The effect of encapsulated glutamine on gut peptide secretion in human volunteers.

CONTEXT: Weight loss and improved blood glucose control after bariatric surgery have been attributed in part to increased ileal nutrient delivery with enhanced release of glucagon-like peptide 1 (GLP-1). Non-surgical strategies to manage obesity are required. The aim of the current study was to assess whether encapsulated glutamine, targeted to the ileum, could increase GLP-1 secretion, improve glucose tolerance or reduce meal size. METHODS: A single-center, randomised, double blind, placebo-controlled, cross-over study was performed in 24 healthy volunteers and 8 patients with type 2 diabetes. Fasting participants received a single dose of encapsulated ileal-release glutamine (3.6 or 6.0 g) or placebo per visit with blood sampling at baseline and for 4h thereafter. Glucose tolerance and meal size were studied using a 75 g oral glucose tolerance test and ad libitum meal respectively. RESULTS: In healthy volunteers, ingestion of 6.0 g glutamine was associated with increased GLP-1 concentrations after 90 min compared with placebo (mean 10.6 pg/ml vs 6.9 pg/ml, p=0.004), increased insulin concentrations after 90 min (mean 70.9 vs 48.5, p=0.048), and increased meal size at 120 min (mean 542 g eaten vs 481 g, p=0.008). Ingestion of 6.0 g glutamine was not associated with significant differences in GLP-1, glucose or insulin concentrations after a glucose tolerance test in healthy or type 2 diabetic participants. CONCLUSIONS: Single oral dosing of encapsulated glutamine did not provoke consistent increases in GLP-1 and insulin secretion and was not associated with beneficial metabolic effects in healthy volunteers or patients with type 2 diabetes.This project was supported by a project grant from the European Union Seventh Framework Programme (FP7/2007-2013; grant agreement n° 266,408) as part of a larger collaboration called Full4Health. Claire Meek receives salary funding from the Wellcome Trust Translational Medicine and Therapeutics Programme which is funded by the Wellcome Trust in association with Glaxo SmithKline. FMG and FR were funded by the Wellcome Trust (WT088357/Z/09/Z and WT084210/Z/07/Z.)This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.peptides.2015.10.00

Comorbidities in rheumatoid arthritis: analysis of hospital discharge records

Objective: Arthritis is often associated with comorbidities. For many of them, such as hypertension, cardiovascular disease, chronic pulmonary disease, and upper gastrointestinal disease, arthritis and its treatment may also represent a risk factor. This study is concerned with an evaluation of the frequency of comorbidities in a cohort of patients with rheumatoid arthritis (RA). Methods: The discharge diagnoses of patients with RA during the period 1 January 1997 to 31 December 2000 were retrieved from the database of the Department of Internal Medicine of the University of Genova, Italy. The diagnosis of RA was made if the patient's discharge record contained the code 714 of the International Classification of Diseases, IX revision, as first 3 numbers. The other diagnoses were also recorded along with demographic data, type and duration of hospital stay, and performed procedures. Results: During the study period, 427 patients with RA were admitted to the hospital for a total number of 761 admissions, which represented 2.2% of total admissions. Ninety-one (21.3%) patients did not have comorbidities, whereas 336 (78.6%) had one or more comorbidities. The most frequently observed comorbidities were cardiovascular diseases (34.6%), including hypertension (14.5%) and angina (3.5%), followed by gastrointestinal (24.5%), genito-urinary (18.7%) and respiratory (17%) diseases. There was a male predominance (p=0.004) within patients with comorbidities, who were significantly older (64.2±3.2 years vs. 57.2±4.2 years; p<0.001) and required longer periods of hospital stay (22.7 days vs. 12.5 days; p<0.001). Conclusions: Comorbidities are present in nearly 80% of RA inpatients. Comorbidity is a good predictor of health outcome, health services utilization, and medical costs. Because RA comorbidity can act as confounder, it should be considered in epidemiologic studies and clinical trials

High levels of osteopontin associated with polymorphisms in its gene are a risk factor for development of autoimmunity/lymphoproliferation

The autoimmune/lymphoproliferative syndrome (ALPS) displays defective function of Fas, autoimmunities, lymphadenopathy/splenomegaly, and expansion of CD4/CD8 double-negative (DN) T cells. Dianzani autoimmune/lymphoproliferative disease (DALD) is an ALPS variant lacking DN cells. Both forms have been ascribed to inherited mutations hitting the Fas system but other factors may be involved. A pilot cDNA array analysis on a DALD patient detected overexpression of the cytokine osteopontin (OPN). This observation was confirmed by enzyme-linked immunosorbent assay (ELISA) detection of higher OPN serum levels in DALD patients (n = 25) than in controls (n = 50). Analysis of the OPN cDNA identified 4 polymorphisms forming 3 haplotypes (A, B, and C). Their overall distribution and genotypic combinations were different in patients (N = 26) and controls (N = 158) (P <.01). Subjects carrying haplotype B and/or C had an 8-fold higher risk of developing DALD than haplotype A homozygotes. Several data suggest that these haplotypes influence OPN levels: (1) in DALD families, high levels cosegregated with haplotype B or C; (2) in healthy controls, haplotype B or C carriers displayed higher levels than haplotype A homozygotes; and (3) in AB and AC heterozygotes, mRNA for haplotype B or C was more abundant than that for haplotype A. In vitro, exogenous OPN decreased activation-induced T-cell death, which suggests that high OPN levels are involved in the apoptosis defect

Alpine ethnobotany in Italy: traditional knowledge of gastronomic and medicinal plants among the Occitans of the upper Varaita valley, Piedmont

A gastronomic and medical ethnobotanical study was conducted among the Occitan communities living in Blins/Bellino and Chianale, in the upper Val Varaita, in the Piedmontese Alps, North-Western Italy, and the traditional uses of 88 botanical taxa were recorded. Comparisons with and analysis of other ethnobotanical studies previously carried out in other Piemontese and surrounding areas, show that approximately one fourth of the botanical taxa quoted in this survey are also known in other surrounding Occitan valleys. It is also evident that traditional knowledge in the Varaita valley has been heavily eroded. This study also examined the local legal framework for the gathering of botanical taxa, and the potential utilization of the most quoted medicinal and food wild herbs in the local market, and suggests that the continuing widespread local collection from the wild of the aerial parts of Alpine wormwood for preparing liqueurs (Artemisia genipi, A. glacialis, and A. umbelliformis) should be seriously reconsidered in terms of sustainability, given the limited availability of these species, even though their collection is culturally salient in the entire study area

Impact of dense-water flow over a sloping bottom on open-sea circulation: Laboratory experiments and an Ionian Sea (Mediterranean) example

The North Ionian Gyre (NIG) displays prominent inversions on decadal scales. We investigate the role of internal forcing induced by changes in the horizontal pressure gradient due to the varying density of Adriatic Deep Water (AdDW), which spreads into the deep layers of the northern Ionian Sea. In turn, the AdDW density fluctuates according to the circulation of the NIG through a feedback mechanism known as the bimodal oscillating system. We set up laboratory experiments with a two-layer ambient fluid in a circular rotating tank, where densities of 1000 and 1015ĝ€¯kgĝ€¯m-3 characterize the upper and lower layers, respectively. From the potential vorticity evolution during the dense-water outflow from a marginal sea, we analyze the response of the open-sea circulation to the along-slope dense-water flow. In addition, we show some features of the cyclonic and anticyclonic eddies that form in the upper layer over the slope area. We illustrate the outcome of the experiments of varying density and varying discharge rates associated with dense-water injection. When the density is high (1020ĝ€¯kgĝ€¯m-3) and the discharge is large, the kinetic energy of the mean flow is stronger than the eddy kinetic energy. Conversely, when the density is lower (1010ĝ€¯kgĝ€¯m-3) and the discharge is reduced, vortices are more energetic than the mean flow - that is, the eddy kinetic energy is larger than the kinetic energy of the mean flow. In general, over the slope, following the onset of dense-water injection, the cyclonic vorticity associated with current shear develops in the upper layer. The vorticity behaves in a two-layer fashion, thereby becoming anticyclonic in the lower layer of the slope area. Concurrently, over the deep flat-bottom portion of the basin, a large-scale anticyclonic gyre forms in the upper layer extending partly toward a sloping rim. The density record shows the rise of the pycnocline due to the dense-water sinking toward the flat-bottom portion of the tank. We show that the rate of increase in the anticyclonic potential vorticity is proportional to the rate of the rise of the interface, namely to the rate of decrease in the upper-layer thickness (i.e., the upper-layer squeezing). The comparison of laboratory experiments with the Ionian Sea is made for a situation when the sudden switch from cyclonic to anticyclonic basin-wide circulation took place following extremely dense Adriatic water overflow after the harsh winter in 2012. We show how similar the temporal evolution and the vertical structure are in both laboratory and oceanic conditions. The demonstrated similarity further supports the assertion that the wind-stress curl over the Ionian Sea is not of paramount importance in generating basin-wide circulation inversions compared with the internal forcing

Clinical, pathological, and prognostic features of rare BRAF mutations in metastatic colorectal cancer: a bi-institutional retrospective analysis (REBUS study)

n/

Biogeochemical, isotopic and bacterial distributions trace oceanic abyssal circulation

We explore the possibility of tracing routes of dense waters toward and within the ocean abyss by the use of an extended set of observed physical and biochemical parameters. To this purpose, we employ mercury, isotopic oxygen, biopolymeric carbon and its constituents, together with indicators of microbial activity and bacterial diversity found in bottom waters of the Eastern Mediterranean. In this basin, which has been considered as a miniature global ocean, two competing sources of bottom water (one in the Adriatic and one in the Aegean seas) contribute to the ventilation of the local abyss. However, due to a recent substantial reduction of the differences in the physical characteristics of these two water masses it has become increasingly complex a water classification using the traditional approach with temperature, salinity and dissolved oxygen alone. Here, we show that an extended set of observed physical and biochemical parameters allows recognizing the existence of two different abyssal routes from the Adriatic source and one abyssal route from the Aegean source despite temperature and salinity of such two competing sources of abyssal water being virtually indistinguishable. Moreover, as the near-bottom development of exogenous bacterial communities transported by convectively-generated water masses in the abyss can provide a persistent trace of episodic events, intermittent flows like those generating abyssal waters in the Eastern Mediterranean basin may become detectable beyond the availability of concomitant measurements.We explore the possibility of tracing routes of dense waters toward and within the ocean abyss by the use of an extended set of observed physical and biochemical parameters. To this purpose, we employ mercury, isotopic oxygen, biopolymeric carbon and its constituents, together with indicators of microbial activity and bacterial diversity found in bottom waters of the Eastern Mediterranean. In this basin, which has been considered as a miniature global ocean, two competing sources of bottom water (one in the Adriatic and one in the Aegean seas) contribute to the ventilation of the local abyss. However, due to a recent substantial reduction of the differences in the physical characteristics of these two water masses it has become increasingly complex a water classification using the traditional approach with temperature, salinity and dissolved oxygen alone. Here, we show that an extended set of observed physical and biochemical parameters allows recognizing the existence of two different abyssal routes from the Adriatic source and one abyssal route from the Aegean source despite temperature and salinity of such two competing sources of abyssal water being virtually indistinguishable. Moreover, as the near-bottom development of exogenous bacterial communities transported by convectively-generated water masses in the abyss can provide a persistent trace of episodic events, intermittent flows like those generating abyssal waters in the Eastern Mediterranean basin may become detectable beyond the availability of concomitant measurements. © 2016 Rubino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Identification of a novel zinc metalloprotease through a global analysis of clostridium difficile extracellular proteins

Clostridium difficile is a major cause of infectious diarrhea worldwide. Although the cell surface proteins are recognized to be important in clostridial pathogenesis, biological functions of only a few are known. Also, apart from the toxins, proteins exported by C. difficile into the extracellular milieu have been poorly studied. In order to identify novel extracellular factors of C. difficile, we analyzed bacterial culture supernatants prepared from clinical isolates, 630 and R20291, using liquid chromatography-tandem mass spectrometry. The majority of the proteins identified were non-canonical extracellular proteins. These could be largely classified into proteins associated to the cell wall (including CWPs and extracellular hydrolases), transporters and flagellar proteins. Seven unknown hypothetical proteins were also identified. One of these proteins, CD630_28300, shared sequence similarity with the anthrax lethal factor, a known zinc metallopeptidase. We demonstrated that CD630_28300 (named Zmp1) binds zinc and is able to cleave fibronectin and fibrinogen in vitro in a zinc-dependent manner. Using site-directed mutagenesis, we identified residues important in zinc binding and enzymatic activity. Furthermore, we demonstrated that Zmp1 destabilizes the fibronectin network produced by human fibroblasts. Thus, by analyzing the exoproteome of C. difficile, we identified a novel extracellular metalloprotease that may be important in key steps of clostridial pathogenesis