Placental barrier breakage in preeclampsia: ultrastructural evidence.

OBJECTIVE: It is known that the placenta acts as an immunological barrier between the mother and fetal "graft" allowing two antigenically different organisms to tolerate one another. Preeclampsia may be considered as a fetal rejection consequent to severe damage at placental endothelial and syncytiotrophoblast level. In order to verify this placental barrier damage we undertook the present study by electron microscopy. STUDY DESIGN: 14 placentae from preeclaptic women, and the same number of placentae from healthy controls were examined. RESULTS: The results showed that endothelial cells from preeclamptic placentae express various and severe alterations, consisting of swollen and bulbous cytoplasm, degenerated inter-endothelial junctions with consequent crossing of fetal blood cells outside the vessels. CONCLUSIONS: These lesions could be the ultrastructural evidence of the placental barrier breakage leading to rejective reaction we presumed to be basis of preeclampsia.

Increased HLA-DR homozygosity associated with pre-eclampsia.

It is generally accepted that maternal recognition of paternally derived fetal antigens occurs during normal pregnancy and may be beneficial for implantation and maintenance of gestation. Thus, we have investigated the human leukocyte class II DR antigens (HLA-DR), whose role in self and non-self recognition is well known, in women with pre-eclampsia, their partners and in control couples. The HLA-DR antigens were tested in 70 pre-eclamptic primigravidae women and their partners and 70 healthy control couples using the serological Terasaki technique. Our results did not show any particular HLA-DR antigen to be correlated with pre-eclampsia, but a statistically significant increase of only one identifiable HLA-DR antigen, which was presumed to express homozygosity at the HLA-DR locus, in the pre-eclamptic women and their partners: 67.1 versus 7. 9% in the control couples (P < 0.000001). The analysis of HLA-DR compatibility between pre-eclamptic women and their partners showed a statistically highly significant increase of the female-to-male compatibility (P = 0.0003) and a lower but significant male-to-female compatibility in comparison with controls (P = 0.014). From our results, it emerges that HLA-DR homozygosity and reduced antigenic disparity seem to be associated to a major risk for pre-eclampsia, which consequently appears to be a 'couple's disease'.

Gestosis and fetal rejection: immunopathogenetic role of HLA-DR.

In this study we faced the problem of etiopathogenesis of EPH Gestosis, focusing our attention on the role of immunitary aspects in determining its onset. We typed HLA-DR in 20 couples with gestosic patient and in 20 control couples. Blood samples were taken into heparin-treated test tubes, from all the couples and HLA typed through standard lymphotoxicity technique in accordance with Terasaky (1). Our results in couples with a gestosic patient, showed homozygosis in 65% of patients and in 70% of partners; in 35% of cases homozygosis was present in both partners, and these were the most severe cases. It is also worth mentioning that in all the couples with gestosic patient, at least one of the partners resulted homozygotic. Homozygosis would therefore represent a predisposing factor in the etiopathogenesis of gestosis, and pre-conception HLA-DR typing of the couple could prove to be a valid alarm signal for gestosis risk.

Immunohistochemical study of placental endothelium in physiologic and gestosis-complicated pregnancies.

In this study we examined the placentae of gestosic patients and controls, with immunoistochemical method and HLA-DR monoclonal antibody, in order to show the role of placental endothelium in gestosic pathology onset. Our results show a marked expression of class II histocompatibility antigens in gestosic placentae with respect to controls. We suppose, in gestosic patients, a role for a particular, genetically determined HLA haplotype which increases disease receptivity.

Cell-mediated immunity in the course of cervical ectropion.

In the present study we evaluated cellular immunitary response in course of asymptomatic ectropion. Biopsies of the injured and healthy zones of the exocervix were carried out. All biopsies were examined by an immuno-histo-chemical method (Avidin-Biotin Complex, ABC) with monoclonal antibodies, in order to phenotype T lymphocytic subpopulations, in particular T helper lymphocytes (CD4), T suppressor lymphocytes (CD8) and Langerhans cells (CD1), which are basic elements of the monocytic-macrophagic series. Our preliminary findings showed a reduction of CD4, CD8 and CD1 lymphocytic subpopulations in ectropion zones, while these subpopulations are normally present in healthy zones of the exocervix. These findings support the hypothesis that, in ectropion, as in HPV infections and in CIN, a localized immuno-deficiency may appear and depress immuno-surveillance and cell-mediated response. In conclusion, it may be supposed that ectropion represents a non-stable lesion, which therefore needs suitable therapeutic intervention.

[Clinico-morphological changes in ectropion after treatment with polydeoxyribonucleotide (PDRN)]. / Modificazioni clinico-morfologiche dell'ectropion dopo trattamento con polidesossiribonucleotide (PDRN).

Thirty patients in fertile age affected by ectropion were treated with Polydeoxyribonucleotide (PDRN) (*) vaginal suppositories for 24 days. No other local or general therapy was allowed. The following parameters were evaluated: local symptomatology, tolerability and compliance, vaginal cytology, colposcopic examination, bioptic sampling of affected area prior to and after treatment, and local immune response. The results show the efficacy of PDRN. In fact, after the treatment: reduction of subjective symptomatology with decrease of average score for each symptom; excellent or good tolerability and acceptability; reduced inflammation; increased iodine-dark areas; reestablishment of normal balance in T- and B-lymphocytic populations have been found.

[Myasthenia gravis and pregnancy. Review of the literature and considerations on the immunoprotective effect of alpha-fetoprotein through the observation of a clinical case]. / Miastenia gravis e gravidanza. Revisione della letteratura e considerazioni sull'azione immuniprotettiva dell' alpha-fetoproteina attraverso l'osservazione di un caso clinico.

Myasthenia gravis is an autoimmune disorder characterized by a reduction of muscular strength. It is associated with production of anti-acetylcholine-receptor antibodies and with the consequent decrease of muscular acetylcholine receptors. The Authors have studied this pathology during the pregnancy and the puerperium in a myasthenic patient and in her newborn, evaluating seric AChRAbs title and seric alpha-fetoprotein levels, to investigate the possible correlation among these parameters and MG. The study shows that with low seric levels of AChRAbs the mother had a progressive symptomatological impairment of MG from 36th week of pregnancy to term and in puerperium too; the newborn didn't show any sign of pathology. The possible immuno-protective role of alpha-FP in maternal and fetal MG evolution is discussed.

[Topical therapy with placental polydeoxyribonucleotide in cervical ectopy and ectropion]. / Terapia topica con polidesossiribonucleotide placentare nella ectopia e nell'ectropion cervicali.

Twenty outpatients, aged 18-45 yrs, with cervical ectropion have been treated with vaginal suppositories of PDRN (a placental derivate). The drug has been given randomly in two preparations of 5 g and 10 g, however both containing the same amount of the active component (5 mg). The results show the effectiveness of the eutrophic and antiphlogistic action of both preparations, with a remarkable reduction of the leukorrhea. The patients preferred the vaginal suppositories of 5g both for the greater maniability and for the smaller vaginal discharge after the administration. The reduction of the excipients in the new vaginal tablets, besides improving the compliance of patients, brings about a longer contact of the drug with the vaginal walls, hence a better bioavailability of the active principle.

Evaluation of the central dopaminergic activity in gestational hyperprolactinaemia by means of the electroretinographic technique.

Electroretinography, a simple, bloodless technique commonly used in ophthalmological diagnostic practice, seems to give important informations on the level of activity of the retinal and/or other central dopaminergic systems. The Authors have employed this technique in a group of 30 normal pregnant women in the ninth month of gestation, in order to evaluate the dopaminergic activity in a condition of physiological hyperprolactinemia, such as pregnancy, and in a group of 25 normal nonpregnant control women. The b wave amplitude of the electroretinographic traces was significantly higher in pregnant women than in controls, suggesting an over-activity of dopaminergic systems in late pregnancy. The possible interpretations of these data are discussed.

Dilemmas in intrauterine fetal growth retardation. The significance of anticomplement and heparin-like activities of placenta at term and the prognostic value of HCS and E3 maternal plasma concentrations during pregnancy.

The Authors studied the behaviour of anticomplement and heparin-like activities in human term placentas in relation to intrauterine fetal growth retardation. These two biological activities might be involved in regulatory mechanisms of great importance for the fetal growth. The anticomplement activity was significantly lower in IUGR placentas than in controls, while no change was found in heparin-like activity. The decrease of anticomplement activity might be associated to immunological mechanisms, possibly related to a placental microcirculation damage, with consequent fetal growth retardation. For what concerns HCS and E3 plasma levels during pregnancy, a significant reduction of HCS in IUGR subjects was observed, confirming a decreased functional activity of placenta. The E3 levels, on the contrary, were slightly, but not significantly lower in IUGR patients.

Bromocryptine-cyclofenil associated therapy: an effective and safe mode of treatment of female normoprolactinemic infertility.

In 51 infertile normoprolactinemic women, aged 19 to 44 years, with anovulatory menstrual cycles and with no endocrine disorders, who had never conceived after the currently employed drugs for female sterility (human chorionic gonadotropin, human menopausal gonadotropin, clomiphene, cyclofenil, bromocryptine itself) a new therapeutic approach was tried: cyclofenil and bromocryptine in association. Before the treatment, a standard luteinizing hormone (LH)-releasing hormone (LHRH) test (100 micrograms intravenously) was performed for each woman to evaluate serum gonadotropin and prolactin response; furthermore, the urinary estrogen excretion or the serum 17-beta-estradiol concentration had been evaluated in all women. The schedule of treatment was as follows: cyclofenil, 600 mg/day, from the 5th to the 12th day of the cycle and bromocryptine, 2.5 mg/day, from the 5th to the 26th day. This scheme was employed for three successive trials at the most. Forty pregnancies (80%) were achieved with the associated therapy, almost all (37) within the second treatment cycle. Thirty-one women delivered a vital baby, five are now pregnant, four aborted spontaneously. All seven women who had been unsuccessfully treated with bromocryptine alone, conceived after the associated regimen. In view of the excellent therapeutic results achieved in our hands, it is justified to consider our proposed scheme cyclofenil-bromocryptine an effective therapy for the management of infertile normo-prolactinemic women.