• Title/Summary/Keyword: time-dependent effects

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Gemcitabine-induced Cell Death in Lung Cancer Cells : the Role of p53 (폐암 세포에서 Gemcitabine에 의한 세포 사멸과 p53의 역할)

  • Kim, Doh-Hyung;Bae, Gang-U;Yong, Wha-Shim;Choi, Eun-Kyung;Kim, Youn-Seup;Park, Jae-Seuk;Jee, Young-Koo;Lee, Kye-Young
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.3
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    • pp.275-284
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    • 2002
  • Background : Gemcitabine is a new anti-cancer agent for treating non-small cell lung cancer. Functioning as an antimetabolite, it induces anti-cancer effects by suppressing DNA synthesis after being incorporated into the DNA as a cytosine arabinoside analogue. When Gemcitabine is incorporated into the DNA, the p53 gene may be activated by induction of the DNA defect. However, there are a few studies on the molecular mechanisms of Gemcitabine-induced cell death. This study examined the role of p53 in Gemcitabine-induced cell death. Methods : A549 and NCl-H358 lung cancer cells were used in this study. The cell viability test was done using a MTT assay at Gemcitabine concentrations of 10nM, 100nM, 1uM, 10uM and 100uM. A FACScan analysis with propium iodide staining was used for the cell cycle analysis. Western blot analysis was done to investigate the extent of p53 activation. For the functional knock-out of p53, stable A549-E6 cells and H358-E6 cells were transfected pLXSN-16E6SD which is over expresses the human papilloma virus E6 protein that constantly degrades p53 protein. The functional knock out of p53 was confirmed by Western blot analysis after treatment with a DNA damaging agent, doxorubicine. Results : Gemcitabine exhibited cell toxicity in dose-dependent fashion. The cell cycle analysis resulted in an S phase arrest. Western blot analysis significant p53 activation in time-dependent manner. Gemcitabine-induced cytotoxicity was reduced by 20-30% in the A549-E6 cells and the 30-40% in H358-E6 cells when compared with the A549-neo and H358-neo control cells. Conclusion : Gemcitabine induces an S phase arrest, as expected for the anti-metabolite, and activates the p53 gene, Furthermore, p53 might play an important role in Gemcitabine-induced cell death. Further investigation into the molecular mechanisms on how Gemcitabine activates the p53 gene and its signaling pathway are recommended.

Effect of Electron Beam Irradiation on the Development and Reproduction of Phthorimaea operculella (Lepidoptera: Gelechiidae) (전자빔 조사가 감자뿔나방의 발육과 생식에 미치는 영향)

  • Cho, Sun-Ran;Ahn, Hyeonmo;Eom, Taeil;Kyung, Yejin;Lee, Seung-Ju;Kim, Hyun Kyung;Koo, Hyun-Na;Kim, Gil-Hah
    • Korean journal of applied entomology
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    • v.60 no.2
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    • pp.255-262
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    • 2021
  • The potato tuber moth, Phthorimaea operculella (Zeller) has been known as a quarantine pest of potato. This study investigated inhibition doses of electron beam irradiation (EBM) by comparing their effects on the development and reproduction and DNA damage of the insect pest. Eggs (0-12 h old), larvae (3rd and 5th instar), pupae (less than 1 d old after pupation) and adults (less than 1 d old after emergence) were irradiated with increasing doses of EBM. The EBM with 150 Gy could not completely prevent the hatchability of eggs and pupation of the hatched larvae. The hatchability from the irradiated eggs were 19.3%. However, adult emergence from the irradiated eggs were completely inhibited. When 3rd and 5th instar larvae were irradiated at 100 Gy, the adult emergence from the irradiated larvae and the fecundity of the adults were completely inhibited. When pupae and adults were irradiated at 300 Gy and 400 Gy, respectively, the hatchability of the F1 eggs was completely inhibited. The alkaline comet assay on the level of DNA damage by EBM in P. operculella adults indicates that the EBM increased DNA damage level in a dose-dependent manner, and the damage was repaired in a time-dependent manner. These results may recommend EBM of 150 Gy as a phytosanitary treatment for P. operculella. However further confirmative study is required for the practical application of this EBM dose for P. operculella disinfestation.

Effect of 17β-estradiol on Ecdysteroid Pathway Related Genes in the Brackish Water Flea Diaphanosoma celebensis (17β-estradiol이 기수산 물벼룩의 Ecdysteroid 경로에 미치는 영향)

  • In, Soyeon;Yoo, Jewon;Cho, Hayoung;Lee, Young-Mi
    • Journal of Marine Life Science
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    • v.5 no.2
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    • pp.35-42
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    • 2020
  • 17β-estradiol (E2) is a natural hormone secreted by ovary, and continuously discharged from household and livestock wastewater into aquatic environment. Due to its strong estrogenic activity, it has adverse effects on development and reproduction in crustacean as an endocrine disrupting chemical. Although ecdysteroid signaling pathway play a key role in development in crustacean, little information on transcriptional modulation of ecdysteroid-related genes in response to E2 is available in small crustacean. Here, we investigated the acute toxicity of E2 to obtain 24-h LCx values in the brackish water flea Diaphanosoma celebensis. Time-dependent expression patterns of seven ecdysteroid pathway - related genes (CYP314a1, EcRA, EcRB, USP, ERR, Vtg, VtgR) were further examined using quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR). As results, 24-h LC50 and LC10 values were 9.581 mg/l and 4.842 mg/l, respectively. The mRNA expression of CYP314a1, EcRA, USP, VtgR was significantly up-regulated at 12 or 24 h after exposure to E2. These findings indicate that E2 can affect their molting and reproduction by modulating the expression of ecdysteroid pathway - related in D. celebensis. This study will be useful for better understanding of molecular mode of action of endocrine disrupting chemicals on molting process in small crustacean.

Optimization of β-Glucan Extraction Process from Rice Bran and Rice Germ Using Response Surface Methodology (미강과 배아로부터 β-glucan의 추출조건 최적화 및 기능성 생리활성)

  • Jeon, Ju-Yeong;Park, Ji-Hae;Kim, Se-Hwan;Choi, Yong-Hee
    • Food Engineering Progress
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    • v.13 no.1
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    • pp.8-15
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    • 2009
  • This study was investigated on optimal conditions of the functional activities of ${\beta}$-glucan which was extracted from rice bran (RB) and rice germ (RG) using response surface methodology. The extraction temperature was varied in the $80-100^{\circ}C$, the extraction time between 2-10 min, and the ethanol concentration was in the interval of 30-70%. A central composite design was applied to investigate the effects of independent variables of extraction temperature ($X_1$), extraction time ($X_2$) and ethanol concentration ($X_3$) on dependent variables such as electron donating ability of RB ($Y_1$), electron donating ability of RG ($Y_2$), total phenolics of RB ($Y_3$), total phenolics of RG ($Y_4$), ${\beta}$-glucan contents of RB ($Y_5$) and ${\beta}$-glucan contents of RG ($Y_6$). As a result, the highest $Y_1$ level was 84.02% at $92.60^{\circ}C$, 2.75 min and 60.41% in saddle point. This value was affected by extraction temperature (P<0.05). The value of $Y_2$ was found to be the highest at $87.52^{\circ}C$, 2.23 min and 54.40% in saddle point. The highest $Y_3$ level was $98.56^{\circ}C$, 6.69 min and 40.26% in saddle point, and this extraction was greatly influenced by extraction temperature (P<0.01) and ethanol concentration (P<0.05). The value of $Y_4$ was found to be highest at $95.73^{\circ}C$, 9.19 min and 53.67% in minimum point. The value of $Y_5$ was found to be the highest at $96.23^{\circ}C$, 7.70 min and 63.69% in saddle point. The value of $Y_6$ was found to be highest at $87.82^{\circ}C$, 2.10 min and 50.03% in minimum point, and this extraction was greatly influenced by extraction time (P<0.01).

Differential Effects of Recovery Efforts on Products Attitudes (제품태도에 대한 회복노력의 차별적 효과)

  • Kim, Cheon-GIl;Choi, Jung-Mi
    • Journal of Global Scholars of Marketing Science
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    • v.18 no.1
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    • pp.33-58
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    • 2008
  • Previous research has presupposed that the evaluation of consumer who received any recovery after experiencing product failure should be better than the evaluation of consumer who did not receive any recovery. The major purposes of this article are to examine impacts of product defect failures rather than service failures, and to explore effects of recovery on postrecovery product attitudes. First, this article deals with the occurrence of severe and unsevere failure and corresponding service recovery toward tangible products rather than intangible services. Contrary to intangible services, purchase and usage are separable for tangible products. This difference makes it clear that executing an recovery strategy toward tangible products is not plausible right after consumers find out product failures. The consumers may think about backgrounds and causes for the unpleasant events during the time gap between product failure and recovery. The deliberation may dilutes positive effects of recovery efforts. The recovery strategies which are provided to consumers experiencing product failures can be classified into three types. A recovery strategy can be implemented to provide consumers with a new product replacing the old defective product, a complimentary product for free, a discount at the time of the failure incident, or a coupon that can be used on the next visit. This strategy is defined as "a rewarding effort." Meanwhile a product failure may arise in exchange for its benefit. Then the product provider can suggest a detail explanation that the defect is hard to escape since it relates highly to the specific advantage to the product. The strategy may be called as "a strengthening effort." Another possible strategy is to recover negative attitude toward own brand by giving prominence to the disadvantages of a competing brand rather than the advantages of its own brand. The strategy is reflected as "a weakening effort." This paper emphasizes that, in order to confirm its effectiveness, a recovery strategy should be compared to being nothing done in response to the product failure. So the three types of recovery efforts is discussed in comparison to the situation involving no recovery effort. The strengthening strategy is to claim high relatedness of the product failure with another advantage, and expects the two-sidedness to ease consumers' complaints. The weakening strategy is to emphasize non-aversiveness of product failure, even if consumers choose another competitive brand. The two strategies can be effective in restoring to the original state, by providing plausible motives to accept the condition of product failure or by informing consumers of non-responsibility in the failure case. However the two may be less effective strategies than the rewarding strategy, since it tries to take care of the rehabilitation needs of consumers. Especially, the relative effect between the strengthening effort and the weakening effort may differ in terms of the severity of the product failure. A consumer who realizes a highly severe failure is likely to attach importance to the property which caused the failure. This implies that the strengthening effort would be less effective under the condition of high product severity. Meanwhile, the failing property is not diagnostic information in the condition of low failure severity. Consumers would not pay attention to non-diagnostic information, and with which they are not likely to change their attitudes. This implies that the strengthening effort would be more effective under the condition of low product severity. A 2 (product failure severity: high or low) X 4 (recovery strategies: rewarding, strengthening, weakening, or doing nothing) between-subjects design was employed. The particular levels of product failure severity and the types of recovery strategies were determined after a series of expert interviews. The dependent variable was product attitude after the recovery effort was provided. Subjects were 284 consumers who had an experience of cosmetics. Subjects were first given a product failure scenario and were asked to rate the comprehensibility of the failure scenario, the probability of raising complaints against the failure, and the subjective severity of the failure. After a recovery scenario was presented, its comprehensibility and overall evaluation were measured. The subjects assigned to the condition of no recovery effort were exposed to a short news article on the cosmetic industry. Next, subjects answered filler questions: 42 items of the need for cognitive closure and 16 items of need-to-evaluate. In the succeeding page a subject's product attitude was measured on an five-item, six-point scale, and a subject's repurchase intention on an three-item, six-point scale. After demographic variables of age and sex were asked, ten items of the subject's objective knowledge was checked. The results showed that the subjects formed more favorable evaluations after receiving rewarding efforts than after receiving either strengthening or weakening efforts. This is consistent with Hoffman, Kelley, and Rotalsky (1995) in that a tangible service recovery could be more effective that intangible efforts. Strengthening and weakening efforts also were effective compared to no recovery effort. So we found that generally any recovery increased products attitudes. The results hint us that a recovery strategy such as strengthening or weakening efforts, although it does not contain a specific reward, may have an effect on consumers experiencing severe unsatisfaction and strong complaint. Meanwhile, strengthening and weakening efforts were not expected to increase product attitudes under the condition of low severity of product failure. We can conclude that only a physical recovery effort may be recognized favorably as a firm's willingness to recover its fault by consumers experiencing low involvements. Results of the present experiment are explained in terms of the attribution theory. This article has a limitation that it utilized fictitious scenarios. Future research deserves to test a realistic effect of recovery for actual consumers. Recovery involves a direct, firsthand experience of ex-users. Recovery does not apply to non-users. The experience of receiving recovery efforts can be relatively more salient and accessible for the ex-users than for non-users. A recovery effort might be more likely to improve product attitude for the ex-users than for non-users. Also the present experiment did not include consumers who did not have an experience of the products and who did not perceive the occurrence of product failure. For the non-users and the ignorant consumers, the recovery efforts might lead to decreased product attitude and purchase intention. This is because the recovery trials may give an opportunity for them to notice the product failure.

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Clinical Applications and Efficacy of Korean Ginseng (고려인삼의 주요 효능과 그 임상적 응용)

  • Nam, Ki-Yeul
    • Journal of Ginseng Research
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    • v.26 no.3
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    • pp.111-131
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    • 2002
  • Korean ginseng (Panax ginseng C.A. Meyer) received a great deal of attention from the Orient and West as a tonic agent, health food and/or alternative herbal therapeutic agent. However, controversy with respect to scientific evidence on pharmacological effects especially, evaluation of clinical efficacy and the methodological approach still remains to be solved. Author reviewed those articles published since 1980 when pharmacodynamic studies on ginseng have intensively started. Special concern was paid on metabolic disorders including diabetes mellitus, circulatory disorders, malignant tumor, sexual dysfunction, and physical and mental performance to give clear information to those who are interested in pharmacological study of ginseng and to promote its clinical use. With respect to chronic diseases such as diabetes mellitus, atherosclerosis, high blood pressure, malignant disorders, and sexual disorders, it seems that ginseng plays preventive and restorative role rather than therapeutics. Particularly, ginseng plays a significant role in ameliorating subjective symptoms and preventing quality of life from deteriorating by long term exposure of chemical therapeutic agents. Also it seems that the potency of ginseng is mild, therefore it could be more effective when used concomitantly with conventional therapy. Clinical studies on the tonic effect of ginseng on work performance demonstrated that physical and mental dysfunction induced by various stresses are improved by increasing adaptability of physical condition. However, the results obtained from clinical studies cannot be mentioned in the indication, which are variable upon the scientist who performed those studies. In this respect, standardized ginseng product and providing planning of the systematic clinical research in double-blind randomized controlled trials are needed to assess the real efficacy for proposing ginseng indication. Pharmacological mode of action of ginseng has not yet been fully elucidated. Pharmacodynamic and pharmacokinetic researches reveal that the role of ginseng not seem to be confined to a given single organ. It has been known that ginseng plays a beneficial role in such general organs as central nervous, endocrine, metabolic, immune systems, which means ginseng improves general physical and mental conditons. Such multivalent effect of ginseng can be attributed to the main active component of ginseng,ginsenosides or non-saponin compounds which are also recently suggested to be another active ingredients. As is generally the similar case with other herbal medicines, effects of ginseng cannot be attributed as a given single compound or group of components. Diversified ingredients play synergistic or antagonistic role each other and act in harmonized manner. A few cases of adverse effect in clinical uses are reported, however, it is not observed when standardized ginseng products are used and recommended dose was administered. Unfavorable interaction with other drugs has also been suggested, which the information on the products and administered dosage are not available. However, efficacy, safety, interaction or contraindication with other medicines has to be more intensively investigated in order to promote clinical application of ginseng. For example, daily recommended doses per day are not agreement as 1-2g in the West and 3-6 g in the Orient. Duration of administration also seems variable according to the purpose. Two to three months are generally recommended to feel the benefit but time- and dose-dependent effects of ginseng still need to be solved from now on. Furthermore, the effect of ginsenosides transformed by the intestinal microflora, and differential effect associated with ginsenosides content and its composition also should be clinically evaluated in the future. In conclusion, the more wide-spread use of ginseng as a herbal medicine or nutraceutical supplement warrants the more rigorous investigations to assess its effacy and safety. In addition, a careful quality control of ginseng preparations should be done to ensure an acceptable standardization of commercial products.

Beneficial Effects of Acanthopanax senticosus Extract in Type II Diabetes Animal Model via Down-Regulation of Advanced Glycated Hemoglobin and Glycosylation End Products (제2형 당뇨 동물모델에서 가시오가피 추출물의 당화혈색소 및 최종당화산물 억제를 통한 혈당조절 효과)

  • Kwon, Han Ol;Lee, Minhee;Kim, Yong Jae;Kim, Eun;Kim, Ok-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.7
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    • pp.929-937
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    • 2016
  • The purpose of this study was to investigate the effect of Acanthopanax senticosus extract (ASE) (ethanol : DW=1:1, v/v) on inhibition of type 2 diabetes using an OLETF rat model via regulation of HbA1c and AGEs levels. Supplementation with ASE 0.1% and 0.5% effectively lowered levels of glucose, insulin, oral glucose tolerance test, and Homa-insulin resistance, suggesting reduced insulin resistance. Blood levels of HbA1c and AGEs were significantly reduced in a dose-dependent manner. As oxidative stress plays a key role in accelerating production of HbA1c and AGEs, which worsen symptoms of type 2 diabetes, levels of malonaldehyde and pro-inflammatory cytokines were measured. Lipid peroxidation in both blood and liver tissues was significantly reduced, and induction of pro-inflammatory cytokines interleukin-${\beta}$ and tumor necrosis factor-${\alpha}$, which elevate production of HbA1c and AGEs, was inhibited (P<0.05). To evaluate the possible cellular events after AGEs receptor activation, genetic expression of protein kinase C (PKC)-${\delta}$ and transforming growth factor (TGF)-${\beta}$ was measured by real-time polymerase chain reaction. Supplementation with both ASE 0.1% and 0.5% significantly inhibited mRNA expression of PKC-${\delta}$ and TGF-${\beta}$, indicating that ASE may have beneficial effects on preventing insulin-resistant cells or tissues from progressing to diabetic complications. Taken together, ASE has potential to improve type 2 diabetes by inhibiting insulin resistance and protein glycosylation, including production of HbA1c and AGEs. Anti-oxidative activities of ASE are a main requisite for reducing production of HbA1c and AGEs and are also related to regulation of the PKC signaling pathway, resulting in suppression of TGF-${\beta}$, which increases synthesis of collagen, prostaglandin, and disease-related proteins.

Removal Effects of Bifenthrin and Metalaxyl Pesticides during Preparation and Fermentation of Baechu Kimchi (배추김치의 제조 및 발효과정 중 Bifenthrin과 Metalaxyl 농약의 제거 효과)

  • Jung, Ji-Kang;Park, So-Yeon;Kim, So-Hee;Kang, Jeong-Mi;Yang, Ji-Young;Kang, Soon-Ah;Chun, Hae-Kyoung;Park, Kun-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.9
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    • pp.1258-1264
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    • 2009
  • The removal effects of two commonly used pesticides of Bifenthrin and Metalaxyl during preparation and fermentation of kimchi were studied. The two pesticides were applied to Baechu cabbages intentionally for 20 seconds; the applied amounts of Bifenthrin and Metalaxyl were 3.02$\pm$0.09 ppm and 6.79$\pm$0.17 ppm, respectively. The Baechu cabbages were washed by water 3 times. Then the residual amounts of the two pesticides of Bifenthrin and Metalaxyl were measured and the removal rates were 21.7% and 16.1%, respectively. When Baechu cabbages were brined with 10% salt solution for 12 hours after the application of the two pesticides, the removal rates significantly increased to 98.7% and 60.8%, and when brined and washed 3 times by water, the removal rates even more increased to 99.7% and 73.4% respectively. Then we made kimchi and investigated the quantities of the residual pesticides during the fermentation at $4^{\circ}C$ for 3 weeks. The residual amounts of the pesticides in kimchi decreased in a time dependent manner, finally the amounts of the pesticides to 0.35$\pm$0.04 ppm and 0.48$\pm$0.06 ppm while the removal rates of the two pesticides were 57.8% and 81.0%, respectively. When the kimchi was fermented at $4^{\circ}C$ and $10^{\circ}C$ for 3 weeks, the removal rates of Bifenthrin were 57.8% and 72.2% and those of Metalaxyl were 81.0% and 85.6%, respectively. Consequently, it appeared that the residual pesticides can be removed during preparation, especially brining; the fermentation process of kimchi also removed the residual pesticides effectively, especially at higher temperature and long period.

The Effects of Aminophylline on the Superoxide Anion Generation of Neutrophils from Established Human Sepsis Caused by Acute Pneumonia (급성 폐렴에 의한 패혈증 환자에서 Aminophylline이 혈중 호중구의 과산화물 음이온 유리에 미치는 영향)

  • Kim, Yong-Hoon;Park, Jun-Young;Cha, Mi-Kyong;Lee, Sang-Moo;Kim, Hyeon-Tae;Uh, Soo-Taek;Chung, Yeon-Tae;Park, Choon-Sik
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.1
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    • pp.16-22
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    • 1993
  • Background: The Microbicidal and cytotoxic activities of neutrophils are to a large extent dependent on a burst of oxidative metabolism which generates superoxide anion, hydrogen peroxide, and other reactive products of oxygen. The respiratory burst of PMN is initiated by intracellular calcium mobilization that follows immune or particular stimulation and is very sensitive to modulation by c-AMP or adenosine. Despite its antagonism against adenosine, earlier study has demonstrated potent theophylline inhibition of the PMN respiratory burst at variable ranges of blood concentrations of theophylline in the healthy normal volunteers and in the septic animals pretreated or early post-treated with aminophylline (AMPH) or pentoxifylline. However it is unclear whether theophylline inhibits the superoxide generation or not in the established human sepsis caused by acute pneumonia, as taking into consideration of the fact that full activation of neutrophils have occurred within minutes after the septic insult in the animal experiments. Methods: We measured the $O_2$ generation of peripheral arterial neutrophils obtained from 11 human septic subjects caused by acute pneumonia before and 1 hour after completion of continuous AMPH infusion. Patients were identified and studied within 48 hour of admission. All subjects were administered an intravenous loading and maintenance dose of AMPH. The generation of $O_2$ was measured at a discrete time point (60 min) by the reduction of ferricytochrome c.PMA (10 ${\mu}g/ml$) was used as a stimulating agent. PMNs were isolated at a concentration of $2{\times}10^6$ cells/ml. The arterial oxygen tension, blood pressure and heart rates were also checked to evaluate the systemic effects of AMPH in the acute pneumonia. Results: The mean serum concentration of AMPH at 60 minutes was $8.8{\pm}0.6{\mu}g/ml$. Sixty minutes after AMPH infusion the generatition of $O_2$ was decreased from $0.076{\pm}0.034$ to $0.013{\pm}0.004$(OD) (p<0.05) and from $0.177{\pm}0.044$ to $0.095{\pm}0.042$(OD) (p<0.01) in the resting and stimulated PMNs respectively. $PaO_2$ was not changed after AMPH infusion. Conclusion: AMPH may compromise host defense by significant inhibition of neutrophil release of superoxide anion and it had no effect on improving $PaO_2$ in the acute pneumonia.

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Effects of Cultivated Wild Panax ginseng Extract on the Proliferation, Differentiation and Mineralization of Osteoblastic MC3T3-E1 Cells (산양삼(cultivated wild Panax ginseng) 추출물이 조골세포 활성에 미치는 영향)

  • Seo, Hyun-Ju;Eo, Hyun Ji;Kim, Hyun Jun;Jeon, Kwon Seok;Park, Gwang Hun;Hong, Se Chul;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.33 no.4
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    • pp.227-236
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    • 2020
  • Panax ginseng C.A. Meyer (P. ginseng) is known to exert a wide range of pharmacological effects both in vitro and in vivo. Although studies on ginsenoside, antioxidant activity, and anticancer effect of the cultivated wild Panax ginseng (CWP) have been conducted, there is little research on the effect of CWP extract on bone metabolism. In this study, we investigated the potential anti-osteoporotic properties of CWP on the growth and differentiation of MC3T3-E1 cells. CWP significantly increased the viability and proliferation of MC3T3-E1 cells. CWP activated intracellular alkaline phosphatase (ALP) activity in MC3T3-E1 cells. In addition, CWP increased the mineralized nodules in MC3T3-E1 cells. Furthermore, CWP increased the expression of genes such as Runx2, ALP, OPN and OCN associated with osteoblast growth and differentiation in a dose-dependent manner.