Investigation of TAp63 gene expression and follicle count using melatonin in cisplatin-induced ovarian toxicity

Background: Premature ovarian failure is among the most important side effects of chemotherapy during reproductive period. Preserving ovarian function is gradually gaining importance during oncologic treatment. The present study aims to investigate the potential of melatonin to protect from cisplatin-induced ovarian toxicity in rats.Methods: Twenty-nine female rats were divided to three groups: Saline control group (group 1), cisplatin group (group 2), and cisplatin and melatonin group (group 3). While the rats in groups 2 and 3 were administered 5 mg/kg single dose of cisplatin via intra-peritoneal (IP) route, the rats in group 3 were started on melatonin (20 mg/kg IP) before cisplatin administration and continued during 3 consecutive days. Ovaries were removed one week after cisplatin administration in all groups. Blood samples were obtained before the rats were decapitated. Histological evaluation, follicle count, and classification were performed. TAp63 mRNA expression was evaluated using mRNA extraction and real-time polymerase chain reaction (PCR) method. Serum estradiol (E2) and anti-Mullerian hormone (AMH) values were measured with enzyme immune-assay technology.Results: While primordial follicles were seen to decrease in group 2 as compared to group 1 (p=0.023), primordial follicle count was observed to be preserved significantly in melatonin group as compared to group 2 (p=0.047). Moreover, cisplatin-induced histo-pathological morphology was preserved in favor of normal histology in melatonin group. A significant difference was not observed between groups with regard to mean serum AMH and E2 values (p=0.102 and p=0.411, respectively). While TAp63 gene expression significantly increased in group 2 as compared to control group (p=0.001), we did not detect a statistically significant difference in cisplatin and melatonin group, although gene expression decreased (p=0.34).Conclusions: We conclude that concurrent administration of melatonin and cisplatin may protect from ovarian damage

The prevelance of human papillomavirus (HPV) genotypes detected by PCR in women with normal and abnormal cervico-vaginal cytology

Objectives: Cervical cancer is the second most common type of cancer for women worldwide with a great proportion proved to be related to human papillomavirus (HPV) infection. As infection with HPV is the strongest risk factor for cervical neoplasia, detection of HPV genotypes in cervical and vaginal specimens of women with normal and abnormal cytology seems to be of paramount importance in cervical cancer screening. The objective of the study is to evaluate the prevalence and HPV genotypes among women with normal or abnormal Pap smear tests. Material and methods: This retrospective study was conducted in a tertiary care university hospital in western Turkey. A total of 201 patients in whom both HPV typing and Pap test was performed between 2012 and 2016 in our obstetrics and gynecology department were enrolled in this study. Clinical and laboratory data were obtained for all participants. Cervical smears of the patients were classified by the Bethesda system and HPV analyses were done using the polymerase chain reaction (PCR) method. Results: This study included 201 women, 72 of whom had normal and 129 of whom had abnormal Pap smear results. HPV DNA was detected in 91 (45.2%) of the 201 investigated women. Out of 72 patients with normal cervico-vaginal cytology, HPV positivity was detected in 35 (49%) patients, whereas 33 (35%) patients out of 94 with ASCUS , 18 (62%) patients out of 29 with LSIL and 5 (83%) patients out of 6 with HSIL had HPV positivity. Out of 35 HPV positive women that had normal pap test results, 25 (75%) were found to have high risk HPV (HR-HPV) genotypes. In women with ASCUS, LSIL and HSIL, HR-HPV genotype rates were found to be 94%, 89% and 100% respectively. The most common identified HPV types were HPV58, HPV16, HPV31, HPV33, HPV11 and HPV35. Conclusions: The frequency of HPV infection was found to be higher in our study compared to previous reports. Moreover, although HR-HPV genotypes were also detected in patients with normal cervical cytology, a majority of patients with HR-HPV genotypes were associated with abnormal cervical smear cytology including high rates of atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion

Waardenburg syndrome [Waardenburg sendromu]

Waardenburg Syndrome (WS) is an autosomal dominant syndrome characterized with hearing loss and pigmentation disorders. Its frequency has been reported to be 1/20.000-40.000. Among its clinical features dystopia canthorum, high broad nasal root, synorphrys, heterochromia iridium or isochromic blue irides of both eyes, white forelock, pigmentary disorders and congenital sensorineural hearing loss can be enumerated. This syndrome is clinically and genetically heterogenous and classified into four types, WS type 1 and 3 are differentiated from type 2 and 4 by the presence of dystopia canthorum. WS type 3 also has also similar characteristics in addition to extremity abnormalities. WS type 4 is also associated with Hirschsprung Syndrome. WS type 4 also discriminates from the other 3 types by its autosomal recessive characteristics

Waardenburg Syndrome in the Turkish deaf population

WOS: 000237311700005PubMed: 16719276Waardenburg syndrome in the Turkish deaf population: Waardenburg Syndrome (WS) is an autosomal, dominantly inherited disorder that accounts for more than 2% cases of congenital deafness. The aim of this study is to determine the WS incidence among deaf pupils. Dysmorphological examination was performed on 720 children who were attending 7 special schools in Turkey and who had hearing disabilities. All subjects in the study were examined for WS diagnostic criteria. We detected 49 patients (6.8%) with WS among the 720 children examined. Six patients had WS type 1 (12.2%) and 43 had type 2 (87.8%). We observed 2 to 5 major diagnostic criteria for WS. Out of all the subjects in the study, only two patients have deaf first degree relatives. All subjects had been previously examined by physicians for deafness but none of them had been then diagnosed to have Waardenburg Syndrome. Instead, they were all misdiagnosed as to have nonsyndromic deafness. Awareness of WS diagnostic criteria by the physicans will provide accurate diagnosis for many deaf pupils and their first degree relatives who are able-to-hear WS patients and whose children are at risk for deafness

EFFECTS OF CYP2C19 AND P2Y12 GENE POLYMORPHISMS ON CLINICAL RESULTS OF PATIENTS USING CLOPIDOGREL AFTER ACUTE ISCHEMIC CEREBROVASCULAR DISEASE

silan, coskun/0000-0002-8352-6571; Silan, Coskun/0000-0002-8352-6571WOS: 000352978700004PubMed: 25937796The CY2C19 and P2Y12 gene polymorphisms are responsible for resistance to clopidogrel, known as drug unresponsiveness. In this study we researched the effect of gene polymorphism on clinical results of patients who began clopidogrel therapy after acute ischemic cerebrovascular disease. The study included 51 patients. The patient group included patients who had begun prophylactic clopidogrel due to acute ischemic cerebrovascular disease in the last 2 years. All patients were monitored by the Neurology Outpatient Clinic at Canakkale Onsekiz Mart University Research Hospital, Canakkale, Turkey, and only those monitored for at least 1 year were included in the study. When the *1, *2 and *3 alleles of the CYP2C19 gene polymorphism were evaluated, two patients were homozygotes for *2/*2, 13 patients were heterozygous for *1/*2 and 36 patients were homozygotes for the wild type *1/*1. No patient had the *3 allele. Three heterozygous patients, one for *2/*2 and two for *1/*2, stopped clopidogrel therapy due to repeated strokes and began taking warfarin. When evaluating P2Y12 52 (G>T) and 34 (C>T) polymorphisms, all alleles were of the wild type. The CYP2C19 and P2Y12 gene polymorphisms may cause recurring strokes linked to insufficient response to treatment of ischemic cerebrovascular disease. In our patient group, three patients suffered repeated strokes and these patients had the CYP2C19*2 gene polymorphism. As a result, before medication use, genetic testing is important for human life, quality of life and economic burden.Department of Scientific Research Projects Commission, Canakkale Onsekiz Mart University, Canakkale, TurkeyCanakkale Onsekiz Mart UniversityThe present study was supported by the Department of Scientific Research Projects Commission, Canakkale Onsekiz Mart University, Canakkale, Turkey. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article

A Case With Short Stature, Growth Hormone Deficiency and 46, XX, Xq27-qter Deletion

We report a case of 11-year-old girl with growth retardation and 46, XX, Xq27-qter deletion. The endocrinologic evaluation revealed growth hormone deficiency. In karyotype analysis  46, XX, Xq27-qter deletion was determined. The deletion of terminal region of chromosome 27 is most commonly being detected during the evaluation of infertility, premature ovarian insufficiency or in screening for fragile X carrier status. To our knowledge, this is the first reported case with 46, XX, Xq27-qter deletion and growth hormone deficiency. Furthermore, this case might facilitate future search for candidate genes involved in growth hormone deficiency

Branchio-ocuto-facial syndrome with the atresia of external ear

WOS: 000233098700020PubMed: 15936829We report an 8-year-old child with branchio-oculo-facial syndrome. He showed atresia of external ear, preauricular pit, maxillar and mandibular hypoplasia, mild ptosis on the left side, Lacrimal duct obstruction, unilateral branchial cyst, hypertrichosis of the neck, left foot showed mild syndactily of fourth and fifth toes and dental abnormalities. His mother had pseudocleft of the lip which Led to the diagnosis. The importance of serial observations in patients with rare genetic disorders is emphasized. (c) 2005 Elsevier Iretand Ltd. All rights reserved

Mutation profiles detected by new generation dna sequence analysis in gynecological cancers, single centre case series results

Amacımız, yaş ve aile hikayesinden bağımsız olarak merkezimizde over (OC) ve endometriyum kanseri (EC) tanısı ile cerrahisi ve ardından genetik mutasyon analizi uygulanan hastalarımızın mutasyon sıklığını ve sekanslarını araştırmaktır. Son yıllarda önleyici stratejilerin gelişimi dışında tedavi seçeneklerindeki fırsatlar ve genetik çalışmaların artışı herediter kanserlere ilgiyi arttırmıştır. En sık görülen herediter jinekolojik kanserler; herediter meme over kanseri (HBOC) ve Lynch Sendromu (LS) dur. Hastalığın düşük prevalansı, test pahalılığı ve etik sebepler popülasyon bazlı taramayı kullanışsız hale getirmektedir. Birimimizde 01.04.2018-01.10.2019 tarihleri arasında genetik araştırması yapılan 37 EC ve 15 OC tanısı almış hastamız çalışmaya dahil edilmiştir. BRCA1/2 ve LS genlerini de içeren (MLH1, MSH2, MSH6, PMS 2) 25 genden oluşan geniş ailevi panel testi uygulanmıştır. Ailevi gen paneli testi yapılan 27 EC hastamızda, 1 MLH1 ve 1 ATM geninde patolojik mutasyon saptandı (%3.7 LS,%3.7 non LS). 11 hastada önemi belirsiz varyant mutasyon (VUS) görüldü (%40.7). BRCA mutasyon araştırması yapılan 20 EC’li hastamızda patolojik mutasyon saptanmadı. BRCA mutasyonu araştırılan 14 OC’lu hastamızda 3 patolojik varyant identifiye edildi ve hepsi BRCA1 genindeydi (HBOC %21,4). Ailevi kanser paneli değerlendirilen 4 OC’lu hastada 1 MSH6 ve 1 ATM geninde patolojik mutasyonlar izlendi. Over ve endometriyum kanserlerinde ailevi geniş mutasyon verilerinin çoğalması ve literatürde paylaşımı VUS oranlarını azaltacak, BRCA ve LS dışındaki genlerin jinekolojik kanserlerdeki rolünü ortaya çıkartacak ve yeni tarama algoritmalarını oluşturacaktır.Our objective is to investigate the mutation frequency and sequences of our patients, who underwent surgery with a diagnosis of ovarian (OC) and endometrial cancer (EC) and subsequently underwent genetic mutation analysis, regardless of age and family history. In recent years, apart from the development of preventive strategies, opportunities in treatment options and increase in genetic studies have increased the interest in hereditary cancers. The most common hereditary gynecological cancers are hereditary breast ovarian cancer (HBOC) and Lynch Syndrome (LS). The low prevalence of the disease, cost of testing, and ethical reasons make population-based screening impractical. 37 patients diagnosed with endometrial cancer and 15 patients diagnosed with ovarian cancer were included in the study, and their genetic research was conducted in our department between 01.04.2018 and 01.10.2019. A large familial panel test consisting of 25 genes including BRCA1/2 and LS genes (MLH1, MSH2, MSH6, PMS 2) was performed. Pathological mutation was found in 1 MLH1 and 1 ATM genes in 27 patients with endometrial cancer who underwent familial gene panel test (3.7% LS, 3.7% non LS). Eleven patients had a variant mutation of uncertain significance (VUS) (40.7%). No pathological mutation was found in our 20 patients with endometrial cancer who were investigated for BRCA mutation. In our 14 patients with ovarian cancer whose BRCA mutation was investigated, 3 pathological variants were identified, and all of them were in BRCA1 gene (HBOC 21.4%). Pathological mutations in 1 MSH6 and 1 ATM genes were observed in 4 patients with ovarian cancer whose familial cancer panel was evaluated. The proliferation of comprehensive familial mutation data in ovarian and endometrial cancers and their sharing in the literature will reduce VUS rates, reveal the role of genes other than BRCA and LS in gynecological cancers, and create new screening algorithms

Anophthalmia, cleft lip/palate, absent vomer bone, nystagmus, and mental-motor retardation: A new syndrome or Fryns "anophthalmia-plus" syndrome?

Saglam, Ibrahim/0000-0002-1706-4444WOS: 000256241500005PubMed: 18452356Objective: We report that a 4-year-old boy presented with right unilateral complete cleft lip and palate, right anophthalmos, left congenital nystagmus, absence of the vomer bone, mental-motor retardation, and normal lymphocyte karyotype (46, XY). Methods: For reconstruction of the deformities, we performed cleft lip repair by Millard's rotation-advancement technique and planned cleft palate repair. Conclusions: This combination of cleft lip and palate, anophthalmos, congenital nystagmus, absent vomer bone, and mental-motor retardation has not, to our knowledge, previously been described. We suggest that this represents either another case of the rare Fryns "anophthalmia-plus" syndrome or a new syndrome