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Biomedical subjects

R Marr

Publications and source records attributed to R Marr.

7 recordsLinked to original sources

Stabilisation of crosslinked ultra-high molecular weight polyethylene (UHMW-PE)-acetabular components with alpha-tocopherol.

A stabilisation of crosslinked ultra-high molecular weight polyethylene (UHMW-PE) with alpha-tocopherol (vitamin E) used for endoprostheses can increase its resistance against oxidative degradation remarkably. However, the method used for conventional UHMW-PE of adding alpha-tocopherol to the UHMW-PE powder before processing can not be applied for crosslinked UHMW-PE, since the alpha-tocopherol hinders the crosslinking process, which would be accompanied by a heavy degradation of this vitamin. The alpha-tocopherol has therefore to be added after the crosslinking process. This paper presents two methods for a stabilisation of finished products with alpha-tocopherol. In method 1, UHMW-PE-cubes (20 x 20 x 20 mm3) were stored in pure alpha-tocopherol under inert atmosphere at temperatures from 100 degrees C to 150 degrees C resulting in a high mass fraction of alpha-tocopherol in the edge zones. For further homogenisation, the cubes were stored in inert atmosphere at temperatures from 160 degrees C to 200 degrees C. In method 2, supercritical CO2 was used to incorporate the vitamin into the UHMW-PE. In an autoclave vessel, the cubes were treated with alpha-tocopherol dissolved in supercritical CO2 for several hours at temperatures from 100 degrees C to 170 degrees C. In both cases, the mass fraction of alpha-tocopherol was detected with the help of a FTIR-microscope. Both methods are well suited to stabilise crosslinked UHMW-PE with alpha-tocopherol. A stabilisation of the sensitive edge layer as well as a nearly homogenous distribution with varying alpha-tocopherol content may be realised by varying the process parameters. Using method 2, standard hip cups were stabilized nearly homogeneously with varying mass fraction of alpha-tocopherol. No oxidation of the UHMW-PE could be detected by infrared spectroscopy (FTIR) and HPLC studies showed a very low degradation of the alpha-tocopherol for both processes.

Acetabulum↗

An antiaggregation gene therapy strategy for Lewy body disease utilizing beta-synuclein lentivirus in a transgenic model.

Current experimental gene therapy approaches for Parkinson's disease (PD) and dementia with Lewy bodies (DLB) include the use of viral vectors expressing antiapoptosis genes, neurotrophic factors and dopaminergic system enzymes. However, since increasing evidence favors a role for alpha-synuclein accumulation in the pathogenesis of these disorders, an alternative therapy might require the transfer of genes that might block alpha-synuclein accumulation. beta-Synuclein, the nonamyloidogenic homologue of alpha-synuclein, has recently been identified as a potential candidate. Thus, in vivo transfer of genes encoding beta-synuclein might provide a novel approach to the development of experimental treatments for PD and DLB. To assess this possibility and to better understand the mechanisms involved, a lentiviral vector expressing human (h) beta-synuclein (lenti-beta-synuclein) was tested in a transgenic (tg) mouse model of halpha-synuclein aggregation. This study showed that unilateral intracerebral injection of lenti-beta-synuclein reduced the formation of halpha-synuclein inclusions and the accumulation of halpha-synuclein in synapses and ameliorated the neurodegenerative alterations in the tg mice. Both in vivo and in vitro coimmunoprecipitation and immunoblot experiments show that the mechanisms of beta-synuclein neuroprotection involve binding of this molecule to halpha-synuclein and Akt, resulting in the decreased aggregation and accumulation of halpha-synuclein in the synaptic membrane. Together, these data further support a role for beta-synuclein in regulating the conformational state of alpha-synuclein and suggest that this gene transfer approach might have potential for the development of alternative therapies for PD and DLB.

Animals↗

The Effect of Ternary Complex Formation on the Partitioning of Pyrene and Anthracene in Aqueous Solutions Containing Sodium Dodecyl Sulfate and M-gamma-cyclodextrin

The partitioning behavior of pyrene and anthracene between n-decane and aqueous solutions containing a partially methylated gamma-cyclodextrin (M-gamma-CD) and sodium dodecyl sulfate (SDS) was studied by extraction experiments. At concentrations below the aqueous solubility of pyrene and anthracene both were found to form 1:1 complexes with M-gamma-CD. Formation constants were determined as 1843 M-1 for pyrene and 624 M-1 for anthracene. In micellar solutions of SDS pyrene was found to be better solubilized than anthracene. At constant concentrations of M-gamma-CD the dependence of the partition coefficients on increasing concentrations of SDS could be divided into three linear regions. At concentrations below a critical surfactant concentration (CSCSDS) the partition coefficients of both polyaromatic hydrocarbons as well as the fluorescence intensity of pyrene increased linearly with the addition of SDS. In the fluorescence spectra of anthracene the addition of SDS led to a shift of the maxima to higher wavelengths. These data suggest the formation of ternary complexes of M-gamma-CD with each of the polyaromatic hydrocarbons and SDS. The ternary complex with anthracene was found to be more stable than that of pyrene, which resulted in higher partition coefficients than seen with pyrene. Increasing the surfactant concentrations above the CSCSDS the partition coefficients remained constant until micelles were formed and another linear increase of the partition coefficients could be observed. CSCSDS and the critical micellization concentration (CMC) were found to increase linearly with cyclodextrin concentration. For CSCSDS a molar ratio of 3/1 was found for M-gamma-CD/SDS. Mixed micelles between SDS and gamma-CD are supposed to be formed above CSCSDS. Copyright 1997Academic Press

Journal Article↗

The Effect of Sodium Dodecyl Sulfate and M-alpha-Cyclodextrin on the Solubility and Partitioning of Xylenes in Aqueous Solutions

The solubility and the partitioning of p- and o-xylene in aqueous solutions containing M-alpha-CD, a partially methylated alpha-cyclodextrin, and the anionic surfactant sodium dodecyl sulfate (SDS) were studied by extraction experiments to evaluate the applicability of liquid membrane permeation for the separation of xylene isomeres. Experiments were carried out with the pure xylenes and 1:1 mixtures of o- and p-xylene. The interactions of M-alpha-CD and SDS and their effects on the solubility and partitioning of xylenes were investigated. M-alpha-CD was found to form 1:1 complexes with p- and o-xylene. Formation constants were determined as 141 M-1 for p-xylene and 48 M-1 for o-xylene, respectively, which are higher than those reported with nonmethylated alpha-CD. This can be explained by additional hydrophobic interactions with the methyl groups of the cyclodextrin. In contrast to the solubility in CD solutions, o-xylene was found to be more soluble than p-xylene in aqueous solutions of SDS. At constant concentrations of M-alpha-CD the addition of SDS led to the displacement of p-xylene from the cyclodextrin cavity, which resulted in a decrease in its solubility. This decrease lasted until micelles were formed. Due to the solubilization of p-xylene in the micelles, further addition of SDS resulted in a linear increase in the solubility of p-xylene. However, at constant CD concentrations the solubility of o-xylene increased with the addition of SDS until about 5 mmol/liter SDS. This might be attributed to the formation of a ternary complex consisting of cyclodextrin, o-xylene, and SDS. At SDS concentrations greater than 5 mmol/liter, the solubility of o-xylene decreased, which was probably due to the formation of a more stable complex between SDS and M-alpha-CD. An addition of SDS beyond a critical concentration (CMC), where micelles are formed, resulted again in a linear increase of o-xylene solubility. The CMC was found to depend linearly on the concentration of M-alpha-CD in aqueous solution. Extraction experiments with a 1:1 mixture of o- and p-xylene showed that the two xylenes and SDS are in competition for M-alpha-CD. Since surfactants are always present when using emulsion liquid membranes and due to the complex interactions between SDS, the xylenes, and M-alpha-CD, no sufficient selectivity for the separation of the xylenes by liquid membrane permeation could be achieved.

Journal Article↗