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Biomedical subjects

M Akerlund

Publications and source records attributed to M Akerlund.

At least 37 records · Page 2Linked to original sources
PubMed1995

Potential use of oxytocin and vasopressin V1a antagonists in the treatment of preterm labour and primary dysmenorrhoea.

In order to study the involvement of oxytocin (OT) and vasopressin (AVP) in mechanisms of uterine activation and to clarify the therapeutic potential of antagonists to these hormones in preterm labour and primary dysmenorrhoea, studies of human uterine contractility in vivo and in vitro as well as measurements of OT and AVP V1a receptors were performed. Good correlations between OT receptor concentrations and effects on contractility were observed in both the pregnant and non-pregnant states, which indicates that OT acts specifically on its own receptor in the uterus. For AVP there was lack of such correlation which may suggest that this hormone influences both the OT and AVP V1a receptor sites. At the onset of labour both preterm and at term no marked increase in the OT receptor concentration was observed, but OT may still be involved in the initiation of labour, being produced locally in the uterus and not detectable in plasma. We observed a reduced OT receptor concentration in advanced labour and after OT infusion, which suggests that OT influences its own receptor. The AVP V1a receptor concentration and the effect of AVP on the uterus were about equal to those for OT, and the concentration of AVP V1a receptors also tended to decrease in advanced labour, observations which support an involvement also of AVP in the mechanisms of labour. In non-pregnant women AVP receptors as well as uterine effects of AVP in vitro and in vivo were about five times higher than those for OT, and the effect of AVP was increased premenstrually. This firmly supports an aetiological role of this peptide in the uterine hyperactivity of primary dysmenorrhoea. We have also shown that the analogue 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-OT, which blocks both the OT and AVP V1a receptor sites, given by intravenous infusion inhibits both preterm labour and dysmenorrhoea, and this is in agreement with our receptor and contractility findings.

Arginine Vasopressin↗
PubMed1994

Vascularization of human endometrium. Uterine blood flow in healthy condition and in primary dysmenorrhoea.

The anatomy of the human uterine vascular tree changes repeatedly with the variations in hormonal state during each menstrual cycle, with progressive differentiation of arterioles up to the premenstrual state. Hormonal factors also influence the innervation of uterine arteries, both cholinergic, adrenergic and peptidergic, and regulate the spontaneous contractile activity of the smooth muscle of vessel walls as well as the motor responses of these tissues to different vasoactive substances. The smaller branches of uterine arteries, i.e., the resistance arteries appear to be of particular importance in the regulation of uterine blood flow, since they are most densely innervated. Furthermore, the most effective uterine vasoconstrictors in vitro, vasopressin, endothelin, oxytocin and noradrenaline have a more pronounced effect on these vessels than on the main branches of the uterine artery. Vascular compression may also result from changes in the myometrial activity. A hormonal disturbance may cause dysfunctional bleeding by changing vessel growth as well as the uterine smooth muscle activity of both vessels and myometrium. An example of the latter phenomenon is primary dysmenorrhoea, women with this condition having an increased secretion of vasopressin. By an action on type V1 vasopressin receptors of the uterus, this peptide causes myometrial hyperactivity and vasoconstriction, with resultant uterine ischemia and pain. Further support for a pathophysiological role of vasopressin and also of oxytocin in dysmenorrhoea is the therapeutic effect of a competitive type V1 vasopressin and oxytocin receptor antagonist in the condition.

Arteries↗
PubMed1994

Receptors for and myometrial responses to oxytocin and vasopressin in preterm and term human pregnancy: effects of the oxytocin antagonist atosiban.

OBJECTIVE: Our purpose was to study myometrial oxytocin and type V1 vasopressin receptors, the in vitro contractile effects of these hormones, and the influence of an oxytocin antagonist. STUDY DESIGN: Women delivered by cesarean section preterm (n = 51) and at term (n = 71), with and without labor contractions, gave myometrium for the estimation of oxytocin and V1 vasopressin receptors. The in vitro myometrial effects of the peptides and the influence on these of the competitive oxytocin receptor blocking agent 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin were also tested. RESULTS: The median concentration of oxytocin receptors was 116 fmol/mg protein (range 15 to 372 fmol/mg protein) in patients delivered preterm not in labor, 134 fmol/mg protein (27 to 1421 fmol/mg protein) in the beginning of labor, and 46 fmol/mg protein (9 to 140 fmol/mg protein) in advanced labor. At term the corresponding concentrations were 172 (25 to 629), 223 (24 to 414), and 70 (21 to 92) fmol/mg protein. The concentration of V1 vasopressin receptors also decreased in advanced labor. In advanced labor after oxytocin infusion a reduction in the concentration of the receptor for this hormone was observed, which appeared to be related to the duration and dose of treatment. Oxytocin receptors did not vary between women with different indications for cesarean section. The oxytocin effects in vitro and the degree of inhibition by the antagonist of oxytocin responses correlated with the concentration of oxytocin receptors but not with that of V1 vasopressin receptors. No correlation was seen between the response to vasopressin and concentrations of oxytocin or V1 vasopressin receptors. CONCLUSIONS: The effect of oxytocin on the myometrium in pregnancy is mediated by an oxytocin receptor, whereas vasopressin acts on both oxytocin and vasopressin receptors. The initiation of labor both preterm and at term may be primarily related to increased release of oxytocin, which is locally produced in the uterus and not detectable in the plasma, but oxytocin and vasopressin receptors may play a role in the regulation of labor. The analog 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin, which blocks both the oxytocin and the V1 vasopressin receptor, should inhibit labor both preterm and at term, the former confirming results of recent clinical studies in Sweden and the United States.

Cesarean Section↗
PubMed1994

Antagonists for the human oxytocin receptor: an in vitro study.

The oxytocin antagonist [Mpa1, D-Tyr(Et)2, Thr4, Orn8]-oxytocin has been successfully used for treating premature labour. The interactions of this antagonist with neurohypophysialhormone receptors in the human myometrium were investigated. Competition curves among [3H]oxytocin, [3H]arginine vasopressin, [3H][1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)2-(O-methyl)-tyrosine, 8-arginine] vasopressin, the corresponding unlabelled peptides and a series of oxytocin antagonists including [Mpa1,D-Tyr(Et)2,Thr4,Orn8]-oxytocin were constructed from results taken from the myometrium of pregnant women and rabbits, and were analysed simultaneously using the computer program LIGAND. The biological activity of [Mpa1,D-Tyr(Et)2,Thr4,Orn8]-oxytocin in the human uterus was investigated by studying its effect on oxytocin-induced intracellular Ca2+ mobilization in human myometrial cells in culture that were expressing high concentrations of oxytocin receptors. The results indicate that [Mpa1,D-Tyr(Et)2,Thr4,Orn8]-oxytocin and related antagonists are selective for the oxytocin receptor in the myometrium of pregnant rabbits but not of pregnant women. In women, they bind with high affinity to the V1 vasopressin receptor. In myometrial cells [Mpa1,D-Tyr(Et)2,Thr4,Orn8]- oxytocin inhibits the oxytocin-induced increase in intracellular Ca2+ concentration in a dose-dependent fashion, with an IC50 value of 5 nmol l-1. The uterine relaxant effect of this antagonist might result not only from the block of the oxytocin receptor, but also from interaction with the V1 vasopressin receptor.

Animals↗
PubMed1994

Oral contraceptive tablets containing 20 and 30 micrograms of ethinyl estradiol with 150 micrograms desogestrel. Their influence on lipids, lipoproteins, sex hormone binding globulin and testosterone.

The effect of two oral contraceptive (OC) pills, both containing 150 micrograms of desogestrel, but with 20 (Mercilon) or 30 micrograms (Marvelon/Desolett) of ethinyl estradiol on plasma levels of lipids, lipoproteins and sex hormone binding globulin (SHBG), total and free testosterone were compared in a double-blind, randomized, two-center study in a total of 60 women over one year. A significant rise with Marvelon but not with Mercilon was seen in total cholesterol, HDL cholesterol, HDL-3 and apolipoprotein B, whereas LDL cholesterol decreased with Mercilon only. These effects resulted in significant differences between the two groups in the magnitude of responses in all these parameters except HDL-3. HDL-2, apolipoprotein A-1 and total phospholipids were elevated with both pills after treatment and with no difference in the degree of response between groups. The HDL/LDL cholesterol ratio tended to increase in both groups and that of apolipoproteins A-1/B in the women on Mercilon. Total triglycerides increased in both groups, but more in the women on Marvelon. Total testosterone decreased, particularly in the Marvelon group, whereas the two pills caused a similar increase in SHBG and decrease in free testosterone. It is concluded that the direction of changes in plasma lipids and lipoproteins with both these pills may as a whole be interpreted as beneficial, and that the differences in effect on LDL cholesterol and apolipoprotein B may suggest a slightly advantageous effect of Mercilon in this aspect. However, the clinical significance of these changes is uncertain. The results indicate a lack of androgenicity of both pills.

Adult↗
PubMed1993

The relationship between cadmium and lead burdens and preterm labor.

OBJECTIVE: To study the possible involvement of lead and cadmium in mechanisms of preterm labor. METHOD: Estimations of lead and cadmium in blood, myometrium and placenta of Swedish and Polish women in preterm labor (n = 17) or delivered at term (n = 13). RESULT: There was a positive correlation between pregnancy week and content of lead in blood. The mean blood concentration of cadmium in preterm delivered women, 2.0 micrograms/l, was significantly higher than that in term delivered patients, 0.6 microgram/l. In Polish patients the concentration of lead in blood, 37.9 micrograms/l, was higher than that in Swedish women of 11.2 micrograms/l. Cadmium concentrations in myometrium and placenta of Polish women, 0.2 and 0.3 microgram/g, respectively, were also significantly higher than the corresponding concentrations in Swedish patients, 0.04 and 0.1 microgram/g and this difference remained when only nonsmokers were compared. Smokers and nonsmokers did not have significantly different cadmium levels. CONCLUSION: These results do not support the concept of lead causing increased myometrial activity in preterm labor, but indicate a higher uptake of lead and cadmium of Polish than of Swedish women. Further investigations are warranted to delineate the importance of the elevated concentration of cadmium in the blood of women with preterm labor.

Adult↗
PubMed1993

Comparative profiles of reliability, cycle control and side effects of two oral contraceptive formulations containing 150 micrograms desogestrel and either 30 micrograms or 20 micrograms ethinyl oestradiol.

OBJECTIVE: To compare two oral contraceptive pills, both containing 150 micrograms desogestrel, but with either 20 micrograms (Mercilon) or 30 micrograms (Marvelon/Desolett) ethinyl oestradiol (EE), regarding reliability, cycle control and side effect profile. DESIGN: A double blind, randomised, multicentre study over one year with follow up after three, six and 12 months. The women noted tablet intake and all bleedings on specifically designed diary cards. SETTING: University clinics, central hospitals and private gynaecological practices in Norway, Sweden and Denmark. SUBJECTS: One thousand women aged 18 to 40 years requesting oral contraceptive pills. MAIN OUTCOME MEASURES: Reliability, cycle control, side effects, blood pressure, body weight and haemoglobin. RESULTS: In a total of 4543 cycles with the 20 micrograms EE dose pill and 4688 cycles with the 30 micrograms EE dose pill, the number of pregnancies ascribed to method failure were 0 and 2, respectively. Irregular bleeding (break-through bleeding or spotting) was significantly more frequent with the 150/20 combination in about two-thirds of the cycles randomly distributed over the one year of the study. Mean blood pressure decreased slightly, particularly in the group on the 150/20 combination (about 1 mmHg), whereas mean body weight increased approximately 0.5 kg in the group with the 150/30 combination after 12 months. Haemoglobin did not change. Side effects other than bleeding problems were rare, but dizziness and mood changes were more frequent in the group on the 150/20 combination. Due to side effects, more women on the 150/20 combination discontinued the study during the one to three and four to six month periods, and women on this pill were also less positive about continuing the study drug at the end of the trial. CONCLUSIONS: Both pills have high contraceptive reliability and are well tolerated, but with the 150/20 combination the cycle control is less effective. However, in view of the potentially increased safety profile of the 150/20 combination, many women can be expected to accept some additional discomfort due to irregular bleeding.

Adolescent↗
PubMed1992

Treatment of cancer patients with a low-density-lipoprotein delivery vehicle containing a cytotoxic drug.

A cytotoxic drug (vincristine, VC) was incorporated into low-density lipoprotein (LDL) and given to cancer patients for the first time by repeated intravenous injection. Individuals presenting with ovarian or endometrial cancer received four or five weekly doses of 1.4 mg/m2 LDL/VC. The uptake of LDL/VC by the adrenal cortex and the liver was minimised by concurrent administration of prednisolone and chenodeoxycholic acid. No febrile, allergic or other reaction attributable to the LDL occurred, and no side effect on haemopoietic, adrenal or liver functions was observed. The neurotoxic side effects commonly seen during VC therapy appeared to be reduced. These results suggest that directed cytotoxic therapy might be achieved in humans through the use of LDL as a carrier. Thus, dose-range and comparative studies using LDL/VC vs VCSO4 are warranted in malignancies in which treatment with the latter drug has been established.

Adenocarcinoma↗
PubMed1992

Genital tract infections associated with the intrauterine contraceptive device can be reduced by inserting the threads into the uterine cavity.

OBJECTIVE: To study the influence of the position of the threads of an intrauterine contraceptive device (IUCD) on the development of genital tract infection. DESIGN: A multicentre randomized controlled trial. SUBJECTS: Women requesting an IUCD. INTERVENTIONS: The women were randomized to be fitted with an IUCD either with the threads contained in the uterine cavity (threads-up group) (n = 208) or passing through the cervix to the vagina in the usual way (threads-down group) (n = 237). Multiple centre study with follow-up at three months, 1 and 2 years. At the final visit 'missing' threads were retrieved using a disposable instrument (Retrievette). MAIN OUTCOME MEASURES: The occurrence of infection in the lower or upper genital tract. RESULTS: 63 women in the threads-up group and 78 in the threads-down groups dropped out. Previous gynaecological infection was reported by 21 and 48 women in the threads-up and threads-down group, respectively (odds ratio 0.44, 95% CI 0.24 to 0.79), 21 and 53 subjects had signs of infection at gynaecological examination (odds ratio 0.39, 95% CI 0.21 to 0.69) and a wet-smear was pathological in 33 and 79 (odds ratio 0.38, 95% CI 0.23 to 0.61). In the threads-up group the vaginal pH was also lower at the final check up after 2 years. Spontaneous descent of the threads occurred in 11% of the threads-up group and in six women in the threads-down group the threads were in the cervix. In 93 women the threads were easily retrieved by means of the Retrievette, four women insisted on the threads remaining in the uterus and in 18 thread removal was performed under local or general anaesthesia. CONCLUSIONS: Infectious complications in women using an IUCD are more frequent if the threads lead from the uterine cavity to the vagina. This problem can be reduced by inserting the threads so that they remain entirely within the uterine cavity, a feasible procedure now that an effective instrument for IUCD thread retrieval is available.

Adult↗
PubMed1992

Stimulation of vasopressin release in women with primary dysmenorrhoea and after oral contraceptive treatment--effect on uterine contractility.

OBJECTIVE: To study aspects of the aetiology of primary dysmenorrhoea and mechanisms underlying the therapeutic effect in this condition of an oral contraceptive. INTERVENTION: Intrauterine pressure was recorded before and during infusion of hypertonic saline (5% NaCl, 0.06 ml/kg/min) over 75 min on the first day of bleeding in women with dysmenorrhoea and after 3 weeks of oral contraceptive treatment. Plasma sampling every 15 min of ongoing infusion for the estimation of osmolality, arginine vasopressin, oxytocin and the prostaglandin (PG) F-metabolite, 15-keto-13,14-dihydro-PGF2 alpha. SUBJECTS: Ten healthy nulliparous women with moderate to severe primary dysmenorrhoea. MAIN OUTCOME MEASURES: Plasma levels of posterior pituitary hormones and the PGF-metabolite. Total pressure area (TPA) of the recording curve. RESULTS: In dysmenorrhoea before infusion the plasma concentration of vasopressin was in mean 2.18, oxytocin 5.05 and the PGF-metabolite 321.5 pmol/l, and the TPA 3.8 kPa x 10 min. After oral contraceptive treatment the vasopressin level and the TPA were significantly reduced. At both sessions apart from intensifying the pain, the saline infusion increased vasopressin and oxytocin levels as well as the TPA, whereas the concentration of the PGF-metabolite at both sessions decreased. CONCLUSION: Confirmation is provided of the elevated secretion of arginine vasopressin and PGF2 alpha, as well as increased uterine activity in primary dysmenorrhoea. The observations are in agreement with the concept that a lowered level of vasopressin and a decreased uterine activity contributes to the beneficial effect of OCs in the condition. Stimulation of the secretion of vasopressin increases the uterine activity and symptoms of primary dysmenorrhoea, but results suggest that this effect does not involve a mechanism of increased PGF-synthesis. The role of oxytocin in dysmenorrhoea can not yet be defined.

Adult↗
PubMed1991

Influence of high lead and cadmium soil content on human reproductive outcome.

The influence of lead and cadmium on human reproductive outcome was studied in areas of Eastern Poland with high specific soil contamination with these heavy metals. By personal interviews, information on socioeconomic background factors as well as obstetrical and gynecological histories were obtained from 136 women living in villages with high amounts of lead and cadmium and from 269 women of nearby villages with no increased content of these metals. Physical examination and estimations of blood concentrations of lead and cadmium were also performed in 89 and 175 women from these areas, respectively. In the contaminated areas, there were significantly fewer women with three or more pregnancies (39 vs. 52%) and deliveries at full term (35 vs. 44%) than in nearby villages with normal concentrations of these heavy metals, and the weight of preterm newborns was lower (1930 vs. 2225 g). Furthermore, hypertension was more common (15 vs. 22%) and of higher magnitude (mean blood pressure 140 vs. 129 mmHg) in the study group than in the control women. The mean blood concentrations of lead in the two groups. 675 and 621 micrograms/dl did not differ statistically, whereas the concentrations of cadmium of 29 and 25 micrograms/dl were significantly higher in the study than in the control group. There was a significant correlation between cadmium levels and number of preterm deliveries. These results suggest that cadmium and lead could be factors of importance in reproductive outcome.

Adult↗
PubMed1991

Innervation of the human uterine artery and contractile responses to neuropeptides.

The intrinsic innervation of the human uterine artery was investigated histochemically, and the motor responses to some of the demonstrated peptides and other humoral factors were studied on isolated vascular preparations. There were nerves with specific immunoreactivities for tyrosine hydroxylase, dopamine beta-hydroxylase, neuropeptide-Y (NPY), vasoactive intestinal peptide (VIP) and peptide histidine methionine, and enzymatic reactivity for acetylcholine esterase. The most effective stimulator of smooth muscle contractility was arginine vasopressin followed in order by oxytocin, noradrenaline together with NPY, noradrenaline alone and dopamine. No effect was seen with acetylcholine and tyrosine, and VIP caused inconsistent relaxation of contractile activity induced by PGF2 alpha. These results suggest that the uterine blood flow is regulated by complex interactions of factors, some occurring in nerve terminals and some being circulating humoral factors.

Adult↗
PubMed1991

Differences in vasomotor responses between main stem and smaller branches of the human uterine artery.

Specimens of the human uterine artery and its branches were taken at hysterectomy. By microscopical dissection, three groups of arteries were obtained with respect to size-main stem, medium and small branches (inner diameters of greater than 1, 0.6-0.8 and less than 0.4 mm, respectively). The contractile effects of different vasoactive substances were studied and the responses expressed as percentages of that of K(+)-depolarization calculated. The most potent vasoconstrictor (the lowest EC50 concentration) was arginine vasopressin (AVP) followed in order by endothelin, oxytocin, prostaglandin (PG)F2 alpha, noradrenalin and dopamine. Angiotensin had inconsistent effects. Atrial natriuretic peptide (ANP) counteracted the contractile effects of endothelin. AVP, endothelin, oxytocin and noradrenalin were significantly more potent on the smallest branches than on the main stem of the artery. Since the former type of vessel represents resistance arteries, the present results suggest that AVP, endothelin, oxytocin and noradrenalin could be of specific importance in the regulation of uterine blood flow. PGF2 alpha, dopamine and angiotensin appear to be of minor importance from this aspect but ANP could play a role by regulating the effects of endothelin.

Adult↗
PubMed1990

The influence of lead ions on uterine activity in the rat.

Spontaneous uterine activity and reactivity to oxytocin, naproxen and PGF2 alpha were studied in vitro in 80 rats, which for 2-8 weeks had been exposed to different concentrations and combinations of Pb2+, Zn2+ and Cu2+ in their water supply or had been given clean water for control. In rats given only Pb2+ in concentrations of 1000 and 500 ppm for 6 weeks the uterine activity was significantly increased, whereas in groups given the other ions alone, or Pb2+ for 6 weeks followed by 2 weeks of clean water or Zn2+ or Cu2+ no change was observed. The responses to the oxytocin, naproxen and PGF2 alpha did not differ. These results suggest that contamination with lead ions might be one of the etiological factors involved in conditions with increased uterine activity.

Animals↗
PubMed1990

Effects of a tocolytic oxytocin analogue on lipid and carbohydrate metabolism.

The effect of a newly developed tocolytic oxytocin analogue, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin on lipid and carbohydrate metabolism was investigated. Oxytocin and vasopressin both stimulated lipogenesis in isolated rat adipocytes, an effect which was dose-dependently inhibited by the oxytocin analogue. In vivo, intravenous injection of 10 nmol/kg body weight of the analogue to 11 healthy subjects caused an initial, but insignificant peak after 4 min in both plasma glucose and glycerol, which thereafter remained at basal level. It is concluded that although an antagonistic effect of the analogue on vasopressin- and oxytocin-stimulated lipogenesis could be demonstrated in vitro, the effect on lipid and carbohydrate metabolism in vivo in humans is insignificant.

Adipose Tissue↗