Processed Bushi powder for ethical dispensing, called TJ-3022, is a herbal drug of processed Aconiti tuber (Aconitum carmichaeli Debeaux) and TJ-3023 is newly developed to contain a higher proportion of diester alkaloid of aconitine (Aconitum carmichaeli Debeaux and Aconitum japonicum Thunberg). Safety of TJ-3022 and TJ-3023 was evaluated by measuring the level of aconitum alkaloids in healthy adult volunteers. Forty subjects were assigned to one of two groups (each 20 subjects): TJ-3022 group or TJ-3023 group. The subjects received the powdered processed Aconiti tuber 3 g/day and the blood concentrations of aconitum alkaloids were measured at 90 min and 72 h after taking the study drug. The serum concentrations of aconitum alkaloids after 90 min and 72 h in the TJ-3023 group were higher than those in the TJ-3022 group. As for the chronological changes in the serum concentration, a significant decrease was observed in the TJ-3022 group, while no significant decrease was seen in the TJ-3023 group, which suggests that an analgesic effect in TJ-3023 was stronger than in TJ-3022. Aconitum alkaloids, which always have been believed to have the blood concentration below the measurement limit in human, were detected for the first time, although the detected amounts were minute. The results suggest that TJ-3023 shows sufficient analgesic effect with smaller dose than TJ-3022.
Oseltamivir (Tamiflu®, Roche Laboratories, Inc.) is a neuraminidase inhibitor that can cause jumpdown behaviors in children. There is a mouse slip-down model, in which the dopamine D2 receptor activity is increased by serum sialoglycolipids and the mouse jump-down behavior appears in response to the dopamine D2 receptor agonist, PPHT. The present study examined the effect of oseltamivir on jump-down behavior in mice. Oseltamivir sialylates a serum glycolipid and this modified glycolipid induces jump-down behavior via the stimulation of dopamine D2 receptors. This mechanism may be involved in the abnormal behavior of children taking oseltamivir.
The current study was undertaken in an attempt to characterize the functional properties of urothelial α1A adrenergic receptors, especially in modulating the micturition reflex. The expression of α1A receptors in rat bladder was analyzed by immunohistochemistry and Western blotting. As a functional study, we obtained continuous infusion cystometrograms in conscious rats using noradrenaline (NA) and subtype selective α1 adrenergic receptor antagonists, tamsulosin (α1A/α1D selective) and silodosin (α1A superselective). α1A receptors were immunohistochemically detected in rat urothelium. Intravesical infusion of NA (60 μM) significantly shortened the intercontraction interval (ICI). Pretreatment with tamsulosin at a dose of 0.4 μg/kg i.v. abolished intravesical NA infusioninduced reduction of ICI. Neither intravesical infusion of tamsulosin (20 μM) nor that of silodosin (0.2 μM) significantly altered ICI. After intravesical infusion of silodosin, intravesical NA infusion did not affect ICI. Urothelial α1A receptors might modulate bladder afferent activity under pathophysiological conditions with augmented concentrations of NA in blood or urine.
Phenomenon of the heart rate variability (HRV) during various meditation techniques has been reported. However, most of these techniques emphasized the skill of slow breathing (< 0.15 Hz). This paper reports our study on HRV during meditation which emphasizes inward attention. Inward attention has been an important approach for the Zen-meditation practitioners to enter into transcendental consciousness. Two groups of subjects were investigated, 10 experimental subjects with Zen-meditation experience and 10 control subjects without any meditation experience. We analyzed HRV both in time and frequency domains. The results revealed both common and different effects on HRV between inward-attention meditation and normal rest. The major difference of effects between two groups were the decrease of LF/HF ratio and LF norm as well as the increase of HF norm, which suggested the benefit of a sympathovagal balance toward parasympathetic activity. Moreover, we observed regular oscillating rhythms of the heart rate when the LF/HF ratio was small under meditation. According to previous studies, regular oscillations of heart rate signal usually appeared in the low-frequency band of HRV under slow breathing. Our findings showed that such regular oscillations could also appear in the high-frequency band of HRV but with smaller amplitude.
Small cell carcinoma of the gallbladder is very rare, but shows high malignant potential with frequent metastasis. Chemotherapeutic regimens for the treatment of gallbladder small cell carcinoma have not yet been established. In this study, we examined in vivo chemosensitivity tests for the GB-04-JCK human gallbladder small cell carcinoma, which were previously established as a serial-transplantable xenograft in nude mice. We used four anticancer drugs: docetaxel, irinotecan, nedaplatine and gemcitabine. Docetaxel maximally suppressed xenograft tumor growth in mice (P < 0.01), and showed complete tumor regression after chemotherapy day 35. Irinotecan and nedaplatine suppressed tumor growth without complete regression (P < 0.01). Gemcitabine did not affect tumor growth significantly. This in vivo experimental study proposed chemotherapeutic regimens for human gallbladder small cell carcinoma.
Excessive nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS) aggravates acute lung injury (ALI) by producing peroxinitrite. We previously showed that the expression of iNOS and lung injury were suppressed by inhalation of a novel iNOS inhibitor, ONO-1714, in mice with Candida-induced ALI, and that nitric oxide produced by iNOS and apoptosis of epithelial cells were found to have a crucial role in Candida-induced ALI. In the present study, we investigated the effect of NO on the apoptosis of alveolar epithelial cells in Candida-induced ALI. Mice were pretreated by inhalation of ONO-1714 or saline (vehicle control of ONO-1714), and were given an intravenous injection of Candida albicans to induce ALI. After 24 h from injection of Candida albicans, we performed bronchoalveolar lavage and removed lung tissues. We assessed apoptosis on the basis of TUNEL staining and caspase 3 activity. Our results showed that apoptosis was suppressed by inhibition of iNOS-derived NO production by ONO-1714 inhalation. The augmented production of NO increased FasL, TNF-α, and mRNA production of Bax of lung that induced apoptosis of alveolar epithelial cells. Inhibition of iNOS-derived NO production by ONO-1714 inhalation ameliorated Candida-induced ALI and improved survival by suppressing apoptosis of alveolar epithelial cells.
Estrogen receptor (ER) α and β and aromatase are expressed in various cell-types and compartments of the penis, including the epidermis of glans penis. Here, we hypothesize that estrogen helps maintain the viability and integrity of glans penis and test the hypothesis by treating lesioned glans penis with either 17β-estradiol or vehicle only. Estrogen was found to facilitate wound healing and increase vascular endothelial growth factor (VEGF) immunoreactivity compared to control, as revealed by scanning electron microscopy, histology, and immunohistochemistry. We conclude that estrogen plays a role in maintaining glans penis integrity, in part, by facilitating penile healing, possibly via up-regulating VEGF levels.