Sparganum症 1例

신대환 충남대학교 의과대학 지역사회의학연구소 1985 충남의대잡지 Vol.12 No.2

Aug. 1985, live moving folded milky colored band like single worm, Sparganum, was collected from the abdominal wall of 22 year old male. It was 5mm in width and 7cm in length. Species identification was not performed.

Pharmacokinetic scaling of epirubicin using allometric and species-invariant time methods

신대환,박승혁,정성우,권오승,박천웅,김한,정연복 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.5

The pharmacokinetics of epirubicin, an anthracycline, were investigated after intravenous bolus administration (5 mg/kg) in mice, rats, rabbits and dogs. Based on animal data, we predicted the following human pharmacokinetic parameters using allometric scaling: 120 and 35.2 L/h for total body clearance (CLt) using simple and maximum life-span potential (MLP)-corrected allometry, respectively; 702 L for steady-state volume of distribution (Vdss). The scaled Vdss value was twofold lower than the corresponding values in humans. However, the scaled CLt values were consistent with those clinically observed in humans (35.6–133.4 L/h). We also predicted human parameters using species-invariant time transformations (equivalent time, kallynochrons, apolysichrons and dienetichrons). The mean Vdss (854 L) obtained using kallynochrons and that derived from simple allometry were comparable. The lowest CLt (121 L/h) derived using kallynochrons was comparable to that obtained using simple allometry. The results of this study also indicated that the predicted human CLt generated using MLP-corrected allometry can be used for the selection of a safe dose for studies in healthy adult human volunteers. These results suggest that such approaches may be useful in designing pharmacokinetic studies for novel anthracyclines.

Validation of high-performance liqid chromatography method to determine epirubicin and its pharmacokinetics after intravenous bolus administration in rats

신대환,박승혁,권오승,박천웅,한건,정연복 한국약제학회 2013 Journal of Pharmaceutical Investigation Vol.43 No.3

We investigated the pharmacokinetics of epirubicin,an anthracycline derivative antibiotics, after intravenous (i.v.) bolus administration in rats. To analyze epirubicin levels in the plasma, bile, urine and tissue samples, we developed an high-performance liqid chromatography (HPLC)-based method which was validated for a pharmacokinetic study by suitable criteria. The plasma concentration of epirubicin after i.v. bolus administration was rapidly disappeared within 10 min from the blood circulation. The mean plasma half-lives at a phase (t1/2a) when administered at the dose of 2, 5, 10, 25 and 50 mg/kg were 2.14–2.61 min. The values of t1/2b at the corresponding doses increased two folds (from 150 to 291 min) with increasing doses. The CLt values significantly decreased with the increase in dose. In contrast, Vdss values increased about 1.5 times with the increase in dose from 2 to 50 mg/kg. Of the various tissues, epirubicin mainly distributed to the kidney, lung, heart and liver after i.v. bolus administration. The epirubicin concentrations in various tissues at 24 h after i.v. bolus administration were below 1.0 lg/g tissue. Epirubicin was excreted largely in the bile after i.v. bolus administration at the dose of 2, 10and 50 mg/kg. The cumulative amount of epirubicin in the urine 72 h after dosage represented 20 % of the amount excreted in the bile 12 h after high dosage, indicating that i.v. administered epirubicin was mainly excreted in the bile. In conclusion, epirubicin was rapidly cleared from the blood circulation and transferred to tissues such as the kidney and liver 2 h after i.v. bolus administration. Moreover, the majority of epirubicin appears to be excreted in the bile by 12 h after i.v. bolus administration.

錦江流域 淡水魚의 Sparganum에 關한 調査硏究

辛大煥,羅榮彦,權斗星 충남대학교 의과대학 지역사회의학연구소 1987 충남의대잡지 Vol.14 No.1

Prevalence of the plerocercoid larva in the fresh-water fishes in Keum-river basin was surveyed from April to September, 1986. To observe whether this plerocercoid larva is really sparganum or not, and can be transfered to the paratenic host or not, a study was performed with the adequate experimental animal (domestic fowl and cat). It was collected the 1096 fresh-water fishes that was ranged 8.0^-16.0cm in length. The results obtained were as follows; 1. A number of ova of Diphyllobothrium spp, was confirmed under the microscopic study, 5 days after experimental infection through the mouth, and them sacrificed to the experimental animal (final host, cat). The adult worm of Diphylobothrium spp., 9.5cm in length, was obtained and that worm was located in the upper position of rectum, Therefore, this plerocercoid larva was confirmed as Sparganum. 2. Transference to the paratenic host (dowestic fowl) was not resulted. 3. Among the total number of 1096 fresh-water fishes, only the Z. platypus was infected with 107 worms corresonding to 9.8%. 4. Infection rate according to the length of Z. platypus was 66. 4% at 12-13. 9cm in length, and this percentage was the highest prevalent rate.

고양이의 Toxoplasma 抗體價 測定 및 腸內 奇生蟲 感染에 關한 硏究

辛大煥,金明海,李英河,羅榮彦 충남대학교 의과대학 지역사회의학연구소 1988 충남의대잡지 Vol.15 No.2

In order to confirm the intestinal helminthes, protozoa and Toxoplasma antibody titers from 41 cats, author performed the autopsy, stool examination, and Sabin & Feldman dye Test. 1. Total infection rates were 68.3%, and double infection rates were 29.3%. From 41 cats, 8 species were identified to Isospora felis(2.4%), Toxocara cati(7.3%), Ancylostoma sp(2.4%), Taenia taeniaeformis(51.2%), Diphyllobothrium mansoni(19.5%), Hymenolepis nana(2.4), Clonorchis sinensis (7.3,%), and metagonmus yokogawai(4.9%). 2. Habored region of each parasites was mainly small intestine, especially duodenum, and only Clonorchis sinensis was harbored in liver and bile duct. 3. Egg occurrence rate was 33.3% (T. taeniaeforis), 66.7(C. sinensis), and 100%(D. mansoni, M. yokogawai, I. felis). 4. Sabin & Feldman dye test titer was positive reaction in 14 cases corresponding to 34.190, and 27 cases were considered as negative.

忠南 一部地域의 寄生蟲 感染率 調査

辛大渙 충남대학교 의과대학 지역사회의학연구소 1977 충남의대잡지 Vol.4 No.2

A survey of intestinal parasites by fecal examination and intradermal test with the antigens of Clonorchis and Paragcnimus carried out in several localities of Chung-chung. nam Do, from August to September, 1977. A total of 1632 fecal specimens and intradermal test of 2278 cases were examined. And the results are summarized as follows: 1. The prevalence rate of intestinal helminth revealed 78.7% (male 76.3, female 81.7) in the 1632 fecal specimens and the rate of Ascaris lumbricoides showed 50.5%, Trichocephalus trichiurus 56.0%, hookworm 0.3%, Clonorchis sinensis 1.1%, Enterobius vermicularis 5.0%, Hymenolepis nana 0.7%, Taenia spp. 0.4%, and 1 case of each Fasciolidae and Trichostrongylus orientaifs, respectively. 2. The prevalence rate of intestinal protozoa in Anmyeon Myeon Seosan Gun was 16.4%(male 15.6, female 18.2) among 1050 stool specimens. The rate of each species showed Entamoeba histolytica 3.2%, Entamoeba coli 9.5%, Endolimax nana 3.5%, Giardia lamblia 5.0% and lodamoeba bu¨tschlii 0.1%. 3. The positive reaction rate of Clonorchis were 137 cases (6.0%) out of 2278 (male 1147, female 1131) intradermal tests, and the rate of each locality showed 21.5% in Jewon Myeon Kumsan Gun, 7.2% in Kereong Myeon Gongju Gun, 3.2% in Daehogie Myeon Dangjin Gun and 3.6% in Anmyeon Myeon Seosan Gun. 4. The Paragonimus positive reaction rate was 2.8% among the same intradermal cases and the highest rate showed in Jewon Myeon Kumsan Gun (10.0%).

Extensive Intracellular Accumulation of ID-6105, a Novel Anthracycline, in SK-OV-3 Ovarian Cancer Cells

신대환,최규석,박상애,조병석,이홍섭,류중수,김태용,이종길,송석길,정연복 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.10

We investigated the anticancer activity of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, on weakly doxorubicin (Dox)-resistant SK-OV-3 ovarian cancer cells, and elucidated the relationship between its anticancer activity and accumulation in cells compared with those of Dox. Accumulation of ID-6105 in the cells was time- and concentration-dependent, a result of drug-induced cytotoxicity in the cells. SK-OV-3 cells were preloaded with ID-6105 or Dox for 12 h at concentrations ranging from 100 to 2000 nM and then incubated with drug-free medium for 0-48 h. Cell viability was measured using a proliferation-based assay (XTT assay). The inhibitory effects of ID-6105 on cell viability were more pronounced than those of Dox. The IC50 values of ID-6105 after 24- and 48-h incubation with drug-free medium were 1.58 and 0.084 μM, while those of Dox were 2 and 0.334 μM, respectively. To investigate the relationship between the intracellular levels and the cytotoxic effects of the drugs, we preloaded SKOV-3 cells with ID-6105 or Dox (100-2000 nM) for 12 h and then measured the intracellular levels of drugs by HPLC in drug-free medium for 0-48 h. After preloading the drugs, the intracellular concentrations of ID-6105 at time 0 were 1.3-, 1.8-, and 1.4-fold larger than those of Dox at initial concentrations of 500, 1000, and 2000 nM, respectively. The extent of ID-6105 accumulation in the cells was more pronounced than that of Dox. These findings suggest that ID-6105 effluxed less from the cells than Dox, resulting in its extensive cytotoxicity compared with that of Dox. These results show that accumulation of ID-6105 within tumor cells may be important for the inhibitory effects of this drug in cancer cells. ID-6105 has an antiproliferative effect on SK-OV-3 cells that is due to its cytotoxicity. This effect is more pronounced than that of Dox, and may be attributed to extensive accumulation of ID-6105 in the cells.

Enhanced Anticancer Effect of Liposome Encapsulated Choline Kinase-siRNA in Mice

신대환,김진석,심재연,김정현,이승윤,Shuhua Xuan,김우영,원권연 한국고분자학회 2014 Macromolecular Research Vol.22 No.3

The anticancer effect of choline kinase (ChK)-siRNA for breast cancer was evaluated using PEGylatedliposomes both in vitro and in vivo. The optimal size and zeta-potential of siRNA/liposome complex were achievedusing condensing agents of hyaluronic acid (HA) and protamine with weight ratios of (ChK-siRNA+HA+protamine):liposome between 0.05 and 0.0037. Suppression of the expression of ChK-mRNA and the resulting cellgrowth inhibition by the treatment with ChK-siRNA was the highest when using 2.5 and 5 mol% PEGylated liposomes. A pharmacokinetic study after intravenous injection into mice showed that the area under the curve (AUC)and blood half-life (t1/2, α and t1/2, β) of ChK-siRNA in 5 mol% PEGylated liposomes were 19 times and 2.2 to 10.5times higher than that of naked siRNA, respectively. In vivo study showed that PEG-lipo with siRNA exhibitedmuch better tumor growth inhibition and increased survival time than the free siRNA in an MDA-MB-231-bearingxenograft nude mouse model, presumably due to the increased half-life and the passive targeting effect mediated bythe PEGylated liposome. The data clearly show that the PEGylated liposome, together with appropriate condensingagents, could serve as an effective delivery system for the ChK-siRNA therapeutics for breast cancer.

유혈목이(Natrix tigrina)의 腸間膜에 寄生한 鉤頭蟲의 Cystacanth幼蟲에 對한 硏究

辛大煥,沈雲澤 충남대학교 의과대학 지역사회의학연구소 1984 충남의대잡지 Vol.11 No.1

The intensity, morphology and tegumental ultrastructure of cystacanth of Acanthocephala is described from the mesntery of snakes(Natrix tigrina) which caught at a certain locality in Chungchung Buk-Do. The results are briefly summarized as follows: 1. The intensity of cystacanth in the mesentery of N tigrina showed 1,039 worms from 30 snakes, and larger snakes were infested more worms. 2. Morphology of cystacanth:conic form, 3.1^mm in length, 0.6^mm in width, aspinose on metasoma, neck absent. Proboscis nearly cylindrical, 0.75mmin length, 17 to 18 longitudinal, regularily alternating row of 24 to 25 spines. Proboscis receptacle double-walled. It has morphological similarity with the genus Centrorhynchus. 3. The cross-sectioned preparations of the cystacanth reavealed several differences from the proboscis, anteriall and middle portion of metasoma. Tegument, musculature and fragments of testis showed in the pseudocoelom of metasoma. 4. Scanning electron micrograph of the cystacanth showed the basic feature of the worm on light microscopical observations, except the more clearly and detailed arrangement of spines on proboscis. 5. The ultrastructure of the tegument of cystacanth showed seveveral different zones in their construction. These are the outermost epicuticle, plasma membrane, striped zone, vesicle zone, felt zone and radial zone. The thicker epicuticle was well developed and the layers beneath the cuticle contained numerous microtubule-like structures, vesicles, fibrous strands as well as glycogen particles.

Hepatic uptake of epirubicin by isolated rat hepatocytes and its biliary excretion after intravenous infusion in rats

신대환,박승혁,정성우,박천웅,한건,정연복 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.12

Anthracycline anticancer agents are widelyused in the cancer chemotherapy for hepatocelluar carcinoma. However, accurate kinetic analyses of the hepatocellularuptake and efflux of the drugs have not beenreported. We, therefore, investigated the hepatobiliarytransport of epirubicin, an anthracycline derived antibiotic,after intravenous (i.v.) infusion in rats. The hepatic uptakemechanisms of epirubicin were also investigated in isolatedrat hepatocytes. To analyze epirubicin levels in the biologicalsamples, we used an HPLC-based method whichhas been validated for a kinetic study by suitable criteria. The uptake process of epirubicin by the hepatocytesrevealed one saturable component, with a Km of 99.1 lg/mL and Vmax of 3.70 lg/min/106 cells. The initial uptakevelocity of epirubicin was significantly inhibited in atemperature-dependent manner. The velocity was alsoreduced in the presence of metabolic inhibitors such asrotenone or carbonylcyanide-p-(trifluoromethoxy)-phenylhydrazone. Substrates for organic anion transporters suchas bromosulfophthalein and taurocholate significantlyinhibited the initial uptake velocity of epirubicin. We alsoattempted to determine the hepatobiliary transport of epirubicinafter i.v. infusion in vivo. At steady-state after i.v. infusion of epirubicin (10–160 lg/min/kg), the drug wasextensively accumulated in the liver, followed by excretioninto bile. Furthermore, the CLbile,plasma and CLbile,liverdecreased with a corresponding increase in the Css,plasmaand Css,liver. In conclusion, present studies using isolated rathepatocytes and in vivo i.v. infusion demonstrate that epirubicin is likely to be taken up into liver cells viaorganic anion transporting polypeptides, and that its biliaryexcretion might be mediated via specific transporters.