Biomedical subjects

J Ellermann

Publications and source records attributed to J Ellermann.

17 recordsLinked to original sources

PubMed2006

Reduced cellular toxicity of a new silver-containing antimicrobial dressing and clinical performance in non-healing wounds.

Bacterial colonisation of wounds may delay wound healing. Modern silver-containing dressings are antimicrobial, yet cellular toxicity is a serious side-effect. We provide data for a newly formulated silver-containing ointment dressing, Atrauman Ag, for antimicrobial activity and cytotoxicity. Atrauman Ag effectively killed a panel of commensal skin as well as pathogenic bacterial strains while cytotoxicity for HaCaT keratinocytes was only around 10%. With these favourable in vitro tests, Atrauman Ag was analysed in 86 patients with traumatic and non-healing wounds of different aetiologies. The wound state was evaluated for 3 subsequent dressing changes. The slough score was reduced from 59.2 to 35.8%, granulation tissue increased from 27 to 40% and epithelialisation went up from 12.1 to 24%. We conclude that Atrauman Ag has a superior profile of antimicrobial activity over cellular toxicity and the low silver ion release rate may prevent interference with wound-healing mechanisms.

Aged↗

PubMed1997

Detection of 13C-labeled metabolites in the in vivo canine heart by B1 insensitive heteronuclear coherent polarization transfer and comparison of signal enhancement with NOE.

A recently developed adiabatic coherent polarization transfer enhancement technique [H. Merkle, H. Wei, M. Garwood, K. Uğurbil. J. Magn. Reson, 99, 480-494 (1992)] was employed to perform 13C spectroscopy in the intact canine heart in vivo during [2-13C]-acetate infusion into the left descending coronary artery, the results were compared with 13C spectra obtained with conventionally employed nuclear Overhauser enhancement. The results demonstrate that both methods can be performed by using surface coils to obtain in vivo 13C spectra and that coherent polarization transfer provides better enhancement than NOE for [2-13C]-acetate but not for short T2 compounds.

Acetates↗

PubMed1994

[Quantitative evaluation of myocardial perfusion with ultrafast magnetic resonance tomography].

With the advent of ultrafast Magnetic Resonance Imaging (MRI), it is now possible to produce images with high temporal resolution. This gives the opportunity to record the passage of the paramagnetic contrast material Gadolinium-DTPA through the tissue of the heart muscle, yielding information on regional myocardial perfusion. We assessed the accuracy of MRI to detect and quantify reductions in coronary flow secondary to stenosis in dogs and patients. Regional blood flow was measured in dogs by left atrial injection of microspheres labeled with different radioactive isotopes. Signal intensity (SI) curves were generated in regions of interest over the myocardium and the cavum of the left ventricle. A newly developed two-compartment model based on the indicator-dilution method was used for interpretation of the SI-curves. In an optimization process the free parameters of the model equation were fitted to the measured SI-curves. The following flow parameters were determined: model parameter Q*, time to peak intensity (T), maximum signal intensity (SImax) and mean transit time (MTT) as calculated from a gamma variate fit. Absolute blood flow values were calculated for the parameters MTT and Q* assuming that the intravascular volume represents 10% of the total myocardial tissue volume. Measurements were performed on a 1.5 T Magnetom SP (Siemens AG, Erlangen) using a Turbo Flash sequence (TR = 6.5 ms, TE = 3 ms, TI = 100 ms, Flip Winkel = 9 degrees). Endsystolic images (voxel size = 1.8, 2.7, 15 mm3) were taken with an 18-cm Helmholtz surface coil in the short-axis view. A Gd-DTPA bolus (0.05 mmol/kg) was injected into the left atrium of 3 anesthetized closed-chest dogs. From the myocardial SI-curves the different parameters of myocardial perfusion were compared with flow assessed by microsphere injection over a wide range of myocardial blood flows (from 0.04 ml/min/g to 7.6 ml/min/g). A third-order polynominal fit showed a good correlation for the parameter Q* and MTT, whereas T and SImax were found to have a poor correlation. The linear regression analysis for a limited range of < 2 ml/min/g showed a superior estimation of myocardial perfusion for the parameter Q* than MTT. Blood flow > 2 ml/min/g was significantly underestimated by the MRT-measurements, but the parameter Q* showed the smallest amount of the divergent changes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1993

Contrast-enhanced first pass myocardial perfusion imaging: correlation between myocardial blood flow in dogs at rest and during hyperemia.

The sensitivity of contrast-enhanced MR first pass perfusion imaging in detection and quantification of hypoperfused myocardium was evaluated using an instrumented, closed-chest dog model where graded regional hypoperfusion was induced by applying predetermined levels of stenosis to the left anterior descending artery (LAD). All measurements were performed at rest and under stress induced by dipyridamole (DIP). Myocardial perfusion was assessed both with MR and radiolabeled microspheres injected immediately before the administration of the MR contrast agent. Ultrafast MR imaging was performed using a Turbo FLASH sequence with a 180 degrees inversion prepulse. A Gd-DTPA bolus was injected into the left atrium and T1-weighted images were acquired with every heart beat. Signal intensity measured from the images in regions of the LAD and left circumflex (LCx) perfusion beds was plotted against time to generate signal intensity versus time curves (SI time curve). Various flow indices were derived according to the indicator dilution theory, and compared with and without volume correction due to vasodilation to the myocardial blood flow (MBF) calculated from radiolabeled microspheres. Correlation of the MR and MBF data demonstrated that different transmural and regional myocardial perfusion levels can be easily visualized in the perfusion images and accurately monitored by the SI time curves. Detection of the impairment of myocardial perfusion improved significantly after administration of DIP. The inverse mean transit time calculated from the SI time curve was found to yield a linear correlation to absolute MBF derived from the microsphere data. These results suggest that with intracardiac injections of exogenous contrast agent, myocardial perfusion can be assessed parametrically with first pass contrast enhanced ultrafast MRI.

Animals↗

PubMed1993

Imaging at high magnetic fields: initial experiences at 4 T.

This article reviews the preliminary experiences and the results obtained on the human brain at 4 T at the University of Minnesota. Anatomical and functional images are presented. Contrary to initial expectations and the early results, it is possible to obtain high-resolution images of the human brain with exquisite T1 contrast, delineating structures especially in the basal ganglia and thalamus, which were not observed clearly in 1.5-T images until now. These 4-T images are possible using a new approach that achieves maximal contrast for different T1 values at approximately the same repetition time and has built-in tolerance to variations in B1 magnitude. For functional images, the high field provides increased contribution from the venuoles and the capillary bed because the susceptibility-induced alterations in 1/T2* from these small-diameter vessels increase quadratically with the magnitude of the main field. Images obtained with short echo times at 4 T, and by implication at lower fields with correspondingly longer echo times, are expected to be dominated by contributions from large venous vessel or in-flow effects from the large arteries; such images are undesirable because of their poor spatial correspondence with actual sites of neuronal activity.

Brain↗

PubMed1992

Primary phase of hepatocytic autophagocytosis under ischaemic conditions.

Increased autophagocytosis in hepatocytes was found in response to conditions of ischaemia/hypoxia. Initial stages proved to be recordable. These were found to become manifest through the formation of phospholipid membrane structures, approximately 5 nm in width, coalescing in circular formations with vesicular extensions. They may further develop to form multilayer myelin structures. Enveloped cytoplasmic regions and organelles were unchanged, at the beginning, and subsequently coalesced typically into autophagolysosomes and autophagic vacuoles. Verification will be necessary to find out if these initial stages occur only in response to hypoxia or constitute a phenomenon of general validity.

Animals↗

PubMed1992

Ultrastructure and biochemistry of ischemic damages of small intestinal epithelial cells.

Ischemia (one hour) and following reperfusion (up to one hour) of the small intestine induce biochemical changes which are indices for the formation and action of oxygen free radicals and which occur predominantly during the reperfusion period. But the villi and the epithelial cells show different patterns of damage, occurring both at the end of the ischemic period and during the reperfusion period. Although the quantitative morphological changes are increased during the reperfusion in comparison with the ischemic phase the quality of the pattern of structural damage is the same in both periods of the experiment. This pattern of the damage includes: 1. the neighbourhood of groups of villi with total ischemic-lytic dissolution of the villi, of villi with damage of the epithelial cells at the tip and at the lateral area and of normal villi; 2. the different degree of structural damage of neighbouring epithelial cells within one villus whose cells are either of regular structural or damaged at subcellular organelles including the plasma membrane or of those being necrotically destroyed and on the way of release into the luminal space; 3. a differentiation of the structural changes of the microvilli and other organelles within single and neighbouring epithelial cells. The biochemical findings on purine nucleotide metabolism and on the formation of oxygen free radicals as "mean values" of a homogenate from a large group of cells cannot reflect the morphological-ultrastructural changes of single villi or even single epithelial cells. The possible reasons for the mosaicism of the morphological changes during ischemia and reperfusion are discussed.

Adenosine Triphosphate↗

PubMed1992

Electron microscopic and 31-P NMR studies of ischemic injured rat livers during preservation and reflow.

Ischemic injury induced during preservation and reperfusion contributes to post-operative failure in liver transplantation. Hepatic injury and recovery from preservation was studied in an isolated rat liver model reperfused with oxygenated erythrocytes. In order to correlate morphological and functional findings, 31-P nuclear magnetic resonance spectroscopy and electron microscopy were used to investigate metabolic and ultrastructural changes during 6 hours of reperfusion. Following cold preservation, EM's showed a primary sinusoidal cell injury, whereas the hepatocytes were well maintained. During reperfusion, hepatocytes displayed further damage. The simultaneous presence of vacuolarly degenerated mitochondria and mitochondria of increased activity was noted. 31-P NMP spectra demonstrated initially a partial ATP-recovery. The maximum level of 60% of the control ATP-value could not be further increased. EM and 31-P NMR indicate that the progressive injury to the liver is due to microcirculatory malfunction induced by an endothelial cell damage, followed by injured hepatocytes themselves, and the consequent intracellular energy crisis that is produced.

Animals↗

PubMed1991

Non-invasive 1H NMR spectroscopy of the rat brain in vivo using a short echo time STEAM localization sequence.

Fully localized proton NMR spectra were obtained from the brains of normal anaesthetized rats in vivo using stimulated echo (STEAM) spectroscopy sequences. Investigations were carried out at 2.35 T using a 40 cm bore magnet equipped with an actively shielded gradient system. Localized shimming resulted in water proton linewidths of 6.5-7.8 Hz permitting excellent water suppression. Thus, high-quality proton NMR spectra (TE = 20 ms) were acquired within measuring times of 1.5-6.4 min from 64 to 125 microL volumes-of-interest. The spectra show metabolite resonances due to N-acetyl aspartate, glutamate, creatine and phosphocreatine, cholines, taurine and inositols. The assignments of strongly spin-coupled resonances were confirmed by comparison with spectra from model solutions obtained under identical experimental conditions to those used in vivo. T1 relaxation times as well as relative metabolite concentrations were evaluated from spectra obtained for repetition times ranging from 900 to 6000 ms. Sequential acquisitions of 1.5 min spectra before, during and after killing the animals exhibited a rapid accumulation of lactate, but did not reveal significant changes in other metabolite levels for several hours post mortem.

Animals↗

PubMed1991

Effect of pentoxiphylline on the recovery of the preserved rat liver: 31P NMR and ultrastructural studies.

Hepatic failure often occurs following transplantation. This is primarily due to cold ischemia during preservation, warm ischemia during implantation, and finally reperfusion damage after transplantation and reflow. The possibility that this ischemia and reperfusion-induced damage can be reduced by preischemic application of a xanthine derivative (pentoxiphylline) was examined using 31P NMR spectroscopy and electron microscopy (EM) studies of bioenergetic and ultrastructural changes in oxygenated erythrocyte-perfused rat livers. EM illustrated that the hepatocytes and the mitochondria appeared to be relatively unaffected by cold preservation of the liver, whereas the endothelial cells lining the sinusoids became disrupted. After reperfusion, NMR spectroscopy showed a partial recovery of ATP levels, and EM indicated progressive mitochondrial injury. This progressive injury to the liver was probably due to endothelial cell damage which resulted in microcirculatory malfunction and free radical formation during reperfusion. Pentoxiphylline pretreated livers showed better preservation of the cell morphology and exhibited better ATP recovery than untreated livers. Pentoxiphylline is known to prevent the loss of precursors of ATP resynthesis by inhibiting AMP dephosphorylation during ischemia and improves the microcirculation via vasodilatory properties following ischemia. Thus, it is concluded that pentoxiphylline may ameliorate ischemia-induced cell damage during transplantation.

Adenosine Monophosphate↗

PubMed1991

Ultrastructure of the liver after hypoxia in the postnatal period.

Repeated phases of hypoxia (8 h daily for 2 to 5 days at pO2 11.33 kPa = 5.000 m in altitude) were induced to Sprague-Dawley rats in the postnatal period as well as up to the 64th day of age, and after different recovery phases the ultrastructure of hepatocytes was qualitatively and quantitatively analysed. Major results were as follows: 1. Increases in body and liver weights were delayed but were balanced off after 64 days. 2. Qualitative alterations are reversible spherical transformations of mitochondria, a degradation of lipids and a slight increase in autophagocytosis. 3. The quantitative mitochondrial parameters (volume density, number per unit area, average volume) were not even adjusted to control values after 64 days. Granular endoplasmic reticulum and ribosomes/polysomes were insignificantly reduced in comparison to control animals, structure and arrangement are regular. Lipids and glycogen were differently altered. 4. The findings of the hepatocytes after postnatal hypoxia were reversible, though the majority of parameters had not yet returned to normal after 2 months. An adaptation to repetitive hypoxic conditions is not provable.

Animals↗

PubMed1990

Two genetically distinct methyl-coenzyme M reductases in Methanobacterium thermoautotrophicum strain Marburg and delta H.

Methyl-coenzyme M reductase (MCR) catalyzes the methane-forming step in methanogenic archaebacteria. The reductase has been characterized in detail from Methanobacterium thermoautotrophicum strain Marburg and delta H, which grow on H2 and CO2 as energy source. During purification of the enzyme we have now discovered a second methyl-coenzyme M reductase (MCR II) in the two strains, which elutes at lower salt concentration from anion-exchange columns than the enzyme (MCR I) previously characterized. MCR II is similar to MCR I in that it is also composed of three different subunits alpha, beta, and gamma but distinct from MCR I in that the gamma subunit is 5 kDa smaller, as revealed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The N-terminal amino acid sequences of the alpha, beta, and gamma subunits of MCR II and MCR I were found to be different in several amino acid positions. The respective sequences showed, however, strong similarities indicating that MCR II was not derived from MCR I by limited proteolysis. The relative amounts of MCR I and MCR II present in the cells were affected by the growth conditions. When the cultures were supplied with sufficient H2 and and CO2 and the cells grew exponentially, essentially only MCR II was found. When growth was limited by the gas supply, MCR I predominated.

Amino Acid Sequence↗

PubMed1989

Methyl-coenzyme-M reductase from Methanobacterium thermoautotrophicum (strain Marburg). Purity, activity and novel inhibitors.

Methyl-coenzyme-M reductase from Methanobacterium thermoautotrophicum (strain Marburg) was purified to a stage where, besides the alpha, beta and gamma subunits, no additional polypeptides were detectable in the preparation. Under appropriate conditions the enzyme was found to catalyze the reduction of methyl-CoM with 7-mercaptoheptanoylthreonine phosphate (H-S-HTP) to CH4 at a specific rate of 2.5 mumol.min-1.mg protein-1. This finding contradicts a recent report that methyl-CoM reductase is only active when some contaminating proteins are present. The two polypeptides encoded by the open reading frames ORF1 and ORF2 of the methyl-CoM reductase transcription unit did not co-purify with the alpha, beta and gamma subunits. They were neither required nor did they stimulate the activity under the assay conditions. 3-Bromopropanesulfonate (apparent Ki = 0.05 microM) and 2-azidoethanesulfonate (apparent Ki = 1 microM) were found to be two new competitive inhibitors of methyl-CoM reductase. Both inhibitors were considerably more effective than the "classical" 2-bromoethanesulfonate (apparent Ki = 4 microM).

Cloning, Molecular↗

PubMed1988

The final step in methane formation. Investigations with highly purified methyl-CoM reductase (component C) from Methanobacterium thermoautotrophicum (strain Marburg).

Methyl-coenzyme M reductase (= component C) from Methanobacterium thermoautotrophicum (strain Marburg) was highly purified via anaerobic fast protein liquid chromatography on columns of Mono Q and Superose 6. The enzyme was found to catalyze the reduction of methylcoenzyme M (CH3-S-CoM) with N-7-mercaptoheptanoylthreonine phosphate (H-S-HTP = component B) to CH4. The mixed disulfide of H-S-CoM and H-S-HTP (CoM-S-S-HTP) was the other major product formed. The specific activity was up to 75 nmol min-1 mg protein-1. In the presence of dithiothreitol and of reduced corrinoids or titanium(III) citrate the specific rate of CH3-S-CoM reduction to CH4 with H-S-HTP increased to 0.5-2 mumol min-1 mg protein-1. Under these conditions the CoM-S-S-HTP formed from CH3-S-CoM and H-S-HTP was completely reduced to H-S-CoM and H-S-HTP. Methyl-CoM reductase was specific for H-S-HTP as electron donor. Neither N-6-mercaptohexanoylthreonine phosphate (H-S-HxoTP) nor N-8-mercaptooctanoylthreonine phosphate (H-S-OcoTP) nor any other thiol compound could substitute for H-S-HTP. On the contrary, H-S-HxoTP (apparent Ki = 0.1 microM) and H-S-OcoTP (apparent Ki = 15 microM) were found to be effective inhibitors of methyl-CoM reductase, inhibition being non-competitive with CH3-S-CoM and competitive with H-S-HTP.

Disulfides↗

PubMed1988

Effect of pentoxifylline on the ischemic rat kidney monitored by 31P NMR spectroscopy in vivo.

The effect of pentoxifylline on the recovery of renal energy metabolism after ischemia and reperfusion was studied by 31P nuclear magnetic resonance spectroscopy in vivo. Rat kidneys were exposed to 15, 30 and 60 min, respectively, of ischemia by clamping the arteria renalis. Pre-ischemic application of pentoxifylline improves the recovery of renal energy metabolism. The concentration of ATP was found to be higher in pentoxifylline pretreated kidneys than in controls after ischemia. The 5'-nucleotidase inhibiting activity of pentoxifylline is suggested to be the mechanism responsible for the protective effect of the drug. 31P NMR spectroscopy proved to be a powerful tool for continuous follow-up of drug effects on metabolic processes.

Adenine Nucleotides↗

PubMed1987

On the role of N-7-mercaptoheptanoyl-O-phospho-L-threonine (component B) in the enzymatic reduction of methyl-coenzyme M to methane.

The reduction of methyl-coenzyme M (CH3SCoM) to methane in methanogenic bacteria is dependent on component B (N-7-mercaptoheptanoyl-O-phospho-L-threonine, HSHTP). We report here that S-methyl-component B (N-7-(methylthio)heptanoyl-O-phospho-L-threonine, CH3SHTP) can substitute for neither CH3SCoM nor HSHTP in the methyl-CoM reductase reaction. Rather, CH3SHTP proved to be an inhibitor competitive with HSHTP (apparent Ki = 6 microM) and noncompetitive with CH3SCoM. These results make it very unlikely that HSHTP functions as a methyl group carrier. A role for HSHTP as direct electron donor for CH3SCoM reduction to CH4 is proposed.

Chromatography, Gas↗

PubMed1987

31P-NMR spectroscopy and ultrastructural studies on nephrotoxicity of cyclosporine A.

NMR-spectroscopy and electron microscopy were applied in order to find out whether nephrotoxic effects of cyclosporine A in combination with ischaemia on rat kidney are of significance for the energy metabolism of the organ. CSA was administered in daily doses of 15 mg/kg rat over 20 days. Use was made of the particular advantage of 31P-NMR-spectroscopy to follow up the dynamics of high-energy phosphate concentrations in the same tissue. Ultrastructural changes were observed in the region of the proximal tubule. Some mitochondria showed degenerative changes, others increased density of cristae. The total number of mitochondria was increased. This observation together with the coexistence of vacuolarly degenerated mitochondria and mitochondria with increased activity after CSA treatment is interpreted as expression of a compensatory mechanism that keeps constant the totality of high-energy phosphates despite damage to some mitochondria.

Adenine Nucleotides↗