Inhibition of release of vasoactive and inflammatory mediators in airway and vascular tissues and macrophages by a Chinese herbal medicine formula for allergic rhinitis

Herbal therapies are being used increasingly for the treatment of allergic rhinitis. The aim of this study was to investigate the possible pharmacological actions and cellular targets of a Chinese herbal formula (RCM-101), which was previously shown to be effective in reducing seasonal allergic rhinitis symptoms in a randomized, placebo-controlled clinical trial. Rat and guinea pig isolated tissues (trachea and aorta) were used to study the effects of RCM-101 on responses to various mediators. Production of leukotriene 134 in porcine neutrophils and of prostaglandin E-2 and nitric oxide (NO) in Raw 264.7 cells were also measured. In rat and guinea pig tracheal preparations, RCM-101 inhibited contractile responses to compound 48/80 but not those to histamine (guinea pig preparations) or serotonin (rat preparations). Contractile responses of guinea pig tracheal preparations to carbachol and leukotriene C-4. and relaxant responses to substance P and prostaglandin E2 were not affected by RCM-101. In rat aortic preparations, precontracted with phenylephrine, endothelium-dependent relaxant responses to acetylcholine and endothelium-independent relaxant responses to sodium nitroprusside were not affected by RCM-101. However, RCM-101 inhibited relaxations to L-arginine in endothelium-denuded rat aortic preparations, which had been pre-incubated with lipopolysaccharide. RCM-101 did not affect leukotriene 134 formation in isolated porcine neutrophils, induced by the calcium ionophore A23187; however, it inhibited prostaglandin E-2 and NO production in lipopolysaccharide-stimulated murine macrophages (Raw 264.7 cells). The findings indicate that RCM-101 may have multiple inhibitory actions on the release and/or synthesis of inflammatory mediators involved in allergic rhinitis

Statistical Performance Analysis of an Ant-Colony Optimisation Application in S-NET

Kenneth MacKenzie, Philip K. F. Hölzenspies, Kevin Hammond, Raimund Kirner, Vu Thien Nga Nguyen, Iraneus te Boekhorst, Clemens Grelck, Raphael Poss, Merijn Verstraaten, 'Statistical Performance Analysis of an Ant-Colony Optimisation Application in S-NET'. Paper presented at the 2nd Workshop on Feedback-Directed Compiler Optimization for Multi-Core Architectures. Berlin, Germany, 12 January 2013.We consider an ant-colony optimsation problem implemented on a multicore system as a collection of asynchronous stream- processing components under the control of the S-NET coordina- tion language. Statistical analysis and visualisation techniques are used to study the behaviour of the application, and this enables us to discover and correct problems in both the application program and the run-time system underlying S-NET

Inhibition of release of inflammatory in primary and cultured cells by a Chinese herbal medicine formula for allergic rhinitis

BACKGROUND - We demonstrated that a Chinese herbal formula, which we refer to as RCM-101, developed from a traditional Chinese medicine formula, reduced nasal and non-nasal symptoms of seasonal allergic rhinitis (SAR). The present study in primary and cultured cells was undertaken to investigate the effects of RCM-101 on the production/release of inflammatory mediators known to be involved in SAR. METHODS - Compound 48/80-induced histamine release was studied in rat peritoneal mast cells. Production of leukotriene B4 induced by the calcium ionophore A23187 was studied in porcine neutrophils using an HPLC assay and lipopolysaccharide-stimulated prostaglandin E2 production was studied in murine macrophage (Raw 264.7) cells by immune-enzyme assay. Expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) was determined in Raw 264.7 cells, using western blotting techniques. RESULTS - RCM-101 (1-100 microg/mL) produced concentration-dependent inhibition of compound 48/80-induced histamine release from rat peritoneal mast cells and of lipopolysaccharide-stimulated prostaglandin E2 release from Raw 264.7 cells. Over the range 1 - 10 microg/mL, it inhibited A23187-induced leukotriene B4 production in porcine neutrophils. In addition, RCM-101 (100 microg/mL) inhibited the expression of COX-2 protein but did not affect that of COX-1. CONCLUSION - The findings indicate that RCM-101 inhibits the release and/or synthesis of histamine, leukotriene B4 and prostaglandin E2 in cultured cells. These interactions of RCM-101 with multiple inflammatory mediators are likely to be related to its ability to reduce symptoms of allergic rhinitis

Enhanced magnetization of ultrathin NiFe2_2O4_4 films on SrTiO3_3(001) related to cation disorder and anomalous strain

NiFe$_2$O$_4$ thin films with varying thickness were grown on SrTiO$_3$(001) by reactive molecular beam epitaxy. Soft and hard x-ray photoelectron spectroscopy measurements reveal a homogeneous cation distribution throughout the whole film with stoichiometric Ni:Fe ratios of 1:2 independent of the film thickness. Low energy electron diffraction and high resolution (grazing incidence) x-ray diffraction in addition to x-ray reflectivity experiments were conducted to obtain information of the film surface and bulk structure, respectively. For ultrathin films up to 7.3 nm, lateral tensile and vertical compressive strain is observed, contradicting an adaption at the interface of NiFe$_2$O$_4$ film and substrate lattice. The applied strain is accompanied by an increased lateral defect density, which is decaying for relaxed thicker films and attributed to the growth of lateral grains. Determination of cationic site occupancies in the inverse spinel structure by analysis of site sensitive diffraction peaks reveals low tetrahedral occupancies for thin, strained NiFe$_2$O$_4$ films, resulting in partial presence of deficient rock salt like structures. These structures are assumed to be responsible for the enhanced magnetization of up to $\sim$250\% of the NiFe$_2$O$_4$ bulk magnetization as observed by superconducting quantum interference device magnetometry for ultrathin films below 7.3 nm thickness.Comment: 11 pages, 9 figure

Panax ginseng C.A Meyer root extract for moderate Chronic Obstructive Pulmonary Disease (COPD): study protocol for a randomised controlled trial

Chronic obstructive pulmonary disease (COPD) impairs quality of life and leads to premature mortality. COPD sufferers experience progressive deterioration of lung function and decreased ability to undertake day-to-day activities. Ginseng has been used for thousands of years in Chinese medicine for respiratory symptoms. Several controlled clinical trials using ginseng for COPD have shown promising clinical effect, however these studies were generally small and with some potential bias, prompting the need for rigorously designed studies

Inhibition of release of inflammatory mediators in primary and cultured cells by a Chinese herbal medicine formula for allergic rhinitis

BACKGROUND: We demonstrated that a Chinese herbal formula, which we refer to as RCM-101, developed from a traditional Chinese medicine formula, reduced nasal and non-nasal symptoms of seasonal allergic rhinitis (SAR). The present study in primary and cultured cells was undertaken to investigate the effects of RCM-101 on the production/release of inflammatory mediators known to be involved in SAR. METHODS: Compound 48/80-induced histamine release was studied in rat peritoneal mast cells. Production of leukotriene B(4 )induced by the calcium ionophore A23187 was studied in porcine neutrophils using an HPLC assay and lipopolysaccharide-stimulated prostaglandin E(2 )production was studied in murine macrophage (Raw 264.7) cells by immune-enzyme assay. Expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) was determined in Raw 264.7 cells, using western blotting techniques. RESULTS: RCM-101 (1–100 μg/mL) produced concentration-dependent inhibition of compound 48/80-induced histamine release from rat peritoneal mast cells and of lipopolysaccharide-stimulated prostaglandin E(2 )release from Raw 264.7 cells. Over the range 1 – 10 μg/mL, it inhibited A23187-induced leukotriene B(4 )production in porcine neutrophils. In addition, RCM-101 (100 μg/mL) inhibited the expression of COX-2 protein but did not affect that of COX-1. CONCLUSION: The findings indicate that RCM-101 inhibits the release and/or synthesis of histamine, leukotriene B(4 )and prostaglandin E(2 )in cultured cells. These interactions of RCM-101 with multiple inflammatory mediators are likely to be related to its ability to reduce symptoms of allergic rhinitis

Visualizing the role of Cbl-b in control of islet-reactive CD4 T cells and susceptibility to Type 1 Diabetes

The E3 ubiquitin ligase Cbl-b regulates T cell activation thresholds and has been associated with protecting against Type 1 diabetes, but its in vivo role in the process of self-tolerance has not been examined at the level of potentially auto-aggressive CD4+ T cells. Here we visualize the consequences of Cbl-b deficiency on self-tolerance to lysozyme antigen expressed in transgenic mice under control of the insulin promoter (insHEL). By tracing the fate of pancreatic islet-reactive CD4+ T cells in pre-diabetic 3A9-TCR x insHEL double-transgenic mice, we find that Cbl-b deficiency contrasts with AIRE or IL-2 deficiency because it does not affect thymic negative selection of islet-reactive CD4+ cells nor the numbers of islet-specific CD4+ or CD4+ FOXP3+ T cells in the periphery, although it decreased differentiation of inducible Treg (iTreg) cells from TGF-b treated 3A9-TCR cells in vitro. When removed from Tregs and placed in culture, Cblb-deficient islet-reactive CD4+ cells reveal a capacity to proliferate to HEL antigen that is repressed in wild-type cells. This latent failure of T cell anergy is nevertheless controlled in vivo in pre-diabetic mice, so that islet-reactive CD4+ cells in spleen and pancreatic lymph node of Cblb-deficient mice show no evidence of increased activation or proliferation in situ. Cblb-deficiency subsequently precipitated diabetes in most TCR:insHEL animals by 15 wks of age. These results reveal a role for peripheral T cell anergy in organ-specific self-tolerance, and illuminate the interplay between Cblb-dependent anergy and other mechanisms for preventing organ-specific autoimmunity

Protective Immunity against Respiratory Syncytial Virus in Early Life after Murine Maternal or Neonatal Vaccination with the Recombinant G Fusion Protein BBG2Na

Maternal and neonatal immunization were evaluated for their capacity to induce protective immunity against respiratory syncytial virus (RSV) lower respiratory tract infections in early life. Murine models were studied by use of a novel recombinant vaccine candidate, designated BBG2Na, which was derived in part from the RSV (Long) G protein. Maternal immunization resulted in the passive transfer of high levels of RSV-A antibodies to the offspring, which protected them from RSV challenge for up to 14 weeks. Indeed, protection correlated with the detection of RSV antibodies in the serum. Neonatal immunization with BBG2Na induced significant antibody responses even in the first week of life. Most importantly, these neonatal responses were not inhibited by the presence of RSV maternal antibodies. Consequently, the combination of maternal and neonatal immunization with BBG2Na resulted in the continual presence of protective levels of antibodies in the offsprin