Drug Discoveries and Therapeutics最新文献_第6页

Astragalus root increases Treg and Th17 involvement in embryo implantation and pregnancy maintenance by decreasing CTLA-4⁺ Tregs. 黄芪能通过减少 CTLA-4+ Tregs 增加 Treg 和 Th17 对胚胎植入和妊娠维持的参与。

IF 3.1

Drug Discoveries and Therapeutics Pub Date : 2024-03-20 Epub Date: 2024-02-21 DOI: 10.5582/ddt.2023.01100

Kyoko Kobayashi, Kenroh Sasaki

{"title":"Astragalus root increases Treg and Th17 involvement in embryo implantation and pregnancy maintenance by decreasing CTLA-4+ Tregs.","authors":"Kyoko Kobayashi, Kenroh Sasaki","doi":"10.5582/ddt.2023.01100","DOIUrl":"10.5582/ddt.2023.01100","url":null,"abstract":"Maintenance of pregnancy is highly dependent on the maternal immune system. High levels of regulatory T cells (Tregs) accumulate in the maternal placenta to suppress immunoreactivity against fetal antigens. We assessed whether Astragalus root (AsR) and AsR-containing Kampo medicines modulate immunoreactivity and thereby increase mouse litter size. AsR-exposed murine splenocytes exhibited significantly increased IL-2 secretion. In AsR-exposed mice, total Tregs were significantly increased, whereas cytotoxic T lymphocyte antigen 4 (CTLA-4)-positive Tregs were decreased in AsR-exposed mice. Tregs express IL-2 receptor subunit alpha and are activated by IL-2. CTLA-4 interacts with B7 expressed in antigen-presenting cells (APCs) with high affinity, and CTLA-4/B7 signaling plays a critical role in inhibiting APC activity, thereby suppressing CD4+ T cell proliferation and activation. The decrease in CTLA-4+ Tregs in AsR-exposed mice is thought to induce an increase in CD4+ T cells, leading to increased IL-2 secretion from CD4+ T cells followed by Treg activation. Th17 cells prevent trophoblast apoptosis, resulting in trophoblast invasion into the decidua. AsR increases Th17 cells, thereby inducing dose-dependent increases in litter size. Although Keishikaogito (KO)- and Ogikenchuto (OK)-exposed mice exhibited increased IL-2 secretion and splenic Tregs, KO also increased CTLA-4+ Tregs. Therefore, KO promoted immunosuppression by increasing CTLA-4+ Tregs, which induced a decrease in Th17 and exerted little effect on litter size. Therefore, an increase in both Tregs and Th17 cells can be considered necessary for embryo implantation and pregnancy maintenance.","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":" ","pages":"24-33"},"PeriodicalIF":3.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139933488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A systematic review of the mechanistic actions of microRNAs within integrated traditional Chinese medicine and western medical treatment for endometriosis. 中西医结合治疗子宫内膜异位症中 microRNA 的作用机制系统综述。

IF 1.9

Drug Discoveries and Therapeutics Pub Date : 2024-03-20 Epub Date: 2024-02-28 DOI: 10.5582/ddt.2024.01004

Lisha Li, Yiqin Zhang, Jing Zhou, Jing Wang, Ling Wang

{"title":"A systematic review of the mechanistic actions of microRNAs within integrated traditional Chinese medicine and western medical treatment for endometriosis.","authors":"Lisha Li, Yiqin Zhang, Jing Zhou, Jing Wang, Ling Wang","doi":"10.5582/ddt.2024.01004","DOIUrl":"10.5582/ddt.2024.01004","url":null,"abstract":"Endometriosis (EM), also known as Zhengjia in traditional Chinese medicine, is a common disease that significantly impacts women's health. An integrated treatment approach combining traditional Chinese medicine (TCM) and western medicine has demonstrated significant clinical efficacy in the management of this condition. Specifically, it has been effective in addressing blood circulation and other diseases. MicroRNAs (miRNAs), which are molecules important in gene regulation, have been implicated in various physiologic and pathologic processes. In this review, we systematically summarized the potential mechanisms underlying the integrated EM treatment, with a focus on the role of microRNAs (miRNAs). Current research suggests that integrated TCM and western medicine treatment may exert their therapeutic effects on EM by influencing the expression of miRNAs. Through miRNA modulation, such a treatment approach may inhibit the growth of ectopic lesions and alleviate clinical symptoms. This review will shed light on the specific miRNAs that have been implicated in the integrated treatment of EM, as well as their potential mechanisms of action. By consolidating the existing evidence, we aim to provide clinicians and researchers with a clearer understanding of the therapeutic benefits of the integrated approach and potentially identify new avenues for improving clinical treatment outcomes. Ultimately, this review will contribute to the growing body of knowledge in this field, providing a basis for further research and the development of more targeted and efficient treatment strategies for EM.","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":" ","pages":"1-9"},"PeriodicalIF":1.9,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparison of the physicochemical properties of branded and generic glucose-added maintenance hypotonic infusion fluids to assess the potential for phlebitis and incompatibility with other drugs. 比较品牌和非专利添加葡萄糖的低渗维持性输液的理化性质，以评估发生静脉炎和与其他药物不相容的可能性。

IF 3.1

Drug Discoveries and Therapeutics Pub Date : 2024-03-20 Epub Date: 2024-02-21 DOI: 10.5582/ddt.2023.01091

Sawako Takei, Soh Katsuyama, Yusuke Hori

{"title":"Comparison of the physicochemical properties of branded and generic glucose-added maintenance hypotonic infusion fluids to assess the potential for phlebitis and incompatibility with other drugs.","authors":"Sawako Takei, Soh Katsuyama, Yusuke Hori","doi":"10.5582/ddt.2023.01091","DOIUrl":"10.5582/ddt.2023.01091","url":null,"abstract":"In Japan, the switch from branded to generic infusion fluids has been promoted as a national policy. Recently, as generic products have been in short supply, the switch from generic to branded infusion fluids has increased. However, certain additives for injectable infusion fluids, such as nonvolatile acids like acetic acid and hydrochloric acid, are not required to be listed in the package insert. We hypothesized that the addition of nonvolatile acids may be one of the reasons for the differences in physicochemical properties between the branded and generic infusion fluids. We have previously reported that in other types of electrolyte infusion fluids, a variation in pH can cause incompatibility with other drugs, and variation in titratable acidity and osmolality can lead to phlebitis. Glucose-added maintenance hypotonic infusion fluid (listed as type-3G) is commonly used as a maintenance solution when energy support is needed. However, nonvolatile acid is added to prevent the caramelization of glucose, resulting in higher osmolality and titratable acidity and lower pH. Therefore, we hypothesized that both phlebitis and incompatibility with other drugs are likely to occur; hence, we measured and evaluated the physicochemical properties of branded and generic type-3G infusion fluids. We show that the osmolality, pH, and titratable acidity of all evaluated branded and generic products differed significantly and that these properties should be evaluated together to avoid phlebitis and incompatibility with other drugs when switching between branded and generic type-3G infusion fluids.","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":" ","pages":"71-74"},"PeriodicalIF":3.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139933489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evolving immune evasion and transmissibility of SARS-CoV-2: The emergence of JN.1 variant and its global impact. SARS-CoV-2 不断演变的免疫逃避和传播性：JN.1 变体的出现及其全球影响。

IF 3.1

Drug Discoveries and Therapeutics Pub Date : 2024-03-20 Epub Date: 2024-02-22 DOI: 10.5582/ddt.2024.01008

Guanyong Ou, Yang Yang, Shengjie Zhang, Shiyu Niu, Qingxian Cai, Yingxia Liu, Hongzhou Lu

{"title":"Evolving immune evasion and transmissibility of SARS-CoV-2: The emergence of JN.1 variant and its global impact.","authors":"Guanyong Ou, Yang Yang, Shengjie Zhang, Shiyu Niu, Qingxian Cai, Yingxia Liu, Hongzhou Lu","doi":"10.5582/ddt.2024.01008","DOIUrl":"10.5582/ddt.2024.01008","url":null,"abstract":"The continuous evolution of SARS-CoV-2 variants constitutes a significant impediment to the public health. The World Health Organization (WHO) has designated the SARS-CoV-2 variant JN.1, which has evolved from its progenitor BA.2.86, as a Variant of Interest (VOI) in light of its enhanced immune evasion and transmissibility. The proliferating dissemination of JN.1 globally accentuates its competitive superiority and the potential to instigate fresh surges of infection, notably among cohorts previously infected by antecedent variants. Notably, prevailing evidence does not corroborate an increase in pathogenicity associated with JN.1, and antiviral agents retain their antiviral activity against both BA.2.86 and JN.1. The sustained effectiveness of antiviral agents offers a beacon of hope. Nonetheless, the variant's adeptness at eluding the immunoprotective effects conferred by extant vaccines highlights the imperative for the development of more effective vaccines and therapeutic approaches. Overall, the distinct evolutionary trajectories of BA.2.86 and JN.1 underscore the necessity for ongoing surveillance and scholarly inquiry to elucidate their implications for the pandemic's evolution, which requires the international communities to foster collaboration through the sharing of data, exchange of insights, and collective scientific endeavors.","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":" ","pages":"67-70"},"PeriodicalIF":3.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139933490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Medication incidents associated with the provision of medication assistance by non-medical care staff in residential care facilities. 与安老院非医疗护理人员提供药物协助有关的用药事故。

IF 3.1

Drug Discoveries and Therapeutics Pub Date : 2024-03-20 Epub Date: 2024-02-28 DOI: 10.5582/ddt.2023.01073

Hayato Kizaki, Daisuke Yamamoto, Hideyuki Maki, Kotaro Masuko, Yukari Konishi, Hiroki Satoh, Satoko Hori, Yasufumi Sawada

{"title":"Medication incidents associated with the provision of medication assistance by non-medical care staff in residential care facilities.","authors":"Hayato Kizaki, Daisuke Yamamoto, Hideyuki Maki, Kotaro Masuko, Yukari Konishi, Hiroki Satoh, Satoko Hori, Yasufumi Sawada","doi":"10.5582/ddt.2023.01073","DOIUrl":"10.5582/ddt.2023.01073","url":null,"abstract":"The shift towards community-based care in Japan has led to increased medication assistance for older people by non-medical care staff. These staff members help take pre-packaged medications, apply patches, and administer eye drops. This study assessed the risks associated with such assistance by reviewing medication-related incidents across 106 residential care facilities between April 1, 2015, and March 31, 2016. An analysis of incident reports showed that all incidents were minor, with no serious outcomes. The incidents were categorized into four types: dropped drugs, misdelivery/misuse of medicines, forgetting to take medicines, and loss of medicines, with dropped drugs being the most frequent. Most incidents occurred in the morning and primarily involved residents with intermediate nursing care needs. These findings indicate a low risk of serious incidents because of medication assistance from non-medical staff. However, the frequency and nature of the incidents were influenced by the timing of medication administration and the care needs of the residents. These insights highlight the need for customized approaches to medication assistance, considering the residents' care levels and potentially optimizing medication administration times to improve safety in residential care settings.","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":" ","pages":"54-59"},"PeriodicalIF":3.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quantitative parameters of contrast-enhanced ultrasound effectively promote the prediction of cervical lymph node metastasis in papillary thyroid carcinoma. 对比增强超声的定量参数可有效促进甲状腺乳头状癌颈淋巴结转移的预测。

IF 3.1

Drug Discoveries and Therapeutics Pub Date : 2024-03-20 Epub Date: 2024-02-15 DOI: 10.5582/ddt.2023.01095

Biao Su, Lisha Li, Yingchun Liu, Hui Liu, Jia Zhan, Qiliang Chai, Liang Fang, Ling Wang, Lin Chen

{"title":"Quantitative parameters of contrast-enhanced ultrasound effectively promote the prediction of cervical lymph node metastasis in papillary thyroid carcinoma.","authors":"Biao Su, Lisha Li, Yingchun Liu, Hui Liu, Jia Zhan, Qiliang Chai, Liang Fang, Ling Wang, Lin Chen","doi":"10.5582/ddt.2023.01095","DOIUrl":"10.5582/ddt.2023.01095","url":null,"abstract":"Papillary thyroid carcinoma (PTC), the most common endocrine tumor, often spreads to cervical lymph nodes metastasis (CLNM). Preoperative diagnosis of CLNM is important when selecting surgical strategies. Therefore, we aimed to explore the effectiveness of quantitative parameters of contrast-enhanced ultrasound (CEUS) in predicting CLNM in PTC. We retrospectively analyzed 193 patients with PTC undergoing conventional ultrasound (CUS) and CEUS. The CUS features and quantitative parameters of CEUS were evaluated according to PTC size ≤ 10 or > 10 mm, using pathology as the gold standard. For the PTC ≤ 10 mm, microcalcification and multifocality were significantly different between the CLNM (+) and CLNM (-) groups (both P < 0.05). For the PTC > 10 mm, statistical significance was noted between the two groups with respect to the margin, capsule contact, and multifocality (all P < 0.05). For PTC ≤ 10 mm, there was no significant difference between the CLNM (+) and CLNM (-) groups in all quantitative parameters of CEUS (all P > 0.05). However, for PTC > 10 mm, the peak intensity (PI), mean transit time, and slope were significantly associated with CLNM (all P < 0.05). Multivariate analysis showed that PI > 5.8 dB was an independent risk factor for predicting CLNM in patients with PTC > 10 mm (P < 0.05). The area under the curve of PI combined with CUS (0.831) was significantly higher than that of CUS (0.707) or PI (0.703) alone in the receiver operator characteristic curve analysis (P < 0.05). In conclusion, PI has significance in predicting CLNM for PTC > 10 mm; however, it is not helpful for PTC ≤ 10 mm.","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":" ","pages":"44-53"},"PeriodicalIF":3.1,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lack of information on gender differences in the package inserts of prescription drugs in Japan. 日本处方药的包装说明中缺乏有关性别差异的信息。

IF 3.1

Drug Discoveries and Therapeutics Pub Date : 2024-01-12 Epub Date: 2023-12-15 DOI: 10.5582/ddt.2023.01093

Narumi Maida, Shingo Kondo, Masanori Ogawa, Naoko Hayashi, Hiroki Iwata, Noriko Kobayashi, Katsunori Yamaura

{"title":"Lack of information on gender differences in the package inserts of prescription drugs in Japan.","authors":"Narumi Maida, Shingo Kondo, Masanori Ogawa, Naoko Hayashi, Hiroki Iwata, Noriko Kobayashi, Katsunori Yamaura","doi":"10.5582/ddt.2023.01093","DOIUrl":"10.5582/ddt.2023.01093","url":null,"abstract":"The package inserts of prescription drugs provide essential information for the proper administration of pharmacotherapy. The incidence of adverse reactions for several drugs is known to be higher in women than in men. However, no studies have examined whether information on gender differences is included in Japanese package inserts. Therefore, this study investigated information on gender differences in the package inserts of Japanese prescription drugs, using the drug information database JAMES provided by the Medical Information System Development Center and the Japan Pharmaceutical Information Center. Non-proprietary names of prescription drugs were yielded 1,679 in Japan. Of the 1,679 ingredients in package inserts of prescription drugs, 76 (4.5%) included information on gender differences. The number of inserts that contained information on gender differences in the \"DOSAGE AND ADMINISTRATION,\" \"ADVERSE REACTIONS,\" and \"PHARMACOKINETICS\" sections was 3, 16, and 62, respectively. Furthermore, in the \"ADVERSE REACTIONS\" section, 15 of the 16 inserts mentioned a higher frequency of adverse reactions in women compared with men. Importantly, most of the inserts with information on gender differences in the \"PHARMACOKINETICS\" section mentioned a higher area under the curve for women than for men. Most of the package inserts of prescription drugs with information on gender differences provide useful information aimed at preventing risks in women. However, there is an extreme lack of information on gender differences in the package inserts of prescription drugs in Japan, and we consider enhancing information on gender difference as an urgent issue.","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":" ","pages":"396-403"},"PeriodicalIF":3.1,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138808663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generic selection criteria for safety and patient benefit [Ⅻ]: Comparing the physicochemical and pharmaceutical properties of brand-name and generic tulobuterol tape. 安全性和患者受益的通用选择标准[Ⅻ]:比较品牌和仿制特洛特罗胶带的物理化学和药物性能。

IF 3.1

Drug Discoveries and Therapeutics Pub Date : 2024-01-12 Epub Date: 2023-12-03 DOI: 10.5582/ddt.2023.01076

Ken-Ichi Shimokawa, Kayo Yotsukura, Mitsuru Nozawa, Yuko Wada, Fumiyoshi Ishii

{"title":"Generic selection criteria for safety and patient benefit [Ⅻ]: Comparing the physicochemical and pharmaceutical properties of brand-name and generic tulobuterol tape.","authors":"Ken-Ichi Shimokawa, Kayo Yotsukura, Mitsuru Nozawa, Yuko Wada, Fumiyoshi Ishii","doi":"10.5582/ddt.2023.01076","DOIUrl":"10.5582/ddt.2023.01076","url":null,"abstract":"Physicochemical properties (drug release, peel strength, adhesion, and stiffness) of Hokunalin® Tape (Hokunalin) and 13 generic transdermal bronchodilator patches containing tulobuterol were characterized and evaluated for comparison. Drug-release studies evaluating sustained release behavior demonstrated better performance by the drug Hokunalin, than the generics MED, YP, Sawai, and Teikoku. Hokunalin yield a 16.2% release 1 hour after initiation, 30.1% at 3 hours, 50.0% at 8 hours. In comparison, the generics MED, YP, Sawai, and Teikoku showed an intermediate release behavior to that of Hokunalin, with more than 80% release after 8 hours. A 90-degree peel adhesion test for tape peel strength demonstrated that the generic MED (4.99 N), YP (3.26 N), Sawai (4.17 N), and Teikoku (4.37 N) tapes yielded significantly higher values compared to Hokunalin (2.66 N). Probe tack tests, evaluating adhesive strength, yielded significantly higher values for the generics HMT (4.89 N)and Towa (4.25 N) compared to Hokunalin (3.66 N). Furthermore, for the stiffness-softness test, a significantly higher value was obtained for each generic yielded compared to Hokunalin (3.7-degree). These factors are important components of product qualities that affect treatment efficacy, including \"ease of application\" and other usability factors.","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":" ","pages":"409-414"},"PeriodicalIF":3.1,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138478976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single intratracheal administration toxicity study on safety of vapor inhalation of electrolyzed reduced water in rats. 关于大鼠吸入电解还原水蒸汽安全性的单次气管内给药毒性研究

IF 3.1

Drug Discoveries and Therapeutics Pub Date : 2024-01-12 Epub Date: 2023-12-22 DOI: 10.5582/ddt.2023.01080

Yuko Imanaka Wada, Yoshinao Okajima, Yutaka Oshima, Ken-Ichi Shimokawa, Masahiro Okajima, Fumiyoshi Ishii

{"title":"Single intratracheal administration toxicity study on safety of vapor inhalation of electrolyzed reduced water in rats.","authors":"Yuko Imanaka Wada, Yoshinao Okajima, Yutaka Oshima, Ken-Ichi Shimokawa, Masahiro Okajima, Fumiyoshi Ishii","doi":"10.5582/ddt.2023.01080","DOIUrl":"10.5582/ddt.2023.01080","url":null,"abstract":"The effects of acute intratracheal administration of electrolyzed reduced water (ERW; alkaline electrolyzed water) were investigated in rats. In this study, no deaths or near-deaths were recorded in either group, namely those treated with ERW or purified water (maximum doses of 900 mg/kg). The main symptoms observed in the rats were decreased spontaneous movements and abnormal breath sounds, which were considered to be transient symptoms caused by intratracheal administration. In addition, low values of alkaline phosphatase, total protein and lactate dehydrogenase were found in BALF tests, but these values were considered to be of low toxicological significance, since they are usually high in the presence of lung inflammation or cellular damage. This suggests that the alkalinity of ERW partially contributes to broken peptide bonds in proteins. There were no significant increases in bronchoalveolar lavage fluid protein in either group. ERW did not cause an increase in the influx of neutrophils, eosinophils, basophils, or lymphocytes, suggesting that intratracheal administration of ERW did not cause lung inflammation. ERW did not cause abnormalities in the body or pathological changes in the lungs. Aggregates of alveolar macrophages, as a measure of inflammation, were observed in both groups. These may be transient symptoms due to intratracheal administration, not due to ERW toxicity. This study confirmed the safety of intratracheal ERW infusion and demonstrated the low risk of acute toxicity for inhalation exposure to ERW aerosol or vapor. Therefore, ERW may be an effective air purifier against viruses or bacteria.","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":" ","pages":"404-408"},"PeriodicalIF":3.1,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of D-amino acid oxidase activity in rat kidney using a D-kynurenine derivative, 6-methylthio-D-kynurenine: An in vivo microdialysis study. 用d -犬尿氨酸衍生物6-甲基硫代d -犬尿氨酸评价大鼠肾脏d -氨基酸氧化酶活性:体内微透析研究。

IF 3.1

Drug Discoveries and Therapeutics Pub Date : 2024-01-12 Epub Date: 2023-12-03 DOI: 10.5582/ddt.2023.01083

Takeshi Fukushima, Ayano Kansaku, Maho Umino, Tatsuya Sakamoto, Mayu Onozato

{"title":"Evaluation of D-amino acid oxidase activity in rat kidney using a D-kynurenine derivative, 6-methylthio-D-kynurenine: An in vivo microdialysis study.","authors":"Takeshi Fukushima, Ayano Kansaku, Maho Umino, Tatsuya Sakamoto, Mayu Onozato","doi":"10.5582/ddt.2023.01083","DOIUrl":"10.5582/ddt.2023.01083","url":null,"abstract":"D-Amino acid oxidase (DAO), a D-amino acid metabolizing enzyme, is reportedly associated with the psychiatric disease schizophrenia, suggesting a role for DAO inhibitors in its treatment. We have previously reported that DAO catalyzes the conversion of nonfluorescent 6-methylthio-D-kynurenine (MeS-D-KYN) to fluorescent 5-methylthiokynurenic acid (MeS-KYNA) in vitro. The present study aimed to determine the potential of MeS-D-KYN in evaluating DAO activity in vivo using renal microdialysis technique in rats. Male Sprague-Dawley rats were subjected to linear microdialysis probe implantation in the left kidney. Continuous perfusion of MeS-D-KYN was maintained, and DAO activity in the kidney cortex was evaluated by measuring the MeS-KYNA content in the microdialysate. The microdialysate was collected every 30 min and analyzed by high-performance liquid chromatography with fluorescence detection, monitored at 450 nm with an excitation wavelength of 364 nm. A significant production of MeS-KYNA was observed during, but not before, infusion of MeS-D-KYN, indicating that this compound is not endogenous. MeS-KYNA production was suppressed by the co-infusion of DAO inhibitor, 5-chlorobenzo[d]isoxazol-3-ol (CBIO), suggesting that MeS-D-KYN was converted to MeS-KYNA by renal DAO. Moreover, oral administration of CBIO effectively suppressed DAO activity in a dose-dependent manner. DAO converted MeS-D-KYN to MeS-KYNA in vivo, suggesting the potential of this compound in evaluating DAO activity. The use of the renal microdialysis technique developed in this study facilitates the monitoring of DAO activity in live experimental animals.","PeriodicalId":47494,"journal":{"name":"Drug Discoveries and Therapeutics","volume":" ","pages":"434-439"},"PeriodicalIF":3.1,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138478975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0