Endotoxin lipopolysaccharide (LPS) causes tumor necrosis factor-α (TNF-α)-mediated myocardial contractile depression. Tolerance to the cardiac toxicity of LPS can be induced by a prior exposure to ...LPS or by pretreatment with glucocorticoids. The mechanisms by which the myocardium acquires tolerance to LPS remain unknown. LPS causes phosphorylation and degradation of inhibitory κB-α (IκB-α), releasing nuclear factor-κB (NF-κB) to activate TNF-α gene transcription. We hypothesized that LPS induces supranormal synthesis of myocardial IκB-α protein and thus renders the myocardium tolerant to subsequent LPS. Rats were challenged with LPS after pretreatment with LPS, dexamethasone, or saline. In saline-pretreated rats, LPS caused a rapid decrease in myocardial IκB-α protein levels, activation of NF-κB, and increased TNF-α production. These events were followed by myocardial contractile depression. After the initial decrease in myocardial IκB-α, IκB-α protein levels rebounded to a level greater than control levels by 24 h. Dexamethasone pretreatment similarly increased myocardial IκB-α protein levels. In rats pretreated with either LPS or dexamethasone, myocardial IκB-α protein levels remained similar to control levels after LPS challenge. The preserved level of myocardial IκB-α protein was associated with diminished NF-κB activation, attenuated myocardial TNF-α production, and improved cardiac contractility. We conclude that LPS and dexamethasone upregulate myocardial IκB-α protein expression and that an increased level of myocardial IκB-α protein may promote cardiac tolerance to LPS by inhibition of NF-κB intranuclear translocation and myocardial TNF-α production.
The microstructure evolution of bicrystal samples during directional solidification was studied, both by simulation and experiment, to explore the mechanism of competitive growth. A new orientation ...relationship of bicrystal samples, the non-uniplanar case, is proposed, which expands the orientation relationship of bicrystal samples from two dimensions to three dimensions. The results show that, in the non-uniplanar case, the favorably oriented grain overgrows the unfavorably oriented grain by developing new dendrites in the lateral gap where the primary dendrites of the unfavorably oriented grain diverge from the mold wall. During this process, the grain boundary is found to move in two directions, one perpendicular to the grain boundary and the other parallel to the grain boundary. To characterize the state of dendrite growth, a three-dimensional reference frame is constructed. In this reference frame, the mechanism of competitive growth can be categorized as a converging case, a non-uniplanar case and a diverging case. Furthermore, the simulation results are in good agreement with the experimental findings.
Department of Surgery, University of Colorado Health Sciences
Center, Denver, Colorado 80262
Lipopolysaccharide (LPS) and tumor necrosis
factor (TNF)- independently induce cardioprotection against ...ischemia
in the rat at 24 h after administration, suggesting that endogenously
synthesized TNF- may play a role in LPS-induced protection. The
purposes of this study were 1 ) to
delineate the time course of LPS-induced cardiac functional protection
against ischemia and its relation with myocardial and circulating
TNF- profile, 2 ) to examine
whether prior protein synthesis inhibition abrogates the protection,
and 3 ) to assess the effects of
TNF- inhibition and neutralization on the protection. Rats were
treated with LPS (0.5 mg/kg ip). Cardiac functional resistance to
normothermic global ischemia-reperfusion was examined at sequential
time points after LPS treatment in isolated hearts by the Langendorff
technique. Myocardial and circulating TNF- was determined by
enzyme-linked immunosorbent assay at 1-24 h after LPS treatment.
Protection was apparent at 24 h, 3 days, and 7 days but not at 2 or 12 h. Maximal protection at 3 days was abolished by cycloheximide
pretreatment (0.5 mg/kg ip 3 h before LPS treatment). Increases in
myocardial and circulating TNF- preceded the acquisition of
protection. Dexamethasone pretreatment (4.0 or 8.0 mg/kg ip 30 min
before LPS treatment) abolished peak increase in myocardial TNF- and
substantially suppressed circulating TNF- (54.3 and 85.9%
inhibition, respectively) without an influence on the maximal
protection. Similarly, maximal protection was not affected by TNF
binding protein (40 or 80 µg/kg iv immediately after LPS treatment).
The results suggest that LPS-induced cardiac functional protection
against ischemia is a delayed and long-lasting protective response that
may involve de novo protein synthesis. Although LPS-induced increase in
myocardial and circulating TNF- precedes the delayed protection, it
may not be required for the delayed protection.
ischemia-reperfusion; cycloheximide; dexamethasone; tumor necrosis
factor binding protein; rat
The shape evolution and shape coexistence phenomena in neutron-rich nuclei at \(N\approx60\), including Kr, Sr, Zr, and Mo isotopes, are studied in the covariant density functional theory (DFT) with ...the new parameter set PC-PK1. Pairing correlations are treated using the BCS approximation with a separable pairing force. Sharp rising in the charge radii of Sr and Zr isotopes at N=60 is observed and shown to be related to the rapid changing in nuclear shapes. The shape evolution is moderate in neighboring Kr and Mo isotopes. Similar as the results of previous Hartree-Fock-Bogogliubov (HFB) calculations with the Gogny force, triaxiality is observed in Mo isotopes and shown to be essential to reproduce quantitatively the corresponding charge radii. In addition, the coexistence of prolate and oblate shapes is found in both \(^{98}\)Sr and \(^{100}\)Zr. The observed oblate and prolate minima are related to the low single-particle energy level density around the Fermi surfaces of neutron and proton respectively. Furthermore, the 5-dimensional (5D) collective Hamiltonian determined by the calculations of the PC-PK1 energy functional is solved for \(^{98}\)Sr and \(^{100}\)Zr. The resultant excitation energy of \(0^+_2\) state and E0 transition strength \(\rho^2(E0;0^+_2\rightarrow0^+_1)\) are in rather good agreement with the data. It is found that the lower barrier height separating the two competing minima along the \(\gamma\) deformation in \(^{100}\)Zr gives rise to the larger \(\rho^2(E0;0^+_2\rightarrow0^+_1)\) than that in \(^{98}\)Sr.
Background: The purposes of this study were to (1) determine whether functional heat-shock protein 72 (HSP-72) may be delivered into the heart, (2) determine whether HSP-72 itself is protective ...against endotoxin (lipopolysaccharide LPS)-induced cardiodepression, and (3) compare relative protection and time courses required for protection for thermally induced HSP-72 versus liposomally introduced HSP-72.
Methods: HSP-72 was introduced (liposomal HSP-72) or induced (heat shock, 42°C× 15 minutes, 24 hours before) in rat heart before LPS administration (0.5 mg/kg intraperitoneal or ex vivo coronary infusion). Western blot analysis for HSP-72 was used to confirm its expression. Left ventricular developed pressure (Langendorff) was used as an index of cardiac function.
Results: Direct intracoronary perfusion of liposomal HSP-72 delivered functioning HSP-72 into the myocardium. LPS induced cardiodepression; however, heat shock pretreatment abolished LPS-induced contractile dysfunction. A direct connection was found between HSP-72 and protection derived from liposomal transfer experiments that similarly reduced LPS-induced cardiodepression.
Conclusions: (1) HSP-72 prevents LPS-induced myocardial contractile dysfunction, (2) liposomal transfer of HSP-72 into the myocardium provides the first direct mechanistic connection between myocardial HSP-72 and protection against LPS, (3) HSP-72 induction requires 24 hours and liposomal transfer of HSP-72 requires 90 minutes, and (4) HSP-72 may offer a clinically acceptable means of protecting the heart. (Surgery 1999;126:135-41.)
In order to explore the spatial, temporal, and chemical characteristics of fine particulate matter (PM2.5) pollution in Handan city, China, a comprehensive dataset including continuous online ...observations at four air quality monitoring stations in 2013 and 2014, and the concentrations of water-soluble inorganic ions (WSII) (NO3−, SO42−, NH4+, Cl−, Na+, Mg2+, K+, Ca2+) in PM2.5 samples collected in four representative seasons in 2013 and 2014 are analyzed in this study. And the principal component analysis (PCA) method is applied to identify the source of WSII in Handan. Our results indicate that PM2.5 concentration decreased from 139.4μg/m3 in 2013 to 116.0μg/m3 in 2014 on annual average. Spatial variations of PM2.5 mass are not pronounced, indicating that PM2.5 is nearly evenly spread over the study area. The seasonal variations of PM2.5 concentration are significant, normally with 1.7 to 2.4 times higher in winter than in summer. The concentrations of TWSII (total water-soluble inorganic ions) remain relatively stable in two years, with annual averages of 63.1μg/m3 in 2013 and 57.2μg/m3 in 2014. SNA (SO42−, NO3−, NH4+) dominates in the TWSII, accounting for ~87% of the TWSII. Similar to PM2.5, WSII exhibits obvious seasonal variations with higher concentrations in autumn and winter, lower in spring and summer. PM2.5 samples are acidic in spring, summer and autumn of 2013, while in winter of 2013 and all seasons of 2014, they are alkaline. SO42−, NO3− are formed mainly through homogeneous reactions, heterogeneous reactions also exist in winter. Finally, the major sources of WSII in Handan are identified as the mixture of secondary origin, coal combustion, biomass burning (46.1%), dust sources (25.8%), and motor vehicle (12.3%).
•The annual average concentrations of PM2.5 were 139.4 and 116.0μg/m3 in 2013 and 2014, respectively.•SO42-, NO3- and NH4+ accounted for 85.5%-87.2% of TWSII in 2013 and 2014.•SO42- and NO3- are formed mainly through homogenous reactions, the heterogeneous reactions also occur in winter.•Secondary origin aerosol, coal combustion, and biomass burning are the major sources of WSII.
The Chinese tortrix, Cydia trasias (Meyrick) (Lepidoptera: Tortricidae), is a major pest of the Chinese scholar‐tree (Japanese pagoda tree), Sophora japonica L.. Cydia trasias has two or three ...generations in Beijing, China and overwinters as larvae in seed pods, bark crevices, and twigs of the Chinese scholar‐tree (Chen, 1992; Chen & Qi, 1992). The larvae attack both petioles and seed pods. During outbreaks, the larvae can cause extensive leaf drop, bare twigs, and seed pod damage, reducing the ornamental and economic value of the tree (Enda & Yamazaki, 1987; Chen, 1992). Since the Chinese scholar‐tree is one of the most popular ornamental trees in urban and suburban areas, trees are sprayed with insecticide to control C. trasias outbreaks. Earlier field trials showed that C. trasias can be controlled by mating disruption (Zhang et al., 2001). In our early paper and patent (Fu & Meng, 1997; Meng et al., 1998), we reported E8,E10‐dodecadienyl acetate (E8,E10‐12:Ac) as a pheromone component of C. trasias, but the identification of C. trasias sex pheromone was not complete. We report here the identification and field testing of the female‐produced sex pheromone in C. trasias.
R. T. Rowland, X. Meng, J. C. Cleveland Jr, D. R. Meldrum, A. H. Harken and J. M. Brown
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
Myocardial tolerance ...to ischemia and reperfusion (I/R) injury can be
achieved by either acute or delayed cardioprotective mechanisms. Ischemic
preconditioning has been demonstrated to be a powerful acute
cardioprotective stimulus. We have reported that lipopolysaccharide (LPS)
pretreatment induces delayed myocardial adaptation to I/R injury. To
optimize myocardial protection, we examined the ability of delayed
myocardial adaptation to enhance acute ischemic preconditioning in the
isolated working rat heart. Male Sprague-Dawley rats were divided into
control, acute transient ischemia (TI); 5-min global ischemia, 37 degrees
C, delayed (LPS; 500 micrograms/kg i.p.), or combined (LPS + TI)
cardioprotective groups. Delayed cardioprotection involved LPS injection 72
h before heart isolation. All hearts were subjected to 20-min global
ischemia (37 degrees C) and 30-min reperfusion. Coronary effluent collected
during reperfusion was assayed for creatine kinase (CK) activity. Both TI
and LPS treatment improved postischemic aortic flow recovery (29 +/- 4.5
and 44 +/- 4.0%, respectively; P < 0.05, LPS vs. TI) compared with
control hearts (11 +/- 2.2%; P < 0.05, TI or LPS vs. control). When TI
was applied to LPS-treated hearts (LPS + TI), aortic flow recovery was
further enhanced (57 +/- 3.8%; P < 0.05 vs. TI or LPS alone). CK release
during 20 and 30 min of reperfusion was decreased in all treated hearts
compared with control hearts (P < 0.05). These results indicate that
delayed myocardial adaptation and acute ischemic preconditioning
independently activate protective mechanisms against ischemia. Enhanced
protection occurs when induced delayed mechanisms are combined with acute
cardioprotective stimuli, which optimize postischemic myocardial function
and reduce myocellular necrosis.
Endotoxin and proinflammatory cytokines induce nitric oxide synthase (NOS), and nitric oxide (NO) plays an important role in promoting endotoxin shock. However, the role of NOS in endotoxemic cardiac ...contractile dysfunction is not defined. To determine whether endotoxemic cardiac contractile dysfunction involves NOS, the present study used a rat model of endotoxemia without shock and examined the effects of glucocorticoids (dexamethasone, a potent inhibitor of inducible NOS, iNOS, expression), isoform nonselective NOS inhibitor (NG-monomethyl-L-arginine, L-NMA) and iNOS selective inhibitor (S-methylisothiourea sulfate, SMT) on cardiac contractile dysfunction. A sublethal dose of endotoxin (from Salmonella typhimurium, .5 mg/kg, i.p.) was given to adult rats, and left ventricular developed pressure (LVDP) examined by Langendorff technique was attenuated in hearts isolated at 4 or 6 h (66.7 +/- 3.4 and 60.3 +/- 5.5 mmHg, respectively, p < .05 vs. 102 +/- 2.4 mmHg in saline control) after endotoxin treatment. Pretreatment of rats with dexamethasone (4.0 mg/kg, i.v., -30 min) partially abolished endotoxin-induced contractile dysfunction at 6 h (LVDP 87.6 +/- 6.8 mmHg, p < .05 vs. endotoxin alone at 6 h). However, pretreatment with L-NMA (30 mg/kg, i.v., -5 min) or SMT (5.0 mg/kg, i.v., -1 min) failed to prevent the contractile dysfunction. Moreover, infusion of L-NMA or SMT in vitro could not restore contractile function in hearts isolated at 6 h after endotoxin treatment. In contrast, inhibition of NOS with L-NMA or SMT in vitro further attenuated coronary flow in endotoxin-treated hearts. Thus, endotoxemic cardiac contractile dysfunction in this non-shock rat model may not involve NOS, and inhibition of NOS may deteriorate coronary perfusion in endotoxemic heart.
•A rapid immunomagnetic beads-based ELISA was successfully developed to detect β-casein in bovine milk.•The procedure of the developed ELISA can be fulfilled within 30min.•Application results ...correlate well with Kjejdahl method.
An immunomagnetic beads-based enzyme-linked immunosorbent assay (IMBs-ELISA) was developed for the detection of β-casein in bovine milk. Immunomagnetic beads (IMBs) were employed as the solid phase. The anti-β-casein monoclonal antibody (McAb) bound to IMBs was used as capture probe and an anti-β-casein polyclonal antibody (PcAb), labelled with horseradish peroxidase (HRP), was employed as detector probe. Three reaction and two washing steps were needed. Each reaction needed 10min or less, which significantly shortened detection compared with classic sandwich ELISA. β-Casein in bovine milk was detected across a linear range (2–128μgmL−1). Application results were in accordance with the Kjejdahl method, which suggests the IMBs-ELISA is rapid and reliable for the detection of β-casein in bovine milk.
