• Journal of Animal Science and Technology
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• 제57권11호
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• pp.40.1-40.7
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• 2015

Background: Activation of peroxisome proliferator activated receptor gamma ($PPAR{\gamma}$) in the alveolar macrophages (AM) by selective synthetic $PPAR{\gamma}$ ligands, improves the ability of the cells to resolve inflammation. In birds, respiratory macrophages are known as free avian respiratory macrophages (FARM) and show distinct functional differences from AM. The effects of treating FARM with $PPAR{\gamma}$ ligands are unclear. Methods: FARM were harvested by lavage of chicken respiratory tract and their morphology assessed at microscopic level. The effects of $PPAR{\gamma}$ agonists on the FARM in vitro viability, phagocytic capacity and proinflammatory cytokine (TNF-${\alpha}$) production were assessed. Results: FARM had eccentric nucleus and plasma membrane ruffled with filopodial extensions. Ultrastructurally, numerous vesicular bodies presumed to be lysosomes were present. FARM treated with troglitazone, a selective $PPAR{\gamma}$ agonist, had similar in vitro viability with untreated FARM. However, treated FARM co-cultured with polystyrene particles, internalized more particles with a mean volume density of 41 % compared to that of untreated FARM of 21 %. Further, treated FARM significantly decreased LPS-induced TNF-${\alpha}$ production in a dose dependent manner. Conclusion: Results from this study show that $PPAR{\gamma}$ synthetic ligands enhance phagocytic ability of FARM. Further the ligands attenuate production of proinflammatory cytokines in the FARM, suggesting potential therapeutic application of $PPAR{\gamma}$ ligands in the management of respiratory inflammatory disorders in the poultry industry.

• 약학회지
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• 제45권6호
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• pp.694-700
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• 2001

Synthetic pyrethroids are analysis of a natural chemical moiety, pyrethrin derived from the pyrethrum plant Chrysanthemum. The natural pyrethrin structure has been modified to be highly lipophilic and photostable, creating an effective pesticide and resulting in an increased presence in the environment. Worldwide, they are commonly used insecticides against ticks, mites, mosquitoes, and as treatment for human head lice and scabies. Therefore, human exposure to their compounds in extensive. Several studies on the effects of pyrethroids on thyroid hormone regulation, estrogen and androgen function have been reported and yet little has been done try assess their potential hormonal activities. Among humans, a pyrethroid compound was suggested to be the causal agent for gynecomastia in a group of Haitian men. The reports suggest that some pyrethroid compounds are capable of disrupting endocrine function. Therefore, we examined estrogenic/antiestrogenic potential of three pyrethroid insecticides, that is permethrin, allethrin and fenvalerate in human breast cancer cell and action mechanism mediated by the estrogen receptor. Fenvalerate showed weak estrogenic activity but aallethrin and permethrin showed no effect. In combination with high levels (10$^{-10}$ M, 10$^{-11}$ M) of 17$\beta$-estradiol and three synthetic pyrethroids inhibited cert proliferations in MCF7-BUS cell by 17$\beta$-estradiol. Whereas, fenvalerate increased cell proliferative activity at lower level of estradiol (10$^{-12}$ M, 10$^{-13}$ M). The relative affinities to the estrogen receptor were observed by allethrin and permethrin treatment, but not by fenvalerate. These results indicated that some of pyrethroid insecticides may modulate estrogen functions in human breast cancer cell. The action mechanisms of estrogen receptor mediated antiestrogenicity by allethrin and permethrin were postulated.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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• pp.86-86
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• 1995

The analysis of membrane receptors for hormones and neurotransmitters has progressed considerably by pharmacological and biochemical means and more recently by the use of specific anti-receptor antibodies. A 14-mer peptide (from Phe102 to Leu115 of ${\beta}$2-adrenergic receptor) was synthesized and this peptide was coupled to carrier protein Keyhole Limpet Hemocyanin(KLH) by glutaraldehyde method. A 0.5mg of KLH-coupled peptide was emulsified with equal volume of complete Freund's adjuvant and injected via popliteal lymph node to each of the three Newzealnd White rabbits. Booster injections were repeated at 4 weeks interval for three times with incomplete Freund's adjuvants. One week after the final injection, serum was prepared from ear artery. Nonspecific immunoglobulins were removed by passing the serum through KLH-Sepharose 6B affinity matrix and further by incubation with bovine lung aceton powder. The titer of the antibody for synthetic peptide which was determined by enzyme linked immunosorbent assay(ELISA) was about l/l,000. The antibody produced in this study revealed 67kDa protein band in the western blot of partially purified guinea pig lung ${\beta}$-adrenergic receptor preparation. The antibody inhibited ${\beta}$-adrenergic antaginist [3H] Dihydroalprenolol binding to soluble ${\beta}$-adrenergic receptor by 25% while control sera did not show any inhibitory effects, The result of this study suggests that the peptide sequence selected in this study may play some important roles in adrenergic receptor-ligand interaction.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.242-242
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• 1996

The influence of glucocorticoids on the secretory responses of catecholamines (CA) evoked by acetylcholine (ACh), DMPP, McN-A-343, excess K$\^$+/ and Bay-K-8644 from the isolated perfused rat adrenal gland and to clarify the mechanism of its action. The perfusion of the synthetic glucocorticoid dexamethasone (10-100 uM) into an adrenal vein for 20min produced relatively a dose-dependent inhibition in CA secretion evoked by ACh (5.32mM), excess K$\^$+/ (56mM), DMPP (a selective nicotinic receptor agonist, 100uM for 2min), McN-A-343 (a muscarinic receptor agonist, 100uM for 4min), Bay-K-8644 (a calcium channel activator, 10 uM for 4min) and cyclopiazonic acid (a releaser of intracellular Ca$\^$2+/, 10uM for 4min).

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.207.3-208
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• 2003

Peroxisome proliferator-activated receptor (PPAR), a member of the nuclear hormone receptor superfamily, is a transcription factor activated by specific natural or synthetic ligands. It is involved in various cellular processes including adipogenesis, inflammation, cell cycle progression and carcinogenesis. Here, we report the production and characterization of a PPARgamma subtype-specific monoclonal antibody P${\gamma}$ 48.34A, which was raised against full-length human PPARgamma protein. (omitted)

• Toxicological Research
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• 제26권4호
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• pp.237-243
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• 2010

Endocrine disrupting chemicals (EDCs) have been shown to interfere with physiological systems, i.e., adversely affecting hormone balance (endocrine system), or disrupting normal function, in the female and male reproductive organs. Although endocrine disruption is a global concern for human health, its impact and significance and the screening strategy for detecting these synthetic or man-made chemicals are not clearly understood in female and male reproductive functions. Thus, in this review, we summarize the interference of environmental EDCs on reproductive development and function, and toxicological mechanism(s) of EDCs in in vitro and in vivo models of male and female reproductive system. In addition, this review highlights the effect of exposure to multiple EDCs on reproductive functions, and brings attention to their toxicological mechanism(s) through estrogen receptors.

• Bulletin of the Korean Chemical Society
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• 제34권2호
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• pp.549-552
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• 2013

An efficient and alternative synthesis of enantiomerically pure (+)-(S)-4-(4-((4-chlorophenyl)(pyrid-2-yl)methoxy]piperidin-1-yl)butanoic acid, bepotastine (1) is described. The key resolution of (R/S)-bepotastine l-menthyl ester (3) is achived via diastereomeric salt crystallization using N-benzyloxycarbonyl-L-aspartic acid (NCbzLAA) as the resolving agent to provide (S)-bepotastine l-menthyl ester (S)-3. Hydrolysis of (S)-bepotastine l-menthyl ester (S)-3 afforded the desired bepotastine (1) with good yields and enantiopurity (> 99%). Finally, bepotastine besilate (4) and bepotastine calcium (5) are achived by salt formation of bepotastine (1) with benzene sulfonic acid and calcium salt respectively. The reaction conditions were optimized to make suitable for commercial scale production.

• Archives of Pharmacal Research
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• 제23권3호
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• pp.202-205
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• 2000

A convenient pathway for synthesis of trans-metanicotine analogues was developed. trans-Metanicotine, a subtype(${\alpha}4{\beta}2$)-selective ligand for neuronal nicotinic acetylcholine receptor, is under clinical phase for Alzheimer's disease. Zn-mediated allylation of allyl bromide and acetaldehyde followed by Heck reaction with 3-bromopyridine gave 5-pyridin-3-yl-pent-4-en-3-ol (2). Tosylation of 5-pyridin-3-yl-pent-4-en-3-ol followed by substitution reaction with methylamine in sealed tube gave methyl-(1-methyl-4-pyridin-3-yl-but-3-enyl)-amine (4) in good yields. Thus, trans-metanicotine analogues modified at the $\alpha$-position of the methylamino group with various functional groups can be obtained in 4 steps.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.187.1-187.1
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• 2003

Type 2 diabetes is characterized by high level of blood glucose and insulin and impaired action. In recent years, the treatment of type 2 diabetes has been revolutionized with the advent of thiazolidinedione (TZD) class of molecules that ameliorate insulin resistance and thereby normalize elevated blood glucose levels. These TZDs are synthetic, high-affinity ligands of peroxisome proliferator activated receptor-gamma (PPAR${\gamma}$); a member of the nuclear receptor family that controls the expression of genes in the target tissues of insulin action. (omitted)

• IMMUNE NETWORK
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• 제22권1호
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• pp.6.1-6.19
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• 2022

Chimeric antigen receptor (CAR) T cells, which express a synthetic receptor engineered to target specific antigens, have demonstrated remarkable potential to treat haematological malignancies. However, their transition beyond haematological malignancy has so far been unsatisfactory. Here, we discuss recent challenges and improvements for CAR T cell therapy against solid tumors: Antigen heterogeneity which provides an effective escape mechanism against conventional mono-antigen-specific CAR T cells; and the immunosuppressive tumor microenvironment which provides physical and molecular barriers that respectively prevent T cell infiltration and drive T cell dysfunction and hypoproliferation. Further, we discuss the application of CAR T cells in infectious disease and autoimmunity.