Following the global trend of reducing animal testing, various reconstructed human epidermis (RHE) models for skin irritation test (SIT) have been developed, verified, validated and included in OECD ...TG 439. We developed a new RHE called EPiTRI and a SIT method using EPiTRI (EPiTRI-SIT model) following the OECD guidelines. EPiTRI possesses morphological, biochemical and physiological properties similar to human epidermis with well-differentiated multilayered viable cells with barrier function. The EPiTRI-SIT model was tested for 20 reference chemicals in Performance Standard of OECD TG 439 (GD 220), showing good predictive capacity with 100% sensitivity, 70% specificity and 85% accuracy. EPiTRI had sensitivity in detecting di-n-propyl disulphate, as an irritant chemical (UN GHS Category 2), whereas most validated reference methods detected it as a non-irritant. An international validation study of EPiTRI-SIT was conducted in four laboratories to confirm the within- and between-laboratory reproducibility, as well as predictive capacity. The phase I/II within-laboratory and between-laboratory reproducibility was 100%/95% and 95%, respectively. The overall sensitivity, specificity and accuracy of EPiTRI-SIT was 96%, 70% and 83%, respectively, which fulfilled the OECD criteria. Thus, EPiTRI, meets the criteria of Performance Standards of OECD TG 439 (GD 220) and is suitable for screening irritating chemicals in vitro.
•Structure and function of new reconstructed human epidermis,EPiTRI, similar to human epidermis.•International validation study of EPiTRI-SIT meets the acceptance criteria of OECD GD 220.•EPiTRI-SIT classify di-n-propyl disulphide as an irritant whereas VRMs as non-irritant chemical.
Plant-based drugs of abuse are as old as recorded human history. Although traditional addictive substances, such as opium, cannabis and coca, have been controlled by the United Nations anti-drug ...conventions, many, if not most, natural plants with addictive or abuse liability remain elusive. Therefore, the United Nations Office on Drugs and Crime (UNODC) has warned the emerging threat from new psychoactive substances (NPS), which are mostly derived or modified from the constituents of natural origin. For example, synthetic cannabinoids and synthetic cathinones are derived from the cannabis and khat plant, respectively. In this review, we briefly discussed the chemistry, pharmacology and toxicology of five common NPS of natural origin, i.e., khat, kratom, salvia, magic mushroom and mandrake. Through the review, we hope that professionals and general public alike can pay more attention to the potential problems caused by natural NPS, and suitable control measures will be taken.
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•New psychoactive substances, which are mostly not controlled by the UN conventions, are a new threat to global public health.•Although most NPS are synthetic chemicals, they are usually derived from natural origin.•The chemistry, pharmacology and toxicology of five NPS of natural origin, khat, kratom, salvia, magic mushrooms and mandrake, are reviewed.
Use of New Psychoactive Substances (NPS) has posed a global threat to public health and the security of the population. As of December 2019, the NPS items identified in total have outnumbered by ...three to one the controlled substances listed in the 1961 and 1971 UN Drug Conventions. However, most of these NPS have not been scheduled by the United Nations because of their easy modification on the chemical structures to shun control. Currently, the scheduling and control of NPS is mostly at the national level and a rational scheduling of NPS by objective assessments is essential but often lacking. To rationally schedule NPS, the NPS misuse situation was firstly estimated with the Taiwanese Substance Misuse Monitoring and Reporting Systems (SMMRS) from 2006 through 2019. Then, the assessment of drug-related harms with an expert Delphi procedure for drug scheduling was performed. The epidemiological analysis revealed that among 37 substances commonly misused in Taiwan, heroin posed the highest risk, followed by (meth)amphetamine and ketamine. Of note, misuse of NPS, such as ketamine, synthetic cannabinoids (JWHs, AM-2201, XJR-11), synthetic cathinones (MDPV, bk-MDMA, 4 -MMCetc.), phenethylamines (PMMA, FMA, 2C-B, 2C-E etc.), piperazines (BZP, TFMPP) and tryptamines (5-MeO-DIPT) has been on the rise. Though perceived drug-related harms differed among experts with different professional backgrounds, the differences were not significant. Four dimensions of drug-related harms- addiction, misuse, social harm and physical harm- integrated from Nutt's model and scheduling criteria of Taiwan's Statute for the Prevention and Control of Illicit Drugs (SPCID), were further divided into 11 indicators and applied to assess harms of the 37 substances. Among the 11 indicators that corresponded to the four dimensions, 7 had significant prediction capabilities. Additionally, prevalence of misuse nationally was an important predictor of harm assessment. These indicators of harm assessment of drug misuse can help develop a proper scheduling system for the management of controlled/illicit drugs. In conclusions, drug scheduling is the first step toward proper management of drug use problems. Facing the threats of NPS, it is imperative to implement a rational and effective scheduling system for appropriate management. This study provides a mechanism to scrutinize, and improve, the current evaluation process for NPS scheduling.
•A novel dual dispersive liquid–liquid microextraction (dDLLME) was developed.•DDLLME was an environmental friendly method to determine phenylpropenes.•Six phenylpropenes was quantified in 22 ...essential oils, spices and massage oils.•Nutmeg had the most enormous of safrole and myristicin in essential oil.
A novel, simple and quick sample preparation method was developed and used for pre-concentration and extraction of six phenylpropenes, including anethole, estragole, eugenol, methyl eugenol, safrole and myristicin, from oil samples by dual dispersive liquid–liquid microextraction. Gas chromatography-mass spectrometry was used for determination and separation of compounds. Several experimental parameters affecting extraction efficiency were evaluated and optimized, including forward-extractant type and volume, surfactant type and concentration, water volume, and back-extractant type and volume. For all analytes (10–1000ng/mL), the limits of detection (S/N≧3) ranged from 1.0 to 3.0ng/mL; the limits of quantification (S/N≧10) ranged from 2.5 to 10.0ng/mL; and enrichment factors ranged from 3.2 to 37.1 times. Within-run and between-run relative standard deviations (n=6) were less than 2.61% and less than 4.33%, respectively. Linearity was excellent with determination coefficients (r2) above 0.9977. The experiments showed that the proposed method is a simple, effective, and environmentally friendly method of analyzing phenylpropenes in oil samples.
Flow chemistry-based syntheses of deuterium-labeled analogs of important antidiabetic chalcones were achieved via highly controlled partial C≡C bond deuteration of the corresponding ...1,3-diphenylalkynones. The benefits of a scalable continuous process in combination with on-demand electrolytic D2 gas generation were exploited to suppress undesired over-reactions and to maximize reaction rates simultaneously. The novel deuterium-containing chalcone derivatives may have interesting biological effects and improved metabolic properties as compared with the parent compounds.
Illegal drug use has caused considerable health and social costs. Access to medical treatment has been one of the most cost‐effective interventions to reduce problematic drug use. Accessibility to ...treatment, which can be analyzed by the spatial approach such as geographic information system (GIS), has thus been utilized as a measure of the proportion of population that reaches appropriate health services. In this study, the association of accessibility coverage to medical facilities and socioeconomic status with human immunodeficiency virus (HIV) risk for heroin users was evaluated by GIS analysis in Kaohsiung, Taiwan. Data of 7890 heroin users were collected from 2011 to 2015 and categorized into five risk groups according to their income and distance to treatment settings. The results of this GIS‐based analysis show that the areas with over 50% accessibility coverage rate had less amounts of HIV cases with statistical significance. Inconvenient access to medical facilities could result in poor treatment outcomes such as higher HIV incidences. Therefore, in order to effectively reduce HIV incidences among the heroin users, the accessibility coverage and locations of medical treatment facilities should meet the needs of drug users. It is also advised that the formulation of policies associated with illegal drug use problems should be evidence‐based and geographical indicators could serve for this purpose from either prevention or intervention perspective.
Zinc oxide nanoparticles (nano-ZnO) are one of the most commonly used nanomaterials in industrial products including paints, cosmetics, and medical materials. Since ZnO is a well-known photocatalyst, ...it is important to further study if nano-ZnO cause phototoxic effect on skin cells under UVA-irradiation and visible light illumination. Human-derived keratinocytes (HaCaT) were treated with 1-20 microg/mL of nano-ZnO (< 50 nm) and then exposed to UVA (0.5-2 J/cm2). Twenty four hours later, cell viability, membrane integrity, and oxidative DNA damage were determined by MTS assay, lactate dehydrogenase (LDH) release, and the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct, respectively. High concentration of nano-ZnO (10-20 microg/mL) significantly induced cytotoxicity, whereas 0.5-2 J/cm2 of UVA irradiation dose-dependently aggravated nano-ZnO-induced cell death via induction of LDH release and DNA damage. The level of photocytotoxicity is mainly dependent on the level of reactive oxygen species (ROS) production. UVA irradiation of nano-ZnO in methanol induced lipid peroxidation in a light dose and substrate dose response manner. Electron spin resonance (ESR) spin trapping studies confirmed that both hydroxyl radical and superoxide anion radical were formed during photoirradiation, while nano-ZnO-induced hydroxyl radical formation is not evolved from superoxide. In addition, nano-ZnO dose-dependently induced single strand DNA break in supercoiled phi x 174 plasmid DNA. Under visible light illumination, nano-ZnO induced the LDH leakage, hydroxyl radical generation, and 8-OHdG formation in a dose-dependent manner. Collectively, these results suggest the photocytotoxic and photogenotoxic effects of nano-ZnO on human skin keratinocytes.
Illegal drug use has long been a global concern. Taiwan and Korea are geographically adjacent and both countries have experienced the illegal use problems of methamphetamine, a predominant prototype ...of New Psychoactive Substances (NPS). NPS, a term coined by the United Nations Office on Drugs and Crime (UNODC) in recent years, have not been scrutinized for their safety and may become a new threat to public health and security worldwide. To conduct evidence-based drug policy, it is imperative to estimate the trend and pattern of illegal drug use. Therefore, this study aims to analyze and compare the current status of drug-related seizures, arrests and illegal drug use, with a focus on methamphetamine and NPS, between Taiwan and Korea.
Data of illegal drug (including NPS)-related seizures and arrests were collected via anti-drug related agencies of both countries from 2006 through 2014.Since listing of NPS as controlled substances was a result of NPS abuse liability through official evaluation, the items of controlled NPS were used as an indicator of emerging use. These data obtained from Taiwan and Korea was then compared.
The results showed that while methamphetamine remained as a predominant drug in both Taiwan and Korea for decades, different illegal drug use patterns have been observed in these two countries. In Taiwan, the major illegal drugs were methamphetamine, heroin, and ketamine, whereas in Korea those were methamphetamine and cannabis. By comparison of per capita illicit drug seizures, the illegal drug use situation in Taiwan was at a higher stake than that in Korea. In terms of NPS use, ketamine has been a major drug in Taiwan, but it was seldom found in Korea. Besides ketamine, the major type of NPS was synthetic cathinones in Taiwan whereas it was synthetic cannabinoids and phenethylamines in Korea. The difference in the numbers of controlled NPS items between Taiwan (23) and Korea (93) may be due to the implementation of temporary control on NPS in Korea since 2011.
While the problem of methamphetamine still lingers, NPS have emerged as a new issue in both countries. However, the NPS pattern was different between Taiwan and Korea. Although the controlled NPS items in Taiwan were far less than those in Korea, the quantity of total NPS seizures, especially with ketamine, was much larger in Taiwan than in Korea. Different NPS pattern may also imply they were from different sources. Factors other than geographical proximity, such as drug policy and availability and accessibility to drugs, should be taken into account for the current status of illegal drug use in Korea and Taiwan.
The unique geographic features of Taiwan are attributed to the rich indigenous and endemic plant species in Taiwan. These plants serve as resourceful bank for biologically active phytochemicals. ...Given that these plant-derived chemicals are prototypes of potential drugs for diseases, databases connecting the chemical structures and pharmacological activities may facilitate drug development. To enhance the utility of the data, it is desirable to develop a database of chemical compounds and corresponding activities from indigenous plants in Taiwan. A database of anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan was constructed. The database, TIPdb, is composed of a standardized format of published anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan. A browse function was implemented for users to browse the database in a taxonomy-based manner. Search functions can be utilized to filter records of interest by botanical name, part, chemical class, or compound name. The structured and searchable database TIPdb was constructed to serve as a comprehensive and standardized resource for anticancer, antiplatelet, and antituberculosis compounds search. The manually curated chemical structures and activities provide a great opportunity to develop quantitative structure-activity relationship models for the high-throughput screening of potential anticancer, antiplatelet, and antituberculosis drugs.
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