Use of a Caco-2 permeability assay to evaluate the effects of several Kampo medicines on the drug transporter P-glycoprotein

In modern medical care in which Kampo and Western drugs are often combined, it is extremely important to clarify drug–drug interaction (DDI) to ensure safety and efficacy. However, there is little evidence of DDI in Kampo medicines. Therefore, as part of our studies to clarify the DDI risk for Kampo medicines, we evaluated the effects of five Kampo medicines [yokukansan (YKS), rikkunshito (RKT), shakuyakukanzoto (SKT), hangeshashinto (HST), and goshajinkigan (GJG)] that are widely used in Japan, on drug transporter P-glycoprotein (P-gp) using a Caco-2 permeability assay. These Kampo medicines inhibited the P-gp transport of digoxin through a Caco-2 cell monolayer. The IC50 values were 1.94–10.80 mg/ml. Of the five Kampo medicines, YKS showed the strongest inhibition (IC50 = 1.94 mg/ml), which was attributed to Uncariae Uncis Cum Ramulus. Unfortunately, we could not find the active ingredients responsible for its action. Finally, the Igut/IC50 values for the five Kampo medicines were calculated, and the DDI risk was objectively evaluated according to the criteria in the DDI guidance issued by the Japanese Ministry of Health, Labor, and Welfare and the US Food and Drug Administration. The Igut/IC50 values for the five Kampo medicines were ≤3.4. As these values were <10, they were evaluated as having a weak P-gp inhibitory effect that does not require further verification in humans, suggesting that the DDI risk due to P-gp inhibition for these Kampo medicines is low. The results should provide useful clinical information on the safety and efficacy of the combined use of Kampo and Western medicines

Wiping Movement with Paper after the Excretion : A Comparative Study between the Physically Unimpaired and Post-Stroke Hemiplegic Patients

The purpose of this study is to clarify the difference between patients with cerebrovascular accident hemiplegia (CVA) and healthy volunteers in wiping movement after excretion. The authors analyzed the movement of defecation by observation and questionnaire. The results show that there were six types of wiping movement in healthy volunteers. There was a significant difference in wiping types between healthy volunteers and CVA. Most CVA wiped with paper after excretion, in the sitting position from the front, while there were a variety of types among healthy volunteers. Moreover, there was a gender difference in wiping movement; the male wiped from the back whereas the female had the tendency to wipe from the front. It was infered that this difference was the influence of external genitals. It was suggested that it is necessary to consider the type of wiping before the onset of CVA of each patient when an occupational therapist perform the training operation of defecation for the CVA

Nematode-Applied Technology for Human Tumor Microenvironment Research and Development

Nematodes, such as Caenorhabditis elegans, have been instrumental to the study of cancer. Recently, their significance as powerful cancer biodiagnostic tools has emerged, but also for mechanism analysis and drug discovery. It is expected that nematode-applied technology will facilitate research and development on the human tumor microenvironment. In the history of cancer re-search, which has been spurred by numerous discoveries since the last century, nematodes have been important model organisms for the discovery of cancer microenvironment. First, microRNAs (miRNAs), which are noncoding small RNAs that exert various functions to control cell differentia-tion, were first discovered in C. elegans and have been actively incorporated into cancer research, especially in the study of cancer genome defects. Second, the excellent sense of smell of nematodes has been applied to the diagnosis of diseases, especially refractory tumors, such as human pancreatic cancer, by sensing complex volatile compounds derived from heterogeneous cancer microenvi-ronment, which are difficult to analyze using ordinary analytical methods. Third, a nematode model system can help evaluate invadosomes, the phenomenon of cell invasion by direct observation, which has provided a new direction for cancer research by contributing to the elucidation of complex cell–cell communications. In this cutting-edge review, we highlight milestones in cancer research history and, from a unique viewpoint, focus on recent information on the contributions of nematodes in cancer research towards precision medicine in humans