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S Filippi

Publications and source records attributed to S Filippi.

36 records · Page 2Linked to original sources
PubMed2000

Combined inhibition of indoleamine 2,3-dioxygenase and nitric oxide synthase modulates neurotoxin release by interferon-gamma-activated macrophages.

We evaluated the synthesis of nitric oxide (NO) and of the neurotoxic kynurenine metabolites 3OH-kynurenine and quinolinic acid (QUIN) in interferon-gamma (IFN-gamma)-activated macrophages of the murine BACl.2F5 cell line with the aim of investigating the roles of mononuclear phagocytes in inflammatory neurological disorders. IFN-gamma induced indoleamine 2,3-dioxygenase (IDO) and NO synthase (NOS) and increased the synthesis of 3OH-kynurenine, QUIN, and NO that accumulated in the incubation medium where they reached neurotoxic levels. Macrophage exposure to norharmane, an IDO inhibitor, resulted in a decreased formation of not only the kynurenine metabolites but also NO. The inhibition of NO synthesis could not be ascribed to reduced NADPH availability or decreased NOS induction. Norharmane inhibited NOS activity also in coronary vascular endothelial cells and in isolated aortic rings. Our findings suggest that activated macrophages release large amounts of neurotoxic molecules and that norharmane may represent a prototype compound to study macrophage involvement in inflammatory brain damage.

Animals↗
PubMed1999

Studies on the mechanisms involved in the ATP-induced relaxation in human and rabbit corpus cavernosum.

The effect of ATP in human and rabbit corpus cavernosum (CC) smooth muscle was investigated. Strips of human CC were vertically mounted in an organ bath and the tonic tension was recorded. ATP (0.1-3 mM) induced a concentration-dependent relaxant effect, with a pD2 value of 3.01+/-0.3. The purine-induced relaxation was not affected by L-NAME (100 microM). In rabbit CC, ATP also induced a concentration-dependent relaxation, which was not influenced by L-NAME or by indomethacin (3 microM), with a pD2 value of 3.1 +/-0.4. The ATP-induced relaxant effect in rabbit CC was increased by both the inhibitor of adenosine reuptake, dipyridamole (3 microM) and by the inhibitor of adenosine deaminase, EHNA (0.3 microM). Moreover CGS 15943 (3 microM), an A2a adenosine antagonist, reduced the ATP-induced relaxation. UTP was not able to produce relaxation. The two ATP analogues 2-methylthioATP and alpha,beta-methylene ATP were able to induce relaxation in rabbit CC, with the following order of potency: 2-methylthioATP > ATP > alpha,beta-methylene ATP thus suggesting a role for P2y receptors. However, reactive blue (500 microM), an unspecific P2y antagonist, did not modify the ATP relaxant response. The inhibition of phospholipase C by U73122 (3 microM) and of the endoplasmic reticulum Ca2+ATPase by thapsigargin (1 microM) did not modify the ATP-induced relaxation. The P2x specific antagonist PPADS (30 microM) and suramine (500 microM) were not able to modify the ATP relaxation either in the absence or presence of CGS 15943 (3 microM). These results confirm that ATP acts as a potent and NO-independent relaxant agent of human and rabbit CC. Our findings also show that the ATP effect is partially attributable to the metabolic breakdown of ATP to adenosine, which acts through A2a receptor stimulation, but is also due to a direct stimulation of P2 receptors that are different from the classical P2y and P2X receptor subtypes for ATP.

Adenine↗
PubMed1999

Immunohistochemical expression of fatty acid synthase, apoptotic-regulating genes, proliferating factors, and ras protein product in colorectal adenomas, carcinomas, and adjacent nonneoplastic mucosa.

The normal mucosa-adenoma-carcinoma sequence in colon pathology provides an attractive model of tumor progression. The role of tumor suppressor genes, oncogenes, and proliferative markers in tumorogenesis has evolved considerably in the last decade. By immunohistochemistry means, we have studied p53, bcl-2, c-myc, p21-ras, ki67, and fatty acid synthase (a fatty-acid-synthesizing enzyme) in normal, dysplastic, and neoplastic mucosa. The results were correlated with clinicopathological features and overall survival (OS). Formalin-fixed, paraffin-embedded archival material from 100 nonconsecutive adenomas and 100 adenocarcinomas (ADCs), including adjacent-to-tumor nonneoplastic mucosa (ANNM), from patients with a 5-year follow-up period were studied. Negative controls were obtained from colon resections for nonneoplastic disease. Fatty acid synthase was associated with ADC (P = 0.0001). p53 protein was associated with high-grade dysplasia adenoma (AHGD), ADC (P = 0.0001), and pT stage (P = 0.003). bcl-2 was associated with adenomas with low-grade dysplasia (P = 0.009); c-myc was associated with ANNM (P = 0.005) and pT stage (P = 0.006). p21-ras was associated with AHGD (P = 0.0001) and ANNM (P = 0.01). Ki67 was associated with AHGD (P = 0.02) and ADC (P = 0.0001). Univariate analysis on neoplastic tissue revealed histological grade, pT stage, pN stage, p21-ras, and p53 to be significant markers of OS; p21-ras, p53, and c-myc were reliable markers when evaluated on ANNM. Multivariate analysis revealed pT stage, pN stage, and p21-ras to be independent prognosticators of OS on ADC; p21-ras and c-myc staining in the ANNM were correlated with worse survival (OS). We suggest that the evaluation in concert of clinicopathological data and immunohistochemical markers on both normal and abnormal colon tissue provides an attractive model of tumor progression; moreover, it may give important messages about the prediction of survival.

Adenoma↗
PubMed1997

Vasorelaxant effects induced by the antiangiogenic drug linomide in aortic and saphenous vein preparations of the rabbit.

1. Linomide (N-phenylmethyl-1,2-dihydro-4-hydroxyl-1-methyl-2-oxoquinoline-3-carb oxa mide) inhibits vascular proliferation and has been proposed as an antiangiogenic drug. We have investigated the vascular effect of linomide in rabbit aortic and saphenous vein ring preparations and in rat cultured vascular smooth muscle cells (VSMCs). 2. Linomide (25-300 micrograms ml-1) did not alter the basal tone of the preparations. The drug induced a concentration-dependent relaxant effect in aortic rings with endothelium, preconstricted by noradrenaline (NA), 5-hydroxytryptamine (5-HT) and by the thromboxane mimetic U46619. 3. The degree of relaxation induced by linomide was significantly reduced by exposure to the cyclooxygenase inhibitors indomethacin (3 microM) and acetylsalicylic acid (500 microM), and was not influenced by pretreatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (100 microM) in aortic rings with endothelium, preconstricted with NA. 4. Endothelium removal significantly reduced the relaxant response to linomide in aortic ring preparations. 5. A concentration-dependent relaxant response was observed also in rabbit saphenous vein preparations deprived of endothelium and preconstricted either by NA or U46619. The degree of relaxation obtained in a high potassium solution was consistently smaller than that observed in NA-pretreated venous preparations. 6. The vasorelaxant effect of linomide was consistently blunted by the adenylate cyclase inhibitor SQ 22536 (50 microM), both in intact aortic rings and in those deprived of endothelium. 7. In rat cultured vascular smooth muscle cells, linomide (100-200 micrograms ml-1) induced a significant increase in cyclic AMP levels, which was blocked by exposure to 50 microM SQ 22536. 8. In endothelium-deprived aortic ring preparations, the linomide-induced relaxant effect was greatly reduced in high potassium medium (KCl = 25 mM). Pretreatment with the ATP potassium channel inhibitor glibenclamide (3 microM) significantly reduced the linomide-induced relaxation. 9. The results show that linomide possesses a vasorelaxant effect which is attributable to both endothelium-dependent and -independent properties. While the former component of the drug's activity is apparently due to the release of a prostanoid from endothelial cells, the endothelium-independent mechanism involved in linomide relaxation is linked to cyclic AMP accumulation and to ATP-sensitive potassium channel activation in VSMCs.

Animals↗
PubMed1997

Identification, characterization, and biological activity of endothelin receptors in human ovary.

We previously reported the expression of endothelin-1 (ET-1) in granulosa cells (GCs) of the human ovary and the presence of ET-1-like immunoreactivity in human follicular fluid obtained from women in an in vitro fertilization program. In follicular fluid, but not in plasma, the levels of ET-1-like immunoreactivity were higher in gonadotropin-stimulated vs. spontaneous cycles, suggesting hormonal regulation of follicular ET-1. To identify and characterize ET receptors in human ovary, we performed autoradiography, radioligand binding, and functional studies. Mathematical analysis of families of self- and cross-competition curves among [125I]ET-1, [125I]ET-3, and selective analogs indicates that human ovary expresses both subtypes of ET receptors, i.e. ETA and ETB receptors. However, the concentration of the ETB site was 100-fold lower than that of the ETA one. By using [125I]ET-1, we demonstrated that the density of binding sites in human ovary is not affected by the hormonal milieu (similar concentrations in normal cycling, postmenopausal, and combined oral contraceptive-treated women). In situ binding studies indicate that the majority of ETA and ETB receptors are expressed in the blood vessels of the ovary. In particular, ETA receptors are abundant in the ovulatory follicles and localized in the theca interna, in close proximity to the granulosa layer. Few GCs of the ovulatory follicle were specifically labeled. Conversely, in the rat ovary, used as a control, ETB receptors were predominantly expressed and localized in GCs. Accordingly, ETB receptors negatively regulated estrogen accumulation in rat GCs. In human granulosa-luteal cells, neither ET-1 (unselective ligand) nor ET-3 or sarafotoxin 6c (ETB ligands) affected estrogen or progesterone secretion. ET-1 was 2.5-fold more potent than noradrenaline in eliciting contraction of ovarian artery, acting through the ETA receptor. Our results indicate that in human ovary, at variance with rat ovary, the endothelin system is primarily involved in the regulation of ovarian blood flow and not steroidogenesis.

Adult↗
PubMed1996

Thapsigargin inhibits the response to acetylcholine and substance P but does not interfere with the responses to endothelium-independent agents.

We investigated the influence of the Ca(2+)-ATPase inhibitor thapsigargin (TG) on the vasorelaxant response to different endothelium-dependent and endothelium-independent relaxing agents in an isolated thoracic aorta preparation of the rabbit, precontracted by norepinephrine (NE). Pretreatment with 100 microM L-arginine methyl ester (L-NAME) an inhibitor of nitric oxide (NO) synthesis, completely prevented acetylcholine (ACh)-induced relaxation; the inactive stereoisomer D-NAME did not modify the effect of ACh. The exposure of the preparations to 1 microM TG induced a slowly developing slight increase in the basal tension during 30-min contact. The same concentration of TG also slightly reduced the response to the subsequent administration of NE. The antagonist effect of TG on the ACh response was concentration dependent in the range between 0.1 and 10 microM. A 30-min pretreatment with 1 microM TG appeared to be sufficient to induce a consistent antagonism of the ACh (0.01-10 microM) concentration-relaxant effect curve, since an increase to 60 min did not produce a further significant increment in the degree of the antagonist effect. The concentration-dependent relaxation induced by substance P (SP 0.1-3 nM) was also significantly antagonized by 1 microM TG. The effect of the calcium ionophore A23187 (0.01-1 microM) was reduced by the Ca(2+)-ATPase inhibitor only at the higher concentrations tested (0.3-1 microM). However, a 30-min contact time with 1 microM TG was completely ineffective in antagonizing the concentration-relaxant response curves to the two nitrovasodilators sodium nitroprusside (SNP 0.1-100 microM) and nitroglycerin (NTG 1-300 nM) and to the cyclic GMP analogue 8-Bromo-cyclic GMP (3-100 microM). The effects of the beta-adrenoceptor agonist isoprenaline (ISO 0.1-10 microM) and of the direct adenylate cyclase activator forskolin (FK 0.01-10 microM) were also completely unaffected by 1 microM TG. These results demonstrate that TG affects the response to agents that induce an endothelium-dependent relaxation through receptor-dependent calcium mobilization. However, they do not support the hypothesis that sarcoplasmic pump activity is essential for the development of a vasorelaxant response to endothelium-independent agents.

Acetylcholine↗
PubMed1994

Sialorrhea from fourth ventricle hydrocephalus. Case report.

The case of a 50-year-old man with tetraventricular hypertensive hydrocephalus is presented, remarkable for fourth ventricle dilatation. This patient showed a significant sialorrhea as the main symptom, which is quite unusual. This condition was successfully treated by cerebrospinal fluid diversion. The uncommon features of this case are summarized.

Cerebral Ventricles↗
PubMed1994

Effects of aging and hypertension on vasorelaxant activity of calcitonin gene-related peptide: a comparison with other vasodilator agents.

We investigated the influence of aging and hypertension on the vasorelaxant effect of calcitonin gene-related peptide (CGRP), examining the responses to stimulation of perivascular vasodilatory nerves and to administration of the peptide in isolated mesenteric vascular bed preparations of young (aged 2-3 months) and old (aged 18 months) normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). We used preparations preconstricted by perfusion with 100 microM methoxamine with addition of 5 microM guanethidine. The stimulation-induced vasorelaxation in the preparations of young SHR animals was significantly lower than that in those of age-matched WKY rats. Moreover, the vasodilator response to stimulation displayed an age-dependent decline in vascular beds of normotensive animals. The degree of the relaxant response to CGRP (0.01-1 microM) did not differ significantly between vascular preparations of normotensive and hypertensive rats; but was significantly reduced in preparations of both SHR and WKY rats aged 18 months as compared with those of young animals. An age-dependent decrement in the vascular reactivity, qualitatively similar to that observed with CGRP, was also detected with two other vasodilators, i.e., the endothelium-dependent vasodilator acetylcholine (ACh 0.1-100 microM) and the directly acting nitrovasodilator sodium nitroprusside (SNP, 1-10 microM). We conclude that the vascular sensitivity to CGRP, as well as that to other vasodilator agents acting by different mechanisms, decreases with age in both normotensive and genetically hypertensive rats.

Acetylcholine↗
PubMed1993

Age-dependent modifications of the role of prostanoids in cardiac preparations from normotensive and hypertensive rats.

The cardiac response to field stimulation of adrenergic nerve terminals in isolated atrial preparations from adult (6-month-old) normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats was enhanced in comparison to that observed in the atrial tissue of young (2-month-old) animals of both strains; the increase in the sympathetic response was significantly higher in preparations from SHR than in those from age-matched WKY rats. The sensitivity of cardiac adrenergic neurotransmission to the prejunctional inhibitory effects exerted by exogenously administered prostaglandin E2 (0.1 nM-1 microM) and iloprost (0.1-10 microM) did not show any strain-dependent difference in preparations from both young and adult rats. Moreover, acetylsalicylic acid (500 microM) induced a similar degree of potentiation of the response to sympathetic stimulation in atrial tissues of young WKY and SH animals; however, the effect of the cyclo-oxygenase inhibitor was completely missing in preparations from adult rats of both strains. Finally, arachidonic acid (10 microM) inhibited the adrenergic response to a greater extent in preparations from young and adult SH rats than in those from age-matched normotensive rats. The results of the study indicate that, at least in cardiac preparations, changes in the modulatory role of endogenous prostaglandins occur as age-dependent processes and, therefore, may not be indicative of possible differences in the role of prostaglandins between hypertensive and normotensive animals. The possible significance of the dissimilar response to arachidonic acid, detected as the only difference between preparations from SH and WKY rats, is discussed.

Age Factors↗
PubMed1993

Modulation of adrenergic responses by prostanoids in the isolated mesenteric vascular bed of the rat.

1. The influences of PGE2, PGE1, iloprost and carbocyclic thromboxane A2 (cTxA2) on the response to adrenergic nerve stimulation, exogenous noradrenaline and perfusion with methoxamine, have been compared in the rat mesenteric vascular bed. 2. PGE2, PGE1 and cTxA2 enhanced the vasoconstrictor response elicited by field stimulation, as well as that induced by noradrenaline and methoxamine. 3. Iloprost did not affect the increase in perfusion pressure induced by field stimulation, slightly reduced the vasoconstrictor response to high concentrations of noradrenaline, and significantly attenuated the increase in vascular tone induced by perfusion with methoxamine. 4. These findings suggest that, in the rat mesenteric vascular bed, prejunctional mechanisms are not involved in the interference exerted by different prostanoids on the vascular response to adrenergic activation.

Alprostadil↗
PubMed1993

Blockade of adenosine receptors unmasks a stimulatory effect of ATP on cardiac contractility.

1. The effects of ATP, alpha,beta-methylene ATP and beta,gamma-methylene ATP on the contractile tension of guinea-pig isolated left atria were evaluated. 2. ATP (1-100 microM) produced a concentration-dependent negative inotropic effect; this response was converted to a positive inotropic effect in the presence of the antagonist of adenosine A1 receptors, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 0.1 microM), and in the presence of 8-phenyltheophylline (10 microM), an antagonist of A1 and A2 receptors. 3. The positive inotropic effect of ATP was antagonized by the P2 receptor antagonist, suramin (500 microM). Reactive blue 2 (30-500 microM), a putative P2y receptor antagonist, concentration-dependently reduced and finally abolished the effect of ATP. 4. In the presence of 8-phenyltheophylline, the stable analogues of ATP, alpha,beta-methylene ATP and beta,gamma-methylene ATP (1-30 microM), produced a concentration-dependent increase in atrial contractility of a lesser degree than that induced by ATP. 5. The results suggest that when inhibitory adenosine receptors are blocked, ATP produces a positive inotropic effect, probably mediated by P2y receptor stimulation.

Adenosine Triphosphate↗
PubMed1993

Cardiovascular effects of capsaicin-sensitive neurons.

Calcitonin gene-related peptide, the main transmitter released from capsaicin-sensitive sensory-motor fibers, has positive inotropic and chronotropic effects on the heart and causes vasodilatation in the coronary arteries and elsewhere in the peripheral vasculature. We review some aspects of the cardiovascular actions induced by exogenous calcitonin gene-related peptide and by release of the peptide following activation of capsaicin-sensitive nerves. The efferent function of cardiac sensory-motor neurones is modulated by a number of endogenous substances of physiopathological interest, including opioid peptides, norepinephrine and adenosine. The receptors involved in the prejunctional regulation due to these substances have been characterized. Studies on the mesenteric bed of the rat have shown that, at least in such a resistance vascular bed, the relaxing effect of calcitonin gene-related peptide is mediated by a direct mechanism independent of endothelium-derived nitric oxide release. In cultured human endothelial cells from the umbilical cord vein, calcitonin gene-related peptide, at nM concentrations, stimulates cell growth in a dose-dependent manner. The possible implications of calcitonin gene-related peptide in the physio-pathological regulation of the cardiovascular system and in the trophism of vascular tissues are discussed.

Animals↗
PubMed1992

The inhibitory effect of opioid and alpha 2-adrenoceptor agonists on cardiac sensory neurones is pertussis toxin-insensitive.

The role of pertussis toxin-sensitive G proteins on the alpha 2-adrenoceptor and mu-opioid receptor-mediated inhibition of the efferent function of capsaicin-sensitive neurones was investigated in guinea-pig atria pretreated with guanethidine. In the presence of atropine, CGP 20712A (2-hydroxy-5-(2-[hydroxy-3-(4-[(1-methyl- 4-trifluormethyl)1H-imidazol-2-yl]-phenoxy)propyl]aminoethoxyl+ ++)-benzamide) and prazosin, [D-Ala2,NMe-Phe4,Gly5-ol]enkephalin (DAGO, 0.1-3 microM) and 2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo(4,5-d)azepine (BHT 920, 0.01-1 microM) reduced the positive inotropic effect induced by transmural stimulation of preparations obtained from control and from pertussis toxin-treated animals. These results suggest that pertussis toxin-sensitive G proteins are not involved in the inhibitory regulation of the efferent function of capsaicin-sensitive nerve terminals in cardiac tissue induced by alpha 2 and opioid receptor stimulation.

Adrenergic alpha-Agonists↗
PubMed1992

Positive inotropic effects of CGRP and isoprenaline: analogies and differences.

In guinea-pig isolated left atria, electrically stimulated at 1 Hz, isoprenaline and calcitonin gene-related peptide (CGRP) induced a positive inotropic effect in the same concentration range (0.3-100 nM). The increase in contractile tension induced by both agonists was associated with a reduction in time to peak tension and relaxation time. However CGRP was more active than isoprenaline in reducing the time to peak; this effect was more evident when the bath temperature was reduced from 30 degrees to 24 degrees C. The positive inotropic effects of isoprenaline and CGRP were potentiated by forskolin (30 nM), a direct activator of adenylcyclase; on the other hand, cholera toxin (1 microgram/ml), which irreversibly ribosylates Gs protein, did not modify the effect of CGRP, while antagonizing the concentration-response curve for isoprenaline. It is concluded that the increase in atrial contractile tension produced by isoprenaline and CGRP are linked to the adenylcyclase system in a different manner.

Animals↗
PubMed1991

Modulation by adrenergic transmitters of the efferent function of capsaicin-sensitive nerves in cardiac tissue.

In atrial preparations obtained from reserpine-pre-treated guinea-pigs, incubated in the presence of 1 microM atropine plus 1 microM CGP 20712A (a beta 1 blocking drug), a positive inotropic effect due to CGRP release from capsaicin-sensitive sensory neurons was induced by electrical field stimulation (EFS). This response was concentration-dependently reduced by noradrenaline (0.01-3 microM), neuropeptide Y (NPY, 3-300 nM) and adenosine triphosphate (ATP, 1-30 microM). On the other hand, the overflow of [3H]-noradrenaline from sympathetic nerve terminals induced by EFS in isolated atria obtained from normal untreated animals was not modified in 10 nM calcitonin gene-related peptide (CGRP). Substance P (SP) and neurokinin A (NKA), at concentrations ranging from 0.01 to 1 microM did not affect the cardiac response to field stimulation of adrenergic terminals of atrial tissue. These findings demonstrate that all the co-transmitters stored in adrenergic nerve terminals have a modulatory role on the efferent function of cardiac capsaicin-sensitive sensory neurons, while cardiac adrenergic neurotransmission is not influenced by the peptidergic transmitters released from sensory neurons.

Adenosine Triphosphate↗
PubMed1977

[Presence and etio-epidemiological significance of halophilic vibriones in various material].

In this work data of isolation of halophilic vibrios from coastal water of central Tyrrhenian sea are reported, and the epidemiological significance of such strains is discussed. V. Parahaemolyticus was identified in 8 out of 20 samples of sea water. V. alginolyticus was identified in 8 out of 26 samples of fishes and mussels examined and in 8 out of 20 sea water samples. Halophilic vibrios had not been isolated from 12 samples of sewage water and from 27 healthy or pathological human stool samples. From 6 different samples (sewage water and human stools included) bacteriophages active against V. parahaemolyticus were isolated. This study demonstrates that in our geographical area V. parahaemolyticus is present. The pathogenicity of such strains cannot be demonstrated because of the lack of available experimental models in vitro and/or in vivo. It is also impossible to assume their etiological rôle in human pathology, due to the absence of specific epidemics or single cases in our country.

Animals↗
PubMedDate not supplied

[Isolation of halophilic vibrios as possible agents of food poisoning (author's transl)].

Seventy-six halophilic vibrio strains were isolated from different marine sources such as coastal waters, fishes and mussels. Twenty strains were identified as Vibrio parahaemolyticus, 44 as Vibrio alginolyticus and 12 other strains could not be classified because of their atypical biochemical activities. Further investigations are necessary in order to assess if the present strains of V. parahaemolyticus can have a role in food poisoning outbreaks or human sporadic enteritis in our geographic area.

Food Contamination↗