Martti O. Pulkkinen

Reduced maternal plasma and urinary estriol during ampicillin treatment.

Abstract Noninfected mothers who received ampicillin during pregnancy showed reduction of maternal plasma and urinary estriol. Neither the drug itself nor its metabolites could be shown to exercise any chemical disturbances upon the determination methods.

Oviductal function is critical for very early human life.

For normal fertilization, the ovum must be picked up from the ovarian surface or from the abdominal cavity into the ampulla. The rapid transport of gametes includes a complex reorganization of the oviductal smooth muscle electrical activity that precedes the mechanical activity. The 3-day stay at the ampulla-isthmic junction requires both signals from the ovum to the oviduct and vice versa, supporting the ovum and regulating its to-and-fro movements. Oviductal fluid, a principal factor in tubal function, coats the newly fertilized egg, activates transcription and gives a signal for sperm fertility potential. Early blocks to embryo development in in vitro conditions, as compared to in vivo success, means that critical developments during the first cell cycles of embryonic life in the oviduct are actively regulated by oviductal embryotrophic factors. These have been used clinically in co-culture systems. Lytic factors are weak in human and other primates, predisposing to high incidence of tubal pregnancies, with considerable impact on medical practice. Diverse oviductal factors affect the incidence, infection being the most significant. Optimal oviductal function is necessary to provide a proper environment for early human life.

The effect of nimesulide and naproxen on the uterine and ovarian arterial blood flow velocity. A Doppler study

Background. To measure the effect of oral naproxen and nimesulide treatments on the uterine and ovarian arterial blood flow velocity in both eumenorrheic and dysmenorrheic women.

Electrical activity in the human oviduct during the menstrual cycle

Electrical activity in 25 isolated human oviducts on different days of the menstrual cycle was recorded with six simultaneous suction electrodes in at least 18 locations. During the follicular phase, electrical activity consisted of a smooth, single slow spike that lasted 3 to 6 seconds, and on which was superimposed a fast spike(s) in the ampulla immediately after menstruation. The shape of this activity changed at midcycle, first in the ampulla and later in the isthmus, to a burst of potentials; in the ampulla it sometimes changed to a slow wave on which was superimposed a series of fast spikes. The pacemakers were stable and their number few. The electrical activity spread with a velocity of 1 to 3 mm/sec. The probability of spread toward the uterus varied with the location in the oviduct and with the day of the cycle. After menstruation, electrical activity spread in the uterine direction. On cycle day 12, activity spread toward the ampullary-isthmic junction (AIJ) from both ends of the oviduct. On days 14 and 15, it spread a short distance from the ampulla to the isthmus, through the AIJ. On cycle day 18, spread toward the uterus covered the uterine half of the ampulla. AIJ, and the isthmus. Two to 5 days later, no constant features could be detected in the spread. These findings suggest that the human oviduct functions like the oviducts of other mammalian species, with the spread of electrical activity and the transport of ova being related.

Suppression of uterine activity by prostaglandin synthetase inhibitors.

Abstract. During hypertonic saline induction, the evolution of intrauterine pressure, the oxytocin response and abortion were delayed in naproxen‐treated patients. The PG synthesis inhibitors naproxen, mefenamic acid and ibuprofen decreased the high uterine resting pressure (‘tone’), the frequency of contractions but not always the active pressure (‘amplitude’) in dysmenorrheic patients, with a coincident decrease in pain.

Collagen types and fibronectin in the uterine muscle of normal and hypertensive pregnant patients

Specimens from the uterine wall were obtained from 16 patients at 31 to 40 weeks of pregnancy: 10 underwent surgical procedures for a hypertensive disorder and six for abnormality of the birth canal or faulty presentation. Collagen types I, III, and V and fibronectin antibodies were used for immunohistologic studies. Collagen types I and V were located mainly around single cells, but type III and fibronectin were found mainly around cell bundles. Collagenous structures in the uterine muscle of patients with hypertensive disorder in pregnancy were torn. Abundant fibronectin fluorescence was detected in the lobuli within the disrupted tissue. Disruption of the uterine structure correlated with the amount of urinary protein excreted.

Group I and Group II Phospholipase A2 in Serum during Normal and Pathological Pregnancy

Phospholipase A2 groups I (pancreatic) and II (synovial) could be a link between local and systemic changes in pregnancy, reflected in catalytic activity. We studied whether normal pregnancy, preeclampsia, preterm labor and four other diseases have processes involving serum phospholipase A2s. Pancreatic and synovial-type phospholipase A2 were measured in the serum of 59 normal pregnant women and 89 patients with pathological pregnancy by newly developed time-resolved fluoroimmunoassays, and the catalytic activity by a radiochemical method using micellar phosphatidylcholine as substrate. During pregnancy weeks 6-14, synovial-type phospholipase A2 and catalytic activity were elevated 2- to 4-fold, but at 37 weeks values were normal. Pregnancy-induced hypertensive diseases increased by 4- to 10-fold the concentration of synovial-type phospholipase A2, reflected in catalytic activity. In 8 out of 14 cases, the enzyme was increased if the fetus was to be delivered prematurely. The enzymes studied remained within the reference interval in cases of hepatogestosis, fetal asphyxia, diabetes and twin pregnancy. Newly developed specific immunoassays for measuring different types of phospholipase A2 in serum can provide insights for clinical follow-up.

Proton NMR Spectroscopy of the Phospholipids in Human Uterine Smooth Muscle and Placenta

The parameters regulating the fluidity of myometrial and placental phospholipids include double bonds, fatty acid chain lenght and the cholesterol/phospholipid ratio. The transformation of these parameters was studied during pregnancy and labor. Myometrial and placental tissue samples were collected from 24 patients: 6 were nonpregnant, 6 early-pregnant, 6 late-pregnant not in labor and 6 in labor. After butanol extraction, tissue cholesterol and lipid phosphorus were determined. Proton NMR spectroscopy of the phospholipids was performed at 500 MHz. The myometrial cholesterol/phospholipid ratio was slightly elevated in pregnant patients not in labor. The uterine muscle of the nonpregnant patients contained more CH=CH groups in the phospholipids than that of the late-pregnant patients. There were 29 more double bonds in placental than in uterine tissue per 100 fatty acid molecules. The average fatty acid chain length varied from 14.0 to 18.8. The placenta has longer fatty acid chains than the uterine smooth muscle. The myometrial carbon chain was shortened on the average by 1.4 and the placental by 1.0 carbon atoms, when the patient went into clinical labor. These findings suggest fluidity changes in myometrial and placental phospholipids during human pregnancy and labor.

Myometrial estrogen and progesterone receptor binding in pregnancy: inhibition by the detergent action of phospholipids.

We characterized the phospholipid inhibition of estradiol and progesterone binding to guinea-pig and human myometrial receptors. Of twelve compounds studied, phosphatidylinositol (PI), lysophosphatidic acid and lysophosphatidylcholine (lyso-PC) were the most active inhibitors (50% inhibition at 10(-5) M). Lyso-PC with fatty acid chain length C14:0 inhibited ligand binding both to estrogen receptor (ER) and progesterone receptor (PR), C16:0 only to PR and C18:0 neither to ER nor to PR. The lyso-derivates were more inhibitory than the parent compounds. The ionic detergent (sodium taurocholate) inhibited both ER and PR binding, but the non-ionic detergent (Triton X-100) only PR. Triton X-100 enhanced the PI-induced inhibition of ER binding by a factor of 10. PR was more sensitive to inhibition than ER in all cases. The type of inhibition was non-competitive. At term pregnancy, ligand binding to myometrial ER or PR was low or absent in humans, but moderate in the guinea-pig. Phospholipid extracts of human decidua and fetal membranes contained PI and phosphatidylserine rather than lyso-PC. The extract was a potent inhibitor of ligand binding to PR (50% inhibition at 10(-6) M phospholipid phosphorus), but not to ER. The physicochemical environment, modulated by phospholipids acting as detergents, may regulate sex steroid function also in vivo. This might have special significance for pregnancy maintenance.

Low serum progesterone levels and tubal dysfunction-A possible cause of ectopic pregnancy

We analyzed 22 human oviducts by the suction electrode method for electrical activity (preceding and reflecting the mechanical activity), as related to serum progesterone levels. Eleven patients had high progesterone levels (greater than or equal to 20 nmol/L), but the other 11 patients had low levels. When the serum progesterone level was low, the oviductal electrophysiologic characteristics were those associated with poor ovum transfer: low probability of prouterine propagation of the activity at the fimbrial end of the tube: high-frequency but low number of electrical bursts, reflecting possible weak propulsive force; and a high occurrence rate of sine-wave-like activity and inactive areas where ovum retention can occur. These phenomena could be related to the higher incidence of ectopic pregnancies in patients with luteal phase defect.