Effects of ketamine on nicorandil induced ATP-sensitive potassium channel activity in cell line derived from rat aortic smooth muscle

Purpose : Nicorandil opens adenosine triphosphate-sensitive potassium (KATP) channels in the cardiovascular system and is being increasingly used for the treatment of angina pectoris. In the present study, we tested whether intravenous anesthetic agent ketamine affected nicorandil-induced native vascular KATP channel activation. Methods : We used excised inside-out patch clamp configurations to investigate the direct effects of ketamine racemate and S-(+)-ketamine on the activities of KATP channels in cultured rat aortic smooth muscle cells. Furthermore, we also investigated whether intracellular MgADP could modulate ketamine inhibition. Results : Nicorandil significantly activated KATP channel activity, whereas this channel activity was completely blocked by glibenclamide, a specific KATP channel blocker. Ketamine racemate inhibited the nicorandil induced KATP channel activity (IC50=34 1M, n=14), but S-(+)-ketamine was less potent than ketamine racemate in blocking nicorandil induced KATP channel activities (IC50=226 7M, n=10). Application of MgADP to the intracellular side of the channel was able to decrease the inhibitory potency of ketamine racemate on nicorandil induced KATP channel activities. Conclusions : Our results indicate that ketamine inhibits nicorandil induced KATP channel activities in a dose dependent and stereoselective manner. Furthermore, increase of intracellularMgADP attenuates the inhibitory potency of ketamine racemate

Development of an Ultra-Rapid Diagnostic Method Based on Heart-Type Fatty Acid Binding Protein Levels in the CSF of CJD Patients.

Creutzfeldt-Jakob disease (CJD) is a transmissible, fatal, neurodegenerative disease in humans. Recently, various drugs have been reported to be useful in the treatment of CJD; however, for such treatments to be useful it is essential to rapidly and accurately diagnose CJD. 124 CJD patients and 87 with other diseases causing rapid progressive dementia were examined. Cerebral spinal fluid (CSF) from CJD patients was analyzed by 2D-PAGE and the protein expression pattern was compared with that from healthy subjects. One of three CJD-specific spots was found to be fatty acid binding protein (FABP), and heart-type FABP (H-FABP) was analyzed as a new biochemical marker for CJD. H-FABP ELISA results were compared between CJD patients and patients with other diseases (n = 211). Visual readout accuracy of the Rapicheck((R)) H-FABP test panel for CSF was analyzed using an independent measure of CSF H-FABP concentration. The distribution of H-FABP in the brains of CJD patients was examined by immunohistochemistry. ELISA sensitivity and specificity were 90.3% and 92.9%, respectively, and Rapicheck((R)) H-FABP sensitivity and specificity were 87.9% and 96.0%, respectively. ELISA and Rapicheck((R)) H-FABP assays provided comparable results for 14-3-3 protein and total tau protein. Elevated H-FABP levels were associated with an accumulation of abnormal prion protein, astrocytic gliosis, and neuronal loss in the cerebral cortices of CJD patients. In conclusion, Rapicheck((R)) H-FABP of CSF specimens enabled quick and frequent diagnosis of CJD. H-FABP represents a new biomarker for CJD distinct from 14-3-3 protein and total tau protein.The original publication is available at www.springerlink.co

Clinical, serologic and magnetic resonance imaging of 3 cases of inflammatory myopathy with abundant macrophages in the Japanese population

We report the first 3 cases of inflammatory myopathy with abundant macrophages (IMAM) to be found in an Asian country. Diagnosis of IMAM was based on the infiltration of CD68+ macrophages into biopsied specimens, particularly the fascia. Proximal skeletal muscle symptoms and signs, elevation of creatine kinase, and myogenic changes in electromyography were found in all of the cases, and magnetic resonance imaging clearly revealed thickening of the fascia. Since dermatomyositis (DM)-specific skin alterations were not found, none of the patients in this study fulfilled Bohan and Peter\u27s criteria for DM; however, anti-PL-7 antibody was detected in case number 1. In addition, CD20+ B-cell infiltration into the fascia was also detected in all of the cases, indicating further transition to DM. Severe illness, namely macrophage activation syndrome and acute respiratory distress syndrome, occurred in case 1 but was resolved with intensive combination therapy. The other 2 cases also required glucocorticoids to achieve remission

MM2 cortical form of sporadic Creutzfeldt-Jakob disease without progressive dementia and akinetic mutism : A case deviating from current diagnostic criteria

Sporadic Creutzfeldt-Jakob disease (sCJD) is classified into six types based on codon 129 polymorphism in the PRNP gene and the protease-resistant prion-related protein, PrP [1,2]. This classification corresponds well with the clinical course and the pathological findings. MM2-cortical type sCJD (MM2C-sCJD) is clinically characterized by slow progressive dementia, increased levels of 14-3-3 protein in the cerebrospinal fluid (CSF), and no periodic synchronous discharge (PSD) in electroencephalography [3]. We report the case of a patient presented with chronic progressive cortical symptoms. Based on the initial clinical findings, corticobasal syndrome (CBS) was suspected although he did not develop akinetic mutism during the lifetime. The postmortem pathological and anatomical findings confirmed MM2C-sCJD. As per the existing diagnostic criteria, our case was difficult to diagnose during the patient’s lifetime. Therefore, this is an important case for considering future revisions of the diagnostic criteria for MM2C-sCJD

A Single-Nucleotide Polymorphism of PARK2 Affects the Phenotype in Sporadic Parkinson Disease

Objective: Sporadic Parkinson\u27s disease (PD) is thought to be a complex multifactorial, age-related neurodegenerative disease caused by theinteraction between genetic and environmental factors. Whether PARK2, a major responsible gene causing familial PD, affects to the diseasesusceptibility or the phenotypic variability in sporadic PD remains controversial. In this study, we perform the sequence analysis of PARK2 andassess the correlation between clinical features of sporadic PD patients and the detected variants. Materials and Methods: A total of 92 sporadicPD patients were sequenced and underwent the clinical examinations. MIBG scintigraphy was performed in 61 patients and the cardiacuptake was measured as the heart/mediastinum (H/M) ratio. Results: We only detected two novel variants (R51R, L272I) in 3 patients andthree common polymorphisms, S167N, V380L, and R366W, which had the allele frequencies of 38.6%, 7% and 0.5%, respectively. There wereno significant difference of the allele frequencies between patients and controls. On the evaluation of clinical features, the patients with S167Nhad the younger onsets of age and the tendency of preserved cardiac uptake of MIBG in the early Hoehn and Yahr (HY) stage compared tothe patients without S167N. Conclusions: These results suggest the common polymorphisms of PARK2 might affect the phenotype of sporadicPD without altered susceptibility to PD