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Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disorder characterized by eosinophilic hyaline inclusions in neuronal and somatic cells on histopathologic examination.1,2NIID occurs in both sporadic and hereditary forms, and shows various clinical manifestations, including dementia and cerebellar ataxia.3NIID is a rare disease, and can be difficult to distinguish from other leukoencephalopathies. Several recent case reports have described NIID following the description of pathognomonic MRI and skin biopsy findings of NIID.4The time points at which the eosinophilic intranuclear inclusions of NIID may form and be detectable in CNS and systemic organs remain to be elucidated. We present a case of sporadic NIID demonstrating eosinophilic intranuclear inclusions in a renal biopsy obtained 12 years preceding diagnosis.

We examined pharmacological profiles of KT3–671, 2-propyl-8-oxo-l-[(2‘-(lH-tetrazole-5-yl) biphe-nyl-4-yl)methyl]-4,5,6,7-tetrahydro-cycloheptimidazole, a newly synthesized nonpeptide angiotensin II (AII) receptor antagonist in various in vitro and in vivo studies. KT3–671 displaced specific binding of [125I]Sar1Ile8-AII to AT1receptor with a Kivalue of 0.71 ± 0.14 x 10-9Min rat liver membranes, but had no affinity for AT2receptor in bovine cerebellar membranes (Ki> 10-5M). In isolated rabbit aorta, KT3–671 produced a parallel right-ward shift in the concentration-response curve for AH with a pA2value of 10.04 ± 0.12, but had no effect on K.CI-, norepinephrine (NE)-, and serotonin (5-HT)-induced contractions. In conscious normotensive rats, KT3–671 (0.3–10 mg/kg, p.o.) inhibited the All-induced pressor response dose dependently. In renal arteryligated hypertensive rats, KT3–671 (0.1–3 mg/kg, p.o.) decreased arterial blood pressure (BP) dose dependently. The hypotensive action of 3 mg/kg KT3–671 was maintained for at least 24 h. These results suggest that KT3–671 is a potent AT1subtype-selective and competitive nonpeptide AII receptor antagonist and has an orally active antihypertensive effect without agonistic activity.

Pharmacologic properties of KT2–962 (6-iso-propyl-3-[4-(p-chlorobenzenesulfonylamino)butyl]-azu-lene-1-sulfonic acid sodium salt, KT) were studied in isolated rat aorta, rat tail artery, rabbit aorta, rabbit renal artery, and pig coronary artery. KT competitively inhibited the contractions induced by thromboxane A2(TXA2) mimetic, U46619 (pA2values 9.95, 8.85, 7.87, 8.49, and 9.12, respectively). KT also inhibited the contraction of rabbit aorta induced by prostaglandin2α, (PGF2α, pA2value 7.85) and the contraction of guinea pig ileum induced by LTD4(pA2value 5.48) but did not alter the contractions induced by norepinephrine (NE). Ca2+, serotonin, and histamine. KT did not alter the contractions of guinea pig ileum, which did not contract with U46619, induced by PGE2and PGF2α, KT inhibited the aggregations of rabbit platelets induced by U46619, arachidonic acid, and collagen (IC50values 7.9, 140, and 16 μM, respectively) but not those induced by ADP. It also inhibited the specific binding of TXA2/PGH2receptor antagonist, [3H]SQ29,548, to rabbit gel-filtered platelets with an IC50value of 1.5 × 10-8M.In in vivo experiments with mice, oral administration of KT protected the U46619-induced sudden death with the minimum effective dose of 0.3 mg/kg and provided such protection for ≥8 h at 1.0 mg/kg. These results indicate that KT is a new nonpros-tanoid type TXA2/PGH2receptor antagonist that is orally effective and long acting.