Different methylation levels in the KLF4, ATF3 and DLEC1 genes in the myometrium and in corpus uteri mesenchymal tumours as assessed by MS-HRM

Mesenchymal tumours of the corpus uteri comprise common benign lesions – leiomyomas and very rare malignant variants – sarcomas. It can be difficult to distinguish between the particular types of mesenchymal tumours pre-surgically. Primarily, leiomyomas and the very aggressive leiomyosarcomas can be easily misdiagnosed when using only imaging devices. Therefore, a reliable non-invasive marker for these tumour types would provide greater certitude for patients that the lesion remains benign. Our collection comprises 76 native leiomyomas, an equal number of healthy myometrium samples and 49 FFPE samples of various types of sarcomas. The methylation level was assessed by MS-HRM method and we observed differences in the methylation level between healthy, benign and (semi)malignant tissues in the KLF4 and DLEC1 genes. The mean methylation levels of leiomyomas compared to myometrium and leiomyosarcomas were 70.7% vs. 6.5% vs. 39.6 % (KLF4) and 66.1% vs. 14.08% vs. 37.5% (DLEC1). The ATF3 gene was differentially methylated in leiomyomatous and myometrial tissues with 98.1% compared to 76.6%. The AUC values of the predictive logistic regression model for discrimination between leiomyomas and leiomyosarcomas based on methylation levels were 0.7829 (KLF4) and 0.7719 (DLEC1). Finally, our results suggest that there should be distinct models for the methylation events in benign leiomyomas and sarcomas, and that the KLF4 and DLEC1 genes can be considered potential methylation biomarkers for uterine leiomyomas.     

Effects of ischemia and omeprazole preconditioning on functional recovery of isolated rat heart

Objective

The aim of this study was to compare protective effects of ischemic and potential protective effects of pharmacological preconditioning with omeprazole on isolated rat heart subjected to ischemia/reperfusion.

Methods

The hearts of male Wistar albino rats were excised and perfused on a Langendorff apparatus. In control group (CG) after stabilization period, hearts were subjected to global ischemia (perfusion was totally stopped) for 20 minutes and 30 minutes of reperfusion. Hearts of group II (IPC) were submitted to ischemic preconditioning lasting 5 minutes before 20 minutes of ischemia and 30 minutes of reperfusion. In third group (OPC) hearts first underwent preconditioning lasting 5 minutes with 100μM omeprazole, and then submitted 20 minutes of ischemia and 30 minutes of reperfusion.

Results

Administration of omeprazole before ischemia induction had protective effect on myocardium function recovery especially regarding to values of systolic left ventricular pressure and dp/dt max. Also our findings are that values of coronary flow did not change between OPC and IPC groups in last point of reperfusion.

Conclusion

Based on our results it seems that ischemic preconditioning could be used as first window of protection after ischemic injury especially because all investigated parameters showed continuous trend of recovery of myocardial function. On the other hand, preconditioning with omeprazole induced sudden trend of recovery with positive myocardium protection, although less effective than results obtained with ischemic preconditioning not withstand, we must consider that omeprazole may be used in many clinical circumstances where direct coronary clamping for ischemic preconditioning is not possible.     

Baseline leptin levels predict change in leptin levels during weight loss in obese breast cancer survivors

Leptin is an adipocyte-derived hormone involved in regulation of satiety, and it also appears to have a role in breast cancer risk. Leptin therefore might be a useful indicator of the potential preventive effects of weight loss in breast cancer survivors. In this study we examined whether the change in leptin levels could be predicted by weight loss in obese breast cancer survivors. The subjects in this study were participating in a randomized trial of an individualized approach towards weight loss in Detroit, MI. Breast cancer survivors (body mass index of 30-44 kg/m(2)) were enrolled and fasting blood samples were obtained for leptin analysis over 1 year of study. Leptin levels were available from at least two time points for 36 women, and weight change ranged from a gain of 11% to a loss of 25% of baseline weight. Using a repeated-measures regression model, both baseline leptin level and concurrent percent body fat were found to synergistically predict leptin levels. Thus, for women with the same body fat, those with higher baseline leptin levels are predicted to exhibit smaller decreases in leptin with weight loss. Similar results were obtained for body weight and body weight change, but the associations with body fat were stronger. Breast cancer survivors with initially higher leptin levels may differ with regard to regulation of change in leptin during weight loss resulting in relatively smaller changes in leptin with equivalent amounts of weight loss.     

Epilepsia partialis continua in children with fulminant subacute sclerosing panencephalitis

Various inflammatory diseases of central nervous system, including subacute sclerosing panencephalitis, could cause epilepsia partialis continua. Two boys with epilepsia partialis continua with onset in terminal phase of atypical subacute sclerosing panencephalitis have been reported. Children were not vaccinated against measles, and the second case had history of measles at an early age. In both cases, the onset of subacute sclerosing panencephalitis was characterized by altered behavior and cognitive decline with very fast mental and neurological deterioration. One boy was suffering from complex partial seizures and myoclonic jerks synchronous with periodic electroencephalographic pattern. Diagnosis was proved by increased titers of antimeasles antibodies in both serum and cerebrospinal fluid. In terminal phase of the disease, epilepsia partialis continua of localized group of the muscles was diagnosed, with good response to intravenous infusion of midazolam. Surface electroencephalographic recordings during epilepsia partialis continua did not show the epileptic discharges. During the terminal phase of the disease, no other type of seizures and movement disorders were recognized, except epilepsia partialis continua. In spite of the treatment, period from the onset of disease to death lasted less than 3 months, suggesting very fulminant course of subacute sclerosing panencephalitis.