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Biomedical subjects

F Franconi

Publications and source records attributed to F Franconi.

At least 19 recordsLinked to original sources

Evaluating SPIO-labelled cell MR efficiency by three-dimensional quantitative T2* MRI.

An in vitro MR-assay for superparamagnetic iron oxide (SPIO) particle cell labelling assessment via three-dimensional quantitative T(2) (*) MR microscopy was proposed. On high-resolution images, and due to the high susceptibility difference between the particles and the surrounding medium, SPIO internalized in cells induces signal loss which may be counted and measured on T(2) (*) maps. The increase in both labelled cell percentage and the average perturbation volume with an added amount of iron in the incubation medium proved that intracellular iron uptake is dependent upon the initial concentration of incubation iron. It also proved that the observed increases in total cellular iron uptake measured by inductively coupled plasma optical emission spectroscopy are due to both an increase in the iron mass per cell and also an increase in labelled cell concentration. MR results were compared with Prussian blue staining histology. The sensitivity of the MR methodology was then used to distinguish labelling differences for two different types of particle coating. The MRI-assay we proposed is a compulsory tool to optimize labelling efficiency in order to improve in vivo cell detection. Key parameters for detection, such as the percentage of cell labelling, the effect on the image for a given amount of internalized iron and labelling distribution among a cell population, are easily obtained. The comparison of different contrast agents for labelling one cell type, the assessment of one type of contrast agent for labelling different cell types and/or the evaluation of labelling strategies, are possible without having recourse to classical methods, and provide improved accuracy, since the principle is based on intracellular relaxivity.

Animals↗

Volumetric assessment of myocardial viability in rats using 3D double contrast enhanced T1 and T2-weighted MRI.

OBJECTIVE: Volumetric evaluation of the myocardial viability post-infarction in rats using 3D in vivo MR imaging at 7 T using injection of an extracellular paramagnetic contrast agent and intravascular superparamagnetic iron oxide nanoparticles in the same imaging session. MATERIALS AND METHODS: Five hours after induction of permanent myocardial infarction in rats (n=6), 3D in vivo T1- and T2-weighted MR Imaging was performed prior to and after Gd-DOTA injection (0.2 mmol/kg) and prior to and after nanoparticle injection (5 mg Fe/kg) to assess infarct size and myocardial viability. RESULTS: 3D MR Imaging using a successive contrast agent injection showed a difference of infarct size after Gd-DOTA injection on T1-weighted images compared to the one measured on T2-weighted images after Gd-DOTA and nanoparticle injection. CONCLUSION: The use of 3D T1- and T2-weighted MR Imaging using a double contrast agents protocol made possible the accurate characterization of myocardial infarction volume and allowed the detection of myocardial viability post-infarction in rats.

Analysis of Variance↗

Prenatal evaluation of kidney function in mice using dynamic contrast-enhanced magnetic resonance imaging.

Glomerular differentiation starts as soon as embryonic stage 12 in mice and suggests that kidneys may be functional at this stage. Dynamic contrast-enhanced magnetic resonance microscopy, a noninvasive imaging technique, was used to assess renal function establishment in utero. Indeed, in adults (n = 3), an intravenous injection of gadolinium-DOTA induced in a first step a massive and rapid drop in kidney signal intensity followed, in a second step, by a drop in bladder signal intensity. The delay in signal changes between kidney and bladder reflected glomerular filtration. Pregnant mice underwent anatomical and dynamic contrast-enhanced magnetic resonance microscopy on postcoital days 12-13 (n = 2), 13-14 (n = 1), 14-15 (n = 3), 15-16 (n = 2), 16-17 (n = 3), 17-18 (n = 3), and 18-19 (n = 1). Kidneys and bladder were unambiguously depicted prior to contrast agent injection on stage 15-16 embryos. Contrast agent injection allowed kidney, detection as early as stage 12-13 but not bladder. Kinetics of signal changes demonstrated that glomerular filtration is established at embryonic stage 15-16 in mice. Thus, anatomical and dynamic contrast-enhanced magnetic resonance microscopy may be a powerful noninvasive method for in vivo prenatal developmental and functional studies.

Animals↗

In vitro antimycotic activity of some plant extracts towards yeast and yeast-like strains.

As part of screening aimed at the selection of novel antimycotic compounds of vegetable origin, leaf extracts of Camellia sinensis L., Cupressus sempervirens L. and Pistacia lentiscus L. and the seed extract of Glycine soja Sieb. et Zucc. were tested against yeast and yeast-like species implicated in human mycoses. Of the extracts only those of C. sinensis (obtained from a commercial preparation of green tea) exhibited broad activity towards Candida glabrata, Clavispora lusitatiae, Cryptococcus laurentii, Filobasidiella neoformans, Issatchenkia orientalis, Saccharomyces cerevisiae and Prototheca wickerhamii strains. MICs ranging from 300 to 4800 microg extract/mL (corresponding to 130-2010 microg/mL total polyphenols) were observed. Concentrations of the C. sinensis extract over 25 000 microg/mL caused a rapid decrease of viable cells of Fil. neoformans and its activity was dose-dependent. Tests carried out using the pure polyphenols present in C. sinensis extract composition, showed that only epicatechin-3-O-gallate (ECG) and epigallocatechin-3-O-gallate (EGCG) possess antimycotic activity.

Antifungal Agents↗

Does parity increase insulin resistance during pregnancy?

AIMS: To study the effect of parity on impairment of insulin sensitivity during pregnancy and on the risk of gestational diabetes (GDM). METHODS: We studied the relationship between parity and peripheral insulin sensitivity index (ISI(OGTT)) or GDM in 1880 caucasian women, who underwent a 100-g, 3-h oral glucose tolerance test (OGTT) between the 24th and 28th gestational week and in 75 women who underwent an OGTT in two consecutive pregnancies. A proxy for beta-cell function (basal plasma C peptide/fasting plasma glucose; CP/FPG) was also measured. RESULTS: By univariate analysis parity was related to decreased ISI(OGTT) and to increased CP/FPG in those with parity > 3 and likewise GDM, diagnosed in 124 women (6.58%), was linearly related to parity (P = 0.0034) and strongly age dependent. The relationships between parity and ISI(OGTT), CP/FPG and GDM were no longer significant after adjustment for age, pregestational body mass index (BMI), and weight gain. GDM was significantly related to age and pregestational weight, while ISI(OGTT) and CP/FPG were inversely related to prepregnancy BMI or weight gain. In comparison with the index pregnancy, the subsequent pregnancy was characterized by an increase in actual and prepregnancy BMI, in 2 h area under curve (AUC) glucose and by a decrease in ISI(OGTT) (P = 0.0001). The longer the time interval between pregnancies and the higher the increment in pregestational BMI or in weight gain during the pregnancy, the greater were the ISI(OGTT) decrease and 2-h AUC glucose increase. CONCLUSIONS: Parity is not directly linked to insulin sensitivity deterioration, to CP/FPG increase during pregnancy, or to GDM appearance, although it is linked through the mediation of progressive ageing and weight gain either before or during pregnancy, when there is a sufficiently long time interval between pregnancies.

Adult↗

Characterization and detection of experimental rat gliomas using magnetic resonance imaging.

Two different experimental rat brain tumours (F98 glioma and 9L glioma) were characterized using T1 and T2, apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR). Even though both tumours appeared homogenous at the early stage of growth, significant differences were measured for all parametric images between tumours and normal brain tissue. Irrespective of the sequence used, tumour lesion/normal parenchyma contrast for the non-infiltrative 9L was twice that of the infiltrative F98 glioma. The use of spin preparation via an inversion pulse in a fast spin echo sequence increases contrast by a factor of 20-30.

Animals↗

Long-term taurine supplementation reduces mortality rate in streptozotocin-induced diabetic rats.

Oxidative stress is implicated in the pathogenesis of diabetes mellitus. Taurine and vitamin E+selenium supplementation has some benefits in experimental models of diabetes mellitus. This study evaluates whether taurine and vitamin E+selenium supplementations reduce a hard end-point such as mortality due to diabetes. Streptozotocin-induced diabetic rats were fed with standard diet or taurine (5%, w/w) or vitamin E (500 UI/Kg)+selenium (8 mg/Kg) enriched diets. Taurine significantly decreased mortality rate (p < 0.04), while vitamin E failed to increase survival. In the late phase of the disease, taurine significantly decreased glycaemia, being vitamin E ineffective. No correlation between glycaemia and survival was found. None of supplementations modified body weight. Thus, only taurine decreases the mortality rate and glycaemia. These results encourage new research in the field, since classical hypoglycaemic agents are unable to decrease mortality in diabetic patients.

Animals↗

Taurine administration during lactation modifies hippocampal CA1 neurotransmission and behavioural programming in adult male mice.

Taurine plays a role in neuronal development. In this study, we examined whether postnatal taurine administration influences the long-term consequences induced by mild neonatal stressors (10 min maternal deprivation plus sham injection, applied daily to neonatal mice up to 21 days). At 30 days of age stressed mice showed higher pain threshold both in the tail-flick--which measures mostly the spinal mechanisms of pain--and in the hot-plate test--which reflects mainly the supraspinal mechanisms of pain. The latter effect was prevented completely by neonatal taurine administration, while the tail-flick test was not affected, thus suggesting that spinal pain is not sensitive to taurine treatment. At 140 days of age, mice which were stressed during the neonatal period showed consistent decrease in immobility time in forced swimming test, and taurine did not influence this parameter. At the same age, the fear/anxiety axis, measured with elevated plus maze test, did not show any consistent changes. Electrophysiological experiments in brain slices obtained from adult mice showed that input-output curves in hippocampal CA1 were increased by taurine administration in lactation. Hence, neonatal administration of taurine might permanently modify the functioning of hippocampus, a brain area which is known to be crucial for learning and memory.

Analysis of Variance↗

Thiolation and nitrosation of cysteines in biological fluids and cells.

Thiols (RSH) are potent nucleophilic agents, the rates of which depend on the pKa of the sulfhydryl. Unlike compounds having other nucleophile moieties (-OH or -NH(2)), RSH are involved in reactions, such as conjugations, redox and exchange reactions. Although protein SH groups (PSH) react like non-protein thiols (NPSH), the biochemistry of proteins is much more complex for reasons such as steric hindrance, charge distribution and accessibility of PSH to the solvent (protein conformation). The reaction rates and types of end-products of PSH vary a lot from protein to protein. The biological problem is even more complex because in all compartments and tissues, there may be specific competition between thiols (namely between GSH and PSH), regulated by the properties of antioxidant enzymes. Moreover, PSH are divided biologically into essential and non-essential and their respective influence in the various biological systems is unknown. It follows that during phenomena eliciting a prompt thiol response (oxidative stress), the antioxidant PSH response and reaction mechanisms vary considerably from case to case. For example, in spite of a relatively low pKa that should guarantee good antioxidant capacity, PSH of albumin has much less propensity to form adducts with conjugating agents than NPSH; moreover, the structural characteristics of the protein prevent albumin from forming protein disulfides when exposed to oxidants (whereas protein-thiol mixed disulfides are formed in relative abundance). On the other hand, proteins with a relatively high reactivity, such rat hemoglobin, have much greater antioxidant capacity than GSH, but although human hemoglobin has a pKa similar to GSH, for structural reasons it has less antioxidant capacity than GSH. When essential PSH are involved in S-thiolation and S-nitrosation reactions, a similar change in biological activity is observed. S-thiolated proteins are a recurrent phenomenon in oxidative stress elicited by reactive oxygen species (ROS). This event may be mediated by disulfides, that exchange with PSH, or by the protein intermediate sulfenic acid that reacts with thiols to form protein-mixed disulfides. During nitrosative stress elicited by reactive nitrogen species (RNS), depending on the oxygen concentration of the system, nitrosation reactions of thiols may also be accompanied by protein S-thiolation. In this review we discuss a number of cell processes and biochemical modifications of enzymes that indicate that S-thiolation and S-nitrosation may occur simultaneously in the same protein in the presence of appropriate interactions between ROS and RNS.

Animals↗

High field magnetic resonance imaging evaluation of superparamagnetic iron oxide nanoparticles in a permanent rat myocardial infarction.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate superparamagnetic iron oxide (SPIO) nanoparticles to discriminate infarcted from normal tissue after myocardial infarction using high field MR imaging (7 tesla). MATERIALS AND METHODS: Permanent myocardial infarction was induced in rats. SPIO nanoparticles (1 mg Fe/kg) were assessed with T1-weighted gradient echo sequence to visualize the myocardial infarction 48 hours after ligature (n = 6). Furthermore, MR Imaging was performed using a T2-weighted RARE sequence and nanoparticles were injected (5 or 10 mg Fe/kg) on 36 rats 5, 24 or 48 hours after infarction. RESULTS: No changes in contrast between normal and infarcted myocardium was observed after nanoparticle injection on T1-weighted images. However, nanoparticles induced a significant contrast increase between normal and infarcted myocardium on T2-weighted images whatever the delay between infarction and imaging (2.99 +/- 1.66 preinjection vs. 7.82 +/- 1.96 after SPIO injection at a dose of 5 mg Fe/kg 5 hours postinfarction, P = 0.0001). CONCLUSIONS: Nanoparticle injection made it possible to discriminate normal from infarcted myocardium on T2-weighted images. However, the high magnetic field prevented the visualization of the T1 effect of SPIO nanoparticles.

Analysis of Variance↗

In utero time-course assessment of mouse embryo development using high resolution magnetic resonance imaging.

Magnetic resonance microscopy, a non-invasive imaging technique was used for a longitudinal follow-up of mouse embryonic development in utero and for the assessment of embryonic kidney function using 50 nm magnetite dextran particles. Even though the morphologic proton images obtained were still far from classical histological slices quality, an in-plan resolution of 195 microm was achieved for a slice thickness of 800 microm. Mouse embryos sub-structures such as the fourth ventricle, the mesencephalic vesicle, the aorta or the liver can be revealed as early as E11/12. Heart, diaphragm, spinal cord, third, fourth and lateral ventricles were unambiguously seen at E13/14; whereas skeleton, tail, kidney and digit can only be seen from E15/16. Kidney and bladder were certainly identified from E16 on. MR microscopy offers a possibility for in utero phenotyping of mice and can therefore be a powerful tool for post-genomic applications.

Animals↗

Chronic taurine supplementation ameliorates oxidative stress and Na+ K+ ATPase impairment in the retina of diabetic rats.

This study evaluates the effect of 4 months supplementation with 2% and 5% taurine (w/w) on the retina of diabetic rats. In non-diabetic rats, taurine does not modify glycemia, body weight, retinal conjugated dienes (CD), lipid hydroperoxide (LP), and Na(+)K(+)ATPase activity. In diabetic rat, at 2, 4, 8, 16 weeks following the onset of diabetes, retinal CD and LP are significantly and progressively increased, while pump activity is gradually and significantly reduced. In taurine supplemented diabetic rats, glycemia is not affected but lipid peroxidation is significantly decreased. Finally, taurine preserves ATPase activity being 5% more effective than 2% taurine. We conclude that taurine supplementation ameliorates biochemical retinal abnormalities caused by diabetes, thereby suggesting that taurine may have a role in the prevention of retinal changes in diabetes.

Animals↗

Quantitative MR renography using a calibrated internal signal (ERETIC).

To measure MR renograms, cortical and medullary kidney signal intensity evolution is followed after contrast agent injection. To obtain an accurate quantitative signal measurement, the use of a reference signal is necessary to correct the potential MRI system variations in time. The ERETIC method (Electronic Reference To access In vivo Concentrations) provides an electronic reference signal. It is synthesized as an amplitude modulated RF pulse applied during the acquisition. The ERETIC method was as precise as the external tube reference method but presents major advantages like its free adjustability (shape, location and magnitude) to the characteristics of the organ studied as well as its not taking room inside the magnet. Even though ERETIC showed a very good intrinsic stability, systems' variations still affect its signal in the same way as real NMR signals are affected. This method can be easily implemented on any imaging system with two RF channels.

Animals↗

Platelet antioxidant enzymes in insulin-dependent diabetes mellitus.

BACKGROUND: The measurement of the peroxidase scavenging system represented by the activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) in blood cells of diabetic patients has, in the past, given equivocal results. Likewise, the role of these intracellular enzymatic scavengers against the oxidative stress of diabetes-associated microangiopathic complications is unknown. METHODS: Choosing platelets as cell model (as commonly done in previous studies), the aim of this study was to relate the platelet content of SOD, catalase and GSH-Px to the presence of diabetes, as well as to the presence of nephropathy and retinopathy in 35 insulin-dependent diabetic patients, as compared to 10 age-matched control subjects. RESULTS: The enzymatic activities were not changed in diabetic patients in comparison with healthy controls. After stratifying patients according to presence of nephropathy (24-h urinary albumin excretion rate persistently > or =20 microg min(-1)) or retinopathy, the group of albuminuric patients was characterized by a significant decrease in SOD activity as compared to those in the normoalbuminuric range (4.36+/-1.06 vs. 6.81+/-2.26 mU 10(-9) platelets; p=0.01). Catalase and GSH-Px did not change. No modification in platelet enzyme activities has been found in diabetic subjects with retinopathy. CONCLUSIONS: These results suggest that diabetic nephropathy, at least in its early stage, may be related to an altered redox state of platelets, as tested by the reduction in SOD activity, thus, indicating that the renal damage in these patients may be associated to a selective increase in platelet susceptibility to variation in the redox state.

Adolescent↗

Therapeutic efficacy of 5-fluorouracil-loaded microspheres on rat glioma: a magnetic resonance imaging study.

The aim of this work was to assess the therapeutic efficacy of an intratumoral bolus injection of 5-fluorouracil (FU) compared to that of drug loaded in biodegradable microspheres, for the treatment of brain tumour. Experiments were carried out using a fast-growing C6-glioma rat model. The therapeutic protocols were performed 12 days after the injection of glioma cells. At this stage, the tumours were installed and the mean volume was 13 +/- 2 microl as measured by proton magnetic resonance (MR) imaging. This technique was used for the follow-up of the tumour volume with respect to time and therapy. In terms of rat survival, both therapies induced a significant 50% increase in animal life span (p < 0.05) compared to animals receiving no drug or unloaded microspheres. Whilst no cure was observed, analysis of the MR images showed that the local and sustained delivery of FU slowed the tumour development in the vicinity of the microspheres by a factor of 3, compared with the bolus intratumoral injection.

Animals↗

Synthesis and antiplatelet activity of some 2,7-di(N-cycloamino)-3-phenyl-1,8-naphthyridine derivatives.

Several 2,7-di(N-cycloamino)-3-phenyl-1,8-naphthyridine derivatives were synthesized and tested for their ability to inhibit human platelet aggregation in vitro induced by arachidonic acid, collagen and ADP. Only five compounds showed any appreciable activity, and the results of all the active derivatives were similar to those of papaverine in the test with arachidonic acid and collagen. Moreover, the most active compounds were investigated in the test with ADP and again showed a significant activity. The tested compounds that possessed the best activity were also shown to increase the c-AMP level significantly without involving the adenylyl cyclase system.

Adenosine Diphosphate↗

Evidence for oxidative activation of c-Myc-dependent nuclear signaling in human coronary smooth muscle cells and in early lesions of Watanabe heritable hyperlipidemic rabbits: protective effects of vitamin E.

BACKGROUND: Oxidized LDL (oxLDL) promotes atherogenesis, and antioxidants reduce lesions in experimental models. OxLDL-mediated effects on c-Myc are poorly characterized, and those on c-Myc nuclear pathways are completely unknown. c-Myc stimulates smooth muscle cell (SMC) proliferation and could be involved in atherosclerosis. We investigated the early effects of oxLDL and alpha-tocopherol on c-Myc, its binding partner Max, and the carboxy-terminal domain-binding factors activator protein-2 and elongation 2 factor in human coronary SMCs. We also investigated whether 9-week treatment of Watanabe heritable hyperlipidemic (WHHL) rabbits with diet-enriched alpha-tocopherol reduces c-Myc expression and oxLDL in the left coronary artery. METHODS AND RESULTS: OxLDL enhanced c-Myc/Max expression and transcription by cotransfection assay and the nuclear activities of E2F and activator protein-2 by binding shift and supershift in coronary SMCs. alpha-Tocopherol significantly reduced these molecular events. Furthermore, alpha-tocopherol reduced early lesions, SMC density, and the immunohistochemical presence of c-Myc, which colocalized with oxLDL/foam cells in the coronaries of WHHL rabbits. CONCLUSIONS: We provide the first evidence that oxLDL and alpha-tocopherol may influence c-Myc activation and several c-Myc-dependent signaling pathways in human coronary SMCs. The observation that in vivo, an antioxidant reduces both c-Myc and oxLDL in early coronary lesions of rabbits is consistent with, but does not prove, the hypothesis that c-Myc-dependent factors activated by oxidative processes contribute to atherogenesis and coronary heart disease.

Animals↗