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The inhibitory effect of Zingiber officinale Rosc (ZOR), an Oriental traditional herbal medicine, on the growth of influenza A/Aichi/2/68 (Aichi) virus was investigated in Madin-Darby canine kidney (MDCK) cells. Direct addition of ZOR (0.1 approximately 100 microg/ml) to the infected cells did not have any inhibitory effect. However, the ZOR-induced conditioned medium (ZOR-CM) of RAW cells, a murine macrophage (Mphi) cell line, exhibited an apparent inhibitory effect on MDCK cells without cytotoxicity. In accordance with the time-dependent inhibitory effect of ZOR-CM, it has been demonstrated that tumor necrosis factor (TNF)-alpha was gradually accumulated in ZOR-CM by the induction of TNF-alpha mRNA expression in ZOR-stimulated RAW cells. Conversely, the inhibitory effect of ZOR-CM was reduced significantly by the removal of TNF-alpha after the formation of an immune complex with anti-TNF-alpha monoclonal antibody. These data suggested that ZOR itself has no inhibitory effect on the growth of influenza virus, but could exert its effect via macrophage activation leading to production of TNF-alpha.

We investigated whether milnacipran, a serotonin-noradrenaline reuptake inhibitor, would have therapeutic effect on oxaliplatin-induced mechanical allodynia in mice. A single intraperitoneal injection of oxaliplatin (3 mg/kg) induced mechanical allodynia, which peaked on day 10 after injection and almost completely subsided by day 20. Ten days post-oxaliplatin injection, the intraperitoneal administration of milnacipran (3-30 mg/kg) significantly and dose-dependently inhibited the established mechanical allodynia. Intrathecal injections of milnacipran (2.1-21 µg/site) also significantly and dose-dependently inhibited mechanical allodynia, but intracisternal and intracereboventricular injections at the same doses did not. The present results suggest that milnacipran is effective against oxaliplatin-induced mechanical allodynia and that the antiallodynic effect is mainly mediated by actions on the spinal cord.Key words milnacipran; oxaliplatin; allodynia; intrathecal injection; spinal cord Oxaliplatin, a third-generation platinum-based chemotherapeutic agent, is a key drug for the treatment of colorectal cancer. However, oxaliplatin frequently causes dose-limiting adverse effects such as acute neurotoxicity and chronic peripheral neuropathy.1) The distressing symptoms of peripheral neuropathy include pain and dysesthesia.2) Although the underlying mechanisms of oxaliplatin-induced peripheral neuropathy are not completely understood, it has been reported that oxalate, a metabolite of oxaliplatin, is involved in acute peripheral neurotoxicity, especially cold dysesthesia.3,4) Several drugs, including calcium gluconate/magnesium sulfate, glutathione, carbamazepine, gabapentin, amifostine, acetyl-Lcarnitine, and α-lipoic acid, have been used to manage oxaliplatin-induced peripheral neuropathy. 4,5) Although these drugs are effective against mild neuropathy, oxaliplatin-induced peripheral neuropathy is still difficult to treat. 4,5)We have recently found that goshajinkigan, a traditional herbal medicine, suppresses oxaliplatin-induced mechanical allodynia and that this effect is, in part, mediated by both descending noradrenergic and serotonergic systems. 6)These findings imply that enhancement of descending monoaminergic systems can inhibit established mechanical allodynia. Although amitriptyline, which inhibits the reuptake of noradrenaline and serotonin, 7) has long been used for the treatment of neuropathic symptoms, especially in postherpetic neuralgia and diabetic neuropathy, it does not prevent chemotherapy-induced peripheral neuropathy in humans. 8) In contrast, prophylactic administration of venlafaxine, a serotonin-noradrenaline reuptake inhibitor (SNRI) with high potency in inhibiting serotonin reuptake, 7) has been reported to reduce oxaliplatin-induced acute neurotoxicity including spontaneous dysesthesia and daily pain in humans.9) Prophylactic administration of duloxetine, a balanced SNRI, 7) has also been reported to reduce the severity of pain after 12 weeks of treatment. 10) In this study, we examined...