María T. Collados

METABOLISM OF HOMOCYSTEINE AND ITS RELATIONSHIP WITH CARDIOVASCULAR DISEASE

Hyperhomocysteinemia, or the rise of plasmatic homocysteine levels above 15 μg/dL, is accepted nowadays as an independent risk factor for cardiovascular disease in men and women. Homocysteine (Hcy) is a non-protein forming aminoacid (aa) derivated from the loss of the methyl group, found within methionine. Methionine regenerates by retrieving the methyl radical from 5-methyltetrahydrofolate (5-MTHF) creating tetrahydrofolate (THF) which will then regenerate to 5-MTHF through the action of methylentetrahydrofolate reductase (MTHFR). This process is called remethylation. Alternatively, Hcy can follow the transsulfuration route, where through cystationine-β-syntetase (CBS), it irreversibly converted into cystationine, a precursor of cysteine, glutathione, and other substances that are finally excreted in the urine. Hyperhomocysteinemia results from inhibition of the remethylation route, or inhibition or saturation of the transsulfuration pathway. Main factors causally associated increased plasmatic Hcy are mutations of the enzymes MTHFR and CBS; varying nutritional and health states; demographic factors; and, others. The most accepted hypotheses about Hcy action in cardiovascular disease are direct endothelial and vessel wall damage; oxidative stress generation; and, stimulation of a procoagulant and proinflammatory state of blood components. Since hyperhomocysteinemia can be effectively treated with folic acid, prospective trials are underway to determine if folate therapy is required to lower Hcy levels in plasma. These studies also attempt to address the impact, if any, of folate therapy in the reduction of cardiovascular risk, and to demonstrate if hyperhomocysteinemia is actually an independent risk factor that can be effectively treated.

Internetwork magnetic field distribution from simultaneous 1.56

Aims. We study the contradictory magnetic field strength distributions retrieved from independent analyses of spectropolarimetric observations in the near-infrared (1.56 µm) and in the visible (630 nm) spectral ranges in internetwork regions. Methods. To solve this apparent controversy, we present simultaneous and co-spatial 1.56 µm and 630 nm observations of an internetwork area. The properties of the circular and linear polarization signals, as well as the Stokes V area and amplitude asymmetries, are discussed. As a complement, we also used inversion techniques to infer the physical parameters of the solar atmosphere. As a first step, the infrared and visible observations are analysed separately to check their compatibility. Finally, the simultaneous inversion of the two data sets is performed. Results. The magnetic flux densities retrieved from the individual analysis of the infrared and visible data sets are strongly correlated. The polarity of the Stokes V profiles is the same at co-spatial pixels in both wavelength ranges. This indicates that both 1.56 µm and 630 nm observations trace the same magnetic structures on the solar surface. The simultaneous inversion of the two pairs of lines reveals an internetwork full of sub-kG structures that fill only 2% of the resolution element. A correlation is found between the magnetic field strength and the continuum intensity: equipartition fields (B ∼ 500 G) tend to be located in dark intergranular lanes, whereas weaker field structures are found inside granules. The most probable unsigned magnetic flux density is 10 Mx/cm 2 .T he net magnetic flux density in the whole field of view is nearly zero. This means that both polarities cancel out almost exactly in our observed internetwork area.

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The use of oral anticoagulants (OA) is problematic due to its association with hemorrhagic complications. OA metabolism relies on the CYP2C9 complex. Genetic variations compromising metabolic competence of this complex may explain the risk of excessive and hazardous anticoagulation. A pharmacogenetics-based approach to this issue could be beneficial for choosing adequate dose and duration of treatment, in addition to having a better understanding of pharmacological interactions to which OA are susceptible. However, evidence from several basic and clinical studies indicates that both a complicated system of regulation of expression of multiple genes and the influence of a wide variety of epigenetic factors could be responsible for adverse drug reactions associated with the use of OA. Emphasis on understanding the gene–environment interactions could attain new paths to facilitate the use of these important drugs in the quotidian clinical practice.

m and 630 nm observations

During pregnancy there are hemostatic changes that result in a hypercoagulable state and can have thrombotic consequences. This condition can be aggravated in women who are carriers of congenital thrombophilic factors. This thrombotic tendency can manifest as thrombotic lesions in the placenta with compromise of utero-placental circulation, which are common characteristics present in obstetric complications, such as preeclampsia/eclampsia, miscarriage, fetal loss, intrauterine growth retardation, and abruptio placentae. In this paper we review data concerning about the association of congenital thrombophilia in pregnancy with obstetric complications, mainly preeclampsia and fetal loss, focusing in factor V Leiden and its related activated protein C resistance, prothrombin mutation G20210A and hyperhomocysteinemia related with C677T mutation of methylenetetrahydrofolate reductase. Although factor V Leiden has been the thrombophilic factor most studied, all three thrombophilic mutations have been related with obstetric complications; however, contradictory results about the specific association of each mutation with each type of obstetric complication are described. These discrepancies could obey to the ethnic difference of the studied groups, or to the fact that some studies were performed in closed populations with few migratory movement, where the genetic pool is relatively homogeneous, as well as the different inclusion and exclusion criteria. Even though this variability is present, the significance of recognizing true associations between these thrombophilic mutations and obstetric complications is essential in order to determine the likelihood of routinely screening for these conditions in pregnant women with risk factors for thrombosis and for carrying out specific prophylactic measures.

Pharmacogenetics of oral anticoagulants

A dysprothrombin designated prothrombin Segovia was isolated from the plasma of an individual with normal prothrombin antigen and prothrombin activity lesser than 25% of the control prothrombin activity. Activation by prothrombinase complex showed a lower amidolytic than clotting activity, which suggests a lesser generation of active intermediates than normal prothrombin. When prothrombin Segovia was activated by prothrombinase complex in the absence of factor Va, no thrombin formation was found by functional activities. SDS-PAGE analysis of the molecules derived by activation with prothrombinase complex, Taipan snake venom and Echis carinatus venom showed an accumulation of molecules not cleaved at bond Arg320-Ile321. This was more evident with Echis carinatus venom, which only acts on this bond. Our data suggest that the alteration of prothrombin Segovia impairs the scission of bond Arg320-Ile321.

Congenital Thrombophilia Associated to Obstetric Complications

We study the polar magnetism near an activity maximum when these regions change their polarity, from which it is expected that its magnetism should be less affected by the global field. To fully characterise the magnetic field vector, we use deep full Stokes polarimetric observations of the 15648.5 {\AA} and 15652.8 {\AA} FeI lines. We observe the north pole as well as a quiet region at disc centre to compare their field distributions. In order to calibrate the projection effects, we observe an additional quiet region at the east limb. We find that the two limb datasets share similar magnetic field vector distributions. This means that close to a maximum, the poles look like typical limb, quiet-Sun regions. However, the magnetic field distributions at the limbs are different from the distribution inferred at disc centre. At the limbs, we infer a new population of magnetic fields with relatively strong intensities (

Purification and characterization of a variant of human prothrombin : Prothrombin Segovia

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Magnetic topology of the north solar pole

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Correlation coefficients between several parameters and CD34+ cell yield in peripheral blood stem cell harvesting by apheresis.

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Characterization of von Willebrand factor in primary pulmonary hypertension

800 G), inclined by 30 deg with respect to the line of sight, and with an azimuth aligned with the solar disc radial direction. We propose that this new population at the limbs is due to the observation of unresolved magnetic loops as seen close to the limb. These loops have typical granular sizes as measured in the disc centre. At the limbs, where the spatial resolution decreases, we observe them spatially unresolved, which explains the new population of magnetic fields that is inferred. This is the first (indirect) evidence of small-scale magnetic loops outside the disc centre and would imply that these small-scale structures are ubiquitous on the entire solar surface. This result has profound implications for the energetics not only of the photosphere, but also of the outer layers since these loops have been reported to reach the chromosphere and the low corona.