Clinical importance of vascular LH/hCG receptors--a review.

It was believed for a long time that functional LH/hCG receptors were present only in gonads. Recent studies have demonstrated, however, that these receptors are also present in several nongonadal organs in the human body. Uterus is one of them. Besides two uterine layers, endothelial cells and smooth muscle of blood vessels in the uterus also contain these receptors. In vivo administration of hCG decreased vascular resistance in the human uterus and in vitro treatment increased vasodilatory and decreased vasoconstrictive eicosanoids in the vessels. These findings led us to investigate whether hCG administration to patients with signs of threatened abortion has any beneficial effect. Patients were treated with either magnesium or progesterone and/or hCG. The results showed that the frequency of patients reaching second trimester was higher when hCG was used, which was paralleled by a significant decrease in uterine vascular resistance. Patients who reached term after treatment had decreased incidence of preterm delivery and intrauterine growth retardation. In conclusion, we suggest that uterine vascular LH/hCG receptors play an important role in the peri-implantation period by increasing uterine blood flow through vasodilatation and also perhaps through angiogenesis and trophoblast invasion, resulting in therapeutic benefit.

[Clinical experiences with a gestodene containing oral contraceptive (femoden)]. / Gesztodén tartalmú hormonális fogamzásgátlóval (Femoden) szerzett klinikai tapasztalatok.

In order to reduce the side-effects (blood-lipid alterations, androgen effects etc.) new gestogens were introduced, while the ethinyl-estradiol component of the pill was unchanged. Authors report about clinical trial on monophasic oral contraceptive containing 0.030 mg ethinyl-estradiol and 0.075 mg gestodene. In a follow up of 92 women, in 1740 cycles no pregnancy and no cardivascular or thromboembolic complication was observed. The frequency of bleeding disorders was below 10% already in the first cycle. The quantity of withdrawal bleeding, as well the frequency of breakthrough bleeding and spotting decreased during the treatment. Significant alteration in body weight or blood pressure did not occur. Femoden containing third generation gestogen has an excellent cycle control and good patient compliance.

[Clinical significance of betadine vaginal suppository treatment in pregnancy]. / Terhesek Betadine hüvelykúp kezelésének klinikai jelentösége.

Clinical experience proved the efficacy of Betadine suppository in the treatment of bacterial vaginosis and mycotic infections of the vagina. Vaginal infections, frequently observed in pregnancy, can led to maternal and fetal complications, thus Betadine should be used both for prevention and therapy. One can ask if iodine absorbed from the vagina can influence the fetal thyroid function? 64 pregnant women received 7 day Betadine suppository (200 mg polyvidonum-iodine PVP) treatment for colpitis on 37-40 gestational week with excellent therapeutic result. TSH levels were measured by immunoassay in the serum of newborns 4-5 days after delivery, no signs of hypothyroidism were observed. Authors recommended 7 day Betadine vaginal suppository regimen for the prevention of intrauterine infections, treatment of mixed (bacterial, mycotical) vaginal infections, and restoration of the normal vaginal equilibrium of bacterias, since the risk of hypothyroidism is negligeable in mature newborns. In case of prematurity hypothyroidism is more frequently found also without iodine treatment therefore TSH level control is recommended in each case.

Effects of chlorpromazine on the rate of synthesis of various glycerolipids from [3H]glucose in the human primordial placenta.

The in vitro effect of chlorpromazine (CPZ) on the biosynthesis of various neutral and phospholipids of the 8-10 week old human placenta from [3H]glucose has been studied. Time course (with 0.5 mM CPZ) and dose-response (with 0.1-1.0 mM CPZ) experiments were performed. In order to investigate the significance of the cationic nature of CPZ, the effects were compared with those of 0.05% (v/v) Triton X-100, a nonionic amphiphile, and with the effects of the combined treatments with CPZ and Triton. The results provide evidence that (I) CPZ and Triton stimulate the formation of phosphatidic acid (PA) from glucose, (II) CPZ but not Triton inhibits the activity of phosphatidic phosphohydrolase (PPH), (III) both compounds inhibit the activity of diacylglycerol (DAG)-acyltransferase with an attendant rise of the levels of DAG and phosphatidylcholine (PC), (IV) the combined treatment decreases PC formation presumably due to inhibition of citidylyl transferase activity, (V) CPZ treatment leads to accumulation of labelled phosphatidylinositol (PI) irrespective of the presence or absence of Triton, and (VI) CPZ cannot promote the formation of PI from PA accumulating in response to Triton. The cationic nature of CPZ seems to play specific roles in the inhibition of PPH activity and in the activation of phosphatidyltransferase, both of which direct intermediates toward PI. On the other hand, the amphipathic nature of CPZ and Triton appears sufficient to account for the inhibited DAG-acyltransferase and citidylyl transferase activities.

Magnesium content of human myometrium and placenta during various stages of gestation, and of different body fluids at term.

Pregnancy is marked by a state of hypomagnesaemia but not much is known about the effects of maternal magnesium deprivation on the fetus. The aim of this study was therefore to measure magnesium concentrations in human myometrial and placental tissues and in different body fluids during pregnancy and at term, using atomic absorption spectrophotometry. The magnesium concentration in umbilical cord blood was higher than in the maternal blood, supporting the existence of an active magnesium transport system. There was also a difference between the magnesium concentration in the amniotic fluid and that in the umbilical cord blood. The magnesium content of myometrium increased from the 32nd week of pregnancy, reaching its maximum level at the 37th week of gestation. Later there was significant decrease in magnesium level until the end of pregnancy. The magnesium content of placental tissue did not change up to the 30th week of pregnancy; however, it then decreased continuously during the last trimester. The significant improvement experienced in certain pathological conditions of pregnancy treatment with magnesium supports the existence of a magnesium deficit induced by pregnancy and the need for magnesium supplementation.

Low concentration of Triton X-100 inhibits diacylglycerol acyltransferase without measurable effect on phosphatidate phosphohydrolase in the human primordial placenta.

Agents causing accumulation of endogenous diacylglycerols (DAG) may be helpful in studies on the intracellular regulatory effects and on the mechanisms of attenuation of this putative second messenger. In a previous study (Tóth et al., BBA 921 (1987) 417-425) we have shown a marked stimulatory effect of low micellar concentration (0.05%, v/v) of Triton X-100 on the labelling of phosphatidic acid with (32P)phosphate in minced human primordial placenta. The present results demonstrate that 0.05% Triton X-100 inhibits nearly completely the conversion of (3H)diacylglycerols into (3H)triacylglycerols in placenta fragments incubated with (3H)glucose. However, this concentration of the detergent does not have any effect on the appearance of label in the sum of acylglycerols (comprising mono-, di- and triacylglycerols) and phosphatidylcholine, indicating a lack of effect on phosphatidate phosphohydrolase. The about 5-fold elevation of (3H)diacylglycerols was attended by an approximately 3-fold rise in (3H)phosphatidic acid and a 1.3-fold increase in the labelling of phosphatidylcholine. These findings provide supportive evidence that 1,2-DAG was formed due to inhibition of DAG-acyltransferase and suggest that some of the DAG was transformed into phosphatidic acid by diacylglycerol-kinase.

Phosphocholine transferase is more efficient than diacylglycerol kinase as possible attenuator of diacylglycerol signals in primordial human placenta.

Diacylglycerols (DAG) are assumed to play intracellular signal roles in rapidly growing tissues like those present in the primordial human placenta. The aim of the present study was to gain information on the capacity of DAG-kinase and CDP-choline: DAG phosphocholine transferase enzymes to eliminate DAG and behave as possible signal attenuators in these tissues. Previous and present results has provided evidence that Triton X-100 (0.05%, v/v), when incubated with placenta mince, (I) causes the accumulation of DAG by inhibiting DAG-acyltransferase and by a suggested acceleration of phosphatidylcholine (PC) decomposition, (II) inhibits the synthesis of PC and (III) increases the formation of phosphatidic acid (PA) without decreasing the conversion of PA into acylglycerols. Inhibition by the synthetic DAG: dioctanoylglycerol (DOCG) and by the DAG-analog: dioctanoylethyleneglycol (DOEG), of the Triton-induced (3H)PA-accumulation from (3H)glucose and of the increased labeling of PA with (32P)phosphate indicated some DAG-attenuating roles of DAG-kinase, but this mechanism appeared not to be very efficient. The low rate of conversion of DOCG into (32P)PADOCG species in incubations with (32P)phosphate confirmed this view. Compared to the rate of formation of PADOCG, DOCG was eliminated in the form of PCDOCG more than one order of magnitude faster. In addition, DOCG stimulated, whereas DOEG inhibited the formation of endogenous PC. These findings suggest that in the primordial human placenta transformation of DAG into PC by phosphocholine transferase and an attending stimulation of PC synthesis represent a more effective attenuator mechanism than the conversion of DAG into PA by DAG-kinase.

The relation between thromboxane and prostaglandin synthesis in human decidua tissue: a comparison of eicosanoid synthesis in minced tissue with that in a cell-free preparation.

Radiotracer studies and radioimmunoassay measurements demonstrate that minced tissues of human decidua produce chiefly thromboxane B2 (TxB2) (70% of total eicosanoids) and small amounts of prostaglandin F2 alpha (PGF2 alpha) (13%) PGD2 (8%), 6-keto-PGF1 alpha (5%) and PGE2 (4%). Inhibition of thromboxane synthesis with a specific inhibitor (OKY-1581: sodium (E)-3-[4(-3-pyridylmethyl)-phenyl]-2-methyl propenoate) increased prostaglandin formation in general, with the main product being PGF2 alpha (38%), a nonenzymic derivative of PGH2. Crude particulate fractions prepared from the same tissue synthesized two major products from [3H]arachidonate, TxB2 and 6-keto-PGF1 alpha (54 and 30%, respectively) and some PGF2 alpha and PGE2 (8-8%). However, in the presence of reduced glutathione (GSH), PGE2 became the main product (81%) (TxB2, 15%; PGF2 alpha, 2%; and 6-keto-PGF1 alpha, 2%). Half-maximal stimulation of PGE2 synthesis occurred at 46 microM GSH. The GSH concentration of tissue samples was found to be 110 +/- 30 microM. We conclude that human first trimester decidua cells possess the key enzymes of prostaglandin and thromboxane synthesis. Apparently, the production of these compounds is controlled by a specific mechanism in the tissue, which keeps PGE and prostacyclin synthesis in a reversibly suppressed state, whereas the formation of thromboxane is relatively stimulated.

Triton X-100 promotes the accumulation of phosphatidic acid and inhibits the synthesis of phosphatidylcholine in human decidua and chorion frondosum tissues in vitro.

Triton X-100 is known to affect phospholipid metabolism and the generation of various signal molecules from cellular phospholipids. In the present work the effect of Triton X-100 on phospholipid metabolism of human decidua and of the primordial placenta (chorion frondosum) was studied. Triton X-100 (0.05%, v/v) added to tissue mince 30 min before the end of a 60 min incubation stimulated 2-4-fold (decidua) and 4-6-fold (placenta) the incorporation of [32P]phosphate ([32P]Pi) into phosphatidic acid, while markedly decreasing the labeling of phosphatidylcholine. Triton X-100 had no effect on the labeling of phosphatidylinositol in the decidua, and only a slight increase was observed in the placenta. When labeled glucose was used to assess phospholipid synthesis, the addition of Triton had no effect on phosphatidic acid, while decreasing the synthesis of phosphatidylcholine. Incorporation of [32P]Pi into phosphatidic acid was not accelerated by a submicellar concentration (0.01%) of Triton, whereas the synthesis of phosphatidylcholine was decreased irrespective of detergent concentration. Anionic or cationic detergents could not mimic the action of Triton on phosphatidic acid synthesis. Although Triton inhibited the synthesis of ATP in a dose-dependent manner, this could not account for the above results. Instead, it is suggested that diacylglycerol kinase and phosphocholine:CTP cytidylyltransferase are possible targets of the action of Triton X-100.

Continuous, high-dose progestogen treatment of endometrial cancer.

The morphological effect of a high-dose progestogen (Depo-Provera) on highly differentiated endometrial carcinoma was studied. Thirteen patients were treated by progestogen only, given at the beginning of the treatment in a weekly dose of 1,000 mg for 3 month. Then, progestogen 500 mg was administered for 12 months. Nine patients were operated after the treatment; in 7 of them, a total histological regression was observed. Histological tests of the intraoperatively gained preparations showed 'disappearance' of the original carcinomatous process; only a serious atrophy of the endometrium could be detected.

Endocrine factors in the etiology of endometrial carcinoma.

In the blood of 39 women with endometrial carcinoma the FSH, LH, estrone, androstendion, estradiol and dehydroepiandrosterone were determined by the RIA method. Compared to the control group the estrone (303.3 +/- 44.3 pmol/l), estradiol (165.2 +/- 29.4 pmol/l) and the androstendion (5.24 +/- 0.44 nmol/l) were significantly higher. The source of the increased estrogen levels was mainly of adrenal origin. The peripheral conversion, i.e. aromatization of androstendion into estrone was particularly marked in the case of adipose patients. The unbalanced estrogen effect in the absence of progesterone is one of the decisive factors in the etiology of endometrial carcinoma.

[Incrustation of marker threads of intrauterine devices in the uterine cavity and cervix uteri]. / Inkrustation der Markierungsfäden von Intrauterinpessaren im Cavum und der Cervix uteri.

If the indicating thread of intrauterine contraceptive devices is situated inside the uterine cavity, it is incrustated in the same way with calcium carbonate like the device itself. In 20 per cent the intracervical part of the thread is incrustated, too. The danger of an ascending inflammatory disease is increasing with the precipitation of substances, probably, denaturated fibrine or mucine according to the infrared spectral analysis.