Biomedical subjects

S Häussermann

Publications and source records attributed to S Häussermann.

6 recordsLinked to original sources

PubMed2006

[Comparison of unspecific bronchial provocation during controlled and spontaneous inhalation].

Using controlled breathing patterns during inhalation of drugs is characterized by a high dose reproducibility which may be of advantage for bronchial provocation testing. In this study 30 healthy subjects with an anamnesis of atopy underwent in a randomized cross-over design bronchial provocation testing with methacholine either with the Viasys-Jäger-APS system or with controlled inhalations (AKITA-System) (controlled inhalation volume and flow). Measured was the frequency of positive test results. Positive test results were defined by a 20 % decline of FEV (1) or a 100 % increase of specific airway resistance (sRaw). There were no significant differences in the prevalence of positive test results obtained with both techniques: APS-FEV (1) : 8, AKITA-FEV (1) : 9; APS-sRaw: 18, AKITA-sRaw: 17. More subjects showed a 100 % increase of sRaw as compared to a 20 % decrease of FEV (1), which may be interesting in order to understand differences in the diagnostic information given by both parameters. However, there were some discrepancies: only in 25 of 30 cases (sRaw: 21 of 30 cases) the results (positive or negative) agreed between both techniques. Although the two techniques for bronchial provocation test showed some discrepancies, these data suggest that controlled inhalations may be an alternative to the APS-system.

Bronchial Provocation Tests↗

PubMed2005

Optimum peripheral drug deposition in patients with cystic fibrosis.

In order to identify the optimum particle size and breathing pattern for high peripheral deposition of inhaled drugs in patients with cystic fibrosis, regional deposition in these patients was studied systematically as a function of particle size, inhalation volume and flow rate. Regional deposition was assessed using the single-breath regional deposition technique in which the concentration profile of inhaled and exhaled non-radioactive, monodisperse test particles is analyzed. Using this technique particle deposition within the functional dead space volume and peripherally can be assessed. Regional deposition was measured in 12 patients with cystic fibrosis using 2, 3, 4, and 5.5 microm particles, inhalation volumes of 500, 1000, 1500, and 2000 cm(3), and inhalation flow rates of 100, 250, 500, and 750 cm(3)/sec. Peripheral deposition was highest when 2-3-microm particles were inhaled with air-flow rates of 250-500 cm(3)/sec. With these parameters peripheral deposition increased with increasing inhalation volume and reached values of about 60% of the total drug inhaled. It has been shown that high peripheral drug deposition can be achieved in patients with CF when inhalations are performed using an optimized combination of particle size and breathing pattern.

Administration, Inhalation↗

PubMed2000

Biphasic effect of protein kinase C activators on spontaneous and glucocorticoid-induced apoptosis in primary mouse thymocytes.

Spontaneous and glucocorticoid (fluocinolone acetonide, FA)-induced apoptosis of primary mouse thymocytes was inhibited by protein kinase C (PKC) activators such as bryostatin-1 and phorbol ester 12-O-tetradecanoyl-phorbol-13 acetate (TPA) within the first 2-4 h of incubation but was enhanced upon prolonged treatment. Only the anti-apoptotic but not the pro-apoptotic effect of TPA was completely suppressed by the PKC inhibitor Goe 6983 and moderately inhibited by Goe 6976. Immunoblot analysis revealed distinct PKC alpha, beta, delta, eta, theta, mu and zeta signals, a very faint PKCepsilon and no PKCgamma signal. Upon prolonged TPA treatment all PKC isoenzymes became downregulated, albeit at different rates (PKCdelta>alpha>mu>beta,theta>>eta,zeta). No significant generation of caspase-derived catalytic PKC fragments, as found to be produced upon induction of apoptosis and to be pro-apoptotic in other systems, was observed in FA- or TPA-treated thymocytes. It is concluded that the early anti-apoptotic effect of TPA depends on the activation of n-type PKC isoenzymes, whereas stimulation of spontaneous and FA-induced apoptosis by TPA ensues, at least partially, from a downregulation (or inactivation) of anti-apoptotic PKC species, i.e. in primary thymocytes PKC activation is primarily involved in a negative regulation of apoptosis.

Animals↗

PubMed2000

A system to reproduce human breathing patterns: its development and validation.

Studies of aerosol deposition in models of the human respiratory tract play a significant role in developing our understanding of drug delivery by inhalation and particle retention in the lungs during exposure to polluted environments. To use replica casts of human airways and compare the results with in vivo data, a device is required to simulate human breathing. The objective of this study was to simulate human breathing for nasal casts. Breathing through the nose is normally limited to about 50 L/min. Therefore, a system was built to simulate human breathing patterns as well as artificial ones up to this flow rate. The system consists of a reciprocating piston in a cylinder, which is displaced by a synchronous motor via a linear actuator. The desired signal to drive the motor is given in real time by purpose-written software. The rotation and position of the motor are controlled by an electronic position control unit. The validation of the system shows that it simulates breathing up to 50 L/min closely even for complex waveforms. At breathing rates above 50 L/min, a slight difference is apparent between the desired breathing pattern and the simulated one. The breathing simulator has been shown to be a reliable tool for reproducing a wide variety of breathing patterns.

Aerosols↗

PubMed1999

Proteolytic cleavage of protein kinase Cmu upon induction of apoptosis in U937 cells.

Treatment of U937 cells with various apoptosis-inducing agents, such as TNFalpha and beta-D-arabinofuranosylcytosine (ara-C) alone or in combination with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), bryostatin 1 or cycloheximide, causes proteolytic cleavage of protein kinase Cmu (PKCmu) between the regulatory and catalytic domain, generating a 62 kDa catalytic fragment of the kinase. The formation of this fragment is effectively suppressed by the caspase-3 inhibitor Z-DEVD-FMK. In accordance with these in vivo data, treatment of recombinant PKCmu with caspase-3 in vitro results also in the generation of a 62 kDa fragment (p62). Treatment of several aspartic acid to alanine mutants of PKCmu with caspase-3 resulted in an unexpected finding. PKCmu is not cleaved at one of the typical cleavage sites containing the motif DXXD but at the atypical site CQND378/S379. The respective fragment (amino acids 379-912) was expressed in bacteria as a GST fusion protein (GST-p62) and partially purified. In contrast to the intact kinase, the fragment does not respond to the activating cofactors TPA and phosphatidylserine and is thus unable to phosphorylate substrates effectively.

Apoptosis↗

PubMed1998

Comparison of DNA adduct levels associated with oxidative stress in human pancreas.

DNA adducts associated with oxidative stress are believed to involve the formation of endogenous reactive species generated by oxidative damage and lipid peroxidation. Although these adducts have been reported in several human tissues by different laboratories, a comparison of the levels of these adducts in the same tissue samples has not been carried out. In this study, we isolated DNA from the pancreas of 15 smokers and 15 non-smokers, and measured the levels of 1,N6-etheno(2'-deoxy)guanosine (edA), 3, N4-etheno(2'-deoxy)cytidine (edC), 8-oxo-2'-deoxyguanosine (8-oxo-dG), and pyrimido[1,2-alpha]purin-10(3H)-one (m1G). Using the same DNA, the glutathione S-transferase (GST) M1, GSTT1, and NAD(P)H quinone reductase-1 (NQO1) genotypes were determined in order to assess the role of their gene products in modulating adduct levels through their involvement in detoxification of lipid peroxidation products and redox cycling, respectively. The highest adduct levels observed were for m1G, followed by 8-oxo-dG, edA, and edC, but there were no differences in adduct levels between smokers and non-smokers and no correlation with the age, sex or body mass index of the subject. Moreover, there was no correlation in adduct levels between edA and eC, or between edA or edC and m1G or 8-oxo-dG. However, there was a significant correlation (r=0.76; p<0.01) between the levels of 8-oxo-dG and m1G in human pancreas DNA. Neither GSTM1 nor NQO1 genotypes were associated with differences in any of the adduct levels. Although the sample set was limited, the data suggest that endogenous DNA adduct formation in human pancreas is not clearly derived from cigarette smoking or from (NQO1)-mediated redox cycling. Further, it appears that neither GSTM1 nor GSTT1 appreciably protects against endogenous adduct formation. Together with the lack of correlation between m1G and edA or edC, these data indicate that the malondialdehyde derived from lipid peroxidation may not contribute significantly to m1G adduct formation. On the other hand, the apparent correlation between m1G and 8-oxo-dG and their comparable high levels are consistent with the hypothesis that m1G is formed primarily by reaction of DNA with a base propenal, which, like 8-oxo-dG, is thought to be derived from hydroxyl radical attack on the DNA.

8-Hydroxy-2'-Deoxyguanosine↗