To evaluate of the role of interleqkin-8 (IL-8), a chemotactic cytokine, in the continuous neutrophil accumulation in the airways of patients with chronic airway disease (CAD) and persistent Pseudomonas aeruginosa infection, we investigated the cell population, IL-8 levels, I-1B levels, tumor necrosis factor (TNF) activities, and neutrophil elastase (NE) activities of bronchoalveolar lavage (BAL) fluids in 17 CAD patients (with P. aeruginosa infections [CAD+PA], n = 9; without any bacterial infections [CAD-PA], n = 8) and 8 normal volunteers. We found significant elevations of neutrophil numbers, IL-8/albumin ratios, and NE/ albumin ratios in BAL fluids from CAD patients, in the following rank order. CAD+PA > CADI-PA > normal volunteers. IL-1IB/albumin ratios were elevated only in CAD+PA, while no TNF bioactivity was detected in BAL fluids. The neutrophil numbers correlated significantly with the IL-8/albumin ratios and NE/albumin ratios in the BAL fluids of CAD patients. When anti-human IL-8 immunoglobulin G was used for neutralizing neutrophil chemotactic factor (NCF) activities in BAL fluids, the mean reduction rate of NCF activities in CAD+PA patients was significantly higher than that in CAD-PA patients. We also evaluated the effects of low-dose, long-term erythromycin therapy in BAL fluids from three CAD+PA and two CAD-PA patients. Treatment with erythromycin caused significant reductions of neutrophil numbers, IL-8/albumin ratios, and NE/albumin ratios in BAL fluids from these patients. To elucidate the mechanism of erythromycin therapy, we also examined whether erythromycin suppressed IL-8 production by human alveolar macrophages and neutrophils in vitrp. We demonstrated a moderate inhibitory effect of erythromycin on IL-8 production in Pseudomonas-stimulated neutrophils but not in alveolar macrophages. Our data support the view that persistent P. aeruginosa infection enhances IL-8 production and IL8-derived NCF activity, causing neutrophil accumulation in the airways and the progressive lung injuries observed in patients with CAD. The clinical eficacy of erythromycin therapy for CAD patients might be partly mediated through a reduced IL-8 production, diminishing neutrophil accumulation and NE release in the airways.
Assessment and support in early labour does not have a clear impact on rate of caesarean section or instrumental vaginal birth, or whether the baby was born before arrival at hospital or in an unplanned home birth. However, evidence suggested that interventions may have an impact on reducing the use of epidural anaesthesia, labour augmentation and on increasing maternal satisfaction with giving birth. Evidence about the effectiveness of early labour assessment versus immediate admission was very limited and more research is needed in this area.
Metal-containing novel heterocyclic antibiotics, micacocidin A (1), B (2), and C (3) have been isolated from the culture filtrate of Pseudomonas sp. No. 57-250. The structure and absolute configuration of micacocidin A, an octahedral Zn2+ complex, was determined by X-ray crystallographic analysis. And then, the structures of the two congeners, micacocidin B (Cu2+ complex) and C (Fe3+ complex) were investigated by employing one dimensional and two dimensional homonuclear and heteronuclear NMR spectroscopies and mass spectrometry.In the accompanied paper1), the taxonomy, fermentation, isolation, physico-chemical properties, and biological activities of micacocidin A, B, and C were reported.Herein, we describe the account of the structure determination of micacocidin A (1) and two congeners (2 and 3), metal chelated antibiotics having specific and excellent activity against Mycoplasma species (Fig. 1).
Materials and Methods
Spectroscopic StudiesLiquid secondary ion mass spectra (LSI-MS) were obtained by using a Hitachi M-90 mass spectrometer (BEE geometry) equipped with cesium ion gun. Samples were dispersed in 3-nitrobenzyl alcohol and introduced into the mass spectrometer on a LSI-MS target. One dimensional (1D) and two dimensional (2D) NMR were
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