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Biomedical subjects

Mariko Matsumoto

Publications and source records attributed to Mariko Matsumoto.

10 recordsLinked to original sources

Developmental toxicity of dibutyltin dichloride in cynomolgus monkeys.

Dibutyltin dichloride (DBTCl) has been shown to be teratogenic in rats. The present study was conducted to determine the teratogenic potential of DBTCl given to pregnant monkeys during the entire period of organogenesis. Cynomolgus monkeys were dosed once daily by nasogastric intubation with DBTCl at 0, 2.5 or 3.8 mg/kg on days 20-50 of pregnancy, the whole period of organogenesis. The pregnancy outcome was determined on day 100 of pregnancy. In both DBTCl-treated groups, a significant increase in the incidence of pregnant females with soft stool and/or diarrhea, and with yellowish stool was observed. Maternal body weight gain at 3.8 mg/kg and food consumption at 2.5 and 3.8 mg/kg were decreased during the administration period. The survival rate of fetuses at terminal cesarean sectioning was decreased in the DBTCl-treated groups and significantly decreased at 2.5 mg/kg. There were no changes in the developmental parameters of surviving fetuses, including fetal body weight, crown-rump length, tail length, sex ratio, anogenital distance and placental weight, in the DBTCl-treated groups. No external, internal or skeletal malformations were found in the fetuses in any group. Although internal and skeletal variations were found, no difference in the incidence of fetal variation was noted between the control and DBTCl-treated groups. No effect on skeletal ossification was observed in fetuses in the DBTCl-treated groups. The data demonstrate that DBTCl is embryolethal but not teratogenic in cynomolgus monkeys.

Administration, Oral↗

Otomycosis: subdermal growth in calcified mass.

Reports on clear identification of fungi in subdermal tissue in chronic fungal external otitis are rare in recent years. Our patient was an immunocompetent adult male with an 8 year history of chronic otitis externa who presented with pustules on the external auditory canal (EAC) and necrosis and perforation of the tympanic membrane. Type I tympanoplasty was performed, but wound healing was delayed and swelling of the EAC occurred. Incision biopsy and staining (Gomori-Grocott and PAS) revealed fungal hyphae within small, calcified, subepidermal masses. A 3 month course of oral itraconazole was effective in healing the lesion. Calcification, a rarely reported finding in otomycosis, may represent a protective reaction against topical use of antifungal drugs.

Biopsy↗

Prenatal developmental toxicity study of the basic rubber accelerator, 1,3-di-o-tolylguanidine, in rats.

Pregnant rats were given 1,3-di-o-tolylguanidine (DTG) by gavage at 0, 10, 20 or 40 mg/kg bw/day on days 6-19 of pregnancy and the pregnancy outcome was determined on day 20 of pregnancy. At 40 mg/kg bw/day, deaths were observed in four out of 24 females. The incidences of females showing mydriasis at 20 and 40 mg/kg bw/day and showing decreased locomotor activity at 40 mg/kg bw/day were significantly increased. Alopecia, bradypnea, prone position and tremor were also observed at mg/kg bw/day. The maternal body weight gain at 20 and 40 mg/kg bw/day and food consumption at 40 mg/kg bw/day were significantly reduced. A significantly decreased weight of the gravid uterus, increased incidence of postimplantation loss, decreased number of live fetuses, and lowered weights of fetuses and placentae were found at 40 mg/kg bw/day. The incidences of the total number of fetuses with external malformations at 40 mg/kg bw/day and with skeletal malformations at 20 and 40 mg/kg bw/day were significantly increased. Significantly higher incidences of fetuses with brachydactyly and short tail and defects of caudal vertebrae, phalanges and metacarpals were observed at 40 mg/kg bw/day. Delayed ossification was also noted at 40 mg/kg bw/day. The data indicate that DTG is teratogenic at maternal toxic doses and the NOAELs of DTG for maternal and developmental toxicity are 10 mg/kg bw/day in rats.

Abnormalities, Drug-Induced↗

Evaluation of developmental toxicity of ultraviolet absorber 2-(3',5'-di-tert-butyl-2'-hydroxyphenyl)-5-chlorobenzotriazole in rats.

2-(3',5'-Di-tert-butyl-2'-hydroxyphenyl)-5-chlorobenzotriazole (DBHCB) is widely used as a UV absorber. In this study, the developmental toxicity of DBHCB was evaluated in rats. Pregnant rats were given DBHCB at 0, 62.5, 250, or 1000 mg kg(-1) day(-1) by gavage on days 5-19 of pregnancy. No deaths were observed in the pregnant rats of any group. No effect of DBHCB on the general conditions, body weight gain, or feed consumption was observed in the pregnant rats. There were no changes in the ovarian weight, gravid uterine weight, or necropsy findings in the maternal rats of the DBHCB-treated groups. No significant effects of DBHCB were found in the number of corpora lutea, implantations, live fetuses, resorptions or dead fetuses, incidence of pre- or postimplantation embryonic loss, viability of fetuses, fetal weight, or sex ratio of live fetuses. No significant difference in the incidence of fetuses with malformations or variations or degree of ossification was detected between the DBHCB-treated and control groups.

Abnormalities, Drug-Induced↗

Reproductive and developmental toxicity screening test of basic rubber accelerator, 1,3-di-o-tolylguanidine, in rats.

Twelve male and female rats per group were exposed to the rubber accelerator 1,3-di-o-tolylguanidine (DTG) by gavage at 0, 8, 20 or 50 mg/kg bw/day. Males were dosed for a total of 49 days beginning 14 days before mating. Females were dosed for a total of 40-49 days beginning 14 days before mating to day 3 of lactation throughout the mating and gestation period. At 50 mg/kg bw/day, deaths were observed in two males and three females. Lowered body weight gain and food consumption were noted in males at 50 mg/kg bw/day and females at 20 and 50 mg/kg bw/day. Mydriasis, decreased locomotor activity, bradypnea, prone position, tremor and/or salivation were observed in males and females at 20 and 50 mg/kg bw/day. No effects of DTG were found on the estrous cyclicity, precoital interval, copulation, fertility and gestational indices, numbers of corpora lutea and implantations, or gestation length. A significant decrease in the number, body weight and viability of offspring and increase in the incidence of fetuses with external malformations were found at 50 mg/kg bw/day. Oligodactyly, anal atresia and tail anomalies were observed. These data suggest that DTG may be teratogenic. The NOAELs of DTG for general and developmental toxicity in rats are 8 and 20 mg/kg bw/day, respectively.

Abnormalities, Drug-Induced↗

Undesirable effects of citrus juice on the pharmacokinetics of drugs: focus on recent studies.

It is well known that intake of grapefruit juice affects the pharmacokinetics of various kinds of drugs. It has been reported that other citrus juices also interact with certain drugs. To re-evaluate citrus juice-drug interactions based on currently available evidence, a literature search was conducted for new and updated information since the grapefruit juice-drug interaction was last reviewed in 1998. MEDLINE (1998-October 2004) was accessed and more than 200 reports were found. The effects of grapefruit juice ingestion on the pharmacokinetics of orally administered drugs have been reported for 40 drugs since the reviews published in 1998. Increases in either area under the concentration-time curve (AUC) or maximum plasma concentration (C(max)) were found with 34 of these, the major mechanism being considered to be inactivation of intestinal cytochrome P450 3A4, a so-called mechanism-based inhibition. Although recent reports point to the inhibitory effects of grapefruit juice on the function of P-glycoprotein, which transports substrates from enterocytes back into the lumen, the contribution to the bioavailability of drugs that are substrates of P-glycoprotein has not been established yet. Dramatic decreases in AUC and C(max) for two drugs in association with grapefruit juice ingestion has been reported and, in these cases, inhibitory effects on organic anion transporting polypeptide, which mediates absorption from the intestinal lumen to enterocytes, might be involved. Other citrus juices such as Seville (sour) orange juice and commonly ingested varieties of orange juice also showed significant effects on the AUC and C(max) of some drugs. Although the situation is complex and uncertainties remain, we recommend that patients avoid citrus juice intake while taking medications and that healthcare providers advise against citrus juice intake in this setting until any interactions with subject drugs can be clarified in clinical studies.

ATP Binding Cassette Transporter, Subfamily B↗

[Progress on OECD chemicals programme (7)--SIAM 15 in Boston, 2002].

The 15th Screening Information Data Set (SIDS) Initial Assessment Meeting (SIAM 15) was held in Boston, USA. The initial assessment documents of twelve substances at SIAM 15 (CAS numbers: 79-39-0, 88-60-8, 92-70-6, 102-76-1, 110-83-8, 135-19-3, 7647-01-0, 8007-18-9, 10043-52-4, 11070-44-3, 25321-09-9, 68186-90-3) were submitted by the Japanese Government with or without the International Council of Chemical Associations (ICCA) and all of them on the human health effect parts were agreed at the meeting. In this report, the human health effect parts in their 12 substance documents are introduced.

Animals↗

[Progress on OECD chemicals programme].

The twelfth SIDS, the Screening Information Data Set, Initial Assessment Meeting (SIAM 12) was held at the Organisation for Economic Co-operation and Development (OECD) headquarters in Paris, France and SIAM 13 was held in Bern, Switzerland, hosted by the European Commission. Two substances at SIAM 12 (CAS No:91-15-6, 123-77-3) and 4 substances at SIAM 13 (CAS No:91-76-9, 112-85-6, 868-77-9, 1477-55-0) were submitted by the Japanese Government and/or International Council of Chemical Associations (ICCA). These substances were agreed at the meetings. In this report, the human health effects of 6 substances above-mentioned are introduced.

Animals↗

Determination of serum C-reactive protein (CRP) in healthy beagle dogs of various ages and pregnant beagle dogs.

Serum C-reactive protein (CRP) concentrations in healthy beagle dogs of various ages and in pregnant beagles were measured by enzyme-linked immunosorbent assay (ELISA). Serum CRP concentrations were 1.5-16.0 microg/ml (mean 7.9 +/- 3.4 microg/ml) in male, and 1.8-18.9 microg/ml (mean 8.3 +/- 4.0 microg/ml) in female dogs. No significant sex-related differences were observed in the values. Further, there were no significant age-related differences either. Serum CRP concentrations increased during pregnancy. The concentration of serum CRP in pregnant dogs peaked at 70.2-90.4 microg/ml (mean 77.5 +/- 7.1 microg/ml) 30 or 45 days after ovulation, demonstrating two characteristic features of CRP concentration change in pregnant dogs.

Aging↗