Kosuke Seiki

Lipocalin-type prostaglandin D synthase is a powerful biomarker for severity of stable coronary artery disease

Lipocalin-type prostaglandin D synthase (L-PGDS), which is responsible for the biosynthesis of prostaglandin (PG) D(2), has been found to be present in the atherosclerotic plaque of the human coronary artery and also to be detectable in human serum. This multicenter cooperative study was designed to establish the diagnostic value of measuring serum L-PGDS for coronary artery disease. The study included 1013 consecutive patients suspected of having stable coronary artery disease who underwent diagnostic coronary angiography. Peripheral blood was collected prior to angiography. The serum level of L-PGDS, as determined by a sandwich ELISA, was 58.1 +/- 2.2, 62.0 +/- 1.8 and 80.6 +/- 2.6 microg/dl for patients with no stenotic lesion (N, n=241), single-vessel coronary artery disease (S, n=351), and multi-vessel coronary artery disease (M, n=421), respectively (N vs. S; P<0.001, S vs. M; P<0.01, N vs. M; P<0.001). Multiple regression analysis indicated that the most powerful independent predictor of the coronary severity score (Gensini Score) was the L-PGDS level (R=0.55, P<0.0001). The serum L-PGDS level is suitable to evaluate the severity of coronary artery disease. The measurement of serum L-PGDS can be a strategy for screening of stable coronary artery disease prior to coronary angiography.

Lipocalin-type prostaglandin D synthase (beta-trace) in cerebrospinal fluid: a useful marker for the diagnosis of normal pressure hydrocephalus.

Lipocalin-type prostaglandin D synthase (PGDS) is considered to be mainly produced in the leptomeninges and secreted into cerebrospinal fluid (CSF). We found PGDS levels in CSF of patients with normal pressure hydrocephalus (NPH) (8.99+/-2.59 microg/ml, mean+/-S.D., n=14) to be significantly lower than levels in a control (15.29+/-5.17, n=14, P<0.0001) and other dementia group (19.14+/-4.34, n=7, P=0.0003). Thus, PGDS level in CSF is a useful marker for the differential diagnosis of NPH from other diseases with dementia.

Acute and transient increase of lipocalin-type prostaglandin D synthase (β-trace) level in cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage

We measured the concentration of lipocalin-type prostaglandin D synthase (PGDS) in cerebrospinal fluid (CSF) and serum in patients 1, 3, 5, 7, 9, 11, 14 and 17 days after subarachnoid hemorrhage (SAH) due to ruptured cerebral aneurysms. The PGDS level in lumbar CSF increased about two-fold at day 3 (20.85 +/- 2.71 microg/ml, mean +/- SE) and at day 5 (25.24 +/- 3.76), as compared with the level at day 1 (11.25 +/- 1.07). The CSF level gradually decreased and returned to the day 1 level at day 17. The serum PGDS level was much lower than the CSF level (0.39 +/- 0.06 at day 1) and almost unchanged until day 17. The neuron-specific enolase level in CSF, as an index of brain damage, was maximum at day 1 (29.83 +/- 7.32 ng/ml) and decreased at day 3 and at day 5 (18.28 +/- 2.65 and 11.95 +/- 1.82, respectively). These results suggest that the transient and delayed increase in the PGDS level in CSF is due to its induction of PGDS in the arachnoid membrane after SAH.

Unique heparan sulfate from shrimp heads exhibits a strong inhibitory effect on infections by dengue virus and Japanese encephalitis virus

The structure and biological activities of a highly sulfated heparan sulfate (HS) extracted from shrimp (Penaeus brasiliensis) heads were characterized. Structurally the shrimp HS was more heterogenous than heparin, although it is still highly sulfated. The molecular mass of the shrimp HS preparation was determined to be 32.3 kDa by gel filtration HPLC. Analysis by surface plasmon resonance demonstrated that various growth/differentiation factors specifically bound to the shrimp HS with comparable affinity. Notably, the shrimp HS had a greater inhibitory effect against infections by dengue virus type 2 as well as Japanese encephalitis virus than heparin. Experiments on anticoagulant activity indicated that the shrimp HS exhibited significant anti-thrombin activity, but less than the commercial heparin. Hence, the HS preparation from shrimp heads, an industrial waste, is a prospective agent for a variety of clinical applications.