• Title/Summary/Keyword: Clinical pharmacology

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Antidiabetic Activity of IH-901 in db/db Mice (db/db 마우스에서 IH-901의 항 당뇨 활성)

  • Choi, Yun-Suk;Han, Gi-Cheol;Han, Eun-Jung;Park, Keum-Joo;Park, Jong-Suk;Sung, Jong-Hwan;Chung, Sung-Hyun
    • YAKHAK HOEJI
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    • v.50 no.6
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    • pp.345-350
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    • 2006
  • The pharmacological properties of ginseng are mainly attributed to ginsenosides, the active constituents that are found in the extracts of different species of ginseng. Lately; the studies on ginsenosides are mainly focused on IH-901, a major intestinal bacterial metabolite of ginsenosides. In this study; we examined the anti-diabetic activity of IH-901 in C57BU61 db/db mice model. IH-901 was administrated orally at a dose of 20 mg/kg for 5 weeks. During the experimental period, body weight and blood glucose levels were measured every week. After 5 weeks, db/db mice were sacrificed and diabetic parameters were analyzed. IH-901 treated group showed a significant decrease in fasting blood glucose levels (from 10.5 mM to 9.4 mM), insulin resistance index (from 163.6 to 100.2) and triglyceride levels (from 115.3 to 70.1) compared to the diabetic control. In Pancreatic islets morphology; IH-901 treated group revealed much less infltrated mononuclear cells, indicating that IH-901 recovered ${\beta}$-cell damage due to hyperglycemia. In addition, IH-901 upregulated expressions of glucose transporter 4 (GLUT4) and PPAR-${\gamma}$ in skeletal muscle and adipose tissue, respectively. Taken together IH-901might be a potential anti-hyperglycemic agent with insulin sensitizing effect.

Progress in the Direct Application of Pharmacogenomics to Patient Care: Sustaining innovation

  • Burckart, Gilbert J.;Frueh, Felix W.;Lesko, Lawrence J.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2006.11a
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    • pp.23-39
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    • 2006
  • The application of the knowledge from the Human Genome Project to clinical medicine will be through both industrial drug development and the application of pharmacogenomics (PG) to patient care. The slow uptake of clinical innovations into clinical practice can be frustrating, but understanding the history of acceptance and sustaining medical innovation is critically important to position PG to succeed. This primarily means that PG tests must have legitimacy; they must be thoroughly validated, must be cost-effective, must be widely accepted by medical practitioners, must be supported by public policy, and must have a way of being easily incorporated into current medical practice. They must also lead to actionalble decisions by health care providers for their patients. Innovative PG assays should be tested in the best US laboratories, and reimbursement for testing must be accepted at the federal and state level. The companies providing these PG tests should be capable of supporting the interpretation and use of the test throughout medical practice. Advances such as the addition of PG information to drug labeling and the routine use of validated biomarkers to determine choice of cancer chemotherapy have been made. The PG research community must pay attention to the principles that have been previously described for acceptance and sustaining medical innovations in order for PG to be widely accepted in clinical medical practice.

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Effects of tianeptine on symptoms of fibromyalgia via BDNF signaling in a fibromyalgia animal model

  • Lee, Hwayoung;Im, Jiyun;Won, Hansol;Nam, Wooyoung;Kim, Young Ock;Lee, Sang Won;Lee, Sanghyun;Cho, Ik-Hyun;Kim, Hyung-Ki;Kwon, Jun-Tack;Kim, Hak-Jae
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.4
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    • pp.361-370
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    • 2017
  • Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.

Kinesin superfamily member 15 knockdown inhibits cell proliferation, migration, and invasion in nasopharyngeal carcinoma

  • Yi Cai;Qianyue Lai;Xuan Zhang;Yu Zhang;Man Zhang;Shaoju Gu;Yuan Qin;Jingshen Hou;Li Zhao
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.5
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    • pp.457-470
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    • 2023
  • The aim of this study was to investigate the role of kinesin superfamily member 15 (KIF15) in nasopharyngeal carcinogenesis (NPC) and explore its underlying mechanisms. We employed various assays, including the CCK-8 assay, flow cytometry, the Transwell and scratch assay, Western blotting, and nude mice transplantation tumor, to investigate the impact of KIF15 on NPC. Our findings demonstrate that KIF15 plays a critical role in the proliferation, apoptosis, migration, and invasion of NPC cells. Furthermore, we discovered that silencing KIF15 inhibits cell proliferation, migration, and invasion while promoting apoptosis, and that KIF15's effect on NPC cell growth is mediated through the PI3K/AKT and P53 signaling pathways. Additionally, we showed that KIF15 promotes nasopharyngeal cancer cell growth in vivo. Our study sheds light on the significance of KIF15 in NPC by revealing that KIF15 knockdown inhibits NPC cell growth through the regulation of AKT-related signaling pathways. These findings suggest that KIF15 represents a promising therapeutic target for the prevention and treatment of NPC.

Assessment of Hepatic Cytochrome P450 3A Activity Using Metabolic Markers in Patients with Renal Impairment

  • Kim, Andrew HyoungJin;Yoon, Sumin;Lee, Yujin;Lee, Jieon;Bae, Eunjin;Lee, Hajeong;Kim, Dong Ki;Lee, SeungHwan;Yu, Kyung-sang;Jang, In-Jin;Cho, Joo-Youn
    • Journal of Korean Medical Science
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    • v.33 no.53
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    • pp.298.1-298.10
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    • 2018
  • Background: The renal function of individuals is one of the reasons for the variations in therapeutic response to various drugs. Patients with renal impairment are often exposed to drug toxicity, even with drugs that are usually eliminated by hepatic metabolism. Previous study has reported an increased plasma concentration of indoxyl sulfate and decreased plasma concentration of $4{\beta}$-hydroxy (OH)-cholesterol in stable kidney transplant recipients, implicating indoxyl sulfate as a cytochrome P450 (CYP) inhibiting factor. In this study, we aimed to evaluate the impact of renal impairment severity-dependent accumulation of indoxyl sulfate on hepatic CYP3A activity using metabolic markers. Methods: Sixty-six subjects were enrolled in this study; based on estimated glomerular filtration rate (eGFR), they were classified as having mild, moderate, or severe renal impairment. The plasma concentration of indoxyl sulfate was quantified using liquid chromatography-mass spectrometry (LC-MS). Urinary and plasma markers ($6{\beta}$-OH-cortisol/cortisol, $6{\beta}$-OH-cortisone/cortisone, $4{\beta}$-OH-cholesterol) for hepatic CYP3A activity were quantified using gas chromatography-mass spectrometry (GC-MS). The total plasma concentration of cholesterol was measured using the enzymatic colorimetric assay to calculate the $4{\beta}$-OH-cholesterol/cholesterol ratio. The correlation between variables was assessed using Pearson's correlation test. Results: There was a significant negative correlation between MDRD eGFR and indoxyl sulfate levels. The levels of urinary $6{\beta}$-OH-cortisol/cortisol and $6{\beta}$-OH-cortisone/cortisone as well as plasma $4{\beta}$-OH-cholesterol and $4{\beta}$-OH-cholesterol/cholesterol were not correlated with MDRD eGFR and the plasma concentration of indoxyl sulfate. Conclusion: Hepatic CYP3A activity may not be affected by renal impairment-induced accumulation of plasma indoxyl sulfate.

Effects of Curcuma long gum preparation on the Blood Alcohol Level and Hangover (울금 검 제제가 알코올의 혈중농도와 숙취에 미치는 영향)

  • Chu, Li-Ying;Nam, Yun-Sung;Cho, Sung-In;Yim, Sung-Hyuk;Chung, Zoo-Chul;Bang, Joon-Seok;Sohn, Uy-Dong;Kim, Jin-Man;Kim, Min-Soo;Koo, Kyo-Hwan;Jeong, Ji-Hoon
    • Korean Journal of Clinical Pharmacy
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    • v.20 no.1
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    • pp.1-8
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    • 2010
  • We conducted a single blind, randomized and crossover clinical trial in order to test the effect of curcuma longa herbal mixture on blood alcohol level and alcohol hangover in 19 healthy volunteers. The herbal mixture did not show a statistical significance in $C_{max}$, $T_{max}$ and AUC in alcohol disposition. The herbal mixture did not also ameliorate blood laboratory result after alcohol consumption. In contrast, the herbal mixture is shown effective on alcohol hangover. In behavior tests, the fewer subjects in the herbal mixture group were impaired with alcohol than in reference group. Moreover, the symptom severity score in the herbal mixture was lower than that in reference group. The symptom severity score was statistically especially in stomach pain, diarrhea, concentration disorder, memory and bad breath at drinking day and one day after drinking. These results indicate that the general symptoms seemed to be recovered as time goes on. From these results, it was suggested that the herbal mixture have a beneficial effect on modulating alcohol hangover.