• Clinical and Experimental Pediatrics
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• 제53권1호
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• pp.56-66
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• 2010

목 적 : Oseltamivir는 neuramidase inhibitor으로 인플루엔자의 치료제로 국내에서 사용하고 있지만, 약제사용으로 인한 부작용이나 효용성 및 내성에 대한 국내 연구는 미흡하여 이에 대해서 연구하고자 하였다. 방 법 : 2008년 1월부터 2008년 6월까지와 2008년 11월부터 2009년 1월까지의 두차례의 인플루엔자 유행기간 동안, 부산 성모 병원에서 독감 유사 증상 있어, 신속 항원 진단법으로 독감 진단받고 입원한 321명의 환아를 대상으로 하여, 환아들을 oseltamivir 치료군과 비치료군으로 무작위하여 전향적인 연구를 시행하였다. 치료군에서는 oseltamivir를 5일간 투여하였고, 비치료군에서는 증상 조절제만 사용하였다. 양군 모두에서 임상증상과 부작용을 관찰하였고 입원 기간 등을 조사하였고, 퇴원 4-8개월 후 전화 상담을 통하여 신경정신학적인 이상 유무를 확인하였다. 바이러스 배양 검사 및 oseltamivir에 대한 내성검사를 실시하였다. 결 과 : 두 기간 동안 본원 소아청소년과에 입원하였던 총 321명의 환아들을 분석하였고, oseltamivir 치료군은 186명, 비치료군은 135명이었다. Oseltamivir 치료군에서 비치료군에 비해 입원 당시 발병후 48시간이 경과한 환아들이 많았음에도 하기도 합병증이 현저히 적었고, 두 기간 동안 의미 있는 입원 기간 단축을 보였다(4.4일 vs. 5.0일) (P =0.000). 두 기간 동안 치료 군에서 경미한 소화기계 부작용을 보였으나 심각한 정신신경학적인 부작용을 보인 예는 없었다. 전반기 동안에는 양군 모두에서 influenza B (치료군 vs. 비치료군; 41.7% vs. 49.6%)가 가장 많이 동정 되었고, A/H3N2, A/H1N1 순으로 동정되었으며, 후반기 동안에는 치료군에서 A/H3N2가 배양된 한명의 환아를 제외하고는 양군 모두에서 A/H1N1이 동정되었다. 전반기동안 배양된 바이러스에 대한 oseltamivir 내성 검사상 치료 시작 전이나 치료 후 48-72시간 모두에서 oseltamivir에 대한 약제 내성은 발견되지 않았다. 결 론 : oseltamivir 치료군에서는 정신신경학적인 부작용을 포함한 다른 심각한 부작용 없이 입원 기간을 단축시키면서 하기도 합병증의 감소를 보이는 임상적인 효용성을 보여 소아 인플루엔자 치료에 있어 oseltamivir 치료의 효용성과 안전성을 보여주었다.

• Tuberculosis and Respiratory Diseases
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• 제48권2호
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• pp.166-179
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• 2000

연구배경: 현재 사용되고 있는 많은 항암제는 암세포의 apoptosis를 유도함으로서 암세포를 사멸시키는 것이 주된 작용 기전이다. 항암제에 의한 치료 실패의 주된 원인은 암세포의 apoptosis에 대한 내성 획득에 의한 것으로 이해되고 있다. 최근의 보고에 의하면 많은 암세포주에서 apoptosis에 대한 내성 획득에 NF-${\kappa}B$의 활성화가 중요한 역할을 한다고 알려져 있지만 일부 세포에서는 상반된 결과를 보이고 있어 apoptosis에 대한 내성 획득과 NF-${\kappa}B$의 활성화와의 관련성은 세포에 따라 차이를 보이고 있다. 본 연구에서는 비소세포폐암 세포주가 TNF-$\alpha$ 유발 apoptosis에 저항을 나타내는 기전에서 NF-${\kappa}B$의 역할을 규명하고자 하였다. 방 법: 비소세포폐암세포주인 NCI-H157 세포에 TNF-$\alpha$ cycloheximide(CHX), TNF-$\alpha$와 CHX를 각각 투여하고 24시간 후 MTT assay로 세포생존율을 평가하였고 apoptosis의 발생 유무는 PARP에 대한 Westrn 분석으로 평가하였다. Ad5LacZ와 $Ad5I{\kappa}B{\alpha}SR$를 20시간 동안 감염시킨 각각의 세포를 1, 5, 10, 20, 50 ng/ml의 TNF-$\alpha$로 24, 48시간 자극 후 MTT assay를 시행하였고, 같은 농도의 TNF-$\alpha$로 24, 48시간 자극 후 PARP에 대한 Western 분석을 시행하였다. $I{\kappa}B{\alpha}$의 분해를 억제하는 proteasome inhibitor 인 MG132를 전처치하고 TNF-$\alpha$로 24, 48 시간 자극 후 MTT assay와 PARP에 대한 Westrn 분석을 시행하였다. $Ad5I{\kappa}B{\alpha}SR$를 감염시킨 세포를 TNF-$\alpha$로 자극한 후 NF-${\kappa}B$의 활성화를 EMSA로 평가하였다. 결 과: 1. TNF-$\alpha$ 단독 투여로는 세포 생존율의 감소와 apoptosis가 관찰되지 않았고 TNF-$\alpha$와 CHX를 같이 투여하였을 때는 세포 생존율의 감소와 함께 apoptosis가 유도되었다. 2. $Ad5I{\kappa}B{\alpha}SR$의 감염으로 $I{\kappa}B{\alpha}$가 과발현된 세포와 MG132를 전처치한 세포에서 TNF-$\alpha$ 자극에 의한 NF-${\kappa}B$의 활성화가 억제되었다. 3. $Ad5I{\kappa}B{\alpha}$ SR를 감염시킨 세포와 MG132를 전처치하여 NF-${\kappa}B$의 활성을 억제한 세포에서 TNF-$\alpha$ 자극 후 세포 생존율이 감소하고 apoptosis가 유도되었다. 결 론: 비소세포폐암 세포주의 TNF-$\alpha$ 유발 apoptosis에 대한 내성은 NF-${\kappa}B$의 활성화에 의해 생성되는 새로운 단백의 발현에 의한 것으로 생각되며, NF-${\kappa}B$ 활성화의 억제로 이를 극복할 수 있을 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제40권2호
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• pp.135-146
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• 1993

연구배경 : 급성 폐동맥색전증에서의 심폐기능 장애는 폐혈관계의 물리적 폐쇄와 신경체액성 반응에 의한 이차적인 기관지 및 혈관의 수축에 의하며, 혈소판에서 유리되는 serotonin이 체액성반응의 주 매개체인 것으로 알려져 있다. Positive End Expiratory Pressure(이하 PEEP 이라 칭함) 호흡요법은 성인성 호흡곤란증후군에서는 그 효과가 입증되어 널리 이용되고 있으나 폐동맥색전증에서의 역할은 아직 알려진 바 없다. 방법 : 연구자는 5-hydroxytryptamine 2 (이하 5-HT2라 칭함) 수용체의 선별 길항제인 ketanserin과 PEEP이 폐동맥색전증의 심폐기능 장애에 미치는 영향을 관찰하고 이들이 폐동맥색전증의 치료에 이용될 수 있을지를 검정해보기위해 한국산 잡견 13마리에 자가혈병을 이용하여 급성 폐동맥색전증을 일으킨후 대조군과 ketanserin 투여군, PEEP 적용군에서 환기 및 혈류역학의 제지표를 측정하여 다음과 같은 결과를 얻었다. 결과: 1) 폐동맥색전증을 일으키는데 사용된 혈병은 체중 Kg당 0.30~0.89($0.63{\pm}0.16$)gm 이었고 세 군간에 유의한 차이가 없었으며 평균 폐동맥압은 11~18($14{\pm}2$)mmHg 에서 색전증 유발 직후 38~46($42{\pm}2$)mmHg 까지 상승하였다. 2) 혈병 투여 30분후의 변화 혈병 투여 30분후 평균 폐동맥압 및 폐혈관저항은 증가하였고 심박출량은 감소하였으며, 동맥혈 산소분압과 산소운반량 및 혼합정맥혈 산소분압은 감소하였고 생리적 단락과 동맥혈 이산화탄소분압은 증가하였으며(p<0.05) 세 군간에 유의한 차이는 없었다. 대조군은 이후 실험기간중 상기 지표에 유의한 변화가 없었다. 3) Ketanserin 투여후의 변화 Ketanserin 투여후 대조군에 비해 평균 폐동맥압과 폐혈관저항은 낮았으며 심박출량은 높았고 생리적단락은 낮았으며 동맥혈 산소분압과 산소운반량은 높았다(p<0.05). 동맥혈 이산화탄소분압은 ketanserin 투여 30분후 감소하였다(p<0.05). 평균 전신동맥압은 ketanserin 122mmHg 에서 101mmHg로 하강하였고 한시간 후에는 투여전 수준으로 상승하였으며 통계적 유의성은 없었다. 혼합정맥혈 산소분압은 대조군에 비해 높은 경향을 보였으며 통계적 유의성은 없었다. 4) PEEP 적용군에서의 변화 PEEP 적용후 동맥혈 산소분압과 폐혈관저항은 증가하였고 심박출량은 감소하였으며 생리적 단락은 감소한 반면 산소운반량은 감소하였다(p<0.05). 한편 동맥혈 이산화탄소분압은 증가하였다(p<0.05). PEEP 제거후 평균 폐동맥압과 폐혈관저항은 감소해 대조군에 비해 낮았으며, 산소운반량과 심박출량은 증가해 대조군에 비해 높았다(p<0.05). 생리적단락은 대조군에 비해 낮았고(p<0.05) 동맥혈 이산화탄소분압은 감소해 대조군과 유의한 차이는 없었다. 혼합정맥혈 산소분압은 대조군에 비해 높았다(p<0.05). 5) 혈병 투여 4시간후 혈소판은 감소하였고 백혈구는 증가하였다(p<0.05). 결론 : 이상의 결과로 5-HT2 수용체의 선별 길항제인 ketanserin은 폐동맥색전증의 치료에 유용할 것으로 생각된다. 한편 PEEP용 적용증에는 혈류역학적 제지표가 악화되었으나 제거후에는 오히려 대조군에 비해 유의하게 호전되었으므로, 폐동맥색전증의 초기에 혈류역학적 상태가 허용되면 조심스럽게 단기간 적용해볼 수 있을 것으로 생각된다.

• 한국응용과학기술학회지
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• 제35권3호
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• pp.956-962
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• 2018

Childhood obesity causes a higher risk of obesity, premature death and disability in adulthood. In addition, obese children experience an increased risk of respiratory problems, hypertension, cardiovascular disease, insulin resistance and psychological effects. This study aimed to investigate how an exercise intervention affects health-related physical fitness and inflammatory-related blood factors in obese children after. We hypothesized that there would be positive effects on serum levels of insulin-like growth factor-1 (IGF-1), connecting peptide(C-peptide) and resistin, as well as in muscle and cardiovascular-related physical capacities, after an exercise intervention in obese children. Thirty-seven obese children haveperformed health-related fitness tests and provided blood samples for the analysis of changes in circulating biomarkers, both before and after an 8-week exercise intervention, which includes stretching, aerobic exercise, resistance exercise and sports games. The results indicate that exercise training beneficially affects body compositions, especially percentage body fat and muscle mass, without influencing to body weight and height. The results of the physical fitness tests show that muscle and cardiovascular capacity were increased in obese children in response to exercise training. Simultaneously, the exercise training decreased circulating levels of C-peptide, which equated to a "large" effect size. Although there were no significant effects on the levels of IGF-1 and resistin, they show a "small" effect size. Therefore, our findings suggest that the exercise intervention have beneficial effects on body composition and physical fitness levels in obese children, whichmight be associated with the decline in circulating C-peptide.

• Clinical and Experimental Pediatrics
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• 제56권4호
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• pp.165-175
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• 2013

Purpose: There was a global increase in the prevalence of oseltamivir-resistant influenza viruses during the 2007-2008 influenza season. This study was conducted to investigate the occurrence and characteristics of oseltamivir-resistant influenza viruses during the 2007-2008 and 2008-2009 influenza seasons among patients who were treated with oseltamivir (group A) and those that did not receive oseltamivir (group B). Methods: A prospective study was conducted on 321 pediatric patients who were hospitalized because of influenza during the 2007-2008 and 2008-2009 influenza seasons. Drug resistance tests were conducted on influenza viruses isolated from 91 patients. Results: There was no significant difference between the clinical characteristics of groups A and B during both seasons. Influenza A/H1N1, isolated from both groups A and B during the 2007-2008 and 2008-2009 periods, was not resistant to zanamivir. However, phenotypic analysis of the virus revealed a high oseltamivir $IC_{50}$ range and that H275Y substitution of the neuraminidase (NA) gene and partial variation of the hemagglutinin (HA) gene did not affect its antigenicity to the HA vaccine even though group A had a shorter hospitalization duration and fewer lower respiratory tract complications than group B. In addition, there was no significant difference in the clinical manifestations between oseltamivir-susceptible and oseltamivir-resistant strains of influenza A/H1N1. Conclusion: Establishment of guidelines to efficiently treat influenza with oseltamivir, a commonly used drug for treating influenza in Korean pediatric patients, and a treatment strategy with a new therapeutic agent is required.

• 한국동물위생학회지
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• 제42권1호
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• pp.1-7
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• 2019

Porcine reproductive and respiratory syndrome (PRRS) is economically the most important and challenging disease in swine industries worldwide and caused by PRRS virus (PRRSV). Previous studies reported that pigs with heterozygous genotypes in the guanylate-binding proteins (GBP1 and GBP5) exhibited increased resistance against PRRSV infection. The present study was conducted to produce higher numbers of the heterozygous pigs based on the PRRS resistant polymorphisms found in GBP1 (GBP1E2 and WUR) and GBP5, and evaluate the resistance of heterozygous pigs against challenge with a type 2 PRRSV (JA142) in comparison with homozygous pigs. In the challenge study, 12, 4 week-old PRRSV-negative piglets were selected based on the genotypes of the 3 polymorphisms (GBP1E2, WUR and GBP5). Among them, 8 piglets [homozygous (n=4) and heterozygous (n=4)] were challenged with JA142 and kept in the same room, and the remaining 4 piglets were kept separately as a negative control. In results, the sperms collected from the boars of GBP1E2-GG genotype produced approximately 28~41% higher numbers of heterozygous piglets as compared with those from the boars of GBP1E2-AG genotype. In the challenge study, we found that heterozygous piglets showed the significantly lower levels of viremia than homozygous piglets at 14, 21 and 28 dpc. Consistently, these heterozygous piglets also exhibited significantly higher ADWG than homozygous piglets. Therefore, in the current study, selection of boars based on SNP markers could increase the production of PRRS resistant piglets and the PRRS resistant pigs were found to be more resistant to PRRSV infection.

• Asian-Australasian Journal of Animal Sciences
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• 제33권5호
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• pp.848-855
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• 2020

Objective: Shearing is one of the practices that is applied periodically to fiber producing animals, which can also alter resistance of animals to high temperatures in especially summer months. This study aimed to investigate effects of shearing on some physiological and hormonal parameters in Akkaraman sheep during summer season. Methods: This study was carried out on 39 non-pregnant Akkaraman ewes (aged 1.5 years at the beginning of experiment). The 39 ewes were chosen randomly from the flock belonging to the Erciyes University and they were assigned to two groups as follows: i) group A (n = 20) designed as the control group, they were shorn and group B (n = 19) designed as the experimental group, they were unshorn. Prior to the shearing (-1 day) and on days 1, 7, 15, 30, 45, 60, 75, and 90 following the shearing, blood samples were taken from the vena jugularis of each sheep. Cortisol, β-endorphin, growth hormone (GH), thyroxine (T₄), triiodothyronine (T₃), and heat shock protein 70 (HSP-70) concentrations were determined using the enzyme immunoassay method. Body weight (BW), rectal temperature (RT), pulse rate (PR), and respiratory rate (RR) of each sheep were recorded at the same time. The data obtained were analyzed using two-way repeated measures analysis of variance. Results: Statistical analysis showed a significant effect of shearing×period interaction (p<0.01) and a significant effect of period (p<0.01) on BW, HSP-70, cortisol, T₄ and RT, PR, GH, β-endorphin, T₃, respectively. Also these analysis showed no significant effect of shearing×period interaction or period on RR. Conclusion: The results showed that the thermoregulation abilities of sheep were affected by shearing treatment and the shorn ewes were less affected by heat stress. In conclusion, based on the data of this study, shearing can be considered as a necessary management practice that requires protection for sheep from the effect of heat stress.

• Journal of Microbiology and Biotechnology
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• 제30권2호
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• pp.172-177
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• 2020

Influenza viruses cause respiratory diseases in humans and animals with high morbidity and mortality rates. Conventional anti-influenza drugs are reported to exert side effects and newly emerging viral strains tend to develop resistance to these commonly used agents. Fritillaria thunbergii (FT) is traditionally used as an expectorant for controlling airway inflammatory disorders. Here, we evaluated the therapeutic effects of FT extracts against influenza virus type A (H1N1) infection in vitro, in ovo, and in vivo. In the post-treatment assay, FT extracts showed high CC50 (7,500 ㎍/ml), indicating low toxicity, and exerted moderate antiviral effects compared to oseltamivir (SI 50.6 vs. 222) in vitro. Antiviral activity tests in ovo revealed strong inhibitory effects of both FT extract and oseltamivir against H1N1 replication in embryonated eggs. Notably, at a treatment concentration of 150 mg/kg, only half the group administered oseltamivir survived whereas the FT group showed 100% survival, clearly demonstrating the low toxicity of FT extracts. Consistent with these findings, FT-administered mice showed a higher survival rate with lower body weight reduction relative to the oseltamivir group upon treatment 24 h after viral infection. Our collective results suggest that FT extracts exert antiviral effects against influenza H1N1 virus without inducing toxicity in vitro, in ovo or in vivo, thereby supporting the potential utility of FT extract as a novel candidate therapeutic drug or supplement against influenza.

• Asian-Australasian Journal of Animal Sciences
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• 제28권9호
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• pp.1354-1361
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• 2015

The complement system is a part of the natural immune regulation mechanism against invading pathogens. Complement activation from three different pathways (classical, lectin, and alternative) leads to the formation of C5-convertase, an enzyme for cleavage of C5 into C5a and C5b, followed by C6, C7, C8, and C9 in membrane attack complex. The C9 is the last complement component of the terminal lytic pathway, which plays an important role in lysis of the target cells depending on its self-polymerization to form transmembrane channels. To address the association of C9 with traits related to disease resistance, the complete porcine C9 cDNA was comparatively sequenced to detect single nucleotide polymorphisms (SNPs) in pigs of the breeds Hampshire (HS), Duroc (DU), Berlin miniature pig (BMP), German Landrace (LR), Pietrain (PIE), and Muong Khuong (Vietnamese potbelly pig). Genotyping was performed in 417 $F_2$ animals of a resource population (DUMI: $DU{\times}BMP$) that were vaccinated with Mycoplasma hyopneumoniae, Aujeszky diseases virus and porcine respiratory and reproductive syndrome virus at 6, 14 and 16 weeks of age, respectively. Two SNPs were detected within the third exon. One of them has an amino acid substitution. The European porcine breeds (LR and PIE) show higher allele frequency of these SNPs than Vietnamese porcine breed (MK). Association of the substitution SNP with hemolytic complement activity indicated statistically significant differences between genotypes in the classical pathway but not in the alternative pathway. The interactions between eight time points of measurement of complement activity before and after vaccinations and genotypes were significantly different. The difference in hemolytic complement activity in the both pathways depends on genotype, kind of vaccine, age and the interaction to the other complement components. These results promote the porcine C9 (pC9) as a candidate gene to improve general animal health in the future.

• Journal of Microbiology and Biotechnology
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• 제28권9호
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• pp.1433-1442
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• 2018

To identify and quantify the effects of a combination of dietary $1{\times}10^8CFU/g$ Lactococcus lactis subsp. lactis I2 ($LI_2$) and 0.1% ${\beta}$-glucooligosaccharides (BGO) on the growth and immunity of olive flounder (Paralichthys olivaceus), a feeding experiment was conducted. Flounder ($14{\pm}0.5g$) were divided into two groups and fed control and synbiotic feeds for 8 weeks. Investigations were carried out on growth and feed utilization, innate immunity, serum biochemical parameters, intestinal lactic acid bacterial (LAB) viability, microvillus length, and changes in the expression levels of genes encoding pro-inflammatory cytokines (tumor necrosis factor $[TNF]-{\alpha}$, interleukin $[IL]-1{\beta}$, and IL-6). Results demonstrated the synbiotic diet had significantly better (p < 0.05) responses in terms of weight gain and specific growth rate, three innate immune parameters (respiratory burst, serum lysozyme, and superoxide dismutase), intestinal LAB viability, and the relative $TNF-{\alpha}$ expression level (p < 0.05). Moreover, after challenge with Streptococcus iniae ($1{\times}10^8CFU/ml$), the synbiotically fed group exhibited significantly higher (p < 0.05) protection against streptococcosis, validating the observed changes in immune parameters and induction of the cytokine-encoding gene. Therefore, according to the results of the present study, synbiotic feed ($LI_2+BGO$) increased growth, modulated innate immune parameters and protected olive flounder against streptococcosis.