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The painful peripheral neuropathy occurring frequently during chemotherapy with paclitaxel or oxaliplatin is one of their dose-limiting factors. We reported previously that substance P is involved in the pathogenesis of pulmonary hypersensitivity reaction to paclitaxel in rats, and an antiallergic agent pemirolast reverses this reaction via the blockade of release of substance P. In the present study, we investigated the involvement of substance P in paclitaxel-induced peripheral neuropathy compared with that by oxaliplatin. In von Frey and acetone tests in rats repeated administration of paclitaxel (6 mg/kg i.p., once a week for 4 weeks) or oxaliplatin (4 mg/kg i.p., twice a week for 4 weeks) induced both mechanical allodynia and cold hyperalgesia. Paclitaxel-induced peripheral neuropathy was reversed primarily by the acute administration of pemirolast (0.1 and 1 mg/kg p.o.). Moreover, coadministration of the receptor antagonists neurokinin 1 [N-acetyl-l-tryptophan 3,5-bis(trifluoromethyl)benzylester (L-732,138), 100 μg/body i.t.] and neurokinin 2 [5-fluoro-3-[2-[4-methoxy-4-[[(R)-phenylsulphinyl]methyl]-1-piperidinyl]ethyl]-1H-indole (GR159897), 100 μg/body i.t.] strongly reversed paclitaxel-induced neuropathy. On the other hand, oxaliplatin-induced peripheral neuropathy was not reversed by pemirolast. In the in vitro study using cultured adult rat dorsal root ganglion neurons paclitaxel (1000 ng/ml) significantly increased the release of substance P, and pemirolast (100 and 1000 nM) significantly inhibited this increase of substance P release. Oxaliplatin, by contrast, did not increase the release of substance P. These results suggest that substance P is involved in paclitaxel-induced neuropathy, and the mechanism of its action is clearly different from that of oxaliplatin.

In clinical practice, the prediction of changes in blood pressure during hemocatharsis therapy depends on invasive monitoring, the physician's experience, or blood pressure measurement when patients ask for it. It is extremely difficult to predict blood pressure variation in patients under general anesthesia or with disturbance of consciousness. Therefore, the prediction of blood pressure variation during hemocatharsis therapy is an important issue. To address this issue, we invented a new noninvasive continuous blood flow monitor using arteriolar blood flow measurement by laser Doppler flowmetry. Then we examined and determined some extremely important phenomena, including the relationship between rapid blood pressure change and arteriolar blood flow, and failures of the cerebral blood flow autoregulatory mechanism, through measurements in clinical practice of hemodialysis, specific hemocatharsis therapy, and drug monitoring. The results suggest that blood pressure variation during hemocatharsis therapy is highly predictable by arteriolar blood flow measurement. Therefore, this new method for arteriolar blood flow measurement might be widely useful for patients under anesthesia, anesthesia monitoring in neonatal infants and animals (no conversation ability), as well as for hemocatharsis therapy.

This study aimed to evaluate the role of the pharmacist as a member of the liver transplant team in controlling tacrolimus concentrations and the incidence of convulsions as a side effect.Interventions of the pharmacist in the liver transplant team include the indications of dose setting, the checking of drug interactions, the monitoring of adverse effects and the instruction for patient compliance. Fifty-two patients who underwent a living-related liver transplantation were enrolled. The total number of 691 whole blood samples were collected during 2 weeks after liver transplantation and then were analyzed by microparticle enzyme immunoassay (MEIA) for tacrolimus trough concentrations.The standard deviation of tacrolimus trough level was 5.9 before pharmacist participation, while it decreased markedly to 3.7 after pharmacist participation. In addition, the variance significantly decreased. Five of 25 patients treated with tacrolimus before pharmacist participation encountered convulsions, however, none of the 27 patients showed any signs of convulsion after pharmacist participation. There was no significant difference in the rejection before (32 %) or after (26 %) pharmacist participation.We conclude that pharmacotherapy in the liver transplant team improved after pharmacist participation.