Whole-brain N-acetylaspartate level and cognitive performance in HIV infection

BACKGROUND AND PURPOSE: In the brain of HIV-infected patients, proton MR spectroscopic studies are typically used to examine small volumes of tissue with single-voxel methods. Since brain disease is diffuse in patients with HIV, such studies preclude assessment of the true extent of the metabolic burden. To assess this extent, the relationship between global neuronal integrity, reflected by the whole-brain N-acetylaspartate (WBNAA) concentration, was correlated with neuropsychological function and the AIDS dementia complex (ADC) stage score. METHODS: WBNAA levels were compared between 15 HIV-infected patients (seven symptomatic, eight asymptomatic) and 13 age- and sex-matched healthy subjects. The patients' WBNAA level was correlated with cognitive performance, as measured with a battery of eight tests (NPZ-8), including the ADC stage score and four total-memory, mood, motor, and processing speed subtests. RESULTS: WBNAA levels were significantly different between patients and healthy subjects (mean +/- sigma, 11.82 +/- 1.40 and 12.91 +/- 1.03 mmol/L, respectively; P =.032) after we adjusted for age and sex effects. Intermediate negative correlations were found between the WBNAA level, the processing speed subtest score (r = -0.50, P =.03), and the ADC stage score (r = -0.44, P =.05). CONCLUSION: The WBNAA concentration complements brain atrophy data with information about the quality of the remaining neuronal and axonal tissue in patients with HIV infection. In HIV-infected patients, its correlation with processing speed and the ADC score indicates that the latter reflects pathologic deficits, which are extensive throughout the brain.     

Synthesis and investigation of alpha-hydroxy-N,N-didesmethyltamoxifen as a proximate carcinogen in the metabolic activation of tamoxifen

Tamoxifen is an adjuvant chemotherapeutic agent for the treatment of breast cancer and a chemoprotective agent for breast cancer prevention. Despite being beneficial in regard to breast cancer, tamoxifen is known to increase the risk of endometrial cancer and thromboembolic events in women; in addition, it induces liver tumors in rats and endometrial tumors in rats and mice. Tamoxifen and its metabolite, N-desmethyltamoxifen, are metabolically activated to DNA binding electrophiles through alpha-hydroxylation, followed by O-esterification, primarily via sulfation. In the present study, we have investigated whether a second desmethylated metabolite of tamoxifen, N,N-didesmethyltamoxifen, is also involved in the metabolic activation of this antiestrogen to a genotoxic species. Alpha-hydroxy-N,N-didesmethyltamoxifen was synthesized, further activated by sulfation, and then reacted with DNA. After enzymatic hydrolysis to deoxynucleosides, HPLC analysis indicated the formation of one major DNA adduct, which was characterized as (E)-alpha-(deoxyguanosin-N(2)-yl)-N,N-didesmethyltamoxifen. Using (32)P-postlabeling, in combination with HPLC, the same adduct was detected in liver DNA from rats treated intraperitoneally with alpha-hydroxy-N,N-didesmethyltamoxifen. In contrast, only a low extent of adduct formation could be found in rats administered N,N-didesmethyltamoxifen. These data indicate that although alpha-hydroxy-N,N-didesmethyltamoxifen can be converted to a genotoxin in rat liver, this pathway is a minor one in the metabolic activation of tamoxifen.     

Disruption of the Cys5-Cys7 disulfide bridge in the platelet glycoprotein Ibbeta prevents the normal maturation and surface exposure of GPIb-IX complexes

This work aimed at elucidating the molecular genetic defect in two related patients with Bernard-Soulier syndrome (BSS) phenotype. Flow cytometric analysis revealed undetectable levels of platelet glycoproteins (GP), Ibalpha and IX, although plasma glycocalicin was detectable in both cases. The complete sequencing of GPIbalpha, GPIbbeta, and GPIX revealed the presence of a single point mutation, a G to A substitution, in codon 30 of GPIbbeta, that changes Cys5 to Tyr. The parents and sibling of the patients, heterozygotes for this mutation, were asymptomatic and they all showed a reduced platelet content of GPIbalpha and GPIX. Transient transfection of the mutant GPIbalpha subunit failed to render surface expression of GPIbalpha and exerted a dominant-negative effect on the surface exposure of the GPIb-IX complex. Metabolic labelling and immunoprecipitation analysis of transfected cells indicated that [5Tyr]GPIbbeta may associate with GPIX and GPIbalpha, but the maturation of the GPIb-IX complex is impaired. Substitution of either Cys5 or Cys7 by Ala failed to show surface expression of GPIb-IX, suggesting that the Cys5- Cys7 disulfide loop in GPIbbeta is essential for the efficient processing and trafficking of GPIb-IX complexes toward the plasma membrane. Our findings indicate that the identified novel GPIbbeta mutation is responsible for the BSS phenotype of the patients and provide an explanation for the molecular mechanism underlying the reduced platelet content of GPIb-IX complex in the heterozygous individuals.     

Informal care and nurses. Relations inside the hospital

The prolongation of a hospital stay or chronic illness in a family may cause a severe deterioration in the health of informal caretakers; therefore, it is necessary that professionals who work in formal institutions act as consultants and that they optimize informal caretakers' abilities so that they learn not only how to care for their ill relatives but also so that they care for themselves. Nonetheless, health centers, who concentrate on the ill patients, do not always consider informal caretakers as part of a family context which bears direct influence on the well-being and health of these people. In this article, the author proposes to: know the relationship models which the professional nursing team establishes with caretakers in the hospital environment; identify the strengths and weaknesses of caretakers, nursing professionals and institutions in order to establish a model for capacity-collaboration relationship. The methodology used was of a qualitative nature, utilizing discussion groups with professionals and semi-structured interviews with caretakers selected from among those who were found in the hospital. We could conclude that in the majority of the wards in the "HMQ" hospital, the patients are considered passive receptors of professional care and their families are left to the side. A model for capacity-collaboration relationship does not appear viable in HMQ due to the presence of certain weaknesses. However, there are certain strengths which could be fortified; these include the desire of the caretakers and the conviction among professionals of the benefits which such a relationship model would provide.     

Gene encoding the prothoracicotropic hormone of a moth is expressed in the brain and gut

The molts of lepidopteran insects are typically controlled by the brain-derived prothoracicotropic hormone (PTTH) that stimulates ecdysteroidogenesis in the prothoracic glands (PGs). We report here that the larvae and pupae of the moth Sesamia nonagrioides can molt without brain (PGs must be present), suggesting that there might be a secondary source of PTTH. We addressed this issue by characterizing spatial and temporal expression patterns of the PTTH gene. To this end we identified a major part of the corresponding cDNA. Protein deduced from this cDNA fragment consisted of 128 amino acids and showed 48-85% homology with the matching regions of PTTHs known from other Lepidoptera. Quantification of PTTH expression in major body organs of the last instar larvae revealed high expression in the brain (fading in post-feeding larvae) and considerable expression in the gut (with a maximum in post-feeding larvae). The content of PTTH message in the gut was enhanced after decapitation. It is concluded that the molts of S. nonagrioides larvae are driven by PTTH gene expression in the gut.     

Influence of oenological practices on the formation of biogenic amines in quality red wines

Changes in the contents of biogenic amines (histamine, putrescine, tyramine, cadaverine, agmatine, ethylamine, isobutylamine, phenyletilamine, isoamylamine, serotonine and tryptamine) were studied during the winemaking process of quality red wines, including an organic wine. The analytical method used was validated in terms of linearity, precision, coefficient of variation and recovery. The limits of detection and quantification of the amines were also calculated. The method involved pre-column automated derivatisation of the amines by treatment with o-phthalaldehyde, after which the derivatives formed were analysed by reverse-phase HPLC. Results showed that grape must already contains biogenic amines and this content tends to increase throughout winemaking and maturation. The organic wine showed higher levels of biogenic amines than the non-organic wine. The fact that malolactic fermentation occurs spontaneously in organic wines, together with low levels of SO₂ because of legal restrictions, could be responsible for the higher levels in biogenic amines found. For the non-organic wine, 2 oenological practices could increase the content in biogenic amines: the addition of press wine to the free run wine, and the treatment with yeast mannoproteins.     

Congenital anomalies of the inferior vena cava: Embryogenesis and MR features

This article describes the MR appearances of the six most common congenital anomalies of the inferior vena cava. As a basis for understanding those anomalies, it describes the embryology of the inferior vena cava, based on an actual study of embryos and fetuses. The article takes a fresh look at the original research in this area, discusses the possible embryogenesis of the relevant anomalies, and describes different opinions on that subject, where different opinions exist.