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Biomedical subjects

F Clemente

Publications and source records attributed to F Clemente.

At least 19 recordsLinked to original sources
PubMed2003

A hybrid mock circulatory system: development and testing of an electro-hydraulic impedance simulator.

Mock circulatory systems are used to test mechanical assist devices and for training and research purposes; when compared to numerical models, however, they are not flexible enough and rather expensive. The concept of merging numerical and physical models, resulting in a hybrid one, is applied here to represent the input impedance of the systemic arterial tree, by a conventional windkessel model built out of an electro-hydraulic (E-H) impedance simulator added to a hydraulic section. This model is inserted into an open loop circuit, completed by another hybrid model representing the ventricular function. The E-H impedance simulator is essentially an electrically controlled flow source (a gear pump). Referring to the windkessel model, it is used to simulate the peripheral resistance and the hydraulic compliance, creating the desired input impedance. The data reported describe the characterisation of the E-H impedance simulator and demonstrate its behaviour when it is connected to a hybrid ventricular model. Experiments were performed under different hemodynamic conditions, including the presence of a left ventricular assist device (LVAD).

Computer Simulation↗
PubMed2002

Study of systolic pressure variation (SPV) in presence of mechanical ventilation.

Systolic pressure variation (SPV) and its components (dUp and dDown) have been demonstrated to be of interest in assessing preload in mechanically ventilated patients. The aim of this paper is to analyse the sensitivity of these variables to preload and volemic changes during mechanical ventilation in different conditions of the cardiovascular system. Computer simulation experiments have been done using a modular lumped parameter model of the cardiovascular system. The effect of mechanical ventilation has been reproduced operating on intrathoracic pressure. Experiments have been performed varying preload through filling pressure. Sensitivity of SVP dUp and dDown is described varying separately left ventricular elastance (Ev), systemic arterial resistance (Ras) and systemic arterial compliance (Cas). The sensitivity of SPV and dDown to preload and filling pressure is appreciable for high values of Ev and for a wide variation of Ras. Preliminary clinical data concerning the three parameters show good correlation with simulation results.

Blood Pressure↗
PubMed2001

Expression of the high molecular weight fibroblast growth factor-2 isoform of 210 amino acids is associated with modulation of protein kinases C delta and epsilon and ERK activation.

The high molecular weight (HMW) fibroblast growth factor (FGF)-2 isoform of 210 amino acids initiated at a CUG start codon possesses a nuclear localization sequence and is not secreted. In contrast, the low molecular weight (LMW) isoform of 155 amino acids initiated at the AUG start codon can be secreted and activates the cell surface FGF receptors. The two isoforms possess different biological properties; however, little is known about the intracrine regulatory mechanisms involved in the biological effects of the HMW FGF-2 isoform. Using pancreatic cells stably transfected with cDNAs leading to the expression of either the HMW FGF-2 (A3 cells) or the LMW form (A5 cells), we provide evidence that the two FGF-2 isoforms differentially modulate PKC levels. The LMW FGF-2 up-regulated the PKC epsilon levels by 1.6-fold; by contrast the HMW isoform down-regulated the level of this PKC isotype by about 3-fold and increased the amount of PKC delta by 1.7-fold. PKC mRNAs were also modified, suggesting that PKC expression was regulated at a pretranslational level. Additionally, expression of different levels of the HMW FGF-2 with an inducible expression system confirmed the role of this isoform on PKC delta and epsilon expressions. Increased activation of ERK-1 and -2 was also observed in cells expressing the HMW FGF-2. By using different PKC inhibitors and a dominant negative PKC delta, it was found that ERK activation was PKC delta-dependent. These data indicate that expression of HMW FGF-2 can modify PKC levels by acting at the intracellular level and that the overexpression of PKC delta induces ERK-1/2 activation. The expression of a dominant negative FGFR1 did not reduce ERK-1/2 activation by the HMW FGF-2, suggesting that ERK activation does not require FGFR activity. The signaling cascade downstream of ERK might be involved in the known mitogenic effect exerted by this FGF-2 isoform.

Animals↗
PubMed2001

Effect of GLP-1 treatment on GLUT2 and GLUT4 expression in type 1 and type 2 rat diabetic models.

Glucagon-like peptide-1 (G LP-1) is an incretin with glucose-dependent insulinotropic and insulin-independent antidiabetic properties that exerts insulin-like effects on glucose metabolism in rat liver, skeletal muscle, and fat. This study aimed to search for the effect of a prolonged treatment, 3 ds, with GLP-1 on glucotransporter GLUT2 expression in liver, and on that of GLUT4 in skeletal muscle and fat, in rats. Normal rats and streptozotocin-induced type 1 and type 2 diabetic models were used; diabetic rats were also treated with insulin for comparison. In normal rats, GLP-1 treatment reduced in the three tissues the corresponding glucotransporter protein level, without modifying their mRNA. In the type 2 diabetic model, GLP-1, like insulin, stimulated in liver and fat only the glucotransporter translational process, while in the muscle an effect at the GLUT4 transcriptional level was also observed. In the type 1 diabetic model, GLP-1 apparently exerted in the liver only a posttranslational effect on GLUT2 expression; in muscle and fat, while insulin was shown to have an action on GLUT4 at both transcriptional and translational levels, the effect of GLP-1 was restricted to glucotransporter translation. In normal and diabetic rats, exogenous GLP-1 controlled the glucotransporter expression in extrapancreatic tissues participating in the overall glucose homeostasis-liver, muscle, and fat-where the effect of the peptide seems to be exerted only at the translational and/or posttranslational level; in muscle and fat, the presence of insulin seems to be required for GLP-1 to activate the transcriptional process. The stimulating action of GLP-1 on GLUT2 and GLUT4 expression, mRNA or protein, could be a mechanism by which, at least in part, the peptide exerts its lowering effect on blood glucose.

Adipose Tissue↗
PubMed2001

IABP assistance: a test bench for the analysis of its effects on ventricular energetics and hemodynamics.

IABP assistance is frequently used to support heart recovery, improving coronary circulation and re-establishing the balance between oxygen availability and consumption. Hemodynamic and energetic parameters (endocardial viability ratio, ventricular energetics) are used to evaluate its effectiveness which depends on internal (timing, balloon volume and position) and external factors (circulatory conditions). Considering short, medium and long-term effects of IABP, the first depends on its mechanical action, the latter on the changes induced in circulatory parameters. The analysis of the first is important because conditions for the onset of a virtuous cycle able to support ventricular recovery are created. Simulation systems could be helpful in this analysis for the implicit reliability and reproducibility of the experiments, provided that they are able to reproduce both hemodynamic phenomena and energetic relationships. The aim of this paper is to present a system originally developed to test mechanical heart assist devices and modified for IABP testing. Data reported here are obtained from in vitro experiments. A partial verification, obtained from the literature is presented.

Coronary Circulation↗
PubMed2001

Mono and bi-ventricular assistance: their effect on ventricular energetics.

When mono- and bi-ventricular mechanical assistance is used for heart recovery, its control strategy and circulatory variables affect ventricular energetics (external work-EW, oxygen consumption-VO2, cardiac mechanical efficiency-CME). This study is based on the data obtained in vitro and presents an analysis of the effects of the mono- and bi-ventricular mechanical assistance on ventricular energetics. The assistance was conducted on the principle of counterpulsation with atrio-arterial connection. It includes the following stages: 1) the characterisation of the isolated ventricle model in terms of EW, VO2 and CME as a function of the filling pressure and peripheral resistance, 2) modelling of left ventricular and pulmonary dysfunction, followed by left ventricular and bi-ventricular assistance. Experimental data enable us to draw the following conclusions: * in general, the greatest hemodynamic improvement does not correspond to the highest energetic improvement, * LVAD assistance deteriorates left ventricular CME while its effect on right ventricular energetics depends on the value of right ventricular elastance (Emax). Right ventricular CME is deteriorated by BVAD assistance irrespective of right Emax, * the energetics optimisation in bi-ventricular assistance is closely related to the right Emax, which could probably be a deciding factor in the choice of the assistance mode.

Elasticity↗
PubMed2001

A hybrid (numerical-physical) model of the left ventricle.

Hydraulic models of the circulation are used to test mechanical devices and for training and research purposes; when compared to numerical models, however, they are not flexible enough and rather expensive. The solution proposed here is to merge the characteristics and the flexibility of numerical models with the functions of physical models. The result is a hybrid model with numerical and physical sections connected by an electro-hydraulic interface - which is to some extent the main problem since the numerical model can be easily changed or modified. The concept of hybrid model is applied to the representation of ventricular function by a variable elastance numerical model. This prototype is an open loop circuit and the physical section is built out of a reservoir (atrium) and a modified windkessel (arterial tree). The corresponding equations are solved numerically using the variables (atrial and arterial pressures) coming from the physical circuit. Ventricular output flow is the computed variable and is sent to a servo amplifier connected to a DC motor-gear pump system. The gear pump, behaving roughly as a flow source, is the interface to the physical circuit. Results obtained under different hemodynamic conditions demonstrate the behaviour of the ventricular model on the pressure-volume plane and the time course of output flow and arterial pressure.

Heart Ventricles↗
PubMed2000

FGF-2 isoforms of 18 and 22.5 kDa differentially modulate t-PA and PAI-1 expressions on the pancreatic carcinoma cells AR4-2J: consequences on cell spreading and invasion.

Pancreatic tumors overexpress FGF-2 and t-PA, but the implication of the growth factor in t-PA synthesis and t-PA-dependent tumor invasion remains unknown. FGF-2 is present in different isoforms: The 18 kDa FGF-2 is secreted, while the 22.5 kDa one is nuclearized and exerts intracrine regulations bypassing cell-surface FGF receptors. Rat pancreatic carcinoma AR4-2J cells producing either the 18 or the 22.5 kDa FGF-2 after transfection with FGF-2 cDNAs have been used to analyze the role of FGF-2 in t-PA expression and t-PA-related cell spreading. The 22.5 kDa FGF-2 reduced t-PA and PAI-1 synthesis 2-fold. Addition of recombinant 18 kDa FGF-2 (rFGF-2) to cell cultures resulted in increased t-PA and decreased PAI-1 expression. By contrast, rFGF-2 did not significantly modify t-PA synthesis in cells producing the 22.5 kDa FGF-2. Cell spreading was t-PA-dependent. Furthermore, cells producing the 22.5 kDa FGF-2 migrated less than control cells and cells producing the 18 kDa FGF-2. Overall, our data show that secretory FGF-2 is involved in t-PA synthesis by pancreatic cancer cells and facilitates cell spreading. The 22.5 kDa FGF-2 exerts opposite effects by decreasing t-PA expression in basal conditions and during rFGF-2 stimulation. Since the expression of the 22.5 kDa FGF-2 is under specific controls, its up-regulation might have the potential to reduce spreading of pancreatic cancer cells.

Animals↗
PubMed2000

Computer simulation of haemodynamic parameters changes with left ventricle assist device and mechanical ventilation.

Left Ventricular Assist Device is used for recovery in patients with heart failure and is supposed to increase total cardiac output, systemic arterial pressure and to decrease left atrial pressure. Aim of our computer simulation was to assess the influence of Left Ventricular Assist Device (LVAD) on chosen haemodynamic parameters in the presence of ventilatory support. The software package used for this simulation reproduces, in stationary conditions, the heart and the circulatory system in terms of pressure and volume relationships. Different circulatory sections (left and right heart, systemic and pulmonary arterial circulation, systemic and pulmonary venous circulation) are described by lumped parameter models. Mechanical properties of each section are modelled by RLC elements. The model chosen for the representation of the Starling's law of the heart for each ventricle is based on the variable elastance model. The LVAD model is inserted between the left atrium and the aorta. The contractility of the heart and systemic arterial resistance were adjusted to model pathological states. Our simulation showed that positive thoracic pressure generated by mechanical ventilation of the lungs dramatically changes left atrial and pulmonary arterial pressures and should be considered when assessing LVAD effectiveness. Pathological changes of systemic arterial resistance may have a considerable effect on these parameters, especially when LVAD is applied simultaneously with mechanical ventilation. Cardiac output, systemic arterial and right atrial pressures are less affected by changes of thoracic pressure in cases of heart pathology.

Animals↗
PubMed2000

Increased HLA-DR homozygosity associated with pre-eclampsia.

It is generally accepted that maternal recognition of paternally derived fetal antigens occurs during normal pregnancy and may be beneficial for implantation and maintenance of gestation. Thus, we have investigated the human leukocyte class II DR antigens (HLA-DR), whose role in self and non-self recognition is well known, in women with pre-eclampsia, their partners and in control couples. The HLA-DR antigens were tested in 70 pre-eclamptic primigravidae women and their partners and 70 healthy control couples using the serological Terasaki technique. Our results did not show any particular HLA-DR antigen to be correlated with pre-eclampsia, but a statistically significant increase of only one identifiable HLA-DR antigen, which was presumed to express homozygosity at the HLA-DR locus, in the pre-eclamptic women and their partners: 67.1 versus 7. 9% in the control couples (P < 0.000001). The analysis of HLA-DR compatibility between pre-eclamptic women and their partners showed a statistically highly significant increase of the female-to-male compatibility (P = 0.0003) and a lower but significant male-to-female compatibility in comparison with controls (P = 0.014). From our results, it emerges that HLA-DR homozygosity and reduced antigenic disparity seem to be associated to a major risk for pre-eclampsia, which consequently appears to be a 'couple's disease'.

Case-Control Studies↗
PubMed2000

A physical model of the human systemic arterial tree.

A physical model of the human arterial tree has been developed to be used in a computer controlled mock circulatory system (MCS). Its aim is to represent systemic arterial tree properties and extend the capacity of the MCS to intraortic balloon pump (IABP) testing. The main problem was to model the aorta simply and to accurately reproduce aortic impedance and related flow and pressure waveforms at different sections. The model is composed of eight segments; lumped parameter models are used for its peripheral loads. After the numerical simulation, the physical model was reproduced as a silicon rubber tapered tube. This rubber was chosen for its stability over time and the acceptable behaviour of its Young's modulus (Ey = 22.23 gf x mm(-2)) with different loads and in comparison with data from the literature (Ey approximately 20.4 gf x mm(-2)). The properties of each segment of the aorta were defined in terms of compliance, resistance and inertance as a function of length, radius and thickness. The variable thickness was obtained using positive and negative molds. Total static compliance of the aorta model is about 1.125 x 10(-3) g(-1) x cm4 x sec2 (1.5 cm3 x mmHg(-1)). Measurements were performed both on numerical and physical models (in open and closed loop configuration). Data reported show pressure and flow waveforms along with input impedance modulus and phase. The results are in good agreement with data from the literature.

Aorta↗
PubMed2000

Computer simulation of hemodynamic parameter changes by mechanical ventilation and biventricular circulatory support.

When a Bi-Ventricular Assist Device (BVAD) is used in conjunction with mechanical ventilation (MV) of the lungs with positive intrathoracic pressure (Pt), the latter influences hemodynamics. The aim of our study was to assess the simultaneous influence of BVAD and MV on hemodynamics. We assumed ventricular pathological conditions as reduced elastances and increased rest volumes. Peripheral systemic arterial resistance was assumed to have different values. Data were obtained by computer simulation. Trends in main hemodynamic variables were compared with clinical data from literature. Simulation showed that systemic venous, pulmonary arterial and left atrial pressures are very sensitive to Pt (-2 to 5 mmHg).

Computer Simulation↗
PubMed1999

The CCKB/gastrin receptor is coupled to the regulation of enzyme secretion, protein synthesis and p70 S6 kinase activity in acinar cells from ElasCCKB transgenic mice.

In order to determine which physiological functions can be regulated by the pancreatic CCKB/gastrin receptor, studies were carried out on pancreatic acini from mice expressing transgenic CCKB/gastrin receptors in the exocrine pancreas (ElasCCKB mice). Acini were stimulated by sulfated gastrin in the presence of SR 27897 (1.8 microM), blocking endogenous CCKA receptors. After 30 min incubation with gastrin, the secretion of chymotrypsinogen and amylase showed superimposable monophasic dose-response curves. Enzyme secretion was detectable and maximal at 100 pM and 1 nM of gastrin, respectively. No increase in chymotrypsinogen and amylase mRNAs was detected for doses of gastrin which specifically occupy the CCKB/gastrin receptor. In contrast, gastrin stimulated total protein synthesis in isolated acini from ElasCCKB mice. [35S]Methionine incorporation into total proteins was increased dose-dependently to a maximum for 30 pM gastrin and inhibited with higher doses (> 300 pM). Gastrin stimulated p70 S6 kinase activity for concentrations ranging from 10 pM to 1 nM. Gastrin-stimulated p70 S6 kinase activity and protein synthesis were blocked by rapamycin and wortmannin. Therefore, in ElasCCKB mice acinar cells, the CCKB/gastrin receptor mediates enzyme release and protein synthesis. However, a more efficient coupling of the CCKB/gastrin receptor to protein synthesis than to enzyme secretion was demonstrated. CCKB/gastrin receptor-stimulated protein synthesis likely results from an enhancement of mRNA translation and involves phosphatidyl inositol 3-kinase and p70 S6 kinase.

Amino Acid Sequence↗
PubMed1999

The influence of simultaneous intra-aortic balloon pumping and mechanical ventilation on hemodynamic parameters--numerical simulation.

Intra-aortic balloon counterpulsation (IABC) is one of the methods to assist circulation. Its application is supposed to increase coronary blood flow (Qcor) and myocardial oxygen supply. Mechanical ventilation of the lungs causes some side effects that influence mainly hemodynamics, i.e. it decreases cardiac output (CO) and systemic aortic pressure (Pas) but increases systemic venous pressure (Pvs). The aim of this study was to assess the influence of IABC on hemodynamic parameters when mechanical ventilation of the lungs is used as well. We assumed pathological conditions of the heart as reduced left ventricle elastance (Ev = 0.77 mmHg/cm3) and increased left ventricle rest volume (V0 = 10 cm3). Also peripheral systemic arterial resistance (Ras) took three different values. CARDIOSIM, a computer simulator of the human cardiovascular system, was used to assess the changes of hemodynamic parameters [CO, Pas, Pvs, and pulmonary arterial pressure (Pap)] when IABC and mechanical ventilation of the lungs were applied simultaneously. Computer simulation showed that application of IABC increased such variables as CO (by approximately equal to 17%), maximum value of Pas (by approximately equal to 20%), while left atrial pressure (Pla) was diminished (by approximately equal to 30%). On the other hand, Pvs and Pap were not strongly affected by IABC, but they were dramatically dependent on intrathoracic pressure. This means that Pvs, Pap, and Pla should be carefully monitored during IABC and artificial ventilation.

Blood Pressure↗
PubMed1999

A simple method for Emax trend evaluation: in vitro and in vivo results.

The aim of this study is the evaluation of end systolic ventricular elastance trend (as a measure of heart contractility) by hemodynamic variables available in intensive care units or during heart surgery: heart rate, cardiac output, left atrial, mean and diastolic arterial pressure. Its basic assumption is the description of ejection as the interaction between variable left ventricular and arterial compliances (reciprocal of the corresponding elastances) connected in parallel. As pressure is the same in each compliance at systole beginning and ending, ventricular elastance can be estimated by assuming that energy variation is the same on both compliances. The algorithm has been tested on a numerical simulator of the circulatory system and on six sheep at basal conditions and during drug infusion. Correlation function in numerical simulation, between true and computed ventricular elastance (range 0.45 divided by 5 mm Hg-cm(-3)), yields 0.985. In vivo comparison between computed ventricular elastance trend and ventricular dp/dt trend yields a correlation function ranging between 0.87 and 0.99. The result of the algorithm cannot be assumed to be Emax value. However, it can be considered a contractility index as it closely follows any change in dp/dt. It can be computed by simple calculations and needs no variables other than those usually measured in intensive care . It allows the extrapolation of useful information for evaluating the trend in heart contractility and for setting up a control strategy for mechanical or pharmacological assistance during heart recovery.

Algorithms↗
PubMed1998

The influence of left ventricle assist device and ventilatory support on energy-related cardiovascular variables.

One of the main purposes in using Left Ventricle Assist Devices (LVAD) to assist recovery in patients with heart failure, is to reduce the external work (EW) of the left natural ventricle. The simultaneous presence of mechanical ventilatory support can affect the value of this variable. The aim of our computer simulation was to trace the influence of LVAD on EW, cardiac mechanical efficiency (CME) and pressure volume area (PVA) in the presence of ventilatory support. Pathological conditions of the heart were reproduced. Peripheral systemic arterial resistance (Ras) was also changed to model physiological and pathological states. The influence of mechanical ventilation was introduced by changing levels of mean thoracic pressure. In this way we were able to predict changes of EW, CME and PVA in both ventricles, during ventilatory (mechanical) and cardiovascular (LVAD) support. Our simulation showed that positive thoracic pressure seems to affect the energy-related cardiovascular variables and should be taken into account during the assessment of LVAD effectiveness. Pathological changes of systemic peripheral resistance have a considerable effect on EW, CME and PVA of left ventricle. On the other hand energy-related parameters of the right ventricle are not especially affected by changes in systemic peripheral resistance.

Computer Simulation↗
PubMed1998

Somatostatin in the prevention of recurrent bleeding after endoscopic haemostasis of peptic ulcer haemorrhage: a preliminary report.

OBJECTIVE: Although endoscopic injection therapy provides excellent initial haemostasis in actively bleeding ulcers, the incidence of recurrent haemorrhage is not negligible. The aim of this study was to compare somatostatin, omeprazole and ranitidine in preventing further haemorrhage after endoscopic injection haemostasis. METHODS: Seventy-three patients with major stigmata of ulcer haemorrhage at endoscopy were treated with epinephrine injection and randomly assigned to receive either omeprazole (n = 24) or ranitidine (n = 24) or somatostatin (n = 25). The three groups were similar in all background variables including mean age, clinical and endoscopic features, severity of bleeding and timing of the haemostatic procedure. All patients underwent a second endoscopic look at 48 h. Failures of treatment or retreatment underwent emergency surgery. RESULTS: There were no statistically significant differences between the groups in terms of initial haemostasis, need for emergency surgery, transfusion requirements, length of hospital stay or mortality. Early recurrent haemorrhage was 5/22 (22.7%) in the ranitidine group, 5/23 (21.7%) in the omeprazole group and 2/23 (8.7%) in the somatostatin group. No major side-effect was noted with drug therapy. CONCLUSIONS: The preliminary results suggest that somatostatin might be more effective than ranitidine and omeprazole in the prevention of recurrent haemorrhage following endoscopic injection therapy of bleeding peptic ulcers.

Adult↗