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Pharmacokinetics of Propentofylline and the Quantitation of Its Metaolite Hydroxypropentofylline in Human Volunteers

  • Kwon, Oh-Seung;Chung, Youn-Bok;Kim, Min-Hee;Hahn, Hoh-Gyu;Rhee, Hee-Kyung;Ryu, Jae-Chun
    • Archives of Pharmacal Research
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    • v.21 no.6
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    • pp.698-702
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    • 1998
  • Propentofylline (PPF, 3-methyl-1-(5-oxohexyl)-7-propylxanthine) has been reported to be effective for the treatment of both vascular dementia and dementia of the Alzheimer type. The pharmacological effects of PPF may be exerted via the stimulation of nerve growth factor, increased cerebral blood flow, and inhibition of adenosine uptake. The objectives of this experiment are to determine the kinetic behavior of PPF, to identify, and to quantify its metabolite in human. Blood samples were obtained from human volunteers following oral administration of 200mg of PPF tablets. For the identification and quantification of the metabolite, 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine (PPFOH), PPFOH was synthesized and identified by gas chromatography/mass spectroscopy (GC/MS) and $^1H$-nuclear magnetic resonance spectroscopy. The molecular weight of synthesized metabolite is 308 dalton. The PPF and PPFOH in plasma were extracted with diethyl ether and identified by electron impact GC/MS. The plasma concentrations of PPF and PPFOH were determined by gas chromatography/nitrogen phosphorus detector in plasma and their pharmacokinetic parameters were determined. The mean half-life of PPF was 0.74 hr. The areas under the curve (AUCs) of PPF and PPFOH were 508 and 460ng.hr/ml, respectively. $C_{max}$ of PPF was about 828.4ng/ml and the peak concentration was achieved at about 2.2 hr ($T_{max}$). These results indicate that PPF is rapidly disappeared from blood due to extensive metabolism into PPFOH.

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COMPARISON OF AFRIKANER- AND BRAHMAN- CROSS CATTLE IN PAPUA NEW GUINEA

  • Holmes, J.H.G.;McKinnon, M.J.;Seifert, G.W.;Schottler, J.H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.5 no.3
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    • pp.419-426
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    • 1992
  • After the virtual eradication of cattle during World War II, Papua New Guinea herds were rebuilt with Shorthorn and Aberdeen Angus cattle from Australia. These, and Red Sindhi and Sahiwal, imported in 1952, were considered unsuitable breeds. In 1954, Department of Agriculture, Stock and Fisheries imported three Brahman bulls and three heifers from Texas and in 1960 began importations of Afrikaner from Queensland. In Central Province, Brahmans were crossed with Angus and at Erap (Morobe) the hottest place in Papua New Guinea, Shorthorns were crossed with Afrikaners. In 1965, Brahman and Brahman-cross were sent to Erap. Records of breeding and growth rates were collected for use in upgrading in cattle of the basis of performance, not pedigree. The data are not ideal for genetic analysis, since no control groups were maintained. Birth weights (BWT), weaning weights (WWT) and calving intervals (CI) were analysed for the period 1969-1978. After exclusion of unsatisfactory data, 2,514 calf records were used, including both breeds from 1969 to 1973, but only Brahman-cross subsequently. Breed mean BWT ranged only from 30.6 to 33.8 kg. As Brahman content increased, BWT decreased and WWT increased; within a genotype, there was a negative maternal effect of high Brahman content on BWT and a positive effect on WWT which ranged from 138 to 174 kg. Afrikaner calves had heavier BWT but lighter WWT. As expected, bulls were heaviest, heifers lightest and mature cows bore and reared heavier calves. Calving interval (405 days, equivalent to 90% calving) was unaffected by breed but 4-year old cows averaged 423 days. Breed differences in BWT and WWT are consistent with the body of literature on performance of Brahmans and Afrikaners. Since cattle tick are not present and internal parasites are insignificant at Erap, the superiority of Brahmans indicates that they were better at utilizing the mediocre quality grazing of the Markham Valley or were more heat tolerant. Performance selection over ten years resulted in the virtual elimination of Afrikaners, with the final genotype approximately 9/16 Brahman, 3/8 Shorthorn and 1/16 Afrikaner.

Isolation and Characterization of Plutella xylostella Granulovirus Isolated in Korea

  • Wang Yong;Choi Jae Young;Kang Joong Nam;Kim Yang-Su;Choi Heekyu;Roh Jong Yul;Li Ming Shun;Jin Byung Rae;Im Dae Joon;Je Yeon Ho
    • International Journal of Industrial Entomology and Biomaterials
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    • v.11 no.2
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    • pp.87-91
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    • 2005
  • We have first isolated and characterized a Plutella xylostella granulovirus ($P_xGV$) from dead larvae of P. xylostella in Korea. The granule of $P_xGV$ was ovoidal shape with an approximate measure of $350-400nm{\times}150-200nm$, and each granule contained one single rod-shape virion with a mean size of $150-180nm{\times}20-30nm$. The major granule protein, granulin, had a molecular weight of approximately 29kDa. Whereas the nucleotide sequence of the granulin gene was identical to that of previously reported $P_xGV$, nucleotide sequences of two of three putative p10 genes were slightly different from those of reported $P_xGV$. These results suggested that the $P_xGV$ isolated in this study was a novel isolate containing different genomic information.

Prader-Willi syndrome: a single center's experience in Korea

  • Kim, Yea Ji;Cheon, Chong Kun
    • Clinical and Experimental Pediatrics
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    • v.57 no.7
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    • pp.310-316
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    • 2014
  • Purpose: Prader-Willi syndrome (PWS) is a complex genetic disorder that results from the lack of paternally expressed genes in the chromosome 15q11-q13 region. This study was performed to delineate the clinical features of PWS infants and toddlers and the effects of two-year growth hormone (GH) treatment according to gender and age at the start of treatment. Methods: The clinical characteristics and the results of the GH treatment were reviewed retrospectively for 30 PWS patients diagnosed by molecular genetic testing and clinical manifestations. Results: The mean age at diagnosis with PWS was 13.7 months (2-47 months of age). All patients showed the characteristics of facial dysmorphism, including brown hair and almond-shaped eyes. Most patients showed developmental delays/mental retardation (93.3%), cryptorchidism (75%), feeding problems in infancy (73.3%), and neonatal or infantile hypotonia (66.7%). Among 30 patients, 14 PWS infants and toddlers had been treated with GH for more than two years. Two years of GH treatment resulted in an improvement in head circumference-standard deviation score (HC-SDS), body weight-SDS, insulin-like growth factor-1 (IGF-1) SDS, IGF binding protein-3 (IGFBP-3) SDS, lean body mass, and bone mineral content, especially in IGFBP-3 SDS and motor development in PWS patients younger than two years of age. There was significant increase in IGF-1 SDS and IGFBP-3 SDS among male PWS patients after GH treatment. Conclusion: Our study showed increases in IGFBP-3 SDS and an improvement in motor development among individuals under two years of age after GH treatment, and significant difference in IGF-1 SDS and IGFBP-3 SDS by gender.

The Effect of Carbon Monoxide on L-type Calcium Channel Currents in Human Intestinal Smooth Muscle Cells

  • Lim, In-Ja
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.6
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    • pp.357-362
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    • 2003
  • Carbon monoxide (CO) is low molecular weight oxide gas that is endogenously produced under physiological conditions and interacts with another gas, nitric oxide (NO), to act as a gastrointestinal messenger. The aim of this study was to determine the effects of exogenous CO on L-type calcium channel currents of human jejunal circular smooth muscle cells. Cells were voltage clamped with 10 mM barium ($Ba^{2+}$) as the charge carrier, and CO was directly applied into the bath to avoid perfusion induced effects on the recorded currents. 0.2% CO was increased barium current ($I_{Ba}$) by $15{\pm}2$% ($mean{\pm}S.E.$, p<0.01, n=11) in the cells. To determine if the effects of CO on barium current were mediated through the cGMP pathway, cells were pretreated with 1-H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, $10{mu}M$), a soluble guanylyl cyclase inhibitor, and exogenous CO (0.2%) had no effect on barium currents in the presence of ODQ ($2{\pm}1$% increase, n=6, p>0.05). CO mediates inhibitory neurotransmission through the nitric oxide pathway. Therefore, to determine if the effects of CO on L-calcium channels were also mediated through NO, cells were incubated with $N^G-nitro-L-arginine$ (L-NNA, 1 mM), a nitric oxide synthase inhibitor. After L-NNA pretreatment, 0.2 % CO did not increase barium current ($4{\pm}2$% increase, n=6, p>0.05). NO donor, SNAP ($20{\mu}M$) increased barium current by $13{\pm}2$% (n=6, p<0.05) in human jejunal smooth muscle cells. These data suggest that CO activates L-type calcium channels through NO/cGMP dependant mechanism.

Comparison of Physicochemical Prolperties of Cowpea and Mung Bean Starches (동부와 녹두전분의 이화학적 특성비교)

  • 윤계순
    • Journal of the Korean Home Economics Association
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    • v.27 no.1
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    • pp.39-46
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    • 1989
  • Mung bean starch gel (Mook) and gel made from starch of cowpea are similar properties in texture. In order to elucidate the similarity between these two starch gels, some physicochemical properties of cowpea starch were compared with those of mung bean starch. Water bildings capacity of cowpea starch (183.6%) was a little low than that of mung bean starch (184.2%). The solobility, swelling power and optical transmitance of the cowpea starch showed a smiliar pattern to mung bean starch, but cowpea starch had a little lower solubility than mung bean starch. Amylogram of mung bean strach (4, 5, 6, 7%) shoved no peak viscosity but cowpea starch (4, 5, 6%) showed peak viscosity and both starches showed high viscosities when cooling. Cowpea and mung bean starches had the blue value of 0.41 and 0.47, the alkali number of 8.4 and 8.0, the amylose content of 30.5 and 32.1%, the molecular weight of amylose of 30,000 adn 29,258 and glucose unit per segment of amylopectin of 27.6 and 26.8 respectively. The shape of cowpea and mung bean strach granules were round and elliptical, and the mean vlalue of major axis, minor axis and the ratio of these were 20.7 and 21.8 ${\mu}{\textrm}{m}$, 14.6 and 14.4 ${\mu}{\textrm}{m}$ and 1.42 and 1.51, respectively. The extent of retrogradation determined by the glucoamylase digestion method and syneresis showed that cowpea starch gel was larger than that syneresis showed than cowpea starch gel was larger than that of mung bean starch gel. The redults of X-ray diffraction studies showed A pattern for two starches, Diffraction peak of gels disappeared with gelatinization of starches but that of two starch gels storaged for 2 days at 5$^{\circ}C$ showed a similar patterm.

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Interaction between Maternal Serum Folate and the Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms on Infant Birthweight

  • Park, Hye-Sook;Kim, Young-Ju;Ha, Eun-Hee;Lee, Bo-Eun;Park, Bo-Hyun;Lee, Hwa-Young;Park, Eun-Ae;Chang, Nam-Soo;Hong, Yun-Chul
    • Molecular & Cellular Toxicology
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    • v.1 no.2
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    • pp.130-136
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    • 2005
  • The purpose of this study was to evaluate whether the interactions between maternal folate deficiency and methylenetetrahydrofolate reductase (MTHFR) polymorphism increase the risk of elevated maternal serum homocysteine, short gestation and reduced infant birthweight. Healthy pregnant (n = 170; 24-28 gestational weeks; 20-40 years old) women were analyzed for the MTHFR genotype and serum levels of folate and homocysteine, and were then followed for gestational age and infant birthweight. The mean infant birthweight was highest in mothers carrying MTHFR CC and with a normal folate range, and they were followed by mothers carrying MTHFR CT or TT and a normal range of folate or a folate deficiency. Birthweight was the lowest in mothers whose carrying MTHFR CC with folate deficiency. Using two way ANOVA, we found that folate level and the MTHFR polymorphism interacted to affect birth-weight of infants (p=0.05). Among those mothers carrying MTHFR CC, those with folate deficiency showed a 543 g reduction in infant birthweight compared with those with normal folate levels. However, infant birthweight was no different for mothers, those who with folate deficiency compared to those with normal range of folate among mothers carrying the MTHFR CT or TT genotypes. This study suggests an interaction between maternal serum folate and the MTHFR polymorphisms of the mother on the risk of delivering reduced birthweight offspring. Folate supplementation of folate deficient pregnant women with the MTHFR wild type is suggested to reduce the risk of low birthweight.

Incidence and Risk Factors of Pulmonary Thromboembolism in Pedicled TRAM Breast Reconstruction (유경횡복직근피판을 이용한 유방복원술시 폐색전증의 발병률과 위험인자)

  • Lee, Sang Hyuk;Lee, Taik Jong;Eom, Jin Sup;Son, Byung Ho;Ahn, Sei Hyun;Lee, Sang Do
    • Archives of Plastic Surgery
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    • v.33 no.2
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    • pp.193-197
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    • 2006
  • Pulmonary thromboembolism is often clinically silent and difficult to diagnose, and can be fatal to patients with belated treatment. This complication is seen in patients who underwent TRAM breast reconstruction. Multiple factors are involved in this disease such as the presence of malignancy itself, major surgery and therapy-related interventions. TRAM surgery is a lengthy procedure involving mastectomy, flap surgery and abdominoplasty. The purpose of this study is to evaluate the incidence and the correlation between presurgical risk factors(BMI and age) of symptomatic pulmonary thromboembolism after TRAM surgery and the incidence. From July 2001 to March 2005 a total of 384 pedicled TRAM reconstruction of breast was performed in 382 patients at Asan Medical Center. The average of Body mass index was $21.9kg/m^2$ and mean age of the patients was 37.9 years old. We diagnosed symptomatic pulmonary thromboembolism using ventilation/perfusion lung scan and pulmonary embolism computed tomography. Incidence of in-hospital symptomatic pulmonary thromboembolism was 1.3%. BMI and age showed no significant statistical relationship to pulmonary thromboembolism. But the incidence of symptomatic pulmonary thromboembolism in obese patients (BMI > 25) was 3.75%. According to the guideline of the 7th American College of Chest Physicians Consensus Conference on Antithrombotic and Thrombolytic Therapy, the incidence of 3.75% was classified as high risk group. The prevention of pulmonary thromboembolism should be considered in cases of obese patients with low molecular weight heparin(BMI > 25).

Evaluation of Pharmacological Effect of Soybean Trypsin Inhibitor-Chondroitin Sulfate Conjugates (Soybean Trypsin Inhibitor와 황산 콘드로이친 포합체의 약리 효과 평가)

  • Choi, Youn-Lim;Nam, Hyun-Gu;Shin, Young-Hee
    • Journal of Pharmaceutical Investigation
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    • v.30 no.3
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    • pp.159-166
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    • 2000
  • Kunitz-type soybean trypsin inhibitor (SBTI) and chondroitin sulfate (A, and C type) were conjugated using sodium periodate method. And the physicochemical, pharmacokinetic properties and immunogenecity of the conjugates (Chon-A-SBTI or Chon-C-SBTI) were characterized. We expected the conjugation using chondroitin sulfate to reduce the immunogenecity and to improve the pharmacological effect. As the results, the mean molecular weight of the conjugate highly increased. After I.V. injection of the radiolabeled conjugates or native SBTI into mice, it was found that native SBTI showed rapid elimination from plasma, whereas Chon-A-SBTI and Chon-C-SBTI were slowly eliminated. Organ distribution of the two agents at 30 min after I.V. injection was different : Chon-A-SBTI or Chon-C-SBTI accumulated to a large extent in the liver (13% in Chon-A-SBTI and 16% in Chon-C-SBTI), whereas native SBTI was taken up more rapidly by the kidney (107% dose/g of tissue) and excreated into the urine (26%). In addition we evaluated the therapeutic value of the conjugates by using the sublethal septic shock model caused by pseudomonal elastase and tested the immunogenecity by passive cutaneous anaphylaxis shock (PCA). The conjugates were more effective than native SBTI against pseudomonal elastase induced septic shock in guinea pig. In case of the conjugates, the pharmacological and therapeutic effect lasted over 3 hours long. In immunogenecity test, both of the conjugates showed the reduction of their immunogenecity, especially Chon-A-SBTI looked most effective.

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Effects of supplemental bacteriophage on the gut microbiota and nutrient digestibility of ileal-cannulated pigs

  • Hyunwoong Jo;Geongoo Han;Eun Bae Kim;Changsu Kong;Beob Gyun Kim
    • Journal of Animal Science and Technology
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    • v.66 no.2
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    • pp.340-352
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    • 2024
  • This study measured the potential changes of the microbiota in the gastrointestinal tract and energy and nutrient digestibility by supplemental bacteriophages in pigs. Twelve castrated male pigs (initial mean body weight = 29.5 ± 2.3 kg) were surgically cannulated using T-cannula. The animals were housed individually in pens equipped with a feeder and a nipple waterer. The pigs were allotted to 1 of 3 experimental diets in a quadruplicated 3 × 2 Latin square design with 3 experimental diets, 2 periods, and 12 pigs resulting in 8 replicates per diet. The 3 diets were a control mainly based on corn and soybean meal with no antibiotics or bacteriophages, a diet containing 0.1% antibiotics, and a diet containing 0.2% bacteriophages. On day 5 of the experimental period, feces were collected and on days 6 and 7, ileal digesta were collected. Genomic DNA for bacteria were extracted from the ileal digesta and feces and the V4 region of the 16S rRNA gene was amplified. The ileal and fecal digestibility of energy, dry matter, organic matter, crude protein, and fiber was unaffected by dietary antibiotics or bacteriophages. At the phylum level, the supplemental antibiotic or bacteriophage tended to result in a higher proportion of Firmicutes (p = 0.059) and a lower proportion of Bacteroidetes (p = 0.099) in the ileal digesta samples compared with the control group with no difference between the antibiotic and bacteriophage groups. At the genus level, the supplemental antibiotic or bacteriophage tended to result in a higher proportion of Lactobacillus (p = 0.062) and a lower proportion of Bacteroides (p = 0.074) and Streptococcus (p = 0.088) in the ileal digesta compared with the control group with no difference between the antibiotic and bacteriophage groups. In the feces, supplemental antibiotics or bacteriophages reduced the proportion of Bifidobacterium compared with the control group (p = 0.029) with no difference between the antibiotic and bacteriophage groups. Overall, supplemental antibiotics and bacteriophages showed positive effect on the microbiota of in the ileal digesta without largely affecting energy or nutrient digestibility, with no differences between the antibiotic and bacteriophage groups in growing pigs.