Role of K+ channels in N-acetylprocainamide-induced relaxation of bovine tracheal smooth muscle

We examined the relaxant effects of N-acetylprocainamide, the major hepatic metabolite of procainamide, on bovine tracheal smooth muscle, focusing on the possible involvement of K+ channels. N-acetylprocainamide produced a concentration-dependent and full inhibition of the tension development elicited by methacholine (0.3 or 1 microM). The potency of N-acetylprocainamide in diminishing methacholine-elicited tension development was one-half of that of procainamide. By comparison, N-acetylprocainamide inhibited high-K+ (40 mM)-induced contraction more potently than procainamide though both inhibitions were largely reduced when compared to those against methacholine-induced contraction. Iberiotoxin (30 nM), Ba(2+) (1 mM) or a combination of both agents significantly attenuated the relaxant effect of N-acetylprocainamide on methacholine-induced contraction, whereas apamin (100 nM), 4-aminopyridine (300 microM), and glibenclamide (10 microM) did not affect it. These results suggest that N-acetylprocainamide, similar to procainamide, elicits tracheal smooth muscle relaxation mainly through the activation of plasma membrane K+ channels.     

Pharmacological properties of excitation-contraction mechanisms in isolated mouse left atria

Effects of 4-aminopyridine (4-AP), nicardipine and ryanodine on the action potential and contractile force were examined in isolated mouse left atria. The mouse left atria had an action potential with an extremely short duration and two phases of repolarization; action potential duration at 50% repolarization was 6.7 +/- 0.4 ms (n = 15). The action potential duration, as well as contractile force, was increased by 4-AP (at 100 micromol/l and 1 mmol/l). Nicardipine (3 micromol/l), which is known to greatly reduce the contractile force in atria of most other experimental animal species, had no significant effect on the action potential and decreased contractile force by only 40% in mouse atria. Ryanodine (10 nmol/l) decreased the contractile force by 90% of basal value. At 100 nmol/l, ryanodine slightly affected the action potential configuration, which could be explained by indirect effects through inhibition of Ca(2+) release from the sarcoplasmic reticulum. The extremely short action potential duration and the highly sarcoplasmic reticulum-dependent contraction of the mouse atria appear to underlie its unique response to agonists.     

Utility of (99m)Tc-HM-PAO SPECT hippocampal image to diagnose early stages of Alzheimer's disease using semiquantitative analysis

OBJECTIVE: Examination of the utility of (99m)Tc-hexamethylpropylene amine oxide ((99m)Tc-HM-PAO) SPECT hippocampal image to diagnose early stages of Alzheimer's disease (AD) using semiquantitative analysis. SUBJECTS: 10 early-stage AD patients and 8 normal sex-matched elderly controls. SETTING: Outpatient division of the Ehime University Hospital. METHOD: We performed (99m)Tc-HM-PAO SPECT perfusion imaging in each subject. A semiquantitative method of assessing regional variation was used. The regions of interest for temporal regions were set at images parallel to the long axis of the hippocampal formation which were reconstructed at 30 degrees negative to the orbitomeatal line and those for other regions were set on ordinary transaxial images. RESULTS: The regional cerebral blood flow ratio of the bilateral medial temporal lobe at the hippocampal image was significantly lower in the AD subjects than in the normally aged controls without any other differences in ordinary transaxial images. CONCLUSION: This study suggests that (99m)Tc-HM-PAO SPECT hippocampal images might be a helpful tool for the diagnosis of very-early-stage AD.     

ZTTA,a Prolyl Endopeptidase Inhibitor,Potentiates the Arginine-Vasopressin-Induced Incorporation of [14C]Leucine in Rat Amygdaloid and Cortical Slices

Pharmaceutical Research -     

Interferon-alpha and dexamethasone inhibit adhesion of T cells to endothelial cells and synovial cells

We investigated whether interferon-gamma (IFN-gamma), interferon-alpha (IFN-alpha) and glucocorticoids affected the adhesion of T cells to human umbilical endothelial cells or human synovial cells. About 30% of peripheral blood T cells could bind to unstimulated endothelial cells, but only a few T cells could bind to unstimulated synovial cells. When both endothelial cells and synovial cells were cultured with recombinant IFN-gamma (rIFN-gamma), the percentage of T cell binding to both types of cells increased in a dose-dependent manner. rIFN-alpha and dexamethasone blocked the T cell binding to unstimulated endothelial cells. Furthermore, rIFN-alpha and dexamethasone suppressed T cell binding to both endothelial cells and synovial cells stimulated by IFN-gamma, and also inhibited intercellular adhesion molecule-1 (ICAM-1) expression on both endothelial cells and synovial cells stimulated by IFN-gamma. These results suggest that IFN-alpha and glucocorticoids may inhibit T cell binding to endothelial cells or synovial cells by modulating adhesion molecule expression on these cells.     

New lanostanoids, elfvingic acids A-H, from the fruit body of Elfvingia applanata

Eight new lanostanoids, 12alpha,15beta-dihydroxy-3,7,11,23-tetraoxolanost-8,(20Z)(22)-dien-26-oic acid (1), 7beta,8beta-epoxy-15beta,20S-dihydroxy-3,12,23-trioxolanost-9(11),16-dien-26-oic acid (2), 7beta,8beta-epoxy-3beta,15beta,20S-trihydroxy-12,23-dioxolanost-9(11),16-dien-26-oic acid (3), 7beta,8beta-epoxy-2alpha,3beta,15beta,20S-tetrahydroxy-12,23-dioxolanost-9(11),16-dien-26-oic acid (4), 7beta,8beta-epoxy-3beta,15beta,20S,28-tetrahydroxy-12,23-dioxolanost-9(11),16-dien-26-oic acid (5), 7beta,8beta-epoxy-3beta,15beta,19,20S-tetrahydroxy-12,23-dioxolanost-9(11),16-dien-26-oic acid (6), 8beta,15beta,20S-trihydroxy-3,7,12,23-tetraoxolanost-9(11),16-dien-26-oic acid (7), 7alpha,8alpha-epoxy-15beta,23xi-dihydroxy-12-oxo-3,4-secolanost-4(28),9(11),(20Z)(22)-trien-3,26-dioic acid (8), and the methyl ester of 8 (8a) were isolated from the fruit bodies of Elfvingia applanata. Their structures were established primarily by NMR experiments, and their biological activity against Kato III and Ehlrich cells was investigated.     

Increased prevalence of vascular dementia in Japan: a community-based epidemiological study

BACKGROUND AND OBJECTIVE: It has been suggested that there is a major difference in the ratio of AD to vascular dementia (VaD) between Japan and Western countries. To determine the type-specific prevalence of dementia in community-dwelling elderly from the Japanese community of Nakayama, all patients with dementing illness underwent a CT scan. METHODS: A door-to-door three-phase population survey was carried out on all persons aged 65 years and older residing at home on the prevalence day (January 1, 1997). The ascertainment of cases was made between January 1997 and March 1998. The study included a psychiatric interview; physical, neurologic, and neuropsychologic examinations; comprehensive laboratory tests; and cranial CT. A public health nurse also interviewed a person close to each subject. Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, third edition-revised, criteria, AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association, and VaD according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition, combined with information from the patient's neurologic history and CT scanning. RESULTS: Of 1438 inhabitants, 1162 (81.0%) completed the protocol. The prevalence of dementia was 4.8%. Of the 60 subjects with dementia, 35% had AD, 47% had VaD, and 17% had dementia resulting from other causes. CONCLUSIONS: The prevalence of dementia was similar to previous reports, but, contrary to results of virtually all studies conducted in developed countries and those recently conducted in Japan, almost half of the cases in the present study appeared to have VaD with neuroradiologic confirmation.