High-dose synthetic progestogens inhibit foam and smooth muscle cell proliferation and atherosclerotic plaque formation in aortas of rabbits fed a hypercholesterolemic diet.

Female rabbits on a hypercholesterolemic atherogenic diet were treated with high doses of the synthetic progestogens norethisterone and medroxyprogesterone acetate in order to clarify the effect and possibly some of the mechanism of action of these hormones on diet-induced atherogenesis. We employed morphometric studies to determine the surface area of the rabbit aorta occupied by and the maximum thickness of lipid plaques. Autoradiography with tritiated thymidine was performed to demonstrate the effect of the progestogens on cell proliferation, which plays a key role in atherogenesis. Medroxyprogesterone acetate-treated and, above all, norethisterone-treated animals exhibit a more marked reduction of atherosclerosis than control rabbits fed the same diet. Our results suggest that both progestogens we used inhibit the development of atherosclerosis mainly by blocking the proliferation of smooth muscle cells in the tunica media and the cell population of the plaque.

Interleukin-3 stimulates prostaglandin E2 release by human fetal membranes at term gestation.

The effect of interleukin-3 (IL-3) on prostaglandin E2 (PGE2) release by human fetal membranes at term gestation was evaluated. It was found that interleukin-3 stimulates in vitro prostaglandin E2 release by these gestational tissues, suggesting that interleukin-3 might be involved in the regulation of arachidonic acid metabolism in the fetal membranes.

Interleukin-2 in human amniotic fluid during pregnancy and parturition: implications for prostaglandin E2 release by fetal membranes.

The potential role of interleukin 2 (IL-2) in human pregnancy was investigated by evaluating the following. (1) The presence and concentrations of IL-2 in amniotic fluid (AF) in 24 women at 16-18 weeks' gestation (Group 1) and in 27 women at term pregnancy, either before the onset of labor (Group 2, n = 10) or during spontaneous active labor (Group 3, n = 17). (2) The production of IL-2 by fetal membranes at term gestation (n = 7). (3) The release of prostaglandin E2 (PGE2) by the above tissues after stimulation with IL-2 (n = 10) or phytohemagglutinin (PHA) (n = 8). Immunoreactive IL-2 was detected only in AF samples obtained from women of Groups 1 and 3; the higher concentration was found in Group 1 samples; IL-2 was not detected in AF samples from women of Group 2. Tissues did not release IL-2. Both IL-2 and PHA exerted a significant stimulatory effect on PGE2 release by tissues. IL-2 stimulated PGE2 release by chorion tissue, but not by amnion tissue. The following conclusions can be drawn: (a) AF IL-2 might play a role in the maternal-fetal immune relationship during early pregnancy and, perhaps, during labor; (b) fetal membranes would not seem to represent a source of AF IL-2 in the absence of labor; (3) IL-2 might influence arachidonic acid metabolism through the cyclooxygenase pathway in the chorion tissue.

Nitric oxide in human fetal membranes at term gestation: effect on prostaglandin E2 release.

OBJECTIVES: To examine the in vitro release of nitric oxide (NO) by human fetal membranes at term gestation and to investigate whether NO could stimulate prostaglandin E2 (PGE2) release by these tissues. STUDY DESIGN: Explants of fetal membranes (n = 17) were incubated either in the presence of sodium nitroprusside (NP), or L-Arginine (L-Arg), or bacterial lipopolysaccharide (LPS), or in the absence of the above substances (controls). NO and PGE2 concentrations in culture medium were assayed by the Griess reaction and radioimmunoassay, respectively. RESULTS: Fetal membranes spontaneously released NO in culture medium; incubation with NP increased the production of both NO and PGE2. L-Arg and LPS enhanced PGE2 output by tissues but did not influence NO production. CONCLUSIONS: An NO-generating activity might be present in human fetal membranes. NO stimulates PGE2 release by these tissues.

Role of microcolposcopy in the diagnostic evaluation of cervical pre-invasive lesions.

The present clinical study was undertaken to assess and compare the value of microcolposcopy and endocervical curettage in the diagnostic workup of patients with abnormal cervical lesions. Microcolposcopic findings were well correlated to histology both on directed biopsy and endocervical curettage specimens. Therefore, both microcolposcopy and endocervical curettage are useful procedures to explore the endocervical mucosa. Microcolposcopy should be mainly indicated in those cases where colposcopy has failed to show any lesion, or when colposcopy is unsatisfactory.

Cytohistology, colposcopy and in situ hybridization in cervical preneoplastic lesions: a correlative study.

Formalin-fixed, paraffin-embedded cervical tissues from 106 patients which exhibited a colposcopically atypical transformation zone, were examined for the presence of HPV DNA by in situ hybridization using biotin-labeled HPV 6/11 and 16/18 DNA probes. From the comparative study between histologic, cytologic, colposcopic findings and virologic results it is confirmed that HPV 6/11 DNA is detected more frequently in the less severe lesions, whereas HPV 16/18 DNA is predominantly found in the most severe dysplastic lesions.

Pregnancy in renal transplantation. Clinical aspects.

Following renal transplantation, it is often possible to achieve parenthood. If a female recipient becomes pregnant she must be considered at high risk and so monitored. The better the renal function before pregnancy, the more satisfactory the obstetric outcome. Pregnancy in transplanted mothers presents many complex medical problems and is related to definite risks to both mother (toxemia, serious infections) and fetus (intrauterine growth retardation, premature labor). If a renal function is compromised prior to conception and there is a further deterioration during pregnancy, termination of pregnancy or premature delivery should be considered to avoid permanent impairment of renal function. Pregnancy is regarded as an immunologically privileged state and that is the reason why the incidence of rejection in pregnant patients is unusual. Rejection occasionally occurs in puerperium. Immunosuppressive drugs must be continued during pregnancy to maintain the integrity of the transplanted kidney. There are no predominant or frequent developmental abnormalities in children of renal transplanted recipients treated with modest doses of immunosuppressive and steroid drugs. Usually the transplanted kidney does not produce any mechanical dystocia in labor and during vaginal delivery there is no apparent mechanical injury to the kidney. Cesarean section is usually necessary for purely obstetric reasons. The possibility of conception in kidney transplants recipients of childbearing age and the fact that pregnancy is not without significant maternal and fetal risks emphasizes the need for counseling, with regard to family planning, all such patients.

[Veralipride in the treatment of hot flushes in the menopause]. / Le véralipride dans le traitement des bouffées de chaleur de la ménopause.

Thirty-six menopausal women and 18 women with surgically-induced menopause were treated with a daily oral dose of 100 mg of veralipride for a period of 20 days followed by 10 days without therapy. Following 2 or 3 treatment periods, the drug was effective in 27 women from the first group and in 13 women from the second group. Six women had to discontinue therapy because of adverse effects. There was no significant variation in FSH or LH serum levels.

Acetylcholine receptors in human oocytes.

Neurotransmitter receptors have been studied by conventional electrophysiological techniques in the membrane of human ovarian oocytes isolated from ovarian fragments obtained from pre-menopausal women undergoing abdominal surgery for gynaecological conditions. Ovarian oocytes respond to acetylcholine (ACh) concentrations as low as 10(-10) M by hyperpolarizing the membrane and by concomitantly increasing input resistance, in a dose-dependent manner. The response lasts as long as the transmitter is present in the extracellular fluid. No response is elicited by ionophoretically applied ACh. The ACh response has an apparent latency of less than 1 s and a reversal potential of about -12 mV. The response to ACh (10(-8) - 10(-3) M) is unaffected by curare (10(-5) - 10(-4) g/ml) and is blocked by atropine (10(-6) - 10(-4) g/ml). This indicates that ACh receptors in the human oocyte membrane are probably muscarinic in nature. No response is elicited by the amino acids glutamate, aspartate and glycine (up to 10(-3) M), or by noradrenaline, adrenaline and 5-hydroxytryptamine (up to 10(-3) M). On the basis of analogies to the response elicited by agents which activate parthenogenetic development in the oocytes of other mammals, it is suggested that the sperm-carried ACh might be involved in activation processes triggered by sperm-egg interaction.

Influence of labour on epidermal growth factor receptor distribution of the human chorion at term gestation.

Chorion was obtained from 10 healthy pregnant women at term gestation who were delivered either vaginally (n = 5) or by elective repeat caesarean section before the onset of labour (n = 5). Epidermal growth factor (EGF) receptors in chorionic tissue were evaluated by means of freeze fracture technique (label fracture). They were found to be significantly less, but more frequently coupled, in specimens obtained after labour than before the onset of labour. These findings suggest that a functional activation of EGF receptors in human chorion might occur during labour.

Release of arachidonic acid metabolites by human fetal membranes: interrelationship between leukotriene B4 and prostaglandin E2.

The objective of this study was to ascertain whether human fetal membranes metabolize arachidonic acid preferentially through the lipoxygenase rather than the cyclooxygenase pathway before labor and whether an interaction between lipoxygenase and cyclooxygenase products is present in these tissues. Reflected fetal membranes were obtained from 8 healthy women at term gestation who were delivered by elective repeat cesarean section before the onset of labor. Tissues were cultured either in the presence or in the absence of the calcium ionophore A23187 for 60 minutes. Leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) were measured in culture medium by radioimmunoassays. Moreover, the effect of different concentrations of exogenously added LTB4 on PGE2 release was evaluated. The basal and stimulated output of LTB4 by tissues was significantly higher than that of PGE2. Addition of LTB4 significantly decreased PGE2 release by tissues. These findings suggest that in the above tissues: 1) the arachidonate lipoxygenase pathway is highly active before labor; 2) LTB4 might play a role in the regulation of PGE2 production.

Three-dimensional architecture of the human myosalpinx isthmus. Scanning electron microscopy after NaOH digestion and ultrasonic microdissection.

The three-dimensional architecture of the human isthmic myosalpinx is directly visualized by means of scanning electron microscopy after removal of interstitial connective tissue through NaOH maceration and ultrasound microdissection. These investigations show that the myosalpinx is composed of irregularly running bundles of smooth muscle cells, changing their orientation within the myosalpinx and displaying longitudinal, oblique and circular directions. The muscular bundles anastomose and intermingle with other bundles running at different levels in the oviduct wall, and actually give rise to a wide and complex muscular network in which no distinct layers are readily discernible. These morphological data are consistent with the physiological findings that the transport of gametes and embryo in very early stages in the isthmic portion of the oviduct tube is the result of a discontinuous pattern of forward and backward movements.