The Effect of Lipopolysaccharide on Ischemic-Reperfusion Injury of Heart: A Double Hit Model of Myocardial Ischemia and Endotoxemia.

INTRODUCTION: Myocardial ischemia may coincide and interact with sepsis and inflammation. Our objective was to examine the effects of bacterial endotoxin on myocardial functions and cell injury during acute ischemia. METHODS: Rabbits were pretreated with incremental doses of E. Coli lipopolysaccharide (LPS) or normal saline. Myocardial ischemia was induced by 50-minute occlusion of left anterior descending artery. S-TNFaR was additionally used to block the effects LPS. RESULTS: Ventricular contractility as it was measured by dp/dt during systole decreased from 2445± 1298 to 1422 ± 944 mm Hg/s, P = .019. Isovolumetric relaxation time as an index of diastolic function was prolonged from 50±18 ms to 102± 64 ms following ischemia. Pretreatment with low concentrations of LPS (<1 µg) had no effect on dp/dt, while at higher concentrations it suppressed both contractility and prolonged IVRT. Cell injury as measured by cardiac troponin I level increased to 15.1± 3.2 ng/dL following ischemia and continued to rise with higher doses of LPS. While blocking TNFa did not improve the myocardial contractility after ischemia, it eliminated additional deleterious effects of LPS. CONCLUSION: Lower doses of LPS had no deleterious effect on myocardial function, whereas higher doses of this endotoxin cause cardiac dysfunction and increased extent of injury.

How reliable are ATP bioluminescence meters in assessing decontamination of environmental surfaces in healthcare settings?

BACKGROUND: Meters based on adenosine triphosphate (ATP) bioluminescence measurements in relative light units (RLU) are often used to rapidly assess the level of cleanliness of environmental surfaces in healthcare and other settings. Can such ATP measurements be adversely affected by factors such as soil and cleaner-disinfectant chemistry? OBJECTIVE: This study tested a number of leading ATP meters for their sensitivity, linearity of the measurements, correlation of the readings to the actual microbial contamination, and the potential disinfectant chemicals' interference in their readings. METHODS: First, solutions of pure ATP in various concentrations were used to construct a standard curve and determine linearity and sensitivity. Serial dilutions of a broth culture of Staphylococcus aureus, as a representative nosocomial pathogen, were then used to determine if a given meter's ATP readings correlated with the actual CFUs. Next, various types of disinfectant chemistries were tested for their potential to interfere with the standard ATP readings. RESULTS: All four ATP meters tested herein demonstrated acceptable linearity and repeatability in their readings. However, there were significant differences in their sensitivity to detect the levels of viable microorganisms on experimentally contaminated surfaces. Further, most disinfectant chemistries tested here quenched the ATP readings variably in different ATP meters evaluated. CONCLUSIONS: Apart from their limited sensitivity in detecting low levels of microbial contamination, the ATP meters tested were also prone to interference by different disinfectant chemistries.

Crystal structure of the minimalist Max-E47 protein chimera.

Max-E47 is a protein chimera generated from the fusion of the DNA-binding basic region of Max and the dimerization region of E47, both members of the basic region/helix-loop-helix (bHLH) superfamily of transcription factors. Like native Max, Max-E47 binds with high affinity and specificity to the E-box site, 5'-CACGTG, both in vivo and in vitro. We have determined the crystal structure of Max-E47 at 1.7 Å resolution, and found that it associates to form a well-structured dimer even in the absence of its cognate DNA. Analytical ultracentrifugation confirms that Max-E47 is dimeric even at low micromolar concentrations, indicating that the Max-E47 dimer is stable in the absence of DNA. Circular dichroism analysis demonstrates that both non-specific DNA and the E-box site induce similar levels of helical secondary structure in Max-E47. These results suggest that Max-E47 may bind to the E-box following the two-step mechanism proposed for other bHLH proteins. In this mechanism, a rapid step where protein binds to DNA without sequence specificity is followed by a slow step where specific protein:DNA interactions are fine-tuned, leading to sequence-specific recognition. Collectively, these results show that the designed Max-E47 protein chimera behaves both structurally and functionally like its native counterparts.

The comparative myocardial protection by propofol and isoflurane in an in vivo model of ischemia reperfusion.

BACKGROUND: Anesthetic Agents protect the heart from ischemic injury during perioperative period. We evaluated the protective effects of 2 anesagents on myocardial ischemia -reperfusion injury in rabbit models. METHODS: 58 anesthetized and mechaniventilated rabbits randomly received isoflurane (ISO) 2%, propofol (PRP), or were observed as the control group for 15 minutes. We applied vascular tourniquet around the left anterior descending artery (LAD). Myocardium was reperfused for 4 hours. Derivative of pressure over time (dP/dT(max)), left ventricular pressure (dLVP), isovolumetric relaxation time (Tau), and segment shortening (SS) were measured over the ischemic and non-ischemic regions of left ventricle (LV). Cardiac troponin I (cTnI), tissue concentrations of tumor necrosis factor á (TNFá), myeloperoxidase activity assay (MPO), and tissue malonyl dialdehyde (MDA) concentrations were measured as indices of cellular injury and inflammatory response. RESULTS: dP/dT(max) values significantly decreased during ischemia. Following reperfusion, dP/dT(max), dLVP, and Tau remained depressed in the control animals. Both PRP and ISO restored the function of the myocardium globally. CONCLUSION: Only ISO improved the recovery of the ischemic myocardium during reperfusion. The effects of PRP were global in nature and involved compensatory hypercontractile state in nonischemic regions of the myocardium. Implication. PRP and ISO protect the heart against an ischemic injury, but only ISO preserves the function of the myocardium at the ischemic region. The survival rate of the PRP-treated group versus the ISO-treated group supports the claim that PRP has smaller contribution to recovery from myocardial ischemia.

Composition, structure, bonding and thermoelectric properties of "CuT2P3" and "CuT4P3", members of the T(1-x)(CuP3)x series with T being Si and Ge.

Through electron microprobe analysis, X-ray and neutron diffraction, it has been established that "CuT(2)P(3)" and "CuT(4)P(3)" (T = Si, Ge) adopt the cubic or tetragonally distorted zinc blende structures in which two element mixtures are present on both atomic sites. One site contains the Cu/T mixture while the other site is occupied by T and P. The structure of "CuT(2)P(3)" and "CuT(4)P(3)" can be derived from that of silicon or germanium, in which the single Si or Ge site is broken into two independent sites by the preferential Cu and P substitution. The phases appear to be members of the extended series with a general formula of T(1-x)(CuP(3))(x). The Cu-P ratio of 1 : 3 provides 4 e(-) per atom and optimizes the atomic interactions. Thermoelectric performance of "CuSi(2)P(3)", "CuGe(2)P(3)" and "CuGe(4)P(3)" was evaluated from low temperatures to 400 K through resistivity, Seebeck coefficient and thermal conductivity measurements. The Ge-containing phases show a metallic-type behaviour and "CuSi(2)P(3)" is semiconducting with a narrow band gap. The ZT values are bigger for the Ge-containing phases and reach values of 8.49 x 10(-3) for "CuGe(2)P(3)" and 1.09 x 10(-2) for "CuGe(4)P(3)" at room temperature.