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M L Rossi

Publications and source records attributed to M L Rossi.

At least 19 recordsLinked to original sources
PubMed2006

Drug-eluting stents: towards new endpoints.

Drug-eluting stents (DES) have significantly reduced the rates of in-stent restenosis (ISR). As previously observed with bare-metal stents (BMS), either patient's clinical characteristics and lesion morphology may influence the risk of recurrence even with DES. In this review we will focus on the most recent available data on clinical settings where DES efficacy on long-term outcomes are largely unknown. In particular, we report on very complex lesions (bifurcations, small vessels, chronic total occlusions, in-stent restenosis) myocardial infarction, multivessel disease, treatment of bypass graft and of unprotected left main disease. Several issues are still open on DES routinary use for these indications, mainly as far as stent thrombosis is concerned. Recent pathological studies show that DES are characterized by chronic inflammatory infiltrates and delayed endothelialization. Therefore, this effect could translate in a ''vulnerable period'' for thromboses longer than with BMS. Even though large meta-analysis have excluded higher rates of stent thrombosis with DES rather than with BMS, few cases of unusual very late stent thrombosis have been described, pointing out that this problem seems to be still unsolved. Although DES provide better angiographic outcomes in each clinical setting, further randomized studies are running to assess their safety and efficacy on currently off-label indications.

Clinical Trials as Topic↗
PubMed2005

Biophysical properties of the silent and activated rat sympathetic neuron following denervation.

A biophysical description of the denervated rat sympathetic neuron is reported, obtained by the two-electrode voltage-clamp technique in mature intact superior cervical ganglia in vitro. At membrane potential values negative to -50 mV, the normal, quiescent neuron displays voltage-dependent K and Cl conductances; following direct or synaptic stimulation (15Hz for 10 s), the neuron moves to a new resting state characterized by increased amplitude and voltage dependence of Cl conductance. Denervation produces two main effects: 1) resting Cl conductance gradually increases while its voltage-dependence decreases; by 30 days a high-conductance resting state prevails, almost independent of membrane potential in the -50/-110 mV range; 2) the increase in amplitude and voltage-dependence of Cl conductance, produced by direct stimulation in control neurons, is less marked in denervated neurons, and is observed over an increasingly small range of membrane potentials. Thirty days after denervation, the prevailing high-conductance resting state appears virtually insensitive to changes in membrane potential and stimulation. Voltage-dependent potassium currents involved in spike electrogenesis (the delayed compound potassium current and the fast transient potassium current) exhibit an early drastic decrease in peak amplitude in the denervated neuron; the effect is largely reversed after 6 days. Remarkable changes in fast transient potassium current kinetics occur following denervation: the steady-state inactivation curve shifts by up to +15 mV toward positive potential and voltage sensitivity of inactivation removal becomes more steep. A comprehensive mathematical model of the denervated neuron is presented that fits the neuron behavior under current-clamp conditions. It confirms that neuronal excitability is tuned by the conductances (mostly chloride conductance) that control the resting membrane potential level, and by fast transient potassium current. Impairment of the latter reduces both inward threshold charge for firing and spike repolarization rate, and fast transient potassium current failure cancels the voltage dependence of both processes.

Animals↗
PubMed2005

Clinical utility of IVUS in 2005.

Intravascular ultrasounds (IVUS) allowed an innovative visualization of coronary artery disease. This technique developed first in the research field and, then, it was introduced in clinical practice as a supplement to coronary angiography in diagnosis of the severity of ischemic heart disease. The characteristic tomographic view of coronary plaque supplied by IVUS allowed to overcome the limitations of coronary angiography and to add important supplemental information in understanding the mechanism of action of several interventional devices. In this review we analyze current indications of use of IVUS in clinical practice and the future applications of IVUS-related techniques for the diagnosis of coronary artery disease.

Humans↗
PubMed2004

Inhibitors of platelets glycoprotein IIb/IIIa (GP IIb/IIIa) receptor: rationale for their use in clinical cardiology.

The glycoprotein IIb/IIIa (GP IIb/IIIa) receptor is the most important receptor involved in platelet aggregation. A stable GP IIb/IIIa inhibition is required when a massive platelet activation triggers thrombosis. Three GP IIb/IIIa inhibitors are currently approved for clinical use: abciximab, tirofiban and integrilin. Their different pharmacodynamic and pharmacokinetic properties reflect a different efficacy in platelet inhibition.

Animals↗
PubMed2002

Quantitative neuropathological analysis of sudden infant death syndrome.

Detailed stereological analyses of specific regions of brains of children who had died from Sudden Infant Death Syndrome (SIDS) was undertaken to determine whether global evidence of an underlying pathology exists, contributing to an increased susceptibility to SIDS. A significant reduction in the total number of neocortical neurones and neurone volume was observed in SIDS normal birth weight (NBW) infants in comparison to controls. A significant reduction in both volume and total neurone number were also noted in the dorsal motor nucleus of the vagus in SIDS NBW group when compared with controls. Anomalies in regions of the brain involved with cardiorespiratory control (brainstem) and arousal (brainstem and neocortex) may play a crucial role in the chain of events resulting in a SIDS event.

Brain Stem↗
PubMed2002

No evidence for calcium electrogenic exchanger in frog semicircular canal hair cells.

We investigated the possibility that, in hair cells mechanically isolated from frog semicircular canals, Ca2+ extrusion occurs via a Na+ : Ca2+ (cardiac type) or a Na+ : Ca2+,K+ (retinal type) exchanger. Cells concurrently imaged during whole-cell patch-clamp recordings using the Ca2+ sensitive fluorescent dye Oregon Green 488 BAPTA-1 (100 micro m) showed no voltage dependence of Ca2+ clearance dynamics following a Ca2+ load through voltage-gated Ca2+ channels. Reverse exchange was probed in hair cells dialyzed with a Ca2+- and K+-free solution, containing a Na+ concentration that saturates the exchanger, after zeroing the contribution to the whole-cell current from Ca2+ and K+ conductances. In these conditions, no reverse exchange current was detected upon switching from a Ca2+-free external solution to a solution containing concentrations of Ca2+ alone, or Ca2+ + K+ that saturated the exchanger. By contrast, the same experimental protocol elicited peak exchange currents exceeding 100 pA in gecko rod photoreceptors, used as positive controls. In both cell types, we also probed the forward mode of the exchanger by rapidly increasing the intracellular Ca2+ concentration using flash photolysis of two novel caged Ca2+ complexes, calcium 2,2'-([1-(2-nitrophenyl)ethane-1,2-diyl]bis(oxy))bis(acetate) and calcium 2,2'-([1-(4,5-dimethoxy-2-nitrophenyl)ethane-1,2-diyl]bis(oxy)) bis(acetate), in the presence of internal K+ and external Na+. No currents were evoked by UV-triggered Ca2+ jumps in hair cells, whereas exchanger conformational currents up to 400 pA, followed by saturating forward exchange currents up to 40 pA, were recorded in rod photoreceptors subjected to the same experimental conditions. We conclude that no functional electrogenic exchanger is present in this hair cell population, which leaves the abundant plasma membrane Ca2+-ATPases as the primary contributors to Ca2+ extrusion.

Animals↗
PubMed2001

Percutaneous coronary revascularisation in women.

Numerous studies of sex differences in morbidity and mortality after an episode of acute coronary disease shown unclear results. In particular is not clear if women undergoing coronary revascularization procedures have adverse in-hospital and long-term outcomes compared with men. Recent clinical trial have provided new insights into this problem. The influence on gender differences for the decision to undertake coronary angiography and percutaneous transluminal coronary angioplasty will be discussed.

Angioplasty, Balloon, Coronary↗
PubMed2001

Characterisation of molecular alterations in microdissected archival gliomas.

Classification of gliomas according to their molecular characteristics may be important in future histopathological diagnosis. However, gliomas frequently display heterogeneity at the histological, biological and molecular level. In this study of archival diagnostic gliomas, precision microdissection was used to enrich samples in the most malignant cells or to investigate intratumoural histological heterogeneity. Analysis of tumour samples microdissected from the most aggressive regions, representative of the histopathological diagnosis, revealed PTEN mutations in 4/14 anaplastic astrocytomas, 4/13 glioblastomas and 1 gliosarcoma, but not in 19 low-grade gliomas. Using a novel PCR procedure and direct sequence analysis of the entire coding sequence, TP53 mutations were detected in 1/3 pilocytic astrocytomas, 3/13 astrocytomas, 4/14 anaplastic astrocytomas, 5/13 glioblastomas and 1 gliosarcoma. All but one of the tumours with TP53 mutation showed p53 immunopositivity, but 5 low-grade and 10 high-grade gliomas had p53 protein nuclear accumulation in the absence of detectable mutation. p53 status was unrelated to p21 expression. Neither PTEN nor TP53 mutations influenced the proliferative index or microvessel density of high-grade astrocytomas. Unusual findings include: TP53 mutation in a juvenile pilocytic astrocytoma; TP53 and PTEN mutations in a de novo glioblastoma, a gliosarcoma with identical mutations in gliomatous and sarcomatous components, and an infratentorial anaplastic astrocytoma with an earlier supratentorial grade II astrocytoma bearing the same TP53 mutation but not the PTEN mutation or loss of heterozygosity (LOH) of 10q23. Similarly, the transition to high-grade histology was associated with acquisition of PTEN mutations and 10q23.3 LOH in two de novo high-grade tumours with regions of low-grade histology.

Adolescent↗
PubMed2001

Regional distribution of calcium currents in frog semicircular canal hair cells.

In the present work we studied the regional expression of voltage-dependent Ca channels in hair cells from the frog semicircular canals, employing whole-cell patch-clamp on isolated and in situ hair cells. Although Ca channels are thought to play a major role in afferent transmission, up to now no data were available regarding their distribution in vestibular organs. The problem appears of interest, especially in the light of recent results showing the presence of multiple Ca current components in semicircular canal hair cells. Our data suggest the presence, in all regions of the crista ampullaris, of two classes of cells, one displaying an inactivating Ca current (R1) and one lacking it. In the former cells, Ca current amplitude decreased from the central to the peripheral zone (the maximal currents being observed in the intermediate zone). Only L-type and R2 current components displayed regional differences in expression, whereas the size and properties of R1, although variable among cells, were not regionalized. However, in cells lacking R1, Ca current amplitudes were similar regardless of cell shape and location. The possible contributions of this Ca current distribution to afferent discharge properties are discussed.

Animals↗
PubMed2001

Dynamics of intracellular calcium in hair cells isolated from the semicircular canal of the frog.

Changes in cytosolic free Ca(2+) concentration ([Ca(2+)]i) were monitored optically in hair cells mechanically isolated from frog semicircular canals using the membrane-impermeant form of the Ca(2+)-selective dye Oregon Green 488 BAPTA-1 (OG, 100 microM). Cells stimulated by depolarization under whole-cell voltage clamp conditions revealed Ca(2+) entry at selected sites (hotspots) located mostly in the lower (synaptic) half of the cell body. [Ca(2+)]i at individual hotspots rose with a time constant tau1 approximately 70 ms and decayed with a bi-exponential time-course (tau2 approximately 160, tau3 approximately 2500 ms) following a 160 ms depolarization to -20 mV. With repeated stimulation [Ca(2+)]i underwent independent amplitude changes at distinct hotspots, suggesting that the underlying Ca(2+) channel clusters can be regulated differentially by intracellular signalling pathways. Block by nifedipine indicated that the L-type Ca(2+)channels are distributed at different densities in distinct hotspots. No diffusion barrier other than the nuclear region was found in the cytosol, so that, during a prolonged depolarization (lasting up to 1s), Ca(2+) was able to reach the cell apical ciliated pole. The effective Ca(2+) diffusion constant, measured from the progression of Ca(2+) wavefronts in the cytosol, was approximately 57 microm(2)/s. Our results indicate that in these hair cells, buffered diffusion of Ca(2+) proceeds evenly from the source point to the cell interior and is dominated by the diffusion constant of the endogenous mobile buffers.

Animals↗
PubMed2001

Laboratory markers of hypercoagulability.

Investigations carried out over the last 40 years have demonstrated that coronary artery thrombosis is the critical event underlying myocardial infarction and unstable angina. The existence of a prolonged hypercoagulable state preceding the thrombotic event has been postulated for some time and significant associations have been established between the plasma concentrations of a number of hemostatic variables and the frequency of myocardial infarction. High plasma fibrinogen, factor VII/VIIa, tissue-type plasminogen activator and plasminogen activator inhibitor levels have been associated with at least as great a risk of developing myocardial (re)infarction or sudden death as high cholesterol levels, especially in the young. In the last year more sensitive assays have been developed, and they should allow a precise biochemical definition of hypercoagulable states. The significance of these new assays and their role in defining a hypercoagulable state in different conditions are analyzed.

Angina, Unstable↗
PubMed2001

Prothrombotic genetic markers.

The last decade has been characterized by an explosion of research studies on genetic epidemiology. In particular, as far as ischemic heart disease is concerned, a lot of research was focused on prothrombotic genetic risk factors. Unfortunately, the success of this approach in the field of venous thrombosis has not been replicated in the field of myocardial infarction. In the present editorial, a comment on the studies already available is provided and the possible limitations of the present approach are analyzed.

Coronary Thrombosis↗
PubMed2001

Hemostatic markers and prognosis in ischemic heart disease.

Failure of traditional risk factors in identifying patients who develop a cardiac event, has led investigators to focus on other factors involved in precipitating cardiac events. As acute or subacute thrombosis is the major complication of atherosclerotic plaque rupture, attention has been dedicated to prothrombotic markers as possible risk factors. Recently, the role of new laboratory markers in predicting the risk of cardiac events has been evaluated in large epidemiological studies. The results of these studies as well as the value and applicability of new prothrombotic markers in the clinical practice are discussed.

Biomarkers↗
PubMed2000

Ca2+-dependent kinetics of hair cell Ca2+ currents resolved with the use of cesium BAPTA.

Hair cells in the frog semicircular canal, studied by the whole-cell patch-clamp technique, display three distinct Ca2+ currents: two non-inactivating components (L type and R type, the latter termed R2 in the following) and a second R type current (termed R1), which runs down first and inactivates in a Ca2+-dependent fashion. Since intracellular EGTA, up to 5 mM, did not display major effects on such inactivation, we used increasing amounts of BAPTA in the patch pipette, to control [Ca2+]i more efficiently and investigate whether modifications in [Ca2+]i at the cytoplasmic side of the channel affect the inactivation of the RI component and in general the gating of all channel types. The results here reported show that (1) K+ currents heavily contaminate recordings obtained using high concentrations of BAPTA in its commercially available K+ salt form; (2) BAPTA Cs+ salt can be satisfactorily employed to obtain reliable recordings; (3) the kinetics of channel gating and R1-channel inactivation are indeed markedly affected by effectively buffering [Ca2+]i.

Animals↗
PubMed2000

Calcium currents in hair cells isolated from semicircular canals of the frog.

L-type and R-type Ca(2+) currents were detected in frog semicircular canal hair cells. The former was noninactivating and nifedipine-sensitive (5 microM); the latter, partially inactivated, was resistant to omega-conotoxin GVIA (5 microM), omega-conotoxin MVIIC (5 microM), and omega-agatoxin IVA (0.4 microM), but was sensitive to mibefradil (10 microM). Both currents were sensitive to Ni(2+) and Cd(2+) (>10 microM). In some cells the L-type current amplitude increased almost twofold upon repetitive stimulation, whereas the R-type current remained unaffected. Eventually, run-down occurred for both currents, but was prevented by the protease inhibitor calpastatin. The R-type current peak component ran down first, without changing its plateau, suggesting that two channel types generate the R-type current. This peak component appeared at -40 mV, reached a maximal value at -30 mV, and became undetectable for voltages > or =0 mV, suggestive of a novel transient current: its inactivation was indeed reversibly removed when Ba(2+) was the charge carrier. The L-type current and the R-type current plateau were appreciable at -60 mV and peaked at -20 mV: the former current did not reverse for voltages up to +60 mV, the latter reversed between +30 and +60 mV due to an outward Cs(+) current flowing through the same Ca(2+) channel. The physiological role of these currents on hair cell function is discussed.

Animals↗
PubMed2000

Synaptic stimulation of nicotinic receptors in rat sympathetic ganglia is followed by slow activation of postsynaptic potassium or chloride conductances.

Two slow currents have been described in rat sympathetic neurons during and after tetanization of the whole preganglionic input. Both effects are mediated by nicotinic receptors activated by native acetylcholine (ACh). A first current, indicated as IAHPsyn, is calcium dependent and voltage independent, and is consistent with an IAHP-type potassium current sustained by calcium ions accompanying the nicotinic synaptic current. The conductance activated by a standard synaptic train was approximately 3.6 nS per neuron; it was detected in isolation in 14 out of a 52-neuron sample. A novel current, IADPsyn, was described in 42/52 of the sample as a post-tetanic inward current, which increased in amplitude with increasing membrane potential negativity and exhibited a null-point close to the holding potential and the cell momentary chloride equilibrium potential. IADPsyn developed during synaptic stimulation and decayed thereafter according to a single exponential (mean tau = 148.5 ms) in 18 neurons or according to a two-exponential time course (tau = 51.8 and 364.9 ms, respectively) in 19 different neurons. The mean peak conductance activated was approximately 20 nS per neuron. IADPsyn was calcium independent, it was affected by internal and external chloride concentration, but was insensitive to specific blockers (anthracene-9-carboxylic acid, 9AC) of the chloride channels open in the resting neuron. It is suggested that gADPsyn represents a specific chloride conductance activatable by intense nicotinic stimulation; in some neurons it is even associated with single excitatory postsynaptic potentials (EPSCs). Both IAHP and IADPsyn are apparently devoted to reduce neuronal excitability during and after intense synaptic stimulation.

Animals↗