Infectious agents in tissues from spontaneous abortions in the first trimester of pregnancy.

Some evidence suggests that intrauterine infection plays a major role in the pathogenesis of early pregnancy loss, but the implication and prevalence of microrganisms in the aetiology of spontaneous abortion during the first trimester of pregnancy has not yet been well established. In this study, we analysed the tissues relative to the product of conception from abortions during the first trimester (51 spontaneous abortions and 56 voluntary pregnancy interruptions) in women attending the Gynecological Sciences Perinatology and Puericulture Department of "Policlinico Umberto I". Specimens were investigated by cultural methods for the presence of yeasts, gram positive, gram negative bacteria, and genital mycoplasma. By molecular diagnostic procedures, DNA sequences of Chlamydia trachomatis, herpes simplex viruses, adenovirus, human papillomaviruses and human polyomaviruses BK and JC were searched. None of these agents could be found in voluntary pregnancy interruption samples, with the exception of 3.6% of specimens positive for adenovirus, whereas spontaneous abortion tissues were positive for at least one microrganism by 31.5%. Data analysis showed the occurrence of both monomicrobial and polymicrobial infections.

Influence of labor on fetoplacental adrenomedullin concentrations.

OBJECTIVE: Circulating adrenomedullin is increased in pregnancy, and placental and fetal membranes participate significantly in its secretion. Recent studies have suggested a potential role for this peptide in the regulation of fetoplacental circulation and placental hormonal secretion. Because adrenomedullin acts also as a uterorelaxant in rats, this study was designed to investigate whether fetoplacental adrenomedullin production changes with human labor, either at term or preterm. STUDY DESIGN: Eighty pregnant women grouped according to gestational age and presence of labor were studied. Adrenomedullin concentrations in plasma, amniotic fluid, and placental tissue extracts were measured by means of radioimmunoassay and immunohistochemistry. In addition, the ability of amnion and chorion-decidua to secrete adrenomedullin was investigated in vitro. RESULTS: Adrenomedullin concentrations in amniotic fluid were higher in preterm labor, whereas no differences were found in adrenomedullin expression or concentrations in tissues or in maternal and fetal plasma between vaginal delivery or elective cesarean section, both at term and preterm. During term labor (8 patients), maternal plasma adrenomedullin concentration decreased with advancing cervical dilatation, being 173 pg/mL at the beginning of the active stage of labor and 57 pg/mL at the time of delivery. Adrenomedullin concentration in the medium of amnion- and chorion-decidua-cultured cells was higher after vaginal delivery. CONCLUSION: These results suggest that a decrease in adrenomedullin production is not involved in the onset of labor in human subjects but rather that it may play a role other than that of a myometrial relaxant in human parturition.

Amniotic fluid nitric oxide metabolite levels and nitric oxide synthase localization in feto-placental tissues are modified in association with human labor.

Nitric oxide (NO) has a relaxant effect on uterine smooth muscle and may be implicated in maintaining uterine quiescence during pregnancy. In order to investigate the role of nitric oxide in human parturition, we have measured NO metabolite levels in maternal and fetal compartments in association with labor, both at term and preterm. We have also examined the localization and distribution of NO synthase (NOS) isoforms in placentas and fetal membranes after term and preterm delivery by means of immunohistochemistry. Although no differences were present in maternal and fetal blood and in maternal urine among groups, we found that NO metabolite concentrations were higher in amniotic fluid collected from women in labor than in non-laboring patients, both at term (15.4+/-1.6 vs. 6.8+/-0.6 microM/mg creatinine) and preterm (16.7+/-2.0 vs. 7.0+/-0.8 microM/mg creatinine). Ir-bNOS staining appeared to be decreased in fetal membranes collected after spontaneous labor at term and preterm. In contrast, a stronger staining for iNOS was detected in trophoblast cells of fetal membranes from women in labor than in those from non-laboring women. We suggest that NOS isoenzymes in fetal placental tissues are differently regulated and might play different roles during pregnancy.

[HPV infection as a disease of couples. Prevalence of the infection in the male partner]. / L'infezione da HPV come malattia di coppia. Prevalenza dell'infezione nel partner maschile.

BACKGROUND: The role of males who are sexual partners of females with genital human papillomavirus (HPV) infection and premalignant lesions is explored in the present study. METHODS: In a period of 6 years, 845 females with genital premalignant and HPV-associated lesions were examined and treated at the Sexual Transmitted Disease Center of S. Gallicano Hospital. The male partners of were asked to attend this Center, and 163 (70%) of them responded. All participants underwent sexual anamnesis, genital inspection and colposcopic examination. RESULTS: Macroscopic lesions were found in 7.4% of the males enrolled. The colposcopic prevalence of HPV infection among the male partners was 21.8% 3 months later among 28 negative patients to the first colposcopic control, 2 were found positive. CONCLUSIONS: These data confirm that the colposcopic evaluation of male partners during an HPV infection of the couple is to be considered for the therapeutic assessment and evolution control of the infection in each couple.

Amniotic fluid concentrations of adrenomedullin in preterm labor.

OBJECTIVE: To determine whether adrenomedullin levels in amniotic fluid were associated with preterm labor. METHODS: We measured immunoreactive adrenomedullin in amniotic fluid collected by amniocentesis from 36 women with clinical diagnosis of preterm labor or preterm premature rupture of membranes (PROM) and from 18 normal pregnant women. RESULTS: Amniotic fluid from cases of PROM and failure to respond to tocolysis were associated significantly with higher amniotic fluid adrenomedullin concentrations (177.0 +/- 22.5 pg/mL and 182.7 +/- 22.0 pg/mL, respectively, P < .01) than that from uncomplicated pregnancies (101.2 +/- 28.1 pg/mL) or preterm labor responsive to tocolysis (102.3 +/- 26.8 pg/mL). CONCLUSION: Amniotic fluid adrenomedullin is higher than normal in cases of PROM and preterm labor unresponsive to tocolysis, perhaps indicating enhanced synthesis from placenta or fetal membranes being stimulated by bacterial products.

Adrenomedullin production is increased in normal human pregnancy.

OBJECTIVE: Adrenomedullin, a recently discovered vasoactive peptide originally identified in pheochromocytoma, has been found to be increased in the plasma of pregnant women at term. This study was designed to elucidate whether adrenomedullin secretion is dependent on gestational age and the possible source and function of this peptide in human pregnancy. STUDY DESIGN: Adrenomedullin concentrations were determined by RIA in amniotic fluid and maternal plasma obtained from 110 pregnant women between 8 and 40 weeks of gestation. Subjects were stratified into five groups according to gestational age. In term patients (n = 15), adrenomedullin was also measured in the umbilical artery and vein separately. RESULTS: High concentrations of adrenomedullin were present in plasma and amniotic fluid samples from patients in the first, second and third trimester. There was no significant difference in mean maternal plasma concentration of adrenomedullin between the five patient groupings. Amniotic fluid adrenomedullin concentrations decreased from 81.2 +/- 11.7 pg/ml at 8-12 weeks of gestation to 63.7 +/- 6.0 pg/ml at 13-20 weeks of gestation and then increased at 21-28 weeks of gestation to 99.1 +/- 10.4 pg/ml. A further increase was found in samples collected after 37 weeks of gestation (132.6 +/- 10.1 pg/ml). In the umbilical vein, adrenomedullin concentration was higher (P < 0.05) than in the artery (65.7 +/- 6.1 pg/ml and 48.5 +/- 5.2 pg/ml respectively), suggesting that adrenomedullin in the fetal circulation derives from the placenta. CONCLUSIONS: Our results demonstrate the presence of adrenomedullin in maternal plasma and amniotic fluid throughout gestation, and show that its production starts very early in gestation, suggesting that this hormone may have an important role in human reproduction, from implantation to delivery.

Immunohistochemical localization of adrenomedullin in fetal and neonatal lung.

Adrenomedullin is a potent hypotensive peptide that has been demonstrated to increase pulmonary blood flow in fetal sheep. To examine whether adrenomedullin plays a role in the transitional changes of human pulmonary blood flow at birth, we have evaluated, by immunohistochemistry, its presence and distribution in fetal lung during gestation using a polyclonal antibody directed toward human adrenomedullin 1-52. We collected lung specimen from abortive fetuses (n = 6), preterm neonates (n = 4). and term infants (n = 3). Two adult lung specimen were used as controls. Immunoreactive adrenomedullin was detected in fetal lung collected as early as at 18 wk of gestation and in all tissues throughout gestation. Adrenomedullin was localized predominantly in the epithelial cells of bronchi, with an apical distribution. Endothelial cells also stained for adrenomedullin. The intensity of staining and the percentage of positive bronchial epithelial cells increased as gestation progressed: but staining for adrenomedullin was absent in tissues collected after breathing and in the adult controls. These findings indicate that adrenomedullin may play an important role in respiratory homeostasis at birth. Moreover, the immunohistochemical expression of AM in the late organogenetic period and its increasing staining during fetal lung development may suggest a possible role in the mechanisms of fetal lung differentiation and/or maturation.

Immunoreactive adrenomedullin in human fetoplacental tissues.

OBJECTIVE: Adrenomedullin is increased in maternal plasma in pregnancy and has been found in very high concentrations in amniotic fluid and umbilical plasma. To identify adrenomedullin-producing tissue in pregnancy we measured adrenomedullin concentration and distribution in fetoplacental tissues. STUDY DESIGN: By use of a specific radioimmunoassay we determined the concentrations of adrenomedullin and, by immunohistochemical studies, its localization and distribution in fetal membranes and placentas collected at elective cesarean section from 11 healthy pregnant women at term. RESULTS: The content of adrenomedullin in placentas (117.7 +/- 7.8 pg/mg wet tissue) and fetal membranes (168.7 +/- 2.3 pg/mg wet tissue) was similar to the adrenomedullin concentration in adrenal medulla (157.3 +/- 4.4 pg/mg wet tissue). Adrenomedullin staining appears to be greater in fetal membranes than in placentas and was localized in amnion and trophoblast cells. In term placentas positive staining was detected predominantly in extravillous trophoblast cells, although a few syncytiotrophoblast cells and endothelial cells of primary villi stained for adrenomedullin. CONCLUSION: This study provides evidence that is consistent with fetoplacental tissues as a site of synthesis or action of adrenomedullin during pregnancy.

Adrenomedullin, a new vasoactive peptide, is increased in preeclampsia.

Adrenomedullin is a novel peptide that elicits a long-lasting vasorelaxant activity. Recently, we found high concentrations of adrenomedullin in maternal and umbilical cord plasma and in amniotic fluid in full-term human pregnancy, indicating a role of this peptide during gestation. To investigate the possibility that adrenomedullin is involved in the pathophysiology of preeclampsia, we measured its concentration in maternal and fetoplacental compartments. We studied 12 normotensive nonpregnant women, 13 hypertensive nonpregnant subjects, 29 patients with preeclampsia, and 30 normotensive pregnant women. In all patients, plasma was collected from the cubital vein, and amniotic fluid samples were obtained by transabdominal amniocentesis or at elective cesarean section. Plasma samples from umbilical vein and placental tissues were collected at delivery. Adrenomedullin was assayed on plasma and amniotic fluid samples using a specific radioimmunoassay, and its localization and distribution on placental sections was determined by immunohistochemistry. Adrenomedullin concentrations were higher in hypertensive than in normotensive nonpregnant patients. Pregnant women had higher adrenomedullin levels than nonpregnant subjects, although maternal plasma adrenomedullin concentrations did not differ between normal pregnant and preeclamptic women. Preeclamptic patients showed higher concentrations (P<0.01) than normotensive pregnant women of adrenomedullin in amniotic fluid (252+/-29 versus 112+/-10 fmol/ micromol creatinine) and umbilical vein plasma (18.1+/-2.1 versus 8. 5+/-1.1 fmol/mL). Increased local production of adrenomedullin is associated with preeclampsia. The fetus seems to be responsible for the higher levels of this hormone. Increased adrenomedullin concentrations may be necessary to maintain placental vascular resistance and/or fetal circulation at a physiological level.

Nitric oxide in preeclampsia: lack of evidence for decreased production.

The purpose of our study was to determine the involvement of the L-arginine-NO system in preeclampsia. We studied 26 patients with preeclampsia and 27 normotensive pregnancies. Maternal and cord plasma, urine and amniotic fluid were assayed for nitric oxide metabolites (nitrite and nitrate) using the Griess reaction. Sections of placenta and fetal membranes were immunostained with polyclonal anti-endothelial and anti-neuronal nitric oxide synthase antibodies. The concentration of nitrate in the amniotic fluid of preeclamptic patients (median 10.3 mumol/mg creatinine) was significantly higher (P < 0.001) than in the normotensive group (5.6 mumol/mg creatinine). Nitrate concentrations in maternal and cord plasma and in urine were similar in the two groups. Endothelial cells of the villi of preeclamptic placentas showed a higher positivity in endothelial nitric oxide synthase immunostaining with respect to normotensive controls. Our results indicate that feto-placental NO production is not reduced in preeclampsia. In contrast, the increased concentrations of NO metabolites in amniotic fluid and the positive immunostaining of endothelial nitric oxide synthase in the placental villi suggest that the placental L-arginine-NO system is up-regulated in preeclampsia.

Alteration of polyunsaturated fatty acid pattern of plasma phospholipids and antioxidants in cervical HPV infection and neoplasia.

The complex interactions between host immunity and infectious diseases have been documented in literature and they play a role in virus infection. Many clinical-experimental reports have stressed the importance of homeostasis of cell membranes and of the 'cell healthy indicators', namely polyunsaturated fatty acids and antioxidants in HIV infection. Today's increased incidence of heterosexual transmission of HIV has showed a strict correlation between HIV and HPV infection. According to some studies, positive HIV subjects have 40-200 times a greater risk of becoming HIV-positive. We have evaluated in 40 women with HIV infection the plasma levels of polyunsaturated fatty acids of phospholipids and vitamin E, determined by GC-MS methods, and the erythrocyte glutathione peroxidase activity (GHS-Px) by spectrophotometric techniques. The alteration of these parameters were correlated with the progression of the infection, i.e. the appearance of dysplastic or neoplastic pathologies on the uterine cervix. The differences were statistically significant (p<0.001) in subjects with cervical cancer with respect to both normal controls and patients with condylomatosis.