Is the diagnostic rate for the common subtypes of A1AT deficiency consistent across two Canadian Provinces?

Background: The diagnosis of alpha-1-antitrypsin (A1AT) deficiency has been hindered by obscurity concerning the testing process and treatment implications. In this study, we aimed to identify regional differences in the diagnostic rates for A1AT deficiency in the western Canadian provinces of British Columbia (BC) and Alberta (AB).

Methods: The number of A1AT deficiency variant genotype (ZZ, SZ, MZ, SS, and MS) diagnoses were reviewed for BC and AB.

Fecal Calprotectin, CRP and Leucocytes in IBD Patients: Comparison of Biomarkers With Biopsy Results.

Background: This study aimed to compare fecal calprotectin (FC) levels with other commonly used parameters as part of patient care during evaluation for inflammatory bowel disease (IBD).

Methods: We recruited adult IBD patients with ulcerative colitis (UC) and Crohn's disease (CD) and compared the results of the patient's biopsy results (i.e.

Null: A novel α-antitrypsin allele with in cis variants Glu366Lys and Ile100Asn.

Background: α-Antitrypsin (A1AT) deficiency predisposes patients to pulmonary disease due to inadequate protection against human neutrophil elastase released during inflammatory responses. A1AT deficiency is caused by homozygosity or compound heterozygosity for A1AT variants; individuals with A1AT deficiency most commonly have at least one Z variant allele (c.1096G > A (Glu366Lys)).

Profound Chemopreventative Effects of a Hydrogen Sulfide-Releasing NSAID in the APCMin/+ Mouse Model of Intestinal Tumorigenesis.

Nonsteroidal anti-inflammatory drugs have been shown to reduce the incidence of gastrointestinal cancers, but the propensity of these drugs to cause ulcers and bleeding limits their use. H2S has been shown to be a powerful cytoprotective and anti-inflammatory substance in the digestive system. This study explored the possibility that a H2S-releasing nonsteroidal anti-inflammatory drug (ATB-346) would be effective in a murine model of hereditary intestinal cancer (APCMin+ mouse) and investigated potential mechanisms of action via transcriptomics analysis.

Hydrogen sulfide protects from colitis and restores intestinal microbiota biofilm and mucus production.

Background: Microbiota dysbiosis and impaired barrier function are among the most prominent features of inflammatory bowel disease. In the gastrointestinal tract, hydrogen sulfide (H(2)S) is an important regulator of mucosal homeostasis. We hypothesized that H(2)S promotes resolution of colonic inflammation through actions on microbiota biofilm and the mucus barrier.

Proresolution effects of hydrogen sulfide during colitis are mediated through hypoxia-inducible factor-1α.

During a course of colitis, production of the gaseous mediator hydrogen sulfide (H2S) is markedly up-regulated at sites of mucosal damage and contributes significantly to healing and resolution of inflammation. The signaling mechanisms through which H2S promotes resolution of colitis are unknown. We hypothesized that the beneficial effects of H2S in experimental colitis are mediated via stabilization of hypoxia-inducible factor (HIF)-1α.

PERP, a host tetraspanning membrane protein, is required for Salmonella-induced inflammation.

Salmonella enterica Typhimurium induces intestinal inflammation through the activity of type III secreted effector (T3SE) proteins. Our prior results indicate that the secretion of the T3SE SipA and the ability of SipA to induce epithelial cell responses that lead to induction of polymorphonuclear transepithelial migration are not coupled to its direct delivery into epithelial cells from Salmonella. We therefore tested the hypothesis that SipA interacts with a membrane protein located at the apical surface of intestinal epithelial cells.

Impaired hydrogen sulfide synthesis and IL-10 signaling underlie hyperhomocysteinemia-associated exacerbation of colitis.

Vitamin B deficiencies, which can lead to hyperhomocysteinemia (Hhcy), are commonly reported in patients with inflammatory bowel disease (IBD) and may be a causative underlying factor. However, the mechanism for this effect is not known. Hydrogen sulfide (H2S) is a gaseous mediator that promotes tissue repair and resolution of inflammation.

The oxido-reductase enzyme glutathione peroxidase 4 (GPX4) governs Salmonella Typhimurium-induced neutrophil transepithelial migration.

Neutrophil (polymorphonuclear leucocytes; PMN) transmigration across mucosal surfaces contributes to dysfunction of epithelial barrier properties, a characteristic underlying many mucosal inflammatory diseases. Using Salmonella enterica serovar Typhimurium (S. Typhimurium) as a prototypic proinflammatory insult, we have previously reported that the eicosanoid hepoxilin A3 (HXA3 ), an endogenous product of 12-lipoxygenase (12-LOX) activity, is secreted from the apical surface of the intestinal epithelium to establish a chemotactic gradient that guides PMN across the epithelial surface.

Salmonella effectors: important players modulating host cell function during infection.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative facultative food-borne pathogen that causes gastroenteritis in humans. This bacterium has evolved a sophisticated machinery to alter host cell function critical to its virulence capabilities.

The ERM protein, ezrin, regulates neutrophil transmigration by modulating the apical localization of MRP2 in response to the SipA effector protein during Salmonella Typhimurium infection.

In human disease induced by Salmonella enterica serovar Typhimurium (S. Typhimurium), transepithelial migration of neutrophils rapidly follows attachment of the bacteria to the epithelial apical membrane. We have previously shown that during S.

Small ubiquitin-related modifier (SUMO)-1 promotes glycolysis in hypoxia.

Under conditions of hypoxia, most eukaryotic cells undergo a shift in metabolic strategy, which involves increased flux through the glycolytic pathway. Although this is critical for bioenergetic homeostasis, the underlying mechanisms have remained incompletely understood. Here, we report that the induction of hypoxia-induced glycolysis is retained in cells when gene transcription or protein synthesis are inhibited suggesting the involvement of additional post-translational mechanisms.

PGC-1alpha is coupled to HIF-1alpha-dependent gene expression by increasing mitochondrial oxygen consumption in skeletal muscle cells.

Mitochondrial biogenesis occurs in response to increased cellular ATP demand. The mitochondrial electron transport chain requires molecular oxygen to produce ATP. Thus, increased ATP generation after mitochondrial biogenesis results in increased oxygen demand that must be matched by a corresponding increase in oxygen supply.

SUMO, hypoxia and the regulation of metabolism.

Post-translational modification is a critical event in the dynamic regulation of protein stability, location, structure, function, activity and interaction with other proteins and as such plays an important role in organism complexity. Over the last 10 years, the extensive and critical role of one such protein modification by SUMO (small ubiquitin-related modifier) has become apparent. The focus of this mini-review will be on recent reports of a possible functional role for the SUMO pathway in the adaptive cellular response to metabolic challenge, such as oxygen deprivation (hypoxia).