Comparative study on saponin fractions from Panax notoginseng inhibiting inflammation-induced endothelial adhesion molecule expression and monocyte adhesion

<p>Abstract</p> <p>Background</p> <p><it>Panax notoginseng </it>is commonly used for the treatment of cardiovascular diseases in China. The present study investigates the effects of three different saponin fractions (<it>ie </it>total saponins, PNS; protopanaxadiol-type saponin, PDS; and protopanaxatriol-type saponin, PTS) and two major individual ingredients (<it>ie </it>ginsenoside Rg₁and Rb₁) from <it>P. notoginseng </it>on the endothelial inflammatory response <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>Recombinant human tumor necrosis factor-α (TNF-α) was added to the culture medium of human coronary artery endothelial cells (HCAECs) to induce an inflammatory response. A cell adhesion assay was used to determine the effect of the <it>P. notoginseng </it>saponin fractions on endothelial-monocyte interaction. The cell adhesion molecule (CAMs) expression, including ICAM-1 and VCAM-1, in the protein level on the surface of endothelial cells were measured by cellular ELISA. CAMs expression in mRNA level was also assayed by qRT-PCR in the HCAECs and the aorta of rat fed with high cholesterol diet (HCD). Western blotting was used to detect effect of the saponin fractions on CAMs protein expression in HCAECs. In addition, nuclear translocation of p65, a surrogate marker for NF-κB activation, was measured by immunostaining.</p> <p>Results</p> <p>Three saponin fractions and two individual ginsenosides exhibited the inhibitory effects on monocyte adhesion on TNF-α-activated HCAECs and expression of ICAM-1 and VCAM-1 at both mRNA and protein levels <it>in vitro</it>. The saponin fractions exhibited a similar trend of the inhibitory effects on the mRNA expression of CAMs in the aorta of HCD-fed rat <it>in vivo</it>. These inhibitory effect of saponin fractions maybe attribute partially to the suppression of the TNF-α-induced NF-κB activation.</p> <p>Conclusion</p> <p>Our data demonstrate that saponin fractions (<it>ie </it>PNS, PDS and PTS) and major individual ginsenosides (<it>ie </it>Rg₁and Rb₁) have potential anti-atherogenic effects. Among the tested saponin fractions, PDS is the most potent saponin fraction against TNF-α-induced monocyte adhesion as well as the expression of adhesion molecules <it>in vitro </it>and <it>in vivo</it>.</p

Clinical and health economic benefits of out-patient lumbar microdiscectomies in Australia.

Introduction: This study reports on the clinical, nursing and health outcomes on the out-patient lumbar microdiscectomy program at a single institution. A multi-disciplinary team approach to the pre- and post-operative planning and education is key to the success of this program. Methods: A retrospective review of prospectively collected data for two patient groups (outpatient microdiscectomy and in-patient microdiscectomy) over a two-year period in a single institution was performed. Clinical, demographical, surgical and economic measures were collected including a 10-point visual analogue pain scale (VAS), patient satisfaction, direct and indirect costs of treatment. Patients included had a single level lumbar disc prolapse with persistent disabling sciatica of more than 8 weeks consistent with failure of conservative measures. Results: Twenty-one out-patient and forty-one in-patient microdiscectomy patients were treated over this period. Post operatively pain levels showed a significant improvement in VAS levels from 5.2 ±2.9 to 1.6 ±0.8 and 0.7 ± 0.8 at day 1 and 7 post-operatively respectively. This was not different across both groups. Patient satisfaction was high in both surgical groups. There was a significant cost savings in out-patient lumbar micro-discectomy with the majority of savings coming from costs associated with staff (nursing, allied health and medical) funding. There was successful discharge 100% of out-patient microdiscectomy patients without readmission. Conclusion: Outpatient lumbar microdiscectomy is a viable option in Australia. It demonstrates no difference in patient outcomes as compared to in-patient lumbar microdiscectomies and has high patient satisfaction outcomes. There are significant benefits in terms of health economics and nursing care in establishing an out-patient lumbar microdiscetomy program

Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial cells (ECs) constantly experience fluid shear stresses generated by blood flow. Laminar flow is known to produce atheroprotective effects on ECs. Nrf2 is a transcription factor that is essential for the antioxidant response element (ARE)-mediated induction of genes such as heme-oxygenase 1 (HO-1). We previously showed that fluid shear stress increases intracellular reactive oxygen species (ROS) in ECs. Moreover, oxidants are known to stimulate Nrf2. We thus examined the regulation of Nrf2 in cultured human ECs by shear stress.</p> <p>Results</p> <p>Exposure of human umbilical vein endothelial cells (HUVECs) to laminar shear stress (12 dyne/cm²) induced Nrf2 nuclear translocation, which was inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, a protein kinase C (PKC) inhibitor, and an antioxidant agent N-acetyl cysteine (NAC), but not by other protein kinase inhibitors. Therefore, PI3K, PKC, and ROS are involved in the signaling pathway that leads to the shear-induced nuclear translocation of Nrf2. We also found that shear stress increased the ARE-binding activity of Nrf2 and the downstream expression of HO-1.</p> <p>Conclusion</p> <p>Our data suggest that the atheroprotective effect of laminar flow is partially attributed to Nrf2 activation which results in ARE-mediated gene transcriptions, such as HO-1 expression, that are beneficial to the cardiovascular system.</p

CTX-M and Plasmid-mediated AmpC-Producing Enterobacteriaceae, Singapore

10.3201/eid1006.030726Emerging Infectious Diseases1061172-117

An expert consensus for the management of chronic hepatitis B in Asian Americans.

BACKGROUND: Hepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide. AIM: To generate recommendations for the management of Asian Americans infected with HBV. METHODS: These guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women. RESULTS: Asian American patients, HBeAg positive or negative, with HBV DNA levels \u3e2000 IU/mL (\u3e10 CONCLUSIONS: Application of the recommendations made based on a review of the relevant literature and the opinion of a panel of Asian American physicians with expertise in HBV treatment will inform physicians and improve patient outcomes

Slit2 prevents neutrophil recruitment and renal ischemia-reperfusion injury

Neutrophils recruited to the postischemic kidney contribute to the pathogenesis of ischemia-reperfusion injury (IRI), which is the most common cause of renal failure among hospitalized patients. The Slit family of secreted proteins inhibits chemotaxis of leukocytes by preventing activation of Rho-family GTPases, suggesting that members of this family might modulate the recruitment of neutrophils and the resulting IRI. Here, in static and microfluidic shear assays, Slit2 inhibited multiple steps required for the infiltration of neutrophils into tissue. Specifically, Slit2 blocked the capture and firm adhesion of human neutrophils to inflamed vascular endothelial barriers as well as their subsequent transmigration. To examine whether these observations were relevant to renal IRI, we administered Slit2 to mice before bilateral clamping of the renal pedicles. Assessed at 18 hours after reperfusion, Slit2 significantly inhibited renal tubular necrosis, neutrophil and macrophage infiltration, and rise in plasma creatinine. In vitro, Slit2 did not impair the protective functions of neutrophils, including phagocytosis and superoxide production, and did not inhibit neutrophils from killing the extracellular pathogen Staphylococcus aureus. In vivo, administration of Slit2 did not attenuate neutrophil recruitment or bacterial clearance in mice with ascending Escherichia coli urinary tract infections and did not increase the bacterial load in the livers of mice infected with the intracellular pathogen Listeriamonocytogenes. Collectively, these results suggest that Slit2 may hold promise as a strategy to combat renal IRI without compromising the protective innate immune response. Copyright © 2013 by the American Society of Nephrology

Bisdemethoxycurcumin Increases Sirt1 to Antagonize t

Curcuminoids are well known for their capabilities to combat risk factors that are associated with ageing and cellular senescence. Recent reports have demonstrated that curcuminoids can extend the lifespan of model organisms. However, the underlying mechanisms by which these polyphenic compounds exert these beneficial effects remain unknown. In this study, t-BHP-induced premature senescence model in human fibroblasts was chosen to explore the protective effects of a curcuminoid, bisdemethoxycurcumin (BDMC), on cellular senescence. The results demonstrated that BDMC attenuated oxidative stress-induced senescence-like features which include the induction of an enlarged cellular appearance, higher frequency of senescence-associated β-galactosidase staining activity, appearance of senescence-associated heterochromatic foci in nuclei, decrease in proliferation capability, and alteration in related molecules such as p16 and retinoblastoma protein. Notably, we found that BDMC treatment activated Sirt1/AMPK signaling pathway. Moreover, downregulating Sirt1 by the pharmacological inhibitor nicotianamine or small interfering RNA blocked BDMC-mediated protection against t-BHP-mediated decrease in proliferation. These results suggested that BDMC prevented t-BHP-induced cellular senescence, and BDMC-induced Sirt1 may be a mechanism mediating its beneficial effects

ZYZ-168 alleviates cardiac fibrosis after myocardial infarction through inhibition of ERK1/2-dependent ROCK1 activation

Selective treatments for myocardial infarction (MI) induced cardiac fibrosis are lacking. In this study, we focus on the therapeutic potential of a synthetic cardio-protective agent named ZYZ-168 towards MI-induced cardiac fibrosis and try to reveal the underlying mechanism. ZYZ-168 was administered to rats with coronary artery ligation over a period of six weeks. Ecocardiography and Masson staining showed that ZYZ-168 substantially improved cardiac function and reduced interstitial fibrosis. The expression of α–smooth muscle actin (α-SMA) and Collagen I were reduced as was the activity of matrix metalloproteinase 9 (MMP-9). These were related with decreased phosphorylation of ERK1/2 and expression of Rho-associated coiled-coil containing protein kinase 1 (ROCK1). In cardiac fibroblasts stimulated with TGF-β1, phenotypic switches of cardiac fibroblasts to myofibroblasts were observed. Inhibition of ERK1/2 phosphorylation or knockdown of ROCK1 expectedly reduced TGF-β1 induced fibrotic responses. ZYZ-168 appeared to inhibit the fibrotic responses in a concentration dependent manner, in part via a decrease in ROCK 1 expression through inhibition of the phosphorylation status of ERK1/2. For inhibition of ERK1/2 phosphorylation with a specific inhibitor reduced the activation of ROCK1. Considering its anti-apoptosis activity in MI, ZYZ-168 may be a potential drug candidate for treatment of MI-induced cardiac fibrosis

Multiphoton Quantum Optics and Quantum State Engineering

We present a review of theoretical and experimental aspects of multiphoton quantum optics. Multiphoton processes occur and are important for many aspects of matter-radiation interactions that include the efficient ionization of atoms and molecules, and, more generally, atomic transition mechanisms; system-environment couplings and dissipative quantum dynamics; laser physics, optical parametric processes, and interferometry. A single review cannot account for all aspects of such an enormously vast subject. Here we choose to concentrate our attention on parametric processes in nonlinear media, with special emphasis on the engineering of nonclassical states of photons and atoms. We present a detailed analysis of the methods and techniques for the production of genuinely quantum multiphoton processes in nonlinear media, and the corresponding models of multiphoton effective interactions. We review existing proposals for the classification, engineering, and manipulation of nonclassical states, including Fock states, macroscopic superposition states, and multiphoton generalized coherent states. We introduce and discuss the structure of canonical multiphoton quantum optics and the associated one- and two-mode canonical multiphoton squeezed states. This framework provides a consistent multiphoton generalization of two-photon quantum optics and a consistent Hamiltonian description of multiphoton processes associated to higher-order nonlinearities. Finally, we discuss very recent advances that by combining linear and nonlinear optical devices allow to realize multiphoton entangled states of the electromnagnetic field, that are relevant for applications to efficient quantum computation, quantum teleportation, and related problems in quantum communication and information.Comment: 198 pages, 36 eps figure