Maria Antonietta Marcialis

Antiviral activity of glycyrrhizic acid

Glycyrrhizic acid inhibits the growth of several DNA and RNA viruses in cell cultures and inactivates Herpes simplex 1 virus irreversibly.

Inhibition of cytokines expression in human microglia infected by virulent and non-virulent mycobacteria

The pathogenesis of tuberculosis (TBC) meningitis is still unknown. As shown by previous studies, human microglia can be the target of mycobacteria, but no data are available about their cellular response to infection. Consequently, we studied the expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and IL-10 in human microglia pure cultures infected with the two variants of Mycobacterium avium (domed-opaque (SmD) and transparent (SmT)) and with Mycobacterium tuberculosis. Results showed that microglia was productively infected by mycobacteria which could grow inside the cells. Mycobacteria internalization was more rapid for M. avium, but M. tuberculosis infection turned out to be more efficient due to the incorporation of densely packed bacteria. TNF-alpha expression was not affected by M. avium, whereas an increase followed by a decrease was observed in M. tuberculosis. Both IL-1 and IL-10 cytokine expression was rapidly inhibited by infection with the more virulent bacteria, whereas the non-pathogenic one had almost no effect. Also, the expression of the co-stimulatory molecule CD137, a member of tumor necrosis factor receptor family, was affected by infection with virulent mycobacteria. Our results show that microglia response to mycobacterial infection is modulated in correlation with virulence, mainly toward inhibition of inflammatory response. This observation might be one of the mechanisms by which non-pathogenic mycobacteria are quickly eliminated, explaining one of the bases of virulence.

Neonatal onset of nephrogenic syndrome of inappropriate antidiuresis

This paper describes the manifestaton in a child of a new syndrome characterized by unusual, severe, persistent hyponatremia associated with hyposmolarity, euvolemia, inappropriately concentrated urine and elevated natriuresis. This is the fourth case of this syndrome reported to date, and the first to be reported in a neonate. The clinical features resemble those typically observed in patients with inappropriate antidiuretic hormone secretion, although high arginine vasopressin (AVP) levels are lacking. The findings led the authors to hypothesise a nephrogenic syndrome of inappropriate antidiuresis (NSIAD). The previously described R137C gain-of-function mutation was detected by means of mutation analysis of the V2R gene. Our results indicate that NSIAD is already present during the neonatal period and that molecular analysis of the V2R receptor should therefore be carried out, in all newborns with prolonged euvolemic hyponatremia with hypo-osmolarity, high urinary sodium and normal/low or undetectable AVP levels.

Fetal programming of neuropsychiatric disorders

Starting from the Developmental Origins of Health and Disease (DOHaD) hypotheses proposed by David Barker, namely fetal programming, in the past years, there is a growing evidence of the major role played by epigenetic factors during the intrauterine life and the perinatal period. Furthermore, it has been assessed that these factors can affect the health status in infancy and even in adulthood. In this review, we focus our attention on the fetal programming of the brain, analyzing the most recent literature concerning the epigenetic factors that can influence the development of neuropsychiatric disorders such as bipolar disorders, major depressive disorders, and schizophrenia. The perinatal epigenetic factors have been divided in two main groups: maternal factors and fetal factors. The maternal factors include diet, smoking, alcoholism, hypertension, malnutrition, trace elements, stress, diabetes, substance abuse, and exposure to environmental toxicants, while the fetal factors include hypoxia/asphyxia, placental insufficiency, prematurity, low birth weight, drugs administered to the mother or to the baby, and all factors causing intrauterine growth restriction. A better comprehension of the possible mechanisms underlying the pathogenesis of these diseases may help researchers and clinicians develop new diagnostic tools and treatments to offer these patients a tailored medical treatment strategy to improve their quality of life. Birth Defects Research (Part C) 108:207-223, 2016.

Urinary metabolomics of bronchopulmonary dysplasia (BPD): preliminary data at birth suggest it is a congenital disease

Abstract Objective: Bronchopulmonary dysplasia (BPD) or chronic lung disease is one of the principal causes of mortality and morbidity in preterm infants. Early identification of infants at the greater risk of developing BPD may allow a targeted approach for reducing disease severity and complications. The trigger cause of the disease comprehends the impairment of the alveolar development and the increased angiogenesis. Nevertheless, the molecular pathways characterizing the disease are still unclear. Therefore, the use of the metabolomics technique, due to the capability of identifying instantaneous metabolic perturbation, might help to recognize metabolic patterns associated with the condition. Methods: The purpose of this study is to compare urinary metabolomics at birth in 36 newborns with a gestational age below 29 weeks and birth weight <1500 g (very low birth weight – VLBW), admitted in Neonatal Intensive Care Unit (NICU) divided into two groups: the first group (18 cases) consisting of newborns who have not yet developed the disease, but who will subsequently develop it and the second group (18 controls) consisting of newborns not affected by BPD. Urine samples were collected within 24–36 h of life and immediately frozen at −80 °C. Results: The 1H-NMR spectra were analyzed using a partial least squares discriminant analysis (PLS-DA) model coupled with orthogonal Signal Correction. Using this approach it was possible with urine at birth to discriminate newborns that will be later have a diagnosis of BPD with a high statistics power. In particular, we found five important discriminant metabolites in urine in BPD newborns: lactate, taurine, TMAO, myoinositol (which increased) and gluconate (which decreased). Conclusion: These preliminary results seem to be promising for the identification of predictor’s biomarkers characterizing the BPD condition. These data may suggest that BPD is probably the result of an abnormal development (respiratory bud, vascular tree, hypodysplasia of pneumocytes) and could be considered a congenital disease (genetics plus intrauterine epigenetics). Early identification of infants at the greater risk of developing BPD may allow a targeted approach for reducing disease severity and complications.

Neonatal hyponatremia: differential diagnosis and treatment

Hyponatremia is very frequent in neonates, especially in VLBW. Recent data have shown that hyponatremia is not so benign as previously believed,and several clinical studies have indicated that preterms with mild to moderate chronic hyponatremia may experience poor growth and development retardation. The aim of this review is to present how to differentiate hypovolemic, euvolemic and hypervolemic hypernatremias, suggesting algorithms for practical management.

Inhibition of poliovirus growth by 2-amino-4,6-dichloropyrimidine

La 2-amino-4,6-dicloropirimidina impedisce la formazione di proteine capsidiche capaci di organizzare con lo RNA virale particelle di poliovius complete ed infettanti.

Should we definitively abandon prophylaxis for patent ductus arteriosus in preterm new-borns?

Although the prophylactic administration of indomethacin in extremely low-birth weight infants reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage, it does not appear to provide any long-term benefit in terms of survival without neurosensory and cognitive outcomes. Considering the increased drug-induced reduction in renal, intestinal, and cerebral blood flow, the use of prophylaxis cannot be routinely recommended in preterm neonates. However, a better understanding of the genetic background of each infant may allow for individualized prophylaxis using NSAIDs and metabolomics.

Renal safety of Non Steroidal Anti Inflammatory Drugs (NSAIDs) in the pharmacologic treatment of patent ductus arteriosus

Patent ductus artteriosus (PDA) often complicates the clinical course of neonates born prematurely and increases their short- and long-term morbidity. Treatment of PDA remains an ongoing debate among neonatologists for various issues such as the timing, the criteria and the methods for its closure. Non steroidal anti inflammatory drugs have been used as the standard pharmacological treatment for PDA. Indomethacin was the first one to be used. Its use though, waned due recognition of renal cerebral and gastrointestinal complications associated with the administration of this drug. Ibuprofen has emerged in clinical practice, as it has been reported to have lower nephrotoxicity. This review will examine existing data in the literature on the early- and long-term nephrotoxicity associated with the two drugs and will discuss present and future directions the management and prevention of this condition.

On the inhibitory effect of 2-amino-4,6-dichloropyrimidine on growth of vaccinia virus.

2-Amino-4,6-dichloropyrimidine prevents mutation of Vaccinia virus. Proteins synthesized in the presence of the drug are not assembled into virions.