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Biomedical subjects

E Marinoni

Publications and source records attributed to E Marinoni.

At least 19 recordsLinked to original sources
PubMed2002

Mechanobiology of engineered cartilage cultured under a quantified fluid-dynamic environment.

Natural cartilage remodels both in vivo and in vitro in response to mechanical forces and hence mechanical stimulation is believed to have a potential as a tool to modulate extra-cellular matrix synthesis in tissue-engineered cartilage. Fluid-induced shear is known to enhance chondrogenesis on animal cells. A well-defined hydrodynamic environment is required to study the biochemical response to shear of three-dimensional engineered cell systems. We have developed a perfused-column bioreactor in which the culture medium flows through chondrocyte-seeded porous scaffolds, together with a computational fluid-dynamic model of the flow through the constructs' microstructure. A preliminary experiment of human chondrocyte growth under static versus dynamic conditions is described. The median shear stress imposed on the cells in the bioreactor culture, as predicted by the CFD model, is 3 x 10(-3) Pa (0.03 dyn/cm(2)) at a flow rate of 0.5 ml/min corresponding to an inlet fluid velocity of 44.2 mum/s. Providing a fluid-dynamic environment to the cells yielded significant differences in cell morphology and in construct structure.

Bioreactors↗
PubMed2002

Maternal nitric oxide supplementation increases adrenomedullin concentrations in growth retarded fetuses.

Nitric oxide (NO) and adrenomedullin (AM) are both involved in the regulation of fetoplacental circulation in human pregnancy. The aim of this study was to investigate the effect of maternal NO supplementation in pregnancies complicated by intrauterine growth retardation (IUGR) on maternal and fetal NO and AM concentrations and their correlation with uteroplacental and fetal blood flow. We studied 20 pregnant women with IUGR and impaired uteroplacental blood flow between 27 and 35 weeks of gestation randomly selected to receive either transdermal glyceryl trinitrate or placebo. Maternal NO metabolites (NOx) and AM concentrations did not change before and after NO treatment. AM levels were significantly higher in growth retarded fetuses whose mothers received NO donors (114.1 +/- 17.6 pg/ml) than in untreated fetuses (59.8 +/- 38.6 pg/ml), whereas NO treatment did not affect significantly fetal NOx levels. Fetal AM correlated with middle cerebral artery pulsatility index in untreated IUGR but not in NO treated pregnancies.

Administration, Cutaneous↗
PubMed2001

Fetomaternal adrenomedullin levels in diabetic pregnancy.

We investigated whether maternal and fetoplacental adrenomedullin, a newly discovered hypotensive peptide involved in the insulin regulatory system, is modified in diabetic pregnancy. We studied its correlation with pregnancy complications associated with this disease. Thirty-six pregnant women with diabetes (13 with type I and 23 with gestational diabetes mellitus) and in 40 uncomplicated pregnancies were included. 10 out of 36 diabetic pregnancies were complicated by gestational hypertension. In each woman, adrenomedullin concentration in maternal and fetal plasma and in amniotic fluid was assessed by specific radioimmunoassay. We found that overall mean amniotic fluid adrenomedullin concentration was higher (p < 0.05) in diabetic (14.7 +/- 1.6 fmol/ml) than in uncomplicated pregnancies (10.8 +/- 0.9 fmol/ml), whereas no differences were present in maternal and fetal plasma adrenomedullin levels between diabetic and uncomplicated pregnant women. High levels of amniotic fluid adrenomedullin were found in both type I and gestational diabetes mellitus pregnancies (13.7 +/- 1.4 and 15.6 +/- 2.2 fmol/ml, respectively). Diabetic pregnancies complicated by gestational hypertension showed lower (p < 0.05) amniotic fluid adrenomedullin concentrations than normotensive diabetic patients. These findings suggest that placental adrenomedullin production is upregulated in diabetic pregnancy, and it may be important to prevent excessive vasoconstriction of placental vessels.

Adrenomedullin↗
PubMed2001

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.

Adrenomedullin↗
PubMed2001

Circulating adrenomedullin is increased in preterm newborns developing intraventricular hemorrhage.

Adrenomedullin is a novel vasoactive peptide that participates in cerebral blood flow regulation and circulates in human plasma. To verify whether plasma adrenomedullin is able to identify preterm newborns at risk of intraventricular hemorrhage (IVH), we performed a case-control study. Plasma samples collected within 6 h after birth in 24 preterm newborns who developed IVH, as diagnosed at 72 h, were assessed for adrenomedullin and compared with those obtained from 48 preterm newborns, matched for gestational age, who did not develop IVH. Cerebral ultrasound and Doppler velocimetry waveform patterns in the middle cerebral artery were also recorded at the time of blood sampling. Adrenomedullin blood concentrations and middle cerebral artery pulsatility index values were significantly higher in infants developing IVH (20.1 +/- 4.5 fmol/mL and 1.71 +/- 0.21 fmol/mL, respectively) than in controls (7.5 +/- 3.0 fmol/mL and 1.49 +/- 0.19 fmol/mL, respectively). Adrenomedullin blood concentrations correlated with middle cerebral artery pulsatility index (r = -0.77, p < 0.01) and with the grade of IVH extension (r = 0.83, p < 0.01). This study suggests that adrenomedullin blood concentration might be a promising tool for identifying preterm infants at risk of IVH immediately after birth, when imaging assessment and clinical symptoms of hemorrhage are still silent.

Adrenomedullin↗
PubMed2001

Adrenomedullin, a new peptide, in patients with insulinoma.

BACKGROUND: It has been demonstrated that adrenomedullin, a newly discovered peptide, affects the release of insulin from pancreatic islets cells, suggesting a role in the insulin-regulating system. OBJECTIVE: To investigate whether adrenomedullin secretion is modified in patients with insulin-secreting islet cell tumours. DESIGN: The study was performed in nine patients with surgically treated insulinoma. Circulating adrenomedullin was assayed using a specific radioimmunoassay and its localization and distribution in the tumour were determined by means of immunohistochemistry. RESULTS: Adrenomedullin concentrations were significantly greater in patients with insulinoma (6.6 +/- 3.2 fmol/ml) than in controls (2.1 +/- 1.1 fmol/ml). In six patients monitored before and after surgery, plasma adrenomedullin decreased from 6.3 +/- 2.9 fmol/ml to 3.0 +/- 1.6 fmol/ml. Immunoreactive adrenomedullin was localized exclusively in the tumours cells, whereas stroma, surrounding pancreas parenchyma and major ducts were negative for the peptide. CONCLUSIONS: Our findings indicate that circulating adrenomedullin is increased in insulinoma and that this increase is related to the neoplastic phenotype.

Adenoma, Islet Cell↗
PubMed2001

Nepadutant pharmacokinetics and dose-effect relationships as tachykinin NK2 receptor antagonist are altered by intestinal inflammation in rodent models.

Tachykinin NK2 receptor antagonists could reduce motility and symptoms during gastrointestinal diseases characterized by local inflammation such as diarrhea or colitis; however, how these conditions change pharmacodynamic and pharmacokinetic characteristics of NK2 receptor antagonists is unknown. We investigated the effect of the peptide NK2 receptor antagonist nepadutant on spontaneous intestinal motility or [betaAla8]NKA(4-10)-induced colonic and bladder contractions in rodent models of intestinal inflammation (enteritis induced by castor oil and rectocolitis induced by local instillation of acetic acid in rats, enteritis induced by bacterial toxins in mice). In the castor oil model, the oral/intraduodenal bioavailability of nepadutant was also determined. The intrarectal (i.r.) administration of nepadutant (100 nmol/kg) did not reduce [betaAla8]NKA(4-10) (10 nmol/kg i.v.)-induced colonic and bladder contractions in normal animals, but the same dose of nepadutant produced an inhibitory effect in the two organs following rectocolitis; in contrast, nepadutant is equieffective by the intravenous route in normal and colitic animals. In this model, nepadutant (100 nmol/kg i.r. or i.v.) decreased spontaneous colonic hypermotility, without affecting motility in controls. The intraduodenal administration of nepadutant (30 nmol/kg), which was ineffective on [betaAla8]NKA(4-10) (10 nmol/kg i.v.)-induced colonic and bladder contractions in control animals, abolished bladder contractions in castor oil-pretreated animals. In this latter group, the oral and intraduodenal bioavailability of nepadutant showed a 7- to 9-fold increase with respect to controls. Oral administration of nepadutant, in nanomolar or subnanomolar dosage, reduced diarrhea induced by bacterial toxins in mice. It is concluded that intestinal inflammation increases nepadutant absorption in the intestine, enhancing its activity. These results suggest that a drug with a limited oral bioavailability could be used for treating gastrointestinal diseases associated with a local inflammation.

Acetates↗
PubMed2001

New placental factors: Between implantation and inflammatory reaction.

The trophoblast invasion is a dynamic changes in cell-cell and cell matrix interaction and it create in the endometrio a reaction similar to the inflammatory reaction. In the recent past most of the investigator in this field had focus on the mediator of this process especially on cytokine and on vasoactive agent. We have studied the inducible isoform of nitric oxide synthase (iNOS), adrenomedullin (AM), fatty acid synthase (FAS), and S-100 protein. Several evidences had lead our choice: the two first factors are essentially local mediator of vasospasm which works in synergy during the inflammatory reaction, but the AM I addition stimulates the DNA synthesis and cell proliferation of Swiss 3T3 fibroblasts, induces the cell cycle progression from G0 to G1 phase and the malignant cell lines express AM mRNA and mRNA for its receptor and the pattern of distribution of ir-AM and its mRNA during murine development is similar to that of other growth factors (TGFb isoforms, PDGF, FGF, IGF 1 and 2); Fatty acid synthase (FAS) is a major biosynthetic enzyme of intracellular fatty acid synthesis, its expression and activity is enhanced in proliferative tissues, such as malignant cells; S-100 is an acid calcium binding protein present in central nervous system where it is in mainly concentrated in the glial cells, astrocytes, Schwann cells, and neurons. It regulates several functions such as cell-cell communication, cell growth, cell structure, energy metabolism, contraction, and intracellular signal transduction. Recently the appearance in blood of S100 in preterm infants has been used as a marker of brain damage in perinatal period. The iNOS, AM, S100 and FAS are localized in both decidual and trophoblastic cells in early pregnancy, but we found that changes in iNOS, S100, AM, and FAS are different in spontaneous abortion (SA) versus voluntary pregnancy termination (VPT). Considering the VPT as non pathologic pregnancy, this difference may reflect functional modifications of placental tissues. Our result shown that AM and NO are increased in VPT vs SA showing that when the process of implantation is on course we found an higher expression that we have during the inflammatory reaction. [Table: see text]

Abortion, Induced↗
PubMed2000

Changes in plasma adrenomedullin levels during the menstrual cycle.

We investigated whether the levels of adrenomedullin, a novel peptide produced by several tissues, including the pituitary gland, change during the ovarian cycle. We studied 13 healthy women with regular menstrual cycles. Plasma samples were collected at 7, 14, 21 and 28 days of the ovarian cycle and assayed for adrenomedullin 1-52 using a specific RIA. LH, FSH, 17beta-estradiol, and progesterone concentrations were also determined. The adrenomedullin profile during ovarian cycle was similar to that of LH; plasma adrenomedullin increased from 10.9 pg/ml at the 7th day to 15.1 pg/ml at the 14th, and decreased to 8.5 pg/ml in the subsequent menses. The changes in plasma adrenomedullin were related to changes in LH and 17beta-estradiol. The cause of the increase in adrenomedullin levels during the late follicular phase of the menstrual cycle is not clear. Since it has been demonstrated that adrenomedullin is involved in the regulation of hypothalamus-pituitary-adrenal gland and its secretion is regulated by sex hormones we speculate that adrenomedullin could also play a role in regulating the hypothalamus-pituitary-ovary feedback. Alternatively it may be involved in the regulation of fluid and electrolyte homeostasis during the menstrual cycle.

Adrenomedullin↗
PubMed2000

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.

Adult↗
PubMed2000

Circulating adrenomedullin is increased in patients with corticotropin-dependent Cushing's syndrome due to pituitary adenoma.

It has been demonstrated that adrenomedullin, a newly discovered peptide with structural similarity to calcitonin gene-related peptide (CGRP), is expressed in pituitary gland and affects basal and corticotropin (ACTH)-releasing factor (CRF)-stimulated ACTH release in animals, thus suggesting its potential role in regulating the hypothalamus-pituitary-adrenal axis. To evaluate whether ACTH and cortisol levels affect adrenomedullin production in humans, we studied 14 patients with Cushing's syndrome due to pituitary adenoma and 8 patients with Cushing's syndrome due to adrenal tumor, with measurement of circulating adrenomedullin by a specific radioimmunoassay (RIA). Adrenomedullin concentrations were significantly higher in patients with pituitary adenoma (37.6 +/- 17.8 pg/mL) versus controls (13.7 +/- 6.1 pg/mL) and patients with adrenal adenoma (17.8 +/- 2.2 pg/mL). After pituitary surgical treatment, plasma adrenomedullin decreased significantly. In one patient with Cushing's syndrome due to pituitary adenoma who underwent simultaneous sampling of the inferior petrosal venous sinuses, the adrenomedullin concentration was significantly higher in plasma collected from the side with the adenoma and increased after CRF administration (delta increase, 42.6%), according to ACTH levels. Our findings indicate that circulating adrenomedullin is increased in Cushing's disease, and the pituitary gland may represent the site of the elevated production of adrenomedullin in this condition.

Adenoma↗
PubMed2000

Adrenomedullin is increased in the fetoplacental circulation in intrauterine growth restriction with abnormal umbilical artery waveforms.

OBJECTIVE: To examine whether adrenomedullin, a novel vasoactive peptide produced by the placenta, participates in the uteroplacental hemodynamic alterations in intrauterine growth restriction, we studied the correlation between adrenomedullin levels and fetoplacental blood flow. STUDY DESIGN: Maternal and umbilical blood samples were collected in pregnancies complicated by intrauterine growth restriction with abnormal umbilical artery Doppler findings and in control pregnancies. Adrenomedullin levels were measured by means of a specific radioimmunoassay, and flow velocimetry waveforms were recorded from uterine, umbilical, and fetal middle cerebral arteries. RESULTS: Mean adrenomedullin values in umbilical plasma were higher (P <.05) in patients with intrauterine growth restriction (63.7 +/- 34.2 pg/mL; n = 16) than in control subjects (38.1 +/- 14.8 pg/mL; n = 16). A significant correlation was found between maternal adrenomedullin levels and umbilical artery pulsatility index. Moreover, fetal adrenomedullin concentrations correlated negatively with middle cerebral artery pulsatility index and positively with umbilical artery pulsatility index/middle cerebral artery pulsatility index ratio. CONCLUSION: This study provides evidence that adrenomedullin is increased in fetuses with intrauterine growth restriction in response to reduced uteroplacental blood flow and suggests that it may participate in the fetal hemodynamic modifications.

Adrenomedullin↗
PubMed1999

Effect of prenatal betamethasone administration on maternal and fetal corticosteroid-binding globulin concentrations.

OBJECTIVE: This study was undertaken to examine the effects of prenatal betamethasone administration on corticosteroid-binding globulin concentrations in maternal and fetal plasma and amniotic fluid. STUDY DESIGN: Two groups of patients with preterm labor at 24 to 35 weeks' gestation who were receiving prenatal betamethasone (2 intramuscular doses of 12 mg) were studied. Maternal plasma was obtained before and at variable intervals until 1 week after betamethasone administration. Umbilical cord blood and amniotic fluid samples were collected at the time of delivery. Samples were also collected from patients at risk for preterm delivery who did not receive glucocorticoids. RESULTS: Betamethasone suppressed maternal cortisol concentration by >70% within 24 hours of injection but did not significantly alter corticosteroid-binding capacity or relative concentrations of corticosteroid-binding globulin isoforms in either maternal or umbilical cord plasma. Betamethasone reduced corticosteroid-binding capacity in amniotic fluid within 24 hours of injection, and values remained suppressed 1 week after treatment. CONCLUSION: Maternal and fetal plasma corticosteroid-binding globulin concentrations were unchanged after maternal betamethasone administration at 24 to 32 weeks' gestation but amniotic fluid corticosteroid-binding globulin concentrations decreased significantly, suggesting different sites of either corticosteroid-binding globulin production or regulation or both.

Amniotic Fluid↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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.

Adrenomedullin↗