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Öğe Altered kynurenine pathway metabolism and association with disease activity in patients with systemic lupus(Springer Wien, 2023) Onmaz, Duygu Eryavuz; Tezcan, Dilek; Yilmaz, Sema; Onmaz, Mustafa; Unlu, AliSystemic lupus erythematosus (SLE) is an autoimmune disease accompanied by increased release of proinflammatory cytokines that are known to activate the indoleamine 2,3-dioxygenase (IDO-1) enzyme, which catalyzes the rate-limiting step of the kynurenine pathway (KP). This study aimed to measure KP metabolite levels in patients with SLE and investigate the relationship between disease activity, clinical findings, and KP. The study included 100 patients with SLE and 100 healthy controls. Serum tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), quinolinic acid (QA) concentrations were measured with tandem mass spectrometry. Serum KYN, KYNA, 3HAA, 3HK, and QA levels of the patients with SLE were significantly higher than the control group. Serum QA levels were elevated in patients with neurological involvement (four patients with peripheral neuropathy and two patients with mononeuropathy), serum KYN levels and KYN/TRP ratio increased in patients with joint involvement, and serum KYN, 3HK, and 3HAA levels and the KYN/TRP ratio were increased in patients with renal involvement. Moreover, KYN and KYN/TRP ratios were positively correlated with the disease activity score. These findings indicated that imbalances in KP metabolites may be associated with the pathogenesis, activation, and clinical manifestations of SLE.Öğe Assessment of ADMA, IMA, and Vitamin A and E Levels in Patients with Acne Vulgaris(Wiley, 2020) Tuncez Akyurek, Fatma; Saylam Kurtipek, Gulcan; Kurku, Huseyin; Akyurek, Fikret; Unlu, Ali; Abusoglu, Sedat; Ataseven, ArzuBackground Acne vulgaris is a common skin disease in adolescents known to be associated with oxidative stress. However, the number of studies in which oxidative stress and antioxidants are evaluated together is limited. Aims In this study, we aimed to investigate L-arginine/nitric oxide (NO) pathway metabolites, ischemia-modified albumin (IMA), and vitamin A and E levels in patients with acne and its association with disease severity. Patients/Methods Ninety patients with acne and 30 healthy adults were included in the study. The serum levels ofL-arjinin, L-arginine metabolites, IMA, and vitamins A and E measured in the patient and control groups. Results Asymmetric dimethylarginine (ADMA), LNG-monomethyl-L-arginine (L-NMMA) and symmetric dimethylarginine (SDMA), and IMA levels were significantly higher in the patients with acne than in the control group (P < .05). The L-arginine/ADMA ratio and citrulline and vitamin A levels were significantly lower in patients with acne than those of the controls (P < .05). ADMA and IMA plasma levels were increased in parallel with the disease severity (P < .05). L-arginine/ADMA ratio, L-arginine, citrulline, and vitamin A plasma levels decreased as the disease became severe (P < .05). Although L-arginine and vitamin E levels were lower in the patient group compared to the control group, the difference was not statistically significant (P > .05). Conclusion These results suggest that IMA and L-arginine-NO pathway associated with ischemia and oxidative stress may play an important role in the pathogenesis and progression of acne vulgaris.Öğe Association between endocrinological, immunological and psychosocial variables in psoriasis patients(Edizioni Minerva Medica, 2016) Bilgic, Ozlem; Bilgic, Ayhan; Sivrikaya, Abdullah; Selvi, Yavuz; Unlu, Ali; Altinyazar, Hilmi C.BACKGROUND: There is limited data concerning the relationship between psychosocial problems of psoriasis patients and the function of their hypothalamic-pituitary-adrenal (IPA) axis and immunologic markers. This study aimed to determine serum levels of basal cortisol and adrenocorticotropic hormone (ACTH) and circulating levels of various cytokines and chemokines and their association with psychological measures in psoriasis patients. METHODS: Serum concentrations of endocrinological and immunological variables were quantified, and psychiatric questionnaires were completed. RESULTS: In psoriasis patients, serum levels of ACTH, TNF-a, IL-6, IL-23, CCL-17, CCL-27, CCL-20 and CXCL-9, current psychiatric symptoms and childhood neglect scores were all higher than in controls. In addition, in psoriasis patients, physical neglect scores were related to lower basal cortisol, whereas recent stressful life events were related to higher IL-6, IL-23 and CCL-20 levels. CONCLUSIONS: The exposure to stressful life events in childhood and just before a flare-up of psoriasis may be related to altered function of the HPA axis and an immune dysregulation in psoriasis.Öğe Association of an Endothelial Nitric Oxide Synthase Gene Polymorphism with Diabetic Retinopathy(Kamla-Raj Enterprises, 2018) Inan, Sibel; Zengin, Nazmi; Ozturk, Banu Turgut; Kerimoglu, Hurkan; Unlu, Ali; Dogan, IsmetThe association of the endothelial nitric oxide synthase (eNOS) G894T gene polymorphism with the severity of diabetic retinopathy (DRP) and macular edema (DME) was investigated. One hundred-seven patients with type-2 diabetes mellitus were included. Forty-five patients served as a control group. eNOS G894T gene polymorphism was analysed by polymerase chain reaction. The mean age was 55.8 +/- 9.4 years in the study group and 51.8 +/- 9.7 years in the control group. There was no significant difference in the genotypes between the diabetic and the control group, or between the non-DRP group and the DRP group. The frequency of the G allele was higher in the proliferative DRP group than that in the non-proliferative DRP group. The GG genotype of G894T gene polymorphism was associated with macular edema and hyperglycaemia. The eNOS G894T gene polymorphism seems to be associated with the DME and unregulated hyperglycaemia.Öğe Comparison between liquid chromatography-tandem mass spectrometry and immunoassay methods for measurement of plasma 25 (OH) vitamin D(Walter De Gruyter Gmbh, 2022) Kader, Saadet; Akdag, Turan; Ecer, Busra; Abusoglu, Sedat; Unlu, AliObjectives Vitamin D is one of the major hormones involved in the metabolism of calcium (Ca) and phosphorus (P). In the present study, we aimed to determine the analytical performance of the immunoassay method used for determining plasma 25-hydroxyvitamin D [25(OH)D] levels in routine clinical practice in laboratories. Methods Venous blood samples were collected from 156 patients for the comparisons and were analyzed with Siemens ADVIA Centaur XPT, the Roche Cobas 6,000's module e601, Abbott Architect i2000, and the liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results The four methods were analyzed and compared through the Passing-Bablok regression for 25(OH)D, and the highest correlation was found at LC-MS/MS and Cobas 6,000's module e601 (r=0.799), LC-MS/MS/Abbott Architect i2000, and LC-MS/MS/Siemens ADVIA Centaur XPT as r=0.736, 0.721, respectively. The correlation coefficient was found between Abbott Architect i2000 with Roche Cobas e601 and Siemens ADVIA Centaur XPT as r=0.934 and r=0.907, respectively. Also, the correlation coefficient was found between Roche Cobas e601 and Siemens ADVIA Centaur XPT as r=0.906. Conclusions The Roche Cobas assay showed better performance, compared with the other assays. Based on our findings, the chemiluminescence methods in automated systems seem to be expedient.Öğe Comparison between liquid chromatography-tandem mass spectrometry and immunoassay methods for measurement of plasma 25 (OH) vitamin D(Walter De Gruyter Gmbh, 2022) Kader, Saadet; Akdag, Turan; Ecer, Busra; Abusoglu, Sedat; Unlu, AliObjectives Vitamin D is one of the major hormones involved in the metabolism of calcium (Ca) and phosphorus (P). In the present study, we aimed to determine the analytical performance of the immunoassay method used for determining plasma 25-hydroxyvitamin D [25(OH)D] levels in routine clinical practice in laboratories. Methods Venous blood samples were collected from 156 patients for the comparisons and were analyzed with Siemens ADVIA Centaur XPT, the Roche Cobas 6,000's module e601, Abbott Architect i2000, and the liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results The four methods were analyzed and compared through the Passing-Bablok regression for 25(OH)D, and the highest correlation was found at LC-MS/MS and Cobas 6,000's module e601 (r=0.799), LC-MS/MS/Abbott Architect i2000, and LC-MS/MS/Siemens ADVIA Centaur XPT as r=0.736, 0.721, respectively. The correlation coefficient was found between Abbott Architect i2000 with Roche Cobas e601 and Siemens ADVIA Centaur XPT as r=0.934 and r=0.907, respectively. Also, the correlation coefficient was found between Roche Cobas e601 and Siemens ADVIA Centaur XPT as r=0.906. Conclusions The Roche Cobas assay showed better performance, compared with the other assays. Based on our findings, the chemiluminescence methods in automated systems seem to be expedient.Öğe Development and validation of a sensitive, fast and simple LC-MS/MS method for the quantitation of favipiravir in human serum(Elsevier, 2021) Onmaz, Duygu Eryavuz; Abusoglu, Sedat; Onmaz, Mustafa; Yerlikaya, Fatma Humeyra; Unlu, AliFavipiravir is a broad-spectrum inhibitor of viral RNA polymerase. It is currently used as a possible treatment for coronavirus disease 2019 (COVID-19). Pre-clinical or clinical trials of favipiravir require robust, sensitive, and accurate bioanalytical methods for quantitation of favipiravir levels. Recently, several studies have been reported about developing a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring favipiravir levels. However, these methods were validated predominantly for plasma samples, electrospray ionization was operated only in negative or positive mode, and clinical application of these methods has not been applied for patients with COVID-19. This study aimed was to develop a validated LC-MS/MS method for the measurement of favipiravir levels in positive and negative electrospray ionization mode and to perform a pilot study in patients with COVID-19 receiving favipiravir to demonstrate the applicability of this method in biological samples. Simple protein precipitation was used for the extraction of favipiravir from the desired matrix. Favipiravir levels were quantitated using MS / MS with an electrospray ionization source in positive and negative multiple reaction monitoring (MRM) mode. The chromatographic detection was performed on a reverse-phase Phenomenex C18 column (50 mm x 4.6 mm, 5 mu m, 100 angstrom) with gradient elution using 0.1% formic acid in water and 0.1% formic acid in methanol as mobile phase. The method was linear over the concentration ranges of 0.048-50 mu g/mL (in negative ionization mode) and 0.062-50 mu g/mL (in positive ionization mode) with a correlation coefficient (r2) better than 0.998. The total run time was 3.5 min. The intra-assay and inter-assay % CV values were less than 7.2% and 8.0%, respectively. A simple, rapid and robust LC-MS / MS method was developed for the measurement of favipiravir and validation studies were performed. The validated method was successfully applied for drug level measurement in COVID-19 patients receiving favipiravir.Öğe Effect of cigarette smoking on serum methylarginine and a-klotho levels(Elsevier Sci Ltd, 2023) Onmaz, Mustafa; Demirbas, Nur; Onmaz, Duygu Eryavuz; Kutlu, Ruhusen; Unlu, AliBackground and aims: Smoking causes many diseases such as cardiovascular, lung dis-eases, stroke and premature aging. However, the role of smoking in the pathogenesis of these diseases is unclear. Increasing evidence suggests that methylarginine pathway metabolites and a-klotho may be strong markers for pathologies such as premature aging, endothelial dysfunc-tion, and oxidant damage. Therefore, the study aimed to measure the serum levels of arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), N-monomethyl-L- arginine (L-NMMA), and a-klotho levels in smokers. Methods and results: This case-control analytical study included 65 smokers and 71 non-smokers. Sociodemographic characteristics, routine biochemistry parameters, Framingham risk scores and Fagerstrom Nicotine Dependence Test (FTND) were recorded. Serum methylarginine and a-klotho levels were analyzed by tandem mass spectrometry and enzyme-linked immunosorbent assay (ELISA), respectively. Serum ADMA (p < 0.001), L-NMMA (p Z 0.024), SDMA (p < 0.001) levels of smokers were higher than non-smokers, and serum a-klotho (p < 0.001) and arginine levels (p < 0.001) were lower. There was a positive correlation between serum ADMA levels with FNDT, age and pack/year in smokers, while there was a negative correlation between klotho levels and age. A positive correlation was found between serum ADMA levels, Framingham risk score and age in non-smokers. Conclusion: Smoking is related to premature aging and is a strong risk factor for various diseases such as cardiovascular, inflammatory, and renal diseases. Elevated serum methylarginine and decreased serum klotho levels were found in smokers. Therefore, our findings suggest that smok-ing may be involved in the pathogenesis of these diseases by affecting a-klotho and methylarginine-related pathways. (c) 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Ital-ian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.Öğe Is there a link between premature ovarian failure and serum concentrations of vitamin D, zinc, and copper?(Lippincott Williams & Wilkins, 2013) Kebapcilar, Ayse Gul; Kulaksizoglu, Mustafa; Kebapcilar, Levent; Gonen, Mustafa Sait; Unlu, Ali; Topcu, Ali; Demirci, FatihObjective: The risk of primary ovarian insufficiency (POI) increases in association with autoimmune conditions. Adequate intake of vitamin D (vit D) and trace elements is required for the immune system to function efficiently. The aim of this study was to evaluate vit D, zinc, and copper blood levels in women with POI who had given birth to at least one child and in women with normal menstrual cycles. Methods: This was a cross-sectional, case-control study involving 63 participants divided into two groups: the study group, which is composed of 35 women with POI, and the control group, which is composed of 28 women with normal menstrual cycles. Serum concentrations of zinc, vit D, and copper were determined for each participant. Results: Women with POI had significantly higher serum copper levels and copper-to-zinc ratio but significantly lower serum vit D and zinc levels when compared with the healthy control group. Serum follicle-stimulating hormone levels were inversely correlated with zinc and vit D levels and positively correlated with the copper-to-zinc ratio and copper levels. Vit D levels were inversely correlated with follicle-stimulating hormone levels, copper-to-zinc ratio, and copper levels and positively correlated with zinc levels. Conclusions: Most women with POI are deficient in vit D. Zinc, copper, and vit D seem to correlate with hormonal status in the participants. The present study may generate hypotheses for future studies that will investigate the possible mechanisms behind alterations in trace elements and vit D deficiency in women with POI and whether these changes could be used to screen for the risk of developing POI.Öğe The role of regulatory T cells in allergic rhinitis and their correlation with IL-10, IL-17 and neopterin levels in serum and nasal lavage fluid(Springer, 2020) Erkan, Kadriye; Bozkurt, Mete K.; Artac, Hasibe; Ozdemir, Hulya; Unlu, Ali; Korucu, Emine N.; Elsurer, CagdasPurpose Allergic rhinitis (AR), is an IgE-mediated inflammation of the nose. Regulatory T cells (Tregs) and inflammatory cytokines have been shown to play a critical role in allergic airway inflammation. The aim of the study was to compare the levels of blood T lymphocyte subsets and IL-10, IL-17 and neopterin concentrations in serum and nasal lavage of patients with AR compared to healthy subjects. Methods The study included 38 subjects with moderate-severe AR and 36 sex- and age-matched controls. Peripheral blood CD3+, CD3+CD4+ and CD4+CD25+Foxp3 percentages were evaluated using flow cytometry. Levels of IL-10, IL-17 and neopterin were measured both in serum and nasal lavage fluid with ELISA and HPLC, respectively. Results No difference was found in the percentages of T lymphocyte subsets between the two groups (p > 0.05). Serum IL-10 levels were similar (p > 0.05), whereas nasal IL-10 was lower in AR subjects compared to control group (2.22 +/- 0.91 and 3.12 +/- 1.45 pg/ml, respectively) (p < 0.05). Mean serum and nasal IL-17 were higher in AR (107.7 +/- 79.61 and 527.36 +/- 738.7 pg/ml) than the control group (76.29 +/- 28.94 and 328.9 +/- 430.8 pg/ml) (p < 0.05 and p > 0.05). There were no significant differences in serum and nasal neopterin levels (p > 0.05). Conclusions Although there were no differences in the distribution of lymphocyte subsets between the AR and control groups, the finding of higher levels of serum and nasal IL-17 and lower levels of nasal IL-10 support the cytokine imbalance in the pathogenesis of AR.Öğe The role of tryptophan metabolic pathway in children with attention deficit hyperactivity disorder with and without comorbid oppositional defiant disorder and conduct disorder(Elsevier Ireland Ltd, 2021) Saglam, Ebru; Bilgic, Ayhan; Abusoglu, Sedat; Unlu, Ali; Sivrikaya, AbdullahAccumulating data presented that tryptophan metabolic pathway (TMP) may play a role in attention-deficit/ hyperactivity disorder (ADHD). However, no study have investigated potential role of TMP in disruptive behavior disorders coexisting with ADHD. This study compared serum levels of tryptophan, kynurenine, kynurenic acid, 3-hydroxykynurenine and 3-hydroxyantranilic acid in medication-free children with ADHD combined presentation (ADHD-C), with ADHD-C and oppositional defiant disorder (ODD), and with ADHD-C and conduct disorder (CD) versus healthy controls. The study also compared several ratios that are previously suggested to reflect the activities of the KP enzymes (kynurenine/tryptophan, kynurenic acid/kynurenine, 3-hydroxykynurenine/kynurenine) or neuroprotective activity (kynurenic acid/3-hydroxykynurenine) among groups. A total of 122 patients were enrolled: 46 children with ADHD-C alone, 43 children with ADHD-C+ODD, 33 children with ADHD-C+CD and 50 healthy controls. Targeted biochemical molecules were assessed by liquid chromatography-mass spectrometry/mass spectrometry. Compared to control group, serum kynurenine levels were significantly higher in the ADHD-C group, serum 3-hydroxykynurenine levels were significantly lower in the ADHD-C and ADHD-C+ODD groups, the serum kynurenic acid/kynurenine ratio was significantly higher in the ADHD-C, ADHD-C+ODD and ADHD-C+CD groups, and the serum 3-hydroxykynurenine/kynurenine ratio was significantly lower in the ADHD-C group. These findings suggest that TMP may play a role in the pathophysiology of ADHD-C.Öğe Serum levels of TWEAK in patients with psoriasis vulgaris(Academic Press Ltd- Elsevier Science Ltd, 2016) Bilgic, Ozlem; Sivrikaya, Abdullah; Toker, Aysun; Unlu, Ali; Altinyazar, CevdetTumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) has been implicated in the pathogenesis of a variety of inflammatory disorders and autoimmune diseases. However, studies conducted on the relationship of TWEAK and psoriasis patients are limited. In this study, we aimed to explore the serum levels of TWEAK and investigated whether TWEAK levels are associated with clinical variables and expression of other well-known psoriasis-related cytokines including IL-6, IL-23 and TNF-alpha. Fortyfive patients with chronic plaque psoriasis and 43 controls were enrolled in this study. The severity of psoriasis was assessed by the Psoriasis Area and Severity Index (PASI). Serum levels of cytokines were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. The mean TWEAK, IL-6, IL-23, and TN-alpha levels were significantly higher in psoriasis patients than in control subjects. However, there were no significant correlations between the psoriasis severity, the illness duration and serum cytokine levels. This study shows that TWEAK may be associated with the pathogenesis of psoriasis, like TNF-alpha, IL-6, and IL-23. (C) 2015 Elsevier Ltd. All rights reserved.Öğe The value of serum asymmetric dimethylarginine levels for the determination of masked hypertension in patients with diabetes mellitus(Elsevier Ireland Ltd, 2013) Taner, Alpaslan; Unlu, Ali; Kayrak, Mehmet; Tekinalp, Mehmet; Ayhan, Selim S.; Aribas, Alpay; Erdem, Said SamiBackground: An increased prevalence of masked hypertension (MHT) has been demonstrated among patients with diabetes mellitus (DM). MHT appears to cause cardiovascular (CV) complications similar to clinically overt hypertension. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide inhibitor and higher plasma levels of ADMA are related to increased CV risk in both the general population and among patients with DM. The aim of this study was to evaluate the relationship between MHT and ADMA in diabetic patients. Methods: This study included DM patients (n = 131) with normal office blood pressure (<140/90 mmHg). None of the participants were using antihypertensive medications. All participants utilized an ambulatory blood pressure monitor (ABPM) for 24 h. Serum ADMA and arginine levels were measured using the fluorescence detector high performance liquid chromatography method. Results: The prevalence of MHT was 24.4% among the study subjects. ADMA levels were increased in the MHT group when compared with normotensive diabetics (6.2 +/- 2.2 vs 4.2 +/- 1.7 mu mol/L p = 0.001, respectively). Furthermore, arginine/ADMA ratio was lower in the MHT group than among the normotensive group (29.9 +/- 12.1 vs 46.0 +/- 19.0 p = 0.001). In the multivariate logistic regression model, ADMA, BMI and HDL levels were found to be independent predictors of MHT Odds ratio: 1.63 (1.28-2.06), 1.19 (1.05-1.35), and 0.95 (0.90-0.99), respectively. The cut-off value of the ADMA was 4.34 mu mol/L with a sensitivity, specificity, positive predictive value, and negative predictive value of 84.4%, 59.6%, of 40.3%, and 92.2%, respectively (AUC - 0.78). Conclusions: Serum ADMA may play a role in both the pathophysiology and screening of MHT in DM subjects. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
