Platelet-associated proteins in human breast cyst fluids

Thrombospondin, beta-thromboglobulin and platelet factor 4 were measured by radioimmunoassay in fluids from 50 human breast cysts. beta-Thromboglobulin concentrations were less than 4-330 ng/ml (median 13.5 ng/ml), while normal plasma contained 14-80 ng/ml. Cyst fluids contained 8-225 ng/ml platelet factor 4 with a median of 25 ng/ml (range in plasma 6.5-29 ng/ml). Thrombospondin levels in cyst fluids were 65-55 000 ng/ml (median 2 500 ng/ml) and 92% contained concentrations above the plasma range (58-215 ng/ml). When cyst fluids were classified by their electrolyte composition, group II cysts had similar levels of platelet factor 4 but significantly higher levels of beta-thromboglobulin and thrombospondin than group I. From the remarkably high concentrations of thrombospondin within cyst fluids and the differences between cyst types, it seems that either the protein is synthesised locally or selectively accumulated. Increased platelet activation is unlikely to be the source of the high thrombospondin levels in group II cysts.     

Metabolism of sodium pentosan polysulphate in man measured by a new competitive binding assay for sulphated polysaccharides--comparison with effects upon anticoagulant activity, lipolysis and platelet alpha-granule proteins

Three human volunteers were injected with a range of doses of pentosan polysulphate, SP54, i.v. or s.c. A competitive binding assay (CBA) for sulphated polysaccharides was used to detect circulating SP54 after doses as low as 1 mg i.v. and a linear relationship was observed between the peak plasma concentration of SP54 measured by CBA and the administered dose. A comparison was made between the clearance of SP54 measured by CBA and its anticoagulant and lipolytic activities. SP54 was detectable by CBA after doses which caused no alteration in activated partial thromboplastin time (APTT) or anti-factor Xa activity but after which a small increase of lipase activity was measurable. After SP54 at 10 mg i.v. or 100 mg s.c. anti-factor Xa activity was 4-6 times greater than would be expected from the in vitro activity of the concentrations of SP54 measured by CBA. Like heparin and other heparin analogues, SP54 caused an increase in plasma concentrations of platelet factor 4 (PF4) without a concomitant rise in beta-thromboglobulin (beta-TG). It is concluded that the newly developed CBA will provide a more sensitive means than conventional bioassays for the determination of plasma concentrations of SP54.     

Agonist and antagonist effects of Sar1-ala8--angiotensin II in salt-loaded and salt-depleted normal man.

1 Three normal subjects were infused with Sar1-ala8-angiotensin II (Saralasin, P113) whilst on a high sodium (200 mEq + normal diet) and a low sodium (10 mEq diet) intake. 2 On the high sodium intake when angiotensin II and plasma renin activity (PRA) were suppressed, P113 infusion (5-10 mug kg-1 min-1) caused a slight rise in BP and a marked drop in urine flow and sodium excretion, with a fall in glomerular filtration rate, and effective renal plasma flow. 3 On the low sodium intake, when angiotensin II and PRA were increased, P113 infusion (5-10 mugkg-1 min-1) caused no change in blood pressure, urine flow or sodium excretion. However, when P113 was infused at an incremental rate starting at 0.25 mug kg-1 min-1 there was a fall in standing BP, which was maximal at an infusion rate of 1 mug kg-1 min-1, and this fall in standing BP was largely abolished as the rate of infusion was increased to 10 mug kg-1 min -1. 4 These results show firstly that angiotension II is involved in maintaning standing blood pressure during dietary sodium depletion in normal man and secondly that P113 does have agonist as well as antagonist activity in normal man, the effect depending on the level of angiotension II and sodium intake. When looking for angiotensin II mediated hypertension it may ne important to use an incremental rate of infusion of P113 as the agonist activity of larger doses may mask its hypotensive action.