Matrix Metalloproteinases 2 and 9 Polymorphism in Patients With Myeloproliferative Diseases: A STROBE-Compliant Observational Study

Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling.The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases.Patients were selected from outpatient clinics of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people.DNA was isolated from peripheral blood. Using polymerase chain reaction–restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gln279Arg polymorphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates.In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-fibrosis provides a better understanding of the pathophysiology of PV and ET diseases and will allow new approaches to diagnosis and treatment.     

Estimation of phase signal change in neuronal current MRI for evoke response of tactile detection with realistic somatosensory laminar network model

Magnetic field generated by neuronal activity could alter magnetic resonance imaging (MRI) signals but detection of such signal is under debate. Previous researches proposed that magnitude signal change is below current detectable level, but phase signal change (PSC) may be measurable with current MRI systems. Optimal imaging parameters like echo time, voxel size and external field direction, could increase the probability of detection of this small signal change. We simulate a voxel of cortical column to determine effect of such parameters on PSC signal. We extended a laminar network model for somatosensory cortex to find neuronal current in each segment of pyramidal neurons (PN). 60,000 PNs of simulated network were positioned randomly in a voxel. Biot–savart law applied to calculate neuronal magnetic field and additional phase. The procedure repeated for eleven neuronal arrangements in the voxel. PSC signal variation with the echo time and voxel size was assessed. The simulated results show that PSC signal increases with echo time, especially 100/80 ms after stimulus for gradient echo/spin echo sequence. It can be up to 0.1 mrad for echo time = 175 ms and voxel size = 1.48 × 1.48 × 2.18 mm³. With echo time less than 25 ms after stimulus, it was just acquired effects of physiological noise on PSC signal. The absolute value of the signal increased with decrease of voxel size, but its components had complex variation. External field orthogonal to local surface of cortex maximizes the signal. Expected PSC signal for tactile detection in the somatosensory cortex increase with echo time and have no oscillation.     

Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats

The present investigation was aimed at studying the possible role of curcumin against N-nitrosodiethylamine (NDEA)-induced toxicity in albino rats. Administration of NDEA to rats at a concentration of 0.1 mg/ml in drinking water ad libitum for 21 days produced toxicity in them, which was evident from histopathological changes in the rat livers, and increased levels of blood serum enzyme markers, i.e. aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase. In addition, the levels of oxidative stress markers like lipid peroxidation (LPO), protein carbonyl (PCC), and glutathione-S-transferase (GST) activity were elevated and the total glutathione (GSH) content was reduced in the livers. The administration of curcumin to rats at concentrations of 10, 20, and 40 mg/ml in drinking water along with 0.1 mg/ml of NDEA for 21 days effectively suppressed NDEA-induced toxicity and also resulted in a dose-dependent reduction in the levels of blood serum enzyme markers (AST, ALT, ALP, and LDH). Moreover, LPO, PCC, and GST activity were reduced and the GSH level was increased upon the administration of curcumin along with NDEA. The results obtained for the comet assay in rat hepatocytes and blood lymphocytes showed a significant dose-dependent decrease in the mean tail length. The micronucleus assay performed on rat hepatocytes also showed a dose-dependent reduction in the frequency of micronucleated cells along with curcumin administration. These results suggest that curcumin has a protective role against NDEA-induced toxicity in albino rats.