Impact of body mass index and vitamin D on serum AMH levels and antral follicle count in PCOS.

OBJECTIVE: To investigate the effects of body mass index (BMI) values and 25(OH) vitamin D levels determined by Endocrine Society on serum Anti Mullerian Hormone (AMH) and antral follicle count (AFC) in women with polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: Sixty infertile women with PCOS and 30 age-matched women with unexplained infertility (UEI), were included. Patients in PCOS and control groups were divided into three subgroups according to their BMI values as normal, overweight and obese. Each BMI group was divided into three subgroups according to vitamin D levels. While AMH and vitamin D levels were determined at first admission, AFC was measured on the third day of cycle. RESULTS: BMI, AFC, and AMH levels of women with PCOS were significantly higher than the UEI group. AMH values of women with PCOS with normal BMI were found to be significantly higher than UEI controls with normal BMI. AMH values of overweight and obese PCOS patients and controls were similar. As BMI values of the PCOS group increased, vitamin D levels decreased significantly. Vitamin D levels of the patients in the PCOS group were found to be significantly lower than the control group. When evaluated according to BMI, the vitamin D levels of normal, overweight and obese women with PCOS were significantly lower than the UEI. CONCLUSIONS: Rising BMI in PCOS leads to a significant decrease in vitamin D and AMH. Deficiency, insufficiency or normality of vitamin D do not affect the main markers of ovarian reserve.

High serum AMH inhibits pathological growth of the low biomass endometrial microbiome.

OBJECTIVE: Although host microbiome play a role in both hormonal status and fertility, this issue has not yet been clarified. Since the endometrium is a sterile tissue, it is accepted that microbiota does not grow under normal conditions. The aim of the study was to reveal the characteristics of endometrial microbiota according to serum AMH levels in women with implantation failure. PATIENTS AND METHODS: Forty-five women aged 20-30 years with two or more implantation failures were included in the study. They were divided into 3 groups according to their serum AMH values: Group 1 -AMH <1.3 ng/ml; Group 2 - AMH between 1.3-2.6 ng/ml; Group 3 - AMH >2.6 ng/ml. Twenty-two healthy fertile women who were the same age as the infertile group and applied for cervical smear screening were accepted as the control group. Following the embryo transfer, the tip of the catheter was inserted into the transport medium under sterile conditions. Sowing was carried out by touching the tips of the catheter to the blood agar medium. After the evaluation of the petri dishes at the end of 48 hours of incubation, colonies were stained with Gram stain. Microorganisms in the colonies were identified with the Vitek-2 device according to their gram-staining characteristics and their antibiograms were made. RESULTS: A negative correlation was detected between low AMH values and the microbiome detection rates in endometrial cultures. In patients with low serum AMH levels, the chance of endometrial microbiota growth was higher in the endometrial culture medium. The most common bacteria were found to be MSSA, MRKNS and lactobacillus. Clinical pregnancy rates were found to be significantly higher in the group with high AMH levels. As AMH levels increased, positive flora detection rates decreased, while clinical pregnancy rates increased. CONCLUSIONS: Low serum AMH level increases the rate of positive endometrial microbiome in culture and decreases clinical pregnancy rates.

Vitamin D supplementation inhibits NF-kß signaling pathway in lean and obese women with PCOS.

OBJECTIVE: This study aims at investigating the effect of vitamin D (VD) replacement therapy on serum nuclear factor-kappa ß (NF-kß) levels in both lean and obese women with Polycystic Ovary Syndrome (PCOS). PATIENTS AND METHODS: 50 women with PCOS with VD levels lower than 20 ng/mL were included in the study. Participants were equally divided into two groups, as lean and overweight/obese PCOS, according to their body mass index (BMI) values. Patients in both groups received 2000 IU/day oral VD replacement for two months. Serum NF-kß, VD, demographic and hormonal values of the patients were recorded before and after VD replacement therapy. RESULTS: Serum insulin and homeostatic model assessment (HOMA-IR) values of overweight/obese women with PCOS were significantly higher than lean women with PCOS. Pre-replacement NF-kß levels were found to be significantly higher in the overweight/obese PCOS group (3.22 ± 1.09 ng/mL) than in the lean PCOS group (1.22 ± 0.43 ng/mL) (p < 0.03). Serum NF-kß levels of the patients in the overweight/obese group (1.10 ± 0.30 ng/mL) and the lean group (0.83 ± 0.10 ng/mL) decreased significantly after VD replacement. No significant difference was found between the groups in terms of HOMA-IR, insulin, and total testosterone levels at the end of VD replacement therapy. CONCLUSIONS: VD replacement therapy contributes to the improvement of subfertility and metabolic imbalance by reducing serum NF-kß levels in both lean and obese women with PCOS.

Preliminary results of blood growth differentiation factor-9 (GDF-9) measurement in cats: future aspects of GDF-9 on stage of the cycle and spaying history.

Growth differentiation factor-9 (GDF-9), an oocyte-derived member of the TGF-ß superfamily, plays an essential role in regulation of follicular development. This study aimed to determine the cyclic changes in serum GDF-9 concentration, compare its levels before and after ovariohysterectomy (OHE), and investigate its potential as a tool in ovarian remnant syndrome (ORS) diagnosis in cats. GDF-9 measurements were performed on 50 cats referred for routine OHE. The stage of the estrous cycle was determined by vaginal cytology and measurement of serum estradiol and progesterone levels was carried out to detect the cyclic changes in circulating GDF-9. One week after OHE, serum samples were collected again from 30 cats to reveal differences in GDF-9 levels. GDF-9 levels in the follicular phase were significantly higher than those in the interestrus (p⟨0.05). The postoperative analysis could be performed. GDF-9 levels slightly decreased one week after OHE (p=0.053). In conclusion, blood GDF-9 levels change during the estrous cycle, and may decrease with age in cats. However, further studies are needed to reveal the efficiency of GDF-9 in ORS diagnosis.

Relationship between serum vitamin D levels semen parameters and sperm DNA damage in men with unexplained infertility.

OBJECTIVE: The aim of the study was to investigate the relationship between serum level of vitamin D, semen analysis parameters and sperm DNA damage in men with unexplained subfertility. PATIENTS AND METHODS: Fifty-eight men diagnosed with unexplained infertility and 50 age and BMI matched fertile men were included in the study. A participant whose semen parameter is normal but pregnancy is not achieved was accepted as unexplained male infertility. Blood samples were taken from all participants following three-day abstinence for measurement of vitamin D. Sperm DNA damage was assessed by Aniline Blue staining of the collected samples. RESULTS: Compared with the fertile men, male patients with unexplained infertility had significantly lower vit D levels (27.00 ng/mL (12.63-39.30) vs. 23.66 ng/mL (7.50-55.00), p<0.004). While the number of patients with vitamin D levels lower than 20 ng/mL was 26 (44.8%) in the infertile group, it was recorded as 5 (10.0%) in the fertile group (p<0.001). DNA damage was found in 31.50% (9.0-71.0) of the infertile men and 26.00% (11.0-54.0) of the fertile men. DNA damage was found to be significantly higher in the unexplained infertile group (p<0.002). In men with unexplained male infertility, serum vit D levels were positively correlated with total sperm count (r = 0.527, p<0.001), total motility (r = 0.527, p<0.001) and sperm morphology (r = 0.416, p = 0.001). There was a negative and significant correlation between vit D levels and sperm DNA damage (r = -0.605, p<0.001). In the logistic regression analysis, serum vit D > 20 ng/mL led to an improvement in fertility outcome. CONCLUSIONS: Men with unexplained infertility exhibit decreased serum vit D levels and increased sperm DNA damage.

Duplication of the pituitary gland and basilar artery, with multiple midline fusion defects and craniofacial anomalies.

Duplication of the pituitary gland (DPG) is a phenomenon with no clear syndromic association. This case adds to the literature as a DPG-plus syndrome patient with multiple fusion defects of unknown etiology, fetal risk factors of first trimester tobacco usage and intrauterine drug exposure. An 8-month old female presented with noisy breathing, poor feeding, cleft palate, seizures and failure to thrive. MRI scan revealed duplicate pituitary gland, tubomammillary fusion, absent cleavage of brainstem and superior cerebellar peduncles, and cervical spinal malformations. We performed an airway evaluation, with a glossomandibulopexy for glossoptosis, and a primary palate repair.

Characteristics of Turkish children with Type 2 diabetes at onset: a multicentre, cross-sectional study.

AIMS: To describe the baseline clinical and laboratory findings and treatment modalities of 367 children and adolescents diagnosed with Type 2 diabetes in various paediatric endocrinology centres in Turkey. METHODS: A standard questionnaire regarding clinical and laboratory characteristics at onset was uploaded to an online national database system. Data for 367 children (aged 6-18 years) newly diagnosed with Type 2 diabetes at 37 different paediatric endocrinology centres were analysed. RESULTS: After exclusion of the children with a BMI Z-score < 1 SD, those with genetic syndromes associated with Type 2 diabetes, and those whose C-peptide and/or insulin levels were not available, 227 cases were included in the study. Mean age was 13.8 ± 2.2 (range 6.5-17.8) years, with female preponderance (68%). Family history of Type 2 diabetes was positive in 86% of the children. The mean BMI was 31.3 ± 6.5 kg/m2 (range 18.7-61) and BMI Z-score was 2.4 ± 0.8 (range 1-5). More than half (57%) of the children were identified by an opportunistic diabetes screening due to existing risk markers without typical symptoms of diabetes. Only 13% (n = 29) were treated solely by lifestyle modification, while 40.5% (n = 92) were treated with metformin, 13% (n = 30) were treated with insulin, and 33.5% (n = 76) were treated with a combination of insulin and metformin initially. Mean HbA1C levels of the insulin and combination of insulin and metformin groups were 98 (11.1%) and 102 mmol/mol (11.5%), respectively, and also were significantly higher than the lifestyle modification only and metformin groups mean HbA1C levels (70(8.6%) and 67 mmol/mol (8.3%), respectively). CONCLUSIONS: An opportunistic screening of children who are at high risk of Type 2 diabetes is essential, as our data showed that > 50% of the children were asymptomatic at diagnosis. The other important result of our study was the high rate of exclusion from the initial registration (38%), suggesting that accurate diagnosis of Type 2 diabetes in youth is still problematic, even for paediatric endocrinologists.

Fukushima radionuclides at air filter and rain water samples collected from Istanbul and their atmospheric removal time.

Accident at Fukushima Daiichi Nuclear Power Plant (FDNPP) is one of the most serious accident in the world after Chernobyl accident. Following the continuing release of radionuclides in air after FDNPP, traces of fission products ((131)I, (134)Cs and (137)Cs) were recorded in the air filter and rain water samples collected from the ÇNAEM area at Istanbul on 4 April 2011. Airborne particle samples were collected daily in air filters and radio assayed with a high purity germanium detector. The fission products (131)I, (134)Cs and (137)Cs were measured with the maximum activity concentrations of 1.03±0.08, 0.25±0.03 and 0.23±0.03 mBq m(-3), respectively. For determination of the origin of the releases the (134)Cs/(137)Cs ratio was calculated between 1.09 and 0.85. The authors find removal times for (137)Cs of 8.13 d, (134)Cs of 7.25 d and (131)I of 6.82 d.

Parity-induced changes in global gene expression in the human mammary gland.

The protective effect of an early first full-term pregnancy in relation to breast cancer risk is well established, but the molecular and cell-specific changes in the human mammary gland involved remain unclear. To identify the molecular changes associated with pregnancy-induced differentiation, we analysed the global gene expression profiles of normal mammary tissues from both a parous and a nulliparous woman, using serial analysis of gene expression. This approach allowed us to identify sets of genes, known and unknown, that are differentially expressed in parous versus age-matched nulliparous mammary gland tissues. The normal mammary gland of a multiparous woman is characterized by several known differentiation markers such as casein kappa, casein beta, keratin 14, CCAAT/enhancer binding protein beta and delta and adipsin. Candidate genes involved in cytoarchitectural remodelling and growth inhibition with a potential role in pregnancy-induced protection against breast cancer were also observed. Several genes that are highly expressed in the nulliparous mammary gland and that are lost after pregnancy, encode for growth promoting, cytoskeletal and extracellular matrix proteins. One of these genes, the small breast epithelial mucin, is almost completely downregulated upon a first full-term pregnancy but is known to be expressed in more than 90% of invasive ductal carcinomas.

Protein biomarkers for breast cancer prevention.

Protein biomarkers suitable for the prevention of breast cancer must be extremely sensitive, easily detectable and highly correlated with the disease. They should be expressed in the reversible phase of carcinogenesis. Among the large number of candidate tumour-associated proteins, those related to the oestrogen/chorionic gonadotropin/insulin pathway seem to be of most interest because these can be causally implicated. They presumably are the first to express differently and are open to hormonal treatments. The biomarkers that give information on membrane receptor-modulated signal transduction should be considered as well. Up to now, only tamoxifen has shown some preventive activity, suggesting that the oestrogen pathway is useful indeed. Fenretinide and recombinant human chorionic gonatotropin (hCG) are also promising. But the financial requirements and the very long assessment periods largely prevent current research. This is precisely why we badly need to give priority to molecular biology research, in particular in the protein compartment There is widespread belief that advanced proteomics together with increased informatics can provide specific combinations of disease-related expression profiles that could identify high-risk groups with much more reliability and allow us to monitor preventive strategies.

Distribution coefficients (Kd) and desorption rates of 137Cs and 241Am in Black Sea sediments.

The distribution coefficients (Kd) and desorption rates of 137Cs and 241Am radionuclides in bottom sediments at different locations in the Black Sea were studied under laboratory conditions. The Kd values were found to be 500 for 137Cs and 3800 for 241Am at the steady state and described exponential curves. Rapid uptake of the radionuclides occurred during the initial period and little accumulation happened after four days. The desorption rates for 137Cs in different bottom sediments were best described by a three-component exponential model. The desorption half-times of 137Cs ranged from 26 to 50 d at the slow components. However, the desorption rate of 241Am described one component for all sediment samples and desorption half-time was found to be 75 d. In general, the results showed that the 241Am radionuclide is more effectively transferred to bottom sediment and has longer turnover time than 137Cs under Black Sea conditions.

Heavy metals in organisms and sediments from Turkish Coast of the Black Sea, 1997-1998.

During the period 1997-1998, macroalgae, sea snail, mussel, fish and sediment samples were collected at different stations of the Turkish Black Sea coast in order to establish the concentration of selected heavy metals. Heavy metals analyzed were Cd, Co, Cr, Ni, Zn, Fe, Mn, Pb and Cu. The results showed that the Turkish Black Sea coast is facing heavy metal pollution. The metal concentrations in macroalgae, sea snail, mussel and sediment samples are very high. However, Cd, Pb and Cu concentrations in anchovy fish decreased, while Co, Fe, Zn, Cr, Mn and Ni contents had changed when compared previous data. The metal levels in macroalgae did not follow the same pattern as concentrations in sediments at the same station. On the other hand, concentrations of Cd, Co, Cr, Zn, Fe, Mn and Cu in sea snail, mussel and fish samples were related to sediment data in the examined stations.

Experimental studies on the biokinetics of 134Cs and 24Am in mussels (Mytilus galloprovincialis).

The biokinetics of 134Cs and 241Am in mussel species contaminated through water pathway has been studied under laboratory conditions. At equilibrium, the concentration factors for 134Cs and 241Am in small and large mussels were 2.80 and 2.57 and 200 and 150, respectively. The concentration factor of 134Cs in soft parts of the mussels was significantly high than whole body and shell tissue. However, the concentration factors of 241Am in soft parts and shell tissue samples were found to have similar rates. The depuration kinetics of the radionuclides were described by two-component exponential models. The biological half-lives at slow components between small and large mussels did not change significant, and were found to be 46.8-46.5 and 72.2-75.3 days for 134Cs and 241Am. The depuration kinetics of 134Cs and 241Am in soft parts described a single-component exponential model and the biological half-lives were found to be 29.4 and 41.1 days, respectively.

High frequency hearing loss in Ullrich-Turner syndrome.

UNLABELLED: A total of 38 patients with Ullrich-Turner syndrome underwent standard otological and audiometric evaluation as well as high frequency audiological tests. Some 26 (68.4%) patients had a history of middle ear infections, and ten (26.3%) had required otolaryngological surgery. Conventional audiometry (125-8000 Hz) demonstrated normal hearing in only 25 of the ears (33%); between 500-4000 Hz, 16 ears (21.0%) had a mixed type and eight ears (10.5%) had conductive hearing loss. High frequency audiometry (8-18 kHz) revealed sensorineural hearing loss in 98.7% of the ears. Our results for conventional audiometry are in accordance with the literature. CONCLUSION: The detection of a high prevalence of hearing loss in the high frequency range brings a significant new perspective to the pursuit of the aetiology of ear and hearing problems in Ullrich-Turner syndrome. This pathology seems to be a premature variant of presbycusis and it may underlie future hearing impairment which will come to clinical attention only after it progresses to conventional testing frequencies. While further studies are underway to evaluate this aspect, routine otological and audiological follow-up of patients with Ullrich-Turner syndrome is warranted from the time of diagnosis.

Eosinophils, major basic protein, and polycationic peptides augment bovine airway myocyte Ca2+ mobilization.

Previous studies in vivo or in isolated airway preparations have suggested that eosinophil-derived polycationic proteins enhance airway smooth muscle tone in an epithelium-dependent manner. We assessed the direct effects of activated human eosinophil supernatant, major basic protein (MBP), and polycationic polypeptides on basal and agonist-stimulated intracellular Ca2+ concentrations ([Ca2+]i) in cultured bovine tracheal smooth muscle (TSM) cells. A 1-h incubation of myocytes with activated eosinophil buffer resulted in a doubling of basal [Ca2+]i and increased responsivity to histamine compared with myocytes that were exposed to sham-activated eosinophil buffer. In addition, concentration-dependent acute transient increases and subsequent 1-h sustained elevations of basal [Ca2+]i were observed immediately after addition of MBP and model polycationic proteins. Finally, both peak and plateau [Ca2+]i responses to bradykinin addition were augmented significantly in cultured myocytes that had been exposed to low concentrations of MBP or model polycationic proteins but were inhibited at greater concentrations. This elevated [Ca2+]i to polycationic proteins was manifest in epithelium-denuded bovine TSM strips as concentration-dependent increased basal tone. We conclude that activated eosinophil supernatant, MBP, and other polycationic proteins have a direct effect on both basal and subsequent agonist-elicited Ca2+ mobilization in cultured TSM cells; TSM strips in vitro demonstrated, respectively, augmented and diminished responses to the contractile agonist acetylcholine. It is possible that alteration in myocyte Ca2+ mobilization induced by these substances may influence clinical states of altered airway tone, such as asthma.

Eagle's syndrome masquerading as pain of dental origin. Case report.

Eagle's syndrome, also known as elongated styloid process, is a condition that may be the source of craniofacial and cervical pain. It is infrequently reported but is probably more common than generally considered. The symptoms related to Eagle's syndrome can be confused with those attributed to a wide variety of facial neuralgias and/or oral, dental and TMJ diseases. In this paper, a case of Eagle's syndrome masquerading as pain of dental origin is presented and the literature is reviewed.

Familial intestinal polyatresia syndrome.

Familial multiple-level intestinal atresia is a rare syndrome with autosomal recessive inheritance. Only a few well-documented families have been reported in the medical literature. In this article two new cases from a consanguineous couple are presented. These are the first reported cases of Familial Intestinal Polyatresia Syndrome from Turkey. The importance of this report is that the recognition of multiple intestinal atresias as an invariably fatal syndrome will be helpful for genetic counselling and attempts at early prenatal diagnosis for successive pregnancies in these couples.

Sanfilippo disease type B. A case report and review of the literature on recent advances in bone marrow transplantation.

A patient with enzymatically proven Sanfilippo disease type B is presented. This type of mucopolysaccharidosis results from deficient o-N-acetylglucosaminidase activity leading to defective degradation of heparan sulphate. As this disease is associated with high morbidity and mortality, different therapeutic approaches are under investigation. Bone marrow transplantation is among these new choices of management. The value of bone marrow transplantation in the mucopolysaccharidoses, especially in MPS IIIB, is discussed with a wide review of the literature.