Can magnesium gluconate be used as an alternative therapy for preeclampsia?

Magnesium (Mg+2) in the body plays a structural and regulatory role and it is involved in fundamental cellular reactions. It is known that Mg+2 blood levels decrease during pregnancy, which has been related to preeclampsia and premature delivery, as well as other pathologies such as cardiovascular alterations and renal, gastrointestinal, neurological, and muscular dysfunctions among others. Mg+2 salts are used to treat its deficiency, and parenteral magnesium sulfate (MgSO4) is relatively effective in preeclampsia and eclampsia. The use of MgSO4 has the main disadvantage that it is mainly administered intravenously which leads to significant toxicity risks. Currently, other magnesium salts are being studied as alternative treatments. Magnesium gluconate (Mg-gluconate) has been used to prevent pregnancy-induced hypertension, showing a greater antioxidant capacity than MgSO4. Mg-gluconate can scavenge hydroxyl and alkoxyl radicals and it has been shown that it can inhibit lipid peroxidation in microsomal membranes treated in vitro with the Fenton reaction. Mg-gluconate seems to be an excellent candidate to replace MgSO4 as a therapy for preeclampsia with severe features.El magnesio (Mg+2) en el organismo, juega un papel estructural y regulador, y participa en reacciones celulares fundamentales. Se sabe que los niveles séricos de Mg+2 disminuyen durante el embarazo, lo cual se ha relacionado con la preeclampsia y el parto prematuro, así como con otras patologías como alteraciones cardiovasculares y disfunciones renales, gastrointestinales, neurológicas, musculares, entre otras. Las sales de Mg+2 se utilizan para tratar su deficiencia, y el sulfato de magnesio parenteral (MgSO4) ha demostrado ser relativamente eficaz en la preeclampsia y la eclampsia. El uso de MgSO4 tiene el principal inconveniente de que se administra principalmente por vía intravenosa, lo cual conlleva a riesgos importantes de toxicidad. Actualmente, se están estudiando otras sales de magnesio como tratamientos alternativos. El gluconato de magnesio (Mg-gluconato) se ha utilizado para prevenir la hipertensión inducida por el embarazo, mostrando una mayor capacidad antioxidante que el MgSO4. El Mg-gluconato es capaz de eliminar radicales hidroxilo y alcoxilo e inhibir la peroxidación lipídica en membranas microsomales tratadas in vitro con la reacción de Fenton. El Mg-gluconato parece ser un excelente candidato para sustituir al MgSO4 como terapia para la preeclampsia con características graves.Sociedad Argentina de Fisiologí

Minority and mode conversion heating in (3He)-H JET plasma

Radio frequency (RF) heating experiments have recently been conducted in JET (He-3)-H plasmas. This type of plasmas will be used in ITER's non-activated operation phase. Whereas a companion paper in this same PPCF issue will discuss the RF heating scenario's at half the nominal magnetic field, this paper documents the heating performance in (He-3)-H plasmas at full field, with fundamental cyclotron heating of He-3 as the only possible ion heating scheme in view of the foreseen ITER antenna frequency bandwidth. Dominant electron heating with global heating efficiencies between 30% and 70% depending on the He-3 concentration were observed and mode conversion (MC) heating proved to be as efficient as He-3 minority heating. The unwanted presence of both He-4 and D in the discharges gave rise to 2 MC layers rather than a single one. This together with the fact that the location of the high-field side fast wave (FW) cutoff is a sensitive function of the parallel wave number and that one of the locations of the wave confluences critically depends on the He-3 concentration made the interpretation of the results, although more complex, very interesting: three regimes could be distinguished as a function of X[He-3]: (i) a regime at low concentration (X[He-3] < 1.8%) at which ion cyclotron resonance frequency (ICRF) heating is efficient, (ii) a regime at intermediate concentrations (1.8 < X[He-3] < 5%) in which the RF performance is degrading and ultimately becoming very poor, and finally (iii) a good heating regime at He-3 concentrations beyond 6%. In this latter regime, the heating efficiency did not critically depend on the actual concentration while at lower concentrations (X[He-3] < 4%) a bigger excursion in heating efficiency is observed and the estimates differ somewhat from shot to shot, also depending on whether local or global signals are chosen for the analysis. The different dynamics at the various concentrations can be traced back to the presence of 2 MC layers and their associated FW cutoffs residing inside the plasma at low He-3 concentration. One of these layers is approaching and crossing the low-field side plasma edge when 1.8 < X[He-3] < 5%. Adopting a minimization procedure to correlate the MC positions with the plasma composition reveals that the different behaviors observed are due to contamination of the plasma. Wave modeling not only supports this interpretation but also shows that moderate concentrations of D-like species significantly alter the overall wave behavior in He-3-H plasmas. Whereas numerical modeling yields quantitative information on the heating efficiency, analytical work gives a good description of the dominant underlying wave interaction physics

Screening Feline Blood Donors for Bartonella henselae Infection: Comparison between Indirect Immunofluorescent Antibody Test (IFAT) and Polymerase Chain Reaction (PCR) Results

In order to minimize pathogen transmission, all blood do- nors should be appropriately screened for infectious agents. Screening for Bartonella spp. infection in feline blood donors is a recommended practice in veterinary blood banks across the world. The aim of this study was to compare results of an indirect immunofluorescence antibody test (IFAT) in identifying Bartonella henselae antibodies with the results of PCR amplification of Bartonella spp. DNA to establish the best IFAT cut off to identify non-bacteremic cats. A secondary aim of this study was to evaluate demographic and clinicopathologic factors that may be associated with Bartonella henselae infection status. From a population of stray cats in Milan city, 82 serum samples were evaluated by IFAT for Bartonella henselae antibodies and PCR was performed on 90 whole blood samples for amplification of Bartonella spp. DNA. A total of 14/82 (17.1%) samples were seropositive with an IFAT titer 651:64 (cut-off for infection). Bartonella spp. DNA was identified in 11/90 (12.2%) samples by PCR. Overall 20/90 (22.2%) infected cats were identified by either IFAT 651:64 and/or PCR-positive results. Hyperbetaglobulinemia (P=0.02) and originating from zone 2 of Milan city (P=0.03) were statistically associated with positive Bartonella infection status. The overall IFAT sensitivity was 50.0%, specificity 87.5%, positive predictive value 35.7% and negative predictive value was 92.65%. The ROC analysis showed that the area under the curve was 0.747 (P=0.0032) and that an IFAT cut off&lt;1:32 had the highest sensitivity in identifying Bartonella PCR-negative cats. When feline blood donors undergo serological screening for Bartonella henselae infection an IFAT cut off &lt;1:32 has the highest sensitivity for identifying non-bacteremic cats. However some serologically negative cats could be bacteremic and therefore screening of a feline blood donor using a combination of IFAT and PCR is recommended. Protein electrophoresis should be performed in all potential donor cats

Observation of Static Pictures of Dynamic Actions Enhances the Activity of Movement-Related Brain Areas

Physiological studies of perfectly still observers have shown interesting correlations between increasing effortfulness of observed actions and increases in heart and respiration rates. Not much is known about the cortical response induced by observing effortful actions. The aim of this study was to investigate the time course and neural correlates of perception of implied motion, by presenting 260 pictures of human actions differing in degrees of dynamism and muscular exertion. ERPs were recorded from 128 sites in young male and female adults engaged in a secondary perceptual task.Our results indicate that even when the stimulus shows no explicit motion, observation of static photographs of human actions with implied motion produces a clear increase in cortical activation, manifest in a long-lasting positivity (LP) between 350–600 ms that is much greater to dynamic than less dynamic actions, especially in men. A swLORETA linear inverse solution computed on the dynamic-minus-static difference wave in the time window 380–430 ms showed that a series of regions was activated, including the right V5/MT, left EBA, left STS (BA38), left premotor (BA6) and motor (BA4) areas, cingulate and IF cortex.Overall, the data suggest that corresponding mirror neurons respond more strongly to implied dynamic than to less dynamic actions. The sex difference might be partially cultural and reflect a preference of young adult males for highly dynamic actions depicting intense muscular activity, or a sporty context

A computational approach to identify whole genome homozygosity mapping across multiple SNP mapping experiments

The recent development of microarray platforms, capable to genotype more than thousands of single nucleotide polymorphisms (SNPs) in individuals, had provided an opportunity to rapidly identify susceptibility loci for complex phenotypes. High density SNP mapping arrays have been widely applied to association studies, to copy number (CN) analysis in cancers and recently to investigate the role of homozygosity extended regions in individuals. Long stretches of CN neutral and homozygous SNPs, defined as runs of homozygosity (ROHs) can be found either in a single individual or shared across samples. The identification of ROHs among affected individuals of the same family or among unrelated ones with same disease, can underline loci potentially implicated in the genetic basis of the disease under study. Therefore the identification of ROHs in affected individuals or pathological datasets gives a chance to identify disease associated loci and new causative mutations. In order to identify ROHs pattern across Affymetrix SNP mapping datasets, we developed a computational strategy including several computational steps: 1) loss of heterozygosity analysis by dChip2007 software; 2) a within-subject step allowing the identification of ROHs in a single sample; 3) an across-subject step extracting the ROH fingerprint of the dataset and 4) the identification of a common ROHs pattern based on frequency across the dataset under study, varying the number of individuals carrying common ROHs; 5) the annotation step allowing the association of genes to selected ROHs. In order to obtain an effective ROHs visualization, we use dChip software for the entire samples dataset. We assess our strategy to two SNP mapping datasets including 100K leukemia and 250K congenital recessive diseases. The procedure allowed the identification of a unique genetic ROH fingerprint of clinical datasets potentially important to discover new diseases associated loci suitable for further investigations

Integrated genomics analysis of gene and miRNA expression profiles in clear cell renal carcinoma cell lines

Clear cell renal cell carcinoma (ccRCC) is the most common and malignant tumor in the adult kidney, representing 75-80% of renal primary malignancies. Inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene, by mutation, deletion and promoter methylation, occurs in most sporadic ccRCCs and in all inherited cases. Recent evidences showed that microRNAs (miRNAs) are often dysregulated in many tumors, including ccRCC. We used Caki-1, Caki-2 and A498 cell lines as in vitro model of ccRCC pathology, and HK-2 (normal proximal tubular epithelial cell line) as reference sample. We characterized the VHL status by direct sequencing and the HIF status by western blot. Affymetrix microarray technology was applied to assess miRNA (onto GeneChip\uae miRNA Array) and gene expression profiles (onto GeneChip\uae Human Gene 1.0 ST Array). Analysis of common differentially expressed miRNAs (DEMs) in RCC cell lines outlined specific miRNAs to be involved in ccRCC and in cancer (e.g. miR-145, miR-29a, miR-342-3p, miR-205, miR-183, miR-197, miR-132, miR-146a and miR-34a). Functional enrichment analysis of common differentially expressed genes (DEGs) highlighted some genes involved in leucocyte transendothelial migration, focal adhesion and p53 signalling pathways (e.g. ATM, FER, CDC27 and GRB10). Additionally, we conducted an integrated analysis to combine gene and miRNA expression profiles and to reconstruct miRNA-gene post-transcriptional regulatory networks involved in RCC pathology. We also compared our expression data with RCC datasets publicly available from NCBI GEO microarray repository. We selected potentially interesting miRNAs and target genes for further validation (by qPCR). This integrated analysis approach may help to unravel the molecular complexity characterizing ccRCC biology, and it will facilitate the elucidation of regulatory circuits important for tumorigenesis and the biological processes under relevant post-transcriptional regulation in ccRCC

Answers and Solutions

Answers and solutions to the puzzles in this issue

Does the Reading of Different Orthographies Produce Distinct Brain Activity Patterns? An ERP Study

Orthographies vary in the degree of transparency of spelling-sound correspondence. These range from shallow orthographies with transparent grapheme-phoneme relations, to deep orthographies, in which these relations are opaque. Only a few studies have examined whether orthographic depth is reflected in brain activity. In these studies a between-language design was applied, making it difficult to isolate the aspect of orthographic depth. In the present work this question was examined using a within-subject-and-language investigation. The participants were speakers of Hebrew, as they are skilled in reading two forms of script transcribing the same oral language. One form is the shallow pointed script (with diacritics), and the other is the deep unpointed script (without diacritics). Event-related potentials (ERPs) were recorded while skilled readers carried out a lexical decision task in the two forms of script. A visual non-orthographic task controlled for the visual difference between the scripts (resulting from the addition of diacritics to the pointed script only). At an early visual-perceptual stage of processing (∼165 ms after target onset), the pointed script evoked larger amplitudes with longer latencies than the unpointed script at occipital-temporal sites. However, these effects were not restricted to orthographic processing, and may therefore have reflected, at least in part, the visual load imposed by the diacritics. Nevertheless, the results implied that distinct orthographic processing may have also contributed to these effects. At later stages (∼340 ms after target onset) the unpointed script elicited larger amplitudes than the pointed one with earlier latencies. As this latency has been linked to orthographic-linguistic processing and to the classification of stimuli, it is suggested that these differences are associated with distinct lexical processing of a shallow and a deep orthography

Changes in Early Cortical Visual Processing Predict Enhanced Reactivity in Deaf Individuals

Individuals with profound deafness rely critically on vision to interact with their environment. Improvement of visual performance as a consequence of auditory deprivation is assumed to result from cross-modal changes occurring in late stages of visual processing. Here we measured reaction times and event-related potentials (ERPs) in profoundly deaf adults and hearing controls during a speeded visual detection task, to assess to what extent the enhanced reactivity of deaf individuals could reflect plastic changes in the early cortical processing of the stimulus. We found that deaf subjects were faster than hearing controls at detecting the visual targets, regardless of their location in the visual field (peripheral or peri-foveal). This behavioural facilitation was associated with ERP changes starting from the first detectable response in the striate cortex (C1 component) at about 80 ms after stimulus onset, and in the P1 complex (100–150 ms). In addition, we found that P1 peak amplitudes predicted the response times in deaf subjects, whereas in hearing individuals visual reactivity and ERP amplitudes correlated only at later stages of processing. These findings show that long-term auditory deprivation can profoundly alter visual processing from the earliest cortical stages. Furthermore, our results provide the first evidence of a co-variation between modified brain activity (cortical plasticity) and behavioural enhancement in this sensory-deprived population