In patients with preserved cardiac function, the incidence of indeterminate results of microvolt TWA is low, and a positive test result is associated with arrhythmic events. Microvolt TWA could be used for risk stratification in this low-risk population.
Accurate structure factors of silicon and diamond have been experimentally determined from powder diffraction data measured at the third-generation synchrotron-radiation source SPring-8, BL02B2. The accuracy of the obtained structure factors has been evaluated by comparing with structure factors in the literature measured by the Pendellösung method and with some from theoretical calculations. The results indicate that the structure factors from powder data are accurate enough to discuss the experimental charge-density distributions of these materials. The number of structure factors of silicon determined in the present study is 104, which is three times more than that of previous Pendellösung data. The experimental charge densities have been obtained by the maximum-entropy method from the present structure factors. The charge densities at bond mid-points for silicon and diamond show good agreement with different kinds of theoretical calculations. The present study proved that the powder diffraction at SPring-8 is a promising method for determination of experimental charge density for a wider range of materials.
Summary The quantification of urinary oxidized tyrosines, dityrosine (DiY), nitrotyrosine (NY), bromotyrosine (BrY), and dibromotyrosine (DiBrY), was accomplished by quadruple liquid chromatography-tandem mass spectrometry (LC/MS/MS). The sample was partially purified by solid phase extraction, and was then applied to the LC/MS/MS using multiplereaction monitoring (MRM) methods. The analysis for the DiY quantification was done first. The residual samples were further butylated with n-butanol/HCl, and the other modified tyrosines were then quantified with isotopic dilution methods. MRM peaks of the modified tyrosines (DiY, NY, BrY, and DiBrY) from human urine were measured and the elution times coincided with the authentic and isotopic standards. The amounts of modified tyrosines in healthy human urine (n = 23) were 8.8 ± 0.6 (DiY), 1.4 ± 0.4 (NY), 3.8 ± 0.3 (BrY), and 0.7 ± 0.1 (DiBrY) µmol/mol of creatinine, respectively. A comparison of the modified tyrosines with urinary 8-oxo-deoxyguanosine, pentosidine, and N ε -(hexanoyl)lysine was also performed. Almost all products, except for NY, showed good correlations with each other. The amounts of the modified tyrosines (NY, BrY, and DiBrY) in the diabetic urine were higher than those in the urine from healthy people.
Background:
Metformin is a popular antidiabetic agent that is also used to treat heart failure patients with type 2 diabetes mellitus. Several reports suggest that metformin may also have cardioprotective effects in patients without diabetes mellitus. In the present study, we investigated the possible therapeutic effect of metformin in heart failure and its underlying molecular mechanisms using a δ-sarcoglycan-deficient mouse model of dilated cardiomyopathy.
Methods and Results:
Thirty-two-week-old δ-sarcoglycan-deficient mice exhibiting established cardiomyopathy with extensive left ventricular dilatation and dysfunction were administered saline or metformin (200 mg/kg per day) for 4 weeks using osmotic mini-pumps. Metformin partially reversed the left ventricular dilatation (reverse remodeling) and significantly improved cardiac function. The hearts of metformin-treated mice showed less fibrosis, less cardiomyocyte hypertrophy, and fewer degenerative subcellular changes than saline-treated mice. These effects were accompanied by restored expression of the sarcomeric proteins myosin heavy chain and troponin I, and their transcription factor, GATA-4. Autophagy was enhanced in the hearts from metformin-treated mice, as indicated by increase of myocardial microtubule-associated protein-1 LC-3 (light chain 3)-II levels and LC3-II/-I ratios as well as levels of cathepsin D and ATP. In addition, increased numbers of autophagic vacuoles and lysosomes were accompanied increased AMP-activated protein kinase activity and suppression of mammalian target of rapamycin phosphorylation. Finally, autophagic flux assays using short-term chloroquine treatment revealed that autophagy was activated in δ-sarcoglycan-deficient hearts and was further augmented by metformin treatment.
Conclusions:
Metformin is a beneficial pharmacological tool that mitigates heart failure caused by δ-sarcoglycan deficiency in association with enhanced autophagy.
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