Plasma and Adipose Tissue Levels of Selected Growth/Inhibitory Factors, Proteolytic Enzymes and Sphingosine-1-Phosphate in Humans

Recent studies have shown that adipose tissue (AT), while implicated in orchestrating the sophisticated process termed “immunometabolism,” may also serve as a potential niche for various bone marrow-derived (stem) cells. However, at present, the direct biochemical and immunomodulatory composition of the human AT environment has not been studied. Several substances that might play a crucial role in regulating stem cell migration and/or homing to AT, have been implicated, namely, hepatocyte/vascular endothelial growth factor (VEGF/HGF), leukemia inhibitory factor (LIF), and sphingosine-1-phosphate (SIP). Therefore, we examined and compared the AT concentrations of these substances between plasma, subcutaneous, and omental AT samples derived from 35 generally healthy subjects. VEGF, HGF, LIF, and metalloproteinases (MMP)-2 and MMP9 levels were measured using ELISA, and S1P concentrations were analyzed using reverse-phase high performance liquid chromatography. We found that AT levels of analyzed growth/inhibitory factors were generally comparable (VEGF and LIF) or even higher (HGF) than the corresponding levels in the peripheral blood, particularly in overweight/obese subjects. In subcutaneous AT, significantly lower VEGF and LIF concentrations were observed, and these were accompanied by higher MMP levels. No depot-specific differences in S1P concentrations were found in all examined groups. Moreover, we established several associations between analyzed molecular substances and body composition, BMI, or adiposity index of the examined patients. In conclusion, our study revealed that human AT possesses relatively high levels of selected growth/inhibitory factors and of chemoattractants involved in the regulation of stem cell trafficking, and these factors are associated with the metabolic status of an individual. Further studies are needed to clearly establish the role of these factors in the regulation of bone marrow-derived (stem) cell homeostasis and homing in human AT

Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial

BACKGROUND: Helicobacter pylori is associated with benign and malignant diseases of the upper gastrointestinal tract, and increasing antibiotic resistance has made alternative treatments necessary. Our aim was to assess the efficacy and safety of a new, single-capsule treatment versus the gold standard for H pylori eradication. METHODS: We did a randomised, open-label, non-inferiority, phase 3 trial in 39 sites in Europe, comparing the efficacy and safety of 10 days of quadruple therapy with omeprazole plus a single three-in-one capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline (quadruple therapy) versus 7 days of omeprazole, amoxicillin, and clarithromycin (standard therapy) in adults with recorded H pylori infection. Patients were randomly assigned treatment according to a predetermined list independently generated by Quintiles Canada (Ville St-Laurent, QC, Canada). Our study was designed as a non-inferiority trial but was powered to detect superiority. Our primary outcome was H pylori eradication, established by two negative (13)C urea breath tests at a minimum of 28 and 56 days after the end of treatment. Our assessment for non-inferiority was in the per-protocol population, with subsequent assessment for superiority in the intention-to-treat population (ie, all participants randomly assigned treatment). This study is registered with ClinicalTrials.gov, number NCT00669955. FINDINGS: 12 participants were lost to follow-up and 101 were excluded from the per-protocol analysis. In the per-protocol population (n=339), the lower bound of the CI for treatment with quadruple therapy was greater than the pre-established non-inferiority margin of -10% (95% CI 15\ub71-32\ub73; p<0\ub70001). In the intention-to-treat population (n=440), eradication rates were 80% (174 of 218 participants) in the quadruple therapy group versus 55% (123 of 222) in the standard therapy group (p<0\ub70001). Safety profiles for both treatments were similar; main adverse events were gastrointestinal and CNS disorders. INTERPRETATION: Quadruple therapy should be considered for first-line treatment in view of the rising prevalence of clarithromycin-resistant H pylori, especially since quadruple therapy provides superior eradication with similar safety and tolerability to standard therapy.Background: Helicobacter pylori is associated with benign and malignant diseases of the upper gastrointestinal tract, and increasing antibiotic resistance has made alternative treatments necessary. Our aim was to assess the efficacy and safety of a new, single-capsule treatment versus the gold standard for H pylori eradication. Methods: We did a randomised, open-label, non-inferiority, phase 3 trial in 39 sites in Europe, comparing the efficacy and safety of 10 days of quadruple therapy with omeprazole plus a single three-in-one capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline (quadruple therapy) versus 7 days of omeprazole, amoxicillin, and clarithromycin (standard therapy) in adults with recorded H pylori infection. Patients were randomly assigned treatment according to a predetermined list independently generated by Quintiles Canada (Ville St-Laurent, QC, Canada). Our study was designed as a non-inferiority trial but was powered to detect superiority. Our primary outcome was H pylori eradication, established by two negative 13C urea breath tests at a minimum of 28 and 56 days after the end of treatment. Our assessment for non-inferiority was in the per-protocol population, with subsequent assessment for superiority in the intention-to-treat population (ie, all participants randomly assigned treatment). This study is registered with ClinicalTrials.gov, number NCT00669955. Findings: 12 participants were lost to follow-up and 101 were excluded from the per-protocol analysis. In the per-protocol population (n=339), the lower bound of the CI for treatment with quadruple therapy was greater than the pre-established non-inferiority margin of -10% (95% CI 15.1-32.3; p<0.0001). In the intention-to-treat population (n=440), eradication rates were 80% (174 of 218 participants) in the quadruple therapy group versus 55% (123 of 222) in the standard therapy group (p<0.0001). Safety profiles for both treatments were similar; main adverse events were gastrointestinal and CNS disorders. Interpretation: Quadruple therapy should be considered for first-line treatment in view of the rising prevalence of clarithromycin-resistant H pylori, especially since quadruple therapy provides superior eradication with similar safety and tolerability to standard therapy. Funding: Axcan Pharma Inc. \ua9 2011 Elsevier Ltd