Boron tracedrugs challenge for neutron dynamic therapy

In this short review we describe our innovative boron tracedrugs and drugs for neutron dynamic therapy (NDT), as a newly emerging challenge beyond conventional drug treatments.     

Moxibustion at mingmen reduces inflammation and decreases IL-6 in a collagen-induced arthritis mouse model

The purpose of this study was to compare the effectiveness of moxibustion (MOX) treatment at the GV4 and CV12 acupoints, and to determine the correlations between MOX treatment and interleukin (IL)-6 and corticosterone levels in a collagen-induced arthritis (CIA) mouse model. CIA mice were immunized twice intradermally over a 3-week interval with bovine type II collagen. After the second immunization (day 21), MOX was applied to the mouse equivalent of the GV4 and CV12 acupoints with a 1mg moxa cone five times/day. Clinical symptoms of CIA were observed three times/week until day 35. The concentrations of IL-6 and corticosterone in the blood samples were measured by immunoassay kits. At day 35, the incidence of CIA was significantly decreased in mice treated with MOX at the GV4 acupoint (78%, n=23, p<0.05), compared to untreated CIA mice (100%) and mice treated with MOX at the CV12 acupoint (100%). IL-6 and corticosterone levels were significantly increased by immunization. IL-6 levels significantly decreased in mice treated with MOX at the GV4 acupoint. These results suggest that MOX treatment suppressed CIA at the GV4 acupoint, not at the CV12 acupoint, possibly through inhibition of IL-6 production.     

Proposal for Japanese encephalitis surveillance using captured invasive mongooses under an eradication project on Okinawa Island, Japan

A project to eradicate invasive small Asian mongooses (Herpestes javanicus) is underway to conserve the unique ecosystem of Okinawa Island, Japan. In the present study, we tried to elucidate whether the mongoose is a host of Japanese encephalitis virus (JEV) and to evaluate the reliability of surveillance of Japanese encephalitis (JE) using this species. Culex tritaeniorhynchus, the main vector mosquito of JEV, feeds on the mongoose. Eighty-five (35.4%) of 240 wild small Asian mongooses captured between 2001 and 2005 had neutralizing antibodies against more than one of four JEV strains. Prevalence rates of JEV antibodies tended to increase with body weight and length of the animals. One of three sentinel mongooses showed a temporal change in antibody titer. These results indicate that the small Asian mongooses on Okinawa Island are sensitive to JEV. From the antibody titers and the locations of capture, the JEV active area was clarified. We propose that surveillance of JE using mongooses captured under the eradication program is reliable.     

Lip Morphology Changes Following Orthognathic Surgery for Class III Malocclusion

Objectives:To test the hypothesis that there is no difference in the morphology of the lips and to determine the degree of improvement in the smile after orthognathic surgery for Class III malocclusion.Materials and Methods:The sample subjects included 30 adult female patients with dento-skeletal Class III malocclusion and 28 adult female volunteers with normal occlusion. Frontal facial photographs were taken before and after treatment, and 35 landmarks were placed on each tracing made from the frontal facial photograph. Thereafter, the landmarks were digitized into an x and y coordinate system with the subnasal point as the origin. The pretreatment rest and smile conditions were compared with the posttreatment conditions, respectively, using paired t-tests. In addition, two sample t-tests were used to test for differences between groups.Results:Both the upper and lower lips in the smiles of the Class III pretreatment group were positioned downward, and the upward movement of the upper lip and commissure points were smaller compared with the control group. When smiling, the horizontal direction of the mouth corners was statistically significantly different between the pretreatment and posttreatment conditions, whereas these were wider in the posttreatment than in the pretreatment conditions. These characteristics of the Class III smile improved after orthognathic treatment, but the differences with the control group remained unchanged immediately after treatment.Conclusion:The hypothesis is rejected. The soft tissue morphology of patients with dento-skeletal Class III malocclusion shows a significant improvement after orthognathic surgery.     

A novel steroidal selective steroid sulfatase inhibitor KW-2581 inhibits sulfated-estrogen dependent growth of breast cancer cells in vitro and in animal models

We screened a series of 17β-(N-alkylcarbamoyl)-estra-1,3,5(10)trine-3-O-sulfamate derivatives, and describe here a potent and selective steroid sulfatase (STS) inhibitor with antitumor effects in breast cancer models in vitro and in vivo. In biochemical assays using crude enzymes isolated from recombinant Chinese hamster ovary cells expressing human arylsulfatses (ARSs), one of the best compounds, KW-2581, inhibited STS activity with an IC₅₀ of 4.0 nM, while > 1000-fold higher concentrations were required to inhibit the other ARSs. The failure to stimulate the growth of MCF-7 human breast cancer cells as well as in uteri in ovariectomized rats indicated the lack of estrogenicity of this compound. In MCF-7 cells transfected with the STS gene, termed MCS-2 cells, KW-2581 inhibited the growth of cells stimulated by estrone sulfate (E1S) but also 5-androstene-3β, 17β-diol 3-sulfate (ADIOLS) and dehydroepiandrostenedione 3-sulfate. We found that oral administration of KW-2581 inhibited both E1S- and ADIOLS-stimulated growth of MCS-2 cells in a mouse hollow fiber model. In a nitrosomethylurea-induced rat mammary tumor model, KW-2581 induced regression of E1S-stimulated tumor growth as effectively as tamoxifen or another STS inhibitor, 667 Coumate. Dose-response studies in the same rat model demonstrated that more than 90% inhibition of STS activity in tumors was necessary to induce tumor shrinkage. STS activity in tumors has well correlated with that in leukocytes, suggesting that STS activity in leukocytes could be used as an easily detectable pharmacodynamic marker. These findings demonstrate that KW-2581 is a candidate for development as a therapeutic agent for the treatment of hormone receptors-positive breast cancer.