Plasma concentrations of 6-keto-prostaglandin F1 alpha in patients with hypertension, cerebrovascular disease or Takayasu's arteritis

The peripheral venous plasma levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were determined by radioimmunoassay in 23 control subjects, 14 patients with essential hypertension, 19 patients with cerebrovascular disease (CVD) not taking aspirin, 12 patients with DVD taking aspirin, and 12 patients with Takayasu's arteritis. There was no significant difference in 6-keto-PGF1 alpha levels between the control subjects and hypertensive patients. In CVD patients and patients with Takayasu's arteritis, the plasma 6-keto-PGF1 alpha levels were significantly lower than those in control subjects. The internal jugular venous and femoral arterial plasma levels of 6-keto-PGF1 alpha and thromboxane B2 (TxB2) were measured in 10 CVD patients not taking aspirin. The patients with occlusive lesions of major arteries exhibited higher TxB2/6-keto-PGF1 alpha ratios in the internal jugular venous plasma.     

The effect of a thromboxane synthetase inhibitor, OKY-046, on urinary excretion of immunoreactive thromboxane B2 and 6-keto-prostaglandin F1 alpha in patients with ischemic cerebrovascular disease

Thromboxane synthetase activity is selectively inhibited by (E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate (OKY-046). A single dose of 100 mg OKY-046 was orally administered to patients with ischemic cerebrovascular disease and healthy volunteers. Platelet aggregation and thromboxane B2 (TXB2) generation of intact and homogenised platelets induced by 1.0 mM sodium arachidonate were measured before and at 1, 4, 6 and 8 h after dosing. OKY-046 inhibited arachidonate-induced aggregation in platelet rich plasma from some, but not all, individuals, whereas platelet TXB2 generation was almost completely inhibited by a single dose of 100 mg OKY-046, in all of the patients and healthy volunteers. Endogenous TXA2 and prostacyclin (PGI2) biosynthesis were assessed by measurement of urinary immunoreactive TXB2 (i-TXB2) and 6-keto-PGF1 alpha (i-6-keto-PGF1 alpha) before and at 0-3, 3-6, 6-9 h after dosing. OKY-046 increased the urinary i-6-keto-PGF1 alpha coincidently with a decrease of urinary i-TXB2, both in patients and healthy volunteers. These effects of a selective thromboxane synthetase inhibitor will improve a disturbed balance between TXA2 and PGI2, associated with the development of ischemic cerebrovascular disease.     

Establishment and characterization of a new erythroblastic leukemia cell line, EEB: phosphatidylglucoside-mediated erythroid differentiation and apoptosis

A new erythroblastic leukemia cell line (EEB) was established from a patient with early erythroblastic leukemia. The cells had features of immature erythroblasts, including an agranular basophilic cytoplasm and CD36, CD71, CD175s (sialyl-Tn) and CD235a (glycophorin A) expression without CD41 expression, myeloperoxidase activity and platelet-peroxidase activity. The cells were confirmed to be of the erythroid lineage based on expression of the gamma-globin message. They were induced to differentiate into benzidine-positive cells by hemin and delta-amino levulinic acid (delta-ALA). An analysis of cell membrane lipids showed that EEB cells contain a type of glycerolipid, phosphatidylglucose (PhGlc), but not unbranched type 2 chains, i antigens. GL-7 which is a recombinant Fab fragment of GL-2 and binds to PhGlc, induced production of hemoglobin F (HbF) associated with accumulation of the gamma-globin (gamma-globin) message in EEB cells. The GL-7-mediated erythroid differentiation was associated with apoptosis. These results suggest that direct signaling to PhGlc mediates erythroid differentiation and apoptosis in EEB cells.     

A new approach to antithrombotic therapy--evaluation of combined therapy of thromboxane synthetase inhibitor and very low dose of aspirin

The effect of a selective thromboxane (TX) synthetase inhibitor (OKY-046), alone and in combination with a very low dose of aspirin, on the platelet function was studied in healthy and diseased subjects. A single dose of 100 mg OKY-046 was orally administered to patients with ischemic cerebrovascular disease (CVD) and healthy volunteers. TXB2 generation and platelet aggregation were measured before and at 1, 4, 6 and 8hr after dosing. In addition, after the administration of a very low dose of aspirin (0.1-0.25 mg/kg/day) for at least one month, a single dose of OKY-046 was given to CVD patients. TXB2 generation and platelet aggregation were measured in the same manner as OKY-046 alone. The effect of OKY-046 on platelet aggregation induced by arachidonic acid (AA) was different in each subject whereas platelet TXB2 generation was almost completely inhibited in all of the patients and healthy volunteers. OKY-046 had a slight inhibitory effect on collagen induced aggregation. A combination of OKY-046 with a very low dose of aspirin, on the other hand, produced additional inhibition of the platelet aggregation induced by both AA and collagen. The present results suggest that the accumulation and metabolism of cyclooxygenase products that accumulate when TX synthetase is blocked, differ in each subject, additional inhibition is caused by the combined use of TX synthetase inhibitor and a very low dose of aspirin because the very low dose of aspirin partially reduces the proaggregatory cyclooxygenase products that accumulate when TX synthetase is blocked.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo effect of fluoride-substituted apatite on rat bone

Different types of calcium phosphate compounds are commercially available for medical and dental applications as bone substitute materials. Biological apatites contain several kinds of minor elements such as carbonate (CO3), magnesium (Mg), and fluoride (F) in enamel, dentin, and bone. It has been shown that F ion and F-substituted apatite promoted osteoblast proliferation and inhibited osteoclast cell activity. The purpose of this study was to investigate the in vivo rat tibia activity on F-substituted apatite (FAp). Apatites of unsintered calcium deficient apatite (CDA), and FAps, with low, medium, and high F concentrations, were implanted in rat tibia for 1 and 2 weeks. Implanted tissues were embedded in paraffin blocks, stained with hematoxylin-eosin and histomorphometrically observed. Results showed that low F concentration induced better and faster new bone formation in vivo compared to CDA. Therefore the results suggested that F as a minor element in bone rendered a suitable effect on bone formation in vivo.