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Synthesis and Antifungal Evaluation of 6-(N-arylamino)-7-methylthio-5,8-quinolinediones

  • Kim, Chung-Kyu;Choi, Jung-Ah;Kim, Sung-Hee
    • Archives of Pharmacal Research
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    • v.21 no.4
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    • pp.440-444
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    • 1998
  • A series of 6-(N-arylamino)-7-methylthio-5,8-quinolinedione derivatives 4a-4l was newly synthesized for the evaluation of antifungal activity. 6-(N-Arylamino)-7-methylthio-5,8-quinolinediones were prepared by regioselective nucleophilic substitution of 6,7-dichloro-5,8-quinolinediones with arylamines in the presence of $Ce^{3+}$, and $Na_2$S/dimethylsulfate. The MIC values of 4a-4l were determined for antifungal susceptibility in vitro against Candida species by agar streak method. The derivatives 4a-4l had generally potent antifungal activities against all human pathogenic fungi. Especially they had the most potent activity against C. krusei at 12.5-0.8 $\mu\textrm{g}$/ml. Compounds 4d, 4g, 4h, 4j and 4k had more potent antifungal activities than fluconazole. Compounds 4g and 4h completely inhibited the fungal growth at 0.8-6.3 $\mu\textrm{g}$/ml against all Candida species, while fluconazole inhibited the growth at 25 $\mu\textrm{g}$/ml. The compounds such as 4g and 4h containing an N-(4-bromo-2-methylphenyl)- or N-(4-bromo-3methylphenyl)amino substituent exhibited the most potent antifungal activities.

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The Effects of Dietary Urea on Microbial Populations in the Rumen of Sheep

  • Kanjanapruthipong, J.;Leng, R.A.
    • Asian-Australasian Journal of Animal Sciences
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    • v.11 no.6
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    • pp.661-672
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    • 1998
  • Two experiments were conducted to examine the effects of a range of concentrations of ruminal fluid ammonia ($NH_3$-N) on forage digestibility, microbial growth efficiency and the mix of microbial species. Urea was either continuously infused directly into the rumen of sheep fed 33.3 glh of oaten chaff (Exp. I) or sprayed onto the oaten chaff (750 g/d) given once daily (Exp. 2). Concentrations of $NH_3$-N increased with incremental addition of urea (p < 0.01). Volatile fatty acids (VFA) concentrations and 24 h in sacco organic matter digestibility in the rumen were higher when supplemental urea was given (p < 0.01). The (C2 + C4) : C3 VFA ratio was lower (p < 0.05) when $NH_3$-N was above 200 mgN/I. The fungal sporangia appearing on oat leaf blades were significantly higher when urea was supplemented, indicating that $NH_3$-N was a growthlimiting nutrient for fungi at levels of $NH_3$-N below 30 mgN/l. The density of protozoa was highest when $NH_3$-N concentrations were adjusted to 30 mgN/I for continuously fed ($4.4{\times}10^5/ml$) and to 168 mgN/1 for once daily feeding ($2.9{\times}10^5/ml$). Thereafter increasing concentrations of $NH_3$-N, were associated with a concomitant decline in protozoal densities. At the concentration of $NH_3$-N above 200 mgN/l, the density of protozoa was similar to the density of protozoa in ruminal fluid of the control sheep ($1.8{\times}10^5/ml$). The efficiency of net microbial protein synthesis in the rumen calculated from purine excretion was 17-47% higher when the level of $NH_3$-N was above 200 mgN/1. The possibilities are that 1) there is less bacterial cell lysis in the rumen because of the concomitant decrease in the protozoal pool and/or 2) microbial growth per se in the rumen is more efficient with increasing $NH_3$-N concentrations.

A comparative study on head posture and craniofacial morphology between koreans and scandinavian caucasians (한국인과 스칸디나비아계 백인의 두부자세와 두개안면구조의 형태에 관한 비교연구)

  • Oh, Yong-Duck;Yoon, Young-Jooh;Kim, Kwang-Won
    • The korean journal of orthodontics
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    • v.29 no.6 s.77
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    • pp.707-720
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    • 1999
  • The purpose of this study was to evaluate racial differences In head posture and the influence of head posture to the craniofacial morphology. The sample group of this study was made up of 51 Korean males and 120 Scandinavian Caucasian males. From the comparison of the cranio-cervical angle and the variables of craniofacial morphology between them, the following results were obtained. 1. The cranio-cervical angle (NSL/OPT) was on average 9.28 degrees larger In Koreans. 2. The length of the anterior cranial base (N-S) was on average 4.66mm shorter in Koreans. 3. The length of the maxillary base (sp-pm and ss-pm) were on average 2.75mm and 4.65mm shorter in Koreans respectively, the anterior maxillary height (n-sp) was on average 2.60mm longer, the posterior dimension (s-pm) was found to be 2.06mm longer in Koreans, and the maxillary inclination (NSL/NL) was identical in both samples. 4. The mandibular body length (pg-tgo) and ramus height (ar-tgo) were identical in the two groups, but the genial angle (ML/RL) was 3.22 degrees smaller and the mandibular plane inclination (NSL/ML) was 2.44 degrees larger in Koreans 5. The maxillary prognathism (s-n-sp and s-n-ss) and the mandibular prognathism (s-n-sm) were identical in both samples. 6. The sagittal jaw relationship (ss-n-pg) was 1.44 degrees larger in the Korean sample, but the vortical jaw relationship (NL/ML) was not significantly different. 7. The anterior facial height (n-gn) was 5.57mm longer in the Korean sample. 8. The mandibular alveolar prognathism (CL/ML) was 5.71 degrees greater and the interincisal angle (ILs/ILi) was 3.08 degrees more acute in Koreans. Taken together these results, craniofacial morphology can be influenced by the head posture defined by cranio-cervical angulation.

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Preconcentration of Copper(II) Using Mesoporous Organo-Silicas and Determination by Flame Atomic Absorption Spectrometry (메조다공성 유기-실리카를 이용한 구리(II)의 예비농축과 불꽃원자 흡수분광법으로의 정량)

  • Moghimi, Ali
    • Journal of the Korean Chemical Society
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    • v.52 no.2
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    • pp.155-163
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    • 2008
  • .A simple and reproducible method for the rapid extraction and determination of trace amounts of copper(II) ions using mesoporous organo-silicas mesoporous silica and atomic absorption spectrometry is presented. Common coexisting ions did not interfere with the separation and determination. The preconcentration factor was 100 (1 ml elution volume) for a 100 ml sample volume. The limit of detection of the proposed method is 1.0 ng ml-1. The maximum sorption capacity of sorbent under optimum conditions has been found to be 5mg of copper per gram of sorbent. The relative standard deviation under optimum conditions was 2.8% (n=10). Accuracy and application of the method was estimated by using test samples of natural and synthetic water spiked with different amounts of copper(II) ion.

Pituitary and Gonadal Response to GnRH in Prepubertal Buffaloes (Bubalus bubalis)

  • Singh, C.;Madan, M.L.
    • Asian-Australasian Journal of Animal Sciences
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    • v.11 no.1
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    • pp.78-83
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    • 1998
  • The objective of this study was to investigate the responsiveness of hypophysis and gonads to synthetic GnRH among prepubertal buffalo heifers at 12 months of age. Peripheral plasma FSH, LH, estradiol and progesterone level were measured in blood samples collected at 1 hr before and up to 18 days subsequent to the administration of $200{\mu}g$ GnRH (n=6) or saline (n=6) in Murrah buffalo heifers. The pretreatment peripheral plasma FSH, LH, estradiol and progesterone among GnRH treated heifers were $7.35{\pm}0.45ng/ml$, $1.08{\pm}0.3ng/ml$, $22.93{\pm}1.06pg/ml$ and $0.27{\pm}0.04ng/ml$ respectively. A quick elevation (p < 0.01) of FSH and LH within five min of GnRH administration was observed in all geifers. Although the peak FSH $(89.57{\pm}23.43ng/ml)$ and LH $(7.52{\pm}3.08ng/ml)$ reached by 10 min of GnRH administration, yet the animals differed both in terms of their amplitude response of FSH and LH release as well as in terms of time which animals took to exhiit maximum response to GnRH administration. The GnRH administration did not cause alteration in plasma estradiol and progesterone level. The present study suggests that the pituitary of 12 month buffalo heifers has capacity to synthesize and store of gonadotropin and have developed receptors for GnRH for a spike of gonadotropin release.

Effect of Nardostachyos Rhizoma on Apoptosis, Differentiation and Proliferation in HL-60 cells

  • Ju Sung-Min;Lee Jun;Choi Ho-Seung;Yoon Sang-Hak;Kim Sung-Hoon;Jeon Byung-Hun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.1
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    • pp.163-170
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    • 2006
  • Nardostachyos Rhizoma (N. Rhizoma) belonging to the family Valerianaceae has been anti-arrhythmic effect, and sedation to the central nerve and a smooth muscle. We reported that the water extract of N. Rhizoma induced apoptotic cell death and differentiation in human promyelocytic leukemia (HL-60) cells. Cytotoxicity of N. Rhizoma was detected only in HL-60 cells (IC50 is about 200 ${\mu}g/ml$). The cytotoxic activity of N. Rhizoma in HL-60 cells was increased in a dose-dependent manner. We used several measures of apoptosis to determine whether these processes were involved in N. Rhizoma-induced apoptotic cell death. The high-dose (200 ${\mu}g/ml$) treatment of N. Rhizoma to HL-60 cells showed cell shrinkage, cell membrane blobbing, apoptotic bodies, and the fragmentation of DNA, suggesting that these cells underwent apoptosis. Treatment of HL-60 cells with N. Rhizoma time-dependently induced activation of caspase-3, caspase-8, and caspase-9 and proteolytic cleavage of poly(ADP-ribose) polymerase. Also, we investigated the effect of N. Rhizoma on cellular differentiation and proliferation in HL-60 cells. Differentiation and proliferation of HL-60 cells was determined through expression of CD11b and CD14 surface antigens using flow cytometry and nitroblue tetrazolium (NBT) assay, and through analysis of cell cycle using propidium iodide assay, respectively. N. Rhizoma induced the differentiation of HL-60 at the low-dose (100 ${\mu}g/ml$) treatment, as shown by increased expression of differentiation surface antigen CD11b, but not CDl4 and increased reducing activity of NBT. When HL-60 cells were treated with N. Rhizoma at concentration of $50{\mu}g/ml\;and\;100{\mu}g/ml$, NBT-reducing activities induced approximately 1.5-fold and 20.0-fold as compared with the control. In contrast, HL-60 cells treated with the N. Rhizoma-ATRA combination showed markedly elevated levels of 26.3-fold at $50{\mu}g/ml$ N. Rhizoma-0.1 ${\mu}M$ ATRA combination and 27.5-fold at 50 ${\mu}g/ml$ N. Rhizoma-0.2 ${\mu}M$ ATRA combination than when treated with N. Rhizoma alone or ATRA alone. It may be that N. Rhizoma plays important roles in synergy with ATRA during differentiation of HL-60 cells. DNA flow-cytometry indicated that N. Rhizoma markedly induced a G1 phase arrest of HL-60 cells. N. Rhizoma-treated HL-60 cells increased the cell population in G1 phase from 32.71% to 42.26%, whereas cell population in G2/M and S phases decreased from 23.61% to 10.33% and from 37.78% to 33.98%, respectively. We examined the change in the $p21^{WAF1/Cip1}\;and\;p27^{Kip1}$ proteins, which are the CKIs related with the G1 phase arrest. The expression of the CDK inhibitor $p27^{Kip1},\;but\;not\;p21^{WAF1/Cip1}$ were markedly increased by N. Rhizoma. Taken together, these results demonstrated that N. Rhizoma induces apoptotic cell death through activation of caspase-3, and potently inhibits the proliferation of HL-60 cells via the G1 phase cell cycle arrest in association with $p27^{Kip1}$ and granulocytic differentiation induction .

Fluorimetric Determination of Iron with N,N'-Oxalylbis(2-pyridyl-3'-sulphobenzoylhydrazone) (N,N'-Oxalylbis(2-pyridyl-3'-sulphobenzoylhydrazone)을 이용한 철의 형광광도법 정량)

  • Bark Ki-Min;Kim Yong-Nam
    • Journal of the Korean Chemical Society
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    • v.37 no.6
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    • pp.585-589
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    • 1993
  • A fluorimetric method for the determination of Fe(Ⅲ) using N,N'-oxalylbis(2-pyridyl-3'-sulphobenzoyl hydrazone)(OPSH) as a emission reagent has been developed. Determination has been performed by measuring the fluorescence intensity of Fe(Ⅲ) complex at 367 nm in aqueous solution (pH 3) with 290 nm excitation. There was a linear relationship between Fe(Ⅲ) concentration and fluorescence intensity over the range 2000∼10 ng/ml. The method has been applied to the determination of Fe(Ⅲ) in synthetic mixtures and tap water

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Changes in Specific Gravity, Total Solid and Protein Contents of Human Milk During the Course of Lactation in Korean Women (한국인 모유의 수유기간별 비중, 충고형분 및 단백질 함량의 변화)

  • 이종숙
    • Journal of Nutrition and Health
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    • v.21 no.2
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    • pp.129-133
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    • 1988
  • The lonitudinal determination of specific gravity, total solid and protein contents of human milk were carried out in 27 Korean women. Human milk samples from the subjects were collected at 15, 30, 60, 90, 120, 150th days of lactation. 1) The average values of specific gravity of the milk was 1, 0281 (S.D. 0.0018, n=12), with a range of 1.0200-1.0383. 2) The average values of total soild of the milk was 12.07g/100ml(S.D. 0.38, n=112), with a range of 9.36-15.88g/100ml. 3) The average values of protein content of the milk was 1.20g/100ml (S.D. 0.14, n=112), with a range of 1.09-1.46g/100ml. A slight decrease of specific gravity and protein content in human milk was found during the course of lactation, but significant decrease was not found in total solid content.

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Anti-Oxidative and Anti-Inflammatory Effects of the Solvent Fraction from Theobroma cacao L. Extract (카카오(Theobroma cacao L.) 용매 분획물의 항산화 및 항염증 효과)

  • Kim, Young-Sun;Lee, Jin-Young;Cho, Young-Je;An, Bong-Jeun
    • Journal of Life Science
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    • v.22 no.10
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    • pp.1330-1338
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    • 2012
  • Solvent extracts of Theobroma cacao L. (TCL) were investigated for anti-oxidative and anti-inflammatory effects in order to consider TCL as a functional ingredient for cosmetic products. TCL(A) extract was fractioned according to polarity with $CHCl_3$, EtOAc, n-BuOH, and water. Following TCL(A) fractionation, the electron-donating ability of the n-BuOH and EtOAc solvent fractions (each 100 ${\mu}g/ml$) was about 76.2% and 53.9%, respectively. The superoxide anion radical inhibitory effect of the n-BuOH and EtOAc solvent fractions (each 50 ${\mu}g/ml$) was about 76.09% and 51.4%, respectively. Results of lipid oxidation showed that $Fe^{2+}$ had a greater chelating effect than $Cu^{2+}$. The $Fe^{2+}$ chelating effect of the EtOAc solvent fraction (50 ${\mu}g/ml$) was about 64%. Hyaluronidase inhibition related to the anti-inflammatory effect was 53.0% with EtOAc at 100 ${\mu}g/ml$, while the lipoxygenase inhibitory effect was about 51.32% at 10 ${\mu}g/ml$. The anti-inflammatory activity in the EtOAc fraction inhibited the generation of nitric oxide. Results also showed that iNOS protein expression increased in RAW264.7 cells. In contrast, at 100 ${\mu}g/ml$ EtOAc, iNOS and COX-2 protein expression significantly decreased in LPS-stimulated RAW 264.7 cells.

Studies on the Formation of L-Threonine by auxotrophic mutants of Brevibacterium flavum (Brevibacterium Flavum의 Auxotrophic Mutants에 의한 L-Threonine 생성(生成)에 관한 연구(硏究))

  • Lee, Kap-Rang;Park, Dong-Cheol
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.16 no.4
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    • pp.251-261
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    • 1987
  • This study was attempted to increase the production of L-Threonine by Brevibacterium Flavum ATCC 14067, To select the strain which produce the highest threonine, mutants ere induced by N-methyl-N'-nitro-N-nitrosoguanidine treatment. The composition of media and cultural condition for its overproduction of threonine were also studied. In a threonine producer, strain B-13(Met-) was the strain producing the highest amount of threonige among methionine, lysine and isoleucine auxotrophs. The following results were obtained. 1. The wild strain and B-13(Met-) produced threonine 1.4mg/ml and 4.86mg/ml , respectively. 2. The optimum composition of medium for producing threonine by Brevibacterium Flavum B-13 was glucose 10%, ammonium sulfate 4%, potassium phosphate monobasic 0.2%, magnesium sulfate 0.05%, biotin $200{\mu}l$, thiamine $300{\mu}l$. Addition of nicotinic acid also led to increase L-threonine production. 3. In addition of organic nutrients to the fermentation medium, peptone n'ere effective and addition of methionine $100{\mu}g/ml$ produced the highest amount of L-Threonine. Aspartic acid and homoserine were also effective when these amino acid were added to the fermentstion medium. 4. Cultural conditon on threonine production by B-16 were investigated. The optimum pH was 7.0-8.0. The highest amount of threnine was produced after 4 days of cultural period.

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