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  1. Article ; Online: Evaluation of organophosphorus pesticide tyrosine adducts for postmortem change by human serum albumin with liquid chromatography quadrupole Orbitrap mass spectrometry.

    Yamagishi, Yoshikazu / Nagasawa, Sayaka / Iwase, Hirotaro / Ogra, Yasumitsu

    Toxicological sciences : an official journal of the Society of Toxicology

    2024  Volume 199, Issue 1, Page(s) 40–48

    Abstract: Organophosphorus pesticides (OPPs) having a phosphate ester moiety, such as malathion (MA) and methidathion (DMTP), are widely used and have been detected in many fatal cases of accidental exposure or suicide in Japan. In forensic toxicology, the ... ...

    Abstract Organophosphorus pesticides (OPPs) having a phosphate ester moiety, such as malathion (MA) and methidathion (DMTP), are widely used and have been detected in many fatal cases of accidental exposure or suicide in Japan. In forensic toxicology, the accurate determination of blood OPP concentration is mandatory to prove death by OPP poisoning. However, fatal pesticide concentration in blood at autopsy varies depending on the circumstances surrounding the dead body. In this study, we found that 16 OPPs were degraded by human serum albumin (HSA) in a temperature-dependent fashion. The mechanism underlying MA, DMTP, azinphos-methyl, etrimfos, fenthion (MPP), pirimiphos-methyl, (E)-dimethylvinphos, (Z)-dimethylvinphos, vamidothion, edifenphos (EDDP), fosthiazate, and pyraclofos degradation involves the formation of adducts with tyrosine residues in HSA. The mass spectra obtained by liquid chromatography quadrupole Orbitrap mass spectrometry revealed that phosphate ester amino acid adducts such as Y-adduct1, Y-adduct2, Y-adduct3, Y-adduct4, and Y-adduct5 were formed in HSA solution incubated with OPPs. These results indicate that the 16 OPPs are postmortem changed by HSA. The detection of phosphate ester amino acid adducts such as Y-adduct1, Y-adduct2, Y-adduct3, Y-adduct4, and Y-adduct5, instead of MA, DMTP, azinphos-methyl, etrimfos, MPP, pirimiphos-methyl, (E)-dimethylvinphos, (Z)-dimethylvinphos, vamidothion, EDDP, fosthiazate, and pyraclofos per se, may be used to determine death by these OPPs poisoning.
    MeSH term(s) Humans ; Organophosphorus Compounds/toxicity ; Organophosphorus Compounds/chemistry ; Tyrosine/analogs & derivatives ; Pesticides/toxicity ; Pesticides/chemistry ; Serum Albumin, Human/chemistry ; Postmortem Changes ; Chromatography, Liquid ; Mass Spectrometry/methods ; Forensic Toxicology/methods
    Chemical Substances Organophosphorus Compounds ; Tyrosine (42HK56048U) ; Pesticides ; Serum Albumin, Human (ZIF514RVZR)
    Language English
    Publishing date 2024-02-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1420885-4
    ISSN 1096-0929 ; 1096-6080
    ISSN (online) 1096-0929
    ISSN 1096-6080
    DOI 10.1093/toxsci/kfae023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Identification, measurement, and evaluation of blood concentrations of insulin glargine and insulin lispro by UPLC-MS-MS in a dead body suspected of insulin overdose.

    Nagasawa, Sayaka / Yamaguchi, Rutsuko / Chiba, Fumiko / Torimitsu, Suguru / Iwase, Hirotaro

    Journal of forensic sciences

    2023  Volume 68, Issue 2, Page(s) 704–710

    Abstract: Insulin preparations, which are drug treatments for diabetes, cause fatal hypoglycemia when an overdose is administered. Cases of homicide and suicide using these preparations have been reported and are of great forensic interest. However, there are few ... ...

    Abstract Insulin preparations, which are drug treatments for diabetes, cause fatal hypoglycemia when an overdose is administered. Cases of homicide and suicide using these preparations have been reported and are of great forensic interest. However, there are few reports assessing the postmortem concentration of insulin preparations, and it is often difficult to determine the cause of death. In the present study, we report a case of a suspected insulin glargine and insulin lispro overdose for suicide. A woman in her 30s had a history of mental illness and diabetes. The day before her death, she reported to her boyfriend that she had taken large doses of insulin preparations and prescription drugs. An autopsy revealed no fatal injuries or lesions. Drug screening tests revealed several prescription drugs, none of which showed toxic concentrations. Analysis using LC-MS/MS detected insulin glargine in the peripheral and cardiac blood at 429 μU/mL and 1362 μU/mL, respectively, whereas insulin lispro was detected in both the peripheral and cardiac blood at levels below the lower limit of quantification (LLOQ; <50 μU/mL). The cause of death was considered likely to be hypoglycemia caused by an overdose of insulin glargine. Insulin glargine is rapidly metabolized after subcutaneous administration and is rarely detected in the blood when used at therapeutic doses. There are no other reports on the quantification of insulin glargine parent compounds in postmortem samples, and this case provides important data on postmortem blood concentrations of insulin glargine intoxication.
    MeSH term(s) Humans ; Female ; Insulin Glargine ; Insulin Lispro ; Chromatography, Liquid ; Hypoglycemic Agents ; Insulin, Long-Acting ; Blood Glucose/analysis ; Tandem Mass Spectrometry ; Insulin ; Hypoglycemia ; Diabetes Mellitus/drug therapy ; Drug Overdose/drug therapy
    Chemical Substances Insulin Glargine (2ZM8CX04RZ) ; Insulin Lispro ; Hypoglycemic Agents ; Insulin, Long-Acting ; Blood Glucose ; Insulin
    Language English
    Publishing date 2023-02-10
    Publishing country United States
    Document type Case Reports
    ZDB-ID 219216-0
    ISSN 1556-4029 ; 0022-1198
    ISSN (online) 1556-4029
    ISSN 0022-1198
    DOI 10.1111/1556-4029.15219
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Evaluation of Post-Mortem Interaction between Hemoglobin and Oxime-Type Carbamate Pesticides.

    Yamagishi, Yoshikazu / Nagasawa, Sayaka / Iwase, Hirotaro / Ogra, Yasumitsu

    Chemical research in toxicology

    2022  Volume 35, Issue 6, Page(s) 1110–1116

    Abstract: Oxime-type carbamate pesticides having an oxime moiety such as aldicarb, butocarboxim, methomyl, oxamyl, and thiofanox are widely used and have been detected in many fatal cases of accidental exposure or suicide. In forensic toxicology, the accurate ... ...

    Abstract Oxime-type carbamate pesticides having an oxime moiety such as aldicarb, butocarboxim, methomyl, oxamyl, and thiofanox are widely used and have been detected in many fatal cases of accidental exposure or suicide. In forensic toxicology, the accurate determination of blood pesticide concentration is obligatory to prove death by oxime-type carbamate pesticide poisoning. However, the fatal pesticide concentration in blood at autopsy differs from that at the time of death. In this study, we found that oxime-type carbamate pesticides were decomposed by Hb in a temperature-dependent fashion. The mechanism underlying methomyl, aldicarb, oxamyl, and thiofanox decomposition involves the formation of adducts with the amino acids in Hb. With regard to butocarboxim, its decomposition involves the oxidation of the free form and the formation of adducts with the amino acids in Hb. The mass spectra obtained by liquid chromatography quadrupole time-of-flight mass spectrometry revealed that carbamylated amino acid adducts such as W
    MeSH term(s) Aldicarb ; Amino Acids ; Autopsy ; Carbamates ; Cholinesterase Inhibitors ; Hemoglobins/analysis ; Humans ; Methomyl/chemistry ; Oximes ; Pesticides/analysis
    Chemical Substances Amino Acids ; Carbamates ; Cholinesterase Inhibitors ; Hemoglobins ; Oximes ; Pesticides ; Methomyl (1NQ08HN02S) ; Aldicarb (8V071SH05P)
    Language English
    Publishing date 2022-05-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639353-6
    ISSN 1520-5010 ; 0893-228X
    ISSN (online) 1520-5010
    ISSN 0893-228X
    DOI 10.1021/acs.chemrestox.2c00092
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Post-mortem interaction between methidathion and human serum albumin in blood.

    Yamagishi, Yoshikazu / Nagasawa, Sayaka / Iwase, Hirotaro / Ogra, Yasumitsu

    The Journal of toxicological sciences

    2022  Volume 47, Issue 4, Page(s) 139–146

    Abstract: Methidathion [3-(dimethoxyphosphinothioylsulfanylmethyl)-5-methoxy-1,3,4-thiadiazol-2-one; hereinafter DMTP], one of the most widely used organophosphorus pesticides, has been detected in some clinical cases of accidental exposure and suicide in Japan. ... ...

    Abstract Methidathion [3-(dimethoxyphosphinothioylsulfanylmethyl)-5-methoxy-1,3,4-thiadiazol-2-one; hereinafter DMTP], one of the most widely used organophosphorus pesticides, has been detected in some clinical cases of accidental exposure and suicide in Japan. It has been reported that DMTP concentration is decreased in blood. In this study, it is difficult to recover DMTP in the free form because DMTP is bound to human serum albumin (HSA). We detected DMTP adducts in HSA by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS). The mass spectra showed that DMTP was preferably bound to the lysine (K), tyrosine (Y), and cysteinylproline (CP) residues of HSA. The concentrations of K-adduct, DMTP-Y-adduct and DMTP-CP-adduct were increased in vitro in a dose-dependent fashion when DMTP concentration was lower than the lethal dose. Furthermore, the DMTP-Y-adduct and DMTP-CP-adduct were also detected in post-mortem blood of an autopsied subject who died by intentional DMTP ingestion. The results suggested that the DMTP-Y-adduct and DMTP-CP-adduct could be used as a biomarker of DMTP poisoning, and the decrease concentration of DMTP in blood after death could be determined on the basis of the concentration of the DMTP-CP-adduct in blood.
    MeSH term(s) Humans ; Organophosphorus Compounds ; Organothiophosphorus Compounds ; Pesticides ; Serum Albumin, Human
    Chemical Substances Organophosphorus Compounds ; Organothiophosphorus Compounds ; Pesticides ; methidathion (Y2P145U7KK) ; Serum Albumin, Human (ZIF514RVZR)
    Language English
    Publishing date 2022-03-31
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 770623-6
    ISSN 1880-3989 ; 0388-1350
    ISSN (online) 1880-3989
    ISSN 0388-1350
    DOI 10.2131/jts.47.139
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  5. Article ; Online: Identification of postmortem paliperidone metabolite in human blood by LC-Q-Orbitrap-MS.

    Yamagishi, Yoshikazu / Inokuchi, Go / Hoshioka, Yumi / Nagasawa, Sayaka / Iwase, Hirotaro / Ogra, Yasumitsu

    Journal of analytical toxicology

    2023  Volume 47, Issue 6, Page(s) 517–522

    Abstract: Paliperidone is a widely used antipsychotic agent detected in many fatal intoxications and suicide cases. In forensic toxicology, the accurate determination of blood paliperidone concentrations is required to prove death by paliperidone poisoning. ... ...

    Abstract Paliperidone is a widely used antipsychotic agent detected in many fatal intoxications and suicide cases. In forensic toxicology, the accurate determination of blood paliperidone concentrations is required to prove death by paliperidone poisoning. However, the lethal concentration of paliperidone in blood at autopsy differs from that at the time of death. In this study, we found that paliperidone was decomposed by hemoglobin (Hb) through the Fenton reaction in a temperature-dependent fashion. The mechanism underlying paliperidone decomposition involves the cleavage of its C-N bond linker moiety. The mass spectra obtained by liquid chromatography-quadrupole orbitrap mass spectrometry revealed the formation of 6-fluoro-3-(4-piperidinyl)benzisoxazole (PM1) in Hb/H2O2 solution incubated with paliperidone, as well as in the blood of individuals who died from intentional ingestion of paliperidone. These results suggest that PM1 is the only metabolite produced from paliperidone as a result of temperature-dependent, postmortem changes induced by Hb via the Fenton reaction and may be useful as a biomarker to correct for the concentration of paliperidone in blood at the time of death in clinical cases.
    MeSH term(s) Humans ; Paliperidone Palmitate ; Autopsy ; Hydrogen Peroxide ; Chromatography, Liquid/methods ; Mass Spectrometry
    Chemical Substances Paliperidone Palmitate (R8P8USM8FR) ; Hydrogen Peroxide (BBX060AN9V)
    Language English
    Publishing date 2023-06-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 752391-9
    ISSN 1945-2403 ; 0146-4760
    ISSN (online) 1945-2403
    ISSN 0146-4760
    DOI 10.1093/jat/bkad033
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  6. Article ; Online: Cardiac Electropharmacological Effects of Antidiarrheal Drug Loperamide and Its Antidote Naloxone in Anesthetized Guinea Pigs.

    Takahara, Akira / Izawa, Sayaka / Seki, Shota / Aimoto, Megumi / Nagasawa, Yoshinobu

    Biological & pharmaceutical bulletin

    2022  Volume 45, Issue 4, Page(s) 542–546

    Abstract: Cardiac electropharmacological effects of an antidiarrheal drug loperamide and its antidote naloxone were assessed in isoflurane-anesthetized guinea pigs. Intravenous administration of loperamide at 0.01-0.1 mg/kg did not affect parameters of ... ...

    Abstract Cardiac electropharmacological effects of an antidiarrheal drug loperamide and its antidote naloxone were assessed in isoflurane-anesthetized guinea pigs. Intravenous administration of loperamide at 0.01-0.1 mg/kg did not affect parameters of electrocardiogram (ECG) or monophasic action potential (MAP) of the right ventricle. Additional administration of loperamide at 1 mg/kg prolonged the QT interval and MAP duration of the ventricle accompanied with increments of the PQ interval and QRS width. The potency of loperamide for QT-interval prolongation was about 100-times lower than that of dofetilide, in spite that similar inhibitory effects on the human Ether-a-go-go Related Gene (hERG) K
    MeSH term(s) Animals ; Antidiarrheals/pharmacology ; Antidiarrheals/therapeutic use ; Antidotes ; Guinea Pigs ; Heart ; Loperamide/pharmacology ; Loperamide/therapeutic use ; Naloxone/pharmacology
    Chemical Substances Antidiarrheals ; Antidotes ; Naloxone (36B82AMQ7N) ; Loperamide (6X9OC3H4II)
    Language English
    Publishing date 2022-04-01
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1150271-x
    ISSN 1347-5215 ; 0918-6158
    ISSN (online) 1347-5215
    ISSN 0918-6158
    DOI 10.1248/bpb.b22-00024
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  7. Article: Congenital Hypofibrinogenemia in a Neonate with a Novel Mutation in the

    Shinozuka, Jun / Okumura, Nobuo / Nagasawa, Mayumi / Nishikado, Motokazu / Kadowaki, Sayaka / Katsuda, Itsuro / Imashuku, Shinsaku

    Pediatric reports

    2021  Volume 13, Issue 1, Page(s) 113–117

    Abstract: Detection of severe hypofibrinogenemia (<50 mg/dL) in a neonate soon after birth is alarming because of the risk of hemorrhage. A female neonate was noted to be hypofibrinogenemic (<50 mg/dL) on day 0 of birth; she showed no thrombocytopenia/coagulopathy ...

    Abstract Detection of severe hypofibrinogenemia (<50 mg/dL) in a neonate soon after birth is alarming because of the risk of hemorrhage. A female neonate was noted to be hypofibrinogenemic (<50 mg/dL) on day 0 of birth; she showed no thrombocytopenia/coagulopathy or hemorrhagic symptoms. Considering the possibility of afibrinogenemia, which may cause bleeding, fresh frozen plasma (FFP) was initiated twice a week to maintain her plasma fibrinogen level at 50-100 mg/dL. Thereafter, we found hypofibrinogenemia in her father and elder sister and plasma fibrinogen levels, determined by clot formation and immunological methods, showed similarly reduced values in both the neonate (proband) and her father. Based on a presumed diagnosis of congenital hypofibrinogenemia, sequencing of the fibrinogen genes was performed, revealing a novel heterozygous mutation of
    Language English
    Publishing date 2021-03-01
    Publishing country Switzerland
    Document type Case Reports
    ISSN 2036-749X
    ISSN 2036-749X
    DOI 10.3390/pediatric13010016
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  8. Article: Homemade blenderized tube feeding improves gut microbiome communities in children with enteral nutrition.

    Katagiri, Sayaka / Ohsugi, Yujin / Shiba, Takahiko / Yoshimi, Kanako / Nakagawa, Kazuharu / Nagasawa, Yuki / Uchida, Aritoshi / Liu, Anhao / Lin, Peiya / Tsukahara, Yuta / Iwata, Takanori / Tohara, Haruka

    Frontiers in microbiology

    2023  Volume 14, Page(s) 1215236

    Abstract: Enteral nutrition for children is supplied through nasogastric or gastrostomy tubes. Diet not only influences nutritional intake but also interacts with the composition and function of the gut microbiota. Homemade blenderized tube feeding has been ... ...

    Abstract Enteral nutrition for children is supplied through nasogastric or gastrostomy tubes. Diet not only influences nutritional intake but also interacts with the composition and function of the gut microbiota. Homemade blenderized tube feeding has been administered to children receiving enteral nutrition, in addition to ready-made tube feeding. The purpose of this study was to evaluate the oral/gut microbial communities in children receiving enteral nutrition with or without homemade blenderized tube feeding. Among a total of 30 children, 6 receiving mainly ready-made tube feeding (RTF) and 5 receiving mainly homemade blenderized tube feeding (HBTF) were analyzed in this study. Oral and gut microbiota community profiles were evaluated through 16S rRNA sequencing of saliva and fecal samples. The α-diversity representing the number of observed features, Shannon index, and Chao1 in the gut were significantly increased in HBTF only in the gut microbiome but not in the oral microbiome. In addition, the relative abundances of the phylum
    Language English
    Publishing date 2023-08-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2023.1215236
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  9. Article ; Online: Usefulness of powdered crown of mandibular first premolars in birth year estimation by radiocarbon dating.

    Saitoh, Hisako / Takeyama, Mirei / Moriya, Toru / Yusa, Kazuyuki / Minegishi, Saki / Torimitsu, Suguru / Chiba, Fumiko / Hoshioka, Yumi / Nagasawa, Sayaka / Iino, Mitsuyoshi / Sakurada, Koichi / Iwase, Hirotaro / Tokanai, Fuyuki

    Journal of forensic and legal medicine

    2023  Volume 100, Page(s) 102607

    Abstract: Background: Radiocarbon (: Materials and methods: Fourteen mandibular first premolars collected from forensic autopsies were analyzed. For nine teeth, each tooth was cut longitudinally: half of the tooth was enamel, and the other half was crown (1). ... ...

    Abstract Background: Radiocarbon (
    Materials and methods: Fourteen mandibular first premolars collected from forensic autopsies were analyzed. For nine teeth, each tooth was cut longitudinally: half of the tooth was enamel, and the other half was crown (1). For the other five teeth, the entire crown was used (2). Thereafter, the
    Results: The absolute error between the actual date of birth (DOB) and the estimated DOB was within the range of 1.0-8.8 years in the enamel of five teeth and 0.1-4.0 years in the crown halves of seven teeth (1). For the five teeth with entire crowns, the absolute errors ranged between 0.3 and 3.0 years (2).
    Conclusion: The absolute error of
    MeSH term(s) Humans ; Bicuspid ; Radiometric Dating ; Powders ; Mass Spectrometry ; Tooth Crown
    Chemical Substances Powders
    Language English
    Publishing date 2023-10-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2268721-X
    ISSN 1878-7487 ; 1752-928X
    ISSN (online) 1878-7487
    ISSN 1752-928X
    DOI 10.1016/j.jflm.2023.102607
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  10. Article ; Online: Dasatinib-induced panniculitis in a patient with chronic myeloid leukaemia.

    Nagasawa, Yusuke / Iinuma, Shin / Fujii, Mizue / Kanno, Kyoko / Honma, Masaru / Yuzawa, Sayaka / Ishida-Yamamoto, Akemi

    European journal of dermatology : EJD

    2021  Volume 31, Issue 1, Page(s) 87–88

    MeSH term(s) Aged ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Dasatinib/adverse effects ; Dasatinib/therapeutic use ; Drug Eruptions/etiology ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Male ; Panniculitis/chemically induced
    Chemical Substances Antineoplastic Agents ; Dasatinib (RBZ1571X5H)
    Language English
    Publishing date 2021-01-25
    Publishing country France
    Document type Case Reports ; Letter
    ZDB-ID 1128666-0
    ISSN 1952-4013 ; 1167-1122
    ISSN (online) 1952-4013
    ISSN 1167-1122
    DOI 10.1684/ejd.2020.3946
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