• Toxicological Research
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• v.26 no.4
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• pp.275-283
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• 2010

Placenta transfer study in non-human primate (NHP) is one of the crucial components in the assessment of developmental toxicity because of the similarity between NHP and humans. To establish the method to determine placenta transfer in non-human primate, toxicokinetics of valproic acid (VPA), a drug used to treat epilepsy in pregnant women, were determined in pregnant cynomolgus monkeys. After mating, pregnancy-proven females were daily administered with VPA at dose levels of 0, 20, 60 and 180 mg/kg by oral route during the organogenesis period from gestation day (GD) 20 to 50. Concentrations of VPA and its metabolite, 4-ene-VPA, in maternal plasma on GDs 20 and 50, and concentrations of VPA and 4-ene-VPA in placenta, amniotic fluid and fetus on GD 50 were analyzed using LC/MS/MS. Following single oral administration of VPA to pregnant monkeys, concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma from all treatment groups up to 4-24 hours post-dose, demonstrating that VPA was absorbed and the monkeys were systemically exposed to VPA and 4-ene-VPA. After repeated administration of VPA to the monkeys, VPA was detected in amniotic fluid, placenta and fetus from all treatment groups, demonstrating that VPA was transferred via placenta and the fetus was exposed to VPA, and the exposures were increased with increasing dose. Concentrations of 4-ene-VPA in amniotic fluid and fetus were below the limit of quantification, but small amount of 4-ene-VPA was detected in placenta. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at dose levels of 20, 60 and 180 mg/kg during the organogenesis period. VPA was transferred via placenta and the fetus was exposed to VPA with dose-dependent exposure. The metabolite, 4-ene VPA, was not detected in both amniotic fluid and fetus, but small amount of 4-ene-VPA was detected in placenta. These results demonstrated that proper procedures to investigate placenta transfer in NHP, such as mating and diagnosis of pregnancy via examining gestational sac with ultrasonography, collection of amniotic fluid, placenta and fetus after Caesarean section followed by adequate bioanalysis and toxicokinetic analysis, were established in this study using cynomolugus monkeys.

• Journal of Veterinary Clinics
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• v.21 no.1
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• pp.1-6
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• 2004

This study was undertaken to provide the appropriate vaccination protocol of canine parvovirus (CPV) vaccine for the companion dogs in Korea. A total of 120 healthy pups (20 pups per group) at 6 weeks of age were randomly assigned to one of four commercially available vaccines [C, G, K, and V groups] and one of vaccination schedules [V2 and V4 groups]. The serological responses to the CPV component of the vaccines were determined by measuring HI titers. The maternal antibodies was declined to under the protective level at 6 weeks of age. Therefore, it was considered that vaccination of pups for CPV should be started at 6 weeks of age. And when the combination vaccine was used, the immunogenicity of V vaccine was superior to the other vaccines and optimum vaccination schedule was 3 times vaccination with 3 weeks-interval starting vaccination at 6 weeks of age. Although pups were vaccinated at 6 weeks of age, the geometric mean CDV titers of pups in all groups by 9 weeks of age were under the protective level. So, hygienic measures including avoiding to exposure to the high risk areas were needed to prevent CPV infection in this period.

• Toxicological Research
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• v.29 no.1
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• pp.53-60
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• 2013

Studies on milk transfer of drugs in non-human primates (NHPs) are among the crucial components in the assessment of peri- and postnatal toxicity because of the similarity between NHPs and humans. To evaluate the milk transfer of valproic acid (VPA) in NHPs, the toxicokinetics of VPA, an antiepileptic drug, were studied in pregnant cynomolgus monkeys. VPA was administered once daily to pregnant cynomolgus monkeys at doses of 0, 30, 90, and 270 mg/kg by oral gavage from Day 100 of gestation (GD 100) to Day 31 of lactation (LD 31). Concentrations of VPA and its metabolite, 4-ene-VPA, in the maternal plasma on GD 100, GD 140, and LD 30, and concentrations of VPA and 4-ene-VPA in the offspring plasma and milk on LDs 30 and 31, respectively, were quantified using liquid chromatography tandem mass spectrometry (LC/MS/MS). After administration of a single oral dose of VPA to pregnant monkeys on GD 100, the concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma of all treatment groups up to 24 hr after administration, which showed that VPA was absorbed and that the monkeys were systemically exposed to VPA and 4-ene-VPA. After administration of multiple doses of VPA to the monkeys, VPA was detected in the pup's plasma and in milk taken on LD 30 and LD 31, respectively, which showed that VPA was transferred via milk, and the pup was exposed to VPA. Further, the concentration of VPA in the milk increased with an increase in the dose. Extremely low concentrations of 4-ene VPA were detected in the milk and in the pup plasma. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at doses of 30, 90, and 270 mg/kg/day from GD 100 to LD 31. VPA was transferred via milk, and the VPA exposure to the pup increased with an increase in the dose of VPA. The metabolite, 4-ene VPA, was present in extremely low concentrations (< 0.5 ${\mu}g/ml$) in the milk and in the pup plasma. In this study, we established methods to confirm milk transfer in NHPs, such as mating and diagnosis of pregnancy by examining gestational sac with ultrasonography, collection of milk and pup plasma and determination of toxicokinetics, using cynomolgus monkeys.

• Environmental Analysis Health and Toxicology
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• v.27
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• pp.3.1-3.4
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• 2012

Objectives: The current use of humidifier detergent and its harmful impact on humans has arisen as a societal environmental health issue. Therefore, in this study we aimed to explore the relationship between demo-socio characteristics and humidifier use, as well as the monthly usage changes in pregnant women; thus, we report the actual status of humidifier usage of Korea's pregnant population. Methods: From a birth cohort of a Mothers and Children's Environmental Health (MOCEH) study, 1,144 pregnant women who responded through questionnaires including demo-socio characteristics, obstetric status and household environment including whether they use humidifier and frequency of use were included in this study. Statistical analyses were performed to explore the relationship between maternal characteristics and the relevance of the use of humidifiers was performed using a chi-square test, a t-test and univariate logistic regression analysis. The monthly usage rate was demonstrated in the graph. Results: The humidifier usage rate in pregnant women was 28.2%. The average frequency of humidifier usage was 4.6 days per week, 7.3 hours per day. The usage rate was higher in the multipara group and the above the age of 34 age group than in the primipara and below the age of 34 groups. Seoul showed a higher usage rate than Cheonan and Ulsan and as the education level and income increased, the usage rate of humidifiers among pregnant women also increased. In the monthly trend of usage rate, the winter season showed the highest usage rate of over 45% and the lowest in late summer and beginning of fall with a value of 12% or less. Conclusions: During pregnancy, the mother's body is especially vulnerable to hazardous environmental exposure that not only affects the pregnant woman but also the fetus. Further research is still needed to elucidate the route and effect of environmental risk factors. Therefore, based on precautionary and preventive principles, special interest and caution in harmful environments are strongly needed not only at an individual level but also at a national level.

• Childhood Kidney Diseases
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• v.10 no.1
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• pp.58-64
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• 2006

In the clinical state of vitamin D deficiency, it is possible that associated phosphate depletion, parathyroid hormone excess, and hypocalcemia may all depress the proximal tubular reabsorption of bicarbonate, in addition to abnormal skeletal modeling or remodeling, Although nutritional rickets is considered a rare disease in developed countries nowadays, cases of vitamin D deficient rickets caused by various unhealthy lifestyles such as insufficient exposure to sunlight, breast feeding infants without giving vitamin D supplements, unbalanced vegetarian diets of breast feeding mothers, low-birth weight, and maternal deficiency of vitamin D or calcium are increasing. Here, we present the case of an 8 month old girl, who was completely breastfed without any weaning diet or infant vitamin supplements. She visited our emergency room with hypocalcemic seizure and subsequently was diagnosed with vitamin D deficient rickets accompanied by overt bone changes and proximal renal lobular acidosis. After intravenous(IV) and oral calcium replacement therapy(IV calcium gluconate injection 1 mEq/kg/day for 6 days, 2 mEq/kg/day for 4 days followed by oral calcium gluconate administration 4 g/day for 3 days) with vitamin D supplement(Alfacalcidol 0.5 mcg/day) during admission, serum calcium level was normalized with clinical improvement. Oral sodium bicarbonate(0.6 g/day) was administered from the $2^{nd}$ hospital day for 2 weeks, which normalized the serum bicarbonate(measured by $tCO_2$) level. Calcium and vitamin D replacement were continued for 2 weeks and 3 months each. After discontinuing medications, follow up laboratory findings showed good maintenance of serum calcium, alkaline phosphate and bicarbonate levels with complete improvement of bone X-ray findings.

• Journal of Preventive Medicine and Public Health
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• v.22 no.1 s.25
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• pp.125-135
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• 1989

This paper was carried out to study on correlation between mentally retardation and lead and zinc. The subjects were 297 mentally retarded children: 132 of Bomyung special school and Sunmyung, which were located in Taegu city of Korea. The former had their parents but the latter had not. The control group 63 children were randomly seleted from the Dong-in primary school near to Medical School of Kyungpook National University. Atomic absorption spectrophotometer, model IL-551 connected with CTF atomizer(IL. 655) was used for the analysis of lead and zinc. The mean value of lead in hair of mentally retarded children was $14.97{\pm}3.71ppm$ which is significantly higher than that of control group, $11.36{\pm}2.83ppm$. But the content of zinc was not significant in both groups. In the lead there was no significant correlation to age but significant negative correlation to IQ. Zinc showed significant correlation to age but not to IQ. Among the handicapped children, no signigicant correlation between orphan group and non orphan group. Handicaps of mentally-retarded children were speech impairment, emotional disturbance, double and triple handicaps, sensory impairment and abnormal dietary patterns. There were significantly higher contents of lead compared with normal group, except the latter two groups. The disease conditions of mentally retarded children were mongolism, autism, cerebral palsy, epilepsy and microcephaly. In comparing with mongolism, significant difference were existent only on the cerebral palsy and group of unknown etiology. We attempted to divide their past history into external etiology and internal etiology, but could not find significant difference. In view of the whole results, the relationship between mentally-retarded children and lead was presumed to be the early time exposure rather than long interval exposure during growth and the contact opportunity was considered important subject in maternal and child health care.

• Journal of Preventive Medicine and Public Health
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• v.4 no.1
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• pp.77-87
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• 1971

A study of the knowledge, attitude and practices about the maternal and child health of 305 married women residing in apartments at the Yonsei Community Health area was conducted during the period from November to December 1970 using designed questionnaire with well trained interviewers. The results and findings obtained from the study are summarized as follows: A. Pregnancy and Birth Questions were asked about their last child. 1. 16.4% of the women were pregnant. 2. Among 281 women who had experienced delivery, 48.0% were assisted by doctor or midwisves for their last delivery, while the rest of women delivered their last baby at home without any professional's assistance. The higher the level of education or the greater exposure to mass communication, the more the deliveries were assisted by doctors or midwives. Those women who were born and raised in cities had more deliveries assisted by doctors and midwives than those who were not. 3. Kinds of delivery sheets used. Among 141 cases of home delivery 68% used cement bag paper or vinyl sheets. Three% used nothing and remained used unsterile materials. 4. Among 141 cases of home delivery, 70.2% used scissors. The rest of them used other methods. 5. 47.3% of the women had a rest for one month or more after birth. The higher the level of education, the longer the period of rest was observed. 6. 52.4% of the women fed the colostrum to their babies. This was not related to the mother's education. 7 About half(42.9%) of the women had poor knowledge about a proper diet for the pre and post natal period. B. Child Health 1. Knowledge and practice regarding to the immunization for their children: Most of the women (93.2%) could name at least one kind of immunization. 20.3% could name 6 kinds of immunization. Mothers education level did not influence their ability to name immunizations. 85.2% of children had been immunized at least once. 2. Morbidity of last born children: 48.1% of their last born children were found to have been sick during the last year. Less than half(41.5%) of the sick children were seen by doctor. 3. Counselling at well baby clinic: Most of the women(76.5%) had no counselling for their children. Registration rate at the well baby clinic at the Severance Hospital was 13.2%. 45.9% wanted to visit to the well baby clinic at the Severance Hospital. 4. Weaning Period: 44.6% said that the beginning of the weaning for their last born children was from 6 months to twelve months of age. The most important reason of weaning was the health of both mothers and children. 5. Knowledge and Practice regarding birth and death Registration: 64.6% of the women could name correctly the Ku-office as the place for the registration. Only 29.2% registered the birth of their last born children within 14 days. C. Knowledge, Attitude and Practice regarding to family planning Most: of the women accepted the idea of family planning. 97.7% could name at least one contraceptive method. 35.4% were found to be current users of contraceptive methods. The ideal number of children was 3.1 in average.

• Journal of Preventive Medicine and Public Health
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• v.15 no.1
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• pp.145-151
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• 1982

Breslau's report on the two stillbirths induced by illuminating gas poisoning made many investigators explore the hazards. of carbon monoxide(CO) poisoning to pregnancy. The pregnant woman, her fetus, and the newborn infant have been identified to be particularly vulnerable to CO even in low concentration. Several factors, such as placental barrier, membrane resistance of maternal and fetal red blood cells etc., were considered to be related to the delayed elimination of CO from fetus. Slower elimination of CO from fetus than from mother was confirmed in several in vivo studies. But there are few studies which have confirmed the difference of carboxyhemoglobin (HbCO) dissociation in adult and fetal bloods. Author investigated the effects of hemoglobin itself on the elimination of CO from mother and fetus. By observing the difference of CO dissociation from adult and fetal hemoglobin at the various partial pressures of oxygen, the author tries to suggest the base of the proper treatment measure for the CO poisoning of pregnant woman and newborn infant. The results were as follows: 1. The total hemoglobin amounts of adults and fetal bloods were $16.1{\pm}0.50gm%\;and\;15.7{\pm}0.32gm%$, respectively. The fetal hemoglobin proportions in adult and fetal bloods were $1.2{\pm}0.15%\;and\;72.7{\pm}3.01%$, respectively. 2. Adult and fetal bloods saturated by CO to 100% HbCO were exposed to ambient air$(21%\;O_2),\;100%\;O_2\;and\;3\;ATAO_2$. After 30 minutes exposure, the HbCO saturations of adult blood were 96.7%, 70.9%, and 52.8%, respectively, and those of fetal blood were 98.5%, 76.1%, and 62.2%, respectively. HbCO dissociation was proportional to the partial pressure of oxygen and the most marked dissociation was shown under 3 ATA $O_2$, HbCO dissociation of fetal blood was slower than that of adult blood in all conditions. According to the above results, it is possible that CO poisoning make more serious damage to the fetus and newborn infant than to the adult due to the delayed dissociation of HbCO. Thus in the treatment of CO poisoning of pregnant woman and newborn infant, hyperbaric oxygen therapy seems to be the most eflective treatment measure, but the duration of hyperbaric oxygenation should be lengthened accordingly.

• Journal of Preventive Medicine and Public Health
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• v.9 no.1
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• pp.11-24
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• 1976

This study was a part of large scale of a prospective study on attitudes of professional students in medicine, nursing and teaching toward population related issues in Korea. The study was first conducted in May 1974 and then in May 1975 for the 1974 class cohot using a questionaire consisted of attitude scales and other items developed by Lee. The purpose of stuay was twohold, namely, to determine the difference in students among specializations on one hand and between the first and second years in the 1974 class cohot regarding tile subject matter. A one-way analysis of variance was used for attitude scale, and absolute and relative frequency were computed for the analysis of non-attitude scale items by employing Fishers' Ratio and Duncan's multiple range test at 5% level and chi square test at 5% level as significance tests. The hypothesis 'students in health profession are more likely to have positive attitudes toward population related issues progressively as class year advances than students in teaching profession' was tested and the following results were obtained: 1) Nursing students were more likely to display favarable attitudes toward family planning than medical or teaching students although the class cohot showed slightly negative improvement in the second year. Medical and teaching students apperaed to have slightly improved attitudes in the second year. 2) Respondents in general perceived national family planning program as a means of population control and this tendency was more true among nursing students as the class year advances than two other professional groups of students. Students in teaching profession appeared to perceive it more as a means to improve individual family welfare while health students were likely to see as to improve maternal and child health. This tendency was progressively improved as the class year advanced. 3) The majority of students regardless of their respective specializations believed that family planning program should be directed toward the improvement of individual family welfare. No progressive changes in the class cohot were observed. 4) About the plan to use contraceptives in future, no singnificant differences were observes among different specializations nor in different class years. However, the majority was confirmed to have a plan to use contracepives in future. An increasing proportion of the undecided category was observed, as class year advanced among health students. 5) Students in health profession were found to be more favorable about 'more leisure opportunities' as motive for limiting number of children whereas education students indicated the reasons as 'facilitate ambitions' and 'economic base' The progressive changes toward positive direction in both groups were observed as the class years advanced. 6) Attitudes toward induced abortions of the health students were observed to be positively related to class years while an inverse relationship was found in teaching students who showed much less favor in the subject matter than health students. This phenomenon may be due to the different exposure to learning environments unique to respective specializations. 7) Health students were found to have more favorable attitudes toward population education in general than the teaching students. The teaching students appeared to have changed more to the negative direction when they became the second year while no such development was observed in health students. The teaching students seemed to hold a very conservative position with regard to sex education in schools. 8) About the equality of sexes, the nursing group was found to be most favorable while the reverse was true in the teaching group. A change in the negative direction as the class year advanced was found in the teaching group. 9) About questions related to fertility values-the 10 percent of respondents regardless of specialization indicated that they would maintain their single status in future, however no change was observed in the second year. The desired number of children was found to be two by the majority of students in nursing, medicine and teaching in order of high proportion. No changes in a different class year were observed. The childless marriage was seen by nursing students as a problem more than other students, but a slight change in positive direction was found when the nursing students became the second year. In summing, as data supported in the above, students in health profession demonstrated more favorable attitudes toward population related issues than the teaching students and this tendency became more apparent in the second year. It was noticed that health students were more conscious about the health aspect of population and family planning program while the teaching students gave more attention to the socioeconomic aspect. The sex variable seemed to have operated in the item related to the equality of sexes. In conclusion, as data presented in the above, the hypothesis of this study was accepted except in the few items. It should be noted that the limitation of this study is the short duration of the observation in measuring the possible attitude changes. It should include curriculum analysis for the respective specializations in order to indentify the area of curriculum impact on students in future study.