Loss of ATP Diphosphohydrolase Activity with Endothelial Cell Activation

Quiescent endothelial cells (EC) regulate blood flow and prevent intravascular thrombosis. This latter effect is mediated in a number of ways, including expression by EC of thrombomodulin and heparan sulfate, both of which are lost from the EC surface as part of the activation response to proinflammatory cytokines. Loss of these anticoagulant molecules potentiates the procoagulant properties of the injured vasculature. An additional thromboregulatory factor, ATP diphosphohydrolase (ATPDase; designated as EC 3.6.1.5) is also expressed by quiescent EC, and has the capacity to degrade the extracellular inflammatory mediators ATP and ADP to AMP, thereby inhibiting platelet activation and modulating vascular thrombosis. We describe here that the antithrombotic effects of the ATPDase, like heparan sulfate and thrombomodulin, are lost after EC activation, both in vitro and in vivo. Because platelet activation and aggregation are important components of the hemostatic changes that accompany inflammatory diseases, we suggest that the loss of vascular ATPDase may be crucial for the progression of vascular injury.     

Mannan-binding lectin-2 (MBL2) gene polymorphisms in prenatal and perinatal cytomegalovirus infections

Cytomegalovirus (CMV) is the leading cause of congenital infections among neonates. About 10% of newborns with such an infection have clinical symptoms at birth and about 1% of infected fetuses die due to developmental malformations. Mannan-binding lectin (MBL) is considered to be an important factor in innate immunity. Its deficiency is believed to predispose to various (including viral) infections. The aim of this study was to investigate the possible role of MBL2 gene polymorphisms in prenatal and perinatal CMV infections. The frequencies of MBL2 gene exon 1 mutations as well as MBL deficiency-associated variants (LXPA/O+O/O) among newborns with confirmed cytomegalovirus infection were not significantly lower than among non-infected individuals. The distribution of MBL2 haplotypes was similar between the groups studied. These data suggest MBL does not have a major influence on susceptibility to prenatal or perinatal CMV infections.     

Multiplex PCR for identification of herpes virus infections in adolescents

The aim of the study was to develop a multiplex PCR (mPCR) for a rapid and simultaneous detection of herpes simplex 1 (HSV-1), herpes simplex 2 (HSV-2), and human cytomegalovirus (HCMV) DNA in squamous oral cells obtained from adolescents. Accuracy of the method was tested in a group of 513 adolescents, almost 11% of subjects were positive for infection with herpes viruses. Correlations with gender, age, and place of residence were sought. A similar incidence of HSV-2 and HCMV was found (4.3% and 5.4%, respectively) and the incidence of HSV-1 was the lowest (1%) in the study group. Conversely to HSV-2, HCMV was detected mostly in the youngest individuals. The same occurrence of all viruses was observed in boys and girls. The mPCR method described is suggested as a useful tool for epidemiologic studies of active herpes infections.     

Daptomycin for eradication of a systemic infection with a methicillin-resistant-Staphylococcus aureus in a biventricular assist device recipient

The rate of infection in patients who require ventricular assist devices is estimated at more than 35%. Infections with multi-resistant organisms such as methicillin-resistant Staphylococcus aureus in ventricular assist device recipients are often difficult to treat and present a high mortality rate. Daptomycin is a new cyclic lipopeptide antibiotic, useful in gram-positive organisms resistant to standard treatment. We report a case of a 65-year-old man suffering from a dilatative cardiomyopathy and concomitant MRSA infection who received a biventricular assist device. The patient had MRSA sepsis develop resistant to conventional therapy, which was successfully treated with daptomycin.     

Behavioral characterization of GLT1 (+/-) mice as a model of mild glutamatergic hyperfunction

GLT1 is one of the major transporters responsible for maintenance of glutamate homeostasis in the brain. In the present study, glutamate transporter 1-deficient GLT1 homozygous (-/-) and heterozygous (+/-) mice were investigated with the intention that they may provide a model of hyperglutamatergic state resulting in various behavioral alterations. The GLT1 (-/-) mice had lower body and brain weight, mild neuronal loss in CA1 hippocampal region as well as focal gliosis and severe focal neuronal paucity in layer II of the neocortex. The short life-span of GLT1 (-/-) precluded us from systematic behavioral studies in these mice. In contrast, GLT1 (+/-) mice exhibiting a 59% decrease in GLT1 immunoreactivity in their brain tissue, showed no apparent morphological brain abnormalities, and their life-span was not markedly different from controls. Behaviorally, GLT1 (+/-) presented moderate behavioral alterations compared to their wildtype littermates, such as: mild sensorimotor impairment, hyperlocomotion (at 3 month of age only), lower anxiety (at 6 months), better learning of cue-based fear conditioning but worse context-based fear conditioning. Our results suggest that GLT1 (+/-) mice may serve as a potentially useful model to study neurodegenerative disease conditions with mild hyperglutamatergic activity.     

Role of fosB in behaviours related to morphine reward and spatial memory

The immediate early genes (IEGs) have been suggested to be implicated in mechanisms of addiction, as well as in learning and memory processes. fosB, which belongs to IEG, has been reported to have pleiotropic impact on response to psychoactive drugs, as well as motivational and stress-related behaviours. In the present study, we used mice with constitutive knock-out of fosB in order to study fosB role in mouse phenotype. We studied rewarding properties of morphine (10 mg/kg i.p.) in conditioned place preference (CPP) paradigm. Additionally, we studied fosB role in spatial memory and spatial working memory using elevated plus maze model of spatial learning (EPMSL) and delayed non-match to place task (DNMTP). In further studies, locomotor, depressive-like and anxiety-like behaviours were measured. Rewarding effects of morphine in fosB −/− mice were abolished whereas spatial learning was impaired. On the other hand, we found no significant differences in locomotor activity, depression-like and anxiety-like behaviours. In summary, our results indicate that mice lacking fosB are less sensitive to rewarding properties of morphine and display spatial memory impairment and suggest involvement of fosB and its proteins in motivational aspects of reinforcers as well as in learning and memory processes.