A possible specific receptor for 3-beta-androstanediol in the human sebaceous gland

Dihydrotestosterone (DHT) does not seem to be the active specific metabolite of testosterone in hypertrophic sebaceous glands of subjects affected by male pattern baldness (MPB) and several results indicate that probably 3-beta-androstanediol (beta DIOL) could be an active form of testosterone in those glands. Cytosol and serum from several patients affected by MPB and subjected to hair autotransplantation, was incubated with both beta DIOL and 3-alpha-androstanediol (alpha DIOL). Binding patterns indicate that alpha DIOL binds to cytosolic proteins probably due to the contaminating sex hormone binding globulin (SHBG), whereas beta DIOL exhibits an atypical binding process in cytosol in the presence of high concentrations of non radioactive beta DIOL. This binding increases progressively up to 2 pmol/mg protein at the limit solubility conditions for the non radioactive steroid. This pattern is not observed in serum from the same patients, where the binding of beta DIOL is typically restricted to the SHBG. These results strongly suggest the existence of a specific beta DIOL-binding protein in the hypertrophic sebaceous glands and explain the lack of specific receptor for DHT in these tissues.     

Free radical production in aortic rings from rats fed a fish oil-rich diet

To study the effect of the degree of unsaturation of dietary fatty acids on the production of free radicals and on the vascular smooth muscle tone in rings of the aorta, Sprague-Dawley rats were fed a semipurified diet containing 5% lipids from either corn oil (CO) or menhaden oil (MO) for 8 wk. The MO diet did not change the basal or NADPH-dependent superoxide anion (O2-*) release. There were no significant differences in phenylephrine-induced contractions between the two groups in intact rings. However, these contractions increased in endothelium-intact aortic rings from the MO group after addition of the nitric oxide (*NO) synthase inhibitor NG-nitro-L-arginine and in endothelium-denuded rings, both indicating a greater endothelial basal *NO production in rats fed with the MO diet. Endothelium-dependent relaxations in response to acetylcholine were more prominent in rings from the MO group. These differences were not due to an increased smooth muscle response to.NO, because relaxations were the same using an exogenous *NO donor. Our results indicate that dietary MO did not modify O2-* release by the vessel wall or relaxation due to the cyclooxygenase pathway, but it potentiated endothelial production of *NO.     

Molecular systematics of South American dolphins Sotalia: sister taxa determination and phylogenetic relationships, with insights into a multi-locus phylogeny of the Delphinidae

The evolutionary relationships among members of the cetacean family Delphinidae, the dolphins, pilot whales and killer whales, are still not well understood. The genus Sotalia (coastal and riverine South American dolphins) is currently considered a member of the Stenoninae subfamily, along with the genera Steno (rough toothed dolphin) and Sousa (humpbacked dolphin). In recent years, a revision of this classification was proposed based on phylogenetic analysis of the mitochondrial gene cytochrome b, wherein Sousa was included in the Delphininae subfamily, keeping only Steno and Sotalia as members of the Stenoninae subfamily. Here we investigate the phylogenetic placement of Sotalia using two mitochondrial genes, six autosomal introns and four Y chromosome introns, providing a total of 5,196 base pairs (bp) for each taxon in the combined dataset. Sequences from these genomic regions were obtained for 17 delphinid species, including at least one species from each of five or six currently recognized subfamilies plus five odontocete outgroup species. Maximum Parsimony, Maximum Likelihood and Bayesian phylogenetic analysis of independent (each fragment) and combined datasets (mtDNA, nuDNA or mtDNA+nuDNA) showed that Sotalia and Sousa fall within a clade containing other members of Delphininae, exclusive of Steno. Sousa was resolved as the sister taxon to Sotalia according to analysis of the nuDNA dataset but not analysis of the mtDNA or combined mtDNA+nuDNA datasets. Based on the results from our multi-locus analysis, we offer several novel changes to the classification of Delphinidae, some of which are supported by previous morphological and molecular studies.     

A new family of quinoline and quinoxaline analogues of combretastatins

The 3-hydroxy-4-methoxyphenyl ring of combretastatin A-4 can be replaced by a 2-naphthyl moiety without significant loss of cytotoxicity and inhibition of tubulin polymerization potency. In this paper we show that the 6- or 7-quinolyl systems can in turn replace both cyclic moieties, keeping in the first case most of the potency as cytotoxic agent and in the second case as inhibitor of tubulin polymerization, related to the activities displayed by model compounds.     

Viral safety characteristics of Flebogamma® DIF,a new pasteurized,solvent-detergent treated and Planova 20 nm nanofiltered intravenous immunoglobulin

A new human liquid intravenous immunoglobulin product, Flebogamma^® DIF, has been developed. This IgG is purified from human plasma by cold ethanol fractionation, PEG precipitation and ion exchange chromatography. The manufacturing process includes three different specific pathogen clearance (inactivation/removal) steps: pasteurization, solvent/detergent treatment and Planova? nanofiltration with a pore size of 20 nm. This study evaluates the pathogen clearance capacity of seven steps in the production process for a wide range of viruses through spiking experiments: the three specific steps mentioned above and also four more production steps. Infectivity of samples was measured using a Tissue Culture Infectious Dose assay (log₁₀ TCID₅₀) or Plaque Forming Units assay (log₁₀ PFU). Validation studies demonstrated that each specific step cleared more than 4 log₁₀ for all viruses assayed. An overall viral clearance between ≥13.33 log₁₀ and ≥25.21 log₁₀, was achieved depending on the virus and the number of steps studied for each virus. It can be concluded that Flebogamma^® DIF has a very high viral safety profile.     

Oxidative damage in the livers of senescence-accelerated mice: a gender-related response

The prevalence of liver diseases emphasizes the need of animal models to research on the mechanism of disease pathogenesis. Furthermore, most of the liver pathologies have the oxidative stress as an important component. The senescence-accelerated mouse strain SAMP8 was proposed as a valuable animal model for the study of liver diseases. To gain a better understanding of the mechanisms underlying degenerative processes in SAMP8 mice livers, we studied the oxidative-induced damage in 5-month-old SAMP8 mice and SAMR1, senescence-accelerated-resistant mice. We found profound differences in the antioxidant response to aging between sexes, with males displaying lowest levels of main antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR) in SAMP8; whereas females had no difference in their activities, except for GR, when compared with their SAMR1 controls. The results obtained show the binomial SOD/CAT as an important factor for counteracting reactive oxygen species-dependent damage. There were not pathological differences at the morphological level between both strains, although the decay in protection against free radicals had an immediate response by increasing lipid and protein oxidative damage in SAMP8 mice liver. At 5 months, both male and female SAMP8 mice confront the oxidative stress challenge to different extents. Indeed, proteins seem to be the most vulnerable biomolecule in SAMP8 male mice.     

Structural requirements of astrovirus virus-like particles assembled in insect cells

Expression of the complete ORF2 of human astrovirus serotype 1 (HAstV-1) in the baculovirus system led to the formation of virus-like particles (VLPs) of around 38 nm. The same kind of VLPs were also obtained either with the expression of a truncated form of ORF2 lacking the first 70 amino acids (aa), or with the same truncated form in which those 70 aa were replaced by the green fluorescent protein. All three kinds of VLPs were equally recognized by an anti-HAstV-1 polyclonal antibody and by two monoclonal antibodies (MAbs; 8E7 and 5B7), indicating a nonessential role of those amino acids neither in the capsid assembly nor in the antigen structure. A second type of structure consisting of 16-nm ring-like units was observed in all of the cases, mostly after disassembling the 38-nm VLPs through the addition of EDTA. The removal of the EDTA and the addition of Mg(2+) ions promoted the reassembly of the 38-nm VLPs. The nature of these 16-nm ring-like structures, capsomers or T = 1 VLPs, still remains unclear. Biochemical analysis revealed no differences between the 38-nm VLPs and the 16-nm structures, whereas antigenically, they shared the 8E7 MAb epitope but differed in the 5B7 MAb epitope, with the latter structures being more readily recognized.     

Estimation of genetic purging under competitive conditions

Inbreeding depression for fitness traits is a key issue in evolutionary biology and conservation genetics. The magnitude of inbreeding depression, though, may critically depend on the efficiency of genetic purging, the elimination or recessive deleterious mutations by natural selection after they are exposed by inbreeding. However, the detection and quantification of genetic purging for nonlethal mutations is a rather difficult task. Here, we present two comprehensive sets of experiments with Drosophila aimed at detecting genetic purging in competitive conditions and quantifying its magnitude. We obtain, for the first time in competitive conditions, an estimate for the predictive parameter, the purging coefficient (d), that quantifies the magnitude of genetic purging, either against overall inbreeding depression (d ≈ 0.3), or against the component ascribed to nonlethal alleles (d_NL ≈ 0.2). We find that competitive fitness declines at a high rate when inbreeding increases in the absence of purging. However, in moderate size populations under competitive conditions, inbreeding depression need not be too dramatic in the medium to short term, as the efficiency of purging is also very high. Furthermore, we find that purging occurred under competitive conditions also reduced the inbreeding depression that is expressed in the absence of competition.