• Reproductive and Developmental Biology
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• v.38 no.3
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• pp.107-114
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• 2014

Oral exposure of humans by excess amounts of arsenic may cause disturbances of the reproductive system. In the present study, such exposure was modelled in rats, with the support of sperm principal parameters and histopathological observations. Male Sprague-Dawley rats were randomly divided into three groups where the group I was served as a normal control, group II was received sodium meta-arsenite as arsenic (10 mg/kg b.w/day) and a combination of sodium meta-arsenite and sodium selenite (3 mg/kg b.w/day) in group III. After 6 weeks, there was no significant change in testis weight and in total motility of all the three experimental groups, whereas, rapid moving spermatozoa, moderately moving spermatozoa and slow moving spermatozoa were significantly decreased in arsenic treated rats as compared to control rats. The other sperm principal parameters like progressiveness, average path velocity, straightness linear velocity (VSL), curvilinear velocity (VCL), straightness, linearity sperm head elongation ratio, area, linearity amplitude of lateral head department (ALH) and beat cross frequency (BCF) were found to be reduced in arsenic intoxicated rats. These results are not correlated with the histological studies. On oral administration of selenium ameliorated the adverse effects of arsenic as compared to arsenic alone treated rats. Our findings clearly demonstrate that administration of selenium could prevent some of the deleterious effects of arsenic in the testis.

• Journal of Applied Biological Chemistry
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• v.55 no.4
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• pp.201-205
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• 2012

The present study was conducted to evaluate of the 1,1-Diphenyl-2-Picrylhydrazyl (DPPH) radical scavenging effect, cytotoxicity and tyrosinase inhibition activities using methanol extracts from different parts of four herb plants. The results showed that whole and root extracts of yarrow the highest total polyphenol and flavonoid contents as well as whole of yarrow revealed the highest DPPH radical scavenging effect. In cytotoxicity test against three cancer cell lines, HeLa (uterus), SK-Hep-1 (liver), and YD-15 (oral), the whole extract of feverfew showed the highest toxicity with $IC_{50}$ values of $102.58-138.68{\mu}g/mL$. Also, mallow root extract ($71.24{\mu}g/mL$) exhibited potent tyrosinase inhibitory activity comparable to arbutin ($69.56{\mu}g/mL$), which was used as the control.

• Journal of The Korean Dental Society of Anesthesiology
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• v.1 no.1 s.1
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• pp.26-31
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• 2001

The wide deep penetrating wound of maxillofacial region should be early closed under emergency general anesthesia for the prevention of complications of bleeding, infection, shock & residual scars. But, if the emergency general anesthesia wound be impossible because of pneumoconiosis, obstructive pulmonary disease & hypovolemic shock, early primary closure should be done under local anesthesia by use of much amount of the anesthetic solution. The maximum dose of dental lidocaine (2% lidocaine with 1 : 100,000 epinephrine) is reported to 7 mg/kg under 500 mg (13.8 ampules) in normal adult. But the maximum permissible dose of dental lidocaine can be changed owing to the general health, rapidity of injection, resorption, distribution & excretion of the drug. The blood level of overdose toxicity is above $4.0{\mu}g/ml$ in central nervous & cardiovascular system. The injection of dental lidocaine 1-4 ampules is attained to the blood level of $1{\mu}g/ml$ in normal healthy adult. The duration of anesthetic action in the dental 2% lidocaine hydrochloride with 1 : 100.000 epinephrine is 45 to 75 minutes and the period to elimination is about 2 to 4 hours. Therefore, authors selected the following anesthetic methods that the first injection of 6 ampules is applied into the deeper periosteal layer for anesthetic action during 1 hour, the second injection into the deeper muscle & fascial layer, the third injection into the superficial muscle and fascial layer, the fourth injection into the proximal skin & subcutaneous tissue and the fifth final injection into the distal skin & subcutaneous tissue. The total 26-28 ampules of dental lidocaine were injected into the wound as the regular time interval during 5-6 hours, but there were no systemic complications, such as, agitation, talkativeness, convulsion and specific change of vital signs and consciousness.

• YAKHAK HOEJI
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• v.38 no.3
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• pp.250-264
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• 1994

Omeprazole(OMZ)-cholestyramine(CHL) and various OMZ-Dowex resin complexes were prepared by reaction between OMZ and activated resins in 0.1N NaOH solution. And their physical properties were tested by means of infrared(IR), differential scaning caloimeter(DSC), X-ray diffraction. Chemical stability of OMZ-CHL was increased markedly compared with OMZ and the decomposition of OMZ-CHL followed the pseudo first-order kinetics and the rate constants were $2.743{\times}10^{-4}/day$ at $20^{\circ}C$, $7.83{\times}10^{-3}day^{-1}$ under 80% RH and $1.68{\times}10^{-2}day^{-1}$ under UV radiation, respectively. On the other hand, the rate constants of OMZ were $2.996{\times}10^{-4}day^{-1}$ at $20^{\circ}C$, $1.17{\times}10^{-2}day^{-1}$ under 85% RH, and $4.07{\times}10^{-2}day^{-1}$ under UV radiation, respectively. The rates of dissolution of OMZ-CHL bulk and OMZ-CHL tablet were 100% and more than 85% in 15 minutes, respectively, which were increased than OMZ base and OMZ-tablet. In the acute toxicological test, the value of oral $LD_{50}$(mouse) was 4.608 g/kg. OMZ-CHL was pelletized using lactose, polyethyle neglycol(PEG), D-sorbitol, Avicel PH 101, sodium laurylsulfate and polyvinylpyrrolidone(PVP) K-30, and enteric coated with HPMCP, Myvacet, acetone, ethanol and cetanol, of which dissolution rate was found to be more than 85% in 10 minutes. From the above results, it was found that OMZ-CHL is a useful means for development of new oral dosage forms of OMZ.

• Microbiology and Biotechnology Letters
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• v.9 no.3
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• pp.117-121
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• 1981

Safety of yellow pigment produced by Monascus sp. CS-2 was evaluated. Acute oral toxicity, pyrogen test, and histamine test, as well as antimicrobial activity were determined. The results obtained were; LD oral in mice was 132.5 mg/20 g, pyrogen test in rabbit was 5 mg/kg, and histamine test in cat was 10 mg/kg. Also the pigment was particularly sensitive to Bacillus subtilis (ATCC 6633), Sarcina lutea (ATCC 9341) and Staphylococcus aureus (ATCC 6538 P), whereas not sensitive to Pseudomonas pyosyanea (ACTC 10490), Bacillus var. mycoides (ATCC 11778), Bordetella bronchiseptica (ATCC 4617) and Staphylococcus epidermidis(ATCC 12228).

• Journal of Society of Preventive Korean Medicine
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• v.17 no.1
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• pp.77-88
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• 2013

Objectives : This study was aim to evaluate effects of pharmacodynamics and toxicity in combination therapy of donepezil with Gongjindan. Methods : After 10mg/kg of donepezil treatment, Gongjindan 100mg/kg was administered within 5 min. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of Gongjindan treatment, and plasma concentrations of donepezil were analyzed using LC-MS/MS methods. PK parameters of donepezil were analysis as compared with donepezil single administered rats. Results : Gongjindan markedly inhibited the absorption of donepezil regardless of sample time, from 30min to 8hrs after end of co-administration comparing with donepezil single treated rats. Especially the absorption of donepezil was significantly decreased at 2hrs after co-administration as compared with donepezil single treated rats, in the present study. Accordingly, the Cmax(-27.76%), $AUC_{0-t}$(-27.22%) and $AUC_{0-inf}$(-26.54%) of donepezil in co-administered rats were significantly decreased as compared with donepezil single treated rats, respectively. Conclusions : Based on the results of the present study, co-administration of Gongjindan decreases the oral bioavailability of donepezil by inhibiting the absorption. It is considered that the more detail pharmacokinetic studies should betested to conclude the effects of Gongjindan on the pharmacokinetics of donepezil, when they were co-administered, like the effects after co-administration with reasonable intervals considering the Tmax of donepezil and after repeated co-administrations.

• Journal of Life Science
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• v.29 no.12
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• pp.1345-1350
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• 2019

Our recent study has revealed that in vivo intestinal transit rate (ITR) in normal mice was significantly increased by the administration of an aqueous extract of dried Gentiana scabra rhizomes and roots (GS-W) in a dose-dependent manner. Following on from our previous study, the effect of GS-W on ITR was measured in mice with experimentally induced gastrointestinal motility dysfunctions (GMDs) in the present study. GS-W showed no significant acute toxicity even at an oral dose of 5 g/kg to mice. ITR was significantly retarded in the GMD mice compared with that in normal mice, and this retardation was significantly recovered by the oral administration of GS-W in a dose-dependent manner. Furthermore, the ITR value of GS-W at a dose of 1 g/kg appeared to be higher than that of cisapride, which was predominantly prescribed for human patients with various GMDs in the late 1900s but was withdrawn from the market in 2000 due to its fatal side effects. The current results suggest that GS-W is a potential substitute for cisapride to prevent or alleviate human GMDs.

• Archives of Pharmacal Research
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• v.25 no.2
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• pp.197-201
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• 2002

${\beta}-lonone$ has been reported to induce the cytochrome P45O (P45O) 2B1 in rats. In this study, the effects of ${\beta}-ionone$ and an isomer, ${\alpha}-ionone$, on liver P45O IA and 2B expression in Sprague Dawley rats were investigated . Subcutaneous administration of ${\alpha}-$ and ${\beta}-lonone$ 72 and 48hr prior to sacrificing the animals induced the liver microsomal P45O 1A and 2B proteins. P45O 2Bl induction was associated with the accumulation of its corresponding mRNA. 1 Induction by ${\beta}-lonone$ was much higher than that by ${\alpha}-ionone$-ionone in both the mRNA and protein levels. When the route of administration was compared, P45O 2B was induced more strongly after oral administration compared to that after subcutaneous injection. A single oral dose of 100, 300 and 600 mg/kg of ${\alpha}-$ and ${\beta}-lonone$ for 24 h induced P45O 2B1 -selective pentoxyresorufin Odepentylase activity comparably in a dose-dependent manner In addition, ${\alpha}-$ and ${\beta}-lonone$ induced the P45O 1A and 2B proteins. These results suggest that ${\alpha}-$ and ${\beta}-lonone$ might be potent P45O 2Bl inducers in rats, and that both ionones may be useful for examining the role of metabolic activation in chemical-induced toxicity where metabolic activation is required.

• Mass Spectrometry Letters
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• v.12 no.4
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• pp.200-205
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• 2021

Polynemoraline C, a pyridocoumarin alkaloid, exhibits anticholinergic, anti-inflammatory, antitumor, and antimicrobial activities. A sensitive analytical method of polynemoraline C in mouse plasma was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Polynemoraline C and ¹³C-caffeine (internal standard) in mouse plasma were extracted using a liquid-liquid extraction method coupled with ethyl acetate. This extraction method resulted in high and reproducible extraction recovery in the range of 73.49%-77.31% with no interfering peaks around the peak retention time of polynemoraline C and ¹³C-caffeine. The standard calibration curves for polynemoraline C were linear over the range of 0.5-200 ng/mL with r² > 0.985. The accuracy, precision, and the stability of the data were within acceptable limits on the FDA guideline. After intravenous and oral administration of polynemoraline C at doses of 5 and 30 mg/kg, respectively, the present method was successfully applied to the pharmacokinetic study of polynemoraline C. Polynemoraline C in mouse plasma showed a multi-exponential elimination pattern with a high volume of distribution values. This compound's absolute oral bioavailability was found to be 17.0%. Polynemoraline C's newly developed LC-MS/MS method can be used for further studies on the efficacy, toxicity, and biopharmaceutics of polynemoraline C, as well as its pharmacokinetic studies.

• Mass Spectrometry Letters
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• v.12 no.1
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• pp.21-25
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• 2021

We aimed to develop and validate a sensitive analytical method of nannozinone A, active metabolite of Nannochelins A extracted from the Myxobacterium Nannocytis pusilla, in mouse plasma using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Mouse plasma samples containing nannozinone A and 13C-caffeine (internal standard) were extracted using a liquid-liquid extraction (LLE) method with methyl tert-butyl ether. Standard calibration curves were linear in the concentration range of 1 - 1000 ng/mL (r2 > 0.998) with the inter- and intra-day accuracy and precision results less than 15%. LLE method gave results in the high and reproducible extraction recovery in the range of 78.00-81.08% with limited matrix effect in the range of 70.56-96.49%. The pharmacokinetics of nannozinone A after intravenous injection (5 mg/kg) and oral administration (30 mg/kg) of nannozinone A were investigated using the validated LC-MS/MS analysis of nannozinone A. The absolute oral bioavailability of nannozinone A was 8.82%. Plasma concentration of nannozinone A after the intravenous injection sharply decreased for 4 h but plasma concentration of orally administered nannozinone A showed fast distribution and slow elimination for 24 h. In conclusion, we successfully applied this newly developed sensitive LC-MS/MS analytical method of nannozinone A to the pharmacokinetic evaluation of this compound. This method can be useful for further studies on the pharmacokinetic optimization and evaluating the druggability of nannozinone A including its efficacy and toxicity.