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Biomedical subjects

F Rossi

Publications and source records attributed to F Rossi.

At least 235 records · Page 13Linked to original sources
PubMed1997

Effects of hyperbaric oxygen exposure on non-adrenergic non-cholinergic responses of rat trachea.

The effects of prolonged (20 day) hyperbaric exposure (HBO) to oxygen on non adrenergic non cholinergic (NANC) contractile and relaxant responses of rat trachea were examined. The electrical field stimulation (EFS) of rat tracheal rings was performed at 30 Hz and contractile and relaxant responses were assessed in the absence or in the presence of pretreatment with L-nitro-arginine-methyl-ester (L-NAME), an inhibitor of NO synthase, and L-Arginine (L-ARG), a precursor of NO synthesis, plus L-NAME. Our data demonstrated that L-NAME significantly (p < 0.05) enhanced the contractile responses induced by EFS (controls 30.6 +/- 0.99%; L-NAME 76.07 +/- 2.00%) and statistically (p < 0.05) reduced the relaxant component of EFS (controls 31.10 +/- 0.46; L-NAME 15.00 +/- 0.12); these effects were reversed when tissues were pretreated with L-ARG plus L-NAME, suggesting that NO plays a modulatory role in cholinergic neurotransmission and participates in EFS relaxant responses. Moreover, prolonged HBO exposure (20 days) at 202.6 and 303.9 kPa did not modify the contractile or relaxant responses induced by EFS, nor modify the L-NAME or L-ARG effects on EFS responses.

Animals↗
PubMed1997

Synthesis of amides with anti-inflammatory and analgesic activities.

A series of N-Aroyl-cyclohexyl- and cyclohexenylamides 3- or 4-methylsubstituted were synthesized and evaluated for their anti-inflammatory and analgesic potencies, and gastrointestinal irritation liability. One compound, N-benzoyl-4-methyl-cyclohexylamide 6a, possessed an anti-inflammatory activity comparable to that of indomethacin.

Amides↗
PubMed1997

Research on heterocyclic compounds. XXXVIII. Synthesis and pharmacological activity of imidazo[1,2-b]pyridazine-2-carboxylic derivatives.

A series of imidazo[1,2-b]pyridazine-2-carboxylic acids, esters and amides was synthesized and tested for antiinflammatory, analgesic and ulcerogenic activities. The ethyl esters were prepared by cyclocondensation of some 3-aminopyridazines with ethyl bromopyruvate, followed by hydrolysis or ammonolysis in order to obtain the corresponding acids and amides. The inhibitory activity on the carrageenan-induced edema in the rat paw and on writhes induced by acetic acid in mice was evaluated, as well as the ulcerogenic action on the rat gastric mucosa. The pharmacological activity was discussed in terms of structure-activity relationships. In particular, the analgestic activity shown by these carboxylic derivatives was compared with that found in other series of imidazo[1,2-b]pyridazine analogues previously examined.

Amides↗
PubMed1997

Posterosuperior glenoid rim impingement as a cause of shoulder pain in top level waterpolo players.

OBJECTIVE: To further define the impingement occurring between the undersurface of the rotator cuff and the posterosuperior glenoid rim as a cause of shoulder pain in waterpolo athletes. EXPERIMENTAL DESIGN: A prospective design was used in the last three years. SETTING: Data were collected in Science Sports Institute of Rome. PARTICIPANTS: Eleven top level waterpolo players of both sexes all members of Italian National Waterpolo teams complaining of shoulder pain. INTERVENTION: All the eleven cases were previously examined with clinical test and X-ray and MR imaging in conventional and functional views, and then underwent arthroscopy. RESULTS: In four cases, X-ray showed erosions of the posterosuperior glenoid and in 5 cases, osteochondral defects on the posterior aspect of humeral head. In eleven cases, MR detected posterosuperior labral damages, partial tears of the undersurface of the rotator cuff and posterosuperior glenoid impingement. Furthermore arthroscopy detected in all cases the pathological findings associated with the posterosuperior glenoid impingement. CONCLUSIONS: Even if the shoulder pain in the overhead athlete may be multifactorial, this study provides further evidence that the posterosuperior glenoid impingement may be the major cause of shoulder pain in waterpolo athletes.

Adolescent↗
PubMed1997

[Problems associated with the use and monitoring of cyclosporin. Experience at a Clinical Pharmacology Service].

BACKGROUND: A study on cyclosporine A (CyA) monitoring in the January 1992-December 1995 period is reported. The aim of this work was to give epidemiological data on the use of CyA, to verify the progressive increase of CyA determinations and to evaluate the use in other diseases as well as to compare the different technics of CyA assay in blood samples, to stress the timing of blood samples and to underline the CyA monitoring importance. METHODS: The CyA dosage was evaluated by fluorescence polarization immunoassay (FPIA) and high-performance liquid chromatography (HPLC). RESULTS: The study showed that 70% of CyA determinations come from patients undergone to renal, bone marrow and liver transplantations; the remaining 30% was associated to other diseases (psoriasis, uveitis, diabetes, rheumatoid arthritis). CONCLUSIONS: The results obtained showed a progressive and constant increase of CyA determinations. Moreover, the use of drug was increased in autoimmune diseases. It is stressed that CyA monitoring in blood samples is essential to optimize the therapeutic efficacy of drug and minimizing its toxicity.

Autoimmune Diseases↗
PubMed1997

[Correlations between the efficacy of thrombolytic therapy and appearance of abnormal Q waves in the early stages of acute myocardial infarction].

BACKGROUND: The purpose of this study was to determine the time course of the appearance of abnormal Q waves on the electrocardiogram (ECG) over the first 6 hrs of the symptoms of acute myocardial infarction (AMI) and to determine what implications, if any, such Q waves have for the efficacy of thrombolytic therapy. Severe myocardial ischemia can produce early QRS changes in the absence of infarction. Abnormal Q waves on the baseline ECG may not be an accurate marker or irreversibly injured myocardium. METHODS: A study of 232 patients with AMI consecutively admitted to our coronary care units was carried out. Patients with previous AMI were not included. The presence and number of abnormal Q waves, as defined by Selvester, on the initial ECG was determined for each patient. The presence or absence and magnitude of ST segment elevation and depression were recorded and these data were used to estimate the left ventricular infarct size should thrombolytic therapy not be given (Aldrich score). Quantitative thallium-201 tomographic imaging was performed after a mean of 42 +/- 40 days from hospital discharge in 145 patients. RESULTS: In patients admitted within 1 hr of symptoms, 53% had abnormal Q waves on the initial ECG independent of the duration of symptoms before therapy (p < 0.001). Despite this finding, the presence of abnormal Q waves on the admission ECG did not eliminate the effect of thrombolytic therapy on reducing final infarct size (p < 0.001). CONCLUSIONS: Abnormal Q waves are a common finding early in the course of AMI. However, there is no evidence that abnormal Q waves are associated with less benefit in terms of reduction of infarct size after thrombolytic therapy.

Coronary Care Units↗
PubMed1996

Leukocyte integrin very late antigen-4/vascular cell adhesion molecule-1 adhesion pathway in splanchnic artery occlusion shock.

We investigated the role played by the very late antigen-4 (VLA-4)/ vascular cell adhesion molecule-1 (VCAM-1) interaction in the pathogenesis of splanchnic artery occlusion shock. Splanchnic artery occlusion shock was induced in anaesthetized rats by clamping splanchnic arteries for 45 min. Sham operated animals were used as controls. Survival time, serum tumour necrosis factor (TNF-alpha), monocyte and lymphocyte cell count and the responsiveness to acetylcholine of aortic rings were studied. Furthermore we investigated the VCAM-1 expression on vessel endothelium and the percentage of VLA-4 positive leukocytes. Splanchnic artery occlusion shocked rats had a decreased survival time (76 +/- 10 min, while sham shocked rats survived more than 4 h), increased serum levels of TNF-alpha (328 +/- 11 U/ml), a decreased number of both monocytes and lymphocytes and reduced responsiveness to acetylcholine (10 nM-10 microM) of aortic rings. In addition we found an increased expression of endothelial VCAM-1 on aortic rings and a reduced percentage of VLA-4 positive lymphocytes and monocytes. Passive immunization with specific antibodies raised against either VCAM-1 or VLA-4 (2 mg/kg, i.v., 3 h before splanchnic artery occlusion shock) increased survival, improved monocyte and lymphocyte count and restored the responsiveness of aortic rings to acetylcholine (P < 0.01). Finally, inhibition of TNF-alpha biosynthesis reversed the increased endothelial expression of VCAM-1 and the reduced percentage of integrin VLA-4 positive leukocytes. Our findings suggest that (i) VLA-4/VCAM-1 interaction has a role in the pathogenesis of circulatory shock; (ii) this interaction might be a target for new therapeutic approaches to the therapy of low-flow states.

Acetylcholine↗
PubMed1996

Cardiovascular responses induced by injection of endothelin-1 into the superior colliculus of rats.

Microinjection of endothelin-1 (1-10-100 pmol) into the superficial layer of the superior colliculus of anaesthetised rats caused dose-dependent decreases in blood pressure. This is unlikely to be a non-specific effect, for angiotensin II (1 nmol) caused increases in blood pressure. Injection of endothelin-1 (10 pmol) into the superior colliculus also caused falls in renal blood flow as measured by an ultrasonic flow probe. Decreases in blood pressure and falls in renal blood flow induced by injection of endothelin-1 into the superior colliculus were unaffected by bilateral vagotomy suggesting that attenuations in the activity of the sympathetic nervous system were involved in these events.

Animals↗
PubMed1996

Priming of monocyte respiratory burst by beta-amyloid fragment (25-35).

In the present study we have examined the ability of the beta-amyloid peptide (A beta(25-35)) to modulate the respiratory burst activity of human monocytes in vitro. Incubation of the cells for 24 h with A beta(25-35) as well as with A beta(1-42) resulted in an enhanced production of reactive oxygen radicals (ROI) in response to phorbol 12-myristate 13-acetate (PMA). Such effect was additively increased by coincubation with interferon-gamma (IFN gamma), and was paralleled by modulation of gene and protein expression of some components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system. Since the effects of A beta(25-35) were also reproduced in primary rat microglia, our findings indicate that A beta(25-35) can potentiate the ability of mononuclear phagocytes to produce ROI, and add further insights into its biological effects.

Amyloid beta-Peptides↗
PubMed1996

Mechanisms of stimulation of the respiratory burst by TNF in nonadherent neutrophils: its independence of lipidic transmembrane signaling and dependence on protein tyrosine phosphorylation and cytoskeleton.

This study concerns the controversial problem of whether the TNF-alpha (TNF) induces a respiratory burst in human neutrophils in suspension. The results have shown that in these cells TNF induces a classical respiratory burst. In fact, the production of oxygen free radicals 1) is linked to the translocation of NADPH oxidase components from cytosol to the plasma membrane, 2) does not take place in neutrophils from a patient lacking the cytochrome b558, and 3) does not involve other sources such as mitochondrial respiratory chain or xanthine oxidase. Signal transduction studies have demonstrated that this respiratory burst 1) is not accompanied by calcium transients, stimulation of phosphoinositide turnover, and phospholipase D activity (moreover, this burst is associated with the stimulation of the activity of phospholipase A2, but not of sphingomyelinase); 2) is strictly dependent on activation of tyrosine kinases, which is functional to the translocation to the plasma membrane of the cytosolic NADPH oxidase component rac; and 3) is dependent on the integrity of the cytoskeleton because it is completely suppressed by cytochalasin B. The integrity of the cytoskeleton is required for a full translocation of all the NADPH oxidase components and for an optimal activation of tyrosine kinases, but not for phospholipase A2 activation. Taken together, these findings demonstrate that TNF activates the NADPH oxidase through stimulation of tyrosine kinases, whose function is cytoskeleton-dependent, and raise the problem of whether the activation of this respiratory burst involves signals arising from TNF-activated beta2 integrins.

Cell Separation↗
PubMed1996

Different thermostabilities of FLP and Cre recombinases: implications for applied site-specific recombination.

Genomic manipulations using site-specific recombinases rely on their applied characteristics in living systems. To understand their applied properties so that they can be optimally deployed, we compared the recombinases FLP and Cre in two assays. In both Escherichia coli and in vitro, FLP shows a different temperature optimum than Cre. FLP is more thermolabile, having an optimum near 30 degrees C and little detectable activity above 39 degrees C. Cre is optimally efficient at 37 degrees C and above. Consistent with FLP thermolability, recombination in a mammalian cell line mediated by a ligand- regulated FLP-androgen receptor fusion protein is more efficient at 35 degrees C than at higher temperatures. We also document a mutation in a commercially available FLP plasmid (FLP-F70L) which renders this recombinase even more thermolabile. The different temperature optima of FLP, FLP-F70L and Cre influence their strategies of usage. Our results recommend the use of Cre for applications in mice that require efficient recombination. The thermolabilities of FLP and FLP-F70L can be usefully exploited for gain of function and cell culture applications.

Amino Acid Sequence↗
PubMed1996

Involvement of U1 small nuclear ribonucleoproteins (snRNP) in 5' splice site-U1 snRNP interaction.

U1 small nuclear ribonucleoprotein (snRNP) is an important ribonucleoprotein involved early in the spliceosome formation to commit pre-mRNAs to the splicing pathway. We have determined the association and dissociation kinetics of the 5' splice site-U1 snRNP interaction using purified U1 snRNP and a short RNA oligonucleotide comprising the 5' splice site (5'-SS) consensus sequence of pre-mRNAs (5'-SS RNA oligo). The association is rapid, does not require ATP, and is almost irreversible. Surprisingly, oligonucleotide-directed cleavage of the U1 small nuclear RNA (snRNA) 5' end sequence with RNase H has no significant effect on the rate of association of the 5'-SS RNA oligo, but it does lead to rapid dissociation. This provides evidence that U1-specific snRNP proteins are critical for the 5' splice site recognition while base pairing ensures the stability of the interaction. The recognition of the 5' splice site by U1 snRNP does not result from the individual action of one or more proteins but rather from their organization around U1 snRNA. A consequence of this organization is that the U1-C protein makes direct contacts with the site, as it becomes cross-linked to the RNA oligo upon exposition of the reactions to shortwave UV light.

Cell-Free System↗
PubMed1996

Synergistic induction of nitric oxide by beta-amyloid and cytokines in astrocytes.

The deposition of beta-amyloid peptides in the brain in form of senile plaque is the key event responsible for Alzheimer pathology. Among various mechanisms that have been proposed to explain the neurotoxicity of beta-amyloid deposits, a new one, recently identified in our laboratory, suggests that beta-amyloid peptides may be indirectly toxic for neurons by activating microglial cells to produce NO (2). We have investigated if astrocytes, nerve cells that play an important role in many brain diseases, also might be involved in a similar mechanism of neuronal damage. The results have demonstrated that (1) beta-amyloid peptide (25-35), in the presence of IFN gamma or TNF alpha, induces the production of NO in the astrocyte cell line C6, while neither cytokine was effective per se; (2) NO generation is also synergically induced by beta-amyloid peptide (25-35) in the presence of IL-1 beta, the latter being a cytokine able to activate astrocytes per se; (3) the effect of beta-amyloid peptide (25-35) is due to the induction of the expression of the gene of inducible NO-synthase. These findings suggest that astrocytes, activated by deposited beta-amyloid peptides and cytokines, may play a role in neuronal damage via the indirect NO mechanism.

Alzheimer Disease↗
PubMed1996

Beta-amyloid (25-35) peptide and IFN-gamma synergistically induce the production of the chemotactic cytokine MCP-1/JE in monocytes and microglial cells.

The molecular mechanisms involved in the development of senile plaques characteristic of aging and Alzheimer's disease are poorly understood. In this study, we examined whether human monocytes and murine microglial cells stimulated with the active fragment of amyloid beta-protein (Abeta(25-35)) express the monocyte chemotactic protein-1 (MCP-1)/JE. We show that upon incubation with Abeta(25-35), human monocytes accumulate MCP-1 mRNA and produce significant amounts of MCP-1. The effect of Abeta(25-35) on MCP-1 secretion was neither mimicked by a scrambled analogue nor affected by polymyxin B sulfate, even though the latter almost completely abolished the effect of LPS on MCP-1 expression. Murine microglial cells stimulated with Abeta(25-35) also expressed high levels of JE mRNA (the murine counterpart of MCP-1) and released bioactive chemotactic factors. In addition, we report that IFN-gamma significantly synergizes with Abeta(25-35) either in human monocytes or in murine microglial cells, and that Abeta(25-35) plus/minus IFN-gamma-mediated early induction of MCP-1 mRNA does not require new protein synthesis. Finally, we provide evidence that the Abeta(25-35)- and Abeta plus IFN-gamma-induced production of MCP-1 is, in large part, mediated in an autocrine fashion by endogenous TNF-alpha. Taken together, our findings uncover another novel biologic action of Abeta(25-35) and might help in better understanding the mechanisms underlying mononuclear phagocyte recruitment and activation into amyloid deposits.

Amyloid beta-Peptides↗
PubMed1996

Excision of Ets by an inducible site-specific recombinase causes differentiation of Myb-Ets-transformed hematopoietic progenitors.

BACKGROUND: The Myb-Ets protein encoded by the E26 acute avian leukemia virus is a paradigm for the function of fused transcriptional activator oncoproteins. Myb-Ets transforms hematopoietic progenitor cells (myb-Ets progenitors, MEPs) that can be induced to differentiate into eosinophilic and myeloid cells by the activation of pathways involving Ras and/or protein kinase C. The Ets portion of the fusion protein seems to be required to maintain the multipotency of MEPs: MEPs transformed with a temperature-sensitive E26 mutant with a lesion in Ets (ts 1.1) and shifted to the non-permissive temperature predominantly form erythroid cells, but also form eosinophilic and myeloid cells. This interpretation is complicated, however, by the observation that ts 1.1-transformed MEPs differ from MEPs transformed with wild-type E26 in that they expressed erythroid and eosinophil markers even at the permissive temperature. RESULTS: In order to alleviate the problems associated with the use of temperature-sensitive mutants we have designed a vector that allows the inducible deletion of the Ets domain. To this end, we introduced FLP recombinase target sites into the E26 virus on the 5' and 3' sides of Ets and included within the same retroviral vector sequences encoding and estrogen-dependent FLP recombinase. This construct, termed FRV-3, is capable of transforming cells to produce a phenotype indistinguishable from that of MEPs obtained with wild-type virus. Hormone treatment of MEPs transformed with FRV-3 induced erythroid differentiation in a subpopulation of the cells; this subpopulation was found to have completely excised ets. However, in contrast to previous results obtained with ts 1.1-transformed MEPs, no differentiation along the eosinophilic and myeloid lineages was seen in hormone-treated FRV-3-transformed MEPs. CONCLUSIONS: Our results demonstrate the feasibility of using a site-specific recombinase to excise a fused oncoprotein domain encoded by a retrovirus. More specifically, they show that the Ets portion of the Myb-Ets protein selectively inhibits differentiation of MEPs along the erythroid lineage, and suggests that Ets is also required for their differentiation along the eosinophil and, possibly, myeloid lineages.

Animals↗