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Biomedical subjects

M Marchi

Publications and source records attributed to M Marchi.

At least 19 recordsLinked to original sources
PubMed2003

Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen, or vindesine plus tamoxifen: a prospective randomized study.

This study aimed to verify whether the advantage in terms of response rate and survival of dacarbazine plus tamoxifen over dacarbazine alone in metastatic malignant melanoma reported in a previous randomized trial was due to a specific interaction of dacarbazine with tamoxifen. A total of 125 patients with locoregional or disseminated malignant melanoma were randomized to receive dacarbazine (250 mg/m(2) days 1-5 every 3 weeks) plus tamoxifen (arm A) or vindesine (3 mg/m(2) every week for 6 weeks, then every 2 weeks) plus tamoxifen (arm B). Of the 125 randomized patients, 57 and 59 were evaluable in arm A and B, respectively. The complete response rates were the same (2% versus 2%) and the complete plus partial response rates were similar (11% versus 14%) in the two groups. There was no significant difference in survival. Neither response or survival correlated with gender. In conclusion, when combined with tamoxifen, dacarbazine does not have a specific effect on response or survival compared with vindesine. The lower response rate to dacarbazine plus tamoxifen (11%) than that reported in the previous trial (28%) might be explained by actual differences in patient and/or participating centre accrual characteristics in the presence of apparently identical eligibility criteria.

Adult↗
PubMed2002

Detection of early ischemia in severe head injury by means of arteriovenous lactate differences and jugular bulb oxygen saturation. Relationship with CPP, severity indexes and outcome. Preliminary analysis.

UNLABELLED: Early ischemia may be highly relevant in patients with severe head injuries. The aims of the study were: 1) to define if abnormal arteriovenous lactate difference (AVDL) and jugular bulb oxygen saturation (SjO2) are found in the early 24 hrs post injury; 2) to compare if abnormalities of SjO2 and of AVDL were associated with a specific typology of severity indexes and outcome; 3) to detect any association between abnormal AVDL and SjO2 with levels of cerebral perfusion pressure (CPP). The study involved 29 patients, with CPP, AVDL and SjO2 measured within 24 hours post-injury. RESULTS: 1) Abnormal AVDL was found in 21% while abnormal SjO2 was detected in 38% of the patients; 2) abnormal AVDL was associated with cases of most severe injury; 3) CPP level below 60 mmHg was associated with abnormal AVDL and SjO2. Low CPP appeared to be the most likely measurable cause of early ischemia. Abnormalities of AVDL appeared to be more sensitive, than SjO2, with regard to detection of the most severe cases.

Adult↗
PubMed2002

Ultrasound measurement of visceral and subcutaneous fat in morbidly obese patients before and after laparoscopic adjustable gastric banding: comparison with computerized tomography and with anthropometric measurements.

BACKGROUND: There are now a variety of methods to assess body fat distribution, anthropometric (waist circumference and waist/hip W/H ratio), computed tomography (CT), and ultrasound (US) measurements, with CT considered as the reference method. Bariatric surgery leads to a significant and usually durable weight loss in morbidly obese patients; when assessing its results, it is of interest to measure changes of total fat tissue and of body fat distribution. METHODS: In this study, we compared anthropometric, US, and CT measurements of body fat distribution under basal conditions and 1 year after laparoscopic adjustable gastric banding (LAGB); 120 morbidly obese patients were considered at baseline, and 40 patients were re-evaluated 1 year after LAGB. RESULTS: Thickness of visceral and subcutaneous fat measured through CT and US methods was superimposable both under basal conditions and 1 year after LAGB, and the highest correlation was found between CT and US data on visceral fat, followed by CT and US data on subcutaneous fat; a fair correlation was also found between CT and US data on visceral fat and waist circumference. CONCLUSION: We suggest that evaluation of body fat distribution is accomplished by US instead of CT measurement, because of its lower cost and low exposure risk. Waist circumference stands as a reasonable surrogate of both methods, while W/H ratio is poorly correlated with other measures of body fat distribution.

Adipose Tissue↗
PubMed2001

Dynamics of hydration in hen egg white lysozyme.

We investigate the hydration dynamics of a small globular protein, hen egg-white lysozyme. Extensive simulations (two trajectories of 9 ns each) were carried out to identify the time-scales and mechanism of water attachment to this protein. The location of the surface and integral water molecules in lysozyme was also investigated. Three peculiar temporal scales of the hydration dynamics can be discerned: two among these, with sub-nanosecond mean residence time, tau(w), are characteristic of surface hydration water; the slower time-scale (tau(w) approximately 2/3 ns) is associated with buried water molecules in hydrophilic pores and in superficial clefts. The computed tau(w) values in the two independent runs fall in a similar range and are consistent with each other, thus adding extra weight to our result. The tau(w) of surface water obtained from the two independent trajectories is 20 and 24 ps. In both simulations only three water molecules are bound to lysozyme for the entire length of the trajectories, in agreement with nuclear magnetic relaxation dispersion estimates. Locations other than those identified in the protein crystal are found to be possible for these long-residing water molecules. The dynamics of the hydration water molecules observed in our simulations implies that each water molecule visits a multitude of residues during the lifetime of its bound with the protein. The number of residues seen by a single water molecule increases with the time-scale of its residence time and, on average, is equal to one only for the water molecules with shorter residence time. Thus, tau(w) values obtained from inelastic neutron scattering and based on jump-diffusion models are likely not to account for the contribution of water molecules with longer residence time.

Animals↗
PubMed2001

Comment on "Efficient stress relaxation in molecular dynamics simulations of semiflexible n-alkanes".

Contrary to the findings of Mülders, Toxvaerd, and Kneller [Phys. Rev. E 58, 6766 (1998)] (MTK), we are unable to discern any difference in the behavior of long chain alkanes simulated by molecular dynamics at constant pressure using either atomic or molecular scaling schemes. This result confirms our previous study [M. Marchi and P. Procacci, J. Chem. Phys. 109, 5194 (1998)] on hydrated proteins published at the same time as the MTK's paper. This Comment indicates that errors in the calculation of the pressure tensor might be responsible for at least a part of the MTKs results.

Letter↗
PubMed2001

Temporal profile of serum anti-inflammatory and pro-inflammatory interleukins in acute ischemic stroke patients.

The presence of an inflammatory response in the pathophysiology of acute brain ischemia is relatively well established, but less is known about the anti-inflammatory mechanisms. The aim of the present study was to evaluate part of the immune response in acute stroke patients and to analyze a possible correlation with other hematological parameters, clinical outcome, size of infarct and subtypes of strokes. We prospectively studied 42 stroke patients, without signs of infections or inflammatory diseases, at days 0, 1, 3, 7 and 14, and 39 healthy control subjects. We measured serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) and the pro-inflammatory cytokine interleukin-6 (IL-6) by ELISA method. We observed a highly inverse correlation between these two molecules in control subjects (r=-0.78, p=0.0000001), and this correlation was lost in stroke patients. Patients had significantly lowered IL-10 serum levels soon after the acute event (p=0.00005), with a slight increase at the seventh day. On the other hand, patients had increased IL-6 serum levels compared with controls after day one until day 14 (p<0.04), with a maximum increase at day 3. Interleukin-6 correlated with clinical outcome whereas interleukin-10 did not. Low levels of interleukin-10 indicate that the antiinflammatory response is down-regulated in acute stroke patients. The pro-inflammatory response begins 24 hours after the onset of acute cerebral ischemia, as indicated by the increased serum levels of interleukin-6. The physiological balance between these two molecules is altered in acute stroke patients.

Acute Disease↗
PubMed2001

In vivo NO/cGMP signalling in the hippocampus.

In the hippocampus of freely-moving rats, basal extracellular levels of cGMP are inhibited by L-NARG or ODQ whereas they are increased by NO donors or phosphodiesterase inhibitors. Activation of NMDA receptors also augments cGMP dialysate levels in a MK-801 and L-NARG sensitive manner, an effect dramatically diminished during ageing. Experiments with AMPA, AMPA receptor antagonists and cyclothiazide revealed complex relationships with GABAergic circuits that potently control the NO/cGMP pathway. Furthermore, the activity of this neurochemical cascade is also modulated by hippocampal nicotinic receptors via enhancement of endogenous glutamate release and stimulation of NMDA receptors. From a behavioural point of view, increased hippocampal excitation leads to the appearance of epileptic-like manifestations that, however, seem unrelated to the increase of NO/cGMP formation.

Aging↗
PubMed2000

Study of the bidirectional transport of choline by blocking choline carriers from outside or inside brain nerve terminals.

Membrane carriers can operate bidirectionally. We studied, in rat neocortex synaptosomes, the choline carrier by comparing the ability of the transport inhibitor hemicholinium-3, present outside or inside the nerve terminals, to prevent uptake and release of [(3)H]choline. Because hemicholinium-3 is membrane-impermeable, it was previously entrapped into synaptosomes during homogenization of brain tissue. External and internalized hemicholinium-3 produced similar maximal inhibition (80-90%) of [(3)H]choline uptake. Also comparable (approximately 30 nM) are the potency of externally applied hemicholinium-3 and the estimated potency of the entrapped inhibitor. Exposure to ouabain elicited release of both [(3)H]acetylcholine and [(3)H]choline from synaptosomes prelabeled with [(3)H]choline. The ouabain (300 microM)-evoked release of [(3)H]choline only was blocked by externally added (IC(50) approximately 10 nM) or internalized (estimated IC(50) approximately 5 nM) hemicholinium-3. Release of previously taken up [(3)H]choline elicited by 100 microM external choline (homoexchange) was prevented by external (IC(50) approximately 30 microM) or entrapped (estimated IC(50) approximately 20 microM) hemicholinium-3. The results suggest that the choline carriers fit into the alternating-access model proposed for classical transmitter transport. Entrapping nonpermeant ligands into synaptosomes could allow investigation of the inward-facing conformation of native transporters and how cytoplasmic ligands affect the bidirectional transport of neurotransmitters.

Acetylcholine↗
PubMed1999

Granulocyte-macrophage colony-stimulating factor induces expression of heparin-binding epidermal growth factor-like growth factor/diphtheria toxin receptor and sensitivity to diphtheria toxin in human neutrophils.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a widely expressed EGF superfamily member that induces mitogenic and/or chemotactic activities toward different cell types through binding to EGF receptors 1 or 4. Membrane-bound HB-EGF exerts growth activity and adhesion capabilities and possesses the unique property of being the receptor for diphtheria toxin (DT). Using molecular and functional techniques, we show that human polymorphonuclear granulocytes (PMN), which did not express HB-EGF in resting conditions, expressed it at mRNA and protein level, following incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF). Other classic agonists for PMN (including lipopolysaccharide, phagocytable particles, tumor necrosis factor-alpha, or G-CSF) failed to induce HB-EGF. The effects of GM-CSF on HB-EGF mRNA levels were concentration-dependent, reached a plateau after 1 to 2 hours of stimulation, and did not require protein synthesis. After GM-CSF treatment, membrane-bound HB-EGF was detected by flow cytometry. At the same time, PMN acquired sensitivity to the apoptosis-promoting effect of DT, which, moreover, specifically suppressed the GM-CSF-induced priming of formyl-methionyl-leucyl-phenylalanine-stimulated superoxide anion release. Finally, soluble HB-EGF was detected in the PMN culture medium by a specific enzyme-linked immunosorbent assay. Thus, we provide evidence that HB-EGF is specifically inducible by GM-CSF in PMN and represents a novel peptide to be included in the repertoire of PMN-derived cytokines.

Diphtheria Toxin↗
PubMed1999

Interleukin-10 (IL-10) selectively enhances CIS3/SOCS3 mRNA expression in human neutrophils: evidence for an IL-10-induced pathway that is independent of STAT protein activation.

We have recently shown that, in human neutrophils, interleukin-10 (IL-10) fails to induce specific DNA-binding activities to the gamma-interferon response region (GRR), a regulatory element located in the FcgammaRI gene promoter, which is required for transcriptional activation by IL-10 and interferon gamma (IFNgamma) in monocytic cells. In this study, we report that IL-10 is also unable to induce the binding of STAT1 or STAT3 to the serum-inducible element (hSIE/m67), despite the fact that both proteins are expressed in neutrophils. Whereas IFNgamma and granulocyte colony-stimulating factor (G-CSF) are efficient inducers of STAT1 and STAT3 tyrosine phosphorylation in polymorphonuclear neutrophils (PMN), IL-10 fails to trigger STAT1 and STAT3 tyrosine and serine phosphorylation, therefore explaining its inability to induce the FcgammaRI expression in these cells. By contrast, we demonstrate that IL-10 alone represents an efficient stimulus of CIS3/SOCS3 mRNA expression in neutrophils. CIS3/SOCS3 belongs to the recently cloned cytokine-inducible SH2-containing protein (CIS) gene family (which also includes CIS1, CIS2, CIS4, CIS5, and JAB) that is believed to be, at least in part, under the control of STAT transcription factors and whose products are potential modulators of cytokine signaling. Moreover, IL-10 synergizes with lipopolysaccharide (LPS) in upregulating CIS3/SOCS3 mRNA expression in PMN through a mechanism that involves mRNA stabilization. In contrast to CIS3/SOCS3, mRNA transcripts encoding other family members are unaffected by IL-10 in neutrophils. Finally, transfection of CIS3/SOCS3 in murine M1 myeloid cells suppresses LPS-induced growth arrest, macrophage-like differentiation, and nitric oxide synthesis, but not IL-6 mRNA expression. Collectively, our data suggest that, in neutrophils, the activation of STAT1 and STAT3 phosphorylation is neither required for CIS3/SOCS3 induction by IL-10 nor involved in the regulatory effects of IL-10 on cytokine production.

Animals↗
PubMed1999

An approximate CUSUM procedure for surveillance of health events.

The CUSUM method is frequently used by epidemiologists for detecting a shift in the incidence of rare health events. An exact solution for a Poisson process has been proposed by other works, but potential applications have been limited by the fact that the size, the structure of the at-risk population and the baseline rate may not be constant during the period of surveillance. Furthermore, for practical use tables of critical values are available only for some expected values and in any case less then 9. This paper proposes an approximate CUSUM procedure, based on the normal approximation to a Poisson process, which may be an efficient solution of the problems previously pointed out. Analyses of simulated and actual data sets illustrate the usefulness of the proposed procedure. An application to mortality data for respiratory diseases in a north Tuscany area, characterized by the presence of chemical plants, is showed. No shift in the mortality rate during the 1980-1989 period was detected compared with the 1970-1979 period, in contrast with the result obtained with the standard CUSUM method for a Poisson variate.

Air Pollutants↗
PubMed1999

Intracerebral administration of L-kynurenine decreases N-methyl-D-aspartate receptor-mediated production of cGMP in the cerebellum and hippocampus of unanaesthetized rats subjected to transcerebral microdialysis.

The effects of intracerebral administration of L-kynurenine (L-KYN) on the N-methyl-D-aspartate (NMDA) receptor-mediated, nitric oxide (NO)-dependent cGMP responses have been studied in vivo in the cerebellum and hippocampus of freely-moving rats subjected to transcerebral microdialysis. Administration of exogenous NMDA in the cerebellum through the dialysis probe evoked a 3-fold increase of basal extracellular levels of cGMP that was concentration-dependently reduced by co-infusion of L-KYN. In the hippocampus, local administration of cyclothiazide caused a significant enhancement of the cyclic nucleotide dialysate concentrations that was accompanied by behavioural manifestations characteristic of preconvulsive states. Co-infusion of L-KYN largely decreased the neurochemical effects of cyclothiazide and completely prevented the appearance of the behavioural episodes. It is concluded that administration of L-KYN by increasing endogenous kynurenic acid concentrations might exert neuroprotective and anticonvulsive effects through blockade of the NMDA receptor/NO/cGMP pathway.

Animals↗
PubMed1999

Gene expression and production of the monokine induced by IFN-gamma (MIG), IFN-inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma-inducible protein-10 (IP-10) chemokines by human neutrophils.

Monokine induced by IFN-gamma (MIG), IFN-inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma-inducible protein of 10 kDa (IP-10) are related members of the CXC chemokine subfamily that bind to a common receptor, CXCR3, and that are produced by different cell types in response to IFN-gamma. We have recently reported that human polymorphonuclear neutrophils (PMN) have the capacity to release IP-10. Herein, we show that PMN also have the ability to produce MIG and to express I-TAC mRNA in response to IFN-gamma in combination with either TNF-alpha or LPS. While IFN-gamma, alone or in association with agonists such as fMLP, IL-8, granulocyte (G)-CSF and granulocyte-macrophage (GM)-CSF, failed to influence MIG, IP-10, and I-TAC gene expression, IFN-alpha, in combination with TNF-alpha, LPS, or IL-1beta, resulted in a considerable induction of IP-10 release by neutrophils. Furthermore, IL-10 and IL-4 significantly suppressed the expression of MIG, IP-10, and I-TAC mRNA and the extracellular production of MIG and IP-10 in neutrophils stimulated with IFN-gamma plus either LPS or TNF-alpha. Finally, supernatants harvested from stimulated PMN induced migration and rapid integrin-dependent adhesion of CXCR3-expressing lymphocytes; these activities were significantly reduced by neutralizing anti-MIG and anti-IP-10 Abs, suggesting that they were mediated by MIG and IP-10 present in the supernatants. Since MIG, IP-10, and I-TAC are potent chemoattractants for NK cells and Th1 lymphocytes, the ability of neutrophils to produce these chemokines might contribute not only to the progression and evolution of the inflammatory response, but also to the regulation of the immune response.

Apoptosis↗
PubMed1999

Nicotinic receptors modulating ACh release in rat cortical synaptosomes: role of Ca2+ ions in their function and desensitization.

Cholinergic nerve terminals in the central nervous system are endowed with both muscarinic and nicotinic autoreceptors, mediating inhibition, and enhancement of acetylcholine release, respectively. Exogenous acetylcholine inhibited the K+(15 mM)-evoked overflow of [3H]acetylcholine from superfused rat neocortical synaptosomes; however, in the presence of atropine, this muscarinic inhibition was reversed into a nicotinic potentiation when acetylcholine was added concomitantly with high-K+, but not before depolarization. Increasing concentrations of acetylcholine (plus atropine), nicotine and (+)-anatoxin-a produced elevations of the K+-evoked [3H]acetylcholine overflow resulting in bell-shaped concentration-response curves. Synaptosomes pretreated with different concentrations (10 microM to 0.001 microM) of acetylcholine or nicotine responded to a subsequent nicotinic stimulus (10 microM acetylcholine plus 0.1 microM atropine, in 15 mM K+) in a manner reflecting varying degrees of desensitization. This desensitization could be reversed by washings with standard medium and desensitization was attenuated when external Ca2+ ([Ca2+]e) was decreased. Lowering of [Ca2+]e or chelation of internal Ca2+ with 1,2-bis(2-aminophenoxy)ethone-N,N,N',N'-tetracetic acid acetoxymethylester (BAPTA-AM) permitted the nicotinic response to acetylcholine alone (no atropine added) to prevail over the muscarinic response. Pretreatment with BAPTA-AM could however not prevent desensitization by acetylcholine (10 or 0.001 microM). The data indicate that Ca2+ ions are involved in determining the balance between muscarinic and nicotinic autoreceptor function and in the desensitization of nicotinic autoreceptors.

Acetylcholine↗
PubMed1999

Evidence for calcium-dependent vesicular transmitter release insensitive to tetanus toxin and botulinum toxin type F.

Whether exocytosis evoked by a given releasing stimulus from different neuronal families or by different stimuli from one neuronal population occurs through identical mechanisms is unknown. We studied the release of [3H]noradrenaline, [3H]acetylcholine and [3H]dopamine induced by different stimuli from superfused rat brain synaptosomes pretreated with tetanus toxin or botulinum toxin F, known to block exocytosis by cleaving VAMP/synaptobrevin. The external Ca2(+)-dependent [3H]transmitter overflows evoked by KCl were similarly inhibited by tetanus toxin or botulinum toxin F; the toxins cleaved similar amounts of synaptosomal synaptobrevin, as determined by western blot analysis, suggesting prevalent involvement of synaptobrevin-II. GABA uptake-mediated release of the three [3H]transmitters was that differentially sensitive to the toxins: only the release of [3H]noradrenaline, which is dependent on external Ca2+, but not of [3H]acetylcholine and [3H]dopamine was blocked. Neither toxin affected the [3H]transmitter overflows evoked by the Ca2(+) ionophore ionomycin. Cadmium blocked the K(+)-evoked release of all [3H]transmitters and the GABA-evoked release of [3H]noradrenaline; the GABA-evoked releases of [3H]acetylcholine and [3H]dopamine and those elicited by ionomycin were insensitive to cadmium. The results suggest that tetanus toxin and botulinum toxin F selectively affect exocytosis linked to activation of voltage-sensitive Ca2(+) channels; the Ca2(+)-dependent, exocytotic-like release induced by stimuli not leading to activation of voltage-sensitive Ca2+ channels seems insensitive to these clostridial toxins.

Animals↗
PubMed1999

Methodological problems and the role of statistics in cluster response studies: a framework.

More and more citizens urge public health authorities to investigate reports of disease excess in their neighbourhood. These environmental concerns are legitimate and it is part of good public health practice to respond to these complaints. However, the methodological and practical problems are severe and a lot of controversy exists about the usefulness of these investigations. To clarify the possibilities and limitations in this situation, this paper proposes a typology of cluster studies. According to this framework, cluster response is distinguished from two other types of cluster studies: Cluster monitoring. screening proactively for clusters to act as an early warning system, and cluster research, scrutinizing clustering to generate and test aetiological hypotheses. To each of these three types of cluster studies corresponds a different public health context; respectively public health action, public health surveillance and public health research. Probably, part of the controversy mentioned stems from not acknowledging sufficiently the corresponding intrinsic differences in rationality and practical constraints. Cluster response is crisis management and not scientific research. In a relatively short time, an informed decision should be taken by a multidisciplinary team of experts using readily available information and knowledge. In accordance with this point of view, cluster reports should be handled stepwise and the role of statistics is to quantify a cluster exploring different points of view as an input to the decision process.

Cluster Analysis↗
PubMed1998

Prematurely detected traumatic carotid-cavernous sinus fistula, by means of unintentional contralateral inferior petrosal sinus catheterization: bilateral jugular bulb oxygen saturation findings.

A traumatic carotid-cavernous sinus fistula (CCSF) was prematurely suspected following the detection of arterial-like hemoglobin oxygen saturation values, sampled from a catheter placed for cerebrovenous monitoring. A high-resolution scan of jugular foramina revealed that the catheter tip had been unintentionally placed in the inferior petrosal sinus, contralateral to the CCSF, instead of in the superior jugular bulb. Jugular bulb hemoglobin oxygen saturation (SjO2), ipsilateral to CCSF, later approached arterial hemoglobin oxygen saturation (SaO2) values.The possibility and consequences of unintentional catheterization of the inferior petrosal sinus, and of extracerebral contamination of blood in the jugular bulb due to blood in the inferior petrosal sinus, are discussed. We also discuss the reliability of SjO2 monitoring in the present CCSF case.

Carotid Sinus↗