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Corian®, a solid-surface composite (SSC), is composed of alumina trihydrate and acrylic polymer. The aim of the present study was to examine the pulmonary toxicity attributed to exposure to SSC sawing dust. Male mice were exposed to either phosphate buffer saline (PBS, control), 62.5, 125, 250, 500, or 1000 µg of SSC dust, or 1000 µg silica (positive control) via oropharyngeal aspiration. Body weights were measured for the duration of the study. Bronchoalveolar lavage fluid (BALF) and tissues were collected for analysis at 1 and 14 days post-exposure. Enhanced-darkfield and histopathologic analysis was performed to assess particle distribution and inflammatory responses. BALF cells and inflammatory cytokines were measured. The geometric mean diameter of SSC sawing dust following suspension in PBS was 1.25 µm. BALF analysis indicated that lactate dehydrogenase (LDH) activity, inflammatory cells, and pro-inflammatory cytokines were significantly elevated in the 500 and 1000 µg SSC exposure groups at days 1 and 14, suggesting that exposure to these concentrations of SSC induced inflammatory responses, in some cases to a greater degree than the silica positive control. Histopathology indicated the presence of acute alveolitis at all doses at day 1, which was largely resolved by day 14. Alveolar particle deposition and granulomatous mass formation were observed in all exposure groups at day 14. The SSC particles were poorly cleared, with 81% remaining at the end of the observation period. These findings demonstrate that SSC sawing dust exposure induces pulmonary inflammation and damage that warrants further investigation. Abbreviations: ANOVA: Analysis of Variance; ATH: Alumina Trihydrate; BALF: Bronchoalveolar Lavage Fluid; Dpg: Geometric Mean Diameter; FE-SEM: Field Emission Scanning Electron Microscopy; IACUC: Institutional Animal Care and Use Committee; IFN-γ: Interferon Gamma; IL-1 Β: Interleukin-1 Beta; IL-10: Interleukin-10; IL-12: Interleukin-12; IL-2: Interleukin-2; IL-4: Interleukin-4; IL-5: Interleukin-5; IL-6: Interleukin-6; KC/GRO: Neutrophil-Activating Protein 3; MMAD: Mass Median Aerodynamic Diameter; PBS: Phosphate-Buffered Saline; PEL: Permissible Exposure Limit; PM: Polymorphonuclear Leukocytes; PNOR: Particles Not Otherwise Regulated; SEM/EDX: Scanning Electron Microscope/Energy-Dispersive X-Ray; SSA: Specific Surface Area; SSC: Solid Surface Composite; TNFα: Tumor Necrosis Factor-Alpha; VOC: Volatile Organic Compounds; σg: Geometric Standard Deviation. [ABSTRACT FROM AUTHOR]

ANCA-associated vasculitides (AAV), classified into granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis represent a group of disorders characterized by necrotizing vasculitis of small vessels, endothelial injury and tissue damage. The outcomes and prognosis of AAV have undergone significant changes with the introduction of glucocorticoids (GCs) and other immunosuppressants (cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil). The enhanced understanding of pathogenesis has subsequently led to the incorporation into clinical practice of drugs targeting specific therapeutic targets. After an extensive literature search of Pubmed, Medline, Embase of the most recent evidence, we provide an overview of available treatments, highlighting how newer drugs have integrated into standard protocols. Our review also explores potential new therapeutic targets, including B cell depletion and inhibition, T cell inhibition, complement inhibition, and IL-5 and IgE inhibition. There is hope that the new treatment targets currently under study in AAV may enable a faster and more lasting clinical response, ensuring the reduction of possible side effects from therapies. Moreover, numerous aspects necessitate further exploration in the future, such as tailoring of GCs, integration of GCs-sparing agents, efficacy of combination therapy, optimal maintenance therapy, to reduce organ-damage and improve quality of life. [ABSTRACT FROM AUTHOR]

In many types of cancer, presence of eosinophils in tumors correlate with an improved disease outcome. In line with this, activated eosinophils have been shown to reduce tumor growth in colorectal cancer (CRC). Interleukin (IL)-33 has recently emerged as a cytokine that is able to inhibit the development of tumors through eosinophils and other cells of the tumor microenvironment thereby positively influencing disease progress. Here, we asked whether eosinophils are involved in the effects of IL-33 on tumor growth in CRC. In models of CT26 cell engraftment and colitis-associated CRC, tumor growth was reduced after IL-33 treatment. The growth reduction was absent in eosinophil-deficient ΔdblGATA-1 mice but was restored by adoptive transfer of ex vivo-activated eosinophils indicating that the antitumor effect of IL-33 depends on the presence of eosinophils. In vitro, IL-33 increased the expression of markers of activation and homing in eosinophils, such as CD11b and Siglec-F, and the degranulation markers CD63 and CD107a. Increased expression of Siglec-F, CD11b and CD107a was also seen in vivo in eosinophils after IL-33 treatment. Viability and cytotoxic potential of eosinophils and their migration properties toward CCL24 were enhanced indicating direct effects of IL-33 on eosinophils. IL-33 treatment led to increased levels of IL-5 and CCL24 in tumors. Our data show that the presence of eosinophils is mandatory for IL-33-induced tumor reduction in models of CRC and that the mechanisms include eosinophil recruitment, activation and degranulation. Our findings also emphasize the potential use of IL-33 as an adjuvants in CRC immunotherapy. AOM: azoxymethane; bmRPMI: bone marrow RPMI; CRC: colorectal cancer; CFSE: carboxyfluorescein succinimidyl ester; DSS: dextran sulfate sodium; EPX: eosinophil peroxidase; INF-γ: interferon gamma; ILC: innate lymphoid cell; IL-33: interleukin-33; IL-5: interleukin-5; MDSC: myeloid derived suppressor cells; NK cells: natural killer cells; P/S: penicillin/streptomycin; rm: recombinant mouse; T regs: regulatory T cells; TATE: tumor associated tissue eosinophilia; TNF-α: tumor necrosis factor alpha [ABSTRACT FROM AUTHOR]

Severe eosinophilic asthma (SEA) is associated with multiple exacerbations. Fractional exhaled nitric oxide (FeNO), a biomarker of airway T2 inflammation, is known to be correlated with the risk of exacerbations. While the use of FeNO is well established to predict the therapeutic response to dupilumab (anti-IL-4/IL-13), it remains uncertain for biologics targeting the IL-5 pathway. We conducted an observational, retrospective, monocentric analysis of adults with SEA who started mepolizumab (anti-IL-5) or benralizumab (anti-IL-5R) between January 1, 2016 and December 31, 2020. Data were collected for 109 patients. All participants reported uncontrolled asthma with a median of 3 annual exacerbations and a median Asthma Control Test score of 12. They all had an initial blood eosinophilia >300/mm3, with a median at 610/mm3 (IQR 420-856). Patients with a baseline FeNO ≥50 ppb reported more exacerbations in the previous year than those with a FeNO <50 ppb (p = 0.02). After initiation of treatment, change in FeNO was not associated with therapeutic response. However, decrease in the annual number of exacerbations was significantly greater in patients with a baseline FeNO ≥50 ppb than in those with a baseline FeNO <50 ppb (-3.3 ± 2.7 vs −0.9 ± 2.4, respectively; p = 0.01). There was no association between baseline FeNO values and subsequent lung function, asthma control or reduction of oral corticosteroids use. In this real-world cohort, adults with SEA who had a baseline FeNO ≥50 ppb experienced a greater decrease in exacerbations after 12 months of anti-IL-5 or IL-5R biologics than those with a FeNO <50 ppb. [ABSTRACT FROM AUTHOR]

Treatment with biologics has significantly reduced the social and economic burden of severe asthma. However, some patients may still feature a suboptimal control of their symptoms while on therapy. In this subset of asthmatic patients, a benefit from a dual biologic therapy has sporadically been reported in literature. Our aim is to add our experience to the limited body of evidence supporting combination biologic therapies. Here we present the case of a 68-year-old nonsmoker female, with an allergic and eosinophilic corticosteroid-dependent severe asthma. She displayed well controlled comorbidities and good adherence to the inhaled therapy. Omalizumab was started in 2008 with an initial remarkable clinical improvement. After nine years of biologic therapy, she reported a gradual worsening of her symptoms and exacerbations. Mepolizumab was then added in 2019. The addition of Mepolizumab resulted in a meaningful amelioration of her quality of life, asthma control, number of exacerbations and 6-minute-walking-distance at 3-year follow-up. The average Prednisone dosage was tapered from 25 mg to 20 mg daily. No adverse events were observed since the introduction of the second biologic. Our experience indicates that Mepolizumab may be beneficial and safe as an add-on biologic in a patient whose allergic and eosinophilic asthma remains uncontrolled despite treatment with an anti-IgE strategy. Further studies on a larger number of patients are required to demonstrate whether the positive outcomes published so far are replicable on a larger scale. [ABSTRACT FROM AUTHOR]

Vaccines prevent disease and disability; save lives and represent a good assessment of health interventions. Several systematic reviews on the efficacy and effectiveness of COVID-19 vaccines have been published, but the immunogenicity and safety of these vaccines should also be addressed. This systemic investigation sought to explain the efficacy, immunogenicity, and safety of new vaccination technologies against SARS-CoV-2 in people over 18 years old. Original research studying the effectiveness on mRNA, protein subunit vaccines, and viral vector vaccines against SARS-CoV-2 in people over 18 years old was analyzed. Several databases (Web of Science, Scopus, MEDLINE and EMBASE) were searched between 2012 and November 2022 for English-language papers using text and MeSH terms related to SARS-CoV-2, mechanism, protein subunit vaccine, viral vector, and mRNA. The protocol was registered on PROSPERO, CRD42022341952. Study quality was assessed using the NICE methodology. We looked at a total of six original articles. All studies gathered and presented quantitative data. Our results suggest that new vaccinations could have more than 90% efficacy against SARS-CoV-2, regardless of the technology used. Furthermore, adverse reactions go from mild to moderate, and good immunogenicity can be observed for all vaccine types. [ABSTRACT FROM AUTHOR]

Add-on therapy with monoclonal antibodies is the recommended therapy for severe asthmatic patients refractory to maintenance treatment. In randomized control trials, mepolizumab reduced the number of exacerbations, the need of oral corticosteroids (OCS), increased asthma control, and lung function in a population of uncontrolled severe eosinophilic asthmatic patients. In this piece of work, we aimed to assess mepolizumab efficacy and safety in a cohort of patients with severe eosinophilic asthma in real-life conditions. A retrospective study was carried out at eight hospitals from Asturias (Spain). The sample included patients treated with mepolizumab from 1 January 2016 to 31 March 2019. Demographic and clinical variables were collected, including OCS use, asthma control, lung function, and exacerbation rate. Sixty-nine patients (72% women) with mean age 56 ± 13 years were included. Annual exacerbation rate decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) (p < 0.001). The number of patients requiring OCS treatment decreased from 25 patients (36%, mean prednisone dose = 18 mg/day) to 13 patients (19%, mean prednisone dose = 9 mg/day) (p < 0.001). Twelve patients (48%) stopped OCS treatment. Forced expired volume in one second (FEV1) as percentage increased from 68% (SD 20) to 76% (SD 21) (p < 0.001). Fifty-six patients (81%) were considered responders to mepolizumab. No serious adverse events were detected during the study period. Overall, this study demonstrates mepolizumab efficacy and safety in a cohort of patients with uncontrolled severe eosinophilic asthma in routine clinical practice. [ABSTRACT FROM AUTHOR]

The skin is a vital organ of the human body, serving numerous protective and functional roles that are essential for survival. Residing in the epidermis are various epidermal proteases responsible for the establishment and regulation of barrier function. The human tissue kallikrein-related peptidase family conserves homeostasis of the skin barrier through their roles in desquamation, antimicrobial defense, innate immune response, and barrier maintenance. The activity of kallikreins is tightly regulated and dysregulation of kallikrein activity is seen to contribute to the formation of several inflammatory skin disorders. This review highlights the roles of kallikreins in skin homeostasis and pathologies. Due to their part in these skin disorders, inhibitors of the skin kallikreins have become attractive therapeutics. Over the past few years, both natural and synthetic inhibitors of several kallikreins have been identified and are undergoing further development as treatments to restore compromised barrier function. This review summarizes the kallikrein inhibitors under development for this purpose. These inhibitors remain promising therapeutics in cases of severe skin inflammation not well managed by current therapies. [ABSTRACT FROM AUTHOR]

Protein glycosylation influences characteristics such as folding, stability, protein interactions, and solubility. Therefore, glycan moieties of therapeutic proteins and proteins that are likely associated with disease pathogenesis should be analyzed in-depth, including glycan heterogeneity and modification sites. Recent advances in analytical methods and instrumentation have enabled comprehensive characterization of highly complex glycosylated proteins. The following aspects should be considered when analyzing glycosylated proteins: sample preparation, chromatographic separation, mass spectrometry (MS) and fragmentation methods, and bioinformatics, such as software solutions for data analyses. Notably, analysis of glycoproteins with heavily sialylated glycans or multiple glycosylation sites requires special considerations. Here, we discuss recent methodological advances in MS that provide detailed characterization of heterogeneous glycoproteins. As characterization of complex glycosylated proteins is still analytically challenging, the function or pathophysiological significance of these proteins is not fully understood. To reproducibly produce desired forms of therapeutic glycoproteins or to fully elucidate disease-specific patterns of protein glycosylation, a highly reproducible and robust analytical platform(s) should be established. In addition to advances in MS instrumentation, optimization of analytical and bioinformatics methods and utilization of glycoprotein/glycopeptide standards is desirable. Ultimately, we envision that an automated high-throughput MS analysis will provide additional power to clinical studies and precision medicine. [ABSTRACT FROM AUTHOR]

Introduction: Anti-interleukin (IL)-5 therapy is a novel drug class clinically effective in patients with diverse eosinophil-related disorders such as allergic eosinophilic asthma, eosinophilic granulomatosis with polyangiitis (EGPA), nasal polyposis, eosinophilic COPD, and other non-pulmonary disorders such as eosinophilic esophagitis. Chronic eosinophilic pneumonia (CEP) is a steroid responsive disorder, however, relapses are common following corticosteroid tapering. Case Study: We present the case of a 42-year-old woman with steroid-dependent relapsing CEP successfully treated with anti-IL-5 antibody. Results: Treatment with anti-IL-5 antibody resulted in remission with the ability to taper off the steroids, and no recurrence of the disease for 6 months. Conclusion: Our case report supports the potential use of anti-IL-5 therapy for remission of patients with CEP with recurrent relapses. Whether, it would also be an effective initial therapy might also be an area that deserves future investigation. [ABSTRACT FROM AUTHOR]

Use of probiotic supplements as a non-chemical approach to promote health has increased in animal production. The present study evaluated the effect of oral probiotic administration on growth and global gene expression profile in dairy cows. Lactating Holstein-Friesian cows received a daily dose (50 ml) of a commercial probiotic (containing Lactobacillus acidophilus, Saccharomyces cerevisiae, Enterococcus faecium, Aspergillus oryza and Bacillus subtilis) for 60 days. A microarray experiment was performed with blood collected at day-0 and day-60. Although probiotic supplementation had no effect on body weight, PCV and total protein concentration in plasma (P > 0.05), per cent lymphocyte count increased (P < 0.05), and per cent neutrophil count decreased (P < 0.05) in probiotic-treated animals. Gene expression analysis identified 10,859 differentially expressed genes, 1168 up-regulated and 9691 down-regulated genes, respectively, following probiotic treatment. Single experiment pathway analysis identified 87 bovine pathways impacted by probiotic treatment. These pathways included the Toll-like receptor (TLR), inflammation response and Wingless signalling pathways. Oral administration of probiotics to dairy cows had a systemic effect on global gene expression, such as on genes involved in immunity and homeostasis. The results of this study show that the utilization of probiotics in animal agriculture impacts genes important to dairy cow health and production. [ABSTRACT FROM AUTHOR]

Purpose: To compare the levels of cytokines and growth factor in aqueous humor of the patients with chronic primary angle closure glaucoma (PACG) and cataract. Methods: Aqueous humor samples were collected from 19 chronic PACG patients and compared with 14 nonglaucomatous controls presenting for cataract surgery. The levels of 27 cytokines and growth factors were measured in the aqueous samples using multiplex bead immunoassay and compared across groups. Results: Significantly higher levels of interleukin (IL)-8 (p < 0.001), eotaxin (p < 0.001), interferon gamma-induced protein (IP)-10 (p < 0.001) and macrophage inflammatory protein-1-beta (MIP-1β;p < 0.001) were observed in aqueous of chronic PACG patients compared to controls. In comparison to controls, significantly lower levels of IL-9 (p = 0.001), IL-17 (p < 0.001), tumor necrosis factor-alpha (TNF-α;p < 0.001), granulocyte–macrophage colony-stimulating factor (GM-CSF;p < 0.001), and IL-5 (p = 0.001) were observed in chronic PACG eyes. All other assayed cytokines—IL-1β, interleukin-1 receptor antagonist (IL-1rα), IL-6, IL-7, IL-10, IL-12, IL-13, IL-15, fibroblast growth factor-basic (FGF-basic), granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1-alpha (MIP-1α), and vascular endothelial growth factor (VEGF) —showed no significant difference between the groups. Conclusions: These results suggest that the aqueous cytokine levels of chronic PACG eyes differ significantly from nonglaucomatous eyes. This is the first study reporting significantly increased levels of eotaxin, MIP-1β, and IP-10 and lower levels of TNF-α, IL-5, IL-9, IL-17, and GM-CSF in chronic PACG patients, suggesting a plausible role of these inflammatory cytokines in its pathogenesis. [ABSTRACT FROM AUTHOR]

Hemodialysis-associated eosinophilia (HAE) is believed to be associated with allergic reactions to dialyzer materials. This study aimed to investigate the use of Polyflux membranes to improve HAE. Thirty-one patients suffering from HAE were included. Patients were dialyzed with polysulfone membranes when they developed HAE. After that, patients were dialyzed with Polyflux membranes three times every week, 4 h every time without changing the dialysis parameters and medication. Levels of peripheral eosinophils, hsCRP, IgE, C3a, IL-5 and peripheral CD4+ lymphocytes and CD8+ lymphocytes were assessed before Polyflux treatment, and at 4th, 8th and 12th weeks of treatment. Any symptoms including chest tightness and skin itching were observed during the study period. After 12 weeks of Polyflux membrane dialysis and compared with polysulfone membrane dialysis, levels of peripheral eosinophils were significantly decreased (1.26 ± 0.61 vs. 0.71 ± 0.29 × 109/L,p < 0.001); serum IL-5 levels were significantly decreased (24.43 ± 10.21 vs. 9.11 ± 4.21 pg/mL,p < 0.001); and chest tightness and skin itching were significantly improved (45.2% vs. 19.4%,p = 0.028). After 12 weeks, there was no significant change in serum levels of hsCRP (2.00 ± 0.94 vs. 1.81 ± 0.79 mg/L,p = 0.352), IgE (104.61 ± 98.79 vs. 114.95 ± 101.07 IU/mL,p = 0.422) and C3a (121.61 ± 34.04 vs. 120.29 ± 32.81 µg/L,p = 0.316), and in peripheral levels of CD4+ (589 ± 181 vs. 569 ± 171 cells/mm3,p = 0.672) and CD8+ (443 ± 123 vs. 414 ± 140 cells/mm3,p = 0.395) cells. Eosinophil count was correlated with serum IL-5 levels (r = 0.873,p < 0.001). Changing to a Polyflux membrane may alleviate HAE and reduce serum IL-5 levels. Therefore, this could be a strategy to manage HAE in the clinical practice. [ABSTRACT FROM AUTHOR]

The role of IL-1β in regulating the expression and secretion of cytokines and chemokines by human adipocytes was examined. Adipocytes were incubated with human IL-1β for 4 or 24 h. The expression of a panel of 84 cytokine/chemokine genes was probed using PCR arrays. IL-1β stimulated the expression of >30 cytokine/chemokine genes on the arrays; 15 showed >100-fold increases in mRNA at 4 or 24 h includingCSF3, CXCL1, CXCL2, CXCL12andIL8. CSF3exhibited a 10 000-fold increase in mRNA at 4 h.ADIPOQwas among the genes whose expression was inhibited. Protein arrays were used to examine the secretion of cytokines/chemokines from adipocytes. IL-1β stimulated the secretion of multiple cytokines/chemokines including MCP-1, IL-8, IP-10, MIP-1α and MCP-4. The most responsive was IP-10, which exhibited a 5000-fold increase in secretion with IL-1β. IL-1β is likely to play a substantial role in stimulating the inflammatory response in human adipocytes in obesity. [ABSTRACT FROM AUTHOR]

The commercially available alpha-asarone injections (CA-ARE) were frequently found to cause severe anaphylactic reactions by the solubilizer contained in the formulation such as polysorbate 80 and propylene glycol. This study aimed to develop a new ARE injection using Kolliphor HS 15 as solubilizing agent (HS 15-ARE) by the dissolution method to resolve its poor solubility problem and reduce the anaphylaxis of CA-AREs caused by Polysorbate 80. The HS 15-ARE micelle showed a homogeneous round shape with the mean particle size of around 13.73 ± 0.02 nm, polydisperse index (PDI) of 0.19 ± 0.01 and solubilizing efficiency of 95.7% ± 2.4%. In vitro and in vivo studies showed that HS 15-ARE is a stable injection presenting the same pharmacokinetic profile with CA-ARE. Moreover, improved therapeutic effect was observed for HS 15-ARE in treating asthma compared to CA-ARE ( p < 0.05) with no anaphylactic reactions observed. These results demonstrate that the new formulation of ARE (HS 15-ARE) has a great potential for replacing CA-AREs injections. [ABSTRACT FROM AUTHOR]

Cytokines and chemokines are the cell signaling proteins which are considered as important biomarkers of inflammation and immunity. However the fragile nature of these markers results in the concentration variation due to various external factors. We assessed the influence of commonly used anticoagulants (EDTA and heparin) on various cytokine levels from 32 paired plasma samples using highly sensitive multiple cytokine estimation assay. Out of 17 cytokines estimated, 15 were detectable in more than 80% of the samples from both the groups. TNF-α, IFN-γ, IL-4, IL-5, and G-CSF levels were significantly higher ( p values < 0.05 for all) in plasma with EDTA, whereas the levels of IL-6, IL-8, IL-10, IL-17, MIP-1β, GM-CSF and MCP-1 were found to be significantly higher ( p values < 0.05 for all) in plasma with heparin. There was no significant difference in the levels of IL-7, IL-12 (P70) and IL-13 in both the groups. The study showed that the anticoagulants significantly affect the measurement of certain cytokines. Hence, it is important to choose an appropriate anticoagulant before the estimation of cytokines for reliable use of plasma cytokines as biomarkers in patient management. [ABSTRACT FROM AUTHOR]

Idiopathic hypereosinophilic syndrome (IHES) is characterized by blood hypereosinophilia with no underlying cause and eosinophilia-associated organ dysfunction. Thirty-three patients, 20 female (61%) and 13 male (29%), with a median age of 56 years at diagnosis (range 16-77 years) were included in the study. The median blood eosinophilia at diagnosis was 7.6 × 109/L and the median percentage of eosinophils in the bone marrow was 39.5%. The most common clinical manifestations were splenomegaly and cardiac involvement. Corticosteroids (CS) as monotherapy were initiated in all study patients. The median starting dose of prednisone was 30 mg daily (range 5-85 mg), and the maintenance dose varied from 5 mg twice weekly to 60 mg daily. Overall, 21 patients (64%) responded to CS within a week. Seven patients (21%) were resistant or intolerant to CS. Five patients (15%) achieved a 50% reduction of blood eosinophilia. In conclusion, CS were found to be highly effective in IHES with manageable side effects. [ABSTRACT FROM AUTHOR]

It has been more than 25 years since Mycobacterium paratuberculosis was first proposed as an etiologic agent in Crohn's disease based on the isolation of this organism from several patients. Since that time, a great deal of information has been accumulated that clearly establishes an association between M. paratuberculosis and Crohn's disease. However, data are conflicting and difficult to interpret and the field has become divided into committed advocates and confirmed skeptics. This review is an attempt to provide a thorough and objective summary of current knowledge from both basic and clinical research from the views and interpretations of both the antagonists and proponents. The reader is left to draw his or her own conclusions related to the validity of the issues and claims made by the opposing views and data interpretations. Whether M. paratuberculosis is a causative agent in some cases or simply represents an incidental association remains a controversial topic, but current evidence suggests that the notion should not be so readily dismissed. Remaining questions that need to be addressed in defining the role of M. paratuberculosis in Crohn's disease and future implications are discussed. [ABSTRACT FROM AUTHOR]

Introduction. Thyroid dysfunction during pregnancy may result in both maternal and neonatal complications. Subacute thyroiditis (SAT) is an extremely rare cause of both hyper- and hypothyroidism in pregnant women. Case description. A case of first trimester SAT is presented. Diagnosis of SAT was based on fine-needle aspiration biopsy. The disease resolved spontaneously without need for prednisone administration but a hypothyroid phase treated with T4 throughout pregnancy occurred. The pregnancy resulted in a healthy full term infant. We measured various cytokine levels in an attempt to follow their course during SAT as well as throughout the remaining period of pregnancy. Serum thyreoglobulin (Tg) levels correlated best with thyroid function tests (TFTs) and the course of SAT. Conclusions. The diagnosis of SAT at a pregnancy setting may be intriguing. The measurement of circulating cytokines is not helpful in the differential diagnosis or monitoring of the disease. [ABSTRACT FROM AUTHOR]

Preparations of Echinacea (Asteraceae) are frequently consumed for the control and prevention of rhinovirus-induced colds and other respiratory disorders. Since it is now generally believed that the symptoms of rhinovirus colds are due to the enhanced secretion of inflammatory chemokines and cytokines, we decided to analyze the effects of rhinovirus infection and Echinacea treatment [defined extracts of E. purpurea (L.) Moench] on cytokine/chemokine gene expression and protein secretion in a line of human tracheo- bronchial epithelial cells. Among the collection of more than 50 cytokines and chemokines present in the gene arrays, 12 showed significant induction of expression by the virus (> 2-fold), some of them by more than 5-fold. However, not all of these resulted in similar changes in the corresponding proteins, presumably as a consequence of post-transcriptional changes. A total of 16 cytokines, mostly chemokines, showed substantial protein increases, including several, such as the well known pro-inflammatory cytokines IL-6 and IL-8 (CXCL8), which were induced in the absence of additional transcription. These results support the concept that virus-induced multiple inflammatory cytokines are responsible for the cold symptoms. In most cases, one or both Echinacea preparations reversed the viral stimulation, thus providing a basis for the anti-inflammatory properties attributed to Echinacea. [ABSTRACT FROM AUTHOR]

Both bacille Calmette-Guerin (BCG) and dehydroepiandrosterone induce Th1 immune responses and suppress Th2 allergic reactions. To investigate whether a combined administration of BCG and dehydroepiandrosterone treat asthma more effectively, BALB/c mice (n = 8 per group) with established airway hyper-responsiveness were treated with BCG and/or dehydroepiandrosterone. Combined treatment with 2 × 105 colony-forming units (CFUs) of BCG and 0.01% dehydroepiandrosterone was the most effective one at suppressing eosinophilia in bronchoalveolar lavage fluids. In addition, this combination also was better at suppressing hypersensitivity as compared to BCG alone (13.7 ± 4.0- versus 3.6 ± 0.5-fold increase in the sensitivity index; P < .05) in male mice. Similarly, the effect of the combined treatment was superior to that of individual treatments at decreasing the serum ovalbumin-specific immunoglobulin E (IgE) level. However, the addition of 0.1% dehydroepiandrosterone to BCG significantly decreased the efficacy of BCG on hypersensitivity in female mice. In male mice, the suppressive effect of the treatments on hypersensitivity tended to be lower, and the baseline interferon-γ /interleukin-5 (IFN-γ /IL-5) ratio in the splenocyte supernatant was significantly higher as compared to female mice. In conclusion, treatment with an appropriate combination of BCG and dehydroepiandrosterone had additive therapeutic effects on mice with established asthma. Androgens in males and dehydroepiandrosterone overdose might reduce the efficacy of BCG. [ABSTRACT FROM AUTHOR]

In an environmental intervention study in public housing, we examined monthly Juniper Paediatric Asthma Quality of Life (QOL) Questionnaires for 51 children. Longitudinal analysis and spline models were used to identify time periods with significant improvements in QOL to inform judgments about causality. We found significant improvements in QOL, with moderate improvements before environmental interventions, increased rates of improvement immediately after, and reduced rates more than 5 months post-intervention. Effect modification analyses identified high-risk subpopulations and emphasized the importance of environmental, social, and economic conditions. Our results demonstrate the value of longitudinal techniques in evaluating the benefits of environmental interventions for asthma. [ABSTRACT FROM AUTHOR]

In previous studies, we have shown strong adjuvant activity for Ottawa dust (EHC-93) after coexposure of the BALB/cmouse to EHC-93 and ovalbumin. Mice were intranasally sensitized at days 0 and 14 with 200μg ovalbumin and 150μg EHC-93, and challenged with ovalbumin at days 35, 38, and 41 with 200μg ovalbumin. Mice were autopsied at day 42. This adjuvant activity was shown for the antibody response to ovalbumin (immunoglobulins E, G1, and G2a), histopathological lesions in the lung, cytokines, and the numbers of eosinophils in lung lavages. To study the mechanisms of this adjuvant activity, mice (BALB/cC.D2-Vil6) with natural-resistance-associated macrophage protein (Nramp1s), BALB/cmice pretreated with the antioxidantN-acetylcysteine (NAC), mice (B6.129P2-Nos2tmLau) deficient in inducible nitric oxide synthase (iNOS), and mice with interleukin-4 (IL-4) deficiency (BALB/cIl4