Vedolizumab for inflammatory bowel diseasesI

Aim of review. To present literature data on administration of vedolizumab at inflammatory bowel diseases. Summary. The vedolizumab is anti-α4β7-integrin humanized class IgG1 antibodies which suppresses migration of leukocytes in intestinal tissue, interfering thereby with development of pathologic inflammation. GEMINI-1 study of ulcerative colitis has demonstrated efficacy of the drug in remission induction (clinical response rate of 47,1% of patients, clinical remission of 16,9% and endoscopic remission of 40,9% at the 6th week) and in remission maintenance (percent of patients in clinical remission at 52nd week at drug injection every 4 weeks - 44,8%). Similar efficacy was demonstrated for Crohn's disease (GEMINI-2) study in remission induction (clinical response rate - 31,4% of patients, clinical remission - 14,5%) and remission maintenance (percentage of patient in clinical remission by 52nd week at injection of the drug every 4 weeks - 39%). The results received in clinical trials were confirmed by clinical data in the different countries. Safety profile investigations demonstrated low system immune suppression due to specific action mechanism of the drug. Besides, due to α4β7 integrin heterodimer selectivity of vedolizumab, it provides selective block of intestinal leukocyte migration, without affection of central nervous system therefore the risk of the progressing multifocal leukoencephalopathy is not established. Conclusion. Present clinical trials has demonstrated that vedolizumab is effective and safe in treatment of inflammatory bowel diseases

Irritable bowel syndrome in the Russian Federation: results of the ROMERUS multicenter observational study

Background. Irritable bowel syndrome (IBS) is one of the most common functional disorders of the gastrointestinal tract. According to Russian guidelines, a standard examination using laboratory and instrumental evaluation methods, including colonoscopy, should be performed to establish the diagnosis of IBS. Aim. To characterize the Russian population of IBS patients. Materials and methods. A multicenter observational prospective study ROMERUS was conducted at 35 clinical centers in the Russian Federation. The study included male and female patients aged 18 to 50 with a diagnosis of IBS based on the Rome IV criteria, with no signs of structural gastrointestinal disease. The follow-up duration was 6 months and included three patients' visits to the study site. During the study, data were collected on patients' demographic and clinical characteristics, medical history, and drug therapy. The secondary parameters included the assessment of the proportion of patients with a diagnosis of IBS confirmed by a standard examination among all patients meeting the Rome IV criteria, the evaluation of the change over time of the IBS symptoms, quality of life (QoL), and adherence to therapy. Characterization of the population was performed using descriptive statistics methods. The standard examination results were presented as the percentage of patients with IBS confirmed by the standard examination among all patients meeting the Rome IV criteria, with a two-sided 95% confidence interval. Results. The study included 1004 patients with a diagnosis of IBS according to the Rome IV criteria, with 790 (78.7%) patients included in the final analysis. The mean age of patients was 34.07.5 years; they were predominantly female (70.4%), Caucasian (99.4%), married (55.1%), urban residents (97.5%) with higher education (64.5%) and a permanent position (74.9%). Patients enrolled in the study have low physical activity and lack a healthy diet. The smoking rate was 26.3%. IBS symptoms with predominant constipation (IBS-C) were observed in 28.1% of patients; 28.9% had IBS with predominant diarrhea (IBS-D), 11.9% had mixed-type IBS, and 31.1% had non-classified IBS. The main IBS symptoms were pain (99.7%), abdominal distension (71.1%), and fullness (36.8%). Biliary tract dysfunction (18.9%) and gastritis (17.2%) were the most frequently reported comorbidities. Prior to enrollment, 28% of patients received drug therapy. The most commonly prescribed drug during the study was mebeverine (54.1%). At 6 months of follow-up, there was a significant reduction of abdominal pain, bloating, and distention, and a twofold reduction in the incidence of constipation and diarrhea in the subgroups of patients with IBS-C and IBS-D, respectively. The overall QoL score measured by the IBS-QoL questionnaire increased from 83.0 to 95.2 points (p0.05) during the study. In the overall assessment of their condition, 69.6% of patients noted no symptoms and 25.3% reported marked improvement, 35% were asymptomatic according to the physician's overall assessment of the patient's condition, and 51.8% showed significant improvement. Conclusion. IBS patients in the Russian Federation were characterized. The diagnosis of IBS, established following the Rome IV criteria, is confirmed by the results of a standard examination in 96.3% of patients. The Rome IV criteria for the IBS diagnosis make it possible to establish a diagnosis with a probability of 94.7%. For 6 months of follow-up, there was a clinical improvement with a decrease in the severity of symptoms and a QoL improvement

Variations in the 6.2 μ\mum emission profile in starburst-dominated galaxies: a signature of polycyclic aromatic nitrogen heterocycles (PANHs)?

Analyses of the polycyclic aromatic hydrocarbon (PAH) feature profiles, especially the 6.2 $\mu$m feature, could indicate the presence of nitrogen incorporated in their aromatic rings. In this work, 155 predominantly starburst-dominated galaxies (including HII regions and Seyferts, for example), extracted from the Spitzer/IRS ATLAS project (Hern\'an-Caballero & Hatziminaoglou 2011), have their 6.2 $\mu$m profiles fitted allowing their separation into the Peeters' A, B and C classes (Peeters et al. 2002). 67% of these galaxies were classified as class A, 31% were as class B and 2% as class C. Currently class A sources, corresponding to a central wavelength near 6.22 $\mu$m, seem only to be explained by polycyclic aromatic nitrogen heterocycles (PANH, Hudgins et al. 2005), whereas class B may represent a mix between PAHs and PANHs emissions or different PANH structures or ionization states. Therefore, these spectra suggest a significant presence of PANHs in the interstellar medium (ISM) of these galaxies that could be related to their starburst-dominated emission. These results also suggest that PANHs constitute another reservoir of nitrogen in the Universe, in addition to the nitrogen in the gas phase and ices of the ISM

Comment on "Ab initio calculations of the lattice parameter and elastic stiffness coefficients of bcc Fe with solutes" Comp. Mat. Sci. v.126 pp.503-513 (2017)

In a recent paper, the authors propose to separately calculate the volumetric and chemical contributions to the elastic stiffness coefficients of systems containing solutes, as it is "computationally more efficient". We show that this is not the case and further that their methodology and hence their results are incorrect. There is no short cut for performing the desired calculations, if done rigorously, as we show in our 2012 work

Colonic growth factors (G-CSF, GM-CSF) and chemokines (MCP-1, MIP-1β) in severe ulcerative colitis

Aim of investigation. To determine the content of growth factors (G-CSF, GM-CSF) and chemokines (MCP-1, MIP-1β) in resected colon specimens of patients with severe ulcerative colitis (UC). Material and methods. Overall 48 biopsy specimens of the colonic mucosa resected at 7 patients with total UC were investigated. All patients underwent colectomy due to severe disease, resistant to conservative treatment. Inflammation activity was determined according to severity of erosive and ulcerative lesions of the colon. Growth factor and chemokine levels in supernatant fluid after centrifugal separation of homogenate of 10 mg biopsy specimen were investigated by the protein analyzer «Bio-Plex» («Bio-Rad», USA). Biopsy specimens of uninvolved colonic mucosa resected in 10 cancer patients were used as a control. Results. Growth factor and chemokine levels were significantly elevated in colonic biopsy specimens of UC patients in comparison to that of controls: G-CSF 52,5±17,0 and 0,4±0,1 pg/10 mg (p MIP-1β - in 17 (89,4%) and 12 (63,1%) of 19 colonic biopsies of UC patients with severe inflammatory activity. Conclusions. Significant increase in neutrophil growth factor level G-CSF and monocyte chemokine MCP-1 was observed in colonic biopsy specimens of UC patients at widespread destructive and inflammatory ulcerative process

FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease

Iron deficiency anemia (IDA) is common in chronic diseases and intravenous iron is an effective and recommended treatment. However, dose calculations and inconvenient administration may affect compliance and efficacy. We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen (FCM) with individually calculated iron sucrose (IS) doses in patients with inflammatory bowel disease (IBD) and IDA

Proteomic dataset: Profiling of cultivated Echerichia coli isolates from Crohn's disease patients and healthy individuals

One of the dysbioses often observed in Crohn's disease (CD) patients is an increased abundance of Escherichia coli (10–100 fold compared to healthy individuals) (Gevers et al., 2014). The data reported is a large-scale proteome profile for E. coli isolates collected from CD patients and healthy individuals. 43 isolates were achieved from 30 CD patients (17 male, 12 female, median age 30) and 19 isolates from 7 healthy individuals (7 male, median age 19). Isolates were cultivated on LB medium at aerobic conditions up to medium log phase. Protein extraction was performed with sodium deoxycholate (DCNa) and urea, alcylation with tris(2-carboxyethyl)phosphine and iodacetamide. Protein trypsinolysis was performed as described in (Matyushkina et al., 2016). Total cell proteomes were analysed by shotgun proteomics with HPLC-MS/MS on a maXis qTOF mass-spectrometer. The data including HPLC-MS/MS raw files and exported Mascot search results was deposited to the PRIDE repository project accession: PXD010920, project https://doi.org/10.6019/PXD010920. Keywords: E. coli, Proteome, Crohn's disease, HPLC-MS/M

Genome analysis of E. coli isolated from Crohn’s disease patients

Abstract Background Escherichia coli (E. coli) has been increasingly implicated in the pathogenesis of Crohn’s disease (CD). The phylogeny of E. coli isolated from Crohn’s disease patients (CDEC) was controversial, and while genotyping results suggested heterogeneity, the sequenced strains of E. coli from CD patients were closely related. Results We performed the shotgun genome sequencing of 28 E. coli isolates from ten CD patients and compared genomes from these isolates with already published genomes of CD strains and other pathogenic and non-pathogenic strains. CDEC was shown to belong to A, B1, B2 and D phylogenetic groups. The plasmid and several operons from the reference CD-associated E. coli strain LF82 were demonstrated to be more often present in CDEC genomes belonging to different phylogenetic groups than in genomes of commensal strains. The operons include carbon-source induced invasion GimA island, prophage I, iron uptake operons I and II, capsular assembly pathogenetic island IV and propanediol and galactitol utilization operons. Conclusions Our findings suggest that CDEC are phylogenetically diverse. However, some strains isolated from independent sources possess highly similar chromosome or plasmids. Though no CD-specific genes or functional domains were present in all CD-associated strains, some genes and operons are more often found in the genomes of CDEC than in commensal E. coli. They are principally linked to gut colonization and utilization of propanediol and other sugar alcohols

Genetic diversity of Escherichia coli in gut microbiota of patients with Crohn’s disease discovered using metagenomic and genomic analyses

Abstract Background Crohn’s disease is associated with gut dysbiosis. Independent studies have shown an increase in the abundance of certain bacterial species, particularly Escherichia coli with the adherent-invasive pathotype, in the gut. The role of these species in this disease needs to be elucidated. Methods We performed a metagenomic study investigating the gut microbiota of patients with Crohn’s disease. A metagenomic reconstruction of the consensus genome content of the species was used to assess the genetic variability. Results The abnormal shifts in the microbial community structures in Crohn’s disease were heterogeneous among the patients. The metagenomic data suggested the existence of multiple E. coli strains within individual patients. We discovered that the genetic diversity of the species was high and that only a few samples manifested similarity to the adherent-invasive varieties. The other species demonstrated genetic diversity comparable to that observed in the healthy subjects. Our results were supported by a comparison of the sequenced genomes of isolates from the same microbiota samples and a meta-analysis of published gut metagenomes. Conclusions The genomic diversity of Crohn’s disease-associated E. coli within and among the patients paves the way towards an understanding of the microbial mechanisms underlying the onset and progression of the Crohn’s disease and the development of new strategies for the prevention and treatment of this disease