1.Synthesis of precursor of anti-inflammatory agents by using highly reactive zinc.
Aishah AJ ; Nobuhito K ; Tokuda M
The Medical Journal of Malaysia 2004;59 Suppl B():210-211
Highly reactive zinc metal was prepared by electrolysis of a N,N-dimethylformamide (DMF) solution containing naphthalene and a supporting electrolyte in a one-compartment cell fitted with a platinum cathode and a zinc anode. This highly reactive electrogenerated zinc (EGZn/Naph) was used for transformation of ethyl 2-bromoacrylate into the corresponding organozinc compound, which can not be achieved by the use of usual zinc metals. Reaction of the organozinc compounds thus prepared with various aryl halides in the presence of 5 mol% of palladium catalyst gave the corresponding cross-coupling products in high yields. These cross-coupling reactions were successfully applied to a synthesis of the precursor of anti-inflammatory agents such as ibuprofen, naproxen, cicloprofen and suprofen.
Anti-Inflammatory Agents, Non-Steroidal/*chemical synthesis
;
Catalysis
;
Electrolysis
;
Ibuprofen/chemical synthesis
;
Naphthalenes
;
Naproxen/chemical synthesis
;
Prodrugs/*chemical synthesis
;
Propionic Acids/chemical synthesis
;
Suprofen/chemical synthesis
;
Zinc/*pharmacology
2.28-day Repeated Dose Oral Toxicity Test of Coix lacryma-jobi L. var. ma-yuen Stapf in Rats
Hirotaka HAYASHI ; Takanari ARAI ; Jeffry M. STRONG ; Harukuni TOKUDA ; Yasuko SHIMANO ; Yasuyuki OHTA ; Toshiki ENOMOTO ; Kazuo UEBABA ; Tomihisa OHTA ; Nobutaka SUZUKI
Japanese Journal of Complementary and Alternative Medicine 2009;6(3):131-135
Coix lacryma-jobi L. var.ma-yuen Stapf (coix seed) is a grass crop that has long been used in traditional medicine as a nourishing food. However, high-intake safety of the extract of the husks, pellicles and astringent skin of coix seed has rarely been evaluated. We performed a 28-day repeated dose oral toxicity test of hot water extract of all parts of Coix seed in rats. The extract showed no significant toxicity on body weight, blood analyses, urinalysis and histopathological examination in acute toxicity tests.
3.Association between surgical procedures under general anesthesia in infancy and developmental outcomes at 1 year: the Japan Environment and Children's Study.
Yoshiko KOBAYASHI ; Narumi TOKUDA ; Sho ADACHI ; Yasuhiro TAKESHIMA ; Munetaka HIROSE ; Masayuki SHIMA
Environmental Health and Preventive Medicine 2020;25(1):32-32
BACKGROUND:
The neurotoxicity of general anesthesia to the developing human brains is controversial. We assessed the associations between surgery under general anesthesia in infancy and development at age 1 year using the Japan Environment and Children's Study (JECS), a large-scale birth cohort study.
METHODS:
In the JECS, 103,062 pregnancies and 104,065 fetuses were enrolled between January 2011 and March 2014. Of the 100,144 registered live births, we excluded preterm or post-term infants, multiple births, and infants with chromosomal anomalies and/or anomalies of the head or brain. Data on surgical procedures under general anesthesia in infancy were collected from self-administered questionnaires by parents at the 1-year follow-up. Developmental delay at age 1 year was assessed using the Japanese translation of the Ages and Stages Questionnaires, Third Edition (J-ASQ-3), comprising five developmental domains.
RESULTS:
Among the 64,141 infants included, 746 infants had surgery under general anesthesia once, 90 twice, and 71 three or more times. The percentage of developmental delay in the five domains of the J-ASQ-3 significantly increased with the number of surgical procedures. After adjusting for potential confounding factors, the risk of developmental delays in all five domains was significantly increased in infants who had surgery under general anesthesia three times or more (adjusted odds ratios: for communication domain 3.32; gross motor domain 4.69; fine motor domain 2.99; problem solving domain 2.47; personal-social domain 2.55).
CONCLUSIONS:
Surgery under general anesthesia in infancy was associated with an increased likelihood of developmental delay in all five domains of the J-ASQ-3, especially the gross motor domain at age 1 year. The neurodevelopment with the growth should be further evaluated among the children who had surgery under general anesthesia.
TRIAL REGISTRATION
UMIN Clinical Trials Registry (number: UMIN000030786 ).
Anesthesia, General
;
adverse effects
;
Anesthetics, General
;
adverse effects
;
Child Development
;
drug effects
;
Cohort Studies
;
Female
;
Humans
;
Infant
;
Infant, Newborn
;
Japan
;
Male