Inhalers and nebulizers: basic principles and preliminary measurements

Inhalers are hand-held devices which are used for administration of therapeutic aerosols via inhalation. Nebulizers are larger devices serving for home and hospital care using inhaled medication. This contribution describes the basic principles of dispersion of aerosol particles used in various types of inhalers and nebulizers, and lists the basic physical mechanisms contributing to the deposition of inhaled particles in the human airways. The second part of this article presents experimental setup, methodology and preliminary results of particle size distributions produced by several selected inhalers and nebulizers

The role of the combined use of experimental and computational methods in revealing the differences between the micron -size particle deposition patterns in healthy and asthmatic subjects

Quantification of airway deposition of aerosol particles is essential for the assessment of health risks of detrimental particles. Knowledge of deposition distribution is important also in the case of treatment with aerosolised drugs. It is also worth considering that deposition of inhaled particles in severe asthmatics can be different from the deposition in healthy subjects due to the modified breathing parameters, airway geometry and lobar flow distribution. The aim of this study was to apply combined experimental and numerical techniques to quantify the upper airway and bronchial deposition of the inhaled microparticles in healthy individuals in comparison with asthma patients. Idealised and realistic physical and digital replicas of the human airways were constructed. Deposition fractions and efficiencies of inhaled polydisperse mannitol and chitosan particles in different airway sections were measured and calculated. Deposition fraction of polydisperse mannitol particles in the idealised airway geometry assuming breathing conditions of healthy subjects was 21.9% and 18.3% when determined experimentally and by numerical simulations, respectively. Experimental measurements of deposition fraction of chitosan particles in the same geometry, but assuming breathing parameters characteristic of severe asthmatics yielded 32%, while simulations provided 30.1% for the same conditions. Extrathoracic deposition fraction of mannitol particles in healthy subjects measured in the realistic geometry was 71.1%, while bronchial deposition fraction was 5.3%. The corresponding simulations yielded 76.2% and 8.9% deposition fractions in the upper and bronchial airways, respectively. There was a good agreement between the experimental and simulation deposition results also in the different predefined sections of the airways. Present pilot study proved that lobar flow redistribution due to severe asthma significantly modified the deposition distribution of micro-particles. Although the present results refer only to small groups of healthy and asthmatic individuals, it clearly demonstrates the capability of carefully validated models to simulate the deposition of micron-size particles in larger populations of both groups

Chemical and toxicological characterisation of anticancer drugs in hospital and municipal wastewaters from Slovenia and Spain

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Molecular Nutrition & Food Research / Impact of Weight Loss Strategies on ObesityInduced DNA Damage

Scope Obesity causes DNA damage, which is causally related to several disorders including cancer, infertility, and cognitive dysfunctions. The aim of this study is to investigate whether weight loss improves the integrity of the genetic material. Methods and Results Overweight mice are fed ad libitum either with a Western diet (WD), with a 40% caloric restricted WD, or with a high carbohydrate low protein (HCLP) diet. Caloric restriction and also the HCLP diet lead to ca. 30% weight loss, which is paralleled by decreased DNA damage (“comet” formation) and oxidative damage of purines in inner organs, additionally the activity of nucleotide excision repair increased. The effects are more pronounced in animals that have received the HCLP chow. Results of biochemical analyses indicate that the reduction of DNA damage is associated with a decrease of proinflammatory cytokines and lower insulin levels. Conclusion The study indicates that weight loss may prevent obesityassociated adverse health effects due to reduction of overall DNA damage.(VLID)489498

Use of HuH6 and other humanderived hepatoma lines for the detection of genotoxins: a new hope for laboratory animals?

Cell lines which are currently used in genotoxicity tests lack enzymes which activate/detoxify mutagens. Therefore, rodent-derived liver preparations are used which reflect their metabolism in humans only partly; as a consequence misleading results are often obtained. Previous findings suggest that certain liver cell lines express phase I/II enzymes and detect promutagens without activation; however, their use is hampered by different shortcomings. The aim of this study was the identification of a suitable cell line. The sensitivity of twelve hepatic cell lines was investigated in single cell gel electrophoresis assays. Furthermore, characteristics of these lines were studied which are relevant for their use in genotoxicity assays (mitotic activity, p53 status, chromosome number, and stability). Three lines (HuH6, HCC1.2, and HepG2) detected representatives of five classes of promutagens, namely, IQ and PhIP (HAAs), B(a)P (PAH), NDMA (nitrosamine), and AFB1 (aflatoxin), and were sensitive towards reactive oxygen species (ROS). In contrast, the commercially available line HepaRG, postulated to be a surrogate for hepatocytes and an ideal tool for mutagenicity tests, did not detect IQ and was relatively insensitive towards ROS. All other lines failed to detect two or more compounds. HCC1.2 cells have a high and unstable chromosome number and mutated p53, these features distract from its use in routine screening. HepG2 was frequently employed in earlier studies, but pronounced inter-laboratory variations were observed. HuH6 was never used in genotoxicity experiments and is highly promising, it has a stable karyotype and we demonstrated that the results of genotoxicity experiments are reproducible.(VLID)473572

Potent protection of gallic acid against DNA oxidation: Results of human and animal experiments

a b s t r a c t Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a constituent of plant derived foods, beverages and herbal remedies. We investigated its DNA protective properties in a placebo controlled human intervention trial in single cell gel electrophoresis experiments. Supplementation of drinking water with GA (12.8 mg/person/d) for three days led to a significant reduction of DNA migration attributable to oxidised pyrimidines (endonuclease III sensitive sites) and oxidised purines (formamidopyrimidine glycosylase sensitive sites) in lymphocytes of healthy individuals by 75% and 64% respectively. Also DNA damage caused by treatment of the cells with reactive oxygen species (ROS) was reduced after GA consumption (by 41%). These effects were paralleled by an increase of the activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase and glutathion-S-transferase-) and a decrease of intracellular ROS concentrations in lymphocytes, while no alterations of the total antioxidant capacity (TAC), of malondialdehyde levels in serum and of the urinary excretion of isoprostanes were found. Experiments with rats showed that GA reduces oxidatively damaged DNA in lymphocytes, liver, colon and lungs and protects these organs against ␥-irradiation-induced strand breaks and formation of oxidatively damaged DNAbases. Furthermore, the number of radiation-induced preneoplastic hepatic foci was decreased by 43% after oral administration of the phenolic. Since we did not find alterations of the TAC in plasma and lipid peroxidation of cell membranes but intracellular effects it is likely that the antioxidant properties of GA seen in vivo are not due to direct scavenging of radicals but rather to indirect mechanisms (e.g. protection against ROS via activation of transcription factors). As the amount of GA used in the intervention trial is similar to the daily intake in Middle Europe (18 mg/person/day), our findings indicate that it may contribute to prevention of formation of oxidatively damaged DNA in humans

Mobile phone specific electromagnetic fields induce transient DNA damage and nucleotide excision repair in serum-deprived human glioblastoma cells

<div><p>Some epidemiological studies indicate that the use of mobile phones causes cancer in humans (in particular glioblastomas). It is known that DNA damage plays a key role in malignant transformation; therefore, we investigated the impact of the UMTS signal which is widely used in mobile telecommunications, on DNA stability in ten different human cell lines (six brain derived cell lines, lymphocytes, fibroblasts, liver and buccal tissue derived cells) under conditions relevant for users (SAR 0.25 to 1.00 W/kg). We found no evidence for induction of damage in single cell gel electrophoresis assays when the cells were cultivated with serum. However, clear positive effects were seen in a p53 proficient glioblastoma line (U87) when the cells were grown under serum free conditions, while no effects were found in p53 deficient glioblastoma cells (U251). Further experiments showed that the damage disappears rapidly in U87 and that exposure induced nucleotide excision repair (NER) and does not cause double strand breaks (DSBs). The observation of NER induction is supported by results of a proteome analysis indicating that several proteins involved in NER are up-regulated after exposure to UMTS; additionally, we found limited evidence for the activation of the γ-interferon pathway. The present findings show that the signal causes transient genetic instability in glioma derived cells and activates cellular defense systems.</p></div