Biomedical subjects

Rainer Müller

Publications and source records attributed to Rainer Müller.

17 recordsLinked to original sources

PubMed2006

New anisotropic ceramic membranes from chemically fixed dissipative structures.

The formation of highly ordered capillaries in alginate gels is due to a dissipative convective process resulting from opposing diffusion gradients and friction. Ceramic membranes with an anisotropic pore structure have been gained from this self-organization process by incorporating inorganic particles into the gel matrix, followed by subsequent ion exchange, drying, and sintering. The aim of this study was to overcome existing preparative deficiencies and to optimize the capillary structure and surface properties with respect to specific technical applications. A new method of ion exchange was introduced, and the sintering program was improved to obtain reproducible product quality. By controlling the parameters of the self-organization reaction, the overall porosity of the ceramic membranes was adjusted to selected values between 60% and 83%. Capillary sizes were varied between 8 and 50 microm. Further modification by metal plating, particle coating, or hydrophobization led to an extended spectrum of applicability of the ceramic membranes. For the first time, anisotropic capillary ceramics have been characterized in detail as to their technical use as catalyst supports, filter membranes, or other solid-fluid and solid-gas contact processes.

Journal Article↗

PubMed2006

Chemiluminescence-based detection and comparison of protein amounts adsorbed on differently modified silica surfaces.

The biological consequences of protein adsorption on biomaterial surfaces are considered to be of utmost importance for their biocompatibility. A new method based on amino group-labeling coupled to a chemiluminescence reaction for direct determination of proteins adsorbed on material surfaces was employed. This method was used to explore the effects of surface chemistry and surface roughness on protein adsorption in a silicon oxide model system. Corundum sandblasting was applied to silicon wafers to create roughened surfaces while immobilization of fluorocarbon-, hydrocarbon-, and poly(ethylene glycol)-containing silanes produced surfaces of varying wettability. The adsorption behavior of two complex body fluids, human serum and saliva, and of two purified components, human serum albumin and fibronectin, was strongly influenced by the surface parameters. A general tendency to higher amounts of adsorbed protein was found on roughened surfaces and modification with poly(ethylene glycol) or with fluorocarbon moieties reduced protein adsorption. The values obtained with the new method could be confirmed by a colorimetric determination of protein amounts adsorbed on identically modified silica beads and were in accordance with those previously reported utilizing established methods for protein quantification. The presented method, which was methodically simple to perform and allowed the simultaneous measurement of a large number of samples, may be of future value for high-throughput surveying of the protein adsorption characteristics of biomaterials.

Adsorption↗

PubMed2006

A prospective study on radiation-induced changes in hearing function.

PURPOSE: To quantitate changes in hearing function after radiotherapy for head-and-neck tumors. METHODS AND MATERIALS: At the Department of Radiotherapy and Radiation Oncology, 32 patients were irradiated for head-and-neck tumors. Three-dimensional treatment planning was applied. Total tumor doses were 30.0-77.6 Gy, local doses to the inner ear (n = 64) ranged from 1.7 to 64.3 Gy. Audiometry was performed before the onset of radiotherapy (RT), at a tumor dose of 40 Gy or at the end of palliative treatment, at the end of curative RT, and 2-6 months post-RT. Assays applied were frequency-specific threshold measurements for air and bone conduction, measurements according to Weber and Rinne, tympanometry and assessment of the stapedius reflex. RESULTS: Age and prior disease significantly decreased, whereas previous or concurrent alcohol consumption significantly increased hearing ability. A significant reduction in hearing ability during RT was found for high frequencies (at 40 Gy) and low frequencies (at end of RT), which persisted after RT. No differences were observed for air or bone conduction. None of the other assays displayed time- or dose-dependent changes. Dose-effect analyses revealed an ED50 (dose at which a 50% incidence is expected) for significant changes in hearing thresholds (15 dB) in the range of 20-25 Gy, with large confidence limits. CONCLUSIONS: Radiation effects on hearing ability were confined to threshold audiogram values, which started during the treatment without reversibility during 6 months postradiotherapy.

Adult↗

PubMed2006

Influence of surface pretreatment of titanium- and cobalt-based biomaterials on covalent immobilization of fibrillar collagen.

Collagen type-I is a major component of the extracellular matrix of most tissues and it is increasingly utilized for surface engineering of biomaterials to accelerate receptor-mediated cell adhesion. In the present study, coatings with layers of fibrillar type-I collagen were prepared on titanium, titanium alloy, and cobalt alloy to improve initial osteoblast adhesion and implant-tissue integration. To suppress the quick in vivo degradation rate of collagen the deposited layers were covalently immobilized at the metal surfaces as well as chemically cross-linked. The application of different oxidation techniques to the metallic substrates resulted in surfaces with varying hydroxyl group contents, which directly influenced the amount of immobilized silane coupling agents. It was found that a high density of surface-bound coupling agents increased the stability of the covalently linked collagen layers. After coating of metallic biomaterials with a cross-linked collagen layer, an improved cellular response of human osteoblast-like cells (MG-63) in vitro could be recognized.

Biocompatible Materials↗

PubMed2006

The promotion of oriented axonal regrowth in the injured spinal cord by alginate-based anisotropic capillary hydrogels.

Appropriate target reinnervation and functional recovery after spinal cord injury depend on longitudinally directed regrowth of transected axons. To assess the capacity to promote directed axon regeneration, alginate-based highly anisotropic capillary hydrogels (ACH) were introduced into an axon outgrowth assay in vitro and adult rat spinal cord lesions in vivo. In an entorhino-hippocampal slice culture model, alginate-based scaffolds elicit highly oriented linear axon regrowth and appropriate target neuron reinnervation. Coating of alginate-based ACH with the extracellular matrix components collagen, fibronectin, poly L-ornithine and laminin did not alter the axon regrowth response as compared to uncoated alginate-based ACH. After implantation into acute cervical spinal cord lesions in adult rats, alginate-based ACH integrate into the spinal cord parenchyma without major inflammatory responses, maintain their anisotropic structure and in parallel to findings in vitro induce directed axon regeneration across the artificial scaffold. Furthermore, adult neural progenitor cells (NPC), which have been shown to promote cell-contact-mediated axon regeneration, can be seeded into alginate-based ACH as a prerequisite to further improve the regenerative capacity of these artificial growth supportive matrices. Thus, alginate-based ACH represent a promising strategy to induce directed nerve regrowth following spinal cord injury.

Alginates↗

PubMed2006

Influence of polysaccharide coating on the interactions of nanoparticles with biological systems.

Since dextran (DEX) grafted with poly(epsilon-caprolacton) (PCL) side chains (PCL-DEX) copolymers could form nanoparticles with a well defined core-shell structure, we investigated the ability of the DEX coating to modify the interactions with the biological media. We first studied the influence of the DEX coating on the phagocytosis of the nanoparticles by human TPH-1 and J774 murine macrophage-like cell lines. Then, the activation of the complement system (CH50 measurement) at the surface of the particles and the adsorption of plasma proteins (2D-PAGE) were investigated, too. It was found that the modification of the surface with DEX significantly reduced the cytotoxicity towards J774 macrophages: the IC50 was increased from 10 to 600 microg/ml. However, the DEX coating could activate complement, probably due to a loop-like conformation of DEX similar to that of cross-linked DEX in Sephadex (a strong complement activator). In addition, depending on whether the DEX loops were large or compact, preferential adsorption, apolipoproteins or immunoglobulins, was observed.

Adsorption↗

PubMed2006

Pharmacologic modulation of skeletal muscle metabolism: a microdialysis study.

Microdialysis is a valuable tool to measure tissue responses. We hypothesized that skeletal muscle metabolism can be modulated by microdialysis applied drugs which alter cytosolic calcium concentration. With approval of the local animal care committee, the hind limbs of sacrificed male Sprague Dawley rats were perfused either with Ringer's solution or with dantrolene 1 microM at 30 ml hr(-1) and 21 degrees. Microdialysis probes in both hind limbs were perfused at 1 microl min(-1) either with sorbitol 80 mM, calcium 20 mM, 40 mM, 80 mM, caffeine 40 mM, 80 mM, and halothane 10 vol% respectively, and at the contralateral adductor muscle with Ringer as control. Lactate was measured spectrophotometrically in the dialysate at 15 min. intervals. Lactate levels as measured by intramuscular microdialysis were not influenced by intramuscular application of sorbitol 80 mM compared to control measurements with Ringer's solution. Local application of calcium 20 mM, 40 mM, 80 mM, caffeine 40 mM, 80 mM, and halothane 10 vol% via microdialysis increased lactate concentrations, while organ perfusion by dantrolene 1 microM reduced the caffeine-induced lactate increase. Modulation of intramuscular lactate metabolism by exogenous compounds via microdialysis probes generates new insights in skeletal muscle metabolism.

Animals↗

PubMed2006

The dose-response relationship and regional distribution of lactate after intramuscular injection of halothane and caffeine in malignant hyperthermia-susceptible pigs.

We hypothesized that IM halothane and caffeine injection increases local lactate concentration dose-dependently in malignant hyperthermia-susceptible (MHS) and nonsusceptible (MHN) pigs and that the hypermetabolic reaction measured by regional distribution of lactate and carbon dioxide is limited to a small muscle volume. Microdialysis probes were placed in the hindlimbs of 7 MHS and 7 MHN pigs and perfused with Ringer's solution. After equilibration, boluses of increasing halothane and caffeine concentrations were injected. For the second hypothesis regarding regional distribution, microdialysis probes were positioned in 7 MHS and 6 MHN pigs at the injection site for halothane and caffeine and at a distance of 10 mm and 25 mm. Lactate was measured in the dialysate by spectrophotometry. In addition, PCO2 was measured in the halothane experiments. Halothane and caffeine increased IM lactate dose-dependently in MHS pigs significantly more than in MHN pigs. Lactate and PCO2 were increased only at the injection site but not at 10 mm and 25 mm distance. MH susceptibility leads to a leftward shift of the dose-response curve for IM lactate after local injection of halothane and caffeine. The increase of lactate and carbon dioxide levels after local MH trigger injection is limited to a small area around the probe.

Anesthetics, Inhalation↗

PubMed2005

Inhibition of sarcoplasmic Ca2+-ATPase increases caffeine- and halothane-induced contractures in muscle bundles of malignant hyperthermia susceptible and healthy individuals.

BACKGROUND: Malignant hyperthermia (MH) is triggered by halogenated anaesthetics and depolarising muscle relaxants, leading to an uncontrolled hypermetabolic state of skeletal muscle. An uncontrolled sarcoplasmic Ca2+ release is mediated via the ryanodine receptor. A compensatory mechanism of increased sarcoplasmic Ca2+-ATPase activity was described in pigs and in transfected cell lines. We hypothesized that inhibition of Ca2+ reuptake via the sarcoplasmic Ca2+-ATPase (SERCA) enhances halothane- and caffeine-induced muscle contractures in MH susceptible more than in non-susceptible skeletal muscle. METHODS: With informed consent, surplus muscle bundles of 7 MHS (susceptible), 7 MHE (equivocal) and 16 MHN (non-susceptible) classified patients were mounted to an isometric force transducer, electrically stimulated, preloaded and equilibrated. Following 15 min incubation with cyclopiazonic acid (CPA) 25 microM, the European MH standard in-vitro-contracture test protocol with caffeine (0.5; 1; 1.5; 2; 3; 4 mM) and halothane (0.11; 0.22; 0.44; 0.66 mM) was performed. Data as median and quartiles; Friedman- and Wilcoxon-test for differences with and without CPA; p < 0.05. RESULTS: Initial length, weight, maximum twitch height, predrug resting tension and predrug twitch height of muscle bundles did not differ between groups. CPA increased halothane- and caffeine-induced contractures significantly. This increase was more pronounced in MHS and MHE than in MHN muscle bundles. CONCLUSION: Inhibition of the SERCA activity by CPA enhances halothane- and caffeine-induced contractures especially in MHS and MHE skeletal muscle and may help for the diagnostic assignment of MH susceptibility. The status of SERCA activity may play a significant but so far unknown role in the genesis of malignant hyperthermia.

Journal Article↗

PubMed2005

Interactions of blood proteins with poly(isobutylcyanoacrylate) nanoparticles decorated with a polysaccharidic brush.

The aim of this work was to examine the in vitro interactions of core-shell poly(isobutylcyanoacrylate)-polysaccharide nanoparticles (NP) with blood proteins. The particles were prepared by initiating the emulsion polymerization of isobutylcyanoacrylate (IBCA) in the presence of dextran 71 or 15 kDa, heparin, a blend of dextran 71 and heparin, or dextran sulphate in aqueous medium at pH 1. The mechanisms of polymerisation were redox radical (Rad) or anionic (An), resulting in differences in the spatial arrangement of the polysaccharide chains at the NP surface, i.e. "loops" and "trains" by anionic polymerization, "brush" by radical polymerization. Surface composition of NPs was determined by X-ray photo-electron spectroscopy (XPS) and surface charge by zeta potential measurements. In the presence of citrated blood plasma, efficacy of the steric repulsive effect of the NP dextran shell towards protein adsorption decreased in the order: Dex71-Rad > Dex15-Rad > Dex71-AnDex15-An. Dextran-coated NPs adsorbed ApoA-I and fibrinogen from plasma. Concerning activation of complement in serum, the effect was sharp: Dex71-Rad was a very low activator whereas Dex15-An, Dex15-Rad and Dex71-An were strong activators. In citrated plasma, the steric repulsive effects of Hep-Rad and Dex-Hep-Rad NPs were similar to Dex71-An, and Dex-Sulph-Rad NPs adsorbed twice more proteins than Hep-Rad. Hep-Rad, Dex-Hep-Rad and Dex-Sulph-Rad NPs adsorbed IgG and fibrinogen. Complement was not activated in serum in the presence of Hep-Rad and Dex-Hep-Rad and a slight adsorption of C3 was noted. C3 was completely adsorbed on Dex-Sulph-Rad. The exquisite sensitivity of blood proteins to differences in the nature and outermost structure of the polysaccharides-coated NPs is highlighted by the present results.

Adsorption↗

PubMed2005

Surface engineering of stainless steel materials by covalent collagen immobilization to improve implant biocompatibility.

It was shown recently that the deposition of thin films of tantalum and tantalum oxide enhanced the long-term biocompatibility of stainless steel biomaterials due to an increase in their corrosion resistance. In this study, we used this tantalum oxide coating as a basis for covalent immobilization of a collagen layer, which should result in a further improvement of implant tissue integration. Because of the high degradation rate of natural collagen in vivo, covalent immobilization as well as carbodiimide induced cross-linking of the protein was performed. It was found that the combination of the silane-coupling agent aminopropyl triethoxysilane and the linker molecule N,N'-disulphosuccinimidyl suberate was a very effective system for collagen immobilizing. Mechanical and enzymatic stability testing revealed a higher stability of covalent bound collagen layers compared to physically adsorbed collagen layers. The biological response induced by the surface modifications was evaluated by in vitro cell culture with human mesenchymal stem cells as well as by in vivo subcutaneous implantation into nude mice. The presence of collagen clearly improved the cytocompatibility of the stainless steel implants which, nevertheless, significantly depended on the cross-linking degree of the collagen layer.

Adsorption↗

PubMed2005

Fatal Clostridium tertium septicemia in a nonneutropenic patient.

Clostridium tertium septicemia is a rare condition that predominantly occurs in neutropenic patients with concomitant abdominal disease. We report the fatal case of a nonneutropenic, 51-year-old patient with mechanical ileus and post-operative C. tertium septicemia, resulting in widespread pathology with multi-organ failure. As C. tertium is aerotolerant, often gram-variable and mostly resistant to broad-spectrum cephalosporins, differentiation is difficult and empirical therapeutic strategies may fail.

Anti-Bacterial Agents↗

PubMed2004

Protecting nanoscaled non-oxidic particles from oxygen uptake by coating with nitrogen-containing surfactants.

To suppress the reactivity of nanoscaled non-oxidic powders of titanium nitride (TiN) and silicon carbonitride (SiCN) against hydrolysis and oxidation, chemical surface modification with nitrogen-containing surfactants was investigated. Among these surfactants, long-chain primary amines, ethylenediamines, guanidines, nitriles, isocyanates, and succinimides were examined. Thermogravimetry, elemental analysis, and behavior against the water-vapor adsorption of the modified particles were used as methods to estimate the protective capacity of the organic coating material. The best results were obtained by using the long-chain amines and octadecylisocyanate, which were indicated by a significant shift of the powder oxidation toward the higher temperatures and an increase of the particle hydrophobicity. A long-chain succinimide was found to be the most effective in dispersing nanoscaled TiN in organic media. Preparation of a stable aqueous dispersion without significant changes in the elemental composition of the powder was achieved by the application of an ionic surfactant to the surface-modified particles.

Hydrolysis↗

PubMed2003

Suitability of cefotiam and cefuroxime axetil for the perioperative short-term prophylaxis in tonsillectomy patients.

The efficacy of the perioperative short-term prophylaxis with cefotiam (CAS 66309-69-1) and cefuroxime axetil (CAS 64544-07-6) was analysed by the assessment of the pharmacological kinetics in the serum and the tonsil tissue in 50 patients with recurrent tonsillitis. Twenty-four patients received 1 g cefotiam by the intravenous route 30 min to 4 h before the tonsillectomy, and 26 patients received 250 mg cefuroxime axetil orally 1 to 6 h before the tonsillectomy. Bactericidal serum levels were reached for cefotiam up to 4 h after intravenous application and for cefuroxime axetil up to 3 h after oral application. In the tissue of the tonsil there were proved levels which were definitely above the MIC 90 (MIC = minimum inhibitory concentration) known for the clinically relevant germs for cefotiam after 30 min up to 2 h, for cefuroxime axetil after only 2 h. Considering the distribution areas, the capacity of the protein binding and the microbiological measuring methods, one can expect an efficient antibiotic coverage after an intravenous one-shot bolus injection of 1 g cefotiam from 30 min to 4 h and after oral application of 250 mg cefuroxime axetil on an empty stomach from 1 to 6 h. Because of the short duration of a tonsillectomy and the serum and tonsil tissue kinetics cefotiam and cefuroxime axetil are suitable for the perioperative antibiotic prophylaxis of high-risk patients.

Adolescent↗

PubMed2002

Influence of surface charge density on protein adsorption on polymeric nanoparticles: analysis by two-dimensional electrophoresis.

Plasma protein adsorption is regarded as a key factor for the in vivo organ distribution of intravenously administered colloidal drug carriers, and strongly depends on their surface characteristics, e.g. surface hydrophobicity or charge. A range of polymeric nanoparticles with a steep variation of the surface charge density was synthesized as model drug carriers. Physicochemical parameters, i.e. particle size, surface charge density, hydrophobicity and surface topography were determined. Two-dimensional electrophoresis (2-DE) was employed for determination of particle interactions with human plasma proteins. Increasing surface charge density showed an increase in plasma protein adsorption, but did not show differences in the detected protein species. For the first time it was possible to show plasma protein adsorption patterns on a range of nanoparticles with variation of only one parameter, i.e. the charge, while size and surface hydrophobicity remain practically unchanged. The knowledge about the interactions of proteins with particulate surfaces can be exploited for the future controlled design of colloidal drug carriers and possibly in the controlled creation of biocompatible surfaces of other devices that come into contact with proteins (e.g. microparticles and implants).

Adsorption↗

PubMedDate not supplied

The ryanodine contracture test may help diagnose susceptibility to malignant hyperthermia.

PURPOSE: The ryanodine contracture test (RCT) using the plant alkaloid ryanodine as the triggering agent has been proposed to reduce equivocal results of the in vitro caffeine-halothane-contracture test (IVCT), which is the accepted and standardized procedure to diagnose malignant hyperthermia (MH). However, the response of skeletal muscle of non-MH affected patients (controls) to ryanodine has not yet been characterized. METHODS: Skeletal muscle biopsies were studied in 33 controls and in six patients with a history of fulminant MH. Following the IVCT, the RCT was performed in all specimens using ryanodine 1 micro M. Onset time of contracture and time to reach a contracture level of 10 mN above lowest resting tension and above predrug tension were calculated. RESULTS: With the standard IVCT, all controls were labelled MH non-susceptible; all clinically diagnosed MH patients were labelled MH susceptible. With ryanodine, control muscle differed from MH susceptible muscle regarding onset time of contracture (26 vs 3.8 min, P < 0.05) and time to reach a contracture of 10 mN (49 vs 12.5 min, P < 0.05; all median). Tissue viability and patient's age significantly influenced contracture times. CONCLUSIONS: Despite the highly specific binding of ryanodine at the myocytic sarcoplasmic reticulum, the wide range of contracture times of the controls points toward heterogeneity of ryanodine receptors within physiologic limits. This may also be caused in part by tissue viability and the patients' age. The ryanodine contracture test performed in addition to the IVCT may add clarity into diagnosing a patient as MH-susceptible or not.

Adult↗

PubMedDate not supplied

Synthesis and biological evaluation of folate receptor-targeted boronated PAMAM dendrimers as potential agents for neutron capture therapy.

Successful treatment of cancer by boron neutron capture therapy (BNCT) requires the selective delivery of (10)B to constituent cells within a tumor. The expression of the folate receptor is amplified in a variety of human tumors and potentially might serve as a molecular target for BNCT. In the present study we have investigated the possibility of targeting the folate receptor on cancer cells using folic acid conjugates of boronated poly(ethylene glycol) (PEG) containing 3rd generation polyamidoamine dendrimers to obtain (10)B concentrations necessary for BNCT by reducing the uptake of these conjugates by the reticuloendothelial system. First we covalently attached 12-15 decaborate clusters to 3rd generation polyamidoamine dendrimers. Varying quantities of PEG units with varying chain lengths were then linked to these boronated dendrimers to reduce hepatic uptake. Among all prepared combinations, boronated dendrimers with 1-1.5 PEG(2000) units exhibited the lowest hepatic uptake in C57BL/6 mice (7.2-7.7% injected dose (ID)/g liver). Thus, two folate receptor-targeted boronated 3rd generation polyamidoamine dendrimers were prepared, one containing approximately 15 decaborate clusters and approximately 1 PEG(2000) unit with folic acid attached to the distal end, the other containing approximately 13 decaborate clusters, approximately 1 PEG(2000) unit, and approximately 1 PEG(800) unit with folic acid attached to the distal end. In vitro studies using folate receptor (+) KB cells demonstrated receptor-dependent uptake of the latter conjugate. Biodistribution studies with this conjugate in C57BL/6 mice bearing folate receptor (+) murine 24JK-FBP sarcomas resulted in selective tumor uptake (6.0% ID/g tumor), but also high hepatic (38.8% ID/g) and renal (62.8% ID/g) uptake, indicating that attachment of a second PEG unit and/or folic acid may adversely affect the pharmacodynamics of this conjugate.

Animals↗