In August 2013, the Pharmaceutical Society of Japan held the Third National Student Workshop in Tokyo. A total of 88 people—70 sixth-year undergraduate students from 70 universities, and 18 alumni who had participated in the First and the Second Workshops—attended this Workshop. The theme of this Workshop was “Contribution to medical care and society: How will I act as a pharmacist in the future?” The first day took the form of a World Café, with participants exchanging information on such topics as, “The purpose for choosing a pharmacy major, and my achievement status”, “My favorite aspects of my college”, and “My dreams and paths: Painting my future image”. Later that day, participants discussed and gave presentations on the ways they would be contributing as pharmacists to society and medical care. On the second day, participants discussed and gave presentations on the efforts they would like to make as pharmacists to contribute to society and medical care. The final session was a general assembly for discussion on the ways they would be contributing as pharmacists to society and medical care. Throughout the two days, attendees participated in discussions with an awareness of their common ground, in that they all had national qualification in spite of different intended paths. In this article, 4 sixth-year students (their status at the time of the symposium) from the Workshop introduce outlines of the discussions and products from each group.
Although Japanese medical and pharmaceutical educators have been interested in outcome-based education (OBE) in recent years, there are still many difficulties and problematic concepts involved in curriculum building, especially in determining objectives and assessment methods. From 2015, OBE will be incorporated in a model core curriculum of pharmaceutical education in Japan. In this paper, we will introduce the outline of an operative sample of OBE derived from the National Competency Standards Framework for Pharmacists in Australia. The products shown in this paper are examples of standards, elements, and some rubric scales and descriptors in the domain of “Practical ability in pharmaceutical therapy”, as presented by the Ministry of Education, Culture, Sports, Science and Technology of Japan, and as proposed by many participants attending The Pharmaceutical Society of Japan's 3rd advanced workshop for pharmaceutical educators in 2013. We expect a helpful outline will enable each educational institution to design an appropriate OBE curriculum.
The third advanced workshop of the Pharmaceutical Society of Japan for pharmaceutical teachers was held from October 12th to 14th, 2013, and participants discussed an outcome-based approach to curriculum development in pharmacy education. In this article, I report the outcome-based spiral curriculum model of group 2A, which was designed to enable pharmacy students to understand a patient's condition, and to provide a basic practical ability in medical therapy. In the curriculum, pharmacy students will learn biochemistry and functional morphology in the first and second years, skills to interview patients in the third year, pathophysiology and pharmacotherapeutics in the third and fourth years, skills to estimate patient disease from physical examination in the fourth year, and practice in understanding real patient conditions in a clinical clerkship in the fifth year. The curriculum also included learning and evaluation methods.
The empowerment approach to patients with diabetes is a philosophy that was introduced by Robert M. Anderson and Martha M. Funnell of Michigan Diabetes Research and Training Center in the 1990s. This approach is based on the observation that more than 98% of diabetes care is performed by patients themselves. Dr. Anderson, Ms. Funnell, and their colleagues found that every patient has a right and an ability to solve his/her own problem in his/her own diabetes. Therefore healthcare providers should provide support for patients own endeavors. Empowerment has three essential elements: 1) the patient is centered, they make a final decision of their daily self-management, and are responsible for those decisions and the results; 2) patient support is the main role of healthcare providers; and 3) patient and healthcare providers should collaborate. In this author's opinion, it is important for healthcare providers to improve their communication skills to use the empowerment approach to help patients change their behaviors in the real world. To encourage empowerment, we created a unique learning program for healthcare providers, named “Diabetes Theater”. This program is an interactive workshop comprising two parts: drama and discussion.
Diabetes Theater (DT) is reenactment of pharmacists treating their patients during medical interviews. DT shows different pharmacists treating their patients using different methods. After the performance, the participants can learn from reflecting on the plays and their own work. At the 134th Annual Meeting of the Pharmaceutical Society of Japan, Kumamoto we performed 3 plays. The plays were about a diabetic patient with hypoglycemia who consults 3 pharmacists who have 3 different approaches. Clinical pharmacists in Kumamoto performed and created DT. After DT, we received responses for each play from participants. Some participants stated that it is necessary for pharmacists to respect patients' feelings and that pharmacists should speak to patients in layman's terms. Participants generally understood the purpose of DT. Some participants said that they do not have enough time to console patients. Pharmacists who performed as patients said that they were better able to see from the patients' point of view during medical interviews.
We started Diabetes Theater (DT), a program for medical staff, with a short drama and discussion with attendees in 2009. The program has two parts. One is a short drama enacting realistic scenes between medical staff and patients. After that, facilitators prompt responses from the audience. The basic concept of the program is empowerment for patients: a process of empowerment in terms of discovery and development of one's own life. People are empowered when they have sufficient knowledge to make rational decisions, sufficient control and resources to implement their decisions, and sufficient experience to evaluate the effectiveness of their decisions. We performed DT at the Annual Meeting of the Pharmaceutical Society of Japan, Kumamoto. Thereafter, we researched the positive educational effects of the program by issuing a questionnaire; the results are presented herein, along with some of our views on the benefits of a drama program on pharmacist training and undergraduate education. The total number of respondents was 78 (M/F, 40/38). Hospital pharmacists comprised 38%; students 26%; academia 19%; community pharmacists 9%; and others 8%. In conclusion, DT was well accepted by attendances as a unique program to learn effective patient communication skills and thereby achieve better patient-pharmacist relations. Our findings suggest that DT might be an interesting approach to improve attitudes of pharmacists in diabetes care with the aim of empowerment.
The number of Japanese patients with chronic diseases is increasing year by year largely because of the acceleration of demographic aging and lifestyle changes in Japan. Although many patients with chronic diseases receive their medications from pharmacists, many community pharmacists have not changed their communication style with their patients. Empowerment is the basic idea that patient support is not widely known by pharmacists but the certified diabetes educator (CDE). We started Diabetes Theater, a program for healthcare providers that includes short drama and discussion with attendees, in 2009. The concept of the program is empowerment for patients: a process to help patients make better healthcare decisions. In addition, we launched another educational program to help community pharmacists learn about communication skills with diabetes patients named “The Three star Pharmacist Training Program” in 2012. In this article, we discuss our forthcoming plans to spread these ideas of empowerment among pharmacists.
Exploiting the ability of coiled-coil peptides to induce dimer formation, we designed an artificial epidermal growth factor receptor (EGFR) in which dimerization is essential for increasing the tyrosine kinase activity of its intracellular domain. Using leucine-zipper coiled-coil peptides, the surface-exposed E3 ((EIAALEK)3) tag sequence was fused with EGFR (E3-EGFR) lacking domains I-III and a part of IV, which participate in dimerization of EGFR after binding to natural ligand (that is, epidermal growth factor). To dimerize E3-EGFR we synthesized conjugates of two K4 ((KIAALKE)4) peptides, called K4-conjugates, with linker lengths approximately 10 angstrom that mimic the distance of EGFR dimerization. Receptor phosphorylation of E3-EGFR was found to increase within 5 min in CHO cells expressing E3-EGFR after treatment with K4 conjugates. Increased lamellipodia formation and migration of the cells was also observed when treated with the artificial ligands. This receptor model can be applied to a wide variety of membrane-associated proteins to control cellular processes and to elucidate the functional mechanisms of these proteins using chemical biology.
Many tryptophan-based dimeric diketopiperazine (DKP) alkaloids including WIN 64821 and ditryptophenaline, which exhibit fascinating biological activities, have been isolated from fungi. These alkaloids possess a unique architecture; therefore several total syntheses of these compounds have been accomplished via bio-inspired reactions. Despite these elegant strategies, we were convinced that a more direct bio-inspired solution for the preparation of tryptophan-based DKP alkaloids was possible because in a true biosynthesis, direct dimerization of tryptophan occurs in aqueous media without incorporation of a protecting group on the substrates. Thus we developed direct bio-inspired dimerization reactions in aqueous, acidic media, along with a novel biomimetic pathway, to provide C2-symmetric and non-symmetric dimeric compounds from commercially available amine-free tryptophan derivatives using Mn(OAc)3, VOF3, and V2O5 as one-electron oxidants. In addition, concise two-pot or three-step syntheses of the naturally occurring dimeric DKP alkaloids (+)-WIN 64821, (−)-ditryptophenaline, and (+)-naseseazine B were accomplished with total yields of 20%, 13%, and 20%, respectively. The present synthesis has several noteworthy features: 1) the tryptophan-based C2-symmetric and non-symmetric dimeric key intermediates can be prepared on a multigram scale in one step; 2) the developed oxidation reaction was carried out in aqueous, acidic solution without deactivation of the metal oxidants; 3) protection of the primary amine can be avoided by salt formation in aqueous acid; 4) for the total two-pot operation, the reaction media are environmentally friendly water and ethanol; 5) satisfactory total yields are obtained compared with previously reported syntheses.
NMR spectroscopy enables structural analyses of proteins and has been widely used in the structural biology field in recent decades. NMR spectroscopy can be applied to proteins inside living cells, allowing characterization of their structures and dynamics in intracellular environments. The simplest “in-cell NMR” approach employs bacterial cells; in this approach, live Escherichia coli cells overexpressing a specific protein are subjected to NMR. The cells are grown in an NMR active isotope-enriched medium to ensure that the overexpressed proteins are labeled with the stable isotopes. Thus the obtained NMR spectra, which are derived from labeled proteins, contain atomic-level information about the structure and dynamics of the proteins. Recent progress enables us to work with higher eukaryotic cells such as HeLa and HEK293 cells, for which a number of techniques have been developed to achieve isotope labeling of the specific target protein. In this review, we describe successful use of electroporation for in-cell NMR. In addition, 19F-NMR to characterize protein-ligand interactions in cells is presented. Because 19F nuclei rarely exist in natural cells, when 19F-labeled proteins are delivered into cells and 19F-NMR signals are observed, one can safely ascertain that these signals originate from the delivered proteins and not other molecules.
We recently succeeded in producing nanostructures made of RNA-protein (RNP) complexes. We show that RNA and the ribosomal protein L7Ae can form a triangular-like nanostructure that consists of three L7Ae proteins, which form the apices of the triangle, bound to one RNA scaffold. This shape is created through a 60° kink introduced into the RNA structure on L7Ae binding. By varying the size of the RNA scaffold we could in turn alter the overall size of the triangular nanostructure. Several functions can be added to this nanostructure by the introduction of effector proteins fused to L7Ae. The design and construction of functional RNP nanostructures that detect specific cancer cells are discussed herein. In parallel, we developed synthetic RNP translational switches to control production levels of particular proteins depending on certain input(s) within the intracellular environment. The RNP-binding module was successfully incorporated into mRNA to generate functional RNP switches. The designed ON/OFF translational switches detect expression of the trigger factor and repress or activate expression of a desired protein (e.g., apoptosis regulator) in target mammalian cells. Taken together, RNP-binding module could be employed for constructing designer genetic switches and functional nanostructures to regulate cellular processes.
Artificial zinc finger proteins (ZFPs) consist of Cys2-His2-type modules composed of approximately 30 amino acids that adopt a ββα structure and coordinate a zinc ion. ZFPs recognizing specific DNA target sequences can substitute for the binding domains of various DNA-modifying enzymes to create designer nucleases, recombinases, and methylases with programmable sequence specificity. Enzymatic genome editing and modification can be applied to many fields of basic research and medicine. The recent development of new platforms using transcription activator-like effector (TALE) proteins or the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) system has expanded the range of possibilities for genome-editing technologies. These technologies empower investigators with the ability to efficiently knockout or regulate the functions of genes of interest. In this review, we discuss historical advancements in artificial ZFP applications and important issues that may influence the future of genome editing and engineering technologies. The development of artificial ZFPs has greatly increased the feasibility of manipulating endogenous gene functions through transcriptional control and gene modification. Advances in the ZFP, TALE, and CRISPR/Cas platforms have paved the way for the next generation of genome engineering approaches. Perspectives for the future of genome engineering are also discussed, including applications of targeting specific genomic alleles and studies in synthetic biology.
To summarize our electroanalytical research in the biomedical field over the past 43 years, this review describes studies on specular reflection measurement, redox potential determination, amperometric acid sensing, HPLC with electrochemical detection, and potential oscillation across a liquid membrane. The specular reflection method was used for clarifying the adsorption of neurotransmitters and their related drugs onto a gold electrode and the interaction between dental alloys and compound iodine glycerin. A voltammetric screening test using a redox potential for the antioxidative effect of flavonoids was proposed. Amperometric acid sensing based on the measurement of the reduction prepeak current of 2-methyl-1,4-naphthoquinone (VK3) or 3,5-di-tert-buty1-1,2-benzoquinone (DBBQ) was applied to determine acid values of fats and oils, titrable acidity of coffee, and enzyme activity of lipase, free fatty acids (FFAs) in serum, short-chain fatty acids in feces, etc. The electrode reactions of phenothiazines, catechins, and cholesterol were applied to biomedical analysis using HPLC with electrochemical detection. A three-channel electrochemical detection system was utilized for the sensitive determination of redox compounds in Chinese herbal medicines. The behavior of barbituric acid derivatives was examined based on potential oscillation measurements.
I have been engaged in research and education in the fields of immunology and biochemistry at a medical college and college of pharmacy for 40 years. The original reasons why I began studying cytokines and some of the interests that have motivated me to continue working in the field of cytokine research are described: 1) the roles of cytokines in various immunological and inflammatory diseases (e.g., chemokines in bacterial infections and inflammatory diseases, particularly the role of interleukin-5 and eotaxins in eosinophilia); 2) the role of focal adhesion kinase in antiapoptosis and metastasis of melanoma; 3) recent findings on the role of JAK2/STAT pathways, particularly how JAK2V617F mutation induces dysregulated proliferation and tumorigenesis; and 4) the interactions of various chemical compounds and natural products in cytokine gene activation and signaling. Previous discoveries and published findings by my research group are described, along with comments and discussion pertaining to recent developments in the field.
Alzheimer's disease (AD) has become a serious social problem in Japan. However, effective preventive and fundamental therapeutic methods for AD have not yet been developed. Using a new strategy in the course of our survey of numerous natural resouces having neurotrophic activity, we isolated a variety of active constituents and proved their pharmacological properties. As a result, we successfully found nobiletin, a compound with anti-dementia activity that comes from citrus peels. Also, we have demonstrated that nobiletin ameliorates cognitive impairment in several dementia model animals such as chronically amyloid β(Aβ) infused rats, amyloid precursor protein transgenic (APPTg) mice, olfactory-bulbectomized (OBX) mice, N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801)-treated mice, senescence-accelated mice and bilaterial common carotid arteries occlusion mice. In a APPTg mouse of AD, nobiletin greatly improved memory impairment, and this was accompanied by a marked decrease in Aβ deposition. Also, in OBX mice memory impairment was markedly recoverd by nobiletin, accompanied by improvement of a decrease indensity of cholinergic neurons. Interestingly, nobiletin improves age-related congnitive impairment and decreased hyperphosphorylation of tau as well as oxidative stress in senescence-accelerated mice. In cultured cells, nobiletin reversed the Aβ-induced inhibition of glutamate-induced increases in cAMP response element binding protein (CREB) phosphorylation and modulated gen expression of thioredoxin-interacting protein and NMDA resceptor subunits. These results suggest that nobiletin prevents memory impairment and exhibits a protecting action against neurodgeneration in AD model animals. Nobiletin and citrus peels thus have potential as functional foods for prevention of dementia.
Intravenous injection often causes vascular injury such as venous irritation, vascular pain, and phlebitis. Vascular injury deteriorates the patient's QOL and sometimes limits the continuation of injection therapy. Pharmaceutical intervention and pharmacological mechanisms used to reduce vascular injury induced by vinorelbine and epirubicin were reviewed. A multivariate logistic regression analysis revealed that the dose of vinorelbine (≥40 mg) was a significant predictor for venous irritation. Alteration of the volume of normal saline for vinorelbine dissolution, from 50 to 100 mL, significantly decreased the grade of venous irritation. On the other hand, the phlebitis scores were significantly higher in patients treated with epirubicin ready-to-use solution compared with lyophilized powder. The change of formulation of epirubicin to lyophilized powder decreased the risk of venous irritation. The concentration inducing 50% cell viability inhibition was lower in the order of vesicant, irritant, and nonvesicant drugs on porcine aorta endothelial cells (PAECs), suggesting that the injuring effects of anticancer drugs on PAECs may be relevant as an indicator of the frequency of their vascular injury. The exposure to vinorelbine of PAECs rapidly depleted intracellular glutathione levels and increased intracellular reactive oxygen species production. Moreover, exposure to epirubicin increased intracellular lipid peroxide levels and enhanced the phosphorylation of p38 mitogen-activated protein kinase. These results demonstrate that oxidative stress plays an important role in vinorelbine- and epirubicin-induced endothelial cell injury, and may therefore increase the potential for vascular injury upon intravenous injection.
Drug transporters play an important role in the clinical pharmacokinetics of many therapeutic agents. Although it is estimated that about half of all therapeutic agents are chiral, there has been little information on the stereoselective pharmacokinetics related to drug transporters. This review focuses on the drug transporters contributing to the stereoselective pharmacokinetics of fexofenadine enantiomers in humans. Fexofenadine is administered clinically as a racemic mixture, and the plasma concentration of (R)-fexofenadine is about 1.5-fold higher than that of the (S)-enantiomer. Because fexofenadine is poorly metabolized by cytochrome P450s, its pharmacokinetics depends on its drug-transporter activities. First, we examined whether drug-transporter polymorphisms influence fexofenadine enantiomer pharmacokinetics. The findings suggested that a combination of multiple transporters involving organic anion transporting polypeptide (OATP) 2B1, P-glycoprotein (P-gp), and multidrug resistance-associated protein 2 (MRP2) react to stereoselective fexofenadine exposure. Subsequently, we evaluated the roles of P-gp and OATPs in fexofenadine enantiomer pharmacokinetics using these inducer/inhibitors. Coadministration of P-gp inducer/inhibitors significantly altered the pharmacokinetics of fexofenadine enantiomers. In addition, the OATP inhibitors rifampicin and apple juice also affected fexofenadine enantiomer pharmacokinetics. Moreover, in in vitro studies, the uptake of both fexofenadine enantiomers into OATP2B1 cRNA-injected oocytes was significantly higher than that into water-injected oocytes, and this effect was greater for (R)-fexofenadine. Taken together, these studies indicated that multiple transporters including P-gp, OATPs, and MRP2 play important roles in fexofenadine enantiomer pharmacokinetics. Furthermore, OATP2B1 is a key determinant of the stereoselective pharmacokinetics of fexofenadine, and drug transporters may have chiral discrimination ability.
Intracellular membrane trafficking between membranous compartments is essential for organelle biogenesis, structure, and identity. Rab/Ypt GTPases are well-characterized regulators of intracellular membrane trafficking, functioning as molecular switches that alternate between GTP- and GDP-bound forms. In Saccharomyces cerevisiae, 11 Rab/Ypt GTPases have been identified and their functions are known to be conserved in their mammalian counterparts. In yeast, the secretory pathway is regulated by sequential activation and inactivation (the so-called Rab cascade) of three types of yeast Rab protein -Ypt1p, Ypt31p/32p and Sec4p -via specific guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). In addition to these Rabs, we and others have recently demonstrated that Ypt6p is predominantly localized to the early Golgi compartment, and functions as another regulator of anterograde transport for intra-Golgi trafficking in the secretory pathway. On the other hand, the endocytic pathway is known to be regulated by three yeast Rab5s (Vps21p, Ypt52p and Ypt53p) and one Rab7 (Ypt7p). Rab5 and Rab7 are key determinants of endosome identity, and the Rab5-Rab7 cascade is important for the progression from early to late endosome. Our recent study demonstrates that the endocytic pathway branches into two vacuolar targeting pathways, the Rab5-dependent vacuole protein sorting (VPS) pathway and the Rab5-independent pathway. In this review, we focus on recent advances in our understanding of molecular mechanisms that regulate the localization and activity of yeast Rab GTPases in intracellular membrane trafficking.
Menkes disease (MD) is a neurodegenerative disorder characterized by copper deficiency. It is caused by defective intestinal absorption of copper resulting from a deficiency of a copper-transporting ATPase, ATP7A. We investigated the effects of combination therapy with copper and disulfiram, a known lipophilic chelator. We synthesized a copper-disulfiram complex (Cu-DSF) and determined its crystal structure by X-ray crystallographic analysis. Unfortunately, Cu-DSF was not orally bioavailable due to its lipophilicity. We therefore planned to use cyclodextrin as a solubilizing agent to increase the water solubility of Cu-DSF. After comparisons of the effects of cyclodextrins (α, β, γ), it was found that addition of β-cyclodextrin (β-CyD) increased the solubility of Cu-DSF. Moreover, the modified β-CyD, hydroxypropyl-β-cyclodextrin, was yet more effective as a solubilizing agent. For the development of a convenient method to determine the concentration of Cu-DSF included by β-cyclodextrins, a standard curve based on UV-visible(VIS) absorption was derived.
Much of the damage to health caused by drugs could be prevented by appropriate care. A well-defined duty of care and further information are required for healthcare professionals. Although there are many litigation cases to use as references, neither the extent of the duty of care nor the obligation to explain medication according to the type of drug prescribed has yet been fully established. Thus, we systematically collected decided cases of adverse drug events, and assessed the degree of the duties of care and information. Specifically, we collected decided cases in which physicians, dentists, pharmacists, nurses, or hospitals had been sued. Data were derived from Bessatsu Jurist Iryo-kago Hanrei Hyakusen, Hanrei Jihou, and Hanrei Times from 1989 to November 2013, and information on precedents in the records of the Supreme Court of Japan from 2001 to November 2013. We analyzed the cases, and assessed the following according to the type of drug: (1) standards and explanations when dealing with drugs that were critical issues in litigation, and (2) the degree of the physician's or pharmacist's duties of care and information. In total, 126 cases were collected. The number of drug categories classified was 27, and 9 were considered of practical importance. After this systematic review, we found a trend in the degree of the required level of care and information on several drugs. With respect to duties of care and information, the gap between the required level and actual practice suggests that healthcare professionals must improve their care and explanations.
In the 11-week practical hospital training of pharmaceutical students in Nagoya University Hospital, a clinical practice program has been implemented with the objective of compensating for any deficits students may have in skills and attitudes due to insufficiencies in their formal education. The program aims to enable the students to observe patients from various angles, obtain from them information necessary for drug therapy, and propose multiple treatment methods according to the patient's background and situation. Tests are conducted before and after the program to assess the students' knowledge and to confirm whether lectures on basic knowledge of practical skills had been provided and whether practical skill training had been performed. The rate of correct answers on the postprogram test rose significantly after the practice program compared with the preprogram scores, thus confirming that the students' knowledge improved. Because the content of their knowledge and the experience that they had acquired previously was in accordance with older guidelines, however, it will be necessary to update students' knowledge regularly and to instill knowledge, skills, and attitudes that they will be able to apply in actual medical practice. In the questionnaire after the end of the program, more than 80% of the students indicated that they had benefitted. Many responded that this program would be useful for their practical hospital training on the wards and for their future work. This suggests that the program is extremely beneficial to the students.
A nationwide survey was conducted to verify relations between the workload of home-visiting service by community pharmacists and outcomes. Data were collected on 5447 patients from 1890 pharmacies. Most (61.9%) pharmacists visited patients' homes twice monthly, spending there a net average of 20.6 work minutes. At the time of the survey, 29.8% of the patients had improvement of adherence compared with at start of home visits; 65.5% had no change, and 1.4% had gotten worse. Similarly, 41.6% had decreased unused medications, 54.4% had no change, and 2.3% had increased. Home-visiting pharmacists found adverse drug events (ADEs) caused by drug administration in 14.4% of their patients. They dealt with 44.2% of these cases by discontinuing administration of the responsible drug, 24.5% by reducing the dosage, and 18.3% by changing drugs, with a total of 88.1% having been improved. Prescription changes intended to correct problems occurred in 37.1% of the patients. In patients whom the pharmacists visited more often, a higher percent had ADEs, had their prescription changed to correct problems, and had improved adherence and unused medications. The average actual work time was longer in patients whose outcomes improved than in those whose outcomes did not. A higher involvement in homecare by pharmacists was found to improve outcomes of drug treatment.
In Japan, it is illegal to sell pharmaceuticals on Internet auction sites, although a considerable number of pharmaceuticals are listed on such sites. We investigated the current situation regarding the illegal trade in pharmaceuticals on Japanese Internet auction sites and the responses of site administrators to such transactions. We searched for pharmaceuticals and “gray” items that were suspected of being pharmaceuticals on Yahoo-oku! (Yahoo! Auctions, Japan) over a 37-day period and then submitted violation reports indicating that selling pharmaceuticals is illegal or that the description of an item was insufficient. The reports were directed to the site administrators and forwarded to the sellers. One hundred and six pharmaceutical products and 34 gray items were identified during the study period. After the submission of the violation reports, only 28 of the pharmaceutical products and one of the gray items were deleted by the administrator, while 18 of the pharmaceutical products and 7 of the gray items were withdrawn by their sellers. However, 41 pharmaceuticals and 20 gray items were sold. Most of the gray items were listed using characteristic terms or abbreviations without photographic images. More than 70% of the identified pharmaceuticals had a contraindication(s) other than hypersensitivity. In conclusion, the illegal trade in pharmaceuticals on Internet auction sites remains a serious problem in Japan, and the responses of site administrators to such transactions are inadequate. The government and pharmaceutical industry may have to take measures such as providing public and administrative guidance to stop the illegal trade in pharmaceuticals on the Internet.
Recently, illegal herbal or liquid products containing psychoactive compounds have been a serious problem damaging human health and causing numerous traffic accidents. Reports indicate that most of those herbal products contain various types of synthetic cannabinoids. There are many on-site drug-testing devices; however, synthetic cannabinoids are not targeted compounds for such devices. In this study, we evaluated the on-site drug-testing device “K2/Spice Test” for the detection of 12 different types of 38 synthetic cannabinoids (including 13 naphthoylindole-type synthetic cannabinoids) and a natural cannabinoid (Δ9-tetrahydrocannabinol). Although this device is primarily used for the detection of metabolites of naphthoylindole-type synthetic cannabinoids in urine samples, we applied it to detect synthetic cannabinoids in illegal herbal products for rapid screening analyses. As a result of the on-site examination of synthetic cannabinoids, 10 naphthoylindole-type synthetic cannabinoids [five narcotics (JWH-018, JWH-073, AM-2201, MAM-2201, and JWH-122); five designated substances (JWH-015, JWH-200, AM-1220, JWH-019, and JWH-020)], and two other types of synthetic cannabinoid [designated substances (a benzoylindole AM-694 and a naphthoylnaphthalene CB-13)] showed positive results (the limit of detection ranged from 50 to 250 μg/mL). Furthermore, MeOH extracts of illegal herbal products containing naphthoylindole-type synthetic cannabinoids also showed positive results (the limit of detection ranged from 2.5 to 10 mg herbal products/mL). Therefore, we found that this device may be useful for the on-site examination of some naphthoylindole-type synthetic cannabinoids not only in urine samples but also in illegal herbal products.