2,155 research outputs found
Unravelling the role of NAADP/TPC2 Ca2+ signalling during angiogenesis and tumor progression
No full textTwo pore channels (TPCs) represent an emerging class of ion channels principally involved
in calcium (Ca2+) mobilization elicited by nicotinic acid adenine dinucleotide phosphate
(NAADP) [1, 2]. TPCs localize in the endo-lysosomal compartments and they exist in three
isoforms. In particular, we have previously demonstrated the pivotal role of NAADP/TPC2
pathway in angiogenesis and mouse melanoma [3, 4].
In this study, we have explored and characterized the potentiality of Naringenin (Nar), a
natural flavonoid, with the aim to investigate a novel pharmacological tool able to interfere
with TPC2 activity both in endothelium and in B16 melanoma cells.
We demonstrated that Nar impairs intracellular Ca2+ responses of endothelial cells
stimulated with VEGF, histamine or NAADP-AM, but not with ATP or Angiopoietin-1
(known to elicit NAADP-independent responses). In addition, we have observed that Nar is
able to inhibit angiogenesis in vitro and in an established in vivo murine model. Taken as a
whole the present data suggest that Nar inhibition of TPC2 activity and the observed
inhibition of angiogenic response to VEGF are linked by impaired intracellular Ca2+
signalling.
Several experimental evidence have shown that Ca2+ is involved in fundamental cancer cell
activities such as proliferation, migration, invasiveness, metastasis dissemination and
survival of tumor cells [5]. Based on this evidence we have focused our attention on the
study of VEGF-dependent Ca2+ signalling in melanoma cancer cells [4].
In this work, we also demonstrated that Nar inhibits VEGF and NAADP-dependent Ca2+
release also in B16 melanoma cells. Moreover, Nar impairment of B16 migration/
proliferation and vasculogenic mimicry strengthens the hypothesis that TPC2 represent a
potential target for control of the progression of melanoma and possibly other tumors.
References:
1. Calcraft, P.J., et al., NAADP mobilizes calcium from acidic organelles through two-pore channels.
Nature, 2009. 459(7246): p. 596-600.
2. Pitt, S.J., B. Reilly-O'Donnell, and R. Sitsapesan, Exploring the biophysical evidence that mammalian
two-pore channels are NAADP-activated calcium-permeable channels. J Physiol, 2016. 594(15): p.
4171-9.
3. Favia, A., et al., VEGF-induced neoangiogenesis is mediated by NAADP and two-pore channel-2-
dependent Ca2+ signaling. Proc Natl Acad Sci U S A, 2014. 111(44): p. E4706-15.
4. Favia, A., et al., NAADP-Dependent Ca(2+) Signaling Controls Melanoma Progression, Metastatic
Dissemination and Neoangiogenesis. Sci Rep, 2016. 6: p. 18925.
5. Monteith, G.R., N. Prevarskaya, and S.J. Roberts-Thomson, The calcium-cancer signalling nexus. Nat
Rev Cancer, 2017. 17(6): p. 367-38
Renal Failure of the Surviving Fetus After Intrauterine Death of the Co-Twin
No full textTwin pregnancies are considered at a higher risk for fetal mortality than singleton pregnancies. The antenatal death of one of the twins is associated with an increasing rate of cerebral impairment and lesions in other organs in the surviving fetus, especially if the pregnancy is monochorionic. We describe a case of isolate renal failure becoming evident gradually after birth in a surviving twin after the antenatal death of the co-twin. Considering the deleterious effects of vascular disruption in a surviving twin, our findings suggest careful investigation of renal function, even if no intrauterine signs of diminished renal function were previously detected
Feasibility of transferring intensive cared preterm infants from incubator to open crib at 1600 grams
No full textBackground: Ability to maintain a normal body temperature in an open crib is an important physiologic competency generally requested to discharge preterm infants from the hospital. The aim of this study is to assess the feasibility of an early weaning protocol from incubator in preterm newborns in a Neonatal Intensive Care Unit. Methods. 101 infants with birth weight < 1600 g were included in this feasibility study. We compared 80 newborns successfully transferred from an incubator to open crib at 1600 g with 21 infants transferred at weight ≥ 1700 g. The primary outcome was to evaluate feasibility of the protocol and the reasons for the eventual delay. Secondary outcomes were the identification of factors that would increase the likelihood of early weaning, the impact of an earlier weaning on discharge timing, and the incidence of adverse outcomes. Newborns in the study period were then compared with an historical control group with similar characteristics. Results: Early weaning was achieved in 79.2% of infants without significant adverse effects on temperature stability or weight gain. Delayed weaning was mainly due to the need of respiratory support. Gestational age affected the likelihood of early weaning (OR 1.7282 95% CI: 1.3071 - 2.2850). In the multivariate linear regression, early weaning reduced length of stay (LOS) by 25.8 days (p < 0.0001). Conclusions: Preterm infants can be weaned successfully from an incubator to an open crib at weight as low as 1600 grams without significant adverse effect. Early weaning significantly reduces LOS in preterm newborns. © 2014 Barone et al.; licensee BioMed Central Ltd
An epidemiological analysis of retinopathy of prematurity over 10 years.
No full textPURPOSE: To analyze the incidence of retinopathy of prematurity (ROP) in a single neonatal intensive care unit over 10 years to clarify its ROP profile and how it was modified by advances in neonatal care.
METHODS: Epidemiological data related to incidence and severity of ROP were collected over 10 years. Premature infants with a birth weight of less than 1,500 g underwent a screening fundus examination and ROP was defined according to the International Classification of Retinopathy of Prematurity. The survival rates and incidence of ROP were calculated and compared for two consecutive time periods (1995-1999 vs 2000-2004), dividing the study population into subgroups according to their birth weights and gestational age.
RESULTS: Data of 607 preterm infants were collected. Survival rate significantly improved in the later time period (from 76.6% to 88.6%). The incidence of total, severe, and surgical ROP did not differ overall in the two time periods despite changes in survival rate, although some changes occurred in the most immature infants over time.
CONCLUSION: Increased survival of immature infants seemed to correlate with an increased risk for severe ROP and need for retinal ablation therapy, even if the incidence did not reach statistical significance
"The love that made hell, paradise." Ouida re-writing the Paolo and Francesca theme in Held in Bondage
No full textThe bestselling Victorian author Ouida reveals in her novels, and, in particular, Held in Bondage, an extraordinary knowledge od Dante, by using characters and themes from the Commedia. The Paolo and Francesca theme actually constitutes part of the plot of the novel and is to be found in many of her other works, short stories and non-fiction writing
Neonatal colour Doppler US Study: normal values of cerebral blood flow velocities in preterm infants in the first month of life
No full textThe aim of this study is to generate normal reference values of cerebral blood flow velocities (CBFV) and Doppler indices (DI) in the anterior (ACA) and the middle (MCA) cerebral arteries during the first month of life in "healthy" preterm infants. CBFV were obtained with color Doppler technique in seventy selected preterm infants divided in four groups of gestational age (GA) (25 to 28; 29 to 30; 31 to 32; 33 to 35 wk). Our data demonstrate that CBFV increase with rising GA, birth weight (BW) and postnatal age. Additionally, we can provide the median values, tenth and ninetieth percentiles of CBFV and DI, in the ACA and MCA in each GA group as reference normal values of CBFV and DI in preterm newborn
Cardiac adverse effects of early dexamethasone treatement in preterm infants: a randomized clinical trial
No full textThis study evaluates the effects of early administration of dexamethasone on left ventricle dimensions and their clinical significance in preterm infants. Fifty preterm infants with birth weight < or = 1250 g and gestational age < or = 30 weeks were randomly assigned after 72 hours of life to the dexamethasone group (n = 25) or to the control group (n = 25). The treated infants received dexamethasone intravenously from the 4th day of life for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the 7th day). Serial echocardiographic measurements of end systolic interventricular septum thickness, end diastolic interventricular septum thickness, end systolic left ventricle posterior wall thickness, end diastolic left ventricle posterior wall thickness, left ventricle end diastolic diameter, and left ventricle end systolic diameter were taken before starting dexamethasone, on days 3 and 7 of treatment, 7 days after the interruption of treatment, and at the 28th day of life. Five infants of each group were excluded by the final analysis because of the lack of a complete cardiac evaluation, leaving 20 treated and 20 control infants. Infants receiving dexamethasone had a significantly larger increase in mean septal and left posterior wall thickness during the treatment and 7 days after the dexamethasone weaning. The mean left ventricle diameter of treated infants was significantly lower than that of control infants from the 7th day of treatment to the 28th day of life. Four neonates (20%) in the dexamethasone group developed left ventricular myocardial hypertrophy without left ventricle outflow tract obstruction, showing signs of decreased cardiac output and ischemic changes on ECG. The daily fluid intake was increased to 200 ml/kg to ensure an adequate preload volume, and the complete resolution of left ventricle hypertrophy was obtained within the 2nd to 3rd week after dexamethasone weaning. Preterm infants receiving an early (< 96 hours of life) short course of dexamethasone develop a left ventricular myocardial hypertrophy that can be symptomatic and clinically significant. Preterm infants included in future studies with the goal to find the minimum dose and duration of dexamethasone treatment should be strictly monitored echocardiographically for this side effec
Early visual assessment in preterm infants with and without brain lesions: correlation with visual and neurodevelopmental outcome at 12 months.
No full textBACKGROUND: Several studies have reported the development of various aspects of visual function in infancy and early childhood in both preterm and term-born infants, but only a few studies have focused on the predictive power of neonatal visual findings in infants with brain lesions.
AIMS: To explore visual findings at term age, and at 3 and 12 months corrected age in preterm infants (gestational age <33 weeks) with and without brain lesions; to compare the assessment at term age and at 12 months; and to assess the relationship between visual findings and neurodevelopmental outcome at 12 months.
STUDY DESIGN: Cranial ultrasound scans (US) were classified in normal, mild or major abnormalities. One-hundred and forty-five infants were assessed with age specific tests for visual function at term age, and at 3 and 12 months. Neurodevelopmental assessment (Griffiths' Scales) was performed at 12 months.
RESULTS: A good correlation was found between early and late visual assessment and neurodevelopment outcome. Of the 121 infants with normal neonatal visual assessment, 119 were also normal at 12 months and 116 had normal developmental quotient. Of the 24 infants with abnormal neonatal visual assessment, 12 were also abnormal at 12 months. All the false positives had normalised by 3 months. Of the 35 infants with major US abnormalities, 20 had normal and 15 abnormal scores on the neonatal assessment. At 1 year 17 had normal and 18 abnormal scores.
CONCLUSION: A normal visual assessment at term age is a good predictor of normal visual and neurodevelopmental outcome at 12 months. An abnormal visual examination in the neonatal period was a less reliable prognostic indicator, infant should be reassessed at 3 months
HERStory Makers 2023: Francesca Fotheringham
No full textFrancesca Fotheringham is a postdoctoral research associate at the University of Edinburgh studying educational psychology with a focus on neurodiversity. She took part in HERStory Makers 2023.What is HERStory Makers?HERStory Makers is a social media competition for female-identifying early career researchers to share their research, their career journeys, and to inspire the next generation. Winners are selected by public vote. HERStory Makers is also part of EXPLORATHON, Scotland's contribution to European Researchers' Night.In 2022-23, EXPLORATHON Francescasupported by the Engineering & Physical Sciences Research Council [grant number EP/X020762/1].Author contributions to contentFrancesca conceived, planned, and recorded the video content. Kirsty Ross edited the video content to insert HERStory Maker credits, added subtitles, and reduce video length to below Twitter/X limit of 2 mins and 20 secs.</p
Intrauterine infection caused by herpes simplex virus type-1 in the setting of recurrent maternal infection
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