ABSTRACT
OBJECTIVES: HIF-1 alpha (hypoxia-inducible factor-1 alpha) mediates the responses of mammalian cells to hypoxia/ischemia by inducing the expression of adaptive gene products (e.g., vascular endothelial growth factor (VEGF) and erythropoietin (EPO)). Persistent pulmonary hypertension of the newborn (PPHN) and cyanotic congenital heart disease (CCHD) are common neonatal diseases considered as paradigms of hypoxemia. Since the expression HIF-1 alpha, VEGF and EPO in newborns diagnosed with these diseases has yet to be studied, we set out to define the expression of these genes in peripheral blood from newborn infants diagnosed with PPHN and CCHD. DESIGN AND METHODS: The mRNA transcripts encoding HIF-1 alpha, VEGF and EPO were measured by RT-PCR in healthy newborn infants and infants diagnosed with PPHN and CCHD. RESULTS: An important increase in HIF-1 alpha expression was observed in both pathological conditions, accompanied by significant increases in VEGF and EPO expression when compared to healthy infants. CONCLUSIONS: HIF-1 alpha mRNA expression increases in newborn infants with PPHN or CCHD, as does the expression of its target genes VEGF and EPO.
Subject(s)
Erythropoietin , Heart Diseases , Hypoxia-Inducible Factor 1, alpha Subunit , Hypoxia , Persistent Fetal Circulation Syndrome , Vascular Endothelial Growth Factor A , Erythropoietin/blood , Erythropoietin/genetics , Heart Diseases/blood , Heart Diseases/congenital , Heart Diseases/physiopathology , Humans , Hypoxia/blood , Hypoxia/pathology , Hypoxia-Inducible Factor 1, alpha Subunit/blood , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Infant , Infant, Newborn , Persistent Fetal Circulation Syndrome/blood , Persistent Fetal Circulation Syndrome/genetics , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor A/geneticsABSTRACT
OBJECTIVE: To determine sildenafil citrate (SC) genotoxicity and cytotoxicity in the Callithrix jacchus. STUDY DESIGN: Fifteen organisms were assigned to one of three groups as follows: experimental (25 mg/kg of SC); negative control (glucose solution 5%); and positive control (3 mg/kg of cytocine arabinoside). Systemic hemodynamic changes were monitored in each animal before and after each treatment. A drop of blood was obtained before and after the treatment at 24-120 h. Smears were made and the frequency of micronucleated erythrocytes (MNE), micronucleated polychromatic erythrocytes (MNPCE) and polychromatic erythrocytes (PCE) was counted. RESULTS: No significant differences in MNE, MNPCE and PCE were found in the group that received sildenafil and negative control. A significant increase in genotoxicity and cytotoxicity was observed in the positive control group. No changes were observed in systemic hemodynamic changes. CONCLUSION: The macro-dose of SC lacks genotoxic, cytotoxic or systemic hemodynamic changes effects in this species.