Although it is known that endothelin (ET-1) is elevated in heart failure (HF), it remains unclear if chronic ET(A/B) receptor antagonism affects the progression of HF, particularly by affecting ...coronary vasoactivity and left ventricular (LV) diastolic function.
We examined the effects of an ET(A/B) receptor antagonist, L-753,037 (oral bid for 6 weeks, n=7), and vehicle (n=8) in conscious dogs with previously implanted aortic, coronary sinus and left atrial catheters, LV pressure gauge, aortic flow probe, LV dimension crystals and pacers.
Baseline hemodynamics were similar in the two groups. During the development of rapid pacing-induced HF, treatment with the ET(A/B) antagonist significantly reduced total peripheral resistance and increased cardiac output compared to vehicle. After 2 weeks of pacing, LV diastolic function (tau) was improved (P<0.05) in the ET(A/B) antagonist group (+6+/-2 ms) compared to the vehicle group (+12+/-2 ms). In addition, ET(A/B) antagonist treatment attenuated the increase in mean left atrial pressure and LV end-diastolic pressure that occurred during heart failure in vehicle-treated animals. However, LV systolic function (LV dP/dt, fractional shortening and Vcfc) neither at rest nor in response to dobutamine was altered by ET(A/B) antagonist treatment. Also, ET(A/B) antagonist treatment did not affect the progressive increases in LV dimension. After 6 weeks of pacing, maximal Ca(2+) transport in isolated cardiac sarcoplasmic reticulum (SR) was reduced (P<0.02) in the vehicle-treated compared to the ET(A/B) antagonist-treated dogs (1.34+/-0.09 vs. 1.60+/-0.06 micromol/mg/min, respectively). The improvement in SR function in the ET(A/B) antagonist-treated dogs was associated with a significant attenuation of the reduction in protein expression of SERCA2a and calsequestrin observed in the vehicle-treated dogs. Coronary arteries isolated from the dogs treated with the ET(A/B) antagonist exhibited enhanced (P<0.01) coronary endothelium-dependent relaxation compared to the vehicle group, while coronary responses to an NO donor were identical in the two groups. Plasma NO levels in the coronary sinus during the late stage of HF were higher (P<0.05) in the ET(A/B) antagonist group (40+/-2 microM) compared to the vehicle group (18+/-2 microM).
We conclude that in conscious dogs during the development of HF induced by rapid pacing, chronic inhibition of ET(A/B) receptors does not affect resting myocardial contractile function nor reserve, but reduces vascular resistance and improves LV diastolic function. After 6 weeks of pacing, the reduction in intracellular Ca(2+) regulation by the SR is also attenuated, and endothelium-dependent coronary relaxation is improved, which appears to be related to the preservation of coronary NO levels.
The synthesis of bacteriophage T4 DNA is catalyzed by a complex of five proteins that includes the T4 DNA polymerase protein, one single-stranded DNA binding protein, and three T4-coded polymerase ...accessory proteins. The accessory proteins form two subassemblies, one consisting of a tightly-bound complex of gene 44 and 62 proteins and the other an oligomer of the gene 45 protein (product of gene 45, gp45). On the basis of equilibrium sedimentation, velocity sedimentation, and chemical cross-linking studies, aqueous gp45 was thought to exist as a noncovalent trimer at pH 7. However, independent studies employing a combination of gel filtration and sucrose gradient sedimentation suggested that gp45 exists as a dimer in solution. We report an investigation into the stoichiometry of gp45 association in solution using a combination of ion spray mass spectrometry (MS) and microbore size exclusion chromatography. In 10 mM NH sub(4)OAc (pH 2.5), both homodimer and trimer were observed by ion spray MS. Further experiments on two representative gp45 dimer ions using tandem mass spectrometry confirmed their structures as noncovalent gas-phase association complexes. Judging from size exclusion chromatography, a gp45 homotrimer was the predominant species in 10 mM sodium phosphate at pH 6.8, although a corroborating mass spectrum could not be obtained at that pH.
We characterized the pathologic changes in 50 spleens from patients with autoimmune hemolytic anemia and in 13 spleens from patients with congenital hemolytic anemia. The major pathologic findings in ...autoimmune hemolytic anemia were mild to pronounced cord congestion and variable white pulp area, erythrophagocytosis in conjunction with an increased polymorphonuclear neutrophil reaction, and increased deposition of hemosiderin and extramedullary hematopoiesis. In contrast, both the severity and the frequency of polymorphonuclear neutrophil reactions, deposition of hemosiderin, and extramedullary hematopoiesis were less in patients with congenital hemolytic anemia, and prominent cord congestion associated with an empty or collapsed sinus was noted in patients with hereditary spherocytosis. The activity of erythrophagocytosis in the sinus was more distinct in patients with congenital hemolytic anemia, especially those with nonspherocytic congenital hemolytic anemia, than in patients with autoimmune hemolytic anemia. These findings are consistent with the existence of different mechanisms of trapping and destruction of erythrocytes in autoimmune hemolytic anemia and congenital hemolytic anemia.
Ten reactive metabolites of five polycyclic aromatic hydrocarbons and styrene were investigated to determine the generality of ester adduct formation with human hemoglobin in the form of RBC and ...hydrolysis to the corresponding tetrahydrotetrols or dihydrodiols. No exceptions were noted among the compounds tested, which included the anti-diol epoxides of benzoapyrene (BaP), chrysene, and benzaanthracene; the syn-diol epoxide of BaP; a mixture of syn- and anti-diol epoxides of benzoepyrene; and epoxides of styrene, benzoepyrene, BaP, and cyclopentac,dpyrene. A test of the propensity of the simplest benzylic epoxide, styrene oxide, to form esters that hydrolyze via a BAL1 mechanism was performed. Hydrolysis of styrene oxide-adducted hemoglobin in H2(18)O at neutral pH yielded 18O incorporation results that suggest this mechanism of hydrolysis is operant to a minor degree in styrene oxide-hemoglobin ester adducts. A method was developed for the isolation and quantification of the polycyclic aromatic alcohols, which consists of enzymatic proteolysis, immunoaffinity chromatography, and gas chromatography-mass spectrometry or fluorimetry. The method allows for routine analysis of hemoglobin from individual samples as small as 1 ml of whole blood. Analysis of blood from different human populations revealed that hemoglobin adducts of the anti-diol epoxide of BaP dominated the spectrum of adducts formed by the selected metabolites.
The push for high capacity cathodes capable of Li storage greater than Li/TM (TM=transition metal) ratio of one in Li-ion batteries (LIB) is extremely challenging, but necessary to increase energy ...densities. The rock-salt layered lithium oxide material, Li
2
MnO
3
, is particularly well studied and can release essentially all of its Li during electrochemical charge on the first cycle yielding over 400 mAh/g (cycled >4.6 V vs. Li metal), but this process is irreversible, and capacity rapidly fades. Recently we have been studying the electrochemical behavior of higher lithium-content containing phase, Li
5
FeO
4
(LFO) (a defect anti-fluorite structure, with large lithium content, Li/Fe = 5), in the following three roles: (1) as a reversible 2.8 to 3.0 V cathode, (2) as a Li-source additive to enable Si anode for LIBs, and (3) as a hybrid Li-ion•Li-O
2
cathode material.
1
As reported by our group, this LFO can provide over 700 mAh/g specific capacity below 4.4 V vs. Li metal
2
which now identifies it as an ideal candidate for a myriad of energy storage applications. This poster highlights the LFO material and addresses the following aspects: (1) synthesis of LFO, (2) electrode fabrication, blends and implementation in LIB full cells. The LFO is particularly effective at full cell cycle improvement due to both elimination of high first cycle irreversible capacity losses (ICL), and cycle-to-cycle inefficiencies. Lastly we will back-up our findings through a number of characterization methods in addition to first principles modeling. For example we make use of
novel fast operando Mössbauer spectroscopy
in order to decipher the charge compensation and the stability of tetravalent iron (Fe
4+
) during real-time cycling of Li/LFO pouch cells. All these results taken together have given us ample understanding of the material, its versatility and extreme effectiveness in energy storage.
1 L. Trahey, et al.,
Electrochem. and Solid State Lett.
,
14
, A64 (2011)
2 C. S. Johnson, et al.,
Chemistry of Materials
,
22
, 1263-1270 (2010)
This work was supported as part of the Center for Electrochemical Energy Science (CEES), an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences. Use of the Center for Nanoscale Materials, (Raman) The Advanced Photon Source (operando XRD), and the Electron Microscopy Center (SEM) is supported by the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357.
Specific 3Hestradiol-17 beta (3HE2) binding activity (EBA) with characteristics of an estrogen receptor (ER) was demonstrated in cytosols and nuclear extracts of the female turtle, Chrysemys picta. ...Three different receptor assays (dextran-coated charcoal assay, hydroxylapatite batch procedure, and DNA-cellulose chromatography) were evaluated in terms of their applicability in analyzing large numbers of samples. For the measurement of cytosolic EBA, the hydroxylapatite batch procedure was found to be the most reliable assay. On the other hand, the dextran-coated charcoal assay was found to be the most appropriate method for the measurement of nuclear EBA. Turtle hepatic EBA binds 3HE2 with high affinity (cytosolic, 17.4 +/- 2.8 X 10(9) M-1; nuclear, 17.7 +/- 1.9 X 10(9) M-1), limited capacity (cytosolic, 133.7 +/- 4.6 fmol/g tissue; nuclear, 81.1 +/- 9.0 fmol/g tissue), and strict steroid specificity. The EBA bound natural estrogens (E2, estrone, estriol) as well as the nonsteroidal estrogen, diethylstilbestrol, but exhibited little affinity for androgens, progesterone, or corticosterone. The turtle hepatic EBA resembled mammalian and avian ERs in terms of binding characteristics; however, unlike mammalian and avian ERs it was shown to be heat-labile. Incubation at 30 degrees caused rapid loss of 3HE2 binding activity in both cytosolic and nuclear fractions. The exchange between 3HE2 and the endogenously bound estrogen was slow at 4 and 15 degrees, but the exchange process was facilitated in the presence of the chaotropic salt, NaSCN. Establishment of quantitation methods for both cytosolic and nuclear forms of EBA will enable future investigation of the mechanism and regulation of estrogen action in the liver of this turtle species.
We report a new vertical structure InP enhancement-mode MISFET. These transistors are made on an Fe-doped semi-insulating InP epitaxial layer grown by organometallic vapor-phase epitaxy (OMVPE) on an ...n-type InP substrate. Thermally evaporated borosilicate is used as the gate insulator. Transconductances as high as 100 mS/mm have been achieved with a gate length of approximately 2.8µm. The novelty and potential advantages of the vertical structure are discussed.
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