Kinetics of cytokine expression in cirrhotic rats

AbstractBackgroundCytokines are involved in liver injury and cirrhosis and systemic and hepatic cytokine levels may help predict cirrhosis evolution. However, the relevant survey has not been performed.MethodsMale Sprague-Dawley rats (240–270g) received either common bile duct ligation (BDL, animal model of cholestatic liver injury) or sham operation (control). Five rats were sacrificed and liver and serum were collected from each in weeks 1, 2, 4, 6, 8 and 10 after surgery. Hepatic expression of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) were analyzed by immunohistochemial staining. The corresponding serum levels were measured by ELISA.ResultsCompared to the corresponding sham groups, hepatic expression of these cytokines in BDL rats was significantly and progressively enhanced during cirrhosis development. However, serum IFN-γ levels of BDL rats did not change significantly. Serum TNF-α of BDL rats increased gradually and reached a peak in week 6. Serum TGF-β level was elevated up to week 8, whereas IL-10 level decreased progressively until week 6.ConclusionCirrhosis development in BDL rats is associated with progressively enhanced expression of hepatic pro-inflammatory and anti-inflammatory cytokines, which is not in accord with the corresponding serum concentration. The circulating cytokine concentration may not totally reflect the hepatic expression level throughout the development of cirrhosis

Analysis of the Optimal Frequency Band for a Ballistic Missile Defense Radar System

In this paper, we consider the anti-attack procedure of a ballistic missile defense system (BMDS) at different operating frequencies at its phased-array radar station. The interception performance is measured in terms of lateral divert (LD), which denotes the minimum acceleration amount available in an interceptor to compensate for prediction error for a successful intercept. Dependence of the frequency on estimation accuracy that leads directly to prediction error is taken into account, in terms of angular measurement noises. The estimation extraction is performed by means of an extended Kalman filter (EKF), considering two typical re-entry trajectories of a non-maneuvering ballistic missile (BM). The simulation results show better performance at higher frequency for both tracking and intercepting aspects

Thickness dependence of the interfacial Dzyaloshinskii-Moriya interaction in inversion symmetry broken systems

In magnetic multilayer systems, a large spin-orbit coupling at the interface between heavy metals and ferromagnets can lead to intriguing phenomena such as the perpendicular magnetic anisotropy, the spin Hall effect, the Rashba effect, and especially the interfacial Dzyaloshinskii-Moriya (IDM) interaction. This interfacial nature of IDM interaction has been recently revisited because of its scientific and technological potential. Here, we demonstrate an experimental technique to straightforwardly observe the IDM interaction, namely Brillouin light scattering. The non-reciprocal spin wave dispersions, systematically measured by Brillouin light scattering, allow not only the determination of the IDM energy densities beyond the regime of perpendicular magnetization but also the revelation of the inverse proportionality with the thickness of the magnetic layer, which is a clear signature of the interfacial nature. All together, our experimental and theoretical approaches involving double time Green,s function methods open up possibilities for exploring magnetic hybrid structures for engineering the IDM interaction

Safety and Efficacy of Dacomitinib in Korean Patients with KRAS Wild-Type Advanced Non–Small-Cell Lung Cancer Refractory to Chemotherapy and Erlotinib or Gefitinib: A Phase I/II Trial

IntroductionDacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor ([HER]-1/EGFR, HER-2, and HER-4) tyrosine kinase inhibitor, demonstrated antitumor activity in Western patients with non–small-cell lung cancer (NSCLC) at a dose of 45 mg once daily. We report data from a phase I/II, multicenter, open-label study of Korean patients with refractory KRAS wild-type adenocarcinoma NSCLC (defined as patients with evidence of disease progression during or within 6 months of treatment with chemotherapy and gefitinib or erlotinib).MethodsThe phase I dose-finding portion identified the recommended phase II dose (RP2D) in Korean patients, evaluated safety, and characterized the pharmacokinetics of dacomitinib. In the phase II portion, patients received dacomitinib at the RP2D. The primary end point was progression-free survival at 4 months (PFS4m).ResultsTwelve patients enrolled in phase I, and 43 patients enrolled in phase II at the RP2D of 45 mg once daily. In phase II, PFS4m was 47.2% (95% confidence interval [CI], 31.6–61.3; one-sided p-value = 0.0007). Median PFS was 15.4 weeks (95% CI, 9.7–17.6); median overall survival was 46.3 weeks (95% CI, 32.7–not reached); and the objective response rate was 17.1% (95% CI, 7.2–32.1). Common treatment-related adverse events were dermatitis acneiform, diarrhea, and paronychia; there were no treatment-related grade 4 or 5 adverse events. Pharmacokinetic parameters of dacomitinib in Korean patients were similar to those reported in Western patients. By patient report, NSCLC symptoms “cough” and “pain” showed improvement within 3 weeks of initiating treatment.ConclusionsDacomitinib was well tolerated and had antitumor activity in Korean patients with NSCLC who had previously progressed on chemotherapy and an epidermal growth factor receptor tyrosine kinase inhibitor

Inelastic J/ψJ/\psi production in polarized photon-hadron collisions

Presented here is a calculation of inelastic $J/\psi$ production in polarized photon-hadron collisions under the framework of NRQCD factorization formalism. We consider the photoproduction of \jpsi in the energy range relevant to HERA. The Weizs\"acker-Williams approximation is adopted in the evaluation of the cross sections for $ep$ collisions. We found that this process can give another independent test for the color-octet mechanism, and the different features for the two color-octet processes may provide further informations on the mechanism for inelastic \jpsi photoproduction. And the discrepancy on the production asymmetry $A$ between various sets of polarized gluon distribution functions is also found to be distinctive.Comment: 14pages, 6 PS figure

Alpha 1,3-Galactosyltransferase Deficiency in Pigs Increases Sialyltransferase Activities That Potentially Raise Non-Gal Xenoantigenicity

We examined whether deficiency of the GGTA1 gene in pigs altered the expression of several glycosyltransferase genes. Real-time RT-PCR and glycosyltransferase activity showed that 2 sialyltransferases [α2,3-sialyltransferase (α2,3ST) and α2,6-sialyltransferase (α2,6ST)] in the heterozygote GalT KO liver have higher expression levels and activities compared to controls. Enzyme-linked lectin assays indicated that there were also more sialic acid-containing glycoconjugate epitopes in GalT KO livers than in controls. The elevated level of sialic-acid-containing glycoconjugate epitopes was due to the low level of α-Gal in heterozygote GalT KO livers. Furthermore, proteomics analysis showed that heterozygote GalT KO pigs had a higher expression of NAD+-isocitrate dehydrogenase (IDH), which is related to the CMP-N-acetylneuraminic acid hydroxylase (CMAH) enzyme reaction. These findings suggest the deficiency of GGTA1 gene in pigs results in increased production of N-glycolylneuraminic acid (Neu5Gc) due to an increase of α2,6-sialyltransferase and a CMAH cofactor, NAD+-IDH. This indicates that Neu5Gc may be a critical xenoantigen. The deletion of the CMAH gene in the GalT KO background is expected to further prolong xenograft survival

The effect of alpha lipoic acid in a porcine in-stent restenosis model

SummaryBackgroundThe aim of this study was to investigate the effect of alpha lipoic acid (α-LA) on a porcine in-stent restenosis (ISR) model.MethodsIn protocol 1, porcine vascular smooth muscle cells (PVSMC) were stimulated by granulocyte-colony stimulating factor (G-CSF) in the presence or absence of α-LA. MTT (3-[4,5-dimethylthiazole-2-yl] 2,5-diphenyl tetrazolium bromide) assay and western blotting were used to determine the cell growth inhibitory rate and anti-inflammatory effect associated with nuclear factor-κb (NF-κb) and extracellular signal-regulated kinase (ERK). In protocol 2, 28 days after balloon overdilation injuries, 24 bare metal stents were placed in coronary artery of 12 pigs. The pigs were randomly divided to receive control diet with or without α-LA (100mg/kg). In protocol 3, 8 control stents and 8 α-LA coated stents were randomly implanted in 2 coronary arteries of 8 pigs and follow-up coronary angiogram and histopathologic assessment were performed 4 weeks after stenting.ResultsProtocol 1. The proliferation of PVSMC was inhibited and protein expression of NF-κb and ERK were attenuated by α-LA pretreatment. Protocol 2. On histopathologic analysis, the neointimal area (4.0±1.0mm2 vs. 1.5±0.7mm2, p<0.001) and histopathologic area of stenosis (66.7±10.7% vs. 24.2±9.7%, p<0.001) were reduced in the α-LA feeding group compared to controls. Protocol 3. On histopathologic analysis, the neointimal area (3.9±0.8mm2 vs. 1.0±0.4mm2, p<0.001), and the histopathologic area of stenosis (67.1±8.8% vs. 17.4±10.0%, p<0.001) were reduced in the α-LA coated stent group compared to the control stent group.Conclusionsα-LA feeding and α-LA coated stents inhibit neointimal hyperplasia in porcine ISR, possibly through inhibiting the activation of NF-κb pathway and proliferation of PVSMC