Background Hyperuricemia associates with atherosclerosis complications, but it is uncertain whether this relationship is causal in nature. The urate transporter GLUT9 (encoded by the SLC2A9 gene) is ...a major genetic determinant of serum uric acid level in humans. Because polymorphisms are distributed randomly at mating (Mendelian randomization), studies based on GLUT9 polymorphisms may provide unconfounded assessment of the nature of the link between uric acid and atherosclerosis. Study Design Cross-sectional study. Setting & Participants Family-based study including 449 individuals in 107 families in a genetically homogeneous population in Southern Italy. Factor Serum uric acid level, rs734553 allele, and age. Outcome Ultrasound biomarkers of atherosclerosis (intima-media thickness IMT and internal diameter) and pulse wave velocity (PWV). Results Serum uric acid level was dose-dependently associated with the T allele of rs734553, a polymorphism in SLC2A9 ( P = 8 × 10-6 ). Serum uric acid level was a strong modifier of the relationship between age and IMT in fully adjusted analyses (β = 0.33; P = 0.01), whereas no such relationship was found for internal diameter (β = −0.15; P = 0.3) or PWV (β = 0.10; P = 0.6). The T allele coherently associated with carotid IMT, internal diameter, and PWV and emerged as an even stronger modifier of the age-IMT and age–internal diameter relationships in both crude and fully adjusted (β = 0.40 P < 0.001 and β = 0.48 P = 0.003, respectively) analyses. Limitations This is a hypothesis-generating study. Conclusions Results in this family-based study implicate uric acid as an important modifier of the age-dependent risk for atherosclerosis. Trials testing uric acid–lowering interventions are needed to prove this hypothesis.
Abstract
Emulsion styrene—butadiene rubber (ESBR) has been the workhorse of the tire industry since World War II. With the development of solution polymers, ESBR has seen a steady decrease in its use ...in tire applications. A novel ESBR has been developed which imparts some of the rheological behavior previously only observed in solution polymers. This new ESBR was prepared by blending a high molecular weight elastomer with a low molecular weight elastomer, each having a unique styrene-butadiene composition. A two-phase co-continuous morphology was observed by scanning probe microscopy when the bound styrene difference between the two components was greater than 18%, consistent with the two glass transition temperatures measured by thermal analysis. Blending also served to reduce the amount of very high molecular weight material (> 107 g/mol) readily observed in 1502- and 1712-type polymers by thermal field flow fractionation (ThFFF). ThFFF was found to be superior to size exclusion chromatography for fully characterizing the molecular weight and molecular weight distribution of the polymers. Time—temperature superposition was performed to characterize the viscoelastic behavior in the rubbery plateau and terminal zones. The ESBR blends showed a cross-over in the terminal flow region that was not observed in 1502- and 1712-type polymers.
Albuminuria in the Normal Range Zoccali, Carmine, MD; Mallamaci, Francesca, MD
Journal of the American College of Cardiology,
04/2013, Letnik:
61, Številka:
15
Journal Article
Recenzirano
Odprti dostop
Policies based on classical risk factors detection and screening represent the cornerstone of current CVD prevention strategies but novel biomarkers are under intensive investigation. Because chronic ...kidney disease (CKD) has now emerged as an epidemiological problem of dimensions even larger than that of type 2 diabetes mellitus, research on biomarkers of kidney function and damage represents an attractive research area for investigators with various cultural backgrounds including renal and cardiovascular medicine, diabetology, endocrinology, and nutrition at large. The relationship between exposure to risk factors and health risks is typically population dependent.
Experimental and clinical evidence implicates the 2 major adipose tissue cytokines, adiponectin (ADPN) and leptin (LEP), in renal damage. The interpretation of the link between these cytokines and ...renal outcomes is strictly context-sensitive. Albuminuria is a feature of renal disease in the ADPN null mouse and this alteration can be reversed by supplementing ADPN. Accordingly, in young normoalbuminuric obese individuals low ADPN is associated with higher albumin excretion rate. Conversely, high ADPN is associated with more severe proteinuria in chronic kidney disease patients, possibly underlying a protective response aimed at countering the high renal and cardiovascular risk of high proteinuria. LEP administration ameliorates insulin resistance in insulin-resistant patients with hereditary lipodystrophy--a disease characterized by severe LEP deficiency and renal disease--and the same intervention reverses both, insulin resistance and renal damage in a mouse model of LEP deficiency. However, LEP may exert noxious effects on the kidney (particularly renal fibrosis) if administered in conditions of LEP sufficiency or excess.
1 Zeneca Pharmaceuticals,
Wilmington, Delaware 19850; and
2 School of Medicine,
University of Pennsylvania, Philadelphia, Pennsylvania 19104
The present study characterized metabolic changes
in the ...heart associated with long-term exposure to hypoxia, a potent
stimulus for pulmonary hypertension and right ventricular hypertrophy. When anesthetized rats adapted to chronic hypoxia spontaneously respired room air, their mean right intraventricular peak systolic pressure (RVSP) was twice that in normal control animals with the same
arterial P O 2 . RVSP was linearly
related to right ventricular mass ( r = 0.78). Oxidative capacity (O 2
consumption) of homogenates of right and left ventricles from both
groups of rats was measured with one of the following substrates:
pyruvate, glutamate, acetate, and
palmitoyl- L -carnitine. Oxidation
of all substrates was significantly greater in the left than in the
right ventricle in normal rats but not in hypoxia-adapted animals,
where it was the same, within the experimental error.
O 2 consumption by the left
ventricle was greater in control than in experimental rats, but right
ventricular O 2 consumption was
similar in the two groups. Maximal reaction velocity of
cytochrome- c oxidase was about the
same in the two ventricles, and there were no significant differences
between control and hypoxia-adapted animals. HPLC analyses showed
significantly higher aspartate levels and aspartate-to glutamate
concentration ratios in both ventricles of hypoxic rats than in
corresponding tissues from controls, indicative of a decreased flux
through the malate-aspartate shuttle under conditions of O 2 limitation. Myocardial
glutamine levels were lower in hypoxic rats, and glutamine-to-glutamate
concentration ratios decreased, although primarily in the
pressure-overloaded right ventricle. These findings indicate that
normal energy metabolism in the left ventricle differs from that in the
right and that the differences, particularly those of amino acid
metabolism, are markedly influenced by chronic exposure to hypoxia.
oxidative capacity; glycolysis; amino acids; mitochondrial
oxidative phosphorylation; pulmonary hypertension
Previous equilibrium binding experiments (S.A. Winkle and T.R. Krugh, Nucleic Acids Res. 9, 3175-3186 (1981)) suggested that the carcinogen N-hydroxy-N-acetyl-2-aminofluorene might exhibit ...preferential binding to a small number of sites on phiX174 DNA. To examine whether the covalently binding analogue N-acetoxy-N-acetyl-2-aminofluorene (acetoxyAAF) also possesses high affinity sites, the plasmid pBR322 was reacted with 3H labeled acetoxyAAF to give one to sixteen adducts per DNA molecule. Thus only higher affinity sites would be affected. The DNA was subsequently cleaved with either Alu I, Hae III, Hha I, Hinf I or Hpa II restriction endonuclease and the restriction fragments isolated by gel electrophoresis. Examination of the distribution of 3H acetoxyAAF among the fragments was not random but, rather, with each enzyme, the acetoxyAAF was found predominantly in a few fragments. The locations of the bands containing the acetoxyAAF for each enzyme overlap--suggesting that there are regions on pBR 322 which contain high affinity sites for acetoxyAAF binding.
A significant amount of progress has been achieved on characterizing the interaction of the IgE Fc molecule with the Fc epsilon RI alpha. However, there is yet no definitive structural information ...which precisely defines the nature of this interaction. It is clear that this information will only be provided by the resolution of the X-ray crystallographic structures of the IgE Fc molecule, the Fc epsilon RI alpha subunit extracellular domain, and the IgE Fc-Fc epsilon RI alpha complex. It is anticipated that these structures will be determined in the near future, and that they may provide some insight into the development of potential therapeutics effective in the management of IgE-mediated allergic diseases.
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