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Investigation of Zinc on hemorheological parameters in a rat model of diabetes
(Elsevier GmbH, 2024) Pastacı, Özsobacı, N.; Karış, D.; Ercan, A.M.; Özçelik, D.
Diabetes mellitus (DM) is a complex, chronic metabolic disorder characterized by impaired regulation of blood glucose levels. Zinc (Zn) is an essential trace elements that plays a role in various physiological processes within the body, including those related to diabetes. The current study was investigated the effect of Zn supplementation on hemorheological parameters in a rat model of DM. After induction of DM, 32 male Wistar albino rats were divided into four groups: control, Zn, DM, and Zn+DM. Whole blood viscosity (WBV) was determined by using digital cone and plate viscometer and plasma viscosity (PV) was determined by a Coulter Harkness capillary viscometer. The rats in the DM Group showed a decrease in both Zn levels and body weight, as well as an increase in glucose levels when compared to the control group. Diabetic rats supplemented with Zn displayed lower blood glucose levels and higher concentrations of Zn compared to the DM Group. The higher PV and lower hematocrit level were measured in DM Group than control group and lower PV, higher hematocrit level were measured in Zn+DM group than DM Group. The WBV was measured at four different shear rates (57.6–115.2 - 172.8–230.4 s ?1). A statistically significant increase was observed in the DM group compared to the control group. Additionally, a statistically significant decrease was observed in the Zn+DM Group compared to the DM Group at a shear rate of 230.4 s?1. Erythrocyte rigidity index (Tk) and oxygen delivery index (ODI) were computed under conditions of high shear rate. The rats in the DM group exhibited a reduction in ODI and an elevation in Tk in comparison to the control group. Conversely, the diabetic rats supplemented with Zn exhibited decreased Tk and increased ODI compared to the DM Group. Zn supplementation seems to have a potential beneficial effect for protecting adverse affect of diabetes on hemorheogical parameters and for maintaining vascular health. © 2024 Elsevier GmbH
In vivo and in vitro effects of cord blood hematopoietic stem and progenitor cell (HSPC) expansion using valproic acid and/or nicotinamide
(Elsevier Masson s.r.l., 2024) Gencer, E.B.; Akin, H.Y.; Toprak, S.K.; Turasan, E.; Yousefzadeh, M.; Yurdakul-Mesutoglu, P.; Cagan M.
Background: High self-renewal capacity and most permissive nature of umbilical cord blood (CB) results with successful transplant outcomes but low hematopoietic stem and progenitor cell (HSPC) counts limits wider use. In order to overcome this problem ex vivo expansion with small molecules such as Valproic acid (VPA) or Nicotinamide (NAM) have been shown to be effective. To the best of our knowledge, the combinatory effects of VPA and NAM on HSPC expansion has not been studied earlier. The aim of this study was to analyze ex vivo and in vivo efficacy of VPA and NAM either alone or in combination in terms of expansion and engraftment. Methods: A total of 44 CB units were included in this study. To determine the ex vivo and in vivo efficacy, human CB CD34+ cells were expanded with VPA and/or NAM and colony forming unit (CFU) assay was performed on expanded HSPC. Xenotransplantation was performed simultaneously by intravenous injection of expanded HSPC to NOD-SCID gamma (NSG) mice (n = 22). Significance of the difference between the expansion groups or xenotransplantation models was analyzed using t-test, Mann-Whitney, ANOVA or Kruskal-Wallis tests as appropriate considering the normality of distributions and the number of groups analyzed. Results: In vitro CD34+ HSPC expansion fold relative to cytokines-only was significantly higher with VPA compared to NAM [2.23 (1.07–5.59) vs 1.48 (1.00–4.40); p < 0.05]. Synergistic effect of VPA+NAM has achieved a maximum relative expansion fold at 21 days (D21) of incubation [2.95 (1.00–11.94)]. There was no significant difference between VPA and VPA+NAM D21 (p = 0.44). Fold number of colony-forming unit granulocyte-macrophage (CFU-GM) colonies relative to the cytokine-only group was in favor of NAM compared to VPA [1.87 (1.00–3.59) vs 1.00 (1.00–1.81); p < 0.01]. VPA+NAM D21 [1.62 (1.00–2.77)] was also superior against VPA (p < 0.05). There was no significant difference between NAM and VPA+NAM D21. Following human CB34+ CB transplantation (CBT) in the mouse model, fastest in vivo leukocyte recovery was observed with VPA+NAM expanded cells (6 ± 2 days) and the highest levels of human CD45 chimerism was detectable with VPA-expanded CBT (VPA: 5.42 % at day 28; NAM: 2.45 % at day 31; VPA+NAM 1.8 % at day 31). Conclusion: Our study results suggest using VPA alone, rather than in combination with NAM or NAM alone, to achieve better and faster expansion and engraftment of CB HSPC. © 2024 Elsevier Masson SAS
The impact of continuous and intermittent ketogenic diets on cognitive behavior, motor function, and blood lipids in TgF344-AD rats
(Impact Journals LLC, 2024) Rutkowsky, J.M.; Roland, Z.; Valenzuela, A.; Nguyen, A.B.; Park, H.H.; Six, N.; Dursun I.
Studies suggest that ketogenic diets (KD) may improve memory in mouse models of aging and Alzheimer’s disease (AD). This study determined whether a continuous or intermittent KD (IKD) enhanced cognitive behavior in the TgF344-AD rat model of AD. At 6 months-old, TgF344-AD and wild-type (WT) littermates were placed on a control (CD), KD, or IKD (morning CD and afternoon KD) provided as two meals per day for 2 or 6 months. Cognitive and motor behavior and circulating ?-hydroxybutyrate (BHB), AD biomarkers and blood lipids were assessed. Animals on a KD diet had elevated circulating BHB, with IKD levels intermediate to CD and KD. TgF344-AD rats displayed impaired spatial learning memory in the Barnes maze at 8 and 12 months of age and impaired motor coordination at 12 months of age. Neither KD nor IKD improved performance compared to CD. At 12 months of age, TgF344-AD animals had elevated blood lipids. IKD reduced lipids to WT levels with KD further reducing cholesterol below WT levels. This study shows that at 8 or 12 months of age, KD or IKD intervention did not improve measures of cognitive or motor behavior in TgF344-AD rats; however, both IKD and KD positively impacted circulating lipids. © 2024 Rutkowsky et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Downregulation of stearoyl-CoA desaturase 1 (SCD-1) promotes resistance to imatinib in chronic myeloid leukemia
(Mattioli 1885, 2022) Günes, Buket Altınok; Hekmatshoar, Yalda; Özkan, Tülin; Bozkurt, Süreyya; Aydos, Oya Sena Erdoğan; Büyükaşık, Yahya; Aladağ, Elifcan; Asuman Sunguroğlu
Chronic myeloid leukemia (CML) is a malignant hematopoietic stem cell disease resulting in the fusion of BCR and ABL genes and characterized by the presence of the reciprocal translocation t(9;22)(q34;q11). BCR-ABL, a product of the BCR-ABL fusion gene, is a structurally active tyrosine kinase and plays an important role in CML disease pathogenesis. Imatinib mesylate (IMA) is a strong and selective BCR-ABL tyrosine kinase inhibitor. Although IMA therapy is an effective treatment, patients may develop resistance to IMA therapy over time. This study investigated the possible genetic resistance mechanisms in patients developing resistance to IMA. We did DNA sequencing in order to detect BCR-ABL mutations, which are responsible for IMA resistance. Moreover, we analyzed the mRNA expression levels of genes responsible for apoptosis, such as BCL-2, P53, and other genes (SCD-1, PTEN). In a group of CML patients resistant to IMA, when compared with IMA-sensitive CML patients, a decrease in SCD-1 gene expression levels and an increase in BCL-2 gene expression levels was observed. In this case, the SCD-1 gene was thought to act as a tumor suppressor. The present study aimed to investigate the mechanisms involved in IMA resistance in CML patients and determine new targets that can be beneficial in choosing the effective treatment. Finally, the study suggests that the SCD-1 and BCL-2 genes may be mechanisms responsible for resistance.
Increased levels of nerve growth factor accompany oxidative load in recurrent pregnancy loss. machine learning applied to FT-raman spectra study
(Springer, 2023) Depciuch, Joanna; Jakubczyk, Pawel; Paja, Wieslaw; Pancerz, Krzysztof; Wosiak, Agnieszka; Bahat, Pinar Yalcin; Toto, Omer Faruk; Bulut, Huri; Guleken, Zozan
The presented article is focused on developing and validating an efficient, credible, minimally invasive technique based on spectral signatures of blood serum samples in patients with diagnosed recurrent pregnancy loss (RPL) versus healthy individuals who were followed at the Gynecology department. A total of 120 participants, RPL disease (n = 60) and healthy individuals (n = 60), participated in the study. First, we investigated the effect of circulating nerve growth factor (NGF) in RPL and healthy groups. To show NGF's effect, we measured the level of oxidative loads such as Total Antioxidant Level (TAS), Total Oxidant Level (TOS), and Oxidative Stress Index (OSI) with Beckman Coulter AU system and biochemical assays. We find a correlation between oxidative load and NGF level. Oxidative load mainly causes structural changes in the blood. Therefore, we obtained Raman measurements of the participant's serum. Then we selected two Raman regions, 800 and 1800 cm(-1), and between 2700 cm(-1) and 3000 cm(-1), to see chemical changes. We noted that Raman spectra obtained for RPL and healthy women differed. The findings confirm that the imbalance between reactive oxygen species and antioxidants has important implications for the pathogenesis of RPL and that NGF levels accompany the level of oxidative load in the RPL state. Biomolecular structure and composition were determined using Raman spectroscopy and machine learning methods, and the correlation of these parameters was studied alongside machine learning technologies to advance toward clinical translation. Here we determined and validated the development of instrumentation for the Analysis of RPL patients' serum that can differentiate from control individuals with an accuracy of 100% using the Raman region corresponding to structural changes. Furthermore, this study found a correlation between traditional biochemical parameters and Raman data. This suggests that Raman spectroscopy is a sensitive tool for detecting biochemical changes in serum caused by RPL or other diseases.
Differentiation of claustrum resting-state functional connectivity in healthy aging, alzheimer's disease, and parkinson's disease
(John Wiley and Sons Inc, 2022) Ayyıldız, Sevılay; Velioğlu, Halil Aziz; Ayyıldız, Behçet; Sütçübaşı, Bernis; Hanoğlu, Lütfü; Bayraktaroğlu, Zübeyir; Yıldırım, Süleyman; Atasever, Alper; Yuluğ, Burak
The claustrum is a sheet-like of telencephalic gray matter structure whose function is poorly understood. The claustrum is considered a multimodal computing network due to its reciprocal connections with almost all cortical areas as well as subcortical structures. Although the claustrum has been involved in several neurodegenerative diseases, specific changes in connections of the claustrum remain unclear in Alzheimer's disease (AD), and Parkinson's disease (PD). Resting-state fMRI and T1-weighted structural 3D images from healthy elderly (n = 15), AD (n = 16), and PD (n = 12) subjects were analyzed. Seed-based FC analysis was performed using CONN FC toolbox and T1-weighted images were analyzed with the Computational Anatomy Toolbox for voxel-based morphometry analysis. While we observed a decreased FC between the left claustrum and sensorimotor cortex, auditory association cortex, and cortical regions associated with social cognition in PD compared with the healthy control group (HC), no significant difference was found in alterations in the FC of both claustrum comparing the HC and AD groups. In the AD group, high FC of claustrum with regions of sensorimotor cortex and cortical regions related to cognitive control, including cingulate gyrus, supramarginal gyrus, and insular cortex were demonstrated. In addition, the structural results show significantly decreased volume in bilateral claustrum in AD and PD compared with HC. There were no significant differences in the claustrum volumes between PD and AD groups so the FC may offer more precise findings in distinguishing changes for claustrum in AD and PD.
Anti-apoptotic effects of valproic acid treatment on dopaminergic neuronal loss in a 6-hydroxydopamine model of parkinson’s disease in rats
(2022) Cumbul, Alev; Genç, Ece; Keleş, Çiğdem Elif; Uslu, Ünal; Eyüboğlu, Siğnem
Aim: Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons resulting in deterioration of motor activity in patients. Currently, available therapies including Levodopa (L-DOPA) are more geared toward the treatment of symptoms. Therefore, developing effective neuroprotective therapies is needed. Valproic acid (VPA) has shown potent neuroprotective effects on dopamine (DA) neurons in various brain regions. The aim of this study is to investigate whether VPA attenuates the neuronal loss when co-treated with L-DOPA in a 6-hydroxydopamine (6-OHDA) induced PD model in rats. Methods: Male Wistar Albino rats received intranigral injection of 6-OHDA unilaterally. Twelve days later rats received either saline, L-DOPA, VPA, or L-DOPA+ VPA for 9 days. To determine whether rats had dopaminergic neuronal loss apomorphine-induced rotation test was used. Immunohistochemical analyses were performed in the Substantia Nigra pars compacta (SNpc) by measuring the tyrosine hydroxylase (TH) positive neurons and the apoptotic neurons. Results: 6-OHDA injection showed clinically impairment of the motor function with histologically significant damage to the dopaminergic neurons. VPA administration combined with L- DOPA protected neurons in SNpc by increasing the TH positive neurons and by decreasing the apoptotic neurons. L-DOPA given as a monotherapy, on the other hand, was ineffective on these parameters. Conclusion: Our experiments demonstrated that VPA had a neuroprotective effect when used with L-DOPA in the PD rat model.
Is adrenomedullin upregulation due to apical periodontitis independent of periodontal disease?
(SPRINGER, 2022) Ersahan, Şeyda; Özçelik, Fatih; Şirin, Dursun Ali; Hepsenoğlu, Yelda Erdem; Özçelik, İlbey Kayra; Topbaş, Celalettin
To investigate the relationship between apical periodontitis [AP] severity and inflammatory markers [interleukin (IL)-12, tumor necrosis factor-alpha (TNF-alpha), and Mid-Regional Pro Adrenomedullin (MR-proADM)] in patients with AP. A total of 162 subjects were divided into three categories: AP group (n=80), periodontitis (P) group (n= 42), healthy control group (n = 40). The scoring of disease severity in 80 AP patients without any periodontal disease, using dental radiographs, was based on The Abscess Score (AS), as those having at least 1 tooth with AP and severity of PAI 3-4 were classified as AS 1 (mild); those with only1 tooth and severity of PAI 5 as AS 2 (moderate) and those having > 2 tooth with severity of PAI 5 as AS 3 (severe). Blood samples were collected from all of the patients. Enzyme-linked immunosorbent assay was used to evaluate the samples. The MR-pro ADM levels of both the AP and P groups were considerably higher than the control group (p < 0.01). The IL-12 levels of the AP group were higher than the P and control groups (p < 0.05). TNF-alpha levels of the P group were significantly higher than both the AP and control groups (p < 0.01). MR-pro ADM levels of both the AP and Periodontitis groups were higher than the control group. TNF-alpha was a biomarker of periodontitis, while IL-12 was a biomarker of apical periodontitis.
The investigation of the effects of postnatal alcohol exposure on molecular content and antioxidant capacity of mice liver tissue
(PERGAMON-ELSEVIER SCIENCE LTD, 2022) Algburi, Ali Forat; Dursun, İlknur; Ustaoğlu, Şebnem Garip
One of the most common causes of fetal alcohol spectrum disease (FASD) characterized with neuro-developmental disorder and growth retardation, is the postnatal alcohol consumption. Since studies in literature are mainly focused on alcohol-induced effects on brain tissues, the molecular effects of postnatal alcohol con-sumption on fetal liver are not clarified yet. The aim of this study is to determine the postnatal alcohol consumption-induced structural and compositional changes on liver tissue and the antioxidant capacity of liver. Newborn mice were divided into 3 groups as control group without any treatment, alcohol group treated with 3.0 g/kg of ethanol in 0.02 ml/g of artificially enriched milk between Postnatal Days (PD) 3-20 and intragastric intubation control group which was intragastrically intubated in the same method as the alcohol group but without ethanol/milk. These postnatal days in mice refers prenatal period (third trimester) of gestation in human. The biomolecular changes were determined by ATR-FTIR spectral analysis of the samples, besides the biochemical measurement of total protein content and antioxidant capacity of liver tissue. The result of the current study shows that while there was a slight increase in total lipid content, significant decrease in unsat-urated lipid and total protein contents and total antioxidant capacity of liver were observed in alcohol-treated group. Thus, it is concluded that postnatal alcohol treatment causes significant changes in tissue proteins and lipids by inducing lipid peroxidation and changes in protein conformations of the liver tissue. In addition to that alcohol consumption also reduce the antioxidant capacity of liver tissue.
Single session anodal transcranial direct current stimulation on different cortical areas effects on pain modulation in healthy subjects
(HOGREFE PUBLISHING CORP, 2022) Erdoğan, Ezgi Tuna; Küçük, Zeynep; Eskikurt, Gökçer; Kurt, Adnan; Ermutlu, Numan; Karamürsel, Sacit
Transcranial direct current stimulation (tDCS) studies in healthy volunteers have shown conflicting results in terms of modulation in pain thresholds. The aim of this study was to investigate how single session anodal tDCS and modulated tDCS (mtDCS) of distinct cortical areas affected pain and perception thresholds in healthy participants. Five different stimulation conditions were applied at different cortical sites to 20 healthy volunteers to investigate the effects of tDCS and mtDCS (20 Hz) on pain and perception thresholds. TDCS over the motor cortex (M1), mtDCS over the motor cortex, tDCS over the dorsolateral prefrontal cortex (DLPFC), mtDCS of the DLPFC, and mtDCS over the occipital cortex were the stimulation conditions. All of the stimulations were anodal. The stimulations were given in a randomized order at 20-minute intervals. For comparison, electrical pain and perception thresholds were obtained from the right middle finger before and during the tDCS. After each measurement, participants were asked to give a score to their pain. In repeated measures analysis of variance (RM-ANOVA) test, the Condition x Time interaction showed no significant influence on changes in pain, perception thresholds, and pain scores (p = .48, p = .89, and p = .50, respectively). However, regardless of the condition types, there was a significant difference in pain and perceptual thresholds during tDCS (p = .01, p = .025, respectively). Our findings did not support difference in pain and perception modulation by a single session anodal tDCS over M1 and DLPFC compared to the occipital cortex in healthy volunteers. The increase in all thresholds during tDCS, irrespective of conditions, and peripheral sensations, including an active control group, taken together, suggest a placebo effect of active tDCS. Future studies about pain and perception in healthy subjects should consider the level of experimental pain and a strong placebo effect.
Morphometric evaluation of second to difth metacarpals for retrograde intramedullary headless screw fixation
(Universidad de la Frontera, 2022) Örs, Abdullah; Çolak, Tuncay; Bamaç, Belgin; Işık, Medine; Özbek, Aydın; Akansel, Gür; Memişoğlu, Kaya; Ayyıldız, Behçet
Intramedullary headless screw fixation has come to the fore in the treatment of metacarpal fractures in recent years with its advantages. Our aim was to evaluate the metacarpal morphometry for retrograde intramedullary entrance and to determine the optimal entry point. Computed tomography images of 105 patients including 64 men and 41 women, were examined. Distal and proximal metacarpal widths, medullary cavity width, cortex thickness and the measurements of the optimal entry site in volar-dorsal and radio-ulnar directions were measured in both coronal and sagittal planes. In the sagittal plane, the second metacarpal had the widest proximal width (16.29 mm), distal width was greatest in the third metacarpal (14.34 mm) which was significantly different between the sexes (p<0.001). Third metacarpal had the widest medullary cavity width in the sagittal plane (4.12 mm). In the coronal plane, it was the second metarcarpal with the widest proximal (16.14 mm) and distal width (13.92 mm) and was also the longest (66.32 mm). Unlike the sagittal plane, the medullary cavity width in the coronal plane was at the widest (4.06 mm) in fifth metacarpal. The points determined for optimal entry were respectively (4.60 mm; 4.97 mm; 4.55 mm; 4.36 mm) in the dorsal-volar plane, close to the dorsal side. There was no significant difference between the sexes for optimal insertion point in the sagittal planes in all the measured metacarpals. Considering its three dimensional structure, metacarpal bones have irregular morphometric properties and these features differ in sagittal and coronal planes. The optimal entry site is located in the midline in the coronal plane, while it is located in the sagittal plane close to the dorsal part. Knowing these properties can reduce the complication rate by reducing entry attempts and help select the correct material.
The prognostic and predictive values of differential expression of exosomal receptor tyrosine kinases and associated with the PI3K/AKT/mTOR signaling in breast cancer patients undergoing neoadjuvant chemotherapy
(Springer Science and Business Media Deutschland GmbH, 2022) Güney Eskiler, Gamze; Kazan, Nur; Hacıefendi, Ayten; Deveci Özkan, Asuman; Özdemir, Kayhan; Özen, Miraç; Koçer, Havva Belma; Yılmaz, Fahri; Kaleli, Süleyman; Şahin, Elvan; Bilir, Cemil
Purpose: Cancer cell-derived exosomes are the mediator of the tumor microenvironment and the molecular content of exosomes presents a promising prognostic or predictive marker in tumor progression and the treatment response of cancer patients. The aim of this study was to identify the expression levels of receptor tyrosine kinases (RTKs) and AKT1 and mTOR before and after neoadjuvant chemotherapy (NACT) in the exosomes of BC patients compared with healthy females. Methods: After isolating exosomes in the serum of 25 BC patients and characterization by flow cytometry, the mRNA levels of FGFR2, FGFR3, PDGFRB, AKT1 and mTOR in the exosomes were analyzed by RT-PCR. Results: Our preliminary findings showed that FGFR2, PDGFRB, AKT1 and mTOR levels were significantly upregulated in BC patients before NACT compared with the healthy group (p < 0.05). Furthermore, the mRNA levels PDGFRB and AKT1 were significantly down-regulated after NACT compared with control. PDGFRB expression level could predict pathological non-response and significantly correlated with tumor size after NACT. Conclusion: Therefore, especially FGFR2, PDGFRB and AKT1 could be a therapeutic target as a prognostic marker, whereas PDGFRB may be a promising predictive indicator of therapy response in BC patients. However, the prognostic or predictive role of RTKs and PI3K/AKT/mTOR signaling in the exosomes should be further investigated in a large patient population.
The relationship between clinical parameters and hepatocyte growth factor/c-Met levels in the sperm of infertile males
(IMR PRESS, 2022) Kayan, Başak Özge; Hançer, Veysel Sabri; Görmüş, Uzay; Özcan, Cenk; Abike, Faruk; Baykal, Cem Murat
Objective: Hepatocyte growth factor is a pleiotropic cytokine with potent mitogenic activity in many organs and tissues. The receptor for hepatocyte growth factor is c-Met, a transmembrane glycoprotein with tyrosine kinase activity. We investigated the relationships between hepatocyte growth factor and c-Met expression levels on sperm motility and male infertility. Methods: The study was designed as a prospective cohort, single-center clinical trial and was conducted between March 2015 and June 2016. The control group consisted of 31 healthy male volunteers with children, while the study group consisted of 61 men who were diagnosed with male infertility after presenting to the In Vitro Fertilization Unit of our Institute. All participants in the study were aged 18-60 years. Sperm samples were taken from each participant and divided in two. The fresh sample was examined immediately for expression of c-Met, while the other was stored frozen and evaluated later for hepatocyte growth factor. Primary outcome measures were the levels of hepatocyte growth factor and c-Met expression, while secondary outcome measures were the correlation of these levels with sperm count, morphology and motility. Results: The c-Met expression level in the control group (26.53 +/- 3.50, 19.43-32.73) was significantly lower than in the infertile group (27.95 +/- 2.86, 21.58-33.07) (p = 0.039). HGF expression was also significantly lower in the control group (3.25 +/- 1.76, 0.83-8.25) than in the infertile group (4.87 +/- 4.11, 1.01-21.58) (p = 0.043). In the overall group, c-Met expression showed a positive correlation with sperm motility percentage and a negative correlation with sperm count and sperm morphology percentage. Conclusions: The c-Met receptor and its ligand, hepatocyte growth factor, appear to be fundamental regulators of spermatogenesis, sperm motility and fertilization capacity.
Time kill-assays of antibiotic combinations for multidrug resistant clinical isolates of OXA-48 carbapenemase producing Klebsiella pneumoniae
(AkJournals, 2022) Erdem, Fatma; Díez-Aguilar, María; Öksüz, Lütfiye; Kayacan,Çiğdem; Abulaila, Ayham; Öncül, Oral; Morosini, María Isabel; Cantón, Rafael; Aktaş, Zerrin
Treatment of infections caused by OXA-48 carbapenemase producing multidrug-resistant isolates often necessitates combination therapy. In vitro effect of different antibiotic combinations against multidrug-resistant (MDR) Klebsiella pneumoniae isolates were evaluated in this study. Meropenem-tobramycin (MER+TOB), meropenem-ciprofloxacin (MER+CIP), colistin-meropenem (COL+MER), colistin-ciprofloxacin (COL+CIP) and colistin-tobramycin (COL+TOB) combinations were tested by time kill-assays. Each antibiotic alone and in combination at their Cmax values were tested against 4 clinical K. pneumoniae isolates at 1, 2, 4, 6, 8, 12 and 24 h. Effect of colistin and its associations were also assessed at 30 min. Bactericidal activity was defined as ?3log10 CFU mL-1 decrease compared with initial inoculum. Synergy was defined as ?2log10CFU mL-1 decrease by the combination compared with the most active single agent. Presence of bla OXA-48, bla NDM, bla VIM, bla IMP, bla KPC and bla CTX-M-1 genes was screened by PCR using specific primers. The bla OXA-48 gene was identified together with bla CTXM-1 group gene in all isolates. COL+MER demonstrated to be synergistic and bactericidal. MER+TOB showed synergistic and bactericidal effect on two strains although, regrowth was seen on other two strains at 24 h. MER+CIP exhibited indifferent effect on the strains. Combination therapy could be a potential alternative to treat MDR K. pneumoniae infections. This combination might prevent resistance development and secondary effects of colistin monotherapy. MER+TOB and MER+CIP might have an isolate-dependent effect, that may not always result in synergism
Geometric morphometric study of anterior branches of external carotid artery and carotid bifurcation by 3D-CT angiography
(Springer, 2022) Demirtaş, İsmet; Ayyıldız, Behçet; Demirbaş, Ahmet Taha; Ayyıldız, Sevilay; Sönmez Topçu, Feyza; Kuş, Koral Çağlar; Kurt, Mustafa Ayberk
Purpose The aim of our study was to determine the variations of the anterior branches of the external carotid artery (ECA) and investigate the morphometric and geometric features of the anterior branches of the ECA and carotid bifurcation (CB). Methods A total of 563 ECAs were included from 288 patients in the study. Classifcation and exit angles of anterior branches of ECA and determination of vertebral levels of CB and anterior branches were performed. Results The anterior branch variants of the ECA were observed in 8 diferent subgroups. The most common variations were type Ia 42.3% (n=120) on the right and type Ib 40.9% (n=114) on the left. When looking at the vertebral levels, CB was detected at C4 level in 32.9% of total ECAs (n=185), STA was at C4 level in 33.4% of total ECAs (n=188), LA was at C3 level in 50.1% of total ECAs (n=282), and FA was at C2 level in 37.3% of total ECAs. The mean CB angle in all cases was 59.93°±16.04. In the anterior branches of the ECA in cases belonging to the Type I group, the widest angle belonged to FA (R=116.88±27.04°, L=110.32°±25.94). Conclusion In conclusion, a new classifcation of the variations of the anterior branches of the ECA was made on the basis of the CTA images to gain more practicality in surgical procedures. This study revealed for the frst time the angular and level relationship between CB and ECA anterior branches.
Manual versus automated volume reduction of cord blood
(TR- Dizin, 2022) Yurdakul Mesutoğlu, Pınar; Gençer Öncül, Emine Begüm; Akın, Hasan Yalım; Beksaç, Meral
Objectives: All cord blood banks all over the world follow a common procedure, concentrating progenitor cells by volume reduction, with the main purpose of optimizing the use of storage space. The main objective of this study was to compare CD34 and total nucleated cell recovery rates and red blood cell depletion efficiencies following cord blood processing using automated Sepax or manual CellEffic cord blood processing systems. Methods: Nine cord blood units with high volumes were divided into 2 equal fractions and processed with CellEffic cord blood and Sepax. Total nucleated cell, mononuclear cells, CD34+, red blood cell and total nucleated cell viability, and clonogenic assays were performed, and recovery rates were calculated on pre- and post-process cord blood units and after freeze/thaw process. In the comparison group, post-thaw differential cell counting was also performed. Results: Our results showed that post-process total nucleated cell viability with CellEffic cord blood was slightly higher than Sepax, whereas Sepax post-process total nucleated cell/ mononuclear cell values were superior to CellEffic cord blood. Postthaw red blood cell depletion was better for CellEffic cord blood. Post-thaw Sepax colony-forming unit counts were higher than CellEffic cord blood. In addition, CD45+CD71+ cells were lower, whereas CD45+CD34+CD38? cells were higher for the CellEffic cord blood system. Conclusion: Despite the fact that there is a need for well-trained personnel for processing cord blood units with CellEffic cord blood, it may be an attractive alternative to Sepax system for cord blood processing, particularly for cord blood units with low volumes, at banks with low budget where the cord blood turnover rates are relatively low.
Aberrant activation-induced cytidine deaminase gene expression links BCR/ABL1-negative classical myeloproliferative neoplasms
(TR- Dizin, 2022) Dermenci, Hasan; Dağlar Aday, Aynur; Akadam Teker, Ayşegül Başak; Hançer, Veysel; Gelmez, Metin Yusuf; Nalçacı, Meliha; Yavuz, Akif Selim
Aim: Activation-induced cytidine deaminase (AID) has been associated with tumor initiation and development because of its ability to generate DNA damage and somatic mutations that cause genomic instability. This study aimed to investigate the relationship between AID expression levels and the risk of developing BCR/ABL1-negative myeloproliferative neoplasms (MPNs) by comparing the AID expression levels of the patients and controls. Methods: This case-control study was conducted on 117 cases (64 essential thrombocythemia, 23 primary myelofibrosis, and 30 polycythemia vera) with MPNs and 69 healthy controls. The JAK2 V617F somatic mutation analysis was performed using a real-time polymerase chain reaction (RT-PCR). The relative expression levels of AID in the patient and the control groups were analyzed using quantitative RT-PCR and the 2-??CT method. Results: AID expression levels were significantly higher in the patient group compared to the control group (p<0.001). AID expression levels were higher in patients with the JAK2 V617F mutation compared to patients without the mutation, but the difference was not statistically significant. Conclusion: The results of our study suggest that although overexpression of AID does not seem to support the JAK2 driver gene, it may contribute to the development of MPNs through other mechanisms.
The effect of omentectomy on the blood levels of adipokines in obese patients with endometrial cancer
(Elsevier Science, 2022) Comba, Cihan; Özdemir, İsa Aykut; Demirayak, Gökhan; Erdoğan, Şakir Volkan; Demir, Ömer; Özlem Yıldız, Güneş; Bulut, Huri; Karakaş, Sema; Gülseren, Varol; Afşar, Selim; Güngördük, Kemal
Objective To investigate the blood levels of adipokines in obese patients with endometrial cancer who have and have not undergone omentectomy. Methods Between September 2017 and September 2019, the study recruited 54 patients with endometrial cancer. Measurements were taken of blood levels of human leptin, perilipin-1, adiponectin, adipolin, resistin, visfatin, and estrone preoperatively and postoperatively before adjuvant therapy or at the end of one month. The serum samples were separated by centrifugation for 10 mins at 3,000 revolutions/min, then stored at ?80 °C until assay. Results In this prospective study, a total of 54 endometrial cancer patients were analyzed in two separate groups according to the omentectomy status. Comprehensive staging surgery with omentectomy and without omentectomy was performed in 26 patients and 28 patients, respectively. The age, body mass index, body fat index, waist circumference, and skin thickness values of the patients with and without omentectomy were found to be similar. No statistically significant difference was determined between the patients with and without omentectomy in respect of the blood level of the adipokines measured preoperatively. A strong statistically significant correlation was determined between the pre and postoperative levels of Human Leptin (p = 0.002), perilipin-1(p = 0.001), adipolin (p < 0.001), adiponectin (p < 0.001), resistin (p = 0.001), visfatin (p < 0.001), and estrone (p = 0.004) (r = ?0.43, ?0.47, 0.75, 0.84, ?0.47, - 0.58, ?0.41, respectively) Conclusions Omentectomy affected the postoperative blood levels of adipokines in obese patients with endometrial cancer. As omentectomy may have some positive effects on metabolism in these patients, it may be considered during endometrial cancer surgery due to the possible positive metabolic effects.
The improved killing of both androgen-dependent and independent prostate cancer cells by etoposide loaded SPIONs coupled with NIR irradiation
(Royal Society of Chemistry, 2022) Onbaşlı, Kübra; Demirci, Gözde; Muti, Abdullah; Sennaroğlu, Alphan; Yağcı Acar, Havva; Erkısa Genel, Merve; Ulukaya, Engin
Etoposide (Eto) is a toxic drug that shows promise in treating prostate cancer (PCa) but confers significant side effects, and has poor solubility and bioavailability. Nanoparticles are quite successful in overcoming such problems. Multifunctional nanoparticles that provide an opportunity to perform combination therapy have attracted great interest in recent years. Superparamagnetic iron oxide nanoparticles (SPIONs) are popular in various biomedical applications, including magnetic resonance imaging, drug delivery, magnetic hyperthermia and recently in photothermal therapy, combining imaging with therapy. Here, for the enhanced killing of PCa cells that are either androgen-dependent or not, the combination of SPION based Eto delivery and mild hyperthermia triggered by laser irradiation is proposed for the first time in the literature. For the encapsulation of Eto, highly stable, small, polyacrylic acid coated SPIONs were conjugated with bovine serum albumin (BSA) (Eto-BSA@PAA@SPION). Eto-BSA@PAA@SPION with 9% drug content produced better chemotherapeutic outcomes than free Eto on both androgen-dependent/castration sensitive LNCaP and androgen-independent/castration-resistant PC3 and DU145 PCa cells by enhancing drug internalization. Single and short irradiation of Eto-BSA@PAA@SPION treated cells at 808 nm improved the drug release and sensitized cells for Eto, hence, increasing the toxicity dramatically in all studied PCa cell lines. Caspase-mediated apoptosis, DNA damage, and ROS generation were detected in the treated cells, increasing with the Eto dose and laser treatment. The IC50 for Eto is reduced to 0.08 ?g mL-1, 0.13 ?g mL-1 and 2.8 ?g mL-1 with laser/Eto-BSA@PAA@SPION for LNCaP, DU145 and PC3 cells, respectively. These are the lowest IC50 values seen in the literature for Eto on these cell lines so far, suggesting that the demonstrated nanoparticles and treatment approaches have great potential to treat various PCa cells at low doses of the drug under mild laser treatment conditions.
Serum neutrophil gelatinase-associated lipocalin concentrations are significantly associated with the severity of COVID-19 in pregnant patients
(Saudimedj, 2022) Can, Esra; Ölmez, Fatma; Bulut, Huri; Oğlak, Süleyman Cemil
Objectives: To evaluate serum neutrophil gelatinaseassociated lipocalin (NGAL) concentrations of pregnant women complicated with coronavirus disease 2019 (COVID-19) and investigate its diagnostic value for the severity of COVID-19. Methods: Of the 46 pregnant women with COVID-19 included in the study, we further classified these women into 2 subgroups: the non-severe COVID-19 group (n=25) and the severe COVID-19 group (n=21). Results: Neutrophil gelatinase-associated lipocalin plasma concentrations were significantly higher in pregnant women complicated with severe COVID-19 (90 [53.1-207.7] ng/ml) compared to those from Original Article pregnant women with non-severe COVID-19 (51.8 [39.6-70.3] ng/ml) and healthy pregnant women (44.3 [32.2-54.1] ng/ml, p<0.001). Also, at a cutoff value of 72 ng/ml, NGAL predicted severe COVID-19 with a sensitivity rate of 57% and a specificity rate of 84%. Serum NGAL level (adjusted hazard ratio [aHR]=1.020, 95% confidence interval [CI]= [1.006-1.035], p=0.007), and D-dimer level (aHR=2.371, 95% CI= [1.085-5.181], p=0.030) were the variables that were revealed to be significantly associated with the disease severity. Conclusion: We demonstrated that NGAL was highly associated with COVID-19 severity. We consider that NGAL might be a useful biomarker to diagnose the disease severity in patients with COVID-19.

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