We investigated whether cement pastes are a possible source of ecotoxicologically potent substances. For this purpose, leaching according to DIN EN 16637-2 was performed on portland cement pastes as ...well as blast furnace slag cement with and without an air entraining agent (AEA). The AEA, consisting of wood rosin and resin, contained the stabiliser drometrizole and the biocide octylisothiazolinone (OIT), which was confirmed by our non-target screening (NTS). Our ecotoxicological studies (Daphnia magna, Aliivibrio fischeri and Desmodesmus subspicatus) of the pure cement eluates showed no effects at all. In these samples, it was possible to attribute up to 85 % of the dissolved organic carbon (DOC) to acetate, formate and diethylene glycol (DiEG). Eluates from cement pastes with AEA contained up to 70 μg/L octylisothiazolinone (OIT), and no drometrizole was found. Around 90 % of the total OIT release happened within the first 6 h. It was possible to attribute the observed ecotoxicological effects mainly to the OIT concentrations. Additional leaching with elevated sulphate concentrations (800 mg/L) did not influence the release of DOC and OIT or increase the ecotoxicological effects. As a consequence, we advise curing the cement paste for 24 h prior to use, as this largely avoids the release of OIT and the observed ecotoxicological effects.
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•Dissolved organic carbon of cement paste eluates mainly consists of grinding aids.•Non-Target Screening identified organic substances released.•Adding air entraining agent caused adverse ecotoxicological effects.•Ecotoxicological effects could be linked to the occurrence of chemicals.
Introduction
In the time of increasing resistance and paucity of new drug development there is a growing need for strategies to enhance rational use of antibiotics in German and Austrian hospitals. ...An evidence-based guideline on recommendations for implementation of antibiotic stewardship (ABS) programmes was developed by the German Society for Infectious Diseases in association with the following societies, associations and institutions: German Society of Hospital Pharmacists, German Society for Hygiene and Microbiology, Paul Ehrlich Society for Chemotherapy, The Austrian Association of Hospital Pharmacists, Austrian Society for Infectious Diseases and Tropical Medicine, Austrian Society for Antimicrobial Chemotherapy, Robert Koch Institute.
Materials and methods
A structured literature research was performed in the databases EMBASE, BIOSIS, MEDLINE and
The Cochrane Library
from January 2006 to November 2010 with an update to April 2012 (MEDLINE and
The Cochrane Library
). The grading of recommendations in relation to their evidence is according to the AWMF Guidance Manual and Rules for Guideline Development.
Conclusion
The guideline provides the grounds for rational use of antibiotics in hospital to counteract antimicrobial resistance and to improve the quality of care of patients with infections by maximising clinical outcomes while minimising toxicity. Requirements for a successful implementation of ABS programmes as well as core and supplemental ABS strategies are outlined. The German version of the guideline was published by the German Association of the Scientific Medical Societies (AWMF) in December 2013.
A growing body of evidence indicates that microglia actively remove synapses in vivo, thereby playing a key role in synaptic refinement and modulation of brain connectivity. This phenomenon was ...mainly investigated in immunofluorescence staining and confocal microscopy. However, a quantification of synaptic material in microglia using these techniques is extremely time-consuming and labor-intensive. To address this issue, we aimed to quantify synaptic proteins in microglia using flow cytometry. With this approach, we first showed that microglia from the healthy adult mouse brain contain a detectable level of VGLUT1 protein. Next, we found more than two-fold increased VGLUT1 immunoreactivity in microglia from the developing brain (P15) as compared to adult microglia. These data indicate that microglia-mediated synaptic pruning mostly occurs during the brain developmental period. We then quantified the VGLUT1 staining in microglia in two transgenic models characterized by pathological microglia-mediated synaptic pruning. In the 5xFAD mouse model of Alzheimer Disease microglia exhibited a significant increase in VGLUT1 immunoreactivity before the onset of amyloid pathology. Moreover, conditional deletion of TDP-43 in microglia, which causes a hyper-phagocytic phenotype associated with synaptic loss, also resulted in increased VGLUT1 immunoreactivity within microglia. This work provides a quantitative assessment of synaptic proteins in microglia, under homeostasis and in mouse models of disease.
Aliment Pharmacol Ther 2011; 33: 149–159
Summary
Background Effectiveness of medical therapies in chronic pancreatitis has been described in small studies of selected patients.
Aim To describe ...frequency and perceived effectiveness of non‐analgesic medical therapies in chronic pancreatitis patients evaluated at US referral centres.
Methods Using data on 516 chronic pancreatitis patients enrolled prospectively in the NAPS2 Study, we evaluated how often medical therapies pancreatic enzyme replacement therapy (PERT), vitamins/antioxidants (AO), octreotide, coeliac plexus block (CPB) were utilized and considered useful by physicians.
Results Oral PERT was commonly used (70%), more frequently in the presence of exocrine insufficiency (EI) (88% vs. 61%, P < 0.001) and pain (74% vs. 59%, P < 0.002). On multivariable analyses, predictors of PERT usage were EI (OR 5.14, 95% CI 2.87–9.18), constant (OR 3.42, 95% CI 1.93–6.04) or intermittent pain (OR 1.98, 95% CI 1.14–3.45). Efficacy of PERT was predicted only by EI (OR 2.16, 95% CI 1.36–3.42). AO were tried less often (14%) and were more effective in idiopathic and obstructive vs. alcoholic chronic pancreatitis (25% vs. 4%, P = 0.03). Other therapies were infrequently used (CPB – 5%, octreotide – 7%) with efficacy generally <50%.
Conclusions Pancreatic enzyme replacement therapy is commonly utilized, but is considered useful in only subsets of chronic pancreatitis patients. Other medical therapies are used infrequently and have limited efficacy.
Hereditary pancreatitis (HP) is a rare, early-onset genetic disorder characterized by epigastric pain and often more serious complications. We now report that an Arg-His substitution at residue 117 ...of the cationic trypsinogen gene is associated with the HP phenotype. This mutation was observed in all HP affected individuals and obligate carriers from five kindreds, but not in individuals who married into the families nor in 140 unrelated individuals. X-ray crystal structure analysis, molecular modelling, and protein digest data indicate that the Arg 117 residue is a trypsin-sensitive site. Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis.
BACKGROUND Hereditary pancreatitis (HP) is a rare autosomal dominant disorder with variable expression and an overall lifetime penetrance of 80%. We hypothesised that (1) monozygotic twins within ...similar environments would develop the typical signs of HP at a similar age, and (2) if penetrance were due to modifier genes or environment, all twin pairs would be concordant for expression of HP. AIM Identify monozygotic twins with HP and determine the penetrance, concordance, and age of onset of symptoms. METHODS Twins from HP kindreds were identified from the Midwest Multicenter Pancreatic Study group database, referrals, and literature searches. Each twin set was assessed for phenotypic expression, concordance, and difference in age of phenotypic onset of pancreatitis. The difference in onset of symptoms for symptomatic affected non-twin sibling pairs as well as non-twin pairs that were mutation, sex, and age matched were calculated as two comparison groups. RESULTS Seven of 11 monozygotic pairs identified were suitable for evaluation and four were concordant for pancreatitis. Forty eight affected sibling pairs and 33 pairs of mutation, sex, and age matched (cationic trypsinogen R122H (30 pairs) and N29I (three pairs)) subjects were identified for comparison groups. The median (quartiles Q1, Q3) difference in the age of phenotypic onset in the concordant twins was 1 (0, 2.4) years, 2 (1, 6) for the affected siblings, and 7 (2, 15) years in the comparison control group. Three of the seven sets of twins (43%) were discordant for phenotypic expression of pancreatitis. The overall penetrance in the seven pairs of monozygotic twins was 78.6%. CONCLUSIONS Genetic and/or environmental factors contribute to expression and age of onset of HP. Nuclear genes or general environmental factors alone cannot explain the 80% penetrance. Determining the mechanism of non-penetrance may help in developing a strategy to prevent the phenotypic expression of pancreatitis in individuals with an underlying genetic predisposition.
Cereals are a good source of phenolic acids, most of which are present in bound form. The aim of this study was to develop a method for quantifying total phenolic acids in cereals that includes a ...robust step for hydrolysis of bound forms. Different hydrolysis procedures were evaluated. Acid hydrolysis, even with subsequent use of enzymes, proved unsuitable for releasing bound phenolic acids from the cereal matrix. Base hydrolysis (3 M, 90 min) resulted in the highest extractability, with average recoveries of 88–108% for cereal phenolic acids. The phenolic acid content in cereals (two cultivars each of rye, barley, and oats, and eight cultivars of wheat) varied up to 2-fold between cereal genotypes and 1.5-fold within genotypes. The highest content was found in rye, followed by wheat, barley, and oats. Ferulic acid dominated in all cereals, amounting to 48–72% of total phenolic acid content.
The detection and evaluation of steatorrhea in a rapid, quantitative fashion are clinically needed in patients with suspected steatorrhea. Our aim was to evaluate the acid steatocrit method, on ...random spot stools in adults with and without steatorrhea, relative to the qualitative (microscopic) and quantitative assessments for fecal fat.
Stool samples were collected 72 h after a diet of 100 g of fat per day and randomly from 15 healthy controls, 14 patients with chronic pancreatitis, and seven patients with small bowel disease. All stools had quantitative, qualitative, and acid steatocrit analyses performed for fecal fat.
The sensitivity and specificity for the detection of steatorrhea by the spot stool qualitative fecal fat were 78 and 70%, respectively. The spot stool acid steatocrit correlated linearly with the 72-h stool quantitative fecal fat (g/24 h), r = 0.761 and p < 0.001. The acid steatocrit on random spot stools, compared with the 72-h stool quantitative fecal fat, revealed a sensitivity of 100%, a specificity of 95%, and a positive predictive value of 90% for the detection of steatorrhea. It also estimated the quantitative fecal fat.
The acid steatocrit can be performed accurately on random spot stools and can be used to detect the presence of steatorrhea and estimate the quantitative fecal fat. This assay can be done with readily available equipment for rapid evaluation. Use of a spot stool sample simplifies the acid steatocrit, further improving on the practicality of this test. This study also confirms the clinical usefulness of this simplified method to detect steatorrhea.
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