Spatial approximation between the C-terminus of VIP and the N-terminal ectodomain of the VPAC1 receptor.

Vasoactive intestinal peptide (VIP) exerts many biological functions through interaction with the VPAC1 receptor, a class II G protein-coupled receptor. Photoaffinity labeling studies associated with receptor mapping and three-dimensional molecular modeling demonstrated that the central part of VIP (6-24) interacts with the N-terminal ectodomain of VPAC1 receptor. However, the domain of the VPAC1 receptor interacting with the C-terminus of VIP is still unknown. A photoaffinity probe, Bpa28-VIP, was synthetized by substitution of amidated Asn28 of VIP by amidated photoreactive para-benzoyl-L-Phe (Bpa). Bpa28-VIP was shown to be a hVPAC1 receptor agonist in CHO cells expressing the recombinant VPAC1 receptor. After obtaining a covalent 125I-[Bpa28-VIP]/hVPAC1 complex, it was cleaved by CNBr, PNGase F, and endopeptidase Glu-C and the cleavage products were analyzed by electrophoresis. The data demonstrated that 125I-[Bpa28-VIP] was covalently bonded to the 121-133 fragment within the N-terminal ectodomain of the receptor. This fragment is adjacent to those covalently attached to the central part (6-24) of VIP.

[Entero-vesical fistula caused by a foreign body]. / Fistola entero-vescicale da corpo estraneo.

An entero-vesical fistula due to intestinal foreign body is rare. A case is presented and the clinical diagnostic and therapeutic aspects of this lesion are discussed.

[Indications, value and limitations of azygos-portal disconnection in the treatment of esophageal varices]. / Indicazione, valore e limiti della deconnessione azygos-portale nella terapia delle varici esofagee.

Satisfactory results obtained, lasting for years in some cases, following azygos-portal disconnection in selected patients with bleeding oesophageal varices, portal hypertension, splenopathy and gastroduodenal ulcer are referred to. It is suggested that wider use should be made of this technique, particularly in patients in poor condition, because the long-term picture does not include the hyperammoniaemic encephalopathy often associated with extensive portosystemic shunts.

[3 cases of aberrant pancreas]. / A proposito di tre casi di pancreas aberrante.

Three cases of aberrant pancreas in a gastrointestinal site are described. The relevant literature is examined, together with the symptomatology, diagnosis and treatment of this form. Attention is drawn to the frequency and possible occurence of aberrant pancreas in cases of gastrointestinal bleeding.

[Video-laparoscopic cholecystectomy with suprapubic approach. Technical note]. / Colecistectomia per via videolaparoscopica con approccio sovrapubico. Note di tecnica.

The authors describe a personal variant of the videolaparoscopic technique of cholecystectomy. This is characterised by the use of an open access to the abdominal cavity following the execution of pneumoperitoneum through an incision in a non-umbilical but suprapubic site, and the use of only three incisions and therefore only three operating trocars. Twenty-nine cholecystectomies have been performed using this personal technique of which only 2 had to be converted to open surgery. The reasons were not attributable to the technique and no complications were observed. The authors also performed a total of 99 laparoscopic cholecystectomies between February 1993 and September 1994 with a total of 4 reconversions and 1 complication (choleperitoneum). Concomitant lithiasis of the choledochus was present in 4 cases and treated with operative ERCP prior to laparoscopic cholecystectomy. Throughout this period only 4 cholecystectomies were performed using a laparotomic access roule owing to concomitant choledochal lithiasis and non-cannulatable papilla during ERCP. The reasons that led the authors to prefer the suprapubic access route were both aesthetic and technical owing to the reduced interference of the videocamera with other instruments, whereas the use of only 3 trocars was also based on the need to economise as well as on aesthetic grounds.

[Esophago-jejunal anastomosis after total gastrectomy with circular suturing: using a personal method]. / Anastomosi esofago-digiunale dopo gastrectomia totale con suturatrice circolare: accorgimento tecnico personale.

The authors describe a personal technique of oesophagus-jejunum anastomosis post total gastrectomy for gastric cancer, inspired by the Oesophagel transection technique. This consists of introducing into the oesophagus the detachable head of the circular stapler by gastrotomy before sectioning the oesophagus and removing the stomach and subsequently carrying out anastomosis as usual. The principal advantage of this technique is in respect to the oesophageal margins to be anastomosed which remain immune to ischemic lesions, lacerations and retractions of the mucosa, with a minor incidence of anastomotic leakage.

[Pheochromocytoma. A case report]. / Feocromocitoma. Presentazione di un caso.

The pheochromocytoma is a catecholamine-secreting tumor, localized in the adrenal gland in 90% of the cases and in extra-adrenal site in the remaining 10%. It can be single or associated with other endocrine neoplasms. On the basis of the case presented, the several clinical manifestations, the treatment of the disease and especially the recent development in imaging as MIBG, TAC, RNM are discussed.

[Randomized clinical analysis of a series of 306 patients operated on for benign pathology of the terminal choledochus]. / Analisi clinica randomizzata su di una serie di 306 pazienti operati per patologia benigna del coledoco terminale.

Personal experience in the surgical management of the common bile duct is described. Over 100 cases of benign disease of the terminal choledocus are examined in a random assessment of 300 cases. The diagnostic and therapeutic techniques adopted are discussed.

The VPAC1 receptor: structure and function of a class B GPCR prototype.

The class B G protein-coupled receptors (GPCRs) represents a small sub-family encompassing 15 members, and are very promising targets for the development of drugs to treat many diseases such as chronic inflammation, neurodegeneration, diabetes, stress, and osteoporosis. The VPAC1 receptor which is an archetype of the class B GPCRs binds Vasoactive Intestinal Peptide (VIP), a neuropeptide widely distributed in central and peripheral nervous system modulating many physiological processes including regulation of exocrine secretions, hormone release, foetal development, immune response … VIP appears to exert beneficial effect in neurodegenerative and inflammatory diseases. This article reviews the current knowledge regarding the structure and molecular pharmacology of VPAC1 receptors. Over the past decade, structure-function relationship studies have demonstrated that the N-terminal ectodomain (N-ted) of VPAC1 plays a pivotal role in VIP recognition. The use of different approaches such as directed mutagenesis, photoaffinity labeling, Nuclear Magnetic Resonance (NMR), molecular modeling, and molecular dynamic simulation has led to demonstrate that: (1) the central and C-terminal part of the VIP molecule interacts with the N-ted of VPAC1 receptor which is itself structured as a « Sushi ¼ domain; (2) the N-terminal end of the VIP molecule interacts with the first transmembrane domain of the receptor where three residues (K(143), T(144), and T(147)) play an important role in VPAC1 interaction with the first histidine residue of VIP.

VPAC1 receptor binding site: contribution of photoaffinity labeling approach.

The vasoactive intestinal peptide (VIP) is a prominent 28 aminoacid neuropeptide with wide distribution in both central and peripheral nervous systems, where it plays important regulatory role in many physiological processes. VIP has a large spectrum of biological functions including exocrine secretions, hormone release, foetal development, immune response and also exerts beneficial effect in neuro-degenerative and inflammatory diseases. Few years ago, it has been shown that VIP can be a promising anti-inflammatory agent. VIP mechanisms of action implicate two sub-types of receptors (VPAC1 and VPAC2) which are members of class B receptors belonging to the super-family of G protein-coupled receptor (GPCR). Because, VPAC1 receptor plays an important role in the modulation of the ant-inflammatory response and represent an archetype of class B GPCR, we have extensively studied the structure-function relationship of this receptor, which allowed us to define the molecular basis of that receptor in term of affinity, specificity, desensitization and coupling to adenylyl cyclase. Those studies showed the crucial role of the N-terminal ectodomain (N-ted) of VPAC1 receptor in VIP binding. Using different techniques including photoaffinity labeling, NMR, molecular modeling and molecular dynamic simulation, it has been possible to define how VIP interacts with its receptor. We have shown that most of the VIP molecule, 1-28 (alpha-helix) sequence, tightly binds the N-ted part of the receptor which is himself structured as a <> domain. In contrast, the N-terminal part of the specific antagonist PG97-269 is in physical contact with the N-ted but in different region. These studies define the molecular mechanism implicated in the activation of class B VPAC1 receptor and should allow the development of new VIP pharmacology using rational synthesis of agonist molecules.