Objective: A method for the determination of acetochlor and its metabolites in urine by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established. Methods: After cleaned-up by a HLB extraction cartridges, the urine was eluted with 1% acetic acid acetonitrile solution. The target compounds were separated by ACQUITY UPLC®HSS T3 Column (2.1 mm×100 mm×1.8 μm) by using 1% formic acid solution and acetonitrile as mobile phase with gradient elution program, and analyzed in positive electrospray ionization mode by liquid chromatography tandem mass spectrometry. Results: All the target compounds showed good linear relationships in the range of 1-50 μg/L, and the correlation coefficients (r) were higher than 0.997. The recoveries rates at three different spiked levels for all target compounds in blank matrices were 107.6%-129.1%, and the relative standard deviations (RSD) were 1.5%-9.9% (n=6) . The limits of detection and quantitation of the method were 0.04-0.11 μg/L and 0.15-0.42 μg/L, respectively, and target substances were detected in all urine samples from occupational exposure workers to acetochlor. Conclusion: This method is suitable for rapid screening and analysis of acetochlor and metabolites in urine with the advantages of accuracy, rapidity, simplicity, high sensitivity and good specificity.
Acetonitriles ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Humans ; Solid Phase Extraction ; Tandem Mass Spectrometry ; Toluidines

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. Trial Registration ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
China ; Crotonates ; administration & dosage ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; therapeutic use ; Multicenter Studies as Topic ; Multiple Sclerosis ; drug therapy ; metabolism ; Proportional Hazards Models ; Toluidines ; administration & dosage ; adverse effects ; therapeutic use

Incidence of parasitic diseases in Korea has been changing recently. The incidence of some parasitic diseases such as toxocariasis and cryptosporidiosis has increased, while that of soil-transmitted helminthic diseases has drastically decreased. Malaria reemerged in 1993 but has decreased in the 2010s. Here, common parasitic diseases that can be encountered in the clinical field are introduced, along with therapeutic agents such as anthelmintics, anti-malarial drugs, and anti-protozoan drugs to help general physicians select the appropriate medicine for parasitic diseases. Currently, soil-transmitted helminths are not a public health problem. On the other hand, the egg positive rate of Clonorchis sinensis has not decreased rapidly due to the habit of eating raw fresh water fishes in endemic areas; however, due to low worm density, it is difficult to detect infected persons only by clinical symptoms. Toxocariasis and ocular acanthamoebiasis can be detected more frequently due to appropriate diagnostic tools and physicians' concern. Cases of intestinal trematodiases, intestinal protozoasis, and vaginal trichomoniasis have decreased year by year. Since enterobiasis, pediculosis, and scabies are contact-borne diseases, local transmission and resurgence are always possible. Only a few antiparasitic agents can be prescribed in the clinics: albendazole, praziquantel, metronidazole, chloroquine, primaquine, and crotamiton. It may be helpful to general physicians to be reminded of the indications, prescription methods, and side effects described briefly for each drug that can be prescribed for parasitic diseases. Further information can be gathered from the Korea Pharmaceutical Information Service (http://www.kpis.or.kr/). For accurate diagnosis and prescription, a parasitologist may be consulted.
Albendazole ; Animals ; Anthelmintics ; Antiparasitic Agents ; Chloroquine ; Clonorchis sinensis ; Cryptosporidiosis ; Eating ; Enterobiasis ; Fishes ; Fresh Water ; Hand ; Helminths ; Humans ; Incidence ; Information Services ; Korea ; Lice Infestations ; Malaria ; Metronidazole ; Ovum ; Parasitic Diseases ; Praziquantel ; Prescriptions ; Primaquine ; Public Health ; Scabies ; Toluidines ; Toxocariasis

Amitraz is acaricidal and insecticidal pesticide used worldwide to control ticks and mites in plants and animals. Amitraz poisoning is characterized by clinical toxidrome such as central nervous system, respiratory depression, bradycardia, hypotension, hypothermia, and hyperglycemia. Toxic mechanism of amitraz is mainly alpha2-agonistic function and poisonings may occur by any route. Such clinical symptoms and signs of acute amitraz poisoning were possible to be thought as a toxidrome of acute organophosphate poisoning. We reported a 68-year-old woman that initially was misdiagnosed as acute organophosphate poisoning on the ground of symptoms and signs of mental change, respiratory depression, bradycardia, and hypotension. However, the serum level of pseudocholinesterase level at emergency room admission was within normal level and a vacant bottle of amitraz pesticide was founded around the yard of the patient. The patient was totally recovered from acute amitraz poisoning 2 days later after mechanical ventilation and conservative cares including atropine injection.
Animals ; Atropine ; Bradycardia ; Central Nervous System ; Emergencies ; Female ; Humans ; Hyperglycemia ; Hypotension ; Hypothermia ; Mites ; Organophosphate Poisoning ; Organophosphates ; Pseudocholinesterase ; Respiration, Artificial ; Respiratory Insufficiency ; Ticks ; Toluidines

Demodex mites are considered part of the normal skin flora. Typically, Demodex is harmless and causes no clinical symptoms. We present a 43-year-old woman with pruritic erythematous plaque and papulopustular eruptions on the right cheek. The patient was treated seborrheic dermatitis in face from several years ago. However, the lesion was aggravated after continuous topical steroid usage for several months at a local clinic. Histological examinations revealed Demodex mites in the follicular ostia with perivascular and perifollicular lymphohistiocytic inflammation. Treatment was initiated with metronidazole at a dose of 250 mg three times per day and then crotamiton ointment once daily. The lesion showed marked improvement after six weeks of treatment with mild residual erythema. The findings presented here indicate that Demodex infestation should be considered in the differential diagnosis of unilateral follicular eruptions of the face.
Adult ; Cheek ; Dermatitis, Seborrheic ; Diagnosis, Differential ; Erythema ; Female ; Humans ; Inflammation ; Metronidazole ; Mites ; Skin ; Toluidines

Crusted (Norwegian) scabies is a clinical variant of human infestation with Sarcoptes scabiei, and is characterized by extensive, heavily crusted skin lesions. It usually affects immunocompromised patients. The diagnosis is commonly missed, and can lead to mismanagement. Here we report a case of crusted scabies misdiagnosed as a cutaneous side reaction due to allopurinol in a 48 year old male patient with acquired perforating dermatosis who had been treated with allopurinol for about 20 weeks. The lesion showed pruritic, excessive hyperkeratotic scaly crusts and fissures on the hands, and on pelvic, genital and inguinal areas. His skin lesions disappeared after treatment with 10% crotamiton cream for 2 weeks.
Allopurinol ; Hand ; Humans ; Immunocompromised Host ; Male ; Sarcoptes scabiei ; Scabies ; Skin ; Skin Diseases ; Toluidines

This article reviews newly available knowledge regarding occupational cancer based on an assessment of International Agency for Research on Cancer (IARC) Monograph program from 2006 to 2010. The IARC reviewed the agents to evaluate the carcinogenicity in humans according to their priority. During the last five years, the IARC has reviewed many kinds of agents, including all of the Group 1 carcinogenic agents. Agents belonging to groups other than Group 1 were also reviewed. A few agents, such as shiftwork and firefighting, were reviewed for the first time after introducing the IARC Monograph Program. Most of the reassessed Group 1 agents were reaffirmed, showing that there was sufficient evidence to prove their carcinogenicity to human beings. However, some carcinogens were correlated to the new cancer site, since it was deemed that sufficient evidence was present. For example, larynx and ovary cancer deemed to have sufficient evidence of carciongenicity relating to asbestos exposure, joining lung cancer and mesothelioma. Some agents, such as benzo(a)pyrene, ortho-toluidine, 1,3-butadiene, and others belonging to Group 2A were upgraded to Group 1 based on newly identified epidemiologic findings, along with sufficient animal and mechanistic evidence. Benzo(a)pyrene and benzidine-based dyes were classified as human carcinogens based on sufficient animal and pervasive mechanistic evidence. This new data shows that not only chemical agents but also working conditions, such as stress and shiftwork were found to apply to human carcinogenicity. The IARC listed these agents in order to prioritize their review regarding their carcinogenicity to humans. There is a great need to study these newly emerging agents suspected to relate human carcinogenicity, and deem they are worthy of notice.
Animals ; Asbestos ; Benzo(a)pyrene ; Butadienes ; Carcinogens ; Coloring Agents ; Firefighters ; Humans ; International Agencies ; Larynx ; Lung Neoplasms ; Mesothelioma ; Ovarian Neoplasms ; Polymethacrylic Acids ; Toluidines

Scabies is one of the most common world-wide arthropod-born diseases in both humans and animals caused by the "itch" mite Sarcoptes scabiei. The incidence of scabies has shown a tendency to increase for the last several years in Korea. The previous peak incidence in Korea was between the early 1970s and early 1980s. A substantial part of the cyclic resurgence of scabies has been considered the result of inexperience and indifference of medical doctors toward the disease. The recent resurgence is presumed to be derived from not only indifference of the doctors but also an increase in elderly patients admitted to nursing homes and eldercare hospitals. Scraping using mineral oil for scabies patients is a very simple and effective method for definite diagnosis. A new diagnostic method using a dermoscope is also effective, especially for very young patients. Lindane and crotamiton are two available antiscabietic preparations in Korea. Crotamiton is less effective, while infants and pregnant women should not use lindane. In conclusion, medical personnel should be alert coping with the resurgence of scabies, and it is strongly suggested that other antiscabietic drugs such as permethrin, ivermectin, etc. should be made available for resistant patients in the near future in the Republic of Korea.
Aged ; Animals ; Arthropods ; Female ; Humans ; Incidence ; Infant ; Ivermectin ; Korea ; Lindane ; Mineral Oil ; Mites ; Nursing Homes ; Permethrin ; Pregnant Women ; Republic of Korea ; Sarcoptes scabiei ; Scabies ; Skin ; Skin Diseases ; Toluidines

Chromatography, Gas ; methods ; Humans ; Trifluralin ; blood