Val1483Ile polymorphism in the fatty acid synthase gene was associated with depressive symptoms under the influence of psychological stress

金沢大学医薬保健研究域薬学系Background: To study the association between lipid-metabolism and depressive symptoms, genetic polymorphisms in serotonin transporter linked promoter region (5-HTTLPR) and fatty acid synthase gene (FASN) were investigated. Method: A cross-sectional study was conducted on 177 women (n = 166) and men (n = 15) recruited from workers in a hospital and nursing homes in Japan. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression (CES-D) scale and perceived psychological stress was measured using visual analogue scale (VAS). The genotypes of 5-HTTLPR (insertion/deletion; L/S), and FASN (Val1483Ile) were determined by the PCR methods. Linear regression analysis was performed, in which CES-D scores served as a dependent variable, and VAS scores, gene polymorphism, and confounders as independent variables. Results: Under the influence of perceived stress, S/S carriers of the 5-HTTLPR gene showed significantly higher CES-D scores in comparison with L/L + L/S carriers (F = 8.2, standardised β = 0.15, p < 0.05). Regression analysis also confirmed that CES-D scores in participants with Ile/Ile + Val/Ile genotypes of the FASN gene were significantly higher than those with Val/Val genotype (F = 8.4, standardised β = 0.16, p < 0.05). In relation to physical features, BMI among participants with S/S genotype of 5-HTTLPR was significantly lower compared with those with L/L + L/S genotypes. Conclusions: The Val1483Ile polymorphism in the FASN was associated with depressive symptoms under the influence of psychological stress. The S variant of 5-HTTLPR was related with less obese. © 2011 Elsevier B.V. All rights reserved

Investigation of Antibiotic Use at a Dental Teaching Hospital in Yogyakarta, Indonesia: A Review from Guidelines

医薬保健研究域薬学系Objective: To investigate prescription of antibiotics by dental practitioners at a dental teaching hospital in Yogyakarta, Indonesia, and to establish whether it conforms to major guidelines. Methods: A cross-sectional study of adult outpatients’ medical records was conducted in order to scrutinize antibiotic prescriptions. The results were compared with recommendations in four published guidelines. Results: Dental practitioners prescribed a wide range of antibiotics to treat 121 diagnoses. Amoxicillin (78.8%) was most commonly prescribed, followed by clindamycin (9.9%), metronidazole (5.0%), and lincomycin (2.1%). Among all prescriptions, 79.5% were for generic antibiotics. The most common diagnoses were dental pulp gangrene followed by dental pulp necrosis (26.7% and 8.8%, respectively). According to guidelines-1 through-4, the percentages of antibiotic prescriptions that were evaluated as appropriate for the reported diagnosis were 15.1%, 7.2%, 7.5%, and 16.3%, respectively. However, 9.9%, 84.0%, 83.7% and 67.8% of prescriptions could not be classified as appropriate or inappropriate because the respective guidelines neither listed the antibiotic nor gave statement regarding appropriate indications. Conclusion: Our results suggest that significant inappropriate antibiotic prescribing occurred at a dental teaching hospital in Yogyakarta, Indonesia, according to major antibiotics guidelines. However, the four guidelines failed to list some antibiotics, failed to list indications for prescription in some cases, and were inconsistent in their recommendations. There is a need to introduce specific institutional guidelines. Our findings should be helpful for developing public health policy guidelines to minimize inappropriate antibiotic prescribing at dental hospitals

A cross-sectional investigation of the quality of selected medicines in Cambodia in 2010.

Access to good-quality medicines in many countries is largely hindered by the rampant circulation of spurious/falsely labeled/falsified/counterfeit (SFFC) and substandard medicines. In 2006, the Ministry of Health of Cambodia, in collaboration with Kanazawa University, Japan, initiated a project to combat SFFC medicines. To assess the quality of medicines and prevalence of SFFC medicines among selected products, a cross-sectional survey was carried out in Cambodia. Cefixime, omeprazole, co-trimoxazole, clarithromycin, and sildenafil were selected as candidate medicines. These medicines were purchased from private community drug outlets in the capital, Phnom Penh, and Svay Rieng and Kandal provinces through a stratified random sampling scheme in July 2010. In total, 325 medicine samples were collected from 111 drug outlets. Non-licensed outlets were more commonly encountered in rural than in urban areas (p < 0.01). Of all the samples, 93.5% were registered and 80% were foreign products. Samples without registration numbers were found more frequently among foreign-manufactured products than in domestic ones (p < 0.01). According to pharmacopeial analytical results, 14.5%, 4.6%, and 24.6% of the samples were unacceptable in quantity, content uniformity, and dissolution test, respectively. All the ultimately unacceptable samples in the content uniformity tests were of foreign origin. Following authenticity investigations conducted with the respective manufacturers and medicine regulatory authorities, an unregistered product of cefixime collected from a pharmacy was confirmed as an SFFC medicine. However, the sample was acceptable in quantity, content uniformity, and dissolution test. The results of this survey indicate that medicine counterfeiting is not limited to essential medicines in Cambodia: newer-generation medicines are also targeted. Concerted efforts by both domestic and foreign manufacturers, wholesalers, retailers, and regulatory authorities should help improve the quality of medicines

Erroneous formulation of delayed-release omeprazole capsules: Alert for importing countries

Background: Poor drug quality is a matter of serious concern, especially in countries where drug regulation and law enforcement are constrained by limited resources. This study was carried out to investigate the cause of quality failure of omeprazole in Cambodia in 2010 and Myanmar in 2014. Methods: We conducted pharmacopoeial quantity, content uniformity and dissolution tests of 156 samples of omeprazole capsules collected in Cambodia in 2010 and Myanmar in 2014. High failure rates were found, especially in dissolution testing, and detailed investigation of several unacceptable samples was carried out by means of in-vitro dissolution profiling, scanning electron microscopy (SEM) and X-ray computed tomography (X-ray CT) to identify the cause of failure. Results: Dissolution profiling with and without the acid stage showed that acid caused premature omeprazole release, indicating that the enteric coating of the omeprazole granules was ineffective. SEM examination of two failed samples revealed cracked and broken granules mixed with apparently intact omeprazole granules in the capsule. X-ray CT examination indicated that some granules of failed samples completely lacked enteric coating, and others had incomplete and non-uniform enteric coating or malformation. Conclusions: Omeprazole capsules collected in Myanmar and Cambodia showed high failure rates in pharmacopoeial tests, especially dissolution tests. Some samples were found to have ineffective or absent enteric coating of the granules, resulting in premature dissolution and degradation in acidic conditions. This is a potentially serious public health issue that needs to be addressed by regulatory authorities in Cambodia and Myanmar, possibly through a collaborative initiative with manufacturers. © 2017 The Author(s)

Adherence of Community Pharmacies in Riyadh, Saudi Arabia, to Optimal Conditions for Keeping and Selling Good-Quality Medicines

医薬保健研究域薬学系Exposure to excessive temperature during distribution or storage has unfavorable consequences on the quality of medicines, particularly in hot climates. This could be one of the possible reasons behind the existence of substandard amoxicillin in community pharmacies in Riyadh, Saudi Arabia. This study explored the conditions under which medicines were kept in a random sample of 181 community pharmacies in Riyadh. The pharmacist in charge in each pharmacy was interviewed and our observations about the quality of storage were recorded. The inspection revealed that in 9% of the sample the readings of the existing room thermometers were >25℃, and that 13% of the sample lacked thermometers. Also in 33% of the sample the readings of the refrigerator thermometers were outside the accepted range, and 7% of the sample lacked refrigerator thermometers. About 15% of pharmacists were not informed about the local regulations of community pharmacy practice, neither before nor after taking up their current positions. Surprisingly, incorrect answers to simple questions about the system were frequently given by the informed pharmacists. Certain aspects of substandard storage conditions existed, in varying degrees, in significant percentages of pharmacies regardless of the pharmacists’ qualifications, experience, or awareness about the local regulations of community pharmacy practice. Stricter monitoring by the authorities regarding the adherence of community pharmacies to optimal conditions of storing medicines is recommended. Continuing education of community pharmacists must also be improved

What Do Customers Demand from Drug Stores in Japan? Construct Validity and Factor Structure of a Cross-Sectional Survey.

医薬保健研究域薬学系Studies concerning patient demands are mainly conducted at hospitals and pharmacies, whereas few surveys have been conducted on drug stores. The demand for drug stores is estimated to be increasing with growing needs for self-medication. Thus, conducting a customer survey at drug stores is thought to be valuable. The aim of the current study was to clarify the structure of customers’ demands for drug stores. The survey was conducted on 190 customers of 19 drug stores in Japan. The questionnaire consisted of 24 items using a 9-point Likert scale. The IBM SPSS Statistics version 23 (IBM Japan, Tokyo, Japan) and Amos version 5 (IBM Japan, Tokyo, Japan) were utilized to perform factor analysis. Gender did not influence the response to each question. Factor analysis showed that the structure of customers’ demands consisted of three factors: (1) an explanation about medicine, (2) staff’s manners, and (3) location of drug stores. Because fit indices suggested a good fit, this three-factor solution was adopted as the final factor structure. This study demonstrated the structure of customers’ demands for drug stores, with the potential for use in promotion of self-medication

The Quality of Medicines in Community Pharmacies in Riyadh, Saudi Arabia: A Lot Quality Assurance Sampling (LQAS)-Based Survey

医薬保健研究域薬学系Objectives: To classify community pharmacies (CPs) in Riyadh, Saudi Arabia, in terms of the quality of medicines sold by them, using the lot quality assurance sampling (LQAS) technique with a predefined threshold. Methods: Riyadh CPs were divided into 2 categories (“lots” for the purpose of LQAS), i.e., chain and independent CPs. Upper and lower rate thresholds for CPs that sell low-quality medicines were predefined as 20% and 5%, respectively. Consumer and provider risks were predefined as 0.05 and 0.10, respectively. The calculated number of randomly selected CPs required in each lot was 36; then, sale of low-quality medicines in >3 CPs implies a prevalence of >20% of such CPs according to LQAS. A randomly selected brand of amoxicillin (selected as a quality indicator of medicines because it is both widely counterfeited and heat-sensitive) was purchased from each pharmacy by a “mystery shopper”, checked for authenticity, and analyzed for drug content and content uniformity using a validated HPLC method. Results: Substandard amoxicillin was purchased in 9 pharmacies (4 chains and 5 independent). Both lots were thus rejected as unacceptable, which may indicate that consumers in Riyadh are at risk of purchasing substandard medicines at CPs. Conclusions: The quality of medicines sold in CPs in Riyadh did not meet our acceptability criterion, and appropriate intervention by decision makers is recommended. LQAS proved to be a practical, economical, and statistically valid sampling method for surveying the quality of medicines. It should enable decision makers to allocate resources for improvement more efficiently

Public health concerns for anti-obesity medicines imported for personal use through the internet: a cross-sectional study.

医薬保健研究域薬学系Objective: To explore the circulation of anti-obesity medicines via the internet and their quality. Design: Cross-sectional study. Setting: Internet pharmacies and pharmaceutical suppliers accessible from Japan. Participants: Anti-obesity medicines were purchased using relevant keywords on Japanese Google search engine. Blogs and advertisement-only sites were excluded. Primary and secondary outcome measures: The authenticity of the samples was investigated in collaboration with the manufacturers of the samples and medicine regulatory authorities. Quality of the samples was assessed by pharmacopoeial analyses using high-performance liquid chromatography. Results: 82 samples were purchased from 36 internet sites. Approximately half of the sites did not mention a physical address, and 45% of the samples did not contain a package insert. A variety of custom declarations were made for the shipments of the samples: personal health items, supplement, medicines, general merchandise, tea and others. Among 82 samples, 52 samples were analysed to check their pharmacopoeial quality. Authenticity responses were received from only five of 20 manufacturing companies. According to the pharmacopoeial analyses and authenticity investigation, three of the samples were identified as counterfeits and did not contain any active ingredients. Two of these samples were confirmed as counterfeits by the manufacturer of the authentic products. The manufacturer of the other sample did not respond to our request for an authenticity check even after several communication attempts. These counterfeit cases have been reported at the rapid alert system of Western Pacific Region of the WHO. Conclusions: Many counterfeit and unapproved anti-obesity medicines may be easily bypassing regulatory checks during shipping and are widely circulated through the internet. Regulatory authorities should take measures to prevent these medicines from entering countries to safeguard their citizens

Survey to Identify Substandard and Falsified Tablets in Several Asian Countries with Pharmacopeial Quality Control Tests and Principal Component Analysis of Handheld Raman Spectroscopy.

医薬保健研究域薬学系The World Health Organization has warned that substandard and falsified medical products (SFs) can harm patients and fail to treat the diseases for which they were intended, and they affect every region of the world, leading to loss of confidence in medicines, health-care providers, and health systems. Therefore, development of analytical procedures to detect SFs is extremely important. In this study, we investigated the quality of pharmaceutical tablets containing the antihypertensive candesartan cilexetil, collected in China, Indonesia, Japan, and Myanmar, using the Japanese pharmacopeial analytical procedures for quality control, together with principal component analysis (PCA) of Raman spectrum obtained with handheld Raman spectrometer. Some samples showed delayed dissolution and failed to meet the pharmacopeial specification, whereas others failed the assay test. These products appeared to be substandard. Principal component analysis showed that all Raman spectra could be explained in terms of two components: the amount of the active pharmaceutical ingredient and the kinds of excipients. Principal component analysis score plot indicated one substandard, and the falsified tablets have similar principal components in Raman spectra, in contrast to authentic products. The locations of samples within the PCA score plot varied according to the source country, suggesting that manufacturers in different countries use different excipients. Our results indicate that the handheld Raman device will be useful for detection of SFs in the field. Principal component analysis of that Raman data clarify the difference in chemical properties between good quality products and SFs that circulate in the Asian market. Copyright © 2018 by The American Society of Tropical Medicine and Hygiene