Browsing by Author "Cansu, A"

Now showing 1 - 18 of 18
  • No Thumbnail Available
    Item
    Effect of valproic acid treatment on penile structure in prepubertal rats
    Kutlu, Ö; Cansu, A; Karagüzel, E; Gürgen, SG; Koç, Ö; Gür, M; Özgür, GK
    Introduction: The aim of this study was to determine the histological effects of valproic acid (VPA) on the penis in prepubertal rats. Methods: Twelve male Wistar rats (21-24 days old) were divided equally into 2 experimental groups, and given tap water (control group) or 300 mg/kg/day VPA via gavage for 30 days. After the penes had been harvested, the antiangiogenic and antifibrogenic properties of VPA were evaluated immunohistochemically using vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), transforming growth factor-beta 1 (TGF-beta 1) and Masson's trichrome staining. Apoptosis was determined by caspase-3 and caspase-9 immunoreactions. Results were expressed as histochemical score (HSCORE), a semi-quantitative analysis for the intensity of immunohistochemical reactivity. Results: Immunohistochemical HSCORE decreased for VEGF and TGF-beta 1 staining and increased for iNOS staining in rats treated with VPA compared with the control group. Intensities of caspase-3 and caspase-9 labeling were also significantly increased by administration of VPA. Masson's trichrome staining exhibited a fairly diminished level of collagen in the corpus cavernosum of rats treated with VPA. Conclusion: In the light of these results, the administration of VPA from prepuberty to adulthood led to increased apoptosis and deterioration of the smooth muscle/collagen ratio in rat's corpus cavernosum. (C) 2011 Elsevier B.V. All rights reserved.
  • No Thumbnail Available
    Item
    An investigation of the effects of chronic zonisamide, sultiam, lacosamide, clobazam, and rufinamide anti-seizure medications on foliculogenesis in ovarian tissue in prepubertal non-epileptic rats
    Kart, PO; Gürgen, SG; Esenülkü, G; Dilber, B; Yildiz, N; Yazar, U; Sarsmaz, HY; Topsakal, AS; Kamasak, T; Arslan, EA; Sahin, S; Cansu, A
    We aimed to determine the morphological and histological effects of zonisamide, sultiam, lacosamide, clobazam, and rufinamide on ovarian folliculogenesis in rats. Sixty female Wistar rats were divided into six experimental groups as control, zonisamide, sultiam, lacosamide, clobazam, and rufinamide groups; control solution and drugs were administered by gavage for 90 days. The number of healthy follicles in the control group was significantly higher than in the anti-medication groups (p < 0.001), and the number of corpus luteum was significantly lower (p < 0.001). There was a significant difference in the number of TUNEL positive apoptotic follicles between the control and drug groups (p < 0.001). With EGF, IGF-1, and GDF-9 staining, a very strong immunoreaction was observed in the ovarian multilaminar primary follicle granulosa cells and oocytes in the control group compared to the drug group (p < 0.001). Long-term anti-seizure medication with zonisamide, sultiam, lacosamide, clobazam, and rufinamide from prepubertal to adulthood causes apoptosis and disruption of folliculogenesis in the ovarian follicles of nonepileptic rats.
  • No Thumbnail Available
    Item
    EFFECTS OF VALPROATE AND TOPIRAMATE ON PANCREATITIS IN RATS
    Cansu, A; Turkyilmaz, S; Çelik, K; Gurgen, SG; Vanizörkural, B; Erçin, C; Alhan, E
  • No Thumbnail Available
    Item
    The relationship between oxidative stress and apoptosis of histopathological changes in the ovary made by mad honey containing grayanotoxin
    Sarsmaz, HY; Gürgen, SG; Cansu, A; Türkmen, S; Gündüz, A
    The purpose of this study is to determine the effects of grayanotoxin in mad honey on ovarian tissue folliculogenesis in terms of cell death and nitric oxide expression. Three groups of 18 female Sprague-Dawley rats were formed. The first group received mad honey (80 mg/kg), the second group received normal honey (80 mg/kg), and the third group was the control. The first and second groups received normal and mad honey by oral gavage for 30 days before being sacrificed under anesthesia. Caspase 3 immunostaining showed a moderate to strong response, particularly in the mad honey group. In the mad honey group, immunostaining for caspase 8 and caspase 9 revealed a moderate immunoreaction in the granulosa cells of the Graaf follicles. The majority of Graaf follicles exhibited TUNEL positive in the mad honey group. The iNOS immunoreaction revealed a high level of expression in the mad honey group. In all three groups, eNOS immunostaining showed weak reactivity. According to the findings of apoptotic and nitric oxide marker expression, it was determined that mad honey may result in an increase in follicular atresia in ovarian follicles when compared to normal honey and control groups.
  • No Thumbnail Available
    Item
    Effects of chronic amiodarone treatment on rat testis
    Özkaya, AK; Dilber, E; Gürgen, SG; Kutlu, Ö; Cansu, A; Gedik, Y
    Amiodarone is a potent agent used to treat tachyarrhythmias, which are especially refractory to other medications, in both adults and children. Although widely used as an antiarrhythmic drug, amiodarone causes many serious adverse effects that limit its use. This study investigated the possible morphological and apoptotic effects of amiodarone on rat testes. Amiodarone was administered to male Sprague-Dawley rats at doses of 20 or 200 mg/kg/day for 14 days. A histopathological examination of testicular tissue revealed the presence of inflammatory cells in the seminiferous tubule lumen together with swelling and vacuolization in the cytoplasm of some spermatogonia; these effects occured in a dose-dependent manner. Immunohistochemical staining showed evidence of apoptosis, including caspase-3, caspase-9, Bax and increased DNA fragmentation was detected via a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. In conclusion, the results show that chronic amiodarone treatment causes dose dependent degenerative and apoptotic effects on rat testes. (C) 2016 Elsevier GmbH. All rights reserved.
  • No Thumbnail Available
    Item
    Vitamin D protects against hippocampal apoptosis related with seizures induced by kainic acid and pentylenetetrazol in rats
    Sahin, S; Gürgen, SG; Yazar, U; Ince, I; Kamasak, T; Arslan, EA; Durgut, BD; Dilber, B; Cansu, A
    Objectives: The hippocampus is susceptible to damage in patients with epilepsy and in animals with seizures caused by excitotoxic agents. The effect of vitamin D on hippocampal apoptosis related with seizures has not been reported. However, epileptic patients have an increased risk of hypovitaminosis D which is most likely due to the effects of antiepileptic drugs. Therefore, in this study, it was aimed to evaluate the effects of vitamin D on hippocampal apoptosis related with seizures by using pentylenetetrazol (PTZ) and kainic acid (KA) in rats. Methods: Male Sprague Dawley rats, aged 5.5 weeks, were randomly divided into six groups: control, vitamin D, PTZ, KA, PTZ + vitamin D and KA + vitamin D groups. The groups that received vitamin D were given 500 IU/kg of vitamin D daily for two weeks in addition to a standard diet. At the end of this period, PTZ and KA were applied to trigger seizures in the rats in the seizure groups. 24 h after the administration of PTZ and KA, the rats were decapitated. In the hippocampal region, apoptosis was assessed by TUNEL and brain-derived neurotrophic factor (BDNF), Bax, caspase-3 and c-fos activation were evaluated by immunohistochemical method. Results: BDNF level increased while c-fos, Bax and caspase-3 levels decreased (p < 0.0001, in all) in the hippocampal neurons of the groups that were pre-treated with vitamin D before the administration of PTZ and KA, in comparison with the PTZ and KA groups. Vitamin D significantly decreased the number of apoptotic cells in these rats in comparison with the PTZ and KA groups (p < 0.0001). Conclusion: This study indicates that vitamin D has neuroprotective effects on hippocampal apoptosis induced by PTZ and KA in rats. With this study it is suggested that keeping vitamin D levels within normal limits may be beneficial for patients with epilepsy, especially children.
  • No Thumbnail Available
    Item
    Oleuropein Has Modulatory Effects on Systemic Lipopolysaccharide-Induced Neuroinflammation in Male Rats
    Sahin, S; Sahin, E; Esenülkü, G; Renda, G; Gürgen, SG; Alver, A; Abidin, I; Cansu, A
    Background: Neuroin fl ammation induced by systemic in fl ammation is a risk factor for developing chronic neurologic disorders. Oleuropein (OLE) has antioxidant and anti-in fl ammatory properties; however, its effect on systemic in fl ammation-related neuroin fl ammation is unknown. Objectives: This study aimed to determine whether OLE protects against systemic lipopolysaccharide (LPS)-induced neuroin fl ammation in rats. Methods: Six-wk-old Wistar rats were randomly assigned to 1 of the following 5 groups: 1 ) control, 2 ) OLE-only, 3 ) LPS & thorn; vehicle, 4 ) OLE & thorn; LPS (O-LPS), and 5 ) a single-dose OLE & thorn; LPS (SO-LPS group). OLE 200 mg/kg or saline as a vehicle was administered via gavage for 7 d. On the seventh day, 2.5 mg/kg LPS was intraperitoneally administered. The rats were decapitated after 24 h of LPS treatment, and serum collection and tissue dissection were performed. The study assessed astrocyte and microglial activation using glial fi brillary acidic protein (GFAP) and CD11b immunohistochemistry, nod -like receptor protein -3, interleukin (IL)-1 beta , IL -17A, and IL -4 concentrations in prefrontal and hippocampal tissues via enzyme-linked immunosorbent assay, and total antioxidant/oxidant status (TAS/TOS) in serum and tissues via spectrophotometry. Results: In both the O-LPS and SO-LPS groups, LPS-related activation of microglia and astrocytes was suppressed in the cortex and hippocampus ( P < 0.001), excluding cortical astrocyte activation, which was suppressed only in the SO-LPS group ( P < 0.001). Hippocampal GFAP immunoreactivity and IL -17A concentrations in the dentate gyrus were higher in the OLE group than those in the control group, but LPS-related increases in these concentrations were suppressed in the O-LPS group. The O-LPS group had higher cortical TAS and IL -4 concentrations. Conclusions: OLE suppressed LPS-related astrocyte and microglial activation in the hippocampus and cortex. The OLE-induced increase in cortical IL -4 concentrations indicates the induction of an anti-in fl ammatory phenotype of microglia. OLE may also modulate astrocyte and IL -17A functions, which could explain its opposing effects on hippocampal GFAP immunoreactivity and IL -17A concentrations when administered with or without LPS.
  • No Thumbnail Available
    Item
    Methylphenidate has dose-dependent negative effects on rat spermatogenesis: decreased round spermatids and testicular weight and increased p53 expression and apoptosis
    Cansu, A; Ekinci, Ö; Ekinci, Ö; Serdaroglu, A; Erdogan, D; Coskun, ZK; Gürgen, SG
    In the present study, we aimed to evaluate the possible effects of methylphenidate on rat testes. Forty-two Wistar rats were randomly distributed into three experimental groups of 14 rats each. For 90 days, each group via gavage received the following: group I = tap water (control group), group 2 = 5 mg/kg/day of ritalin (methylphenidate, MPH), and group 3 = 10 mg/kg/day of ritalin. After sacrificing the animals, the body weights as well as the absolute and relative testicular weights were measured. Testes were sampled, fixed, and processed and, by histopathological examination, quantitative morphometric analysis of Sertoli cells, spermatocytes, and spermatids was performed in stages II, V, and XII. Immunohistochemistry was performed for transforming growth factor (TGF)-beta 1 and p53, and the apoptotic index was assessed through the TUNEL method. Group 2 had a reduction of round spermatids in stage II. Group 3 had reduction in both stage 11 and stage V spermatids, as well as lower testicular weight. The p53 expression was increased in group 3. In groups 2 and 3, the TGF-beta 1 expression was reduced and the apoptotic index by TUNEL was increased. Body weights remained stable on either group. Our results showed that methylphenidate might negatively affect spermatogenesis not only by reducing testicular weight and amount of round spermatids but also by increasing apoptotic death and p53 activation. The findings of the study, however, must be cautiously interpreted.
  • No Thumbnail Available
    Item
    The effect of mad honey on testosterone levels of male rats
    Tatli, O; Karaca, Y; Turkmen, S; Gulgen, GS; Sahin, A; Eryigit, U; Fazli, O; Karaguzel, E; Mentese, A; Orem, A; Cansu, A; Turedi, S; Gunduz, A
    OBJECTIVE: We aimed to investigate the effect of mad honey on sexual performance. BACKGROUND: In traditional medicine in Turkey, mad honey is used to improve appetite, to heighten mental alertness, to reduce joint pain, to eliminate gastrointestinal system pains and to increase sexual performance. METHODS: In this experimental animal study eighteen Sprague Dawley male rats were randomized into three groups, a control group, a normal honey group and a mad honey group. Rats in the treatment groups were given a daily dose of 80 mg/kg normal honey or mad honey throughout the 30-day study period. Total testosterone, free testosterone, FSH, LH, estradiol, and progesterone levels were subsequently investigated from blood sera on day 30. RESULTS: Comparison of blood total testosterone levels among the groups revealed significantly higher levels in the mad honey group compared to the normal honey and control groups (p = 0.006, p = 0.00). Free testosterone levels were also significantly higher in the mad honey group than in the normal honey and control groups (p = 0.023, p = 0.01). No statistically significant differences were determined for other hormonal measurements. CONCLUSIONS: This study revealed a significant increase in both total and free testosterone levels in mad-honey group (Tab. 1, Fig. 2, Ref. 16). Text in PDF www.elis.sk.
  • No Thumbnail Available
    Item
    THE EFFECTS OF VALPROIC ACID AND OXCARBAZEPINE ON RAT UTERINE IMPLANTATION
    Cansu, A; Gurgen, SG; Erdogan, D; Coskun, ZK
  • No Thumbnail Available
    Item
    The effect of valproic acid and oxcarbazepine on the distribution of adhesion molecules in embryo implantation
    Gürgen, SG; Erdogan, D; Coskun, ZK; Cansu, A
    This study was intended to investigate the effect of valproate (VPA) and oxcarbazepine (OXC) on embryo implantation in terms of extracellular matrix protein distribution. Thirty female rats (Wistar albino) were assigned to three groups of 10 animals each. Group 1 was administered two doses of saline solution, group 2, two doses of VPA at 300 mg/kg/day and group 3, two doses of OXC at 100 mg/kg/day, for a period of 3 months. Female rats with vaginal plugs mated with males for one night were placed into separate cages. Day of mating was taken as day 0, and implantation areas were obtained with rats being sacrificed on the morning of day 7. Immunohistochemical staining and electron microscopic protocols were then applied. At electron microscopic evaluation, extraembryonic endoderm and ectoderm layers could not be distinguished in semi-thin sections in the VPA group, while they were partially differentiated in the OXC group. At immunohistochemical staining, laminin was observed in the primary embryonic endoderm cell visceral and parietal layers, the uterine luminal epithelial cells and the secondary decidual zone in the control group. In the VPA group, it was weakly expressed in some embryo trophoectoderm cells and uterine luminal epithelial cells and moderately in some decidual cells. In the OXC group, it was moderately expressed in some trophoectoderm and decidual cells. Collagen IV was localized in the ectoplacental cone cells and secondary decidual zone and weak in the luminal epithelial cells in the control group. In the VPA and OXC groups, collagen IV was negative in all embryonic and maternal structures in the VPA and OXC groups. Vimentin was moderately expressed in the luminal epithelium and strongly expressed in the primary decidual zone and ectoplacental cone cells in the control group. In the VPA group, it was negative in the embryo trophoectoderm, decidual and uterine luminal epithelial cells, while in the OXC group it was moderately localized in the ectoplacental cone cells. The use of VPA and OXC has a negative effect on the expression of extracellular matrix proteins that play a key role in embryo implantation in young rats. This may lead to pregnancies ending in failure. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
  • No Thumbnail Available
    Item
    Histologic and morphologic effects of valproic acid and oxcarbazepine on rat uterine and ovarian cells
    Cansu, A; Erdogan, D; Serdaroglu, A; Take, G; Coskun, ZK; Gurgen, SG
    P>Purpose: To determine the histologic and morphologic effects of valproic acid (VPA) and oxcarbazepine (OXC) on rat uterine and ovarian cells. Methods: Fifty-six female prepubertal Wistar rats (21-24 days old and weighing between 47.5 and 58.1 g) were divided equally into four groups, which were given drinking water (controls), 300 mg/kg/day of VPA, 100 mg/kg/day of OXC or VPA + OXC via gavage, for 90 days. Ovaries and uteri of rats on proestrous and diestrous phases of estrous cycle were extirpated and placed in a fixation solution. The tissue specimens were assessed with apoptosis (TUNEL) staining protocols, eosinophil counting, and electron microscopic techniques. Results: In uteri, apoptosis in stroma, mitochondrial swelling, and cristolysis were observed in the VPA group, and OXC led to negative effects on epithelial cell and intracellular edema. In ovaries, both drugs increased apoptosis and intracytoplasmic edema. Organelle structure disruption was also observed in the OXC group. More conspicuous degenerative modifications were determined in the VPA + OXC group. In uteri, the number of TUNEL-positive luminal epithelial cells was 7.20 +/- 1.32 in controls, and significantly increased to 29.60 +/- 1.58, 34.20 +/- 2.53, and 54.80 +/- 2.04 in VPA, OXC, and VPA + OXC groups, respectively (p < 0.001). The highest number of TUNEL-positive glandular epithelium cells was observed in the VPA + OXC group; however, the number of TUNEL-positive stroma cells was highest in the VPA group. The highest number of eosinophils in stroma was in the VPA group. Conclusion: VPA and OXC trigger apoptotic and degenerative effects on rat uterine and ovarian cells. VPA also prevents implantation of embryo to the uterus and causes abortion via endometrial eosinophil infiltration.
  • No Thumbnail Available
    Item
    Phenotypic variability and novel variants in TBC1D24-associated epilepsy: Insights from a multicentre study
    Karakayali, B; Türkdogan, D; Ayaz, A; Geckinli, BB; Ayça, S; Özcan, S; Uzunhan, TA; Ayvaz, A; Uyanik, B; Cansu, A; Özkan, P; Basarir, G; Dündar, NO; Gençpinar, P; Kara, B; Polat, H; Akbeyaz, H
  • No Thumbnail Available
    Item
    Effects of valproic acid, levetiracetam, carbamazepine, lamotrigine, and topiramate on LIF, E-cadherin, and FOXO1 mediator molecules in rat embryo implantation
    Kart, PÖ; Yildiz, N; Gürgen, SG; Sarsmaz, HY; Cansu, A
    Background: This study investigated the effects of valproic acid (VPA), levetiracetam (LEV), carbamazepine (CBZ), lamotrigine (LTG), and topiramate (TPM) on LIF, E-cadherin, and FOXO1 mediator molecules during implantation in rat embryos. Materials and methods: Sixty female rats were divided into six experimental groups, and the control solution and drugs were administered by gavage for 90 days. At the end of three months, implantation sites were obtained, and histological and immunohistochemical staining protocols were applied. Results: Embryonic trophectoderm cells were surrounded by inflammatory cells in the VPA group. Increased eosinophilic staining was seen in the primary decidual zone cells in the CBZ group, mast cells in the LTG group, and intense inflammatory cells in the TMP group. LIF staining in the VPA, CBZ, LTG, and TPM groups showed weak to moderate LIF expression (p < 0.001). In E-cadherin staining, the LTG group showed moderate and the TPM group showed weak immune reactions (p < 0.001). Embryonic cells and primary decidual zone cells in control, LEV, CBZ, and LTG groups showed weak to strong expression of FOXO1, while VPA and TPM groups showed no reaction (p < 0.001). Conclusions: In summary, antiseizure medication use had a negative effect on the expression of proteins that play key roles in embryo implantation in young non-epileptic rats to varying degrees.
  • No Thumbnail Available
    Item
    Evaluation of abdominal computed tomography findings in patients with COVID-19: a multicenter study
    Onur, MR; Özbay, Y; Idilman, I; Karaosmanoglu, AD; Ramadan, SU; Barlik, F; Aydin, S; Odaman, H; Altay, C; Akin, IB; Dicle, O; Appak, O; Gülpinar, B; Erden, A; Kula, S; Çoruh, AG; Öz, DK; Kul, M; Uzun, C; Karavas, E; Levent, A; Artas, H; Eryesil, H; Solmaz, O; Kaygusuz, TO; Farasat, M; Kale, AB; Düzgün, F; Pekindil, G; Apaydin, FD; Duce, MN; Balci, Y; Esen, K; Kahraman, AS; Karaca, L; Özdemir, ZM; Kahraman, B; Tosun, M; Nural, MS; Camlidag, I; Onar, MA; Balli, K; Güler, E; Harman, M; Elmas, NZ; Öztürk, C; Güngör, O; Herek, D; Yagci, AB; Erol, C; Seker, M; Islek, I; Can, Y; Aslan, S; Bilgili, MYK; Göncüoglu, A; Keles, H; Sarikaya, PZB; Bakir, B; Kartal, MGD; Durak, G; Oguzdogan, GY; Alper, F; Yalçin, A; Gürel, S; Alan, B; Gündogdu, E; Aydin, N; Cansu, A; Kus, CC; Tuncer, EO; Piskin, FC; Er, HC; Degirmenci, B; Özmen, MN; Kantarci, M; Karçaaltincaba, M
    PURPOSETo evaluate the frequency of abdominal computed tomography (CT) findings in patients with coronavirus disease-2019 (COVID-19) and interrogate the relationship between abdominal CT findings and patient demographic features, clinical findings, and laboratory test results as well as the CT atheroscle-rosis score in the abdominal aorta.METHODSThis study was designed as a multicenter retrospective study. The abdominal CT findings of 1.181 patients with positive abdominal symptoms from 26 tertiary medical centers with a positive polymerase chain-reaction test for severe acute respiratory syndrome coronavirus 2 were reviewed. The frequency of ischemic and non-ischemic CT findings as well as the association between CT findings, clinical features, and abdominal aortic calcific atherosclerosis score (AA-CAS) were recorded.RESULTSIschemic and non-ischemic abdominal CT findings were detected in 240 (20.3%) and 328 (27.7%) patients, respectively. In 147 patients (12.4%), intra-ab-dominal malignancy was present. The most frequent ischemic abdominal CT findings were bowel wall thickening (n = 120; 10.2%) and perivascular infil-tration (n = 40; 3.4%). As for non-ischemic findings, colitis (n = 91; 7.7%) and small bowel inflammation (n = 73; 6.2%) constituted the most frequent disease processes. The duration of hospital stay was found to be higher in patients with abdominal CT findings than in patients without any positive findings (13.8 & PLUSMN; 13 vs. 10.4 & PLUSMN; 12.8 days, P < 0.001). The frequency of abdominal CT findings was significantly higher in patients who did not survive the infection than in patients who were discharged after recovery (41.7% vs. 27.4%, P < 0.001). Increased AA-CAS was found to be associated with a higher risk of ischemic conditions in abdominal CT examinations.CONCLUSIONAbdominal symptoms in patients with COVID-19 are usually associated with positive CT findings. The presence of ischemic findings on CT correlates with poor COVID-19 outcomes. A high AA-CAS is associated with abdominal ischemic findings in patients with COVID-19.
  • No Thumbnail Available
    Item
    Shared Biological Pathways and Processes in Patients with Intellectual Disability: A Multicenter Study
    Günay, C; Aykol, D; Özsoy, O; Sönmezler, E; Hanci, YS; Kara, B; Sünnetçi, DA; Cine, N; Deniz, A; Özer, T; Ölçülü, CB; Yilmaz, O; Kanmaz, S; Yilmaz, S; Tekgül, H; Yildiz, N; Arslan, EA; Cansu, A; Dündar, NO; Kusgoz, F; Didinmez, E; Gençpinar, P; Uzunhan, TA; Ertürk, B; Gezdirici, A; Ayaz, A; Ölmez, A; Ayanoglu, M; Tosun, A; Topçu, Y; Kiliç, B; Aydin, K; Çaglar, E; Kosvali, OE; Okuyaz, C; Besen, S; Orgun, LT; Erol, I; Yüksel, D; Sezer, A; Atasoy, E; Toprak, U; Güngör, S; Ozgor, B; Karadag, M; Dilber, C; Sahinoglu, B; Yalçin, EU; Hacifazlioglu, NE; Yaramis, A; Edem, P; Tekin, HG; Yilmaz, U; Ünalp, A; Turay, S; Biçer, D; Mert, GG; Çetin, ID; Kirik, S; Öztürk, G; Karal, Y; Sanri, A; Aksoy, A; Polat, M; Özgün, N; Soydemir, D; Uzan, GS; Üstebay, D; Gök, A; Yesilmen, MC; Yis, U; Karakülah, G; Bursali, A; Oktay, Y; Kurul, SH
    Background Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses. Method In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Results Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was ID. The most frequently overrepresented GO biological process, cellular component, and molecular function terms were regulation of membrane potential, ion channel complex, and voltage- gated ion channel activity/voltage-gated channel activity, respectively. Conclusion Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients.
  • No Thumbnail Available
    Item
    Optic neuritis in Turkish children and adolescents: A multicenter retrospective study
    Direk, MÇ; Besen, S; Öncel, I; Günbey, C; Özdogan, O; Orgun, LT; Sahin, S; Cansu, A; Yildiz, N; Kanmaz, S; Yilmaz, S; Tekgül, H; Türkdogan, D; Ünver, O; Thomas, GO; Basibüyük, S; Yilmaz, D; Kurt, AN; Gültutan, P; Özsoy, Ö; Yis, U; Kurul, SH; Güngör, S; Özgör, B; Karadag, M; Dündar, NO; Gençpinar, P; Bildik, O; Orak, SA; Kabur, ÇÇ; Kara, B; Karaca, Ö; Canpolat, M; Gümüs, H; Per, H; Yilmaz, Ü; Karaoglu, P; Ersoy, Ö; Tosun, A; Öztürk, SB; Yüksel, D; Atasoy, E; Gücüyener, K; Yildirim, M; Bektas, Ö; Çavusoglu, D; Yarar, Ç; Güngör, O; Mert, GG; Sarigeçili, E; Edizer, S; Çetin, ID; Aydin, S; Diler, B; Özdemir, AA; Erol, I; Okuyaz, Ç; Anlar, B
    Background: Various etiologies may underlie optic neuritis, including autoantibody-mediated disorders described in the last decade. We re-examined demographic, clinical, laboratory features and prognostic factors in pediatric patients with autoimmune optic neuritis according to current knowledge.Methods: Cases of pediatric ON from 27 centers in Turkiye diagnosed between 2009 and 2022 were included for retrospective evaluation.Results: The study included 279 patients, 174 females and 105 males, with a female-to-male ratio of 1.65. The average age at onset was 12.8 +/- 3.4 years, and mean follow-up, 2.1 years (range: 1-12.1 years). Patients <10 years old were grouped as prepubertal and those >= 10 years old as others. The diagnoses made at the end of follow-up were multiple sclerosis associated optic neuritis (n = 90, 32.3 %), single isolated optic neuritis (n = 86, 31 %), clinically isolated syndrome (n = 41, 14.7 %), myelin oligodendrocyte glycoprotein antibody associated optic neuritis (n = 22, 7.9 %), and relapsing isolated optic neuritis (n = 18, 6.5 %). Predominant diagnoses were myelin oligodendrocyte glycoprotein antibody associated optic neuritis and acute disseminated encephalomyelitis associated optic neuritis in the prepubertal group and multiple sclerosis associated optic neuritis in the older group. Recurrences were observed in 67 (24 %) patients, including 28 with multiple sclerosis associated optic neuritis, 18 with relapsing isolated optic neuritis, 11 with myelin oligodendrocyte glycoprotein antibody associated optic neuritis, 8 with aquaporin-4 antibody related optic neuritis, and 2 with chronic relapsing inflammatory optic neuropathy. Recurrences were more common among female patients. Findings supporting the diagnosis of multiple sclerosis included age of onset >= 10 years (OR=1.24, p = 0.027), the presence of cranial MRI lesions (OR=26.92, p<0.001), and oligoclonal bands (OR=9.7, p = 0.001). Treatment in the acute phase consisted of intravenous pulse methylprednisolone (n = 46, 16.5 %), pulse methylprednisolone with an oral taper (n = 212, 76 %), and combinations of pulse methylprednisolone, plasmapheresis, or intravenous immunoglobulin (n = 21, 7.5 %). Outcome at 12 months was satisfactory, with 247 out of 279 patients (88.5 %) demonstrating complete recovery. Thirty-two patients exhibited incomplete recovery and further combination treatments were applied. Specifically, patients with relapsing isolated optic neuritis and aquaporin-4 antibody related optic neuritis displayed a less favorable prognosis.Conclusion: Our results suggest optic neuritis is frequently bilateral in prepubertal and unilateral in peri- or postpubertal patients. Age of onset 10 or older, presence of oligoclonal bands, and brain MRI findings reliably predict the development of multiple sclerosis. The risk of developing multiple sclerosis increases mostly during the second and third years of follow-up. Relapsing isolated optic neuritis remains a separate group where the pathogenesis and outcome remain unclear. Investigation of predisposing and diagnostic biomarkers and long follow-up could help to define this group.
  • No Thumbnail Available
    Item
    Effects of treatment with clinically relevant valproate, carbamazepine, oxcarbazepine, topiramate, lamotrigine and levetiracetam on ovarian folliculogenesis in young rats
    Cansu, A; Gurgen, SG; Demirhan, YN; Kart, PO; Yildirim, M; Alver, A; Yenilmez, E; Sonmez, FM
    Aim: To determine the effects of valproate (VPA), carbamazepine (CBZ), oxcarbazepine (OXC), topiramate (TPM), lamotrigine (LTG), and levetiracetam (LEV) on ovarian folliculogenesis in young rats. Methods: Forty-nine female Wistar rats, aged 21-24 days, were divided equally into 7 experimental groups. These were given tap water over 21-24 days (control group), 300 mg/kg of VPA, 150 mg/kg of CBZ, 150 mg/kg of OXC, 100 mg/kg of TPM, 10 mg/kg of LTG, or 50 mg/kg of LEV daily in 2 doses via oral gavage until the end of puberty. At the end of the study, the estrous cycle of each rat was monitored daily, and those rats in pro-estrus or di-estrus were sacrificed and the ovaries removed. Serial sections obtained from the ovaries were stained with hematoxylin and eosin, and the corpora lutea and follicles were enumerated. Apoptotic cells were detected using the TUNEL technique. Various serial sections were immunohistochemically stained with proliferating cell nuclear antigen (PCNA), growth differentiation factor (GDF)-9, caspase-3, caspase-9, transforming growth factor beta 1 (TGF-1), and epidermal growth factor (EGF), and evaluated and photographed under a light microscope. Key Findings: The number of corpora lutea was significantly increased in the VPA, CBZ, OXC, and LTG groups compared to the control group (p < 0.001). The number of TUNEL-positive ovarian follicles was 3.3 +/- 1.1 (median, 3), 6.1 +/- 0.9 (median, 6), and 5.7 +/- 0.8 (median,6) in the control, OXC and LEV groups, respectively (p < 0.001). The number of TUNEL-positive granulosa cells was higher in all the groups treated with antiepileptics, with the exception of the TPM group, compared to the control group (p < 0.001). HSCOREs for immunohistochemical staining using PCNA, GDF-9, TGF-1 and EGF were significantly higher in the control group than in the others (p < 0.001). HSCORE for staining using caspase-3 was significantly higher in the VPA, CBZ, OXC and LEV groups, while the HSCORE was significantly lower in the TPM group than in the control group. HSCORE for staining using caspase-9 was significantly higher in the VPA, CBZ and OXC groups, while it was significantly lower in the TPM group than in the control group (p < 0.001). Significance: Exposure to VPA, CBZ, OXC, TPM, LTG and LEV caused different levels of impaired folliculogenesis in young rats.