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Biomedical subjects

M J German

Publications and source records attributed to M J German.

8 recordsLinked to original sources
PubMed2007

Preliminary work on the development of a novel detection method for osteoporosis.

Osteoporosis affects both the organic and mineral phases of bone resulting in a decrease in resistance to fracture. Dual x-ray absorptiometry (DEXA) scans are used for diagnosing osteoporosis, which is conventionally characterised by a decrease in mineral density. Unfortunately, some patients who suffer osteoporotic fractures have normal bone density, because both the organic and the mineral phase are affected. However, there are currently no methods of evaluating the health of the organic phase. Patients undergoing treatment for osteoporosis have reported hardening of their fingernails. As the properties of nail and bone may be linked in a comparable, measurable way, this work used both mechanical (nano-indentation) and chemical (Raman spectroscopy) methods to evaluate differences between fingernails sourced from osteoporotic and non-osteoporotic patients. The difference in mean modulus between the nails sourced from the groups was 1.1 GPa. The disulphide bond content of fingernail samples from each group was measured by Raman spectroscopy and disulphide bond content of fingernail was found to be significantly lower in the osteoporotic group. It can be concluded that a relationship between the mechanical and chemical properties of nail and bone may exist in a measurable way. This work has suggested that changes in the organic phase of bone are reflected in similar proteins, such as keratin, from which fingernails are composed. Collagen and keratin are two distinct structural proteins, but they share the need for protein sulphation and disulphide bond formation, via cysteine, for their structural integrity. A disorder of either process should lead to disordered collagen and keratin synthesis.

Bone Density↗
PubMed2006

Bone marrow cell gene expression and tissue construct assembly using octacalcium phosphate microscaffolds.

Calcium phosphates have been widely used in bone and soft tissue applications and are of considerable interest as scaffold materials due to properties of osteoconduction, resorbability and in some cases osteoinduction. These materials are microcrystalline and as such are processed using sintering, surface coating or cement technologies. However calcium phosphates containing HPO(4)(2-) ions often have layered crystal structures and can form macrocrystals in an aqueous environment at room temperature and pressure. This study aimed to investigate the potential of octacalcium phosphate (OCP) crystals for the attachment, proliferation and differentiation of bone marrow stromal cells and the potential of these cell seeded crystals as 'building blocks' for manufacture of self-supporting macroscale tissue constructs. An inverse relationship between cell number and crystal surface area was found and marrow cells grown on OCP crystals expressed osteocalcin and osteopontin mRNA, markers of osteoblastic differentiation, even in the absence of inductive media additives. Self-supporting crystal tissue macroscale constructs could be fabricated by culturing cell loaded crystals in moulds of the desired shape. Due to the low packing efficiency as a consequence of the high aspect ratio of OCP crystals, this microscaffold approach may offer the potential for ex vivo construction of large volumes of tissue which forms as a physiologically vascularised tissue.

Animals↗
PubMed2005

Synthesis and properties of amphiphilic networks 3: preparation and characterization of block conetworks of poly(butyl methacrylate-block-(2,3 propandiol-1-methacrylate-stat-ethandiol dimethacrylate)).

Amphiphilic conetwork polymers were prepared and studied as substrates in the culture of dermal fibroblasts. Both block and random conetworks polymers were produced by radical polymerization of either low-molecular weight monomers or oligomeric macromonomers. The oligomeric macromonomers were prepared by methacrylation of biscarboxy oligo(butyl methacrylates) (OBMA). The latter were synthesized by ozononolysis of poly(butyl methacrylate-co-butadiene) materials. The hydrophilic component was derived from copolymerization with 2,3 propandiol-1-methacrylate and cross-linking was provided by inclusion of ethandiol dimethacrylate (EDMA). None of the synthesized materials showed indications of cytotoxicity to human dermal fibroblasts. All of the block conetworks were highly phase separated and possessed pores on the micron length scale. The equilibrium water contents of the latter could be controlled by addition of EDMA. Block conetworks that did not contain EDMA were highly swollen and had smoother surfaces than those that contained EDMA. The former were poor substrates for cell proliferation (as measured by monitoring DNA content) whilst the latter class gave increasing levels of DNA during culture; an indicator proliferation. The performance of these materials in cell culture was also dependent on the fraction of OBMA in the formulation. Increasing the fractions of BMA, either in the random terpolymer or block networks, system had the effect of increasing both cell proliferation and viability (as measured by the Alamar Blue assay).

Biocompatible Materials↗
PubMed2005

Protein aggregation, metals and oxidative stress in neurodegenerative diseases.

There is clear evidence implicating oxidative stress in the pathology of many different neurodegenerative diseases. ROS (reactive oxygen species) are the primary mediators of oxidative stress and many of the aggregating proteins and peptides associated with neurodegenerative disease can generate hydrogen peroxide, a key ROS, apparently through interactions with redox-active metal ions. Our recent results suggest that ROS are generated during the very early stages of protein aggregation, when protofibrils or soluble oligomers are present, but in the absence of mature amyloid fibrils. The generation of ROS during early-stage protein aggregation may be a common, fundamental molecular mechanism underlying the pathogenesis of oxidative damage, neurodegeneration and cell death in several different neurodegenerative diseases. Drugs that specifically target this process could be useful in the future therapy of these diseases.

Humans↗
PubMed2005

The use of fingernails as a means of assessing bone health: a pilot study.

BACKGROUND: Anecdotally, patients volunteer reports of increasing hardness of their fingernails within months of starting diverse treatments for osteoporosis. The properties of both nail and bone may be linked in a comparable, measurable way. METHODS: We examined the fingernails of two groups of patients, with (n = 9) and without (n = 13) osteoporosis at either the hip or lumbosacral spine. We performed nanoindentation to assess the degree of nail brittleness and Raman spectroscopy to assess the disulfide bond content of nail. RESULTS: The mean moduli of fingernails of patients with low bone mineral density (BMD) are lower than those of patients with normal BMD. The mean difference in mean modulus between the groups was found to be 0.996 (p = 0.15 between groups). The spectroscopy data also showed differences between the two sets of nails. The disulfide bond content of the nails sourced from osteoporotic patients was lower than that from healthy patients (p = 0.06 between groups). CONCLUSIONS: Bone collagen and nail keratin are two distinct structural proteins, and both require protein sulfation and disulfide bond formation, via cysteine, for structural integrity. A disorder of either process may lead to disordered collagen and keratin synthesis. This is reflected in the structural abnormalities seen in clinical syndromes in which there is either protein deficiency, disorders of sulfur metabolism, or cystathione beta-synthase deficiency. The relationship between nail and bone may exist in a measurable way. This pilot study should lead to further work to explore this relationship. Could nail prove to be a valuable adjunct to diagnosis or provide a means of more rapid follow-up after commencement of therapy?

Aged↗
PubMed1998

Exchange of perfluorodecalin for gas or oil: a model for avoiding slippage.

BACKGROUND: The introduction of liquid perfluorocarbons as an intraoperative tool has greatly facilitated retinal re-apposition in giant retinal tears (GRT) and relieving retinotomies (RR). Slippage of the retina can occur during the exchange of heavy liquids for oil or gas, especially if the fill of perfluorocarbons is subtotal. METHODS: We have used a model eye chamber to study the surface interactions of perfluorodecalin (PFD) with silicone oil and air to evaluate possible mechanisms of slippage. RESULTS: The results demonstrate that it is possible during a PFD/air exchange to trap a wedge of aqueous which is displaced laterally and forced posteriorly during removal of the PFD, whereas during a PFD/silicone oil exchange the remaining aqueous is displaced laterally and upwards and thus trapped above the silicone oil/PFD interface. CONCLUSIONS: We believe that during PFD/air exchange the displacement of the aqueous posteriorly can cause slippage and that this could be avoided by performing a direct PFD/silicone oil exchange.

Air↗