119 results on '"B. Balestra"'
Search Results
52. Colonic Mucosal Mediators From Patients With Irritable Bowel Syndrome Excite Guinea Pig Enteric Cholinergic Motor Neurons via Purinergic, Prostaglandin, and TRPV1 Pathways
- Author
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Giovanni Carini, Roberto De Giorgio, Cesare Cremon, Lara Bellacosa, Giovanni Dothel, Vincenzo Stanghellini, Roberto Corinaldesi, Valentina Vasina, Fabrizio De Ponti, Marcello Tonini, Lisa Zecchi, B. Balestra, and Giovanni Barbara
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Purinergic receptor ,Gastroenterology ,TRPV1 ,Prostaglandin ,medicine.disease ,Guinea pig ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,medicine ,Cholinergic ,business ,Irritable bowel syndrome - Published
- 2011
53. OC.05.4: MUCOSAL MEDIATORS FROM PATIENTS WITH IRRITABLE BOWEL SYNDROME STIMULATE ENTERIC CHOLINERGIC MOTOR NEURONS IN VITRO VIA PURINERGIC, PROSTAGLANDIN, AND TRPV1 PATHWAYS
- Author
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R. De Giorgio, Vincenzo Stanghellini, Lara Bellacosa, Giovanni Carini, Marcello Tonini, Giovanni Barbara, Lisa Zecchi, Giovanni Dothel, Cesare Cremon, Roberto Corinaldesi, Valentina Vasina, B. Balestra, and F. De Ponti
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medicine.medical_specialty ,Hepatology ,business.industry ,Purinergic receptor ,Gastroenterology ,TRPV1 ,Prostaglandin ,medicine.disease ,In vitro ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,medicine ,Cholinergic ,business ,Irritable bowel syndrome - Published
- 2011
54. ['Cardiac ballet' with and without amiodarone]
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B, Balestra and T, Hess
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Male ,Electrocardiography ,Torsades de Pointes ,Cardiac Pacing, Artificial ,Amiodarone ,Humans ,Coronary Disease ,Female ,Aged - Abstract
Two well documented cases of torsades de pointes under amiodarone therapy are discussed. This special form of ventricular tachycardia is also known as "twisting around the points" or "cardiac ballet". Our first case involves recurrent torsades de pointes manifesting almost 2 weeks following onset of amiodarone therapy. They were successfully treated by overpacing. In the second case the isolated torsade de pointes was probably not caused by the longlasting and successful use of amiodarone but reflected severe ischemic heart disease and slight hypokalemia. This was confirmed in the one year follow-up, as torsade de pointes was no longer present despite increased dosage of amiodarone. Amiodarone-induced torsades de pointes is very rare. Most cases reported in the literature are poorly documented or were caused by other factors (electrolyte disturbances, other antiarrhythmic medication). If amiodarone has been administered as a matter of utmost necessity, other etiologies must be excluded or eliminated before amiodarone therapy is stopped when torsades de pointes occurs. Torsade de pointes due to amiodarone arises independently of the duration of therapy, the administered dosage and the extent of QT-prolongation. Holter monitoring does not allow a prediction and the benefit of electrophysiological studies is still controversial. The management of patients with amiodarone-induced torsades de pointes includes administration of magnesium and, frequently, overpacing. Due to the long half-life of amiodarone, prolonged temporary pacing may be required. General experience suggested that amiodarone can be used safely in patients who have developed torsades de pointes with other agents.
- Published
- 1993
55. 997 Enteric Nitrergic Neuron Defect and Gut Dysfunction in a Rat Model of Parkinson's Disease
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Marisa Faniglione, Mario Colucci, Giovanna Levandis, Marila Cervio, Michael Schemann, Roberto De Giorgio, Simone Vigneri, Rosaria Greco, Marcello Tonini, B. Balestra, Fabio Blandini, and Cristina Tassorelli
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Parkinson's disease ,Hepatology ,business.industry ,Rat model ,Gastroenterology ,medicine ,Anatomy ,medicine.disease ,business ,Nitrergic Neuron ,Neuroscience - Published
- 2009
56. Two subtypes of enteric non-opioid sigma receptors in guinea-pig cholinergic motor neurons
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Stefano M. Candura, Teresa Coccini, Marcello Tonini, Nerio Iapadre, Lucio G. Costa, B. Balestra, and Luigi Manzo
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Male ,medicine.medical_specialty ,Rimcazole ,Guinea Pigs ,Carbazoles ,Myenteric Plexus ,In Vitro Techniques ,Dextromethorphan ,Guanidines ,chemistry.chemical_compound ,Phenazocine ,Parasympathetic Nervous System ,Internal medicine ,medicine ,Haloperidol ,BMY-14802 ,Animals ,Receptors, sigma ,Cholinergic neuron ,Receptor ,Pharmacology ,Motor Neurons ,Electric Stimulation ,Endocrinology ,Pyrimidines ,chemistry ,Opioid ,Anti-Anxiety Agents ,Receptors, Opioid ,Cholinergic ,medicine.drug ,Antipsychotic Agents - Abstract
In the longitudinal muscle-myenteric plexus preparation (LMMP) of the guinea-pig ileum, the non-opioid sigma receptors agonists, 1,3-di-ortho-tolylguanidine (DTG) and (+)N-allyl-N-normetazocine [(+)SKF 10,047], had opposite effects on nerve-mediated cholinergic contractions caused by electrical field stimulation. DTG (0.1-10 microM) inhibited and (+)SKF 10,047 (0.1-10 microM) markedly enhanced these contractile responses. Both effects were evaluated in the presence (0.5 or 1 microM) of the putative antagonists at central sigma sites: haloperidol, rimcazole, BMY 14802 and dextromethorphan. Haloperidol and dextromethorphan were ineffective. Rimcazole antagonized the effect of both DTG and (+)SKF 10.047. BMY 14802 antagonized the (+)SKF 10.047-mediated excitatory response only. These results suggest that two sigma receptor subtypes are present in enteric cholinergic motor neurons innervating the longitudinal coat. Rimcazole and BMY 14802 may provide useful tools for the characterization of peripheral non-opioid sigma receptors.
- Published
- 1991
57. CS3.6 EXPRESSION OF 5-HYDROXYTRYPTAMINE RECEPTORS IN THE GUINEA PIG COLON AND THEIR ROLE IN THE CONTROL OF PROPULSIVE ACTIVITY AND GUT WALL ACCOMMODATION
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Marcello Tonini, B. Balestra, Mario Colucci, R. De Giorgio, Marila Cervio, and Marisa Faniglione
- Subjects
Guinea pig ,5-hydroxytryptamine receptors ,Hepatology ,business.industry ,Gastroenterology ,Medicine ,Anatomy ,business ,Cell biology - Published
- 2008
58. Excitatory effect of colonic mast cell mediators of irritable bowel syndrome patients on enteric cholinergic motor neurons
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Giovanni Barbara, R. De Giorgio, Elisa Fogacci, R. Vicini, Cesare Cremon, B. Balestra, E. Cervio, Marcello Tonini, Giovanni Carini, Lara Bellacosa, Vincenzo Stanghellini, Roberto Corinaldesi, and G. Di Nardo
- Subjects
medicine.anatomical_structure ,Hepatology ,business.industry ,Immunology ,Gastroenterology ,medicine ,Excitatory postsynaptic potential ,Cholinergic ,medicine.disease ,Mast cell ,business ,Irritable bowel syndrome - Published
- 2006
59. Endomorphin-1 imparis propulsion by inhibiting excitatory and inhibitory transmission in the guinea pig isolated colon
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B. Balestra, Marcello Tonini, Roberto De Giorgio, Giovanni Barbana, Catia Sternini, Fabrizio De Ponti, and Laura Anselmi
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Guinea pig ,chemistry.chemical_compound ,chemistry ,Hepatology ,Excitatory postsynaptic potential ,Gastroenterology ,Endomorphin-1 ,Inhibitory transmission ,Pharmacology ,Biology - Abstract
Endomorphin-1 Impairs Propulsion By Inhibiting Excitatory And Inhibitory Transmission In The Guinea Pig Isolated Colon Marcallo Tonini, Fabrizio De Ponti, Dept of Internal Medicine, Univ of Pavia, Pavia Italy; Giovanni Barbara, Roberto De Giorgio, Dept Internal Med & Gastroenterof, Univ of Bologna, Bologna Italy; Laura Anselmi, Barbara Balestra, Dept of Internal Medicine, Univ of Pavia, Pavia Italy; CaUa Sternini, CURE and Dept Medicine and Neurobiology, UCLA, Los Angeles, CA
- Published
- 2001
60. Role of galanin receptor 1 in the galanin-induced inhibition of intestinal motility
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Valeria Spelta, Catia Sternini, John H. Walsh, Marcello Tonini, Helen Won, Thomas Pham, Joseph R. Reeve, Gianluigi D'Agostino, and B. Balestra
- Subjects
medicine.medical_specialty ,Endocrinology ,Hepatology ,Chemistry ,Internal medicine ,Gastroenterology ,medicine ,Galanin ,Galanin receptor 1 ,Intestinal motility - Published
- 2000
61. 4-Oxystilbene compounds are selective antagonists for neuronal nicotinic α-bungarotoxin receptors
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Luigi Villa, Milena Moretti, Fabrizio Eusebi, L. Maggi, F. Clementi, B. Balestra, F. Berti, Eleonora Palma, C. Gotti, Marco Pallavicini, G. Rossoni, and G.E. Rovati
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Nicotinic agonist ,Chemistry ,Physiology (medical) ,General Neuroscience ,Pharmacology ,Bungarotoxin ,Receptor - Published
- 1998
62. Ligand-regulated μ opioid receptor endocytosis reduces the responsiveness of neurons to opioids
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Catia Sternini, B. Balestra, J. Minnis, Nicholas C. Brecha, Marcello Tonini, and E. Fiori
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Hepatology ,Opioid receptor ,medicine.drug_class ,Chemistry ,Gastroenterology ,medicine ,Endocytosis ,Ligand (biochemistry) ,Cell biology - Published
- 1998
63. Nicotinic acetylcholine receptors in human neuroblastoma cells
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Cecilia Gotti, L. Briscini, M. Oortgiesen, B. Balestra, Milena Moretti, Francesco Clementi, and Claudia Verderio
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Pharmacology ,Ganglion type nicotinic receptor ,Nicotinic agonist ,Chemistry ,Muscarinic acetylcholine receptor M5 ,Muscarinic acetylcholine receptor ,Muscarinic acetylcholine receptor M4 ,Muscarinic acetylcholine receptor M3 ,Muscarinic acetylcholine receptor M2 ,Alpha-4 beta-2 nicotinic receptor - Published
- 1995
64. Structure and distribution of nicotinic receptors in human brain
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B. Balestra, Cecilia Gotti, Francesca Rubboli, Francesco Clementi, and E. Perry
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Pharmacology ,Ganglion type nicotinic receptor ,medicine.anatomical_structure ,Nicotinic agonist ,Nicotinic Receptors ,Chemistry ,medicine ,Distribution (pharmacology) ,Human brain ,Alpha-4 beta-2 nicotinic receptor ,Cell biology - Published
- 1995
65. New assay for antibody detection in myasthenia gravis
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B. Balestra, C. Gotti, F. Clementi, Socrates J. Tzartos, and Renato Mantegazza
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Neurology ,business.industry ,Pediatrics, Perinatology and Child Health ,Immunology ,Medicine ,Neurology (clinical) ,business ,medicine.disease ,Genetics (clinical) ,Myasthenia gravis ,Antibody detection - Published
- 1994
66. Functional alpha6-containing nicotinic receptors are present in chick retina.
- Author
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S, Vailati, W, Hanke, A, Bejan, B, Barabino, R, Longhi, B, Balestra, M, Moretti, F, Clementi, and C, Gotti
- Abstract
Despite the fact that the neuronal chick alpha6 subunit was first cloned several years ago and recently has been shown to form acetylcholine (ACh)-activated channels in heterologous systems, no information is yet available concerning the structure and function of the alpha6-containing nicotinic receptors in neuronal tissues. Using subunit-specific antibodies directed against two different epitopes of the chick alpha6 subunit, we performed immunoprecipitation experiments on immunopurified alpha6-containing receptors radiolabeled with the nicotinic agonist [3H]epibatidine (Epi): almost all of the alpha6 receptors contained the beta4 subunit, 51% the beta3 subunit, 42% the alpha3 subunit, and 7.5% the beta2 subunit. Western blot analyses of the purified receptors confirmed the presence of the alpha3, beta3, beta2, and beta4 subunits, and the absence of the alpha4, alpha5, and alpha7 subunits. The alpha6-containing receptors bind [3H]Epi (Kd = 35 pM) and a number of other nicotinic agonists with very high affinity, the rank order being Epi >> cytisine > nicotine > 1, 1-dimethyl-4-phenylpiperazinium > acetylcholine > carbamylcholine. The alpha6 receptors also have a distinct antagonist pharmacological profile with a rank order of potency of alpha-conotoxin MII > methyllycaconitine > dihydro-beta-erythroydine > MG624 > d-tubocurarine > decamethonium > hexamethonium. When reconstituted in lipid bilayers, the alpha6-containing receptors form functional cationic channels with a main conductance state of 48 pS. These channels are activated by nicotinic agonists in a dose-dependent manner, and blocked by the nicotinic antagonist d-tubocurarine.
- Published
- 1999
67. Integrating Pharmacomechanical Treatments for Pulmonary Embolism Management within a Hub-and-Spoke System in the Swiss Ticino Region.
- Author
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Guarnieri G, Constantin FD, Pedrazzini G, Ruffino MA, Sürder D, Petrino R, Zucconi EC, Gabutti L, Ogna A, Balestra B, and Valgimigli M
- Abstract
The Swiss Ticino regional pulmonary embolism response team (PERT) features direct access to various pharmacomechanical PE management options within a hub/spoke system, by integrating evidence, guidelines' recommendations and personal experiences. This system involves a collaborative management of patients among the hospitals distributed throughout the region, which refer selected intermediate-high or high PE patients to a second-level hub center, located in Lugano at Cardiocentro Ticino, belonging to the Ente Ospedaliero Cantonale (EOC). The hub provides 24/7 catheterization laboratory activation for catheter-based intervention (CBI), surgical embolectomy and/or a mechanical support system such as extracorporeal membrane oxygenation (ECMO). The hub hosts PE patients after percutaneous or surgical intervention in two intensive care units, one specialized in cardiovascular anesthesiology, to be preferred for patients without relevant comorbidities or with hemodynamic instability and one specialized in post-surgical care, to be preferred for PE patients after trauma or surgery or with relevant comorbidities, such as cancer. From April 2022 to December 2023, a total of 65 patients were referred to the hub for CBI, including ultrasound-assisted catheter-directed thrombolysis (USAT) or large-bore aspiration intervention. No patient received ECMO or underwent surgical embolectomy.
- Published
- 2024
- Full Text
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68. Freshwater algal biofilm assemblages are more effective than invertebrate assemblages at aggregating microplastics.
- Author
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Barnes J, Balestra B, Knee KL, Frederick JA, Landaverde N, and Meiller J
- Abstract
Microplastics, plastic particles less than 5 mm in length, are a ubiquitous pollutant in the environment, but research on freshwater microplastic contamination is lacking. A possible fate of microplastics in freshwater environments is to become entangled or aggregated in biofilms, which are matrices of algae, bacteria, and micro invertebrates that grow on underwater surfaces, following a progression of settling algae, periphyton, and finally invertebrate colonization. This in-situ study at the Oasis Marina at National Harbor in Oxon Hill, Maryland, examined how the taxonomic assemblages of freshwater biofilms in the Potomac River are associated with the number of microplastics aggregated within them. Aluminum discs, acting as artificial substrate for biofilm growth, were deployed at the water's surface and at 2 m depth to survey biofilm assemblage and were sampled monthly from October 2021-October 2022. Microplastic abundances in the water column were measured every 2 weeks over the same period. Spatial and temporal trends in trapped and suspended microplastics, water quality parameters (temperature, dissolved oxygen, pH, salinity, conductivity, turbidity, ammonia, nitrate, and phosphate), and biofilm assemblages were measured and compared to explore factors affecting the abundance of microplastics and their partitioning between the water column and biofilms. Water quality had no measurable impact on microplastic abundance in the water column at either depth, but temperature was negatively correlated to microplastic abundance in biofilms. As the weather warmed and biofilms progressed to invertebrate settling, they tended to contain fewer microplastics. This may have occurred because less biologically rich biofilms, primarily composed of unicellular algal colonies, provide a favorable surface for microplastic deposition. Understanding seasonal changes in biofilm assemblage and microplastic abundance may help track the fate of microplastics in freshwater systems, particularly in their interactions with lower trophic organisms., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)
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- 2023
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69. Comparative Study of Salivary, Duodenal, and Fecal Microbiota Composition Across Adult Celiac Disease.
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Panelli S, Capelli E, Lupo GFD, Schiepatti A, Betti E, Sauta E, Marini S, Bellazzi R, Vanoli A, Pasi A, Cacciatore R, Bacchi S, Balestra B, Pastoris O, Frulloni L, Corazza GR, Biagi F, and Ciccocioppo R
- Abstract
Background: Growing evidence suggests that an altered microbiota composition contributes to the pathogenesis and clinical features in celiac disease (CD). We performed a comparative analysis of the gut microbiota in adulthood CD to evaluate whether: (i) dysbiosis anticipates mucosal lesions, (ii) gluten-free diet restores eubiosis, (iii) refractory CD has a peculiar microbial signature, and (iv) salivary and fecal communities overlap the mucosal one., Methods: This is a cross-sectional study where a total of 52 CD patients, including 13 active CD, 29 treated CD, 4 refractory CD, and 6 potential CD, were enrolled in a tertiary center together with 31 controls. A 16S rRNA-based amplicon metagenomics approach was applied to determine the microbiota structure and composition of salivary, duodenal mucosa, and stool samples, followed by appropriate bioinformatic analyses., Results: A reduction of both α- and β-diversity in CD, already evident in the potential form and achieving nadir in refractory CD, was evident. Taxonomically, mucosa displayed a significant abundance of Proteobacteria and an expansion of Neisseria , especially in active patients, while treated celiacs showed an intermediate profile between active disease and controls. The saliva community mirrored the mucosal one better than stool., Conclusion: Expansion of pathobiontic species anticipates villous atrophy and achieves the maximal divergence from controls in refractory CD. Gluten-free diet results in incomplete recovery. The overlapping results between mucosal and salivary samples indicate the use of saliva as a diagnostic fluid.
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- 2020
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70. IMAGES IN CLINICAL MEDICINE. In Vitro Exflagellation of Plasmodium vivax.
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Balestra B and Carnino L
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- Humans, Male, Young Adult, Flagella, Malaria, Vivax parasitology, Plasmodium vivax cytology
- Published
- 2016
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71. [Tooth-pick? Picking the Right Tooth].
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Apicella L, Cassis PR, and Balestra B
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- Aged, 80 and over, Diagnosis, Differential, Humans, Male, Tomography, X-Ray Computed, Chondrocalcinosis diagnosis, Facial Pain surgery, Maxillary Sinusitis diagnosis, Maxillary Sinusitis etiology, Odontoid Process, Postoperative Complications diagnosis, Postoperative Complications etiology, Tooth Eruption, Ectopic complications, Tooth Eruption, Ectopic diagnosis, Tooth Extraction
- Abstract
We report about an 80-year-old patient, who underwent the extraction of an upper molar tooth because of facial pain. In the course of time the patient developed a maxillary sinusitis in presence of an ectopic tooth. Given that the patient got fever, neck pain and -stiffness, a purulent meningitis was first suspected. The liquor analysis was normal and the CT-scan showed a calcification around the dens axis. We finally diagnosed a “Crowned Dens”-syndrome.
- Published
- 2016
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72. Response of colonic motility to dopaminergic stimulation is subverted in rats with nigrostriatal lesion: relevance to gastrointestinal dysfunctions in Parkinson's disease.
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Levandis G, Balestra B, Siani F, Rizzo V, Ghezzi C, Ambrosi G, Cerri S, Bonizzi A, Vicini R, Vairetti M, Ferrigno A, Pastoris O, and Blandini F
- Subjects
- Animals, Chromatography, High Pressure Liquid, Constipation etiology, Constipation physiopathology, Disease Models, Animal, Dopaminergic Neurons, Down-Regulation, Fluorescent Antibody Technique, Gastrointestinal Diseases etiology, Gastrointestinal Motility drug effects, Gastrointestinal Motility physiology, Image Processing, Computer-Assisted, Male, Oxidopamine administration & dosage, Oxidopamine toxicity, Parkinsonian Disorders complications, Rats, Rats, Sprague-Dawley, Real-Time Polymerase Chain Reaction, Substantia Nigra drug effects, Colon metabolism, Gastrointestinal Diseases physiopathology, Parkinsonian Disorders physiopathology, Receptors, Dopamine D2 biosynthesis, Substantia Nigra injuries
- Abstract
Background: Constipation is extremely common in patients with Parkinson's disease (PD) and has been described in PD animal models. In this study, we investigated whether a PD-like degeneration of dopaminergic neurons of the substantia nigra can influence peristalsis in colonic segments of rats by impacting on enteric dopaminergic transmission., Methods: Male, Sprague-Dawley rats received a unilateral injection of neurotoxin 6-hydroxydopamine (6-OHDA), or saline, into the medial-forebrain-bundle. Peristaltic activity was recorded in isolated colonic segments, in baseline conditions and following exposure to combinations of D2 receptor (DRD2) agonist sumanirole and antagonist L-741626. Dopamine levels and DRD2 expression were assessed in the ileum and colon of animals. We also investigated the involvement of the dorsal motor nucleus of the vagus (DMV) - a potential relay station between central dopaminergic denervation and gastrointestinal (GI) dysfunction - by analyzing cytochrome c oxidase activity and FosB/DeltaFosB expression in DMV neurons., Key Results: We observed profound alterations in the response of colonic segments of 6-OHDA lesioned animals to DRD2 stimulation. In fact, the inhibition of colonic peristalsis elicited by sumanirole in control rats was absent in 6-OHDA-lesioned animals. These animals also showed reduced DRD2 expression in the colon, along with elevation of dopamine levels. No significant changes were detected within the DMV., Conclusions & Inferences: Our results demonstrate that selective lesion of the nigrostriatal dopaminergic pathway subverts the physiological response of the colon to dopaminergic stimulation, opening new perspectives in the comprehension and treatment of GI dysfunctions associated with PD., (© 2015 John Wiley & Sons Ltd.)
- Published
- 2015
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73. Paleoceanography. Onset of Mediterranean outflow into the North Atlantic.
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Hernández-Molina FJ, Stow DA, Alvarez-Zarikian CA, Acton G, Bahr A, Balestra B, Ducassou E, Flood R, Flores JA, Furota S, Grunert P, Hodell D, Jimenez-Espejo F, Kim JK, Krissek L, Kuroda J, Li B, Llave E, Lofi J, Lourens L, Miller M, Nanayama F, Nishida N, Richter C, Roque C, Pereira H, Sanchez Goñi MF, Sierro FJ, Singh AD, Sloss C, Takashimizu Y, Tzanova A, Voelker A, Williams T, and Xuan C
- Subjects
- Atlantic Ocean, Mediterranean Sea, Paleontology, Climate Change, Seawater, Water Movements
- Abstract
Sediments cored along the southwestern Iberian margin during Integrated Ocean Drilling Program Expedition 339 provide constraints on Mediterranean Outflow Water (MOW) circulation patterns from the Pliocene epoch to the present day. After the Strait of Gibraltar opened (5.33 million years ago), a limited volume of MOW entered the Atlantic. Depositional hiatuses indicate erosion by bottom currents related to higher volumes of MOW circulating into the North Atlantic, beginning in the late Pliocene. The hiatuses coincide with regional tectonic events and changes in global thermohaline circulation (THC). This suggests that MOW influenced Atlantic Meridional Overturning Circulation (AMOC), THC, and climatic shifts by contributing a component of warm, saline water to northern latitudes while in turn being influenced by plate tectonics., (Copyright © 2014, American Association for the Advancement of Science.)
- Published
- 2014
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74. Colonic mucosal mediators from patients with irritable bowel syndrome excite enteric cholinergic motor neurons.
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Balestra B, Vicini R, Cremon C, Zecchi L, Dothel G, Vasina V, De Giorgio R, Paccapelo A, Pastoris O, Stanghellini V, Corinaldesi R, De Ponti F, Tonini M, and Barbara G
- Subjects
- Adult, Animals, Colon immunology, Colon metabolism, Colon pathology, Female, Guinea Pigs, Humans, Intestinal Mucosa immunology, Intestinal Mucosa pathology, Irritable Bowel Syndrome immunology, Irritable Bowel Syndrome pathology, Male, Mast Cells immunology, Mast Cells pathology, Motor Neurons metabolism, Myenteric Plexus metabolism, Cholinergic Neurons metabolism, Culture Media, Conditioned pharmacology, Intestinal Mucosa metabolism, Irritable Bowel Syndrome metabolism, Mast Cells metabolism
- Abstract
Background: Mediators released in the mucosal milieu have been suggested to be involved in visceral hypersensitivity and abdominal pain in patients with irritable bowel syndrome (IBS). However, their impact on myenteric neurons remains unsettled., Methods: Mucosal biopsies were obtained from the descending colon of patients with IBS and controls. Mucosal mast cells were identified immunohistochemically. The impact of spontaneously released mucosal mediators on guinea pig electrically stimulated longitudinal muscle myenteric plexus (LMMP) preparations was assessed in vitro by means of selective receptor antagonists and inhibitors., Key Results: Patients with IBS showed an increased mast cell count compared with controls. Application of mucosal mediators of IBS to LMMPs potentiated cholinergic twitch contractions, an effect directly correlated with mast cell counts. Enhanced contractions were inhibited by 50.3% with the prostaglandin D2 antagonist BW A868C, by 31.3% and 39% with the TRPV1 antagonists capsazepine and HC-030031, respectively, and by 60.5% with purinergic P2X antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid. Conversely, the serotonin1-4, histamine1-3, tachykinin1-3 receptor blockade, and serine protease inhibition had no significant effect., Conclusions & Inferences: Colonic mucosal mediators from patients with IBS excite myenteric cholinergic motor neurons. These effects were correlated with mast cell counts and mediated by activation of prostanoid receptors, TRPV1, and P2X receptors. These results support the role of mucosal inflammatory mediators and mast cell activation in altered motor function of IBS., (© 2012 Blackwell Publishing Ltd.)
- Published
- 2012
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75. Fetopathy probably associated to self-medication with a blocker of the renin-angiotensin system.
- Author
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Esposito F, Galfetti M, Lava SA, Balestra B, and Bianchetti MG
- Subjects
- Adrenergic beta-Antagonists therapeutic use, Adult, Angiotensin II Type 1 Receptor Blockers therapeutic use, Antimalarials therapeutic use, Cesarean Section, Female, Fetal Growth Retardation diagnosis, Humans, Hydroxychloroquine therapeutic use, Infant, Newborn, Kidney diagnostic imaging, Kidney drug effects, Losartan therapeutic use, Lupus Erythematosus, Systemic drug therapy, Male, Metoprolol therapeutic use, Oligohydramnios diagnosis, Pregnancy, Ultrasonography, Angiotensin II Type 1 Receptor Blockers adverse effects, Fetal Growth Retardation chemically induced, Losartan adverse effects, Oligohydramnios chemically induced, Renin-Angiotensin System drug effects, Self Medication adverse effects
- Published
- 2011
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76. Inhaled ammonium persulphate inhibits non-adrenergic, non-cholinergic relaxations in the guinea pig isolated trachea.
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Dellabianca A, Faniglione M, De Angelis S, Colucci M, Cervio M, Balestra B, Tonini S, and Candura SM
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- Administration, Inhalation, Animals, Carbachol pharmacology, Carbon Monoxide physiology, Cell Count, Cholinergic Agonists pharmacology, Electric Stimulation, Eosinophils pathology, Guinea Pigs, Male, Muscle Contraction drug effects, Muscle Contraction physiology, Muscle Relaxation physiology, Muscle, Smooth drug effects, Muscle, Smooth innervation, Muscle, Smooth physiology, Neutrophils pathology, Nitric Oxide physiology, Trachea pathology, Trachea physiology, Vasoactive Intestinal Peptide physiology, Ammonium Sulfate pharmacology, Muscle Relaxation drug effects, Trachea innervation
- Abstract
Background: Persulphates can act both as irritants and sensitizers in inducing occupational asthma. A dysfunction of nervous control regulating the airway tone has been hypothesized as a mechanism underlying bronchoconstriction in asthma., Objectives: It was the aim of this study to investigate whether inhaled ammonium persulphate affects the non-adrenergic, non-cholinergic (NANC) inhibitory innervation, the cholinergic nerve-mediated contraction or the muscular response to the spasmogens, carbachol or histamine, in the guinea pig epithelium-free, isolated trachea., Methods: Male guinea pigs inhaled aerosols containing ammonium persulphate (10 mg/m(3) for 30 min for 5 days during 3 weeks). Control animals inhaled saline aerosol. NANC relaxations to electrical field stimulation at 3 Hz were evaluated in whole tracheal segments as intraluminal pressure changes. Drugs inactivating peptide transmission, nitric oxide synthase, carbon monoxide production by haem oxygenase-2 and soluble guanylyl cyclase were used to assess the involvement of various inhibitory neurotransmitters. Carbachol and histamine cumulative concentration-response curves were obtained., Results: In both groups, nitric oxide and carbon monoxide participated to the same extent as inhibitory neurotransmitters. In exposed animals, the tracheal NANC relaxations were reduced to 45.9 +/- 12.1% (p < 0.01). The cholinergic nerve-mediated contractions to electrical field stimulation and the muscular response to histamine were not modified by ammonium persulphate exposure. The muscular response to carbachol was unaffected up to 1 microM. Conversely, the response to the maximal concentration of carbachol (3 microM) was increased (p < 0.01)., Conclusion: Ammonium persulphate inhalation at high concentrations impairs the nervous NANC inhibitory control in the guinea pig airways. This may represent a novel mechanism contributing to persulphate-induced asthma., (Copyright 2009 S. Karger AG, Basel.)
- Published
- 2010
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77. Functional and neurochemical changes of the gastrointestinal tract in a rodent model of Parkinson's disease.
- Author
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Blandini F, Balestra B, Levandis G, Cervio M, Greco R, Tassorelli C, Colucci M, Faniglione M, Bazzini E, Nappi G, Clavenzani P, Vigneri S, De Giorgio R, and Tonini M
- Subjects
- Animals, Colon innervation, Colon physiopathology, Disease Models, Animal, Enteric Nervous System metabolism, Enteric Nervous System pathology, Enteric Nervous System physiopathology, Gastrointestinal Diseases metabolism, Ileum innervation, Ileum physiopathology, Immunohistochemistry, Male, Neuronal Plasticity physiology, Nitrergic Neurons metabolism, Nitrergic Neurons pathology, Nitric Oxide metabolism, Oxidopamine, Parkinsonian Disorders complications, Rats, Rats, Sprague-Dawley, Gastrointestinal Diseases etiology, Gastrointestinal Diseases physiopathology, Gastrointestinal Motility physiology, Parkinson Disease complications
- Abstract
Patients with Parkinson's disease develop motor disturbances often accompanied by peripheral autonomic dysfunctions, including gastrointestinal disorders, such as dysphagia, gastric stasis and constipation. While the mechanisms subserving enteric autonomic dysfunctions are not clearly understood, they may involve the enteric dopaminergic and/or nitrergic systems. In the present study, we demonstrate that rats with unilateral 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons develop a marked inhibition of propulsive activity compared to sham-operated controls, as indicated by a 60% reduction of daily fecal output at the 4th week of observation. Immunohistochemical data revealed that 6-hydroxydopamine treatment did not affect the total number of HuC/D-positive myenteric neurons in both the proximal and distal segments of ileum and colon. Conversely, in the distal ileum and proximal colon the number of nitrergic neurons was significantly reduced. These results suggest that a disturbed distal gut transit, reminiscent of constipation in the clinical setting, may occur as a consequence of a reduced propulsive motility, likely due to an impairment of a nitric oxide-mediated descending inhibition during peristalsis.
- Published
- 2009
- Full Text
- View/download PDF
78. Adenosine A1 and A3 receptor agonists inhibit nonadrenergic, noncholinergic relaxations in the guinea pig isolated trachea.
- Author
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Dellabianca A, Faniglione M, De Angelis S, Tonini S, Balestra B, Colucci M, Cervio M, Clavenzani P, Chiocchetti R, De Giorgio R, and Candura SM
- Subjects
- Adenosine A1 Receptor Agonists, Adenosine A3 Receptor Agonists, Animals, Guinea Pigs, In Vitro Techniques, Male, Muscle Relaxation, Nitric Oxide Synthase Type I metabolism, Adenosine metabolism, Neurons metabolism, Receptor, Adenosine A1 metabolism, Receptor, Adenosine A3 metabolism, Trachea physiology
- Abstract
Background: Adenosine affects the tone and reactivity of airways by activating specific membrane receptors, named A(1), A(2a), A(2b) and A(3). It affects cellular activities either directly by regulating membrane ion exchanges and polarization, or indirectly by modifying neurotransmitter release., Objectives: We assessed the effect of A(1) and A(3) receptor activation on electrically induced nonadrenergic, noncholinergic (NANC) relaxations in the guinea pig isolated trachea and the localization of A(1) and A(3) receptors in tracheal inhibitory neurons., Methods: NANC responses at 3 Hz were evaluated in the presence of 2-chloro-N(6)-cyclopentyladenosine (CCPA), a selective A(1) agonist, and 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA), a selective A(3) agonist, before and after the administration of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A(1) antagonist, or 9-chloro-2-(2-furanyl)-5-((phenylacetyl)amino[1,2,4]triazolo[1,5-c])quinazoline (MRS 1220), a selective A(3) antagonist, respectively. For immunohistochemistry, tissues were exposed to antibodies to HuC/D, a general neuronal marker, neuronal nitric oxide synthase (nNOS), and A(1) or A(3) adenosine receptors and processed by indirect immunofluorescence., Results: CCPA (10 nM-3 microM) inhibited NANC relaxations. DPCPX (10 nM) failed to antagonize the effect of CCPA, but inhibited per se NANC relaxations (range 0.1-100 nM). CCPA (10 nM-10 microM) contracted unstimulated tracheal preparations, an effect antagonized by 10 nM DPCPX, with a pK(B) value of 8.43. Cl-IB-MECA (10 nM-3 microM) inhibited NANC relaxations through a mechanism antagonized by MRS 1220 (100 nM). A(1)- and A(3)-positive neurons containing nNOS were detected in tracheal sections., Conclusions: Enogenous adenosine may induce airway hyperresponsiveness by inhibiting NANC relaxations via A(1) and A(3) receptors., (Copyright 2008 S. Karger AG, Basel.)
- Published
- 2009
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79. Effects of esomeprazole on glutathione levels and mitochondrial oxidative phosphorylation in the gastric mucosa of rats treated with indomethacin.
- Author
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Pastoris O, Verri M, Boschi F, Kastsiuchenka O, Balestra B, Pace F, Tonini M, and Natale G
- Subjects
- Animals, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Anti-Inflammatory Agents, Non-Steroidal toxicity, Anti-Ulcer Agents administration & dosage, Anti-Ulcer Agents pharmacology, Dose-Response Relationship, Drug, Electron Transport Complex I metabolism, Electron Transport Complex II metabolism, Esomeprazole administration & dosage, Gastric Mucosa metabolism, Gastric Mucosa pathology, Glutathione Disulfide metabolism, Indomethacin administration & dosage, Intubation, Gastrointestinal, Male, Membrane Transport Proteins metabolism, Mitochondria metabolism, Necrosis, Oxidative Phosphorylation drug effects, Rats, Rats, Wistar, Spectrophotometry methods, Stomach Diseases chemically induced, Stomach Diseases metabolism, Stomach Diseases pathology, Esomeprazole pharmacology, Gastric Mucosa drug effects, Glutathione metabolism, Indomethacin toxicity, Mitochondria drug effects
- Abstract
Proton pump inhibitors exert their preventive and healing effects on gastropathy induced by nonsteroidal anti-inflammatory drug (NSAIDs) by a dual action: the antisecretory and the antioxidant effect. The latter was investigated by using esomeprazole against indomethacin-induced gastric mucosa lesions in rats and assessed by a histomorphometric analysis. Treatment by intragastric gavage were 1% methocel as vehicle; esomeprazole 10, 30, or 60 micromol/kg; indomethacin 100 micromol/kg; and esomeprazole 10, 30, or 60 micromol/kg plus indomethacin 100 micromol/kg. The evaluation of glutathione (GSH) levels and respiratory chain complex activities [nicotinamide adenine dinucleotide, reduced (NADH)-ubiquinone oxidoreductase, succinate dehydrogenase, cytochrome C reductase, cytochrome oxidase] was performed in the isolated gastric mucosa. Esomeprazole (10-60 micromol/kg) dose dependently reversed, up to complete recovery, the inhibitory effect of indomethacin on GSH levels (approximately 60% inhibition) and mitochondrial enzyme activities (inhibition ranging from 60% to 75%). Indomethacin-induced mucosal injuries were reduced by esomeprazole. Thus, in addition to inhibiting acid secretion, the gastroprotective effect of esomeprazole can be ascribed to a reduction in gastric oxidative injury.
- Published
- 2008
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80. [Exposure to ammonium persulphate by inhalation: effect on the NANC inhibitory neurotransmitters in the guinea pig trachea].
- Author
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Dellabianca A, Tonini S, Faniglione M, De Amici E, De Angelis S, Balestra B, and Candura SM
- Subjects
- Ammonium Sulfate administration & dosage, Animals, In Vitro Techniques, Inhalation, Male, Swine, Ammonium Sulfate adverse effects, Neurotransmitter Transport Proteins drug effects, Trachea drug effects
- Abstract
To evaluate the effect of ammonium persulphate (AP) inhalation on NANC inhibitory (i-NANC) neurotransmitters of guinea pig airways, we exposed eight guinea pigs to AP (1 mg/m3), by aerosol inhalation for 30 minutes daily for three weeks. Control animals inhaled saline aerosol. After the last exposure, the isolated trachea was mounted in an organ bath and electrically stimulated in the presence of hyoscine, piperoxane and propranolol. The i-NANC responses were evaluated as decreases in intraluminal pressure and expressed as area under the curve (AUC, Pa x seconds). The isolated tracheae were treated with a-chymotrypsin, L-NAME, zinc protoporphyrin IX and ODQ, that inhibit the production or action of the single neurotransmitters, like peptides, NO and CO. In the exposed individuals, the NANC relaxations were below 50%, as compared to controls (P < 0.01). NO and CO were the neurotransmitters responsible for all the i-NANC responses, in similar proportions either in exposed individuals or in controls. In conclusion, ammonium persulphate exposure impairs the i-NANC control of airway tone without specifically affecting any neurotransmitter.
- Published
- 2007
81. [Recent insights into the pathogenesis of abdominal symptoms in functional bowel disorders].
- Author
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Cervio E, Rondanelli M, Balestra B, Dellabianca A, Agazzi A, Giacosa A, and Tonini M
- Subjects
- Animals, Disease Models, Animal, Dyspepsia drug therapy, Enterochromaffin Cells physiology, Gastrointestinal Agents pharmacology, Gastrointestinal Agents therapeutic use, Gastrointestinal Motility drug effects, Humans, Ileum physiology, Immunohistochemistry, Irritable Bowel Syndrome drug therapy, Irritable Bowel Syndrome metabolism, Muscle, Smooth drug effects, Muscle, Smooth metabolism, Peristalsis drug effects, Peristalsis physiology, Receptors, Serotonin drug effects, Serotonin Agents pharmacology, Serotonin Agents therapeutic use, Serotonin Antagonists pharmacology, Serotonin Antagonists therapeutic use, Dyspepsia etiology, Gastrointestinal Motility physiology, Irritable Bowel Syndrome physiopathology, Receptors, Serotonin physiology, Serotonin physiology
- Abstract
In the gut, 5-HT acts as a paracrine signalling molecule released by enterochromaffin cells and as a transmitter released by some descending serotonergic interneurons. It has a prominent role in the regulation of motility, vascular tone, secretion and perception both in normal and under certain pathophysiological conditions, such as the carcinoid syndrome and the irritable bowel syndrome (IBS). Serotonin is known to markedly influence bowel function by activating at least five receptor types (5-HT(1,2,3,4,7)). Among all 5-HT receptors, those belonging to the 5-HT3 (a ionotropic receptor) and 5-HT4 (a metabotropic receptor) type are the most extensively studied in gastroenterology, resulting in commercially available (although not worldwide) serotonergic agents for the treatment of IBS and functional dyspepsia. Recently, 5-HT7 receptors have been found to participate in the accommodation process of the circular muscle during the preparatory phase of ileal peristalsis. Since an exaggerated accommodation of the gut wall may contribute to abdominal distension and bloating, 5-HT7 receptor ligands may offer innovative opportunities for the pharmacological treatment of functional bowel disorders.
- Published
- 2007
82. Role of galanin receptor 1 in peristaltic activity in the guinea pig ileum.
- Author
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Sternini C, Anselmi L, Guerrini S, Cervio E, Pham T, Balestra B, Vicini R, Baiardi P, D'agostino GL, and Tonini M
- Subjects
- Acetylcholine metabolism, Animals, Dose-Response Relationship, Drug, Electric Stimulation, Guinea Pigs, Immunohistochemistry, Microscopy, Confocal, Muscle Contraction drug effects, Muscle Contraction physiology, Muscle, Smooth drug effects, Muscle, Smooth physiology, Myenteric Plexus physiology, Neurons drug effects, Neurons metabolism, Organ Culture Techniques, Synaptic Transmission drug effects, Synaptic Transmission physiology, Galanin pharmacology, Ileum physiology, Myenteric Plexus drug effects, Peristalsis physiology, Receptor, Galanin, Type 1 metabolism
- Abstract
Galanin effects are mediated by distinct receptors, galanin receptor 1 (GAL-R1), GAL-R2 and GAL-R3. Here, we analyzed 1) the role of GAL-R1 in cholinergic transmission and peristalsis in the guinea-pig ileum using longitudinal muscle-myenteric plexus preparations and intact segments of the ileum in organ bath, and 2) the distribution of GAL-R1 immunoreactivity in the myenteric plexus with immunohistochemistry and confocal microscopy. Galanin inhibited electrically stimulated contractions of longitudinal muscle-myenteric plexus preparations with a biphasic curve. Desensitization with 1 microM galanin suppressed the high potency phase of the curve, whereas the GAL-R1 antagonist, RWJ-57408 (1 microM), inhibited the low potency phase. Galanin (3 microM) reduced the longitudinal muscle contraction and the peak pressure, and decreased the compliance of the circular muscle. All these effects were antagonized by RWJ-57408 (1 or 10 microM). RWJ-57408 (10 microM) per se did not affect peristalsis parameters in normal conditions, nor when peristalsis efficiency was reduced by partial nicotinic transmission blockade with hexamethonium. In the myenteric plexus, GAL-R1 immunoreactivity was localized to neurons and to fibers projecting within the plexus and to the muscle. GAL-R1 was expressed mostly by cholinergic neurons and by some neurons containing vasoactive intestinal polypeptide or nitric oxide synthase. This study indicates that galanin inhibits cholinergic transmission to the longitudinal muscle via two separate receptors; GAL-R1 mediates the low potency phase. The reduced peristalsis efficiency could be explained by inhibition of the cholinergic drive, whereas the decreased compliance is probably due to inhibition of descending neurons and/or to the activation of an excitatory muscular receptor. Endogenous galanin does not appear to affect neuronal pathways subserving peristalsis in physiologic conditions via GAL-R1.
- Published
- 2004
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83. 5-HT4 receptors contribute to the motor stimulating effect of levosulpiride in the guinea-pig gastrointestinal tract.
- Author
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Tonini M, De Giorgio R, Spelta V, Bassotti G, Di Nucci A, Anselmi L, Balestra B, and De Ponti F
- Subjects
- Animals, Colon drug effects, Electric Stimulation, Guinea Pigs, In Vitro Techniques, Indoles pharmacology, Male, Muscle Contraction physiology, Muscle, Smooth physiology, Myenteric Plexus drug effects, Myenteric Plexus physiology, Pyloric Antrum drug effects, Pyloric Antrum physiology, Receptors, Serotonin physiology, Serotonin Antagonists pharmacology, Sulfonamides pharmacology, Dopamine Antagonists pharmacology, Muscle Contraction drug effects, Muscle, Smooth drug effects, Receptors, Serotonin drug effects, Sulpiride analogs & derivatives, Sulpiride pharmacology
- Abstract
Background: The dopamine D2 receptor antagonist levosulpiride is a substituted benzamide derivative, whose gastrokinetic properties are exploited clinically for the management of functional dyspepsia. However, for other benzamide derivatives, such as cisapride and mosapride, agonism towards serotonin 5-HT4 receptors is considered the main mechanism leading to gastrointestinal prokinesia., Aims: To assess whether levosulpiride is able to activate 5-HT4 receptors in the guinea-pig isolated gastrointestinal tract., Materials and Methods: Circular muscle strips from gastric antrum, and colonic longitudinal muscle strips were used to detect electrically stimulated neurogenic contractions. The effect of levosulpiride was assessed in the absence and presence of GR125487, a selective 5-HT4 receptor antagonist. Furthermore, potential interaction of levosulpiride with 5-HT3 receptors and tissue cholinesterases was assessed in unstimulated ileal longitudinal muscle-myenteric plexus preparations., Results: Antral and colonic strip contractions were cholinergic/tachykinergic in nature. Micromolar concentrations of levosulpiride potentiated submaximal responses, through a mechanism competitively antagonized by GR125487 (pKB=9.4). In LMMPs, levosulpiride slightly affected contractions caused by the 5-HT, receptor agonist 2-methyl-5-HT, and had no effect on contractions to exogenous acetylcholine., Conclusions: Our results indicate that levosulpiride acts as a moderate agonist at the 5-HT4 receptor. This property, together with antagonism at D2 receptors, may contribute to its gastrointestinal prokinetic effect.
- Published
- 2003
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84. [A case of pseudophlebitis of the great saphenous vein: focal nodular myositis of the gracilis muscle].
- Author
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Cantarelli L, Passega-Sidler E, Taddei L, and Balestra B
- Subjects
- Aged, Diagnosis, Differential, Female, Humans, Muscle, Skeletal surgery, Phlebitis pathology, Phlebitis surgery, Thrombophlebitis diagnosis, Muscle, Skeletal blood supply, Phlebitis diagnosis, Saphenous Vein
- Abstract
A case of focal myositis in a healthy 68-year-old woman is described. The patient was admitted for evaluation of a painful soft-tissue mass localised on the medial side of the left thigh, initially misdiagnosed as thrombophlebitis of the v. saphena magna. Laboratory data were normal, in particular sedimentation rate and muscle enzyme levels. After exclusion of venous thrombosis, the mass localised in the left m. gracilis was surgically removed. Histologic examination of the biopsy specimen showed muscle cell necrosis and severe inflammation, with lymphocytic infiltration leading to the diagnosis of focal myositis. This is a rare benign inflammatory pseudotumour of skeletal muscle. The aetiology and pathogenesis of the disease remain unclear. It is most commonly seen in the lower extremities and may mimic thrombophlebitis or soft-tissue neoplasm. Ultrasound and magnetic-resonance scans are helpful, but definitive diagnosis is obtained only by histology. Because recurrent lesions in other skeletal muscles are possible, and a third of patients develop polymyositis, a follow-up of several years is recommended.
- Published
- 2000
85. Mycotic aneurysms of the aorta caused by infection with Pasteurella multocida.
- Author
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Balestra B
- Subjects
- Aneurysm, Infected microbiology, Aortic Aneurysm microbiology, Humans, Male, Middle Aged, Pasteurella Infections microbiology, Aneurysm, Infected etiology, Aortic Aneurysm etiology, Pasteurella Infections complications, Pasteurella multocida isolation & purification
- Abstract
We evaluated a patient for mycotic aneurysms caused by Pasteurella multocida. We treated Pasteurella aortitis medically with ciprofloxacin, and the patient has had long-term survival.
- Published
- 2000
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86. Chick optic lobe contains a developmentally regulated alpha2alpha5beta2 nicotinic receptor subtype.
- Author
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Balestra B, Vailati S, Moretti M, Hanke W, Clementi F, and Gotti C
- Subjects
- Animals, Antibodies immunology, Blotting, Western, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Central Nervous System drug effects, Central Nervous System metabolism, Chickens, Gene Expression Regulation, Developmental, In Vitro Techniques, Lipid Bilayers metabolism, Nicotinic Agonists pharmacology, Precipitin Tests, Prosencephalon drug effects, Prosencephalon metabolism, Pyridines pharmacology, Receptors, Nicotinic classification, Receptors, Nicotinic genetics, Receptors, Nicotinic immunology, Tritium, Receptors, Nicotinic metabolism, Tectum Mesencephali metabolism
- Abstract
The most widely expressed neuronal nicotinic acetylcholine receptor subtype in chick brain is that containing the alpha4 and beta2 subunits. However, immunoprecipitation and localization studies have shown that some brain areas also contain the alpha2 and/or alpha5 subunits, whose role in the definition of receptor properties is still intriguing. Using subunit-specific polyclonal antibodies, we found that the optic lobe is the chick central nervous system region that expresses the highest level of alpha2-containing receptors. Immunoprecipitation studies of these immunopurified alpha2-containing receptors labeled with the nicotinic agonist [(3)H]epibatidine showed that almost all of them contained the beta2 subunit and that more than 66% contained the alpha5 subunit. Western blot analyses of the purified receptors confirmed the presence of the alpha2, alpha5, and beta2 subunits and the absence of the alpha3, alpha4, alpha6, alpha7, alpha8, beta3, and beta4 subunits. The alpha2-containing receptors are developmentally regulated: their expression increases 25 times from embryonic day 7 to posthatching day 1 in the optic lobe, compared with an increase of only 5-fold in the forebrain. The alpha2-containing optic lobe receptors bind [(3)H]epibatidine (K(d) = 29 pM) and a number of other nicotinic agonists with very high affinity and have a pharmacological profile very similar to that of the alpha4beta2 subtype. They form functional cationic channels when reconstituted in lipid bilayers, with pharmacological and biophysical properties different from those of the alpha4beta2 subtype. These channels are activated by nicotinic agonists in a dose-dependent manner and are blocked by the nicotinic antagonist d-tubocurarine.
- Published
- 2000
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87. [Acute necrotizing hepatitis: an unusual side effect of oral anticoagulants].
- Author
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Capoferri M, Realini S, and Balestra B
- Subjects
- Administration, Oral, Aged, Anticoagulants administration & dosage, Biopsy, Chemical and Drug Induced Liver Injury pathology, Drug Hypersensitivity pathology, Female, Humans, Liver drug effects, Liver pathology, Necrosis, Phenprocoumon administration & dosage, Recurrence, Anticoagulants adverse effects, Chemical and Drug Induced Liver Injury etiology, Drug Hypersensitivity etiology, Phenprocoumon adverse effects
- Abstract
We report the case of a severe relapsing phenprocoumon-induced hepatitis. The first episode of hepatitis was thought to be caused by another drug (Verapamil). The anticoagulation with Phenprocoumon was therefore continued after healing of liver inflammation. The relapse typically developed after a shorter exposition-time supporting the hypothesis of an allergic etiology. Fortunately we didn't find any cross-reaction between Phenprocoumon and Acenocoumarol. The patient could thus be anticoagulated orally without complications. If long term anticoagulation is absolutely essential, it is reasonable to prescribe a different Coumarin-derivate. In the case of a cross-reaction, the therapy should be continued with low-molecular weight heparin.
- Published
- 2000
88. [An "exotic" lymphadenopathy: Kikuchi-Fujimotor histiocytic necrotizing lymphadenitis. Case report and discussion].
- Author
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Bernasconi C, Rusca T, and Balestra B
- Subjects
- Adult, Biopsy, Needle, Diagnosis, Differential, Female, Histiocytes pathology, Histiocytic Necrotizing Lymphadenitis pathology, Humans, Lymph Nodes pathology, Histiocytic Necrotizing Lymphadenitis diagnosis
- Abstract
The case of a 25 year old women with isolated inguinal lymphadenopathy and persistent fever caused by necrotizing inguinal lymphadenitis Kikuchi-Fujimoto is reported. Diagnostic and differential diagnostic aspects of this self-limited disorder with unclear pathogenesis are discussed.
- Published
- 2000
89. beta3 subunit is present in different nicotinic receptor subtypes in chick retina.
- Author
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Vailati S, Moretti M, Balestra B, McIntosh M, Clementi F, and Gotti C
- Subjects
- Animals, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Carbachol pharmacology, Chickens, Dose-Response Relationship, Drug, Nicotinic Agonists pharmacology, Protein Isoforms chemistry, Protein Isoforms metabolism, Pyridines pharmacology, Receptors, Nicotinic chemistry, Receptors, Nicotinic immunology, Tritium, alpha7 Nicotinic Acetylcholine Receptor, Receptors, Nicotinic metabolism, Retina metabolism
- Abstract
Although the neuronal nicotinic beta3 subunit was cloned several years ago, it has only recently been shown to form heteromeric channels when associated with other nicotinic subunits, and very little information is available concerning its assembly in the native nicotinic receptors of the nervous system. Using subunit-specific antibodies and immunoprecipitation experiments, we have identified the retina as being the chick central nervous system (CNS) area that expresses the highest level of the beta3 subunit. Sequential immunopurification experiments showed that there are at least two populations of beta3-containing receptors in chick retina: in one, the beta3 subunit is associated with the alpha6 and beta4 subunits; in the other more heterogeneous population, the beta3 subunit is associated with the alpha2, alpha3, alpha4, beta2 and beta4 subunits. Both of these receptor populations bind [3H]epibatidine and a number of nicotinic receptor agonists with high affinity (nM) and nicotinic receptor antagonists with a lower affinity (microM). The greatest pharmacological difference between the two populations is the affinity for the alpha-conotoxin MII, which inhibits binding to alpha6-containing receptors and not that to beta3-containing receptors. We also searched for the presence of the beta3 subunit associated with the alpha-bungarotoxin binding subunits alpha7 and/or alpha8 in retina and chick brain. Immunoprecipitation studies using anti-beta3 antibodies did not detect any specific alpha-bungarotoxin labeled receptors, thus, indicating that the beta3 subunit is not present in the alpha-bungarotoxin receptors of these areas.
- Published
- 2000
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90. Prejunctional muscarinic inhibitory control of acetylcholine release in the human isolated detrusor: involvement of the M4 receptor subtype.
- Author
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D'Agostino G, Bolognesi ML, Lucchelli A, Vicini D, Balestra B, Spelta V, Melchiorre C, and Tonini M
- Subjects
- Adult, Aged, Aged, 80 and over, Autoreceptors drug effects, Choline metabolism, Electric Stimulation, Feedback physiology, Humans, In Vitro Techniques, Male, Middle Aged, Muscarine analogs & derivatives, Muscarine pharmacology, Muscle Contraction drug effects, Muscle, Smooth drug effects, Muscle, Smooth innervation, Neuromuscular Junction drug effects, Neuromuscular Junction metabolism, Receptor, Muscarinic M4, Receptors, Muscarinic drug effects, Urinary Bladder drug effects, Urinary Bladder innervation, Acetylcholine metabolism, Muscarinic Antagonists pharmacology, Muscle, Smooth metabolism, Receptors, Muscarinic metabolism
- Abstract
1. Experiments were carried out in human detrusor strips to characterize muscarinic receptor subtypes involved in the prejunctional regulation of acetylcholine (ACh) release from cholinergic nerve terminals, and in the postjunctional smooth muscle contractile response. 2. In detrusor strips preincubated with [3H]-choline, electrical field stimulation (600 pulses) delivered in six trains at 10 Hz produced a tritium outflow and a contractile response. In the presence of 10 microM paraoxon (to prevent ACh degradation) the tritium outflow was characterized by HPLC analysis as [3H]-ACh (76%) and [3H]-choline (24%). 3. Electrically-evoked [3H]-ACh release was abolished by tetrodotoxin (TTX: 300 nM) and unaffected by hexamethonium (10 microM), indicating a postganglionic event. It was reduced by physostigmine (100 nM) and the muscarinic receptor agonist, muscarone (10 nM-1 microM), and enhanced by atropine (0.1-100 nM). These findings indicate the presence of a muscarinic negative feedback mechanism controlling ACh release. 4. The effects of various subtype-preferring muscarinic receptor antagonists were evaluated on [3H]-ACh release and muscle contraction. The rank potency (-log EC50) orders at pre- and postjunctional level were: atropine > or = 4-diphenyl-acetoxy-N-piperidine (4-DAMP) > mamba toxin 3 (MT-3) > tripitramine > para-fluorohexahydrosiladiphenidol (pF-HHSiD) > or = methoctramine > or = pirenzepine > tripinamide, and atropine > or = 4-DAMP > pF-HHSiD >> pirenzepine = tripitramine > tripinamide > methoctramine >> MT-3, respectively. 5. The comparison of pre- and post-junctional potencies and the relationship analysis with the affinity constants at human cloned muscarinic receptor subtypes indicates that the muscarinic autoreceptor inhibiting ACh release in human detrusor is an M4 receptor, while the receptor involved in muscular contraction belongs to the M3 subtype.
- Published
- 2000
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91. Antibodies against neuronal nicotinic receptor subtypes in neurological disorders.
- Author
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Balestra B, Moretti M, Longhi R, Mantegazza R, Clementi F, and Gotti C
- Subjects
- Binding, Competitive, Bridged Bicyclo Compounds, Heterocyclic metabolism, Bungarotoxins metabolism, Humans, Myasthenia Gravis immunology, Nervous System Diseases physiopathology, Protein Isoforms immunology, Pyridines metabolism, Receptors, Drug metabolism, Tumor Cells, Cultured, Antibodies analysis, Nervous System Diseases immunology, Neurons metabolism, Receptors, Nicotinic immunology
- Abstract
Patients with myasthenia gravis (MG) have antibodies to the muscle nicotinic acetylcholine receptor (mAChR) which are responsible for their muscle weakness: but some patients with MG and other neuroimmunological disorders have autonomic symptoms. We characterised the neuronal forms of AChRs (nAChRs) into two neuroblastoma cell lines and developed immunoprecipitation assays to test for antibodies to the alpha7- and alpha3-containing nAChR subtypes, present in the autonomic ganglia. We then tested 70 sera samples from MG patients, 38 from subjects with other neurological diseases, and 30 from healthy individuals, for antibodies to these two forms of neuronal AChR subtypes. We used the alpha7 subtype extracted from the human neuroblastoma IMR32 cell line labeled with 125IalphaBungarotoxin (alphaBgtx), and the alpha3-containing subtype extracted from the human neuroblastoma SY5Y cell line labeled with 3H-Epibatidine (Epi). Nine subjects (five MG, one GBS, one CIPD and two LEMS) were positive for the alpha7 subtype; and four for the alpha3-containing subtype (two MG patients, one LEMS and the same GBS patient). None of the MG patients with undetectable levels of antibodies against muscle AChR were positive. The patients with serum antibodies to alpha7 or alpha3-containing neuronal AChRs showed a range of clinical features including autonomic symptoms and thymoma in two MG patients. These results indicate that patients with MG and other immune-mediated disorders can have antibodies to neuronal AChRs, and that these may contribute to the clinical characteristics of the diseases.
- Published
- 2000
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92. Role of agonist-dependent receptor internalization in the regulation of mu opioid receptors.
- Author
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Sternini C, Brecha NC, Minnis J, D'Agostino G, Balestra B, Fiori E, and Tonini M
- Subjects
- Acetylcholine metabolism, Animals, Electric Stimulation, Endocytosis drug effects, Endocytosis physiology, Enkephalin, Ala(2)-MePhe(4)-Gly(5)- pharmacology, Enteric Nervous System drug effects, Enteric Nervous System metabolism, Guinea Pigs, Ileum cytology, Ileum drug effects, Ileum innervation, Morphine pharmacology, Naltrexone analogs & derivatives, Naltrexone pharmacology, Narcotic Antagonists pharmacology, Neurons drug effects, Neurons metabolism, Opioid Peptides metabolism, Organ Culture Techniques, Receptors, Opioid, mu drug effects, Receptors, Opioid, mu agonists, Receptors, Opioid, mu metabolism
- Abstract
Organotypic cultures and ileal neuromuscular preparations were used to determine (i) whether endogenous release of opioids by electrical stimulation induces mu receptor endocytosis, and (ii) whether and under which conditions ligand-induced mu receptor endocytosis influences the responsiveness of neurons expressing native mu receptors. In longitudinal muscle-myenteric plexus preparations, electrical stimulation at 20 Hz induced a prominent endocytosis of mu receptors in enteric neurons, indicating endogenous release of opioids. A similar massive endocytosis was triggered by exogenous application of the mu receptor agonist, [D-Ala(2),MePhe(4), Gly-ol(5)] enkephalin, whereas exogenous application of morphine was ineffective. [D-Ala(2),MePhe(4),Gly-ol(5)] enkephalin and morphine induced a concentration-dependent inhibition of neurogenic cholinergic twitch contractions to electrical stimulation at 0.1 Hz. beta-Chlornaltrexamine shifted to the right the inhibitory curve of both agonists with a concentration-dependent reduction of the maximum agonist response, which is consistent with the existence of spare mu opioid receptors. Under these conditions, the induction of mu receptor endocytosis by exogenously applied [D-Ala(2), MePhe(4),Gly-ol(5)] enkephalin diminished the inhibitory effect of this agonist on twitch contractions and tritiated acetylcholine release. In contrast, there was no reduction of the inhibitory effect of morphine, which failed to induce mu receptor endocytosis, on neurogenic cholinergic response. These results provide the first evidence for the occurrence of mu receptor endocytosis in neurons by endogenously released opioids and show that agonist-dependent mu receptor endocytosis could serve as a mechanism to regulate mu opioid receptor responsiveness to ligand stimulation when the opioid receptor reserve is reduced.
- Published
- 2000
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93. Functional alpha6-containing nicotinic receptors are present in chick retina.
- Author
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Vailati S, Hanke W, Bejan A, Barabino B, Longhi R, Balestra B, Moretti M, Clementi F, and Gotti C
- Subjects
- Amino Acid Sequence, Animals, Antibodies immunology, Chickens, Lipid Bilayers metabolism, Membrane Potentials, Molecular Sequence Data, Receptors, Nicotinic chemistry, Receptors, Nicotinic immunology, Retina physiology, Tectum Mesencephali metabolism, Tectum Mesencephali physiology, Receptors, Nicotinic metabolism, Retina metabolism
- Abstract
Despite the fact that the neuronal chick alpha6 subunit was first cloned several years ago and recently has been shown to form acetylcholine (ACh)-activated channels in heterologous systems, no information is yet available concerning the structure and function of the alpha6-containing nicotinic receptors in neuronal tissues. Using subunit-specific antibodies directed against two different epitopes of the chick alpha6 subunit, we performed immunoprecipitation experiments on immunopurified alpha6-containing receptors radiolabeled with the nicotinic agonist [3H]epibatidine (Epi): almost all of the alpha6 receptors contained the beta4 subunit, 51% the beta3 subunit, 42% the alpha3 subunit, and 7.5% the beta2 subunit. Western blot analyses of the purified receptors confirmed the presence of the alpha3, beta3, beta2, and beta4 subunits, and the absence of the alpha4, alpha5, and alpha7 subunits. The alpha6-containing receptors bind [3H]Epi (Kd = 35 pM) and a number of other nicotinic agonists with very high affinity, the rank order being Epi >> cytisine > nicotine > 1, 1-dimethyl-4-phenylpiperazinium > acetylcholine > carbamylcholine. The alpha6 receptors also have a distinct antagonist pharmacological profile with a rank order of potency of alpha-conotoxin MII > methyllycaconitine > dihydro-beta-erythroydine > MG624 > d-tubocurarine > decamethonium > hexamethonium. When reconstituted in lipid bilayers, the alpha6-containing receptors form functional cationic channels with a main conductance state of 48 pS. These channels are activated by nicotinic agonists in a dose-dependent manner, and blocked by the nicotinic antagonist d-tubocurarine.
- Published
- 1999
- Full Text
- View/download PDF
94. [Recurrent subacute encephalopathy in the framework of idiopathic hypereosinophilic syndrome].
- Author
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Balestra B, Pedrazzi P, and Regli F
- Subjects
- Aged, Aged, 80 and over, Anti-Inflammatory Agents therapeutic use, Brain Diseases drug therapy, Follow-Up Studies, Glucocorticoids therapeutic use, Humans, Hypereosinophilic Syndrome drug therapy, Magnetic Resonance Imaging, Male, Methylprednisolone therapeutic use, Prednisone therapeutic use, Time Factors, Brain Diseases diagnosis, Hypereosinophilic Syndrome diagnosis
- Abstract
History: An 81-year-old man, previously good health, suddenly developed confusion and rapidly progressive severe tetraparesis., Investigations: Peripheral blood and bone marrow revealed marked eosinophilia: allergic, parasitic, neoplastic or vasculitic causes were excluded. Magnetic resonance imaging demonstrated multiple lesions in the cortical and subcortical white matter., Diagnosis, Treatment and Course: The findings indicated idiopathic hypereosinophilic syndrome involving the central nervous system and treatment with high doses of glucocorticoids was started. After a stormy course almost complete recovery occurred., Conclusion: Idiopathic hypereosinophilic syndrome can rarely manifest itself a an isolated severe subacute encephalopathy.
- Published
- 1999
- Full Text
- View/download PDF
95. Activation and internalization of the mu-opioid receptor by the newly discovered endogenous agonists, endomorphin-1 and endomorphin-2.
- Author
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McConalogue K, Grady EF, Minnis J, Balestra B, Tonini M, Brecha NC, Bunnett NW, and Sternini C
- Subjects
- Animals, Cell Line metabolism, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, Enkephalins pharmacology, Flow Cytometry, Guinea Pigs, Ileum drug effects, Ileum innervation, Ileum physiology, In Vitro Techniques, Male, Muscle Contraction drug effects, Muscle, Smooth drug effects, Muscle, Smooth physiology, Myenteric Plexus cytology, Myenteric Plexus drug effects, Myenteric Plexus metabolism, Neurons metabolism, Rats, Tissue Distribution physiology, Analgesics, Opioid pharmacology, Oligopeptides pharmacology, Receptors, Opioid, mu drug effects, Receptors, Opioid, mu metabolism
- Abstract
The multiple effects of opiate alkaloids, important therapeutic drugs used for pain control, are mediated by the neuronal miro-opioid receptor. Among the side effects of these drugs is a profound impairment of gastrointestinal transit. Endomorphins are opioid peptides recently isolated from the nervous system, which have high affinity and selectivity for micro-opioid receptors. Since the miro-opioid receptor undergoes ligand-induced receptor endocytosis in an agonist-dependent manner, we compared the ability of endomorphin-1, endomorphin-2 and the micro-opioid receptor peptide agonist, [D-Ala2,MePhe4,Gly-ol5]-enkephalin (DAMGO), to induce receptor endocytosis in cells transfected with epitope-tagged micro-opioid receptor complementary DNA, and in myenteric neurons of the guinea-pig ileum, which naturally express this receptor. Immunohistochemistry with antibodies to the FLAG epitope or to the native receptor showed that the micro-opioid receptor was mainly located at the plasma membrane of unstimulated cells. Endomorphins and DAMGO induced micro-opioid receptor endocytosis into early endosomes, a process that was inhibited by naloxone. Quantification of surface receptors by flow cytometry indicated that endomorphins' and DAMGO stimulated endocytosis with similar time-course and potency. They inhibited with similar potency electrically induced cholinergic contractions in the longitudinal muscle-myenteric plexus preparation through an action antagonized by naloxone. The apparent affinity estimate of naloxone (pA2 approximately 8.4) is consistent with antagonism at the micro-opioid receptor in myenteric neurons. These results indicate that endomorphins directly activate the micro-opioid receptor in neurons, thus supporting the hypothesis that they are ligands mediating opioid actions in the nervous system. Endomorphin-induced micro-opioid receptor activation can be visualized by receptor endocytosis.
- Published
- 1999
- Full Text
- View/download PDF
96. Selective effects of a 4-oxystilbene derivative on wild and mutant neuronal chick alpha7 nicotinic receptor.
- Author
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Maggi L, Palma E, Eusebi F, Moretti M, Balestra B, Clementi F, and Gotti C
- Subjects
- Acetylcholine pharmacology, Amino Acid Substitution, Animals, Antibodies immunology, Binding, Competitive drug effects, Bungarotoxins metabolism, Bungarotoxins pharmacology, Chickens, Cholinergic Agents pharmacology, Dose-Response Relationship, Drug, Female, Immunochemistry, Membrane Potentials drug effects, Muscles drug effects, Muscles metabolism, Mutation, Neurons metabolism, Oocytes, Quaternary Ammonium Compounds chemistry, Radioligand Assay, Receptors, Nicotinic genetics, Receptors, Nicotinic immunology, Stilbenes chemistry, Stilbenes metabolism, Xenopus, alpha7 Nicotinic Acetylcholine Receptor, Neurons drug effects, Quaternary Ammonium Compounds pharmacology, Receptors, Nicotinic metabolism, Stilbenes pharmacology
- Abstract
1. We assessed the pharmacological activity of triethyl-(beta-4-stilbenoxy-ethyl) ammonium (MG624), a drug that is active on neuronal nicotinic receptors (nicotinic AChR). Experiments on the major nicotinic AChR subtypes present in chick brain, showed that it inhibits the binding of [125I]-alphaBungarotoxin (alphaBgtx) to the alpha7 subtype, and that of [3H]-epibatidine (Epi) to the alpha4beta2 subtype, with Ki values of respectively 106 nM and 84 microM. 2. MG624 also inhibited ACh elicited currents (I(ACh)) in the oocyte-expressed alpha7 and alpha4beta2 chick subtypes with half-inhibitory concentrations (IC50) of respectively 109 nM and 3.2 microM. 3. When tested on muscle-type AChR, it inhibited [125I]-alphaBgtx binding with a Ki of 32 microM and ACh elicited currents (I(ACh)) in the oocyte-expressed alpha1beta1gammadelta chick subtype with an IC50 of 2.9 microM. 4. The interaction of MG624 with the alpha7 subtype was investigated using an alpha7 homomeric mutant receptor with a threonine-for-leucine 247 substitution (L247T alpha7). MG624 did not induce any current in oocytes expressing the wild type alpha7 receptor, but did induce large currents in the oocyte-expressed L247T alpha7 receptor. The MG624 elicited current (I(MG62)) has an EC50 of 0.2 nM and a Hill coefficient nH of 1.9, and is blocked by the nicotinic receptor antagonist methyllycaconitine (MLA). 5. These binding and electrophysiological studies show that MG624 is a potent antagonist of neuronal chick alpha7 nicotinic AChR, and becomes a competitive agonist following the mutation of the highly conserved leucine residue 247 located in the M2 channel domain.
- Published
- 1999
- Full Text
- View/download PDF
97. Endomorphin-1 and endomorphin-2 activate mu-opioid receptors in myenteric neurons of the guinea-pig small intestine.
- Author
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Tonini M, Fiori E, Balestra B, Spelta V, D'Agostino G, Di Nucci A, Brecha NC, and Sternini C
- Subjects
- Acetylcholine pharmacology, Animals, Dose-Response Relationship, Drug, Electric Stimulation, Female, Guinea Pigs, Ileum drug effects, Intestine, Small drug effects, Male, Naltrexone analogs & derivatives, Naltrexone pharmacology, Regression Analysis, Somatostatin analogs & derivatives, Somatostatin pharmacology, Analgesics, Opioid pharmacology, Myenteric Plexus drug effects, Oligopeptides pharmacology, Receptors, Opioid, mu drug effects
- Abstract
The novel opioid tetrapeptides, endomorphin-1 and endomorphin-2, recently isolated from bovine and human brain bind with high affinity and selectivity to central mu-opioid receptors. In the digestive tract, a comprehensive pharmacological analysis of the receptors involved in endomorphin action has not been reported. In this study, we analyzed the effects of endomorphin-1 and endomorphin-2 on longitudinal muscle-myenteric plexus preparations (LMMPs) from the guinea-pig ileum. Both peptides (30 pM - 1 microM) inhibited (-log EC50 values: 8.61 and 8.59, respectively) the amplitude of electrically-induced twitch contractions in a concentration-dependent fashion, up to its abolition. Conversely, in unstimulated LMMPs, they failed to affect contractions to applied acetylcholine (100 nM). In stimulated LMMPs, the highly selective mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), caused a concentration-dependent (30 nM-1 microM), parallel rightward shift of endomorphin-1 and endomorphin-2 inhibitory curves, without depression of their maximum. Following Schild analysis, calculated pA2 values were 7.81 and 7.85, respectively, with slopes not different from unity. Concentration-response curves to both peptides were not affected by 30 nM naltrindole (a selective delta-receptor antagonist) or 30 nM nor-binaltorphimine (a selective kappa-receptor antagonist). These results demonstrate that endomorphins selectively activate mu-opioid receptors located on excitatory myenteric plexus neurons, and that they act as full agonists.
- Published
- 1998
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98. 4-Oxystilbene compounds are selective ligands for neuronal nicotinic alphaBungarotoxin receptors.
- Author
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Gotti C, Balestra B, Moretti M, Rovati GE, Maggi L, Rossoni G, Berti F, Villa L, Pallavicini M, and Clementi F
- Subjects
- Animals, Antibody Specificity, Cell Line, Chickens, Guinea Pigs, Iodine Radioisotopes, Radioligand Assay, Rats, Receptors, Nicotinic immunology, Recombinant Proteins immunology, Recombinant Proteins metabolism, Stilbenes pharmacology, Synaptic Transmission, Vagus Nerve drug effects, Vagus Nerve physiology, Bungarotoxins metabolism, Neurons metabolism, Receptors, Nicotinic metabolism, Stilbenes metabolism
- Abstract
1. Starting from the structure of an old 4-oxystilbene derivate with ganglioplegic activity (MG624), we synthesized two further derivates (F2 and F3) and two stereoisomers of F3 (F3A and F3B), and studied their selective effect on neuronal nicotinic acetylcholine receptor (AChR) subtypes. 2. MG 624, F3, F3A and F3B inhibited of 125I-alphaBungarotoxin (alphaBgtx) binding to neuronal chick optic lobe (COL) membranes, with nM affinity, but inhibited 125I-alphaBgtx binding to TE671 cell-expressed muscle-type AChR only at much higher concentrations. 3. We immobilized the alpha7, beta2 and beta4 containing chick neuronal nicotinic AChR subtypes using anti-subunit specific antibodies. MG 624, F3, F3A and F3B inhibited 125I-alphaBgtx binding to the alpha7-containing receptors with nM affinity, but inhibited 3H-Epi binding to beta2-containing receptors only at very high concentrations (more than 35 microM); their affinity for the beta4-containing receptors was ten times more than for the beta2-containing subtype. 4. Both MG624 and F3 compounds inhibited the ACh evoked currents in homomeric oocyte-expressed chick alpha7 receptors with an IC50 of respectively 94 and 119 nM. 5. High doses of both MG 624 and F3 depressed the contractile response to vagus nerve stimulation in guinea pig nerve-stomach preparations although at different IC50s (49.4 vs 166.2 microM) The effect of MG624 on rat nerve-hemidiaphragm preparations was 33 times less potent than that of F3 (IC50 486 vs 14.5 microM). 6. In conclusion, MG624 and F3 have a high degree of antagonist selectivity for neuronal nicotinic alphaBgtx receptors containing the alpha7 subunit.
- Published
- 1998
- Full Text
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99. [Painful discoloration of the forearm].
- Author
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Balestra B and Reiner M
- Subjects
- Adult, Biperiden administration & dosage, Heroin Dependence diagnosis, Humans, Ischemia diagnosis, Rhabdomyolysis chemically induced, Biperiden adverse effects, Emergencies, Hand blood supply, Ischemia chemically induced, Purpura chemically induced, Skin Diseases, Vascular chemically induced, Substance Abuse, Intravenous diagnosis
- Published
- 1998
100. Successful treatment of Salmonella aortitis with ciprofloxacin.
- Author
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Balestra B, Sepic A, and Noseda G
- Published
- 1998
- Full Text
- View/download PDF
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