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Biomedical subjects

E V Cosmi

Publications and source records attributed to E V Cosmi.

At least 19 recordsLinked to original sources

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.

Adrenomedullin

Fatty acid pattern of human prostasome lipid.

Prostasomes are organelles of prostatic origin found in human semen. Their average diameter is about 150 nm and they appear as a lipoprotein membrane surrounding less organized material. Their lipid composition is peculiar, having much cholesterol and sphingomyelin. On the other hand, many of their proteins possess catalytic activity and are involved in the immune response. In previous work, we have shown that prostasomes may fuse to sperm at slightly acidic pH values, thereby modifying the composition of the sperm plasma membrane. In this paper, we examine the fatty acid pattern of prostasome lipid and find that it is completely different from that of sperm membrane lipid. Polyunsaturated phosphatidylcholines, common in sperm membrane, are rare in prostasome. Therefore, the fusion between prostasomes and sperm should stabilize sperm plasma membrane by enriching it in cholesterol, sphingomyelin, and saturated glycerophospholipid. This would prevent the untimely occurrence of the acrosome reaction.

Cytoplasmic Granules

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

Effect of betamethasone in vivo on placental corticotropin-releasing hormone in human pregnancy.

OBJECTIVE: The objective was to determine the effects of in vivo administration of prenatal betamethasone in patients at 26 to 35 weeks' gestation on corticotropin-releasing hormone concentrations in maternal and fetal plasma and amniotic fluid, and on corticotropin-releasing hormone localization in placenta and fetal membranes. STUDY DESIGN: A total of 49 pregnant women at risk for preterm delivery between 26 and 35 weeks' gestation were studied. Twenty-six patients received betamethasone (12 mg intramuscularly) for stimulation of fetal lung maturity. Cord blood, amniotic fluid, placental tissue, and fetal membranes were obtained from 22 of these patients at delivery by elective cesarean section at 33.8+/-2.4 weeks' gestation. In control patients (n=23) at comparable gestational age, blood samples were taken for hormone analysis (n=8), and cord blood, amniotic fluid, and tissues were collected at elective cesarean section at 34.1+/-2.3 weeks' gestation. Concentrations of corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol were determined by radioimmunoassay. Localization of tissue immunoreactive corticotropin-releasing hormone was assessed by immunohistochemistry. RESULTS: Betamethasone caused approximately 90% reduction in maternal cortisol and 50% reduction in maternal plasma adrenocorticotropic hormone. In patients at >30 weeks' gestation, there was a significant increase in maternal plasma corticotropin-releasing hormone concentrations after betamethasone; maternal corticotropin-releasing hormone was not altered significantly in untreated patients. Corticotropin-releasing hormone levels were raised in umbilical cord blood by 48 hours and in amniotic fluid 1 week after betamethasone administration. There was increased immunohistochemical staining for corticotropin-releasing hormone in placental syncytiotrophoblast and in fetal membranes of patients treated with betamethasone. CONCLUSIONS: These studies provide the first evidence for in vivo stimulation of plasma corticotropin-releasing hormone, likely of placental origin, by glucocorticoids in third trimester human pregnancy. The results suggest that increases in endogenous cortisol during normal gestation may contribute to placental corticotropin-releasing hormone output and to the rise in maternal plasma corticotropin-releasing hormone concentrations during late pregnancy.

Adrenocorticotropic Hormone

The effect of glucocorticoid therapy on fetal lung maturity indices in hypertensive pregnancies.

OBJECTIVE: To assess fetal lung maturity tests in hypertensive pregnancies and to examine the effect of glucocorticoid therapy. METHODS: In a cohort study involving 68 pregnant women with hypertension, 34 received antenatal betamethasone before amniocentesis and 34 did not. Controls were 68 women with uncomplicated pregnancies, matched for gestational age at amniocentesis and fetal gender. Amniotic fluid (AF) samples were analyzed by lamellar body count, planimetric and stechiometric lecithin-sphingomyelin ratio (L/S), and presence of phosphatidylglycerol. RESULTS: Fetal lung maturity, as determined by lamellar body counts and by planimetric L/S, was lower in hypertensive pregnancies not treated with steroids than in controls (19,600 +/- 14,500 versus 39,800 +/- 22,700, P < .009, and 1.9 +/- 0.6 versus 3.9 +/- 1.8, P < .01, respectively). In the period of 24 to 33 weeks' gestation, the percentage of untreated pregnancies with mature lamellar body counts and mature L/S was significantly lower than that of controls (13% versus 33%, P < .001; 6% versus 40%, P < .002 and P < .003, respectively). In contrast, in patients treated with betamethasone, the percentage of cases with mature indices for both tests was not significantly different from that of controls, but was higher than that of untreated hypertensive patients (40% versus 13%, P < .001; 33% versus 6%, P < .001). Phosphatidylglycerol did not differ among groups. From 34 to 38 weeks, no difference was found in the percentage of mature cases for lamellar bodies in pregnant women with hypertension not treated with steroids in comparison with controls (68% versus 84%), nor between cases treated and controls (74% versus 84%). In the same period, no difference in L/S values was found among groups, and the percentage of cases positive for phosphatidylglycerol was lower in hypertensive pregnancies than in controls (47% versus 95%, P < .001) and was not affected by steroid treatment (37% versus 95%, P < .001). CONCLUSION: Fetal lung maturity, as reflected in AF tests, is delayed in hypertensive pregnant patients, and steroids increase all lung maturity indices except phosphatidylglycerol between 24 and 33 weeks' gestation.

Adult

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.

Adult

The effect of polyhydramnios and oligohydramnios on fetal lung maturity indexes.

The influence of amniotic fluid (AF) volume on common fetal lung maturity (FLM) indices was evaluated. Cases diagnosed with altered AF volume as estimated by ultrasound (n = 71; polyhydramnios = 33, oligohydramnios = 38) were matched to controls by: gestational age (GA) at amniocentesis, GA at delivery, neonatal weight, sex, and pregnancy complication. FLM was assessed on AF specimens obtained by transabdominal amniocentesis by planimetric and stechiometric L/S, phosphatidylglycerol (PG), and lamellar bodies counts (LB). In cases with polyhydramnios, L/S ratios (planimetric and stechiometric) were statistically lower in cases with respect to controls (2.1 +/- 0.9 vs. 2.8 +/- 1.0, p = 0.007, and 4.8 +/- 2.4 vs. 5.9 +/- 2.7, p < 0.04; respectively). Absence of PG was more frequent in (70.8% vs. 50%, p = 0.02). LB counts were lower in cases than in controls (15.5 +/- 12.1 x 10(3)/microL vs. 21.9 +/- 14.3 x 10(3)/microL, p < 0.05). In cases with oligohydramnios, no difference was found for planimetric and stechiometric L/S in comparison to controls (2.6 +/- 1.2 vs. 2.6 +/- 1.0, N.S. and 4.9 +/- 2.1 vs. 4.6 +/- 1.8, N.S.; respectively), absence of PG (62.5% vs. 50%, N.S.), and LB counts (27.2 x 10(3)/microL +/- 12.8 x 10(3)/microL vs. 28.6 x 10(3)/microL +/- 24.1 x 10(3)/microL, N.S.). In conclusion, oligohydramnios was not associated with altered FLM indices; in cases with polyhydramnios all FLM indices were significantly lower.

Adult

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.

Adrenomedullin

New peptides, hormones and parturition.

This brief review emphasizes the importance of three novel discovered factors produced by fetal membranes, placenta and/or by the fetus itself in regulating uterine contractility. We have shown that, as reported for other hormones and substances, nitric oxide and endothelin may influence myometrial activity in an autocrine/paracrine manner interacting with other well-known agents such as prostaglandins, oxytocin and hormones. We also demonstrated that different isoforms of nitric oxide synthase (NOS) may play different roles throughout gestation and during labor. We have suggested that another peptide produced by trophoblast cells, adrenomedullin, may affect, directly or indirectly, myometrial contractility during pregnancy, although much remains to be learned about the mechanisms controlling adrenomedullin expression by the feto-placental tissues cells during pregnancy. Continued research is necessary to better define the complex interactions that result in parturition, both at term and preterm, and to allow a more rational approach to management of the premature labor, exploring new possible pharmacological solutions.

Adrenomedullin

Ovarian blood flow before and after conservative laparoscopic treatment for endometrioma.

To evaluate the vascular changes in ovaries affected by endometriomas 28 women with ovarian endometriosis underwent transvaginal ultrasound with color flow imaging and blood flow analysis of the ovarian artery before and after laparoscopic conservative treatment of the ovarian cyst. Mean pulsatility index (P.I.) and resistance index (R.I.) of the ovarian artery on the side affected by endometrioma were compared using Student's t-test. Mean P.I. after laparoscopy (1.59) was significantly lower (p = 0.001) than before surgical intervention (2.17). Analogously the mean R.I. was significantly different (p = 0.001) when compared before (0.81) and after (0.73) laparoscopy. Color Doppler velocimetry may add greater understanding of the ovarian hemodynamic changes that occur after conservative surgery on the ovary.

Adult

Pregnancy-associated breast cancer.

Pregnancy-associated breast cancer, which is defined as all breast cancer diagnosed during pregnancy or within the following year, is a relatively rare finding. Due to the particular difficulties in the diagnosis of breast cancer during this period, pregnant women tend to present more advanced disease at diagnosis. Four cases of pregnancy-associated breast cancer referred to our Institute are described as a contribution to the knowledge of this disease.

Adult

Prostasome to sperm transfer of CD13/aminopeptidase N (EC 3.4.11.2).

Prostasomes are membranous vesicles (150-200 nm in diameter) that are present in human semen. They are secreted by the prostate gland and contain large amounts of cholesterol, sphingomyelin and Ca2+. In addition, some of their proteins are enzymes. Prostasomes enhance the motility of ejaculated spermatozoa and are involved in a number of additional biological functions. In previous papers, we demonstrated that lipid can be transferred from prostasomes to sperm by a fusion process occurring at slightly acidic pH. CD (cluster antigens) are ubiquitous proteins; in this paper, we demonstrate that CD13/aminopeptidase N is present is semen, where it is bound to prostasomes. Upon mixing prostasomes and sperm at slightly acidic pH (7 or less), aminopeptidase is transferred from prostasomes to sperm. This evidence comes from enzymatic activity determinations and from the use of the monoclonal antibody, anti-human CD13. The transfer was about 8% of total prostasomal activity at pH 5 and with a prostasome to sperm ratio of 2 (on a protein basis). The transfer did not occur at pH 8.0, but was measurable at pH 7. Therefore, this mechanism may represent a means of modifying the composition and the biological properties of ejaculated sperm.

Antigens, CD

Fusion of sperm with prostasomes: effects on membrane fluidity.

Prostasomes are membranous vesicles (150-200 nm diameter) present in human semen. They are secreted by the prostate gland and contain large amounts of cholesterol, sphingomyelin, and Ca2+. In addition, some of their proteins are enzymes. Prostasomes enhance the motility of ejaculated sperm and are involved in a number of biological functions. In this work, we study the fusion of prostasomes to sperm by determining the relief of octadecylrhodamine self-quenching and the fluidity of membranes by measuring the fluorescence anisotropy of diphenylhexatriene. We present the following findings: (a) the contact of sperm cells with prostasomes at slightly acidic pH causes the fusion of the membranes; (b) the amount of transferred lipid depends on the prostasome/sperm ratio; (c) the fluidity of sperm is much higher than that of prostasomes; (d) the fusion changes some properties of sperm cells, such as fluidity, which decreases greatly; and (e) the extent of fluidity variations depends on the prostasome to sperm ratio. We propose that the H(+)-dependent fusion of prostasomes to sperm may have physiological consequences. In fact, this process can modify the lipid and protein pattern of sperm plasma membranes.

Humans

Bone mass density in post-menopausal women.

OBJECTIVES: To evaluate the effect of age, years since menopause and body weight on bone mass density (BMD) in 283 patients. METHODS: Bone mass density was assessed by bone computerized mineralometry at two sites of the forearm. RESULTS: The mean distal BMD and ultra BMD in the postmenopausal group were negatively correlated with age (P < 0.001, r = -0.48 and P < 0.001, r = -0.50, respectively) and years since menopause (P < 0.001, r = -0.32 and P < 0.001, r = -0.33, respectively). When body-mass index was regressed against distal and ultra distal BMD, positive correlations were found (P = 0.008 and P = 0.007). CONCLUSIONS: From our data, forearm computerized mineralometry seems to be a reliable method for the evaluation of the effects of age and body-mass index on bone mass.

Adult

Intraamniotic surfactant for prevention of neonatal respiratory distress syndrome (IRDS): rationale and personal experience.

OBJECTIVE: To evaluate the efficacy of intramniotic instillation of supplementary surfactant for the prophylaxis of neonatal IRDS in an emergency obstetric setting. STUDY DESIGN: Supplementary natural surfactant (SS) was administered intra-amniotically (80 mg in 1 ml) under ultrasound guidance in the proximity of the fetal nostrils and mouth in six pregnant women at 24-32 weeks gestation, with immature amniotic fluid indices of fetal lung maturity, and whose delivery was imminent because of severe fetal distress, deteriorating maternal conditions, or refractory vaginal bleeding. The administration of SS was preceded by IV aminophylline to the mother (a bolus of 240 mg over 10 min, and a maintenance dose of 0.02-0.1 mg kg-1 min-1) in order to elicit sustained fetal breathing movements. RESULTS: The clinical conditions of the six newborn infants were good with no respiratory problems in four cases, and with mild IRDS in the remaining two, which, however, resolved uneventfully. CONCLUSIONS: It is suggested that this prophylactic approach has a great potential for becoming a reliable option for the antenatal prevention of IRDS.

Amnion