• 한국발생생물학회지:발생과생식
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• 제20권3호
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• pp.187-196
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• 2016

The objective of the current study was to determine acute plasma stress responses in two size groups of juvenile Epinephelus akaara (average body weight: $8.4{\pm}2.1$ and $3.3{\pm}0.6g$; 150 and 120 days after hatch, respectively) exposed to abrupt salinity drops (from 34 practical salinity unit, PSU seawater to 18, 10 PSU (experiment 1) or 26, 18, 10 PSU (experiment 2), respectively). Plasma glucose, glutamic oxalate transaminase, glutamic pyruvate transaminase, red blood cell counts, and gill histology were determined during 72 h exposure. Significantly increased plasma glucose, glutamic oxalate transaminase levels, and red blood cell counts were observed in fish exposed to 18 or 10 PSU. Histological changes, such as hyperplasia and lifting of epithelium in the gill secondary lamellae, were also observed in fish exposed to 18 or 10 PSU at 72 h post-drop. E. akaara exposed to sudden salinity drops to 18 or 10 PSU still seems to undergo the primary adjustment phase before fish reaches a new homeostasis, whereas fish exposed to 26 PSU seems to mount osmotic changes. Therefore, the no observed adverse effect levels for 72 h acute salinity challenge was 26 PSU in our study, and salinity drop to 18 PSU and below can possibly cause acute adverse effect, in which fish could be vulnerable to additional stresses such as a temperature changes or handling stress.

• Molecular & Cellular Toxicology
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• 제2권1호
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• pp.48-53
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• 2006

[ ${\alpha}-Naphthylisothiocyanate$ ] (ANIT) induces intrahepatic cholestasis, involving damage to biliary epitheial cells. This study investigates hepatic gene expression and histopathological alterations in response to ANIT treatment in order to elucidate early time response of ANIT-induced hepatotoxicity. ANIT was treated with single dose (3, 6, and 60 mg/kg) in corn oil by oral gavage. Serum biochemical and histopathological observation were performed for evaluation of hepatotoxicity level. Affymetrix oligo DNA chips were used for gene expression profile by ANIT-induced hetpatoxicity. Hepatic enzyme levels (ALT, AST, and ALP) were increased in 24 hr high dose group. In microscopic observations, moderate hepatocellular necrosis, were confirmed 24 hr high dose groups. We found that gene expression patterns were dependent on time and dose. Our selected genes were related inflammation and immunomodulation. In this study, ANIT-induced hepatotoxicity was involved in acute phase responses and provides evidence for role of neutrophil could be mechanism associated with ANIT-mediated hepatotoxicity.

• 대한약침학회지
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• 제9권2호
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• pp.113-127
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• 2006

Objectives : We review a result of studies until the present and suggest the method of medical treatment for the clinical treatment of Scolopendrid Herbalacupuncture. Methods : We analysis the paper of the bibliographic studies, the experiment studies and the clinical studies from 2001 developed Scolopendrid Herbalacupuncture and grope for the course of studies. Results : 1. Scolopendrid Herbalacupuncture is proved the clinical safety by the aninmal and human tests. 2. The pharmacological action of Scolopendra subspinipes mutilans L. Koch is anti-convulsive action, analgesic action, lowering blood pressure, anti-inflammatory action, anti-tumor action and microbe inhibition 3. Scolopendrid Herbalacupuncture has been a fine effect to the entrapment neuropathy and inflammatory. 4. Scolopendrid Herbalacupuncture was thought effective on a acute phase and to the excessive symptoms. The Sub-chronic toxicity experiment observing the response after hypodermic medication over 90 days, The Genetic-mutagenic toxity experiment and the clinical effect studies are necessary.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.63-67
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• 2016

Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose ($1{\times}10^6cells/kg$), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.

• Journal of Animal Science and Technology
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• 제49권2호
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• pp.213-224
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• 2007

급성기 반응중인 가금의 비장세포와 PBMC 증식도를 alamar blue(alamar blue) 환원량으로 측정하기 위한 조건들을 조사하였다. 갓 부화한 육계병아리(Ross 종) 수컷에 기초사료를 급여하고, 9, 11 및 13일령에 각각 복강내 LPS를 주입으로 급성기 반응중인 14일령 육계병아리의 혈액에서 PBMC와 비장에서 비장세포를 분리하였다. alamar blue 환원량은 비장세포에서는 4, 24, 48, 96 및 120시간, PBMC는 4, 8, 12, 24 및 48시간에 그리고 웰당 103, 104 및 105개로 분배하고, 배양액 ml 당 0.0, 1.0, 5.0 및 10.0㎍의 Con A를 첨가하며, 배양액 중 2.5%의 자가혈청과 FBS를 첨가하여 측정하였다. 1.alamar blue 환원량은 배양시간의 경과(R2=0.825~1.000)에 따라 그리고, 세포수(R2= 0.999)의 증가에 따라 직선적으로 증가하였다.2. 급성기 반응중인 병아리에서, alamar blue 환원량은 대조구에 비해 비장세포는 24시간이후, PBMC는 4시간이후부터 105개의 세포접종시 유의하게(p<0.05) 높았다.3.급성기 반응중인 병아리의 비장세포와 PBMC에서 alamar blue 환원량은 Con A 농도에 관계없이 대조구에 비해 높았으며, 배양액 ml 당 Con A 1.0 또는 5.0 ㎍ 첨가에 비해 10.0㎍ 첨가시 유의하게(p<0.05) 높았다.4. 그리고, 배양액중 2.5%의 자가혈청은 급성기 반응과 관계없이 FBS에 비해 alamar blue 환원량을 유의하게 높였다. 본 연구는 alamar blue 환원량 평가에 의한 급성기 반응중인 가금의 비장세포와 PBMC의 증식도 측정에는 alamar blue 첨가 후 PBMC는 4시간, 비장세포는 24시간 배양, 세포수는 웰 당 105개, 그리고, Con A는 배양액 ml 당 10.0 ㎍이 적당하다는 것을 나타낸다.

• 생명과학회지
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• 제19권2호
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• pp.284-288
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• 2009

선천성 면역은 숙주의 물리적 방어벽을 뚫고 침입하는 감염성 질병 원인균에 대항하는 첫 번째 방어로서 아주 중요한 역할을 한다. Mannose-binding lectin (MBL 또는 mannan-binding protein, MBP)은 혈청 내에 존재하는 면역성 단백질로서 감염 후 즉시 유발되는 acute phase response의 특정 단백질이다. MBL 단백질은 세균, 바이러스, 곰팡이, 기생충 등의 탄수화합물 구조에 결합하여 식균 작용을 돕거나 보체경로를 활성화 시킨다. MBL 단백질은 C-말단이 탄수화물을 인식하는 도메인이며, 연결 목 부위와 콜라겐 부위로 구성되어 있다. 혈청 내의 MBL 농도가 낮으면 높은 빈도로 면역결핍현상이 관찰된다고 알려져 있다. MBL 단백질의 기능과 유전에 대해 많은 연구가 되어져 왔으나 아직 MBL 단백질 복합체 등에 대한 연구는 많이 이루어져 있지 않다. 따라서 MBL 연구에 필수적인 MBL cDNA 제조와 재조합 단백질의 합성, 그리고 재조합 단백질을 항원으로 사용하여 polyclonal antibody를 생산한 연구 결과를 보고하는 바이다. 본 연구결과로 획득한 MBL cDNA, 재조합 단백질과 anti-MBL 항체는 앞으로의 MBL 연구에 절대적으로 필요한 도구가 될 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1999-2006
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• 2016

Background: Acute promyelocytic leukemia (APML) is characterized by the reciprocal translocation t(15;17) (p22;p12) resulting in the PML-$RAR{\alpha}$ fusion gene. A dual diagnostic and follow up approach was applied including cytogenetic demonstration of the t(15;17) translocation and detection dg PML-$RAR{\alpha}$ chimeric transcripts by molecular means. Purpose: Conventional cytogenetics involving bone marrow is beset with high probability of poor metaphase index and was substituted with phytohemagglutinin (PHA)-induced peripheral blood culture based cytogenetic analysis as a diagnostic & follow up modality in APML patients of Kashmir (North India). Both qualitative (RT-PCR) and quantitative (Q-PCR) tests were simultaneously carried out to authenticte the modified cytogenetics. Materials and Method: Patient samples were subjected to the said techniques to establish their baseline as well as follow-up status. Results: Initial cytogenetics revealed 30 patients (81%) Positive for t(15;17) whereas 7 (19%) had either cryptic translocation or were negative for t(15;17). Two cases had chromosome 16q deletion and no hallmark translocation t(15;17). Q-PCR status for PML-$RAR{\alpha}$ was found to be positive for all patients. All the APML patients were reassessed at the end of consolidation phase and during maintenance phase of chemotherapy where 6 patients had molecular relapse, wherein 4 also demonstrated cytogenetic relapse. Conclusions: It was found that PHA-induced peripheral blood cytogenetics along with molecular analysis could prove a reliable modality in the diagnosis and assessment of follow up response of APML patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9961-9966
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• 2014

Background: Some reports have suggested that chronic myeloid leukemia (CML) patients have a higher prevalence of M-bcr than acute lymphoblastic leukemia (ALL) patients, which show a higher prevalence of m-bcr. However, the relationship between BCR-ABL subtypes and progression of CML and ALL remains unclear. Materials and Methods: 354 CML chronic phase (CML-CP) patients, 26 CML blastic phase (CML-BP) patients and 72 ALL patients before treatment with BCR-ABL positive were recruited for blood routine examination and bone marrow smear cytology. Some 80 CML-CP and 32 ALL patients after imatinib (IM) treatment were followed-up for BCR-ABL relative concentrations detected after treatment for 3, 6 and 9 months and 1 year. Results: Before treatment, CML-CP patients showed lower BCR-ABL relative concentrations with a higher proportion of M-bcr (42.7%) compared to CML-BP and ALL patients while ALL patients had a higher BCR-ABL relative concentration with high expression of m-bcr (51.4%). Patients with M-bcr demonstrated higher WBC counts than those with m-bcr and the mixed group and higher PLT counts were noted in the CML-CP and ALL groups. After imatinib (IM) treatment, patients with m-bcr showed higher BCR-ABL relative concentrations in both CML-CP and ALL groups. Conclusions: This study identified the BCR-ABL gene as an important factor in CML and ALL cases. The M-bcr subtype was associated more with CML while the m-bcr subtype was associated more with ALL. Patients with m-bcr seem to have a poorer response to IM in either CML or ALL patients compared to M-bcr patients.

• Archives of Pharmacal Research
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• 제29권10호
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• pp.911-920
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• 2006

Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

• The Korean Journal of Pain
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• 제23권4호
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• pp.236-241
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• 2010

Background: Selective inhibitors of cycloosygenase (COX)-2 are commonly used analgesics in various pain conditions. Although their actions are largely thought to be mediated by the blockade of prostaglandin (PG) biosynthesis, evidences suggesting endogenous opioid peptide link in spinal antinociception of COX inhibitor have been reported. We investigated the roles of opioid receptor subtypes in the spinal antionociception of selective COX-2 inhibitor. Methods: To examine the antionociception of a selective COX-2 inhibitor, DUP-697 was delivered through an intrathecal catheter, 10 minutes before the formalin test in male Sprague-Dawley rats. Then, the effect of intrathecal pretreatment with CTOP, naltrindole and GNTI, which are ${\mu}$, $\delta$, and k opioid receptor antagonist, respectively, on the analgesia induced by DUP-697 was assessed. Results: Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2 Naltrindole and GNTI attenuated the antinociceptive effect of intrathecal DUP-697 during both phases of the formalin test, CTOP reversed the antinociception of DUP-697 during phase 2, but not during phase 1, Conclusions: Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. The $\delta$ and $\kappa$ opioid receptors are involved in the activity of COX-2 inhibitor on the facilitated state as well as acute pain at the spinal level, whereas the ${\mu}$ opioid receptor is related only to facilitated pain.