Photopolymers contaning hydrophilic carboxyl groups and photosensitive benzalacetophenone groups are synthesized by condensing the terpolymer comprizing 4-(vinylbenzyloxy) acetophenone, methacrylic acid and 2-HPM (or 2-HEMA, MMA) copolymers with benzaldehyde in alkaline catalyzer. Aqueous alkaline developing solution commercially available for negative type presensitizesd plate can be used for development of these photopolymers.
Sensitivity of the copolymer is estimated to be 35 mJ/cm² for UV light. These copolymers are applied to lithographic plate (under coat: diazonium polymer 0.2 μm thickness, top coat 4-(VBz) BAp copolymer 1.0-1.2 μm thickness), and the images with high quality are produced by a lithographic proofing machine. The Printing plate of these copolymers shows high resistivity in use of UV ink. These plates can be well preserved at high temperature (70°C) with high moisture condition.

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Uricosuric agents, such as benzbromarone and probenecid, are of limited use due to the risk of their drug-induced liver injury (DILI) and drug-drug interactions (DDIs). We have developed a novel uricosuric agent, dotinurad, that has a potent pharmacological effect while avoiding these risks. Inhibitory effect of dotinurad on mitochondrial function, an index of hepatotoxicity, was weak and there was no observation suggesting a risk of DILI taking into consideration the clinical dose or exposure. According to the guideline, dotinurad was assessed not to have a risk of DDI caused by inhibition of CYPs or transporters.

In confirmatory phase II and long-term studies, dotinurad decreased serum urate levels at low doses and almost patients receiving maintenance dose (2 or 4 mg) achieved a serum urate level ≤ 6.0 mg/dL. Moreover, there was no finding to raise safety concern including liver injury. Dotinurad is characterized as a selective urate reabsorption inhibitor (SURI), which is defined as a potent URAT1 inhibitor with minimal effect on urate secretion transporters, including ABCG2 and OAT1/3. Our findings suggested that SURI is promising in view of superior hypouricemic effect, lower DDIs risk, and lower inhibitory effect on excretion of substances such as indoxyl sulfate known as uremic toxin.

Dotinurad has been approved in Japan, and described in the Guidelines for Management of Hyperuricemia and Gout 3rd edition, 2022 supplement version with its pharmacological classification as an SURI. Its efficacy and safety will be further evaluated in the clinical use.

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　68歳，男性．1カ月以上続く不明熱の原因検索目的で当院に紹介された．各種検査で異常を認めず，詳細な問診で発汗の自覚がないことが判明したため，発汗テストを行った．広範囲で発汗を認めず，特発性後天性全身性無汗症（acquired idiopathic generalized anhidrosis：AIGA）と診断した．炎症反応上昇を伴わず，発汗障害を認める患者には，本疾患を鑑別疾患に挙げる必要がある．

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ドチヌラド（ユリス^®錠）は、（株）で創製され、第Ⅲ相試験から持田製薬（株）とともに開発され2020年1月「痛風・高尿酸血症」を適応症として製造販売承認された。本剤は選択的で強力な尿酸トランスポーター1（urate transporter 1:URAT1）阻害作用を示し、さらに、肝障害の原因の1つと考えられているミトコンドリア呼吸阻害やCYP2C9阻害による薬物相互作用が少ないと期待される新規の選択的尿酸再吸収阻害薬（selective urate reabsorption inhibitor: SURI）である。

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沖縄県におけるミバエ類侵入警戒用モニタリングトラップの防蟻剤として用いられてきたフジタングル^®（工業株式会社）（旧剤）が製造中止になったことから，その代替資材としてTree Tanglefoot Pest Barrier^® (The Tanglefoot^® Company, Michigan, USA)（新剤）のアリの侵入防止能力及び物理的性質について旧剤との比較を行った。新剤のアリの侵入防止能力においては５１日間の調査期間をとおして旧剤と有意な差は見られず，また溶解や硬化もみられなかった。これらの結果から，新剤のミバエ類侵入警戒モニタリングトラップ用防蟻剤としての有効性を考察する。

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カマボコにラクトンを添加して加熱肉のpHを6以下にする場合,ラクトン添加後の放置時間および放置方法がカマボコの足にいかなる影響を与えるか,またカマボコの足の補強方法として用いられている坐り法あるいは2段加熱法などをラクトンを添加したカマボコに,どの程度適用し得るかをアラボノ-γ-ラクトン,グルコノ-δ-ラクトンを用いて比較検討した。
(1) ラクトン添加前のすり身のpHが6.1付近でラクトン添加量が0.5%の場合,アラボノ-γ-ラクトンを添加したすり身を,20℃で2～2.5時間放置してから整形した場合には,カマボコの足の著しい低下は認められなかったのに反し,グルコノ-δ-ラクトンを添加したものは30分間の放置で足の低下をきたす。
(2) ラクトン添加前のpHが6.5付近のすり身にラクトン0.3%を添加し,これを整形したのち再すりつぶしを行なわず加熱する場合には,グルコノ-δ-ラクトンを添加したカマボコでも放置時間による足の著しい低下はみられなかった。なおアラボノ-γ-ラクトンを添加したカマボコは無添加のカマボコと同程度に,坐りによる足の増強効果が認められ,放置時間に伴う足の低下はなかった。
(3) ラクトンを添加したすり身を2段加熱した場合,1段目40℃の加熱ではアラボノ-γ-ラクトンを添加したカマボコでは,かなり足の増強効果が認められたが,グルコノ-δ-ラクトンを添加したカマボコではほんどその効果が認められなかった。

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  In this study, a survey was conducted to determine the rate of drug-dispensing errors with the use of medicine bags printed with photographs of prescribed medicines (hereafter “medicine bag”) for a 6-week period from June 20 to July 31, 2005. During this period, 393928 prescriptions were filled in 127 medical facilities that use the medicine bag. The efficacy of the medicine bag in the prevention of drug-dispensing errors was investigated. A total of 6550 (1.66%) drug-dispensing errors were identified: 70.6% were identified at the inspecting stage; 27.4% at the providing medicine and information stage; and 2% after the medication was dispensed. The drug-dispensing errors identified in the inspecting and providing stages included a) using the wrong contents, b) dispensing the wrong drugs, c) missing drugs, d) calculation errors, e) weighing/measuring errors, and f) others. No significant difference was observed in the error rates; thus it was assumed that the type of error was not dependent on the stage at which dispensing errors was discovered. However, it was found that approximately 25% of errors at the providing stage were discovered as a result of the medicine bag. Errors of types a), b), and c) were often discovered because the photograph was printed on the medicine bag. Therefore it was assumed that the photographs contributed to the discovery of drug-dispensing errors.

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It is known that there are species differences in the purine metabolic system between humans and rodents (e.g. urate oxidase (Uox), and hypoxanthine phosphoribosyltransferase (HPRT), etc.). URAT1 (SLC22A12) is renal urate (UA) reabsorption transporter and the target for UA-lowering therapies. In humans, URAT1 deficiency has a significant UA-lowering effect (ULE), but not in Urat1-knokout (KO) mice. The aim of this study is the establishment and urate kinetic profiling of high HPRT activity Urat1-Uox double knockout (DKO) mice and the investigation of the effect of xanthine oxidoreductase inhibitor (XOI), topiroxostat in this model mice. Topiroxostat 1 mg/kg (Top) was administered to DKO mice for 7 days by feeding diet. Oxypurines (UA, hypoxanthine and xanthine) and creatinine in plasma and urine were measured by HPLC. DKO mice showed a significant decrease in plasma UA levels, increased fractional excretion of UA (FE_UA), and enhanced Top-induced ULEs, compared with Uox-KO only. Thus, high HPRT activity seems to be important for producing ULE by URAT1 inhibition. The combination therapy of URAT1 inhibition and XOI showed an effective ULEs, suggesting that it is useful for the treatment of hyperuricemia.

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It is known that there are species differences in the purine metabolic system between humans and rodents (e.g. urate oxidase (Uox), and hypoxanthine phosphoribosyltransferase (HPRT), etc.). URAT1 (SLC22A12) is renal urate (UA) reabsorption transporter and the target for UA-lowering therapies. In humans, URAT1 deficiency has a significant UA-lowering effect (ULE), but not in Urat1-knokout (KO) mice. The aim of this study is the establishment and urate kinetic profiling of high HPRT activity Urat1-Uox double knockout (DKO) mice and the investigation of the effect of xanthine oxidoreductase inhibitor (XOI), topiroxostat in this model mice. Topiroxostat 1 mg/kg (Top) was administered to DKO mice for 7 days by feeding diet. Oxypurines (UA, hypoxanthine and xanthine) and creatinine in plasma and urine were measured by HPLC. DKO mice showed a significant decrease in plasma UA levels, increased fractional excretion of UA (FE_UA), and enhanced Top-induced ULEs, compared with Uox-KO only. Thus, high HPRT activity seems to be important for producing ULE by URAT1 inhibition. The combination therapy of URAT1 inhibition and XOI showed an effective ULEs, suggesting that it is useful for the treatment of hyperuricemia.

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The differences of purine metabolism of mice from that of human are known to be not only conserved uricase (Uox), but also low hypoxanthine phosphoribosyltransferase (HPRT) activity. The aim of this study is the establishment of high HPRT activity-Uox knockout mice as mouse model for the study of purine metabolism in human and the investigation of the effect of Allopurinol and Topiroxostat on HPRT. Allopurinol 30 mg/kg (Allo) and Topiroxostat 1 mg/kg (Top) were administered to the model mice for 7 days by feeding diet. Oxypurines (urate (UA), hypoxanthine (HX) and xanthine (XA)) and creatinine (Cr) in plasma and urine were measured by HPLC. Plasma UA value and urinary UA/Cr ratio significantly decreased in Allo and Top. Although the plasma UA-lowering effect was equivalent in Allo and Top, the urinary HX+XA/Cr ratio in Top 1 was significantly lower than those in Allo. Moreover, urinary oxypurine/Cr ratio demonstrated a significant lowering effect in Top, but not in Allo. In conclusion, Topiroxostat has a potent plasma UA-lowering effect and didn't affect the salvage pathway unlike Allopurinol, efficiently resulted in decreased total oxypurine excretion.

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Hereditary renal hypouricemia type-1 (RHUC1) is a rare disease associated with markedly lower plasma urate (UA) and increased fractional excretion of UA (FE_UA) due to URAT1 dysfunction, and exercise-induced acute kidney injury (EIAKI) is known to be a serious complication, but its pathogenesis is unknown. The aim of this study is the investigation of pathogenesis of EIAKI and the effect of topiroxostat, a non-purine-type xanthine oxidoreductase inhibitor (XOI) using high HPRT activity Urat1-Uox double knockout (DKO) mice establishing as novel animal model of RHUC1. DKO mice were used in a forced swimming test as loading exercise to explore the onset mechanism of EIAKI and evaluate related purine metabolism and renal injury parameters. In DKO mice, exercise exacerbated renal injury and functional markers, and increased urinary UA/Cr ratio and plasma UA. In addition, NLPR3 inflammasome activation and increased IL-1β were observed in the kidney. Finally, we demonstrated that topiroxostat improved renal injury and functional parameters of EIAKI. The pathogenic mechanism of EIAKI was found to be due to increased levels of IL-1β via NLRP3 inflammasome signaling associated with excessive urinary UA excretion. In addition, topiroxostat, a non-purine-type XOI, appears to be a promising therapeutic agent for the treatment of EIAKI.

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  To ascertain the prevalence of allergy symptoms and consumer measures for eye, nose, skin, food, and asthma by prefecture. The self-evaluation questionnaire was mailed to 100,000 subjects throughout Japan by the OTC distribution network of Fujiyakuhin Co., Ltd. The prevalence of allergy symptoms for eye, nose, skin, food, and asthma was 17.3, 26.7, 14.5, 4.5, and 5.4%, respectively. These values were comparable with those of previous studies. The ratio of consultation behavior in respondents reporting allergy symptoms was estimated to be 26.4-82.1%. The usage rate of OTC drugs in respondents reporting non-consultation and the rate of combined use of prescription and OTC drugs were 2.9-51.1% and 7.0-44.1%, respectively. The positive likelihood ratio for subjective allergy in persons having an allergy history of “both parent and child” was 13.9, and this ratio for subjective child allergy in persons having an allergy history of “either parents” and “both parents” was 4.39 and 15.7. The relationship between consumer measures and the allergy history of subjects and families was observed in various combinations. In this study, the allergy prevalence of eye and food not reported in a previous study was estimated. Furthermore, it appears that there are points which make one think anew about the allergy information offered to consumers and patients by both OTC manufacturers/distributors and pharmacists.

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