• Title/Summary/Keyword: Combined drug treatment

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Synergic Effect of Trimebutine Combined with Mosapride on Gastrointestinal Dysfunction and Visceral Pain Induced in Stress Models

  • Park, Young-Joon;Park, Yong-Sul;Chung, Zoo-Chul;Nam, Yun-Sung;Chung, Yoon-Hee;Cho, Kwan-Hyung;Choi, Sung-Up;Sohn, Uy-Dong;Park, Eon-Sub;Je, Hyun-Dong;Lee, Choong-Ho;Lee, Moo-Yeol;Jeong, Ji-Hoon
    • Biomolecules & Therapeutics
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    • v.19 no.1
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    • pp.84-89
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    • 2011
  • The present study was undertaken to determine whether combined treatment with prokinetic trimebutine and mosapride has a synergic effect on gastrointestinal motility and visceral pain associated with gastrointestinal dysfunction. To develop effective gastroprokinetic agents with greater potencies than trimebutine or mosapride for the treatment of gastrointestinal tract disease, a mixture of trimebutine and mosapride was designed and prepared. In the present study, treatment with trimebutine alone showed a dose-dependent effect on propelling movements of normal small and large intestine in mice, whereas mosapride effected only small intestine motility. Co-administration of trimebutine with mosapride, a well-established prokinetic drug, produced a synergistic influence on normal small intestine motility, but demonstrated an unclear effect on large intestine motility, with a slight tendency to reduce the propelling time. In a stress model, the small and large intestine motilities were significantly decreased. The reduction of intestine motility was restored to a normal level and the restoring effect was more pronounced in the combined treatment with trimebutine plus mosapride than treatment with trimebutine or mosapride alone. Furthermore, treatment with trimebutine plus mosapride significantly decreased acute visceral pain which was not controlled by trimebutine or mosapride alone. These data suggest that combination therapy with trimebutine plus mosapride has a synergic effect on small and large intestine motility and visceral pain control in gastrointestinal disorders.

Combined Lowering Effects of Rosuvastatin and L. acidophilus on Cholesterol Levels in Rat

  • Wang, Lijun;Zhou, Baihua;Zhou, Xue;Wang, Yang;Wang, Hongwei;Jia, Shengying;Zhang, Zhipeng;Chu, Chao;Mu, Jianjun
    • Journal of Microbiology and Biotechnology
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    • v.29 no.3
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    • pp.473-481
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    • 2019
  • Statins are a class of lipid-lowering drugs commonly used in the prevention of cardiovascular diseases. However, statin therapy presents many limitations, which have led to an increased interest in non-drug therapies, such as probiotics, to improve blood cholesterol levels. Indeed, probiotic strains such as Lactobacillus acidophilus have been found to improve blood lipid profiles, especially in reducing total cholesterol and LDL-C levels. In this study, we established a high-cholesterol rat model and studied the effect of Lactobacillus acidophilus administration alone or in combination with rosuvastatin. We were able to show that Lactobacillus exerts a cholesterol-lowering effect. Additionally, we observed that when administered together, rosuvastin and Lactobacillus exert a combined cholesterol-lowering effect. Altogether, our data advocate for the possibility of establishing probiotics as non-drug supplements for the treatment of hypercholesterolemia.

A Case of Therapeutic Laser for Suggested Drug Induced Liver Injury Patient during Treatment of Korean Medicine (한방치료 중 약인성 간손상으로 추정되는 환자에 대한 치료레이저 치험 1례)

  • Lim, Kyeong-Tae;Shin, Byung-Cheul;Hwang, Eui-Hyoung;Heo, In;Kim, Byung-Jun;Heo, Kwang-Ho
    • Journal of Korean Medicine Rehabilitation
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    • v.26 no.3
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    • pp.183-189
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    • 2016
  • A 84 year old male patient with amyotrophic lateral sclerosis (ALS) was treated by Jeungsonbaekchulsan and Gakbyeongyeonsu-tang for ten days. In the course of treatments, this patient was evaluated with Roussel Uclaf Casusality Assessment Method (RUCAM), showing results of drug induced liver injury. Herb medicine was immediately discontinued, followed by therapeutic laser treatments once a day for one week combined with 2 weeks of GODEX$^{(R)}$ administration. Transaminase results were lowered and changes in blood test results were time-effective changes. Therapeutic laser therapy could be considered effective on drug induced liver injury with further studies.

Adverse Drug Reactions with Oseltamivir Treatment in the South Korea Outbreak of 2009 Pandemic Influenza A(H1N1) (2009년 국내 신종플루 유행시기의 Oseltamivir 부작용 평가)

  • Do, Youn-A;Lee, Suk-Hyang
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.4
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    • pp.353-363
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    • 2011
  • The World Health Organization (WHO) declared the outbreak of H1N1 pandemic in 2009. South Korea also had outbreaks of H1N1 virus and used oseltamivir in large volume with increased reports of adverse drug reaction(ADR). The present study was aimed to investigate the ADR frequency, the factors related to ADR, and characteristics of oseltamivir's ADR. Participants for the study were patients randomly drawn from those who were prescribed oseltamivir for treatment from CHA Bundang Medical Center during October 1 and October 30. The information examined as factors related to ADR were collected by a subsequent cross-sectional telephone survey. The factors are the following; a) age; b) gender; c) patient medical history; d) diagnosis of H1N1 virus; e) adherence; f) whether taking other medication with oseltamivir or not; and g) the number of combined medications. We also asked ADR after taking oseltamivir. Total subjects were 86 patients. The average age is $22.6{\pm}18.48$ years old. The gender was 45.3% women and 54.7% men. Half (50%) of all respondents showed one or more ADR, 67.4% were positively diagnosed for H1N1 virus, and 54.7% were completed the full course of oseltamivir (i.e. twice daily x 5days). The most frequently reported ADR symptoms were: dizziness (15.1%), nausea (11.6%), lethargy (10.4%), diarrhea (10.4%), abdominal pain (8.1%), headache and vomiting (6.9%). ADR classifications by categories are gastro intestinal (44.2%), neuropsychiatric events (22.1%), systemic symptom (20.9%), skin events (5.8%), eye events (4.7%), and other cases (2.3%). The onset of ADR 'after taking 1~3 doses' was 69.7%. No increase in neuropsychiatric events was detected in children and adolescents. No factors examined for the study do have significant influence on the presence of ADR. This study showed that ADR of oseltamivir have occurred in half of the patients. The use of oseltamivir is essential for treatment and prophylaxis of influenza A(H1N1). But mass treatment should be properly monitored for ADR.

Differential Sensitivity of Wild-Type and BRAF-Mutated Cells to Combined BRAF and Autophagy Inhibition

  • Yeom, Hojin;Hwang, Sung-Hee;Han, Byeal-I;Lee, Michael
    • Biomolecules & Therapeutics
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    • v.29 no.4
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    • pp.434-444
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    • 2021
  • BRAF inhibitors are insufficient monotherapies for BRAF-mutated cancer; therefore, we investigated which inhibitory pathway would yield the most effective therapeutic approach when targeted in combination with BRAF inhibition. The oncogenic BRAF inhibitor, PLX4720, increased basal autophagic flux in BRAF-mutated cells compared to wild-type (WT) BRAF cells. Interestingly, early autophagy inhibition improved the effectiveness of PLX4720 regardless of BRAF mutation, whereas late autophagy inhibition did not. Although ATG5 knockout led to PLX4720 resistance in both WT and BRAF-mutated cells, the MEK inhibitor trametinib exhibited a synergistic effect on PLX4720 sensitivity in WT BRAF cells but not in BRAF-mutated cells. Conversely, the prolonged inhibition of endoplasmic reticulum (ER) stress reduced basal autophagy in BRAF-mutated cells, thereby increasing PLX4720 sensitivity. Taken together, our results suggest that the combined inhibition of ER stress and BRAF may simultaneously suppress both pro-survival ER stress and autophagy, and may therefore be suitable for treatment of BRAF-mutated tumors whose autophagy is increased by chronic ER stress. Similarly, for WT BRAF tumors, therapies targeting MEK signaling may be a more effective treatment strategy. Together, this study presents a rational combination treatment strategy to improve the efficacy of BRAF inhibitors depending on BRAF mutation status.

Combined Treatment with 5-Fluorouracil and Capsaicin Induces Apoptosis in HT-29 Human Colon Cancer Cells (5-Fluorouracil과 Capsaicin의 병용에 의한 HT-29 대장암세포 사멸 증진 효과)

  • Lee, Yun-Seok;Lee, Jong-Suk;Kim, Jung-Ae
    • YAKHAK HOEJI
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    • v.53 no.4
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    • pp.184-188
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    • 2009
  • Fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs in the treatment of advanced colorectal cancer patients. Capsaicin (N-vanillyl-8-methyl-alpha-nonenamide), a spicy component of hot pepper, is a homovanillic acid derivative that preferentially induces cancer cells to undergo apoptosis. The purpose of the present study is to examine whether capsaicin enhances the anticancer effect of 5-fluorouracil in HT-29 human colon cancer cells by inducing apoptosis, and whether PPARgamma is involved in the capsaicin action in combination treatment with 5-FU. Treatment of the cells with either 5-FU or capsaicin alone for 48 h had little effect on the cell viability up to $50{\mu}M$ concentration, whereas co-treatment of the cells with capsaicin in the presence of 5-FU for 48 h significantly decreased the cell viability in a concentration-dependent manner. In addition, caspase-3 activity, a marker enzyme for apoptosis, was significantly increased by the combined treatment with 5-FU and capsaicin compared to the 5-FU or capsaicin alone treatment. Also, treatment with troglitazone, a peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) agonist, further enhanced the effect of the combination treatment on the cell viability and caspase-3 activity, and bisphenol A diglycidyl ether (BADGE), a $PPAR{\gamma}$ antagonist, blocked the effect of the combination treatment. These results suggest that the combination treatment of HT-29 cells with 5-FU and capsaicin induces apoptotic cell death at relatively low concentration than each drug alone, and the combination treatment may be associated with the $PPAR{\gamma}$ pathway activation.

Clinical Characteristics of Pulmonary Tuberculosis Presenting Prolonged Fever Despite Primary Short-Course Anti-tuberculosis Treatment (1차 항결핵약제 치료 후에도 지속적으로 발열을 보인 폐결핵 환자의 임상상)

  • Kim, Eun-Kyung;Hwang, Jung-Hwa;Song, Kun-Sick;Lim, Chae-Man;Lee, Sang-Do;Koh, Youn-Suck;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong;Shim, Tae-Sun
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.2
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    • pp.169-178
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    • 2000
  • Background : Usually fever subsides within one week in over 90% of pulmonary tuberculosis (TBp) patients after the start of short-course anti-tuberculosis therapy, but occasionally it persists over two weeks after treatment. When the fever persists, drug resistance, combined infection, or drug fever, and so on, are considered as an etiology and, in some cases, drugs are changed. But inadvertent discontinuation of a short-course regimen inevitably will extend the duration of treatment, and the treatment completion may be delayed. This study was performed to investigate the causes of prolonged fever (PF) and to identify the predictors of PF in drug-susceptible TBp patients in Korea. Method : Five hundred-ninety-eight patients, who were admitted to Asan Medical Center from January 1996 to March 1999, diagnosed with TBp and prescribed short-course, anti-tuberculosis treatment, were reviewed. PF was defined as having fever over two weeks despite treatment. The causes of PF were analyzed. Drug-sus-ceptible TBp patients who presented no causes for PF, except turberculosis itself, were selected(n=22), and they were compared with those who had no fever at diagnosis (n=22) and those who had fever at diagnosis, which had subsided within two weeks after treatment (n=22). Clinical, laboratory, and radiological parameters were compared among the three groups. Results : Twenty-eight (4.8%) of 598 patients showed PF over two weeks despite short-course treatment. The causes of PF were drug fever (n=2), multi-drug resistant tuberculosis (n=3), disseminated Mycobacterium kansasii infection (n=1), and drug-susceptible tuberculosis itself (n=22). The patients with PF had more risk factors for tuberculosis, long duration of symptoms before treatment, night sweats, weight long, numerous acid fast bacilli on sputum smear, anemia, hyponatremia, hypoalbuminemia, over three lung cavity numbers and extensive infiltration, indicating that they had prolonged and extensive lung diseases. Conclusion : The main cause of PF in TBp despite short-course regimen seems to be drug-susceptible but extensive disease in Korea. Any changes to the drug regiment provided for TBp patients with prolonged fever despite treatment should be carefully considered.

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Susceptibility of β-Lactam Antibiotics and Genetic Mutation of Drug-Resistant Mycobacterium tuberculosis Isolates in Korea

  • Park, Sanghee;Jung, Jihee;Kim, Jiyeon;Han, Sang Bong;Ryoo, Sungweon
    • Tuberculosis and Respiratory Diseases
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    • v.85 no.3
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    • pp.256-263
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    • 2022
  • Background: Mycobacterium tuberculosis (Mtb) is resistant to the β-lactam antibiotics due to a non-classical transpeptidase in the cell wall with β-lactamase activity. A recent study showed that meropenem combined with clavulanate, a β-lactamase inhibitor, was effective in multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). However, in Korea, clavulanate can only be used as drugs containing amoxicillin. In this study, we investigated the susceptibility and genetic mutations of drug-resistant Mtb isolates to amoxicillin-clavulanate and meropenem-clavulanate to improve the diagnosis and treatment of drug-resistant TB patients. Methods: The minimum inhibitory concentration (MIC) of amoxicillin-clavulanate and meropenem-clavulanate was examined by resazurin microtiter assay. We used 82 MDR and 40 XDR strains isolated in Korea and two reference laboratory strains. Mutations of drug targets blaC, blaI, ldtA, ldtB, dacB2, and crfA were analyzed by polymerase chain reaction and DNA sequencing. Results: The MIC90 values of amoxicillin/clavulanate and meropenem/clavulanate in drug-resistant Mtb isolates were 64/2.5 and 16/2.5 mg/L, respectively. Gene mutations related to amoxicillin/clavulanate and meropenem/clavulanate resistance could not be identified, but T448G mutation was found in the blaC gene related to β-lactam antibiotics' high susceptibility. Conclusion: Our results provide clinical consideration of β-lactams in treating drug-resistant TB and potential molecular markers of amoxicillin-clavulanate and meropenem-clavulanate susceptibility.

A Study on the Antibacterial Activity of Combined Administration of Jakyakgamcho-tang and Antibiotics Against MRSA (MRSA에 대한 작약감초탕과 항생제 병용투여의 항균활성에 관한 연구)

  • Dam Hee Kang;Ok Hwa Kang;Hee-Sung Chae;Dong Yeul Kwon
    • Korean Journal of Pharmacognosy
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    • v.54 no.2
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    • pp.72-79
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    • 2023
  • MRSA is Staphylococcus aureus resistant to β-lactam antibiotics, and is a worldwide infectious disease. Even with the discovery of new antibiotics, resistance develops rapidly, so new alternatives are needed. Jakyakgamcho-tang (JGT) is a combination of Jakyak and Gamcho, and has been mainly used as an antispasmodic and analgesic in oriental medicine. This study was conducted to find out whether there is an effect on MRSA in relation to the anti-inflammatory effect of JGT and the antibacterial effect of Jakyak and Gamcho found in previous studies. In this study, in order to investigate the antibacterial activity of JGT and the combined effect of existing antibiotics, after extracting JGT with 70% EtoH, the disc diffusion method, minimum inhibitory concentration (MIC), drug combination effect (FICI), and time-kill analysis (Time-kill assay), metabolic inhibition, Western blot and qRT-PCR analysis were used to confirm the antibacterial activity mechanism of MRSA of JGT. As a result of the experiment, all of MRSA showed antibacterial activity in JGT's disc diffusion method, and the MIC was 250-1000 ㎍/mL. When existing antibiotics and JGT were combined with drugs, most had synergy or partial synergy. In addition, it was confirmed that the degree of bacterial growth was suppressed over time when simultaneous administration for 24 hours. JGT showed a synergistic effect when administered together with the ATPase-inhibitor DCCD, suggesting that it affected the inhibition of ATPase. As a result of observing the expression of PBP2a, and hla protein in the JGT-treated group and the untreated control group through wstern blot, it was confirmed that the protein expression of the JGT-treated group was significantly suppressed, and the expression levels of mecA, mecR1 and hla genes were also suppressed during JGT treatment. was observed by qRT-PCR. Combining the results of the experiment, it can be seen that JGT has antibacterial activity in MRSA, and when combined with existing antibiotics, the effect was increased compared to treatment with the drug alone. This suggests that JGT can be an alternative to treatment for antibiotic resistance of MRSA.

The Effect of Injection of Steroid and 5-Fluorouracil on Hypertrophic Scars of Rabbit (가토의 비후성 반흔에서 스테로이드와 5-플루오르우라실 투여 효과)

  • Kim, Kyung-Rak;Ryu, Sun-Youl
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.33 no.3
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    • pp.210-217
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    • 2011
  • Purpose: This study was to evaluate the synergistic effects of combined therapy of steroid and anti-neoplastic drug injection on hypertrophic scars in a rabbit model. Methods: Adult male white rabbits weighing about 2.5 kg were used. After full thickness wounding (about 6 mm) over the ventral surface of each ear sized was made, either saline (control group), triamcinolone, 5-fluoruracil, and mixture of triamcinolone and 5-fluoruracil were injected once 16 days after the wound was made. Rabbits were sacrificed 2, 4 and 8 weeks after injection, and tissue specimens were prepared for histologic and histomorphometric examinations. Results: With the combined injection of triamcinolone and 5-fluoruracil, collagen fiber thickness was arranged in a somewhat irregular manner 2 weeks after injection. After 4 weeks, blood vessels and inflammatory cells were decreased, and collagen fibers were arranged in an almost parallel manner. By 8 weeks, almost same amount of connective tissue compared with adjacent normal tissue was observed. Conclusion: These results indicated that combined injection of triamcinolone and 5-fluoruracil reduced the amount of hypertrophic scars by inhibition of fibroblasts and inflammatory cells. Therefore, combined injection of triamcinolone and 5-fluoruracil is a more potent and effective treatment of hypertrophic scars compared with the single injection of either triamcinolone or 5-fluorouracil.