Caterina Guiot

Umbilical doppler waveforms and placental villous angiogenesis in pregnancies complicated by fetal growth restriction

OBJECTIVE To test the hypothesis that the characteristics of umbilical artery Doppler flow velocity waveforms in growth-restricted fetuses indicate angiogenesis within placental stem and gas-exchanging villi. METHODS We examined 18 placentas from singleton fetuses that were normal structurally and chromosomally but were growth-restricted, preterm, and complicated by preeclampsia. Ten cases with positive end-diastolic flow and eight with absent or reverse end-diastolic flow were compared with six gestational age-matched controls. Sections of villous placenta were examined to determine structural composition (percentage of fibrinoid, intervillous space, and villous tissue), relative proportion of villous types (stem, immature intermediate, and gas-exchanging villi), and the frequency distribution of stem arterial vessel calibers and their branching pattern. RESULTS Placentas with positive end-diastolic flow had a significantly (P < .05) higher percentage of gas-exchanging villi (median 69.6%, range 62.5-80.8%) than those with absent or reverse end-diastolic flow (58.3%, 29.9-71.9%) or controls (60.8%, 43.1-65.6%). The gas-exchanging villi from placentas with absent or reverse end-diastolic flow were slender, elongated, poorly branched, and poorly capillarized. There was a progressive trend toward reduced branching of the stem arteries from the controls (median 22%, range 2-38%), through the positive end-diastolic group (17%, 11-20%), to the absent or reverse end-diastolic group (13%, 4-23%). CONCLUSION Compared with absent or reverse end-diastolic flow, the placentas from growth-restricted fetuses with positive end-diastolic flow showed a normal pattern of stem artery development, accompanied by increased capillary angiogenesis and terminal villous development. These features suggest an adaptive pathway for the placenta in the face of uteroplacental ischemia.

Is three-dimensional power Doppler ultrasound useful in the assessment of placental perfusion in normal and growth-restricted pregnancies?

To investigate three‐dimensional (3D) power Doppler ultrasound indices in the assessment of placental perfusion and their relationship to gestational age (GA), placental position and umbilical artery Doppler flow velocity waveform (FVW) patterns in normal and intrauterine growth‐restricted (IUGR) pregnancies.

Preparation and characterization of dextran nanobubbles for oxygen delivery

Dextran nanobubbles were prepared with a dextran shell and a perfluoropentan core in which oxygen was stored. To increase the stability polyvinylpirrolidone was also added to the formulation as stabilizing agent. Rhodamine B was used as fluorescent marker to obtain fluorescent nanobubbles. The nanobubble formulations showed sizes of about 500nm, a negative surface charge and a good capacity of loading oxygen, no hemolytic activity or toxic effect on cell lines. The fluorescent labelled nanobubbles could be internalized in Vero cells. Oxygen-filled nanobubbles were able to release oxygen in different hypoxic solutions at different time after their preparation in in vitro experiments. The oxygen release kinetics could be enhanced after nanobubble insonation with ultrasound at 2.5MHz. The oxygen-filled nanobubble formulations might be proposed for therapeutic applications in various diseases.

Ultrasound-mediated oxygen delivery from chitosan nanobubbles

Ultrasound (US) energy combined with gas-filled microbubbles has been used for several years in medical imaging. This study investigated the ability of oxygen-loaded chitosan bubbles to exchange oxygen in the presence or in the absence of US. Oxygen delivery is enhanced by sonication and both frequency and time duration of US affected the exchange kinetics.

Growth model for multicellular tumor spheroids

Most organisms grow according to simple laws, which in principle can be derived from energy conservation and scaling arguments, critically dependent on the relation between the metabolic rate B of energy flow and the organism mass m. Although this relation is generally recognized to be of the form B(m)=mp, the specific value of the exponent p is the object of an ongoing debate, with many mechanisms being postulated to support different predictions. We propose that multicellular tumor spheroids provide an ideal experimental model system for testing these allometric growth theories, especially under controlled conditions of malnourishment and applied mechanical stress.

Fractal parameters and vascular networks: facts & artifacts

BackgroundSeveral fractal and non-fractal parameters have been considered for the quantitative assessment of the vascular architecture, using a variety of test specimens and of computational tools. The fractal parameters have the advantage of being scale invariant, i.e. to be independent of the magnification and resolution of the images to be investigated, making easier the comparison among different setups and experiments.ResultsThe success of several commercial and/or free codes in computing the fractal parameters has been tested on well known exact models. Based on such a preliminary study, we selected the code Frac-lac in order to analyze images obtained by visualizing the angiogenetic process occurring in chick Chorio Allontoic Membranes (CAM), assumed to be paradigmatic of a realistic 2D vascular network. Among the parameters investigated, the fractal dimension Df proved to be the most robust estimator for CAM vascular networks. Moreover, only Df was able to discriminate between effective and elusive increases in vascularization after drug-induced angiogenic stimulations on CAMs.ConclusionThe fractal dimension Df is likely to be the most promising tool for monitoring the effectiveness of anti-angiogenic therapies in various clinical contexts.

Modelling the feto-placental circulation. I: A distributed network predicting umbilical haemodynamics throughout pregnancy

The modifications of the Doppler flow velocity parameters occurring in the feto-placental circulation throughout pregnancy have been reproduced on the basis of a mathematical model. Some simple assumptions were made, such as the progressive development of a dichotomous villous vessel network and the increase of the perfusion pressure and of the umbilical arteries dimensions throughout pregnancy. Moreover, both the viscous and capacitive characteristics of the vascular bed were taken into consideration in order to predict the mean values of blood volume, flow and velocity and the pulsatility index. Their value is shown to depend on few parameters, and mainly on the cross-sectional area ratio between the vessels belonging to two succeeding generations.

Scaling, growth and cyclicity in biology: a new computational approach

BackgroundThe Phenomenological Universalities approach has been developed by P.P. Delsanto and collaborators during the past 2–3 years. It represents a new tool for the analysis of experimental datasets and cross-fertilization among different fields, from physics/engineering to medicine and social sciences. In fact, it allows similarities to be detected among datasets in totally different fields and acts upon them as a magnifying glass, enabling all the available information to be extracted in a simple way. In nonlinear problems it allows the nonscaling invariance to be retrieved by means of suitable redefined fractal-dimensioned variables.ResultsThe main goal of the present contribution is to extend the applicability of the new approach to the study of problems of growth with cyclicity, which are of particular relevance in the fields of biology and medicine.ConclusionAs an example of its implementation, the method is applied to the analysis of human growth curves. The excellent quality of the results (R2 = 0.988) demonstrates the usefulness and reliability of the approach.

Radio hyperthermia for re-treatment of superficial tumours.

Purpose: Relapse remains an unsolved problem for previously radio-treated patients. Our purpose is to evaluate the role of radio-hyperthermia (RT-HT) in the retreatment of superficial recurrences. Materials and methods: From 1998 to 2007, 51 patients affected by four histological types (breast recurrences (group A), melanoma recurrences (group B), head and neck recurrences (group C), and others (group D)) of 76 superficial lesions, were enrolled at Mauriziano Hospital at the Research Institute of Cancer Care Candiolo (IRCC) in Turin. All patients had previously undergone RT except 6 patients of group B. The total mean retreatment dose was 31.8 Gy (20–60 Gy), while the mean of HT sessions was 5 (1 to 8), temperature ranged from 38.5°C (T min) to 44°C (T max). Results: Acute cutaneous toxicity was 77.6% G1, 22.4% G2, none for G3. Forty-five days later we observed: for group A 65.9% complete response (CR), 29.5% partial response (PR), 4.5% non-response (NR); for group B 33.3% CR, 25% PR and 41.7% NR; for group C 40% CR, 13.3% PR, 46.7% NR, for group D 60% CR and 40% NR. 18 months later group A presented 72.7% local control (LC), 20.5% stable disease (SD) and 6.8% non-control (NC), group B 50% LC, 16,7% SD and 33.3% NC, group C 33.3% LC, 40% SD and 26.7% NC, group D 40% LC and 60% NC. Early response, size of lesions ≤3 cm, T max ≥42°C and RT doses ≥40 Gy were predictive outcome factors. Conclusions: We confirmed that radio-hyperthermia is useful in re-irradiation with a very high patient compliance.

Ultrasound-activated decafluoropentane-cored and chitosan-shelled nanodroplets for oxygen delivery to hypoxic cutaneous tissues

Ultrasound (US)-activated perfluoropentane-cored oxygen-loaded nanobubbles (OLNBs) were recently proposed as adjuvant therapeutic tools for pathologies of different etiology sharing hypoxia as a common feature (e.g. diabetes-associated chronic wounds, anaerobic infections, cancer). Here we introduce a new platform of oxygen nanocarriers, constituted of 2H,3H-decafluoropentane (DFP) as core fluorocarbon and chitosan as shell polysaccharide, and available either in liquid or gel formulations. Such oxygen-loaded nanodroplets (OLNDs) display spherical morphology, ∼700 nm diameters, cationic surfaces, good oxygen carrying capacity (without singlet oxygen generation after sterilization by ultraviolet-C rays), and no toxic effects on human keratinocytes. In vitro, OLNDs are more effective in releasing oxygen to hypoxic environments than former OLNBs, either with or without complementary US administration (f = 1 MHz; P = 5 W). In vivo, sonication of topically applied OLNDs appears essential to allow significant and time-sustained oxygen release. Taken together, the present data suggest that US-activated chitosan-shelled/DFP-cored OLNDs might be innovative, suitable and cost-effective devices to treat several hypoxia-associated pathologies of the cutaneous tissues.