Effects on pulmonary health of neighboring residents of concentrated animal feeding operations: exposure assessed using optimized estimation technique

Potential adverse health effects of concentrated animal feeding operations (CAFOs), which were also shown in the authors' Lower Saxony Lung Study, are of public concern. The authors aimed to investigate pulmonary health effect of neighboring residents assessed using optimized estimation technique. Annual ammonia emission was measured to assess the emission from CAFO and from surrounding fields. Location of sampling points was optimized using cluster analysis. Individual exposure of 457 nonfarm subjects was interpolated by weighting method. Mean estimated annual ammonia levels varied between 16 and 24 μg/m3. Higher exposed participants were more likely to be sensitized against ubiquitous allergens as compared to lower exposed subjects (adjusted odds ratio [OR] 4.2; 95% confidence interval [CI] 1.2-13.2). In addition, they showed a significantly lower forced expiratory volume in 1 second (FEV?) (adjusted mean difference in % of predicted -8%; 95% CI -13% to -3%). The authors' previous findings that CAFOs may contribute to burden of respiratory diseases were confirmed by this study.     

Effects of yogurt and applesauce on the oral bioavailability of nilotinib in healthy volunteers

Nilotinib, a potent orally bioavailable BCR-ABL tyrosine kinase inhibitor, is currently available as a hard gelatin capsule that must be swallowed whole. For patients who may have difficulty swallowing the intact capsule, an alternative mode of administration is desirable. The authors compared the bioavailability of nilotinib from the following administrations in 48 healthy subjects: (1) 400 mg nilotinib given as two 200-mg nilotinib intact capsules; (2) contents of two 200-mg nilotinib capsules, each capsule dispersed in 1 teaspoon of nonfat plain yogurt; and (3) contents of two 200-mg nilotinib capsules, each capsule dispersed in 1 teaspoon of applesauce. Nilotinib absorption was modestly increased following the administration of nilotinib dispersed in yogurt. The geometric mean ratios (90% confidence intervals) for nilotinib C(max), AUC(0-tlast), and AUC(0-inf) were 1.31 (1.22-1.41), 1.11 (1.05-1.16), and 1.08 (1.02-1.15), respectively. Administration of nilotinib dispersed in applesauce showed equivalent bioavailability compared with administration of nilotinib as intact capsules. The geometric mean ratios (90% confidence intervals) for nilotinib C(max), AUC(0-tlast), and AUC(0-inf) were 0.95 (0.88-1.02), 0.99 (0.94-1.04), and 0.97 (0.90-1.03), respectively. Each treatment was well tolerated in the study subjects. The data support a feasible alternative method of nilotinib administration; each capsule's contents may be dispersed in 1 teaspoon of applesauce and taken immediately.     

N-Methylated sst2 Selective Somatostatin Cyclic Peptide Analogue as a Potent Candidate for Treating Neurogenic Inflammation

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Characterization of three synuclein genes in Xenopus laevis

The synuclein family consists of three small intracellular proteins mainly expressed in neural tissues, and has been associated with human neurodegenerative diseases. We have examined the spatial and temporal expression patterns of three synuclein genes during embryogenesis of Xenopus laevis. The Xenopus synucleins were firstly expressed in the developing nervous system at the tail bud stages. At tadpole stages, Xenopus snca was expressed in the brain, branchial arch and somite, and sncbb signals were detected in entire brain and spinal cord. However, sncg was only expressed in the peripheral nervous system including trigeminal nerve and dorsal root ganglion. RT‐PCR indicated that expression of synucleins was up‐regulated at the end of neurulation, and then maintained at later examined stages. Our study provides the spatiotemporal expression patterns of the synuclein family genes in Xenopus embryos, and forms a basis for further functional analysis of synucleins. Developmental Dynamics 240:2028–2033, 2011. © 2011 Wiley‐Liss, Inc.     

Thermal anemometric assessment of coronary flow reserve with a pressure-sensing guide wire: an in vitro evaluation

Assessment of coronary flow reserve (CFR) with a commercially available pressure-sensor-tipped guide wire using the principle of thermal anemometry could provide major clinical benefits both in determining and in distinguishing between epicardial and microvascular coronary artery disease. In constant-temperature thermal anemometry, the electrical power required to maintain an element at a constant temperature is a measure for the local shear rate. Here, the feasibility of applying this thermoconvection method to a pressure-sensing guide wire is investigated using an in vitro model. A theoretical relation between electrical power and steady shear rate based on boundary layer theory was tested in an experimental set-up. In steady flow, a reproducible relation between electrical power and shear rate was obtained with an overheat temperature of 20K, which was in good agreement with theory. The relation between shear rate and flow, however, depends on geometry of the artery and position of the guide wire inside the vessel. Although this means that this thermoconvection method is less useful for absolute flow measurements, CFR could be assessed even for unsteady flow using the steady calibration curve with a mean relative difference of (3±5)% compared to CFR derived from the golden standard using an ultrasonic flow measurement device.     

Assaying embryotoxicity in the test tube: current limitations of the embryonic stem cell test (EST) challenging its applicability domain

Testing for embryotoxicity in vitro is an attractive alternative to animal experimentation. The embryonic stem cell test (EST) is such a method, and it has been formally validated by the European Centre for the Validation of Alternative Methods. A number of recent studies have underscored the potential of this method. However, the EST performed well below the 78% accuracy expected from the validation study using a new set of chemicals and pharmaceutical compounds, and also of toxicity criteria, tested to enlarge the database of the validated EST as part of the Work Package III of the ReProTect Project funded within the 6th Framework Programme of the European Union. To assess the performance and applicability domain of the EST we present a detailed review of the substances and their effects in the EST being nitrofen, ochratoxin A, D-penicillamine, methylazoxymethanol, lovastatin, papaverine, warfarin, β-aminopropionitrile, dinoseb, furosemide, doxylamine, pravastatin, and metoclopramide. By delineation of the molecular mechanisms of the substances we identify six categories of reasons for misclassifications. Some of these limitations might also affect other in vitro methods assessing embryotoxicity. Substances that fall into these categories need to be included in future validation sets and in validation guidelines for embryotoxicity testing. Most importantly, we suggest conceivable improvements and additions to the EST which will resolve most of the limitations.     

Calvaria bone chamber--a new model for intravital assessment of osseous angiogenesis

The faith of tissue engineered bone replacing constructs depends on their early supply with oxygen and nutrients, and thus on a rapid vascularization. Although some models for direct observation of angiogenesis are described, none of them allows the observation of new vessel formation in desmal bone. Therefore, we developed a new chamber model suitable for quantitative in vivo assessment of the vascularization of bone substitutes by intravital fluorescence microscopy. In the parietal calvaria of 32 balb/c mice a critical size defect was set. Porous 3D-poly(L-lactide-co-glycolide) (PLGA)-blocks were inserted into 16 osseous defects (groups 3 and 4) while other 16 osseous defects remained unequipped (groups 1 and 2). By placing a polyethylene membrane onto the dura mater, the angiogenesis was mainly restricted to the osseous margins (groups 2 and 4). Microvascular density, angiogenesis, and microcirculatory parameters were evaluated repetitively during 22 days. In all animals, only a mild inflammatory reaction was observed with a climax after 2 weeks. The implantation of PLGA scaffolds resulted in a vascular growth directed towards the center of the defect as demonstrated by the significantly (p < 0.05) enhanced central microvascular densitiy from day 3 to day 22 when compared with unequipped chambers. The additional application of polyethylene membrane was found to reduce significantly the microvessel density mainly in the center of both scaffolds and defects. The present calvaria bone chamber allows for the first time to assess quantitatively the angiogenesis arising from desmal bone directly in vivo. Therefore, this chronic model may support the future research in the biological adequacy of bone substitutes.