Melatonin in preservation solutions prevents ischemic injury in rat kidneys.

Transplantation is lifesaving and the most effective treatment for end-stage organ failure. The transplantation success depends on the functional preservation of organs prior to transplantation. Currently, the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) are the most commonly used preservation solutions. Despite intensive efforts, the functional preservation of solid organs prior to transplantation is limited to hours. In this study, we modified the UW solution containing components from both the UW and HTK solutions and analyzed their tissue-protective effect against ischemic injury. The composition of the UW solution was changed by reducing hydroxyethyl starch concentration and adding Histidine/Histidine-HCl which is the main component of HTK solution. Additionally, the preservation solutions were supplemented with melatonin and glucosamine. The protective effects of the preservation solutions were assessed by biochemical and microscopical analysis at 2, 10, 24, and 72 h after preserving the rat kidneys with static cold storage. Lactate dehydrogenase (LDH) activity in preservation solutions was measured at 2, 10, 24, and 72. It was not detectable at 2 h of preservation in all groups and 10 h of preservation in modified UW+melatonin (mUW-m) and modified UW+glucosamine (mUW-g) groups. At the 72nd hour, the lowest LDH activity (0.91 IU/g (0.63-1.17)) was measured in the mUW-m group. In comparison to the UW group, histopathological damage score was low in modified UW (mUW), mUW-m, and mUW-g groups at 10, 24, and 72 hours. The mUW-m solution at low temperature was an effective and suitable solution to protect renal tissue for up to 72 h.

Use of telomerase promoter mutations to mark specific molecular subsets with reciprocal clinical behavior in IDH mutant and IDH wild-type diffuse gliomas.

OBJECTIVE Recent studies have established that hemispheric diffuse gliomas may be grouped into subsets on the basis of molecular markers; these subsets are loosely correlated with the histopathological diagnosis but are strong predictors of clinical tumor behavior. Based on an analysis of molecular and clinical parameters, the authors hypothesized that mutations of the telomerase promoter (TERTp-mut) mark separate oncogenic programs among isocitrate dehydrogenase 1 and/or 2 (IDH) mutant (IDH-mut) and IDH wild-type (IDH-wt) diffuse gliomas independent of histopathology or WHO grade. METHODS Four molecular subsets of the combined statuses of IDH and TERT-promoter mutations (double mutant, IDH only, TERT only, and double negative) were defined. Differences in age, anatomical location, molecular genetics, and survival rates in a surgical cohort of 299 patients with a total of 356 hemispheric diffuse gliomas (WHO Grade II, III, or IV) were analyzed. RESULTS TERTp-mut were present in 38.8% of IDH-mut and 70.2% of IDH-wt gliomas. The mutational status was stable in each patient at 57 recurrence events over a 2645-month cumulative follow-up period. Among patients with IDH-mut gliomas, those in the double-mutant subset had better survival and a lower incidence of malignant degeneration than those in the IDH-only subset. Of patients in the double-mutant subset, 96.3% were also positive for 1p/19q codeletions. All patients with 1p/19q codeletions had TERTp-mut. In patients with IDH-mut glioma, epidermal growth factor receptor or phosphatase and tensin homolog mutations were not observed, and copy-number variations were uncommon. Among IDH-wt gliomas, the TERT-only subset was associated with significantly higher age, higher Ki-67 labeling index, primary glioblastoma-specific oncogenic changes, and poor survival. The double-negative subset was genetically and biologically heterogeneous. Survival analyses (Kaplan-Meier, multivariate, and regression-tree analyses) confirmed that patients in the 4 molecular subsets had distinct prognoses. CONCLUSIONS Molecular subsets result in different tumor biology and clinical behaviors in hemispheric diffuse gliomas.

Perchlorate Exposure Through Water and Milk in Istanbul.

Perchlorate is a chemical pollutant that inhibits iodide uptake and may possibly impair thyroid function. Our previous study found widespread perchlorate exposure in non-pregnant, non-lactating, healthy women residing in Istanbul. The aim of this study is to assess the relative amounts of perchlorate exposure attributable to consumption of municipal water, bottled water and boxed milk available in Istanbul. Only trace levels of perchlorate were found in treated municipal water (58 % detectable, mean = 0.13 µg/L, maximum = 0.75 µg/L) and bottled water (7.4 % detectable, mean = 

IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation.

The single nucleotide polymorphism rs55705857, located in a non-coding but evolutionarily conserved region at 8q24.21, is strongly associated with IDH-mutant glioma development and was suggested to be a causal variant. However, the molecular mechanism underlying this association has remained unknown. With a case control study in 285 gliomas, 316 healthy controls, 380 systemic cancers, 31 other CNS-tumors, and 120 IDH-mutant cartilaginous tumors, we identified that the association was specific to IDH-mutant gliomas. Odds-ratios were 9.25 (5.17-16.52; 95% CI) for IDH-mutated gliomas and 12.85 (5.94-27.83; 95% CI) for IDH-mutated, 1p/19q co-deleted gliomas. Decreasing strength with increasing anaplasia implied a modulatory effect. No somatic mutations were noted at this locus in 114 blood-tumor pairs, nor was there a copy number difference between risk-allele and only-ancestral allele carriers. CCDC26 RNA-expression was rare and not different between the two groups. There were only minor subtype-specific differences in common glioma driver genes. RNA sequencing and LC-MS/MS comparisons pointed to significantly altered MYC-signaling. Baseline enhancer activity of the conserved region specifically on the MYC promoter and its further positive modulation by the SNP risk-allele was shown in vitro. Our findings implicate MYC deregulation as the underlying cause of the observed association.

Perchlorate levels found in tap water collected from several cities in Turkey.

Perchlorate is an inorganic anion that inhibits iodide transport to the thyroid by sodium-iodide transporters. Because perchlorate is highly soluble, stable, and mobile in water, drinking water is a potential source of perchlorate exposure. When exposed to perchlorate, thyroid dysfunction can be observed in sensitive populations (pregnant woman, infants, and children), especially those with iodide deficiency. The aim of this study was to determine the perchlorate levels in tap water from five cities in Turkey. Perchlorate concentrations of 145 tap water samples collected from Ankara, Isparta, Istanbul, Kayseri, and Sakarya were determined by liquid chromatography-tandem mass spectrometry. Mean and median values were found to be 0.15 and 0.07 µg/L, respectively. The median values (25-75 % percentile) of Istanbul, Ankara, Sakarya, Isparta, and Kayseri were 0.08 µg/L (0.04-0.09 µg/L), 0.07 µg/L (0.07-0.21 µg/L), 0.04 µg/L (0.04-0.04 µg/L), 0.03 µg/L (0.02-0.07 µg/L), and 0.25 µg/L (0.23-0.31 µg/L), respectively. The median perchlorate level observed in Kayseri was significantly higher than those found at other cities (p < 0.05). Perchlorate concentrations in water samples were lower than the interim drinking water health advisory level (15 µg/L) determined by the US Environmental Protection Agency. This study showed that perchlorate in drinking water is not the main source of exposure in these cities. Future studies should be performed to determine perchlorate levels in other potential sources, such as food products.

Quantification of fibrin degradation products in glioma and meningioma patients.

BACKGROUND: DR-70 is an immunoassay for fibrin and FDP in plasma and it has been shown useful in detection of over 14 different cancers. This study investigated the validity of the DR-70 test in gliomas as well as meningiomas. METHODS: 77 brain tumor patients as well as 40 healthy individuals were prospectively included in the study and investigated using DR-70 kit. The glioma cohort of 33 patients consisted of 1, 11, 6 and 15 WHO grade 1, 2, 3 and 4 gliomas, respectively. The meningioma cohort of 44 patients contained 38, 5 and 1 WHO grade 1, 2 and 3 tumors. RESULTS: Test results were significantly higher than control values for both gliomas and meningiomas. The most balanced sensitivity and specificity values were obtained at cut-off level of 0.5 µg/ml FDP for both gliomas and meningiomas. Above this cutoff level the relative-risk for having a glioma was 5.1 times higher compared to controls with sensitivity and specificity of 76% and 85%, respectively. The relative-risk for meningioma was 5.8 with a sensitivity and specificity of 87% and 85%, respectively. CONCLUSION: FDP testing, which is a nonspecific cancer screening tool, is sensitive to the two most common primary brain malignancies, gliomas and meningiomas.

Iodine status in Turkish populations and exposure to iodide uptake inhibitors.

Perchlorate, nitrate, and thiocyanate are competitive inhibitors of the sodium iodide symporter of the thyroid membrane. These inhibitors can decrease iodine uptake by the symporter into the thyroid gland and may disrupt thyroid function. This study assesses iodine status and exposure to iodide uptake inhibitors of non-pregnant and non-lactating adult women living in three different cities in Turkey (Istanbul, Isparta and Kayseri). We measured iodine and iodide uptake inhibitors in 24-hr urines collected from study participants (N = 255). All three study populations were mildly iodine deficient, with median urinary iodine (UI) levels of 77.5 µg/L in Istanbul, 58.8 µg/L in Isparta, and 69.8 µg/L in Kayseri. Perchlorate doses were higher in the study population (median 0.13 µg/kg/day), compared with a reference population (median 0.059 µg/kg/day), but lower than the U.S. EPA reference dose (0.7 µg/kg/day). Urinary thiocyanate levels increased with increasing exposure to tobacco smoke, with non-smokers (268 µg/L) significantly lower than light smokers (1110 µg/L), who were significantly lower than heavy smokers (2410 µg/L). This pilot study provides novel data indicating that study participants were moderately iodine deficient and had higher intakes of the iodide uptake inhibitor perchlorate compared with a reference population. Further investigation is needed to characterize the thyroid impact resulting from iodine deficiency coupled with exposure to iodide uptake inhibitors such as perchlorate, thiocyanate and nitrate.