Alterations in the immunoreactivity of laminin, type IV collagen and α3ß1 integrin in diabetic rat ovarian follicles.

AIM: In order to determine the possible effects of diabetes, we aimed to investigate the expression of extracellular matrix proteins in the theca and granulosa layers in different follicular stages. METHODS: Thirty-two adult Wistar albino male rats were divided into 4 groups as control and sampled groups. Four, eight and twelve weeks after inducing diabetes with an intraperitoneal injection of streptozotocin (40 mg/kg), the expressions of laminin, type IV collagen and α3ß1 integrin in ovarian tissues were evaluated by immunohistochemical method. RESULTS: In our study, in the first month of diabetes, a significant increase was observed in laminin, type IV collagen and α3ß1 integrin expressions in all follicle types compared to the control group in both the theca and granulosa layers. Laminin and type IV collagen immunoreactivity tended to increase in D2 and D3 groups also. Integrin expression did not change in the newly formed follicles in the D2 and D3 groups, however, it tended to change and increase in the developing follicles. CONCLUSIONS: The changes in the expression of laminin, type IV collagen and α3ß1 integrin, which are the extracellular matrix proteins in the follicle, along with diabetes, show that diabetes plays a role in the regulation of follicular development (Tab. 4, Fig. 36, Ref. 29).

The investigation of the antitumoral effect of Cornus mas L in mice with ehrlich solid tumor.

AIM: Cornus mas L is commonly used due to its anti-inflammatory, anti-carcinogenic and anti-oxidant properties. In the study, the effects of C. mas L extract on a solid tumor were examined in the Ehrlich solid tumor model developed in Balb/C type mice. METHODS: Ehrlich acid tumor (EAT) cells (1x106 EAT cell) from the stock animal were injected subcutaneously (s.c.) through the nape of the mice. Treatment groups of solid tumor-induced animals received 100 mg/kg and 200 mg/kg of C. mas L extract intraperitoneally (i.p.) for 14 days. RESULTS: Tumor volumes and animal weights were found to be statistically significant compared to the control group (p < 0.05). AgNOR staining was performed in tumor tissues. Statistically significant differences were observed between the groups in terms of TAA/NA ratio (p < 0.05). Immunohistochemical and biochemical parameters were also evaluated. An estimation of tumor proliferation of the lung, liver, brain, kidney, testis and tumor antioxidant parameters viz. lipid peroxidation, reduced glutathione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) was made. CONCLUSIONS: Our study showed that the anti-tumor effect of C. mas L in assisted tumor development with EAT cells, was mediated by the enhancement of oxidative stress with multiple mechanisms (Tab. 6, Fig. 12, Ref. 38).

Neurofibromatosis type 1 and malignancy in childhood.

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary neurocutaneous syndrome characterized by multi-system involvement and an increased incidence of both benign and malignant tumors. In this study, we evaluated the clinical presentation and prognosis of NF1 and malignancy. Between 1975 and 2013, 26 (5%) of the 473 patients with NF1 at our center developed non-neurofibroma neoplasms. The patient files of 26 subjects with tumors, other than optic glioma, were analyzed retrospectively to evaluate clinical features and treatment results. The age at diagnosis of NF1 ranged from 3 months to 16 years (median 5.5 years). The age range at tumor diagnosis was 1.5-33 years (median 8 years) in these 26 patients. The tumor histological subtypes included the following: 12 soft-tissue tumors (6 malignant peripheral nerve sheath tumors (MPNST), 5 rhabdomyosarcomas (RMS) and 1 malignant fibrous histiocytoma), 11 brain tumors (6 low-grade gliomas, 3 high-grade gliomas, and 2 medulloblastoma), 2 neuroblastomas and 1 non-Hodgkin's lymphoma. Twelve of 26 patients were alive at the time of the study. Although benign brain tumors with NF1 are more common, high-grade brain tumors also occur. Thus, careful and regular follow-up is crucial for early detection of malignancy in NF1 patients.

Association of interleukin-23 receptor gene polymorphism with Behçet disease.

BACKGROUND: Behçet disease (BD) is a chronic, multisystemic disease characterized by relapsing episodes of a wide spectrum of clinical symptoms. Several genetic and immunological factors have been suggested to be involved in the aetiopathogenesis of BD. AIM: To investigate the association between BD and five single nucleotide polymorphisms (SNP) in the gene for interleukin (IL)-23 receptor (IL-23R). METHODS: We recruited 123 patients with BD and 168 controls. A detailed phenotypic investigation of BD was made for each patient. Five SNPs in the IL-23R gene (rs11209026, rs7517847, rs11805303, rs1004819, rs17375018) were investigated. RESULTS: We found that patients with BD had a lower frequency of the rs17375018 GA and AA genotypes, and a higher frequency of the rs17375018 G allele, and these were statistically significant. The rs11209026 G allele frequency was higher in male patients with BD than in male controls, and the rs7517847 G allele was higher in patients with genital ulcers. The rs11805303 G and rs1004819 G alleles were more frequent in patients with papulopustular lesions. CONCLUSIONS: The rs17375018 variant in the IL-23R gene seems likely to be a strong susceptibility factor for BD in the Turkish population. As this variant was also shown to have a higher frequency in BD patients from different ethnic backgrounds in two previous studies, it may be specific for BD.

Measurement and assessment of grief in a large international sample.

BACKGROUND: In 2022, the International Classification of Diseases (ICD-11) and an update of the Diagnostic Statistical Manual of Mental Disorders (DSM 5 TR) were released for implementation worldwide and now include the new Prolonged Grief Disorder (PGD). The newest definition of PGD is based on robust clinical research from the Global North yet until now has not been tested for global applicability. METHODS: The current study assesses the new PGD ICD-11 criteria in a large international sample of 1393 bereaved adults. The majority of the sample was included from the USΑ. Additionally, we conduct a sub-sample analysis to evaluate the psychometric properties, probable caseness of PGD, and differences in network structure across three regions of residency (USA, Greece-Cyprus, Turkey-Iran). RESULTS: The psychometric validity and reliability of the 33-item International Prolonged Grief Disorder Scale (IPGDS) were confirmed across the whole sample and for each regional group. Using the strict diagnostic algorithm, the probable caseness for PGD for the whole sample was 3.6 %. Probable caseness was highest for the Greece-Cyprus group (6.9 %) followed by Turkey-Iran (3.2 %) and the USA (2.8 %). Finally, the network structure of the IPGDS standard items and cultural supplement items (total of 33 items) confirmed the strong connection between central items of PGD, and revealed unique network connections within the regional groups. LIMITATIONS: Future research is encouraged to include larger sample sizes and a more systematic assessment of culture. CONCLUSION: Overall, our findings confirm the global applicability of the new ICD-11 PGD disorder definition as evaluated through the newly developed IPGDS. This scale includes culturally sensitive grief symptoms that may improve clinical precision and decision-making.

Primitive neuroectodermal tumors of the central nervous system associated with genetic and metabolic defects.

AIM: To evaluate the genetic, congenital and metabolic disorders which were detected concurrently with primitive neuroectodermal tumors (PNET) of the central nervous system in children. METHODS: Medical records of 1030 children who were admitted to our department with diagnosis of brain tumor between 1975 and 2005 were reviewed retrospectively. Medulloblastoma and supratentorial PNETs were detected in 289 patients. They were reviewed for associated metabolic conditions, genetic and congenital defects. RESULTS: One of the following conditions were detected in 10 patients with medulloblastoma and supratentorial PNETs: Neurofibromatosis type 1, Gorlin syndrome, juvenile polyposis coli, cancer prone syndrome of total premature chromatid separation and Fanconi anemia, bilateral retinoblastoma, L-2-hydroxyglutaric aciduria, Gilbert syndrome, gray platelet syndrome, cleft lip-palate and left renal agenesis. In the patients with multiple malignant diseases, cancer prone syndrome of total premature chromatid separation and Fanconi anemia, Gorlin syndrome and juvenile polyposis coli were diagnosed after diagnosis of the malignant tumors. Medulloblastoma was the first manifestation in the case with Gorlin syndrome. In case with retinoblastoma, pineal PNET was detected 2 months after diagnosis of retinoblastoma. Cleft lip-palate and L-2-Hydroxyglutaric aciduria were detected previously in the patients before their brain tumors whereas Gray platelet, Gilbert syndrome and left renal agenesis were diagnosed during treatment of medulloblastoma. CONCLUSION: Associated genetic, metabolic and congenital conditions were detected in 3.5% of the cases. Thus the patients with PNET should be followed for these defects.

Malign peritoneal mesothelioma with nephrotic syndrome.

Nephrotic syndrome may occur in malignancies like Hodgkin Disease and other solid tumors due to glomerulonephritis, amyloidosis or other causes. However, it is rare in peritoneal mesothelioma. We report a 42-year old female patient with peritoneal mesothelioma and nephrotic syndrome together with a review of literature (Tab. 1, Fig. 3, Ref. 7).

ABO and Rh blood groups frequency in women with HER2 positive breast cancer.

PURPOSE: The role of genetic factors in the development of cancer is widely accepted. Data on the role of ABO blood group and Rh factor in breast cancer is inconclusive. The aim of this study was to investigate the presence of a possible association between HER2 (+) breast cancer in Turkish women and ABO blood groups and Rh factor. METHODS: In 294 female patients with HER2 (+) breast cancer, ABO blood groups and Rh factor were examined. The relationship of blood groups with age, menopausal status, and family history of cancer, estrogen receptor (ER), progesterone receptor (PR) and HER2 status of these patients was evaluated. Blood groups distribution of 22,821 healthy blood donors was also assessed and compared with the patients' blood groups distribution. RESULTS: The median patient age was 47 years (range 20-80) and 56% of the patients were premenopausal. ER and PR were positive in 50 and 60% of the patients, respectively. Overall, the ABO blood group distribution of the 294 HER2 (+) breast cancer patients was similar to that of the healthy blood donors (p=0.36). Likewise there was no correlation between blood type and ER, PR and menopausal status. Rh (-) patients had more frequent family cancer history and this difference was significant for patients with blood group B Rh (-) and O Rh (-) (p = 0.04). CONCLUSION: In the present study we didn't find any relationship between HER2 status and ABO blood group and Rh factor. However, further studies with larger number of patients are needed to establish the role (if any) of blood groups in patients with breast cancer.

Concomitant temozolomide and radiotherapy versus radiotherapy alone for treatment of newly diagnosed glioblastoma multiforme.

PURPOSE: To study the efficacy and safety of radiotherapy (RT) with concomitant and subsequent temozolomide in comparison to RT alone in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM) after brain surgical intervention. METHODS: Twenty patients received cranial fractionated RT (60 Gy total dose: 2 Gy/day, 5 days/week, for 6 weeks) with concomitant oral temozolomide (75 mg/m(2)/day x 7 days/ week, for 6 weeks) followed by temozolomide monotherapy (200 mg/m(2)/day × 5 days every 28 days for 6 cycles). Another 20 patients received only cranial RT (Co-60 teletherapy, 60 Gy in 30 fractions). RESULTS: At the end of the study the median time to progression free survival (PFS) was 13 months in the temozolomide plus RT treatment group and 5 months in the RT-alone group (p=0.0001). Median overall survival (OS) in the temozolomide plus RT and the RT-alone group was 19 and 11.5 months, respectively (p=0.0264). The main side effect in the temozolomide plus RT group was myelosuppression. Concomitant treatment resulted in grade 3 hematologic toxicity in 6 patients. CONCLUSION: These data show that the combination of temozolomide, concomitant and subsequent to RT seems more effective than RT alone in patients with newly diagnosed GBM and that multimodality treatment is safe and well tolerated.

Evaluation of skeletal changes associated with surgically rapid palatal expansion without pterygomaxillary separation.

INTRODUCTION: To evaluate skeletal and nasal volume changes before and after surgery in surgically assisted rapid palatal expansion (SARPE) without pterygomaxillary separation and compare the dental changes by digital model analysis and radiographic analysis. SETTING AND SAMPLE: Population A total of 18 patients (10 females and 8 males) aged 15-33 years and with completed skeletal development, who were referred to Oral and Maxillofacial Surgery Department, Dentistry Faculty, Istanbul University and who had SARPE indication were included in the study. MATERIALS AND METHODS: Skeletal changes, lower nasal volume, transverse diameters of bony nasolacrimal duct and dental changes have been evaluated by using Cone beam computed tomography (CBCT) before and 6 months after the surgery. CBCT data was determined by Mimics v.18.01. Dental changes have been also evaluated by digital model analysis program 'Shape Orthoanalyzer' and the data are compared with those obtained using CBCT. RESULTS: The results obtained from dental measurements made using CBCT and those obtained using scanning three-dimensional (3D) models were consistent with each other. CBCT demonstrated that lower anterior nasal volume and transverse diameters of bony nasolacrimal duct showed statistically significant increase before and after the surgery. CONCLUSIONS: According to the study findings, SARPE without pterygomaxillary separation was noted to be an effective procedure. Lower nasal volumes were increased and the maxilla expanded in the transverse direction in all patients. Dental evaluations that were performed in this digital model analysis also supported our findings in CBCT. Transverse diameters of the bony nasolacrimal duct were shortened at all patients.

Capecitabine and oxaliplatin (XELOX) as first-line treatment for patients with metastatic colorectal cancer.

PURPOSE: For almost 40 years, 5-fluorouracil (5-FU) had been the only drug with demonstrated activity against (CRC), commonly used in combination with leucovorin (LV). Oxaliplatin and capecitabine are two relatively novel drugs used in the treatment of CRC. These drugs have been found to act synergistically, both in vivo and in vitro and their combination (XELOX) is highly active in metastatic colorectal cancer (mCRC). The aim of this study was to determine the safety and efficacy of XELOX in patients with mCRC. METHODS: The study endpoints were response rates, toxicity, progression free (PFS) and overall survival (OS). XELOX was administered as first line treatment to patients with mCRC. Patient selection criteria included histological confirmation of mCRC, ECOG performance status (PS)

The functional role of nuclear factor kappa-kappaB1 -94 ins/del ATTG promotor gene polymorphism in Behçet's disease: an exploratory study.

Behçet's Disease (BD) is a systemic immunoinflammatory disease. The pathogenesis of BD is unknown, although raised levels of several pro-inflammatory cytokines have been reported. Nuclear factor kappa B (NF-kappaB) is a family of critical transcriptional factors involved in the regulation of a large variety of inflammatory responses and apoptosis. In this study we investigated the -94 insertion/deletion ATTG promoter polymorphism of the NF-kappaB1 gene (NFKB1) in 86 patients with BD and 100 healthy controls. The frequency of the -94ins ATTG (I) allele was 61.6% in patients with BD and 59% in controls and the frequency of the -94 del ATTG (D) allele was 38.4% in patients with BD and 41% in controls. The frequency of the -94ins ATTG (I) allele was significantly higher in patients with ocular involvement (P = 0.03). In the genotype study, the overall frequencies of II, ID and DD were 40.7%, 41.9%, and 17.4% in the patient group and 30%, 58% and 12% in the control group (P: 0.08). The II genotype was significantly higher in patients with ocular involvement, genital ulcers or papulopustular lesions. The frequency of the II, ID and DD genotypes showed no marked difference in patients with erythema nodosum, pathergy positivity, arthritis or vascular involvement. No difference was found for gender, positive family history or age at disease onset. This study provides evidence that the -94ins/del ATTG promoter polymorphism of NFKB1 may have functional consequences in BD, especially in patients with ocular involvement.

Anatomical and functional aspects of ligaments between the malleus and the temporomandibular joint.

The aim of this paper is to investigate the anatomical topography and the relationship between the ligaments, malleus and temporomandibular joint (TMJ) and to determine the role of these ligaments on the movement of the malleus. The malleus, incus, petrotympanic fissure (PTF), chorda tympani, anterior malleolar ligament (AML), discomallear ligament (DML), malleomandibular ligament, sphenomandibular ligament and articular disc were explored in 15 skulls. Traction and tension tests were carried out to clarify their role in malleolar movement. In 12 of the cases, two separate ligaments were connected to the anterior of the malleus, whereas a single ligament from the anterior of the malleus to the PTF was observed in 3 cases. In 12 cases, the DML united the retrodiscal tissues. In the other 3 cases, the medial and the lateral parts of the ligament were connected to the retrodiscal tissue after passing through the PTF. The thickness of the ligaments differed among specimens. When tension was applied to the DML no malleolar movement occurred, but when the AML was overstretched, significant movement was observed in 5 cadavers; little movement in 6 cadavers, and no movement in 4 cadavers. This study suggests that extreme stretching of the condyle in conjunction with the ligaments between the ossicles of the inner ear and the TMJ could be the reason for unexplained otological problems.

Larynx osteosarcoma: case report.

We present the case of a laryngeal osteosarcoma in a 69-year-old man, which generated many diagnostic and treatment difficulties. The patient was admitted to the hospital because of persisting hoarseness and a laryngeal tumor was seen on laryngoscopy. Total laryngectomy was performed and the pathological examination of the resected material showed osteosarcoma of the larynx. Postoperative radiotherapy was planned but the patient declined any treatment. He was readmitted to the hospital 5 months later with a neck tumor and enlarged lymph nodes on the right side of the neck. Chemotherapy started and during treatment metastatic lymph nodes on the left side of the neck and pulmonary metastases were detected.

The use of reconstruction plates to treat benign mandibular pathological lesions: A retrospective clinical study.

INTRODUCTION: The purpose of this retrospective clinical study was to evaluate the indications for and the utility of reconstruction plates in the management of benign mandibular pathological lesions. The complications associated with plate use were also assessed. PATIENTS AND METHODS: The clinical and radiological data of 23 patients (16 males, 7 females) with large, benign mandibular pathologies were evaluated. During operations, reconstruction plates were used to prevent mandibular fracture or to allow for bone reconstruction after segmental or disarticulation resection. The mean follow-up time was 11.2months. RESULTS: Condylar sag was observed in one patient who had undergone disarticulation resection. A reconstruction plate was removed from one patient because of pain. A plate became exposed in one patient who had undergone a disarticulation resection. Two patients reported slight paraesthesia. Screw-loosening was observed in one patient who had received a non-locking plate. CONCLUSION: Reconstruction plates can be safely used to manage benign mandibular lesions. Preoperative bending of the plates on individualised models is useful for reducing the time required for plate adaptation during operation. Locking reconstruction plates are preferable for preventing screw-loosening. All complications can be managed with careful follow up.

Behavioural characterization of AnkyrinG deficient mice, a model for ANK3 related disorders.

ANK3 encodes AnkyrinG (AnkG), a member of the Ankyrin family that is expressed in several different isoforms in many tissues. A unique serine-rich domain and tail domain in the two largest isoforms of AnkG (270 and 480kDa), restrict AnkG to the axon initial segment and nodes of Ranvier of myelinated neurons. At these sites, AnkG is a master regulator, coordinating the strict clustering of components necessary for proper action potential initiation and propagation along the axon. These components include voltage-gated sodium channels, potassium channels and members of the L1 cell adhesion molecule family. Genetic variation in the ANK3 gene has been linked to a range of neuropsychiatric and neurodevelopmental disorders in human, including schizophrenia, bipolar disorder, intellectual disability and autism spectrum disorders. Here, we study the effect of reduced expression of the large isoforms of Ank3 on cognition and behaviour using a heterozygous knockout mouse model. In three independent behavioural tests, being the open field test, elevated plus maze and social interaction test, we found evidence for increased anxiety in our Ank3 mouse model. Besides, we observed specific neuroanatomical defects in heterozygous knockout mice, including a smaller cingulate cortex, granular retrosplenial cortex, primary motor cortex and fimbria of the hippocampus.

Using progenitor strain information to identify quantitative trait nucleotides in outbred mice.

We have developed a fast and economical strategy for dissecting the genetic architecture of quantitative trait loci at a molecular level. The method uses two pieces of information: mapping data from crosses that involve more than two inbred strains and sequence variants in the progenitor strains within the interval containing a quantitative trait locus (QTL). By testing whether the strain distribution pattern in the progenitor strains is consistent with the observed genetic effect of the QTL we can assign a probability that any sequence variant is a quantitative trait nucleotide (QTN). It is not necessary to genotype the animals except at a skeleton of markers; the genotypes at all other polymorphisms are estimated by a multipoint analysis. We apply the method to a 4.8-Mb region on mouse chromosome 1 that contains a QTL influencing anxiety segregating in a heterogeneous stock and show that, under the assumption that a single QTN is present and lies in a region conserved between the human and mouse genomes, it is possible to reduce the number of variants likely to be the quantitative trait nucleotide from many thousands to <20.

The effect of venous thromboembolism on survival of cancer patients and its relationship with serum levels of factor VIII and vascular endothelial growth factor: a prospective matched-paired study.

BACKGROUND: Venous thromboembolism (VT) increases mortality and morbidity in cancer patients. The primary aim of this study was to evaluate the effect of VT on the survival of cancer patients and its relationship with serum vascular endothelial growth factor (VEGF) and plasma factor VIII levels. PATIENTS AND METHODS: Eighty-two patients with locally advanced or metastatic cancer were included in this study between September 2001 and March 2004, and 31 of them had VT. Fifty-one matched-paired cancer patients without VT were prospectively selected as a control group in the same period. Criteria for the selection of control group patients were having the same malignancy, stage, metastatic site, performance status and age (+/-5 years) as patients in the VT group. RESULTS: Plasma factor VIII and serum D-dimer levels in the VT group were significantly higher than those in the control group (p=0.030 and p=0.016, respectively). However, mean serum VEGF levels were similar in both groups (p=0.199). In the VT group, the median survival of patients who had higher serum VEGF levels (>150 pg/mL) was significantly shorter than that of patients in the same group with lower serum VEGF levels (p=0.005). The median survival of the VT group was 14 months, whereas it was 25 months in the control group (p=0.199). CONCLUSION: There was a worse prognostic trend for cancer patients with VT. Nevertheless, the difference in survival was not statistically significant between the groups. Plasma factor VIII and serum D-dimer levels might have prognostic value in cancer patients with VT. Cancer patients with VT and higher serum VEGF levels had a significantly poorer prognosis.

Double superior vena cava.

Duplication of superior vena cava (SVC) is a rare anomaly. The incidence of double SVC in general population is 0.3% whereas in patients with congenital heart disease it varies between 10-11%. Double SVC cases have clinical importance if especially the one on the left side drains into the left atrium. Moreover, double SVC is surgically important in the presence of congenital heart disease. In this article, we presented adult patients who incidentally diagnosed with double SVC, one drained into the right atrium while the other into the left atrium and discussed the embryologic basis of these patent vessels.