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Biomedical subjects

G Hildebrand

Publications and source records attributed to G Hildebrand.

7 recordsLinked to original sources

Comparison between RGD-peptide-modified titanium and borosilicate surfaces.

The use of synthetic peptides containing adhesive sequences, such as the Arg-Gly-Asp (RGD) motif, represents a promising strategy to control biological interactions at the cell-material interface. These peptides are known to improve the tissue-material contact owing to highly specific binding to cellular membrane receptors known as integrins, thereby promoting the adhesion, migration and proliferation of cells. The peptides were coupled to borosilicate glass and titanium surfaces using silanisation chemistry. A tryptophan residue was incorporated into the amino acid sequences of selected peptides to facilitate the detection of the covalently bound peptides. Successful peptide immobilisation was proven by fluorimetric measurements. The confocal imaging analysis suggests a homogeneous distribution of the immobilised peptide across the biomaterial surface. In vitro cell proliferation assays were employed to compare the adhesion potentials of the well-known RGD-containing peptides GRGDSP, GRADSP and RGDS to the three peptides designed by our group. The results demonstrate that the RGD sequence is not necessarily required to enhance the adhesion of cells to non-biological surfaces. Moreover, it is shown that the number of adhering cells can be increased by changes in the peptide hydrophobicity. Changes in the cytoskeleton are observed depending on the type of RGD-peptide modification.

3T3 Cells↗

Fiber-optic luminescent sensors with composite oxygen-sensitive layers and anti-biofouling coatings.

Anti-biofouling polymers containing phosphorylcholine (PC)-substituted methacrylate units have been prepared by copolymerization with dodecyl methacrylate and used to coat luminescent oxygen sensors. Nanometer-sized coatings of such materials are shown to reduce significantly the adhesion of marine bacteria (more than 70%) and thrombocytes (more than 90%) to the surface of tris-(4,7-diphenyl-1,10-phenanthroline)ruthenium(II)-doped silicone layers. A thorough analytical characterization of both the PC-coated and the uncoated dyed films has demonstrated that the anti-biofouling layers do not alter dramatically the performance of the fiber-optic oxygen sensors in aqueous media and are mechanically stable for more than one year of continuous immersion. The slope of the linear calibration plots in the 0-8 mg L(-1) oxygen concentration range (ca. 1.0 L mg(-1)) decreases 8-11% after applying the 50-nm protective layer with no change in the sensor precision (1.1-1.9% RSD, n = 6). The response time of the 200-microm O2-sensitive layers (1.5-6 min) increases up to 2-fold, depending on the nature of the PC polymer used, but the temperature effect on the sensor response (0.020 L mg(-1) degrees C(-1)) remains essentially unchanged. Oxygen detection limits as low as 0.04 mg L(-1) have been measured with the coated optodes. The novel biofouling-resistant optosensors have been successfully validated against a commercial oxygen electrode and are shown to respond faster than the electrochemical device for large oxygen concentration changes. The biomimetic coatings will be particularly useful for drift-free long-term operation of environmental optosensors and in vivo fiber-optic oxygen analyzers.

Bacterial Adhesion↗

Blood cell adhesion on sensor materials studied by light, scanning electron, and atomic-force microscopy.

Unwanted interactions of biomedical sensors with surrounding tissues, body fluids, and cells are one of the most crucial problems affecting their long-term stability. In vivo processes were simulated in a computer-controlled bioreactor connected to a flow chamber system. Optical sensor materials were inserted into a parallel-plate chamber and monitored by light microscopy in order to get information about the number of adhered cells. Tests with thrombocyte-enriched plasma show that novel phosphorylcholine (PC)-polymer-coated sensors appear to be more bioinert, and thus demonstrate better haemocopatibility in comparison with untreated glass sensors. The influence of different materials on the morphology of adhered cells was investigated by off-line methods such as scanning electron microscopy (SEM) and atomic-force microscopy (AFM). SEM showed a reduction in the number of adhered thrombocytes and the lack of any fibrin network on the PC-polymer-modified glass surface, in contrast to the pure glass surface. AFM gives topographical information, and the calculated contact areas and cell volumes indicate smaller interactions between cells and sensor material in the case of PC-polymer-coated sensors.

Bioreactors↗

Self-treatment of acute migraine with subcutaneous sumatriptan using an auto-injector device: comparison with customary treatment in an open, longitudinal study.

In a multicenter open longitudinal clinical trial where 479 patients suffering from migraine with or without aura were recruited, patients treated at home one to three migraine attacks with their customary treatment, and subsequently, over a 3-month period, one to three migraine attacks with 6 mg sumatriptan sc using an autoinjector. The headache response to customary treatment was 19% at 1 h and 30.5% at 2 h, and was not significantly different when only attacks treated "adequately" according to accepted treatment recommendations were considered: 16% at 1 h and 35% at 2 h. In contrast, 69% and 82% of patients treated with 6 mg sumatriptan sc had mild headache or no headache at 1 and 2 h respectively, regardless of migraine type or duration of symptoms prior to treatment. Other migraine symptoms (nausea, vomiting, photo- and phonophobia) were effectively treated with sumatriptan. Recurrence of migraine was observed in 31% of patients and was well controlled by a second injection of sumatriptan. It is concluded that 6 mg sumatriptan sc, self-administered using an autoinjector, is well tolerated and more effective than most currently used acute treatments for migraine in a population of severely affected patients consulting a neurologist.

Acute Disease↗

Function tests on the neuroendocrine hypothalamo-pituitary system following acute midbrain syndrome, with special reference to computertomographical and magnetic resonance imaging results.

Seventeen patients underwent a neuroendocrinological function test at a mean 6.3 years following a severe craniocerebral trauma (CCT) accompanied by midbrain syndrome. An insulin hypoglycaemia test (IHT) and the combined pituitary anterior lobe test (CPALT) were applied. Whereas the IHT as maximum stimulator of the hypothalamo-pituitary system (HPS) showed an adequate reserve capacity, the CPALT yielded a partial limitation of the secretion dynamic in the somatotropic, adrenocorticotropic axis as well as a dysfunction in the FSH secretion. Neuroradiological tests could not establish substantial injury in the regio hypothalamica in any patient.

Adolescent↗

CD4 and CD7 molecules as targets for drug delivery from antibody bearing liposomes.

We have examined two T lymphocyte cell surface molecules, CD4 and CD7, as targets for specific delivery of drugs from antibody-directed liposomes. The efficiency of uptake by peripheral lymphocytes, thymocytes, and two CEM sublines (CEM.MRS and CEM-T4) of anti-CD4 and anti-CD7 liposomes containing methotrexate was evaluated by the methotrexate-mediated inhibition of the incorporation of d-[3H]Urd into DNA. This was compared with similar liposomes targeted to MHC-encoded HLA class I molecules, which are known to be efficiently taken up by T cells. Despite the lower expression of CD7 molecules relative to HLA class I on most cell lines, CD7 was shown to be a good target for drug delivery. The results of an internalization study using radiolabeled Protein A showed that a higher proportion of CD7 molecules was internalized than HLA class I molecules. CD4-targeted liposomes, in contrast, were relatively ineffective for drug delivery for lymphoid cells, and only partially inhibited CEM-T4 cells. The lack of toxicity correlated with poor internalization of the target molecule on most cell lines. The drug effect of anti-CD4 liposomes was more pronounced on HeLa-T4, which is an epithelial cell line transfected with the CD4 gene. In contrast to lymphoid cells, these cells efficiently internalized CD4 molecules. PMA is known to down-regulate surface expression of CD4 molecules on various T cells. Internalization of CD4 was induced by PMA, but PMA failed to induce cytotoxicity of CD4-targeted liposomes for CEM.MRS. The internalized drug was probably degraded rapidly because internalized anti-CD4 antibody-bound Protein A was degraded very rapidly.

Antibodies, Monoclonal↗

[Complications and risks of brachial plexus anaesthesia with special reference to long-term damage (author's transl)].

During 1974-1978 620 regional anaesthesias involving the brachial plexus were performed. Three techniques, viz: supraclavicular, axillary, interscalene were employed. The data are analysed with a view to comparing the efficacy and safety of the techniques with a special reference to long-term damage. Transient injury to the brachial plexus was observed in 3 of 342 patients who had Kulenkampff's supraclavicular plexus anaesthesia. After 3 months all after-effects had disappeared. Plexus block via the axillary route proved to be the safest technique. Detailed inquiries and follow-up examinations established that none of the techniques had caused irreversible damage to the brachial plexus.

Anesthesia, Conduction↗