Tight control of disease activity fails to improve body composition or physical function in rheumatoid arthritis patients.

OBJECTIVE: RA typically features rheumatoid cachexia [loss of muscle mass (MM) and excessive total fat mass (TFM), especially trunk FM], which contributes to physical disability. Since rheumatoid cachexia is driven by inflammation, it would be anticipated that the success of tight control of disease activity, such as treat-to-target (T2T), in attenuating inflammation would benefit body composition and physical function. This aim of this cross-sectional study was to assess the impact of T2T on body composition and objectively assessed function in RA patients. METHODS: A total of 82 RA patients exclusively treated by T2T, were compared with 85 matched sedentary healthy controls (HCs). Body composition was estimated by DXA, with appendicular lean mass the surrogate measure of total MM. Physical function was assessed by knee extensor strength, handgrip strength, 30 s sit-to-stands, 8' up and go, and 50' walk (tests which reflect the ability to perform activities of daily living). RESULTS: Although generally well treated (mean DAS28 = 2.8, with 49% in remission), RA patients had ∼10% proportionally less appendicular lean mass and were considerably fatter (by ∼27%), particularly in the trunk (∼32%), than HCs. All measures of function were 24-34% poorer in the RA patients relative to HC. CONCLUSIONS: Despite marked improvements in disease control (most patients achieving or approaching remission), the relative loss of MM and increased adiposity in RA patients compared with matched HCs was similar to that observed pre-T2T. Additionally, performance of objective function tests was unchanged from that reported by our group for pre-T2T RA patients. Thus T2T, even in responsive RA patients, did not attenuate rheumatoid cachexia or improve objectively assessed function.

Influence of tea drinking on manganese intake, manganese status and leucocyte expression of MnSOD and cytosolic aminopeptidase P.

OBJECTIVE: Since black tea contains high levels of manganese (Mn), we investigated the relationship between dietary Mn intake, circulating Mn levels and leucocyte expression of two Mn-dependent enzymes in tea drinkers and non-tea drinkers. DESIGN: We assessed Mn intakes (food frequency questionnaire), fasting whole blood and plasma Mn levels, and quantitative expression of peripheral blood mononuclear cell Mn-dependent superoxide dismutase (MnSOD) and cytosolic aminopeptidase-P (cAP-P). SETTING AND SUBJECTS: In total, 24 tea drinkers (> or = 1 l black tea/day) and 28 non-tea drinkers were recruited from the staff and students of King's College London by circular email. RESULTS: Dietary Mn intakes (mean (range)) were significantly lower (P < 0.0001) in non tea drinkers (3.2 mg/day (0.5-6.5)) than tea drinkers (5.5 mg/day (2-12) or 10 mg/day (5-20) depending upon the value used for Mn levels of black tea). Whole blood, plasma Mn levels and expression of MnSOD and cAP-P did not differ between the groups. In a continuous analysis, whole blood Mn levels and expression of MnSOD correlated inversely but no other parameters associated with each other. CONCLUSIONS: Tea drinking is a major source of dietary Mn and intakes commonly exceed proposed adequate intake values of 1.8-2.3 mg Mn/day and, on occasion, exceed upper limits of 10-11 mg/day. Dietary Mn intake has little influence on markers of Mn status or expression of Mn-dependent enzymes. Fasting whole blood Mn levels and leucocyte expression of MnSOD could, together, be further investigated as markers of Mn status.

Cryptic dehalogenase and chloroamidase genes in Pseudomonas putida and the influence of environmental conditions on their expression.

Mutants of two strains of Pseudomonas putida expressed two cryptic chloroamidases (C-amidase and H-amidase) and one cryptic dehalogenase (DehII). The mutants were selected on either 2-chloropropionamide (2CPA) or 2-monochloropropionate (2MCPA), developing as papillae in parental colonies growing on a metabolisable support substrate. Mutants expressing C-amidase were selected if 2CPA was utilised as either a carbon or a nitrogen source. H-amidase mutants were selected only if 2CPA was used as a nitrogen source. Growth temperature and pH affected the frequency of papillae production, although different temperatures and pHs did not affect the overall growth characteristics of the parental colonies. Decreasing growth temperature increased the frequency of 2cpa+ papillae formation, but decreased the frequency of 2mcpa+ papillae formation. Low pH (6.0) prevented the formation of 2mcpa+ and 2cpa+ papillae. However, in the case of the 2cpa+ papillae, decreasing the growth temperature also allowed papillae formation at pH 6.0.

Interactions between populations ofPseudomonas putida leading to the expression of a cryptic dehalogenase gene (dehll).

In appropriate environments containing 2-monochloropropionic acid (2MCPA), mutations in a population of nondehalogenatingPseudomonas putida, strain PP40-040 (parent population), resulted in the formation of 2mcpa(+) papillae as a result of the decryptification of adehII gene. Increasing the size of the parent population, for example by increasing the availability of a metabolizable substrate such as succinate or lactate, increased the number of 2mcpa(+) papillae formed because there were more parent cells available for mutation to the 2mcpa(+) phenotype. The presence of a dehalogenating population, such asP. putida strain PP3, in close proximity to the non-dehalogenating population, also increased the number of 2mcpa(+) papillae formed. This was due to the excretion of dehalogenases into the growth medium, which caused localized dehalogenation of the available 2MCPA, yielding a metabolizable substrate. This substrate stimulated the growth of the non-dehalogenating population, in turn increasing the number of 2mcpa(+) papillae formed. Barriers, such as dialysis membranes, which prevented the excretion of the dehalogenases into the growth medium, prevented the stimulation of 2mcpa(+) papillae formation by preventing release of metabolizable substrates from 2MCPA breakdown. Cell-free extracts (CFE) from dehalogenase-producing populations had a similar effect for the same reason. CFE without dehalogenase activity or in which the dehalogenase activity had been destroyed by heating failed to stimulate parent population growth and 2mcpa(+) papillae formation. In the case ofPseudomonas putida strain PP3, which carries an easily transposed dehalogenase-encoding transposon, treatment of CFE with DNAase eliminated an additional factor involved in the formation of 2mcpa(+) papillae.