Interaction between cytokine gene polymorphisms and the effect of physical exercise on clinical and inflammatory parameters in older women: study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Aging is associated with chronic low-grade inflammatory activity with an elevation of cytokine levels. An association between regular physical activity and reduction of blood levels of anti-inflammatory cytokines is demonstrated in the literature pointing to an anti-inflammatory effect related to exercise. However, there is no consensus regarding on which type of exercise and which parameters are the most appropriate to influence inflammatory markers. Evidence indicates that the single nucleotide polymorphism (SNP) can influence the synthesis of those cytokines affecting their production. METHODS: The design is a randomized controlled trial. The aim of this study is to compare the effect of two protocols of exercises, aerobic and muscle strengthening, on the physical performance (PP) and the serum levels of sTNFR-1, sTNFR-2, IL-6, IL-10 e BDNF; and to investigate the interaction between the cytokines genes SNP and the effect of physical activity on elderly women. The main outcomes are: serum levels of sTNFR-1, sTNFR-2, IL-6, IL-10 e BDNF, measured by the ELISA method; genotyping of TNF-alpha (rs1800629), IL6 (rs1800795), IL10 (rs1800896) and BDNF (rs6265 e rs4923463) SNP by the TaqMan Method (Applied Biosystems, Foster City, CA); and PP assessed by Timed Up and Go, 5-chair sit to stand from a chair and 10-meter walk tests. Secondary outcomes include: Geriatric Depression Scale, aerobic capacity, assessed by the 6-minute walk and the Shuttle Walking tests; lower limbs muscle strength, using an isokinetic dinamometer (Biodex Medical Systems Inc, USA); cortisol awakening response and Perceived Stress Scale. Both exercise protocols will be performed three times a week for ten weeks, 30 sessions in total. DISCUSSION: Investigate the effect of both protocols of exercise on the levels of inflammatory cytokine levels can contribute to standardize and to guide clinical practice related to treatment and prevention of functional changes due to chronic inflammatory activity in elderly. This will be the first study to analyze the interaction between genetic factors and exercise effects in elderly. This approach could develop new perspectives on preventive and treatment proposals in Physical Therapy and in the management of the elderly patient. Trial Registration: RBR9v9cwf.     

THE DISTRIBUTION OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASE IN THE HYPOTHALAMUS

Abstract— Quantitative measurements of capacities of microgram-sized samples of tissue to hydrolyze adenosine 3',5'-phosphate (cyclic AMP) and guanosine 3',5'-phosphate (cyclic GMP) have been made in 32 discrete regions of the rabbit hypothalamus. The capacities to hydrolyze the two cyclic nucleotides were found to be distributed over a 3-fold range and to vary in parallel from region to region. Notable exceptions, however, were observed. A positive association was found between the capacity to hydrolyze cyclic AMP and the reported density of catecholaminergic innervation. No clear relationship was observed between the distributions of the cyclic nucleotide phosphodiesterase activities and that of other enzymes and neurotransmitters.     

The self-association of chorismate mutase/prephenate dehydratase from Escherichia coli K12

The state of association of chorismate mutase/prephenate dehydratase (EC 5.4.99.5/ 4.2.1.51) from E. coli K12 has been studied using ultracentrifugal techniques. The smallest species inferred is a dimer of molecular weight 73,000–84,000, with a $\text{s}{}_{\mathrm{<mtext>20,w</mtext>}}{}^0$ of 5.02 S at pH 8.2, I = 0.013 M. This species undergoes a concentration-dependent self-association which results in an equilibrium mixture of dimer, tetramer, and probably octamer, with a M_r of 164,000 at an enzyme concentration of 8.0 mg/ml under the same conditions. Addition of the feedback inhibitor phenylalanine (2 mm) or increase in ionic strength (I = 0.40 M), or a decrease in pH to 7.4 displaces this equilibrium toward the higher-molecular-weight forms of the enzyme, resulting in M_r values of 273,000, 254,000, and 257,000, respectively. This behavior partially explains the allosteric kinetics and inhibitor binding observed previously with this enzyme.     

The genetic toxicity of 1,2-dibromo-3-chloropropane, 1,2-dibromo-3- chloro-2-methylpropane,and 1,2,3-tribromo-2-methylpropane

1,2-Dibromo-3-chloro-2-methylpropane (DBCMP) and 1,2,3- tribromo-2-methylpropane (TBMP) are contaminants formed during the manufacture of bromobutyl rubber. These chemicals are structurally similar to 1,2-dibromo-3-chloropropane (DBCP), a known genotoxin and rodent carcinogen. The present study compared the genotoxic properties of DBCMP and TBMP to those of DBCP. In the Salmonella assay, DBCP was positive in strains TA98, TA-100 and TA-1535 in the presence of exogenous activation; DBCP was weakly active in TA-1535 in the absence of activation. Neither DBCMP nor TBMP produced reproducible evidence of mutagenic activity in the Salmonella assay despite the use of several different variations of this test. In the mouse lymphoma gene mutation assay DBCP and TBMP were positive in the presence and absence of activation, while DBCMP was positive only in the absence of activation. All three test compounds were active in the Syrian hamster embryo morphologic transformation assay. The results indicated that both DBCMP and TBMP exhibited some genotoxic activity as did DBCP. The presence of the methyl group on the 2-carbon position essentially eliminated the mutagenicity of DBCMP and TBMP in the Salmonella assay.abbreviations CHO Chinese hamster ovary cells - DBCMP 1,2-dibromo-3-chloro-2-methylpropane - DBCP 1,2-dibromo-3-chloropropane - DMEM Dulbecco's Eagle's minimal E medium - MNNG N-methyl-N'-nitro-N-nitrosoguanidine - S-9 microsomal fraction from rodent liver - TBMP 1,2,3-tribromo-2-methylpropane - TBP 1,2,3-tribromopropane - TFT trifluorothymidine