Disentangle beneficial effects of strain engraftment after fecal microbiota transplantation in subjects with MetSyn.

Fecal Microbiota Transplantation (FMT) has emerged as a potential modality for mitigating microbiome-associated diseases. Despite this potential, the precise causal pathways by which specific gut microbiota strains induce remission remain inadequately elucidated. In this study, we aimed to discern the impact of engraftment of donor-infused strains on alterations in plasma metabolites, subsequently contributing to the amelioration of clinical parameters involved in subjects with metabolic syndrome (MetSyn) receiving an FMT. We observed that a higher fraction of donor strains engrafted in the recipient is correlated to a reduction in diastolic blood pressure and found specific strain associations through canonical correlation analysis. Integrating the metabolomics profile shows that engraftment of Collinsella aerofaciens and Fusocatenibacter saccharovorans was related to a reduction in 2-oxoarginine in plasma, which was subsequently correlated to a reduction in diastolic blood pressure. In conclusion, we applied a novel framework to elucidate on the complex and heterogenous FMT intervention, establishing a connection between engrafted microbiota and clinical outcome parameters. Our findings underscore the potential therapeutic efficacy of FMT in ameliorating MetSyn, demonstrating a potential contribution of microbial strain engraftment to the improvement of MetSyn via modulation of circulating metabolites.

Oral Anaerobutyricum soehngenii augments glycemic control in type 2 diabetes.

This randomized, double-blind, placebo-controlled trial investigated the impact of 14-day Anaerobutyricum soehngenii L2-7 supplementation on postprandial glucose levels in 25 White Dutch males with type 2 diabetes (T2D) on stable metformin therapy. The primary endpoint was the effect of A. soehngenii versus placebo on glucose excursions and variability as determined by continuous glucose monitoring. Secondary endpoints were changes in ambulatory 24-h blood pressure, incretins, circulating metabolites and excursions of plasma short-chain fatty acids (SCFAs) and bile acids upon a standardized meal. Results showed that A. soehngenii supplementation for 14 days significantly improved glycemic variability and mean arterial blood pressure, without notable changes in SCFAs, bile acids, incretin levels, or anthropometric parameters as compared to placebo-treated controls. Although well-tolerated and effective in improving glycemic control in the intervention group, further research in larger and more diverse populations is needed to generalize these findings.

Oral histidine affects gut microbiota and MAIT cells improving glycemic control in type 2 diabetes patients.

Amino acids, metabolized by host cells as well as commensal gut bacteria, have signaling effects on host metabolism. Oral supplementation of the essential amino acid histidine has been shown to exert metabolic benefits. To investigate whether dietary histidine aids glycemic control, we performed a case-controlled parallel clinical intervention study in participants with type 2 diabetes (T2D) and healthy controls. Participants received oral histidine for seven weeks. After 2 weeks of histidine supplementation, the microbiome was depleted by antibiotics to determine the microbial contribution to histidine metabolism. We assessed glycemic control, immunophenotyping of peripheral blood mononucelar cells (PBMC), DNA methylation of PBMCs and fecal gut microbiota composition. Histidine improves several markers of glycemic control, including postprandial glucose levels with a concordant increase in the proportion of MAIT cells after two weeks of histidine supplementation. The increase in MAIT cells was associated with changes in gut microbial pathways such as riboflavin biosynthesis and epigenetic changes in the amino acid transporter SLC7A5. Associations between the microbiome and MAIT cells were replicated in the MetaCardis cohort. We propose a conceptual framework for how oral histidine may affect MAIT cells via altered gut microbiota composition and SLC7A5 expression in MAIT cells directly and thereby influencing glycemic control. Future studies should focus on the role of flavin biosynthesis intermediates and SLC7A5 modulation in MAIT cells to modulate glycemic control.

Faecal Microbiota transplantation affects liver DNA methylation in Non-alcoholic fatty liver disease: a multi-omics approach.

Individuals with nonalcoholic fatty liver disease (NAFLD) have an altered gut microbiota composition. Moreover, hepatic DNA methylation may be altered in the state of NAFLD. Using a fecal microbiota transplantation (FMT) intervention, we aimed to investigate whether a change in gut microbiota composition relates to altered liver DNA methylation in NAFLD. Moreover, we assessed whether plasma metabolite profiles altered by FMT relate to changes in liver DNA methylation. Twenty-one individuals with NAFLD underwent three 8-weekly vegan allogenic donor (n = 10) or autologous (n = 11) FMTs. We obtained hepatic DNA methylation profiles from paired liver biopsies of study participants before and after FMTs. We applied a multi-omics machine learning approach to identify changes in the gut microbiome, peripheral blood metabolome and liver DNA methylome, and analyzed cross-omics correlations. Vegan allogenic donor FMT compared to autologous FMT induced distinct differential changes in I) gut microbiota profiles, including increased abundance of Eubacterium siraeum and potential probiotic Blautia wexlerae; II) plasma metabolites, including altered levels of phenylacetylcarnitine (PAC) and phenylacetylglutamine (PAG) both from gut-derived phenylacetic acid, and of several choline-derived long-chain acylcholines; and III) hepatic DNA methylation profiles, most importantly in Threonyl-TRNA Synthetase 1 (TARS) and Zinc finger protein 57 (ZFP57). Multi-omics analysis showed that Gemmiger formicillis and Firmicutes bacterium_CAG_170 positively correlated with both PAC and PAG. E siraeum negatively correlated with DNA methylation of cg16885113 in ZFP57. Alterations in gut microbiota composition by FMT caused widespread changes in plasma metabolites (e.g. PAC, PAG, and choline-derived metabolites) and liver DNA methylation profiles in individuals with NAFLD. These results indicate that FMTs might induce metaorganismal pathway changes, from the gut bacteria to the liver.

Gut microbiome transitions across generations in different ethnicities in an urban setting-the HELIUS study.

BACKGROUND: During the course of history, various important lifestyle changes have caused profound transitions of the gut microbiome. These include the introduction of agriculture and animal husbandry, a shift from a nomadic to a more sedentary lifestyle, and recently increased levels of urbanization and a transition towards a more Western lifestyle. The latter is linked with shifts in the gut microbiome that have a reduced fermentative capability and which are commonly associated with diseases of affluence. In this study, in which 5193 subjects are included, we investigated the direction of microbiome shifts that occur in various ethnicities living in Amsterdam by comparing 1st and 2nd generation participants. We furthermore validated part of these findings with a cohort of subjects that moved from rural Thailand to the USA. RESULTS: The abundance of the Prevotella cluster, which includes P. copri and the P. stercorea trophic network, diminished in the 2nd generation Moroccans and Turks but also in younger Dutch, whilst the Western-associated Bacteroides/Blautia/Bifidobacterium (BBB) cluster, which has an inverse correlation with α-diversity, increased. At the same time, the Christensenellaceae/Methanobrevibacter/Oscillibacter trophic network, which is positively associated with α-diversity and a healthy BMI, decreased in younger Turks and Dutch. Large compositional shifts were not observed in South-Asian and African Surinamese, in whom the BBB cluster is already dominant in the 1st generation, but ASV-level shifts towards certain species, associated amongst others with obesity, were observed. CONCLUSION: The Moroccan and Turkish populations, but also the Dutch population are transitioning towards a less complex and fermentative less capable configuration of the gut microbiota, which includes a higher abundance of the Western-associated BBB cluster. The Surinamese, whom have the highest prevalence of diabetes and other diseases of affluence, are already dominated by the BBB cluster. Given the continuous increase in diseases of affluence, this devolution towards low-diversity and fermentatively less capable gut microbiome compositions in urban environments is a worrying development. Video Abstract.

Identifying Gut Microbiota associated with Gastrointestinal Symptoms upon Roux-en-Y Gastric Bypass.

PURPOSE: Roux-en-Y gastric bypasses (RYGB) are frequently accompanied by long-term gastrointestinal (GI) symptoms. Direct mechanistic insight into the causation of these symptoms is lacking, but changes in the intestinal microbiome have been proposed to play a role. With this study, we aimed to investigate whether a microbial predisposition exists before RYGB which is associated with GI symptoms during follow-up and to evaluate which microbial groups are involved. MATERIALS AND METHODS: In total, 67 RYGB patients were included. Shotgun metagenomic sequencing was performed on fecal samples obtained just before and 1 year after surgery. To assess GI symptoms, patients filled out Gastrointestinal Quality of Life Index (GIQLI) questionnaires and were divided into groups based on their total GIQLI score and change in score (postsurgery versus baseline). Extremely randomized tree predictor models were used to identify the most distinctive microbial species associated with postoperative GI symptoms. RESULTS: Beta diversity differed significantly between baseline and 1-year post-surgery samples, with the post-surgery microbiome resembling a more dysbiotic profile. The most predictive species regarding total GIQLI (AUC 0.77) or delta GIQLI score (AUC 0.83) were identified. Many of these species are known butyrate producers or species known to support them and/or species with anti-inflammatory properties, including Coprococcus eutactus, Faecalibacterium prausnitzii, and Ruminococcus callidus. CONCLUSION: Beneficial commensal gut microbiota related to a high GI score were associated to adequate intestinal fermentative capacity, suggesting these species might have protective properties against postoperative GI malfunctioning.

Recent insights into the role of microbiome in the pathogenesis of obesity.

Obesity is a risk factor for many chronic diseases and its rising prevalence the last couple of decades is a healthcare concern in many countries. Obesity is a multifactorial problem that is not only limited in its causation by diet and lack of exercise. Genetics but also environmental factors such as the gut microbiome should similarly be taken into account. A plethora of articles have been published, that from various different angles, attempt to disentangle the complex interaction between gut microbiota and obesity. Examples range from the effect of the gut microbiota on the host immune system to the pathophysiological pathways in which microbial-derived metabolites affect obesity. Various discordant gut microbiota findings are a result of this complexity. In this review, in addition to summarizing the classical role of the gut microbiome in the pathogenesis of obesity, we attempt to view both the healthy and obesogenic effects of the gut microbiota as a consequence of the presence or absence of collective guilds/trophic networks. Lastly, we propose avenues and strategies for the future of gut microbiome research concerning obesity.

Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome.

Accumulating evidence shows that microbes with their theater of activity residing within the human intestinal tract (i.e., the gut microbiome) influence host metabolism. Some of the strongest results come from recent fecal microbial transplant (FMT) studies that relate changes in intestinal microbiota to various markers of metabolism as well as the pathophysiology of insulin resistance. Despite these developments, there is still a limited understanding of the multitude of effects associated with FMT on the general physiology of the host, beyond changes in gut microbiome composition. We examined the effect of either allogenic (lean donor) or autologous FMTs on the gut microbiome, plasma metabolome, and epigenomic (DNA methylation) reprogramming in peripheral blood mononuclear cells in individuals with metabolic syndrome measured at baseline (pre-FMT) and after 6 weeks (post-FMT). Insulin sensitivity was determined with a stable isotope-based 2 step hyperinsulinemic clamp and multivariate machine learning methodology was used to uncover discriminative microbes, metabolites, and DNA methylation loci. A larger gut microbiota shift was associated with an allogenic than with autologous FMT. Furthemore, the data results of the the allogenic FMT group data indicates that the introduction of new species can potentially modulate the plasma metabolome and (as a result) the epigenome. Most notably, the introduction of Prevotella ASVs directly correlated with methylation of AFAP1, a gene involved in mitochondrial function, insulin sensitivity, and peripheral insulin resistance (Rd, rate of glucose disappearance). FMT was found to have notable effects on the gut microbiome but also on the host plasma metabolome and the epigenome of immune cells providing new avenues of inquiry in the context of metabolic syndrome treatment for the manipulation of host physiology to achieve improved insulin sensitivity.

Characterization and pro-inflammatory responses of spore and hyphae samples from various mold species.

Mold particles from Aspergillus fumigatus, Penicillium chrysogenum, Aspergillus versicolor, and Stachybotrys chartarum have been linked to respiratory-related diseases. We characterized X-ray-inactivated spores and hyphae fragments from these species by number of particles, morphology, and mycotoxin, ß-glucan and protease content/activity. The pro-inflammatory properties of mold particles were examined in human bronchial epithelial cells (BEAS-2B) and THP-1 monocytes and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1. Spores from P. chrysogenum and S. chartarum contained some hyphae fragments, whereas the other preparations contained either spores or hyphae. Each mold species produced mainly one gelatin-degrading protease that was either of the metallo- or serine type, while one remains unclassified. Mycotoxin levels were generally low. Detectable levels of ß-glucans were found mainly in hyphae particle preparations. PMA-differentiated THP-1 macrophages were by far the most sensitive model with effects in the order of 10 ng/cm2 . Hyphae preparations of A. fumigatus and P. chrysogenum were more potent than respective spore preparations, whereas the opposite seems to be true for A. versicolor and S. chartarum. Hyphae fragments of A. fumigatus, P. chrysogenum, and A. versicolor enhanced the release of metalloprotease (proMMP-9) most markedly. In conclusion, species, growth stage, and characteristics are all important factors for pro-inflammatory potential.

Monitoring of occupational and environmental aeroallergens-- EAACI Position Paper. Concerted action of the EAACI IG Occupational Allergy and Aerobiology & Air Pollution.

Exposure to high molecular weight sensitizers of biological origin is an important risk factor for the development of asthma and rhinitis. Most of the causal allergens have been defined based on their reactivity with IgE antibodies, and in many cases, the molecular structure and function of the allergens have been established. Significant information on allergen levels that cause sensitization and allergic symptoms for several major environmental and occupational allergens has been reported. Monitoring of high molecular weight allergens and allergen carrier particles is an important part of the management of allergic respiratory diseases and requires standardized allergen assessment methods for occupational and environmental (indoor and outdoor) allergen exposure. The aim of this EAACI task force was to review the essential points for monitoring environmental and occupational allergen exposure including sampling strategies and methods, processing of dust samples, allergen analysis, and quantification. The paper includes a summary of different methods for sampling and allergen quantification, as well as their pros and cons for various exposure settings. Recommendations are being made for different exposure scenarios.

Exposure to thoracic dust, airway symptoms and lung function in cement production workers.

Cement dust exposure has previously been associated with airway symptoms and ventilatory impairment. The aim of the present study was to examine lung function and airway symptoms among employees in different jobs and at different levels of exposure to thoracic dust in the cement production industry. At the start of a 4-yr prospective cohort study in 2007, exposure to cement dust, symptoms and lung function were recorded cross-sectionally in 4,265 employees in 24 European cement plants. Bronchial exposure was assessed by 2,670 full-shift dust samples with cyclones collecting the thoracic aerosol fraction. A job exposure matrix was constructed by grouping dust concentrations according to job type and plant. Elevated odds ratios for symptoms and airflow limitation (range 1.2-2.6 in the highest quartile), but not for chronic bronchitis, were found in the higher quartiles of exposure compared with the lowest quartile. Forced expiratory volume in 1 s (FEV(1)) showed an exposure-response relationship with a 270-mL deficit of FEV(1) (95% CI 190-300 mL) in the highest compared with the lowest exposure level. The results support the hypothesis that exposure to dust in cement production may lead to respiratory symptoms and airway obstruction.

Occupational exposure to bacterial single cell protein induces inflammation in lung and blood.

Bacterial single cell protein (BSCP) is used as a protein enrichment in livestock and fish feed, and is extracted from dried bacterial mass. In the production of BSCP, workers are exposed to organic dust containing high levels of endotoxins that may induce acute airway inflammation. However, the long term effect on the airways of such exposure is not known, and we have examined inflammatory markers in induced sputum and blood among BSCP exposed workers. We included 21 non-smoking production workers (age 31-42 (range; mean 35)) without respiratory symptoms and 21 healthy non-exposed references (age 21-52 (range; mean 34)). Airborne endotoxin concentrations were measured, and induced sputum samples and blood samples were collected from the workers and non-exposed references. The airborne endotoxin concentration measured in inhaled air during the work shift was 430 EU/m(3) (50-2000) (median (range)). The percentage of neutrophils in induced sputum was 79% (66-93) (median (25th-75th percentiles)) and 31% (25-45) (p < 0.001) for operators and references, respectively. Protein analysis in induced sputum supernatant showed significantly elevated levels of interleukins IL-1beta and IL-12 (p < 0.05), while blood analysis showed significantly elevated levels of PDGF-BB (platelet-derived growth factor-BB) and RANTES (regulated upon activation normally T cell expressed and secreted) (p < 0.05). Workers exposed to BSCP had an airway inflammation characterized by a high level of neutrophils. However, only a few cytokines were elevated in lung and blood, which could imply low inflammatory activity suggestive of possible adaptation mechanisms due to daily exposure to BSCP, or that the inflammation reaction was a dose-related response occurring at higher levels.

Generation and homogeneity of aerosols in a human whole-body inhalation chamber.

INTRODUCTION: A 16 m(3) whole-body exposure chamber for human exposure to aerosols is described. Several modifications of the aerosol generation and distribution system were needed to ensure a stable aerosol concentration in the chamber, especially when a cyclone pre-classifier was used. RESULTS: After these modifications, stable aerosol concentrations of aluminium oxide with a volume median diameter of 5.7 microm, and approximately 3 microm when the cyclone was used, could be achieved after 1 h of aerosol generation. Aerosol concentrations of 1-8 mg m(-3) generated without the cyclone could be maintained for at least 2 h after the aerosol level had stabilized. The temporal variability [coefficient of variation (CV)] of the aerosol concentration was 4-6%, while concentrations <1 mg m(-3) showed greater relative variability. The spatial variability at 3.8 mg m(-3) without a volunteer in the chamber was 4.8%. With a volunteer in the chamber who performed 30 min of ergometric cycling during 2 h of aerosol exposure, the exposure estimated by personal sampling was 15-17% lower than monitored with an optical particle counter. The variability of personally measured exposure was higher than of stationary measurements showing CVs of 10-19%. CONCLUSIONS: These results show that controlled exposure of human volunteers to a range of concentrations can be achieved with good accuracy in this inhalation chamber. The results compare favourably with other chambers described in the literature. Personal sampling showed lower aerosol concentrations than estimated in an empty chamber and the variability was significantly higher than measured stationary.

Exposure to fibres, crystalline silica, silicon carbide and sulphur dioxide in the norwegian silicon carbide industry.

OBJECTIVES: The aim of this study was to assess personal exposure to fibres, crystalline silica, silicon carbide (SiC) and sulphur dioxide in the Norwegian SiC industry. METHODS: Approximately 720 fibre samples, 720 respirable dust samples and 1400 total dust samples were collected from randomly chosen workers from the furnace, processing and maintenance departments in all three Norwegian SiC plants. The respirable dust samples were analysed for quartz, cristobalite and non-fibrous SiC content. Approximately 240 sulphur dioxide samples were collected from workers in the furnace department. RESULTS: The sorting operators from all plants, control room and cleaning operators in Plant A and charger, charger/mix and payloader operators in Plant C had a geometric mean (GM) of fibre exposure above the Norwegian occupational exposure limit (OEL) (0.1 fibre cm(-3)). The cleaner operators in Plant A had the highest GM exposure to respirable quartz (20 mug m(-3)). The charger/mix operators in Plant C had the highest GM exposure to respirable cristobalite (38 mug m(-3)) and the refinery crusher operators in Plant A had the highest GM exposure to non-fibrous SiC (0.65 mg m(-3)). Exposure to the crystalline silica and non-fibrous SiC was generally low and between 0.4 and 2.1% of the measurements exceeded the OELs. The cleaner operators in Plant A had the highest GM exposure to respirable dust (1.3 mg m(-3)) and total dust (21 mg m(-3)). GM exposures for respirable dust above the Norwegian SiC industry-specific OEL of 0.5 mg m(-3) were also found for refinery crusher operators in all plants and mix, charger, charger/mix and sorting operators in Plant C. Only 4% of the total dust measurements exceeded the OEL for nuisance dust of (10 mg m(-3)). Exposure to sulphur dioxide was generally low. However, peaks in the range of 10-100 p.p.m. were observed for control room and crane operators in Plants A and B and for charger and charger/mix operators in Plant C. CONCLUSION: Workers in the SiC industry are exposed to a mixture of several agents including SiC fibres, quartz, cristobalite, non-fibrous SiC and sulphur dioxide. Exposure levels were generally below the current Norwegian OELs; however, high exposure to fibres and respirable dust still occurs in the furnace department.

Circulating lipopolysaccharides in the blood from "bioprotein" production workers.

BACKGROUND: Workers producing bacterial single-cell protein (BSCP), "bioprotein," are exposed to organic dust containing high levels of endoxins (lipopolysaccharides, LPS). Workers in this industry have complained of episodes of fever, fatigue, chest tightness, skin dryness and rubor. The aim of the present study was to quantify LPS and inflammatory mediators in plasma among the workers and non-exposed control subjects. METHODS: We included eight non-smoking production workers, aged 32-51 (median 38), and eight non-smoking, non-exposed controls, aged 30-51 (median 39). Airborne and plasma endotoxin concentrations were measured, as well as plasma hsCRP and different cytokines, chemokines and metalloproteinases. RESULTS: The workers who did not use personal respiratory protection were exposed to varying airborne levels of endotoxin, 430 (75-15 000) EU/m3 (median, range). The level of plasma LPS was significantly elevated (p = 0.01) among the workers compared to the non-exposed controls. The workers also had elevated levels of MCP-1 (p = 0.02), MIP-1alpha (p = 0.05) and MMP-3 (p = 0.04). IL-6 and hsCRP were also elevated among the exposed group, but not significantly (p = 0.10 and p = 0.07, respectively). CONCLUSIONS: In this study, we detected LPS in plasma of individuals exposed to high levels of LPS at their workplace. This finding is supported by elevated levels of several inflammatory cytokines among the workers, significantly exceeding that of the non-exposed control group. To the best of our knowledge, this is the first time that plasma LPS, together with increased inflammatory markers in plasma, has been detected in an occupational setting.

Antibody response to long-term and high-dose mould-exposed sawmill workers.

Exposure to moulds is thought to cause adverse health effects ranging from vague subjective symptoms to allergy and respiratory diseases. Until now, most studies have been emphasizing low levels of exposure. In Norwegian sawmills during the 1980s, extensively high spore counts up to 10(7) spores/m3 air were reported. By using serum samples obtained from sawmill workers during that period, in addition to control sera, we studied the antibody response of all classes and IgG subclasses to Rhizopus microsporus at different levels of exposure. Antigen specificity was further studied by Western blotting. Exposure to R. microsporus was accompanied by R. microsporus-specific antibody production against a wide range of antigenic components most likely of both protein and carbohydrate nature. Increasing levels of mould-specific IgG1, IgG2, IgG4 and IgA antibodies were associated with increased exposure, while the highest levels of exposure were associated with a somewhat reduced level of mould-specific IgE antibodies. In conclusion, the present study strongly suggests that high mould exposure can induce a strong IgG and IgA response in a dose-dependent manner.

Determinants of microbial exposure in grain farming.

OBJECTIVES: Exposure to organic dust containing high concentrations of microorganisms is common in grain farming, although the farmers have practices to counteract microbial growth to obtain optimal grain yields. We investigated the influence of weather and production practices on personal microbial exposure during grain work. METHODS: Airborne dust was collected by personal sampling during threshing and storage work on 92 Norwegian farms. The personal exposure for bacteria, endotoxin, fungal spores and hyphae, beta-(1-->3)-glucans and actinomycetes was quantified and compared with climatic data expressed as fungal forecasts from the grain growth season and production practices as reported by farmers. RESULTS: Farmers were exposed to a geometrical mean of 4.4 mg m(-3) inhalable dust [geometrical standard deviation (GSD) = 4.0], 4 x 10(6) m(-3) bacteria and fungal spores (GSD = 5.2 and 5.9, respectively), 5.9 x 10(3) EU m(-3) of endotoxins (GSD = 8.6), 2 x 10(5) m(-3) actinomycetes (GSD = 15.3), 120 mug m(-3) beta-(1-->3)-glucans (GSD = 4.7) and 5 x 10(5) AU m(-3) of hyphae (GSD = 4.4). Univariate associations were found between one or several of these microbial factors and work operation, visible fungal damage, grain species, lodging of grain, storage technology or harvester type. As assessed by general linear models, storage work was the main predictive determinant for microbial exposure, although grain species and visible fungal damage also were also important. Wet and warm weather throughout the grain growth season were associated with elevated exposure for inhalable dust, beta-(1-->3)-glucans, endotoxins and hyphae during threshing. The beta-(1-->3)-glucan exposure could biologically be explained by the fungal spore and hyphal exposure, both variables contributing equally. However, spores were most important during storage work, whereas only hyphae were predictive during threshing. CONCLUSIONS: Farmers were exposed to high levels of microorganisms and their components during dusty grain work. Dust prevention and protection may reduce microbial exposure, and may be particularly important in areas with frequent fungal forecasts, when fungal damage has been observed, during storage work or when handling barley.

Administration of prednisolone phosphate-liposomes reduces wound contraction in a rat partial-thickness wound model.

Macrophages play an important role in the inflammatory phase of wound healing and their activity regulates fibroblasts and keratinocytes. Modulation of macrophage function may result in improvement of the wound healing process. Prednisolone phosphate (PLP) encapsulated into liposomes was administered to partial-thickness wounds in rats. A single dose of 75 microg/kg, applied directly after wounding, resulted in up to a 30% reduction of wound contraction at 28 days after wounding. This effect could not be achieved in the group that was administered free PLP or liposomes containing phosphate-buffered saline to the wound. The number of myofibroblasts was up to 50% lower in wounds treated with the liposomal PLP at 4 days after wounding. The number of macrophages present in the wounds was not statistically different between groups. Most probably, the production of cytokines and growth factors by macrophages is altered after phagocytosing the liposomes, resulting in reduced wound contraction.

Airborne fibres in the norwegian silicon carbide industry.

Morphology of silicon carbide (SiC) fibres from the Norwegian SiC industry has been studied by scanning electron microscopy (SEM). The fibres are an unwanted side-product in SiC production. They represent a probable cause of the observed increased occurrence of lung diseases among SiC workers. The main aim of this work is to give a detailed description of the morphological variation of the fibres. Furthermore, it is important to study the occurrence of various morphological types with respect to job types and process parameters. SiC fibres accounted for >90% of all fibres observed. Eight categories of SiC fibres are described based on their morphology. The most frequent fibre category had a smooth surface and accounted for more than half of the observed SiC fibres. The diameter distributions of the eight fibre types were significantly different except for two of the categories. More than 99% of the SiC fibres observed were <3 microm in diameter, satisfying one WHO criterion for health relevant fibres. The aspect ratio and diameter of health-relevant fibres generally followed a lognormal distribution for different fibre categories, whereas fibre length did not. The proportions of SiC fibres (all categories) did not differ significantly between the plants. The proportions differed between plants for two SiC fibre categories including the most dominant type. For two SiC fibre categories and the SiC cleavage fragments differences were observed between job groups. Two other fibre categories were correlated with type of SiC produced (i.e. black or green SiC) and sawdust added to the raw material mix.