• YAKHAK HOEJI
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• 제56권3호
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• pp.164-172
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• 2012

This study was aimed to increase the solubility, dissolution and permeation rates of atorvastatin calcium (ATC) using bile salt and/or 2-hydroxypropyl-${\beta}$-cyclodextrin ($HP{\beta}CD$). From solubility studies, sodium deoxycholate (SDC) among bile salts studied was found to have the highest solubilizing effect on ATC ($4.4{\pm}0.4$ mg/ml), and the order of increasing solubility was SDC>sod. cholate>sod. glycocholate>sod. taurodeoxycholate>sod. taurocholate>conjugated bile acid. ATC solid dispersions were prepared at various ratios of drug to SDC and/or $HP{\beta}CD$, and evaluated by differential scanning calorimetry (DSC), dissolution studies and dissolution-permeation studies. DSC curves showed amorphous state of ATC in the physical mixture and solid dispersion. Dissolution rates of ATC-SDC solid dispersions and physical mixture were markedly increased at pH 6.8, but decreased at pH 1.2 with greater proportions of SDC due to the precipitation of SDC, compared with that of drug alone. On the other hand, dissolution rates of ATC-$HP{\beta}CD$ solid dispersion and physical mixture at pH 1.2 were varied with the ratio of drug to carriers. From duodenal permeation studies, it was found that fluxes of ATC (donor dose: 0.5 mg/3.5 ml) in the presence of 25 mM sodium glycocholate, SDC, sod. cholate and sod. taurocholate $(5.7{\pm}0.9$, $5.6{\pm}0.9$, $4.8{\pm}0.7$ and $4.6{\pm}0.9\;{\mu}g/cm^2/hr$, respectively) were enhanced, compared with drug alone ($3.4{\pm}0.9\;{\mu}g/cm^2/hr$). In the dissolution-permeation studies, 1 : 9 : 10 (w/w) ATC-SDC-$HP{\beta}CD$ solid dispersion increased the flux 2.2 times, compared with 1 : 5 : 4 (w/w) ATC-lactose-corn starch mixture as control. In conclusion, solid dispersions with bile salt and $HP{\beta}CD$ were found to be an effective means for increasing the dissolution and permeation rates of ATC.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.817-819
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• 2013

Background: The present study was designed to comparatively assess alteration of biochemical parameters in bile duct cancer and gall stone disease. Materials and Methods: A hospital based case-control study was carried out in the Department of Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between $1^{st}$ January 2010 and $31^{st}$ December 2012. The variables collected were age, gender, serum total cholesterol, total bilirubin, AST, ALT, serum alkaline phosphatase, albumin and hemoglobin. One way ANOVA was used to examine the statistical significance of differences between groups. A post-hoc LSD test was applied for the comparison of means of control versus case groups. A p-value of <0.05 (two-tailed) was considered significant. Results: The mean age of cases and controls was $53.2{\pm}21.2$ years. The levels of serum cholesterol were higher in cases of cancer $192.5{\pm}21.5$ mg/dl in comparison to stone cases $168.7{\pm}16.1$ mg/dl (p value: 0.0001). The total bilirubin showed the marked difference in cases of cancer $7.6{\pm}3.2$ mg/dl in comparison to stone cases $2.5{\pm}0.8$ mg/dl of bile duct. There was discernible divergence in values of alkaline phosphatase in cases of cancer $251.5{\pm}20.1$ IU/l when compared to stone cases $173.2{\pm}12.6$ IU/l of bile duct. In contrast, there was no apparent deviation in values of aspartate transaminases and alanine transaminases in cases of cancer $59.1{\pm}8.9$ IU/l and $105.5{\pm}26.5$ IU/l when compared to stone cases $56.9{\pm}7.9$ IU/l and $84.5{\pm}13.5$ IU/l respectively. Conclusions: LFT analysis for pre-operative assessment was a good predictive marker in setting apart bile duct cancer and gall bladder stone.

• The Korean Journal of Cytopathology
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• 제17권1호
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• pp.38-45
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• 2006

Bile duct brush cytology has been employed as a diagnostic tool for the evaluation of pancreatic and biliary tract strictures. The specificity of this method is high however, its sensitivity is quite low. A recent study employing liquid based cytology (LBC) reported results comparable to those achieved via conventional cytology. Therefore, we have attempted to prospectively evaluate the diagnostic utility of bile duct brush cytology in pancreaticobiliary diseases. A total of 46 cases with bile duct stricture were enrolled including 11 cases of benign stricture, 29 cases of bile duct carcinoma, 3 cases of gallbladder cancer, and 3 cases of pancreatic cancer. Both conventional smear and LBC using $MonoPrep2^{TM}$ system were conducted in each case. The cytological diagnosis of each case was classed into the following categories; benign, suspicious for malignancy, and malignancy. The diagnostic accuracy of both cytologic methods was investigated. LBC evidenced a high rate of material insufficiency (13/46), which was attributed to low cellularity. The kappa index of both cytological methods was 0.508. Cytological and tissue diagnoses were correlated in 25 cases conducted from biopsy or operation. The sensitivity, specificity, positive predictive value, and negative predictive value were 41.2% (7/17), 100% (8/8), 100% (7/7), and 44.4% (10/18) in conventional smear; 58.8% (10/17), 87.5% (7/8), 90.9% (10/11), and 50.0% (7/14) in LBC; and 94.1% (16/17), 87.5% (7/8), 94.1% (16/17), and 87.5% (7/8) in any one of both cytological methods, respectively. Based on these results, the sensitivity of LBC was found to be superior to that of conventional smear and we were able to obtain higher positive predictive value upto 94.1% by simultaneously conducting both cytologic methods.

• Applied Microscopy
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• 제22권2호
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• pp.15-29
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• 1992

The gallbladder is known to have the function of the storage and the concentration of the bile produced by the liver. This function is carried out by the removal of water and inorganic electrolytes. Extrahepatic cholestasis or the impairment of excretion of the bile leads to the distension and loss of the function of the gallbladder. The purpose of this study was to examine the ultrastructural characteristics of the normal gallbladder epithelial cells, and their structural changes induced by the ligation of common bile duct of the rabbit. Common bile duct ligation was performed under ether anesthesia. The rabbits were sacrificed on the 1st, 3rd, 5th, 7th and 14th day, respectively after operations. The tissue blocks of the gallbladder were fixed in 2.5% glutaraldehyde-1.5% paraformaldehyde prior to fixation in 1% osmium tetroxide, and embedded in the araldite mixture, and observed with JEM 100 CX-II electron microscope. The results were as follows: 1. The normal gallbladder epithelium of adult rabbit demonstrated two cell types, the ordinary epthelial cell and the dark cell. The dark cells have electron dense cytoplasm, and were found much infrequently, whereas ordinary epthelial cells were found quite numerous. 2. The ordinary epthelial cells of normal gallbladder were provided with the regular microvilli at the free surface and the images of pinocytotic activities in the apical cytoplasm, and exhibit highly convoluted lateral surfaces with elaborated microfolds. These figures of the cells suggest that they are resorptive in functional activity. 3. In the early stages (1st, 3rd, 5th day groups) following the ligation, the apical cytoplasm of some cells is protruding from the free surface and lost their microvilli. Numerous mucous granules filled in the apical and supranuclear cytoplasm compactly. 4. In the late stages (7th, 14th day groups) following the ligation, many light cells containing mumerous mucous granules are seen, between the ordinary epthelial cells. Mucous granules are fused each other, and are discharged into the lumen from the apical cytoplasm. The lateral membranes are straight or undulating without any interdigitations. From the above results, it was concluded that in the cholestasis induced by the common bile duct ligation, there is a tendency for the mucosal epithelium of the rabbit gallbladder to have secretory rather than an absorptive function.

• Korean Journal of Food Science and Technology
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• 제29권3호
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• pp.417-426
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• 1997

Rice bran protein hydrolysates were prepared and some of their physicochemical properties were investigated to utilize rice bran as starting material for functional food ingredient. Rice bran proteins (RBP) were prepared from defatted rice bran by alkaline extraction and isoelectric precipitation. The enzyme for hydrolysis of RBP was selected through measuring relative activity by pH-drop method and comparing the degree of hydrolysis (DH) of hydrolysates. The enzymatic hydrolysates prepared by $Esperase^{\circledR}$ treatment were partitioned into two fractions by ultrafiltration(UF) with a 10 kDa molecular weight cut-off membrane. Each fraction was applied to a cholic acid-conjugated ${\omega}-aminohexyl$ Sepharose 4B column and the bile acid-binding components were obtained by eluting with deoxycholate. Gel permeation chromatography on a Sephadex G-50 column revealed that molecular weight of the bile acid-binding fraction of UF permeate was distributed in ranges of $2\;kDa{\sim}10\;kDa$ and $0.2\;kDa{\sim}0.6\;kDa$. Three peaks (R-1, R-2 and R-3) were obtained by prep-HPLC of bile acid-binding fraction of UF retentate and analyzed for total and free amino acid composition. The results showed that proline content of the bile-acid binding polypeptides and peptides was four times as much as that of rice bran protein and that the peak corresponding to higher average hydrophobicity had a higher free amino acid content. Average hydrophobicity slightly increased with enzymatic hydrolysis.

• YAKHAK HOEJI
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• 제40권3호
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• pp.311-319
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• 1996

DWP305, a preparation containing combination of ursodeoxycholic acid(UDCA), silymarin and vitamins ($B_1\;and\;B_2$), is a drug currently being developed for hep atic disorders. In order to evaluate the changes in hepatic function by multiple oral administration(2 and 4 weeks) of DWP305 in rats, several biochemical parameters in blood, bile acid composition, and the accumulation of UDCA and lithocholic acid(LCA),a toxic metabolite formed by enterobacteria, were examined using HPLC. In blood biochemical findings, DWP305 did not affect the normal level and there was no difference in total bile acid composition for UDCA, cholic acid(CA), deoxycholic acid(DCA), chenodeoxycholic acid(CDCA) and LCA compared to the UDCA administered group, although total ratio of UDCA and CA was different from normal group. In case of ratio of taurine and glycine conjugated forms, DWP305(186mg/kg as a UDCA) administered group was also similar to normal group and UDCA administered group, while high dosing of DWP305 was not different in the ratio of UDCA administered group(930mg/kg) but normal group. And the ratio of LCA was in order of UDCA(930mg/kg), DWP305(930mg/kg as a UDCA), UDCA(186mg/kg) and DWP305(186mg/kg as a UDCA) administered group, which was less than 4%. The free form of UDCA as well as most of bile acids was not detected at all in rat liver, indicating that there's no accumulation. These results suggest that multiple dosing of DWP305 in rats may not affect hepatic biotransformation and metabolism of bile acids.

• Applied Microscopy
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• 제34권2호
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• pp.121-130
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• 2004

In this study, ultrastructural change of the bile duct fibroblast at infected rat with Clonorchis sinensis, and the distribution of lectin receptors and actin protein in cultured bile duct infected with Clonorchis sinensis. It explored using colloidal gold label complex with lectin WGA purified from wheat germ (Triticum vulgaris) and anti actin antibody purified actin (43 kDa) isolated from chicken back muscle. The lectin WGA with protein A gold complex labeled sections of the cultured fibroblast revealed gold particles specifically distributed on the multi vesicular form Golgi complex and cell surface of the fibroblast. The actin antibody with protein A gold complex labeled sections of the cultured fibroblast revealed gold particles specifically distributed on the cytoplasm of the fibroblast. Labeling of cultured fibroblast in rat bile duct infected with Clonorchis sinensis was then quantified and compared to that of cultured Fibroblast in Rat Bile duct. These results indicate that lectin WGA receptors are located in the multi vesicular form Golgi complex in the cytoplasm to the cytoplasmic process of the Rat bile duct fibroblast infected with Clonorchis sinensis. Therefore, the GlcNAc and NeuNac regions on the cell surface and cytoplasmic process appear to be functionally associated with cell-recognition and protection from other cell of the tissue, and linked with secretion and exocytosis of the fibroblst cytoplasm. GlcNAc and NeuNAc product in the multi vesicular form Golgi complex then it is transported to cell surface. Actin protein is many appears that infected fibroblast rather than normal fibroblast. The fibroblast of infected with Clonorchis sinensis are against of the physical and chemical stimulation. Then development of cytoplasmic process is relative some stimulation.

• Bulletin of the Korean Chemical Society
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• 제8권2호
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• pp.118-122
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• 1987

The micelle formation of NaDC was studied by fluorometric and viscometric measurements. The thermodynamic parameters of the primary and secondary micellization of the bile salt were evaluated. The primary micelle formation was appeared to be an entropy driven process due to hydrophobic effect, while the major driving force for secondary micelle formation of the bile salt is the large negative enthalpy. The secondary micelle provides less hydrophobic environment to pyrene than the primary micelle does. The cooperative aggregation of primary micelles via hvdrogen bond formation was proposed for the secondary micelle formation.

• Korean Journal of Radiology
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• 제2권3호
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• pp.175-178
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• 2001

We describe the imaging features of two cases of biliary ascariasis. Ultrasonography and CT showed no specific abnormal findings, but MR cholangiography clearly demonstrated an intraductal linear filling defect that led to the correct diagnosis. MR cholangiography is thus a useful technique for the diagnosis of biliary ascariasis.

• 월간산업보건
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• 통권13호
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• pp.42-42
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• 1989