Anatomical Studies of Cca Penetration Associated With Conventional (Tooth) and With Micro (Needle) Incising

Individual tooth and needle incisions were made on radial and tangential surfaces of white spruce and jack pine heartwood test samples. The samples were pressure-treated with CCA preservative and then dissected in various planes to examine patterns of preservative penetration. Lateral movement of preservative from incisions was generally greater in the radial than in the tangential direction (average R/T ratio about 1.5). Longitudinal movement was in the range of 15 to 20 times that of lateral movement. Ray tissue facilitates movement in the radial plane, but difficulty is encountered in traversing latewood bands. An individual tooth incision resulted in a larger zone of treated wood but also in a greater amount of wood tissue damage than a needle incision. When compared as ratios of treated wood area to damaged wood area at a depth of 9 mm beneath the original treated surface, needle incisions were decidedly superior. For an equivalent degree of preservative treatment, conventional incising teeth damaged about ten times the amount of wood tissue as did incising needles

Including Pathogen Risk in Life Cycle Assessment of Wastewater Management. 1. Estimating the Burden of Disease Associated with Pathogens

The environmental performance of wastewater and sewage sludge management is commonly assessed using life cycle assessment (LCA), whereas pathogen risk is evaluated with quantitative microbial risk assessment (QMRA). This study explored the application of QMRA methodology with intent to include pathogen risk in LCA and facilitate a comparison with other potential impacts on human health considered in LCA. Pathogen risk was estimated for a model wastewater treatment system (WWTS) located in an industrialized country and consisting of primary, secondary, and tertiary wastewater treatment, anaerobic sludge digestion, and land application of sewage sludge. The estimation was based on eight previous QMRA studies as well as parameter values taken from the literature. A total pathogen risk (expressed as burden of disease) on the order of 0.2–9 disability-adjusted life years (DALY) per year of operation was estimated for the model WWTS serving 28 600 persons and for the pathogens and exposure pathways included in this study. The comparison of pathogen risk with other potential impacts on human health considered in LCA is detailed in part 2 of this article series

Has the ClOpidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT) of early beta-blocker use in acute coronary syndromes impacted on clinical practice in Canada? Insights from the Global Registry of Acute Coronary Events (GRACE)

BACKGROUND: The COMMIT/CCS-2 trial, published in 2005, demonstrated no net benefit of early beta-blocker (BB) therapy in acute coronary syndromes (ACS). We sought to assess the short-term impact of this landmark trial by comparing the use of early BB therapy in patients with a broad spectrum of ACS before and after 2005. METHODS: Using data from the Global Registry of Acute Coronary Events and Canadian Registry of Acute Coronary Events, we compared the rates of BB use within the first 24 hours of presentation in the periods 1999 to 2005 and 2006 to 2008, after stratifying patients by the type of ACS (ST-segment elevation myocardial infarction [STEMI] and non-ST-segment elevation ACS [NSTEACS]) and clinical presentation. RESULTS: Of the 14,231 patients with ACS, 77.7% received BB therapy within 24 hours of presentation (78.5% and 77.4% in the STEMI and NSTEACS groups, respectively). The early use of BB declined in the STEMI group (80.3% to 76.7%, P = .005) but increased in the NSTEACS group (75.4% to 78.9%, P \u3c .001) after 2005. Long-term BB use, higher systolic blood pressure, and higher heart rate were independent predictors of early BB use. Conversely, patients who were female, older, Killip class \u3e1, and had cardiac arrest at presentation were less likely to receive early BB. Multivariable analysis showed a trend toward lower use of BB among patients with STEMI (adjusted odds ratio 0.76, 95% CI 0.57-1.00, P = .055) and a trend toward more frequent BB use among patients with NSTEACS (adjusted odds ratio 1.22, 95% CI 0.96-1.55, P = .11) after 2005. The temporal trends in the early use of BB differed between patients with STEMI and patients with NSTEACS (P for interaction with period \u3c.001). CONCLUSIONS: Most patients with STEMI or NSTEACS were treated with early BB therapy. In accordance with the COMMMIT/CCS-2 trial, patients with lower systolic blood pressure and higher Killip class in the real world less frequently received early BB therapy. Since the publication of COMMIT/CCS-2, there has been no significant change in the use of BB in patients with STEMI or NSTEACS after controlling for their clinical characteristics

Impact of Organic Solvents on Cytochrome P450 Probe Reactions: Filling the Gap with ( S

(S)-Warfarin 7-hydroxylation and midazolam 1′-hydroxylation are among the preferred probe substrate reactions for CYP2C9 and CYP3A4/5, respectively. The impact of solvents on enzyme activity, kinetic parameters, and predicted in vivo hepatic clearance (Cl(H)) associated with each reaction has not been evaluated. The effects of increasing concentrations [0.1–2% (v/v)] of six organic solvents (acetonitrile, methanol, ethanol, dimethyl sulfoxide, acetone, isopropanol) were first tested on each reaction using human liver microsomes (HLMs), human intestinal microsomes (midazolam 1′-hydroxylation only), and recombinant enzymes. Across enzyme sources, relative to water, acetonitrile and methanol had the least inhibitory effect on (S)-warfarin 7-hydroxylation (0–58 and 9–96%, respectively); acetonitrile, methanol, and ethanol had the least inhibitory effect on midazolam 1′-hydroxylation (0–29, 0–22, and 0–20%, respectively). Using HLMs, both acetonitrile and methanol (0.1–2%) decreased the V(max) (32–60 and 24–65%, respectively) whereas methanol (2%) increased the K(m) (100%) of (S)-warfarin-hydroxylation. (S)-Warfarin Cl(H) was underpredicted by 21–65% (acetonitrile) and 13–84% (methanol). Acetonitrile, methanol, and ethanol had minimal to modest impact on both the kinetics of midazolam 1′-hydroxylation (10–24%) and predicted midazolam Cl(H) (2–20%). In conclusion, either acetonitrile or methanol at ≤0.1% is recommended as the primary organic solvent for the (S)-warfarin 7-hydroxylation reaction; acetonitrile is preferred if higher solvent concentrations are required. Acetonitrile, methanol, and ethanol at ≤2% are recommended as primary organic solvents for the midazolam 1′-hydroxylation reaction. This information should facilitate optimization of experimental conditions and improve the interpretation and accuracy of in vitro-in vivo predictions involving these two preferred cytochrome P450 probe substrate reactions