Telbivudine versus lamivudine in patients with chronic hepatitis B

BACKGROUND: Reducing hepatitis B virus (HBV) replication to minimal levels is emerging as a key therapeutic goal for chronic hepatitis B. METHODS: In this double-blind, phase 3 trial, 1370 patients with chronic hepatitis B were randomly assigned to receive 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy end point was noninferiority of telbivudine to lamivudine for therapeutic response (i.e., a reduction in serum HBV DNA levels to fewer than 5 log 10 copies per milliliter, along with loss of hepatitis B e antigen [HBeAg] or normalization of alanine aminotransferase levels). Secondary efficacy measures included histologic response, changes in serum HBV DNA levels, and HBeAg responses. RESULTS: At week 52, a significantly higher proportion of HBeAg-positive patients receiving telbivudine than of those receiving lamivudine had a therapeutic response (75.3% vs. 67.0%, P = 0.005) or a histologic response (64.7% vs. 56.3%, P = 0.01); telbivudine also was not inferior to lamivudine for these end points in HBeAg-negative patients. In HBeAg-positive and HBeAg-negative patients, telbivudine was superior to lamivudine with respect to the mean reduction in the number of copies of HBV DNA from baseline, the proportion of patients with a reduction in HBV DNA to levels undetectable by polymerase-chain-reaction assay, and development of resistance to the drug. Elevated creatine kinase levels were more common in patients who received telbivudine, whereas elevated alanine aminotransferase and aspartate aminotransferase levels were more common in those who received lamivudine. CONCLUSIONS: Among patients with HBeAg-positive chronic hepatitis B, the rates of therapeutic and histologic response at 1 year were significantly higher in patients treated with telbivudine than in patients treated with lamivudine. In both the HBeAg-negative and the HBeAg-positive groups, telbivudine demonstrated greater HBV DNA suppression with less resistance than did lamivudine. (ClinicalTrials.gov number, NCT00057265.) Copyright © 2007 Massachusetts Medical Society.published_or_final_versio

Biochemical and structural characterisation of a haloalkane dehalogenase from a marine Rhodobacteraceae

types: Journal Article; Research Support, Non-U.S. Gov'tCopyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. NOTICE: This is the author’s version of a work accepted for publication by Elsevier. Changes resulting from the publishing process, including peer review, editing, corrections, structural formatting and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in FEBS Letters Vol. 588, Issue 9, pp. 1616 – 1622 DOI: 10.1016/j.febslet.2014.02.056A putative haloalkane dehalogenase has been identified in a marine Rhodobacteraceae and subsequently cloned and over-expressed in Escherichia coli. The enzyme has highest activity towards the substrates 1,6-dichlorohexane, 1-bromooctane, 1,3-dibromopropane and 1-bromohexane. The crystal structures of the enzyme in the native and product bound forms reveal a large hydrophobic active site cavity. A deeper substrate binding pocket defines the enzyme preference towards substrates with longer carbon chains. Arg136 at the bottom of the substrate pocket is positioned to bind the distal halogen group of extended di-halogenated substrates.Wellcome TrustEPSRCHRMUniversity of ExeterBBSR

Light and brominating activity in two species of marine diatom

Marine organisms mediate the formation of volatile inorganic (e.g. HOBr) and organic halogens (e.g. CHBr3) and contribute to the sea-to-air emission of bromine and iodine. This air-sea halogen exchange has implications for atmospheric chemistry. It is important to establish the physiological function of halogen metabolism in key groups of marine organisms to permit predictive model development. In this study a series of laboratory experiments was performed to investigate the link between the availability of photosynthetically active radiation (PAR) and brominating activity, as measured by the bromination of phenol red, in two cold-water marine diatoms (Thalassiosira antarctica, CCAP 1085/25; Porosira glacialis, CCMP 668). Brominating activity in T. antarctica was found to change in response to short term changes in photon flux density and to have a strong positive linear relationship with gross photosynthetic rate up to 260 µmol O2 (mg chla)-1 hr-1. Experiments performed across multiple diel cycles showed that light-phase brominating activities in T. antarctica were a factor of 2.8 (±1.0) higher than those measured in the dark. Whilst P. glacialis showed no response to short term changes in PFD, measurements across a number of diel cycles revealed that light-phase brominating activities in this diatom were significantly higher than those in the dark by a factor of 1.3 (±0.3). The addition of 0.1 µM H2O2 to the medium of T. antarctica cultures led to a significant increase in brominating activity by a factor of 2.4 (±0.3) relative to no-addition controls but no such response was seen in P. glacialis. These results suggest that there is a link between PAR light availability and brominating activity in marine diatoms but that the nature of this relationship differs between species. By establishing a potential link with common ecosystem model state variables (light and photosynthesis) this work provides the first step towards developing a predictive capability for brominating activity in the marine environment. More work is needed to assess the potential for developing generalised parameterisations between PAR light availability and brominating activity in diatom species representative of a wider range of ocean regions

Tannins, Peptic Ulcers and Related Mechanisms

This review of the current literature aims to study correlations between the chemical structure and gastric anti-ulcer activity of tannins. Tannins are used in medicine primarily because of their astringent properties. These properties are due to the fact that tannins react with the tissue proteins with which they come into contact. In gastric ulcers, this tannin-protein complex layer protects the stomach by promoting greater resistance to chemical and mechanical injury or irritation. Moreover, in several experimental models of gastric ulcer, tannins have been shown to present antioxidant activity, promote tissue repair, exhibit anti Helicobacter pylori effects, and they are involved in gastrointestinal tract anti-inflammatory processes. The presence of tannins explains the anti-ulcer effects of many natural products

Patterns of Chemical Diversity in the Mediterranean Sponge Spongia lamella

The intra-specific diversity in secondary metabolites can provide crucial information for understanding species ecology and evolution but has received limited attention in marine chemical ecology. The complex nature of diversity is partially responsible for the lack of studies, which often target a narrow number of major compounds. Here, we investigated the intra-specific chemical diversity of the Mediterranean sponge Spongia lamella. The chemical profiles of seven populations spreading over 1200 km in the Western Mediterranean were obtained by a straightforward SPE-HPLC-DAD-ELSD process whereas the identity of compounds was assessed by comparison between HPLC-MS spectra and literature data. Chemical diversity calculated by richness and Shannon indexes differed significantly between sponge populations but not at a larger regional scale. We used factor analysis, analysis of variance, and regression analysis to examine the chemical variability of this sponge at local and regional scales, to establish general patterns of variation in chemical diversity. The abundance of some metabolites varied significantly between sponge populations. Despite these significant differences between populations, we found a clear pattern of increasing chemical dissimilarity with increasing geographic distance. Additional large spatial scale studies on the chemical diversity of marine organisms will validate the universality or exclusivity of this pattern

Evolutionary History of Cer Elements and Their Impact on the C. elegans Genome

We report the results of sequence analysis and chromosomal distribution of all distinguishable long terminal repeat (LTR) retrotransposons (Cer elements) in the Caenorhabditis elegans genome. Included in this analysis are all readily recognizable full-length and fragmented elements, as well as solo LTRs. Our results indicate that there are 19 families of Cer elements, some of which display significant subfamily structure. Cer elements can be clustered based on their tRNA primer binding sites (PBSs). These clusters are in concordance with our reverse transcriptase- and LTR-based phylogenies. Although we find that most Cer elements are located in the gene depauperate chromosome ends, some elements are located in or near putative genes and may contribute to gene structure and function. The results of RT-PCR analyses are consistent with this prediction

Siboglinid-Bacteria Endosymbiosis: A Model System for Studying Symbiotic Mechanisms

Siboglinid worms are a group of gutless marine annelids which are nutritionally dependent upon endosymbiotic bacteria.1,2 Four major groups of siboglinids are known including vestimentiferans, Osedax spp., frenulates and moniliferans.3–5 Very little is known about the diversity of bacterial endosymbionts associated with frenulate or monoliferan siboglinids. This lack of knowledge is surprising considering the global distribution of siboglinids; this system is likely among the most common symbioses in the deep sea. At least three distinct clades of endosymbiotic γ-proteobacteria associate with siboglinid annelids.6 Frenulates harbor a clade of γ-proteobacteria that are divergent from both the thiotrophic bacteria of vestimentiferans and monoliferans as well as the heterotrophic bacteria of Osedax spp.6,7 We also discuss priorities for future siboglinid research and the need to move beyond descriptive studies. A promising new method, laser-capture microdissection (LCM), allows for the precise excision of tissue regions of interest.8 This method, when used in concert with molecular and genomic techniques, such as Expressed Sequence Tag (EST) surveys using pyrosequencing technology, will likely enable investigations into physiological processes and mechanisms in these symbioses. Furthermore, adopting a comparative approach using different siboglinid groups, such as worms harboring thiotrophic versus methanotrophic endosymbionts, may yield considerable insight into the ecology and evolution of the Siboglinidae