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Biomedical subjects

H Weber

Publications and source records attributed to H Weber.

At least 19 recordsLinked to original sources
PubMed2006

KATP channel openers of the benzopyran type reach their binding site via the cytosol.

BACKGROUND AND PURPOSE: ATP-sensitive K+ (KATP) channels are composed of pore-forming subunits (Kir6.x) and of sulphonylurea receptors (SUR). Both sulphonylureas and K(ATP) channel openers act by binding to SUR. Sulphonylureas reach their binding site from the cytosol but it remains unknown whether this holds for openers too. EXPERIMENTAL APPROACH: A poorly membrane-permeant sulphonic acid derivative of the benzopyran-type opener, bimakalim, was synthesized, descyano-bimakalim-6-sulphonic acid (BMSA). Binding of BMSA and bimakalim was compared in membranes and intact cells expressing the Kir6.2/SUR2B channel and channel opening was compared in inside-out patches and whole cells. KEY RESULTS: In membranes, bimakalim and BMSA bound to Kir6.2/SUR2B with Ki values of 61 nM and 4.3 microM, showing that the negative charge decreased affinity 69-fold. In intact cells, however, binding of BMSA was much weaker than in membranes (75-fold) whereas that of bimakalim was unchanged. The Ki value of BMSA decreased with increasing incubation time. In inside-out patches, bimakalim (1 microM) and BMSA (100 microM) opened the Kir6.2/SUR2B channel closed by MgATP to a similar degree whereas in whole-cell experiments, only bimakalim was effective. CONCLUSIONS AND IMPLICATIONS: Despite its negative charge, BMSA is an effective channel opener. The fact that BMSA binds and acts more effectively when applied to the inner side of the cell membrane shows that benzopyran openers reach their binding site at SUR from the cytosol. This suggests that the binding pocket of SUR is only open on the cytoplasmic side.

Benzopyrans↗
PubMed2006

Influence of selenium treatment on the acute toxicity of dibutyltin dichloride in rats.

BACKGROUND/AIMS: Dibutyltin dichloride (DBTC) is an organotin compound used as a model for acute pancreatitis. The aim was to determine the effect of various doses of Na-selenite on the pathogenesis and course of DBTC-induced toxic changes in organs and serum of rats. METHODS: Experimental pancreatitis was induced by intravenous administration of 6 mg kg(-1) BW DBTC. Na-selenite was applied as a single intravenous dose of 5 mg kg(-1) BW and as daily oral dose of 1 mg kg(-1) BW. Malondialdehyde (MDA) was detected to observe the level of oxidative stress. The tin concentration in bile and urine shows the elimination of DBTC. Organ changes were indicated by serum parameters as well as histology. RESULTS: DBTC causes an acute pancreatitis, cholestasis and liver lesions determined by specific elevated serum parameters and several histological lesions. Na-selenite significantly diminished MDA concentration, lipase, bilirubin and transaminases as well as organ injuries compared to only DBTC-treated rats. CONCLUSIONS: The treatment with Na-selenite in the scope of DBTC-induced pancreatitis points to a reduced oxidative stress characterized by diminished MDA serum levels and a milder course of pancreatitis. The generation of DBTC-Na-selenite complexes could also be a mechanism to decrease the toxicity of organotin compounds like DBTC.

Alkaline Phosphatase↗
PubMed2006

Development and application of a specially designed heating system for temperature-programmed high-performance liquid chromatography using subcritical water as the mobile phase.

A specially designed heating system for temperature-programmed HPLC was developed based on experimental measurements of eluent temperature inside a stainless steel capillary using a very thin thermocouple. The heating system can be operated at temperatures up to 225 degrees C and consists of a preheating, a column heating and a cooling unit. Fast cycle times after a temperature gradient can be realized by an internal silicone oil bath which cools down the preheating and column heating unit. Long-term thermal stability of a polybutadiene-coated zirconium dioxide column has been evaluated using a tubular oven in which the column was placed. The packing material was stable after 50h of operation at 185 degrees C. A mixture containing four steroids was separated at ambient conditions using a mobile phase of 25% acetonitrile:75% deionized water and a mobile phase of pure deionized water at 185 degrees C using the specially designed heating system and the PBD column. Analysis time could be drastically reduced from 17 min at ambient conditions and a flow rate of 1 mL/min to only 1.2 min at 185 degrees C and a flow rate of 5 mL/min. At these extreme conditions, no thermal mismatch was observed and peaks were not distorted, thus underlining the performance of the developed heating system. Temperature programming was performed by separating cytostatic and antibiotic drugs with a temperature gradient using only water as the mobile phase. In contrast to an isocratic elution of this mixture at room temperature, overall analysis time could be reduced two-fold from 20 to 10 min.

Chromatography, High Pressure Liquid↗
PubMed2006

Ultrasonography of the temporal, periorbital and carotid arteries in the diagnosis of giant cell arteritis and its neuroophthalmological complications.

AIM: Evaluation of the diagnostic contribution of colour duplex sonography of the superficial temporal and the carotid arteries and Doppler sonography of the periorbital arteries by analysing the results in patients with giant cell arteritis with and without neuroophthalmological complications and patients with other diagnoses and neuroophthalmological complications. METHODS: In a case control study, ultrasonographic findings in patients with neuroophthalmological complications (25 giant cell arteritis, 23 non giant cell arteritis) were compared to those of 62 patients suffering from giant cell arteritis without neuroophthalmological complications. Concentric hypoechogenic mural thickening (a so-called halo) was considered as an ultrasonographic finding typical of giant cell arteritis. Absent or retrograde signals not corresponding to carotid occlusive disease were classified as Doppler sonographic findings typical of giant cell arteritis of the periorbital arteries. RESULTS: There are higher rates of abnormalities in Doppler sonography of the periorbital arteries as well as halos in combination with stenosis of the temporal arteries in patients with giant cell arteritis with neuroophthalmological complications. This suggests that in patients with giant cell arteritis and neuroophthalmological complications, the haemodynamic situation is more severely disturbed. Patients suffering from giant cell arteritis with and without neuroophthalmological complications had the same rate of temporal artery abnormalities on colour duplex sonography (72 vs. 71 %), whereas abnormalities in the periorbital arteries were clearly different (40 vs. 8 %). Only 1 patient with giant cell arteritis without neuroophthalmological complication had anomalies of the carotid arteries typical of giant cell arteritis. In patients with other diagnoses and neuroophthalmological complications, the rate of anomalies in temporal artery colour duplex sonography and Doppler sonography of the periorbital arteries was 9 % and 0 %. CONCLUSION: Colour duplex sonography of the superficial temporal and carotid arteries and Doppler sonograpy of the periorbital arteries are complementary methods and should be part of the evaluation of all patients suspected to suffer from giant cell arteritis.

Aged↗
PubMed2006

[Exercise training in cardiac patients: usefulness of the cardiopulmonary exercise test].

Exercise training is currently including in the treatment of coronary arterial disease patients, in patients with left ventricular dysfunction as well as in patients who underwent cardiac transplantation or cardiac surgery. However methods of prescribing exercise-training programs are difficult to determine and must be adapted for each patient Exercise test with gas analysis through the determination of anaerobic threshold may help to understand the physiopathological mechanism related to exercise limitation in these patients. Exercise test may help to precise exercise intensity during cardiac rehabilitation and may assess the benefits on exercise tolerance.

Exercise Test↗
PubMed2006

[Case report: equine arteritis virus (EAV) as the cause of abortion in alpacas?].

Here we report a case of a late abortion of a primiparous alpaca where genome fragments of the equine viral arteritis virus (EAV) could be detected in fetal tissues using reverse transcription polymerase chain reaction (RT-PCR). All five alpacas of the herd had virus neutralizing antibodies against EAV. EAV thus must be regarded as a potential agent for abortions in alpacas. Possible routes of introduction of the virus are discussed.

Abortion, Veterinary↗
PubMed2005

Calpain activation contributes to oxidative stress-induced pancreatic acinar cell injury.

Oxygen radicals have been implicated as mediators in the pathogenesis of pancreatic acinar cell necrosis. However, the sequence of events between the oxidative insult and cell damage remains unclear. In the current study, we investigated whether the Ca(2+)-regulated cytosolic cysteine protease calpain is activated by oxidative stress and contributes to oxidant-induced acinar cell damage. Isolated rat pancreatic acinar cells were exposed to hydrogen peroxide (H(2)O(2))-generated oxidative stress in the presence or absence of the Ca(2+) chelator 1,2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM) and different calpain inhibitors including benzyloxycarbonyl-valyl-phenylalanine methyl ester. Calpain activation was studied by fluorescence spectrophotometry and immunoblotting. Cell injury was assessed by lactate dehydrogenase (LDH) release and characterization of the cellular ultrastructure including fluorescence-labeled actin filaments. Exposure of acinar cells to H(2)O(2) provoked a time- and dose-dependent increase in calpain proteolytic activity involving the ubiquitous isoforms mu- and m-calpain. The activation of calpain reflected the time course of developing cytotoxicity as demonstrated by increased LDH release. Inhibition of oxidant-induced calpain activity by BAPTA-AM and various calpain inhibitors provoked a decline in oxidant-induced cell injury. In particular, changes in the actin filament organization characterized by an increase in the basolateral actin and by a detachment of actin from the cell membrane in the region of membrane blebs were clearly reduced. In summary, our findings suggest that acinar cell damage through oxidative stress requires activation of calpain and that the actin cytoskeleton belongs to the cellular targets of the protease. The results support the hypothesis that calpain activation may play a role in the development of acute pancreatitis.

Animals↗
PubMed2005

Effects of luteinizing hormone and human chorionic gonadotropin on corpus luteum cells in a spheroid cell culture system.

The human corpus luteum (CL) is a highly vascularized, temporarily active endocrine gland and consists mainly of granulosa cells (GCs), theca cells (TCs), and endothelial cells (ECs). Its cyclic growth and development takes place under the influence of gonadotropic hormones. If pregnancy does occur, human chorionic gonadotropin (hCG) takes over the function of luteinizing hormone (LH) and, in contrast to LH, extends the functional life span of the CL. In this study, we investigated the effects of hCG and LH in a spheroidal cell culture model of CL development. Our data indicate that GCs secrete factors under the control of hCG that increase sprout formation of EC-spheroids. We demonstrate that the most prominent of these factors is VEGF-A. Furthermore, we found that both LH and hCG decrease sprout formation of GC-spheroids. After forming EC-GC coculture spheroids and consequently bringing GCs and ECs in close contact, sprouting increased under the influence of hCG, however not under LH. These experiments provide evidence for an hCG dependent functional switch in the GCs after coming in contact with ECs. Moreover, it demonstrates the considerably different effects of hCG and LH on GCs although their signaling is transmitted via the same receptor.

Cells, Cultured↗
PubMed2005

[Vertebrobasilar ischemia as a complication of temporal arteritis. Results of a prospective, clinical, ultrasonographic study].

BACKGROUND: Cerebral symptoms in temporal arteritis (TA) may occur if large arteries are affected. To avoid progression of the disease, the immediate administration of adequate doses of steroids is mandatory. PURPOSE: The prevalence and severity of vertebrobasilar ischemia (VBI) and its relation to structural abnormalities of the vertebral arteries were studied. METHODS: Clinical and ultrasound data were analyzed in a hospital-based group of 91 patients who received the diagnosis of TA following standard criteria. RESULTS: In contrast to the occurrence of neuro-ophthalmological complications (27.5%), the rate of VBI was low (4.4%). TIA occurred in three cases and mild stroke in one. Ultrasound demonstrated severe occlusive disease of the extradural parts of the vertebrobasilar arteries consisting of hypoechogenic, concentric, mural thickening. The same was found in the superficial temporal arteries. CONCLUSIONS: In elderly patients presenting with VBI, TA affecting the vertebral arteries should be considered. In experienced hands, ultrasonography allows the atraumatic preliminary diagnosis of TA.

Aged↗
PubMed2005

Isolation and characterization of potentially human pathogenic, cytotoxin-producing aeromonas strains from retailed seafood in Berlin, Germany.

The presence of potentially human pathogenic strains of Aeromonas was investigated in 84 samples of seafood which were purchased from retail traders in Berlin, Germany in spring 2000. A total of 134 Aeromonas strains were isolated on selective [GSP agar and Aeromonas (Ryan) agar] and unselective (standard count agar and enterohaemolysin agar) media from 27 (32.1%) of the samples and were classified as Aeromonas hydrophila (67.9%), A. caviae (26.1%) and A. sobria (6.0%) by biotyping. Thirteen (48.1%) of the 27 positive samples contained more than one species of Aeromonas. Production of haemolysins on enterohaemolysin agar was found with 132 (98.5%) of the strains at 28 degrees C and with 130 strains (97.0%) at 37 degrees C growth temperature. Vero cytotoxins were produced by 99 (73.9%) of the strains when grown at 28 degrees C but only by 24 of the strains (17.9%) at 37 degrees C. The latter strains were identified as A. hydrophila (n = 22) and A. sobria (n = 2) which came from 17 (20.2%) samples of raw seafood and from ready-to-eat salted herring 'Matjes' products. Cytotoxin-encoding genes for aerolysin (aer) and haemolysin A (hlyA) were investigated by PCR. Aer and hlyA genes were detected in both, strains which produced toxins only at 28 degrees C and strains which produced toxins at 37 degrees C. Our data indicate that raw seafood and ready-to-eat fish products can harbour potential human pathogenic, cytotoxin producing Aeromonas strains.

Aeromonas↗
PubMed2004

The Tomato mosaic virus 30 kDa movement protein interacts differentially with the resistance genes Tm-2 and Tm-2(2).

In tomato plants ( Lycopersicon esculentum Mill.), the genes Tm-2 and Tm-2(2) confer resistance to Tomato mosaic virus (ToMV). Sequence analysis of ToMV strains able to break the Tm-2 or Tm-2(2) resistance revealed distinct amino acid exchanges in the viral 30 kDa protein, suggesting that the movement protein is recognized by both resistance genes to induce the plant defense reaction. To analyze the interactions between the ToMV movement protein and the Tm-2 and Tm-2(2) genes in detail, we generated transgenic tomato lines expressing various movement protein gene constructs. Crosses of the transgenic tomato lines with cultivars containing either the Tm-2 or the Tm-2(2) gene demonstrated that both genes are able to elicit a hypersensitive reaction in response to movement proteins from resistance inducing ToMV strains. However, the domains and the structural requirements for induction of the necrotic response by the ToMV movement protein are completely different for either resistance gene. In the context of the Tm-2 gene, the resistance determinant lies within the N-terminal 188 amino acids of the ToMV movement protein. Interaction of the 30 kDa protein with the Tm-2(2) gene requires two distinct domains localized at the C-terminus and in a different region of the protein, respectively.

Genes, Plant↗
PubMed2004

New natural products from the sponge-derived fungus Aspergillus niger.

Fractionation of the EtOAc extract of a static culture of Aspergillus niger isolated from the Mediterranean sponge Axinella damicornis yielded eight secondary metabolites, out of which seven compounds (2-8) proved to be new natural products, whereas one was identified as the known fungal pigment cycloleucomelone (1). The new compounds included the 3,3'-bicoumarin bicoumanigrin (2), the structurally unusual 4-benzyl-1H-pyridin-6-one derivatives aspernigrins A and B (3 and 4), and pyranonigrins A-D (5-8), the latter featuring a novel pyrano[3,2-b]pyrrole skeleton hitherto unprecedented in nature. All structures were elucidated on the basis of extensive one- and two-dimensional NMR spectroscopic studies ((1)H, (13)C, COSY, HMQC, HMBC, NOE difference spectra) and mass spectral analysis. For the two chiral molecules 4 and 5, the absolute configurations were established by quantum chemical calculations of their circular dichroism (CD) spectra. In each case, two independent methods, i.e., a molecular dynamics approach taking into consideration the molecular flexibility, and a conformational analysis followed by Boltzmann weighting of the single CD spectra calculated for the conformers thus obtained, led to identical results without the need of any empirical comparison of chiroptical data reported for reference compounds. Bicoumanigrin (2) showed moderate cytotoxicity against human cancer cell lines in vitro. In addition, aspernigrin B (4) was found to display a strong neuroprotective effect against glutamic acid.

Animals↗
PubMed2004

Seed development and differentiation: a role for metabolic regulation.

During seed growth, the filial organs, Vicia embryos and barley endosperm, differentiate into highly specialized storage tissues. Differentiation is evident on structural and morphological levels and is reflected by the spatial distribution of metabolites. In Vicia embryos, glucose is spatially correlated to mitotic activity whereas elongating and starch accumulating cells contain high levels of sucrose. Seed development is also regulated by phytohormones. In pea seeds, GA-deficiency stops seed growth before maturation. In Arabidopsis seeds, ABA regulates differentiation and inhibits cell division activity. The ABA pathway, in turn, is linked to sugar responses. In young Vicia embryos, invertases in maternal tissues control both concentration and composition of sugars. Embryonic and endospermal transfer cell formation represents an early differentiation step. Establishing an epidermis-localised sucrose uptake system renders the embryo independent from maternal control. cDNA array analysis in barley seeds revealed a massive transcriptional re-programming of gene expression during the transition stage, when gene clusters related to transport and energy metabolism are highly transcribed. Sucrose represents a signal for differentiation and up-regulates storage-associated gene expression. Sucrose signalling involves protein phosphorylation. Sucrose non-fermenting-1-related protein kinases are apparently induced in response to high cellular sucrose, and could act as mediators of sucrose-specific signals. Energy metabolism changes during seed development. In Vicia embryos metabolic responses upon hypoxia and low energy charge levels are characteristic for young undifferentiated stages when energy demand and respiration are high. During the transition stage, the embryo becomes adapted to low energy availability and metabolism becomes energetically more economic and tightly controlled. These adaptations are embedded in the embryo's differentiation program and coupled with photoheterotrophic metabolism. In Vicia cotyledons, ATP content increases in a development-dependent pattern and is associated with the greening process. The main role of seed photosynthesis is to increase internal O2 contents and to control biosynthetic fluxes by improving energy supply.

Carbohydrate Metabolism↗
PubMed2004

Analysis of nonylphenol polyethoxylates and their metabolites in water samples by high-performance liquid chromatography with electrospray mass spectrometry detection.

Evidence that some alkylphenol polyethoxylates (APEOs) breakdown products are estrogenic has intensified the interest over their environmental and human health effects. Different quantitative methods but one single preparation and extraction method for the analysis of nonylphenol polyethoxylates (NPEOs) and their metabolites in water samples using solid-phase extraction (SPE) and high-performance liquid chromatography (HPLC) with electrospray mass spectrometry detection (ESI-MS), are described. Quantification limits range about the low ng/l for the enrichment of 500 ml water samples and mean recoveries of 70% are achieved. These methods were subsequently applied to water samples coming from Austrian treatment plants.

Austria↗
PubMed2003

[Present state of ultrasonographic diagnosis of temporal arteritis. Results of a prospective study].

Temporal arteritis (TA) is a treatable systemic vasculitis with particular affinity for the temporal and orbital arteries. In a prospective study of 115 patients, we evaluated the diagnostic contribution of duplex sonography of the superficial temporal (STA), okzipital (OCCA), and carotid arteries and Doppler sonography of the supratrochlear artery (DSASTR) in patients suspected of having TA. Forty-seven patients had TA: in the STA, periarterial hypoechogenic tissue (halo) was found in 60% (OCCA 48%) and halo and stenosis in 19% (OCCA 15%) of the TA patients and in 4% of patients with other diseases. The DSASTR was abnormal in 13% of the TA patients. Arteriosclerotic carotid disease was found in 72%, >50% stenosis in 13% of the TA patients. Duplex sonography of the STA reached a diagnostic sensitivity/specificity of 78/96% compared to diagnosis and 91/82% compared to histology. In the STA/OCCA, duplex sonography is a helpful new atraumatic method for the diagnosis of TA, and DSASTR is helpful in detecting TA of the orbital arteries.

Aged↗