Biomedical subjects

Paolo Toti

Publications and source records attributed to Paolo Toti.

At least 19 recordsLinked to original sources

PubMed2007

Nestin expression in adult and developing human kidney.

Nestin is considered a marker of neurogenic and myogenic precursor cells. Its arrangement is regulated by cyclin-dependent kinase 5 (CDK5), which is expressed in murine podocytes. We investigated nestin expression in human adult and fetal kidney as well as CDK5 presence in adult human podocytes. Confocal microscopy demonstrated that adult glomeruli display nestin immunoreactivity in vimentin-expressing cells with the podocyte morphology and not in cells bearing the endothelial marker CD31. Glomerular nestin-positive cells were CDK5 immunoreactive as well. Western blotting of the intermediate filament-enriched cytoskeletal fraction and coimmunoprecipitation of nestin with anti-CDK5 antibodies confirmed these results. Nestin was also detected in developing glomeruli within immature podocytes and a few other cells. Confocal microscopy of experiments conducted with antibodies against nestin and endothelial markers demonstrated that endothelial cells belonging to capillaries invading the lower cleft of S-shaped bodies and the immature glomeruli were nestin immunoreactive. Similar experiments carried out with antibodies raised against nestin and alpha-smooth muscle actin showed that the first mesangial cells that populate the developing glomeruli expressed nestin. In conclusion, nestin is expressed in the human kidney from the first steps of glomerulogenesis within podocytes, mesangial, and endothelial cells. This expression, restricted to podocytes in mature glomeruli, appears associated with CDK5.

Aborted Fetus↗

PubMed2006

Differential regulation of colony stimulating factor 1 and macrophage migration inhibitory factor expression by inflammatory cytokines in term human decidua: implications for macrophage trafficking at the fetal-maternal interface.

Macrophages are a major component of the leukocyte population of human pregnant endometrium. Although several crucial functions have been ascribed to these cells, the mechanisms underlying macrophage trafficking in the placental bed are poorly understood. The aim of this study was to evaluate the in vivo expression of two potentially antagonistic macrophage-targeting chemokines, colony stimulating factor 1 (CSF1, also known as M-CSF) and macrophage migration inhibitory factor (MIF), in term decidua, and to examine the effects of the inflammatory cytokines tumor necrosis factor (TNF, also known as TNF alpha) and interleukin 1beta (IL1B) on CSF1 and MIF expression in cultured decidual cells. The expression of CSF1 and MIF in term decidua was evaluated by immunohistochemistry. Cultured decidual cells were primed with estradiol (E2) or with E2+medroxyprogesterone acetate (MPA), and then incubated with corresponding steroid(s) with or without TNF or IL1B. The levels of CSF1 and MIF protein and mRNA were assessed by ELISA and quantitative RT-PCR, respectively. Immunostaining for CSF1 and MIF was observed in term decidua. The levels of secreted CSF1 and MIF were similarly unchanged whether the decidual cells were incubated with E2 or with E2+MPA. The CSF1 levels significantly increased in cultures exposed to E2 or E2+MPA plus TNF or IL1B. In contrast, the MIF levels in TNF- and IL1B-treated cells were not changed significantly from the control cultures. The ELISA data were confirmed by quantitative RT-PCR analysis. These results indicate that CSF1 and MIF are involved in regulating macrophage trafficking at the fetal-maternal interface, and suggest a mechanism by which inflammatory cytokines influence pregnancy by regulating decidual macrophage infiltration.

Cell Movement↗

PubMed2006

Human endometrium expresses urocortin II and III messenger RNA and peptides.

Urocortin II and urocortin III are recently identified corticotropin-releasing factor-related neuropeptides, and their endometrial expression throughout the menstrual cycle and in early pregnancy was evaluated in the present study by semiquantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. The endometrial expression of urocortin II mRNA was significantly (P<.01) higher in the early proliferative phase of the menstrual cycle than in other phases and maternal decidua (MD), whereas that of urocortin III mRNA was higher (P<.01) in MD than in all other endometrial samples. Both peptides were immunolocalized in epithelial, stromal, and endothelial cells.

Adult↗

PubMed2006

Urocortin 2 and urocortin 3 are expressed by the human placenta, deciduas, and fetal membranes.

OBJECTIVE: Urocortin 2 (UCN2) and urocortin 3 (UCN 3) are recently identified neuropeptides showing homology to corticotropin-releasing factor (CRF). In the present study, we evaluated their expression and localization in gestational tissues (placenta, decidua, fetal membranes), and their effect on placental adrenocorticotropic hormone secretion. STUDY DESIGN: The study was performed in a tertiary clinical care center. Tissues were obtained at first (n = 8; 8-11 weeks of pregnancy) and third (n = 8; 38-40 gestational weeks) trimester. The mRNA expression was evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR); the cellular localization by immunohistochemistry; ACTH levels were measured in media collected from cultured placental villi. RESULTS: All tissues analyzed expressed UCN2 and UCN3 mRNA. UCN2 and UCN3 were localized in cytotrophoblast and syncytiotrophoblast cells; UCN2 was present in maternal and fetal vessels and in amniotic cells, while UCN3 was absent. Finally, UCN2 and UCN3 did not stimulate ACTH secretion. CONCLUSION: Gestational tissues differentially express UCN2 and UCN3 and, despite their homology to CRF, they did not stimulate placental ACTH secretion.

Adrenocorticotropic Hormone↗

PubMed2006

Histopathology of explanted AlphaCor due to keratoprosthesis extrusion.

AlphaCor keratoprosthesis (KPro) is a new-concept poly (2-hydroxyethyl methacrylate) one-piece KPro that makes possible a two-step implantation technique easy to perform with a short learning curve. In literature an 18% incidence of AlphaCor removal due to melting complications is reported. The histopathology of corneal tissue removed during a re-operation while bearing an AlphaCor KPro has previously been described in the literature only in one report. Herein, the first histological features of an AlphaCor-corneal complex explanted because of KPro extrusion is described. The histopathology of the AlphaCor-corneal complex is characterized by mild inflammation in the corneal tissues, limited to the region surrounding the anteriorized and extruded part of the KPro. It is not possible to fully understand the mechanisms that trigger the device extrusion. One possible explanation could be a dislocation of the prosthesis in the corneal pocket due to the untied fixation stitch. Another explanation could be a foreign body reaction induced by KPro.

Aged↗

PubMed2006

Urocortin expression is downregulated in human endometrial carcinoma.

Urocortin (UCN) is a 40-amino acid neuropeptide sharing 45% sequence homology with corticotropin-releasing factor (CRF). The human endometrium expresses both UCN and CRF, and CRF/UCN receptors type-1 (CRF-R1) and -2 (CRF-R2). CRF-R1 activation inhibits cell growth and proliferation of a tumor cell line derived from the human endometrium, and the UCN signaling pathway has been implicated in tumorigenesis of several tissues. Therefore, we investigated whether UCN mRNA and peptide are expressed by human endometrial adenocarcinoma, and whether their expression changes compared to controls. Samples of well (grade 1; n = 6 endometrioid adenocarcinoma, of whom n = 1 with squamous differentiation, and n = 1 clear-cell carcinoma) and poorly differentiated (grade 3; n = 3 endometrioid adenocarcinoma) endometrial adenocarcinoma were collected from nine women (age range 61-79 years) enrolled at the time of diagnosis. Healthy endometrium was collected from postmenopausal women (controls; n = 13; age range 64-78 years), who underwent hysterectomy for uterine prolapse. Immunohistochemistry was used to evaluate cellular UCN localization, with the intensity of immunostaining scored on a subjective scale. Quantitative real-time reverse transcriptase (RT)-PCR analysis was used to estimate mRNA expression changes and restriction analysis was used to confirm PCR products identity. UCN mRNA expression was significantly reduced (P < 0.0001) in endometrial adenocarcinoma than in healthy controls. Immunoreactive UCN was found in luminal and glandular epithelial cells in healthy, but not in neoplastic samples. UCN mRNA and peptide expressions are decreased in endometrial adenocarcinoma. These data and the evidence that endometrial cancer expresses UCN receptors and UCN is involved in tumorigenesis of several tissues together suggest a role for UCN in endometrial tumoral cell growth and proliferation.

Adenocarcinoma↗

PubMed2006

Regulation of monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha and interleukin-1beta in first trimester human decidual cells: implications for preeclampsia.

The current study describes a statistically significant increase in macrophages (CD68-positive cells) in the decidua of preeclamptic patients. To elucidate the regulation of this monocyte infiltration, expression of monocyte chemoattractant protein-1 (MCP-1) was assessed in leukocyte-free first trimester decidual cells. Confluent decidual cells were primed for 7 days in either estradiol or estradiol plus medroxyprogesterone acetate to mimic the decidualizing steroidal milieu of the luteal phase and early pregnancy. The medium was exchanged for a serum-free defined medium containing corresponding steroids +/- tumor necrosis factor (TNF)-alpha or interleukin (IL)-1beta. After 24 hours, enzyme-linked immunosorbent assay measurements indicated that the addition of medroxyprogesterone acetate did not affect MCP-1 output, whereas 10 ng/ml of TNF-alpha or IL-1beta increased output by 83.5-fold +/- 20.6 and 103.1-fold +/- 14.7, respectively (mean +/- SEM, n = 8, P < 0.05). Concentration-response comparisons revealed that even 0.01 ng/ml of TNF-alpha or IL-1beta elevated MCP-1 output by more than 15-fold. Western blotting confirmed the enzyme-linked immunosorbent assay results, and quantitative reverse transcriptase-polymerase chain reaction confirmed corresponding effects on MCP-1 mRNA levels. The current study demonstrates that TNF-alpha and IL-1beta enhance MCP-1 in first trimester decidua. This finding suggests a mechanism by which recruitment of excess macrophages to the decidua impairs endovascular trophoblast invasion, the primary placental defect of preeclampsia.

Antineoplastic Agents, Hormonal↗

PubMed2006

Tumor necrosis factor-alpha and interleukin-1beta regulate interleukin-8 expression in third trimester decidual cells: implications for the genesis of chorioamnionitis.

Chorioamnionitis is associated with intense neutrophil infiltration of the decidua. We therefore determined whether chorioamnionitis enhances decidual interleukin-8 (IL-8) expression and examined cytokine-regulated decidual IL-8 expression. Decidua from chorioamnionitis-complicated pregnancies, but not term controls, displayed marked IL-8 immunohistochemical staining and a dense neutrophil infiltrate. Reverse transcriptase-polymerase chain reaction of microdissected decidual cells identified IL-8 mRNA, confirming decidual synthesis of IL-8. Confluent leukocyte-free term decidual cells were primed with 10(-8) mol/L estradiol (E2) or E2 + 10(-7) mol/L medroxyprogesterone acetate to mimic the steroidal milieu of pregnancy. Compared with cultures maintained in E2 alone, E2 + medroxyprogesterone acetate neither significantly affected IL-8 levels nor altered the response to the cytokines. The addition of 1.0 ng/ml tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1beta) increased IL-8 secretion levels by 236.6 +/- 51.4- and 1062.6 +/- 254.3-fold, respectively (n = 8, mean +/- SEM, P < 0.05), as measured by enzyme-linked immunosorbent assay. Concentration-response studies revealed that 0.01 ng/ml TNF-alpha and IL-1beta elevated IL-8 output by 10- and 100-fold, respectively. Western blotting confirmed these results, and quantitative reverse transcriptase-polymerase chain reaction demonstrated parallel changes in mRNA levels. In conclusion, IL-8 is strongly expressed in term decidua during chorioamnionitis, and TNF-alpha and IL-1beta enhance IL-8 expression in term decidual cells, suggesting that these cytokines are important regulators of chorioamnionitis-related decidual neutrophil infiltration.

Cells, Cultured↗

PubMed2005

Kinetic and stability studies on the chloroperoxidase complexes in presence of tert-butyl hydroperoxide.

The inactivation of native chloroperoxidase (CPO) from Caldariomyces fumago in the presence of tert-butyl hydroperoxide (tert-BuOOH) was investigated. A kinetic analysis was made and the inactivation constants (V(3) and K(3)) were evaluated. In prolonged times, uni-exponential equation describes the enzyme time course inactivation. A method based on the rate of inactivation of the enzyme in the presence of the inactivating molecule tert-BuOOH was also performed. A second group of inactivation constants (j(3) and K) was obtained, which is sufficiently close to the first two, thus verifying that the decreasing of enzyme absorbance corresponds to the decay of activity.

Binding Sites↗

PubMed2005

A linearization method for low catalytic activity enzyme kinetic analysis.

A kinetic analysis was made and a linear plot based on the general rate equation derived by Laidler [Can. J. Chem. 33, 1614-1624] is proposed. This linearization method allows determining the kinetic parameters (K(m), k(cat)) and [E](0) for enzymes with low catalytic activity. The method was applied to chloroperoxidase from Caldariomyces fumago [EC 1.11.1.10], whose kinetic parameters K(m)(app), k(cat)(app), and [E](0) with monochlorodimedone as substrate, were obtained by using the linearization plot and the V(max) value (calculated by Eadie-Hofstee plot). This plot could also be useful to the study of abenzyme kinetics provided the concentration of the latter is either higher or equal than K(m) value.

Catalysis↗

PubMed2005

Amniotic membrane graft: histopathological findings in five cases.

Amniotic membrane transplantation (AMT) is an effective treatment for ocular surface reconstruction; however, the mechanisms through which amniotic membrane (AM) exerts its effects as well as its fate after transplantation have not been entirely elucidated and have been investigated only in part. We evaluate the integration of AM in the host cornea in five patients who underwent AMT as the result of Bowen's disease, band keratopathy, radio- or cryotherapy-induced keratopathy, chemical burn or post-herpetic deep corneal ulcer with descemetocele. Due to persistent opacification in four cases and a progressing tumor in one case, penetrating keratoplasty (PK) and enucleation were performed as early as 2 months and up to 20 months after AMT. The corneas were analyzed histopathologically. To evaluate AM remnants, corneas were stained with periodic acid Schiff's reaction (PAS), Alcian blue, and Gomory and Masson trichrome; immunostaining including collagens III and IV antibodies was also performed. None of the corneas showed remnants of AM. In all cases, we observed discontinuity of Bowman's membrane. In three cases, the corneal epithelium was completely restored, ranging from three to six cell layers. In the other two cases, we detected an intense inflammatory reaction with rich neovascularization; the epithelial surface of the central cornea was completely restored, while at the periphery of the cornea goblet mucus-producing cells were present. Although clinically useful in all cases, restoration of a stable corneal epithelium through AMT is limited by the extent and severity of limbal stem cell deficiency (LSCD). The lack of histologically documented AM remnants in our cases seems to explain the efficacy of AMT more through its biological properties than through its mechanical properties.

Aged↗

PubMed2005

Amniotic membrane transplantation in ocular surface disorders.

Chronic ocular surface disorders, which can result in severe functional impairment, have been viewed for decades as untreatable diseases. In 1995, the reintroduction of amniotic membrane transplantation (AMT), either alone or associated with limbal stem cell transplantation, has offered new hope of using tissue and cell therapy strategies to repair ocular surface disorders. Amniotic membrane (AM) has been found to exert its effects by acting as a substrate for the growth of ocular surface epithelia, by suppressing inflammation and scarring and by serving as an anti-microbial barrier. Moreover, AM has recently been used as a substrate for ex vivo expansion of corneal epithelial cells for ocular surface reconstruction. Notwithstanding the substantial agreement among Authors regarding its clinical efficacy, there are still many uncertainties regarding the fate of grafted AM and consequently the mechanisms through which it exerts its long-term effects. Further studies including controlled clinical trials with numerous cases are required to understand which ocular surface conditions are certain to benefit from AM transplantation and how its mechanical properties interact with the mediators produced to favor ocular surface reconstruction.

Amnion↗

PubMed2005

Dysplasia epiphysealis hemimelica in a young girl: role of MRI in the diagnosis and follow-up.

This report describes a sporadic case of dysplasia epiphysealis hemimelica that developed in the proximal tibia of a 21-month-old girl. Three years after the surgical intervention the patient has made complete clinical recovery with a normal range of motion, a walk with no limping or pain, no leg length discrepancy or angular knee deformity. Even though the proximal tibia does not represent an infrequently involved site, we report the clinical, pathological and radiological features of our case both for the extreme rarity of dysplasia epiphysealis hemimelica and the very young age of the patient. The authors underline also the role of magnetic resonance imaging in the diagnosis, management and follow-up of this very rare condition.

Arthrography↗

PubMed2005

Mechanisms of abruption-induced premature rupture of the fetal membranes: thrombin-enhanced interleukin-8 expression in term decidua.

Recent evidence has linked preterm premature rupture of the fetal membranes (PPROM) to placental abruption. Because neutrophils are a rich source of proteases that can degrade extracellular matrix in abruption-associated PPROM, we examined whether decidual neutrophil infiltration complicates abruption-associated PPROM. Accordingly, immunostaining for the neutrophil marker CD15 was performed in placentas obtained after overt abruption (decidual hemorrhage) with or without PPROM and in control placentas. Abruptions were associated with a marked decidual neutrophil infiltration that peaked after PPROM, whereas decidua from gestational age-matched controls were virtually devoid of neutrophils. Neutrophil infiltrates co-localized with fibrin deposition. Because abruptions elicit intense decidua-enhanced thrombin production, we examined the regulation of abruption-induced neutrophil infiltration. Expression of the primary neutrophil chemoattractant interleukin-8 (IL-8) was evaluated in leukocyte-free term decidual cells incubated with estradiol (E2; control) or with E2+medroxyprogesterone acetate (to mimic pregnancy)+/-thrombin. After 24 hours, enzyme-linked immunosorbent assay measurements indicated that thrombin (0.1 to 2.5 U/ml) elicited a dose-dependent elevation in secreted IL-8 (P<0.05) with 2.5 U/ml of thrombin increasing IL-8 levels by >14-fold in E2 and E2+medroxyprogesterone incubations. Results were validated by Western blot and quantitative reverse transcriptase-polymerase chain reaction. In summary, thrombin-enhanced IL-8 expression in term decidual cells may explain how abruption-associated PPROM promotes decidual neutrophil infiltration.

Abruptio Placentae↗

PubMed2005

Histologic chorioamnionitis and severity of illness in very low birth weight newborns.

OBJECTIVE: Estimating the risk of in-hospital mortality in the neonatal intensive care unit provides important information for health care providers, and several neonatal illness severity scores have been developed. Histologic chorioamnionitis (HCA) is a known cause of neonatal morbidity and mortality. To date, the relationship between HCA and neonatal illness severity scores has not been rigorously tested. In this study, the relationships among HCA, initial illness severity, and neonatal outcomes were analyzed in very low birth weight (VLBW) newborns admitted to the neonatal intensive care unit. DESIGN: Prospective. SETTING: Neonatal intensive care unit. PATIENTS: A total of 116 VLBW inborn infants (gestational age, 28.1 +/- 2.82 wks; birth weight, 1009 +/- 312 g) were categorized as HCA-positive (n = 67) and HCA-negative (n = 49). INTERVENTIONS: Placental histology was performed to identify HCA. Illness severity evaluation included several different neonatal illness severity scores-Clinical Risk Index for Babies (CRIB), CRIB-II, Score for Neonatal Acute Physiology-II (SNAP-II), and Score for Neonatal Acute Physiology Perinatal Extension-II (SNAPPE-II)-as well as the recording of severe morbidity and in-hospital mortality. MEASUREMENTS AND MAIN RESULTS: HCA-positive VLBW newborns showed significantly lower gestational age (p < .0001) and birth weight (p = .0010), together with higher CRIB, CRIB-II, SNAP-II, and SNAPPE-II scores at admission to the NICU (p </= .0001) and mortality rate (p = .0018) than HCA-negative infants. After adjustment for gender and gestational age in a multivariable logistic regression analysis, HCA was found to be an independent predictor of high illness severity: CRIB > 5 (odds ratio [OR], 21.37; 95% confidence interval [CI], 6.24-73.21); CRIB-II > 10 (OR, 56.17; 95% CI, 6.75-467.2); SNAP-II > 22 (OR, 43.05; 95% CI, 11.9-155.7), and SNAPPE-II > 42 (OR, 48.95; 95% CI, 10.18-235.4) (all p values <.0001). CONCLUSIONS: Our findings indicate that HCA is a major predictor of morbidity and mortality in VLBW newborns.

Chorioamnionitis↗

PubMed2005

Transient hypothyroxinemia of prematurity and histological chorioamnionitis.

BACKGROUND: Transient hypothyroxinaemia of prematurity (THOP) is a common condition of preterm infants whose causes remain unclear. We tested the hypothesis that THOP is associated with histological chorioamnionitis (HCA). METHODS: Whole blood T4 and TSH concentrations on day 4 and at 40 weeks' postmenstrual age (rtx-T4 and rtx-TSH), placental histology and illness severity were prospectively evaluated in 155 very low birth weight (VLBW) infants. RESULTS: HCA-positive infants showed significantly decreased blood total T4 concentrations on day 4, as compared to the HCA-negative population (P<0.0001), along with comparable TSH, rtx-T4, and rtx-TSH blood concentrations. None of the infants showed evidence of hypothyroidism during the study. A total T4 < or = 4.4 microg/dL on postnatal day 4 identified HCA-positive newborns with 90.8%, sensitivity, 94.7%, specificity, 96.7% positive predictive and 85.7% negative predictive values. HCA (OR: 32.19; 95% CI: 8.95-115.64), birth weight < or = 880 g (OR: 4.1; 1.15-14.64), and RDS (OR: 3.71, 95% CI: 1.13-12.25) were independently associated with evidence of hypothyroxinaemia on day 4. CONCLUSION: Our findings indicate a previously un-recognized relationship between HCA and THOP, hence suggesting a predominant role for a fetal systemic inflammatory response syndrome in the pathogenesis of THOP.

Age Factors↗

PubMed2005

Inhibin alpha-subunit and the inhibin coreceptor betaglycan are downregulated in endometrial carcinoma.

OBJECTIVE: In the present study we evaluated the protein distribution and mRNA levels of inhibin alpha-subunit and its coreceptor betaglycan in endometrial adenocarcinoma. DESIGN: Two groups of postmenopausal women were studied: the first group had recently diagnosed endometrial adenocarcinoma (n = 16; age range 61-79 years), and the second group (n = 12; age range 64-78 years) had undergone hysterectomy for uterine prolapse and served as control. METHODS: Inhibin alpha-subunit and betaglycan gene expression and tissue distribution were evaluated by semiquantitative RT-PCR and immunohistochemistry respectively. RESULTS: Inhibin alpha-subunit and betaglycan mRNAs were expressed by both healthy and tumoral endometria, but their expression was significantly lower in endometrial carcinoma (P < 0.001, based on Student's t test). Inhibin alpha-subunit expression was much weaker in the glands of tumours than in non-neoplastic specimens. Betaglycan protein was identified in the epithelial cells lining non-tumoral endometrium, and in endothelial cells of both normal and tumoral endometria. Well-differentiated neoplastic cells had a faint and scarce betaglycan staining, and poorly differentiated cells did not express betaglycan at all. CONCLUSIONS: The lower inhibin alpha and betaglycan expression in endometrial adenocarcinoma suggests that the inhibin action may be disrupted. However, the expression of betaglycan in the endothelia of the tumour vasculature suggests that a selective vascular response to inhibin may be possible in these tumours.

Activin Receptors↗

PubMed2004

Oral mucosal microvascular abnormalities: an early marker of bronchopulmonary dysplasia.

An abnormal pulmonary vasculature has been reported as an important component of bronchopulmonary dysplasia (BPD). We tested the hypothesis of an early abnormal vascular network pattern in infants with BPD. Fifteen infants with BPD (nine boys and six girls; gestational age 27.5 +/- 2.0 wk; birth weight 850 +/- 125 g) and 15 sex- and gestational age-matched infants (nine boys and six girls; gestational age 27.6 +/- 2.6 wk; birth weight 865 +/- 135 g) were examined on postnatal days 1 and 28. BPD infants showed a significantly higher prevalence of histologic chorioamnionitis (p = 0.009), as well as higher intubation duration (p = 0.0004), oxygen supplementation (p < 0.0001), and initial illness severity (p = 0.0002) than the BPD-negative population. The lower gingival and vestibular oral mucosa was chosen as the study area. The blood vessel area was determined, and the oral vascular networks were characterized by analyzing their complexity (D, at two scales: D 1-46, D 1-15), tortuosity (Dmin), and randomness (L-Z) of the vascular loops. Infants with BPD showed a significantly lower blood vessel area as well as a higher vascular network complexity (D 1-46, D 1-15, and L-Z) than control subjects (p < 0.0001). Our findings provide a new early clinical sign in BPD and stress the importance of an early disorder in the oral mucosal vascularization process in the disease pathogenesis.

Adult↗