CD74 deficiency ameliorates Pseudomonas aeruginosa-induced ocular infection

Eye trauma and contact lens wear are the main factors that predispose to the development of infectious keratitis. The existing therapies fail to control the inflammation-driven tissue damage that occurs during Pseudomonas aeruginosa infection. Antibiotic treatment reduces bacterial burdens, but better interventions are needed to alleviate tissue damage resulting from local inflammation. We have previously documented that inhibition of macrophage migration inhibitory factor (MIF) reduces the bacterial levels and the inflammatory damage during keratitis. Here, we report that mice deficient for CD74, the putative MIF receptor, developed milder Pseudomonas aeruginosa-induced disease, characterized by decreased proinflammatory mediators and reduced bacterial presence in the cornea. However, topical inhibition of MIF using antibodies applied to the cornea further promoted recovery from disease, suggesting that in addition to MIF-dependent signaling events, MIF-triggered CD74-independent signaling pathways regulate sensitization to P. aeruginosa-induced infection

Low pre-transplant levels of mannosebinding lectin are associated with viral infections and mortality after haematopoietic allogeneic stem cell transplantation

Background: Mannose-binding lectin (MBL) is a key component of innate immunity. Low serum MBL levels, related to promoter polymorphism and structural variants, have been associated with an increased risk of infection. The aim of this work was to analyse the incidence and severity of infections and mortality in relation to the MBL2 genotype and MBL levels in patients underwent allogeneic haematopoietic stem cell transplantation (Allo-HSCT). Results: This was a prospective cohort study of 72 consecutive patients underwent Allo-HSCT between January 2007 and June 2009 in a tertiary referral centre. Three periods were considered in the patients? follow-up: the early period (0?30 days after Allo-HSCT), the intermediate period (30?100 days after Allo-HSCT) and the late period (> 100 days after Allo-HSCT). A commercial line probe assay for MBL2 genotyping and an ELISA Kit were used to measure MBL levels. A total of 220 episodes of infection were collected in the 72 patients. No association between donor or recipient MBL2 genotype and infection was found. The first episode of infection presented earlier in patients with pre-transplant MBL levels of < 1000 ng/ml (median 6d vs 8d, p = 0.036). MBL levels < 1000 ng/ml in the pre-transplant period (risk ratio (RR) 2.48, 95% CI 1.00?6.13), neutropenic period (0?30 days, RR 3.28, 95% CI 1.53?7.06) and intermediate period (30?100 days, RR 2.37, 95% CI 1.15?4.90) were associated with increased risk of virus infection. No association with bacterial or fungal disease was found. Mortality was associated with pre-transplant MBL levels < 1000 ng/ml (hazard ratio 5.55, 95% CI 1.17?26.30, p = 0.03) but not with MBL2 genotype. Conclusions: Patients who underwent Allo-HSCT with low pre-transplant MBL levels presented the first episode of infection earlier and had an increased risk of viral infections and mortality in the first 6 months post-transplant. Thus, pre-transplant MBL levels would be important in predicting susceptibility to viral infections and mortality and might be considered a biomarker to be included in the pre-transplantation risk assessment.This work was supported by grants from the Fondo de Investigaciones Sanitarias (Ministry of Health of Spain) PI04/0492 to MC Fariñas and Instituto de Investigación Sanitaria Valdecilla (IDIVAL) API 06/01. The content of the paper is solely the responsibility of the authors and does not necessarily represent the official views. The funding body was not involved in the design of the study, collection or analysis of the data, interpretation of the data, or in the writing of the manuscript

Development of wide-band geometry dependent RF planar spiral inductor SPICE model

Parameterized wide-band geometry dependent SPICE models for oil-chip planar spiral inductors are developed in the paper. Model descriptions are presented in the form of PSpice model and in schematic view. The models are realized in the Cadence Capture and Cadence PSpice environment. The developed computer models can be used For adequate computer modeling and simulation of RF circuits. The geometry dependence of the model parameters allows geometry optimization and design automation of spiral inductors. The simulation results are compared to the measurement data for the model verification demonstrating the validity of the computer models

Automated parameter extraction of geometry dependent RF planar inductor model

An approach is proposed in the present paper to parameter extraction of geometry dependent RF planar spiral inductor model. A direct extraction procedure is developed and realized in the Cadence PSpice and Cadence Probe environment based on the measured two-port S-parameters. To minimize the error for the full range of operation a Genetic Algorithm (GA) optimization procedure is applied in MATLAB environment. The approach is useful in RF model design, as the S-parameters can be easily measured for a given microelectronic technology. The proposed model extraction approach is characterized by a very good accuracy

Antioxidant activity of Aronia melanocarpa fruit juice in vitro

Aronia melanocarpa fruit juice (AMFJ) used in this experiment was very rich in phenolic substances, anthocyanins being the main flavonoid group. The antioxidant action of AMFJ was determined in vitro through measuring its Trolox equivalent antioxidant capacity (TEAC), superoxide dismutase (SOD)-like activity and catalase (CAT)-like activity. The TEAC of AMFJ was 63±0.8 mM. The SOD-like activity of 1 ml AMFJ was equivalent to that of 230.3±8.4 U SOD and was equal to that of 12.3 mg L-ascorbic acid and 11.4 mg Trolox, respectively. The CAT-like activity of 1 ml AMFJ was equivalent to the activity of 3223.5±91.3 U CAT and was equal to that of 6.4 mg L-ascorbic acid, while Trolox did not show such an activity. The pronounced antioxidant action of AMFJ is probably due to its high content of phenolic compounds

Protective Effect of Spin-Labeled 1-Ethyl-1-nitrosourea against Oxidative Stress in Liver Induced by Antitumor Drugs and Radiation

This study was carried out to investigate possible protection effect of 1-ethyl-3-[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)]-1-nitrosourea (SLENU), synthesized in our laboratory, against oxidative liver injuries induced in mice treated by antitumor drugs: doxorubicin (DOX), bleomycin (BLM), or gamma irradiation (R). Specifically, alterations in some biomarkers of oxidative stress, such as lipid peroxidation products measured as malondialdehyde (MDA) levels and activities of the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), were studied in liver homogenates isolated from tumor bearing C57 black mice after i.p. treatment with solutions of DOX (60 mg/kg), BLM (60 mg/kg), or after total body gamma-irradiation with a single dose of 5 Gy. The same biomarkers were also measured after i.p. pretreatment of mice with SLENU (100 mg/kg). Statistical significant increased MDA levels and SOD and CAT enzymes activities were found in the liver homogenates of tumor bearing mice after alone treatment with DOX or gamma-irradiation compared to the control mice, while these parameters were insignificantly increased after BLM administration compared to the same controls

50 YEARS ROUMEN TSANEV INSTITUTE OF MOLECULAR BIOLOGY A NEW ANTIOXIDANT WITH NATURAL ORIGIN CHARACTERIZED BY ELECTRON PARAMAGNETIC RESONANCE SPECTROSCOPY METHODS

ABSTRACT Formerly, naturally isolated SQGD exhibited good in vitro radical scavenging capacity towards 1

Redox-modulating and/or antioxidant properties of nitroxides – a potential reason for decreasing side-effects of cancer therapy

The existing therapeutic approaches – radiation therapy and conventional chemotherapy of cancer, suffer of serious side-effects as a result of increased generation of reactive oxygen and nitrogen species (ROS/RNS) in non-cancer cells and tissues. Currently, the development of oxidative stress in non-cancer tissues of cancer-bearing organism is a serious problem of cancer therapy. It is necessary to ask about a combination of substances expressing a therapeutic synergism as a result of differentiated effects on cancer and normal cells: substances with increased ROS/RNS-scavenging properties targeting normal cells and substances with increased ROS/RNS-generating properties targeting cancer cells. In this context, the redox-modulators are one of the most attractive candidates. The present review outlines the basic principle of this novel therapeutic strategy, focusing on nitroxide derivatives as one of the most promising redox-modulators with antioxidant ability