Kiyomi Sadamoto

Quantitative analyses of schizophrenia-associated metabolites in serum: serum D-lactate levels are negatively correlated with gamma-glutamylcysteine in medicated schizophrenia patients.

The serum levels of several metabolites are significantly altered in schizophrenia patients. In this study, we performed a targeted analysis of 34 candidate metabolites in schizophrenia patients (n = 25) and compared them with those in age- and gender-matched healthy subjects (n = 27). Orthogonal partial least square-discriminant analysis revealed that complete separation between controls and patients was achieved based on these metabolites. We found that the levels of γ-glutamylcysteine (γ-GluCys), linoleic acid, arachidonic acid, D-serine, 3-hydroxybutyrate, glutathione (GSH), 5-hydroxytryptamine, threonine, and tyrosine were significantly lower, while D-lactate, tryptophan, kynurenine, and glutamate levels were significantly higher in schizophrenia patients compared to controls. Using receiver operating characteristics (ROC) curve analysis, the sensitivity, specificity, and the area under curve of γ-GluCys, a precursor of GSH, and D-lactate, a terminal metabolite of methylglyoxal, were 88.00%, 81.48%, and 0.8874, and 88.00%, 77.78%, and 0.8415, respectively. In addition, serum levels of D-lactate were negatively correlated with γ-GluCys levels in patients, but not in controls. The present results suggest that oxidative stress-induced damage may be involved in the pathogenesis of schizophrenia.

Organ accumulation in mice after inhalation of single or mixed essential oil compounds.

Essential oils are composed of multiple components. It is thought that the effect of essential oils is due to specific component ratios, which may differ from the original ratio when the essential oil is absorbed. However, very little detailed research exists in this area. We studied the distribution of essential oil components after inhalation of single and mixed components in mice. This research was done using four main components of Alpinia zerumbet (Pers.) B. L. Burtt. and R. M. Sm.: α‐pinene, p‐cymene, 1,8‐cineole, and limonene. After inhalation of single or mixed components for 90 min, component levels in the brain and liver of mice were measured. The results indicated that the amount of α‐pinene in the brain and liver was twofold greater after mixed‐component inhalation than that after single‐component inhalation. In a comparison of the components of the mixed inhalation, the ratio of α‐pinene increased to about three times that of 1,8‐cineole. It is thought that the absorption via the nasal mucus greatly influences this phenomenon. The results of this investigation of the bodily distribution of essential oil volatile components may provide clues for elucidating their action. Copyright

Determination of L-tryptophan and L-kynurenine in Human Serum by using LC-MS after Derivatization with (R)-DBD-PyNCS:

Concentrations of L-tryptophan (L-Trp) and its metabolite, L-kynurenine (L-KYN), in sera of 19 normal subjects (age: 23.6 ± 3.5 y, male: 8, female: 11) were determined by high-performance liquid chromatography with mass-spectrometric detection, following their derivatization with (R)-(–)-4-(N, N-dimethylaminosulfonyl)-7-(3-isothiocyanatopyrrolidin-1-yl)-2,1,3-benzoxadiazole (DBD-PyNCS). A significant positive correlation between L-Trp and L-KYN concentrations was observed (r = 0.532, P < 0.05). Serum L-Trp concentration in male subjects (95.65 ± 4.27 μM) was significantly higher than that in female subjects (79.20 ± 3.34 μM; P < 0.05), while no significant differences in L-KYN concentration or the L-KYN:L-Trp ratio were observed between male and female subjects.

Vagus nerve stimulation induced long-lasting enhancement of synaptic transmission and decreased granule cell discharge in the hippocampal dentate gyrus of urethane-anesthetized rats

Vagus nerve stimulation (VNS) ameliorates deficits of hippocampal functions, such as contextual learning and memory, probably through direct modulation of neuronal activity. Previous studies showed that VNS enhanced excitatory synaptic transmission in the hippocampal CA3 area via activation of β-adrenergic receptors. However, effects of VNS on excitatory synaptic transmission and action potential (AP) discharge of granule cells (GCs) in the dentate gyrus have not been studied. Urethane-anesthetized rats were used to investigate whether VNS influences synaptic transmission efficacy at perforant path-GC synapses and population spike discharge in the dentate gyrus. Intermittent burst stimulation of the left vagus nerve (30Hz for 30s at an inter-train interval of 5min for 1h) significantly enhanced the perforant path-GC synaptic transmission efficacy in the dentate gyrus for at least 2h, indicating that VNS can induce a long-lasting enhancement of synaptic transmission in this area, similar to the situation observed in the CA3 area. In contrast, a 60-min period of VNS significantly reduced population spike amplitude (a parameter reflecting synchronized AP discharge of GCs) for a given excitatory postsynaptic potential. These findings suggest that acute VNS enhances the excitatory synaptic transmission and reduces synchronized AP discharge of GCs in the dentate gyrus. It is likely that enhancement of excitatory synaptic transmission and reduction of GC excitability contribute VNS treatment efficacy for learning deficits and intractable epilepsy, respectively.

Determination of Free Fatty Acids in Human Serum by HPLC with Fluorescence Detection

It has been suggested that serum concentrations of polyunsaturated essential fatty acids correlate with the symptoms or severity of various diseases, including depression and Alzheimer-type dementia, and that determination of serum fatty acids might be important for disease diagnosis. Thus, we developed to analyze serum fatty acids in healthy individuals by using a high-performance liquid chromatography method with fluorescence detection, because free fatty acids have a carboxyl group that can be derivatized with a fluorescent reagent, 4-N,N-dimethylaminosulfonyl-7-N-(2-aminoethyl)amino-2,1,3-benzoxadiazole. This approach could quantify five types of free fatty acids [α-linolenic acid (ALA), palmitoleic acid (PLA), arachidonic acid (AA), linoleic acid (LA) and oleic acid (OA)] in human serum. The detection limits of the method were in the range of 2.29-4.75 fmol (signal-to-noise ratio 3), and absolute concentrations of ALA, PLA, AA, LA and OA were 8.27 ± 1.04, 18.8 ± 2.95, 49.9 ± 4.03, 230 ± 18.1 and 201 ± 22.1 µM, respectively.

HPLC-fluorescence determination of thiol compounds in the serum of human male and female subjects using HILIC-mode column

High-performance liquid chromatography-fluorescence detection using a hydrophilic interaction chromatography-mode column (ZIC®-HILIC) was used to determine four kinds of thiol compounds in human serum. Sera were obtained from 34 subjects for this study (17 male subjects aged 22-38 years and 17 female subjects aged 18-38 years). Serum cysteine, cysteinylglycine, glutathione, and γ-glutamylcysteine, derivatized with ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate, were separated on the ZIC®-HILIC column and quantified. The serum concentrations of cysteine, cysteinylglycine, glutathione and γ-glutamylcysteine were 226 ± 4.7, 23.4 ± 1.3, 3.7 ± 0.2 and 3.2 ± 0.1 μm, respectively. In addition, the concentrations of serum thiol compounds from male subjects were significantly higher than those of the female subjects (p < 0.05).

What is the factor that most influences QOL among rheumatoid arthritis patients

Abstract We attempted to elucidate the factors which affect the quality of life (QOL) among patients with rheumatoid arthritis (RA). Ninety-five patients who satisfied the American Rheumatism Association criteria for RA were asked to fill in a modified arthritis impact measurement scale, version 2 (AIMS2) and complete a Lorishs face scale (FS) test. The same questionnaire and FS test were completed by 75 healthy persons as controls. We used Lorishs FS for our assessment of QOL. The investigation was undertaken to analyze the relationship between FS and each item on the questionnaire. For average FS score, there was no significant difference between the RA group and the controls. However, RA group scores covered a wider range than those of the controls. From the correlation analysis, physical stress, pain factors, and some of the activities of daily living (ADL) factors showed a strong correlation with FS. ADL factors which strongly correlated with FS were those related to activities of the lower limbs. Other ADL factors were moderately correlated with FS. Socioeconomic factors were not significantly correlated with FS. There was no significant difference between the QOL of RA patients and that of healthy controls. The QOL was correlated with pain and stress factors rather than with ADL factors among patients with RA.

Expected Information of Users for the OTC Drugs in Japan

Background: The safety of self medication with OTC (Over the Counter) is of concern since the recent change in selling of OTC drugs in Japan. However, there have been few objectives and subjective evaluations for the safety of OTC drugs in daily use. Method: A questionnaire about OTC drugs was composed, and distributed to users who were first informed about the purpose of the research. Result: The most common item is instruction on the outer box, and instruction on container (bottle) is less than 20%. And less than 30% of users review the package insert. Conclusion: From this study, we recognize that information of outer box is the most common information source for all users.

Thrombotic thrombocytopenic purpura in a patient with a diffuse form of systemic sclerosis

This paper presents a patient with a rapidly progressive diffuse form of systemic sclerosis, in whom a clinical course thrombotic thrombocytopenic purpura (TTP) also developed. In spite of treatment with plasmapheresis, predonisolone, aspirin and vincristine, she died of pulmonary bleeding. From the analysis of four other reported cases of scleroderma with TTP and this case, the outcome of TTP seems to be closely related to clinical manifestations. It is suggested that a diffuse form of scleroderma with interstitional manifestations would develop a worse outcome; on the other hand, a limited form without interstitional manifestations has a successful outcome.

Determination of sex-based differences in serum γ-linoleic acid and dihomo-γ-linoleic acid using gas chromatography–mass spectrometry

Because serum unsaturated fatty acids can provide useful information on disease diagnosis, the simultaneous determination of several fatty acids in small volumes of human serum would be beneficial for clinical applications. In the present study, serum fatty acids were extracted with n-heptane/chloroform from 10μL of serum collected from 26 healthy Japanese subjects (11 men, ages 23-37 years; 15 women, ages 18-37 years) after deproteinization with perchloric acid, derivatization to their methyl ester using p-toluenesulfonic acid as an acid catalyst, and subsequent separation and measurement by gas chromatography-mass spectrometry (GC-MS) in the selected ion monitoring mode. Nine types of fatty acids (palmitoleic acid [PLA], oleic acid [OA], linoleic [corrected] acid [LA], γ-linolenic acid [GLA], α-linolenic acid [ALA], dihomo-GLA [DGLA], arachidonic acid [AA], eicosapentaenoic acid [EPA], and docosahexaenoic acid [DHA]) were analyzed in the serum within 35 min by GC-MS. The concentrations of these fatty acids in serum ranged from 3.64±0.38μM (GLA) to 413±26.3 μM (LA). Among these nine fatty acids, GLA and DGLA levels were significantly lower in women than in men (p=0.0034 and 0.0012, respectively), suggesting that there may be sex-based differences in the biosynthetic production or metabolic processes of GLA and DGLA in humans.