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Biomedical subjects

F Rossi

Publications and source records attributed to F Rossi.

At least 361 records · Page 20Linked to original sources
PubMed1994

Effect of telenzepine, an M1-selective muscarinic receptor antagonist, in patients with nocturnal asthma.

Muscarinic M1-receptor antagonists can prevent the induction of a long-lasting excitatory postsynaptic potential in autonomic ganglia. As the prolonged occupation of M1-receptors is a possible protective mechanism against vagal overstimulation, M1-antagonists might prove to be effective in preventing nocturnal wheeze. The aim of the present study was to investigate whether telenzepine, an M1-selective muscarinic receptor antagonist, administered orally at different doses (1.5 mg, 3 mg, 5 mg) for one week, reduced airway obstruction in patients with nocturnal asthma in comparison with placebo. Peak expiratory flow rate (PEFR) difference between each study medication (arithmetic means from values on days 4, 5 and 6) and baseline at 6 a.m. and at midnight on day 5 did not differ significantly. Treatment with placebo nocte (at night, 9 p.m.), or telenzepine 1.5 mg nocte, telenzepine 3 mg nocte and telenzepine 5 mg nocte did not affect significantly the 24-h time course of PEFR. The results of this study indicate that the use of telenzepine via the oral route at a dose of up to 5 mg is not effective in preventing nocturnal asthma.

Administration, Oral↗
PubMed1994

Effect of salmeterol and formoterol in patients with chronic obstructive pulmonary disease.

In the present trial we investigated the time course of inhaled salmeterol and formoterol bronchodilation in comparison with that of inhaled salbutamol and placebo in 16 patients with moderate to severe chronic obstructive pulmonary disease (COPD). The study was performed using a single-blind crossover randomized study. The bronchodilator activity of 200 micrograms salbutamol, 50 micrograms salmeterol, 24 micrograms formoterol and placebo, which were all inhaled from a metered dose inhaler, was investigated. Our results showed that salmeterol and formoterol are efficacious in reducing airflow obstruction in patients suffering from COPD. We found similar times of onset to improve FEV1 by 15% for salmeterol and formoterol (salbutamol behaving faster), while the duration of action showed the expected differences between the two long-acting drugs and salbutamol. The results indicate that long-acting beta 2-agonists appear to be very effective in improving airway limitation in patients suffering from COPD. Although the onset of bronchodilation after inhaling salmeterol and formoterol is slightly delayed compared with salbutamol, this is of little clinical importance since in these patients salmeterol and formoterol must be intended for maintenance treatment and not immediate symptomatic relief.

Administration, Inhalation↗
PubMed1994

K+ channels and guinea-pig trachea: a possible functional modulation by GABAB receptors.

K+ channel activators represent a novel class of smooth muscle relaxant agents. There is now much evidence demonstrating that K+ channels, localized to prejunctional neurons and post-junctional smooth muscle membranes, can regulate airway smooth muscle activity, inducing smooth muscle cell membrane hyperpolarization. K+ channel activity may be influenced by some neurotransmitters, such as adenosine, serotonin and noradrenaline. More recently, it has been observed that the stimulation of GABAB receptors influences K+ channels in the hippocampus, dorsal rafe and spinal cord neurons. The aim of this study was to investigate the effects of levcromakalim in guinea-pig trachea at pre- and post-junctional sites and to evaluate whether GABAB receptors may modulate K+ channel activation. Levcromakalim (from 1 nM to 1 microM) relaxed guinea-pig trachea (IC50 10 +/- 0.9 nM) previously contracted by KCl (30 mM). This effect was reversed by a pretreatment with tetraethylammonium (10 mM) (IC50 120 +/- 0.7 nM). A 30-min pretreatment with baclofen (1 microM) or phaclofen (1 microM) failed to modify the effects of levcromakalim (IC50 18 +/- 1.0 nM and 14 +/- 0.6 nM, respectively). The contractile responses to electrical field stimulation (71.20 +/- 5.12% of acetylcholine--100 microM--contraction) was significantly (P < 0.05) reduced by a pretreatment with levcromakalim (10 nM) (54.00 +/- 6.68%). This reduction was antagonized by tetraethylammonium (10 nM) (72.20 +/- 14.27%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Pulmonary penetration of dirithromycin in patients suffering from acute exacerbation of chronic bronchitis.

The aim of this study was to evaluate the concentrations of dirithromycin, a new macrolide antibiotic, in bronchial secretions (BS), bronchial mucosa (BM), epithelial lining fluid (ELF) and serum in 25 patients with acute exacerbation of chronic bronchitis after a 5-day, once-daily, dirithromycin regimen. All patients received dirithromycin, 500 mg (two 250 mg tablets) given orally once daily at 08.00 fasted, for 5 consecutive days. They were divided into five groups (n = 5 in each group) according to sampling time (24, 48, 72, 96 and 120 h, after the last dose). Mean serum concentrations remained low throughout the study (0.44 microgram/ml at 24 h, 0.31 microgram/ml at 48 h, 0.33 microgram/ml at 72 h, 0.12 microgram/ml at 96 h and 0.11 microgram/ml at 120 h, respectively), although they were higher than the MICs for Moraxella catarrhalis for up to 72 h and than that for Streptococcus pneumoniae for up to 120 h after the last dose. By contrast, in all other samples, mean concentrations were higher than the MICs for many relevant respiratory pathogens for at least 3 days, and higher than that for S. pneumonia and M. catarrhalis for up to 120 h (mean concentrations measured 2.67, 2.15, 1.74, 0.27 and 0.17 micrograms/ml, respectively, in BS; 2.59, 2.59, 1.96, 0.41 and 0.27 micrograms/g, respectively, in BM; 2.21, 2.25, 1.57, 0.22 and 0.15 micrograms/ml, respectively, in ELF). These findings demonstrate that dirithromycin is concentrated in each of these potential sites of infection for up to 3 days after a 5-day course of therapy. Therefore, short-term therapy with dirithromycin may be useful for many respiratory infections.

Anti-Bacterial Agents↗
PubMed1994

Cholinesterase inhibition by vecuronium and pancuronium in human airways.

Vecuronium (100 microM) but not pancuronium (100 microM) increased the sensitivity of human isolated bronchial preparations (HBP) to exogenous acetylcholine (ACh). The pD2 values obtained from concentration-dependent contractions were: control, 4.59 +/- 0.29 vecuronium, 5.86 +/- 0.31. Vecuronium or pancuronium (100 microM) significantly decreased (50%) the neostigmine contractions in HBP. In addition, vecuronium was more potent than pancuronium in preventing exogenous ACh degradation. These results suggest that vecuronium and pancuronium may have physiological effects in human airways by inhibiting both the tissue cholinesterases and muscarinic (M3) receptors.

Bronchi↗
PubMed1994

Cobalt blocks L-glutamate-induced apnea and arterial hypotension in the nucleus tractus solitarii of anaesthetized rats.

The local application of cobalt reversibly blocks calcium-channel conductance and therefore synaptic transmission. In this study pretreatment with a solution of cobalt (100 mM) in the nucleus tractus solitarii (NTS) of anaesthetized rats significantly blocked the apnea (P < 0.01) and arterial hypotension induced by L-glutamate (25 mM) and N-methyl-D-aspartate (0.4 mM) microinjected in the NTS. We conclude that cobalt causes these effects by acting at the postsynaptic level.

Anesthesia↗
PubMed1994

Effects of the polyamine spermidine on NMDA-induced arterial hypertension in freely moving rats.

We investigated the effect of the polyamine spermidine (SPD) (0.01-1 microgram/rat) on hypertension induced by N-methyl-D-aspartate (NMDA) (0.1 microgram/rat) microinjected into the latero-caudal periaqueductal gray (PAG) area of freely moving rats. Pretreatment with a low dose of SPD (0.01 microgram/rat) significantly increased NMDA-induced hypertension. On the contrary, higher doses of SPD (0.1 and 1 microgram/rat) significantly decreased NMDA-induced cardiovascular changes. SPD alone did not modify arterial blood pressure. Arcaine (1 microgram/rat), a putative antagonist at the polyamine recognition site on NMDA receptors, when microinjected into the PAG area, prevented the negative but not the positive modulatory effects of SPD on the NMDA-induced cardiovascular changes. Pretreatment with SPD did not affect cardiovascular effects induced by quisqualic acid (QUIS), a non-NMDA receptor agonist. These data, in agreement with the in vitro results, suggest that at the level of the PAG area, the polyamines also show multiple actions at NMDA receptors in vivo.

Animals↗
PubMed1994

Metabotropic glutamate receptors are involved in the control of breathing at the medulla oblongata level of anaesthetized rats.

The goal of the present study was to identify sites in the medulla oblongata where metabotropic glutamate receptors are involved in regulating respiration. Unilateral microinjections (50 nl) of L-glutamate (L-glu) (10-25-50 mM) into the nucleus tractus solitarii (NTS) of anaesthetized rats elicited apnea (8.6 +/- 0.3 sec; 21.3 +/- 3.6 sec; 66.3 +/- 16.5 sec respectively; N = 6) and arterial hypotension (7.3 +/- 2.4 mmHg; 10.1 +/- 2.3 mmHg; 35.3 +/- 7.5 mmHg respectively; N = 6). Similarly, in other rats 1-aminocyclopentane-1, 3-dicarboxylic acid (ACPD) (1-5-10 mM), a selective agonist of metabotrophic glutamate receptors, also induced apnea (22.4 +/- 2.5 sec; 32.5 +/- sec; 92.5 +/- 1.4 sec respectively; N = 6) and arterial hypotension (12.7 +/- 2.2 mmHg; 19.6 +/- 4.3 mmHg; 26.5 +/- 1.5 mmHg respectively; N = 6). Paired experiments showed that unilateral microinjections of L-glu (50 mM) and ACPD (1 mM) into the nucleus retroambigualis (NRA) of anaesthetized rats elicited apnea (20.2 +/- 2.6 sec and 33.8 +/- 3.2 sec respectively; N = 6) and arterial hypotension (15.7 +/- 3.7 mmHg and 22.5 +/- 4.5 mmHg respectively; N = 6). The ACPD effects on apnea and hypotension in NTS and NRA were not prevented by a 3 min pretreatment with L-AP3 (30 mM), a putative antagonist of metabotropic glutamate receptors (19.5 +/- 1.4 sec; 12.3 +/- 3.2 mmHg and 30.6 +/- 2.9 sec; 23.4 +/- 3.8 mmHg respectively; N = 6). These data suggest that metabotropic glutamate receptors are involved in NTS and NRA regulation of cardiorespiratory functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1994

Cellular plasticity at the climbing fibre-Purkinje cell synapse as a model of plasticity in adulthood and ageing.

In the adult brain there is a high degree of plasticity which is documented here for climbing fibre terminal arborization impinging upon the proximal Purkinje cell dendrites. Such an arborization presents a more distal compartment, including 90% of branches and varicosities, whose integrity depends on the target and a more proximal compartment which survives to target degeneration. The same terminal arborization enlarges its territory of innervation through collateral sprouting when nearby Purkinje cells are deprived of their climbing fibres or when embryonic Purkinje cells are placed on the surface of an intact cerebellum. In the latter case axonal elongation occurs in the absence of degeneration products and of macrophage/microglia or astrocyte activation. In addition, the embryonic Purkinje cells are able to invade the intact host molecular layer where they develop dendritic arbours which become also innervated by climbing fibre collaterals.

Aging↗
PubMed1994

Bilateral asymmetry of cerebral blood velocity in cluster headache.

In this study, 69 episodic cluster headache (CH) patients (40 in the active phase, 29 in remission period) underwent a complete TCD examination in order to verify the relationship between cerebral blood velocities (CBVs) and the clinical profile of the disease. Fifteen patients were examined during both phases, while 7 were monitored during a spontaneous attack. Sixty-three healthy sex and age-matched controls were also studied. We measured widespread, asymmetric CBV activation during the active phase, bilaterally in the anterior circulation and also in the posterior circulation. A relative reduction of CBV on the anterior cerebral artery pain side, also during remission, suggests a relationship between local vasodilation and the autonomic symptoms ipsilateral to pain during CH attacks.

Adult↗
PubMed1994

Relation between L-arginine-nitric oxide pathway and endothelin-1 effects in periaqueductal gray area of rats.

Injection of N omega-nitro-L-arginine methyl ester (L-NAME), an L-arginine analogue and a potent inhibitor of nitric oxide (NO) synthase, in dorsolateral periaqueductal gray (PAG) area of freely moving rats at doses from 0.1 to 1 mumol per rat, dose-dependently increased arterial blood pressure (BP). Endothelin-1 (ET-1) injected in the same area at doses from 0.1 to 1 pmol per rat also induced pressor effects. Administration of L-NAME (1 mumol per rat) in the PAG area 10 min before ET-1 significantly (p < 0.01) potentiated ET-1-induced hypertension. Pretreatment with L-arginine (1 mumol per rat), precursor of NO, significantly (p < 0.01) decreased L-NAME-induced potentiation of ET-1 pressor effects. L-Arginine also prevented the ET-induced increase in arterial BP and reversed L-NAME-induced hypertensive effect. Prazosin and propranolol, adrenergic blocking agents, and reserpine, a depletor of catecholamine stores, reduced either ET-1 or L-NAME pressor effects. Our data suggest the presence of NO synthase in the PAG area, considered an important cerebral area in coordinating physiologic responses such as cardiovascular and respiratory adjustment. Moreover, our results suggest that even at the PAG area level, functional antagonism exists between NO and ET-1, possibly contributing, through sympathetic outflow, to central regulation of arterial BP.

Animals↗
PubMed1994

Serum digoxin levels after concomitant ticarcillin and clavulanic acid administration.

Recently it has been recognized that steady-state serum digoxin concentrations may increase or fall to ineffective levels when the glycoside is administered together with several antibiotics. Our study was designed to assess if serum digoxin levels may be modified by the concomitant use of a ticarcillin and clavulanic acid. The study was carried out in 15 hospitalized patients suffering from exacerbation of their chronic bronchitis without liver disease and renal failure. Serum digoxin levels were not significantly modified by the concomitant use of a ticarcillin and clavulanic acid, although peak digoxin serum concentrations were slightly lower. However, the average time to achieve the maximum concentration and area under the curve over 24 h did not change.

Aged↗
PubMed1994

Intracellular retention of hepatitis B virus surface protein mutants devoid of amino-terminal pre-S1 sequences.

To study the mechanism of L protein-mediated, intracellular (pre-Golgi) retention of hepatitis B virus (HBV) surface proteins, a collection of HBV preS-S open reading frame variants bearing wild-type or modified preS extensions was expressed in human cells. When the secretion phenotype of the corresponding proteins was analysed, all surface proteins with rearranged preS domains were found to be at least partially retained. This held true, in particular, for two variant proteins lacking preS1 amino acids 1 to 19 (ayw), the preS1 myristylated N terminus and a putative retention domain, and for another variant lacking the entire preS1 domain plus the N-terminal portion (amino acids 1 to 12) of the preS2 domain. All the retained variants underwent intracellular dimerization/oligomerization via disulphide bonds to a degree comparable to that observed in well exported natural proteins. Our results show that retention can take place in the absence of L N-terminal sequences and does not imply inhibition of covalent oligomerization.

Base Sequence↗
PubMed1994

Cardiotoxicity of doxorubicin: effects of drugs inhibiting the release of vasoactive substances.

The therapeutic usefulness of doxorubicin, an antineoplastic drug, is limited by its cardiotoxicity whose mechanism is as yet unknown. Several hypotheses have been postulated including also the release of vasoactive substances, so the aim of the present investigations was to study the relationship between the release of vasoactive substances and the development of doxorubicin-induced cardiotoxicity. The effects of the following drugs on doxorubicin-induced (cumulative dose of 20 mg/kg intraperitoneally) cardiotoxicity in rats have been evaluated: verapamil (1 and 10 mg/kg orally), that inhibits the slow channel influx of calcium and catecholamine release, acetylsalicylic acid (50 and 100 mg/kg orally), that inhibits the prostaglandin biosynthesis and release, and cromolyn sodium (cromolyn; 1 and 10 mg/kg orally), that inhibits the secretion of histamine. Our results showed that verapamil reduced and delayed doxorubicin-induced mortality, and limited doxorubicin-induced body weight decrease and ECG changes. Acetylsalicylic acid and cromolyn did not protect against doxorubicin-induced cardiotoxicity. These findings suggest that the release of vasoactive substances does not play a prevalent role in the development of doxorubicin-induced cardiotoxicity. The protective effect of verapamil is probably due to the inhibition of doxorubicin-induced intracellular calcium overload.

Animals↗
PubMed1994

Identification of human cytomegalovirus strain with immediate-early (IE) antigen-specific monoclonal antibody is prevented by point mutation in IE gene.

In an AIDS patient with a disseminated human cytomegalovirus (HCMV) infection, presence of HCMV in blood was repeatedly excluded by the shell vial culture method with the HCMV immediate-early (IE) antigen-specific monoclonal antibody (MAb) 5D2 currently employed for rapid HCMV identification, whereas it was repeatedly confirmed by all other assays (conventional virus isolation from blood, antigenemia, and DNAemia). Sequence analysis of the HCMV strain revealed a point mutation in exon 2 of the IE gene, which led to a serine-to-proline substitution at position 20 of the corresponding protein. Cloning and expression of a region of the IE gene containing the mutation showed that this was responsible for the lack of reactivity of MAb 5D2. A pool of IE antigen-reactive MAbs instead of a single MAb must be used for rapid HCMV identification to detect all viral strains.

AIDS-Related Opportunistic Infections↗
PubMed1994

Treatment of polyarteritis nodosa related to hepatitis B virus with interferon-alpha and plasma exchanges.

OBJECTIVES: To test the effectiveness of and tolerance to interferon-alpha 2b (INFa2b) in association with plasma exchanges for the treatment of polyarteritis nodosa (PAN) related to hepatitis B virus (HBV). METHODS: A prospective, non blinded, multicentre trial was carried out in which patients with multisystemic HBV-related PAN were included. Each patient received the association of INFa2b and plasma exchanges. The end point of the study was control of the disease (recovery or remission) or death. RESULTS: Six patients were included in the study. Each patient had histopathological or arteriographic evidence of vasculitis and was infected with actively replicating HBV. All patients were alive at the end of the study and no longer presented clinical or laboratory evidence of systemic vasculitis. HBeAg/anti-HBeAb seroconversion was observed in four patients (66.6%) and HBsAg/anti-HBsAb in 3/6 (50%). Two patients are still being treated with INFa2b because of chronic active hepatitis. CONCLUSIONS: It is considered that this new therapeutic approach to HBV-related PAN effectively cured systemic vasculitis and was associated with control of HBV infections. Antiviral therapy may have a role to play as the first line treatment regime of virus-induced vasculitis.

Adult↗
PubMed1994

A role for thyroid hormones in cold-induced elevation of blood pressure and cardiac hypertrophy.

The systolic blood pressures of two groups of rats that were exposed to cold (5 degrees C) for 4 weeks were elevated significantly above that of warm-acclimated controls maintained at 24 degrees C. At this time these groups were given the antithyroid drug aminotriazole in their food at 0.3 g/kg. At the same time, one group was given 15.8 micrograms thyroxine (T4)/kg body mass per day, while the second received 31.6. The doses were chosen as replacement (15.8 micrograms/kg) and twice replacement (31.8 micrograms/kg) for the rats. The results of the study revealed that both groups receiving aminotriazole and T4 had reductions in blood pressure within 1 week of initiation of treatment. Blood pressures reached control level after 5 weeks. Cardiac hypertrophy accompanying cold-induced hypertension was reduced with the lower dose of T4 and prevented with the higher dose. Serum concentrations of T4 and triiodothyronine (T3) in the two treated groups were reduced, while serum thyroid-stimulating hormone concentration and thyroid mass were increased above that of the warm-acclimated control group. This suggests that the rats were hypothyroid relative to the warm-acclimated control group. However, the treated rats grew at the same rate as nontreated, cold-exposed controls and had similar food and water intakes, a similar dipsogenic response to acute administration of isoproterenol, and similar colonic temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitrole↗