• Macromolecular Research
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• 제12권3호
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• pp.269-275
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• 2004

To graft N-isopropylacrylamide (NIPAAm) onto alginate, varying dosages of ${\gamma}$-rays were irradiated onto alginate films in deionized water and methanol media, which are non-solvents of alginate. We investigated the hydrogels graft ratio, mechanical strength, swelling kinetics and ratio, and behavior with respect to drug release. The graft yield of NIPAAm increased upon increasing the irradiation dose. The use of the aqueous solution increased the graft yield relative to that obtained in methanol. The mechanical strength of the grafted hydrogels increased after grafting with NIPAAm. In a study of the swelling kinetics, we found that all hydrogels reached an equilibrium swollen state within 3 h. The equilibrium swelling ratio of the hydrogels decreased upon increasing the irradiation dose. The swelling ratio of the hydrogels decreased dramatically between 30 and 35$^{\circ}C$ because phase separation of NIPAAm occurred at 32$^{\circ}C$. The swelling process, with respect to the temperature change, was repeatable. An NIPAAm-grafted alginate containing a drug sustained its release rate until 3 h after an initial high drug release caused by a burst effect.

• Biomolecules & Therapeutics
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• 제7권1호
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• pp.22-28
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• 1999

Induction of apoptosis is considered to be the underlying mechanism that accounts for the efficiency of chemotherapeutic drugs. It has recently been proposed that doxorubicin (DOX) can induce apoptosis in human leukemic cells via the Fas/Fas Ligand (FasL) system. Comparison of Fas and FasL mRNA expression between drug- and anti-Fas antibody(Fas-Ab)- induced apoptosis was analyzed for examining the role of Fas/FasL system in the mediation of drug-induced apoptosis. After HL-60 cells were routinely cultured, MTT assay was performed for cytotoxicity test. Giemsa staining was carried out to monitor the apoptosis morphologically. By semiquantitative RT-PCR analysis, the expression of Fas and FasL at 4, 10, 24 hours was determined after DOX and Fas-Ab treatment. Dose-dependent cytotoxicity was induced by DOX-treatment, while Fas-Ab treatment showed the similar dose-dependent pattern but the cytotoxicity is not reached at LD$_{50}$ at 100 ng/ml concentration of Fas-Ab. In the 10ng/m1 DOX and 10ng/m1 Fas-Ab treated group, typical apoptotic cell morphology was shown such as fragmented nuclei and cell membrane budding in the Giemsa-stained slide. Fas mRNA expression was not changed significantly in the both groups. But, FasL mRNA expression was induced significantly at initial period of apoptosis. In this study, Fas/FasL interaction assumed to be involved in drug-induced apoptosis.s.

• The Korean Journal of Pain
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• 제35권1호
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• pp.59-65
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• 2022

Background: There is still unmet need in treating neuropathic pain and increasing awareness regarding the use of drug combinations to increase the effectiveness of treatment and reduce adverse effects in patients with neuropathic pain. Methods: This study was performed to determine the individual and combined effects of pregabalin, tianeptine, and clopidogrel in a rat model of neuropathic pain. The model was created by ligation of the L5-L6 spinal nerve in male Sprague-Dawley rats; mechanical allodynia was confirmed using von Frey filaments. Drugs were administered to the intrathecal space and mechanical allodynia was assessed; drug interactions were estimated by isobolographic or fixed-dose analyses. Results: Intrathecal pregabalin and tianeptine increased the mechanical withdrawal threshold in a dose-dependent manner, but intrathecal clopidogrel had little effect on the mechanical withdrawal threshold. An additive effect was noted between pregabalin and tianeptine, but not between pregabalin and clopidogrel. Conclusions: These findings suggest that intrathecal coadministration of pregabalin and tianeptine effectively attenuated mechanical allodynia in the rat model of neuropathic pain. Thus, pregabalin plus tianeptine may be a valid option to enhance the efficacy of neuropathic pain treatment.

• 생약학회지
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• 제35권2호통권137호
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• pp.122-127
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• 2004

This study was conducted to investigate the safety and efficacy of an oriental herbal composition, Kamihonghwatang(KH-19), for the reduction of the side effects of chemotherapeutic drug. KH-19 prevented the reduction of white blood cells including lymphocytes, monocytes and eosinophiles in C57BL/6 mice injected with fluorouracil, a commonly used anticancer drug. KH-19 also prevented the reduction of cell densities in bone marrow and spleen of fluorouracil-injected mice. To evaluate the safety of KH-19, single-dose toxicity test was conducted using SD rats. No dead animal was found and the minimum lethal dose of KH-19 was more than 5000 mg/kg.

• Archives of Pharmacal Research
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• 제13권1호
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• pp.108-112
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• 1990

It was confirmed that extracts of some plants were used in folklore medicine as hypoglycemic agents. Of these plants is Azadirachta indica ("neem") which grows in tropical regions. The present study deals with biochemical effects of the "neem" leaf water extract given orally to experimental aminals, especially the hypoglycemic characteristics. Normals as well as alloxan diabetic rats have been used in this work. The results showed that the "neem" leaf extract produced some hypoglycemia in normal rats when given in two doses, while in diabetic rats there was a decrease in blood sugar, but it could not alleviate the diabetic in body weight loss and high percentage mortality, especially with a high dose. It was observed increased with concomitant decrease in the liver fat as compared to normal levels. There was also a drop in liver proteins which was dose-related. The results were compared wiht those obtained with an oral hypoglycemic drug (Glibenclamide).glycemic drug (Glibenclamide).

• Toxicological Research
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• 제13권3호
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• pp.183-186
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• 1997

Acute toxicity of pectenotoxin 2 (PTX2) was examined in mice. Treatment of mice with a toxic dose of PTX2 resulted in clinical signs such as ataxia, cyanosis and an abrupt decrease in body temperature. Histopathological studies revealed that the liver is the major target organ for PTX2. Activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and sorbitol dehydrogenase (SDH) were significantly elevated by PTX2 administration. Glucose-6-phosphatase activities were not changed by the treatment. The PTX2 treatment decreased relative liver weight without changing the body weight. The effect of PTX2 on hepatic drug metabolizing enzyme system was determined. An ip dose of PTX2 (200 $\mu$g/kg) induced a significant decrease in the hepatic microsomal protein content. Cytochrome P-450 content, cytochrome b$_5$ content, NADPH cytochrome c reductase, aminopyrine N-demethylase activities, or hepatic glutathione content were not altered by PTX2 treatment.

• Biomolecules & Therapeutics
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• 제4권3호
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• pp.251-256
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• 1996

The metabolism of carbinoxamine, 2-[(4-chlorophenyl)-2-pyridinyl-methoxy]-N, N-dimethylethaneamine, was studied in adult male volunteers after an oral dose of 15 mg. Solvent extracts of urine obtained with or without enzyme hydrolysis were analyzed by gas chromatography-mass spectrometry after derivatization with MSTFA/TMSCl (N-methyl-N-trimethylsilyltrifluoroacetamide/trimethyl chlorosilane). The structures of metabolites were determined based on the electron impact (EI) and chemical ionization (CI) mass spectra. Nonconjugated metabolites identified in the urine were carbinoxamine, nor-carbinoxamine, and bits-nor-carbinoxamine. Parent drug, nor-carbinoxamine, and bits-nor-carbinoxamine were also detected as conjugated forms. These metabolites observed in human urine were different from those previously reported in the rat. Urinary excretions of carbinoxamine were reached to maxima in 4 hours after drug administration with 4.9%-8.1% and 2.5-4.2% of the dose excreted during 24 h as carbinoxamine and its glucuronide, respectively.

• 약학회지
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• 제23권1호
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• pp.11-16
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• 1979

Benorylate and ethoxybenzamide have been used alone or in combination as an analgesic, antipyretic and antiinflammatory agent. We investigated the significance of the differences of analgesic activities between single and concurrent administration of benorylate and ethoxybenzamide and lorazepam in mice and also antipyretic activity between single and concurrent administration of benorylate and ethoxybenzamide in rats. 1). Concurrent administration of each half dose of benorylate and ethoxybenamide showed much inhibiting effect on the acetic acid-induced writhing syndrome of mice than the above drug alone, and the some increased analgesic response by hot plate method. 2). The synergistic and analgesic effect of combined administration of benorylate and lorazepam was found to be significant. 3). Antipyretic effect of half-dose combined administration of benorylate and ethoxybenzamide on the rat pyrexia induced by yeast(s.c.) and T.T.G. (i.v.) was shown to be similar to the effect of each drug.

• International journal of thyroidology
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• 제11권2호
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• pp.71-74
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• 2018

Adverse events such as hemoptysis and gastrointestinal hemorrhage during tyrosine kinase inhibitor treatment are relatively rare, but the severity of the bleeding can be higher than other common adverse events. It is necessary to educate patients about its possibility so that they can be found early. In this case report of radioiodine refractory thyroid cancer patient, hemoptysis and gastrointestinal bleeding has occurred following lenvatinib administration. Drug interruption and dose modification and dose interruption were required in addition to management for bleeding itself. It is necessary to confirm the high risk of bleeding before the administration of tyrosine kinase inhibitors, and to appropriately control the follow-up interval and drug dosage accordingly.

• Translational and Clinical Pharmacology
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• 제26권3호
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• pp.115-117
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• 2018

This tutorial explains the basic principles of mechanistic ligand-receptor interaction model, which is an operational model of agonism. A growing number of agonist drugs, especially immune oncology drugs, is currently being developed. In this tutorial, time-dependent ordinary differential equation for simple $E_{max}$ operational model of agonism was derived step by step. The differential equation could be applied in a pharmacodynamic modeling software, such as NONMEM, for use in non-steady state experiments, in which experimental data are generated while the interaction between ligand and receptor changes over time. Making the most of the non-steady state experimental data would simplify the experimental processes, and furthermore allow us to identify more detailed kinetics of a potential drug. The operational model of agonism could be useful to predict the optimal dose for agonistic drugs from in vitro and in vivo animal pharmacology experiments at the very early phase of drug development.