Publications by authors named "Ilker Sen"

51 Publications

[Comparison of magnetic resonance imaging-transrectal ultrasound fusion prostate biopsy with standard systematic biopsy: A single center experience.]

Arch Esp Urol 2021 Oct;74(8):790-795

Department of Urology. School of Medicine, Gazi University. Ankara. Turkey.

Objective: To compare systematic biopsy with MRI-TRUS fusion prostate biopsy in terms of cancer detection rates.

Patients And Methods: The data of the patients who had a Prostate Imaging Reporting and Data System (PI-RADS) score of 3 or more lesions on mpMRI and underwent MRI-TRUS fusion biopsy with simultaneous 12-core standard systematic biopsy from June 2016 to June 2019 in our tertiary center were retrospectively reviewed. Clinical, radiological and pathological data were recorded. Statistical difference among the groups was determined by using McNemar tests.

Results: A total of 344 patients were included in the study. As a result of transrectal targeted and systematic combined biopsy, 117 patients were diagnosed with prostate cancer. Benign pathology rates in patients with PI-RADS 3, PI-RADS 4, and PI-RADS 5 lesions were 93.8%, 68.5%, and 46.4%, respectively. Patients were divided into two groups as ISUP grade 1 and ISUP grade ≥2 and cancer detection rates (CDRs) were found significantly higher in transrectal targeted biopsy compared with the systematic biopsy (12.5% vs. %6.4, p=0.007 and 17.4% vs. 8.7%, p<0.001, respectively). Targeted biopsy CDRs were found significantly higher in the high PSA density group (24.5% vs. 41.4%, p=0.001) unlike the systematic biopsy.

Conclusion: Transrectal targeted biopsy was superior to systematic biopsy in the diagnosis of prostate cancer. Clinicians should be more selective when making a biopsy decision for patients with PI-RADS 3 lesions. PSA density can be used as a criterion for patient selection for targeted biopsy.
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October 2021

Use of PASEF for Accelerated Protein Sequence Confirmation and De Novo Sequencing with High Data Quality.

Methods Mol Biol 2022 ;2313:207-217

Biologics CMC and Developability, Institut de Recherche Pierre Fabre (IRPF)-Centre d'Immunologie Pierre-Fabre (CIPF), Saint-Julien-en-Genevois, France.

Biopharmaceutical sequences can be well confirmed by multiple protease digests-e.g., trypsin, elastase, and chymotrypsin-followed by LC-MS/MS data analysis. High quality data can be used for de novo sequencing as well. PASEF (Parallel Accumulation and Serial Fragmentation) on the timsTOF instrument has been used to accelerate proteome and protein sequence studies and increase sequence coverage concomitantly.Here we describe the protein chemical and LC-MS methods in detail to generate high quality samples for sequence characterization from only 3 digests. We applied PASEF to generate exhaustive protein sequence coverage maps by combination of results from the three enzyme digests using a short LC gradient. The data quality obtained was high and adequate for determining antibody sequences de novo.Nivolumab and dulaglutide were digested by 3 enzymes individually. For nivolumab, 94/94/90% sequence coverage and 86/84/85% fragment coverage were obtained from the individual digest analysis with trypsin/chymotrypsin/elastase, respectively. For dulaglutide, 96/100/90% sequence coverage and 92/90/83% fragment coverage were obtained. The merged peptide map from the 3 digests for nivolumab resulted in ∼550 peptides; enough to safely confirm the full sequences and to determine the nivolumab sequence de novo.
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http://dx.doi.org/10.1007/978-1-0716-1450-1_12DOI Listing
January 2022

External validation of a prostate cancer nomogram on magnetic resonance/transrectal ultrasound fusion biopsy in men with prior negative systematic biopsy.

Int J Clin Pract 2021 Oct 9;75(10):e14654. Epub 2021 Aug 9.

Department of Urology, School of Medicine, Gazi University, Ankara, Turkey.

Objective: To observe how the nomogram, which was created by Truong et al, works in an independent patient group by performing external validation.

Patients And Methods: One hundred and eighty-one patients who had at least one prior negative 12-core standard systematic biopsy and lesions with PI-RADS scores of 3 or higher that were detected as a result of mpMRI were included in the study. Targeted biopsy with 12-core standard systematic biopsy was performed on all patients. Clinical and pathological features of the patients were recorded. The discrimination, calibration and decision curve analysis were performed to externally validate the nomogram.

Results: A total of 181 patients with previous negative 12-core systematic biopsies were analysed. One hundred and thirty-four patients (74%) had benign pathology. Radiological volume and PI-RADS scores of 4 and 5 were found as independent predictors of benign pathology. The area under the curve (CI 95%) was found to be 0.80 (0.73-0.87), indicating good discrimination. The median residual was calculated as -0.0873, the intercept as -0.0690, the slope as 0.8927 and r as 0.2586, indicating good calibration. The standardised net benefit of follow-up decisions was found to be 0.54 and 0.36 at the probability threshold of 0.7 and 0.8, respectively.

Conclusion: The original model showed good discrimination and calibration with our data. Defining a high probability threshold for clinical use would be appropriate for centres with high benign biopsy rates similar to our centre.
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http://dx.doi.org/10.1111/ijcp.14654DOI Listing
October 2021

Diagnostic accuracy of Ga-PSMA PET/MRI and multiparametric MRI in detecting index tumours in radical prostatectomy specimen.

Int J Clin Pract 2021 Aug 20;75(8):e14287. Epub 2021 May 20.

Department of Urology, School of Medicine, Gazi University, Ankara, Turkey.

Objective: To evaluate the diagnostic accuracy of the gallium ( Ga) prostate-specific membrane antigen (PSMA) positron emission tomography/magnetic resonance imaging (PET/MRI) and multiparametric MRI (mpMRI) by region-based comparison of index tumour localisations using histopathological tumour maps of patients who underwent radical prostatectomy because of clinically significant prostate cancer.

Patients And Methods: The study included 64 patients who underwent radical prostatectomy after primary staging with mpMRI and Ga-PSMA PET/MRI. Diagnostic analysis was performed by dividing the prostate into four anatomic regions as left/right anterior and left/right posterior. The extension of the lesions in mpMRI and the pathological uptake in Ga-PSMA PET/MRI were matched separately for each region with the extension of the index tumour into each region.

Results: The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and the accuracy of mpMRI and Ga-PSMA PET/MRI are shown as 55.7%, 91.8%, 80.6%, 77.2%, 78.1%, and 60.8%, 94.3%, 86.8% 79.8%, 83.5%, respectively. Ga-PSMA PET/MRI has higher sensitivity and specificity compared with mpMRI. However, no statistically significant difference was found (P = .464). Combined imaging had significantly higher diagnostic accuracy compared with mpMRI and Ga-PSMA PET/MRI (change in AUC: 0.084 and 0.046, P < .001 and P = .028, respectively), while no statistically significant difference was found between mpMRI and Ga-PSMA PET/MRI (change in AUC: 0.038, P = .246).

Conclusion: Ga-PSMA PET/MRI had higher clinical diagnostic accuracy in prostate cancer compared with mpMRI. Diagnostic accuracy was significantly increased in the combined use of both imaging modalities.
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http://dx.doi.org/10.1111/ijcp.14287DOI Listing
August 2021

New Peak Detection Performance Metrics from the MAM Consortium Interlaboratory Study.

J Am Soc Mass Spectrom 2021 Apr 12;32(4):913-928. Epub 2021 Mar 12.

FUJIFILM Diosynth Biotechnologies, 101 J. Morris Commons Lane, Morrisville, North Carolina 27560, United States.

The Multi-Attribute Method (MAM) Consortium was initially formed as a venue to harmonize best practices, share experiences, and generate innovative methodologies to facilitate widespread integration of the MAM platform, which is an emerging ultra-high-performance liquid chromatography-mass spectrometry application. Successful implementation of MAM as a purity-indicating assay requires new peak detection (NPD) of potential process- and/or product-related impurities. The NPD interlaboratory study described herein was carried out by the MAM Consortium to report on the industry-wide performance of NPD using predigested samples of the NISTmAb Reference Material 8671. Results from 28 participating laboratories show that the NPD parameters being utilized across the industry are representative of high-resolution MS performance capabilities. Certain elements of NPD, including common sources of variability in the number of new peaks detected, that are critical to the performance of the purity function of MAM were identified in this study and are reported here as a means to further refine the methodology and accelerate adoption into manufacturer-specific protein therapeutic product life cycles.
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http://dx.doi.org/10.1021/jasms.0c00415DOI Listing
April 2021

Real-world efficacy and safety of Ledipasvir + Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience.

Turk J Gastroenterol 2020 12;31(12):883-893

Division of Gastroenterology, Kanuni Sultan Suleyman Training and Research Hospital, İstanbul, Turkey.

Background/aims: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population.

Material And Methods: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)±ribavirin (RBV) orombitasvir/paritaprevir/ritonavir±dasabuvir (PrOD)±RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed.

Results: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90±54.60 U/L to 17.00±14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51±4.54 to 7.32±3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0±16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%).

Conclusion: LDV/SOF or PrOD±RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.
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http://dx.doi.org/10.5152/tjg.2020.20696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928249PMC
December 2020

Peak Filtering, Peak Annotation, and Wildcard Search for Glycoproteomics.

Mol Cell Proteomics 2020 Dec 8;20:100011. Epub 2020 Dec 8.

Research and Development Group, Protein Metrics Inc, Cupertino, California, USA. Electronic address:

Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational modifications. Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5. Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra. Here, we discuss recent improvements to Byonic, a glycoproteomics search program, that address these three issues. Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da. Also, new is glycan "wildcard" search, which allows an unspecified mass within a user-set mass range to be applied to N- or O-linked glycans and enables assignment of spectra with unanticipated glycans. Finally, the next release of Byonic supports user-specified peak annotations from user-defined posttranslational modifications. We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
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http://dx.doi.org/10.1074/mcp.RA120.002260DOI Listing
December 2020

Comparison of corporal plication for the correction of congenital penile curvature in pre-pubertal and post-pubertal patients: Does age matter?

Andrologia 2021 Apr 10;53(3):e13965. Epub 2021 Jan 10.

Department of Urology, Gazi University Faculty of Medicine, Ankara, Turkey.

We retrospectively reviewed and compared the results of corporal plication procedures for the correction of congenital penile curvature (CPC) between pre-pubertal and post-pubertal boys and find whether age matters in the success rates. We reviewed the records of 32 patients with CPC without hypospadias treated by simple plication near the 12 o'clock position between 1998 and 2018 in our clinic. Patients under 13 years of age and not had puberty yet were accepted as pre-pubertal. Residual curvature less than 10° during follow-up was accepted as a surgical success. The mean age of the pre-pubertal group was 8.3 (2-12) years, while 16.2 (14-21) for the post-pubertal patients. The mean follow-up was 38.7 (24-154) months in the pre-pubertal group and 45.1 (23-150) months in the post-pubertal group. The success rates of corporal plication in pre-pubertal and post-pubertal groups were 78% and 83% respectively (p = .753). The success rates of corporal plication were similar between pre-pubertal and post-pubertal boys. However, as the series was small further studies should be favoured to determine the effect of age on success rates.
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http://dx.doi.org/10.1111/and.13965DOI Listing
April 2021

The Relationship between Insulin Resistance and Liver Damage in non-alcoholic Fatty Liver Patients.

Sisli Etfal Hastan Tip Bul 2020 11;54(4):411-415. Epub 2020 Dec 11.

Department of Gastroenterology, University of Health Sciences Turkey, Sisli Hamidiye Etfal Teaching and Research Hospital, Istanbul, Turkey.

Objectives: Non-alcoholic fatty liver disease (NAFLD) is closely associated with diseases, such as obesity, diabetes mellitus, metabolic syndrome, which are characterized by insulin resistance. NAFLD is thought to be a manifestation of metabolic syndrome in the liver. Liver fibrosis has a high prognostic significance in non-alcoholic steatohepatitis (NASH). In this study, the relationship between insulin resistance and the histopathological changes in the liver was investigated in biopsy-proven NAFLD patients.

Methods: In this study, 85 biopsy-proven NAFLD patients (64 NASH, 21 non-NASH) and 40 healthy control subjects were enrolled. Insulin resistance was calculated using the "homeostasis model assessment of insulin resistance" (HOMA-IR).

Results: C reactive protein, total cholesterol, low-density lipoprotein, triglyceride, body mass index (BMI), HOMA-IR levels were significantly higher in the NAFLD group compared to the control group. In the NASH group, the HOMA-IR level was significantly higher than the non-NASH group (p=0.026). When NAFLD patients with advanced fibrosis (stage 3-4, n=27) and without fibrosis (stage 0-2, n=58) are compared, in advanced fibrosis group BMI (35.2±4.6 kg/m and 32.7±4.1 kg/m, respectively; p=0.031) and HOMA-IR (6.3 [5.8-6.8] and 3.4 [2.6-4.8], respectively, p=0.001) levels were higher significantly. In the covariance analysis, when confounding factors, such as BMI, age and gender, were corrected, it was observed that the elevation of HOMA-IR level in the advanced fibrosis group continued statistically significantly.

Conclusion: HOMA-IR levels were high in NAFLD patients with advanced fibrosis. HOMA-IR, which can be easily measured in daily practice, is an independent predictor for fibrosis.
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http://dx.doi.org/10.14744/SEMB.2018.83604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751232PMC
December 2020

Liver and pancreas: 'Castor and Pollux' regarding the relationship between hepatic steatosis and pancreas exocrine insufficiency.

Pancreatology 2020 Jul 19;20(5):880-886. Epub 2020 May 19.

Professor of Gastroenterology, Department of Gastroenterology, Sisli Hamidiye Etfal Education and Research Hospital, Turkey. Electronic address:

Background: Pancreatic exocrine insufficiency (PEI) is found in 30-50% of diabetes mellitus (DM). Insulin resistance is triggering factor in both DM and nonalcoholic fatty liver disease (NAFLD). Therefore, we aimed to investigate frequency of PEI in NAFLD, and relationship of fecal pancreatic elastase (PE) levels with liver histology and pancreatic fat.

Methods: Ninety-seven biopsy proven NAFLD patients and 50 controls were enrolled. Pancreas exocrine functions were measured by PE. Magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) was used to quantify fat.

Results: NAFLD patients had significantly lower PE levels than controls (297 [204-517] vs. 500 [298-678] μg/g, p < 0.01). PEI (PE < 200 μg/g) ratio of NAFLD patients (22.7%, n = 22) was higher than PEI ratio of controls (6%, n = 3) (p = 0.011). Among diabetic (n = 35) NAFLD patients, 9 (25.7%) exhibited PEI, compared to 13 (21%) of non-diabetics. There was no significant difference in patients with and without DM in terms of PEI (p = 0.592). Among NASH (n = 68) patients 16 (23.5%) exhibited PEI, compared to (20.7%) of non-NASH (p = 0.76). Multiple analysis revealed NAFLD as a predictor of PEI independent of age, sex and DM (OR = 4.892, p = 0,021). Mean pancreas MRI-PDFF was significantly higher in diabetics (13.7% ± 3.6% vs. 8.7% ± 5.1%, p = 0.001). There was no significant pancreas MRI-PDFF difference between NASH and non-NASH (P = 0.95). Mean pancreas MRI-PDFF was significantly higher in patients with PEI (13.7% ± 3.4% vs. 8.9% ± 5.2%, P < 0.01).

Conclusion: This is the first study demonstrating the high frequency of PEI in NAFLD independent of DM. Moreover, increasing pancreatic steatosis appears to be associated with higher frequency of PEI in NAFLD.
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http://dx.doi.org/10.1016/j.pan.2020.04.020DOI Listing
July 2020

Assessment of biosimilarity under native and heat-stressed conditions: rituximab, bevacizumab, and trastuzumab originators and biosimilars.

Anal Bioanal Chem 2020 Jan 18;412(3):763-775. Epub 2019 Dec 18.

Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.

Biosimilars are highly similar to, but not identical with, their originator products. As a result, structural differences between originators and biosimilars can be difficult to detect and characterize without the appropriate analytical tools. Therefore, we first focus on identifying initial structural differences between rituximab, bevacizumab, and trastuzumab originator and biosimilar pairs and later address how these differences change after applying thermal stress at 40 °C with orbital shaking for 4 weeks. Prior to incubation, we detected comparable secondary and tertiary structures for each pair and identified different levels of soluble aggregates, charge variants, and molecular weight variants due to differences in glycoforms and the number of C-terminal lysine groups. Over the course of incubation, we compared differences in charge variants and unfolding patterns. Taken together, our study provides a comparability exercise, providing information on the minor differences present between originator and biosimilar products and how those differences are impacted by stress.
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http://dx.doi.org/10.1007/s00216-019-02298-9DOI Listing
January 2020

Multifaceted assessment of rituximab biosimilarity: The impact of glycan microheterogeneity on Fc function.

Eur J Pharm Biopharm 2020 Jan 10;146:111-124. Epub 2019 Dec 10.

Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, United States; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, United States. Electronic address:

Biosimilars are poised to reduce prices and increase patient access to expensive, but highly effective biologic products. However, questions still remain about the degree of similarity and scarcity of information on biosimilar products from outside of the US/EU in the public domain. Thus, as an independent entity, we performed a comparative analysis between the innovator, Rituxan® (manufactured by Genentech/Roche), and a Russian rituximab biosimilar, Acellbia® (manufactured by Biocad). We evaluated biosimilarity of these two products by a variety of state-of-the-art analytical mass spectrometry techniques, including tandem MS mapping, HX-MS, IM-MS, and intact MS. Both were found to be generally similar regarding primary and higher order structure, though differences were identified in terms of glycoform distribution levels of C-terminal Lys, N-terminal pyroGlu, charge variants and soluble aggregates. Notably, we confirmed that the biosimilar had a higher level of afucosylated glycans, resulting in a stronger FcγIIIa binding affinity and increased ADCC activity. Taken together, our work provides a comprehensive comparison of Rituxan® and Acellbia®.
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http://dx.doi.org/10.1016/j.ejpb.2019.12.003DOI Listing
January 2020

Investigating the relationships between quality of life, fatigue and leisure time physical activity in prostate cancer patients.

J Back Musculoskelet Rehabil 2019 ;32(3):497-503

Department of Urology, Faculty of Medicine, Gazi University, Ankara, Turkey.

Objectives: The aim of this study was to investigate the relationship between the parameters of fatigue, quality of life and leisure time physical activity in prostate cancer (PCa) patients. This is the first study in the literature to report interaction between these parameters from the perspective of physiotherapy and rehabilitation.

Materials And Methods: Fifty-eight out-patients were enrolled in this study. In an oncologic rehabilitation unit, Functional Assessment of Chronic Illness Therapy-Fatigue Questionnaire (FACIT-F), Functional Assessment of Cancer Therapy-Prostate Questionnaire (FACT-P) and Godin Leisure Time Exercise Questionnaire (GLTEQ) were utilized to evaluate fatigue, quality of life and physical activity, respectively. Frequencies and the relationships between the results of the parameters were analyzed.

Results: The average age of patients was 67.68 ± 7.54 years. Mean scores of FACIT-F [42.94 ± 8.25] and FACT-P [118.81 ± 13.39] were determined. The median score of GLTEQ was 14 (0-70). There were positive correlations between FACIT-F and FACT-P (r= 0.633, p< 0.001); GLTEQ and FACT-P (r= 0.275, p< 0.05) and; FACIT-F and GLTEQ (r= 0.297, p< 0.05).

Conclusion: Increased fatigue and decreased leisure time physical activity level may affect quality of life negatively. Moreover, it was observed that decreasing leisure time physical activity level affects fatigue negatively. Accordingly, physiotherapists with PCa patients may focus on developing physical activity levels in various ways to address the multidimensional problems of fatigue and quality of life.
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http://dx.doi.org/10.3233/BMR-181220DOI Listing
August 2019

Differential Quantitative Determination of Site-Specific Intact N-Glycopeptides in Serum Haptoglobin between Hepatocellular Carcinoma and Cirrhosis Using LC-EThcD-MS/MS.

J Proteome Res 2019 01 29;18(1):359-371. Epub 2018 Oct 29.

Department of Surgery , University of Michigan Medical Center , Ann Arbor , Michigan 48109 , United States.

Intact N-glycopeptide analysis remains challenging due to the complexity of glycopeptide structures, low abundance of glycopeptides in protein digests, and difficulties in data interpretation/quantitation. Herein, we developed a workflow that involved advanced methodologies, the EThcD-MS/MS fragmentation method and data interpretation software, for differential analysis of the microheterogeneity of site-specific intact N-glycopeptides of serum haptoglobin between early hepatocellular carcinoma (HCC) and liver cirrhosis. Haptoglobin was immunopurified from 20 μL of serum in patients with early HCC, liver cirrhosis, and healthy controls, respectively, followed by trypsin/GluC digestion, glycopeptide enrichment, and LC-EThcD-MS/MS analysis. Identification and differential quantitation of site-specific N-glycopeptides were performed using a combination of Byonic and Byologic software. In total, 93, 87, and 68 site-specific N-glycopeptides were identified in early HCC, liver cirrhosis, and healthy controls, respectively, with high confidence. The increased variety of N-glycopeptides in liver diseases compared to healthy controls was due to increased branching with hyper-fucosylation and sialylation. Differential quantitation analysis showed that 5 site-specific N-glycopeptides on sites N184 and N241 were significantly elevated in early HCC compared to cirrhosis ( p < 0.05) and normal controls ( p ≤ 0.001). The result demonstrates that the workflow provides a strategy for detailed profiles of N-glycopeptides of patient samples as well as for relative quantitation to determine the level changes in site-specific N-glycopeptides between disease states.
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http://dx.doi.org/10.1021/acs.jproteome.8b00654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465142PMC
January 2019

Changes in Liver Tissue Trace Element Concentrations During Hepatitis B Viral Infection Treatment.

Biol Trace Elem Res 2019 Apr 20;188(2):245-250. Epub 2018 Jun 20.

General Surgery Department, Mersin University, Mersin, Turkey.

Approximately 350-400 million people in the world have Hbs Ag (hepatitis B virus surface antigen) positivity. In the international guidelines, the permanent suppression of replication in chronic hepatitis B virus (HBV) infection therapy is reported as the primary therapeutic goal. Trace elements play a key role in liver diseases. The aim of our study is to determine some trace element concentrations in the liver during HBV treatment periods. The measurement of 11 trace elements (manganese, lead, nickel, chromium, cadmium, iron, copper, zinc, silver, cobalt, and aluminum) was carried out by the method of inductively coupled plasma mass spectrometry in liver biopsy materials (before starting treatment and at the sixth month of the treatment period). There was an increase in zinc and copper concentrations in liver materials at the sixth month of treatment compared to the pre-treatment values (the median zinc value was 48.05 μg/g before treatment and 74.9 μg/g at 6 months after initial treatment, p = 0.035; median copper was 2.82 μg/g before treatment and 5.31 μg/g after 6 months, p = 0.002). General estimations indicated that zinc (p = 0.002), iron (p = 0.0244), copper (p = 0.0003), and aluminum (p = 0.0239) values may be effective in HAI (histological activity index) changes. Only iron levels could be at a very low level effective on the changes caused by fibrosis (p = 0.0002). Liver tissue zinc and copper levels increased in parallel with the improvement of inflammation in antiviral-treated HBV patients. In addition, the levels of zinc and copper in the liver tissue can be useful markers for liver tissue damage detection.
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http://dx.doi.org/10.1007/s12011-018-1414-yDOI Listing
April 2019

Parsimonious Charge Deconvolution for Native Mass Spectrometry.

J Proteome Res 2018 03 8;17(3):1216-1226. Epub 2018 Feb 8.

Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Science4Life, Utrecht University and Netherlands Proteomics Centre , Padualaan 8, 3584 CH Utrecht, The Netherlands.

Charge deconvolution infers the mass from mass over charge (m/z) measurements in electrospray ionization mass spectra. When applied over a wide input m/z or broad target mass range, charge-deconvolution algorithms can produce artifacts, such as false masses at one-half or one-third of the correct mass. Indeed, a maximum entropy term in the objective function of MaxEnt, the most commonly used charge deconvolution algorithm, favors a deconvolved spectrum with many peaks over one with fewer peaks. Here we describe a new "parsimonious" charge deconvolution algorithm that produces fewer artifacts. The algorithm is especially well-suited to high-resolution native mass spectrometry of intact glycoproteins and protein complexes. Deconvolution of native mass spectra poses special challenges due to salt and small molecule adducts, multimers, wide mass ranges, and fewer and lower charge states. We demonstrate the performance of the new deconvolution algorithm on a range of samples. On the heavily glycosylated plasma properdin glycoprotein, the new algorithm could deconvolve monomer and dimer simultaneously and, when focused on the m/z range of the monomer, gave accurate and interpretable masses for glycoforms that had previously been analyzed manually using m/z peaks rather than deconvolved masses. On therapeutic antibodies, the new algorithm facilitated the analysis of extensions, truncations, and Fab glycosylation. The algorithm facilitates the use of native mass spectrometry for the qualitative and quantitative analysis of protein and protein assemblies.
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http://dx.doi.org/10.1021/acs.jproteome.7b00839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838638PMC
March 2018

Biosimilarity under stress: A forced degradation study of Remicade® and Remsima™.

MAbs 2017 10 8;9(7):1197-1209. Epub 2017 Aug 8.

a Department of Pharmaceutical Sciences , University of Michigan , 428 Church Street, Ann Arbor , MI.

Remsima™ (infliximab) is the first biosimilar monoclonal antibody (mAb) approved by the European Medical Agency and the US Food and Drug Administration. Remsima™ is highly similar to its reference product, Remicade®, with identical formulation components. The 2 products, however, are not identical; Remsima™ has higher levels of soluble aggregates, C-terminal lysine truncation, and fucosylated glycans. To understand if these attribute differences could be amplified during forced degradation, solutions and lyophilized powders of the 2 products were subjected to stress at elevated temperature (40-60°C) and humidity (dry-97% relative humidity). Stress-induced aggregation and degradation profiles were similar for the 2 products and resulted in loss of infliximab binding to tumor necrosis factor and FcγRIIIa. Appearances of protein aggregates and hydrolysis products were time- and humidity-dependent, with similar degradation rates observed for the reference and biosimilar products. Protein powder incubations at 40°C/97% relative humidity resulted in partial mAb unfolding and increased asparagine deamidation. Minor differences in heat capacity, fluorescence, levels of subvisible particulates, deamidation and protein fragments were observed in the 2 stressed products, but these differences were not statistically significant. The protein solution instability at 60°C, although quite significant, was also similar for both products. Despite the small initial analytical differences, Remicade® and Remsima™ displayed similar degradation mechanisms and kinetics. Thus, our results show that the 2 products are highly similar and infliximab's primary sequence largely defines their protein instabilities compared with the limited influence of small initial purity and glycosylation differences in the 2 products.
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http://dx.doi.org/10.1080/19420862.2017.1347741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627586PMC
October 2017

Detection and Measurement of Methionine Oxidation in Proteins.

Curr Protoc Protein Sci 2017 02 2;87:14.16.1-14.16.11. Epub 2017 Feb 2.

Janssen Research & Development, LLC, Spring House, Pennsylvania.

Methionine oxidation is a prevalent modification found in proteins both in biological settings and in the manufacturing of biotherapeutic molecules. In cells, the oxidation of specific methionine sites can modulate protein function or promote interactions that trigger signaling pathways. In biotherapeutic development, the formation of oxidative species could be detrimental to the efficacy or safety of the drug product. Thus, methionine oxidation is a critical quality attribute that needs to be monitored throughout development. Here we describe a method using LC/MS/MS to identify site-specific methionine modifications in proteins. Antibodies are stressed with hydrogen peroxide, and the level of Met oxidation is compared to that of reference molecules. The protocols presented here are not specific to methionine and can be used more generally to identify other PTM risk sites in molecules after various types of treatments. © 2017 by John Wiley & Sons, Inc.
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http://dx.doi.org/10.1002/cpps.25DOI Listing
February 2017

Automated Antibody De Novo Sequencing and Its Utility in Biopharmaceutical Discovery.

J Am Soc Mass Spectrom 2017 05 19;28(5):803-810. Epub 2017 Jan 19.

Protein Metrics Inc, 1622 San Carlos Ave, Suite C, San Carlos, CA, 94070, USA.

Applications of antibody de novo sequencing in the biopharmaceutical industry range from the discovery of new antibody drug candidates to identifying reagents for research and determining the primary structure of innovator products for biosimilar development. When murine, phage display, or patient-derived monoclonal antibodies against a target of interest are available, but the cDNA or the original cell line is not, de novo protein sequencing is required to humanize and recombinantly express these antibodies, followed by in vitro and in vivo testing for functional validation. Availability of fully automated software tools for monoclonal antibody de novo sequencing enables efficient and routine analysis. Here, we present a novel method to automatically de novo sequence antibodies using mass spectrometry and the Supernovo software. The robustness of the algorithm is demonstrated through a series of stress tests. Graphical Abstract ᅟ.
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http://dx.doi.org/10.1007/s13361-016-1580-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392168PMC
May 2017

Value of Cystatin C-Based e-GFR Measurements to Predict Long-Term Tenofovir Nephrotoxicity in Patients With Hepatitis B.

Am J Ther 2019 Jan/Feb;26(1):e25-e31

Department of Gastroenterology, Sisli Hamidiye Etfal Education and Research Hospital, Istanbul, Turkey.

Background: Cystatin C is a genuine marker for detecting minor reductions in estimated glomerular filtration rate (e-GFR).

Study Question: We aimed to investigate the efficiency of cystatin C levels in predicting nephrotoxicity due to antiviral therapy in patients with chronic hepatitis B virus infection.

Study Design: Seventy-six naive hepatitis B virus patients and 44 controls were enrolled in this prospective cohort study.

Measures And Outcomes: Serum cystatin C, phosphate and creatinine levels, and urinary albumin/creatinine ratios of all patients were measured at baseline, 3rd, 12th, and 24th months. Nephrotoxicity was determined according to the amount of change in creatinine level at the fourth year of treatment compared with baseline ([INCREMENT]Cr0-4).

Results: Mean age was 36.1 ± 9.2 years and 40 (52.2%) of patients were women. There was no significant difference between baseline values of tenofovir disoproxil fumarate and entecavir groups. Although the creatinine level at the fourth year of treatment was statistically nonsignificant compared with baseline in the entecavir group, it was significantly higher in the fourth year of tenofovir treatment compared with baseline (0.95 ± 0.27 mg/dL vs. 0.76 ± 0.16 mg/dL, P = 0.002). While the increase in [INCREMENT]Cr0-4 was ≥0.2 mg/dL in 43.2% of patients in the tenofovir group, this rate was 18.8% in the entecavir group. Diagnostic accuracy in identifying decreased renal function as area under the curve (AUC) was high for baseline serum cystatin C level; furthermore, the highest AUC was calculated for cystatin C plus creatinine-based e-GFR equation (AUC: 0.81, P < 0.001).

Conclusions: Long-term tenofovir disoproxil fumarate nephrotoxicity can be predicted by serum cystatin C plus creatinine-based e-GFR measured before treatment.
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http://dx.doi.org/10.1097/MJT.0000000000000518DOI Listing
April 2019

Successful treatment of sodium oxalate induced urolithiasis with Helichrysum flowers.

J Ethnopharmacol 2016 Jun 13;186:322-328. Epub 2016 Apr 13.

Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler, 06330 Ankara, Turkey. Electronic address:

Ethnopharmacological Relevance: Helichrysum (Asteraceae) flowers, known as "altın otu, yayla çiçeği, kudama çiçeği" , are widely used to remove kidney stones and for their diuretic properties in Turkey.

Aim Of The Study: To determine the curative effect of infusions prepared from capitulums of Helichrysum graveolens (M. Bieb.) Sweet (HG) and H. stoechas ssp. barellieri (Ten.) Nyman (HS) on sodium oxalate induced kidney stones.

Materials And Methods: Infusions prepared from the capitulums of HG and HS were tested for their curative effect on calcium oxalate deposition induced by sodium oxalate (70mg/kg i.p.). Following the injection of sodium oxalate for 5 days, plant extracts were administered to rats at two different doses. Potassium citrate was used as positive control. Water intake, urine volume, body, liver and kidney weights were measured; biochemical and hematological analyses were conducted on urine and blood samples. Additionally, histopathological examinations were done on kidney samples.

Results: H. stoechas extract showed prominent effect at 156mg/kg dose (stone formation score: 0.33), whereas number of kidney stones was maximum in sodium oxalate group (stone formation score: 2.33). The reduction in the uric acid and oxalate levels of urine samples and the elevation in the urine citrate levels are significant and promising in extract groups. Some hematological, biochemical and enzymatic markers are also ameliorated by the extracts.

Conclusions: This is the first report on the curative effect of immortal flowers. Our preliminary study indicated that Helichrysum extracts may be used for treatment of urolithiasis and Helichrysum extracts are an alternative therapy to potassium citrate for patients suffering from kidney stones.
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http://dx.doi.org/10.1016/j.jep.2016.04.003DOI Listing
June 2016

Serum ST2 in inflammatory bowel disease: a potential biomarker for disease activity.

J Investig Med 2016 06 21;64(5):1016-24. Epub 2016 Mar 21.

Department of Gastroenterology, Sisli Hamidiye Etfal Education and Research Hospital, Istanbul, Turkey.

ST2, a specific ligand of interleukin 33, was described as a biomarker protein of inflammatory processes and overexpression of ST2 in ulcerative colitis (UC) was shown previously. We aimed to investigate the potential relationship of serum ST2 levels with the clinical, endoscopic and histopathological activity scores in UC and Crohn's disease (CD). Serum ST2 levels were determined in 143 patients with inflammatory bowel disease (IBD) (83 UC and 60 CD), in 50 healthy controls (HC), and in 32 patients with irritable bowel syndrome (IBS). Serum ST2 levels were elevated in IBD (56.8 (41.9-87.2) pg/mL) compared to HC and IBS (30.7 (20.2-54.3), p<0.001 and 39.9 (25.9-68.7) pg/mL, p=0.002, respectively). No significant difference was found between UC (54.2 (41.3-93.0) pg/mL) and CD (63.8 (42.7-88.4) pg/mL) and between IBS and HC. Serum ST2 levels were significantly increased in active UC compared to inactive UC (72.5 (44.1-99.5) vs 40.0 (34.7-51.6) pg/mL, p<0.001) and in active CD in comparison with inactive CD (63.8 (42.7-88.4) vs 48.4 (29.6-56.9) pg/mL, p=0.036). Patients with CD showing fistulizing behavior had significantly higher ST2 levels compared to patients with inflammatory and stricturing CD (p<0.001). Clinical activity scores of patients with UC and CD were correlated with serum ST2 levels (r=0.692, p<0.001 and r=0.242, p=0.043, respectively). Serum ST2 levels showed stepwise increases with the increasing histopathological scores of patients with UC and CD (p<0.001 for both). The present study highlights significant associations between ST2 and IBD presence and activity and demonstrates elevated serum ST2 levels in patients with active CD as a novel finding.
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http://dx.doi.org/10.1136/jim-2016-000062DOI Listing
June 2016

Etiopathogenesis, Prevention, and Treatment of Thromboembolism in Inflammatory Bowel Disease.

Clin Appl Thromb Hemost 2017 Sep 18;23(6):501-510. Epub 2016 Feb 18.

1 Department of Gastroenterology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey.

The close relationship between inflammation and thrombosis affects the progression and severity of inflammatory bowel disease (IBD). The prevalence of venous thromboembolism (VTE) varies between 1% and 7% among patients with IBD. The VTE risk in patients with IBD is at least 3 times higher than that in the normal general population. The absolute risk is very high during hospitalization, active disease, and surgery. The IBD-related VTE occurs at younger ages and recurs more frequently. The development of thrombosis in IBD is due to the interaction of many hereditary and acquired risk factors. Each patient diagnosed with IBD should be evaluated for a personal and family history of thrombosis and for prothrombotic drug use. Although procoagulant factors are increased during the natural course of inflammation, natural anticoagulants and fibrinolytic activity are decreased. Although IBD is accepted as a prothrombotic condition, there is no treatment that can remove this risk from daily practice. Patient training is required to control important factors, such as long-term immobilization and smoking. Oral contraceptives and hormone replacement therapy should be avoided. Inducing permanent disease remission must be the key approach for the prevention of thrombosis. Low-molecular-weight heparin (LMWH) is the basis of prophylactic treatment, which reduces the thrombosis risk by 50%. Prophylaxis with LMWH should be administered to all patients with IBD hospitalized due to disease attack or surgery. Long-term or even life-long anticoagulation therapy should be planned if there is insufficient disease control, recurrent VTE attacks, positive thrombophilia tests, or thrombosis in vital veins.
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http://dx.doi.org/10.1177/1076029616632906DOI Listing
September 2017

Chemerin: a new biomarker to predict postendoscopic retrograde cholangiopancreatography pancreatitis.

Eur J Gastroenterol Hepatol 2016 Jun;28(6):714-21

aDepartment of Gastroenterology, Sisli Hamidiye Etfal Education and Research Hospital bDepartment of Biochemistry, Bakirkoy Dr. Sadi Konuk Education and Research Hospital, Istanbul, Turkey.

Introduction: Individuals with increased visceral adiposity are considered to be more sensitive and more prone to severe acute pancreatitis because of the inflammatory microenvironment they have. We hypothesized that insulin resistance, adipokines, and proinflammatory cytokines that markedly affect the course of pancreatitis can contribute toward development of postendoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis (PEP) and aimed to investigate the association between PEP risk and preprocedural serum vaspin, chemerin, tumor necrosis factor α, interleukin-6 (IL-6) levels, and homeostasis model assessment of insulin resistance.

Patients And Methods: Eighty-two patients with a diagnosis of choledocholithiasis and 30 controls were enrolled. Preprocedural chemerin, vaspin, IL-6, and well-known PEP risk factors were compared between PEP and non-PEP groups.

Results: The mean age of the patients was 56.3±14.4 years; 52 patients were women. Adipocytokine levels, BMIs, and waist circumferences of the patient group were found to be higher than those of the controls. Total cannulation success and the mean procedure time were 82.9% and 28.7±8.8 min, respectively. PEP developed in 12 (14.6%) patients. Chemerin levels in the PEP group were higher than those in the non-PEP group (580.2±172.5 vs. 392.2±168.2 ng/ml, P<0.01). Insulin resistance was higher in the PEP group than the non-PEP group (P=0.001), but there was no significant difference between PEP and non-PEP groups in terms of preprocedural vaspin, tumor necrosis factor α, IL-6, and C-reactive protein levels. According to logistic regression analysis, increased chemerin levels, homeostasis model assessment of insulin resistance 2.5 or greater, and pancreatic duct cannulation were found to be independent risk factors for PEP [odds ratio (OR)=1.006, P=0.006; OR=4.57, P=0.05; OR=6.54, P=0.02].

Conclusion: Elevated serum chemerin levels and insulin resistance are independent risk factors of PEP development.
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http://dx.doi.org/10.1097/MEG.0000000000000597DOI Listing
June 2016

Angiogenesis in Inflammatory Bowel Disease.

Int J Inflam 2015 29;2015:970890. Epub 2015 Dec 29.

Department of Gastroenterology, Şişli Hamidiye Etfal Training and Research Hospital, Şişli, 34360 Istanbul, Turkey.

Angiogenesis is an important component of pathogenesis of inflammatory bowel disease (IBD). Chronic inflammation and angiogenesis are two closely related processes. Chronic intestinal inflammation is dependent on angiogenesis and this angiogenesis is modulated by immune system in IBD. Angiogenesis is a very complex process which includes multiple cell types, growth factors, cytokines, adhesion molecules, and signal transduction. Lymphangiogenesis is a new research area in the pathogenesis of IBD. While angiogenesis supports inflammation via leukocyte migration, carrying oxygen and nutrients, on the other hand, it has a major role in wound healing. Angiogenic molecules look like perfect targets for the treatment of IBD, but they have risk for serious side effects because of their nature.
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http://dx.doi.org/10.1155/2015/970890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709626PMC
February 2016

Role of Bismuth in the Eradication of Helicobacter pylori.

Am J Ther 2017 Nov/Dec;24(6):e751-e757

Department of Gastroenterology, Sisli Hamidiye Etfal Training and Research Hospital, Sisli, Istanbul, Turkey.

Bismuth salts exert their activity within the upper gastrointestinal tract through action of luminal bismuth. Bismuth exerts direct bactericidal effect on Helicobacter pylori by different ways: forms complexes in the bacterial wall and periplasmic space, inhibits different enzymes, ATP synthesis, and adherence of the bacteria to the gastric mucosa. Bismuth also helps ulcer healing by acting as a barrier to the aggressive factors and increasing mucosal protective factors such as prostaglandin, epidermal growth factor, and bicarbonate secretion. To date, no resistance to bismuth has been reported. Also synergism between bismuth salts and antibiotics was present. It was shown that metronidazole and clarithromycin resistant H. pylori strains become susceptible if they are administered together with bismuth. Bismuth-containing quadruple therapy was recommended both by the Second Asia-Pacific Consensus Guidelines and by the Maastricht IV/Florence Consensus Report as an alternative first choice regimen to standard triple therapy, in areas with low clarithromycin resistance, and it is recommended as the first-line therapeutic option in areas with a high prevalence of clarithromycin resistance. Greater than 90% eradication success can be obtained by bismuth-containing quadruple therapy. Choosing bismuth as an indispensable part of first-line therapy is logical as both metronidazole and clarithromycin resistances can be overcome by adding bismuth to the regimen.
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http://dx.doi.org/10.1097/MJT.0000000000000389DOI Listing
June 2018

Preventive treatment of calcium oxalate crystal deposition with immortal flowers.

J Ethnopharmacol 2015 Apr 21;163:60-7. Epub 2015 Jan 21.

Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey.

Ethnopharmacological Relevance: A number of medicinal plants are used for their diuretic, urolithiatic and anti-inflammatory effects on urinary system problems in Turkey and the most common traditional remedy for kidney stones is the tea of immortal flowers. The aim of this study is to evaluate the preventive effect of infusions prepared from capitulums of Helichrysum graveolens (M.Bieb.) Sweet (HG) and Helichrysum stoechas ssp. barellieri (Ten.) Nyman (HS) on formation of kidney stones.

Materials And Method: Sodium oxalate (Ox-70mg/kg intraperitoneally) was used to induce kidney stones on Wistar albino rats. At the same time, two different doses of the plant extracts (HG: 62.5 and 125mg/kg; HS: 78 and 156mg/kg) were dissolved in the drinking water and administered to animals for 5 days. Potassium citrate was used as positive control in the experiments. During the experiment, water intake, urine volume and body weights of the animals were recorded. At the end of the experiments, liver, kidney and body weights of the animals were determined; biochemical analysis were conducted on urine, blood and plasma samples. Histopathological changes in kidney tissues were examined and statistical analysis were evaluated.

Results: HS extract showed the highest preventive effect at 156mg/kg dose (stone formation score: 1.16), whereas a number of kidney stones were maximum in sodium oxalate group (stone formation score: 2.66). Helichrysum extracts decreased urine oxalate and uric acid levels and increased citrate levels significantly. In addition, Helichrysum extracts regulated the negative changes in biochemical and hematological parameters occurred after Ox injection.

Conclusions: We conclude that Helichrysum extracts could reduce the formation and growth of kidney stones in Ox-induced urolithiasis and can be beneficial for patients with recurrent stones. In addition, this is the first study on the preventive effect of immortal flowers.
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http://dx.doi.org/10.1016/j.jep.2015.01.009DOI Listing
April 2015

Hepatic granulomas in Turkey: a 6-year clinicopathological study of 35 cases.

Turk J Gastroenterol 2014 Oct;25(5):524-8

Department of Gastroenterology, Gazi University Faculty of Medicine, Ankara, Turkey.

Background/aims: Granulomas are focal aggregates of modified macrophages that are surrounded by a rim of lymphocytes and fibroblasts. The present study aimed to evaluate the prevalence and etiology of hepatic granulomas (HGs) in the Department of Gastroenterology with a wider population.

Materials And Methods: We performed a retrospective study on 2662 liver biopsy specimens analyzed between 2005 and 2011 at Gazi University Department of Gastroenterology to determine the presence of HGs.

Results: There were 16 cases with primary biliary cirrhosis, of whom 14 without any other causative etiology. There were 6 cases of sarcoidosis, 2 cases of Fasciola hepatica infection, 2 cases of hepatitis C, and 2 cases of hepatitis B. One case had both tuberculosis and rheumatoid arthritis and one case had both tuberculosis and brucellosis. There was also one case each of leishmaniasis and Hodgkin's lymphoma. The diagnosis of autoimmune hepatitis was found in two cases. One case had immune cholangiopathy.

Conclusion: The leading causative etiology of HGs was primary biliary cirrhosis, followed by sarcoidosis. As a study performed in a center that accepts patient profiles throughout Turkey, tuberculosis took a minor part in HG etiology. A drug-affected or toxic case of HG was not observed.
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http://dx.doi.org/10.5152/tjg.2014.5417DOI Listing
October 2014

Management of lower urinary tract dysfunction in multiple sclerosis: a systematic review and Turkish consensus report.

Neurourol Urodyn 2013 Nov 11;32(8):1047-57. Epub 2013 Jun 11.

Cerrahpaşa Faculty of Medicine, Department of Urology, İstanbul University, İstanbul, Turkey.

Aims: Since lower urinary tract dysfunction (LUTD) related to multiple sclerosis (MS) has a different behavior pattern than other types of neurogenic voiding dysfunction, we aimed to prepare a national consensus report for the management of LUTD due to multiple sclerosis in light of available literature.

Methods: A search of available databases yielded an evidence base of 125 articles after the application of inclusion/exclusion criteria. When sufficient evidence existed, recommendations A (high), B (moderate), or C (low) were made according to the strength of evidence; recommendation D was provided when insufficient evidence existed.

Results: Available data did not support the use of invasive urodynamics in the initial evaluation of patients with MS and LUTD. Clinical studies on the safety and efficacy of antimuscarinics and alpha-blockers in these patients were scarce and low quality. Desmopressin could be used in MS-related overactive bladder symptoms owing to its short-term effects as an adjunctive treatment. Intravesical botulinum toxin type A treatment in patients with MS and detrusor overactivity was recommended in cases of medical treatment failure or severe side effects due to antimuscarinics. Pelvic floor rehabilitation together with neuromuscular electrical stimulation was also recommended as it increased symptomatic treatment success. This systematic review was not able to find any evidence-based cut off post-void residual value for the recommendation to start clean intermittent catheterization in MS-related LUTD.

Conclusions: Patients with MS and LUTD could be best managed through the use of this consensus report.
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http://dx.doi.org/10.1002/nau.22374DOI Listing
November 2013
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