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Biomedical subjects

H Windt

Publications and source records attributed to H Windt.

8 recordsLinked to original sources

Validation of an environmental exposure unit for controlled human inhalation studies with grass pollen in patients with seasonal allergic rhinitis.

BACKGROUND: There is an increasing need for allergen inhalation systems to perform basic clinical research and test anti-allergic drugs under well-controlled conditions. This requires stability of environmental conditions like temperature and humidity, as well as allergen concentration and reproducible induction of allergic symptoms. OBJECTIVE: The aim of this study was to validate an environmental exposure unit for controlled human pollen inhalation studies in participants with seasonal allergic rhinitis. METHODS: Temperature, relative humidity, and air flow rate were kept constant with an air conditioning system. Pollen atmosphere was generated using a specially designed feeding system and monitored online by laser counter and offline using rotating rod samplers. Efficacy (total nasal symptom score, nasal air flow rate, nasal secretion) and safety (lung function) parameters were evaluated at different pollen concentrations and repeated allergen challenges. RESULTS: Temperature, humidity, and air flow rate in the environmental exposure unit remained constant within a range of <2%. The spatial distribution and the temporal stability of the pollen concentration varied only slightly over 4 h (+/-10% and <4%, respectively). Dose-dependent induction of allergic rhinitis symptoms, reduction in nasal air flow rate, and increase in nasal secretion were observed over time. These effects were reproducible from day to day. Lung function remained clinically normal at all concentrations and from day to day. CONCLUSIONS: Thus, pollen exposure in the environmental exposure unit is an effective, reproducible, safe, and suitable method for single-centre clinical studies on the efficacy of anti-allergic treatment or basic clinical research.

Adult↗

Automatization for development of HPLC methods.

Within the frame of inprocess analytics of the synthesis of pharmaceutical drugs a lot of HPLC methods are required for checking the quality of intermediates and drug substances. The methods have to be developed in terms of optimal selectivity and low limit of detection, minimum running time and chromatographic robustness. The goal was to shorten the method development process. Therefore, the screening of stationary phases was automated by means of switching modules equipped with 12 HPLC columns. Mobile phase and temperature could be optimized by using Drylab after evaluating chromatograms of gradient elutions performed automatically. The column switching module was applied for more than three dozens of substances, e.g. steroidal intermediates. Resolution (especially of isomeres), peak shape and number of peaks turned out to be the criteria for selection of the appropriate stationary phase. On the basis of the "best" column the composition of the "best" eluent was usually defined rapidly and with less effort. This approach leads to savings in manpower by more than one third. Overnight, impurity profiles of the intermediates were obtained yielding robust HPLC methods with high selectivity and minimized elution time.

Autoanalysis↗

Inhalation studies with the Göttingen minipig.

A method for inhalative exposure of minipigs to aerosols and gases has been developed. Minipigs are exposed via mask inhalation to the test substance using a computer-controlled exposure system that permits simultaneous exposure of groups of four animals in parallel to different controlled dose levels. We studied inhalation treatment of verapamil, a cardiovascular drug, and show good absorption and favorable pharmacokinetics when compared with iv drug application. The results shown in this study encourage inhalation studies with the Göttingen minipig.

Aerosols↗

Micronucleus induction in V79 cells after direct exposure to whole cigarette smoke.

Previous investigations on the effects of cigarette smoke on cultured cells have used mainly smoke condensate dissolved in culture medium. A system has been designed which allows direct exposure of cells to fresh cigarette smoke, without an intervening layer of growth medium between the cells and the smoke. Preliminary results have been obtained which demonstrate the viability of the system. V79 cells were cultured on porous membranes (Transwell; Costar). During smoke exposure only the lower surface of each Transwell is supplied with culture medium from the bottom of the culture chambers. In this way the cells had direct contact with the atmosphere at the upper surface and could be exposed directly to the test compound. The constructed exposure system consists of a smoke generator and an exposure unit containing six Transwells, the latter contained in an incubator. Cigarette smoke was generated using a standard 2 s, 35 ml puff once per min. The puff is diluted with conditioned air from the incubator and injected into the exposure unit. Following exposure of the cells to air only for 3 h there was no effect upon V79 cell viability. However, after exposure to smoke containing between 88 and 224 mg/m3 particulate matter, an inhibition of cell proliferation and induction of micronuclei was measured. When a Cambridge filter pad was placed between the cigarette and the cell exposure system to remove particulate matter cell proliferation was also reduced and an increased frequency of micronuclei above the control value was measured.

Aerosols↗

Induction of protective immunity by aerosol or oral application of candidate vaccines in a dose-controlled pig aerosol infection model.

In order to outline basic concepts for the design of a bacterial aerosol infection model, the development of a pig model with Actinobacillus pleuropneumoniae is described. First, reproducibility of aerosol parameters should be maintained by optimizing generating and sampling conditions. Survival rates of the chosen strain must be predictable. Secondly, inhalation conditions for the recipients have to be standardized to enable the determination of deposition sites and the dose administered. Subsequently, dose-response relationship should be evaluated to find a suitable challenge dose. Furthermore, it seems necessary to establish methods to obtain local specimens for determination of the local immune responses. The present study demonstrates that after aerosol challenge pigs were completely protected after inhalation and partially protected after oral application of A. pleuropneumoniae vaccines and describes techniques to administer bacteria in a dose-dependent, viable way. Using the infection model several stages of the disease from acute pleuropneumonia to chronic infection can be induced for research purposes.

Actinobacillus Infections↗

Cluster arousal analysis in chronic pain-disturbed sleep.

A new cluster arousal analysis system was developed to quantify microdisturbances in the sleep architecture. The system was evaluated in 10 healthy volunteers and the sleep of 23 outpatients with chronic low back pain was investigated before and after a special rehabilitative training. The comparison of sleep parameters before and after the treatment showed a significant reduction of the cluster disturbed sleep (CDS), whereas sleep efficiency and the number of stage shifts remained unchanged. The reduction of the CDS correlated with a reduction of depression scale. This cluster arousal analysis appears to be a sensitive tool for evaluating alterations in the sleep microstructure.

Journal Article↗