• Toxicological Research
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• v.22 no.4
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• pp.431-438
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• 2006

The object of this study was to obtain acute toxicity information (single oral dose toxicity) of lyophilized water extract of Puerariae Radix (PR) in both male and female mice. In order to investigate the 50% lethal dose $(LD_{50})$, approximate lethal dosage (ALD), test substances were once orally administered to female and male ICR mice at dose levels of 2000 and 0 (control) mg/kg (body wt.) according to the recommendation of KFDA Guidelines [2005-60, 2005]. The mortality and body weight changes, clinical signs and gross observation were monitored during 14 days after dosing. Organ weight and histopathology of 12 principal organs were measured. As the results, we could not find any mortality, clinical signs, body weight changes and gross findings except for PR extracts unrelated sporadic findings. In addition, no abnormal changes related PR extracts treatment on the organ weight and histopathology of principal organs were detected except for some sporadic findings including hyperplasia of lymphoid follicles in the popliteal lymph nodes and spleen as pharmacological effects of PR extracts. The results obtained in this study suggest that the PR extracts does not cause any toxicological signs except for pharmacological effects of enhancement of Immune system. The $LD_{50}$ and ALD of PR extracts in both female and male mice were considered as over 2000 mg/kg because no mortalities were detected up to 2000mg/kg that was the highest dose recommended by KFDA and Organization for Economic Co-Operation and Development.

• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.84-88
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• 2013

High risk of cardiovascular diseases caused by existing PPAR-${\gamma}$ agonists such as rosiglitazone and pioglitazone has been recently reported. CKD-501 is a novel selective PPAR-${\gamma}$ agonist as a potential target to reduce cardiovascular risk in non-insulin dependent diabetes mellitus (NIDDM). In this study, We investigated potential cardiotoxicity of CKD-501 and compared its toxicity with that of rosiglitazone or pioglitazone using db/db mice. After 12-week repeated administration of CKD-501 at doses of 3, 10 and 30 mg/kg/day or rosiglitazone at doses of 10 and 30 mg/kg/day or pioglitazone at doses of 200 and 540 mg/kg/day, animals were sacrificed for investigation of potential toxicities. Diameters of left ventricles and areas of cardiomyocytes were measured. And lipid accumulation and apoptosis in heart muscle were examined by oil red O staining and TUNEL staining, respectively. Diameters of left ventricles were significantly increased in high dose treatment group of pioglitazone compared to control (p<0.05), while other groups showed a tendency for an increase. All test articles induced significantly the increase of area of cardiomyocytes in heart compared to control (p<0.01), in regular order as pioglitazone > CKD-501 ${\geq}$ rosiglitazone. However, lipid accumulation and apoptotic changes in heart were not observed in all dosing groups. Taken together, the myocardial cell hypertrophy of CKD-501 are relatively lower than that of pioglitazone and similar to rosiglitazone. And it is suggested that the myocardial cell hypertrophy of CKD-501 are less adverse in clinical use for the management of the NIDDM.

• Natural Product Sciences
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• v.8 no.2
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• pp.44-47
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• 2002

The effects of Eurycoma longifolia Jack on masculine copulatory behaviour were studied in the middle aged male Sprague-Dawley rats, 9 months old and retired breeders after dosing them with 500 mg/kg twice daily for 10 days prior to test. The test lasted for 30 minutes after a 20 minute adaptation period, was carried out on the 11th day during the dark phase of the light-dark cycle (2000-0700 hours) and in subdued light, using a modified copulation cage but with the presence of a piece of mirror of appropriate size to facilitate observation. Results showed that the mean values of EL-1, EL-2 and EL-3 of the control middle aged male rats were 103.20 sec, 91.21 sec and 80.00 sec but were significantly (p<0.05) increased to 118.40-120.20 sec, 101.24-171.28 sec and 100.42-110.21 sec respectively in the methanol-chloroform, methanol-butanol-water and methanol-butanol treated middle aged male rats. However, further results also showed that PEI-1 and PEI-2 of the control middle aged male rats were 182.30 sec and 257.2 sec but were significantly (p<0.05) decreased to 100.42-121.31 sec and 40.21-132.31 sec respectively in the methanol-chloroform-butanol-water and methanol-butanol treated middle aged male rats. In conclusion, this study showed that although E. longifolia Jack continued to enhance the sexual activity of the middle aged male rats by extending the duration of coitus and decreasing the refractory period between the different series of copulation, but to a smaller degree as compared to sexually active, adult male rats (Ang and Sim, 1997).

• Toxicological Research
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• v.17 no.3
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• pp.225-234
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• 2001

The present study was conducted to investigate the effects of Korean red ginseng water extract (KRGWE) on developmental toxicity caused by the environmental estrogen bisphenol A (BPA) in Sprague-Dawley rats. fifty males successfully mated were randomly assigned to five experimental groups, 1.e., group I (vehicle control), group II (BPA 1000mg/kg), group III (KRGWE 400mg/kg), group IV (BPA 1000mg/kg & KRGWE 200mg/kg), and group V (BPA 1000mg/kg & KRGWE 400mg/kg). The test articles were administered by gavage to mated females from gestational days (GD) 1 through 20 (sperm vaginal lavage=day O). All females were subjected to caesarean section on GD 21 and their fetuses were examined for external, visceral, and skeletal abnormalities. In the group II, significant maternal toxic effects including suppressed body weight, decreased body weight gain during pregnancy, and reduced food consumption were observed in pregnant rats. The minimal developmental toxicity including fetal ossification delay was also found in fetuses. In addition, a tendency for increased pregnancy failure, increased pre-and postimplantation loss, and decreased fetal body weight was observed. However, no fetal morpho-logical abnormalities were seen in surviving fetuses at a dose level of 1000mg BPA/kg. On the other hand, the maternal toxicity and developmental toxicity found in the groups IV and V were comparable to those of the group II. There were no adverse signs of either maternal toxicity or developmental toxicity in the group III. These results showed that administration of BPA at a dose level of 1000mg/kg to pregnant rats resulted in significant maternal toxicity and minimal developmental toxicity, and that no protective effects on BPA-induced maternal toxicity and developmental toxicity were found by concomitant gavage dosing of KRGWE.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.108-108
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• 1995

Pharmacokinetic studies on time-course of blood levels, tissue distribution, and excretion of G009, a potential hepatoprotective agent, were performed in male rats after a single oral dose(20mg/kg) of $\^$14/C-labelled G009. The radioactivity concentrations in plasma during 0～3 hours are low, but subsequently increase to a maximum at 12 hours after dosing. $\^$14/C-G009 was well distributed to all tissue. Tissue concentration profiles of radioactivity vary among tissues on time-course after administration. G009(single oral dosage) was distributed and/or absorbed at gastric intestines and excretional organs for initial time of 0-7 hours, and distributed to most tissue at 12-24 hours. In special, the concentration of radioactivity in tiller at 48 hours were 1% of total radioactivity of $\^$14/C-G009 administered. The expired air, urinary and fecal excretion of radioactivity within 24hours after administration were 61.5%, 1.9% and 21.2% of total radioactivity of $\^$14/C-G009 administered. The biliary excretion of radioactivity in rat increased slightly for 0-6 hours after administration. The biliary excretion of radioactivity within 48hours were 1.97%.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.201-209
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• 2018

G protein-coupled receptor 119 (GPR119) is expressed in the pancreas and gastrointestinal tract, and its activation promotes insulin secretion in the beta cells of the pancreatic islets as well as the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells, consequently improving glucose-stimulated insulin secretion. Due to this dual mechanism of action, the development of small-molecule GPR119 agonists has received significant interest for the treatment of type 2 diabetes. We newly synthesized 1,2,4-triazolone derivatives of GPR119 agonists, which demonstrated excellent outcomes in a cyclic adenosine monophosphate (cAMP) assay. Among the synthesized derivatives, YH18968 showed cAMP=2.8 nM; in GLUTag cell, GLP-1secretion=2.3 fold; in the HIT-T15 cell, and insulin secretion=1.9 fold. Single oral administration of YH18968 improved glucose tolerance and combined treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor augmented the glucose lowering effect as well as the plasma level of active GLP-1 in normal mice. Single oral administration of YH18968 improved glucose tolerance in a diet induced obese mice model. This effect was maintained after repeated dosing for 4 weeks. The results indicate that YH18968 combined with a DPP-4 inhibitor may be an effective therapeutic candidate for the treatment of type 2 diabetes.

• Journal of Korean Society of Water and Wastewater
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• v.23 no.4
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• pp.459-469
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• 2009

It is well known that coagulation pretreatment can reduce foulants prior to membrane filtration. The purpose of this research was to investigate the effects of coagulation on fouling of ceramic microfiltration membrane($0.1 {\mu}m$) using pilot plant of $150m^3/day/train$ capacity. Train A membrane system has pretreatment process of ozonation and coagulation while train B has only coagulation. Two types of coagulation operation were investigated: back mixer(rapid mixing with or without slow mixing) which is a conventional mechanically stirred mixer and an inline static mixer. Ozone dose rate for train A was 1 mg/L and ozone contact time was 12 min. The coagulation dose(PACl 10% as $Al_2O_3$) rate was changed 20~40 mg/L according to experimental schedule. In this experimental conditions, the coagulation of back mixer type with rapid mixing(GT=72,000) and slow mixing(GT=45,000) was the best effective in reduction of ceramic membrane fouling regardless preozonation. Especially, the effect of inline static mixer was sensitive to change in water quality. Ozonation mainly affected irreversible fouling rather than reversible fouling in accordance with less adsorption of NOM on the membrane surface. Thus, the increase rate of the nomalized TMP(trans membrane pressure) at $25^{\circ}C$ for train A was relatively lower than that of train B under same coagulation process with same coagulant dosage. The best performance of ceramic membrane appeared in case of combined process with ozonation, therefore this integrated process is able to archive less coagulant dosing and secure a stability of ceramic membrane system.

• Proceedings of the Korea Water Resources Association Conference
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• 2007.05a
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• pp.8-14
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• 2007

Water quality in Lake Rotorua, New Zealand, deteriorated since the 1960s because of excessive phytoplankton growths due principally to increasing nitrogen and phosphorus in the lake waters. Nutrient concentrations in eight of the nine major streams feeding Lake Rotorua have increased since 1965. The groundwater system has a key role in the hydrology of the Lake Rotorua catchment and the groundwater system is probably the control on the time delay between intensification of agricultural land use and response of surface water quality. All major, and many minor streams, in the catchment are fed by springs. Two lithological units are most important to groundwater flow in the Lake Rotorua catchment: Mamaku Ignimbrite, erupted in about 200,000 years ago and Huka Formation sediments which filled the caldera left by the Mamaku Ignimbrite eruption. Rainfall recharge to groundwater in the groundwater catchment of Lake Rotorua is estimated as approximately 17300 L/s. A calibrated steady-state groundwater flow model estimates that approximately 11100 L/s of this flow discharges into streams and then into the lake and the balance travels directly to Lake Rotorua as groundwater discharge through the lake bed. Land use has impacted on groundwater quality. Median Total Nitrogen (TN) values for shallow groundwater sites are highest for the dairy land use (5.965 mg/L). Median TN values are also relatively high for shallow sites with urban-road and cropping land uses (4.710 and 3.620 mg/L, respectively). Median TN values for all other uses are in the 1.4 to 1.5 mg/L range. Policy development for Lake Rotorua includes defining regional policies on water and land management and setting an action plan for Lake Rotorua restoration. Aims in the action plan include: definition of the current nutrient budget for Lake Rotorua, identification of nutrient reduction targets and identification of actions to achieve targets. Current actions to restore Lake Rotorua water quality include: treatment of Tikitere geothermal nitrogen inputs to Lake Rotorua, upgrade of Rotorua City sewage plant, new sewage reticulation and alum dosing in selected streams to remove phosphorus.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.205-210
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• 1992

In order to develop a controlled-release oral drug delivery system (DDS) of theophylline (TP), microporous membrane-coated tablets were prepared and evaluated in vitro and in vivo. Rapidly water-soluble core tablets of TP (300 mg) were prepared by wet granulation and compression technique, Then the core tablets were spray-coated with polyvinylchloride (PVC) in which micronized sucrose particles were dispersed. Effect of formula compositions of coating suspensions on the pharmaceutical characteristics such as membrane strength and dissolution was investigated in vitro. The membranes remained unbroken in pH 1.2 buffer at $37^{\circ}C$ at least for 2 hours after the disintergration test. TP was released from the coated-released tablets at a zero-order rate over 8 hours. The release at pH 1.2 and 4.0 was similar in rate but a little more rapid than that at pH 6.8. The coated tablets were administered to three healthy male volunteers and their saliva profiles of TP were compared with those from the commercial sustained release TP tablets such as Slobid and Asconthin. Saliva TP concentrations from the coated tablets were successfully sustained over 48 hours after the dosing and were comparable to those of the commercial sustained-release tablets. The membrane-coating technique is very simple and does not need any sophisticated equipments. In this respect, the membrane-coated tablets may be superior to the commercial sustained-release tablets and this technique is worth adopting by the pharmaceutical industries.

• Journal of Pharmaceutical Investigation
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• v.24 no.3
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• pp.115-129
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• 1994

In the present study, quantitative and qualitative histology was used to assess the effects of ibuprofen suppositories with various treatments on the rectal mucosa of rats. Two suppositories were prepared with Witepsol W35 and compared with two commercial ibuprofen suppositories Reference I (Showa Pharm.ind., Tokyo, Japan), Reference II (P.Pharm., Seoul, Korea). Single and multiple dose(dosing interval 4 hr, n=4) studies were conducted. All suppositories significantly increased epithelial cell loss, but the extent of rectal irritation was variable. These studies showed that the incorporation of ibuprofen into the suppository bases increases the morphological change in rectal tissue both for the single and multiple administrations of suppositories, but which was significantly recovered within 24 hr although the interanimal variability in scores was very substantial. Multiple administration of ibuprofen suppositories caused significant damage to rectal mucosa, but it must be considered that these were under the severe condition, that is, interval of administration (4 hr) was three times shorter than normal interval of administration and dose was fifteen times larger than usual human dose. Aluminum oxide $(Al_2O_3)$, a dispersing agent, slightly increased the irritation of rectal mucosa in rats at 5 hr and 24 hr after multiple administration, but it was possible to ignore the difference of irritation in the data at 5hr and 24hr after single administration. Finally, it was concluded that Witepsol W35 and ibuprofen had a slight rectal mucosa-irritating effect on the usual human dose, and ibuprofen suppositories prepared with Witepsol W35 or Witepsol W35, $Al_2O_3$ showed almost similar extent of rectal irritation with commercial ibuprofen products.