Behavioral cross-sensitization between cocaine and ethanol is accompanied by parallel changes in the activity of AMPK system

Xu, Shijie,Kang, Ung Gu Elsevier 2019 Pharmacology, biochemistry, and behavior Vol.183 No.-

<P><B>Abstract</B></P> <P>Behavioral sensitization is thought to be relevant to the psychopathology of drug addiction. A previous study from our research group demonstrated cross-sensitization between cocaine and ethanol. Although these findings suggest a common mechanism of action between these two drugs, little is known about the molecular or cellular aspects of this commonality. The AMPK pathway functions as an intracellular energy sensor and plays a critical role in maintaining cellular energy homeostasis. Thus, the present study examined AMPK signaling following reciprocal cross-sensitization between cocaine and ethanol in the rat prefrontal cortex and dorsal striatum. Male Sprague–Dawley rats were repeatedly treated with either cocaine (15 mg/kg, 5 times) or ethanol (0.5 g/kg, 15 times) and then challenged reciprocally with the other drug. When sensitized to either cocaine or ethanol, the phosphorylation in response to additional challenges with the same drug was enhanced, indicating the development of sensitization. However, responses to the cocaine challenge were enhanced in the ethanol-sensitized state, whereas the responses to the ethanol challenge were not apparently enhanced in the cocaine-sensitized state. This was likely due to the ceiling effect of cocaine sensitization, which suggested that cocaine had more robust effects than ethanol. Although the same changes were found for two upstream kinases of AMPK (LKB1 and CaMK4), TAK1 responded differently and was not affected by acute challenges from either cocaine or ethanol. In the prefrontal cortex, there was an increase in activity, whereas there was a decrease in activity in the dorsal striatum. This difference might be due to dopamine D<SUB>1</SUB> receptor dominance in the prefrontal cortex and D<SUB>2</SUB> receptor dominance in the dorsal striatum. Taken together, these results suggest that both cocaine and ethanol may share overlapping molecular pathways in the process of behavioral sensitization. However, the action of cocaine was stronger than that of ethanol.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cross-sensitization occurred between cocaine and ethanol in terms of AMPK and upstream kinase phosphorylations as well as locomotor activity. </LI> <LI> The sensitizing effect of cocaine was more powerful than that of ethanol. </LI> <LI> Cross-sensitization between ethanol and cocaine in the AMPK system suggests that these drugs of dependence may have a common underlying signaling pathway. </LI> </UL> </P>

Determinants of sensitization to allergen in infants and young children

Kim, Hyeong Yun,Shin, Youn Ho,Han, Man Yong The Korean Pediatric Society 2014 Clinical and Experimental Pediatrics (CEP) Vol.57 No.5

Atopic sensitization is a complex phenomenon that changes dynamically with age throughout childhood; its prevalence increases with age in young children. Additionally, with increasing age, the prevalence of sensitization to inhalant allergens and the prevalence of polysensitization to allergens increase. It is also well established that the development of atopic sensitization is the result of a complex interplay of genetic and environmental factors. However, there is considerable heterogeneity in the literature in terms of the effect of different environmental exposures in young children on the subsequent risk of atopic sensitization and allergic diseases. Previous studies on the relationship, in early life, between pet ownership, sex, exposure to secondhand smoke, exposure to traffic-related air pollution components, and atopic sensitization have yielded different results. Recent studies have highlighted the importance of gene-environment interactions, especially during early childhood, on the risk of subsequent atopic sensitization and allergic diseases. Therefore, pediatricians should consider the genetic and environmental determinants of atopic sensitization in infants and young children when diagnosing and treating patients with allergic diseases. Determining ways in which early exposure to these risk factors in young children may be reduced could be beneficial in preventing the likelihood of developing atopic sensitization.

International regulatory requirements for skin sensitization testing

Daniel, Amber B.,Strickland, Judy,Allen, David,Casati, Silvia,Zuang, Valé,rie,Barroso, Joã,o,Whelan, Maurice,Ré,gimbald-Krnel, M.J.,Kojima, Hajime,Nishikawa, Akiyoshi,Park, Hye-Kyung Elsevier 2018 Regulatory toxicology and pharmacology Vol.95 No.-

<P><B>Abstract</B></P> <P>Skin sensitization test data are required or considered by chemical regulation authorities around the world. These data are used to develop product hazard labeling for the protection of consumers or workers and to assess risks from exposure to skin-sensitizing chemicals. To identify opportunities for regulatory uses of non-animal replacements for skin sensitization tests, the needs and uses for skin sensitization test data must first be clarified. Thus, we reviewed skin sensitization testing requirements for seven countries or regions that are represented in the International Cooperation on Alternative Test Methods (ICATM). We noted the type of skin sensitization data required for each chemical sector and whether these data were used in a hazard classification, potency classification, or risk assessment context; the preferred tests; and whether alternative non-animal tests were acceptable. An understanding of national and regional regulatory requirements for skin sensitization testing will inform the development of ICATM's international strategy for the acceptance and implementation of non-animal alternatives to assess the health hazards and risks associated with potential skin sensitizers.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We reviewed regulatory requirements for skin sensitization testing, by chemical sector, of seven countries or regions. </LI> <LI> This review summarizes data needs for hazard classification, potency classification, and risk assessment. </LI> <LI> We identify preferred test methods and note whether non-animal alternative test methods are acceptable. </LI> <LI> This effort will inform an international strategy for implementing non-animal approaches for skin sensitization assessment. </LI> </UL> </P>

정읍시골, 정읍시, 서울시에서의 실내 항원감작과 인구 통계학적 특징의 관련성

정현희 ( Hyun Hee Jung ),권지원 ( Ji Won Kwon ),이소연 ( So Yeon Lee ),서주희 ( Ju Hee Seo ),송영화 ( Young Hwa Song ),김병주 ( Byoung Ju Kim ),김효빈 ( Hyo Bin Kim ),유진호 ( Jin Ho Yu ),홍수종 ( Soo Jong Hong ),박강서 ( Kang Seo 대한천식알레르기학회 2010 천식 및 알레르기 Vol.30 No.4

Background: The prevalence of allergic disease is increasing across the world. The development of allergic disease is associated with allergen sensitization. Objective: We investigated regional differences of allergen sensitization and relations between demographic characteristics and allergen sensitization among Jeongeup Countyside, Jeongeup City and Seoul City in Korea. Method: We conducted a cross-sectional survey of 1,792 children aged 9∼12 years from Jeongeup Countyside, Jeongeup City and Seoul City in Korea. A questionnaire and skin prick test for 16 common allergens were performed. Result: Participants from Jeongeup Countryside and City had more pets or livestock, siblings and breast feeding than those from Seoul City. A higher body mass index and a more frequent history of antibiotic therapy during infancy and parental allergy were found in Seoul City. The rate of sensitization to more than one allergens was higher in Seoul City than Jeongeup Countyside and City. The sensitization rate to cockroach was higher in Jeongeup Countyside and City than in Seoul City. The sensitization rate to Alternaria had a tendency to decrease with urbanization. The sensitization rate to house dust mite and cat were higher in Seoul City than in Jeongeup Countyside and City. Conclusion: The rate and type of allergen sensitization may differ among regions, which may be due to environmental or habitual factors. Therefore, allergen sensitization can be reduced by controlling these factors. (Korean J Asthma Allergy Clin Immunol 2010;30:277-284)

호흡기알레르기질환을 가진 소아청소년에서 알레르기 항원 감작의 변화 분석

조소원,전소영,이혜선,김하민,노윤영,박미르,정재화,김수연,김종덕,김민정,이용주,김경원,손명현,김윤희 대한 소아알레르기 호흡기학회 2023 Allergy Asthma & Respiratory Disease Vol.11 No.1

Purpose: There is a lack of a report about the trajectories of allergen sensitization, although it is important to understand the change of allergen sensitization to manage allergic disease. This study aimed to analyze the change and trajectories of allergen sensitization in children with respiratory and allergic diseases. Methods: From 2006 to 2020, children with respiratory and allergic diseases or screened for allergic sensitization were evaluated. We visualized the alterations and the trajectories of allergen sensitization using stacked area graphs, box plots, and Sankey diagrams. Results: A total of 2,804 subjects were included, and allergic rhino-conjunctivitis was diagnosed in 1,931 children (68.9%). The mean age for the first test was 4.1 years, and that for the second test was 6.5 years. Children sensitized to class 1 food allergen before age 5 showed sensitizations more for other allergens and at a younger age after age 5 than children who were not. The atopic tendency continued once it had been obtained before the early school age in the persistence or the new development of sensitization. Conclusion: Allergen sensitization has changed over time and has shown different patterns according to age. Its trajectory has taken a wide variety of courses in children with respiratory and allergic diseases until the early school age. These changes reflect the allergic diseases and socio-environmental characteristics of children and adolescents. .

단일 기관에서 경험한 소아 아토피피부염 환자의 감작 분포

송아리 ( Ari Song ),이지영 ( Ji Young Lee ),양혜경 ( Hea-kyoung Yang ),김민지 ( Minji Kim ),안강모 ( Kangmo Ahn ),이상일 ( Sang-il Lee ),김지현 ( Jihyun Kim ) 대한천식알레르기학회(구 대한알레르기학회) 2016 Allergy Asthma & Respiratory Disease Vol.4 No.4

Purpose: There are few recent data regarding allergic sensitization of atopic dermatitis (AD) in Korea. The aim of this study was to investigate patterns of sensitization according to age and gender in children with AD.Methods: This retrospective study included 4,661 children with AD from 1998 to 2014. The serum specific IgE (sIgE) levels to egg white (EW), cow’s milk (CM), peanut, wheat, soybean, buckwheat, tree nuts, crustaceans, meat, and house dust mites (HDMs) were reviewed. AD was categorized into the extrinsic (ADe) and intrinsic type (ADi) according to the presence or absence of sensitization. The proportion of patients with sIgE to EW or CM greater than the previously reported diagnostic decision point (DDP) was determined.Results: A total of 4,661 children (2,843 boys and 1,818 girls) were collected. We identified 1,857 of 2,663 children (69.7%) with the ADe type and 806 of 2,663 children (30.3%) with the ADi type. The sensitization rates increased with age (P<0.001). EW (59.3%) was the most commonly sensitized food, followed by CM (46.6%), peanut (32.2%), wheat (31.5%), soybean (28.1%), and buckwheat (23.7%). The most commonly sensitized food groups were tree nuts (56.7%) and crustaceans (28.3%). The rate of sensitization to HDMs was 40.1%. In addition, 11.1% and 7.5% of children had levels of sIgE to EW and CM, respectively, higher than the DDP.Conclusion: The incidence of ADe among children with AD was 69.7% and increased with age. The most commonly sensitized food allergen was EW, followed by CM and peanut. (Allergy Asthma Respir Dis 2016:4:290-295)

THP-1 세포주를 이용한 화장품 원료의 피부 감작성 대체법 활용 연구

김서영 ( Seo Young Kim ),안수선 ( Su Sun An ),김한곤 ( Han Kon Kim ),이태룡 ( Tae Ryong Lee ) 한국동물실험대체법학회 2009 동물실험대체법학회지 Vol.3 No.1

Evaluation of skin sensitization potential is a major part of safety assessment of new ingredients in cosmetics and drugs to be applied topically. Several studies have shown that contact sensitizers induce co-stimulatory molecules on THP-l cells and have suggested that the expression of these co-stimulatory molecules can be used as a predictive in vitro assay system for contact sensitization. Most cosmetic ingredients are non- or slight- or at most moderate sensitizers. In this study, we evaluated the utility of the expression of co-stimulatory molecules on THP-l cells as a predictive in vitro assay system for discrimination of these slight differences in sensitizing potential of cosmetic ingredients. We investigated the expression of CD54 and/or CD86 on the THP-l cells using flow cytometry after a 24 h exposure to cosmetic ingredients such as resveratrol, polydatin (a derivative of resveratrol), and decursin with two different purities (70% and 98%). The resveratrol showed a mild skin sensitization potential and cell cytotoxicity but the polydatin did not induce any up-regulation of these two markers and did not show cell cytotoxicity at the same concentration with resveratrol. Although both decursins with 70% and 98% purities were classified as mild sensitizers, there was also a definite trend that the decursin with 98% purity was less potent sensitizer than the decursin with 70% purity. These data suggested the possibility of using expression of CD54 and/or CD86 in THP-l cell line as a predictive tool evaluating subtle differences in skin sensitization potential of cosmetic ingredients.

THP-1 세포주를 이용한 화장품 원료의 피부 감작성 대체법 활용 연구

김서영 ( Seo Young Kim ),안수선 ( Su Sun An ),김한곤 ( Han Kon Kim ),이태룡 ( Tae Ryong Lee ) 한국동물실험대체법학회 2009 동물실험대체법학회지 Vol.3 No.1

Evaluation of skin sensitization potential is a major part of safety assessment of new ingredients in cosmetics and drugs to be applied topically. Several studies have shown that contact sensitizers induce co-stimulatory molecules on THP-l cells and have suggested that the expression of these co-stimulatory molecules can be used as a predictive in vitro assay system for contact sensitization. Most cosmetic ingredients are non- or slight- or at most moderate sensitizers. In this study, we evaluated the utility of the expression of co-stimulatory molecules on THP-l cells as a predictive in vitro assay system for discrimination of these slight differences in sensitizing potential of cosmetic ingredients. We investigated the expression of CD54 and/or CD86 on the THP-l cells using flow cytometry after a 24 h exposure to cosmetic ingredients such as resveratrol, polydatin (a derivative of resveratrol), and decursin with two different purities (70% and 98%). The resveratrol showed a mild skin sensitization potential and cell cytotoxicity but the polydatin did not induce any up-regulation of these two markers and did not show cell cytotoxicity at the same concentration with resveratrol. Although both decursins with 70% and 98% purities were classified as mild sensitizers, there was also a definite trend that the decursin with 98% purity was less potent sensitizer than the decursin with 70% purity. These data suggested the possibility of using expression of CD54 and/or CD86 in THP-l cell line as a predictive tool evaluating subtle differences in skin sensitization potential of cosmetic ingredients.

Determinants of sensitization to allergen in infants and young children

김형윤,신윤호,한만용 대한소아청소년과학회 2014 Clinical and Experimental Pediatrics (CEP) Vol.57 No.5

Atopic sensitization is a complex phenomenon that changes dynamically with age throughout childhood;its prevalence increases with age in young children. Additionally, with increasing age, the prevalenceof sensitization to inhalant allergens and the prevalence of polysensitization to allergens increase. It isalso well established that the development of atopic sensitization is the result of a complex interplayof genetic and environmental factors. However, there is considerable heterogeneity in the literature interms of the effect of different environmental exposures in young children on the subsequent risk ofatopic sensitization and allergic diseases. Previous studies on the relationship, in early life, between petownership, sex, exposure to secondhand smoke, exposure to traffic-related air pollution components,and atopic sensitization have yielded different results. Recent studies have highlighted the importanceof gene-environment interactions, especially during early childhood, on the risk of subsequent atopicsensitization and allergic diseases. Therefore, pediatricians should consider the genetic and environmentaldeterminants of atopic sensitization in infants and young children when diagnosing and treatingpatients with allergic diseases. Determining ways in which early exposure to these risk factors in youngchildren may be reduced could be beneficial in preventing the likelihood of developing atopic sensitization.

Flow cytometric evaluation of the potential of metal oxide nanoparticles for skin sensitization using 5-Bromo-2-deoxyuridine

Lee Dong Han,Kim Sung-Hyun,Lee Jin Hee,Yang Jun-Young,Seok Ji-Hyun,Jung Kikyung,Lee Jong Kwon 한국독성학회 2021 Toxicological Research Vol.37 No.3

Although skin sensitization potential of various chemicals has been extensively studied, there are only a few reports on nanoparticles induced skin sensitization. Aiming to fill this lacuna, in this study we evaluated the potential of metal oxide nanoparticles (NPs) to induce skin sensitization with flow cytometry. Seven different metal oxide NPs, including copper oxide, cobalt oxide, nickel oxide, titanium oxide, cerium oxide, iron oxide, and zinc oxide were applied to Balb/c mice. After selecting the proper vehicle, the NPs were applied, and the skin sensitization potential were assessed using 5-bromo- 2-deoxyuridine with flow cytometry. Physiochemical properties such as hydrodynamic size, polydispersity, and zeta potential were measured for the NPs prior to the tests. All the seven metal oxide NPs studied showed negative responses for skin sensitization potential. These results suggest that the OECD TG 442B using 5-bromo-2-deoxyuridine with flow cytometry can be applied to evaluate the potential of NPs for skin sensitization.