The enzymatic oxidation of Desferal to a nitroxide free radical

AbstractDesferrioxamine mesylate (Desferal), a transition metal ion chelator, has been used to inhibit the in vitro redox cycling of transition metal ions. ESR spectroscopy was utilized to detect and identify Desferal's one-electron oxidation product. We demonstrate that a horseradish peroxidase/H2O2 system, a xanthine oxidase/hypoxanthine system, and a hydroxyl radical-generating system are all capable of oxidizing Desferal to a nitroxide free radical. The same 9-line ESR spectrum (g = 2.0065, aN = 7.85 G, aH(2) = 6.35 G) was detected in all of the above systems. We, therefore, stress that care must be taken when using Desferal as a transition metal ion chelator to keep its concentration low enough to minimize these reactions, or to use a different metal ion chelator

Child and Parent Report of Parenting as Predictors of Substance Use and Suspensions from School

This study examined how child and parent reports of parenting were related to early adolescent substance use and school suspensions. Data were from two time points six months apart on 321 families with an eighth grade student attending one of five schools in the Pacific Northwest. Child- and parent-report measures of family management practices were moderately correlated (r = .29). Child report, but not parent report, of more positive family management practices uniquely predicted a lower likelihood of adolescent substance use. Also, discrepancies between child and parent report of parenting predicted substance use, with child positive report of family management losing its protective association with adolescent substance use when parents had negative reports of their parenting. Parent report, but not child report, of better parenting predicted lower likelihood of suspensions, suggesting that the salience of child and parent report may depend on the type of behavioral outcome

Child and Parent Report of Parenting as Predictors of Substance Use and Suspensions from School

This study examined how child and parent reports of parenting were related to early adolescent substance use and school suspensions. Data were from two time points six months apart on 321 families with an eighth grade student attending one of five schools in the Pacific Northwest. Child- and parent-report measures of family management practices were moderately correlated (r = .29). Child report, but not parent report, of more positive family management practices uniquely predicted a lower likelihood of adolescent substance use. Also, discrepancies between child and parent report of parenting predicted substance use, with child positive report of family management losing its protective association with adolescent substance use when parents had negative reports of their parenting. Parent report, but not child report, of better parenting predicted lower likelihood of suspensions, suggesting that the salience of child and parent report may depend on the type of behavioral outcome

Hubble Space Telescope Astrometry of the Procyon System

The nearby star Procyon is a visual binary containing the F5 IV-V subgiant Procyon A, orbited in a 40.84 yr period by the faint DQZ white dwarf Procyon B. Using images obtained over two decades with the Hubble Space Telescope, and historical measurements back to the 19th century, we have determined precise orbital elements. Combined with measurements of the parallax and the motion of the A component, these elements yield dynamical masses of 1.478 +/- 0.012 Msun and 0.592 +/- 0.006 Msun for A and B, respectively. The mass of Procyon A agrees well with theoretical predictions based on asteroseismology and its temperature and luminosity. Use of a standard core-overshoot model agrees best for a surprisingly high amount of core overshoot. Under these modeling assumptions, Procyon A's age is ~2.7 Gyr. Procyon B's location in the H-R diagram is in excellent agreement with theoretical cooling tracks for white dwarfs of its dynamical mass. Its position in the mass-radius plane is also consistent with theory, assuming a carbon-oxygen core and a helium-dominated atmosphere. Its progenitor's mass was 1.9-2.2 Msun, depending on its amount of core overshoot. Several astrophysical puzzles remain. In the progenitor system, the stars at periastron were separated by only ~5 AU, which might have led to tidal interactions and even mass transfer; yet there is no direct evidence that these have occurred. Moreover the orbital eccentricity has remained high (~0.40). The mass of Procyon B is somewhat lower than anticipated from the initial-to-final-mass relation seen in open clusters. The presence of heavy elements in its atmosphere requires ongoing accretion, but the place of origin is uncertain.Comment: Accepted by Astrophysical Journa

Nocturia as an Unrecognized Symptom of Uncontrolled Hypertension in Black Men Aged 35 to 49 Years.

Background Hypertension is assumed to be asymptomatic. Yet, clinically significant nocturia (≥2 nightly voids) constitutes a putative symptom of uncontrolled hypertension. Black men with hypertension may be prone to nocturia because of blunted nocturnal blood pressure ( BP ) dipping, diuretic drug use for hypertension, and comorbidity that predisposes to nocturia. Here, we test the hypothesis that nocturia is a common and potentially reversible symptom of uncontrolled hypertension in black men. Methods and Results We determined the strength of association between nocturia (≥2 nightly voids) and high BP (≥135/85 mm Hg) by conducting in-person health interviews and measuring BP with an automated monitor in a large community-based sample of black men in their barbershops. Because nocturia is prevalent and steeply age-dependent after age 50 years, we studied men aged 35 to 49 years. Among 1673 black men (mean age, 43±4 years [ SD ]), those with hypertension were 56% more likely than men with normotension to have nocturia after adjustment for diabetes mellitus and sleep apnea (adjusted odds ratio, 1.56; 95% CI , 1.25-1.94 [ P<0.0001]). Nocturia prevalence varied by hypertension status, ranging from 24% in men with normotension to 49% in men whose hypertension was medically treated but uncontrolled. Men with untreated hypertension were 39% more likely than men with normotension to report nocturia ( P=0.02), whereas men whose hypertension was treated and controlled were no more likely than men with normotension to report nocturia ( P=0.69). Conclusions Uncontrolled hypertension was an independent determinant of clinically important nocturia in a large cross-sectional community-based study of non-Hispanic black men aged 35 to 49 years. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unqiue identifier: NCT 02321618

Viral delivery of superoxide dismutase gene reduces cyclosporine A-induced nephrotoxicity

BACKGROUND: Cyclosporine A (CsA) increases free radical formation in the kidney. Accordingly, this study investigated whether gene delivery of superoxide dismutase (SOD) reduced radical production and nephrotoxicity caused by CsA. METHODS: Rats were given adenovirus (Ad) carrying lacZ or Cu/Zn-SOD genes three days prior to CsA treatment. Histology, glomerular filtration rates (GFRs) and free radical adducts in urine were assessed. RESULTS: SOD activity was increased 2.5-fold three days after viral infection and remained at 2- and 1.6-fold higher 10 and 17 days later. Treatment with CsA for seven days decreased GFR by 70% in rats infected with Ad-lacZ as expected; however, the decrease was diminished significantly in rats receiving Ad-SOD. CsA treatment for two weeks caused a loss of brush border and dilation of proximal tubules, necrosis, and increased leukocyte infiltration into the kidney; these effects were minimized by SOD. Dimethyl sulfoxide (DMSO) was attacked by the hydroxyl radical to produce a methyl radical. Indeed, administration of CsA with 12C-DMSO in rats infected with Ad-lacZ produced a radical adduct with hyperfine coupling constants similar to 4-POBN/methyl radical adduct and another unknown radical adduct. CsA given with 13C-DMSO produced a 12-line spectrum, confirming the involvement of hydroxyl radicals. Free radical adducts detected in urine were increased approximately fivefold by CsA, an effect blocked completely by SOD. CONCLUSIONS: CsA increases free radical formation. Gene delivery of SOD blocks formation of free radicals, thereby minimizing nephrotoxicity caused by CsA

Design and Analysis of a Preconcentrator for the ChemLab

Preconcentration is a critical analytical procedure when designing a microsystem for trace chemical detection, because it can purify a sample mixture and boost the small analyte concentration to a much higher level allowing a better analysis. This paper describes the development of a micro-fabricated planar preconcentrator for the {mu}ChemLab{trademark} at Sandia. To guide the design, an analytical model to predict the analyte transport, adsorption and resorption process in the preconcentrator has been developed. Experiments have also been conducted to analyze the adsorption and resorption process and to validate the model. This combined effort of modeling, simulation, and testing has led us to build a reliable, efficient preconcentrator with good performance

Free Radical-Dependent Dysfunction of Small-for-Size Rat Liver Grafts: Prevention by Plant Polyphenols

BACKGROUND & AIMS: The mechanisms by which small-for-size liver grafts decrease survival remain unclear. This study investigated the role of free radicals in injury to small-for-size grafts. METHODS: Rat liver explants were reduced in size ex vivo and transplanted into recipients of the same or greater body weight, resulting in a graft weight and standard liver weight of approximately 50% and 25%, respectively. A polyphenol extract from Camellia sinenesis (20 microg/mL) or an equivalent concentration of epicatechin was added to the storage solution and the lactated Ringer poststorage rinse solution. RESULTS: Serum alanine aminotransferase release increased from approximately 60 U/L before implantation to 750, 1410, and 2520 U/L after full-size, half-size, and quarter-size transplantation, respectively. Total bilirubin increased slightly after transplantation of full-size and half-size grafts but increased 104-fold in quarter-size grafts. In quarter-size grafts, histological changes included necrosis, leukocyte infiltration, and eosinophilic inclusion body formation. Polyphenol treatment ameliorated these effects by > or =67%. Survival was 30% after transplantation of small-for-size grafts. After polyphenol treatment, survival increased to 70%. Free radicals in bile assessed by spin trapping and 4-hydroxynonenal adducts measured by immunohistochemistry were also greater in reduced-size grafts, an effect ameliorated by polyphenols. Epicatechin, a major polyphenol from Camellia sinenesis, also improved graft function and decreased enzyme release, histopathologic changes, and free radical formation. CONCLUSIONS: Increased formation of free radicals occurs after transplantation of reduced-size livers, which contributes to graft dysfunction and failure. Plant polyphenols decrease liver graft injury and increase survival of small-for-size liver grafts, most likely by scavenging free radicals

Overexpression of Manganese Superoxide Dismutase Prevents Alcohol-induced Liver Injury in the Rat

Mitochondria are thought to play a major role in hepatic oxidative stress associated with alcohol-induced liver injury. Thus, the hypothesis that delivery of the mitochondrial isoform of superoxide dismutase (Mn-SOD) via recombinant adenovirus would reduce alcohol-induced liver injury was tested. Rats were given recombinant adenovirus containing Mn-SOD (Ad.SOD2) or beta-galactosidase (Ad.lacZ) and then fed alcohol enterally for 4 weeks. Mn-SOD expression and activity of Ad.SOD2 in liver mitochondria of infected animals was increased nearly 3-fold compared with Ad.lacZ-infected controls. Mitochondrial glutathione levels in Ad.lacZ-infected animals were decreased after 4 weeks of chronic ethanol, as expected, but were unchanged in Ad.SOD2-infected animals. Alanine aminotransferase was elevated significantly by ethanol, an effect that was prevented by Ad.SOD2. Moreover, pathology (e.g. the sum of steatosis, inflammation, and necrosis) was elevated dramatically by ethanol in Ad.lacZ-treated rats. This effect was also blunted in animals infected with Ad.SOD2. Neutrophil infiltration was increased about 3-fold in livers from both Ad.lacZ- and Ad.SOD2-infected rats by ethanol treatment. Moreover, ESR-detectable free radical adducts in bile were increased about 8-fold by ethanol. Using (13)C-labeled ethanol, it was determined that nearly 60% of total adducts were due to the alpha-hydroxyethyl radical adduct. This increase in radical formation was blocked completely by Ad.SOD2 infection. Furthermore, apoptosis of hepatocytes was increased about 5-fold by ethanol, an effect also blocked by Ad.SOD2. Interestingly, tumor necrosis factor-alpha mRNA was elevated to the same extent in both Ad.lacZ- and Ad.SOD2-infected animals follows ethanol exposure. These data suggest that hepatocyte mitochondrial oxidative stress is involved in alcohol-induced liver damage and likely follows Kupffer cell activation, cytokine production, and neutrophil infiltration. These results also support the hypothesis that mitochondrial oxidant production is a critical factor in parenchymal cell death caused by alcohol