• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.283-291
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• 1999

We have synthesized novel platinum (II) coordination complex containing cis-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,2-bis(diphenylphosphino)ethane (DPPE) as leaving group. Furthermore, nitrate was added to improve the water-solubility. A new series of [Pt(cis-DACH)(DPPE)] $2NO_3(PC)$ was evaluated its antitumor activity on various MKN-45 human gastric adenocarcinoma cell-lines and normal primary cultured kidney cells. The new platinum complex demonstrated high efficacy in the cytotoxicity on MKN-45 cell-lines as well as adriamycin-resistant (MKN-45/ADR) and cisplatin-resistant (MKN-45/CDDP) cells. The cytotoxicities of PC were found quite less than those of cisplatin in rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues using MTT assay, $[^3H]-thymidine$ uptake and glucose consumption tests. Based on these results, this novel platinum (II) coordination complex, was considered as better a valuable lead for improving antitumor activities with low nephrotoxicities in the development of a new clinically available anticancer chemotherapeutic agents.

• Parasites, Hosts and Diseases
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• v.27 no.2
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• pp.87-100
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• 1989

Eimeria tenella, an intracellular protozoan parasite infecting the epithelial cells of the ceca of chickens, causes severe diarrhea and bleeding that can lead its host to death. It is of interest that 2. tenezla first penetrate into the mucosal intraepithelial Iymphocytes (IEL) before they parasitize crypt or villous epithelial cells. This in vitro study was undertaken to know whether the penetration of E. tenella into such a lymphoid cell is a beneficial step for the parasite survival and development. Three sequential experiments were performed. First, the in vitro established bovine kidney cell line, MDBK cells, were evaluated for use as host cells for E. tenella, through morphological observation. Second, the degree of parasite development and multiplication in MDBK cells was quantitatively assayed using radioisotope labelled uracil ($^3H-uracil$) . Third, the E. tenella sporozoites viability was assayed after preincubation of them with thicken spleen cells. E. tenella oocysts obtained from the ceca of the infected chickens were used for the source of the sporozoites. Spleen cells (I) obtained from normal chickens (FP strain) were preincubated with the sporozoites (T) at the E:T ratio of 100:1, 50:1 or 25:1 for 4 or 12 hours, and then the mixture was inoculated into the MDBK cell monolayer. Morphologically the infected MDBK cells revealed active schisogonic cycle of E. tenella in 3~4 days, which was characterized by the appearance of trophozoites, and immature and mature schizonts containing merogoites. The 3H-uracil uptake by E. tenella increased gradually in the MDBK cells, which made a plateau after 48~60 hours, and decreased thereafter. The uptake amount of $^3H-uracil$ depended not only upon the inoculum sixte of the sporozoites but also on the degree of time delay (preincubation; sporozoites only) from excystation to inoculation into MDBK cells. The 3H-uracil uptake became lower as the preincubation time was prolonged. In comparison, after preincubation of sporozoites with spleen cells for 4 or 12 hours, the 3H-uracil uptake was significantly increased compared with that of control group. From the results, it was inferred that, although the penetration of E. tenella sporozoites into the lymphoid cells such as IEL is not an essential step, it should be at least a beneficial one for the survival and development of sporozoites in the chicken intestine.

• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.33-43
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• 1991

To study the age dependent change of Na, K-ATPase in the erythrocyte of hypertensive rat, 1-kidey 1-clip hypertensive rat was made by the removal of right kidney and partial ligation of left renal artery. After 4 weeks, aged erythrocyte fraction was separated by density gradient centrifugation, and Na, K-ATPase activity and $^3H-ouabain$ binding with ghost cell membrane and ouabain sensitive Rb-uptake with whole cell were measured. 1) In the hypertensive rats, blood pressure was significantly increased to 165.5/119.0 mmHg (systolic/diastolic). Mean corpuscular volume and membrane protein(mg) per $10^9RBC$ were decreased and hemoglobin content was increased in the aged erythrocyte. 2) Na, K-ATPase activity in the solution containing 110 mM NaCl and 10 mM KCI, was decreased in hypertensive rat, and decreased in aged erythrocyte of both group. 3) Ouabain sensitive Rb-uptake by low RbCl concentration(4 mM) was slightly decreased in aged erythrocyte compared to that in young erythrocyte of each group, but slightly increased in young erythrocyte in hypertensive rat compared to that in normotensive rat. 4) Ouabain sensitive Rb-uptake by high RbCl concentration(16 mM) was decreased about 30% to 50 % in aged erythrocyte in both group. And in hypertensive rat, especially in young erythrocyte it was significantly decreased compared to that in normotensive rats. 5) $^3H-ouabain$ binding at 0.13 or $1{\times}10^-6M$ ouabain concentration was slightly decreased in aged erythrocyte of normotensive rat, and significantly decreased in aged erythrocyte of hypertensive rats. 6) $^3H-ouabain$ binding at 6 or $64{\times}10^-6M$ ouabain concentration is slightly decreased in aged erythrocyte of both group, but significantly decreased in young and aged erythrocyte of hypertensive rats compared to that of normotensive rats. The present results suggest that (1) in the young erythrocyte of hypertensive rat, the alterations of Na-pump activity that slightly increased in weak stimulation and inhibited in strong stimulation, may be related to increased molecular activity and the decrease in the number of low affinity site without change in high affinity site, (2) in the aged erythrocyte of normotensive rat, inhibited Na-pump may be related to the change in molecular activity of pump. (3) And in the aged erythrocyte of hypertensive rat, it may be related to the decrease in the number of high and low affinity site as well as the change in molecular activity

• The Korean Journal of Nuclear Medicine
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• v.35 no.3
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• pp.185-191
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• 2001

Objectives: Recently, $[methyl-^{11}C]-({\beta}$-Hydroxyethyl)trimethylammonium ($[^{11}C]$choline) Has been discovered to be a very effective tracer in imaging various human tumors using positron omission tomography. Because of the short half-life of C-11, it is very difficult to use in a routine imaging procedure and needs a frequent synthesis of $[^{11}C]$choline. This can be supplemented by the substitution of $[^{11}C]$choline with $[methyl-^{18}F]$fluorocholine. Here, we would like to report ceil uptake and biodistribution of $[^{11}C]$choline and $[^{18}F]$fluorocholine as a basic study. Methods: $[^{11}C]$Choline was prepared by the treatment of $[^{11}C]CH_3I$ with N,N-dimethylaminoethanol and $[^{18}F]$fluorocholine was synthesized from reaction of $CH_2Br[^{18}F]F$ with N,N-dimethylaminoethanol. The radiochemical purity was checked by high performance liquid chromatography (HPLC). The blodistribution of $[^{11}C]$choline and $[^{18}F]$fluorocholine was determined in balb/c mouse at 5 min, 20 min, 40 min and 80 min. The cell uptake was measured using glioma (9L) and colon adenocarcinoma (SW620). Results: The radiochemical purity was more than 98% after purification. In the liver, uptake did not change over time; the uptake was 20%ID/g for $[^{11}C]$choline and 13%ID/g for $[^{18}F]$fluorocholine. In the kidney, radioactivity decreased over time; the uptake was 15%ID/g for $[^{11}C]$choline and 20%ID/g for $[^{18}F]$fluorocholine, 80 min post-injection. The cell uptake of $[^{11}C]$choline was 4.93% for glioma (9L) and 18.69% for colon adenocarcinoma (SW620). For $[^{18}F]$fluorocholine, 1.77% for glioma (9L) and 2.77% for colon adenocarcinoma (SW620). Conclusion: $[^{11}C]$Choline and $[^{18}F]$fluorocholine showed a different cell uptake tendency, depending on cancer cell line.

• The Korean Journal of Nuclear Medicine
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• v.30 no.4
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• pp.524-531
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• 1996

Purpose : To evaluate the pattern- of skeletal metastases and to classify the pattern of renal uptakes on bone scans in renal cell carcinoma. Materials and Methods : We reviewed the bone scans of 158 patients with RCC established pathologically. In order to identify individual scan lesion as a bone metastasis, we reviewed all available correlative radiological studies, follow-up bone scans, and biopsies for each lesion. The metastatic bone lesions were divided into seven anatomic regions; skull, spine, shoulder girdle, sternum, ribs, pelvis, and long bones of extremities. The individual scan lesions were divided into two groups as the pattern of uptakes, hot and cold lesion. In addition, the contours and uptakes of kidneys with RCC were classified into 6 groups ; normal uptake, photon-deficient lesion, faint up-take with enlargement, uneven uptake with enlargement, lateralization with crescentic shape, and increased uptake. Results : Twenty out of 158(12.7%) patients with RCC at varying stages showed 71 metastatic bone lesions at presentation and on follow- up bone scans. Nearly 80% of all metastatic lesions were in the axial skeleton with predominantly increased uptake of the radioactivity However a considerable number(22.5%) showed cold lesions on bone scan. A half of bone scans revealed abnormal uptake of involved kidney and much more(82.4%) in case of bone metastases. Two common patterns of abnormal renal uptake were photon-deficient lesion (50%) and faint uptake with enlargement(24.3%). In four patients with bone pain or pathologic fracture, bone scans were useful for the serendipitious localization of previously unrecognized primary lesion of RCC as well as for the detection of bone metastases from RCC. Conclusion : The understanding of the pat-terns of skeletal metastases and renal uptakes on bone scans in RCC is important for the useful information about primary lesion(RCC) as well as detection of bone metastases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.37 no.1
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• pp.1-8
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• 2023

The aim of this study is to evaluate the antidiabetic effect of the water extract of Aurantii fructus immaturus (WAF), in diabetic models using enzyme, cells and mice, and to suggest a putative mechanism explaining its antidiabetic effect. In an enzyme model using the enzyme α-glucosidase, WAF had no significant effect on α-glucosidase, as compared with acarbose, an antidiabetic drug. Nonetheless, WAF was capable of reducing the blood glucose levels during oral sucrose tolerance test and oral glucose tolerance test, implying that there would be other antidiabetic pathways in no relation to inhibition of α-glucosidase. In cell models using RIN-m5f β-cells and L6 myotubes, WAF, at its non-cytotoxic doses, augmented the secretion of insulin in RIN-m5f β-cells stimulated with 5 mM glucose. In addition, it enhanced the cellular uptake of glucose in L6 myotubes stimulated with deprivation of glucose for 12 h. Therefore, it is most likely that WAF may exert its antidiabetic effects, at least in part, by enhancing insulin secretion and glucose uptake. Meanwhile, in diabetic mice induced with peritoneal injection of streptozotocin (STZ), WAF significantly improved fast blood glucose levels, glycosylated hemoglobin levels, body weight loose, blood pressure, and diabetic adverse effects on functions of the kidney and the liver. Taken together, the water extract of Aurantii fructus immaturus may ameliorate diabetes in mice injected with STZ, at least in part, by enhancing insulin secretion and glucose uptake.

• Korean Journal of Veterinary Research
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• v.34 no.3
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• pp.457-463
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• 1994

Insulin-like growth factor-I(IGF-I) plays an important role in the regulation of mammalian and poultry growth. IGF-I has many actions in different tissues, which include metabolic, mitogenic, and differentiative actions. IGF-I induces insulin-like effects - such as increased cell glucose uptake and glycogen sysnthesis, however several physiological actions of IGF-I may not have been identified yet. In order to investigate the effect on growth in broiler chicken treated with exogenous insulin-like growth factor-I, 30 chickens were injected $50{\mu}g$ reconbinant human IGF- I (rhIGF- I ) per kg body weight as experimental group and 30 ckickens saline subcutanously as control, 3 times according to ages from 2 to 35 days. We established radioimmunoassay method by which we can measure chicken IGF- I (cIGF- I ) as in rhIGF- I assay. The results obtained were as follows; 1) The dilution curve showed in parallelism between rhIGF- I and cIGF- I in the Sep-pak $C_{18}$ cartridge plasma extracts. 2) The body weight of broiler chicken were significantly increased at 31 days($1,176.50{\pm}99.79g$) and 35 days($1,252.84{\pm}125.21g$) of age in treatment groups, compared with control group($1,011.88{\pm}40.22g,\;1,111.32{\pm}153.67g$). The liver and kidney weights on 35 days$(35.24{\pm}5.18g,\;11.05{\pm}1.47g)$ were significantly higher in rhIGF- I treated group than control group($30.95{\pm}4.04g,\;10.01{\pm}1.60g$) 3) The plasma concentration of IGF- l and total protein in rhIGF- I treated group were $58.17{\pm}1.69ng/ml$, $3.75{\pm}0.62g/dl$ respectively compared with control group $45.70{\pm}1.64ng/ml$, $2.32{\pm}0.53g/dl$. The results suggest that exogenous rhIGF- I increased total body weight, liver and kidney weights in broiler chicken, and it may increase IGF- I and total protein concentration in serum.

• Animal Bioscience
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• v.36 no.5
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• pp.740-752
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• 2023

Objective: Dietary phytase increases bioavailability of phytate-bound phosphorus (P) in pig nutrition affecting dietary calcium (Ca) to P ratio, intestinal uptake, and systemic utilization of both minerals, which may contribute to improper bone mineralization. We used phytase to assess long-term effects of two dietary available P (aP) levels using a one-phase feeding system on gene expression related to Ca and P homeostasis along the intestinal tract and in the kidney, short-chain fatty acids in stomach, cecum, and colon, serum, and bone parameters in growing gilts and barrows. Methods: Growing pigs (37.9±6.2 kg) had either free access to a diet without (Con; 75 gilts and 69 barrows) or with phytase (650 phytase units; n = 72/diet) for 56 days. Samples of blood, duodenal, jejunal, ileal, cecal, and colonic mucosa and digesta, kidney, and metacarpal bones were collected from 24 pigs (6 gilts and 6 barrows per diet). Results: Phytase decreased daily feed intake and average daily gain, whereas aP intake increased with phytase versus Con diet (p<0.05). Gilts had higher colonic expression of TRPV5, CDH1, CLDN4, ZO1, and OCLN and renal expression of TRPV5 and SLC34A3 compared to barrows (p<0.05). Phytase increased duodenal expression of TRPV5, TRPV6, CALB1, PMCA1b, CDH1, CLDN4, ZO1, and OCLN compared to Con diet (p<0.05). Furthermore, phytase increased expression of SCL34A2 in cecum and of FGF23 and CLDN4 in colon compared to Con diet (p<0.05). Alongside, phytase decreased gastric propionate, cecal valerate, and colonic caproate versus Con diet (p<0.05). Phytase reduced cortical wall thickness and index of metacarpal bones (p<0.05). Conclusion: Gene expression results suggested an intestinal adaptation to increased dietary aP amount by increasing duodenal trans- and paracellular Ca absorption to balance the systemically available Ca and P levels, whereas no adaption of relevant gene expression in kidney occurred. Greater average daily gain in barrows related to higher feed intake.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.359-366
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• 2001

We have synthesized a novel platinum(II) coordination complex containing cis-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,3-dichloropropane (DCP) as a leaving group. A new series of [Pt(cis- DACH)(DCP)](PC) was evaluated for its cytotoxic activity on MKN-45 human gastric adenocarcinoma cells and normal primary cultured kidney cells. The new platinum complex has demonstrated high efficacy in the cytotoxicity against MKN-45/P, MKN-45/ADM and MKN-45/CDDP cell-lines. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues, determined by MTT assay, the $[^3H]-thymidine$ uptake and glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum(II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new, clinically available anticancer chemotherapeutic agents.

• Biomolecules & Therapeutics
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• v.11 no.2
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• pp.91-98
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• 2003

A new series of highly water soluble platinum(II) complexes[Pt(II)(DL-2-hydroxy-3-methylbutyrate)(trans-l-1,2-dimninocyc1ohexane)] (PC-1) and [Pt(II)DL-2-hydroxy-3-methylbutyrate](cis-1,2-diaminocyclohexane)](PC-2) were synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared(IR), $^{13}C$-nuclear magnetic resonance (NMR)]. In vitro antitumor activity of new Pt(II)complexes was tested against MKN-45, MKN/ADM and MKN/CDDP human gastric adenocarcinoma cell lines using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay for cell survival and proliferation. PC-1 and PC-2 showed active against MKN-45/P, MKN/ADM and MKN/CDDP human gastric cancer cell lines, and the antitumor activity of these compounds were comparable or superior to that of cisplatin. The nephrotoxicities of PC-1 and PC-2 were found quite less then that of cisplatin using MTT and [$^3H$] thymidine uptake tests in rabbit proximal tubule cells, human kidney cortical cells human renal cortical tissues. Based on these results, these novel platinum(II) complex compounds(PC-1 ＆ PC-2) represent a valuable lead in the development of the new anticancer chemotherapeutic agents capable of improving antitumor activity and low nephrotoxicity.