Preventative effects of 1,3-dimethyl- and 1,3-dimethyl-N-propargyl-1,2,3,4-tetrahydroisoquinoline on MPTP-induced Parkinson's disease-like symptoms in mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is well known as an exogenous dopaminergic neurotoxin that induces Parkinson's disease-like symptoms. In addition, 1,2,3,4-tetrahydroisoquinoline (TIQ) derivatives have been investigated as endogenous MPTP mimetic compounds that structurally resemble selegiline, a commercially available drug for treating Parkinson's disease. In the present study, we examined the ability of 1,3-dimethyl-TIQ (1,3-diMeTIQ) and 1,3-dimethyl-N-propargyl-TIQ (1,3-diMe-N-proTIQ) to prevent MPTP-induced Parkinson's disease-like symptoms in mice and to prevent 1-methyl-4-phenylpyridinium ion (MPP+, an active metabolite of MPTP)-induced cytotoxicity in vitro, including its structural stereoselectivity.

Identification of amino acids in the pore region of Kv1.2 potassium channel that regulate its glycosylation and cell surface expression.

The Kv1.4 potassium channel is reported to exhibit higher cell surface expression than the Kv1.1 potassium channel when expressed as a homomer in cell lines.

The importance of brain PGE2 inhibition versus paw PGE2 inhibition as a mechanism for the separation of analgesic and antipyretic effects of lornoxicam in rats with paw inflammation.

Objectives: Lornoxicam is a non-selective cyclooxygenase inhibitor that exhibits strong analgesic and anti-inflammatory effects but a weak antipyretic effect in rat models. Our aim was to investigate the mechanism of separation of potencies or analgesic and antipyretic effects of lornoxicam in relation to its effect on prostaglandin E2 (PGE2) production in the inflammatory paw and the brain.

Methods: A model of acute or chronic paw inflammation was induced by Freund's complete adjuvant injection into the rat paw.

IgM anti-GQ1b monoclonal antibody inhibits voltage-dependent calcium current in cerebellar granule cells.

Miller-Fisher syndrome (MFS), which is known to be associated with anti-GQ1b antibodies and to cause ataxia, is a variant of an acute inflammatory neuropathy. However, the pathogenic role of anti-GQ1b antibodies remains unclear. In this study, we investigated the effects of mouse IgM anti-GQ1b monoclonal antibody (IgM anti-GQ1b mAb) on the spontaneous muscle action potential of a rat spinal cord-muscle co-culture system and on the voltage-dependent calcium channel (VDCC) current in cerebellar granule cells and Purkinje cells using the whole-cell patch clamp technique.

Effect of beta-phenylethylamine on extracellular concentrations of dopamine in the nucleus accumbens and prefrontal cortex.

It is known that psychostimulants stimulate dopamine transmission in the nucleus accumbens. In the present study, we examined the effects of systemically administered beta-phenylethylamine (beta-PEA), a psychomotor-stimulating trace amine, on dopamine concentrations in the nucleus accumbens and prefrontal cortex in freely moving rats, using an in vivo microdialysis technique. Intraperitoneal administration of beta-PEA (12.

Spontaneous platelet aggregation in normal subject assessed by a laser light scattering method: an attempt at standardization.

Platelet aggregometry by the laser light scattering (LS) method is sufficiently sensitive to detect small platelet aggregates that form spontaneously in vitro in the absence of agonists. Platelet aggregation without agonists is named spontaneous platelet aggregation (SPA). Since SPA has been suggested to be associated with various thrombotic diseases, it is essential to measure SPA and to establish a standard range of SPA values.

Cav2.1 voltage-dependent Ca2+ channel current is inhibited by serum from select patients with Guillain-Barré syndrome.

To investigate the pathophysiological mechanisms of immune-mediated peripheral neuropathies, we studied the effects of sera from patients with Guillain-Barré syndrome (GBS) on the Cav2.1 voltage-dependent calcium channel (VDCC) current in Purkinje cells. Using the whole-cell recording technique, Cav2.

Expression and localization of Kv1 potassium channels in rat dorsal and ventral spinal roots.

We investigated the expression and localization of Kv1 channels in dorsal spinal roots (DRs) and ventral spinal roots (VRs) in rats. Among Kv1.1-1.

In vitro response of immunoregulatory cytokine expression in human monocytic cells to human parvovirus B19 capsid.

Human parvovirus B19 is a clinically important pathogen in both children and adults. In adults, it frequently causes acute and chronic arthritis, which may be related to persistent infection. The effect of the capsid of human parvovirus B19 on monocytes, which are thought to be responsible for the first line of defense against parvoviral infection, is not well understood.

Long-term safety study of iguratimod in patients with rheumatoid arthritis.

We conducted a 52-week clinical study of iguratimod in 394 Japanese patients with rheumatoid arthritis to evaluate the long-term safety of the drug. Iguratimod was administered orally at a daily dose of 25 mg for the first 4 weeks and 50 mg for the subsequent 48 weeks. Some of the patients continued the treatment for 100 weeks for their benefit.

Efficacy and safety of iguratimod compared with placebo and salazosulfapyridine in active rheumatoid arthritis: a controlled, multicenter, double-blind, parallel-group study.

We conducted a 28-week, randomized, double-blind, parallel-group study of iguratimod in 376 Japanese patients with active rheumatoid arthritis to compare the efficacy and safety of the drug with those of placebo and salazosulfapyridine. In the American College of Rheumatology (ACR) 20 response rate, iguratimod was superior to placebo (53.8% versus 17.

Inhibitory effects of methyl brevifolincarboxylate isolated from Phyllanthus niruri L. on platelet aggregation.

A platelet-aggregatory inhibitor was isolated from the 50% MeOH extract of Phyllanthus niruri L. leaf. Its structure was determined to be methyl brevifolincarboxylate on the basis of the 1H-, 13C-NMR, and high-resolution mass spectral data.

IgG anti-GalNAc-GD1a antibody inhibits the voltage-dependent calcium channel currents in PC12 pheochromocytoma cells.

We investigated the effects of IgG anti-GalNAc-GD1a antibodies, produced by immunizing rabbits with GalNAc-GD1a, on the voltage-dependent calcium channel (VDCCs) currents in nerve growth factor (NGF)-differentiated PC12 pheochromocytoma cells. VDCCs currents in NGF-differentiated PC12 cells were recorded using the whole-cell patch-clamp technique. Immunized rabbit serum that had a high titer of anti-GalNAc-GD1a antibodies inhibited the VDCCs currents in the NGF-differentiated PC12 cells (36.

Induction of remission of relapsed acute myeloid leukemia after unrelated donor cord blood transplantation by concomitant low-dose cytarabine and calcitriol in adults.

Low-dose cytarabine and calcitriol (LDCA + VD3) combination therapy was performed in two adult patients with acute myeloid leukemia (AML) that relapsed within 1 yr after unrelated donor cord blood transplantation (URD CBT) performed in a relapse or non-remission stage. Concomitant aclarubicin was also administered in one patient. Remission because of recovery of donor cord blood hematopoiesis was obtained in both patients.

Glycosylation and cell surface expression of Kv1.2 potassium channel are regulated by determinants in the pore region.

Voltage-gated K(+) channels contain six membrane spanning segments and a pore-forming domain. We used site-directed mutation to examine the role of specific amino acids in the extracellular region of the pore in Kv1.2.

Injectable porous hydroxyapatite microparticles as a new carrier for protein and lipophilic drugs.

Hydroxyapatite (Ca10 (PO4)6(OH)2) is a biodegradable material that forms a major component of bones and teeth. We prepared injectable spherical porous hydroxyapatite microparticles (SP-HAp) as a drug carrier by the spray-drying method. We then examined the usefulness of SP-HAp as a carrier for drugs such as interferon alpha (IFNalpha), testosterone enanthate (TE), and cyclosporin A (CyA).

Beta-phenylethylamine stimulates striatal acetylcholine release through activation of the AMPA glutamatergic pathway.

Using an in vivo intra-striatal microdialysis technique, we examined the effects of systemically administered beta-phenylethylamine (beta-PEA), a psychomotor stimulating trace amine, on striatal acetylcholine release in freely moving rats. Infusion of N-methyl-D-aspartic acid (NMDA; 10(-5) M) significantly increased acetylcholine release. In addition, locally applied amino-3-hydroxy-5-methylisozasole-4-propionic acid (AMPA; 10(-5) M) significantly increased acetylcholine release in the striatum.

Adenine, an inhibitor of platelet aggregation, from the leaves of Cassia alata.

Adenine was isolated as a platelet aggregating inhibitor from the leaves of Cassia alata by HPLC using a triacontylsilyl silica (C(30)) column. The inhibitory effects of adenine and adenosine (positive control) on the platelet aggregation induced by collagen or adenosine 5'-diphosphate (ADP) as an aggregating agent was evaluated with a platelet aggregometer using a laser-scattering method. As a result, the inhibitory effect of adenine was observed in the platelet aggregation induced by collagen (1.

[A multicenter cross-sectional study on the health related quality of life of patients with rheumatoid arthritis using a revised Japanese version of the arthritis impact measurement scales version 2 (AIMS 2), focusing on the medical care costs and their associative factors].

Objective: To survey the actual conditions of medical care costs incurred by Japanese patients with rheumatoid arthritis, and to investigate impacts of health status, demographic and socioeconomic factors, clinical and laboratory measures, and medications on disease costs.

Methods: Self-reported health status questionnaires of the revised Japanese version of AIMS 2, and reports on out-of-pocket medical care costs were collected from 1471 patients with classical and definite rheumatoid arthritis recruited through the arthritis study group of Ministry of Public Health and Welfare consisting of eleven arthritis centers across the country during three months from September, 1994. Impacts of health status and other demographic and clinical factors on medical care costs were statistically analyzed by using chi-square tests for categorical variables and Spearman's rank correlation analysis for numerical variables.

Health-related quality of life of unrelated bone marrow donors in Japan.

To promote bone marrow donation, both the safety and well-being of healthy unrelated volunteer donors must be protected. This prospective cohort study evaluated donors' health-related quality of life (HRQOL) and identified factors associated with it. Using the Medical Outcomes Study Short Form 36 Health Survey (SF-36) before bone marrow harvesting (BMH), and again 1 week and 3 months after the donors' discharge, we evaluated HRQOL of 565 donors (329 men, 236 women) registered with the Japan Marrow Donor Program (JMDP).