Human liver S9 fractions: metabolism of dehydroepiandrosterone, epiandrosterone, and related 7-hydroxylated derivatives.

Dehydroepiandrosterone (DHEA) and 3beta-hydroxy-5alpha-androstan-17-one (epiandrosterone, EpiA) are both precursors for 7alpha- and 7beta-hydroxylated metabolites in the human brain. These 7-hydroxylated derivatives were shown to exert anti-glucocorticoid and neuroprotective effects. When these steroids are administered per os to humans, the first organ encountered is the liver, where extensive metabolism takes place. The objective of this work was to assess the cofactor dependence and metabolism of DHEA, EpiA, and their 7-hydroxylated derivatives in S9 fractions of human liver, using a radiolabeled steroid substrate for quantification and gas chromatography-mass spectrometry for identification. The best transformation yields were obtained with NADPH and were larger in female than in male. Results showed that both DHEA and EpiA mainly transformed into their 17beta-hydroxylated derivatives, 7- or 16alpha-hydroxylated metabolites under NAD(P)H conditions, and 5alpha-androstane-3,17-dione for EpiA under NAD(P)+ conditions. In turn, 7alpha-hydroxy-DHEA and 7beta-hydroxy-DHEA were partly transformed into each other via a 7-oxo-DHEA intermediate and were reduced into the 17beta-hydroxy derivative, respectively. The same type of transformations occurred for 7alpha-hydroxy-EpiA and 7beta-hydroxy-EpiA, except that no 7-oxo-EpiA intermediate was obtained. These findings determine the presence of enzymes responsible for the 7alpha- and 16alpha-hydroxylation in the human liver, the 11beta-hydroxysteroid dehydrogenase type 1 responsible for the oxidoreduction of the 7-hydroxylated substrates, and the 17beta-hydroxysteroid dehydrogenase responsible for the reduction of 17-oxo-steroids into 17beta-hydroxysteroids.     

Delayed effects of thallium in the rat brain: regional changes in lipid peroxidation and behavioral markers, but moderate alterations in antioxidants, after a single administration.

Thallium (Tl+) toxicity has been related with the generation of reactive oxygen species (ROS) and oxidative stress (OS) in the central nervous system. Since changes in endogenous antioxidant systems might contribute to acute Tl+-induced OS and neurotoxicity, in this study we measured the metal concentration and the levels of lipid peroxidation (LP) in different brain regions (hypothalamus (Ht); cerebellum (Ce); striatum (S); hippocampus (Hc) and frontal cortex (Cx)) in possible correlation with the content of reduced glutathione (GSH), the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), and the animal performance in behavioral tests, all evaluated after a single administration of thallium acetate (8 or 16 mg/kg, i.p.) to rats. Seven days after Tl+ administration, the metal was homogeneously and dose-dependently accumulated in all regions evaluated. LP was increased in Ht, Ce and S, while GSH was depleted in S. Cu,Zn-SOD activity was also decreased in Ht and S. All these changes occurred with 16 mg/kg dose and at 7 days after treatment, but not at 1 or 3 days. In addition, Tl+-treated animals exhibited general hypokinesis, but no changes were observed in spatial learning. Our findings suggest that a delayed response of the brain to Tl+ may be the result of its residual levels. Also, despite the regional alterations produced by Tl+ in LP and the limited changes in endogenous antioxidants, there is a correlation between the Tl+-induced oxidative damage and the affected behavioral tasks, suggesting that, although still moderate, Tl+ evokes neurotoxic patterns under the experimental conditions tested.     

Oftalmoplejía completa izquierda por metástasis ósea de cáncer de próstata

Prognosis in prostate cancer is determined, in greater part, by the presence of metastases. Bone metastases can occur in any part of the skeleton even, for example, at the base of the skull. We present a case of a 78 year old male who, in December 2001, presented with paralysis of the third cranial nerve. The NMR and CAT scans were normal and circulating levels of PSA were elevated. He was referred to the Urology Service where the treatment guidelines included complete androgen block. Subsequently, he developed retro-orbital pain, divergent strabismus and palpebral ptosis. CAT and NMR indicated a soft tissue mass at the sphenoid level. Treatment was Gamma Knife Radio-surgery. Since August 2004, in conjunction with the latest rise in PSA, the patient's general status deteriorated considerably and he was referred to the Oncology Service. there was an increase in the paralysis of the third, fourth and sixth cranial nerve (complete left ophthalmoplegia) and left-central facial paralysis. Metastases from prostate cancer can be disseminated via the lymphatic or the blood system. Currently, there are more metastases from large-size tumours. Metastases are critical in prostate cancer because of their adverse effect on the patient's survival. Measurements of circulating levels of prostate specific antigen and prostate acid phosphatase are very useful in the clinical diagnosis of the primary tumour, or its metastases.     

Modulatory effect of soy isoflavones on biochemical alterations mediated by TPA in mouse skin model.

Exposure to various carcinogenic agents along with other contributing factors increase the risk of cancer formation. The current study assesses the effect of soy isoflavones on the biochemical events associated with tumor promotion in mouse skin. 12-O-tetradecanoyl phorbol-13-acetate (TPA), a well-known tumor promoter on topical application depletes the reduced glutathione content (GSH) and down regulates the activities of its metabolizing enzyme, glutathione-S-transferase (GST) and the activities of antioxidant enzymes. However, the ornithine decarboxylase (ODC) activity and unscheduled DNA synthesis are elevated on single topical application of TPA to the dorsal cutaneous portions of the mice. Topical applications of soy isoflavones, half-an-hour prior to the application of TPA prevented the induction of ODC activity and DNA synthesis mediated by TPA (p < 0.01). The content of GSH, GST and antioxidant enzymes (p < 0.05) was also recovered significantly by soy isoflavones in a dose dependent manner. Parallel to these effects, pretreatment with the soy isoflavones also reduced hydrogen peroxide (H2O2) content (p < 0.05) at 1.0 and 2.0 microg/0.2 ml vehicle/animal. Therefore, we conclude that soy isoflavones are potentially protective against TPA induced biochemical alterations.     

Parents’ Nonstandard Work Schedules and Child Well-Being: A Critical Review of the Literature

This paper provides a comprehensive review of empirical evidence linking parental nonstandard work schedules to four main child developmental outcomes: internalizing and externalizing problems, cognitive development, and body mass index. We evaluated the studies based on theory and methodological rigor (longitudinal data, representative samples, consideration of selection and information bias, confounders, moderators, and mediators). Of 23 studies published between 1980 and 2012 that met the selection criteria, 21 reported significant associations between nonstandard work schedules and an adverse child developmental outcome. The associations were partially mediated through parental depressive symptoms, low quality parenting, reduced parent–child interaction and closeness, and a less supportive home environment. These associations were more pronounced in disadvantaged families and when parents worked such schedules full time. We discuss the nuance, strengths, and limitations of the existing studies, and propose recommendations for future research.     

Discriminative Aspects of SF-36 and QQL-EPM Related to Asthma Control

Aim. To study any discriminative properties of SF-36 and QQL-EPM in stable and non-controlled moderate asthmatic patients. Methods. A total of 63 asthmatic patients were assessed regarding asthma symptoms, FEV1 % predicted value, PEF, ED visits and hospitalizations, QQL-EPM and SF-36 questionnaires. Results. QQL-EPM highlighted significance in all domains to distinguish stable from non-controlled patients (p = 0.0001) while SF-36 was only significant in 3 of its 7 domains (p = 0.009). Conclusion. The study showed that the specific quality of life questionnaire for asthma (QQL-EPM) demonstrates better discriminative properties that characterize asthma control when compared with the more generic SF-36 questionnaire.     

Maternal education level and low birth weight: a meta-analysis

ObjectiveTo assess the association between maternal education level and birth weight, considering the circumstances in which the excess use of technology in healthcare, as well as the scarcity of these resources, may result in similar outcomes.MethodsA meta-analysis of cohort and cross-sectional studies was performed; the studies were selected by systematic review in the MEDLINE database using the following Key**words socioeconomic factors, infant, low birth weight, cohort studies, cross-sectional studies. The summary measures of effect were obtained by random effect model, and its results were obtained through forest plot graphs. The publication bias was assessed by Egger's test, and the Newcastle-Ottawa scale was used to assess study quality.ResultsThe initial search found 729 articles. Of these, 594 were excluded after reading the title and abstract; 21, after consensus meetings among the three reviewers; 102, after reading the full text; and three for not having the proper outcome. Of the nine final articles, 88.8% had quality ≥ six stars (Newcastle-Ottawa Scale), showing good quality studies. The heterogeneity of the articles was considered moderate. High maternal education showed a 33% protective effect against low birth weight, whereas medium degree of education showed no significant protection when compared to low maternal education.ConclusionsThe hypothesis of similarity between the extreme degrees of social distribution, translated by maternal education level in relation to the proportion of low birth weight, was not confirmed.