Clinical effectiveness of biologics in clinical practice

TNF inhibitors are currently considered both effective and cost-effective in patients with active rheumatoid arthritis (RA), particularly in patients who have not responded fully to methotrexate. There is substantial doubt about the cost-effectiveness of TNF inhibitors as initial treatment for active RA. New data from the National Data Bank for Rheumatic Diseases now question the current consensus in methotrexate failures. The data suggest that in routine clinical practice TNF inhibitors provide only modest incremental benefits over best conventional therapy. If confirmed, these observational studies suggest that the economic argument underpinning the widespread use of TNF inhibitors in established RA is unsustainable.     

Mayday - integrative analytics for expression data

Background  

DNA Microarrays have become the standard method for large scale analyses of gene expression and epigenomics. The increasing complexity and inherent noisiness of the generated data makes visual data exploration ever more important. Fast deployment of new methods as well as a combination of predefined, easy to apply methods with programmer's access to the data are important requirements for any analysis framework. Mayday is an open source platform with emphasis on visual data exploration and analysis. Many built-in methods for clustering, machine learning and classification are provided for dissecting complex datasets. Plugins can easily be written to extend Mayday's functionality in a large number of ways. As Java program, Mayday is platform-independent and can be used as Java WebStart application without any installation. Mayday can import data from several file formats, database connectivity is included for efficient data organization. Numerous interactive visualization tools, including box plots, profile plots, principal component plots and a heatmap are available, can be enhanced with metadata and exported as publication quality vector files.     

Is the mitochondrial precursor protein apocytochrome c able to pass a lipid barrier?

To obtain insight into the role of lipids in the translocation of extramitochondrially synthesized proteins, we studied the ability of apocytochrome c to pass lipid bilayers. With polyacrylamide gel electrophoresis, the digestion of externally added apocytochrome c by trypsin, enclosed in lipid vesicles, was followed. The experiments demonstrate that apocytochrome c is able to pass a lipid barrier and this process shows both a lipid- and protein specificity. The most probable molecular mechanisms involved in this phenomenon are discussed.     

Suppression of antibody synthesis to dinitrophenylated bovine gamma globulin in contact-sensitized guinea pigs.

The anti-DNP response to DNP-BGG is substantially suppressed in guinea pigs sensitized to DNCB. The degree of antibody suppression varies with the mode of skin sensitization and with the degree of conjugation of the challenging immunogen. Suppression of the anti-HSA response was also induced by the prior injection of CFA.     

Electroencephalographic changes in the lateral septum complex following systemic administration of DES-TYR1 -α-endorphin,Des-Tyr1-γ-endorphin and haloperidol in rats

The influence of systemically administered Des-Tyr¹-α-endorphin (DTαE), Des-Tyr¹-γ-endorphin (DTγE) and haloperidol on electroencephalographic (EEG) activity of the lateral septum complex (LSC) and the frontal cortex was studied in male rats. DTαE (2 μg) significantly increased whereas DTγE (10 μg) significantly decreased the amounts of activity in the 5 Hz band. In addition, DTαE promoted production of 15 - 20 Hz activity, while DTγE decreased the amount of 20 - 30 Hz activity. EEG activity exhibited a marked variability which persisted throughout the recording session following administration of the peptides. Haloperidol markedly decreased the proportion of 10 - 15 Hz activity. The alterations in EEG of the frontal cortex were similar to those in LSC but less pronounced. The differences in the time course and frequency bands affected suggest that the effects of peptides and haloperidol on EEG activity of LSC are not mediated by the same mechanisms.     

The Effects of Copper Sulfate on Liver Histology and Biochemical Parameters of Term Ross Broiler Chicks

Copper is an essential trace element that is extremely toxic to organisms and organs at high doses. We have investigated the histological and biochemical effects of a toxic dose of copper sulfate on the liver of term Ross broiler chicks. Fertilized eggs were divided into three groups: experimental, injected with 50 mcg/0.1 ml copper sulfate in the air chambers on day 1; sham, injected with 0.1 ml saline; and control, no injection. Term chicks were killed and their livers investigated histologically, with hematoxylin–eosin-stained sections examined under light microscopy, and biochemically, for malondialdehyde and glutathione levels. Histological examinations showed copper-treated samples with granular degeneration and necrosis of hepatocytes and impairment to the cell lining of the remark cords. The samples had a congestive appearance, with blood in the vena centralis and sinusoids, slight connective tissue increase, and lymphocyte infiltration. Control and sham group sections had normal appearances. As oxidative damage parameters, in the copper-treated group, malondialdehyde levels were increased and glutathione levels decreased. In the sham and control groups, there were no significant differences. At this toxic dose, copper sulfate shows oxidative damage according to the histology of term chick liver that are confirmed biochemically by the changes in malondialdehyde and glutathione levels.     

Global introductions of salmon and trout in the genus <Emphasis Type="Italic">Oncorhynchus</Emphasis>: 1870–2007

The purpose of this review is to provide a global perspective on Oncorhynchus salmonine introductions and put-and-take fisheries based on modern stocking programs, with special emphasis on freshwater ecosystems. We survey the global introductions of nine selected salmonines of the genus Oncorhynchus: golden trout, cutthroat trout, pink salmon, chum salmon, coho salmon, masu/cherry salmon, rainbow trout/steelhead, sockeye salmon/kokanee, and chinook salmon. The information is organized on a geographical basis by continent, and then by species and chronology. Two different objectives and associated definitions of ‘success’ for introductions are distinguished: (a) seed introduction: release of individuals with the purpose of creating a wild-reproducing, self-sustaining population; and (b) put-and-take introduction: release of individuals with the purpose of maintaining some level of wild population abundance, regardless of wild reproduction. We identify four major phenomena regarding global salmonine introductions: (1) general inadequacy of documentation regarding introductions; (2) a fundamental disconnect between management actions and ecological consequences of introductions; (3) the importance of global climate change on success of previous and future introductions; and (4) the significance of aquaculture as a key uncertainty in accidental introductions. We conclude this review with a recognition of the need to terminate ongoing stocking programs for introduced salmonines worldwide.