9 results on '"Ghisu N"'
Search Results
2. Cholecystokinin CCK2 receptors mediate the peptideʼs inhibitory actions on the contractile activity of human distal colon via the nitric oxide pathway
- Author
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Fornai, M, Colucci, R, Antonioli, L, Crema, F, Buccianti, P, Chiarugi, M, Baschiera, F, Ghisu, N, Tuccori, M, Blandizzi, C, and Del Tacca, M
- Published
- 2007
- Full Text
- View/download PDF
3. Control of enteric neuromuscular functions by purinergic A(3) receptors in normal rat distal colon and experimental bowel inflammation
- Author
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Antonioli, L, Fornai, M, Colucci, ROCCHINA LUCIA, Ghisu, N, Tuccori, M, Awwad, O, Bin, Anna, Zoppellaro, Chiara, Castagliuolo, Ignazio, Gaion, ROSA MARIA, Giron, MARIA CECILIA, and Blandizzi, C.
- Subjects
Male ,Adenosine ,Enteric nervous system ,Inflammatory bowel disease ,Colitis ,Adenosine Deaminase ,Colon ,Reverse Transcriptase Polymerase Chain Reaction ,Benzenesulfonates ,Receptor, Adenosine A3 ,Fluorescent Antibody Technique ,Myenteric Plexus ,Research Papers ,Electric Stimulation ,Rats ,Rats, Sprague-Dawley ,Disease Models, Animal ,Adenosine, Enteric nervous system, Inflammatory bowel disease, Colitis ,Animals ,Carbachol ,RNA, Messenger - Abstract
Adenosine A(3) receptors mediate beneficial effects in experimental colitis, but their involvement in enteric neuromuscular functions during bowel inflammation is undetermined. This study investigated the regulatory role of A(3) receptors on colonic motility in the presence of experimental colitis.Colitis was induced in rats by 2,4-dinitrobenzenesulfonic acid. A(3) receptors and adenosine deaminase (ADA, adenosine catabolic enzyme) mRNA were examined by RT-PCR. Tissue distribution of A(3) receptors was detected by confocal immunofluorescence. The effects of 2,3-ethyl-4,5-dipropyl-6-phenylpyridine-3-thiocarboxylate-5-carboxylate (MRS1523) (MRS, A(3) receptor antagonist), 2-chloro-N(6) -(3-iodobenzyl)-adenosine-5'-N-methyluronamide (2Cl-IB-MECA) (CIB, A(3) receptor agonist), dipyridamole (DIP, adenosine transport inhibitor) and ADA were assayed on contractile responses evoked by electrical stimulation (ES) or carbachol in colonic longitudinal muscle preparations (LMP).RT-PCR showed A(3) receptors and ADA mRNA in normal colon and their increased level in inflamed tissues. Immunofluorescence showed a predominant distribution of A(3) receptors in normal myenteric ganglia and an increased density during colitis. MRS enhanced ES-induced cholinergic contractions in normal LMP, but was less effective in inflamed tissues. After pretreatment with dipyridamole plus ADA, to reduce extracellular adenosine, CIB decreased cholinergic motor responses of normal LMP to ES, with enhanced efficacy in inflamed LMP. A(3) receptor ligands did not affect carbachol-induced contractions in LMP from normal or inflamed colon.Normally, adenosine modulated colonic cholinergic motility via activation of A(3) receptors in the myenteric plexus. A(3) receptor-mediated tonic inhibitory control by adenosine was impaired in inflamed bowel, despite increased density of functioning and pharmacologically recruitable A(3) receptors.
- Published
- 2010
4. Somatostatin inhibits colon cancer cell growth through cyclooxygenase-2 down-regulation
- Author
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Colucci, R, Blandizzi, Corrado, Ghisu, N, Florio, T, and DEL TACCA, M.
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Mitogen-Activated Protein Kinase 1 ,Cyclooxygenase 2 Inhibitors ,Colon ,Somatostatin, Colon cancer, Cyclooxygenase-2 ,Down-Regulation ,Research Papers ,Colon cancer ,Cyclooxygenase 2 ,Colonic Neoplasms ,Gastrins ,Humans ,Caco-2 Cells ,Protein Tyrosine Phosphatases ,Cyclooxygenase-2 ,Somatostatin ,HT29 Cells ,Oligopeptides ,Protein Kinase C ,Cell Proliferation - Abstract
Cyclooxygenase-2 (COX-2) is expressed in colonic neoplasms, where it supports cell proliferation via prostaglandin E(2) (PGE(2)) production. This study investigated the effects of somatostatin-14 on COX-2 expression, PGE(2) production and proliferation in colon cancer cells.Human colon adenocarcinoma cell lines Caco-2, HT-29 and HCT116 were used. The following techniques were employed: colourimetric assay for cell growth; 5-bromo-2'-deoxyuridine assay for DNA synthesis; enzyme immunoassay for PGE(2); COX-2 mRNA silencing; RT-PCR or Western blot for somatostatin receptor subtypes, cyclooxygenase isoforms, phosphorylated-ERK-1/ERK-2 and phosphorylated-Akt.HT-29 and Caco-2 cells expressed COX-2 and somatostatin receptors (sst(3/4/5) and sst(3/5), respectively). HCT116 cells did express somatostatin receptors (sst(2/3/5)), but not COX-2. Somatostatin-14 inhibited basal COX-2 expression, PGE(2) production, DNA synthesis and growth in Caco-2 cells and these effects were prevented by BN81658 (sst(3) receptor antagonist). Basal proliferation of HT-29, HCT116 and COX-2-silenced Caco-2 cells was not affected by somatostatin-14. Stimulation of HT-29 cells with gastrin-17 elicited increments of ERK-1/ERK-2 and Akt phosphorylation, COX-2 expression, PGE(2) production, DNA synthesis and cell growth, which were all counteracted by somatostatin-14. Somatostatin-14-induced inhibition of COX-2 expression, PGE(2) production and DNA synthesis were blocked by BIM23056 (sst(5) receptor antagonist).Somatostatin decreases COX-2 expression and function in colon cancer cells via activation of sst(3) or sst(5) receptors, and these effects contribute to the inhibitory action of somatostatin on cell proliferation. These findings can be relevant to the development of therapeutic strategies based on the modulation of the COX-2 pathway.
- Published
- 2008
5. Cholecystokinin CCK2 receptors mediate the peptide's inhibitory actions on the contractile activity of human distal colon via the nitric oxide pathway.
- Author
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Fornai, M., Colucci, R., Antonioli, L., Crema, F., Buccianti, P., Chiarugi, M., Baschiera, F., Ghisu, N., Tuccori, M., Blandizzi, C., and Del Tacca, M.
- Subjects
CHOLECYSTOKININ ,COLON (Anatomy) ,INTESTINAL abnormalities ,NITRIC oxide ,PHARMACOLOGY - Abstract
Background and purpose:Cholecystokinin is known to exert stimulant actions on intestinal motility via activation of type 1 cholecystokinin receptors (CCK
1 ). However, the role played by cholecystokinin 2 (CCK2 ) receptors in the regulation of gut motility remains undetermined. This study was designed to examine the influence of CCK2 receptors on the contractile activity of human distal colon.Experimental approach:The effects of compounds acting on CCK2 receptors were assessed in vitro on motor activity of longitudinal smooth muscle, under basal conditions as well as in the presence of KCl-induced contractions or transmural electrical stimulation.Key results:Cholecystokinin octapeptide sulphate induced concentration-dependent contractions which were enhanced by GV150013 (CCK2 receptor antagonist; +57% at 0.01 μM). These effects were unaffected by tetrodotoxin. The enhancing actions of GV150013 on contractions evoked by cholecystokinin octapeptide sulphate were unaffected by Nω -propyl-L-arginine (NPA, neuronal nitric oxide synthase inhibitor), while they were prevented by Nω -nitro-L-arginine methylester (L-NAME, non-selective nitric oxide synthase inhibitor). In the presence of KCl-induced contractions, cholecystokinin octapeptide sulphate elicited concentration-dependent relaxations (-36%), which were unaffected by NPA, but were counteracted by GV150013 or L-NAME. The application of electrical stimuli evoked phasic contractions which were enhanced by GV150013 (+41 % at 0.01 μM).Conclusions and implications:CCK2 receptors mediate inhibitory actions of cholecystokinin on motor activity of human distal colon. It is suggested that CCK2 receptors exert their modulating actions through a nitric oxide pathway, independent of the activity of the neuronal nitric oxide synthase isoform.British Journal of Pharmacology (2007) 151, 1246–1253; doi:10.1038/sj.bjp.0707339; published online 18 June 2007 [ABSTRACT FROM AUTHOR]- Published
- 2007
- Full Text
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6. Influence of the serotonin transporter 5HTTLPR polymorphism on symptom severity in irritable bowel syndrome.
- Author
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Colucci R, Gambaccini D, Ghisu N, Rossi G, Costa F, Tuccori M, De Bortoli N, Fornai M, Antonioli L, Ricchiuti A, Mumolo MG, Marchi S, Blandizzi C, and Bellini M
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- Adult, Female, Genotype, Humans, Male, Irritable Bowel Syndrome genetics, Polymorphism, Genetic genetics, Serotonin Plasma Membrane Transport Proteins genetics
- Abstract
5HTTLPR polymorphism of serotonin transporter yields short (S) and long (L) alleles. SS and LS genotypes are associated with reduced expression of serotonin transporter. This cross-sectional study investigated the association of 5HTTLPR with symptom severity of irritable bowel syndrome (IBS). Patients with IBS (Rome III) and healthy controls were included. Genomic DNA was extracted from saliva, and 5HTTLPR alleles were assessed by polymerase chain reaction. IBS symptom severity was evaluated by means of IBS-SSS questionnaire. Two hundreds and four IBS patients (159 females; mean age: 39.6±12.3 years; 106 with constipation: C-IBS; 98 with diarrhea: D-IBS) and 200 healthy controls (154 females; mean age: 40.4±15.8 years) were enrolled. The overall IBS-SSS value was higher in LS/SS than LL patients (319.0±71.5 versus 283.8±62.3; P = 0.0006). LS/SS patients had also higher values of abdominal pain (59.7±21.0 versus 51.0±18.8; P = 0.020) and bowel dissatisfaction (80.1±23.9 versus 70.5±22.8; P = 0.035). The overall IBS-SSS values in C-IBS and D-IBS patients were 317.2±68.3 and 296.1±71.4, respectively (P = 0.192), with significantly higher values for abdominal distension (65.0±24.4 versus 51.4±24.8; P = 0.0006), but not for bowel dissatisfaction (80.5±21.7 versus 72.9±25.7; P = 0.138). Frequencies of 5HTTLPR genotypes did not differ significantly when comparing IBS patients (overall or upon stratification in C-IBS and D-IBS) with healthy controls. In conclusion, the LS and SS genotypes are significantly correlated with IBS symptom severity, although their possible direct causal role remains to be proven. In addition, the present findings do not support an association of 5HTTLPR with IBS or its clinical presentation in terms of bowel habit predominance.
- Published
- 2013
- Full Text
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7. Atorvastatin prevents endothelial dysfunction in mesenteric arteries from spontaneously hypertensive rats: role of cyclooxygenase 2-derived contracting prostanoids.
- Author
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Virdis A, Colucci R, Versari D, Ghisu N, Fornai M, Antonioli L, Duranti E, Daghini E, Giannarelli C, Blandizzi C, Taddei S, and Del Tacca M
- Subjects
- Analysis of Variance, Animals, Atorvastatin, Blotting, Western, Cyclooxygenase 1 metabolism, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Administration Schedule, Endothelium, Vascular physiopathology, Male, Malondialdehyde metabolism, Mesenteric Arteries physiopathology, Probability, Prostaglandins metabolism, RNA metabolism, Random Allocation, Rats, Rats, Inbred SHR, Rats, Inbred WKY, Reverse Transcriptase Polymerase Chain Reaction, Sensitivity and Specificity, Vasodilation physiology, Cyclooxygenase 2 metabolism, Endothelium, Vascular drug effects, Heptanoic Acids pharmacology, Mesenteric Arteries drug effects, Pyrroles pharmacology, Vasodilation drug effects
- Abstract
We investigated the effect of atorvastatin on cyclooxygenase (COX) contribution to endothelial dysfunction in spontaneously hypertensive rat (SHR) mesenteric resistance arteries. Atorvastatin (10 mg/kg per day, oral gavage) or its vehicle was administered for 2 weeks to male SHR or Wistar-Kyoto rats. Endothelial function of mesenteric arteries was assessed by pressurized myograph. In Wistar-Kyoto rats, relaxation to acetylcholine was inhibited by N(G)-nitro-L-arginine methyl ester and unaffected by SC-560 (COX-1 inhibitor), DuP-697 (COX-2 inhibitor), or ascorbic acid. In SHRs, the response to acetylcholine was attenuated, less sensitive to N(G)-nitro-L-arginine methyl ester, unaffected by SC-560, and enhanced by DuP-697 or SQ-29548 (thromboxane-prostanoid receptor antagonist) to a similar extent. Endothelium-dependent relaxation was normalized by ascorbic acid or apocynin (NADPH oxidase inhibitor), which also restored the inhibition by N(G)-nitro-L-arginine methyl ester. In atorvastatin-treated SHRs, relaxation to acetylcholine was normalized, fully sensitive to N(G)-nitro-L-arginine methyl ester, and not affected by SC-560, DuP-697, SQ 29548, or antioxidants. Dihydroethidium assay showed an increased intravascular superoxide generation in SHRs, which was abrogated by atorvastatin. RT-PCR revealed a COX-2 induction in SHR arteries, which was downregulated by atorvastatin. The release of prostacyclin and 8-isoprostane was higher from SHR than Wistar-Kyoto mesenteric vessels. COX-2 inhibition and apocynin decreased 8-isoprostane without affecting prostacyclin levels. Atorvastatin increased phosphorylated extracellular signal-regulated kinase 1/2, pAkt, peNOS(1177), and inducible NO synthase levels in SHR mesenteric vessels and decreased 8-isoprostane release. In conclusion, COX-2-derived 8-isoprostane contributes to endothelial dysfunction in SHR mesenteric arteries. Atorvastatin restores NO availability by increasing phosphorylated extracellular signal-regulated kinase 1/2, pAkt, peNOS(1177), and inducible NO synthase levels and by abrogating vascular NADPH oxidase-driven superoxide production, which also results in a downregulation of COX-2-dependent 8-isoprostane generation.
- Published
- 2009
- Full Text
- View/download PDF
8. Genetic polymorphisms of thiopurine S-methyltransferase in a cohort of patients with systemic autoimmune diseases.
- Author
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Tani C, Mosca M, Colucci R, Gori G, d'Ascanio A, Ghisu N, Fornai M, Di Paolo A, Blandizzi C, Del Tacca M, and Bombardieri S
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- Adult, Aged, Antimetabolites metabolism, Azathioprine metabolism, Cohort Studies, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, White People, Young Adult, Antimetabolites adverse effects, Autoimmune Diseases drug therapy, Autoimmune Diseases genetics, Azathioprine adverse effects, Methyltransferases genetics, Polymorphism, Single Nucleotide
- Abstract
Objectives: Azathioprine (AZA) is a purine antimetabolite, prodrug widely used as a disease modifying drug in several rheumatic conditions. The aim of the present study was to evaluate the prevalence of TPMT genetic polymorphisms in a cohort of Italian Caucasian patients affected by rheumatic diseases and treated with AZA, and to establish correlations with the tolerability of AZA treatment., Results: Seventy-eight Caucasian patients, 16 males and 62 females, median age 41 years (min-max: 24-76) were enrolled. At the time of evaluation, the median duration of treatment with AZA was 8 months (min-max: 2-150 months); the median dose of AZA per kg of body weight was 1.42 mg (min-max: 0.5-2). Among the 78 patients evaluated, 76 presented a wild type genotype (TPMT *1), while polymorphic alleles were identified in 2 patients (2.6%). Twenty-five patients (32%) experienced different types of adverse events (AE) under AZA treatment. Eighteen patients (23.1%) discontinued AZA because of AE. No correlation was observed between polymorphic TPMT alleles and the development of AE., Conclusions: Our analysis supports the view that TPMT genotyping alone is not sufficient to adequately personalize the AZA dosage in rheumatic patients. Further studies based on phenotypic analysis of TPMT enzyme and assay of AZA metabolite appear to be required.
- Published
- 2009
9. Inducible nitric oxide synthase is involved in endothelial dysfunction of mesenteric small arteries from hypothyroid rats.
- Author
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Virdis A, Colucci R, Fornai M, Polini A, Daghini E, Duranti E, Ghisu N, Versari D, Dardano A, Blandizzi C, Taddei S, Del Tacca M, and Monzani F
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- Allopurinol pharmacology, Animals, Ascorbic Acid pharmacology, Endothelium, Vascular metabolism, Enzyme Inhibitors pharmacology, Hypothyroidism chemically induced, Hypothyroidism metabolism, Hypothyroidism pathology, Male, Mesenteric Arteries metabolism, Methimazole, NADPH Oxidases antagonists & inhibitors, NADPH Oxidases physiology, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide metabolism, Nitric Oxide Synthase Type II metabolism, Rats, Rats, Wistar, Superoxides metabolism, Thyroxine pharmacology, Vasodilation drug effects, Endothelium, Vascular physiopathology, Hypothyroidism physiopathology, Mesenteric Arteries physiopathology, Nitric Oxide Synthase Type II physiology
- Abstract
The time-dependent effects of mild hypothyroidism on endothelial function were assessed in rat mesenteric arteries. Male Wistar rats were treated with methimazole (MMI; 0.003%) or placebo up to 16 wk. Endothelial function of mesenteric small arteries was assessed by pressurized myograph. MMI-treated animals displayed a decrease in serum thyroid hormones, an increment of plasma TSH and inflammatory cytokines, and a blunted vascular relaxation to acetylcholine, as compared with controls. Endothelial dysfunction resulted from a reduced nitric oxide (NO) availability caused by oxidative excess. Vascular-inducible NO synthase (iNOS) expression was up-regulated. S-methylisothiourea (an iNOS inhibitor) normalized endothelium-dependent relaxations and restored NO availability in arteries from 8-wk MMI-animals and partly ameliorated these alterations in 16-wk MMI rats. Similar results were obtained when MMI-induced hypothyroidism was prevented by T(4) replacement. Among controls, an impaired NO availability, secondary to oxidative excess, occurred at 16 wk, and it was less pronounced than in age-matched MMI animals. Both endothelial dysfunction and oxidant excess secondary to aging were prevented by apocynin (nicotinamide adenine dinucleotide phosphate oxidase inhibitor). Mesenteric superoxide production was reduced by S-methylisothiourea and T(4) replacement in MMI animals and abolished by apocynin in controls (dihydroethidium staining). MMI-induced mild hypothyroidism is associated with endothelial dysfunction caused by a reduced NO availability, secondary to oxidative excess. It is suggested that in this animal model, characterized by TSH elevation and low-grade inflammation, an increased expression and function of iNOS, resulting in superoxide generation, accounts for an impaired NO availability.
- Published
- 2009
- Full Text
- View/download PDF
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