• Journal of Pharmaceutical Investigation
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• v.30 no.2
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• pp.107-112
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• 2000

The changes in pharmacokinetic parameters of tolbutamide, such as the area under the plasma concentration-time curve from time zero to time infinity (AUC) and elimination rate constant (Kel) were evaluated after oral administration of the drug to rabbits with acute and chronic alloxan-induced diabetes mellitus (AIDRs). After oral administration, the plasma concentrations of tolbutamide were significantly higher between 9 and 12 hr in chronic AIDRs compared with these in control rabbits. Therefore, the AUC was significantly greater in chronic AIDRs $(3,490{\pm}649\;versus\;5,020{\pm}1,030{\mu}gml{\cdot}hr)$. This could be due to inhibition of tolbutamide metabolism by liver in AIDRs since tolbutamide is essentially completely metabolized in liver. Impaired liver and kidney function in AIDRs were based on blood chemistry and tissue microscopy. The absorption rate constant and Kel were significantly slower in chronic AIDRs compared with those in control rabbits.

• The Journal of Korean Obstetrics and Gynecology
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• v.20 no.3
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• pp.65-80
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• 2007

Purpose: This study is to examine anti-obesity effect and cytotoxicity of the long-term oral administration of Ephedra Sinica(Ma-hwang, ES) Methods: Using diet-induced obesity C57BL/6 mouse model, anti-obesity effect and DNA chip expression and cytotoxicity of the long-term oral administration of this herbal extract were investigated. Results: The herbal extract treated groups were arrested in weight increment only when they were lodged together. Such effects were abolished when they kept individually. ES fed mice behaved very rudely and violently. On the basis of histological studies of liver tissues and also in vitro cytotoxicity tests of the liver and kidney cell lines, no significant toxicity was found by 14 weeks of ES treatments. However, we found significant changes in gene expression profile in ES treated group by micro-array analysis. In case of ES group, up-regulated genes were 113 and down-regulated were 120. Some of lipid metabolism related genes also significantly changed in treatment groups. Conclusion: ES had effects of increasing the basal metabolic rate by stimulating the sympathetic nervous systems.

• The Journal of Korean Medicine
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• v.44 no.3
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• pp.29-38
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• 2023

Objectives: This study aimed to investigate the acute oral toxicity of 77 herbal formulas and performed in male and female Sprague-Dawley (SD) rats as per the guidelines mentioned in Ministry of Food and Drug Safety. Methods: Each sex of SD rat were administered a single dose (2000 or 5000 mg/kg) of 77 herbal formulas via oral gavage; the control group received vehicle only. After administration, the mortality, clinical signs, gross findings, and body weight were followed up for 15 days. Results: After administration of 77 herbal formulas, mortality, clinical signs, body weight changes, and gross findings related to the test substances were not observed in both male and female groups. Conclusion: Our results demonstrate the single-dose oral administration of 77 herbal formulas produced no mortality indicating the approximate lethal dose is greater than 2000 or 5000 mg/kg body weight.

• Journal of Radiation Industry
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• v.17 no.4
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• pp.327-332
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• 2023

This study identified effects of Isoegomaketone for applicable patch on the arthritis in mice. Isoegomaketone (IK) was isolated from Perilla frutescens, which is annual herbal traditional medicinal, aromatic, functional food. IK has various physiological effects such as anti-inflammation, anti-oxidant, and anti-cancer. In the previous study, oral administration of IK to a mouse model of collagen antibody-induced arthritis(CAIA), which is similar to human rheumatoid arthritis(RA), alleviated symptoms. In this study, we attached a patch containing IK to mouse skin to demonstrate whether it had the same efficacy as oral administration in CAIA mouse. As a result of measuring the arthritis score, paw volume, and paw thickness, it was confirmed that arthritis symptoms were alleviated in the group to which the patch containing IK was attached. These results show that IK is effective in alleviating arthritis not only through oral administration but also through patches applied to skin, and that it has potential as a material for future patch development.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.2
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• pp.99-103
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• 2021

In this study, the initial in vivo pharmacokinetic changes according to the routes of drug administration were investigated using bioimaging techniques. The purpose of this study was to quantify the degree of distribution of each major organ in normal mice over time by acquiring Positron Emission Tomography/Computed Tomography images while administering routes F-18 fluorodeoxyglucose such as intravenous, intraperitoneal and per oral, a representative diagnostic radiopharmaceutical. Dynamic Positron Emission Tomography images were acquired for 90 minutes after drug administration. Radioactivity uptake was calculated for major organs using the PMOD program. In the case of intravenous administration, it was confirmed that it spread quickly and evenly to major organs. Compared to intravenous administration, intraperitoneal administration was about three times more absorbed and distributed in the liver and intestine, and it was showed that the amount excreted through the bladder was more than twice. In the case of oral administration, most stayed in the stomach, and it was showed that it spread slowly throughout the body. In comparison with intravenous administration, it was presented that the distribution of kidneys was more than 9 times and the distribution of bladder was 66% lower. Since there is a difference in the initial in vivo distribution and excretion of each administration method, we confirmed that the determination of the administration route is important for in vivo imaging evaluation of new drug candidates.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.65-74
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• 2017

Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta ($IL-1{\beta}$) ($1ng/10{\mu}L$) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A ($GABA_A$) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions. However, intracisternal administration of bicuculline (50 ng) produced a paradoxical anti-allodynic effect under inflammatory pain conditions. Pretreatment with resiniferatoxin (RTX), which depletes capsaicin receptor protein in primary afferent fibers, did not alter the paradoxical anti-allodynic effects produced by the intracisternal injection of bicuculline. Intracisternal injection of bumetanide, an Na-K-Cl cotransporter (NKCC 1) inhibitor, reversed the $IL-1{\beta}$-induced mechanical allodynia. In the control group, application of GABA ($100{\mu}M$) or muscimol ($3{\mu}M$) led to membrane hyperpolarization in gramicidin perforated current clamp mode. However, in some neurons, application of GABA or muscimol led to membrane depolarization in the $IL-1{\beta}$-treated rats. These results suggest that some large myelinated $A{\beta}$ fibers gain access to the nociceptive system and elicit pain sensation via $GABA_A$ receptors under inflammatory pain conditions.

• International Journal of Oral Biology
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• v.45 no.3
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• pp.84-91
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• 2020

The present study investigated the participation of D-serine and NR2 in antinociception produced by blockade of central erythropoietin-producing hepatocellular carcinoma (Eph) A4 (EphA4) signaling in rats with trigeminal neuropathic pain. Trigeminal neuropathic pain was modeled in male Sprague-Dawley rats using mal-positioned dental implants. The left mandibular second molar was extracted under anesthesia, and a miniature dental implant was placed to induce injury to the inferior alveolar nerve. Our current findings showed that nerve injury induced by malpositioned dental implants significantly produced mechanical allodynia; additionally, the inferior alveolar nerve injury increased the expression of D-serine and NR2 subunits in the ipsilateral medullary dorsal horn (trigeminal subnucleus caudalis). Intracisternal administration of EphA4-Fc, an EphA4 inhibitor, inhibited nerve injury-induced mechanical allodynia and upregulated the expression of D-serine and NR2 subunits. Moreover, intracisternal administration of D-amino acids oxidase, a D-serine inhibitor, inhibited trigeminal mechanical allodynia. These results show that D-serine and NR2 subunit pathways participate in central EphA4 signaling after an inferior alveolar nerve injury. Therefore, blockade of D-serine and NR2 subunit pathways in central EphA4 signaling provides a new therapeutic target for the treatment of trigeminal neuropathic pain.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.6
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• pp.565-580
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• 2000

This study was designed to evaluate the influence of cultured epidermal tissue graft and the administration of transforming growth factor(TGF)-${\beta}_3$ on maxillary growth in surgically created palatal defects. A total of 155 rats were divided into 2 groups according to surgical timing : postnatal 2 weeks(n=95), 4 weeks(n=40) and control(unoperated) group(n=20). The postnatal 2-week surgical group was subdivided into 3 groups according to repair methods: conventional surgery(Von Langenbeck technique)group(n=23); cultured tissue graft group(n=25); and full thickness skin graft group(n=25). Additionally, recombinant human TGF-${\beta}_3$ was administered(30ng or 150ng) on collagen matrix in surgically created palatal defects during surgery(9 conventional surgeries, 9 cultured tissue grafts) in 2-week-old rats. The results showed that all types of surgical treatment decreased maxillary growth compared with the control(unoperated) group(p<0.0001). On the other hand, the tissue graft group, whether cultured tissue or grafted skin, contributed to increased maxillary growth(p<0.0001).And exogenous TGF-${\beta}_3$ might play a role in connective tissue proliferation and new bone generation during wound healing on palatal defects. Our results suggest that grafting cultured epidermis with collagen matrix decreases the scar tension on maxillary growth more than conventional palatal surgery does. Therefore, exogenous TGF-${\beta}_3$ may contribute to accelerate wound healing on palatal defects.

• Journal of Korean Academy of Dental Administration
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• v.7 no.1
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• pp.44-49
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• 2019

Halitosis is primarily caused by oral conditions. In particular, volatile sulfur compounds (VSCs) are mainly responsible for intra-oral halitosis. They are closely associated with the water temperature. In this study, we investigated the association between halitosis and water temperature for oral rinse (10℃, 30℃, and 45℃) using the BB checker and oral chroma. The application of BB checker on an empty stomach revealed that halitosis decreased with the use of tongue cleaners (p=0.001) and toothpastes (p=0.002). Furthermore, halitosis decreased after drinking milk (VSCs-induced food intake) (p=0.000). There were no significant differences in the results of oral chroma. Finally, we measured halitosis on an empty stomach and after drinking milk. The BB checker showed increased halitosis after drinking milk (p<0.001). The oral chroma showed decreased hydrogen sulfide (p<0.001) and increased methyl mercaptan (p=0.009) and dimethyl sulfide (p=0.002) after drinking milk. In conclusion, halitosis cannot be modulated using water temperature for oral rinse. The findings of this study cannot be generalized because of the small sample size and the limits of age and sex. Further studies are required to extensively analyze both sexes and various age groups, with more number of subjects.

• Fisheries and Aquatic Sciences
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• v.1 no.1
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• pp.42-47
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• 1998

The chemiluminescent (CL) response of phagocytes from juvenile rockfish, Sebastes schlegeli, which were administered orally with levamisole was investigated. The fish intubated with doses of levamisole either at 0.5mg $kg^-$ or 1 mg $kg^-$body weight showed significant increase in CL responses at two weeks after the administration. The increased extent of CL in the fish exposed to 0.5 mg $kg^-$ body weight was considerably lower than that in the fish exposed to 1 mg $kg^-$. The fish exposed to 5 mg $kg^-$ body weight showed a steady and significant increase of CL response after the intubation. The fish intubated with 10 mg of levamisole $kg^-$ body weight, however, showed no significant differences in CL response after the administration. In the experiment of feeding experimental diet, a lower dose of levamisole induced immunostimulation of phagocytes, but higher doses of levamisole induced immunosuppression of phagocytes. At one week after marking and blood sampling, plasma glucose level was significantly increased in the control group and the group intubated 0.5 mg levamisole/kg body weight. However, the fish in another groups, which were administered higher levels of levamisole, showed no significant difference in glucose level after marking and blood sampling. The result of the present study suggests that levamisole can be used as a potent immunostimulator in rockfish by oral administration, and the immunomodulating activity of levamisole depends on the dosage used.