• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.349-353
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• 1996

The present study examined pharmacokinetic profiles of KBP31705-Cl27 and KBP30603-901, new platinum coordination complexes synthesized as anticancer candidates, in comparison with two well-known platinum-containing anticancer agents, cisplatin and carboplatin in rats. Under sodium pentobarbital anesthesia of male Sprague-Dawley rats, urinary bladder, and femoral artery and vein were catheterized for urine collection, blood sampling and drug injection, respectively Following i.v. administration of cisplatin (2 mg/kg), KBP31705-C127 (2 mg/kg), carboplatin (20 mg/kg) or KBP30603-901 (20 mg/kg), blood samples were collected at 2, 4, 6, 8, 10, 15, 20, 30, 45, 60 and 120 minutes. Urine samples were collected at 1-hr interval for 4 hr. Platinum concentrations in plasma and urine were measured using an inductively coupled plasmamass spectrometer. The plasma concentration-time curves were biphasic for all drugs during the time period studied. Compared with cisplatin, KBP31705-C127 showed similar decay patters in the alpha- and betaphases with slightly lower plasma concentrations. Urinary platinum excretion for cisplatin and KBP31705-C 127 was 56 and 52% of the administered dose in 4 hr, respectively. With regard to carboplatin and KBP 30603-901, a similar decay pattern was also observed in the alpha-phase. The half life of KBP30603-901 in the beta-phase, however, was much longer than that of carboplatin, which was consistent with the urinary excretion results that 46 and 59% of the administered dose were excreted in the urine in 4hr, respectively. The results suggest that platinum coordination complexes are primarily excreted via the renal route and KBP30603-901 can elicit longer duration of action due to slower renal excretion compared to carboplatin.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.126-133
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• 2011

The fruit of Actinidia arguta (AA) has been used mainly for the treatment of skin diseases, diuresis, diabetes mellitus and osteoporosis in Korean traditional medicine. It is known that AA (hardy kiwi) fruit extract has an effect on 2-chloro-1,3,5-trinitrobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice. Mode of action for it is associated with the modulation of biphasic Th1/Th2 cytokines. Furthermore, DA9102 containing AA is a herbal medicine currently under phase II clinical trial for atopic dermatitis in Korea. However, no active principles of AA on the decrease of Th2 cytokines including IL-4 and IL-10 have been identified. In this study, bioactivity-guided fractionation of an alcohol extract from the dried fruits of AA using ELISA assay for IL-4 production led to the isolation of $\alpha$-linolenic acid (I), linoleic acid (II), ethyl linolenate (III), ethyl linoleate (IV) and ethyl stearate (V) as the major active components. These compounds showed the down-regulatory effects of IL-4 production in A23187-stimulated RBL-2H3 cells without cytotoxicity.

• Archives of Plastic Surgery
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• v.32 no.6
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• pp.760-762
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• 2005

Synovial Sarcoma is the fourth most common sarcoma, accounting for 8-10 % of all sarcomas. Synovial sarcoma is highly malignant tumor of mesenchymal origin but rarely occurres in head and neck area. Less than 100 cases of synovial sarcoma occurring in head and neck area have been reported all over the world. Pathologically, there is two type of synovial sarcoma: monophasic variant is composed of only one cell type and "classic" (biphasic) synovial sarcoma has two cellular component, a spindle cell(fibrosarcoma-like) component and a pseudoepithelioma component. Recommended treatment is wide resection with negative margins. The role of chemotherapy and radiation therapy is controversial. We experienced a 42-year-old male patient with slowly enlarging, deep seated mass on right cheek. In the first operation, we suggested that the mass maybe benign tumor. But, initial excisional biopsy specimen of the primary lesion was consistent with synovial sarcoma. The final diagnosis was monophasic synovial sarcoma which was composed of spindle cells. Radical resection was performed two months later because remnant tumor was found on follow up MRI. No further treatment was done. There were no recurrence or metastasis on follow up MRI, chest CT and whole body bone scan after 15 months. This is a report of a rare case of synovial sarcoma of the face with a literature review.

• Journal of Periodontal and Implant Science
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• v.41 no.3
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• pp.123-130
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• 2011

Purpose: The purpose of this study was to determine the biological effects of cyanoacrylate-combined calcium phosphate (CCP), in particular its potential to act as a physical barrier - functioning like a membrane - in rabbit calvarial defects. Methods: In each animal, four circular calvarial defects with a diameter of 8 mm were prepared and then filled with either nothing (control group) or one of three different experimental materials. In the experimental conditions, they were filled with CCP alone (CCP group), filled with biphasic calcium phosphate (BCP) and then covered with an absorbable collagen sponge (ACS; BCP/ACS group), or filled with BCP and then covered by CCP (BCP/CCP group). Results: After 4 and 8 weeks of healing, new bone formation appeared to be lower in the CCP group than in the control group, but the difference was not statistically significant. In both the CCP and BCP/CCP groups, inflammatory cells could be seen after 4 and 8 weeks of healing. Conclusions: Within the limits of this study, CCP exhibited limited osteoconductivity in rabbit calvarial defects and was histologically associated with the presence of inflammatory cells. However, CCP demonstrated its ability to stabilize graft particles and its potential as an effective defect filler in bone augmentation, if the biocompatibility and osteoconductivity of CCP were improved.

• YAKHAK HOEJI
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• v.45 no.1
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• pp.116-124
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• 2001

Nitric oxide is a labile, gaseous, broad spectrum second messenger that used in various tissues and cells. If it is induced by endogenously and exogenously in the neuronal cells, it is able to mediate analgesia or hyperalgesia at the periphery and in the spinal level respectively. This dual role of nitric oxide in the sensory system is very intriguing but has not been fully understood yet. In this experiment, acetylcholine (300 $\mu$g/paw), sodium nitroprusside (600 $\mu$g/paw), and L-arginine (300 $\mu$g/paw) represented antinociceptive effect to noxious topical stimulus, but pronociceptive responses followed by spinally application (20$\mu$g/5$\mu$l, 10$\mu$g/3$\mu$l, 500$\mu$g/5$\mu$l respectively). Calcium ion is critical element which activates nitric oxide synthase, therefore verapamil (300 $\mu$g/paw) and NOS inhibitor (20 mg/kg, L-NAME or L-NOArg) are injected into right hind paw (i.pl.). When verapamil is combined with NOS inhibitors analgesic effects through NO-cGMP pathway are inhibited as compared with ACh alone. Diluted formalin (2.5%), when injected into rats'hind paw (0.05 ml), elicited a biphasic algesic responses and nitric oxide had an analgesic effect on both $A\delta$ and C sensory nerve fibers which manipulate the phases respective1y. Nitric oxides, which produced from constitutive nitric oxide synthase, activated cyclooxygenase-type I and then prostaglandins are produced from them. So, indomethacin and ibuprofen, inhibitors of COX$_1$enzyme, when pretreated intraperitoneally (100 mg/kg) could reduce the hyperalgesic state. From these results, it is possible to imagine that the intrathecally administered NO donors expressed hyperalgesia through both long-term potentiation mechanism and arachidonic acid-prostaglandin cascade.

• The Korean Journal of Zoology
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• v.33 no.1
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• pp.53-62
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• 1990

Fully grown amphibian oocytes undergo their maturation (germinal vesicle breakdown, GVBD) during in vitro follicle culture when they are stimulated with frog pituitary homogenate (FPH) or progesterone. Present experiments were designed to determine whether proteolytic enzymes are involved in the regulation of the matunation process. Treatment of a $\alpha$ -chymoiyypsin inhibitor, N a -tosyl-L-phenylalanine-chloromethyl-ketone(TP) to the oocytes exhibited a biphasic phenomenon, the induction of the maturation without added hormone at relatively low doses (0.001-1 $\mu$M) and inhibition of the hormone induced oocyte maturation at a high dose (100 $\mu$M). Treatment of a trypsin inhibitor, N a -tosyl-L-lysine-chloromethyl ketone(TLCK) to the oocytes did not induce the maturation, but rather suppressed the hormone induced oocyte maturation in a high dose(100 $\mu$ M). Treatment of exogenous iyypsin to the oocyte induced their maturation without added hormone in a dose dependent manner (0.001-1 $\mu$ M). The data presented here indicate that some proteolytic enzymes play a role in the regulation of the maturation(meiotic arrest or reinitiation) in amphibians.

• Journal of Veterinary Clinics
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• v.22 no.3
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• pp.220-227
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• 2005

Although ketamine has been used in the field of anesthetic medicine for its safety and favourable respiratory effects, the cardiovascular effects of ketamine is still controversial. To clarify the action and mechanism of ketamine upon cardiovascular system, arterial blood pressure, tension of aortic ring, left ventricular developed pressure and heart rate were measured in rats, Ketamine produced two types of effects on arterial blood pressure in anesthetized rats; monophasic effect (blood pressure lowering) and biphasic effect (initial transient blood pressure increasing following sustained lowering), The ketamine-induced lowering of aterial blood pressure showed a concentration-dependent manner, inhibited by the pretreament of $MgCl_2$ and potentiated by the pretreatment of $CaCl_2$. The ketamine-induced lowering of aterial blood pressure was suppressed by the pretreatment of nifedipine, verapamil or lidocaine. In phenylephrine-precontracted endothelium intact (+E) aortic rings, ketamine sometimes caused a small enhancement of contraction ($112.5{\pm}3.6{\%}$). However, in many experiments, ketamine produced a concentration-dependent relaxation in +E aortic rings precontracted with either phenylephrine or KCl. Ketamine-induced relaxation was significantly greater in KCl-precontracted strips than phenylephrine-precontracted strips. In phenylephrine-precontracted +E aortic rings, the ketamine-induced vasorelaxation was not suppressed by endothelium removal or by the pretreatment of a nitric oxide synthase inhibitors, L-$N^G$-nitro-arginine and a guanylate cyclase inhibitors, methylene blue, suggesting that the ketamine-induced vasorelaxation is not dependent on the endothelial function. In addition, ketamine elicited an increase in left ventricular developed pressure in perfused hearts accompanied by decrease in heart rate. These results suggest that ketamine could evoke a hypotension due to vasorelaxation and decrease in heart rate in rats. The inhibitory effect of cardiovascular system might be associated with modulation of $Ca^{2+}$ homeostasis.

• Journal of Veterinary Clinics
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• v.24 no.1
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• pp.26-28
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• 2007

An 11-year-old castrated male, Shih-tzu dog was admitted for progressive weight-bearing lameness and mass on the right hindlimb. Radiography and ultrasonography revealed a large well-marginated multinodular mass with mixed echogenicity. On T1 and T2-weighted magnetic resonance imaging (MRI), the mass has a heterogenous signal intensity similar to or higher than muscle. The masses were extended to the pelvic cavi쇼 through obturator foramen and displaced the rectum dorsally. It was diagnosed as synovial sarcoma which was composed with mesenchymal and epithelial elements on histopathological findings of the multifocal biopsied specimen. MRI was helpful to determine the definitive margin for surgical resection of the mass. The mass was recurred at the 6th month after surgery. On the 10th month, the patient was euthanasiuzed by owner's request.

• The Korean Journal of Pain
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• v.30 no.2
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• pp.98-103
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• 2017

Background: The root of Peucedanum japonicum Thunb., a perennial herb found in Japan, the Philippines, China, and Korea, is used as an analgesic. In a previous study, sec-O-glucosylhamaudol (SOG) showed an analgesic effect. This study was performed to examine the antinociceptive effect of intrathecal SOG in the formalin test. Methods: Male Sprague-Dawley rats were implanted with an intrathecal catheter. Rats were randomly treated with a vehicle and SOG ($10{\mu}g$, $30{\mu}g$, $60{\mu}g$, and $100{\mu}g$) before formalin injection. Five percent formalin was injected into the hind-paw, and a biphasic reaction followed, consisting of flinching and licking behaviors (phase 1, 0-10 min; phase 2, 10-60 min). Naloxone was injected 10 min before administration of SOG $100{\mu}g$ to evaluate the involvement of SOG with an opioid receptor. Dose-responsiveness and ED50 values were calculated. Results: Intrathecal SOG showed a significant reduction of the flinching responses at both phases in a dose-dependent manner. Significant effects were showed from the dose of $30{\mu}g$ and maximum effects were achieved at a dose of $100{\mu}g$ in both phases. The ED50 value (95% confidence intervals) of intrathecal SOG was 30.3 $(25.8-35.5){\mu}g$ during phase 1, and 48.0 (41.4-55.7) during phase 2. The antinociceptive effects of SOG ($100{\mu}g$) were significantly reverted at both phases of the formalin test by naloxone. Conclusions: These results demonstrate that intrathecal SOG has a very strong antinociceptive effect in the formalin test and it seems the effect is related to an opioid receptor.

• Journal of Pharmaceutical Investigation
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• v.34 no.3
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• pp.185-192
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• 2004

The objective of this study was to evaluate the effects of surfactant type and concentration upon dissolution rates of carbamazepine from an immediate-release tablet. The dissolution media used in this study were aqueous solutions containing 0.1-2% sodium lauryl sulfate, cetyltrimethylammonium bromide, or polysorbate 80. The solubility of carbamazepine in the dissolution media was determined at first. A dissolution study was then conducted by using the USP dissolution apparatus II (paddle method) with an agitation rate of 75 rpm. Aliquots of the dissolution media were taken at predetermined time intervals, and the amount of carbamazepine dissolved was measured spectrophotometrically at 285 nm. The dissolution data obtained were fitted into a biphasic exponential equation with four parameters. Excellent correlations were observed between the experimental data and the theoretical ones predicted by the equation. This equation permitted the calculation of $T_{50%}$ (the time required for dissolving 50% of carbamazepine) under various experimental conditions. Differentiation of the equation also led to the attainment of dissolution rates at dissolution time points. The addition of a surfactant to an aqueous solution led to increasing the solubility of carbamazepine by 3- to 12-folds, depending upon its type and concentration. This event also resulted in enhancing the magnitude of a sink condition during the dissolution study. As a result, the dissolution rate of carbamazepine was affected by the aqueous surfactant concentration in a proportional manner. Subsequently, $T_{50%}$ values declined rapidly, as the surfactant concentration increased. Such effects were observed in decreasing order of sodium lauryl sulfate, cetyltirmethylammonium bromide, and polysorbate 80. These results clearly demonstrated that it was possible to tailor a dissolution rate and $T_{50%}$ of carbamazepine by manipulating the type and concentration of a surfactant. Relevant information would be beneficial to setting up dissolution specifications for poorly water-soluble drug products.