Biofluid mechanics

T. J. Pedley, The Fluid Mechanics of the Large Blood Vessels (Cambridge University Press, Cambridge, 1980) R. Skalak, N. Ozkaya and T. C. Skalak, Biofluid mechanics, Annual Rev. Fluid Mech. 21, 167-204 (1989). 

Schnek DJ, Lucas CL (1990) Biofluid mechanics. New York University Press, New York... 

Mazumdar, J. N., Biofluid Mechanics, World Scientiflc Pub., Singapore, 1992. 

Although the fluids most often considered in biofluid mechanics studies are blood and air, other fluids such as urine, perspiration, tears, ocular aqueous and vitreous fluids, and the synovial fluid in the joints can also be important in evaluating tissue system behavioral responses to induced chemical and physical stresses. For purposes of analysis, these fluids are often assumed to exhibit Newtonian behavior, although the synovial fluid and blood under certain conditions can be non-Newtonian. Since blood is a suspension it has interesting properties it behaves as a Newtonian fluid for large shear rates, but is highly non-Newtonian for low shear rates. The synovial fluid exhibits viscoelastic characteristics that are particularly suited to its function of j oint lubrication, for which elasticity is beneficial. These viscoelastic characteristics must be accounted for when considering tissue therapy for joint injuries. 

Zima-Kuhsiewicz BE, Diez L, Kowalczyk W, Delgado A (2008) Biofluid mechanical investigations in sequencing batch reactors (SBR). Chem Eng Sci 63(3) 599-608... 

Lee MM, Green FHY, Bjamasson S, Zhang Y, Schilrch S. Surface properties of airway mucus exposed to acid aerosol. In Liepsch D, ed. Biofluid Mechanics. Dus-seldorf VDI Verlag, 1994 133 144. 

Simon, B.R. and Kaufmann, M.V. (1990) Finite element models for arterial wall mechanics and transport. Biofluid Methods in Vascular and Pulmonary Systems, Biomechanical Systems Techniques and Applications, Leondes, C. T. editor, IV, CRC Press, New York, 5.1-5.32... 

Metabolomics works focused on AD investigation are mostly based on the analysis of CSF. Main reason is that CSF composition is directly affected by the CNS. Therefore, alterations due to AD pathology will be more probably observed in this sample than in other biofluids. The role of CSF includes a mechanical protection of CNS against trauma, and transport of nutrients to ensure the homeostasis of CNS cells (113). 

There are obvious limitations in terms of choice of biofluid for instance, urine might not be as appropriate as cerebrospinal fluid for studying neuropathology. There is also the potential for confusion with mixed-toxicity drugs that, for example, affect both liver and kidney, as the biomarkers of toxicity will be a complex combination that relates to both sites and possibly to the multiple mechanisms. However, this offset by the fact that mixed toxicities often have different timescales and such effects can therefore be deconvoluted by making repeated sequential measurements in individual animals. 

Level 2 Classification of Toxicity Samples identified as dissimilar to matched control samples can be fitted to a series of mathematical models that define the multivariate boundaries for known classes of toxicity (Figures 5.4 and 5.5) [6,7,12,63]. Therefore, biofluid or tissue samples from experimental animals treated with novel drugs can be tested to ascertain if the drug induces biochemical effects that would infer a particular site or mechanism of toxicity. 

The value of obtaining multiple datasets from various biofluid samples and tissues of the same animals collected at different time points has been demonstrated. This procedure has been termed integrated metabonomics [2] and can be used to describe the changes in metabolic chemistry in different body compartments affected by exposure to toxic drugs. An illustration of the types of information that can be obtained is shown in Figure 13.3-6, from an NMR spectroscopic study of the acute toxicity of a-naphthylisothiocyanate, a model liver toxin [53]. Such timed profiles in multiple compartments are characteristic of particular types and mechanisms of pathology and can be used to give a more complete description of the biochemical consequences than can be obtained from one fluid or tissue alone [54]. 

What kind of safety concerns should be addressed (in particular mechanical input in single cells and biofluids). 

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