• Title/Summary/Keyword: high dose amino acid

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Peptides derived from high voltage-gated calcium channel β subunit reduce blood pressure in rats

  • Hyung Kyu Kim;Jiyeon Jun;Tae Wan Kim;Dong-ho Youn
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.5
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    • pp.481-491
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    • 2023
  • The β subunits of high voltage-gated calcium channels (HGCCs) are essential for optimal channel functions such as channel gating, activation-inactivation kinetics, and trafficking to the membrane. In this study, we report for the first time the potent blood pressure-reducing effects of peptide fragments derived from the β subunits in anesthetized and non-anesthetized rats. Intravenous administration of 16-mer peptide fragments derived from the interacting regions of the β1 [cacb1(344-359)], β2 [cacb2(392-407)], β3 [cacb3(292-307)], and β4 [cacb4(333-348)] subunits with the main α-subunit of HGCC decreased arterial blood pressure in a dose-dependent manner for 5-8 min in anesthetized rats. In contrast, the peptides had no effect on the peak amplitudes of voltage-activated Ca2+ current upon their intracellular application into the acutely isolated trigeminal ganglion neurons. Further, a single mutated peptide of cacb1(344-359)-cacb1(344-359)K357R-showed consistent and potent effects and was crippled by a two-amino acid-truncation at the N-terminal or C-terminal end. By conjugating palmitic acid with the second amino acid (lysine) of cacb1(344-359)K357R (named K2-palm), we extended the blood pressure reduction to several hours without losing potency. This prolonged effect on the arterial blood pressure was also observed in non-anesthetized rats. On the other hand, the intrathecal administration of acetylated and amidated cacb1(344-359)K357R peptide did not change acute nociceptive responses induced by the intradermal formalin injection in the plantar surface of rat hindpaw. Overall, these findings will be useful for developing antihypertensives.

Characterization of an Anti-gout Xanthine Oxidase Inhibitor from Pleurotus ostreatus

  • Jang, In-Taek;Hyun, Se-Hee;Shin, Ja-Won;Lee, Yun-Hae;Ji, Jeong-Hyun;Lee, Jong-Soo
    • Mycobiology
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    • v.42 no.3
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    • pp.296-300
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    • 2014
  • We selected Pleurotus ostreatus from among several edible mushrooms because it has high anti-gout xanthine oxidase (XOD) inhibitory activity. The maximal amount of XOD inhibitor was extracted when the Pleurotus ostreatus fruiting body was treated with distilled water at $40^{\circ}C$ for 48 hr. The XOD inhibitor thus obtained was purified by Sephadex G-50 gel permeation chromatography, ultrafiltration, $C_{18}$ solid phase extraction chromatography and reverse-phase high-performance liquid chromatography with 3% of solid yield, and its XOD inhibitory activity was 0.9 mg/mL of $IC_{50}$. The purified XOD inhibitor was a tripeptide with the amino acid sequence phenylalanine-cysteine-histidine and a molecular weight of 441.3 Da. The XOD inhibitor-containing ultrafiltrates from Pleurotus ostreatus demonstrated dose-dependent anti-gout effects in a Sprague-Dawley rat model of potassium oxonate-induced gout, as shown by decreased serum urated levels at doses of 500 and 1,000 mg/kg, although the effect was not as great as that achieved with the commercial anti-gout agent, allopurinol when administered at a dose of 50 mg/kg.

General and Genetic Toxicology of Enzyme-Treated Ginseng Extract - Toxicology of Ginseng Rh2+ -

  • Jeong, Mi-Kyung;Cho, Chong-Kwan;Yoo, Hwa-Seung
    • Journal of Pharmacopuncture
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    • v.19 no.3
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    • pp.213-224
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    • 2016
  • Objectives: Ginseng Rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have potent anticancer activity. We conducted general and genetic toxicity tests to evaluate the safety of ginseng Rh2+. Methods: An acute oral toxicity test was performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A 14-day range-finding study was also conducted to set dose levels for the 90-day study. A subchronic 90-day toxicity study was performed at dose levels of 1,000 and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL) of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid-requiring strains of Salmonella typhimurium and Escherichia coli (E. coli), a chromosome aberration test with Chinese hamster lung (CHL) cells, and an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Ministry of Food and Drug Safety. Results: According to the results of the acute oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological effect of ginseng Rh2+ was observed in body-weight changes, food consumption, clinical signs, organ weights, histopathology, ophthalmology, and clinical pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and no target organ was found in this test. In addition, no evidence of mutagenicity was found either on the in vitro genotoxicity tests, including the Ames test and the chromosome aberration test, or on the in vivo in mice bone marrow micronucleus test. Conclusion: On the basis of our findings, ginseng Rh2+ is a non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used as a novel adjuvant anticancer agent that is safe for long-term administration.

Irradiation of Pork Meat for Improvement of Hygienic and Keeping Quality (돈육의 위생화와 품질보존을 위한 감마선 조사)

  • 곽희진;계수경;강일준
    • Journal of the East Asian Society of Dietary Life
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    • v.8 no.4
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    • pp.430-440
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    • 1998
  • Meat is a perishable product since it offers favorable conditions for microbial contamination and multiplication. Besides, undercooked and raw meat has been linked to outbreaks of hemorrhagic diarrhea due to the presence of microbial pathogens. Therefore, this study was conducted to find out the effect of the use of gamma-irradiation in order to improve preservation and eliminate this microorganisms. The Initial level of microbial contamination in pork was 1.1$\times$10$^3$ CFU/g (aerobic bacteria), 5.3$\times$10$^3$CFU/g (psychrophile), 3.1$\times$10$^3$ CFU/g (coliforms) and 3.2$\times$10$^3$ CFU/g(Listeria), All kinds of contaminated microorgnisms were sterilized by gamma irradiation at 3 kGy. The proximate composition of pork was not significantly changed by irradiation dose and storage period. The pH was slightly increased during storage period and titratable acidity decreased. However, no significant changes in pH and acidity were observed by gamma irradiation. There was no difference in total amino acid content regardless of irradiation dose and storage period. Glutamic acid was detected at high levels throughout the storage period. The major mineral compositions of pork were potassium, phosphorus, sodium, magnesium. No significant difference in the components of minerals were observed by gamma irradiation.

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Modification and inactivation of Cu,Zn-superoxide dismutase by the lipid peroxidation product, acrolein

  • Kang, Jung Hoon
    • BMB Reports
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    • v.46 no.11
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    • pp.555-560
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    • 2013
  • Acrolein is the most reactive aldehydic product of lipid peroxidation and is found to be elevated in the brain when oxidative stress is high. The effects of acrolein on the structure and function of human Cu,Zn-superoxide dismutase (SOD) were examined. When Cu,Zn-SOD was incubated with acrolein, the covalent crosslinking of the protein was increased, and the loss of enzymatic activity was increased in a dose-dependent manner. Reactive oxygen species (ROS) scavengers and copper chelators inhibited the acrolein-mediated Cu,Zn-SOD modification and the formation of carbonyl compound. The present study shows that ROS may play a critical role in acrolein-induced Cu,Zn-SOD modification and inactivation. When Cu,Zn-SOD that has been exposed to acrolein was subsequently analyzed by amino acid analysis, serine, histidine, arginine, threonine and lysine residues were particularly sensitive. It is suggested that the modification and inactivation of Cu,Zn-SOD by acrolein could be produced by more oxidative cell environments.

Nutritional Components and Antioxidative Activities of Jujube (Zizyphus jujuba) Fruit and Leaf (대추 열매와 잎의 영양성분 및 항산화 활성)

  • Kim, Il-Hun;Jeong, Chang-Ho;Park, Soo-Jeong;Shim, Ki-Hwan
    • Food Science and Preservation
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    • v.18 no.3
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    • pp.341-348
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    • 2011
  • The nutritional components and antioxidative activities of jujube fruit and leaf were investigated and analyzed to provide basic data for functional food materialization and processing. The nitrogen-free extract contents of the fruit and leaf were 71.92% and 41.51%, respectively. The mineral components of the fruit and leaf were rich in Ca (72.14 and 3,252.09 mg/100 g), K (899.82 and 1,708.12 mg/100 g), and P (172.11 and 286.28 mg/100 g), respectively. The major free sugars of the fruit were glucose (13.01 %) and fructose (7.35%); and of the leaf, sucrose (3.94%) and fructose (0.75%). The ascorbic acid contents were higher in fruit (135.73 mg/100 g) than in the leaf (100.43 mg/100 g). The analysis of the component amino acid showed a relatively high ratio of glutamic acid, aspartic acid, proline, and essential amino acids of leucine, but a low methionine and cystine content. The ABTS and FRAP assays indicated that the butanol fraction of the leaf was a more potent radical scavenger and reducing agent than the other five solvent fractions. The butanol fraction of the leaf also presented inhibitory effects against lipid peroxidation in a dose-dependent manner. Therefore, this study verified that the butanol fraction of the leaf has strong antioxidative activities that are correlated with its high level of phenolics, particularly rutin and quercitrin. These phenolics of jujube leaf can be utilized as effective and safe functional food substances, i.e., natural antioxidants.

Quality Characteristics and Anti-Diabetic Effect of Yacon Vinegar (야콘 식초의 품질특성 및 항당뇨 효과)

  • Lee, Mi-Kyung;Choi, Sa-Ra;Lee, Jin;Choi, Yun-Hong;Lee, Ju-Hye;Park, Kyung-Uk;Kwon, Seung-Hyek;Seo, Kwon-Il
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.1
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    • pp.79-86
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    • 2012
  • This study was performed to investigate the physiochemical properties and anti-diabetic effect of yacon vinegar by two-step fermentation. Yacon was matured at room temperature for 20 days. The sugar content of yacon juice prepared from mature yacon was approximately $14^{\circ}Brix$. In the first stage, yacon wine was produced from the juice at $28^{\circ}C$ for 6 days. In the second stage, acetic acid fermentation was conducted at $30^{\circ}C$ and 200 rpm for 6 days to produce yacon vinegar with 4.75% acidity. The major free sugars of yacon vinegar were glucose and fructose at 2,072.12 mg% and 463.95 mg%, respectively. The acetic acid content was the highest of the major organic acids at 3,881.44 mg%. The total free amino acid content was 62.88 mg% with the main free amino acids being proline, ${\gamma}$-amino-n-butyric acid and ornithine. The major minerals of yacon vinegar were Ca, K and Mg. The in vivo anti-diabetic activity of yacon vinegar was investigated in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice. Diabetic mice were administered orally with 10% yacon juice and two yacon vinegars (5% and 10%) at a dose of 7 mL/kg body weight once per day for 4 weeks. Five% yacon vinegar improved the fasting blood glucose levels and glucose tolerance test significantly compared to the diabetic control group (p<0.05). Yacon vinegar increased the pancreatic C-peptide concentration in a dose-dependent manner. These results show that 5% yacon vinegar has a more potent effect on ameliorating hyperglycemia than 10% yacon juice.

The Efficacy and Safety of High Dose Amino Acid Administration to Preterm Infants in the Early Neonatal Period (미숙아의 출생초기에 고용량 아미노산 투여의 유효성 및 안전성 평가)

  • Yoon, Ji-Hye;Park, Hyo-Jung;Han, Chae-Won;Chang, Hyo-In;Chung, Seon-Young;In, Yong-Won;Lee, Young-Mi;Sohn, Kie-Ho
    • Korean Journal of Clinical Pharmacy
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    • v.22 no.4
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    • pp.316-323
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    • 2012
  • 미숙아는 단백질 대사 속도가 빠르기 때문에 성장이 충분히 이루어질 수 있도록 ASPEN 가이드라인에서는 아미노산 초기용량을 1-2 g/kg/day로 투여하도록 권장하고 있다. 또한 최근 여러 연구에서 출생초기 고용량 (1.5-4 g/kg/day) 아미노산 투여에 대해 보고하고 있다. 이를 근거로 하여 삼성서울병원 신생아 중환자실에서도 2009년 6월부터 아미노산 초기용량을 0.5 g/kg/day에서 1.5~2 g/kg/day으로 증량하여 투여하고 있다. 본 연구에서는 신생아 중환자실에서 정맥영양요법을 받은 미숙아를 대상으로 고용량 아미노산 공급 효과를 평가하고자 하였다. 2009년 6월 기준으로 출생 후 48시간 이내에 0.5 g/kg/day로 아미노산을 투여 받은 저용량 환아군(38명: 대조군)과 1.5~2 g/kg/day로 투여 받은 고용량 환아군(38명: 시험군)의 전자의무기록을 후향적으로 검토하였다. 고용량 아미노산 공급 효과를 체중증가량 및 총 정맥영양기간, 경구 및 경장 영양 시작 시기, 재원기간으로 평가하였고, 안전성 평가를 위해 혈액화학검사 및 합병증을 조사하였다. 또한 두 군의 인구학적 및 주산기 인자, 영양 공급량 등에 대해 조사하였다. 두 군의 인구학적 및 주산기 인자는 재태기간에서만 차이를 보였으며, 시험군에서 재태기간이 길었다(p < 0.05). 초기 아미노산 용량만이 생후 28일간 일평균 체중증가량에 영향을 미치는 인자였으며 시험군의 일평균 체중증가량이 대조군보다 유의하게 큰 것으로 나타났다($12.6{\pm}4.5$ g/day vs $9.8{\pm}4.5$ g/day, p < 0.05). 목표 체중증가량에 도달한 비율도 시험군이 높았다(65.8% vs 47.4%). 총 공급열량, 총 정맥영양 공급 기간과 경구 및 경장 영양 시작 시기는 두 군간 차이가 없었으나 시험군에서 목표열량 도달시간, 신생아 중환자실 재원기간이 단축되었다(p < 0.05). 혈액화학검사 결과 및 대사성 산증, 호흡곤란증후군, 괴사성장염 발생은 두 군간 차이가 없었으며 고혈당 및 감염, 기관지폐이형증, 뇌실내출혈 발생률은 대조군에서 유의하게 높았다(p < 0.05). 연구 결과, 미숙아에서 출생 초기 고용량 아미노산 공급은 혈액화학검사 이상이나 합병증 없이 체중증가와 재원기간 감소에 효과가 있음을 확인하였다. 따라서 미숙아에 대한 출생초기 영양지원으로 1.5~2 g/kg/day 아미노산 공급은 안전하고 효과적이라고 사료된다.

Intravenous administration of L-tryptophan stimulates gastrointestinal hormones and melatonin secretions: study on beef cattle

  • Lee, Sang-Bum;Lee, Kyung-Won;Wang, Tao;Lee, Jae-Sung;Jung, U-Suk;Nejad, Jalil Ghassemi;Oh, Young-Kyoon;Baek, Youl-Chang;Kim, Kyoung Hoon;Lee, Hong-Gu
    • Journal of Animal Science and Technology
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    • v.61 no.4
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    • pp.239-244
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    • 2019
  • This study aimed to determine the effective dose of intravenous administration of L-tryptophan (L-T) on gastrointestinal hormones (GIH) secretions and melatonin using Hanwoo cattle. Three steers ($362{\pm}23kg$) fitted with indwelling jugular vein catheters were assigned in a $3{\times}3$ Latin square design. Treatments were intravenous administration of saline (control), 28.9 mg L-T/kg body weight (BW; low) and 57.8 mg L-T/kg BW (high) L-T for 1 day with 7 days of adaptation. Samples were collected after adaptation period at -60, 0, 30, 60, 90, 120, 150, 180, 240, and 300 min of sampling day. The levels of serum cholecystokinin (CCK) and secretin were higher (p < 0.05) in the high L-T group than those in the other groups. Serum Melatonin (MEL) levels were increased upon L-T administration (p < 0.05) in the high L-T group. Taken together, the effective dose of L-T administration was defined at 57.8 mg L-T/kg BW in order to stimulate increase of GIH and MEL.

A Case of Congenital Partial Nephrogenic Diabetes Insipidus (선천성 부분 신성 요붕증 1례)

  • Mo, Eun Ha;Nam, In Hye;Chung, Min Ja;Yu, Jae Hong
    • Clinical and Experimental Pediatrics
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    • v.45 no.7
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    • pp.902-905
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    • 2002
  • The most common form of genetic nephrogenic diabetes insipidus(NDI), a rare inherited disorder, is congenital and is transmitted in an X-linked recessive mode. It is refractory to the antidiuretic effect of normal to moderately increased levels of plasma arginine vasopressin(AVP) but, in some cases, may respond to high levels of the hormone or its analogue, deamino-D-arginine vasopressin(DDAVP). X-linked congenital NDI has now been linked to over 128 different mutations in diverse coding regions of the AVP receptor 2(AVPR2) gene. The functional effects of these mutations vary from complete loss of responsiveness to a simple shift to the right in the dose response curve. We report a case of congenital partial NDI, with transversion of A to G at codon 280 of the AVPR2 gene, resulting in a subsequent change of amino acid from tyrosine to cysteine, and that has been effective with hydrochlorothiazide and high dose of DDAVP.