Regulation of monocyte IL-10 synthesis by endogenous IL-1 and TNF-alpha: role of the p38 and p42/44 mitogen-activated protein kinases

IL-10 is an anti-inflammatory cytokine with potent immunomodulatory effects, including inhibition of cytokine production. However, regulation of monocyte IL-10 production is poorly understood. In this report we have investigated the mechanisms of LPS-induced IL-10 production by human peripheral blood monocytes and demonstrate that IL-10 synthesis is uniquely dependent on the endogenous proinflammatory cytokines IL-1 and/or TNF-alpha. LPS signal transduction in monocytes has been shown to involve activation of the p38 and p42 mitogen-activated protein kinase (MAPK) cascades. The results in this paper indicate that inhibition of p38 MAPK potently inhibited the production of IL-10, IL-1beta, and TNF-alpha, whereas blockade of the p42/44 MAPK pathway, while partially inhibiting TNF-alpha and IL-1beta production, had no effect on monocyte secretion of IL-10. Furthermore, neither the inhibition of monocyte TNF-alpha induced by IL-10 nor the stimulation of soluble TNF receptor production was affected by inhibition of the p42/44 MAPK pathway, suggesting that this signaling event is not involved in either monocyte production of or anti-inflammatory responses to IL-10. These data raise the interesting possibility that proinflammatory TNF-alpha-mediated effects may be selectively blocked without modulating the induction or the response to IL-10, whereas the signaling events associated with the anti-inflammatory events induced by IL-10 remain to be elucidated.     

Continuous non-invasive blood pressure monitoring by brachial artery displacement method in high-risk surgical patients

Continuous non-invasive blood pressure (CNBP) measurements were compared to invasive radial artery pressure recordings in 26 patients with cardiac, vascular and/or pulmonary disease. Patients were studied during general anaesthesia (n = 6), regional anaesthesia (n = 10), or combined technique (n = 10) for abdominal or transurethral surgery. CNBP was obtained from a cuff placed around the upper arm and simultaneously compared to invasive pressure from the ipsilateral radial artery. A CNBP device (7001 Cortronic) used intermittent oscillometric measurement for calibration. Through a cuff continuously inflated to a pressure of 20 mmHg, a microprocessor-controlled electro-pneumatic acquisition system sensed displacements of the brachial artery wall. Amplified, digitally converted, filtered and transformed data were displayed as a continuous pulse pressure waveform and digital pressure values on the screen. The CNBP method functioned without disturbances before surgery in all patients. Intra-operative use of electrocautery or a spontaneous occurrence of warning on the screen repeatedly triggered oscillometric recalibration, hence CNBP measurements were discontinued in nine patients. Coefficients of correlation (r) of all invasive and CNBP pairs (n = 1111) were 0.68, 0.58 and 0.70 for systolic, diastolic, and mean blood pressures, respectively. Prediction errors (bias, mean +/- SD) were -13.6 +/- 22.5 mmHg (on average CNBP < invasive pressure) for systolic, +13.0 +/- 12.4 mmHg (CNBP > invasive pressure) for diastolic and +5.0 +/- 13.9 mmHg (CNBP > invasive pressure) for mean CNBP, as compared to radial artery pressure values. Absolute errors (precision) were 25.3 +/- 9.4 mmHg for systolic, 17.4 +/- 4.5 mmHg for diastolic, and 13.9 +/- 4.6 mmHg for mean CNBP. During anaesthesia induction (n = 672) the difference between consecutive measurements (trend of pressure changes) with invasive and CNBP method exceeded 20 mmHg in 90 (13.3%) instances for systolic, in 33 (4.9%) instances for diastolic, and in 45 (6.6%) instances for mean blood pressure. In conclusion, the CNBP method by brachial artery wall displacement failed to measure the blood pressure reliably and to display the trend of pressure changes correctly during anaesthesia induction. In its present form this CNBP method should not replace invasive blood pressure monitoring in high-risk patients neither for anaesthesia induction nor during non-thoracic surgical procedures.     

Decreased rejection and improved survival of first and second marrow transplants for severe aplastic anemia (a 26-year retrospective analysis)

Between 1970 and 1996, 333 patients with severe aplastic anemia underwent HLA-matched related marrow transplant after conditioning with cyclophosphamide (CY). Thirty-five percent of patients transplanted between 1970 and 1976 (group 1), 12% of those transplanted between 1977 and 1981 (group 2), and 9% of patients transplanted between 1982 and 1997 (group 3) had graft rejection. Graft rejection occurred later among group 3 patients (median, 180 days) than among those in groups 1 and 2 (medians, 28 and 47 days, respectively; P < .001 group 3 v 2). In group 3, 92% of rejecting patients underwent a second transplant, compared with 78% and 77% in groups 1 and 2, respectively. Group 1 patients received various conditioning regimens before second transplant, whereas most patients of groups 2 and 3 received CY combined with antithymocyte globulin (ATG). Graft-versus-host disease (GVHD) prophylaxis after second transplant consisted of methotrexate (MTX) for all group 1 and 2 patients, whereas group 3 patients received MTX combined with cyclosporine (CSP). Over the three time periods studied, first graft rejection decreased from 35% to 9%, and the proportion of rejecting patients undergoing second transplants increased from 77% to 92%. The 10-year probability of survival after second transplants increased from 5% to 83%. Multivariate analysis showed MTX/CSP GVHD prophylaxis to be a significant factor accounting for the increase in patient survival after second transplant.     

Ability of 16 priority PAHs to be directly cytotoxic to a cell line from the rainbow trout gill

Sixteen polycyclic aromatic hydrocarbons (PAHs) were screened for their ability to be directly cytotoxic to a cell line from the rainbow trout gill, RTgill-W1. Exposure times of 2 h or less were sufficient for direct cytotoxicity to be detected, which appeared to be caused by a common mechanism, the general perturbation of membranes. This was judged by the similarity of results obtained for three fluorescent indicator dyes, alamar Blue, 5-carboxyfluorescein diacetate acetoxymethyl ester (CFDA-AM) and neutral red. Among the 16 PAHs tested, just two- and three-ring PAHs were found to be directly cytotoxic. These were naphthalene approximately = acenaphthylene approximately = acenaphthene > fluorene approximately = phenanthrene. The results suggest that water solubility and lipophilicity are the critical properties determining the direct cytotoxicity of PAHs and that they do so by influencing PAH accumulation in membranes. Only naphthalene was effective at concentrations well below its water solubility limit. Therefore, direct cytotoxicity is likely to be most environmentally relevant only with naphthalene.     

Effects of insulin-like growth factor I combined with growth hormone on glucocorticoid-induced whole-body protein catabolism in man

Treatment with insulin-like growth factor I (IGF-I) alone failed to affect glucocorticoid-induced protein catabolism in a previous study from our laboratory. To assess the effects of the combination of IGF-I and GH in a similar protocol, 24 normal subjects received (in a double-blind, randomized, placebo-controlled manner) s.c. injections of either GH alone (0.3 IU/kg.day), the combination of IGF-I (80 micrograms/kg.day) and GH (0.3 IU/kg.day), or placebo for a period of 6 days during which they were treated with methylprednisolone (0.5 mg/kg.day). Whole-body protein kinetics measured, using the [1-13C]-leucine infusion technique, demonstrated that leucine flux (a parameter of protein breakdown) increased during administration of glucocorticoids alone (placebo group) and during GH-treatment, whereas the glucocorticoid-induced increase was abolished during IGF-I plus GH (P < 0.03 vs. GH). Leucine oxidation (a parameter of irreversible protein catabolism) increased in the placebo group (+60 +/- 14.5%, P < 0.005, day 7 vs. day 1), remained unchanged in the GH group (+2.5 +/- 10%), and decreased in the combination group (-17.7 +/- 3.3%, P < 0.002, day 7 vs. day 1). Glucose MCR decreased in the group receiving placebo (P < 0.05) and remained unchanged during combined treatment with IGF-I plus GH. It is concluded that glucocorticoid-induced protein, catabolism (leucine oxidation) is abolished during coadministration of GH (anticatabolic effect), whereas treatment with IGF-I and GH results in a net anabolic effect without adverse effects on peripheral glucose clearance.     

Characterization and Catalytic Properties of Combustion Synthesized Au/CeO2 Catalyst

Ceria-supported Au catalyst has been synthesized by the solution combustion method for the first time and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). Au is dispersed as Au⁰ as well as Au³⁺ states on CeO₂ surface of 20-30 nm crystallites. On heating the as-prepared 1% Au/CeO₂ in air, the concentration of Au³⁺ ions on CeO₂ increases at the expense of Au⁰. Catalytic activities for CO and hydrocarbon oxidation and NO reduction over the as-prepared and the heat-treated 1% Au/CeO₂ have been carried out using a temperature-programmed reaction technique in a packed bed tubular reactor. The results are compared with nano-sized Au metal particles dispersed on -Al₂O₂ substrate prepared by the same method. All the reactions over heat-treated Au/CeO₂ occur at lower temperature in comparison with the as-prepared Au/CeO₂ and Au/Al₂O₂. The rate of NO + CO reaction over as-prepared and heat-treated 1% Au/CeO₂ are 28.3 and 54.0 mol g^-1 s^-1 at 250 and 300 °C respectively. Activation energy (E _a) values are 106 and 90 kJ mol^-1 for CO + O₂ reaction respectively over as-prepared and heat-treated 1% Au/CeO₂ respectively.     

Starch Hydrolysate,an Optimal and Economical Source of Carbon for the Secretion of Citric Acid by Yarrowia lipolytica (DS-1)

Using Yarrowia lipolytica (DS-1), secretion of citric acid is studied as a function of carbon sources such as glucose, fructose, hydrol, sucrose, cane sugar molasses, kerosene (all available commercially) and tapioca starch hydrolysate, invert sucrose and invert cane sugar molasses (all prepared in laboratory). On the basis of their acceptability by DS-1 for citric and isocitric acid secretion, it is concluded that (a) sucrose and cane sugar molasses (with/without inversion) served as poor carbon sources, (b) fructose, hydrol, impure tapioca starch hydrolysate (96 DE w/w) and invert sucrose served as relatively better carbon sources and (c) purified tapioca starch hydrolysate (96 DE w/w) was the best carbon source to substitute glucose by giving comparable (75%) efficiency of conversion and economical advantage.