| 1. |
- Laurent, Torvald C., et al.
(författare)
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Urinary excretion of hyaluronan in man
- 1987
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - 0036-5513 .- 1502-7686. ; 47:8, s. 793-799
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Tidskriftsartikel (refereegranskat)abstract
- A specific assay for hyaluronan (hyaluronic acid) has been applied to the determination of the polysaccharide in urine. The excretion in 22 healthy subjects was 330 micrograms/24 h (SD 77). The excretion was correlated with body weight and was therefore somewhat higher in males than in females. The molecular weight of the main fraction of urinary hyaluronan was in the range of 4000 to 12,000 in accordance with the hypothesis that it originates from blood and arises by glomerular filtration. A small fraction was of higher molecular weight and could have been produced in the urinary tract. Hyaluronan in male and female urine displayed the same molecular weight distributions. Patients with rheumatoid arthritis and primary biliary cirrhosis showed a two-fold and three-fold increase, respectively, of hyaluronan in urine with concurrently high levels of the polysaccharide in serum. A patient with Werner's syndrome displayed a ten-fold increase of the polysaccharide in both serum and urine.
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| 2. |
- Lebel, L, et al.
(författare)
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Effect of increased hydrostatic pressure on lymphatic elimination of hyaluronan from sheep lung.
- 1988
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Ingår i: Journal of applied physiology. - 8750-7587 .- 1522-1601. ; 64:4, s. 1327-32
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Tidskriftsartikel (refereegranskat)abstract
- The effects of increased hydrostatic pressure on the concentrations of hyaluronan (hyaluronic acid) in lung lymph and serum were investigated in awake sheep with a cannula in the efferent vessel from the caudal mediastinal lymph node. Lung lymph was sampled at base line [left atrial pressure (LAP) 6.5 +/- 1.7 mmHg] and after two increases of LAP to 25.7 +/- 2.2 mmHg (level 1) and 37.0 +/- 5.1 mmHg (level 2). The lung lymph flow increased from 1.9 +/- 0.5 at base line to 9.3 +/- 2.2 and 15.9 +/- 0.7 ml/30 min, and the lymph-to-plasma concentration ratio of total protein decreased from 0.63 +/- 0.02 to 0.32 +/- 0.04 and 0.32 +/- 0.05 at the two elevated levels of LAP, respectively. The hyaluronan concentration in lung lymph was unchanged, and there was a flow-dependent elimination of hyaluronan from the lung that increased from 23 +/- 8 to 87 +/- 19 and 137 +/- 37 micrograms/30 min, respectively. The lung concentration of hyaluronan was 167 +/- 28 micrograms/g fresh lung, and at base line it was calculated that slightly less than 2% of the lung hyaluronan was eliminated by the lymphatic route in 24 h. If extrapolated to 24 h, the elimination rate of hyaluronan seen during elevated LAP would result in lymphatic elimination of 18% of the lung hyaluronan over this time period. Since hyaluronan is responsible for part of the protein exclusion in the extracellular matrix, it is plausible that washout of interstitial hyaluronan contributes to the decrease in albumin exclusion from the interstitium that occurs after an elevation of LAP.
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| 3. |
- Lebel, L, et al.
(författare)
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Increased lymphatic elimination of interstitial hyaluronan during E. coli sepsis in sheep.
- 1989
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Ingår i: American Journal of Physiology. - 0002-9513 .- 2163-5773. ; 256:6 Pt 2, s. H1524-31
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Tidskriftsartikel (refereegranskat)abstract
- The effect of septicemia on the elimination of hyaluronan (HA) from the lung interstitium was investigated in awake sheep with chronic lung lymph and thoracic duct fistulas. The result was compared with that after elevation of left atrial pressure (LAP). Lymph was sampled before and after a 20-min infusion of Escherichia coli (10(9) bacteria/kg body wt.), after elevation of LAP, or both. Infusion of E. coli caused an increased flux of HA in lung lymph and thoracic duct lymph. After an elevation of LAP, the HA flux in lung lymph was increased to a comparable extent. In animals subjected to an increase in LAP and subsequently to infusion of E. coli, no additive effect on HA flux was seen. The weight-average molecular weight of HA in lung lymph was increased both after sepsis and after elevation of LAP. The findings show that sepsis and elevated transvascular hydrostatic pressure result in increased mobilization of HA from the interstitium. This might partly explain the increased HA concentrations in plasma in clinical sepsis and may also lead to a change in the characteristics of the interstitial matrix in this condition.
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| 4. |
- Lebel, L, et al.
(författare)
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A pharmacokinetic model of intravenously administered hyaluronan in sheep.
- 1989
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Ingår i: Pharmaceutical research. - 0724-8741 .- 1573-904X. ; 6:8, s. 677-82
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Tidskriftsartikel (refereegranskat)abstract
- Hyaluronan (HA: hyaluronic acid) is produced in the interstitium and reaches the blood circulation through the lymph. It is rapidly eliminated by means of specific receptors on liver endothelium. The elimination characteristics of intravenously administered HA were studied in 10 conscious sheep at the normal plasma HA concentration by injection of a 3H-labeled tracer and at a very high concentration by an i.v. infusion of unlabeled HA and simultaneous injection of a tracer dose of 3H-labeled HA. At a normal plasma HA concentration (0.12 +/- 0.05 microgram/ml; range, 0.072-0.228 microgram/ml), the apparent T 1/2 of 3H-HA was 5.3 +/- 1.1 min (range, 3.3-6.5 min). At higher plasma concentrations (range, 1.83-3.35 micrograms/ml), the apparent T 1/2 was considerably prolonged (range, 18.2-43.5 min). A one-compartment, nonlinear model was fitted to data obtained from the bolus-infusion study of unlabeled HA. The Michaelis-Menten constant, Km, was 0.12 +/- 0.04 microgram/ml, indicating that a deviation from linear kinetics will occur when the normal plasma concentration is exceeded. The Vmax was 0.062 +/- 0.009 microgram/ml/min. Three-dimensional surface plots showed that the plasma HA concentration and the total hepatic plasma flow influence the apparent metabolic clearance, extraction ratio, turnover, and T 1/2 of intravenously injected hyaluronan. There was a high correlation between T 1/2 as measured by the injected 3H-HA and T 1/2 calculated from the model (r = 0.96).
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