effect of intraperitoneal instillation of 32% dextran 70 on postoperative adhesion formation after tubal surgery.

The intraperitoneal instillation of 32% dextran 70 (HyskonR, Pharmacia AB, Sweden) has previously been reported to prevent the formation of postoperative adhesions. Against this background, the present study was undertaken to evaluate the efficacy of HyskonR in counteracting peritoneal adhesions following tubal microsurgery. 105 infertile women were operated upon in a prospective, randomized, controlled, double-blind, multicenter study. The intra-abdominal adhesions present from the beginning were classified by means of a standardized scoring scale and the extent of adhesions was again evaluated at follow-up laparoscopy 4-10 weeks later. A reduction in the extent of the intra-abdominal adhesions (statistically highly significant) was revealed in both the Hyskon group and the saline control group. The extent of adhesions in the Hyskon group was not lesser than in the saline group, however. The pregnancy rates in the two groups were also similar.

Adult↗
PubMed1984

The prostaglandin-analogue-9-deoxo-16,16-dimethyl-9-methylene-PGE2 inhibits the antidiuretic effect of vasopressin (AVP) in the conscious sheep.

The effects of intravenous infusions of the stable prostaglandin analogue 9-deoxo-16,16-dimethyl-9-methylene-PGE2 (9-methylene-PGE2) in a dosage of 10 or 24 micrograms/min were studied in the consicious euhydrated, dehydrated, and hyperhydrated with the simultaneous administration of exogenous arginine vasopressin (AVP), sheep. The infusions decreased urine osmolality and increased urine flow and renal free water clearance. The results indicate that 9-methylene-PGE2 exhibits its diuretic effect by antagonizing the antidiuretic action of AVP. In the hyperhydrated sheep receiving AVP the syndrome of inappropriate antidiuretic hormone release (SIADH) was simulated. As the prostaglandin analogue effectively blocked the antidiuretic effect of the AVP-administration it appears that 9-methylene-PGE2 may play a future role as a diuretic agent, especially in conditions characterized by water retention and dilutional hyponatremia such as SIADH.

16,16-Dimethylprostaglandin E2↗