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Biomedical subjects

C Daniele

Publications and source records attributed to C Daniele.

At least 19 recordsLinked to original sources

Presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors modulate release of inhibitory amino acids in rat spinal cord dorsal horn.

Local inhibition within the spinal cord dorsal horn is mediated by the neurotransmitters GABA and glycine and strongly influences nociceptive and temperature signaling. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are expressed by inhibitory interneurons and have been shown to modulate GABA release in other regions of the CNS. In the spinal cord, there is morphological evidence for presynaptic AMPA receptor subunits in GABAergic dorsal horn neurons, but functional data are lacking. To determine if AMPA receptors are indeed functional at presynaptic terminals of inhibitory neurons, we recorded evoked and miniature inhibitory postsynaptic currents (mIPSPs) in the superficial dorsal horn of the rat spinal cord. We show that AMPA receptor activation enhances spontaneous release of inhibitory amino acids in the presence of tetrodotoxin onto both lamina II neurons and NK1 receptor-expressing (NK1R+) lamina I neurons. This effect is sensitive to the concentration of extracellular Ca2+, yet is not fully blocked in most neurons in the presence of Cd2+, suggesting possible Ca2+ entry through AMPA receptors. Postsynaptic Ca2+ elevation is not required for these changes. AMPA-induced increases in mIPSP frequency are also seen in more mature dorsal horn neurons, indicating that these receptors may play a role in nociceptive processing in the adult. In addition, we have observed AMPA-induced depression of evoked release of GABA and glycine onto lamina I NK1R+ neurons. Taken together these data support a role for presynaptic AMPA receptors in modulating release of GABA and glycine in the superficial dorsal horn. Because inhibition in the dorsal horn is important for controlling pain signaling, presynaptic AMPA receptors acting to modulate the inhibitory inputs onto dorsal horn neurons would be expected to impact upon pain signaling in the spinal cord dorsal horn.

Age Factors↗

In vitro antifungal and anti-elastase activity of some aliphatic aldehydes from Olea europaea L. fruit.

Olea europaea preparations are traditionally employed in a variety of troubles, including skin infections. Olive extracts and some of their pure compounds have shown antimicrobial activity in vitro. The present study deals with the antifungal activity of some aliphatic aldehydes from olive fruit [hexanal, nonanal, (E)-2-hexenal, (E)-2-heptenal, (E)-2-octenal, (E)-2-nonenal] against Tricophyton mentagrophytes (6 strains), Microsporum canis (1 strains) and Candida spp. (7 strains). The capability of these substances to inhibit elastase, a virulence factor essential for the dermatophytes colonization, and their cytotoxicity on cultures of reconstructed human epidermis, are also described. Aldehydes tested, inhibited the growth of T. mentagrophytes and M. canis in the range of concentration between <1.9 and 125 microg/ml; the unsaturated aldehydes showed the most broad spectrum of activity in that inhibited all strains tested. None of the aldehydes exhibited activity against Candida spp. strains. (E)-2-octenal and (E)-2-nonenal inhibited the elastase activity in a concentration-dependent manner; the anti-elastase activity suggests an additional target of the antimicrobial activity of these compounds. Aldehydes were devoid of cytotoxicity on cultures of human reconstructed epidermis. The antifungal activity of the aldehydes from olive fruit here reported, substantiates the use of olive and olive oil in skin diseases and suggests that these natural compounds could be useful agents in the topical treatment of fungal cutaneous infections.

Antifungal Agents↗

Atractylis gummifera L. poisoning: an ethnopharmacological review.

Atractylis gummifera L. (Asteraceae) is a thistle located in the Mediterranean regions. Despite the plant's well-known toxicity, its ingestion continues to be a common cause of poisoning. The toxicity of Atractylis gummifera resides in atractyloside and carboxyatractyloside, two diterpenoid glucosides capable of inhibiting mitochondrial oxidative phosphorylation. Both constituents interact with a mitochondrial protein, the adenine nucleotide translocator, responsible for the ATP/ADP antiport and involved in mitochondrial membrane permeabilization. Poisoned patients manifest characteristic symptoms such as nausea, vomiting, epigastric and abdominal pain, diarrhoea, anxiety, headache and convulsions, often followed by coma. No specific pharmacological treatment for Atractylis gummifera intoxication is yet available and all the current therapeutic approaches are only symptomatic. In vitro experiments showed that some compounds such as verapamil, or dithiothreitol could protect against the toxic effects of atractyloside, but only if administered before atractyloside exposure. New therapeutic approaches could come from immunotherapy research: some studies have already tried to produce polyclonal Fab fragments against the toxic components of Atractylis gummifera.

Atractylis↗

The antimutagenic activity of Lavandula angustifolia (lavender) essential oil in the bacterial reverse mutation assay.

Essential oils from Melaleuca alternifolia (tea-tree oil) and Lavandula angustifolia (lavender oil) are commonly used to treat minor health problems. Tea-tree oil possesses broad-spectrum antimicrobial activity, and is increasingly used for skin problems. Lavender oil, traditionally used as an antiseptic agent, is now predominantly used as a relaxant, carminative, and sedative in aromatherapy. Despite their growing use no data are available on their mutagenic potential. In this study, after determining the chemical composition of tea-tree oil and lavender oil, by gas-chromatography and mass spectrometry, we investigated their mutagenic and antimutagenic activities by the bacterial reverse mutation assay in Salmonella typhimurium TA98 and TA100 strains and in Escherichia coli WP2 uvrA strain, with and without an extrinsic metabolic activation system. Neither essential oil had mutagenic activity on the two tested Salmonella strains or on E. coli, with or without the metabolic activation system. Conversely, lavender oil exerted strong antimutagenic activity, reducing mutant colonies in the TA98 strain exposed to the direct mutagen 2-nitrofluorene. Antimutagenicity was concentration-dependent: the maximal concentration (0.80 mg/plate) reduced the number of histidine-independent revertant colonies by 66.4%. Lavender oil (0.80 mg/plate) also showed moderate antimutagenicity against the TA98 strain exposed to the direct mutagen 1-nitropyrene. Its antimutagenic property makes lavender oil a promising candidate for new applications in human healthcare.

Animals↗

Endovascular stents: market vigilance and risk factors.

With the aim of enhancing the safety and reliability level of coronary stents, we analyzed data collected from accident reports drawn from the MAUDE database (Manufacturer and User Facility Device Experience Database) of the FDA from 1996 to 2000. This analysis allowed us to highlight problems related to the use of coronary stents by means of the analysis of these reports at different levels, beginning from the causes that can lead to a certain type of accident up to the possible complication related to that event. Moreover we analyzed the procedure outcomes in terms of stent position inside the patient's body and the possible therapies adopted to solve the problems. The results showed that the most probable event that can lead to an accident is the stent separation from the balloon which, alone, turns up in a number of cases equal to the sum of all the others. This result highlights the importance of the technical skill of the operators accomplished by special training and of the importance of clarity and completeness in the instructions for the use of the device. Another critical point is the reliability of the device which must guarantee an adequate safety level when it is used according to the instructions.

Angioplasty, Balloon, Coronary↗

Proposal for a quantitative description of blood spiral flow in medical devices.

The association between specific blood flow patterns and blood behaviour through medical devices suggests that a Lagrangian study may be a useful instrument for the evaluation of the thrombogenic and/or hemolytic potential of certain devices' geometries and biomaterials. In this study a description of blood particle trajectories in terms of their spiral contents is proposed; such a mathematical description for blood spiral flow, computed along several pathlines, is tested for a quantitative determination of the spiralled motion of blood flow into two three-dimensional numerical models, having different design characteristics, of venous cannula inserted in a vessel. As the influence of vortical flow conditions have been observed to have both beneficial and detrimental influence on blood behaviour in terms of blood-device interaction, of the degradation of its components, and of the efficiency of mass-exchange (in red cells oxygenation and plasma filtration, for example), the herein proposed method for the description of spiral laminar motion may be a helpful instrument to build up a tool to investigate, for example, the existence of correlations between level of spiral flow and geometry (as in the present investigated test case), rather than the effects of blood-surface contact. The results obtained in this test case investigation, confirm the effectiveness of the proposed function for a quantitative analysis of spiral flow in medical devices.

Blood Flow Velocity↗

Morphological analysis of in vivo velocity field in the alteration of the vasomotor tone.

Vessel wall remodeling is involved in atherogenesis and in several important vascular diseases affecting mainly aged and prosthetic implanted patients. This adaptive response to pathological states in arterial hemodynamics strongly suggests that flow-derived stresses act as mechanical stimuli to the release of endothelium-derived vasoactive factors, leading to vascular alterations. As the correlation of intimal hyperplasia (IH) with blood flow alterations in arteries has been shown to be significant, and as it is well-known that clinical procedures carry a substantial risk of development of vascular disease, the relevance of local hemodynamics must be investigated to describe changes in compliance matching in prosthetic applications. The aim of our research is to investigate the use of principal components analysis, together with varimax rotation, in the individuation process of morphological characteristics of real time ultrasound in in vivo recordings of blood flow velocities, as provided by two different carotid perivascular manipulations. This would be of use in the clinical assessment of atherogenesis, hypertension, prosthetic replacement or more in general in all applications in which vascular tone may be impaired. Data recordings refer to previous animal experiments where the Moncada model was investigated by means of an ultrasound profilometer. The present study confirms the feasibility of the proposed analysis to follow vascular pathology evolution, distiguishing between an in progress and a static situation.

Animals↗

Pathological patient in protocol definition for bench testing of mechanical cardiac support system.

Clinical techniques for the restoration of a failing heart are mainly based on the use of mechanical assist devices. In recent years, with the growing need for mechanical circulatory support, these devices have been shown to be a useful therapeutic tool, thanks to their intrinsic capability to unload the failing ventricle, allowing the heart to recover. Mechanical circulatory support systems (MCSS) require an accurate biomechanical characterization of the complex interaction that occurs between the patient and the mechanical support. A protocol for MCSS testing is proposed which takes into account several working conditions, in a modified test mock loop apparatus able to mimic various pathological conditions. Both physiological and pathological conditions can be replicated to show the actual efficacy of a MCSS device in correctly supporting a wide spectrum of ventricular conditions. The test bench is able to simulate the recovery of the pathological condition quite accurately, showing, at the same time, that this set up can be a reliable choice to characterize cardiac support devices. Thus the results of this experimentation can be useful to clinicians in forecasting the response of the heart affected by a cardiac disease and to set appropriate parameters for suitable assistance.

Blood Flow Velocity↗

Numerical simulation of a realistic total cavo-pulmonary connection: effect of unbalanced pulmonary resistances on hydrodynamic performance.

Total cavo pulmonary connection (TCPC) is one of the surgical techniques adopted to compensate the failure of the right heart in pediatric patients. The main goal of this procedure is the realization of a configuration for the caval veins and for the pulmonary arteries that can guarantee as low as possible pressure losses and appropriate lung perfusion. Starting from this point of view, a realistic TCPC with extracardiac conduit (TECPC) is investigated by means of Computational Fluid Dynamics (CFD) to evaluate the pressure loss under different pressure conditions, simulating different vessel resistances, on the pulmonary arteries. A total flow of 3 L/min, with a distribution between the inferior vena cava (IVC) and the superior vena cava (SVC) equal to 6/4, was investigated; three different boundary conditions for the pressure were imposed, resulting in three simulations in steady-state conditions, to the right pulmonary artery (RPA) and to the left pulmonary artery (LPA), simulating a balanced (deltaP(LPA-RPA) = 0 mmHg) and two unbalanced pulmonary resistances to blood flow (a pressure difference deltaP(LPA-RPA) = +/- 2 mmHg, respectively). The geometry for the TECPC was realized according to MRI derived physiological values for the vessels and for the configuration adopted for the anastomosis (the extra-cardiac conduit was inclined 22 degrees towards the left pulmonary artery with respect to the IVC axis). The computed power losses agree with previous in vitro Particle Image Velocimetry investigations. The results show that a higher resistance on the LPA causes the greater pressure loss for the TECPC under study, while the minimum pressure loss can be achieved balancing the pulmonary resistances, subsequently obtaining a balanced flow repartition towards the lungs.

Child↗

Flow on the symmetry plane of a total cavo-pulmonary connection.

The flow inside a total cavo-pulmonary connection, a bypass operation of the right heart adopted in the presence of congenital malformation, is here studied for a specific geometry which has been recently introduced in clinics. The analysis has been performed by preliminary experimental observation and a novel Navier-Stokes formulation on the symmetry plane. This method, once some basic hypotheses are verified, allows to reproduce the flow on the symmetry plane of a three-dimensional field by using an extension of the two-dimensional approach. The analysis has confirmed the existence of a central vortex showing that it is not a real vortex (i.e. a place with accumulation of vorticity) but, rather, a weakly dissipative recirculating zone. It is surrounded by a shear layer that becomes spontaneously unsteady at moderately high Reynolds number. The topological changes and energy dissipation have been analysed in both cases of unbalanced and of balanced pulmonary artery and caval flows.

Blood Flow Velocity↗

Hydraulic functional characterisation of aortic mechanical heart valve prostheses through lumped-parameter modelling.

Lumped-parameter modelling techniques are proposed as a method for studying the hydraulic characteristics of mechanical prosthetic heart valves (PHVs). The global hydraulic behaviour of PHVs in the open position was modelled by taking into account the (nonlinear) resistive and (linear) inertial factors governing the time-dependent relationship between transvalvular pressure drop and fluid flow rate, and neglecting the leaflets' opening and closure transient phenomena. Statistically defined indices associated to the parameters' values attest how properly the model describes PHV hydraulic behaviour. Local fluid dynamics is not modelled with this approach. The proposed method was implemented in a software program and applied to the characterisation of the aortic StJude Medical, StJude Medical Hemodynamic Plus and CarboMedics PHVs, basing on steady- and pulsatile-flow hydraulic-bench experimental data. The results showed that reliable parameters expressing hydraulic resistance can be derived from steady-flow data (R(2)>0.995). Inertance parameters derived from pulsatile-flow experiments are liable to a degree of uncertainty (confidence intervals up to 17%), however, comparing the reconstructed vs. measured pressure drop during systolic time demonstrates that this deficiency is mostly due to the missing description of initial, transient oscillations presumably related to the leaflets' opening (not modelled).

Aortic Valve↗

Computational model of the fluid dynamics of a cannula inserted in a vessel: incidence of the presence of side holes in blood flow.

Vascular access methods, performed by the insertion of cannulae into vessels, may disturb the physiological flow of blood, giving rise to non-physiological pressure variations and shear stresses. To date, the hydrodynamic behaviour of the cannulae has been evaluated comparing their pressure loss-flow rate relationships, as obtained from in vitro experiments using a monodimensional approach; this methodology neither furnish information about the local fluid dynamics nor the established flow field in specific clinical work conditions. Since the shear stress is a critical factor in the design of artificial circulatory devices, more knowledge should be necessary about the local values assumed by the haemodynamic parameters during cannulation. An alternative way to investigate the fluid dynamic as accurately as possible is given by numeric studies. A 3D model of cannula concentrically placed in a rigid wall vessel is presented, with the finite element methodology used to numerically simulate the steady-state flow field in two different venous cannulation case studies, with two cannulae having a central hole and two or four side holes, respectively, with the same boundary conditions. Lower velocity and shear stress peak values have been computed for the model with four side holes upstream of the central hole, in the region of the cannula where the inlet flows meet and towards cannula's outlet, due to the increased flow symmetry and inlet area with respect to the model with two side holes. Starting from the investigation of different cannula designs, numerically assessing the local fluid dynamics, indications can be drawn to support both the design phase and the device optimal clinical use, in order to limit risks of biomechanical origin. Thus the presence of four side holes implied, as a consequence of the greater inlet area and of the increased symmetry, a less disturbed blood flow, together with reduced shear stress values. Furthermore, results show that the numerical simulations furnished useful informations on the interaction between vessel and cannula, e.g. on the fluid dynamics establishing in the free luminal space left, in the vessel, by the inserted cannula.

Blood Flow Velocity↗

Potential mechanical blood trauma in vascular access devices: a comparison of case studies.

Since vascular access devices may cause disturbances in blood flow, possibly damaging red blood cells (RBCs), the correlated risk of lysis must be assessed. The monodimensional approach for the evaluation of cannulae hydrodynamic behaviour (in vitro measured flow curves) does not furnish information on the local flow field occurring in specific clinical conditions. Researchers consider the prediction of blood trauma, induced by mechanical loading, to optimize the design phase, and to furnish indications on their optimal clinical use. In this study, a model of cannula inserted in a non compliant wall vessel was used as a test bench in a Computational Fluid Dynamics (CFD) problem. By means of CFD the flow field was 3D analysed to achieve information on velocity and shear stress local values, when cannula is used for inflow and outflow cannulation. A prediction of potential blood corpuscle damage, based on a power law, quantified the potential blood damage. Several numerical simulations, with different cannula/vessel flow rate ratios were provided, to investigate the incidence of local sites in the design on blood damaging potential during cannulation. Several regions appeared to be sensitive to the flow rate not only inside the cannula but also in the space between cannula and vessel, suggesting new indications for the assessment of a quality factor based on the evaluation of induced blood cells injury.

Blood Flow Velocity↗

Comparison of prazosin, terazosin and tamsulosin: functional and binding studies in isolated prostatic and vascular human tissues.

BACKGROUND: Terazosin and tamsulosin are drugs currently used in the treatment of benign prostatic hypertrophy (BPH). The potency of these two alpha(1) receptor antagonists and that of prazosin to inhibit contractions induced by noradrenaline and the binding of [(3)H]-prazosin in human prostate and four different human arterial and venous vessels (saphenous and umbilical veins, renal and mesenteric arteries) was studied. METHODS: By bioassay and binding studies, we examined the receptor affinities of different alpha(1) receptor antagonists in different human tissues. RESULTS: pKb of terazosin, tamsulosin, and prazosin obtained in the prostatic tissues (8.15, 9.64, and 8.59, respectively) were not different from those obtained in the umbilical veins (8.07, 9.56, and 8.30, respectively), in the mesenteric artery (8.27, 10.29, and 9.01, respectively), renal artery (8.35, 10.13, and 8.76, respectively) and saphenous vein (7.8, 10.3, and 9.32, respectively). IC(50) (nM) of prazosin, terazosin, and tamsulosin obtained from binding studies in membrane preparations from prostate tissue were similar to those from umbilical veins, saphenous vein, and renal artery. CONCLUSIONS: All of the evaluated drugs showed similar selectivity for prostatic vs. vascular tissues. Thus, different clinical profiles of the present drugs should not result from their differential affinity for prostatic versus vascular alpha(1)-adrenoceptors.

Adrenergic alpha-1 Receptor Antagonists↗

The influence of the leaflets' curvature on the flow field in two bileaflet prosthetic heart valves.

A successful mechanical prosthetic heart valve design is the bileaflet valve, which has been implanted for the first time more than 20 years ago. A key feature of bileaflet valves is the geometry of the two leaflets, which can be very important in determining the flow field. Laser Doppler anemometry (LDA) was used to perform an accurate study of the velocity and turbulence shear stress peak values (TSS(max)) fields at four distances from the valve plane. TSS(max) is a relevant parameter to assess the risk of hemolysis and platelet activation associated to the implantation of a prosthetic device, continuously interacting with blood. Two bileaflet valves were tested: the St. Jude HP and the Sorin Bicarbon, of the same nominal size (19mm). The former has flat leaflets, whereas the latter's leaflets have a cylindrical surface. A high regime (CO: 6l/min) was imposed, in order to test the two valves at maximum Reynolds number and consequent turbulence generation. The flat-leaflet design of the St. Jude generates a TSS field constant with distance; on the contrary, the Bicarbon's shear stress field undergoes an evident development, with an unexpected central peak at a distance comparable to the valve's dimensions (21mm). The two bileaflet valves tested, although very similar in design, behave very differently as for their turbulence properties. In particular, the concept of curved wake leads to conclude that the curvature of the leaflets' surface must be identified as an important parameter, which deserves careful attention in PHV design and development.

Biomechanical Phenomena↗

A mathematical model of the fetal cardiovascular system based on genetic algorithms as identification technique.

The development of fetal cardiac surgery, considered the ultimate goal in the treatment of congenital cardiac malformations, needs to be supported by detailed knowledge of the blood circulation in the fetal cardiovascular system. The hemodynamic behavior in distal territories is usually inferred from vessel resistance indices, which give limited physiological information. This study presents a mathematical model of the human fetal global cardiovascular system, developed to clarify the relationships and differences existing between upper and lower body circulation. We modelled the heart with two time-varying capacitances, each representing the respective ventricle's pressure-volume relationship. The fetal vascular system was represented using two six-element Windkessel models, for the upper and lower body respectively. We obtained the identification of the set of circuital and elastance function parameters of the model using Genetic Algorithms (GAs), which follow the laws of evolutionary theory. We compared the results of our numerical study on the model identified with data collected from measurements and literature, to validate the proposed global cardiovascular system model of the human fetus. This model is intended as an instrument to investigate the differences in blood distribution between the different vascular districts in the upper and lower fetal body and the role of the aortic isthmus, the small tract of vessel connecting upper and lower fetal vascular beds; it may also represent a useful tool in the assessment of dynamic balance during mechanical assistance of circulation.

Algorithms↗

Pulsatile flow and atherogenesis: results from in vivo studies.

Compliance mismatch between prosthetic vascular replacement (possibly stented) and native artery is considered to be an important factor in implant failure due, e.g., to vascular remodeling, tissutal growth or intimal hyperplasia (IH). From an in vivo study involving altered vascular mechanics (and, consequently, compliance mismatch), carried out using the Moncada model of atherosclerosis development and smooth muscle cell (SMC) proliferation, the hemodynamic assessment was followed by means of real-time multigated ultrasound profilometry, of collared carotid artery using two different models: non-constrictive and constrictive plastic collars, wrapped around the vessel. The experiments provided the real-time measurement of velocity profiles in vivo and the subsequent estimation of wall shear stresses, locally responsible for the altered hemodynamics. Endothelium modifications were correlated with local hemodynamic alterations by using statistical regression analysis of the development of intimal hyperplasia and the mechanical stimulus applied to the endothelium by means of the two different manipulation models. Different correlations were found between wall shear rate and IH in the two models, showing the importance of the vascular pulsatility in determining SMC proliferation. This result could be useful in minimizing the negative consequences of clinical interventions such as graft and/or stent implantation.

Animals↗

On the monodimensional approach to the estimation of the highest reynolds shear stress in a turbulent flow.

The measurement of the Reynolds stress tensor, or at least of some of its components, is a necessary step to assess if the turbulence associated with the flow near prosthetic devices can damage blood constituents. Because of the intrinsic three dimensionality of turbulence, in general, a three-component anemometer should be used to measure directly the components of the Reynolds stress tensor. However, this can be practically unfeasible, especially in vivo; therefore, it is interesting to investigate the possibility of characterizing the turbulent flows that may occur in the circulatory system with the monodimensional data that a less complete equipment (e.g., a pulsed ultrasound Doppler) can yield. From the general expression of the Reynolds stress tensor, the highest shear stress can be deduced, as well as the Reynolds normal stress in the main flow direction. The relation between these two quantities, which is an issue already addressed in previous works, can thus be rigorously formulated in terms of some characteristic parameters of the Reynolds stress tensor, the principal normal stresses and the angles that the directions that define them form with the main flow direction. An experimental verification of the ratio of the two above-mentioned quantitites for the flow across bileaflet valves, investigated by means of two-dimensional laser Doppler anemometry, will illustrate the limitations of the monodimensional approach estimating the maximum load on blood constituents.

Algorithms↗