• Title/Summary/Keyword: Drug response

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Determination of Dosing Weight on Aminoglycosides (Aminoglycosides계 약물의 투약 체중 결정)

  • Lee, Rae Young;Kim, Ho Soon;Shin, Wan Gyoon;Cho, Nam Chun
    • Korean Journal of Clinical Pharmacy
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    • v.9 no.1
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    • pp.15-18
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    • 1999
  • Ascertainment of accurate pharmacokinetic parameters for aminoglycoside dosing remains critical, as the serum drug concentration relates directly to both the therapeutic response and toxic effect. In the initial dosing of aminoglycosides, the volume of distribution is especially important because the dosage is calculated by multiplying the volume of distribution by the desired serum concentration. Aminoglycosides distribute into mainly the extracellular fluid and it has been reported that the volume of distribution is 0.25 L/kg. Penetration of polar aminoglycosides into adipose tissue occurs to some extent, but varies according to the degree of obesity. Therefore, dosages may be overestimated or underestimated according to the type of the dosing weight in overweight or underweight patients. Prior investigations have suggested various dosing weights which are multiplied by the popular volume of distribution to calculate the total volume of distribution. Based on other investigations, we calculated a new dosing weight which was applicable to all patients regardless of obesity in order to use the popular volume of distribution. We estimated IBW+$0.414^{\ast}$(TBW-IBW) as a new dosing weight with the SAS program. A new dosing weight is similar to those of other studies which examined in morbidly obese patients. Consequently we suggests that the dosing weight reported in morbidly obese patients can be extended to a broader patients population. But we found that the volume of distribution per kilogram from our patients was significantly larger than that for foreign patients(0.343L/kg vs 0.25 L/kg)(Kor. J. Clin. Pharm. 1999; 9(1): 15-18)

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A Case of Soyangin Double Primary Cancer Patient with Adverse Reactions induced by Contrast Media (조영제로 과민성 발진이 유발된 소양인 암환자 치험 1례)

  • Park, So-Ra;Lee, Soo-Min;Choi, Seong-Heon;Lee, Jee-Young;Lee, Sung-Un;Jung, Yee-Hong;Lee, Soo-Kyung
    • Journal of Sasang Constitutional Medicine
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    • v.26 no.2
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    • pp.205-212
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    • 2014
  • Objectives Adverse reactions can becaused by contrast media used in computed tomography. The aim of this study was to report the improvement of allergic response caused by contrast media after treatment with Modified Hyeongbangpaedok-san, histamine antagonists and steroids. Methods We retrospectively reviewed the medical records. The patient's subjective symptoms such as rash and pruritus were evaluated by the range of rash and numeric rating scale(NPS). Results All symptoms showed nearly complete remission with continued Korean traditional medical treatment. Conclusions A female patient had been injected with contrast media for Computed tomography(CT) evaluation of lung cancer. Rash and pruritus appeared 1 day after injection. We prescribed Modified Hyeongbangpaedok-san. Patients were treated with both Korean medicine and Western medicine. Consequently, the symtoms were improved significantly after combination treatment of Korean medicine and Western medicine.

Prejunctional Modulation of Non-adrenergic Non-cholinergic Relaxation of the Rabbit Proximal Stomach by Potassium Channels (토끼 위 근위부의 비-아드레날린 비-콜린성 이완반응의 포타슘 체널에 의한 접합전 조절작용)

  • Hong, Eun-Ju;Park, Mi-Sun;Park, Sang-Il;Kim, Myung-Woo;Choi, Su-Kyung;Hong, Sung-Cheul
    • YAKHAK HOEJI
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    • v.41 no.4
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    • pp.399-406
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    • 1997
  • The effects of different $K^+$ channel blockers were investigated on the non-adrenergic non-cholinergic (NANC) relaxations in the circular muscle of the rabbit proximal stomach. Non-selective blockers of $K^+$ channels, 4-aminopyridine (4-AP, 3~30${\mu}M$) and tetraethylammonium (TEA, 100~1000${\mu}M$) significantly enhanced the NANC relaxations in a concentration-dependent manner. The enhancement was more prominent for the NANC relaxations induced by the electric field stimulation (EFS) with lower frequencies. Blockers of large conductance $Ca^{2+}$-activated $K^+$ channels, charybdotoxin and iberiotoxin, a blocker of small conduntance $Ca^{2+}$-activated $K^+$ channels, apamin and a blocker of ATP-sensitive $K^+$ channels, glibenclamide had no effect on the NANC relaxations, respectively. Exogeneous administration of nitric oxide (NO, 1~30${\mu}M$) caused concentration-dependent relaxations which showed a similarity to those obtained with EFS. None of the $K^+$ channel blockers had an effect on the concentration-dependent relaxation in response to NO. These results suggest that prejunctional $K^+$ channels regulate the release of NO from the NANC nerve in the rabbit proximal stomach as the inhibition of prejunctional $K^+$ channels increases the NANC relaxation induced by the EFS.

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Effect of Ullmus macrocarpa Hance Ethanol extract (Ulmus) on Improvement of allergic responses in RBL-2H3 mast Cells (RBL-2H3 비만세포에서 유백피 에탄올 추출물의 알레르기 반응 개선에 대한 효과)

  • Do, Hyun Ju;Oh, Tae Woo
    • Herbal Formula Science
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    • v.29 no.4
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    • pp.191-203
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    • 2021
  • Objectives : In this study, we investigate the anti-allergic effects of Ullmus macrocarpa Hance (Ulmus) on RBL-2H3 mast cell (basophilic leukemia cell line), which are mediated by FcεRIs. Methods : We evaluated the effect of the ethanol extract of Ulmus on the allergic inflammatory response in IgE-antigen-mediated RBL-2H3 cells. Cell toxicity was determined by MTT assay and the markers of degranulation such as beta-hexosaminidase, histamine, PGD2, TNF-α, IL-4, IL-6 production of inflammatory mediators and FcεRI-mediated protein expression by western blot. Results : Ulmus inhibited degranulation and production of allergic mediators (e.g., TNF-α, IL-4, and IL-6) in them. Ulmus reduced histamine levels, expression of FcεRI signaling-related genes such as Lyn, Syk, and Fyn, and extracellular signal-regulated kinase phosphorylation in mast cells. Also, Ulmus reduced PGD2 release and cyclooxygenase-2 expression, and cytosolic phospholipase A2 phosphorylation in FcεRI-mediated RBL-2H3 mast cells. Conclusions : These results indicate that Ulmus exhibits anti-allergic activity through inhibition of degranulation and inflammatory mediators and cytokine release. These findings suggest that Ulmus may have potential as a prophylactic and therapeutic agent for the treatment of various allergic diseases.

Depilatory creams increase the number of hair follicles, and dermal fibroblasts expressing interleukin-6, tumor necrosis factor-α, and tumor necrosis factor-β in mouse skin

  • Tsai, Pi-Fen;Chou, Fen-Pi;Yu, Ting-Shuan;Lee, Huei-Jane;Chiu, Chun-Tang
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.6
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    • pp.497-506
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    • 2021
  • Besides using for hair removal, depilatory agents have been considered to be used as a penetration enhancer for transepidermal drug delivery. To examine the effect in hair follicles (HFs), two commercially available depilatory creams were tested on the dorsal skin of mice to monitor the effect deep into the skin structure. Fifteen male BALB/c mice were used in this study. Depilatory creams were applied to the dorsal skin of the same animal using shaved and untouched treatments as controls to minimize individual differences. Skin samples were collected at three days, one week and two weeks (n = 5 for each) after the treatment, and subjected for hematoxylin-eosin staining, and immunohistochemical analysis for proinflammatory cytokines. The morphological examination showed an increase in the thickness of epidermal layer of the depilatory cream-treated skin at early time points and in the subcutis at two weeks. Depilatory cream promoted entry of anagen phase and increased the number of hair follicles in the subcutis at one and two weeks. Immunohistochemistry showed elevated percentages of dermal fibroblasts expressing interleukin-6, tumor necrosis factor-α, and tumor necrosis factor-β. Shaving process increased the thickness of epidermis and dermis as depilatory creams did, but did neither induce the expression of proinflammatory cytokines in the dermal fibroblasts nor the number of HFs. The results suggested that the commercially available depilatory creams caused a transient minor inflammatory response of the skin and increased the levels of cytokines that might subsequently affect hair growth.

The hyaluronan synthesis inhibitor 7-hydroxy-4-methylcoumarin inhibits LPS-induced inflammatory response in RAW 264.7 macrophage cells

  • Kim, Gwan Bo;Hyun, Chang-Gu
    • Journal of Applied Biological Chemistry
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    • v.64 no.3
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    • pp.263-268
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    • 2021
  • 7-Hydroxy-4-methylcoumarin (7H-4MC) inhibits hyaluronan production in multiple cell lines and tissue types both in vitro and in vivo. It is a commercially available drug approved for human use, called hymecromone, in European and Asian countries to prevent biliary spasms. Nevertheless, as the pharmacological efficacy of 7H-4MC has not yet been reported in macrophages, this study investigated its anti-inflammatory effects and mechanism of action using lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. LPS-induced RAW 264.7 cells were treated with various concentrations of 7H-4MC (62.5, 125, 250, and 500 μM). The application of 7H-4MC significantly reduced nitric oxide and prostaglandin E2 production without cytotoxic effects. Additionally, 7H-4MC strongly decreased the expression of inducible nitric oxide synthase and cyclooxygenase. Furthermore, 7H-4MC reduced the production of proinflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. Finally, 7H-4MC exerted its potent anti-inflammatory actions via the upregulation of IκB-α production, which led to the inhibition of nuclear factor-κB (NF-κB) activity. These results, obtained in macrophage cell lines, suggest that 7H-4MC prevents inflammatory diseases via the NF-κB signaling pathway and that its use could be beneficial for human health. Ultimately, this is the first report describing the anti-inflammatory activity of 7H-4MC in a macrophage cell line.

A mothers' perspective on fish and her child's fish consumption in Surakarta, Indonesia

  • Rahmawaty, Setyaningrum;Ramadhani, Farhanah Erwida;Anwar, Innani Kharisma;Puspitasari, Ola;Dewi, Tri Suci Kusuma;Meyer, Barbara J
    • Nutrition Research and Practice
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    • v.15 no.6
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    • pp.761-772
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    • 2021
  • BACKGROUD/OBJECTIVES: Understanding the factors associated with fish consumption is necessary to determine strategies to improve the fish consumption particularly those high in omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA). The aim of this study was to analyse the correlation between a mother's perspective on fish and actual fish consumption in their children. SUBJECTS/METHODS: Two hundred thirty-one elementary school children grade 3-6 and their mothers in Surakarta were recruited using multi stage random sampling for this study. Data was collected in July and August 2017. A validated questionnaire consisted of 3 topics including knowledge related to the health benefits and organoleptic properties of fish and cooking technique-related attitudes on fish were used to measure the mother's response to the fish properties. A validated food frequency questionnaire and a food picture book of fish specifically designed for the survey were developed and used to assess fish consumption of the children. A χ2 test was used to analyse the correlation between the mothers' perspective on fish and their children's fish consumption. RESULTS: The median fish consumption in children was 65 g/d with fried non-oily or lean fish, e.g., milkfish (locally called Bandeng) and catfish (locally called Lele) were consumed more than oily fish as well as processed fish products. Of all children, 31% met the fish consumption recommended by the Environmental Protection Agency-Food and Drug Administration 2017. There was no relationship between a mother's knowledge related to health benefits, organoleptic properties and cooking technique-related attitude toward fish and her child's fish consumption. CONCLUSIONS: The fish consumption of children is not influenced by their mother's perspective on fish. Nutrition education strategies are warranted to improve fish consumption and maintain the optimal benefits by consuming fish, including fish high in n-3 LCPUFA.

G-Protein-Coupled Receptor 120 Mediates DHA-Induced Apoptosis by Regulating IP3R, ROS and, ER Stress Levels in Cisplatin-Resistant Cancer Cells

  • Shin, Jong-Il;Jeon, Yong-Joon;Lee, Sol;Lee, Yoon Gyeong;Kim, Ji Beom;Lee, Kyungho
    • Molecules and Cells
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    • v.42 no.3
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    • pp.252-261
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    • 2019
  • The omega-3 fatty acid docosahexaenoic acid (DHA) is known to induce apoptosis and cell cycle arrest via the induction of reactive oxygen species (ROS) production and endoplasmic reticulum (ER) stress in many types of cancers. However, the roles of DHA in drug-resistant cancer cells have not been elucidated. In this study, we investigated the effects of DHA in cisplatin-resistant gastric cancer SNU-601/cis2 cells. DHA was found to induce ROS-dependent apoptosis in these cells. The inositol 1,4,5-triphosphate receptor ($IP_3R$) blocker 2-aminoethyl diphenylboninate (2-APB) reduced DHA-induced ROS production, consequently reducing apoptosis. We also found that G-protein-coupled receptor 120 (GPR120), a receptor of long-chain fatty acids, is expressed in SNU-601/cis2 cells, and the knockdown of GPR120 using specific shRNAs alleviated DHA-mediated ROS production and apoptosis. GPR120 knockdown reduced the expression of ER stress response genes, similar to the case for the pre-treatment of the cells with N-acetyl-L-cysteine (NAC), an ROS scavenger, or 2-APB. Indeed, the knockdown of C/EBP homologous protein (CHOP), a transcription factor that functions under ER stress conditions, markedly reduced DHA-mediated apoptosis, indicating that CHOP plays an essential role in the anti-cancer activity of DHA. These results suggest that GPR120 mediates DHA-induced apoptosis by regulating $IP_3R$, ROS, and ER stress levels in cisplatin-resistant cancer cells, and that GPR120 is an effective chemotherapeutic target for cisplatin resistance.

Ginsenoside compound K protects human umbilical vein endothelial cells against oxidized low-density lipoprotein-induced injury via inhibition of nuclear factor-κB, p38, and JNK MAPK pathways

  • Lu, Shan;Luo, Yun;Zhou, Ping;Yang, Ke;Sun, Guibo;Sun, Xiaobo
    • Journal of Ginseng Research
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    • v.43 no.1
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    • pp.95-104
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    • 2019
  • Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.

Effects of Lactobacillus helveticus Fermentation on the Ca2+ Release and Antioxidative Properties of Sheep Bone Hydrolysate

  • Han, Keguang;Cao, Jing;Wang, Jinghui;Chen, Jing;Yuan, Kai;Pang, Fengping;Gu, Shaopeng;Huo, Nairui
    • Food Science of Animal Resources
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    • v.38 no.6
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    • pp.1144-1154
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    • 2018
  • Both the calcium and collagen in bone powder are hard to be absorbed by the body. Although enzymatic hydrolysis by protease increased the bio-availability of bone powder, it was a meaningful try to further increase $Ca^{2+}$ release, oligopeptide formation and antioxidant activity of the sheep bone hydrolysate (SBH) by lactic acid bacteria (LAB) fermentation. Lactobacillus helveticus was selected as the starter for its highest protease-producing ability among 5 tested LAB strains. The content of liberated $Ca^{2+}$ was measured as the responsive value in the response surface methodology (RSM) for optimizing the fermenting parameters. When SBH (adjusted to pH 6.1) supplemented with 1.0% glucose was inoculated 3.0% L. helveticus and incubated for 29.4 h at $36^{\circ}C$, $Ca^{2+}$ content in the fermented SBH significantly increased (p<0.01), and so did the degree of hydrolysis and the obtaining rate of oligopeptide. The viable counts of L. helveticus reached to $1.1{\times}10^{10}CFU/mL$. Results of Pearson correlation analysis demonstrated that LAB viable counts, $Ca^{2+}$ levels, obtaining rates of oligopeptide and the yield of polypeptide were positively correlated with each other (p<0.01). The abilities of SBH to scavenge the free radicals of DPPH, OH and ABTS were also markedly enhanced after fermentation. In conclusion, L. helveticus fermentation can further boost the release of free $Ca^{2+}$ and oligopeptide, enhance the antioxidant ability of SBH. The L. helveticus fermented SBH can be developed as a novel functional dietary supplement product.