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Biomedical subjects

G Rydén

Publications and source records attributed to G Rydén.

At least 19 recordsLinked to original sources

Binding of four oxytocin analogues to myometrial oxytocin and arginine-vasopressin binding sites in pregnant women.

The binding of 3H-oxytocin (3H-OT) and 3H-arginine-vasopressin (3H-AVP) and the displacement from binding sites by four oxytocin analogues were studied in myometrial membrane preparations from full-term pregnant women. Specific 3H-OT binding was saturable with a maximal binding capacity of 76.1 fmol/mg DNA, and a dissociation constant of 0.5 pM. Corresponding values regarding 3H-AVP was 148.6 fmol/mg DNA and 0.7 pM. The oxytocin analogues tested demonstrated a high specific binding to the OT and AVP receptor sites; in fact, the affinity of the analogues to the 3H-AVP binding sites was higher than to the 3H-OT binding sites. The order of potency between the analogues was CAU greater than CAM greater than CAP greater than CAO and CAP greater than CAU greater than CAO greater than CAM for the OT and AVP binding sites, respectively. The displacement of oxytocin and arginine-vasopressin, respectively, from the myometrial receptor sites indicate partly separate binding sites for oxytocin and AVP and might implicate that AVP can be of importance in regulating myometrial activity in pregnancy. The results on oxytocin analogues imply that other pharmacological tests must be performed for quantification of the relaxing effects on the uterus and to determine the optimal analogue for clinical trials in preterm labor and dysmenorrhoea.

Arginine Vasopressin

Neurological condition of large-for-gestational-age infants during the newborn period.

Thirty-two large-for-gestational-age (LGA) infants and 46 appropriate-for-gestational-age (AGA) infants used as controls, were investigated. LGA and AGA infants did not differ regarding instrumental deliveries or asphyxia. The infants were examined on the 1st and 5th days after birth with a standardized neurological assessment. The LGA infants showed a significantly delayed neurological adaptation with fewer optimal responses on day one as compared to the AGA infants. These differences were not observed on day five. There were no neurological differences between prenatally and postnatally detected LGA infants. No significant differences were observed regarding parity on maternal complications, neonatal course, and neurological scores of the LGA infants.

Fetal Macrosomia

Effects of enprofylline, a new xanthine derivate, on human pregnant myometrium.

The recently developed xanthine derivate, enprofylline, was studied in an in vitro system with human pregnant myometrium, in particular its effect on spontaneous myometrial contraction, cyclic adenosine monophosphate content, cyclic adenosine monophosphate protein kinase, and cyclic adenosine monophosphate-and cyclic guanosine monophosphate-dependent phosphodiesterase activity. Enprofylline was shown to be a rather potent smooth muscle relaxant [inhibitory concentration that decreases response by 50% (IC50) = 3 X 10(-5) mol/L] and an almost equally potent cyclic adenosine monophosphate-dependent phosphodiesterase inhibitor (IC50 = 10(-4) mol/L), whereas it was a less potent cyclic guanosine monophosphate-dependent phosphodiesterase inhibitor. Enzyme kinetic studies revealed that enprofylline is a competitive cyclic adenosine monophosphate phosphodiesterase inhibitor. Enprofylline increased the cyclic adenosine monophosphate content in a dose-dependent way with subsequent increased activity of cyclic adenosine monophosphate-dependent protein kinase. It is suggested that enprofylline relaxes myometrial smooth muscles and that this is at least partly the result of interference with the cyclic adenosine monophosphate system.

3',5'-Cyclic-AMP Phosphodiesterases

Forceps or vacuum extraction? A comparison of effects on the newborn infant.

Sixteen women delivered by forceps and 20 women delivered by vacuum extraction (VE) owing to secondary uterine inertia were compared with a control group of 11 women who gave birth spontaneously. The cord arterial pH was lower in the VE group than in the forceps and control groups. Base deficit in both arterial and venous cord blood was greater in the VE group than in the forceps group, probably owing to the longer application and extraction times in VE than in forceps delivery. The incidence of retinal hemorrhage did not differ between the forceps and VE groups. The incidence of cephalhematomata was greater among VE infants than in the forceps and control groups. All infants were examined on the 1st and 5th day by standardized neurological and behavioural examination. There were no significant differences in neurological status between the forceps and VE groups. Thus, in low extraction with no signs of fetal asphyxia, either method can be used with safety if the obstetrician is familiar with both methods of operative vaginal delivery.

Adult

Blood pressure and renal function during normal pregnancy.

In order to obtain reference values during normal pregnancy 24 women with strict criteria for health and normal pregnancy were studied. Greatest interest was focused on blood pressure (BP) measurements and renal function tests. Investigations were made in early second trimester and in the 30th, 33rd and 36th gestational weeks. Gestational age was estimated by ultrasound measurement of crown-rump length before the 14th gestational week. Both systolic and diastolic BP measured in the right arm were about 10 mmHg lower in the left lateral position than when supine or standing. The difference is suggested to be dependent on hydrostatic factors. Diastolic BP should be defined at the fourth phase of the Korotkoff sounds in order to be reliable because of the common phenomenon of late or non-disappearance of the sounds during pregnancy. Diastolic BP in phase IV increased in up to 25% of the cases with 15 mmHg or more from early second trimester to the 36th gestational week in all three positions. Serum creatinine concentration was low in early second trimester and did not change during pregnancy, while serum urea decreased and serum urate increased during pregnancy. The results emphasize the importance of using reference values from a normal pregnant population obtained at different gestational weeks for comparison in studies on certain pathological conditions during pregnancy, especially pre-eclampsia.

Adult

Beta-adrenergic receptors in human myometrium during pregnancy: changes in the number of receptors after beta-mimetic treatment.

The concentration of available beta-adrenoceptors has been studied in the myometrium of women treated with terbutaline for premature uterine contractions and in an untreated control group. Myometrial strips were taken at cesarean section from the lower uterine segment and the uterine fundus. The concentration of beta-adrenoceptors was determined with a radioligand binding assay. In untreated women we found no difference in the concentration of beta-adrenoceptors in the uterine fundus compared to that in the lower uterine segment. The cyclic adenosine monophosphate production after beta-adrenoceptor agonist stimulation in vitro was equal in both locations. In the terbutaline-treated women, the binding site concentrations in both the fundus and lower uterine segment were lower compared to those in the control group. The decrease was most pronounced in the fundus where receptor concentration was only half that found in the control group. The results suggest that treatment with beta-mimetics causes a desensitization in the beta-adrenoceptor system of human myometrium during pregnancy. This desensitization may partly explain the limited duration of the relaxant effect of beta-mimetics often seen in the treatment of preterm labor.

Cyclic AMP

Screening for detection of intra-uterine growth retardation by means of ultrasound.

In a two-stage ultrasound screening program the gestational age was assessed by measurement of the fetal crown-rump length in early pregnancy. At an adjusted gestational age between 32 and 35 completed weeks the biparietal diameter, the abdominal circumference, the abdominal area and the ratio between fetal head area and abdominal area were estimated by means of ultrasound measurement. 'Acute' fetal weight was estimated by calculations from biparietal diameter and abdominal diameters. Percentile curves were constructed for these parameters and cut-off limits were tested for the predictability of intra-uterine growth retardation of the fetus. The abdominal circumference and area estimations were equally good for the detection of intra-uterine growth retardation. The biparietal diameter alone is of limited value for the detection of intra-uterine growth retardation but the combination with abdominal diameters in 'acute' fetal weight estimation can well be used. The ratio between the skull and abdominal areas seems to be of little use for the detection of intra-uterine growth retardation of two reasons: difficulty in measurement and low sensitivity. We consider that the assessment of gestational age in early pregnancy is a necessity both for the identification of suspected IUGR by means of ultrasound and the diagnosis of IUGR by measurement of fetal weight at birth. It is concluded that if the gestational age has been assessed by crown-rump length measurement in early pregnancy, a single estimation of the fetal abdominal circumference between 32 and 35 completed gestational weeks and a cut-off limit at the 15th percentile offers a detection rate of about 90% of the growth retarded infants.

Abdomen

Beta-adrenoceptor function of leukocytes in pregnant women treated with terbutaline for preterm labor.

The correlation between cyclic AMP (cAMP) production in myometrial tissue and that in leukocytes was studied in 21 women delivered by cesarean section for obstetrical reasons. After in vitro beta-adrenoceptor stimulation, cAMP production in myometrial tissue was found to be closely correlated with that in leukocytes (r = 0.96). Using cAMP production in leukocytes as an indicator of the state of the beta receptor function in myometrium, 18 women treated with terbutaline for preterm labor were studied. Repeat analyses of cAMP production were made in leukocytes before, during and after treatment. The results showed a significant reduction in cAMP production 3-5 hours and 1-2 days after terbutaline infusion. The cAMP values remained low during infusion. In women orally treated with terbutaline, a slight reduction in cAMP production was found after the first dose, but there was no significant reduction after 1-14 days of treatment. After cessation of terbutaline treatment, cAMP production remained low during the following 3 days, but after 5-8 days an increase was found in 7 out of 9 patients. It is suggested that a desensitization of the beta-adrenoceptor system in leukocytes appears after beta-adrenoceptor agonist treatment in high doses and that measurement of cAMP production reflects the state of desensitization of the beta-adrenoceptors in myometrial cells too.

Administration, Oral

Changes in the renin-angiotensin-aldosterone and kallikrein-kinin systems during normal and hypertensive pregnancy.

We conducted a prospective and serial study of blood pressure (BP) and of the changes in the renin-angiotension-aldosterone system (RAAS) and of one factor in the kallikrein-kinin system during normal pregnancy and in patients with pre-existing or developing hypertension in pregnancy. Strict diagnostic criteria were used to define pre-eclampsia (PE), essential hypertensives (EH) and other hypertension (OH) in pregnancy. In normotensive pregnant women (n = 26) there was a rise in all components of the RAAS measured: plasma renin activity (PRA), plasma aldosterone concentration (PAC) and urinary aldosterone excretion (tU-Aldo), from week 12 to week 20 of pregnancy, compared with non-pregnant control subjects (n = 24) of similar age. Peak values were observed at week 30, whereafter fairly constant levels were maintained. Plasma and urinary aldosterone levels were increased 6-10 fold. Urinary kallikrein excretion (tU- Kall ) was increased at weeks 12-20, but at weeks 30-36 roughly the same mean values were observed as for non-pregnant control subjects. On the other hand, different results were obtained in the hypertensive patients, especially those with PE (n = 18). PRA was depressed in the PE group to values about those observed in non-pregnant control subjects. PRA was also significantly lower in the PE group than in EH (n = 8) or OH (n = 16) groups. PAC and tU-Aldo were also much lower in PE patients than in normal pregnant women at comparable gestational ages, but not significantly different from EH patients, whereas those with OH had both PAC and tU-Aldo values comparable to normal pregnant women.(ABSTRACT TRUNCATED AT 250 WORDS)

Female

The influence of different positions and Korotkoff sounds on the blood pressure measurements in pregnancy.

The influence of the patient's posture on the measurement of arterial blood pressure has been studied during pregnancy. The blood pressure (BP) measured on the right arm in the left lateral recumbent position is significantly lower than in the supine, sitting, or erect positions. This difference is assumed to be due to hydrostatic factors. The diastolic BP should be read off at Korotkoff IV because the hyperkinetic circulation during pregnancy causes a pronounced variation in BP values when measurements are performed at Korotkoff sound V. The roll-over test seems inappropriate as a screening test to predict pre-eclampsia, because of the numerous false-positive tests. The importance of measuring the BP under standardized conditions during pregnancy in order to detect minimal changes in BP as indicative of pathophysiology in pre-eclampsia is emphasized.

Blood Pressure

Neonatal effects of beta-blocking drugs in pregnancy.

A review is presented as regards the neonatal effects of beta-blocking agents in hypertension during pregnancy. Experience points to low fetal and neonatal risks, but firmly based data concerning the neonates are very scanty. An on-going double-blind study is presented in which pregnant women with hypertension are randomly allocated to either metoprolol or placebo treatment. One of the aims is to study the postnatal adaptation of the infants. The following measurements, recordings and examinations are performed: anthropometric measurements, Apgar score, blood gases and acid-base status in umbilical (venous and arterial) blood, lactate and hypoxanthine in umbilical venous blood, catecholamines in umbilical arterial blood, pulse rate, blood glucose and a quantitative neurobehavioral assessment in the neonatal period.

Adrenergic beta-Antagonists

Terbutaline in the treatment of preterm labour.

Continuous terbutaline infusion in 8 women with premature labour arrested the uterine contractions within 1.5 h in 7 of them when an infusion rate of 10 micrograms/min was used. The plasma concentrations of terbutaline were in the range 10-14 micrograms/L after 1 h. In 4 other women with less severe contractions, labour could be stopped with infusion rates of 5 or 7.5 micrograms/min. A condition approaching steady state seemed to be attained after infusion at a constant rate of 2.5 micrograms/min for 17-34 h with a mean plasma concentration of 6.7 micrograms/L. This value would give a mean total body clearance of 0.30 L/min which is about one third higher than that previously found in healthy men. The terbutaline plasma concentrations determined in this study were compared with simulated curves based on pharmacokinetic parameters obtained in healthy male volunteers. The data correlated well during the first 3 h of infusion, indicating similar distribution kinetics in the patients and the volunteers. After infusion for a longer period (greater than 10 h), the measured plasma concentrations were generally lower than those predicted by the simulation. Treatment of 10 women (7 initially treated intravenously) with terbutaline tablets 5 mg three times daily postponed delivery for more than 7 days in 9 of the patients. The mean plasma concentrations of terbutaline during repeated tablet treatment were 3.4, 4.1 and 4.1 micrograms/L at 1, 2 and 4 h after administration, respectively. No serious side-effects occurred.

Administration, Oral

In vitro study of phosphodiesterase-inhibiting drugs: a complement to beta-sympathomimetic drug therapy in premature labor?

Since terbutaline treatment in premature labor has been shown to increase phosphodiesterase activity in the myometrium, the phosphodiesterase-inhibiting effect of theophylline and papaverine on myometrial preparations from pregnant women has been studied. The patients were either treated with terbutaline during the last 3 weeks of pregnancy or not treated. The results showed that papaverine is about 100 times more potent than theophylline in both phosphodiesterase-inhibiting effect and muscle-relaxing effect. No differences in effects were found in myometrial strips from terbutaline-treated or untreated women. A possible improvement in the tocolytic therapy with a combination of a beta-sympathomimetic and a phosphodiesterase-inhibiting drug is suggested.

3',5'-Cyclic-AMP Phosphodiesterases

Effects of selective beta-adrenergic agonists on spontaneous contractions, cAMP levels and phosphodiesterase activity in myometrial strips from pregnant women treated with terbutaline.

The beta-adrenergic receptor function in terms of cAMP production and phosphodiesterase activity has been studied in myometrial strips taken from pregnant women at cesarean sections. The material consists of 10 patients treated with terbutaline for threatening premature delivery and an untreated control group of 10 patients. The basal levels of cAmP were lower and the cAMP production after receptor stimulation in vitro less in myometrial strips taken from terbutaline-treated women compared to the untreated control group. The phosphodiesterase activity was higher in myometrial strips taken from terbutaline-treated women, indicating a faster rate of degradation of cAMP in these women.

Cyclic AMP