A systematic review of blood-based serotonergic biomarkers in Bulimia Nervosa.

Bulimia Nervosa (BN) is a serious eating disorder, which affects 0.8-2.9% of the young population. The etiology is unknown and biomarkers would support in understanding the pathophysiology of BN, and in identifying BN patients that may benefit from medical treatment. This systematic review aims to answer whether (a) BN deviate from healthy controls in terms of serotonin (5-HT) biomarkers in blood, and whether (b) blood-based 5-HT biomarkers could be used to tailor psychopharmacological treatment in BN. A literature search using PubMed, PsycINFO and Embase was done using the following search terms: "Bulimia Nervosa" AND "serotonin" AND "blood" OR "plasma" OR "serum". 32 studies were included in this systematic review. Several biomarkers and challenge tests were identified and all studies described an association with BN and dysregulation of the 5-HT system compared to healthy controls. Several studies pointed to an association also to borderline symptoms in BN. BN deviate from healthy controls in terms of 5-HT biomarkers in blood supporting an abnormal 5-HT system in BN. 5-HT biomarkers and associated methods could be used to tailor treatment in BN although as yet, most tests described are unpractical for bedside use.

The Murine Lung Microbiome Changes During Lung Inflammation and Intranasal Vancomycin Treatment.

Most microbiome research related to airway diseases has focused on the gut microbiome. This is despite advances in culture independent microbial identification techniques revealing that even healthy lungs possess a unique dynamic microbiome. This conceptual change raises the question; if lung diseases could be causally linked to local dysbiosis of the local lung microbiota. Here, we manipulate the murine lung and gut microbiome, in order to show that the lung microbiota can be changed experimentally. We have used four different approaches: lung inflammation by exposure to carbon nano-tube particles, oral probiotics and oral or intranasal exposure to the antibiotic vancomycin. Bacterial DNA was extracted from broncho-alveolar and nasal lavage fluids, caecum samples and compared by DGGE. Our results show that: the lung microbiota is sex dependent and not just a reflection of the gut microbiota, and that induced inflammation can change lung microbiota. This change is not transferred to offspring. Oral probiotics in adult mice do not change lung microbiome detectible by DGGE. Nasal vancomycin can change the lung microbiome preferentially, while oral exposure does not. These observations should be considered in future studies of the causal relationship between lung microbiota and lung diseases.

A perspective on the developmental toxicity of inhaled nanoparticles.

This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from the respiratory tract to the placenta and fetus, but also that adverse effects may occur secondarily to maternal inflammatory responses. The limited database describes several organ systems in the offspring to be potentially sensitive to maternal inhalation of particles, but large uncertainties exist about the implications for embryo-fetal development and health later in life. Clearly, the potential for hazard remains to be characterized. Considering the increased production and application of nanomaterials and related consumer products a testing strategy for NP should be established. Due to large gaps in data, significant amounts of groundwork are warranted for a testing strategy to be established on a sound scientific basis.

Particles influence allergic responses in mice--role of gender and particle size.

Epidemiological evidence suggesting that exposure to traffic air pollution may enhance sensitization to common allergens in children is increasing, and animal studies support biological plausibility and causality. The effect of air pollution on respiratory symptoms was suggested to be gender dependent. Previous studies showed that allergy-promoting activity of polystyrene particles (PSP) increased with decreasing particle size after footpad injection of mice. The primary aim of this study was to confirm the influence of particle size on the immunoglobulin E (IgE)-promoting capacity of particles in an airway allergy model. A second aim was to examine whether the allergy-promoting capacity of particles was influenced by gender. Female and male mice were intranasally exposed to the allergen ovalbumin (OVA) with or without ultrafine, fine, or coarse PSP modeling the core of ambient air particles. After intranasal booster immunizations with OVA, serum levels of OVA-specific IgE antibodies, and also markers of airway inflammation and cellular responses in the lung-draining mediastinal lymph nodes (MLN), were determined. PSP of all sizes promoted allergic responses, measured as increased serum concentrations of OVA-specific IgE antibodies. Further, PSP produced eosinophilic airway inflammation and elevated MLN cell numbers as well as numerically reducing the percentage of regulatory T cells. Ultrafine PSP produced stronger allergic responses to OVA than fine and coarse PSP. Although PSP enhanced sensitization in both female and male mice, significantly higher IgE levels and numbers of eosinophils were observed in females than males. However, the allergy-promoting effect of PSP was apparently independent of gender. Thus, our data support the notion that ambient air particle pollution may affect development of allergy in both female and male individuals.

Adjuvant and inflammatory effects in mice after subchronic inhalation of allergen and ozone-initiated limonene reaction products.

Inhalation of ozone (O3), a highly toxic environmental pollutant, produces airway inflammation and exacerbates asthma. However, in indoor air, O3 reacts with terpenes (cyclic alkenes), leading to formation of airway irritating pollutants. The aim of the study was to examine whether inhalation of the reaction products of O3 and the terpene, limonene, as well as limonene and low-level O3 by themselves, induced allergic sensitization (formation of specific immunoglobulin [Ig] E) and airway inflammation in a subchronic mouse inhalation model in combination with the model allergen ovalbumin (OVA). BALB/cJ mice were exposed exclusively by inhalation for 5 d/wk for 2 wk and thereafter once weekly for 12 wk. Exposures were low-dose OVA in combination with O3, limonene, or limonene/O3 reaction products. OVA alone and OVA + Al(OH)3 served as control groups. Subsequently, all groups were exposed to a high-dose OVA solution on three consecutive days. Serum and bronchoalveolar lavage fluid were collected 24 h later. Limonene by itself did not promote neither OVA-specific IgE nor leukocyte inflammation. Low-level O3 promoted eosinophilic airway inflammation, but not OVA-specific IgE formation. The reaction products of limonene/O3 promoted allergic (OVA-specific IgE) sensitization, but lung inflammation, which is a characteristic of allergic asthma, was not observed. In conclusion, the study does not support an allergic inflammatory effect attributed to O3-initiated limonene reaction products in the indoor environment.

Airway inflammation and adjuvant effect after repeated airborne exposures to di-(2-ethylhexyl)phthalate and ovalbumin in BALB/c mice.

BACKGROUND: Epidemiological studies have suggested an association between exposure to phthalate plasticizers, including di-(2-ethylhexyl)phthalate (DEHP), and increased prevalence of asthma, rhinitis or wheezing. Furthermore, studies in mice have demonstrated an adjuvant effect from DEHP after parenteral administration with the model allergen ovalbumin (OVA). OBJECTIVE: Exposures to DEHP were investigated for adjuvant effects and airway inflammation in a mouse inhalation model. METHODS: BALB/cJ mice were exposed to aerosols of 0.022-13 mg/m(3) DEHP and 0.14 mg/m(3) OVA 5 days/week for 2 weeks and thereafter weekly for 12 weeks. Mice exposed to OVA alone or OVA+Al(OH)(3) served as control groups. Finally, all groups were exposed to a nebulized 1% OVA solution on three consecutive days. Serum, bronchoalveolar lavage (BAL) fluid, and draining lymph nodes were collected 24h later. RESULTS: In the OVA+Al(OH)(3) group, significantly increased levels of OVA-specific IgE and IgG1 in serum as well as of eosinophils in BAL fluid were observed. DEHP affected OVA-specific IgG1 production in a concentration-dependent manner, whereas little effect was seen on IgE and IgG2a. Dose-dependent increases in inflammatory cells were observed in BAL fluids, leading to significantly higher lymphocyte, neutrophil and eosinophil numbers in the OVA+13 mg/m(3) DEHP group. Ex vivo cytokine secretion by cultures of draining lymph nodes suggested that DEHP has a mixed Th1/Th2 cytokine profile. CONCLUSION: Airborne DEHP is able to increase serum IgG1 and lung inflammatory cell levels, but only at very high concentrations. Realistic DEHP levels do not have an adjuvant effect or induce allergic lung inflammation in the present mouse model.

Does lipophilicity per se induce adjuvant effects? Methyl palmitate as model substance does not affect ovalbumin sensitization.

Anthopogenically introduced substances and pollutants are suspected to promote sensitization and development of allergic airway diseases, that is, acting as adjuvants. Lipophilicity may serve as an immunological warning signal, promoting adjuvant effects. Whether the lipophilicity of an inhaled compound induces immunomodulatory effects was investigated in a murine inhalation model with the highly lipophilic methyl palmitate (MP) as model substance. First, studies of acute effects following a 1-h exposure of up to 348 mg/m3 MP showed no effects on cell composition in bronchoalveolar lavage (BAL) or on lung function parameters. Thus, MP did not possess irritant or inflammatory properties, which may be a precursive stimulus for adjuvant effects. Second, mice were exposed to aerosols of MP, 6 or 323 mg/m3, for 1 h followed by a 20-min low-dose ovalbumin (OVA) inhalation. OVA only and OVA + Al(OH)3 served as control groups. Exposures were performed 5 times/wk for 2 wk followed by a weekly exposure for 10 wk. Finally, the mice were challenged with a high-dose OVA aerosol for 3 consecutive days. Neither OVA-specific immunoglobulin (Ig) G1, IgE, or IgG2a production, nor inflammatory cells in BAL, nor respiratory patterns were significantly affected in the MP groups. The OVA + Al(OH)3 group had a significantly higher IgG1 and IgE production, as well as higher eosinophil infiltration in the BAL fluid. These studies showed that effects of adjuvants not are necessarily due to their lipophilicity; that is, additional structural properties are required.

Adjuvant effects of inhaled mono-2-ethylhexyl phthalate in BALB/cJ mice.

Phthalates, including di(2-ethylhexyl) phthalate (DEHP), are widely used and have been linked with the development of wheezing and asthma. The main metabolite of DEHP, mono-2-ethylhexyl phthalate (MEHP), was investigated for adjuvant effects in a mouse inhalation model. BALB/cJ mice were exposed to aerosols of 0.03 or 0.4 mg/m(3) MEHP 5 days/week for 2 weeks and thereafter weekly for 12 weeks together with a low dose of ovalbumin (OVA) as a model allergen. Mice exposed to OVA alone or OVA+Al(OH)(3) served as negative and positive controls, respectively. Finally, all groups were exposed to a nebulized 1% OVA solution on 3 consecutive days to investigate the development of an inflammatory response. Serum, bronchoalveolar lavage (BAL) fluid, and draining lymph nodes were collected 24h later. In the OVA+Al(OH)(3) group, significantly increased levels of OVA-specific IgE and IgG1 in serum as well as of eosinophils in BAL fluid were observed. OVA-specific IgG1 production in both MEHP groups was significantly increased. OVA-specific IgE and IgG2a were not increased significantly. A dose-dependent increase in inflammatory cells was observed in BAL fluid, leading to significantly higher lymphocyte and eosinophil numbers in the OVA+0.4 mg/m(3) MEHP group. Ex vivo cytokine secretion by cultures of draining lymph nodes suggested a T(H)2 profile of MEHP. In conclusion, MEHP acted as a T(H)2 adjuvant after inhalation. However, it is suggested that the inflammation in the MEHP groups was primarily mediated by an IgG1-dependent mechanism. To address implications for humans, a margin-of-exposure was estimated based on the lack of significant effects on IgE production and inflammation after exposures to 0.03 mg/m(3) MEHP observed in the present study and estimated human exposure levels.