A systemic type I 5 alpha-reductase inhibitor is ineffective in the treatment of acne vulgaris

Excessive sebum production is a central aspect of the pathophysiology of acne vulgaris. Sebaceous gland function is under androgen control and it is hypothesized that dihydrotestosterone is formed by the action of 5 alpha-reductase. Type I is the controlling isoenzyme. This study describes a 3-month, multicenter, randomized, placebo-controlled clinical trial with a potent, selective inhibitor of type I 5 alpha-reductase used alone and in combination with systemic minocycline. Inhibition of type I 5 alpha-reductase was not associated with clinical improvement of acne when used alone and did not enhance the clinical benefit of systemic minocycline. These results indicate the need for further work at the molecular level to better understand the action of androgens on sebaceous gland function.     

A phytoplankton growth assay for routine in situ environmental assessments

This study proposes an ecologically relevant and cost-effective phytoplankton growth assay for routine in situ toxicity assessments. Assay procedures were developed applying, to the extent possible, the rationale behind the design of standard algal assays. Chlorella vulgaris was selected as test species because it grows well immobilized in alginate beads and has a wide geographic distribution. The performance of the assay in a freshwater system impacted by acid mine drainage demonstrated the suitability of assay chambers and procedures. The test system, made of inexpensive materials, allowed the rapid and easy deployment of the assay. The deployment of extra chambers at reference sites provided the ability to periodically check whether algal growth had already reached recommended growth criteria (time at which the assay should end). By deploying chambers filled with control medium at all sites, temperature was identified to explain 95% of the variation in growth. By using an artificial nutrient source shown capable of promoting algal growth according to recommended standards, toxicity from the mine effluent was distinguish from in situ nutrient limitation effects. The very good agreement (r2 = 90%) between mean in situ growth rates estimated by microscopy and by spectrophotometry and their similar coefficient of variation showed the latter to be a suitable straightforward methodology for assay endpoint estimation.     

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.     

Disability and profiles of functioning of patients with Parkinson's disease described with ICF classification

The objective of this study was to describe the functional profiles of patients with Parkinson's disease (PD), and the relationships between impairment in body functions, limitations in activities, and environmental factors, using the World Health Organization's International Classification of Functioning, Disability, and Health (ICF). Patients were consecutively enrolled, and the ICF checklist was administered. Two count-based indices were developed: 'extension', containing ICF categories rated with qualifiers 1-4 and 'severity', containing ICF categories rated with qualifiers 3-4. Categories rated with qualifiers 1-4 in at least 50% of patients are described separately. Spearman's correlation analysis was carried out to identify the relationships between impairments in body functions (BF) and body structures, activities and participation, and environmental factors (EF); linear regressions were performed to identify the best predictors of performance indices in activities and participation. A total of 96 patients were enrolled; 34 categories rated with qualifiers 1-4 in at least 50% of patients are reported, and most of them describe impairment in movement-related functions and limitations in mobility and self-care. Performance indices are significantly lower than capacity and significant relationships with both BF impairments and EF are observed. High difficulties in activities and participation performance are connected with both presence of severe BF symptoms and relevant barriers in EF. Both BF and EF play a relevant role in improving functioning of the patients with PD. The connection between EF barriers and severe problems in activities and participation performance suggests the need of fostering participation of patients with PD by promoting facilitators among EFs. Methodologies and tools are needed to couple information on symptoms, on the difficulties in executing activities, and on environmental features.