Development of Novel Methodology and Its Application for Clarifying the Transport Function of the Blood-brain Barrier
Yakugaku Zasshi. 2021;141(4):447-462. doi: 10.1248/yakushi.20-00232.ABSTRACTThe blood-brain barrier (BBB) consists of brain capillary endothelial cells linked by tight junctions and serves to regulate the transfer of endogenous compounds and xenobiotics between the circulating blood and brain interstitial fluid. We have developed a methodology to characterize brain-to-blood efflux transport in vivo, using the Brain Efflux Index and an in vitro culture model of the BBB, i.e., a conditionally immortalized cell line of the neurovascular unit. Employing these methods, we showed that the BBB plays an important role in protectin...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Tetsuya Terasaki Source Type: research

Study on the Safety of Perinatal Medication
Yakugaku Zasshi. 2021;141(4):463-471. doi: 10.1248/yakushi.20-00184.ABSTRACTWe have been conducting research with the aim of generating evidence for the safety of perinatal drugs. As a result of reviewing the records of inquiries to the Drug Information Office of our hospital, we found a large discrepancy between the description of perinatal drugs in package inserts in Japan and the description of the Pregnancy Risk Category according to the U.S. Food and Drug Administration. In the Japan Environment and Children's Study (JECS), we determined the proportion of drug and supplement use among 97464 pregnant women. We clarifie...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Taku Obara Source Type: research

Activation Mechanism of Prostanoid Receptors  -X-ray Crystallography of EP3 Receptor
Yakugaku Zasshi. 2021;141(4):473-479. doi: 10.1248/yakushi.20-00202.ABSTRACTProstanoids [prostaglandins (PGs) and thromboxanes (TXs)] are a series of bioactive lipid metabolites that function in an autacoid manner via activation of cognate G protein-coupled receptors (GPCRs). The nine subtypes of prostanoid receptors (DP1, DP2, EP1, EP2, EP3, EP4, FP, IP, TP) are involved in a wide range of functions, including inflammation, immune response, reproduction, and homeostasis of the intestinal mucosa and cardiovascular system. Among the prostanoid receptors, the structure of antagonist-bound DP2, which belongs to the chemoattra...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Kazushi Morimoto Source Type: research

Cell Function Research of β-Trefoil Lectins from Mytilidae
Yakugaku Zasshi. 2021;141(4):481-488. doi: 10.1248/yakushi.20-00215.ABSTRACTTwo novel β-trefoil lectins, MytiLec-1 and SeviL were found from mussels in the coast of Yokohama and Nagasaki. MytiLec-1 was purified from gill and mantle of Mytilus galloprovincialis. It was consisted of 149 amino acid residues and there was no similarity with any other proteins when it was discovered. We advocate for this "Mytilectin" as a new protein family because of their novelty of its primary structure and homologues were also found in other mussels. Glycan array analysis revealed that MytiLec-1 specifically bound to the Gb3 ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Yuki Fujii Source Type: research

Strategies for Transporter-targeted Drug Discovery
Yakugaku Zasshi. 2021;141(4):489-490. doi: 10.1248/yakushi.20-00204-F.NO ABSTRACTPMID:33790115 | DOI:10.1248/yakushi.20-00204-F (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Yoshinori Moriyama Yasuo Shinohara Source Type: research

The Molecular Mechanisms of Mitochondrial Calcium Uptake by Calcium Uniporter
Yakugaku Zasshi. 2021;141(4):491-499. doi: 10.1248/yakushi.20-00204-1.ABSTRACTMitochondria play a role as intracellular calcium stores as well as energy conversion functions. Excessive calcium accumulation in mitochondria induces cell death and induces diseases such as ischemia-reperfusion injury. Mitochondrial calcium uptake is considered to be mediated by calcium uniporters, which have attracted much attention as potential drug targets. Although calcium uniporter was shown to function as an ion channel, the molecular mechanisms have long been unclear. In this decade, the molecular composition of the calcium uniporter com...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Takenori Yamamoto Source Type: research

Drug Discovery Targeting an Amino Acid Transporter for Diagnosis and Therapy
Yakugaku Zasshi. 2021;141(4):501-510. doi: 10.1248/yakushi.20-00204-2.ABSTRACTNutrients are essential for all living organisms. Because growing cancer cells have strong metabolic demands, nutrient transporters are constitutively increased to facilitate the nutrient uptake. Among these nutrient transporters, L-type amino acid transporter 1 (LAT1), which transports large neutral amino acids including essential amino acids, is critical for cancer growth. Therefore, LAT1 has been considered as an attractive target for diagnosis and therapy of cancers. We have developed several lines of compounds for cancer diagnosis and therap...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Pattama Wiriyasermkul Satomi Moriyama Pornparn Kongpracha Shushi Nagamori Source Type: research

High-throughput Screening Technology for Selective Inhibitors of Transporters and Its Application in Drug Discovery
Yakugaku Zasshi. 2021;141(4):511-515. doi: 10.1248/yakushi.20-00204-3.ABSTRACTThe first step in small-molecule drug discovery is the identification of hit compounds via high-throughput screening (HTS). In transporter drug discovery, most HTS assays are based on the uptake of labeled substrates, but such functional assays cannot be developed for many transporters, such as intracellular organelle transporters. These transporters remain unexplored in drug discovery despite their promise as drug targets. Affinity selection-mass spectrometry (AS-MS) is a label-free binding assay technology that has been developed as an HTS tech...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Takashi Motoyaji Source Type: research

VNUT Is a Therapeutic Target for Type 2 Diabetes and NASH
Yakugaku Zasshi. 2021;141(4):517-526. doi: 10.1248/yakushi.20-00204-4.ABSTRACTATP, used in cells as an energy currency, also acts as an extracellular signaling molecule. Studies of purinergic receptor subtypes have revealed that purinergic chemical transmission plays important roles in various cell types. The vesicular nucleotide transporter (VNUT), the ninth transporter in the SLC17 organic anion transporter family, is essential for vesicular ATP storage and its subsequent release. The VNUT is localized on the membrane of secretory vesicles and actively transports ATP into vesicles using an electrochemical gradient of pro...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Nao Hasuzawa Keita Tatsushima Rie Tokubuchi Masaharu Kabashima Masatoshi Nomura Source Type: research

Studies on Elastase and Elastase Inhibitor from Aspergillus flavus
Yakugaku Zasshi. 2021;141(4):527-540. doi: 10.1248/yakushi.20-00193.ABSTRACTThe biological properties of elastase and Aspergillus flavus elastase inhibitor (AFLEI) from A. flavus were examined. Pathogenicity of elastase was investigated in mice immunocompromised with cyclophosphamide, cyclosporine, prednisolone and carrageenan. Compared to cyclophosphamide immunocompromised mice treated with the spores of elastase nonproducing strain, cyclophosphamide immunocompromised mice treated with the spores of elastase producing strain had a significantly shorter survival rate. Molecular mass of AFLEI was determined to be 7525.8 Da....
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Toshiaki Nikai Source Type: research

Improvement of Medication Adherence in Psychiatry and Mental Health Literacy Education
Yakugaku Zasshi. 2021;141(4):541-555. doi: 10.1248/yakushi.20-00218.ABSTRACTIn Japan, the number of patients with mental illness is increasing; therefore, the need for national measures, such as suicide prevention measures and measures against alcohol health disorders, and multiple social concerns and needs, such as depression and dementia problems, are increasing. As such, measures for mental health are emphasized. Mental health is a common issue; however, there is still prejudice regarding mental illness, and its understanding and awareness by local residents and medical staff need to be improved. The author introduced a...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Moemi Saito Source Type: research

Chemical Biology Studies Using Vitamin A Analogs
Yakugaku Zasshi. 2021;141(4):557-577. doi: 10.1248/yakushi.20-00230.ABSTRACT"Retinoid" is the general term for vitamin A derivatives and chemical compounds that act like vitamin A. Vitamin A are composed of four isoprene units and are named according to their terminal functional group, such as retinol (OH, 1), retinal (CHO, 2), and retinoic acid (CO2H, 3). Vitamin A usually refers to retinol. In the past few decades, major advances in research on vitamin A have improved our understanding of its fundamental roles and physiological significance in living cells. In this review, three types of chemical biology studie...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Akimori Wada Source Type: research

Modulation of Host Immune System by Staphylococcal Superantigen-like (SSL) Proteins
Yakugaku Zasshi. 2021;141(4):579-589. doi: 10.1248/yakushi.20-00236.ABSTRACTStaphylococcus aureus is a common pathogen causing a wide range of infectious diseases in humans and animals. This bacterium secretes a variety of exoproteins, including toxins known as superantigens, such as toxic shock syndrome toxin-1 (TSST-1) and enterotoxins. Staphylococcal superantigen-like (SSL) proteins are a family of exoproteins showing structural similarities with superantigens but no superantigenic activity. This family is composed of 14 members (SSL1-SSL14), and recent studies have revealed that these members exhibit various immunomodu...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Tsutomu Tsuji Source Type: research

Changes in Test Methods for Internationalization in the Japanese Pharmacopoeia (Part 1): Establishment of a Quantitative Test Method for Clonidine Hydrochloride Using HPLC Analysis
In this study, we synthesized impurities of clonidine hydrochloride and determined their purities using quantitative NMR. In addition, the complete separation conditions of these compounds by HPLC were examined, and simultaneous analysis was performed.PMID:33790124 | DOI:10.1248/yakushi.20-00237 (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Aika Maniwa Genichiro Tsuji Takahito Ito Nahoko Uchiyama Junko Hosoe Takashi Ohtsuki Hiroshi Matsufuji Yosuke Demizu Yukihiro Goda Source Type: research

Stability of Six Drugs in Total Parenteral Nutrition Solution
In this study, we investigated the stability of six drugs, including famotidine, scopolamine butylbromide, furosemide, bromhexine hydrochloride, betamethasone sodium phosphate, and metoclopramide hydrochloride in the infusion bags under dark conditions at 4℃ for 7 days. Additionally, we developed a high-performance liquid chromatography method to determine drug concentrations in the infusions. The concentrations of injected famotidine, scopolamine butylbromide, and betamethasone sodium phosphate remained unchanged when the four chambers of Elneopa NF No. 1 and No. 2 were opened and the infusions were mixed. Their respect...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Takefumi Kumagai Naoko Narahara Eiji Sato Yoshitaka Kihira Yoshino Fujimura Eijiro Kojima Shojiro Ogawa Yuko Date Yasuto Tsuruta Hironori Yoshitomi Hirofumi Inoue Source Type: research

Predicting the Incidence of Venous Thromboembolism Using the Khorana Score: A Literature Review
This study aimed to investigate the usefulness of the Khorana score, using data available in the literature. On July 28, 2020, we collected papers using the following keywords: "cancer", "venous thromboembolism", "deep vein thrombosis", "pulmonary embolism", and "Khorana score" on PubMed. Papers published after 2016 were eligible. The selection criteria were as follows: "English or Japanese", "original paper", "abstract and full text", and "comply with the clinical question". There were 131 papers that matched the keywords, and 15 of ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Akari Nishimura Yoshiaki Ikeda Source Type: research

Development of Novel Methodology and Its Application for Clarifying the Transport Function of the Blood-brain Barrier
Yakugaku Zasshi. 2021;141(4):447-462. doi: 10.1248/yakushi.20-00232.ABSTRACTThe blood-brain barrier (BBB) consists of brain capillary endothelial cells linked by tight junctions and serves to regulate the transfer of endogenous compounds and xenobiotics between the circulating blood and brain interstitial fluid. We have developed a methodology to characterize brain-to-blood efflux transport in vivo, using the Brain Efflux Index and an in vitro culture model of the BBB, i.e., a conditionally immortalized cell line of the neurovascular unit. Employing these methods, we showed that the BBB plays an important role in protectin...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Tetsuya Terasaki Source Type: research

Study on the Safety of Perinatal Medication
Yakugaku Zasshi. 2021;141(4):463-471. doi: 10.1248/yakushi.20-00184.ABSTRACTWe have been conducting research with the aim of generating evidence for the safety of perinatal drugs. As a result of reviewing the records of inquiries to the Drug Information Office of our hospital, we found a large discrepancy between the description of perinatal drugs in package inserts in Japan and the description of the Pregnancy Risk Category according to the U.S. Food and Drug Administration. In the Japan Environment and Children's Study (JECS), we determined the proportion of drug and supplement use among 97464 pregnant women. We clarifie...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Taku Obara Source Type: research

Activation Mechanism of Prostanoid Receptors  -X-ray Crystallography of EP3 Receptor
Yakugaku Zasshi. 2021;141(4):473-479. doi: 10.1248/yakushi.20-00202.ABSTRACTProstanoids [prostaglandins (PGs) and thromboxanes (TXs)] are a series of bioactive lipid metabolites that function in an autacoid manner via activation of cognate G protein-coupled receptors (GPCRs). The nine subtypes of prostanoid receptors (DP1, DP2, EP1, EP2, EP3, EP4, FP, IP, TP) are involved in a wide range of functions, including inflammation, immune response, reproduction, and homeostasis of the intestinal mucosa and cardiovascular system. Among the prostanoid receptors, the structure of antagonist-bound DP2, which belongs to the chemoattra...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Kazushi Morimoto Source Type: research

Cell Function Research of β-Trefoil Lectins from Mytilidae
Yakugaku Zasshi. 2021;141(4):481-488. doi: 10.1248/yakushi.20-00215.ABSTRACTTwo novel β-trefoil lectins, MytiLec-1 and SeviL were found from mussels in the coast of Yokohama and Nagasaki. MytiLec-1 was purified from gill and mantle of Mytilus galloprovincialis. It was consisted of 149 amino acid residues and there was no similarity with any other proteins when it was discovered. We advocate for this "Mytilectin" as a new protein family because of their novelty of its primary structure and homologues were also found in other mussels. Glycan array analysis revealed that MytiLec-1 specifically bound to the Gb3 ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Yuki Fujii Source Type: research

Strategies for Transporter-targeted Drug Discovery
Yakugaku Zasshi. 2021;141(4):489-490. doi: 10.1248/yakushi.20-00204-F.NO ABSTRACTPMID:33790115 | DOI:10.1248/yakushi.20-00204-F (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Yoshinori Moriyama Yasuo Shinohara Source Type: research

The Molecular Mechanisms of Mitochondrial Calcium Uptake by Calcium Uniporter
Yakugaku Zasshi. 2021;141(4):491-499. doi: 10.1248/yakushi.20-00204-1.ABSTRACTMitochondria play a role as intracellular calcium stores as well as energy conversion functions. Excessive calcium accumulation in mitochondria induces cell death and induces diseases such as ischemia-reperfusion injury. Mitochondrial calcium uptake is considered to be mediated by calcium uniporters, which have attracted much attention as potential drug targets. Although calcium uniporter was shown to function as an ion channel, the molecular mechanisms have long been unclear. In this decade, the molecular composition of the calcium uniporter com...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Takenori Yamamoto Source Type: research

Drug Discovery Targeting an Amino Acid Transporter for Diagnosis and Therapy
Yakugaku Zasshi. 2021;141(4):501-510. doi: 10.1248/yakushi.20-00204-2.ABSTRACTNutrients are essential for all living organisms. Because growing cancer cells have strong metabolic demands, nutrient transporters are constitutively increased to facilitate the nutrient uptake. Among these nutrient transporters, L-type amino acid transporter 1 (LAT1), which transports large neutral amino acids including essential amino acids, is critical for cancer growth. Therefore, LAT1 has been considered as an attractive target for diagnosis and therapy of cancers. We have developed several lines of compounds for cancer diagnosis and therap...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Pattama Wiriyasermkul Satomi Moriyama Pornparn Kongpracha Shushi Nagamori Source Type: research

High-throughput Screening Technology for Selective Inhibitors of Transporters and Its Application in Drug Discovery
Yakugaku Zasshi. 2021;141(4):511-515. doi: 10.1248/yakushi.20-00204-3.ABSTRACTThe first step in small-molecule drug discovery is the identification of hit compounds via high-throughput screening (HTS). In transporter drug discovery, most HTS assays are based on the uptake of labeled substrates, but such functional assays cannot be developed for many transporters, such as intracellular organelle transporters. These transporters remain unexplored in drug discovery despite their promise as drug targets. Affinity selection-mass spectrometry (AS-MS) is a label-free binding assay technology that has been developed as an HTS tech...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Takashi Motoyaji Source Type: research

VNUT Is a Therapeutic Target for Type 2 Diabetes and NASH
Yakugaku Zasshi. 2021;141(4):517-526. doi: 10.1248/yakushi.20-00204-4.ABSTRACTATP, used in cells as an energy currency, also acts as an extracellular signaling molecule. Studies of purinergic receptor subtypes have revealed that purinergic chemical transmission plays important roles in various cell types. The vesicular nucleotide transporter (VNUT), the ninth transporter in the SLC17 organic anion transporter family, is essential for vesicular ATP storage and its subsequent release. The VNUT is localized on the membrane of secretory vesicles and actively transports ATP into vesicles using an electrochemical gradient of pro...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Nao Hasuzawa Keita Tatsushima Rie Tokubuchi Masaharu Kabashima Masatoshi Nomura Source Type: research

Studies on Elastase and Elastase Inhibitor from Aspergillus flavus
Yakugaku Zasshi. 2021;141(4):527-540. doi: 10.1248/yakushi.20-00193.ABSTRACTThe biological properties of elastase and Aspergillus flavus elastase inhibitor (AFLEI) from A. flavus were examined. Pathogenicity of elastase was investigated in mice immunocompromised with cyclophosphamide, cyclosporine, prednisolone and carrageenan. Compared to cyclophosphamide immunocompromised mice treated with the spores of elastase nonproducing strain, cyclophosphamide immunocompromised mice treated with the spores of elastase producing strain had a significantly shorter survival rate. Molecular mass of AFLEI was determined to be 7525.8 Da....
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Toshiaki Nikai Source Type: research

Improvement of Medication Adherence in Psychiatry and Mental Health Literacy Education
Yakugaku Zasshi. 2021;141(4):541-555. doi: 10.1248/yakushi.20-00218.ABSTRACTIn Japan, the number of patients with mental illness is increasing; therefore, the need for national measures, such as suicide prevention measures and measures against alcohol health disorders, and multiple social concerns and needs, such as depression and dementia problems, are increasing. As such, measures for mental health are emphasized. Mental health is a common issue; however, there is still prejudice regarding mental illness, and its understanding and awareness by local residents and medical staff need to be improved. The author introduced a...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Moemi Saito Source Type: research

Chemical Biology Studies Using Vitamin A Analogs
Yakugaku Zasshi. 2021;141(4):557-577. doi: 10.1248/yakushi.20-00230.ABSTRACT"Retinoid" is the general term for vitamin A derivatives and chemical compounds that act like vitamin A. Vitamin A are composed of four isoprene units and are named according to their terminal functional group, such as retinol (OH, 1), retinal (CHO, 2), and retinoic acid (CO2H, 3). Vitamin A usually refers to retinol. In the past few decades, major advances in research on vitamin A have improved our understanding of its fundamental roles and physiological significance in living cells. In this review, three types of chemical biology studie...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Akimori Wada Source Type: research

Modulation of Host Immune System by Staphylococcal Superantigen-like (SSL) Proteins
Yakugaku Zasshi. 2021;141(4):579-589. doi: 10.1248/yakushi.20-00236.ABSTRACTStaphylococcus aureus is a common pathogen causing a wide range of infectious diseases in humans and animals. This bacterium secretes a variety of exoproteins, including toxins known as superantigens, such as toxic shock syndrome toxin-1 (TSST-1) and enterotoxins. Staphylococcal superantigen-like (SSL) proteins are a family of exoproteins showing structural similarities with superantigens but no superantigenic activity. This family is composed of 14 members (SSL1-SSL14), and recent studies have revealed that these members exhibit various immunomodu...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Tsutomu Tsuji Source Type: research

Changes in Test Methods for Internationalization in the Japanese Pharmacopoeia (Part 1): Establishment of a Quantitative Test Method for Clonidine Hydrochloride Using HPLC Analysis
In this study, we synthesized impurities of clonidine hydrochloride and determined their purities using quantitative NMR. In addition, the complete separation conditions of these compounds by HPLC were examined, and simultaneous analysis was performed.PMID:33790124 | DOI:10.1248/yakushi.20-00237 (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Aika Maniwa Genichiro Tsuji Takahito Ito Nahoko Uchiyama Junko Hosoe Takashi Ohtsuki Hiroshi Matsufuji Yosuke Demizu Yukihiro Goda Source Type: research

Stability of Six Drugs in Total Parenteral Nutrition Solution
In this study, we investigated the stability of six drugs, including famotidine, scopolamine butylbromide, furosemide, bromhexine hydrochloride, betamethasone sodium phosphate, and metoclopramide hydrochloride in the infusion bags under dark conditions at 4℃ for 7 days. Additionally, we developed a high-performance liquid chromatography method to determine drug concentrations in the infusions. The concentrations of injected famotidine, scopolamine butylbromide, and betamethasone sodium phosphate remained unchanged when the four chambers of Elneopa NF No. 1 and No. 2 were opened and the infusions were mixed. Their respect...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Takefumi Kumagai Naoko Narahara Eiji Sato Yoshitaka Kihira Yoshino Fujimura Eijiro Kojima Shojiro Ogawa Yuko Date Yasuto Tsuruta Hironori Yoshitomi Hirofumi Inoue Source Type: research

Predicting the Incidence of Venous Thromboembolism Using the Khorana Score: A Literature Review
This study aimed to investigate the usefulness of the Khorana score, using data available in the literature. On July 28, 2020, we collected papers using the following keywords: "cancer", "venous thromboembolism", "deep vein thrombosis", "pulmonary embolism", and "Khorana score" on PubMed. Papers published after 2016 were eligible. The selection criteria were as follows: "English or Japanese", "original paper", "abstract and full text", and "comply with the clinical question". There were 131 papers that matched the keywords, and 15 of ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Akari Nishimura Yoshiaki Ikeda Source Type: research

Development of Novel Methodology and Its Application for Clarifying the Transport Function of the Blood-brain Barrier
Yakugaku Zasshi. 2021;141(4):447-462. doi: 10.1248/yakushi.20-00232.ABSTRACTThe blood-brain barrier (BBB) consists of brain capillary endothelial cells linked by tight junctions and serves to regulate the transfer of endogenous compounds and xenobiotics between the circulating blood and brain interstitial fluid. We have developed a methodology to characterize brain-to-blood efflux transport in vivo, using the Brain Efflux Index and an in vitro culture model of the BBB, i.e., a conditionally immortalized cell line of the neurovascular unit. Employing these methods, we showed that the BBB plays an important role in protectin...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Tetsuya Terasaki Source Type: research

Study on the Safety of Perinatal Medication
Yakugaku Zasshi. 2021;141(4):463-471. doi: 10.1248/yakushi.20-00184.ABSTRACTWe have been conducting research with the aim of generating evidence for the safety of perinatal drugs. As a result of reviewing the records of inquiries to the Drug Information Office of our hospital, we found a large discrepancy between the description of perinatal drugs in package inserts in Japan and the description of the Pregnancy Risk Category according to the U.S. Food and Drug Administration. In the Japan Environment and Children's Study (JECS), we determined the proportion of drug and supplement use among 97464 pregnant women. We clarifie...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Taku Obara Source Type: research

Activation Mechanism of Prostanoid Receptors  -X-ray Crystallography of EP3 Receptor
Yakugaku Zasshi. 2021;141(4):473-479. doi: 10.1248/yakushi.20-00202.ABSTRACTProstanoids [prostaglandins (PGs) and thromboxanes (TXs)] are a series of bioactive lipid metabolites that function in an autacoid manner via activation of cognate G protein-coupled receptors (GPCRs). The nine subtypes of prostanoid receptors (DP1, DP2, EP1, EP2, EP3, EP4, FP, IP, TP) are involved in a wide range of functions, including inflammation, immune response, reproduction, and homeostasis of the intestinal mucosa and cardiovascular system. Among the prostanoid receptors, the structure of antagonist-bound DP2, which belongs to the chemoattra...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Kazushi Morimoto Source Type: research

Cell Function Research of β-Trefoil Lectins from Mytilidae
Yakugaku Zasshi. 2021;141(4):481-488. doi: 10.1248/yakushi.20-00215.ABSTRACTTwo novel β-trefoil lectins, MytiLec-1 and SeviL were found from mussels in the coast of Yokohama and Nagasaki. MytiLec-1 was purified from gill and mantle of Mytilus galloprovincialis. It was consisted of 149 amino acid residues and there was no similarity with any other proteins when it was discovered. We advocate for this "Mytilectin" as a new protein family because of their novelty of its primary structure and homologues were also found in other mussels. Glycan array analysis revealed that MytiLec-1 specifically bound to the Gb3 ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Yuki Fujii Source Type: research

Strategies for Transporter-targeted Drug Discovery
Yakugaku Zasshi. 2021;141(4):489-490. doi: 10.1248/yakushi.20-00204-F.NO ABSTRACTPMID:33790115 | DOI:10.1248/yakushi.20-00204-F (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Yoshinori Moriyama Yasuo Shinohara Source Type: research

The Molecular Mechanisms of Mitochondrial Calcium Uptake by Calcium Uniporter
Yakugaku Zasshi. 2021;141(4):491-499. doi: 10.1248/yakushi.20-00204-1.ABSTRACTMitochondria play a role as intracellular calcium stores as well as energy conversion functions. Excessive calcium accumulation in mitochondria induces cell death and induces diseases such as ischemia-reperfusion injury. Mitochondrial calcium uptake is considered to be mediated by calcium uniporters, which have attracted much attention as potential drug targets. Although calcium uniporter was shown to function as an ion channel, the molecular mechanisms have long been unclear. In this decade, the molecular composition of the calcium uniporter com...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Takenori Yamamoto Source Type: research

Drug Discovery Targeting an Amino Acid Transporter for Diagnosis and Therapy
Yakugaku Zasshi. 2021;141(4):501-510. doi: 10.1248/yakushi.20-00204-2.ABSTRACTNutrients are essential for all living organisms. Because growing cancer cells have strong metabolic demands, nutrient transporters are constitutively increased to facilitate the nutrient uptake. Among these nutrient transporters, L-type amino acid transporter 1 (LAT1), which transports large neutral amino acids including essential amino acids, is critical for cancer growth. Therefore, LAT1 has been considered as an attractive target for diagnosis and therapy of cancers. We have developed several lines of compounds for cancer diagnosis and therap...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Pattama Wiriyasermkul Satomi Moriyama Pornparn Kongpracha Shushi Nagamori Source Type: research

High-throughput Screening Technology for Selective Inhibitors of Transporters and Its Application in Drug Discovery
Yakugaku Zasshi. 2021;141(4):511-515. doi: 10.1248/yakushi.20-00204-3.ABSTRACTThe first step in small-molecule drug discovery is the identification of hit compounds via high-throughput screening (HTS). In transporter drug discovery, most HTS assays are based on the uptake of labeled substrates, but such functional assays cannot be developed for many transporters, such as intracellular organelle transporters. These transporters remain unexplored in drug discovery despite their promise as drug targets. Affinity selection-mass spectrometry (AS-MS) is a label-free binding assay technology that has been developed as an HTS tech...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Takashi Motoyaji Source Type: research

VNUT Is a Therapeutic Target for Type 2 Diabetes and NASH
Yakugaku Zasshi. 2021;141(4):517-526. doi: 10.1248/yakushi.20-00204-4.ABSTRACTATP, used in cells as an energy currency, also acts as an extracellular signaling molecule. Studies of purinergic receptor subtypes have revealed that purinergic chemical transmission plays important roles in various cell types. The vesicular nucleotide transporter (VNUT), the ninth transporter in the SLC17 organic anion transporter family, is essential for vesicular ATP storage and its subsequent release. The VNUT is localized on the membrane of secretory vesicles and actively transports ATP into vesicles using an electrochemical gradient of pro...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Nao Hasuzawa Keita Tatsushima Rie Tokubuchi Masaharu Kabashima Masatoshi Nomura Source Type: research

Studies on Elastase and Elastase Inhibitor from Aspergillus flavus
Yakugaku Zasshi. 2021;141(4):527-540. doi: 10.1248/yakushi.20-00193.ABSTRACTThe biological properties of elastase and Aspergillus flavus elastase inhibitor (AFLEI) from A. flavus were examined. Pathogenicity of elastase was investigated in mice immunocompromised with cyclophosphamide, cyclosporine, prednisolone and carrageenan. Compared to cyclophosphamide immunocompromised mice treated with the spores of elastase nonproducing strain, cyclophosphamide immunocompromised mice treated with the spores of elastase producing strain had a significantly shorter survival rate. Molecular mass of AFLEI was determined to be 7525.8 Da....
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Toshiaki Nikai Source Type: research

Improvement of Medication Adherence in Psychiatry and Mental Health Literacy Education
Yakugaku Zasshi. 2021;141(4):541-555. doi: 10.1248/yakushi.20-00218.ABSTRACTIn Japan, the number of patients with mental illness is increasing; therefore, the need for national measures, such as suicide prevention measures and measures against alcohol health disorders, and multiple social concerns and needs, such as depression and dementia problems, are increasing. As such, measures for mental health are emphasized. Mental health is a common issue; however, there is still prejudice regarding mental illness, and its understanding and awareness by local residents and medical staff need to be improved. The author introduced a...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Moemi Saito Source Type: research

Chemical Biology Studies Using Vitamin A Analogs
Yakugaku Zasshi. 2021;141(4):557-577. doi: 10.1248/yakushi.20-00230.ABSTRACT"Retinoid" is the general term for vitamin A derivatives and chemical compounds that act like vitamin A. Vitamin A are composed of four isoprene units and are named according to their terminal functional group, such as retinol (OH, 1), retinal (CHO, 2), and retinoic acid (CO2H, 3). Vitamin A usually refers to retinol. In the past few decades, major advances in research on vitamin A have improved our understanding of its fundamental roles and physiological significance in living cells. In this review, three types of chemical biology studie...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Akimori Wada Source Type: research

Modulation of Host Immune System by Staphylococcal Superantigen-like (SSL) Proteins
Yakugaku Zasshi. 2021;141(4):579-589. doi: 10.1248/yakushi.20-00236.ABSTRACTStaphylococcus aureus is a common pathogen causing a wide range of infectious diseases in humans and animals. This bacterium secretes a variety of exoproteins, including toxins known as superantigens, such as toxic shock syndrome toxin-1 (TSST-1) and enterotoxins. Staphylococcal superantigen-like (SSL) proteins are a family of exoproteins showing structural similarities with superantigens but no superantigenic activity. This family is composed of 14 members (SSL1-SSL14), and recent studies have revealed that these members exhibit various immunomodu...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Tsutomu Tsuji Source Type: research

Changes in Test Methods for Internationalization in the Japanese Pharmacopoeia (Part 1): Establishment of a Quantitative Test Method for Clonidine Hydrochloride Using HPLC Analysis
In this study, we synthesized impurities of clonidine hydrochloride and determined their purities using quantitative NMR. In addition, the complete separation conditions of these compounds by HPLC were examined, and simultaneous analysis was performed.PMID:33790124 | DOI:10.1248/yakushi.20-00237 (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Aika Maniwa Genichiro Tsuji Takahito Ito Nahoko Uchiyama Junko Hosoe Takashi Ohtsuki Hiroshi Matsufuji Yosuke Demizu Yukihiro Goda Source Type: research

Stability of Six Drugs in Total Parenteral Nutrition Solution
In this study, we investigated the stability of six drugs, including famotidine, scopolamine butylbromide, furosemide, bromhexine hydrochloride, betamethasone sodium phosphate, and metoclopramide hydrochloride in the infusion bags under dark conditions at 4℃ for 7 days. Additionally, we developed a high-performance liquid chromatography method to determine drug concentrations in the infusions. The concentrations of injected famotidine, scopolamine butylbromide, and betamethasone sodium phosphate remained unchanged when the four chambers of Elneopa NF No. 1 and No. 2 were opened and the infusions were mixed. Their respect...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Takefumi Kumagai Naoko Narahara Eiji Sato Yoshitaka Kihira Yoshino Fujimura Eijiro Kojima Shojiro Ogawa Yuko Date Yasuto Tsuruta Hironori Yoshitomi Hirofumi Inoue Source Type: research

Predicting the Incidence of Venous Thromboembolism Using the Khorana Score: A Literature Review
This study aimed to investigate the usefulness of the Khorana score, using data available in the literature. On July 28, 2020, we collected papers using the following keywords: "cancer", "venous thromboembolism", "deep vein thrombosis", "pulmonary embolism", and "Khorana score" on PubMed. Papers published after 2016 were eligible. The selection criteria were as follows: "English or Japanese", "original paper", "abstract and full text", and "comply with the clinical question". There were 131 papers that matched the keywords, and 15 of ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Akari Nishimura Yoshiaki Ikeda Source Type: research

Development of Novel Methodology and Its Application for Clarifying the Transport Function of the Blood-brain Barrier
Yakugaku Zasshi. 2021;141(4):447-462. doi: 10.1248/yakushi.20-00232.ABSTRACTThe blood-brain barrier (BBB) consists of brain capillary endothelial cells linked by tight junctions and serves to regulate the transfer of endogenous compounds and xenobiotics between the circulating blood and brain interstitial fluid. We have developed a methodology to characterize brain-to-blood efflux transport in vivo, using the Brain Efflux Index and an in vitro culture model of the BBB, i.e., a conditionally immortalized cell line of the neurovascular unit. Employing these methods, we showed that the BBB plays an important role in protectin...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Tetsuya Terasaki Source Type: research

Study on the Safety of Perinatal Medication
Yakugaku Zasshi. 2021;141(4):463-471. doi: 10.1248/yakushi.20-00184.ABSTRACTWe have been conducting research with the aim of generating evidence for the safety of perinatal drugs. As a result of reviewing the records of inquiries to the Drug Information Office of our hospital, we found a large discrepancy between the description of perinatal drugs in package inserts in Japan and the description of the Pregnancy Risk Category according to the U.S. Food and Drug Administration. In the Japan Environment and Children's Study (JECS), we determined the proportion of drug and supplement use among 97464 pregnant women. We clarifie...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - April 1, 2021 Category: Drugs & Pharmacology Authors: Taku Obara Source Type: research