Effects of hyaluronic acid upon diffusion of solutes and flow of solvent

Ogston, A. G.; Sherman, Thomas F.

doi:10.1113/jphysiol.1961.sp006658

Cited by 112 publications

(37 citation statements)

References 10 publications

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“…In solutions of HA or sulphated proteoglycans, however, the diffusivity of macromolecules is reported to decrease exponentially with increasing concentration of HA (Laurent et al, 1963) or sulphated proteoglycans (Preston and Snowden, 1973). This relationship has also been explained theoretically based on the stochastic model of diffusion (Ogston and Sherman, 1961). Thus, our results indicate that HA and s-GAG have different effects on diffusion in complex in vivo systems compared to in pure solution, or the discrepancy is due to the large differences in HA and proteoglycan concentrations in the solutions compared to tissue.…”

Section: Correlation Between Matrix Content and Diffusionsupporting

confidence: 77%

Comparison of IgG diffusion and extracellular matrix composition in rhabdomyosarcomas grown in mice versus in vitro as spheroids reveals the role of host stromal cells

et al. 2002

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The tumour extracellular matrix acts as a barrier to the delivery of therapeutic agents. To test the hypothesis that extracellular matrix composition governs the penetration rate of macromolecules in tumour tissue, we measured the diffusion coefficient of nonspecific IgG in three rhabdomyosarcoma subclones growing as multicellular spheroids in vitro or as subcutaneous tumours in dorsal windows in vivo. In subcutaneous tumours, the diffusion coefficient decreased with increasing content of collagen and sulphated glycosaminoglycans. When grown as multicellular spheroids, no differences in either extracellular matrix composition or diffusion coefficient were found. Comparison of in vitro vs in vivo results suggests an over-riding role of host stromal cells in extracellular matrix production subjected to modulation by tumour cells. Penetration of therapeutic macromolecules through tumour extracellular matrix might thus be largely determined by the host organ. Hence, caution must be exercised in extrapolating drug penetrability from spheroids and multilayer cellular sandwiches consisting of only tumour cells to tumours in vivo. British Journal of Cancer (2002) The extracellular matrix (ECM) is a potent barrier to the delivery and penetration of complex biopharmaceuticals such as monoclonal antibodies, therapeutic proteins, or genes. Due to the elevated interstitial fluid pressure in tumours , the therapeutic agents must reach the tumour cells by interstitial diffusion. It is not clear whether the network of fibrillar collage or the glycosaminoglycan (GAG) gel plays the most important role in limiting the diffusion of macromolecules through the ECM, and what the role of the host stromal cells is. Netti et al (2000) found that the amount of collagen in tumours correlated inversely with the diffusion coefficient of macromolecules, and collagenase treatment of the tumour increased the diffusion coefficient. Pluen et al (2001) provided further support for the role of collagen by measuring diffusion in tumours grown in subcutaneous tissue and the cranium. Hyaluronidase, on the other hand, is reported to reduce the diffusion coefficient of albumin in lung interstitium (Qiu et al, 1999).We postulated that diffusion of macromolecules is hindered both by the collagen network and by the hydrophilic gel of GAG and proteoglycans. To test this hypothesis we used three distinct clones with different degrees of differentiation and ECM (Groeschel et al, 1994) derived from a rat rhabdomyosarcoma, growing as multicellular spheroids in vitro or subcutaneously in dorsal chambers in mice in vivo. The production of ECM in tumours is the result of an active interaction between the tumour cells and stromal cells of the host (Gullino and Grantham, 1962;Knudson et al, 1984), whereas the extracellular matrix of multicellular spheroids is solely produced by the tumour cells. Comparison of the ECM composition in tumours growing as xenografts in vivo and as multicellular spheroids in vitro, is likely to reveal the influence of the host stromal ce...

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Section: Correlation Between Matrix Content and Diffusionsupporting

confidence: 77%

Comparison of IgG diffusion and extracellular matrix composition in rhabdomyosarcomas grown in mice versus in vitro as spheroids reveals the role of host stromal cells

et al. 2002

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“…The previous, normally protein-poor, intimal plasma filtrate no longer can be maintained. Instead, this dilute filtrate is replaced by virtually pure plasma molecules mixed with soluble matrix molecules from the now unconstrained dissolution of the intimal gel-phase matrix (gel 7 sol) (8,34,44). The overall transmural pressure gradient will now drive a convective flux of this unsieved mixture of macromolecules further into the deeper tissue layers.…”

Section: Discussionmentioning

confidence: 99%

Arterial intimal-medial permeability and coevolving structural responses to defined shear-stress exposures

Fry

2002

American Journal of Physiology-Heart and Circulatory Physiology

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Fry, Donald L. Arterial intimal-medial permeability and coevolving structural responses to defined shearstress exposures. Am J Physiol Heart Circ Physiol 283: H2341-H2355, 2002. First published August 22, 2002 10.1152/ajpheart.00219.2001.-The purpose of this research was to examine the evolution of arterial shear stress-induced intimal albumin permeability and coevolving structural responses in swine arteries. Uniform laminar shear-stress responses were compared with those of a simulated "flow separation" stress field. These fields were created using specially designed flow-configuring devices in an experimentally controlled, metabolically supported, ex vivo thoracoabdominal aorta preparation. The Evans blue dye-albumin complex (EBDalb) permeability patterns that evolved were measured by a reflectometric method. The corresponding tissue structural responses were evaluated by histological, immunostaining, and ultrastructural microscopic techniques. It was shown that when a previously in vivo-adapted artery is challenged by a new mechanochemical environment, it undergoes a sequence of adaptive processes over the ensuing 95 h. Intimal regions of laminar shear-stress exposure (ϳ16 dyn/cm 2 ) responded initially (23 h) with an increase in permeability. With continued stress exposure, intimal-medial structural changes ensued that restored the artery to a physiologically normal permeability. Over this same period, adjacent endothelial regions exposed to simulated flow separation stress fields (ϳ0.03-0.27 dyn/cm 2 ) developed early and progressively increasing permeability. This was associated with formation of local intimal edema, loss of intimal matrix material, and development of distinctively raised, gelatinous-appearing intimal lesions having a potentially preatheromatous architecture.arterial stress adaptation; apoptosis; atheroma; atherosclerosis; endothelial barrier function; flow separation and reattachment phenomenon; porcine artery; gelatinous lesion; laminar shear stress; transendothelial mass transport SINCE THE 1960S, there has been an increasing interest in the effects of various hemodynamic shear-stress exposures on endothelial-intimal permeability, structure (17,21,22), and susceptibility to atherogenesis (4,23,24). Atheroma are slowly developing, raised intimal lesions that are the leading cause of morbidity and death in modern societies. Early studies suggest that hemodynamic factors could influence the endothelial cell surface barrier in an adverse manner to initiate the chain of aberrant interstitial mass transport and cellular events of atherogenesis (2,5,23,27,30). Because one of the initiating events appears to be endothelial barrier failure (3,29,30,42,45), most subsequent work has focused on endothelial cell biology. To do this, special tissue culture systems were developed in which controlled shear stresses could be applied to cultured monolayers of endothelial cells. Endothelial "responses" to these controlled shear-stress exposures were based initially on observations of endothelial cell in...

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“…It is becoming increasingly apparent that its properties are not simply those of a watery solution of protein but more closely resemble a gel with interspaces of molecular size which can restrict distribution of materials (23). Ogston and Sherman (24) have shown that dilute solutions of hyaluronic acid can decrease rates of diffusion by factors up to several fold for large molecules, less for small. Since the process of restriction is largely a mechanical one, it seems unlikely that it would discriminate between two so similar ions.…”

Section: Plateau Extractions Of Rb and Kmentioning

confidence: 99%

Capillary, Interstitial, and Cell Membrane Barriers to Blood-Tissue Transport of Potassium and Rubidium in Mammalian Skeletal Muscle

Sheehan

Renkin

1972

Circulation Research

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Blood-tissue transport of 42 K, 8a Rb, and 22 Na was studied in perfused gracilis muscles of dogs to ascertain the influence of capillary wall, interstitial space, and muscle cell membranes on overall transport kinetics. Single-injection and continuous-infusion techniques were used, with T-1824 or 51 Cr-hemoglobin as nondiffusible references. Results were as follows: (1) Extraction (E) of the diffusible solutes was incomplete even in the earliest samples of venous outflow.(2) E Rb equaled E K in the first few samples, but later, as both declined, the ratio of E Rb to E K became less than one; stable ratios between 0.6 and 0.8 were established in different experiments. (3) E Na was initially slightly less than E Rb or E K but declined much more sharply in successive samples. (4) Steadystate E Rb and E K decreased with increasing blood flow but maintained a constant ratio. Vasomotion sometimes changed E Rb and E K but had little effect on their ratio. Local anesthetics (procaine or cocaine) brought the ratio of E Rb to E K closer to one. Analysis in terms of capillary and interstitial barriers, which do not discriminate between K, Rb, or Na, in series with a muscle cell membrane barrier, which does, leads to the following conclusions. (1) For K, the nondiscriminating barrier (mainly capillary wall) offeis about 70% of the total resistance to transport and the discriminating barrier (cell membrane) about 30%. (2) For Rb, each barrier offers half the total resistance. (3) The resting muscle cell membrane is 2.5 times more permeable to K than to Rb. Local anesthetics reduce cell permeability to both ions and decrease this ratio. (4) For Na, resistance at the capillary wall is about 1.3 times that for K or Rb. Resistance at the cell membrane is, of course, very much greater. KEY WORDS42 K, 86 Rb, -Na permeability muscular contraction single-injection, multiple-tracer method continuous-infusion method capillary extraction ratio permeability-surface area product procaine cocaine norepinephrine dog gracilis muscle• When blood containing a diffusible substance passes through the capillary bed of a tissue, a certain fraction (E) of the substance is removed and the remainder appears in the venous effluent (1-3). On the basis of a simple

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Effects of hyaluronic acid upon diffusion of solutes and flow of solvent

Cited by 112 publications

References 10 publications

Comparison of IgG diffusion and extracellular matrix composition in rhabdomyosarcomas grown in mice versus in vitro as spheroids reveals the role of host stromal cells

Comparison of IgG diffusion and extracellular matrix composition in rhabdomyosarcomas grown in mice versus in vitro as spheroids reveals the role of host stromal cells

Arterial intimal-medial permeability and coevolving structural responses to defined shear-stress exposures

Capillary, Interstitial, and Cell Membrane Barriers to Blood-Tissue Transport of Potassium and Rubidium in Mammalian Skeletal Muscle

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