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Biomedical subjects

F Rossi

Publications and source records attributed to F Rossi.

At least 163 records · Page 9Linked to original sources
PubMed1999

Bioequivalence assessment of two different tablet formulations of diltiazem after single and repeated doses in healthy subjects.

The study was performed on 14 healthy volunteers in order to compare the pharmacokinetics and hence assess the bioequivalence of two different tablet formulations of diltiazem administered orally. The study was carried out after single doses (60 mg) and repeated doses (60 mg three times a day for six days and 60 mg on the seventh day) according to a randomised, cross-over, open design. The pharmacokinetic parameters AUC0-infinity (ng h/ml), Tmax(h) and Cmax (ng/ml) were calculated for the two formulations after a single dose, while AUCt1-t2 (= AUC for a repetitive dose interval or dosing cycle, ng h/ml) and PTF (peak trough fluctuation) were calculated after repeated doses. The bioequivalence assessment was the shortest 90% confidence interval for the ratio (difference) of expected medians in the respective bioequivalence range (0.80-1.20). The results of this study show that, after either a single dose or repeated doses of test or reference formulations of diltiazem, the pharmacokinetics of the two formulations are similar. The ratios of AUC on day 1 (for single-dose treatment) and on day 7 (for repeated-dose treatment), and the corresponding 90% confidence intervals demonstrate bioequivalence between the two formulations of diltiazem within the accepted range of 0.80-1.20 (80-120%).

Adult↗
PubMed1999

Topographic differences in task-dependent facilitation of magnetic motor evoked potentials.

OBJECTIVE: To look for differences in task-dependent facilitation of magnetic motor evoked potentials (MEPs) in proximal and distal upper extremity muscles. BACKGROUND: Postexercise facilitation of MEPs has been demonstrated repeatedly in forearm muscles. Proximal muscles are prominently involved in limb stabilization, a largely isometric activity. In contrast, distal hand muscles specialize in precision movements. Based on these functional differences between proximal and distal muscles, we postulated that there might be topographic differences in task-dependent facilitation of MEPs. METHODS: We studied the effects of isometric exercise and a precision grip task on MEPs in proximal and distal upper extremity muscles. RESULTS: Isometric exercise of the target muscle was associated with significant facilitation of MEPs in biceps and extensor carpi radialis muscles, but not in first dorsal interosseous or abductor digiti minimi muscles. In contrast, a precision grip task was associated with significant post-task facilitation of MEPs in first dorsal interosseous, but not in extensor carpi radialis. CONCLUSIONS: These differences in the facilitation of MEPs depending on the motor task and whether the muscle is proximal or distal may reflect the relative importance of proximal muscles in maintaining posture.

Adult↗
PubMed1999

Mechanisms of axonal plasticity.

GAP-43 plays an important role in axonal plasticity by guiding growth cones rather than supporting axonal elongation. In Purkinje cells that show no regenerative responses and no GAP-43 expression after axotomy, the simple addition of GAP-43 gene induces the formation of branched plexuses typical of sprouting growth. Purkinje cells can express some growth-associated proteins, but never GAP-43, when axotomy is made very close to cell body or when an antibody for the myelin-associated inhibitory molecules is applied to intact cells both in vivo and in vitro. Also in these conditions they are unable to show new axonal profiles even in a permissive environment that allows inferior olive cells to regenerate and reinnervate their target cells. We suggest that GAP-43 is a key molecule to initiate axon growth while other genes are necessary to develop a full regenerative program.

Animals↗
PubMed1999

Effect of hyperbaric oxygen therapy in experimental subcutaneous and pulmonary infections due to Pseudomonas aeruginosa.

About 80% of nosocomial infections are caused by aerobic bacteria. Pseudomonas aeruginosa is a Gram-negative bacterium belonging to the Pseudomonadaceae family; P. aeruginosa is responsible for 6-22% of all hospital infections. The aim of this study was to evaluate the efficacy of hyperbaric oxygen (HBO2) therapy (2 atm abs x 55 min.day-1) alone for 8 days and combined with antibiotic chemotherapy (amikacin 15 mg.kg-1.day-1 for 8 days by intraperitoneal route) in rats infected subcutaneously and via the pulmonary route. In the rats infected by P. aeruginosa, HBO2 induced a reduction in mortality and morbidity with bacteria eradication in blood culture, bronchial aspirate, and skin biopsies when compared to control. These effects were increased by the use of amikacin, an antibiotic used for the treatment of sensitive Gram-negative bacteria.

Amikacin↗
PubMed1999

[Pharmacology of ritodrine].

Tocolytic drugs are used in order to delay or to abolish preterm labour. These drugs inhibit uterine contractions and have different pharmacological properties. The most used tocolytic agents today are beta 2-adrenergic agonists (isoxuprine, ritodrine). The pharmacological actions, pharmacokinetics, toxicological and clinical aspects of ritodrine, a synthetic beta 2-adrenergic agonist with tocolytic properties are described. Findings of many clinical trials are also discussed.

Adrenergic beta-Agonists↗
PubMed1999

A persistent severe autoimmune hemolytic anemia despite apparent direct antiglobulin test negativization.

BACKGROUND AND OBJECTIVE: Not all cases of autoimmune hemolytic anemia (AIHA) are diagnosed by the direct antiglobulin test (DAT). We present and discuss a simple method of enhancing the sensitivity of the standard DAT. DESIGN AND METHODS: We report the case of a five-month-old child diagnosed with a severe IgG-mediated AIHA, characterized by quick DAT negativization despite clinical worsening. Warm AIHA with negative DAT, possibly due to a low affinity autoantibody, unresponsive to conventional therapy, was hypothesized. RESULTS: The DAT resulted strongly positive with anti-IgG serum using a 4C saline for erythrocyte washing, to reduce the dissociation of the supposed low affinity autoantibody. Very intensive cytoreductive treatment was administered twice until clinical remission was obtained. INTERPRETATION AND CONCLUSIONS: The clinical course of AIHA can be dissociated by the DAT. Since autoantibody-mediated hemolysis with negative DAT rarely occurs, once other causes of high reticulocyte count anemia have been ruled out, the DAT after ice-cold saline washing could be a useful and easy means of corroborating the diagnosis of AHIA, when traditional methods fail.

Anemia, Hemolytic, Autoimmune↗
PubMed1998

Nicotinamide-adenine dinucleotide phosphate oxidase assembly and activation in EBV-transformed B lymphoblastoid cell lines of normal and chronic granulomatous disease patients.

This paper deals with the mechanisms of activation of NADPH oxidase investigated using EBV-transformed human B lymphoblastoid cell lines (B cells) from normal subjects and from patients affected by X-linked chronic granulomatous disease (CGD). The results reported are as follows. 1) In normal B cells, the NADPH oxidase components p67phox, p40phox, p22phox, and gp91phox were less expressed than in polymorphonuclear neutrophils. 2) In normal B cells stimulated with PMA, p47phox, p67phox, and p40phox translocated to the membranes as occurs in polymorphonuclear neutrophils. 3) In CGD, B cells expressing p22phox in the absence of gp91phox, p47phox, p67phox, and p40phox did not translocate to the membranes after stimulation with PMA. 4) In PMA-stimulated B cells from an X91+ CGD patient in which p22phox was normally expressed and gp91phox was present but lacked five amino acids, translocation of p47phox to the membranes was unaffected, but p67phox and p40phox were poorly translocated, and the production of O2- was greatly reduced with respect to that by normal B cells. Taken together, these findings indicate that 1) a low expression of some NADPH oxidase components may represent the molecular basis of the low production of O2- in B lymphocytes; 2) the cytosolic components of NADPH oxidase cannot bind to p22phox on the membranes in the absence of gp91phox; 3) p47phox can translocate to the membranes independently of p67phox and p40phox; and 4) gp91phox may have a role in mediating and/or stabilizing the binding of p67phox and p40phox to the membranes of activated cells.

B-Lymphocytes↗
PubMed1998

Retrograde regulation of growth-associated gene expression in adult rat Purkinje cells by myelin-associated neurite growth inhibitory proteins.

Axon regeneration requires that injured neurons reinitiate long-distance growth and upregulate specific genes. To address the question of whether inhibitory environmental cues along the axon could exert a negative, tonic downregulation of growth-associated genes, we have examined adult rat Purkinje cells, which are endowed with poor regenerative capabilities. First we have compared their response to axotomy with that of neurons of the inferior olive, lateral reticular nucleus, and deep cerebellar nuclei, all of which vigorously regenerate into growth-permissive transplants. These injured neurons upregulate the transcription factors c-Jun and JunD, GAP-43, and NADPH diaphorase. In contrast, most axotomized Purkinje cells fail to express any of these markers, showing that the strength of this response parallels the regenerative potential of the examined neuron populations. However, strong upregulation of the same genes can be induced in Purkinje cells after colchicine injection into the uninjured adult cerebellum, indicating that their expression could be controlled by retrograde signals. To assess whether myelin-associated neurite growth inhibitory proteins contribute to this regulation, we applied the neutralizing antibodies IN-1 against one of the main inhibitory components of central myelin (NI-250) either in vivo or in vitro to organotypic cerebellar cultures. Application of IN-1 antibodies induces the upregulation of c-Jun, JunD, and NADPH diaphorase in Purkinje cells, showing that their expression is suppressed constitutively by myelin-associated neurite growth inhibitors. Thus, the inhibitory activity of the IN-1 antigen on axon growth is not restricted to the control of growth cone motility but also involves a retrograde regulation of gene expression in adult central neurons.

Age Factors↗
PubMed1998

Cultured human monocytes release proinflammatory cytokines in response to myelin basic protein.

In human cultured monocytes we examined the ability of myelin basic protein (MBP) to induce the production of proinflammatory cytokines potentially involved in inflammatory demyelination. Northern blots and specific immunoassays demonstrated that monocytes incubated with optimal doses of MBP showed increased mRNA expression and release of tumor necrosis factor (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8) but not of interleukin-12/p40 (IL-12/p40). We also showed that cytokine production by MBP-stimulated monocytes was abrogated by incubation with Dexamethasone. These data suggest that interaction of mononuclear phagocytes with MBP may participate in the regulatory process of cytokine production during inflammatory demyelination and support the beneficial role of corticosteroids therapy in aberrant immune responses to the myelin sheath.

Animals↗
PubMed1998

Neuronorm is a potent and water soluble neurokinin A receptor antagonist.

We report here the synthesis and preliminary pharmacological characterization of a novel water soluble Neurokinin A receptor antagonist named Neuronorm. The synthesis was achieved in high yield by a combination of classical peptide synthesis methodologies, in both solution and solid phase. The pharmacological properties as neurokinin A receptor antagonist were assessed in in vitro experiments on rat vas deferens and guinea pig trachea, and were compared to those of MEN10627.

Animals↗
PubMed1998

Interaction between the N-terminal domain of human DNA topoisomerase I and the arginine-serine domain of its substrate determines phosphorylation of SF2/ASF splicing factor.

Human DNA topoisomerase I, known for its DNA-relaxing activity, is possibly one of the kinases phosphorylating members of the SR protein family of splicing factors, in vivo. Little is known about the mechanism of action of this novel kinase. Using the prototypical SR protein SF2/ASF (SRp30a) as model substrate, we demonstrate that serine residues phosphorylated by topo I/kinase exclusively located within the most extended arginine-serine repeats of the SF2/ASF RS domain. Unlike other kinases such as cdc2 and SRPK1, which also phosphorylated serines at the RS domain, topo I/kinase required several SR dipeptide repeats. These repeats possibly contribute to a versatile structure in the RS domain thereby facilitating phosphorylation. Furthermore, far-western, fluorescence spectroscopy and kinase assays using the SF2/ASF mutants, demonstrated that kinase activity and binding were tightly coupled. Since the deletion of N-terminal 174 amino acids of Topo I destroys SF2/ASF binding and kinase activity but not ATP binding, we conclude that at least two distinct domains of Topo I are necessary for kinase activity: one in the C-terminal region contributing to the ATP binding site and the other one in the N-terminal region that allows binding of SF2/ASF.

Adenosine Triphosphate↗
PubMed1998

The C-terminal domain but not the tyrosine 723 of human DNA topoisomerase I active site contributes to kinase activity.

Human DNA topoisomerase I not only has DNA relaxing activity, but also splicing factors phosphorylating activity. Topo I shows strong preference for ATP as the phosphate donor. We used photoaffinity labeling with the ATP analogue [alpha-32P] 8-azidoadenosine-5'-triphosphate combined with limited proteolysis to characterize Topo I domains involved in ATP binding. The majority of incorporated analogue was associated with two fragments derived from N-terminal and C-terminal regions of Topo I, respectively. However, mutational analysis showed that deletion of the first 138 N-terminal residues, known to be dispensable for topoisomerase activity, did not change the binding of ATP or the kinase activity. In contrast, deletion of 162 residues from the C-terminal domain was deleterious for ATP binding, kinase and topoisomerase activities. Furthermore, a C-terminal tyrosine 723 mutant lacking topoisomerase activity is still able to bind ATP and to phosphorylate SF2/ASF, suggesting that the two functions of Topo I can be separated. These findings argue in favor of the fact that Topo I is a complex enzyme with a number of potential intra-cellular functions.

Adenosine Triphosphate↗
PubMed1998

A novel super-potent neurokinin A receptor antagonist containing dehydroalanine.

We report here the synthesis and preliminary pharmacological characterization of a novel Neurokinin A receptor antagonist. This molecule contains a dehydroalanine residue. It displays a high conformational rigidity and possesses very high activity. Its pharmacological properties as a neurokinin A receptor antagonist were assessed in in vitro experiments on rat vas deferens and were compared to those of Neuronorm and MEN10627.

Alanine↗
PubMed1998

Depressor responses to endothelin-1 into the superior colliculus of rats: predominant role of endothelin ET(B) receptors.

We used in vitro autoradiography to identify the endothelin-1 receptor subtype(s) in the superficial gray layer of the superior colliculus of rats. These studies showed dense binding of (3-[125I]iodotyrosyl13)-[Ala11,15]Ac-endothelin-1-(6-2 1) (BQ3020) (for endothelin ETB receptors), while tissues incubated with [125I]( N-(hexahydro-1-azepinyl)carbonyl)L-Leu(1-Me)D-Trp-D-Tyr (PD151242) (for endothelin ETA receptors) had low binding. In addition, we examined the effects of the endothelin receptor antagonists, (R)-2-[(R)-2-[(S)-2-[[1-hexahydro-1H-azepinyl)]carbonyl]amino-4-++ +methylpentanoyl]-amino-3-(2-pyridyl)propionic acid (FR139317) (endothelin ETA receptor-selective), (+)-(1S,2R,3S)-3-(2-carboxymethoxy-4-methoxyphenyl)-1-(3,4-methylenediox yphenyl)-5-(prop-1-yloxy)indane-2-carboxylic acid (SB209670) (endothelin ETA/ETB receptor non-selective) and N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-metLeu-D-1-m ethoxycarbonylTrp-D-Nle (BQ-788) (endothelin ETB receptor-selective antagonist) on the responses following administration of endothelin-1 into the superficial layer of the superior colliculus. Endothelin-1 microinjected into this nucleus causes decreases in blood pressure (control, 109 +/- 6 mmHg, n = 6; endothelin-1, 72 +/- 5 mmHg, n = 6). These effects were greatly reduced by pre-administration into the superior colliculus of BQ-788 (5 nmol/rat) or SB209670 (3 nmol/rat) (94 +/- 5 and 98 +/- 6%, respectively) but were not affected by FR139317 (5 nmol/rat) (6 +/- 3%). Therefore, together with autoradiography, our functional data showed that endothelin ETB receptors are the predominant mediators of depressor responses induced by endothelin-1 injected into the superior colliculus of the rat.

Animals↗
PubMed1998

Nitric oxide synthesis does not affect depressor responses induced by endothelin-1 into the superior colliculus of rats.

A microinjection of endothelin-1 (ET-1; 10 pmol) into the superior colliculus (SC) of anaesthetised rats caused a decrease in blood pressure. Microinjection into the same nucleus of Nomega-nitro-L-arginine methyl ester (L-NAME; 0.1, 0.5, 1 micromol), an L-arginine analogue and a potent inhibitor of nitric oxide (NO) synthase, increased the basal mean arterial blood pressure. Treatment of SC with L-NAME (1 micromol) did not affect the depressor response induced by injection of ET-1 (10 pmol), into the SC, at the peak of the pressor response to L-NAME. In addition, L-arginine L-ARG) (1 micromol), the substrate for NO synthase, microinjected into the superior colliculus prior to ET-1 did not significantly increase the depressor response to ET-1. These findings, therefore, suggest that within the SC the nitric oxide synthesis does not affect depressor responses induced by ET-1.(c) 1998 The Italian Pharmacological Society

Animals↗
PubMed1998

Pharmacology of nebivolol.

Nebivolol is a new selective beta 1-adrenergic blocking agent, that possesses a peculiar pharmacodynamic profile and an original chemical structure, by which it differs from traditional beta 1-blockers. Nebivolol is a racemic mixture of two enantiomers in equal ratios. It is endowed with a highly selective beta 1-blocking activity, and does not show an intrinsic sympathomimetic activity. Nebivolol is endowed with peripheral vasodilating properties mediated by the modulation of the endogenous production of nitric oxide. It does not significantly decrease airway conductance compared with atenolol and propranolol. Nebivolol does not compromise the left ventricular function, but it may increase stroke volume, and does not reduce heart inotropism during exertion. Nebivolol is quite safe and is well tolerated, also when compared to traditional beta-blockers. The most common adverse effects are dizziness, headache and fatigue. Owing to its combined dual mechanism of action, nebivolol leads to a unique haemodynamic and therapeutic profile by which it may be advantageous in essential hypertension, ischaemic heart disease and congestive heart failure.

Adrenergic beta-Antagonists↗