Mathematical processing of experimental data ignition composite solid propellant solitary heated particles

This article presents a mathematical method for processing experimental data. Were obtained mathematical expressions for delay the ignition of condensed matter by single particles heated from the initial temperature of the particles of the obtained data, and select the most appropriate dependences

Influence of chemical and mechanical stress on precision-cut lung slices

Lungs are exposed to different forms of stress such as chemical substances, allergens or in the form of direct tissue injury. This study examined whether precision-cut lung slices are suitable as a model for studying different types of stress. We established the use of PCLS from sheep to study the response of airways and vessels to mediators. According to in vivo experiments sheep are thought to represent the human pathophysiology better than rodents. We therefore established the use of sheep PCLS and showed that methacholine, serotonin and endothelin-1 lead to a bronchoconstriction, while the response to leukotriene and thromboxane was rather weak. PCLS were also produced from preterm sheep and compared to adult sheep, which revealed a decreased reagibility to methacholine and serotonin in preterm sheep. Comparison of the bronchoconstriction of sheep PCLS with bronchoconstriction data from human PCLS revealed a less satisfactory accordance than the one seen in vivo. Although sheep PCLS may not represent the characteristics of human PCLS completely, the results presented in this thesis indicate that they are closer to human PCLS than PCLS from rodents. Another kind of stress that we examined was chemical stress. This study also aimed at studying the usefulness of PCLS to study respiratory allergens as required in the REACH (Regulation, Evaluation, Authorisation and restriction of CHemicals) process. Bronchoconstriction in PCLS as response to chemical allergen was investigated and compared to bronchoconstriction in vivo. For this purpose a well established sensitisation protocol with TMA, a respiratory allergen and DNCB, a dermal allergen, was used. The early allergic response and airway hyperresponsiveness in mouse PCLS was investigated and compared to data from in vivo invasive measurements. Acquired measurements were comparable suggesting PCLS as a reasonable alternative to invasive lung function measurements. Hence, stress-related bronchoconstriction to chemical allergens may be a suitable predictability for in vivo experiments. Several in vivo and cell culture models have been developed to study the pulmonary responses to mechanical stretch. While providing extremely useful information, these models do also suffer from limitations in being either too complex for detailed mechanical or mechanistic studies, or being devoid of the full complexity present in vivo (e.g. different cell types and interstitial matrix). Therefore, we developed a new model, based on the biaxial stretching of precision-cut lung slices. Single PCLS were mounted on a thin and flexible carrier membrane of PDMS in a bioreactor and the membrane was stretched by applying varying pressures under static conditions. A gene array revealed a general upregulation of immune response and wound healing genes by the slicing process. Stretch markers like amphiregulin were upregulated in PCLS by the slicing process. This upregulation was dependent on tyrosin kinases and the cytoskeleton, but could not be blocked sufficiently, which made it complicated to differentiate a stretch response from the basal increase. Distension of the PCLS was modelled via finite element simulation. According to this analysis, lung tissue was stretched by up to 38% in the latitudinal and by up to 44% in the longitudinal direction resulting in alveolar distension similar to what has been described in intact lungs. Lung slices were stretched dynamically with a frequency of 0.25 Hz for 4h, without causing cell injury. This indicates that the distension of PCLS in the bioreactor may not be suitable to study gene expression but allow the calculation of deformation and occurring forces of the PCLS during the stretching process. PCLS are a suitable model for studying different forms of stress in the lung and allows the investigation of different pathophysiological situations. Additionally, PCLS may serve as a link between different species

Influence of chemical and mechanical stress on precision-cut lung slices

Lungs are exposed to different forms of stress such as chemical substances, allergens or in the form of direct tissue injury. This study examined whether precision-cut lung slices are suitable as a model for studying different types of stress. We established the use of PCLS from sheep to study the response of airways and vessels to mediators. According to in vivo experiments sheep are thought to represent the human pathophysiology better than rodents. We therefore established the use of sheep PCLS and showed that methacholine, serotonin and endothelin-1 lead to a bronchoconstriction, while the response to leukotriene and thromboxane was rather weak. PCLS were also produced from preterm sheep and compared to adult sheep, which revealed a decreased reagibility to methacholine and serotonin in preterm sheep. Comparison of the bronchoconstriction of sheep PCLS with bronchoconstriction data from human PCLS revealed a less satisfactory accordance than the one seen in vivo. Although sheep PCLS may not represent the characteristics of human PCLS completely, the results presented in this thesis indicate that they are closer to human PCLS than PCLS from rodents. Another kind of stress that we examined was chemical stress. This study also aimed at studying the usefulness of PCLS to study respiratory allergens as required in the REACH (Regulation, Evaluation, Authorisation and restriction of CHemicals) process. Bronchoconstriction in PCLS as response to chemical allergen was investigated and compared to bronchoconstriction in vivo. For this purpose a well established sensitisation protocol with TMA, a respiratory allergen and DNCB, a dermal allergen, was used. The early allergic response and airway hyperresponsiveness in mouse PCLS was investigated and compared to data from in vivo invasive measurements. Acquired measurements were comparable suggesting PCLS as a reasonable alternative to invasive lung function measurements. Hence, stress-related bronchoconstriction to chemical allergens may be a suitable predictability for in vivo experiments. Several in vivo and cell culture models have been developed to study the pulmonary responses to mechanical stretch. While providing extremely useful information, these models do also suffer from limitations in being either too complex for detailed mechanical or mechanistic studies, or being devoid of the full complexity present in vivo (e.g. different cell types and interstitial matrix). Therefore, we developed a new model, based on the biaxial stretching of precision-cut lung slices. Single PCLS were mounted on a thin and flexible carrier membrane of PDMS in a bioreactor and the membrane was stretched by applying varying pressures under static conditions. A gene array revealed a general upregulation of immune response and wound healing genes by the slicing process. Stretch markers like amphiregulin were upregulated in PCLS by the slicing process. This upregulation was dependent on tyrosin kinases and the cytoskeleton, but could not be blocked sufficiently, which made it complicated to differentiate a stretch response from the basal increase. Distension of the PCLS was modelled via finite element simulation. According to this analysis, lung tissue was stretched by up to 38% in the latitudinal and by up to 44% in the longitudinal direction resulting in alveolar distension similar to what has been described in intact lungs. Lung slices were stretched dynamically with a frequency of 0.25 Hz for 4h, without causing cell injury. This indicates that the distension of PCLS in the bioreactor may not be suitable to study gene expression but allow the calculation of deformation and occurring forces of the PCLS during the stretching process. PCLS are a suitable model for studying different forms of stress in the lung and allows the investigation of different pathophysiological situations. Additionally, PCLS may serve as a link between different species

Comparison of Airway Responses in Sheep of Different Age in Precision-Cut Lung Slices (PCLS)

Animal models should display important characteristics of the human disease. Sheep have been considered particularly useful to study allergic airway responses to common natural antigens causing human asthma. A rationale of this study was to establish a model of ovine precision-cut lung slices (PCLS) for the in vitro measurement of airway responses in newborn and adult animals. We hypothesized that differences in airway reactivity in sheep are present at different ages.Lambs were delivered spontaneously at term (147d) and adult sheep lived till 18 months. Viability of PCLS was confirmed by the MTT-test. To study airway provocations cumulative concentration-response curves were performed with different allergic response mediators and biogenic amines. In addition, electric field stimulation, passive sensitization with house dust mite (HDM) and mast cells staining were evaluated.PCLS from sheep were viable for at least three days. PCLS of newborn and adult sheep responded equally strong to methacholine and endothelin-1. The responses to serotonin, leukotriene D4 and U46619 differed with age. No airway contraction was evoked by histamine, except after cimetidine pretreatment. In response to EFS, airways in PCLS from adult and newborn sheep strongly contracted and these contractions were atropine sensitive. Passive sensitization with HDM evoked a weak early allergic response in PCLS from adult and newborn sheep, which notably was prolonged in airways from adult sheep. Only few mast cells were found in the lungs of non-sensitized sheep at both ages.PCLS from sheep lungs represent a useful tool to study pharmacological airway responses for at least three days. Sheep seem well suited to study mechanisms of cholinergic airway contraction. The notable differences between newborn and adult sheep demonstrate the importance of age in such studies