• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제22권1호
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• pp.10-15
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• 2011

In this review, we have provided an overview of the environmental risk factors for attention deficit hyperactivity disorder (ADHD), focusing on the major environmental toxicants related to the disorder. Researchers have indicated that since the characteristics of ADHD are complex, the disorder’s etiology involves multiple genes of moderate effect interacting with environmental factors. The possible roles of prenatal and perinatal exposure have been the main focus of research on environmental risk factors for ADHD. Among environmental toxicants, we reviewed the potential effects on the development of ADHD of exposure to lead, nicotine, alcohol, polychlorinated biphenyls (PCBs), and dioxin. Further, for the each neurotoxicant, clinical prevention or intervention strategies aimed at reducing a child’s risk from environmental toxic insults have been presented.

• Genomics & Informatics
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• 제2권2호
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• pp.75-80
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• 2004

In a variety of animal species, the perinatal exposure of experimental animals to the 2,3,7,8-tetrachlorodibenzo­p-dioxin (TCDD) leads to the immune dysfunction, which is more severe and persistent than that caused by adult exposure. We report here the changes of gene expression and the identification of the marker-genes representing the dioxin exposure. The expressions of the transcripts were analyzed using the 11 K oligonucleotide­microarray from the bone marrow cells of male C57BL/6J mice after an intraperitoneal injection of $1{\mu}g$ TCDD/kg body weight at various time intervals: gestational 6.5 day(G6.5), 13.5 day(G13.5), 18.5 day(G18.5), and postnatal 3 (P3W)and 6 week (P6W). The type of self-organizing maps(SOM) representing the specific exposure dioxin could be identified as follows; G6.5D(C14), G13.5D(C0, C5, C10, C18), G18.5D(7): P3W(C2, C21), and P6W(C4, C15, C20). The candidate marker-genes were restricted to the transcripts, which could be consistently expressed greater than $\pm$2-fold in three experiments. The resulting candidates were 85 genes, the characteristics of that were involved in cell physiology and cell functions such as cell proliferation and immune function. We identified the biomarker-genes for dioxin exposure: smc -like 2 from SOM C14 for the dioxin exposure at G6.5D, focal adhesion kinase and 6 other genes from C0, and protein tyrosine phosphatase 4a2 and 3 other genes from C5 for G13.5D, platelet factor 4 from C7 for G18.5D, fos from C2 for P3W.

• 대한방사선기술학회지:방사선기술과학
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• 제41권2호
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• pp.157-162
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• 2018

This study is a search for radiation protection effects of radiation exposure on the organogenic period during the prenatal period, which is known to be the most likely to have congenital malformations by radiation exposure. To study the radiation protection for the mixture of selenium that is strong antioxidant and folic acid that is essential vitamin for DNA synthesis, 2 Gy of radiation was irradiated to pregnant female rats. then, after 14 days of fetal birth, observing blood components, SOD(Superoxide Dismutase), histological changes and external malformations. There was a significant protective effect to reduce blood cell damage(p<0.05) in the irradiation group after selenium and folic acid mixture were administered than irradiation group, and the activation of SOD which is antioxidant enzymes was increased. In addition, confirmed the effect of suppressing the expression of apoptosis of small intestinal cells and the reduction of cerebral cortex layer reduction by radiation. thus, it was confirmed that the congenital malformations were reduced as a result of these protective effects. Based on these results, selenium and folic acid mixture may reduce the incidence of congenital malformations, and it will reduce the damage of the fetus caused by the exposure of the organogenic period due to accidents.

• Toxicological Research
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• 제16권3호
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• pp.229-238
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• 2000

The purpose of reproductive toxicity studies is to evaluate all effects resulting from paternal or maternal exposure that interfere with conception, development, birth, and maturation of offspring. In 1966, the US Food and Drug Administration (US FDA) published guidelines for a three-segment study for drug testing to examine adverse effects on fertility and pregnancy. Three segments were proposed: Segment I, Study of Fertility and General Reproductive Performance, to provide information on breeding, fertility, nidation, parturition, neonatal effects and lactation: Segment II, Teratological study, to provide information on embryo toxicity and teratogenicity: and Segment III. perinatal and Postnatal Study, to provide information on late fetal development, labour and delivery, neonatal viability, and growth and lactation. The classic guideline is still used to this day with only monor modification throughout the world. In the present review, the principles and methods of reproductive toxicity studies are discussed with special attention given to scientific issues.

• Toxicological Research
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• 제12권2호
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• pp.203-211
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• 1996

Methanol has been widely used as an industrial solvent and environmental exposure to methanol would be expected to be increasing. In humans, methanol causes metabolic acidosis and damage to ocular system, and can lead to death in severe and untreated case. Clinical symptoms are attributed to accumulation of forrnic acid which is a metabolic product of methanol. In humans and primates, formic acid is accumulated after methanol intake but not in rodents due to the rapid metabolism of methanol. Neverthless, the developmental and reproductive toxicity were reported in rodents. Previous reports showed that perinatal exposure to ethanol produces a variety of damage in human central nervous system by direct neurotoxicity. This suggests that the mechanism of toxic symptoms by methanol in rodents might mimic that of ethanol in human. In the present study I hypothesized that methanol can also induce toxicity in neuronal cells. For the study, primary culture of rat hippocampal neurons and glias were empolyed. Hippocampal cells were prepared from the embryonic day-17 fetuses and maintained up to 7 days. Effect of methanol (10, 100, 500 and 1000 mM) on neurite outgrowth and cell viability was investigated at 0, 18 and 24 hours following methanol treatment. To study the changes in proliferation of glial cells, protein content was measured at 7 days. Neuronal cell viability in culture was not altered during 0-24 hours after methanol treatment. 10 and 100 mM methanol treatment significantly enhanced neurite outgrowth between 18-24 hours. 7-day exposure to 10 or 100 mM methanol significantly increased protein contents but that to 1000 mM methanol decreased in culture. In conclusion, methanol may have a variety of effects on growing and differentiation of neurons and glial cells in hippocampus. Treatment with low concentration of methanol caused that neurite outgrowth was enhanced during 18-24 hours and the numbers of glial cell were increased for 7 days. High concentration of methanol brought about decreased protein contents. At present, the mechanism responsible for the methanol- induced enhancement of neurite outgrowth is not clear. Further studies are required to delineate the mechanism possibly by employing molecular biological techniques.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.3029-3034
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• 2015

Background: While the perinatal outcomes of active maternal smoking are well documented, results of the effects of environmental tobacco smoke (ETS) exposure during pregnancy are inconsistent. We aimed to examine the effect of ETS exposure, assessed by maternal hair nicotine levels at $35^{th}$ week of gestation, on birth weight and the risk of small for gestational age (SGA) and low birth weight (LBW). Materials and Methods: A total of 871 non-smoking healthy pregnant women were recruited by one Korean hospital between 1 October 2006 and 31 July 2007. Hair samples were collected and anthropometric questionnaires administered at $35^{th}$ week of gestation. The primary outcome was birth weight and secondary outcomes were the risk of babies being SGA and LBW. Results: Log-transformed hair nicotine concentrations were inversely related with birth weight after adjusting for confounding variables (${\beta}=-0.077$, p=0.037). After stratifying hair nicotine levels by tertiles (T1, low [0.0-0.28 ng/mg]; T2, medium [0.29-0.62 ng/mg]; and T3, high [0.63-5.99 ng/mg]), the mean birth weight in each groups were 3,342g (T1) 3,296g (T2) and 3,290 g (T3), respectively. However the difference between groups was not statistically significant by analysis of co-variance (ANCOVA) adjusting for covariates (p=0.062). In logistic regression analysis, the risk of SGA was higher in the T3 (OR=1.59, 95%CI 1.05-2.42) than in the reference group (T1), after controlling for confounding variables. The risk of low birth weight (<2,500g, LBW) was not significantly higher (OR=1.44, 95%CI 0.95-2.19), but the risk of babies being below 3,000g birth weight was increased in the T3 group (OR=1.53, 95%CI 1.00-2.36) compared with that in the T1 group. Conclusions: Maternal ETS exposure during pregnancy was inversely related with birth weight. The risk of SGA increased in the highest ETS exposure group compared with in the low exposure group. To prevent ETS exposure during pregnancy, more comprehensive tobacco control policies are needed.

• Journal of Yeungnam Medical Science
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• 제35권2호
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• pp.156-164
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• 2018

Environmental contaminants are one of the important causal factors for development of various human diseases. In particular, the perinatal period is highly vulnerable to environmental toxicants and resultant dysregulation of fetal development can cause detrimental health outcomes potentially affecting life-long health. Perfluoroalkyl compounds (PFCs), emerging environmental pollutants, are man-made organic molecules, which are widely used in diverse industries and consumer products. PFCs are non-degradable and bioaccumulate in the environment. Importantly, PFCs can be found in cord blood and breast milk as well as in the general population. Due to their physicochemical properties and potential toxicity, many studies have evaluated the health effects of PFCs. This review summarizes the epidemiological and experimental studies addressing the association of PFCs with neurotoxicity and immunotoxicity. While the relationships between PFC levels and changes in neural and immune health are not yet conclusive, accumulative studies provide evidence for positive associations between PFC levels and the incidence of attention deficit hyperactivity disorder and reduced immune response to vaccination both in children and adults. In conclusion, PFCs have the potential to affect human health linked with neurological disorders and immunosuppressive responses. However, our understanding of the molecular mechanism of the effects of PFCs on human health is still in its infancy. Therefore, along with efforts to develop methods to reduce exposure to PFCs, studies on the mode of action of these chemicals are required in the near future.

• Clinical and Experimental Pediatrics
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• 제51권2호
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• pp.170-180
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• 2008

목 적 : 몇몇 항생제가 저산소성 허혈성 뇌 손상에서 뇌 보호 효과를 가진 것으로 밝혀졌지만 아직까지 그 기전에 대해 잘 알려지지 않고 있다. 최근 아미노글루코사이드 계열의 항생제인 G418(geneticin)이 항고사에 의한 암세포 생존을 증가 시키는 것으로 알려졌으며 본 연구는 G418이 주산기 저산소성 허혈성 뇌손상에서 세포 고사를 억제함으로서 뇌 보호 효과를 나타내는지를 알아보고자 하였다. 방 법 : 임신 18일된 백서의 대뇌피질 신경세포를 배양하여 정상산소 상태군와 저산소 상태군으로 나누고, 두 군을 각각 대조군과 G418 $10{\mu}g/mL$으로 처리한 군으로 나누어서 TUNEL 분석과 caspase 3에 대한 면역조직생화학검사를 하였고, 생후 7일된 신생 백서의 좌측 총경동맥을 결찰 후 절단하고 저산소 상태를 유도하여 G418을 저산소 상태 유도 전 30분과 유도 후 30분에 복강 내로 $0.1{\mu}g/kg$ 투여하고 7일 후에 희생시켜 H&E 염색과 caspase-3에 대해 Western blot과 real-time PCR를 하였다. 결 과 : TENEL 분석상 정상산소 상태군과 저산소 상태군 모두에서 대조군보다 G418 투여군에서 통계학적으로 유의하게 고사세포가 감소되었다(P<0.01). Caspase-3에 대한 면역조직화학검사에서 저산소 손상 전에 G418을 투여한 군에서 손상 후에 투여한 군보다 Caspase-3 발현이 적게 나타났다. 저산소 손상 7일 후에 얻은 신생 백서 뇌의 육안적 관찰과 H & E 염색에서 저산소 상태군의 뇌 용적이 정상산소 상태군의 경우보다 감소된 것을 알 수 있었고, 저산소 손상 전에 G418을 투여한 군에서 손상 후에 투여한 군보다 뇌 조직의 손상이 더 적은 것을 볼 수 있었다. Bax/Bcl-2, caspase-3에 대해 Western blot과 real-time PCR 한 경우에 G418 투여한 군에서 Bax/Bcl-2 비율과 caspase-3 발현이 감소되었다. 결 론 : 주산기 저산소성 허혈성 뇌 손상에서 G418는 뇌 조직의 고사를 억제함으로서 뇌보호 효과를 나타내었다.

• Clinical and Experimental Pediatrics
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• 제50권7호
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• pp.686-693
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• 2007

목 적 : Mycophenolate mofetil (MMF)의 활성 대사산물인 (MPA는 IMPDH의 잠재적인 반응 억제제로써 새로운 면역치료제로 사용되고 있다. 이러한 MPA는 신경계에서 흥분독성 손상 후 뇌세포를 보호하고, 미세아교세포에서는 세포사멸사(apoptosis)를 유도하지만, 저산소성 허혈성 뇌질환에서 MPA의 효과는 아직 알려지지 않아, 본 연구에서 Rice-Vannucci 모델을 이용한 신생 백서의 저산소성 허혈성 뇌 손상과 저산소 상태의 태아 백서 뇌세포 배양에서 MPA의 뇌보호 효과를 알아보고자 실험하였다. 방 법 : 생후 7일된 백서의 좌측 총 경동맥을 결찰한 후 저산소 (8% $O_2$) 상태에서 2시간 노출하여, 저산소성 허혈성 뇌 손상을 유발하고 뇌 손상 전후에 MPA(10 mg/kg)를 투여하여 대조군과 비교하였다. 또한, 재태기간 18일된 태아 백서의 대뇌피질 세포를 배양하여 1% $O_2$ 배양기에서 저산소 상태로 세포손상을 유도하여 저산소군, 손상 전후 MPA 투여군($10{\mu}g/mL$)으로 나누어 정상산소군과 비교하였다. 세포사멸사와의 관련을 알아보기 위해서 Bcl-2, Bax, caspase-3 항체로 western blotting하였고 Bcl-2, Bax, caspase-3 primer를 이용하여 real-time PCR을 하였다. 결 과 : 형태학적으로 H&E 염색상 MPA를 투여한 군에서 뇌 보호 효과를 보였다. Western blotting과 real-time PCR을 이용한 저산소성 허혈성 뇌손상 동물 모델뿐만 아니라 저산소 상태로 태아 백서 뇌세포 배양 실험에서도 MPA 투여한 경우 caspase-3의 발현과 Bax/Bcl-2의 비율이 감소함을 보였다. 결 론 : 본 연구에서 MPA가 anti-apoptosis 작용을 통하여 주산기 저산소성 허혈성 뇌 손상에 뇌보호 역할을 하는 것을 알 수 있었고 향후 신생아 저산소성 허혈성 뇌병증의 치료에 임상적 적용이 가능하리라 생각된다.

• Journal of Preventive Medicine and Public Health
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• 제28권2호
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• pp.373-385
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• 1995

The association between blood lead of children and Intelligent Quotient(I.Q) was investigated in a sample of 100 boys and girls aged $6\sim8$ years from one primary school within an industrial area of Pusan. The trained undergraduates in school of public health administered an 1.0. test one by one. Parents answered a questionnaire on demographic, perinatal and socioeconomic variables. Atomic Absorbtion Spectrophotometer was used to determine blood lead levels. The geometric mean of blood lead value was $7.99{\mu}g/dl$. In total children, there was no significant relationship between blood lead level and I.Q. But in the children who were born of gestational age of less than 38 weeks, children with higher levels of blood lead performed more poorly on I.Q test with correlation coefficient from -0.68 to -0.71. But, the children who were born of gestational age of 38 weeks and more were same as total children. These results suggest that exposure to low levels of lead in the children who were born premature probably may result in impaired intelligent development. But, We think that more profound study should be performed with sufficient numbers of subjects.