According to Article 4 of the Food Safety Basic Law (Law No. 48 of 2003), food safety must be ensured by taking necessary measures appropriately at each step of the food supply process both in Japan and overseas. From this viewpoint, for ensuring safety of imported foods further, the quarantine stations have obligations such as confirmation of the import-notification documents submitted under Article 27 of the Law, issue of inspection orders in accordance with Article 26 of the Law for imported foods suspected with high probability of violating the Act (in order to prevent harm to public health from the perspective of food sanitation), and implement of monitoring inspection under Article 28 of the Law to enforce checking of the food-sanitation conditions of various imported foods. If a quarantine station or local organization (including prefectures, cities and specially designated wards that operate public health centers) identify any violation of the Law, the Ministry of Health, Labour and Welfare (hereinafter referred to as “the MHLW”), the quarantine station and the related prefecture shall cooperate to take appropriate measures to help the corresponded importer recall the food as soon as possible. In addition, taking measures to prevent recurrence of such violations by demonstration of examples of violations and guidance to importers. Under the recent situation of accidents such as addition of toxic substances to the food, it is important to make continuous efforts for achieving food safety in exporting countries. With recognition that assurance of the safety of the consumer from foodborn illness, it is necessary for the MHLW, the Agency of Consumer Affaires, local governments and related offices to make active efforts together through risk evaluation, risk management and the risk communication for 1 while measuring the communication.
When food safety is mentioned, people would think about food which is in compliance with Food Sanitation Act and standard, and edible food. Because there is difference in terms of food and additives standards between Japan and other countries, a variety of food cannot be imported from foreign countries to Japan. In addition, in 2006, with the introduction of the Positive List, which takes a close-up of pesticide remained in food and anti-biotic, we adopted an effective policy towards imported food which does not reach the national standards. On one hand, in order to ensure food safety, domestic producers, hotels, fast food stores, and restaurants all try to strengthen management on food quality and employees health. However, food poisoning happens frequently. Chemicals and natural poisoning play a part but the major part is played by micro-organism (bacteria). So it become more and more important to develop food safety policies to avoid harm from bad food. Therefore, as an authority with the responsibility of quarantine, inspection and registration, it is important to conduct food inspection and it is even more important to provide comprehensive suggestions.
An accurate analysis is required to address various issues concerning the food safety. Many risk factors, such as agricultural chemical residues, residual veterinary drugs, mycotoxins, food additives, and carcinogens produced during food processing may be present in foodstuffs. High-performance liquid chromatograph-tandem mass spectrometry (LC-MS/MS) is an analytical system advanced in terms of sensitivity, selectivity, and flexibility. The system has been widely applied to food analysis. Food contains a wide variety of nutritional components, which may cause interference with food analyses. Then, sample preparation to remove such interference and an appropriate choice of an analytical technique is required. Even with LC-MS/MS, the analytical reliability may be reduced by matrix effects, due to interference from food components. In this review, we summarize issues on using LC-MS/MS to achieve good analyses for the food safety and discuss how to address it. The topic especially focuses on matrix effects.
Recently, many accidents relating to food happened in Japan. The consumer's distrust for food, food companies, and the administration is increasing. The consumer especially has an extreme refusal feeling for chemicals such as food additives and agricultural chemicals, and begins to request agricultural chemical-free vegetables and food additive-free food. Food companies also state no agricultural chemicals and no food additives to correspond with consumers' request and aim at differentiating. The food additive is that the Ministry of Health, Labour and Welfare specifies the one that person's health might not be ruined by providing for Food Sanitation Law Article 10 in our country. The standard for food additives and standard for use of food additives are provided according to regulations of Food Sanitation Law Article 11. Therefore, it is thought that the food additive used is safe now. Then, it reports on the procedure and the safety examination, etc. in our country for designation for food additive this time.
Viridicatin derivatives were synthesized from cyanoacetanilides utilizing the CN groups as electron-withdrawing groups and leaving groups. Also, the key scaffolds of glycocitlones were constructed via the intramolecular Houben-Hoesch-type reactions of cyanoacetanilides where the CN groups functioned as electrophiles. It was found that Houben-Hoesch-type reactions of cyanoacetanilides were promoted by α-functionalization such as perfluoroacylation and N,N-dimethylaminomethylenation and that introduction of such substituents at α-position with respect to the CN groups greatly influenced the physical properties and chemical reactivity of the CN groups.
It is shown that glial cells have a pivotal influence on the formation of neuronal network in central nerve system. Moreover, spinal microglia has some important roles in the development and progression of various neurological disorders. Therefore, it is possible that modulation of microglial activity may be sufficient to alleviate those harmful responses. ATP is one of signaling molecules in the spinal cord, and involved in regulation of several microglial functions through the binding of P2X and P2Y receptors. Thus, I focused on the ATP-mediated regulation mechanisms for the two important proteins, which are p38 MAP kinase and excitatory amino acid transporters (EAATs), in cultured spinal microglia. Mounting evidence indicates that p38 in spinal microglia has crucial roles in some neurological diseases. Furthermore, it is recently suggested that microglial EAATs might participate in the homeostasis of glutamate in synapses. This review summarizes our finding regarding the involvement of P2Y receptors and β-adrenergic receptors in the regulation of p38 phosphorylation, and the mechanism of P2X7 receptor-mediated downregulation of EAATs function.
Glycosphingolids and glycoproteins in cell membrane are thought to play important roles in variety biological phenomena. Our interests focused on elucidation of their functions at the molecular level. We are especially interested in organic chemistry and physical chemistry of carbohydrates. Physical part-Surface of Langmuir-Blodgett (LB) films which comprised of various gangliosides, sphingolipids and cholesterol are observed by atomic force microscopy (AFM). We studied distribution of model compounds related to an antigenic epitope from Bupleurum falcatum L. in GM3 (GM3)-DPPC monolayers. We also investigated relation between disease and glycolids in cell membrane. Chemical part-New molecular tools for the elucidation of carbohydrate roles using photoaffinity labeling were developed. We showed that the structural difference between closed ring- and open ring-type carbohydrates affected binding affinity to proteins. This study confirmed that carbohydrate structure, in both non-reducing end and reducing end sugars, is deeply related to the recognition event between carbohydrates and proteins. As a result, they will be used in future studies to elucidate carbohydrate functions on cell surfaces.
Adult T-cell leukemia-lymphoma (ATL) is an aggressive peripheral T-cell neoplasm with a poor prognosis, developing after long-term infection with human T-cell leukemia virus-1 (HTLV-1). Multiple factors (e.g., virus, host cells, epigenetic aberrations, and immune factors) have been implicated in the development of ATL, although the underlying mechanisms of leukemogenesis have not been fully elucidated. Despite recent progress in both chemotherapy and supportive care for hematological malignancies, the prognosis of ATL is still poor; overall survival at 3 years is only 24%. New strategies for the therapy and prophylaxis of ATL (e.g., vaccines and novel molecular target agents) are still required. This article reviews new strategy of ATL treatment targeted for HTLV-1-specific cytotoxic T-lymphocytes (CTLs) and SIRT1, a longevity gene-encoded protein. HTLV-1-specific CTLs play a critical role in the host immune response against HTLV-1. We have described here the decreased frequency and function of HTLV-1-specific CD8+ T cells in ATL patients and the efficient induction of the HTLV-1-specific CTLs response in human leukocyte antigen-A* 0201-transgenic mice by the HTLV-1/hepatitis B core chimeric particle and oligomannose-coated liposomes encapsulating HTLV-1 epitope without adjuvant, suggesting that the efficient antigen delivery system and CTL induction can be exploited to develop a prophylactic vaccine model against tumors and infectious diseases. Furthermore, our studies suggest that SIRT1, a longevity gene-encoded protein, is a crucial anti-apoptotic molecule in ATL cells, and that SIRT1 inhibitors may be useful therapeutic agents for leukemia, especially in patients with ATL. These studies targeted for anti-tumor immunity such as vaccine and SIRT1 may support the new prophylactic and therapeutic approach for ATL.
It has been reported that non-steroidal anti-inflammatory drugs (NSAIDs) interact with aspirin to influence its antiplatelet effect. For example, there have been reported that the rate of platelet aggregation inhibition associated with aspirin was significantly decreased when ibuprofen was taken before administration of aspirin, as compared with aspirin alone. In this study, we investigated the prescriptions on combination of aspirin with NSAIDs. The subjects were consisted of 1212 patients who were prescribed aspirin in March, 2008 in Tokai University Hachioji Hospital. The patients prescribed combination of aspirin with NSAIDs were 8.1% and 18.6% of those were prescribed in the order of adminstration to induce drug interaction. The pharmacists should provide information about drug interactions of aspirin with NSAIDs to the doctors and patients, and it is necessary to pay attention of these interactions.
A series of 3-substituted-2-thioxoquinazolin-4(3H)-one derivatives have been synthesized and their structures have been elucidated on the basis of IR, 1H-NMR, elemental analysis and mass spectroscopic studies. Anti-inflammatory and analgesic activity of the synthesized compounds was evaluated by Carrageenan induced rat paw edema method and Eddy's hot plate method respectively. Among the synthesized compounds N-(4-hydroxyphenyl)-N-(4-oxo-3-phenyl-2-thioxo-3,4-dihydroquinazolin-1(2H)methyl)acetamide (PTQ01) showed excellent anti-inflammatory activity. N-(4-ethoxyphenyl)-N-(3-(naphthalen-2yl)-4-oxo-2-thioxo-3,4-dihydroquinazolin-1(2H)-yl)methyl)acetamide (NTQ02), N-(4-Hydroxyphenyl)-N-((3-naphthalen-2-yl)-4-oxo-2-thioxo-3,4-dihydorquinazolin-1(2H)-ylmethyl)acetamide (NTQ01), N-((3-(4-ethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydoquinazolin-1(2H)-yl)methyl)-N-(4-hydroxyphenyl)acetamide (ETQ01) N-(3-(4-ethoxyphenyl)-4-oxo-2thioxo-3,4-dihydroquinazolin-1(2H)-ylmethyl)-N-(4-hydroxyphenyl)acetamide (ETQ04), N-(4-ethoxyphenyl)-N-((4-oxo-3-phenyl-2-thioxo-3,4-dihydoquinazolin-1(2H)-yl)methyl)acetamide (PTQ02) and N-(4-ethoxyphenyl)-N-(3-(4-ethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydoquinazolin-1(2H)-yl)methyl)acetamide (ETQ02) at a dose of 20 mg/kg exhibited significant anti-inflammatory activity compared to that of standard drug diclofenac sodium. The compound 2-(2,3-dimethylphenyl)(3-(4-ethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydroquinazolin-1-2H)-1ylmethylamino)benzoic acid PTQ03 and sodium 2-(2-((2,6-dichlrophenyl)(3-(4-oxo-2-thioxo-3,4-dihydroquinazolin-1(2H)-yl)methyl)amino)phenylacetate (PTQ04) showed moderate anti-inflammatory activity. The compounds PTQ01, PTQ02, PTQ04, ETQ01 and ETQ02 showed significant analgesic activity compared with that of standard drug pentazocin.
Aspirin irreversibly inhibits the enzyme cyclooxygenase-1 and depresses the production of thromboxane A2, and also exerts antiplatelet effects. On the other hand, it also depresses the production of prostaglandin E2 (PGE2) and induces gastroduodenal lesions, which are often seen in patients taking aspirin. The aim of this study was to clarify the degree of gastroduodenal lesions induced by low-dose aspirin. We investigated the incidence rate of such lesions induced by aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), and performed theoretical evaluations in a retrospective study. The incidence rates of gastroduodenal lesions in the low-dose aspirin (n=1103) and NSAIDs (n=1856) groups were 2.54% and 0.27%, respectively, which was significantly greater in the aspirin group. Furthermore, the calculated value of inhibition rate of gastric PGE2 was significantly correlated with the actual value after administration of aspirin or NSAIDs (r=0.902, p<0.05), which suggested that the calculated value reflected the actual value. The calculated value of aspirin (98.9%) was higher than that of NSAIDs (3.67-70.8%) after administration of the drugs with the standard doses. Our findings indicate that the incidence rate of gastroduodenal lesions induced by low-dose aspirin was higher than that of those induced by NSAIDs. Therefore, we were able to perform a theoretical evaluation of the occurrence of gastroduodenal lesions.
Simultaneous and fractional determination of iron(II) and iron(III) was accomplished with o-hydroxyhydroquinonephthalein (QP) in the presence of poly (N-vinyl pyrrolidone). In the determination of total iron (iron(II)+iron(III)), Beer's law was obeyed in the range of 0.02-0.67 μg·ml−1, with an effective molar absorptivity (at 570 nm) and a relative standard deviation of 1.30×105·l·mol−1·cm−1 and 0.77% (n = 8), respectively. This method was about 10-15 times and more than the methods using 1,10-phenanthroline and 2,2′-bipyridine. In addition, the iron-QP complex was characterized using spectrophotometry and the electron spin resonance. This method was successfully applied to assays of total iron and iron(III) in pharmaceutical preparations.
We investigated the evidence of gastric protection for ulcer and gastritis by Cinnamomi Ramulus (Cinnamomum cassia Blume, Geiji, CR) extract and its several constituents. CR ethanolic extract showed the potent antioxidant activity and cytotoxicity of Helicobacter pylori (H. pylori) and acid-neutralizing capacity. Especially, eugenol exerted a significant antioxidant activity and inhibited the colonization of H. pylori. In vivo test, eugenol and cinnamic acid significantly inhibited HCl/ethanol-induced gastric lesions and increased the mucus content though they didn't inhibit gastric secretion effectively. Taken together, eugenol and cinnamic acid, which were isolated from CR, exhibited the antioxidant activity in vitro and protective effect against gastric damage in vivo through stimulation of mucus secretion and so on. It suggested that they are useful as the neutraceuticals for gastritis.
A facile fluorometric assay using D-kynurenine as a substrate was utilized for evaluating the inhibition of D-amino acid oxidase (DAAO), which is one of the products of a susceptibility gene for schizophrenia, by commercial antipsychotic drugs, namely, chlorpromazine (CPZ), carbamazepine, sulpiride, quetiapine, and imipramine. CPZ inhibited DAAO (65.8 ± 13.2 μM, n = 3) as reported previously, and other drugs also inhibited DAAO activity. Among these, quetiapine had the smallest IC50 value (19.5 ± 2.60 μM, n = 3). The proposed assay can be useful for the evaluation or screening of DAAO-inhibitory drugs.
In recent years, self-medication is promoted to control the health care cost of aged people in Japan. On the other hand, there are many pharmacists who are perplexed in diversification of work with promotion of self-medication because of shortage of information, including the knowledge of an over-the-counter drug, health food, etc. It is therefore needed to design an efficient education program for pharmacists, especially in aging society such as Fukuyama. In this study, we investigated the needs for self-medication of local residents and community pharmacists in order to clarify the high-priority education themes for promotion of self-medication in Fukuyama. The pharmacist's needs were extracted by the KJ method and prioritized by the two-dimensional developed leaf method, and the local resident's needs were extracted by questionnaire survey from 420 general populations who live in Fukuyama. As a result, we found that the community pharmacists were especially in need of acquisition of the knowledge about “health food” and “food”, and the local residents were especially in need of consultation with community pharmacists about “medicine”, “side effect of medicine”, “health food” and “food”. Moreover, we also found that sixty percent of local residents did not have knowledge about interaction of “medicine” and “health food” while the half of them was taking in “health food”. From the above result, knowledge improvement of “health food”, “food” and “interaction of medicine and health food” in addition to “medicine” and “side effect of medicine” is the high-priority education themes for local residents and community pharmacists to promote self-medication in Fukuyama.
To know the actual states of understanding and utilization of “home pharmacy” in regional residents and their regional differences, we performed questionnaire survey for the residents in Ueda-shi in Nagano and the Kita-tama area in Tokyo, where it was found in the past survey that the medical activities as “home pharmacy” in Ueda-shi was remarkably higher than those in the Kita-tama area. By the present survey it was confirmed that the percentages of the person who keeps “home pharmacy” and of the person who fixes a pharmacy to get a filled prescription were remarkably higher in the residents of Ueda-shi than those of the Kita-tama area. The level of understanding of “home pharmacy” was also higher in the residents of Ueda-shi. These results suggested that the spread of “home pharmacy” is influenced by the extent of activity of regional pharmacy and the regional society of pharmacists.
Harmful elements are used as stabilizers and colorants in synthetic resin products. Accidental ingestion of harmful elements from such synthetic resins by infants is a dangerous health hazard. The Japanese Food Sanitation Law and the International Standard ISO 8124-3 “Safety of toys-Part 3: Migration of certain elements” control the levels of migrated harmful elements, such as lead or cadmium, from infants toys. However, the levels of migrated harmful elements from household products that are not infants toys are not controlled, since they are not covered by the law or standard. Therefore, we investigated the level of eight harmful elements (antimony, arsenic, barium, cadmium, chromium, lead, mercury and selenium) migrated from household products made of synthetic resin that infants may swallow by mistake. The extraction test of ISO 8124-3: 2010 was executed in 135 products (total 150 specimens), and the concentration of these elements was measured by inductively coupled plasma mass spectroscopy (ICP-MS). As a result, 1810 mg/kg and 1660 mg/kg of lead, exceeding the maximum acceptable level of the ISO standard, migrated from two products. In addition, lead and/or chromium at levels more than 1/10 of the maximum acceptable levels of the ISO standard migrated from four products. Household products that infants may swallow by mistake should ideally not release harmful elements such as lead and chromium.
Recently, many psychotropic herbal products, named such as “Spice”, were distributed worldwide via the Internet. In our previous study, several synthetic cannabinoids were identified as adulterants in herbal products being available in Japan due to their expected narcotic effects. Among those, two derivatives of Δ9-tetrahydrocannabinol (Δ9-THC), which is major psychotropic cannabinoid of marijuana, cannabicyclohexanol (CCH, 3-[2-hydroxy-4-(2-methylnonan-2-yl)phenyl]cyclohexan-1-ol) and CP-47,497 (3-[2-hydroxy-4-(2-methyloctan-2-yl)phenyl]cyclohexan-1-ol), have been controlled as designated substances (Shitei-Yakubutsu) under the Pharmaceutical Affairs Law since November 2009. CCH was detected together with its trans-form (1-epimer) in many herbal products, and CCH and CP-47,497 have two chiral centers in the structures. However, the pharmaceutical activities of the isomers of CCH have not been reported. This study presents chiral separations of CCH, its trans-form and CP-47,497 in the products using LC-circular dichroism (CD) and LC-MS analyses. The enantiomeric pairs of CCH, its trans-form and CP-47,497 were separated, respectively. Subsequently, the analyses of the herbal products showed that CCH and its trans-form existed as mixtures of enantiomers and the relative ratios of CCH and the trans-form enantiomers ranged from 42/58% to 53/47% and from 33/67% to 52/48%, respectively.