T Akashi

Tokyo Medical University, Edo, Tōkyō, Japan

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Publications (6)17.3 Total impact

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    ABSTRACT: Myasthenia gravis (MG) is an autoimmune disorder generally mediated by antibodies against the acetylcholine receptors of the skeletal muscles. Depending on the disease burden, MG patients may experience chronic dysregulation of both the hormonal stress axis and the immune system, consequently, aggravating the disease itself but also leading to secondary psychopathological abnormalities. A long-term clinical course requires long-term glucocorticoid (GC) therapy, which may change the psychological state by affecting the pituitary-adrenocortical system in MG patients. In this study, we investigated the function of the pituitary-adrenocortical system in MG patients who were treated with prednisolone (PSL) and evaluated their quality of life by using the Medical Outcomes Study 36-item Short-Form Health Survey and the 28-item general health questionnaire (GHQ-28). ACTH and cortisol levels in the plasma of patients who were treated with PSL (PSL[+] group, n = 18) were lower than those in the plasma of patients who were treated without PSL (PSL[-] group, n = 29; P < 0.05 and P < 0.01, respectively). In the PSL(+) group, we confirmed that cortisol levels negatively correlated with daily PSL dosages (P < 0.05). The anxiety and depression scores from the GHQ-28 in the PSL(+) group were lower than those in the PSL(-) group (P < 0.05, respectively). There was no significant correlation between cortisol levels and corticotropin levels in plasma of the PSL(-) group. However, we confirmed that corticotropin levels positively correlated with cortisol levels in plasma (P < 0.01) and negatively correlated with anxiety/insomnia scores from the GHQ-28 (P < 0.05) in the PSL(+) group. In conclusion, low-dose GC treatment complemented the pituitary-adrenocortical system and improved the psychological state in MG patients.
    Clinical neuropharmacology 01/2012; 35(1):30-6. · 2.35 Impact Factor
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    ABSTRACT: The target blood concentrations of tacrolimus (TAC) and cyclosporine (CYA) during continuous intravenous infusion (C(ss)) have been determined based on clinical experience. However, it is desirable that C(ss) should be set so that the AUC after intravenous infusion is equal to the AUC after oral administration (AUC(po)). Accordingly, we performed 12-hour monitoring of blood concentrations to calculate C(ss) from the blood trough levels (C(TL)) on 15 kidney recipients administered TAC and 12 recipients administered CYA (Neoral). We used an area under the trough level (AUTL) as a new pharmacokinetic parameter. The C(ss) was evaluated from C(TL), AUC(po), and AUTL was calculated to be C(ss) = C(TL) x (AUC(po)/AUTL). In addition, AUTL/AUC(po) ratio and blood peak/trough level ratio (C(max)/C(min)) were examined to compare pharmacokinetics of TAC and CYA. The formula for TAC was C(ss) = C(TL) x 1.40 and that for CYA, C(ss) = C(TL) x 2.55. The calculated target C(ss) of TAC was 1.40 times that of C(TL), which was similar to the present clinical C(TL). In contrast, the calculated target C(ss) of CYA was 2.55 times the C(TL), and therefore an extremely high C(ss) was necessary to obtain a sufficient AUC that will be available after oral administration. Consequently, intravenous administration of CYA twice a day was considered to be more appropriate to obtain sufficient CYA pharmacokinetics, rather than a continuous intravenous administration. We conclude that the formula, C(ss) = C(TL) x (AUC(po)/AUTL) was useful to calculate the target blood concentration of calcineurin inhibitors when changing from continuous intravenous infusion to oral administration of these drugs.
    Transplantation Proceedings 06/2005; 37(4):1725-7. · 0.95 Impact Factor
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    ABSTRACT: We investigated peripheral-blood mononuclear cell (PBMC) response to immunosuppressive drugs and its influence on glucocorticoid therapy in ulcerative colitis (UC). IC50s of immunosuppressive drugs on in vitro blastogenesis of PBMCs stimulated with concanavalin A were estimated in 76 UC and 146 healthy subjects. Individual differences in IC50s for prednisolone, methylprednisolone, cyclosporine, and tacrolimus on blastogenesis of PBMCs from UC patients were spread from 11.0 to 1000, 0.6 to 1000, 0.01 to 1000, and 0.001 to 4.6 ng/ml, respectively. Normal upper thresholds for IC50s of these drugs were estimated from the mean + 2 S.D. of the IC50s of healthy PBMCs, and the patients exhibiting IC50s over these levels were arbitrarily considered as resistant. The incidences of resistance to glucocorticoids and cyclosporine in UC were significantly higher than those in healthy subjects (p < 0.0005). In 14 UC patients, there was a significant correlation between amounts of prednisolone (p < 0.05) or period of prednisolone administration (p < 0.05) for UC treatment and prednisolone IC50. The results showed that large individual deviations in PBMC response to the drugs were observed in UC, and UC patients exhibiting low PBMC sensitivity to prednisolone required a high prednisolone amount as well as long period of prednisolone administration for treatment. Thus, the drug sensitivity tests could be informative to single out refractory patients to the immunosuppressive therapy.
    International Immunopharmacology 08/2002; 2(8):1055-63. · 2.42 Impact Factor
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    ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
    Transplantation 04/2001; 71(5):659-60. · 3.78 Impact Factor
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    ABSTRACT: Cellular pharmacodynamics of cyclosporine (INN, cyclosporin) is considered to be closely implicated in clinical efficacy of the drug in kidney transplantation and other immunologic disorders. We applied this strategy to patients with minimal change nephrotic syndrome to predict individual clinical efficacy of cyclosporine. Drug sensitivity tests were carried out with peripheral blood mononuclear cells from 31 patients with minimal change nephrotic syndrome. The 50% lymphocyte-mitosis inhibition of cyclosporine on in vitro blastogenesis of peripheral blood mononuclear cells stimulated with concanavalin A were estimated, and interpatient variations of 50% lymphocyte-mitosis inhibition were evaluated. The relationship between cyclosporine-50% lymphocyte-mitosis inhibition and clinical outcomes indicated a decrease of urinary protein and the period required for complete remission under cyclosporine therapy was examined in 14 patients. We also evaluated the correlation between cyclosporine-50% lymphocyte-mitosis inhibition and interleukin-2 production and percentages of interleukin 2 receptor-positive peripheral blood mononuclear cells in vitro. Cyclosporine 50% lymphocyte-mitosis inhibition on peripheral blood mononuclear cell blastogenesis deviated largely between patients from 0.2 to 86.0 ng/mL. We found a statistically significant negative correlation between cyclosporine-50% lymphocyte-mitosis inhibition in vitro and decreasing rates of urinary protein at 1 week after onset of cyclosporine administration (r = -0.655, P < .02). When we arbitrarily divide the 14 patients who received cyclosporine therapy according to their median 50% lymphocyte-mitosis inhibition of cyclosporine into two groups, that is, a high-sensitivity group (50% lymphocyte-mitosis inhibition < 18.1 ng/mL, n = 6) and a low-sensitivity group (50% lymphocytemitosis inhibition > 18.1 ng/mL, n = 8), the period required for complete remission was significantly shorter in the high-sensitivity group (P < .03). The 50% lymphocyte-mitosis inhibition of cyclosporine on interleukin-2 production in culture medium was correlated with 50% lymphocyte-mitosis inhibition of the drug on peripheral blood mononuclear cell blastogenesis (r = 0.806, P < .02). Decreasing rates of interleukin-2R-positive cells by cyclosporine treatment in vitro were negatively correlated with peripheral blood mononuclear cells blastogenesis in the presence of the drug (r = -0.694, P < .02). Peripheral blood mononuclear cell response to cyclosporine in vitro is closely related to clinical efficacy of the drug in minimal change nephrotic syndrome. Peripheral blood mononuclear cell resistance to cyclosporine was correlated with ability of the cells to express interleukin 2 and interleukin 2R.
    Clinical Pharmacology &#38 Therapeutics 12/2000; 68(5):532-40. · 6.85 Impact Factor
  • Transplantation Proceedings 03/1998; 30(1):36-9. · 0.95 Impact Factor