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.     

Endogenous motion of liver correlates to the severity of portal hypertension

BACKGROUND Degree of portal hypertension(PH) is the most important prognostic factor for the decompensation of liver cirrhosis and death, therefore adequate care for patients with liver cirrhosis requires timely detection and evaluation of the presence of clinically significant PH(CSPH) and severe PH(SPH). As the most accurate method for the assessment of PH is an invasive direct measurement of hepatic venous pressure gradient(HVPG), the search for non-invasive methods to diagnose these conditions is actively ongoing.AIM To evaluate the feasibility of parameters of endogenously induced displacements and strain of liver to assess degree of PH.METHODS Of 36 patients with liver cirrhosis and measured HVPG were included in the casecontrol study. Endogenous motion of the liver was characterized by derived parameters of region average tissue displacement signal(dantero, dretro, d RMS) and results of endogenous tissue strain imaging using specific radiofrequency signal processing algorithm. Average endogenous strain μ and standard deviation σ of strain were assessed in the regions of interest(ROI)(1 cm × 1 cm and 2 cm × 2 cm in size) and different frequency subbands of endogenous motion(0-10 Hz and 10-20 Hz).RESULTS Four parameters showed statistically significant(P 0.05) correlation with HVPG measurement. The strongest correlation was obtained for the standard deviation of strain(estimated at 0-10 Hz and 2 cm × 2 cm ROI size). Three parameters showed statistically significant differences between patient groups with CSPH, but only dretro showed significant results in SPH analysis. According to ROC analysis area under the curve(AUC) of the σROI[0…10 Hz, 2 cm × 2 cm] parameter reached 0.71(P = 0.036) for the diagnosis of CSPH; with a cut-off value of 1.28 μm/cm providing 73% sensitivity and 70% specificity. AUC for the diagnosis of CSPH for μROI[0…10 Hz, 1 cm × 1 cm] was 0.78(P = 0.0024); with a cut-off value of 3.92 μm/cm providing 73% sensitivity and 80% specificity. Dretro parameter had an AUC of 0.86(P = 0.0001) for the diagnosis of CSPH and 0.84(P = 0.0001) for the diagnosis of SPH. A cut-off value of-132.34 μm yielded 100% sensitivity for both conditions, whereas specificity was 80% and 72% for CSPH and SPH respectively.CONCLUSION The parameters of endogenously induced displacements and strain of the liver correlated with HVPG and might be used for non-invasive diagnosis of PH.     

Ofloxacin plus Rifampicin versus Doxycycline plus Rifampicin in the treatment of brucellosis: a randomized clinical trial [ISRCTN11871179]

Background  

The combination therapies recommended by the World Health Organization for treatment of brucellosis are doxycycline plus rifampicin or doxycycline plus streptomycin. Although highly successful results have been obtained with these two regimens, relapse rates as high as 14.4%. The most effective and the least toxic chemotherapy for human brucellosis is still undetermined. The aim of the present study was to investigate the efficacy, adverse effects and cost of ofloxacin plus rifampicin therapy, and doxycycline plus rifampicin therapy and evaluate in the treatment of brucellosis.     

Surfactant-induced cell toxicity and cell lysis. A study using B16 melanoma cells

The effects of a variety of detergents (non-ionic, ionic and bile derivatives) on B16 melanoma cells have been examined. Two main effects can be clearly differentiated: loss of cell viability and cell lysis. Under our conditions, cell-surfactant interaction is highly dependent on the nature of the amphiphile (more specifically, on its critical micellar concentration). Loss of cell viability occurs at surfactant concentrations below the critical micellar concentration, i.e. the incorporation of detergent monomers into the cell membranes is enough to impair their barrier function, so that Trypan Blue is no longer actively secreted outside the cell. On the other hand, cell lysis only occurs at or near the critical micellar concentration of the detergent, i.e. when the bilayer-micelle transition may take place. Comparative studies using B16 cells and phospholipid vesicles indicate that the amount of detergent required to induce cell lysis is the same that produces disruption of the lipid bilayer. Thus, our results suggest that membranes are the primary target for the toxicologic effects of surfactants on cells. Moreover, they provide a rationale for the interpretation of other studies in this field: previous results from different laboratories are shown to fit very well our data.     

Application of classical and model-based spectral methods to ophthalmic arterial Doppler signals with uveitis disease

In this study, Doppler signals recorded from ophthalmic artery of 75 subjects were processed by PC-computer using classical and model-based methods. The classical method (fast Fourier transform) and three model-based methods (Burg autoregressive, moving average, least-squares modified Yule–Walker autoregressive moving average methods) were selected for processing ophthalmic arterial Doppler signals with uveitis disease. Doppler power spectra of ophthalmic arterial Doppler signals were obtained by using these spectrum analysis techniques. The variations in the shape of the Doppler spectra as a function of time were presented in the form of sonograms in order to obtain medical information. These Doppler spectra and sonograms were then used to compare the applied methods in terms of their frequency resolution and the effects in determination of uveitis disease.     

Effects of Lentinan on Cytotoxic Functions of Human Lymphocytes

The in vitro effects of lentinan on natural killer (NK), antibody-dependent cell-mediated cytotoxicity (ADCC), lectin-dependent cell-mediated cytotoxicity (LDCC) and mitogen-induced blast transformation were studied in patients with solid tumors and chroyic lymphocytic leukemia (CLL). NK activity was measured against Cr-labelled K-562 targets, ADCC against antibody-coated chicken red cells. LDCC and natural cell-mediated cytotoxicity (NCMC) was assessed using ³H-thymidine prelabelled HEp-2 targets. Mitogen (PHA-and Con A-) induced blast transformation was measured by thymidine incorporation.

Blastogenesis and LDCC was not influenced by lentinan. 1 μg/ml lentinan increased NCMC of tumor-bearing subjects. The most prominent enhancement of NK and ADCC activity was seen in CLL patients, where a dose-related increase was seen (from 0.01 to 1 μg/ml).