A Meta-analysis of Immune Parameters, Variability, and Assessment of Modal Distribution in Psychosis and Test of the Immune Subgroup Hypothesis.

Immune parameters are elevated in psychosis, but it is unclear whether alterations are homogenous across patients or heterogeneity exists, consistent with the hypothesis that immune alterations are specific to a subgroup of patients. To address this, we examine whether antipsychotic-naïve first-episode psychosis patients exhibit greater variability in blood cytokines, C-reactive protein, and white cell counts compared with controls, and if group mean differences persist after adjusting for skewed data and potential confounds. Databases were searched for studies reporting levels of peripheral immune parameters. Means and variances were extracted and analyzed using multivariate meta-analysis of mean and variability of differences. Outcomes were (1) variability in patients relative to controls, indexed by variability ratio (VR) and coefficient of variation ratio (CVR); (2) mean differences indexed by Hedges g; (3) Modal distribution of raw immune parameter data using Hartigan's unimodality dip test. Thirty-five studies reporting on 1263 patients and 1470 controls were included. Variability of interleukin-6 (IL6) (VR = 0.19), tumor necrosis factor-α (TNFα) (VR = 0.36), interleukin-1ß (VR = 0.35), interleukin-4 (VR = 0.55), and interleukin-8 (VR = 0.28) was reduced in patients. Results persisted for IL6 and IL8 after mean-scaling. Ninety-four percent and one hundred percent of raw data were unimodally distributed in psychosis and controls, respectively. Mean levels of IL6 (g = 0.62), TNFα (g = 0.56), interferon-γ (IFNγ) (g = 0.32), transforming growth factor-ß (g = 0.53), and interleukin-17 (IL17) (g = 0.48) were elevated in psychosis. Sensitivity analyses indicated this is unlikely explained by confounders for IL6, IFNγ, and IL17. These findings show elevated cytokines in psychosis after accounting for confounds, and that the hypothesis of an immune subgroup is not supported by the variability or modal distribution.

In vitro assessment of silver nanoparticles immunotoxicity.

This study aimed to characterize unwanted immune effects of nanoparticles (NP) using THP-1 cells, human whole blood and enriched peripheral blood monocytes. Commercially available silver NP (AgNP < 100 nm, also confirmed by Single Particle Extinction and Scattering) were used as prototypical NP. Cells were treated with AgNP alone or in combination with classical immune stimuli (i.e. LPS, PHA, PWM) and cytokine assessed; in addition, CD54 and CD86 expression was evaluated in THP-1 cells. AgNP alone induced dose-related IL-8 production in all models, with higher response observed in THP-1 cells, possibly connected to different protein corona formation in bovine versus human serum. AgNP potentiated LPS-induced IL-8 and TNF-α, but not LPS-induced IL-10. AgNP alone induced slight increase in IL-4, and no change in IFN-γ production. While responses to PHA in term of IL-4 and IFN-γ production were not affected, increased PWM-induced IL-4 and IFN-γ production were observed, suggesting potentiation of humoral response. Reduction in PHA-induced IL-10 was observed. Overall, results indicate immunostimulatory effects. THP-1 cells work as well as primary cells, representing a useful and practical alternative, with the awareness that from a physiological point of view the whole blood assay is the one that comes closest to reality.

Assessment of anti-inflammatory properties of extracts from Honeysuckle (Lonicera sp. L., Caprifoliaceae) by ATR-FTIR spectroscopy.

Inflammation is a hallmark of some of today's most life-threatening diseases such as arteriosclerosis, cancer, diabetes and Alzheimer's disease. Herbal medicines (HMs) are re-emerging resources in the fight against these conditions and for many of them, anti-inflammatory activity has been demonstrated. However, several aspects of HMs such as their multi-component character, natural variability and pharmacodynamic interactions (e.g. synergism) hamper identification of their bioactive constituents and thus the development of appropriate quality control (QC) workflows. In this study, we investigated the potential use of Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy as a tool to rapidly and non-destructively assess different anti-inflammatory properties of ethanolic extracts from various species of the Genus Lonicera (Caprifoliaceae). Reference measurements for multivariate calibration comprised in vitro bioactivity of crude extracts towards four key players of inflammation: Nitric oxide (NO), interleukin 8 (IL-8), peroxisome proliferator-activated receptor ß/δ (PPAR ß/δ), and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Multivariate analysis of variance (MANOVA) revealed a statistically significant, quantitative pattern-activity relationship between the extracts' ATR-FTIR spectra and their ability to modulate these targets in the corresponding cell models. Ensemble orthogonal partial least squares (OPLS) discriminant models were established for the identification of extracts exhibiting high and low activity with respect to their potential to suppress NO and IL-8 production. Predictions made on an independent test set revealed good generalizability of the models with overall sensitivity and specificity of 80% and 100%, respectively. Partial least squares (PLS) regression models were successfully established to predict the extracts' ability to suppress NO production and NF-κB activity with root mean squared errors of cross-validation (RMSECV) of 8.7% and 0.05-fold activity, respectively.

[IMMUNOHISTOCHEMICAL AND CYTOLOGICAL ASSESSMENT OF LOCAL INFLAMMATORY REACTION IN THE EARLY POSTOPERATIVE PERIOD IN PATIENTS UNDERGOING SURGERY FOR COMPLEX FORMS OF ACUTE PARAPROCTITIS].

The optimal time to fulfill the second (plastic) phase delayed early radical surgery in patients over the complicated forms of acute paraproctitis. On the 7th day after the opening of an abscess in a smear from the surface layer of the wound inflammatory regenerative cytogram type was observed in 66.8% of patients, early regenerative type--at 33.2%. On the 10th day was observed regenerative cytogram type. The dynamics of the concentration of cytokines in wound fluid on the 7th day showed a favorable course of wound healing process, without increasing the levels of proinflammatory cytokines, which allowed to perform the second stage of early delayed surgery in 7-10 days.

Bacteriophage-nanocomposites: an easy and reproducible method for the construction, handling, storage and transport of conjugates for deployment of bacteriophages active against Pseudomonas aeruginosa.

The purpose of this work was proof of concept to develop a novel, cost effective protocol for the binding of bacteriophages to a surface without loss of function, after storage in various media. The technology platform involved covalently bonding bacteriophage 13 (a Pseudomonas aeruginosa bacteriophage) to two magnetised multiwalled carbon nanotube scaffolds using a series of buffers; bacteriophage-nanotube (B-N) conjugates were efficacious after storage at 20 °C for six weeks. B-N conjugates were added to human cell culture in vitro for 9 days without causing necrosis and apoptosis. B-N conjugates were frozen (-20 °C) in cell culture media for several weeks, after which recovery from the human cell culture medium was possible using a simple magnetic separation technique. The retention of viral infective potential was demonstrated by subsequent spread plating onto lawns of susceptible P. aeruginosa. Analysis of the human cell culture medium revealed the production of interleukins by the human fibroblasts upon exposure to the bacteriophage. One day after exposure, IL-8 levels transitorily increased between 60 and 100 pg/mL, but this level was not found on any subsequent days, suggesting an initial but not long lasting response. This paper outlines the development of a method to deliver antimicrobial activity to a surface that is small enough to be combined with other materials. To our knowledge at time of publication, this is the first report of magnetically coupled bacteriophages specific to human pathogens which can be recovered from test systems, and could represent a novel means to conditionally deploy antibacterial agents into living eukaryotic systems without the risks of some antibiotic therapies.

Assessment of the capacity of vehicle cabin air inlet filters to reduce diesel exhaust-induced symptoms in human volunteers.

BACKGROUND: Exposure to particulate matter (PM) air pollution especially derived from traffic is associated with increases in cardiorespiratory morbidity and mortality. In this study, we evaluated the ability of novel vehicle cabin air inlet filters to reduce diesel exhaust (DE)-induced symptoms and markers of inflammation in human subjects. METHODS: Thirty healthy subjects participated in a randomized double-blind controlled crossover study where they were exposed to filtered air, unfiltered DE and DE filtered through two selected particle filters, one with and one without active charcoal. Exposures lasted for one hour. Symptoms were assessed before and during exposures and lung function was measured before and after each exposure, with inflammation assessed in peripheral blood five hours after exposures. In parallel, PM were collected from unfiltered and filtered DE and assessed for their capacity to drive damaging oxidation reactions in a cell-free model, or promote inflammation in A549 cells. RESULTS: The standard particle filter employed in this study reduced PM10 mass concentrations within the exposure chamber by 46%, further reduced to 74% by the inclusion of an active charcoal component. In addition use of the active charcoal filter was associated by a 75% and 50% reduction in NO2 and hydrocarbon concentrations, respectively. As expected, subjects reported more subjective symptoms after exposure to unfiltered DE compared to filtered air, which was significantly reduced by the filter with an active charcoal component. There were no significant changes in lung function after exposures. Similarly diesel exhaust did not elicit significant increases in any of the inflammatory markers examined in the peripheral blood samples 5 hour post-exposure. Whilst the filters reduced chamber particle concentrations, the oxidative activity of the particles themselves, did not change following filtration with either filter. In contrast, diesel exhaust PM passed through the active charcoal combination filter appeared less inflammatory to A549 cells. CONCLUSIONS: A cabin air inlet particle filter including an active charcoal component was highly effective in reducing both DE particulate and gaseous components, with reduced exhaust-induced symptoms in healthy volunteers. These data demonstrate the effectiveness of cabin filters to protect subjects travelling in vehicles from diesel exhaust emissions.

Assessment of atherosclerotic plaques in the rabbit abdominal aorta with interleukin-8 monoclonal antibody-targeted ultrasound microbubbles.

In this study, we aimed to prepare a neovascularization-relevant inflammatory cytokine-targeted ultrasound contrast agent and apply it in the ultrasound imaging of atherosclerotic plaque. An interleukin-8 (IL-8) monoclonal antibody was conjugated to SonoVue microbubbles using the N-succinimidyl-3-(2-pyridyldithio)propionate cross-linking method. Then, a prepared IL-8-targeted contrast agent was used for contrast-enhanced ultrasound (CEU) to detect rabbit abdominal aorta atherosclerotic plaque and to investigate the imaging characteristics of atherosclerotic plaque with the contrast agent. We found that an IL-8 monoclonal antibody can be successfully coupled to SonoVue microbubbles with stable biological characteristics. CEU with this IL-8-targeted contrast agent can increase the atherosclerotic plaque detection sensitivity, with stronger echo, so that three more plaques were detected compared with using non-targeted SonoVue microbubbles. Thus, an inflammatory cytokine-targeting ultrasound contrast agent carrying IL-8 monoclonal antibody can provide unique advantages for researching the characteristics of atherosclerotic plaque.

Assessment of endothelial permeability and leukocyte transmigration in human endothelial cell monolayers.

Increased vascular permeability is the hallmark of inflammation. Here, we describe three methods to assess vascular permeability in cell culture: (1) Impedance measurements of endothelial cell monolayers that allow to monitor changes in cell shape in real time. (2) Diffusion of fluorescently labeled dextran across endothelial cell monolayers to identify openings large enough for bulky molecules. (3) Transmigration of neutrophils through confluent endothelial cell monolayers to study one major process that increases endothelial permeability in inflammation.

[Immunological parameters in the assessment of the activity of a specific process in Mycobacterium tuberculosis-infected children and patients with intrathoracic lymphatic tuberculosis].

The data of a comprehensive study of 86 children aged 6 to 14 years, who were examined and treated at the Research Institute of Phthisiology for various manifestations of tuberculous infection: 25.6% with infected Mycobacterium tuberculosis with varying specific sensitization; 34.9% with minor forms of intrathoracic lymphatic tuberculosis (ITLT), 39.5% with disseminated processes into the intrathoracic lymph nodes, are analysed. Of the greatest informative value in the determination of the activity of tuberculous infection are RM V, VI, VII, and VIII dilutions in combination with immunological parameters of specific immunity: blast transpormation reaction (BTR) to PPD, a complex of serological reactions, IL-8, and lysosomal cationic test (LCT). Most children with ITLT showed a significant cellular response to PPD in the BTR test. It should be noted that on admission to the clinic, neutrophilic granulocytes were functionally inadequate in all the children as shown by LCT. The currently available immunological tests used in combination with the existing methods in the diagnosis of ITLT adequately evaluate the activity of tuberculous infection in children.

Assessment of the VEGF, bFGF, aFGF and IL8 angiogenic activity in urinary bladder carcinoma, using the mice cutaneous angiogenesis test.

Development of new blood vessels in solid tumors depends on changes in equilibrium between angiogenic stimulators and inhibitors. Overexpression of angiogenic growth factors has been shown in bladder carcinoma. The 'mice cutaneous angiogenesis test' is a good method for assessment of the total angiogenic potential of bladder cancer tissue. The analysis of the levels of proangiogenic factors could be useful for the choice of properly directed angiogenesis inhibitors. The aim of our study was to investigate the influence of blocking some angiogenic factors on the angiogenic activity of bladder cancer tissue. Tumor tissue obtained from 12 patients with invasive bladder carcinoma was used. Cancer tissue homogenates were incubated in the presence of specific antibodies against VEGF, bFGF, Il-8 and aFGF. Cytokine levels were determined using the ELISA test. Cutaneous angiogenesis assay in Balb/c mice was performed to detect the angiogenic activity of the tumor tissue. VEGF, bFGF and Il-8 were present in all examined cancer tissues (aFGF level was not estimated). Cytokine concentration and angiogenic activity of bladder cancer tissue showed individual variation. There was no correlation between the cytokines content in tumor tissue and the ability of this tissue to induce angiogenesis. Absorption caused significant reduction in cytokines level. The reduction of angiogenic activity was observed in the cancer tissue of 1 patient after VEGF absorption, in 3 patients' tissue homogenates after incubation with anti-aFGF and in 2 patients' homogenates after bFGF absorption. There was no reduction of angiogenic activity after Il-8 absorption.