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Öğe Altered kynurenine pathway metabolite levels in toddlers and preschool children with autism spectrum disorder(Taylor & Francis Ltd, 2022) Bilgic, Ayhan; Abusoglu, Sedat; Sadic celikkol, Cagla; Oflaz, Mehmet Burhan; Akca, Omer Faruk; Sivrikaya, Abdullah; Baysal, TamerAim There are increasing reports about the potential role of kynurenine pathway metabolites in autism spectrum disorder (ASD). Early childhood is a very crucial period of time for the etiopathogenesis of ASD and previous studies reported an age-dependent alteration in kynurenine metabolism. However, no study specifically examined kynurenine metabolites in very young children with ASD. This study aimed to investigate kynurenine pathway metabolite levels, kynurenine pathway enzyme activities and neuroprotective index (kynurenic acid/3-hydroxykynurenine ratio) in toddlers and preschool children with ASD. Materials and Methods A total of 68 children with ASD and 44 healthy controls aged between 18 and 60 months were included in this study. Serum levels of kynurenine pathway metabolites were determined by liquid chromatography-mass spectrometry/mass spectrometry system. Results Serum 3-hydroxykynurenine and kynurenic acid concentrations were significantly higher in the ASD group than in the control group, whereas serum 3-hydroxyanthranilic acid concentrations were significantly lower. Conclusions These findings showed that the kynurenine pathway may play a role in the etiopathogenesis of ASD in early childhood.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 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 Effects of hydroxychloroquine and its metabolites in patients with connective tissue diseases(Springer Basel Ag, 2021) Onmaz, Duygu Eryavuz; Tezcan, Dilek; Abusoglu, Sedat; Yilmaz, Sema; Yerlikaya, Fatma Humeyra; Onmaz, Mustafa; Abusoglu, GulsumHydroxychloroquine has attracted attention in the treatment of COVID-19. Many conflicting findings have been reported regarding the efficacy and safety of this drug, which has been used safely in the rheumatological diseases for years. However, these studies lacked measurement methods that allow accurate assessment of hydroxychloroquine and its metabolite levels. The aim of this study was to measure hydroxychloroquine and its metabolite levels in whole blood samples of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and scleroderma (Scl) by a robust, simple and accurate validated tandem mass spectrometric method, and to investigate the relationship between these levels with drug-related adverse effects and disease activity scores. The validated LC-MS/MS method was applied to measure blood hydroxychloroquine and its metabolite levels of patients with RA, SLE, SS, Scl. Various haematological and biochemical parameters were measured with Beckman-Coulter AU 5800 and Beckman Coulter LH 780 analyzers, respectively. QTc intervals were calculated with Bazett's formula, and the patients were followed up by clinicians in terms of clinical findings and adverse effects. Hydroxychloroquine levels of patients were similar to previous studies. There was a negative correlation between disease activity scores and hydroxychloroquine levels, while the highest correlation was between QTc interval, creatinine and GFR levels with desethylchloroquine. Bidetylchloroquine had the highest correlation with RBC count and liver function tests. Our findings showed that hydroxychloroquine and its metabolite levels were associated with disease activity scores, renal, hepatic function, QTc prolongation, and hematological parameters.Öğe The Role of Stem Cells Derived From the Mesenchyme of the Umbilical Cord in Reducing Immunosuppressive Drug Doses Used in Allogenic Transplantations(Lippincott Williams & Wilkins, 2022) Evin, Seyda Guray; Sutcu, Mustafa; Aktan, Tahsin Murad; Duman, Selcuk; Harmankaya, Ismail; Abusoglu, SedatBackgroundThis study evaluated the potential of Wharton's jelly mesenchymal stem cells with high tolerogenic properties in reducing immunosuppressive dosage and related adverse effects.MethodsA 4- to 6-week-old, 30-40 g weight, male inbred CD57BL/6 mice were used as skin allograft donors, whereas Balb/c mice with similar characteristics were used as recipients. Wharton's jelly stem cells were obtained from a commercial kit sourced from human umbilical cord. Skin allografts were performed from CD57Bl6 to Balb/c mice (day 0). Group 1 (control) received no treatment. Group 2 received 15 mg/kg cyclosporin A on days 0 to 30. Group 3 received 5.7 x 10(6) and 10.3 x 10(6) cell/kg Wharton's jelly stem cells on days 0 and 3, respectively. Groups 4, 5, and 6 received a combination of 15, 10, and 5 mg/kg per day cyclosporine A (days 0 to 30) with the same stem cell dose with group 3, respectively. Graft rejection was evaluated with digital photography and thermal imaging, histopathology (Banff grading, epithelialization scores, dermoepidermal dissociation), immunochemistry (Ki-67 and Bcl-2), and biochemical methods (interleukin 10, interleukin 2, interferon gamma, tumor necrosis factor alpha) (day 10). Cumulative adverse effects of cyclosporin A occurring in the groups were revealed by histopathological evaluation of kidney and liver (a modified semiquantitative method of infiltration of inflammatory cells around the portal area and lobular region in liver; modification of the Banff rating of proximal tubules and hypertrophia of juxtaglomerular apparatus cells in kidney) (day 30).ResultsThere was no rejection in groups 2, 4, and 5 until the end of study. These were statistically different versus groups 1 (day 10 +/- 0.71), 3 (day 11 +/- 0.82), and 6 (day 11 +/- 0.58) (all P's < 0.05). Groups 4 and 5 have exhibited statistically similar findings in histopathological (4 epithelization score: 3.7 +/- 1.3; 5 epithelization score: 3.5 +/- 0.5; 4 Banff grading score: 0.8 +/- 0.6; 5 Banff grading score: 1.0 +/- 0.5; both P's = 1.00), immunohistochemical (4 Bcl-2 score: 3.5 +/- 0.5, P = 0.618; 5 Bcl-2 score: 3.4 +/- 0.5, P = 1.00; 4 Ki-67 score: 3.7 +/- 0.4, P = 1.00; 5 Ki-67 score: 3.5 +/- 0.5, both P's = 1.00), and levels of cytokines (both P's = 1.00) versus group 2. Adverse effects on kidneys and liver were lowest and statistically similar in groups 3, 5, and 6 (all P's = 00) versus group 1.ConclusionsWharton's jelly mesenchymal stem cells alter bioavailability of cyclosporine, albeit at much lower doses and with fewer systemic adverse effects.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 SARC-F is a Weaker Predictor Compared to Muscle Strength and a Stronger Predictor Compared to Muscle Mass for Mortality and Hospitalization in Hemodialysis Patients(Aves, 2022) Yavuz, Yasemin Coskun; Biyik, Zeynep; Korez, Muslu Kazim; Abusoglu, Sedat; Ahmadli, Nicat; Eryavuz, Duygu; Batur, ElifObjective: It is known that muscle strength and muscle mass decrease in hemodialysis patients. We aimed to compare the effect of SARC-F (strength, assistance with walking, rising from a chair, climbing stairs, and falls) questionnaire with that of handgrip strength and skeletal muscle mass/body mass index on 1-year mortality and hospitalization in hemodialysis patients. Methods: SARC-F test was filled for 67 hemodialysis patients, muscle strength was evaluated with handgrip strength, muscle mass was evaluated by performing bioimpedance analysis, and skeletal muscle mass/body mass index was evaluated by using the formula. Results: The end of 1 year revealed that 12 of 67 patients (17.9%) died. Of the patients, 38 (56.7%) were hospitalized. The number of hospitalizations was in the range of 0-9. The length of hospitalization varied between 2 and 77 days. The patients with low handgrip strength had a 9.86 times higher mortality risk (odds ratio = 9.862, 95% CI = 1.190-81.707, P =.034) and had a 5.27 times higher risk of hospitalization (odds ratio = 5.273, 95% CI = 1.828-15.207, P =.002). The patients who had lower SARC-F had a 3.88 times higher risk of hospitalization (odds ratio = 3.882, 95% CI = 1.340-11.252, P =.012). A positive statistically significant correlation was found between the patients' hospitalization periods and SARC-F scores (Spearman's rho = 0.329, P =.007), and a negative statistically significant correlation was found between the patients' hospitalization periods and handgrip strength scores. The duration of hospitalization was found to be significantly longer in the patients who had low handgrip strength (19.38 +/- 22.25). Conclusion: SARC-F appears to be a weaker parameter than handgrip strength and a stronger parameter than skeletal muscle mass/body mass index on hospitalization and mortality.
