• Title/Summary/Keyword: Body weight distribution

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Fangchinoline Has an Anti-Arthritic Effect in Two Animal Models and in IL-1β-Stimulated Human FLS Cells

  • Villa, Thea;Kim, Mijin;Oh, Seikwan
    • Biomolecules & Therapeutics
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    • v.28 no.5
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    • pp.414-422
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    • 2020
  • Fangchinoline (FAN) is a bisbenzylisoquinoline alkaloid that is widely known for its anti-tumor properties. The goal of this study is to examine the effects of FAN on arthritis and the possible pathways it acts on. Human fibroblast-like synovial cells (FLS), carrageenan/kaolin arthritis rat model (C/K), and collagen-induced arthritis (CIA) mice model were used to establish the efficiency of FAN in arthritis. Human FLS cells were treated with FAN (1, 2.5, 5, 10 µM) 1 h before IL-1β (10 ng/mL) stimulation. Cell viability, reactive oxygen species measurement, and western blot analysis of inflammatory mediators and the MAPK and NF-κB pathways were performed. In the animal models, after induction of arthritis, the rodents were given 10 and 30 mg/kg of FAN orally 1 h before conducting behavioral experiments such as weight distribution ratio, knee thickness measurement, squeaking score, body weight measurement, paw volume measurement, and arthritis index measurement. Rodent knee joints were also analyzed histologically through H&E staining and safranin staining. FAN decreased the production of inflammatory cytokines and ROS in human FLS cells as well as the phosphorylation of the MAPK pathway and NF-κB pathway in human FLS cells. The behavioral parameters in the C/K rat model and CIA mouse model and inflammatory signs in the histological analysis were found to be ameliorated in FAN-treated groups. Cartilage degradation in CIA mice knee joints were shown to have been suppressed by FAN. These findings suggest that fangchinoline has the potential to be a therapeutic source for the treatment of rheumatoid arthritis.

The Effect of Coptidis Rhizoma and Glycyrrhiza Uralensis on Lipid Deposition with Nonalcoholic Fatty Liver Disease (NAFLD) (황련-감초 추출물의 지방축적 감소를 통한 비알콜성지방간 개선 효과)

  • Ahn, Sang Hyun;Kim, Ki Bong
    • The Journal of Pediatrics of Korean Medicine
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    • v.33 no.2
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    • pp.12-21
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    • 2019
  • Objectives Coptidis Rhizoma and Glycyrrhiza Uralensis are herbs that treat obesity and dampness-phlegm. The aim of this study is to investigate the efficacy of Coptidis Rhizoma and Glycyrrhiza Uralensis on lipid deposition with nonalcoholic fatty liver disease (NAFLD). Methods Male 6-week-old C57BL/6 male mice were divided into three groups: control group (Ctrl), high fat diet group (HFF), and high fat diet with Coptidis Rhizoma and Glycyrrhiza Uralensis extract administration group (CGT). Each 10 mice were allocated to each group (total of 30 mice). All mice were allowed to eat fat rich diet freely throughout the experiment. To examine the effect of Coptidis Rhizoma and Glycyrrhiza Uralensis, we observed weight changes, total cholesterol and glucose levels, lipid blot distributions, PGC-1, p-$I{\kappa}B$, and p-JNK. Results Body weights for all mice were measured and analyzed the difference between the groups. Weight gain was significantly lower in CGT group than the HFF group. Total cholesterol and glucose levels were significantly lower in CGT group. The distribution of lipid blots and positive reaction of PGC-1 were significantly lower in CGT group. The positive reaction of p-$I{\kappa}B$ in hepatic tissues was significantly lower in CGT group. The positive reaction of p-JNK in hepatic tissues was significantly lower in CGT group. Conclusions Coptidis Rhizoma and Glycyrrhiza Uralensis have the effect of improving non - alcoholic fatty liver induced insulin resistance through regulation of lipid metabolism.

The Study on Vancomycin Pharmacokinetics and Dosing Guideline in Korean Neonates (한국 신생아에서의 Vancomycin 약동학과 Dosing Guideline에 대한 연구)

  • Choi, Sung Joo;Suh, Okkyung;Lee, Suk Hyang;Shin, Hyun Taek;Ro, Hwan Seong;Pi, Soo-Young
    • Korean Journal of Clinical Pharmacy
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    • v.6 no.2
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    • pp.7-13
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    • 1996
  • The purposes of this study were to define the pharmacokinetic parameters of vancomycin in Korean neonates, to evaluate current neonatal vancomycin dosing guideline being used in a teaching hospital, and to develop the optimal vancomycin dosing guideline. The evaluation of 35 sets of peak and trough concentrations drawn on current dosing regimen showed that $29\%$ of peak concentrations and $46\%$ of though concentrations were within therapeutic range. Otherwise, pharmacokinetic parameters, based on 62 sets of peak and trough serum concentrations obtained from 39 neonates, showed that mean vancomycin clearance (CL), volume of distribution (Vd), and terminal elimination half-life were $0.13\pm0.08\;L/hr,\;0.94\pm0.48\;L,\;and\;5.6\pm2.13$ hours, respectively. Volume of distribution (Vd) normalized for body weight remained constant throughout PCA range, whereas the absolute CL (r=0.74) and normalized CL (r=0.36) showed high correlation with PCA. Also, the normalized CL showed a strong inverse correlation (r=-0.55) with serum creatinine concentrations (SrCr). Based on the high correlation among PCA serum creatinine concentration, CL, and the daily dosage requirements, the following dosing guideline for vancomycin in neonates was suggested: 10 mg/kg $12{\sim}18$ hourly for < 30 weeks PCA and < 0.6 mg/dl SrCr; 10 mg/kg 18 hourly for < 30 weeks PCA and $0.6{\sim}1.2$ mg/dl SrCr; 10 mg/kg 8 hourly for $30\sim44$ weeks PCA and < 0.6 mg/dl SrCr; 10 mg/kg 12 hourly for $30\sim44$ weeks PCA and $0.6{\sim}1.2$ mg/dl SrCr.

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Distribution of Fluoroquinolones in the Carp (Cyprinus carpio) and Eel (Anguilla japonica) following their Oral Administration (양식 잉어 및 뱀장어에 경구투 fluoroquinolone계 항생제의 체내 잔류량의 변화)

  • Jo, Mi-Ra;Park, Kun-Ba-Wui;Lee, Hee-Jung;Kim, Ji-Hoe;Lee, Tae-Seek;Jung, Sung-Hee;Lee, Doo-Seog;Yoon, Ho-Dong;Kim, Poong-Ho
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.43 no.6
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    • pp.623-628
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    • 2010
  • The distribution of fluoroquinolones was investigated in the carp (Cyprinus carpio) and eel (Anguilla japonica) after an oral dose of 20 mg/kg body weight/day for 35 days. Blood samples were collected at 5 and 10 hours and 1, 2, 3, 5, 7, 9, 13, 20, 30, and 35 days after treatment. The fluoroquinolone concentrations were determined high- performance liquid chromatography with an ultraviolet detector. The recovery rates of fluoroquinolones in the fish samples ranged from 91.4-96.6, 91.2-96.5, and 90.4-98.6% for concentrations of 0.1, 0.5, and $1.0\;{\mu}g/g$, respectively. In the blood of carp, ciprofloxacin, enrofloxacin, norfloxacin, and sarafloxacin reached maximums level of 11.03, 9.37, 9.10, and $9.81\;{\mu}g/g$ 10 hours, 1 day, 10 hours, and 10 hours after treatment, respectively. In the eel blood, these reached maximum levels of 12.65, 11.18, 11.91, and $8.74\;{\mu}g/g$ all at 10 hours. Carp sample concentrations of ciprofloxacin, enrofloxacin, norfloxacin, and sarafloxacin were not measurable 20, 30, 20, and 20 days after treatment, respectively, in all experiments (

Calculation of a First-In-Man Dose of 7-O-Succinyl Macrolactin A Based on Allometric Scaling of Data from Mice, Rats, and Dogs

  • Noh, Keumhan;Kang, Wonku
    • Biomolecules & Therapeutics
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    • v.25 no.6
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    • pp.648-658
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    • 2017
  • 7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.

Genetic Identification Monitoring of Cobitidae Distribution in Korea (국내에서 유통되는 미꾸리과(Cobitidae) 어종의 분자동정 모니터링)

  • Kim, Hyunsuk;Shin, Jiyoung;Yang, Junho;Cha, Eunji;Yang, Ji-young
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.55 no.5
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    • pp.742-750
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    • 2022
  • This study aimed to monitor the distribution of Cobitidae in Korea by the identification of species using genetic analysis. Based on the genetic analysis, Cobitidae species in four of five domestic fish farms consisted of only Chinese muddy loach Misgurnus mizolepis, but muddy loach Misgurnus anguillicaudatus was also present it in one fish farm. In the case of imported Cobitidae species, in addition to Chinese muddy loach and muddy loach, the harmful species Paramisgurnus dabryanus, was also present. Chinese muddy loach accounted for 20%, 67%, and 60% of the S6, S7, and S8 samples, respectively. An analysis of the total length, body length, and weight showed that domestic Chinese muddy loach showed higher values than imported muddy loach, and imported Chinese muddy loach showed similar values to P. dabryanus. There were no significant differences in the country of origin of the three species. Thus, the mitochondrial cytochrome c oxidase subunit I gene sequence was analyzed and compared the verification of species identification. The three species of Cobitidae were genetically divided into three groups and determined to have genetic differences. These results indicate that it is necessary to reduce the heterogeneous mixing rate through discriminating species by genetic analysis.

The Relationship of Age, Body Mass Index, and Individual Habit to Bone Mineral Density in Adults (성인의 연령, 체질량지수 및 생활습관과 골밀도의 관계)

  • Park, Soung-Ock;Lee, In-Ja;Shin, Gwi-Soon
    • Journal of radiological science and technology
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    • v.31 no.4
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    • pp.367-377
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    • 2008
  • We studied the change of bone mineral density (BMD) by age, body mass index (BMI), coffee, carbonated drink, alcohol, smoking, and exercise in adults who checked in health center. The number of study subjects was total 268 persons (women of 136 persons and men of 132 persons). The BMD was determined in lumbar spine and femoral neck by dual energy x-ray absorptiometry. And we got some results as below : 1. In women, mean body height was $155.8{\pm}6.0cm$, mean body weight was $56.8{\pm}7.9kg$, and mean BMI was $23.4{\pm}3.1kg/m^2$. In men, mean body height was $169.1{\pm}6.0cm$, mean body weight was $69.0{\pm}9.5kg$, and mean BMI was $24.1{\pm}2.7kg/m^2$. 2. BMD decreased as age increased, and the age was the most determinant factor for BMD (p<0.01). Women's BMD decreased rapidly in the groups aged $\geq$50s, while men's BMD decreased gradually with age. In addition, for both sex, lower BMD was measured in lumbar spine than in femoral neck. 3. BMD increased in high BMI, and BMD with BMI increased distinctly in the group aged 50s. But their relationship was not significant. 4. In view of the distribution by three BMD categories, women's BMD was mostly normal in the groups aged $\geq$40s, but the rate of osteopenia and osteoporosis was similar in the group aged 50s, and the rate of osteoporosis was the highest in the groups aged 60s and 70s. Men's BMD was mostly normal through all groups except the group aged 70s. 5. Coffee and carbonated drink were not influenced in BMD. But alcohol-drinking group showed higher BMD than non-drinking group, and alcohol was statistically significant determinant for BMD (p<0.05). Smoking and exercise were not statistically significant determinant of BMD.

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Effect of Dietary Supplementation of Glutathione on Blood Biochemical Changes and Growth Performances of Holstein Calves

  • Kim, Jong-Hyeong;Mamuad, Lovelia L.;Lee, Hyun-June;Ki, Kwang-Seok;Lee, Wang-Shik;Ha, Jong-K.;Lee, Sang-Suk
    • Asian-Australasian Journal of Animal Sciences
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    • v.24 no.12
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    • pp.1711-1717
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    • 2011
  • The objective of this experiment was to evaluate the effect of dietary supplementation of glutathione (GSH) on health, solid feed consumption, nutrient intake, body weight gain (BWG), feed efficiency, blood metabolites and the occurrence of diarrhea in Holstein neonatal calves. The calves were fed plain milk as a control (CON) or milk with GSH supplementation. Sixteen calves were separated from their mothers immediately after birth, moved into individual cages and fed colostrum for the first three days. For GSH supplementation, three grams of GSH powder were mixed in 1.8 L of heat-treated milk and placed in a plastic bottle with a rubber nipple. The calves were fed GSH-supplemented milk only once out of four daily feedings. For the first 25 d, calves were fed 1.8 L of milk four times per day. Milk feeding frequency was reduced to three times per day from days 26 to 30, followed by twice a day from days 31 to 44, and once a day from days 45 to 49, after which they were weaned at day 50. Body weight gain (BWG), feed consumption, and growth performance were monitored until day 70. The dietary supplementation of GSH had no effect on daily feed intake and growth performance in growing calves. Hematological results revealed red blood cell distribution width (RDW) was lower, and mean corpuscular volume (MCV) was significantly higher in calves fed GSH. Serum lactate dehydrogenase (LDH) concentrations were lower in calves fed GSH. Rectal temperature at day 70 was higher in calves that did not receive GSH, while mean frequency of diarrhea and enteritis was less in calves fed GSH. It is concluded from the present study that BW gain, total dry matter intake (DMI), feed efficiency, and breathing rate did not differ between groups. However, there were some positive blood parameters and the mean frequency of diarrhea and enteritis was less in calves fed GSH compared to CON which did not receive GSH. With the results obtained, supplementation of GSH is highly recommended.

The Effect of Insoluble Dietary Fiber Extracted from Chinese Cabbage Waste on Plasma Lipid Profiles in Rats Fed a High Fat Diet (배추 폐기물로부터 분리한 불용성 식이섬유가 고지방 식이를 급여한 쥐의 혈중 지질농도에 미치는 영향)

  • Liu, Wenli;Ko, Kang-Hee;Kim, Hag-Ryeol;Kim, In-Cheol
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.1
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    • pp.33-40
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    • 2012
  • This study investigated the lipid profiles for the possible improving activity of insoluble dietary fiber extracted from cabbage waste discarded during kimchi manufacture and market distribution. Enzyme-treated Insoluble Dietary Fiber (EIDF) is the remnants of crude dietary fiber (CDF) treated by ${\alpha}$-amylase, protease, and amyloglucosidase after removal of soluble materials from cabbage waste. The insoluble dietary fiber of CDF and EIDF in cabbage waste was $65.33{\pm}0.33%$ and $73.57{\pm}0.09%$, respectively. To examine the effects of EIDF on plasma cholesterol concentration, two group of rats were fed either a high fat diet (HFD) or a HFD containing 0.1~1.0% EIDF for 4 weeks. The body weight of all groups was not significantly different (p<0.05) but the body weight of EIDF+HFD groups was less than that of the HFD group (p<0.1). Compared with the HFD group, EIDF also lowered serum levels of total triglycerides to 11.2~23.3% and cholesterol to 26.8~28.5%. In EIDF+HFD groups, the HDL-cholesterol level increased by 7.2~26.1%, while LDL-cholesterol especially decreased by 51.0~61.4% and VLDL-cholesterol by 16.9~26.4%. The atherogenic index of EIDF+HFD groups was also reduced twice that of the HFD group. From these results, EIDF from cabbage waste could be a potential effective food ingredient for improving lipid profiles.

Pharmacokinetic Preformulation Study of rH IL-2 (인터루킨-2의 제제설계를 위한 체내 동태학적 연구)

  • Seo, Min-Seok;Shim, Chang-Koo;Kwon, Jong-Bum;Na, Do-Sun;Lee, Sun-Bok;Hahm, Kyung-Soo;Han, Moon-Hi
    • YAKHAK HOEJI
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    • v.34 no.4
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    • pp.238-243
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    • 1990
  • Pharmacokinetic characteristics of recombinant human interleukin-2 (rH IL-2) wre studied in the rat. First, different doses of rH IL-2 ranging from 6,400 to 1,600,000 U/kg were injected intravenously and the effect of dose size on the pharmacokinetics was examined. There was no dose dependency in the pharmacokinetics of rHIL-2 in the dose range of 6,400-40,000 U/kg. But at the dose of 1,600,000 U/kg, there was a severe hemolysis throughout the experiment and the pharmacokinetic parameters such as Vdss and CLt were significantly increased compared to those obtained from lower doses. It also showed that this drug is hardly distributed to the peripheral tissues and hardly eliminated from the body, since the valume of distribution (Vdss) and total body clearance (CLt) were 45-75 ml/kg and 1-2 ml/min/kg, respectively. The Vdss is close to the actual plasma volume and the CLt is less than glomerular filtration rate (GFR). Therefore it seemed that rH IL-2 is distributed only in the plasma pool and hardly filtered in the kidney due to its very large molecular weight. Second, rH IL-2 was administered to the rat via several routes such as hepatic portal vein (PV), intraperitoneal (IP), peroral (PO) and intranasal (IN) routes. The bioavailabilities (BA) of PV, IP, PO and IN routes were 96.8, 4.9, 0 and 0.1%, respectively. The addition of some nasal absorption enhancers such as taurocholate, taurodeoxycholate, glycocholate and glycodeoxycholate did not increase the BA of intranasaly administered rH IL-2. The result is contrast to the effect of these bile salts on the nasal absorption of ${\alpha}-inteferon$. Considering it together with the pharmacokinetic parameters, very large molecular weight of rH IL-2 seemed again to be the cause to very poor membrane permeability.

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