Molecular analyses of ADAMTS-1, -4, -5, and IL-17 a cytokine relationship in patients with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that develops due to the impaired immune response in genetically susceptible individuals, and its etiopathogenesis is not fully elucidated. IL-17 A is a cytokine that is produced by a type of immune cell called Th17 cells and is involved in the immune response and inflammation. On the other hand, ADAMTS-1, -4, and - 5 are enzymes that are involved in the breakdown of extracellular matrix proteins, including proteoglycans, which are important components of the intestinal wall. This study aimed to evaluate the relationship between interleukin 17 (IL-17 A) cytokine, which plays a role in the pathogenesis of ulcerative colitis, and the inflammation-controlled a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-1, -4, and - 5 protein members. METHODS: Bowel tissue samples and blood serum from 51 patients with UC and 51 healthy controls were included in this study. mRNA expression levels of the ADAMTS-1, -4, -5, and IL-17 A were analyzed by RT-qPCR, and immunohistochemical analyses were performed to evaluate ADAMTS-1, -4, -5, and IL-17 A proteins in tissue samples. In addition, ELISA analysis determined serum levels of the ADAMTS-1, -4, -5, and IL-17 A. RESULTS: RT-qPCR results reveal that the expression of ADAMTS-1, -4, -5, and IL-17 A genes in the UC tissue samples were significantly high according to the control tissue samples. Also, ADAMTS-1, -4, -5, and IL-17 A proteins revealed enhanced expression pattern UC groups according to the control. Also, ADAMTS-1, -4, -5, and IL-17 A protein showed cytoplasmic localization patterns in both control and UC groups. The serum levels of ADAMTS-1,-5, and IL-17 A were significantly higher in UC samples than in the control group. CONCLUSIONS: We observed a positive correlation between the ADAMTS-1, -5 and IL17A cytokine expression in UC samples. These results provide a new understanding of controlling crucial ADAMTS family protein members by IL-17 A cytokines with UC.

The Role of Endoplasmic Reticulum Stress in Gastroesophageal Reflux Disease Symptoms and Treatment.

BACKGROUND: Gastroesophageal reflux disease is a common condition worldwide. There is no curative treatment for gastroesophageal reflux disease. Endoplasmic reticulum stress leads to the activation of the unfolded protein response and has an important role in inflammation. The aim is to determine the role of endoplasmic reticulum stress in the follow-up of individuals with gastroesophageal reflux disease and the temporal changes of endoplasmic reticulum stress markers with treatment. METHODS: Twenty-four subjects in total were recruited prospectively, of whom 15 had nonerosive reflux disease. Two biopsies from 2 cm above the esophagogastric junction, 2 biopsies from gastric antrum mucosa, and 2 biopsies from gastric corpus mucosa were taken. Simultaneously, 2 tubes of venous blood samples were drawn from each individual (1 tube for studying the genetic markers and 1 tube for analyzing the CYP2C19 polymorphism). RESULTS: The mean age was 42.3 ± 17.6 for women and 34.66 ± 11.2 for men. Pantoprazole, esomeprazole, rabeprazole, and lansoprazole preparations were used for treatment. There was no significant difference between tissue and blood samples for panel genes ATF-6, XBP-1, DDIT-3, DNAJC-10, and EIF-2-AK before treatment. There was a significant decrease in the level of ATF-6, XBP-1, DNAJC-9, EIF2-AK, and NF-2L-2 genes in blood after treatment. In the comparison of proton pump inhibitors, significant decreases in the expression of the ATF-6, XBP-1, and DNAJC-9 mRNAs were detected in blood from individuals after treatment. CONCLUSION: Endoplasmic reticulum stress can be for evaluating the clinical improvement and the effectiveness of treatment in gastroesophageal reflux disease.

Recent trends in the antibiotic resistance of Helicobacter pylori in patient with dyspepsia.

The aim of this study was to determine the resistance status and to identify the point mutations conferring resistance to clarithromycin and fluoroquinolones among dyspeptic patients in Manisa, Turkey. The study included a sample of 140 patients with an indication for upper gastrointestinal endoscopy randomly selected from 2100 dyspeptic patients attending to the Gastroenterology and Endoscopy Unit at Manisa Celal Bayar University Hafsa Sultan Hospital between April 2016 and May 2018. A commercially available GenoType Helico DR test was used to detect the presence of Helicobacter pylori and mutations associated with resistance to clarithromycin and fluoroquinolones in biopsy specimens. In total, 116 (82.9%) of 140 biopsies obtained from the same number of dyspeptic patients were positive for H pylori and 82 (approximately 71%) of them harbored resistance mutations in 23SrRNA and/or gyrA. Resistance to clarithromycin, levofloxacin, or both were detected in 43.1% (50/116), 27.6% (32/116), and 16/116 (13.8%) of tested biopsies, respectively. The most common mutation conferring resistance to clarithromycin was A2147G (96%, 48/50). Resistance to fluoroquinolones was frequently due to mutation in codon 91 and the most common mutation detected was D91G (34.4%). Heteroresistance patterns were observed in 48.0% (24/50) of clarithromycin-resistant samples and 28.1% (9/32) of levofloxacin-resistant samples. The resistance rates and detected mutations in this study are in line with the country data. However, to achieve better H pylori eradication and to prevent the spread of multidrug-resistant strains in Turkey, the molecular-based susceptibility tests should be considered routinely. Further studies are needed to determine the various mutations among resistant strains.

Enzyme Replacement Therapy in a Gaucher Family.

Gaucher disease is a lipid storage disorder due to deficiency of beta glucocerebrosidase. It's an autosomal recessive disease and as a result of this enzyme deficiency, glucocerebroside accumulates in various types of tissues like liver, brain spleen and bone marrow. We aimed to describe the effects of enzyme replacement therapy in three members of a family with Gaucher disease and to emphasize screening of the family members of the patients with Gaucher disease. Furthermore, late diagnosis and treatment in these patients have a minimal effect on improvement of the quality of life, and early diagnosis and treatment are very important in Gaucher disease.

[Determination of drug resistance mutations of NS3 inhibitors in chronic hepatitis C patients infected with genotype 1]. / Genotip 1 ile enfekte kronik hepatit C hastalarinda NS3 inhibitörü ilaçlarin direnç mutasyonlarinin belirlenmesi.

Direct-acting antiviral agents (DAA) such as NS3 protease inhibitors is the first class of drugs used for chronic hepatitis C (CHC) treatment. NS3 inhibitors (PI) with low genetic barrier have been approved to be used in the CHC genotype 1 infections, and in the treatment of compensated liver disease including cirrhosis together with pegile interferon and ribavirin. Consequently, the development of drug resistance during DAA treatment of CHC is a major problem. NS3 resistant variants can be detected before treatment as they can occurnaturally. The aim of this study was to investigate new and old generation NS3 inhibitors resistance mutations before DAA treatment in hepatitis C virus (HCV) that were isolated from CHC. The present study was conducted in 2015 and included 97 naive DAA patients infected with HCV genotype 1, who were diagnosed in Manisa and Kocaeli cities of Turkey. Magnetic particle based HCV RNA extraction and than RNA detection and quantification were performed using commercial real-time PCR assay QIASypmhony + Rotorgene Q/ArtusHCV QS-RGQ and COBAS Ampliprep/COBAS TaqMan HCV Tests. HCV NS3 viral protease genome region was amplified with PCR and mutation analysis was performed by Sanger dideoxy sequencing technique of NS3 protease codons (codon 32-185). HCV NS3 protease inhibitors; asunaprevir, boceprevir, faldaprevir, grazoprevir, pariteprevir, simeprevir and telaprevir were analysed for resistant mutations by Geno2pheno-HCV resistance tool. HCV was genotyped in all patients and 88 patients (n= 88/97, 91%) had genotype 1. Eight (n= 8/97, 8.2%) and 80 (n= 80/97, 82.4%) HCC patients were subgenotyped as 1a and 1b, respectively. Many aminoacid substitutions and resistance mutations were determined in 39/88 (44%) patients in the study group. Q80L, S122C/N, S138W were defined as potential substitutions (6/88 patients; 7%); R109K, R117C, S122G, I132V, I170V, N174S were described as potential resistance (34/88 patients; 39%); V36L, T54S, V55A, Q80H were characterized as resistance (7/88 patients; 8%) and Q80K, A156S were defined as high resistance (3/88 patients; 3%) mutations. Based on resistance and high resistance mutations, clinically significant mutations were defined in 10/88 (11%) of the patients. Our study shows that it is essential to analyse HCV NS3 protease inhibitors drug resistance before DAA treatment of CHC patients. On the other hand, our results pointed out that analysis of NS5A and NS5B genome region mutations may also be required in the near future.

Colonoscopy without sedation.

BACKGROUND/AIMS: In Turkey, colonoscopy is a procedure generally performed with intravenous sedation and analgesia. Most of the complications of colonoscopy are related to sedation. The aims of this study were to determine the percentage of patients who could successfully undergo nonsedated colonoscopy without sedation and to assess patient tolerance and acceptance. METHODS: The study included 120 consecutive patients undergoing colonoscopy by two endoscopists in our endoscopy unit. The procedure routinely began without sedation, which was later given (midazolam and hyoscine butylbromide) only if significant discomfort occurred. Parameters of blood pressure, oxygen saturation and heart rate were measured before and during colonoscopy. After the procedure patients were asked to rate their pain on a four point scale 1=no pain, 2=slight, 3=moderate, 4=severe and they were also asked if they would be willing to undergo colonoscopy again without sedation. RESULTS: Eighty eight percent of all colonoscopies were completed without sedation. Mean PaO2 was 96.46 in nonsedated patients and 93.90 (significant p<0.05) in sedated patients. No difference was found between blood pressure and pulse rate of nonsedated and sedated patients. The mean pain score was 2.0 for the nonsedated patients and 3.8 (significant p<0.05) for the sedated patients. Eighty eight percent of patients stated that they would be willing to undergo colonoscopy without sedation again. CONCLUSIONS: In experienced hands, colonoscopy without sedation can be completed successfully in most patients, without any complications and use of extra instrumentation.