A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial.

Background: Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services.

Methods/design: The Psychosis early Intervention and Assessment of Needs and Outcome (PIANO) trial is part of a larger research program (Genetics, Endophenotypes and Treatment: Understanding early Psychosis - GET UP) which aims to compare, at 9 months, the effectiveness of a multi-component psychosocial intervention versus treatment as usual (TAU) in a large epidemiologically based cohort of patients with FEP and their family members recruited from all public community mental health centers (CMHCs) located in two entire regions of Italy (Veneto and Emilia Romagna), and in the cities of Florence, Milan and Bolzano. The GET UP PIANO trial has a pragmatic cluster randomized controlled design.

Solute transporters and aquaporins are impaired in celiac disease.

Background Information: Celiac disease is a chronic inflammatory disorder of the small bowel induced in genetically susceptible subjects by gluten ingestion. Diarrhoea, weight loss and malabsorption represent the major clinical presentation of the disease. Here we examined the possible alteration in the expression and localization of water channels [AQPs (aquaporins)] and some solute transporters in duodenal mucosa of celiac disease patients.

Relationship between Vac A toxin and ammonia in Helicobacter pylori-induced apoptosis in human gastric epithelial cells.

VacA toxin is one of the most important virulence factors produced by H. pylori even though neither its role nor its action mechanisms are completely understood. First considered as a toxin inducing only cell vacuolation, VacA causes apoptosis of gastric epithelial cells by targeting mitochondria.

Aquaporin-6 is expressed along the rat gastrointestinal tract and upregulated by feeding in the small intestine.

Background: Several aquaporins (a family of integral membrane proteins) have been recently identified in the mammalian gastrointestinal tract, and their involvement in the movement of fluid and small solutes has been suggested. In this direction we investigated, in some regions of the rat gastrointestinal tract, the presence and localization of aquaporin-6, given its peculiar function as an ion selective channel.

Results: RT-PCR and immunoblotting experiments showed that aquaporin-6 was expressed in all the investigated portions of the rat gastrointestinal tract.

Osmotic water permeability of rat intestinal brush border membrane vesicles: involvement of aquaporin-7 and aquaporin-8 and effect of metal ions.

Water channels AQP7 and AQP8 may be involved in transcellular water movement in the small intestine. We show that both AQP7 and AQP8 mRNA are expressed in rat small intestine. Immunoblot and immunohistochemistry experiments demonstrate that AQP7 and AQP8 proteins are present in the apical brush border membrane of intestinal epithelial cells.

Intracellular, intercellular, and stromal invasion of gastric mucosa, preneoplastic lesions, and cancer by Helicobacter pylori.

Background And Aims: It is not clear how Helicobacter pylori, an apparently extracellular pathogen colonizing the luminal side of the gastric epithelium, invariably causes an immune-inflammatory response on the stromal side of the mucosa. Penetration of H pylori into epithelial cell lines and its interaction with immune-inflammatory cells have been documented in vitro. Several investigations also showed in vivo bacterial penetration into the epithelium up to the lamina propria; however, the identification as H pylori of the bacteria-like bodies observed in unchanged, metaplastic, or neoplastic mucosa remained sometimes questionable.

Free-soluble and outer membrane vesicle-associated VacA from Helicobacter pylori: Two forms of release, a different activity.

Helicobacter pylori releases VacA both as free-soluble and as outer membrane vesicle (OMV)-associated toxin. In this study, we investigated the amount of VacA released in each of the two forms and the role of each form in VacA-induced cell vacuolation in vitro. We found that: (1) free-soluble toxin accounted for about 75% of released VacA, while the remaining 25% was OMV-associated; (2) although OMV-associated VacA caused a statistically significant vacuolation, virtually all the vacuolating activity of a H.

Aquaporin-8 is involved in water transport in isolated superficial colonocytes from rat proximal colon.

Water is an essential nutrient because it must be introduced from exogenous sources to satisfy metabolic demand. Under physiologic conditions, the colon can absorb and secrete considerable amounts of water even against osmotic gradients, thus helping to maintain the body fluid balance. Here we describe studies on both aquaporin (AQP) expression and function using cells isolated from the superficial and lower crypt regions of the rat proximal colon.

Expression and immunolocalization of aquaporin-7 in rat gastrointestinal tract.

Background Information: In the gastrointestinal tract of mammals, water can either be secreted with digestive juices or absorbed by the small and large intestine. Transcellular water movement can be mediated by the transmembrane protein family of AQPs (aquaporins), as has also been recently identified in the gastrointestinal tract. However, the localization, expression and functioning of AQPs in the gastrointestinal tract have not been completely characterized.

Vitamin A deficiency alters the bioelectric parameters and RNA content of rat gastric mucosa in vitro.

The present study was aimed to investigate the mechanisms by which vitamin A plays a role in maintaining the efficiency of gastric mucosal barrier. Particularly, we measured electrical parameters and the RNA/DNA ratio of gastric mucosa isolated in vitro from the stomach of rats in which vitamin A-deficiency was induced by means of a vitamin A-free diet and then abolished by means of a massive vitamin A supplementation. Pair-fed vitamin A-nondepleted rats and normal rats fed ad libitum on a standard diet served as controls.

PYY-Tag transgenic mice displaying abnormal (H+-K+)ATPase activity and gastric mucosal barrier impairment.

The mechanism by which the gastrointestinal hormones peptide YY and glucagon inhibit gastric acid secretion is largely unknown. PYY-Tag transgenic mice develop endocrine tumors in the colon that are composed mainly of peptide YY/enteroglucagon-producing L type cells. Therefore we studied the functional activity of such tumors and the gastric functions of PYY-Tag mice.

NSAIDs counteract H. pylori VacA toxin-induced cell vacuolation in MKN 28 gastric mucosal cells.

The relationship between nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori-induced gastric mucosal injury is still under debate. VacA toxin is an important H. pylori virulence factor that causes cytoplasmic vacuolation in cultured cells.

Guanidine transport across the apical and basolateral membranes of human intestinal Caco-2 cells is mediated by two different mechanisms.

The functional characteristics of the intestinal absorption and secretion of guanidine as a model of a nutritionally and metabolically essential organic cation were examined in the Caco-2 human intestinal cell line. Both apical and basolateral transport of [14C]-guanidine were studied using Caco-2 cells grown on polycarbonate permeable membranes. The basolateral-to-apical flux of [14C]-guanidine (i.

Persistence of Helicobacter pylori VacA toxin and vacuolating potential in cultured gastric epithelial cells.

The vacuolating toxin A (VacA) is one of the most important virulence factors in Helicobacter pylori-induced damage to human gastric epithelium. Using human gastric epithelial cells in culture and broth culture filtrate from a VacA-producing H. pylori strain, we studied 1) the delivery of VacA to cells, 2) the localization and fate of internalized toxin, and 3) the persistence of toxin inside the cell.

Helicobacter pylori upregulates expression of epidermal growth factor-related peptides, but inhibits their proliferative effect in MKN 28 gastric mucosal cells.

Acute exposure to Helicobacter pylori causes cell damage and impairs the processes of cell migration and proliferation in cultured gastric mucosal cells in vitro. EGF-related growth factors play a major role in protecting gastric mucosa against injury, and are involved in the process of gastric mucosal healing. We therefore studied the acute effect of H.

Helicobacter pylori vacuolating toxin accumulates within the endosomal-vacuolar compartment of cultured gastric cells and potentiates the vacuolating activity of ammonia.

This study explored the relationship between vacuolating toxin and ammonia in the genesis of Helicobacter pylori-induced vacuolation in cultured human gastric cells and investigated the intracellular sites of toxin accumulation. Neutral red dye uptake and electron microscopy were used in the investigation of the respective roles of, and of the reciprocal interaction between, toxin and ammonia in cell vacuolation and ultrastructural immunocytochemistry was used for the identification of the intracellular sites of internalized toxin. Toxin was found to cause an expansion of the endosomal compartment, where it accumulates after cellular internalization.

Significance of ammonia in the genesis of gastric epithelial lesions induced by Helicobacter pylori: an in vitro study with different bacterial strains and urea concentrations.

Two Helicobacter pylori products cause cell damage both in vivo and in vitro: ammonia, from bacterial urease activity, and a vacuolating toxin named VacA. In this in vitro study, the vacuolating effect of H. pylori broth culture filtrate from a VacA-positive/urease-positive strain is compared with that of a VacA-negative/urease-positive strain and a VacA-negative/urease-negative strain.

Na+,K(+)-ATPase of gastric cells. A target of Helicobacter pylori cytotoxic activity.

The present study shows a direct impairing action of a cytotoxin-producing Helicobacter pylori strain on the Na+,K(+)-ATPase (evaluated as K(+)-dependent phosphatase activity) of human gastric epithelial cells in culture. The toxin itself is likely involved in this action which may also account for the cell edema found in vivo in Helicobacter pylori-colonized stomach.

Dynamics of nonprotein and protein sulfhydryl compounds in rat gastric mucosa: possible implication for cytoprotection and ulcerogenesis.

The hypothesis that nonprotein and protein sulfhydryls in gastric mucosa may play some role in the defensive and offensive processes of gastric epithelium was tested in this study in the intact rat gastric mucosa. Both sulfhydryl compounds presented statistically significant changes during the 24-hour day. The content of nonprotein sulfhydryls was less during the dark span than during the light span, while the circadian acrophase of protein sulfhydryls occurred during dark span.

[Differences in potential and content of the mucus in the stomach of the rat with avitaminosis A].

Vitamin A (vit. A) acts in the synthesis of glycoproteins and in cell surface phenomena of epithelia. Since the glycoproteins of gastric mucus and the integrity of gastric cell membranes are components of gastric barrier (GB), vit.

Circadian rhythmicity of acid secretion and electrical function in intact and injured rat gastric mucosa--the relation of timing to ulcerogenesis.

Alteration of electrical function in mammalian gastric mucosa is considered as an indicator of gastric barrier rupture. Measurements of transmucosal potential difference (PD) and electrical resistance (R) have documented such alterations to a variety of mucosal damaging agents. This study was designed to test whether the rat gastric mucosa exhibits circadian rhythms in acid secretion and electrical function and whether the damage produced by a mucosal acting agent (butyric acid) is also circadian-stage dependent.

Circadian rhythms of acid secretion and electric parameters in rat gastric mucosa in vitro.

In male Wistar rats standardized from birth in LD 12:12 conditions (with light from 0700 to 1900 hr), samples of mucosa from the body of the stomach were isolated in vitro and mounted in a Ussing-type chamber. Spontaneous secretion of the hydrogen ion (H+)during 45 min of incubation was measured. Some electric parameters [transmucosal potential difference (PD) and electrical resistance (R)] were detected in the gastric mucosa both during H+ secretion and during inhibition of acid secretion by cimetidine.

Gastric mucosa permeability and HCO3- secretion 'in vivo' during perfusion of damaging and protective agents across canine Heidenhain pouches.

Unlabelled: Gastric mucosal barrier of 'in vivo' dogs with a Heidenhain pouch (HP) was broken by butyric acid (BA). Cimetidine intravenously (5 mg/kg/h) prevented HCl secretion. Unidirectional fluxes of H+ and Na+, passive mucosal permeability [evaluated with a low-molecular-weight substance, polyethylenglycole 200(PEG 200)] were increased by BA while transparietal potential difference (PD) was depressed.