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Hintergrund In der landwirtschaftlichen Fleischproduktion ist der Zusatz von Enzymen wie Phytase zu Tierfutter weit verbreitet, aber es gibt nur wenig Bewusstsein uber das allergene Potenzial und die Gesundheitsrisiken dieser Pilzenzyme. Patienten und methoden Wir berichten uber acht Patienten, die in einem Betrieb arbeiten, der Phytase‐Granulat herstellt. Alle Patienten litten an einer berufsbedingten Rhinitis, die sechs Monate nach Beginn der Exposition gegenuber Phytase‐Staub auftrat. Asthmatische Symptome und Kontakturtikaria traten ebenfalls auf. Anhand von Prick‐, Epikutan‐ und Basophilenaktivierungstests, die mit dem Fabrikprodukt durchgefuhrt wurden, konnten wir eine Sensibilisierung gegen Phytase nachweisen. Auserdem wurden die IgE‐ und IgG‐Antikorper gegen Phytase bestimmt. Ergebnisse Sieben der acht Patienten zeigten im Pricktest eine positive Reaktion auf Phytase. Bei vier der acht Patienten wurde Phytase‐spezifisches IgE und bei sechs der acht Patienten Phytase‐spezifisches IgG nachgewiesen. Wahrend der Basophilenaktivierungstest bei vier von sieben Patienten positiv ausfiel, war der Epikutantest bei allen getesteten Patienten negativ. Die Versetzung an einen anderen Arbeitsplatz ohne Exposition gegenuber Phytase fuhrte zur vollstandigen Ruckbildung der Symptome. Schlussfolgerungen Enzyme von Schimmelpilzen wie Phytase sind hochwirksame Berufsallergene. Zum Gesundheitsschutz der Beschaftigten ist die konsequente Umsetzung von Arbeitsschutzmasnahmen essentiell.

Objective The intestinal epithelium is a rapidly renewing tissue which plays central roles in nutrient uptake, barrier function and the prevention of intestinal inflammation. Control of epithelial differentiation is essential to these processes and is dependent on cell type-specific activity of transcription factors which bind to accessible chromatin. Here, we studied the role of SET Domain Bifurcated Histone Lysine Methyltransferase 1, also known as ESET (SETDB1), a histone H3K9 methyltransferase, in intestinal epithelial homeostasis and IBD. Design We investigated mice with constitutive and inducible intestinal epithelial deletion of Setdb1, studied the expression of SETDB1 in patients with IBD and mouse models of IBD, and investigated the abundance of SETDB1 variants in healthy individuals and patients with IBD. Results Deletion of intestinal epithelial Setdb1 in mice was associated with defects in intestinal epithelial differentiation, barrier disruption, inflammation and mortality. Mechanistic studies showed that loss of SETDB1 leads to de-silencing of endogenous retroviruses, DNA damage and intestinal epithelial cell death. Predicted loss-of-function variants in human SETDB1 were considerably less frequently observed than expected, consistent with a critical role of SETDB1 in human biology. While the vast majority of patients with IBD showed unimpaired mucosal SETDB1 expression, comparison of IBD and non-IBD exomes revealed over-representation of individual rare missense variants in SETDB1 in IBD, some of which are predicted to be associated with loss of function and may contribute to the pathogenesis of intestinal inflammation. Conclusion SETDB1 plays an essential role in intestinal epithelial homeostasis. Future work is required to investigate whether rare variants in SETDB1 contribute to the pathogenesis of IBD.

Sensitivity and specificity of serological assays are key parameters for the accurate estimation of SARS-CoV-2 sero-prevalence. The aim of this study was to compare eight readily available IgG antibody tests using a panel of well-defined serum samples of pre-pandemic and pandemic origin. A cross-reaction panel included samples of patients with recent infection with either of the endemic Coronaviruses 229E, NL63, HKU1, or OC43. Additionally, samples with high antibody levels against influenza virus, adenovirus, and during acute EBV infection were included. Previous infection with endemic coronaviruses caused a significant amount of cross-reactivity in two of the assays. In contrast, the confidence intervals for the assays of Abbott, DiaSorin, Euroimmun and Roche encompassed the value of 98% for samples with a previous endemic hCoV infection. For all assays, sensitivities were between 91.3 and 98.8%. Assay performance was independent of the usage of either nucleocapsid or spike proteins.

BACKGROUND In agricultural meat production, adding enzymes such as phytase to animal feed is widespread, but there is little awareness of the allergenic potential and health risks of these fungal enzymes. PATIENTS AND METHODS We report on eight patients working in a plant producing phytase granulates. All patients complained about work-related rhinitis occurring within six months of the onset of exposure to phytase dust. Asthmatic symptoms and contact urticaria also occurred. To detect sensitizations to phytase, skin prick-, patch-, and basophil activation test were carried out with the factory product. Levels of IgE and IgG against phytase were also measured. RESULTS There was a positive reaction to phytase with skin prick testing in seven of the eight patients. IgE specific to phytase was detectable in four of the eight patients, and IgG specific to phytase was detectable in six of the eight patients. The basophil activation test was positive in four out of seven patients tested, but the patch test was negative in all patients tested. Transfer to a different workplace with no exposure to phytase completely eliminated the symptoms. CONCLUSIONS Mold enzymes such as phytase are highly potent occupational allergens. Occupational safety measures must be strictly implemented in order to protect the health of workers.

Background Safety and tolerability of venom immunotherapy (VIT) in patients with concomitant disease and comedications, especially β-blockers (BBs) and angiotensin-converting enzyme inhibitors (ACEIs), are under discussion. Objective To identify risk factors for the occurrence of systemic reactions (SRs) during the build-up phase of a 3-day rush VIT with focus on comorbidities and related comedications. Methods Data of 175 three-day rush VIT courses ( Vespula venom, n = 161; honeybee venom, n = 14) were analyzed. Starting with 0.02 μg of venom, the maintenance dose of 100 μg was reached in 15-dose increments within 3 days. Local reactions (LRs) and SRs were documented during the build-up phase. Comorbidities and related comedications were registered. Univariate, bivariate, and multivariate data analysis was performed. Results During the 3-day rush VIT, an LR was seen in 74 (42.3%) of 175, a large LR (>10-cm diameter) in 82 (46.9%) of 175, and SRs in 19 (10.9%) of 175 VIT courses. Multivariate logistic regression revealed that female sex ( P = .01), immunotherapy with honeybee venom ( P = .003), and accompanying ACEI medication ( P = .03) were independent predictors of the development of SRs during the build-up phase of VIT. Conclusion This study revealed that female sex, honeybee VIT, and ACEI use independent predictors for SRs.

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease, and patients with active or recurrent bone inflammation at multiple sites are diagnosed with chronic recurrent multifocal osteomyelitis (CRMO). The Chronic multifocal osteomyelitis (CMO) mouse model develops IL-1β-driven sterile bone lesions reminiscent of severe CRMO. The goal of this study was to evaluate the potential involvement of mast cells in CMO/CRMO. Here, we show that mast cells accumulate in inflamed tissues from CMO mice and that mast cell protease Mcpt1 can be detected in the peripheral blood. A transgenic model of connective tissue mast cell depletion (Mcpt5-Cre:Rosa26-Stopfl/fl-DTa) was crossed with CMO mice and the resulting mice (referred to as CMO/MC–) showed a significant delay in disease onset compared with age-matched CMO mice. At 5-6 months of age, CMO/MC– mice had fewer bone lesions and immune infiltration in the popliteal lymph nodes that drain the affected tissues. In bone marrow-derived mast cell cultures from CMO mice, cytokine production in response to the alarmin IL-33 was elevated compared with wild-type cultures. To test the relevance of mast cells to human CRMO, we tested serum samples from a cohort of healthy controls and from CRMO patients at diagnosis. Interestingly, mast cell chymase was elevated in CRMO patients as well as in patients with oligoarticular juvenile arthritis. Tryptase-positive mast cells were also detected in bone lesions from CRMO patients and patients with bacterial osteomyelitis. Together, our results identify mast cells as cellular contributors to bone inflammation in CMO/CRMO and provide rationale for further study of mast cells as therapeutic targets., Summary: This paper reports that mast cells promote bone loss in an autoinflammatory disease model and that mast cell mediators were detected in autoinflammatory disease patient samples.

Secreted group IIA phospholipase A(2) (sPLA(2)-IIA) is markedly up-regulated in human prostate cancer (PCa) specimens and in some PCa-derived cell lines, indicating an important role of this enzyme in tumourigenesis. In this study, we measured levels of sPLA(2)-IIA, C-reactive protein (CRP), and prostate-specific antigen (PSA) in serum samples obtained from patients with benign prostatic hyperplasia (BPH) and with PCa of different stages. We found that serum levels of sPLA(2)-IIA and CRP in BPH and PCa patients were significantly elevated compared to those of healthy individuals, but the concentrations of these inflammatory biomarkers did not differ between patients with BPH or PCa. Furthermore, serum levels of sPLA(2)-IIA correlated with concentrations of CRP, but not with PSA, Gleason grade or tumour stage. In conclusion, these findings suggest that cancer-related changes are not exclusive factors contributing to elevated serum sPLA(2)-IIA levels and emphasize the utility of sPLA(2)-IIA as a circulating marker of inflammation in patients with BPH and PCa.

All metal implants--and metal-on-metal bearings in particular--corrode and cause a release of metal ions. Because cobalt and chromium have been shown to be carcinogenic and mutagenic in human and animal models, systemic toxicity and cancer risk are considered to be possible disadvantages of the metal-on-metal articulation. This study was designed to investigate the serum concentration profiles of chromium, cobalt and molybdenum after implantation of a Birmingham hip resurfacing arthroplasty (BHR) and a cementless total hip replacement with a 28-mm Metasul articulation (MTHR), over the first 2 years after implantation.We analyzed profiles of metal ion serum levels in 111 patients implanted with a BHR, in 74 patients implanted with an MTHR, and in 130 implant-free probands control subjects using atomic absorption spectrophotometry.Chromium and cobalt concentrations (in microg/L) of all BHR and MTHR patients differed significantly from those of control subjects (chromium:0.25; cobalt: 0.25). The median chromium and cobalt concentrations in BHR patients had increased to 5.1 and 4.3 microg/L 2 years after surgery. Concentrations in BHR patient exceeded those in the unilateral MTHR patients. Molybdenum serum concentrations hardly changed over time in either group and were not significantly different from the concentrations seen in the control subjects.During the first 2 years after surgery, the Birmingham hip resurfacing arthroplasty leads to a significantly greater increase in serum chromium and cobalt levels than the 28-mm metal-on-metal MTHR. Observation of patients over a longer period will be necessary in order to evaluate any chronic adverse effects to the system due to elevated chromium and cobalt serum concentrations.

Cerebral involvement of systemic mastocytosis and intracranial sarcoma of myelogenic origin are well known entities. An 8-year-old girl with an isolated cerebral mast cell tumor is presented. Specific histopathologic stains were used to confirm the diagnosis detecting immunophenotype and proliferative activity. Treatment with irradiation, intrathecal cytarabine, and interferon-alpha2b did not induce regression whereas polychemotherapy did. Systemic combination chemotherapy led to marked transient tumor regression in this proliferating mast cell sarcoma in an unusual intracranial location.

There have only been few investigations comparing total fluoride intake and the fluoride proportion excreted in urine in pre–school children. In addition, the results of available studies are conflicting. Total fluoride intake was assessed in 11 healthy children aged 3–6 years on 2 consecutive days and urinary fluoride excretion was determined. The duplicate–diet approach was used for the assessment of fluoride intake from solid and liquid foods. Fluoride intake from toothbrushing was calculated as the difference between the amount of fluoride in the paste put on the toothbrush and the drinking water (fluoride concentration 0.25 mg/l) used for rinsing vs. the fluoride amounts recovered in the toothpaste spat out and in the rinsing water. Use of fluoridated domestic salt and/or fluoride tablets was recorded. The children’s intake of fluoride from food averaged 202.5±116.2 μg F/day. They swallowed an average amount of 273.9±175.6 μg F/day when brushing their teeth. Daily fluoride ingestion from all sources totalled 930.7±391.5 μg or 53.0±21.4 μg/kg body weight. On average 51.5% of the fluoride ingested was excreted in urine. The wide interindividual variation makes it necessary to evaluate the urinary excretion rate for fluoride in larger study populations with varied fluoride exposure. Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The aim of this investigation was to examine whether near infrared diffuse reflection spectroscopy is an acceptable tool for the determination of cholesterol content in atherosclerotic plaques. Using an FT-spectrophotometer ( λ =1000–2500 nm) and fiberoptic systems ( d =4 mm), the cholesterol content could be determined in mixtures of the primary compounds of the aortic wall with acceptable precision. Considering the inhomogeneous distribution of cholesterol and cholesterol esters in atherosclerotic plaques the determination of total cholesterol using this method is of acceptable efficacy, even though the calibration procedure did not reflect the composition correctly. Using an energy dose of less than 100 mW/cm 2 to avoid damage to endothelial cells, arterial tissue of about 170–200 μm thickness attenuates the reflected NIRS signal by up to 50%. Cholesterol levels could be determined accurately in atherosclerotic lesions in human aortic specimens obtained by autopsy. The correlation coefficient between the NIRS results and those of HPLC analysis calculated in the investigation of 82 different areas of 18 human aortic specimens was 0.926 ( y =0.869 x +0.771, external validation). Acceptable results were also achieved by means of a coronary-catheterlike fiberoptic strand ( d =l mm), despite the worsened signal/noise ratio. The results show that the development of a coronary catheter using NIRS appears to be possible in principle.

The determination of fecal fat, nitrogen and water is important to get evidence for malassimilation and for estimating the efficacy of treatment with pancreatic enzymes. Standard methods for the determination of these parameters (van-de-Kamer method for fat determination, Kjeldahl method for nitrogen determination) are expensive, time-consuming and cumbersome for laboratory assistants. Near infrared (NIR) reflectance spectroscopy was evaluated as a potentially attractive alternative method, especially because the simultaneous measurement of fat, nitrogen and water content is possible. After homogenisation parts of stool samples were packed and thermowelded in a bag of polyethylene/polyamide (PE/PA) film to optimize the handling in the laboratory. Two optical systems were tested: 1. Fiber optic, In-Ga-As-detector, weavelength range 1000–2500 nm, area of measurement diameter 4–mm; 2. Integrating sphere, Ge-detector, wavelength range 1000–1800 nm, area of measurement diameter 10 mm. Forty stool samples were used for calibration, another 20 for validation from both healthy children and patients with cystic fibrosis in an age range from 5 to 18 years. The concentrations of fecal compounds were calculated using the chemometric Partial Least Square (PLS) method with the NIR reflectance spectroscopy measurement data. The calibration were carried out based on results of chemical analysis with standard methods. The regression equations of the external NIR reflectance spectroscopy validations were as follows:1. for the fiber optic system: fat determination y = 0.9737x + 5.7261r = 0.989, nitrogen determination y = 1.0092x+0.0731 r = 0.933, water determination y = 0.9699x+2.0703 r = 0.993;2. for the integrating sphere system: fat determination y = 1.0308x–1.6797 r = 0.998, nitrogen determination y = 0.9529x+0.5302 r = 0.959, water y = 1.0301x–1.8193 r = 0.993.The NIR reflectance spectroscopy method is a precise and alternative method for the determination of fecal fat, nitrogen and water. Moreover, handling is simple, time of analysis is short (4 minutes on average) and all calibrated constituents can be analyzed simultaneously. Therefore, we conclude that NIR reflectance spectroscopy is a reliable and useful method for analysis of fecal components in laboratory medicine.

Background: Determinations of fecal fat and nitrogen reveal evidence of malabsorption and assist in estimating the efficacy of pancreatic enzyme treatment. Seventy-two-hour stool collection, with chemical analysis of fecal fat, and Kjeldahl's method for measurement of fecal nitrogen are generally accepted as standard methods for making these determinations. However, these traditional methods are expensive, time-consuming, and cumbersome. This study evaluated the efficiency and validity of an alternative method, using near-infrared reflectance spectroscopy (NIRS) and compared results with those of the standard methods. Methods: Near-infrared reflectance spectroscopy is a secondary method: The instrument first has to be calibrated with samples analyzed by the standard method. Sixty-three stool samples with known fat content (range 4.79-292.5 mg/g), 24 samples with known nitrogen content (range 5.36-19.38 mg/ g), and 24 samples with known water concentration (range 60.1-82.22%) served for calibration. A further 69 samples were analyzed to validate the procedure. Results: There was a satisfactory correlation between the measurements produced by near-infrared reflectance spectroscopy and those produced by standard methods: fat r = 0.97: nitrogen r = 0.94; water r = 0.96. Conclusions: Near-infrared reflectance spectroscopy appears to be a reliable, simple, and rapid method of measuring different fecal components-as precise and accurate as the standard methods. Stool samples should be analyzed immediately after collecting or stored only a few days before analyzing.

The application of the chemiluminescence system oxalic acid-fluorescer-peroxy compound-carbodiimide to biochemical analysis in protic solvents is described. By measuring the integrated chemiluminescence emission generated by the above reaction, very low concentrations of oxalate (down to 10 nmol l −1 can be determined. Optimized reaction conditions and preanalytical factors permit direct and rapid measurements of urinary oxalate without calcium oxalate precipitation. The system also permit rapid quantitative analysis for urinary porphyrins down to about 200 μg l −1 .

Exhaled breath condensate (EBC) analysis is a promising new method to monitor airway inflammation, however there are still multiple open methodological questions. The purpose of this study was therefore to investigate methodological influences on nitrite in EBC (surface contamination, flow dependency, storage time and inter- and within day variability).EBC samples of 10 healthy children, 10 healthy adults and 71 asthmatic children were collected and nitrite was analysed using the Griess reaction. Collector devices where either air-dried after disinfection or stored in distilled water till usage. Repeatability measurements were performed at three different times during one day and on five consecutive days. Flow dependency was analysed at 200 and 400 ml/s expiratory flow and storage stability was investigated at several time points within the first three hours after collection of the sample. In a preliminary study EBC nitrite was analysed in asthmatic children of different severity.Surface contamination appears to have a profound influence on nitrite levels and both within-day and inter-day variability is high. We found no flow dependency, and storage stability was satisfying although with considerable variety in several samples. There were no significant differences between the nitrite levels of the different asthmatic subgroups nor between the asthmatic children and the controls.These data indicate that EBC nitrite is a substance with a wide variety of influencing factors and different sources of origin. This has to be kept in mind when using exhaled nitrite as a biomarker for airway inflammation.br /

The present study shows that the incubation of human aortic smooth muscle cells (HASMC) and HepG2 cells with atorvastatin and mevastatin as HMG-CoA reductase inhibitors potentiated the interferon-gamma (INF-gamma)-induced group IIA phospholipase A(2) (sPLA(2)-IIA) expression in a dose- and time-dependent manner. The effect of statins on sPLA(2)-IIA expression was reduced by mevalonate, farnesyl pyrophosphate and geranylgeranyl pyrophosphate. Inversely, inhibitors of the farnesyl transferase and geranylgeranyl transferase-I mimicked the effects of statins. Clostridium difficile toxin B (TcdB), Y-27632 and H-1152, functioning as inhibitors of Rho proteins and Rho-associated kinase, also augmented the sPLA(2)-IIA expression in combination with IFN-gamma. The same effects were observed when inhibitors of mitogen-activated/extracellular response protein kinase kinase (MEK), PD98059 or U0126 were used. Further, the Janus kinase-2 (Jak2)-specific inhibitor, AG-490 and inhibitors of nuclear factor-kappaB (NFkappaB) abrogated the sPLA(2)-IIA elevating effects of statins, TcdB and PD98059 in the presence of IFN-gamma. This cytokine alone increased the NFkappaB p65 and CAAT-enhancer-binding protein-beta (C/EBP-beta) activity in HASMC nuclear extract, but only C/EBP-beta was further augmented when the cells were incubated in addition to IFN-gamma with atorvastatin, H-1152, PD98059 or U0126. Moreover, after the incubation of cells with atorvastatin and IFN-gamma the stability of sPLA-(2)IIA mRNA significantly increased in comparison to those after incubation with IFN-gamma alone. In conclusion, the obtained data suggest that (i) the expression of sPLA(2)-IIA is negatively regulated by RhoA/Rho-associated kinase and MEK/ERK signaling pathways and (ii) statins, because of their ability to down-regulate these pathways, can potentiate the IFN-gamma-induced sPLA(2)-II expression at transcriptional and post-transcriptional levels.

Particular danger associated with an arteriosclerotic plaque consists in the possible rupture of its cap, dependent on the thickness of the cap covering the lipid core, its composition and different inflammatory changes. The purpose of this study was to compare the total cholesterol and collagen contents of arterial walls, both measured by near infrared spectroscopy (NIRS), and to test whether the ratios of cholesterol to collagen correlate with histochemical parameters possibly being indicators for plaque stability. NIR spectra of 118 sections from 36 human aortas were measured at 1000-2500 nm. Evaluation was performed by the partial least squares method (PLS), the chemical reference analysis by HPLC. Acceptable results were achieved for calibrations. With these calibrations 38 further aortic sections taken at autopsy were NIR-spectroscopically analysed and ordered in relation to histological findings of fatty deposits, cap thickness over the lipid core, and the ratio of fatty deposits to cap thickness. Correlations were found to exist between the spectroscopically determined total cholesterol concentrations and the histologically estimated fatty deposits (r=0.887), between the spectroscopically determined collagen concentrations and the cap thickness over the lipid core (r=0.441), and between the ratios total cholesterol to collagen and the ratios fatty deposits to cap thickness (r=0.575).

Background: Latex antigens have been found in urban air samples and in debris deposited near freeways. Objective: We investigated whether exposure to road traffic in a large city is associated with allergic sensitization against latex in children. Methods: A population-based sample of 2505 children aged 5 to 11 years was examined in a cross-sectional study in the city of Dresden, Germany. Specific IgE levels against latex and a panel of common aeroallergens (timothy grass, rye, birch, mugwort, Cladosporium herbarum, Dermatophagoides pteronyssinus, cat dander, and dog dander) was determined by using a fluorescence immunoassay (CAP Pharmacia). Traffic exposure was assessed by (1) parental self-report on traffic frequency and truck traffic in the street of residence, (2) traffic counts, and (3) measurements of benzene at 182 points on a 1-km 2 grid for 1 year, which were used to estimate the children's individual exposure at the home address. Results: Eight hundred fifty-four (34.1%) of the children were sensitized against any of the allergens, and 150 (6.0%) had specific IgE (>0.35 kU/L) against latex. The prevalence of latex sensitization was not positively associated with self-reported traffic exposure, traffic counts in the street of residence (adjusted prevalence odds ratio for >5000 vs ≤5000 cars/d, 0.7; 95% confidence interval, 0.4-1.3), or benzene exposure (adjusted prevalence odds ratio for an increase of 1 μg/m 3 air, 0.8; 95% confidence interval, 0.7-1.05). Conclusion: The data suggest that exposure to road traffic is not associated with allergic sensitization to latex in children. (J Allergy Clin Immunol 2000;106:573-8.)