Different pathophysiological models provide insight into the important role of CD83
dendritic cells (DCs) in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). There were 154 ...subjects included in this study: 60 with UC, 19 with CD and 75 in the control group. Colonic biopsy was performed in all subjects. Specimens were incubated with a primary anti-CD83 antibody. Intraepithelial DCs per 100 enterocytes were counted. The results were analysed according to demographic data, type of IBD and histological inflammation pattern. The odds ratio for CD83
DCs=0 in the UC group was 3.4 times higher than that in the control group (OR = 3.4; 95% CI: 1.63-7.14; p = 0.001), and the odds ratio for CD83
DCs ≥1 in the CD group was 5.3 times higher than that in the UC group (OR = 5.3; 95% CI: 1.4-20.2; p = 0.014). The odds ratio for CD83
DCs=0 in the acute inflammation group was 2.7 times higher than that in the group without inflammation (OR = 2.7; 95% CI: 1.2-5.9; p = 0.011). In the group of patients with CD and acute inflammation (n = 11), there was only one subject without CD83
DCs (p = 0,024). These results suggest an association of CD83
DCs with the type of IBD and the histological inflammation pattern.
Point mutations in the 23S rRNA, gyrA, and gyrB genes can confer resistance to clarithromycin (CAM) and levofloxacin (LVX) by altering target sites or protein structure, thereby reducing the efficacy ...of standard antibiotics in the treatment of Helicobacter pylori infections. Considering the confirmed primary CAM and LVX resistance in H. pylori infected patients from southern Croatia, we performed a molecular genetic analysis of three target genes (23S rRNA, gyrA, and gyrB) by PCR and sequencing, together with computational molecular docking analysis. In the CAM-resistant isolates, the mutation sites in the 23S rRNA gene were A2142C, A2142G, and A2143G. In addition, the mutations D91G and D91N in GyrA and N481E and R484K in GyrB were associated with resistance to LVX. Molecular docking analyses revealed that mutant H. pylori strains with resistance-related mutations exhibited a lower susceptibility to CAM and LVX compared with wild-type strains due to significant differences in non-covalent interactions (e.g., hydrogen bonds, ionic interactions) leading to destabilized antibiotic–protein binding, ultimately resulting in antibiotic resistance. Dual resistance to CAM and LVX was found, indicating the successful evolution of H. pylori resistance to unrelated antimicrobials and thus an increased risk to human health.
Medline, PubMed and the Cochrane databases were searched on epidemiology and diagnosis of Helicobacter pylori for the period of April 2011–March 2012. Several studies have shown that the prevalence ...of H. pylori infection is decreasing in adults and children in many countries. Various diagnostic tests are available, and most of them have high sensitivity and specificity. The Maastricht IV/Florence consensus report states that the urea breath test using 13C urea remains the best test to diagnose H. pylori infection. Among the stool antigen tests, the ELISA monoclonal antibody test is recommended. All these tests were used, either as a single diagnostic test or in combination, to investigate H. pylori infection among different populations throughout the world. Of particular interest, current improvements in high‐resolution endoscopic technologies enable increased diagnostic accuracy for the detection of H. pylori infection, but none of these techniques, at present, are specific enough for obtaining a real‐time diagnosis of H. pylori infection.
Idiosyncratic drug-induced liver injury (DILI) is an unpredictable reaction of individuals exposed to a certain drug, and drug-induced autoimmune hepatitis (DIAIH) presents a DILI phenotype that ...mimics idiopathic autoimmune hepatitis (AIH) when considering the clinical, biochemical, serological and histological parameters. We present a case report of a 48-year-old male who was hospitalized due to severe hepatocellular liver injury two months after self-treatment with a muscle-building dietary supplement based on arginine-alpha-ketoglutarate, L-citrulline, L tyrosine, creatine malate and beet extract. His immunology panel was positive with increased IgG levels, and radiologic methods showed no signs of chronic liver disease. He underwent corticosteroid treatment with adequate response. After therapy withdrawal, a clinical relapse occurred. Seven months after the initial presentation, liver MR suggested initial cirrhotic changes in the right liver lobe. A liver biopsy revealed abundant lymphoplasmacytic infiltrate with piecemeal necrosis and grade 2 fibrosis. He responded well to the corticosteroid treatment again, and was further treated with low-dose prednisone without additional relapses. Several years later, further management confirmed the presence of liver cirrhosis with no histological or biochemical signs of disease activity. DIAIH is a DILI phenotype that is difficult to distinguish from idiopathic AIH despite a wide armamentarium of diagnostic methods. It should always be considered among the differential diagnoses in patients presenting with hepatocellular liver injury.
Left-sided and right-sided colorectal cancer (L-CRC and R-CRC) have relatively different clinical pictures and pathophysiological backgrounds. The aim of this study was to investigate the presence of ...DAB adapter protein 2 (DAB2) as a potential molecular mechanism that contributes to this diversity in terms of malignancy and responses to therapy. The expression of the suppressor gene DAB2 in colon cancer has already been analyzed, but its significance has not been fully elucidated. Archived samples from 34 patients who underwent colon cancer surgery were included in this study, with 13 patients with low-grade CRC and 21 with high-grade CRC. Twenty of the tumors were R-CRC, while 14 were L-CRC. DAB2 expression was analyzed immunohistochemically in the tumor tissue and the colon resection margin was used as a control. Tumors were divided into L-CRC and R-CRC, with splenic flexure as the cutoff point for each side. The results showed that R-CRC had lower DAB2 protein expression compared to L-CRC (
= 0.01). High-grade tumors had reduced DAB2 expression compared to low-grade tumors (
= 0.02). These results are consistent with the analysis of
gene expression data that we exported from the TCGA Colon and Rectal Cancer Study (COADREAD). In 736 samples of colon cancer, lower
gene expression was found in R-CRC compared to L-CRC (
< 0.0001).
gene expression was significantly higher in the sigmoid colon than in the cecum and ascending colon (
< 0.01). The analysis confirmed a lower expression of the
in tumors with positive microsatellite instability (
< 0.001). In conclusion, DAB2 has a role in the biological differences between R-CRC and L-CRC and its therapeutic and diagnostic potential needs to be further examined.
Crohn's disease (CD) and ulcerative colitis (UC) are well-defined phenotypes of chronic inflammatory bowel diseases (IBDs). A mechanism of inflammation in these diseases is partially controlled by ...the intestinal dendritic cell (DC). In this study, we observed a mature CD83
DC in colonic bioptic samples, and its correlation with disease phenotype and activity.
The study included 219 subjects: 100 with UC, 44 with CD and 75 healthy subjects. Colonic biopsy specimens were incubated with the primary antibody Anti-CD83. Intraepithelial CD83
DCs were counted per 100 enterocytes. The presence of CD83
DC was analysed according to the type of IBD, histopathologic inflammation activity and treatment outcome.
The presence of mature CD83
DCs (0, ≥1) differed according to disease types of IBD (
= 0.001), histologic inflammation activity (
= 0.049) and applied therapy (
= 0.001). The odds for CD83
DC presence were 5.2 times higher in the CD group than in the control/UC group. The odds for CD83
DC presence were 2.6 times higher in subjects without inflammation or chronic inflammation than with acute inflammation. They were also 3.7 times higher in subjects without therapy. The cut-off value 0.5 CD83
DC (Rock analysis area = 0.699; SE 0.046;
< 0.001; 95% CI: 0.609-0.788) had been assessed as a differentiation marker between UC and CD.
Presence of CD83
DC could be used as a possible parameter in distinction between UC and CD, as well as a predictor of inflammation activity and treatment outcome.
Adropin is a novel peptide mostly associated with energy homeostasis and vascular protection. To our knowledge, there are no studies that investigated its relationship with inflammatory bowel ...diseases (IBD). The aim of this study was to compare serum adropin levels between 55 patients with IBD (30 Ulcerative colitis (UC) patients, 25 Crohn's disease (CD) patients) and 50 age/gender matched controls. Furthermore, we explored adropin correlations with IBD severity scores, hsCRP, fecal calprotectin, fasting glucose and insulin levels. Serum adropin levels were significantly lower in patients with IBD in comparison with the control group (2.89 ± 0.94 vs 3.37 ± 0.60 ng/mL, P = 0.002), while there was no significant difference in comparison of UC patients with CD patients (P = 0.585). Furthermore, there was a negative correlation between adropin and fecal calprotectin (r = -0.303, P = 0.025), whereas in the total study population, we found a significant negative correlation with fasting glucose levels (r = -0.222, P = 0.023). A multivariable logistic regression showed that serum adropin was a significant predictor of positive IBD status when enumerated along with baseline characteristics (OR 0.455, 95% CI 0.251-0.823, P = 0.009). Our findings imply that adropin could be involved in complex pathophysiology of IBD, but further larger scale studies are needed to address these findings.
Point mutations in the 23S rRNA, gyrA, and gyrB genes can confer resistance to clarithromycin (CAM) and levofloxacin (LVX) by altering target sites or protein structure, thereby reducing the efficacy ...of standard antibiotics in the treatment of Helicobacter pylori infections. Considering the confirmed primary CAM and LVX resistance in H. pylori infected patients from southern Croatia, we performed a molecular genetic analysis of three target genes (23S rRNA, gyrA, and gyrB) by PCR and sequencing, together with computational molecular docking analysis. In the CAM-resistant isolates, the mutation sites in the 23S rRNA gene were A2142C, A2142G, and A2143G. In addition, the mutations D91G and D91N in GyrA and N481E and R484K in GyrB were associated with resistance to LVX. Molecular docking analyses revealed that mutant H. pylori strains with resistance-related mutations exhibited a lower susceptibility to CAM and LVX compared with wild-type strains due to significant differences in non-covalent interactions (e.g., hydrogen bonds, ionic interactions) leading to destabilized antibiotic–protein binding, ultimately resulting in antibiotic resistance. Dual resistance to CAM and LVX was found, indicating the successful evolution of H. pylori resistance to unrelated antimicrobials and thus an increased risk to human health.
The primary objective of this study was to compare concomitant and hybrid therapy in the first line eradication treatment of Helicobacter pylori infection in Split-Dalmatia County, Croatia, in which ...clarithromycin resistance is above 20%. The secondary objective of the study was to determine and compare compliance and adverse events rate between these therapeutic protocols.
In an open-label, randomised clinical trial 140 patients total with H. pylori infection were randomly assigned to either concomitant (esomeprazole 40 mg, amoxicillin 1 g, metronidazole 500 mg, clarithromycin 500 mg, twice daily for 14 days) or hybrid (esomeprazole 40 mg and amoxicillin 1 g twice daily during 14 days with adding metronidazole 500 mg and clarithromycin 500 mg twice daily, in the last 7 days,) treatment group.
Eradication rates for concomitant group and hybrid therapy group were 84.1% (58/69) and 83.1% (59/71) respectively in the intention-to-treat analysis and 96.7% (58/60) and 95.2% (59/62) in per-protocol analysis. There was no significant difference between the groups (ITT analysis: P = 0.878; PP analysis: P = 0.675). Adverse events were more frequent in the concomitant group (33.3% vs 18.3%, P = 0.043). There was no difference among groups regarding compliance rate.
Hybrid therapy has similar eradication rate as concomitant therapy, with lower adverse events rate. In the era of increasing antibiotic resistance, eradication regime with less antibiotic's usage, as hybrid therapy, should be reasonable first line treatment choice for H. pylori infection. Clinical Trials, gov: NCT03572777.
Background and Objectives: Helicobacter pylori (H. pylori) infection impairs quality of life. However, whether eradication therapy ameliorates gastrointestinal symptoms remains questionable. The main ...objective of this study was to evaluate the influence of H. pylori eradication therapy on gastrointestinal symptoms. Materials and Methods: A total of 140 patients, 59 women and 81 men, with a mean age of 61 and suffering from H. pylori infection in the University Hospital of Split, Croatia, were enrolled in the study. Patients were randomly assigned to either concomitant or hybrid therapies. The Gastrointestinal Symptom Rating Scale (GSRS) questionnaire was completed by patients prior to and after the eradication therapy. Results: In both groups, the total GSRS score improved significantly after therapy. In the concomitant group, the abdominal pain score, reflux symptoms score and indigestion score decreased significantly after therapy. In the group with hybrid therapy, all five groups of symptoms (abdominal pain, reflux symptoms, indigestion, diarrhea and constipation) significantly decreased after therapy. Patients with adverse events had significantly higher total GSRS scores after eradication therapy. Conclusions: H. pylori eradication therapy could alleviate gastrointestinal symptoms regardless of the treatment used, but the favorable effect seemed to be more pronounced after hybrid therapy.
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