The study aimed at determining the ileal apparent (IAD) and standardised ileal (SID) digestibility of crude protein (CP) and amino acids (AA) in organically cultivated white-flowering faba beans (Vicia faba), and cakes from hemp seed (Cannabis sativa), linseed (Linum usitatissimum) and rapeseed (Brassica napus). The experiment was designed as a four period cross-over trial with six castrated male Yorkshire pigs fitted with post valve T-caecum (PVTC) cannulas. The IAD and SID of CP for the feed ingredients ranged from 79.
View Article and Find Full Text PDFA total of 256 broiler chickens (1 d old) were used in a 32-d growth trial to study the effects of chicory (Cichorium intybus L.) forage and root inclusion on growth performance, digestibility, and gut development. The chicory forage originated from 2 harvests (June and September) and was included at 60 and 120 g/kg.
View Article and Find Full Text PDFThe aim of this study was to examine if atypical parkinsonism affects the communicative ability in conversational interaction. Fifteen persons close to individuals with atypical parkinsonism answered a questionnaire, "Assessment of Change in Communicative Interaction" (ACCI), estimating perceived change in interactive skills compared to before the onset of the disease. The study also examined if perceived change correlated with disease duration.
View Article and Find Full Text PDFInhibition of the BACE-1 protease enzyme has over the recent decade developed into a promising drug strategy for Alzheimer therapy. In this report, more than 20 new BACE-1 protease inhibitors based on α-phenylnorstatine, α-benzylnorstatine, iso-serine, and β-alanine moieties have been prepared. The inhibitors were synthesized by applying Fmoc solid phase methodology and evaluated for their inhibitory properties.
View Article and Find Full Text PDFEnhanced external counterpulsation (EECP) is known to reduce angina pectoris in patients in whom revascularization is not possible. The therapy is associated with few adverse effects. A case with a previously unknown complication - toxic shock syndrome - that occurred twice in an EECP-treated patient is described.
View Article and Find Full Text PDFA feeding trial with growing pigs was carried out in which fish meal was replaced by different levels of Tra catfish (Pangasius hypophthalmus) by-product processing waste water (WW). A control diet included fish meal (FM) as the sole protein supplement (WW0), and there were four experimental diets in which 100% (WW100), 75% (WW75), 50% (WW50), and 25% (WW25), respectively, of the crude protein from FM in WW0 was replaced by WW. Thirty crossbred castrated (Yorkshire × Landrace) male pigs with an initial average body weight of 23.
View Article and Find Full Text PDFBackground: Genes involved in hepatic metabolism have a sex-different expression in rodents. To test whether male and female rat livers differ regarding lipid and carbohydrate metabolism, whole-genome transcript profiles were generated and these were complemented by measurements of hepatic lipid and glycogen content, fatty acid (FA) oxidation rates and hepatic glucose output (HGO). The latter was determined in perfusates from in situ perfusion of male and female rat livers.
View Article and Find Full Text PDFFew other diseases show the degree of phenotypic heterogeneity expressed by HC. The two novel patients reported here with isolated posterobasal LV free wall hypertrophy (and mitral valve prolapse) extend this morphologic diversity even farther, now 3 decades after the introduction of contemporary 2-dimensional imaging.
View Article and Find Full Text PDFBackground: Although the use of TNF inhibitors has fundamentally changed the way rheumatoid arthritis (RA) is treated, not all patients respond well. It is desirable to facilitate the identification of responding and non-responding patients prior to treatment, not only to avoid unnecessary treatment but also for financial reasons. In this work we have investigated the transcriptional profile of synovial tissue sampled from RA patients before anti-TNF treatment with the aim to identify biomarkers predictive of response.
View Article and Find Full Text PDFWe used a validated mail and telephone questionnaire to investigate baseline data on feeding patterns and dietary intake in a random sample of 460 Swedish dogs. In 1999, purebred individuals 1-3 years old in the largest insurance database of Sweden completed the study. Most dogs were fed restricted amounts twice a day, and the feeding patterns seldom were changed after the age of 6 months.
View Article and Find Full Text PDFBackground And Objectives: Although uremic pruritus (UP) is a highly prevalent complication of chronic kidney disease, it remains poorly characterized. There have been no longitudinal studies of natural history, and no health-related quality of life (HR-QOL) instruments have been developed for UP. The objectives of this study were to describe the natural history of UP, to compare rating scales of itching intensity, and to assess usefulness and validity of HR-QOL instruments for UP.
View Article and Find Full Text PDFOur main objective was to obtain baseline data on daily metabolisable energy (ME) intake, activity, and risk factors for obesity in a population of 460 privately owned Swedish dogs in 1999. A previously validated mail-and-telephone questionnaire was used (Sallander et al., 2001a).
View Article and Find Full Text PDFA survey was carried out in the North of Lao PDR to study feeding systems and the performance of pigs in smallholder systems. A total of 341 farmers from five provinces were interviewed. To feed their pigs, farmers mainly rely on feedstuffs produced on the farm and collected from areas near the village.
View Article and Find Full Text PDFBackground: Prostaglandin E2 (PGE2) is involved in several chronic inflammatory diseases including periodontitis, which causes loss of the gingival tissue and alveolar bone supporting the teeth. We have previously shown that tumor necrosis factor alpha (TNFalpha) induces PGE2 synthesis in gingival fibroblasts. In this study we aimed to investigate the global gene expression profile of TNFalpha-stimulated primary human gingival fibroblasts, focusing on signal pathways related to the PGE2-synthesizing enzymes prostaglandin E synthases (PGES), as well as the upstream enzyme cyclooxygenase-2 (COX-2) and PGE2 production.
View Article and Find Full Text PDFReasons For Performing Study: Diets rich in readily fermentable carbohydrates, fed traditionally to meet the increased energy requirements of the performance horse, are associated with a number of gastrointestinal disorders that involve disturbances in the intestinal microbiota, however, these changes are poorly understood.
Objectives: With the long-term objective of improving intestinal health and to increase understanding of the relationship between diet and microbiota, the effect of feeding Standardbred horses a high-energy forage-only (F) diet was studied compared to a more traditional forage-concentrate (C) diet on faecal microbiota.
Methods: Diets were fed in a cross-over design to 6 mature geldings on a scheduled training regime, both periods consisting of 29 days.
Antimicrob Agents Chemother
May 2010
TMC435 is a small-molecule inhibitor of the NS3/4A serine protease of hepatitis C virus (HCV) currently in phase 2 development. The in vitro resistance profile of TMC435 was characterized by selection experiments with HCV genotype 1 replicon cells and the genotype 2a JFH-1 system. In 80% (86/109) of the sequences from genotype 1 replicon cells analyzed, a mutation at NS3 residue D168 was observed, with changes to V or A being the most frequent.
View Article and Find Full Text PDFHighly potent BACE-1 protease inhibitors have been developed from an inhibitors containing a hydroxyethylene (HE) core displaying aryloxymethyl or benzyloxymethyl P1 side chain and a methoxy P1' side chain. The target molecules were synthesized in good overall yields from chiral carbohydrate starting materials. The inhibitors show high BACE-1 potency and good selectivity against cathepsin D, where the most potent inhibitor furnishes BACE-1 K(i) << 1 nM and displays >1000-fold selectivity over cathepsin D.
View Article and Find Full Text PDFIn a preceding study we have described the development of a new hydroxyethylene (HE) core motif displaying P1 aryloxymethyl and P1' methoxy substituents delivering potent BACE-1 inhibitors. In a continuation of this work we have now explored the SAR of the S1' pocket by introducing a set of P1' alkoxy groups and evaluated them as BACE-1 inhibitors. Previously the P1 and P1' positions of the classical HE template have been relatively little explored due to the complexity of the chemical routes involved in modifications at these positions.
View Article and Find Full Text PDFThis work addresses the subject of time-series analysis of comprehensive (1)H-NMR data of biological origin. One of the problems with toxicological and efficacy studies is the confounding of correlation between the administered drug, its metabolites and the systemic changes in molecular dynamics, i.e.
View Article and Find Full Text PDFObjective: High titers of specific anti-citrullinated protein antibodies (ACPAs) are frequently present in the serum of rheumatoid arthritis (RA) patients, but their presence in synovial fluid is less well characterized. The purpose of this study was to compare the levels of antibody to 4 well-defined citrullinated candidate RA autoantigens in serum and synovial fluid and to determine whether antibodies to one citrullinated antigen are dominant over another. Furthermore, we studied their relationships with mutated citrullinated vimentin (MCV), a newly identified RA-specific serum assay, and the classic cyclic citrullinated peptide (CCP) in the synovial fluid of well-defined HLA-DR groups.
View Article and Find Full Text PDFWe herein describe the design and synthesis of a series of BACE-1 inhibitors incorporating a P1-substituted hydroxylethylene transition state isostere. The synthetic route starting from commercially available carbohydrates yielded a pivotal lactone intermediate with excellent stereochemical control which subsequently could be diversified at the P1-position. The final inhibitors were optimized using three different amines to provide the residues in the P2'-P3' position and three different acids affording the residues in the P2-P3 position.
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