Publications by authors named "Murat Dogan"

169 Publications

The impact of adenoid hypertrophy on pulmonary functions measured using impulse oscillometry in preschool-age children.

Eur Arch Otorhinolaryngol 2022 Jul 30. Epub 2022 Jul 30.

Department of Otorhinolaryngology, School of Medicine, Aydin Adnan Menderes University, Aydin, Turkey.

Purpose: To assess pulmonary impedance [resistance (zR5, zR20, R5-20, Fres, and AX) and reactance (zX5 and zX20)] using impulse oscillometry (IOS) in children with adenoid hypertrophy (AH) and its association with the degree of AH, and to evaluate subsequent changes in pulmonary function 3 months after adenoidectomy.

Methods: This prospective cross-sectional study was conducted with 170 preschool-age children [110 with AH and 60 sex- and age-matched healthy controls (HCs)]. Pulmonary function was analyzed using IOS at baseline (1st visit) in all participants and 3 months after adenoidectomy (2nd visit) in patients who underwent the operation.

Results: The IOS parameters of zR5, zR20, R5-20, Fres, and AX were higher, but zX20 was lower, in children with AH compared to the HCs (p < 0.05 for all). The parameters of zR5, Fres, and AX were higher in children with grade IV AH than in those with grade I (p < 0.001). zR5, zR20, R5-20, Fres, and AX decreased, but zX20 increased, after adenoidectomy (2nd visit) compared to baseline (1st visit) (p < 0.05). Post-adenoidectomy (2nd visit) zR5, AX, Fres values were higher in children with AH compared to baseline values in the HCs (1st visit) (p < 0.05). The area under the ROC curve (AUC) value for estimating adenoidectomy was 0.741 for zX20 (CI 0.648-0.834, p < 0.001) with a cut-off value of  ≤ -3.21, sensitivity of 68.8%, and specificity of 70%.

Conclusion: This study shows that IOS is a useful method for demonstrating subclinical bronchial obstruction in preschool-age children with AH with greater pulmonary impedance (resistance and reactance). Pulmonary impedance decreased 3 months after adenoidectomy, but remained higher than in the HCs. The IOS parameter of X20 may be predictive of adenoidectomy. This study evaluated the pulmonary functions of children with adenoid hypertrophy (AH) using impulse oscillometry (IOS) and the association with the scale of AH. Pulmonary functions were analyzed using IOS. The main IOS parameters include resistances (zR5 and zR20), reactance (zX5 and zX20), R5-20 (resistance at 5 Hz minus resistance at 20 Hz), resonant frequency (Fres), and AX. Fres is the point at which reactance is zero and is measured in Hz (1/s). The Reactance Area (AX - "Goldman Triangle") represents the integrated low-frequency respiratory reactance magnitude between 5 Hz and Fres. Faster frequencies of R (~ 20 Hz) reflect larger airways, regarded as resistance around the central airways. Lower frequencies of R (~ 5 Hz) providing information around the entire (small and large) airways. Peripheral (small) airway resistance is defined by R5-20. IOS parameters of zR5, zX20, Fres, and AX differed among AH grades I-IV and compared to the HCs (p < 0.001 for all).
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http://dx.doi.org/10.1007/s00405-022-07521-5DOI Listing
July 2022

Synthesis and biological evaluation of thiosemicarbazone derivatives.

Med Oncol 2022 Jul 21;39(10):157. Epub 2022 Jul 21.

Faculty of Science and Arts, Department of Chemistry, Tokat Gaziosmanpaşa University, 60250, Tokat, Turkey.

In this study, firstly, 22 thiosemicarbazone derivatives (3a-y) were synthesized. Then, ADME parameters, pharmacokinetic properties, drug-like structures, and suitability for medicinal chemistry of these molecules were studied theoretically by using SwissADME and admetSAR programs. According to the results of these theoretical studies, it can be said that the bioavailability and bioactivity of these compounds may be high. In silico molecular docking between ligands (thiosemicarbazone derivatives) and targeted proteins (protein-78 (GRP78) for C6 and quinone reductase-2 (4ZVM for MCF 7) was analyzed using Hex 8.0.0 docking software. According to the docking data, almost all molecules had higher negative E values than Imatinib (already used as a drug). For this, in vitro anticancer studies of these molecules were done. The cytotoxic activities of thiosemicarbazone derivatives (3a-y) were evaluated on C6 glioma and MCF7 breast cancer cell lines at 24 h, and Imatinib was used as the positive control. According to the results of the cytotoxicity assay, it can be said that the five compounds (3b, c, f, g, and m with IC = 10.59-9.08 μg/mL; Imatinib IC = 11.68 μg/mL) showed more potent cytotoxic activity than Imatinib on C6 cell line. Together with to these results ten compounds (3b, d, f, g, I, k, l, m, n, and r with IC = 7.02-9.08 μg/mL; Imatinib IC = 9.24 μg/mL) had a more effective cytotoxic activity against MCF7 cell line than Imatinib. Compound 3 m showed the highest antiproliferative effect against C6 and MCF7 cell lines.
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http://dx.doi.org/10.1007/s12032-022-01784-yDOI Listing
July 2022

The role of immature granulocyte in the early prediction of acute perforated and nonperforated appendicitis in children.

Ulus Travma Acil Cerrahi Derg 2022 Mar;28(3):375-381

Department of Pediatric Surgery, Erciyes University Faculty of Medicine, Kayseri-Turkey.

Background: Acute appendicitis (AA) is the most common reason for pediatric abdominal surgery in the world. Despite ad-vances in science and technology, diagnosing AA is still difficult today, and complications are common as a result. The early prediction of complicated appendicitis is of great importance for the surgical planning, further treatments, and predicting the course of disease. The immature granulocyte (IG) is a new and more effective marker in predicting the severity of inflammation than traditional markers. Our aim is to determine the effectiveness of IG% in the diagnosis and severity of AA.

Methods: Eighty-eight patients diagnosed with AA and a control group of fifty-eight healthy children were included in this prospec-tive study. Patients with pathologically confirmed AA were divided into two subgroups: acute simple appendicitis (ASA) and acute perforated appendicitis (APA). The demographic characteristics, white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR), mean platelet volume (MPV), IG%, and C-reactive protein (CRP) values were analyzed. Receiver operating characteristics (ROC) anal-ysis was used to compare the diagnostic accuracies and predictive performances.

Results: Patients with AA had higher IG%, WBC count, NLR, and MPV value than control group (p=0.28, p=0.22, p<0.001, p=0.001, respectively). Only IG% showed statistically significant difference from other inflammatory markers evaluated in ASA and APA patients (p<0.001). ROC analysis showed that IG% is a good predictor for the presence of APA at an optimal cut-off for IG being 0.2% (sensitivity 81.8%, specificity 85.2%, area under the ROC curve 0.83).

Conclusion: In the present study, we demonstrated that AA patients with higher IG levels might be more likely to develop perforation. The IG values combined with a physical examination, imaging studies, and other laboratory tests may help clinicians to identify high-risk AA patients in the pediatric emergency department.
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http://dx.doi.org/10.14744/tjtes.2021.41347DOI Listing
March 2022

MicroRNAs: Novel Targets in Hepatic Ischemia-Reperfusion Injury.

Biomedicines 2022 Mar 29;10(4). Epub 2022 Mar 29.

Transplant Research Institute, James D. Eason Transplant Institute, Department of Surgery, School of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

Hepatic ischemia-reperfusion injury (IRI) is one of the main factors for early allograft dysfunction (EAD), which may lead to graft rejection, graft loss, or shortened graft life in liver transplantation. Hepatic IRI appears to be inevitable during the majority of liver procurement and transportation of donor organs, resulting in a cascade of biological changes. The activation of signaling pathways during IRI results in the up- and downregulation of genes and microRNAs (miRNAs). miRNAs are ~21 nucleotides in length and well-characterized for their role in gene regulations; they have recently been used for therapeutic approaches in addition to their role as biomarkers for many diseases. miRNAs that are associated with hepatic IRI in in vitro and in vivo animal models are comprehensively summarized in this review. In those studies, the manipulation of miRNAs has been shown for the inhibition of aggravated immune response, reduction of apoptosis, stimulation of tissue repair, and enhancement of cell recovery to attenuate liver damage. Therefore, the utilization of liver-specific miRNA holds great potential as a therapeutic agent to improve early allograft dysfunction, hepatic injury, and patient outcome.
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http://dx.doi.org/10.3390/biomedicines10040791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028838PMC
March 2022

Mortality after kidney transplantation: 10-year outcomes.

Cir Cir 2022 ;90(2):172-179

Division of Kidney Transplantation Inonu University, School of Medicine, Turgut Ozal Medical Center, Malatya.

Objectives: In the past decade, advances in immunological therapy have increased the survival of kidney recipients and their grafts. However, it has not achieved the desired level of improvement. This study aims to reveal the mortality among kidney recipients.

Methods: Medical data of the patients, who had undergone kidney transplantation (KT) between November 2010 and December 2020, were retrospectively reviewed. Inclusion criteria were adult kidney recipients, who had died. Exclusion criteria were pediatric recipients, recipients of en bloc and dual KT, recipients with missing data, and recipients with a primary non-functioning graft. The recipients were grouped according to their donor type; Group 1 (from a living donor) and Group 2 (from a deceased donor). Subgroup analyses were done for mortality by time-period post-transplant and for infectious causes of mortality.

Results: Of 314 recipients, 35 (11.14%) died. Twenty-nine recipients were included in the study (Group 1: 17 and Group 2: 12). The most common cause of mortality was infection (58.6%), and the second was cardiovascular disease (CVD) (24.1%). Sepsis developed in 29.4% of infection-related deaths, while COVID-19 constituted 23.5% of infection-related deaths.

Conclusion: Early diagnosis and treatment of infectious and CVD are important to improve survival in kidney recipients.
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http://dx.doi.org/10.24875/CIRU.21000300DOI Listing
March 2022

Effects of azithromycin on ventricular repolarization in children with COVID-19.

Rev Port Cardiol 2022 Jul 21;41(7):551-556. Epub 2022 Feb 21.

Department of Pediatrics, Pediatric Cardiology Division, Kayseri Education and Research City Hospital, Kayseri, Turkey.

Introduction: Azithromycin is used to treat pediatric COVID-19 patients. It can also prolong the QT interval in adults. This study assessed the effects of azithromycin on ventricular repolarization in children with COVID-19.

Method: The study prospectively enrolled children with COVID-19 who received azithromycin between July and August 2020. An electrocardiogram was performed before, one, three, and five days post-treatment. Using ImageJ®, the following parameters were measured: QT max, QT min, Tp-e max, and Tp-e min. The parameters QTc max, QTc min, Tp-ec max, Tp-ec min, QTcd, Tp-ecd, and the QTc/Tp-ec ratio were calculated using Bazett's formula.

Results: The study included 105 pediatric patients (mean age 9.8±5.3 years). The pretreatment heart rate was higher than after treatment (before 92 [79-108]/min vs. Day 1 82 [69-108)]/min vs. Day 3 80 [68-92.2]/min vs. Day 5 81 [70-92]/min; p=0.05).

Conclusion: Azithromycin does not affect the ventricular repolarization parameters on ECG in pediatric COVID-19 cases.
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http://dx.doi.org/10.1016/j.repc.2021.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858685PMC
July 2022

Targeting Bcl6 in the TREX1 D18N murine model ameliorates autoimmunity by modulating T-follicular helper cells and germinal center B cells.

Eur J Immunol 2022 05 15;52(5):825-834. Epub 2022 Feb 15.

Division of Nephrology, Department of Medicine, Center for Immunity, Inflammation and Regenerative Medicine (CIIR), University of Virginia, Charlottesville, Virginia, United States.

The Three Prime Repair EXonuclease I (TREX1) is critical for degrading post-apoptosis DNA. Mice expressing catalytically inactive TREX1 (TREX1 D18N) develop lupus-like autoimmunity due to chronic sensing of undegraded TREX1 DNA substrates, production of the inflammatory cytokines, and the inappropriate activation of innate and adaptive immunity. This study aimed to investigate Thelper (Th) dysregulation in the TREX1 D18N model system as a potential mechanism for lupus-like autoimmunity. Comparison of immune cells in secondary lymphoid organs, spleen and peripheral lymph nodes (LNs) between TREX1 D18N mice and the TREX1 null mice revealed that the TREX1 D18N mice exhibit a Th1 bias. Additionally, the T-follicular helper cells (Tfh) and the germinal celter (GC) B cells were also elevated in the TREX1 D18N mice. Targeting Bcl6, a lineage-defining transcription factor for Tfh and GC B cells, with a commercially available Bcl6 inhibitor, FX1, attenuated Tfh, GC, and Th1 responses, and rescued TREX1 D18N mice from autoimmunity. The study presents Tfh and GC B-cell responses as potential targets in autoimmunity and that Bcl6 inhibitors may offer therapeutic approach in TREX1-associated or other lupus-like diseases.
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http://dx.doi.org/10.1002/eji.202149324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089306PMC
May 2022

Anxiety and healthcare satisfaction of mothers with children hospitalized in the pediatric emergency service.

Arch Pediatr 2022 Apr 31;29(3):207-212. Epub 2022 Jan 31.

Department of Pediatrics, Faculty of Medicine, Erciyes University, Kayseri, Turkey.

Objectives: This cross-sectional study was conducted to determine the anxiety and healthcare satisfaction levels of mothers with children hospitalized in the pediatric emergency service and the relationship between them.

Methods: The study sample comprised mothers (n = 316) with children hospitalized in the pediatric emergency service of a tertiary hospital in Turkey. Intsitutional and ethics committee approval was obtained, and data were collected using the Questionnare Form, State Anxiety Inventory (SAI), and PedsQL Healthcare Satisfaction Scale (PHSS).

Results: The SAI mean scores of mothers were moderate (45.30 ± 9.29) and their PHSS total mean scores were high (70.74 ± 23.80). In the study, there was a low-level negative correlation between the SAI mean scores of the mothers and the PHSS subscales and total scale mean scores (p < 0.05). We found a relationship between the PHSS mean scores of mothers and the SAI mean scores, maternal age, education level, and waiting time for the examination, explaining 13.5% of the scores on the PHSS scale (p < 0.05).

Conclusion: In this study, the mothers had moderate anxiety and high healthcare satisfaction levels. Anxiety, educational level, and the waiting for an examination affected the healthcare satisfaction of mothers. The anxiety of mothers whose children are hospitalized in the pediatric emergency service should be reduced by conducting interventional studies.
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http://dx.doi.org/10.1016/j.arcped.2022.01.007DOI Listing
April 2022

Targeting Regulatory T Cells for Therapy of Lupus Nephritis.

Front Pharmacol 2021 6;12:806612. Epub 2022 Jan 6.

Center for Immunity, Inflammation and Regenerative Medicine (CIIR), Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, United States.

Lupus glomerulonephritis (LN) is a complex autoimmune disease characterized by circulating autoantibodies, immune-complex deposition, immune dysregulation and defects in regulatory T cell (Tregs). Treatment options rely on general immunosuppressants and steroids that have serious side effects. Approaches to target immune cells, such as B cells in particular, has had limited success and new approaches are being investigated. Defects in Tregs in the setting of autoimmunity is well known and Treg-replacement strategies are currently being explored. The aim of this minireview is to rekindle interest on Treg-targeting strategies. We discuss the existing evidences for Treg-enhancement strategies using key cytokines interleukin (IL)-2, IL-33 and IL-6 that have shown to provide remission in LN. We also discuss strategies for indirect Treg-modulation for protection from LN.
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http://dx.doi.org/10.3389/fphar.2021.806612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775001PMC
January 2022

The relationship between immature platelet fraction and severity of acute bronchiolitis.

Turk J Pediatr 2021;63(6):1056-1063

Departments of Family Medicine, Erciyes University Faculty of Medicine, Kayseri, Turkey.

Background And Objectives: Acute bronchiolitis is one of the most common reasons for hospitalization in infants. Although patients with acute bronchiolitis generally have a good prognosis, death can also occur. In this study, we evaluate the immature platelet fraction (IPF) as an indicator of the severity of acute bronchiolitis.

Methods: In our study, 179 patients diagnosed with acute bronchiolitis were divided into three groups as mild (n: 48; 26.8%), moderate (n: 104; 58.10%) and severe (n: 27; 15.1%) bronchiolitis. There were 80 healthy children in the control group. The diagnostic capacity of IPF and hematological parameters (platelet distribution width (PDW), mean platelet volume (MPV), white blood cell count (WBC), and platelet count (PLT)) values to predict severity of acute bronchiolitis was evaluated using receiver operating characteristic (ROC) curves and their respective areas under the curves (AUCs) calculated with 95% confidence intervals.

Results: The IPF value of patients with acute bronchiolitis was significantly higher than the healthy group (p < 0.001). In addition, a positive correlation was observed between clinical severity of bronchiolitis and IPF. The ROC curve analysis indicated that the IPF cut-off point for predicting severity of acute bronchiolitis was > 3.2% (Sensitivity of 84%, specificity of 97%). We found that the AUCs for IPF, MPV, PDW, WBC and PLT were statistically significant for bronchiolitis relative to the healthy control group. The parameter with the greatest AUC value was IPF.

Conclusion: The IPF may present for diagnosing and evaluating the clinical severity of acute bronchiolitis in children.
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http://dx.doi.org/10.24953/turkjped.2021.06.014DOI Listing
January 2022

Advances and Challenges in Kidney Organoids.

Curr Stem Cell Res Ther 2022 ;17(3):226-236

Center for Immunity, Inflammation, and Regenerative Medicine (CIIR), Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, USA.

The advent of organoids has renewed researchers' interest in in vitro cell culture systems. A wide variety of protocols, primarily utilizing pluripotent stem cells, are under development to improve organoid generation to mimic organ development. The complexity of organoids generated is greatly influenced based on the method used. Understanding the process of kidney organoid formation gives developmental insights into how renal cells form, mature, and interact with the adjacent cells to form specific spatiotemporal structural patterns. This knowledge can bridge the gaps in understanding in vivo renal developmental processes. Evaluating genetic and epigenetic signatures in specialized cell types can help interpret the molecular mechanisms governing cell fate. In addition, development in single-cell RNA sequencing, 3D bioprinting and microfluidic technologies has led to better identification and understanding of a variety of cell types during differentiation and designing of complex structures to mimic the conditions in vivo. While several reviews have highlighted the application of kidney organoids, there is no comprehensive review of various methodologies specifically focusing on kidney organoids. This review summarizes the updated differentiation methodologies, applications, and challenges associated with kidney organoids. Here we have comprehensively collated all the different variables influencing the organoid generation.
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http://dx.doi.org/10.2174/1574888X16666210804113626DOI Listing
April 2022

Interleukin-1β and uric acid as potential second-trimester predictive biomarkers of preeclampsia.

Hypertens Pregnancy 2021 Aug 6;40(3):186-192. Epub 2021 May 6.

University of Health Sciences, Bakirköy Dr. Sadi Konuk Training and Research Hospital, Department of Anesthesia and Reanimation Clinics, Istanbul, Turkey.

The prospective study was conducted at the University Hospital from February 2020 to December 2020. The study population (n = 88) included women who later developed PE (n = 42), as well as women who were healthy at birth (n = 46) in the second trimester of pregnancy. Serum levels of CRP, IL-1β, uric acid, creatinine, AST, ALT, MPV, Hb, PC, vitamin D, Ca, and Mg were compared between the groups. Serum IL-1β and uric acid levels were significantly higher in subjects who eventually developed PE compared with those who did not. IL-1β and uric acid may be a predictive markers for PE. Maternal serum IL-1β and uric acid levels in the second trimester of pregnancy may be a predictive markers for PE.
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http://dx.doi.org/10.1080/10641955.2021.1921793DOI Listing
August 2021

Hybrid cytokine IL233 renders protection in murine acute graft vs host disease (aGVHD).

Cell Immunol 2021 06 23;364:104345. Epub 2021 Mar 23.

Center for Immunity, Inflammation and Regenerative Medicine (CIIR), Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, USA. Electronic address:

Previously, we generated IL233, a hybrid cytokine composed of interleukin (IL)-2 and IL-33, with better therapeutic potential than either cytokine in multiple inflammatory diseases, in part through promoting T-regulatory cells (Tregs). Here we test the potential of IL233 pretreatment in a murine model of excessive Th1 activation, the parent-into-F1 model of acute GVHD (aGVHD). Five days of IL233 pretreatment of the recipients blocked or delayed the aGVHD-linked loss of B cells as seen in either the peripheral blood (day-11) or lymph nodes (day-14). IL233 pretreatment also prevented the expansion of donor CD8 T-cells in blood and LN at day-14 and significantly reduced day-14 serum IFNγ and TNFα compared to saline treated GVHD mice although, the level of Tregs did not statistically differ between saline and IL233-treated mice. Overall, the current study provides support for the use of IL233 as a therapeutic option in excessive Th1/CD8-driven conditions.
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http://dx.doi.org/10.1016/j.cellimm.2021.104345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128039PMC
June 2021

The prognostic and predictive value of platelet parameters in diabetic and nondiabetic patients with sudden sensorineural hearing loss.

Open Life Sci 2020 4;15(1):884-889. Epub 2020 Dec 4.

Kayseri City Hospital, ENT Clinic. Şeker Mah. Molu Cad. Kocasinan, Kayseri, Turkey.

Background: We aimed to evaluate the association between mean platelet volume, platelet distribution width (PDW), platelet count (PC) and plateletcrit (PCT), and the presence of sudden sensorineural hearing loss (SSNHL) and treatment response. In the literature, there is no study that investigates the platelet functions in diabetic patients with SSNHL.

Methods: The patients were retrospectively assigned into Group 1 (68 diabetic patients with SSNHL), Group 2 (63 nondiabetic patients with SSNHL) and Group 3 (64 healthy controls).

Results: PC was not significantly different between the groups ( > 0.05). MPV, PDW and PCT values were significantly higher in Group 1 as compared to Groups 2 and 3 ( < 0.05). Platelet parameters were not significantly different between the patients who were responsive and nonresponsive to the treatment. Therefore, the platelet parameters did not affect prognosis significantly in this study samples ( > 0.05).

Conclusions: This study showed that platelet parameters did not have a significant effect as a prognostic and predictive value in diabetic and nondiabetic patients with SSNHL. Further studies with more homogenous and larger study groups investigating the platelet parameters are needed to demonstrate microvascular damage and vascular alterations induced by diabetes mellitus.
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http://dx.doi.org/10.1515/biol-2020-0083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874536PMC
December 2020

Distribution of α-actinin-3 rs1815739 and angiotensin-1 converting enzyme InDel polymorphisms in Turkish bodybuilders.

Biomed Rep 2020 Dec 20;13(6):67. Epub 2020 Oct 20.

Laboratory of Medical Genetics and Molecular Diagnostics, Üsküdar University, Üsküdar, Istanbul 34662, Turkey.

The determination of the genetic profiles of successful athletes and the effects of these genetic parameters on athletic performance is gaining increasing interest. The majority of studies assessing the genetics of athletes usually analyse the most well-known genetic variations in athletes associated with the different specialties. The aim of the present study was to analyse the InDel and rs1815739 polymorphisms in Turkish bodybuilders. A total of 11 male bodybuilders were recruited and genotyped for these polymorphisms. The respective percentage of the II, ID and DD genotypes were 18, 73 and 9. For the genotype, the respective frequencies were 55 and 45 for the RX and RR genotypes. No XX genotype was detected. The allelic counts were 12 (55%) for I and 10 (45%) for the D alleles of ; and 12 (55%) and 10 (45%) for R and X alleles, respectively, for the genotype. Additionally, 5 athletes had ID + RX genotypes in terms of ACE InDel and ACTN3 rs1815739 polymorphisms, respectively. These results indicate the importance of endurance related alleles of and in bodybuilders. The results of the present are in agreement with previous studies, highlighting a potential association between specific polymorphisms and the endurance-related nature of bodybuilders. Further studies with larger cohorts are required to understand the association between these polymorphisms and specific parameters performance in bodybuilders.
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http://dx.doi.org/10.3892/br.2020.1374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605120PMC
December 2020

The Yin and Yang of Alarmins in Regulation of Acute Kidney Injury.

Front Med (Lausanne) 2020 21;7:441. Epub 2020 Aug 21.

Division of Nephrology, Department of Medicine, Center for Immunity, Inflammation, and Regenerative Medicine (CIIR), University of Virginia, Charlottesville, VA, United States.

Acute kidney injury (AKI) is a major clinical burden affecting 20 to 50% of hospitalized and intensive care patients. Irrespective of the initiating factors, the immune system plays a major role in amplifying the disease pathogenesis with certain immune cells contributing to renal damage, whereas others offer protection and facilitate recovery. Alarmins are small molecules and proteins that include granulysins, high-mobility group box 1 protein, interleukin (IL)-1α, IL-16, IL-33, heat shock proteins, the Ca binding S100 proteins, adenosine triphosphate, and uric acid. Alarmins are mostly intracellular molecules, and their release to the extracellular milieu signals cellular stress or damage, generally leading to the recruitment of the cells of the immune system. Early studies indicated a pro-inflammatory role for the alarmins by contributing to immune-system dysregulation and worsening of AKI. However, recent developments demonstrate anti-inflammatory mechanisms of certain alarmins or alarmin-sensing receptors, which may participate in the prevention, resolution, and repair of AKI. This dual function of alarmins is intriguing and has confounded the role of alarmins in AKI. In this study, we review the contribution of various alarmins to the pathogenesis of AKI in experimental and clinical studies. We also analyze the approaches for the therapeutic utilization of alarmins for AKI.
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http://dx.doi.org/10.3389/fmed.2020.00441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472534PMC
August 2020

Evaluation of the effect of chiropractic manipulative treatment on oxidative stress in sacroiliac joint dysfunction.

Turk J Phys Med Rehabil 2020 Jun 18;66(2):176-183. Epub 2020 May 18.

Department of Medical Biochemistry, Yıldırım Beyazıt University Faculty of Medicine, Ankara, Turkey.

Objectives: This study aims to investigate the effect of chiropractic manipulative treatment on sacroiliac joint dysfunction (SIJD) and its relationship to oxidative stress (OXS) parameters.

Patients And Methods: Thirty-three patients diagnosed with SIJD (20 males, 13 females; mean age 36.3±9.7 years; range, 18 to 60 years) and 30 healthy volunteers (20 males, 10 females; mean age 36.4±12.2 years; range, 20 to 57 years) were included in this cross-sectional, case-control study conducted between February 2017 and September 2017. Manipulation was applied to the patients once a week for a duration of four weeks. The patients were evaluated at pre-treatment and one month after treatment with visual analog scale, SIJD test, and total thiol, native thiol, disulphide, and ischemia-modified albumin (IMA) as OXS indicators.

Results: Prior to treatment, we demonstrated that serum native thiol (μmol/L) and total thiol (μmol/L) levels in the patient group were lower compared to control subjects (p=0.03 and p=0.02, respectively). Serum IMA levels were higher in the patient group (p=0.01). There was no change in OXS parameters after manipulative treatment in the patient group.

Conclusion: Manipulation is useful in SIJD. Thiol/disulphide homeostasis and serum IMA levels may be used to measure the OXS in patients with SIJD.
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http://dx.doi.org/10.5606/tftrd.2020.3301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401678PMC
June 2020

Ovarian incision enhances folliculogenesis: A rat model.

J Obstet Gynaecol Res 2020 Oct 8;46(10):2043-2049. Epub 2020 Jul 8.

Department of Obstetrics and Gynecology, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey.

Aim: To determine whether performing incision on the surface of the ovarian cortex in rats advances follicular development.

Methods: Five to seven separate superficial incisions were performed on the surface of right ovaries of 6-7-month-old albino Wistar rats. Daily 40 IU of gonadotropins were administered for 14 days. On the 15th day, both ovaries of the rats were removed. The right (incised) ovaries were compared with the contralateral ovaries in terms of ovary's weight, numbers of primordial, primary, secondary and antral follicles, their mean percentages and mean Ki-67 proliferation indices.

Results: A total of 22 ovaries were evaluated, with 11 right ovaries (incised) and 11 left ovaries (non-incised). The mean weight of ovaries was greater in the right ovaries than in the left ovaries; however, no statistical difference was found between them (0.77 ± 1.22 vs. 0.22 ± 0.08 gr, P = 0.159). The numbers of secondary and antral follicle were statistically higher in the right ovaries than in the left ovaries (4.4 ± 1.5 vs. 2.1 ± 1.6, P = 0.003 and 18.6 ± 8.7 vs. 11.3 ± 7.5, P = 0.046, respectively). The right ovaries also significantly differed from the left ovaries in terms of mean percentages of primordial and antral follicles (P < 0.05 for both). The mean Ki-67 proliferation index had a marginal difference between the groups (P = 0.064).

Conclusion: Performing incisions on the surface of the ovarian cortex in rats may advance the ovarian follicular development. Future animal studies may provide more evidence regarding potential benefits of mechanical stimulation to the ovaries.
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http://dx.doi.org/10.1111/jog.14373DOI Listing
October 2020

Liver Transplantation for Hepatocellular Carcinoma: Malatya Experience and Proposals for Expanded Criteria.

J Gastrointest Cancer 2020 Sep;51(3):998-1005

Department of Surgery, Liver Transplantation Institute, Inonu University, 44315, Malatya, Turkey.

Survival was examined from a Turkish liver transplant center of patients with HCC, to identify prognostic factors. Data from 215 patients who underwent predominantly live donor liver transplant for HCC at our institute over 12 years were included in the study and prospectively recorded. They were 152 patients within and 63 patients beyond Milan criteria. Patients beyond Milan criteria were divided into two groups according to presence or absence of tumor recurrence. Recurrence-associated factors were analyzed. These factors were then applied to the total cohort for survival analysis. We identified four factors, using multivariate analysis, that were significantly associated with tumor recurrence. These were maximum tumor diameter, degree of tumor differentiation, and serum AFP and GGT levels. A model that included all four of these factors was constructed, the 'Malatya criteria.' Using these Malatya criteria, we estimated DFS and cumulative survival, for patients within and beyond these criteria, and found statistically significant differences with improved survival in patients within Malatya criteria of 1, 5, and 10-year overall survival rates of 90.1%, 79.7%, and 72.8% respectively, which compared favorably with other extra-Milan extended criteria. Survival of our patients within the newly defined Malatya criteria compared favorably with other extra-Milan extended criteria and highlight the usefulness of serum AFP and GGT levels in decision-making.
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http://dx.doi.org/10.1007/s12029-020-00424-wDOI Listing
September 2020

Mechanisms underlying TNFα-induced enhancement of force generation in airway smooth muscle.

Physiol Rep 2019 09;7(17):e14220

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.

Airway diseases such as asthma are triggered by inflammation and mediated by proinflammatory cytokines such as tumor necrosis factor alpha (TNFα). Our goal was to systematically examine the potential mechanisms underlying the effect of TNFα on airway smooth muscle (ASM) contractility. Porcine ASM strips were incubated for 24 h with and without TNFα. Exposure to TNFα increased maximum ASM force in response to acetylcholine (Ach), with an increase in ACh sensitivity (hyperreactivity), as reflected by a leftward shift in the dose-response curve (EC ). At the EC , the [Ca ] response to ACh was similar between TNFα and control ASM, while force increased; thus, Ca sensitivity appeared to increase. Exposure to TNFα increased the basal level of regulatory myosin light chain (rMLC) phosphorylation in ASM; however, the ACh-dependent increase in rMLC phosphorylation was blunted by TNFα with no difference in the extent of rMLC phosphorylation at the EC ACh concentration. In TNFα-treated ASM, total actin and myosin heavy chain concentrations increased. TNFα exposure also enhanced the ACh-dependent polymerization of G- to F-actin. The results of this study confirm TNFα-induced hyperreactivity to ACh in porcine ASM. We conclude that the TNFα-induced increase in ASM force, cannot be attributed to an enhanced [Ca ] response or to an increase in rMLC phosphorylation. Instead, TNFα increases Ca sensitivity of ASM force generation due to increased contractile protein content (greater number of contractile units) and enhanced cytoskeletal remodeling (actin polymerization) resulting in increased tethering of contractile elements to the cortical cytoskeleton and force translation to the extracellular matrix.
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http://dx.doi.org/10.14814/phy2.14220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739507PMC
September 2019

Factors Affecting eGFR Slope of Renal Transplant Patients During the First 2 Years.

Transplant Proc 2019 Sep 7;51(7):2318-2320. Epub 2019 Aug 7.

General Surgery, Inonu University, Malatya, Turkey.

Purpose: In healthy individuals, glomerular filtration rate decreases by 1 mL/min/y after a peak level of 125.0 mL/min has been reached in adulthood. Any reduction greater than this is a progressive slope (slope more negative than -1 mL/min/y, stable [-1 to +1]), or an improvable slope if it shows more of an increase, that is, greater than +1.0 mL/min/y). The aim of the study was to determine the factors affecting estimated glomerular filtration rate (eGFR) slope during the first 2 years of renal transplant in patients with negative pretransplant panel-reactive antibody.

Materials And Methods: The characteristics of 59 renal transplant patients, such as age, sex, etiology, and 2 years of laboratory data, were collected retrospectively. For each patient, the eGFR decline rate (slope) (mL/min-1/1.73 m-1/y-1) was determined by linear regression analysis using all calculated eGFR values over the study period.

Findings: Of 59 patients, 7 (11.8%) had a progressive slope, 22 (37.2%) had a stable slope, and 30 (50.8%) had an improvable slope. The first-year mean tacrolimus level was lower in patients with progressive slope than in the patients with stable slope and improvable slope (P < .022). The determinants of eGFR slope in multiple regression analysis were post-transplant hypertension (β = -0.393; P = .002) and the first-year mean tacrolimus level (β = 0.320; P = .01), whereas age, serum albumin, and 2-year mean tacrolimus level did not reach the level of significance.

Conclusion: Keeping tacrolimus levels high in the first year to prevent eGFR declining is important.
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http://dx.doi.org/10.1016/j.transproceed.2019.01.165DOI Listing
September 2019

Otolin-1, as a Potential Marker for Inner Ear Trauma after Mastoidectomy.

J Int Adv Otol 2019 Aug;15(2):200-203

Department of Biochemistry, Adnan Menderes University School of Medicine, Aydın, Turkey.

Objectives: The aim of this prospective clinical study was to examine the negative effect of drilling by measuring peripheral Otolin-1 levels as a potential biomarker.

Materials And Methods: Patients who underwent mastoidectomy due to chronic otitis media were included in the study. Otolin-1 levels were measured preoperatively and 6 h postoperatively, and total drilling time was noted. Preoperative serum Otolin-1 levels in 31 patients were compared with those in31 age- and sex-matched healthy individuals. Pre- and postoperative serum Otolin-1 levels were also compared.

Results: Tympanoplasty was performed through canal wall-down (n=17) and wall-up mastoidectomy (n=14) in our sample. The mean duration of drilling was 52.7±13.8min. Preoperative serum Otolin-1 levels were significantly lower in patients than in healthy controls (21.0±3.0 vs. 23.5±3.9 pg/mL, p=0.006). We also found significantly higher postoperative serum Otolin-1 levels than preoperative levels (21.0±3.0 vs. 27.0±6.9 pg/mL, p<0.001). An increase in serum Otolin-1 levels during surgery was independently associated with drilling time in multivariate linear regression analysis (r=0.309, p<0.001).

Conclusion: A nearly postoperative increase in serum Otolin-1 levels after mastoidectomy was independently associated with drilling time. We show that serum Otolin-1 levels may be used to indicate inner ear trauma in clinical practice in the future.
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http://dx.doi.org/10.5152/iao.2019.5155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750788PMC
August 2019

Increased TSLP, IL-33, IL-25, IL-19, IL 21 and amphiregulin (AREG) levels in chronic rhinosinusitis with nasal polyp.

Eur Arch Otorhinolaryngol 2019 Jun 19;276(6):1685-1691. Epub 2019 Mar 19.

Department of Biochemistry, Adnan Menderes University Medical School, Aydın, Turkey.

Objective: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease. The surrogate indicating biomarkers in patients with CRSwNP need further evaluation. The aim of this study was to investigate the association of thymic stromal lymphopoietin (TSLP) and amphiregulin (AREG) cytokines in patients with CRSwNP.

Methods: Sinonasal tissue samples were collected from 33 patients with CRSwNP and 29 controls. Levels of AREG, IL-19, IL-21, IL-25, IL-33 and TSLP in nasal polyp and control sinonasal tissues were determined following the enzyme-linked immunosorbent assay method.

Results: We found that AREG, IL-19, IL-21, IL-25, IL-33 and TSLP levels were significantly higher in the CRSwNP group compared to the control group (p < 0.000; p < 0.000; p < 0.000; p < 0.000; p < 0.003; p < 0.021, respectively).

Conclusions: Our findings indicated that AREG, IL-19, IL-21, IL-25, IL-33 and TSLP were significantly increased in tissue samples of CRSwNP patients and may be considered as molecular indicators and targets for therapeutic developments for patients with CRSwNP.
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http://dx.doi.org/10.1007/s00405-019-05379-8DOI Listing
June 2019

Early cochlear implantation: Verbal working memory, vocabulary, speech intelligibility and participant variables.

Cochlear Implants Int 2019 03 8;20(2):62-73. Epub 2019 Jan 8.

e Faculty of Health Sciences , Hacettepe University , Ankara , Turkey.

Objectives: The purpose of this study was to compare performance in the areas of verbal working memory (VWM), vocabulary skills, and speech intelligibility between children with cochlear implants (CIs) and children with typical development (TD). The correlations between participant variables and the scores of children with CIs in VWM and the measures of language were examined. Also, it was important to identify which variables predict VWM in children with CIs.

Methods: A total of 59 children participated in this study with the study group being comprised of 31 children who had received a CI and the control group being comprised of 28 children with TD. The assessment techniques utilized in this study were the backward digit span (BDS), non-word repetition, speech intelligibility, and vocabulary skills.

Results: The study results revealed significant differences in the non-word repetition, speech intelligibility, and vocabulary tasks. The results all favored the typically developing children while the findings for the BDS were equal for both groups.

Discussion: In children with CIs the results for VWM observed in this study are believed to be related to the modality of assessment presentation, prior vocabulary knowledge, and familiarity with the presented material. The results from this study also revealed that the variables which predicted VWM in children with CIs were speech perception, duration of CI use, and vocabulary knowledge.
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http://dx.doi.org/10.1080/14670100.2019.1565077DOI Listing
March 2019

Assessment of antioxidant enzymes, total sialic acid, lipid bound sialic acid, vitamins and selected amino acids in children with phenylketonuria.

Pediatr Res 2018 12 15;84(6):821-828. Epub 2018 Aug 15.

Faculty of Science, Division of Biochemistry, Department of Chemistry, Yuzuncu Yil University, Van, Turkey.

Background: In this study, children with phenylketonuria and healthy control subjects were assessed for glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) activity, malondialdehyde (MDA), glutathione (GSH), retinol, cholecalciferol, α-tocopherol, phylloquinone, total sialic acid (TSA), lipid bound sialic acid (LSA), total antioxidant (TAS), total oxidation (TOS), and amino acid levels, and the relationships of these variables with phenylketonuria were evaluated.

Methods: The study included 60 children with phenylketonuria and 30 control subjects. Children with phenylketonuria were divided into hyperphenylalaninemia (HPA) and amino acid mixture (AAM) groups.

Results: The HPA group had significantly lower levels of GSH-Px, CAT, GSH, TAS, α-aminobutyric acid, and taurine levels (p < 0.01, p < 0.05, p < 0.05, p < 0.001, p < 0.01, p < 0.05, respectively) than the control group. Additionally, the AAM group had significantly lower levels of CAT, TAS, and phylloquinones (p < 0.05, p < 0.05, p < 0.05, respectively) than the control group. It was observed in our study that in the HPA group, a significantly strong positive linear correlation was observed between phenylalanine and α-aminoadipic acid (r = 0.777; p = 0.002).

Conclusions: It was concluded that the levels of α-aminoadipic acid and phylloquinone might be an appropriate choice for the determination of phenylketonuria in parallel with the levels of phenylalanine. α-aminobutyric acid and phylloquinone as a supplement can decrease HPA damage.
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http://dx.doi.org/10.1038/s41390-018-0137-2DOI Listing
December 2018

Utilizing prestin as a predictive marker for the early detection of outer hair cell damage.

Am J Otolaryngol 2018 Sep - Oct;39(5):594-598. Epub 2018 Jul 12.

Adnan Menderes University Medical School, Department of Medical Pharmacology, Aydin, Turkey.

Purpose: To evaluate prestin as a biomarker for the identification of early ototoxicity.

Materials And Methods: Rats (n = 47) were randomly assigned to five groups: low-dose (LAG) or high-dose (HAG) amikacin (200 and 600 mg/kg/day, respectively, for 10 days), low-dose (LCIS)or high-dose (HCIS) cisplatin (single doses of 5 and 15 mg/kg, respectively, for 3 days), and control (n = 8). At the end of the experiment, measurement of distortion product-evoked otoacoustic emissions (DPOAE) were performed to evaluate hearing, then blood samples and both ear tissues were collected under anesthesia. Prestin levels were determined by ELISA. Cochlear damage was evaluated histologically using a 4-point scoring system.

Results: The mean serum prestin levels were 377.0 ± 135.3, 411.3 ± 73.1, 512.6 ± 106.0, 455.0 ± 74.2 and 555.3 ± 47.9 pg/ml for control, LCIS, HCIS, LAG and HAG groups, respectively. There was significant difference between prestin levels of Control-LCIS-HCIS groups (p = 0.031) and prestin levels of Control-LAG-HAG groups (p = 0.003). There were also significant differences in prestin levels between the low- and high-dose cisplatin and amikacin groups (p = 0.028 and p = 0.011, respectively). Each group had significantly lower DPOAE results at 4, 6 and 8 kHz than control groups (p < 0.001). The LAG, HAG, LCIS and HCIS groups had significantly higher cochlear damage scores than the control group (p < 0.05).

Conclusions: Higher doses of cisplatin and amikacin were associated with the greatest increases in serum prestin level and cochlear damage score. The results of this study suggest that prestin is a promising early indicator of cochlear damage.
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http://dx.doi.org/10.1016/j.amjoto.2018.07.007DOI Listing
January 2019

A Novel Technique in the Treatment of Lymphoceles After Renal Transplantation: C-Arm Cone Beam CT-Guided Percutaneous Embolization of Lymphatic Leakage After Lymphangiography.

Transplantation 2018 Nov;102(11):1955-1960

Department of Radiology, Inonu University Faculty of Medicine, Malatya, Turkey.

Background: We aimed to evaluate the efficacy of percutaneous embolization after lymphangiography using C-arm cone-beam computed tomography (CBCT) performed at the site of lymphatic leakage in patients with postrenal transplant lymphocele.

Methods: Between July 2014 and August 2017, 13 patients not responding to percutaneous ethanol sclerotherapy and conservative treatment for recurrent lymphocele after renal transplant were included. The mean age of the patients was 56.38 ± 9.91 (range, 36-70) years, and it comprised 9 men and 4 women. All patients underwent intranodal lymphangiography. C-arm CBCT-guided percutaneous embolization was performed in patients with confirmed lymphatic leakage. Patients who had no lymphatic leakage underwent drainage with fibrin glue injection.

Results: Lymphatic leakage was observed in 9 patients after lymphangiography, and they underwent CBCT-guided percutaneous N-butyl-2-cyanoacrylate embolization. The volume of lymphatic drainage reduced to less than 10 mL in 8 patients. One patient who was not responding to embolization was treated surgically, after percutaneous drainage and fibrin glue injection. Lymphatic leakage was not observed in 4 patients after lymphangiography. Of these, 3 patients showed a reduction in the amount of lymphatic drainage after lymphangiography. All 4 patients underwent percutaneous drainage and fibrin glue injection. One patient did not respond to the treatment and was treated surgically. Prelymphangiography and postlymphangiography and embolization, the volume of lymphatic drainage was 113.07 ± 21.75 mL, and 53.84 ± 30.96 mL, respectively, and statistically significant decrease was detected (P < 0.005).

Conclusions: Lymphangiography and CBCT-guided percutaneous embolization procedures might be an effective treatment method for patients with lymphocele refractory to treatment.
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http://dx.doi.org/10.1097/TP.0000000000002268DOI Listing
November 2018

Management of non-vascular complications following renal transplantation using percutaneous approach.

Ann Ital Chir 2018 ;89:86-91

Objective: Non-vascular complications following renal transplantation can cause graft failure. In this study, we present our two-year experience with percutaneous treatment for non-vascular complications following renal transplantation.

Patients And Methods: A total of 30 patients who underwent percutaneous radiological treatment between March 2014 and July 2016 were included in the study.

Results: Following renal transplantation, a total of 36 percutaneous radiological procedures which includes hydronephrosis secondary to ureteral stricture (n. 15), clinical symptom-producing lymphocele due to pressure (14) and creatinine elevated nondilated grafts (n. 7) after excluding other reasons of creatinine elevation, were performed. Six patients received percutaneous treatment for both ureteral stricture and lymphocele. The patients underwent balloon dilatation and double- J ureteral stent due to ureteral stricture. The mean pre- and post-procedural creatinine levels were 4.36 ± 2.84mg/dL and 2.17 ± 1.24 mg/dL respectively (p=0.004), indicating a significant difference. For lymphocele treatment, sclerosing agents were injected and lymphatic leakage areas were injected with percutaneous glue. The mean pre- and post-procedural creatinine values were 2.97 ± 1.78 mg/dL and 1.75 ± 1.18 respectively (p=0.002), indicating a significant difference. Nephrostomy catheters were placed for patients with elevated creatinine levels and non-dilated collecting system. The mean pre- and post- nephrostomy creatinine levels were 3.55 ± 2.36 mg/dL and 2.57 ± 1.82 mg/dL respectively (p>0.05), indicating no statistically significant difference.

Conclusion: The results of our study suggest that percutaneous treatment is an effective method for the treatment of non-vascular complications following renal transplantation, and, therefore, should be the first option for the preservation of graft functions.

Key Words: Percutaneous treatment, Renal transplantation.
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November 2018
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