• Title/Summary/Keyword: Drug Combinations

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Drug Resistance of Bacterial Flora Isolated from Kunsan Bay (군산 내만에서 분리된 세균총에 대한 약제 내성 조사)

  • Choi, Min-Soon
    • Journal of fish pathology
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    • v.13 no.2
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    • pp.111-119
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    • 2000
  • One hundred and twenty three strains of bacterial flora collected from Kunsan bay and examined for drug resistance to 9 antibiotics. The isolated and examined bacteria were Vibrio spp.(44 strains), Pseudomonas spp.(42 strains), Aeromonas spp.(26 strains), Moraxella spp.(9 strains), Enterobacteria spp.(6 strains), Bordetella spp.(3 strains), Alkaligenesis spp.(3 strains), Staphylococcus spp.(3 strains), and Flavobacterium spp.(2 strains). The drugs used were Ampicillin(AM), Penicillin-G(PM), Rifampicin(RF), Streptomycin(SM), Oxolinic acid (OA), Nalidixic acid(NA), Oxytetracycline(OT), Amikacin(AK), and Enorfloxacin(EF). Forty two strains were found to be sensitive to all drugs. The remaining strains showed resistance to various combinations of drugs. Among the resistant strains were mostly restricted to AM(54 strains/43.9%), PM(47 strains/38.2%), RF(35 strains/28.4%), SM(9 strains), OA(5 strains/ 4.06%), and NA(1 strains/0.8%), in combination at high degree showing 15 different drug resistant patterns. The most frequently showed resistant patterns were AM-PM-RF(16 strains/13.4%), AM-PM(8 strains/6.5%), and PM-RF(7 strains/5.6%). These results suggested that Kunsan bay were contaminated with various strains of highly resistant strains to drugs(AM, PM and RF). These results suggest that high levels of various antibiotics have already been introduced to Kunsan bay. Furthermore it seems that chemotherapy of fish disease has become extremely difficult because of the acquirement of multi-drug resistance to wide range of antibiotics.

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In Vitro Screening of Traditional Medicinal Herbs Combined with Donepezil for Neuroprotective Effects in SH-SY5Y Cells (SH-SY5Y 세포에서 도네페질과 병용투여시 신경보호 효과를 나타내는 한약재의 in vitro 선별 연구)

  • Song, Sue-jin;Liu, Quan Feng;Hong, Min-ho;Kim, Geun-woo;Koo, Byung-soo
    • Journal of Oriental Neuropsychiatry
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    • v.30 no.3
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    • pp.199-207
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    • 2019
  • Objectives: The purpose of this study was to evaluate the neuroprotective effects of donepezil and 33 kinds of herbal extract combinations in SH-SY5Y cells with $A{\beta}_{25-35}$ treatment. Methods: MTT assay was performed to measure the cell viability of each herbal extract combined with donepezil against $A{\beta}$-induced neurotoxicity. The most active extracts were then subjected to assess the effects on CREB phosphorylation and COX-2 expressions through the western blot analysis. Results: There were eight herbal extracts representing significant increase on the cell viability: 1) Erycibe obtusifolia, 2) Polygonum multiflorum, 3) Polygala tenuifolia, 4) Illicium verum, 5) Santalum album, 6) Loranthus parasticus, 7) Platycladus orientalis, and 8) Zanthoxylum piperitum. Especially, when Santalum album and donepezil were treated together, the phosphorylation of CREB significantly increased and COX-2 protein expression was significantly inhibited. Conclusions: Among the screened herbal extracts, combination treatment of each of the eight herbs and donepezil showed neuroprotective effects in SH-SY5Y cells. Additionally, the combination of Santalum album and donepezil suggested cognitive improvement by up-regulation of p-CREB and down-regulation of COX-2.

2-deoxy-D-Glucose Synergizes with Doxorubicin or L-Buthionine Sulfoximine to Reduce Adhesion and Migration of Breast Cancer Cells

  • Mustafa, Ebtihal H;Mahmoud, Huda T;Al-Hudhud, Mariam Y;Abdalla, Maher Y;Ahmad, Iman M;Yasin, Salem R;Elkarmi, Ali Z;Tahtamouni, Lubna H
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3213-3222
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    • 2015
  • Background: Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification. The current work aimed at studying the effects of sub-lethal metabolic oxidative stress on actin cytoskeleton, focal adhesion and cell migration. Materials and Methods: T47D human breast cancer cells were treated with 2-deoxy-D-glucose (2DG), L-buthionine sulfoximine (BSO), or doxorubicin (DOX), individually or in combination, and changes in intracellular total glutathione and malondialdehyde (MDA) levels were measured. The expression of three major antioxidant enzymes was studied by immunoblotting, and cells were stained with fluorescent-phalloidin to evaluate changes in F-actin organization. In addition, cell adhesion and degradation ability were measured. Cell migration was studied using wound healing and transwell migration assays. Results: Our results show that treating T47D human breast cancer cells with drug combinations (2DG/BSO, 2DG/DOX, or BSO/DOX) decreased intracellular total glutathione and increased oxidized glutathione, lipid peroxidation, and cytotoxicity. In addition, the drug combinations caused a reduction in cell area and mitotic index, prophase arrest and a decreased ability to form invadopodia. The formation of F-actin aggregates was increased in treated T47D cells. Moreover, combination therapy reduced cell adhesion and the rate of cell migration. Conclusions: Our results suggest that exposure of T47D breast cancer cells to combination therapy reduces cell migration via effects on metabolic oxidative stress.

Study on the hepatoprotective effects of lemon balm and dandelion leaf extract combination in carbon tetrachloride-mediated liver injured mice (사염화탄소 유도성 급성 간 손상 모델에서 레몬밤과 민들레 잎 추출물의 혼합 비율에 따른 간 보호 효능 연구)

  • Choi, Beom-Rak;Cho, Il Je;Jung, Su-Jin;Kim, Jae Kwang;Lee, Dae Geon;Ku, Sae Kwang;Park, Ki-Moon
    • Herbal Formula Science
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    • v.27 no.3
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    • pp.199-211
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    • 2019
  • Objectives : Present study investigated the hepatoprotective effects of various combinations of lemon balm and dandelion (LD) leaf extract on carbon tetrachloride ($CCl_4$)-induced acute liver injury. Methods : Mice were orally treated with 200 mg/kg of LD extracts [1:1, 1:2, 1:4, 1:6, 1:8, 2:1, 4:1, 6:1, or 8:1 (weight : weight)] for 7 days, and then intraperitoneally injected with $CCl_4$ (0.5 mL/kg). Silymarin (100 mg/kg) was used as reference drug. Body weight gain, relative liver weight, serum biochemistry, histopathologic analyses, and hepatic antioxidant system were examined to elucidate the fittest combination ratio of LD extract. Results : All varying combinations of LD extract significantly increased body weight gain and decreased relative liver weight by $CCl_4$. In addition, LD extract reduced serum aspartate aminotransferase and alanine aminotransferase. Histopathological analyses indicated that LD extract significantly decreased histological activity index score, degenerated hepatocytes, and infiltrated inflammatory cells induced by $CCl_4$. Moreover, LD extract reduced lipid peroxidation, and attenuated the reduction of hepatic glutathione, superoxide dismutase, and catalase by $CCl_4$. Although there were no statistical differences in body weight gain between silymarin- and LD extract-treated groups, administration of 1:1, 2:1, and 4:1 combination of LD extract exhibited more favorable hepatoprotective effects than silymarin. Especially, 2:1 combination of LD extract showed the most potent hepatoprotective effects. Conclusion : Of various combinations of LD extract tested, present results suggest that 2:1 combination of LD extract would be a promising herbal formulation to protect liver from oxidative stress.

Hepatoprotective effect of fermented Schizandrae Fructus Pomace extract and Hoveniae Semen Cum Fructus extract combination mixtures against carbon tetrachloride-induced acute liver injured mice (사염화탄소 유발 급성 간 손상에 대한 발효 오미자박 및 헛개과병 추출물의 혼합 비율에 따른 간 보호효능)

  • Hye-Rim, Park;Kyung Hwan, Jegal;Beom-Rak, Choi;Jae Kwang, Kim;Sae Kwang, Ku
    • Herbal Formula Science
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    • v.31 no.1
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    • pp.53-65
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    • 2023
  • Objectives : Present study investigated the hepatoprotective effects and the optimal mixing ratio of fermented Schizandrae Fructus Pomace (fSFP) and Hoveniae Semen Cum Fructus (HSCF) extract combination in carbon tetrachloride (CCl4)-induced acute liver injury mice. Methods : ICR mice were orally administered with 200 mg/kg of fSFP, HSCF and mixtures of fSFP and HSCF [MSH (w:w); 1:1, 1:2, 1:4, 1:6, 2:1, 4:1, 6:1, and 8:1] for 7 consecutive days. Silymarin (100 mg/kg) was administered as a reference drug. 0.5 mL/kg of CCl4 was injected intraperitoneally to induce acute liver injury. Body weight gain, relative liver weight, serum chemistry, histopathological analysis, and hepatic endogenous antioxidants capacities were observed. Results : All diverse combinations of MSH significantly reduced relative liver weight increase by CCl4. In addition, MSH administrations significantly decreased the elevation of serum alanine aminotransferase and aspartate aminotransferase activities by CCl4. Histopathological observation indicated that all MSH treatments significantly reduced the increase of degenerated hepatocytes, inflammatory cell infiltration, and histological activity index score by CCl4. Moreover, all MSH administrations reduced the elevation of malondialdehyde contents, and ameliorated the reduction of hepatic glutathione contents, superoxide dismutase activity, and catalase activity. Among the various mixing ratio of MSH combinations, MSH 1:1 and 2:1 showed the most potent anti-oxidative stress, and hepatoprotective effect. Conclusion : Present results suggest that 1:1 and 2:1 combinations of MSH is promising herbal formulation with the hepatoprotective effect against oxidative stress.

The Oriental Materia Medica in viewpoint of natural products chem (천연물화학(天然物化學)에서 보는 동의약(東醫藥))

  • Ahn, Byung Zun
    • Journal of Haehwa Medicine
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    • v.4 no.2
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    • pp.309-329
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    • 1996
  • There are the Seven Effect of Drugs and unique processing methods in Chinese traditional medicine. The Seven Effects are single effrect(單行), additive effect(相加, 相須), synergic effect(上乘, 相使), antagonistic effect(相畏, 拮抗), inhibitory effect(相惡), neutralizing effect(相殺) and opposite effect(相反). We are interested in synergic effects of some drugs and components ; Addition of OLDENLANDIA DIFFUSA to Kilkyungtang combanation enhanced the cytotoxic activity of Kilkyungtang against A549 and B16-Fo eells by 20% and 50%, respectively. The Oldenlandia-added kilkyungtang also potentiated the cytotoxicities of mitomycine Cand 5-fluorouracil. ar-tunnerone. isolated from the root of Curcuma longa, potentiated the cytotoxic activity of sesquiphellandrene(isolated from the same root), aurapten(isolated from Aurantii semen)or cyclophosphamide by 10 times. The purpose of the processing(修治) of Chinese grugs is to remove unusable parts of plants and to eliminate toxicities as well as to produse new active components in drugs. On a occasion of study on the anthelmintic drugs against the chinese fluke(Clonorchis sinesis, (肝디스토마), we have observed that the processed mume fruit(鳥梅) possessed a very very potent clonorchicidal effect, while the methanol extract of the non-processed fruit inactive. The active component was isolated from the processed mume and identified as 5-hydroxymethylfurfuryl aldehyde. This substance dose not occur in the immature fruit and was found only in the processed one. Wehave heated the immature fruit in an oven at $90^{\circ}C$ for 52 hrs and found that the heated fruit eame clonorchidal. As demonstrated in these and other example cited in this presentation, the natural products chemistry is contributory to univeiling the drug effect ensued from the processing and the synergic effect of Oriental medical drug combinations, and to rationalization or modernization of the traditional medicine.

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Combination of berberine and ciprofloxacin reduces multi-resistant Salmonella strain biofilm formation by depressing mRNA expressions of luxS, rpoE, and ompR

  • Shi, Chenxi;Li, Minmin;Muhammad, Ishfaq;Ma, Xin;Chang, Yicong;Li, Rui;Li, Changwen;He, Jingshan;Liu, Fangping
    • Journal of Veterinary Science
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    • v.19 no.6
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    • pp.808-816
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    • 2018
  • Bacterial biofilms have been demonstrated to be closely related to clinical infections and contribute to drug resistance. Berberine, which is the main component of Coptis chinensis, has been reported to have efficient antibacterial activity. This study aimed to investigate the potential effect of a combination of berberine with ciprofloxacin (CIP) to inhibit Salmonella biofilm formation and its effect on expressions of related genes (rpoE, luxS, and ompR). The fractional inhibitory concentration (FIC) index of the combination of berberine with CIP is 0.75 showing a synergistic antibacterial effect. The biofilm's adhesion rate and growth curve showed that the multi-resistant Salmonella strain had the potential to form a biofilm relative to that of strain CVCC528, and the antibiofilm effects were in a dose-dependent manner. Biofilm microstructures were rarely observed at $1/2{\times}MIC/FIC$ concentrations (MIC, minimal inhibition concentration), and the combination had a stronger antibiofilm effect than each of the antimicrobial agents used alone at $1/4{\times}FIC$ concentration. LuxS, rpoE, and ompR mRNA expressions were significantly repressed (p< 0.01) at $1/2{\times}MIC/FIC$ concentrations, and the berberine and CIP combination repressed mRNA expressions more strongly at the $1/4{\times}FIC$ concentration. The results indicate that the combination of berberine and CIP has a synergistic effect and is effective in inhibiting Salmonella biofilm formation via repression of luxS, rpoE, and ompR mRNA expressions.

Systemic Analysis of Antibacterial and Pharmacological Functions of Scutellariae Radix (시스템 약리학적 분석에 의한 황금의 항균효과)

  • Kim, Hyo Jin;Bak, Se Rim;Ha, Hee Jung;Kim, Youn Sook;Lee, Boo Kyun;An, Won Gun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.34 no.4
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    • pp.184-190
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    • 2020
  • This study was performed to find antibacterial substances contained in Scutellariae Radix (SR) using a systems pharmacological analysis method and to establish an effective strategy for the prevention and treatment of infectious diseases. Analysis of the main active ingredients of SR was performed using Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform. 36 active compounds were screened by the parameter values of Drug-Likeness (DL), Oral Bioavailability (OB), and Caco-2 permeability (Caco-2), which were based on the drug absorption, distribution, metabolism, and excretion indicators. The UniProt database was used to obtain information on 159 genes associated with active compounds. The main active compounds with antibacterial effects were wogonin, β-sitosterol, baicalein, acacetin and oroxylin-A. Target proteins associated with the antibacterial action were chemokine ligand 2, interleukin-6, tumor necrosis factor, caspase-8,9 and mitogen-activated protein kinase 14. In the future, systems pharmacological analysis of traditional medicine will be able to make it easy to find the important mechanism of action of active substances present in natural medicines and to optimize the efficacy of medicinal effects for combinations of major ingredients to help treat certain diseases.

Hyaluronic Acid Increases Anti-Inflammatory Efficacy of Rectal 5-Amino Salicylic Acid Administration in a Murine Colitis Model

  • Jhundoo, Henusha D.;Siefen, Tobias;Liang, Alfred;Schmidt, Christoph;Lokhnauth, John;Moulari, Brice;Beduneau, Arnaud;Pellequer, Yann;Larsen, Crilles Casper;Lamprecht, Alf
    • Biomolecules & Therapeutics
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    • v.29 no.5
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    • pp.536-544
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    • 2021
  • 5-amino salicylic acid (5-ASA) is a standard therapy for the treatment of mild to moderate forms of inflammatory bowel diseases (IBD) whereas more severe forms involve the use of steroids and immunosuppressive drugs. Hyaluronic acid (HA) is a naturally occurring non-sulfated glycosaminoglycan that has shown epithelium protective effects in experimental colitis recently. In this study, both 5-ASA (30 mg/kg) and HA (15 mg/kg or 30 mg/kg) were administered rectally and investigated for their potential complementary therapeutic effects in moderate or severe murine colitis models. Intrarectal treatment of moderate and severe colitis with 5-ASA alone or HA alone at a dose of 30 mg/kg led to a significant decrease in clinical activity and histology scores, myeloperoxidase activity (MPO), TNF-α, IL-6 and IL-1β in colitis mice compared to untreated animals. The combination of HA (30 mg/kg) and 5-ASA in severe colitis led to a significant improvement of colitis compared to 5-ASA alone. Combined rectal therapy with HA and 5-ASA could be a treatment alternative for severe cases of IBD as it was the only treatment tested that was not significantly different from the healthy control group. This study further underlines the benefit of searching for yet unexplored drug combinations that show therapeutic potential in IBD without the need of designing completely new drug entities.

No more tears from surgical site infections in interventional pain management

  • Seungjin Lim;Yeong-Min Yoo;Kyung-Hoon Kim
    • The Korean Journal of Pain
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    • v.36 no.1
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    • pp.11-50
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    • 2023
  • As the field of interventional pain management (IPM) grows, the risk of surgical site infections (SSIs) is increasing. SSI is defined as an infection of the incision or organ/space that occurs within one month after operation or three months after implantation. It is also common to find patients with suspected infection in an outpatient clinic. The most frequent IPM procedures are performed in the spine. Even though primary pyogenic spondylodiscitis via hematogenous spread is the most common type among spinal infections, secondary spinal infections from direct inoculation should be monitored after IPM procedures. Various preventive guidelines for SSI have been published. Cefazolin, followed by vancomycin, is the most commonly used surgical antibiotic prophylaxis in IPM. Diagnosis of SSI is confirmed by purulent discharge, isolation of causative organisms, pain/tenderness, swelling, redness, or heat, or diagnosis by a surgeon or attending physician. Inflammatory markers include traditional (C-reactive protein, erythrocyte sedimentation rate, and white blood cell count) and novel (procalcitonin, serum amyloid A, and presepsin) markers. Empirical antibiotic therapy is defined as the initial administration of antibiotics within at least 24 hours prior to the results of blood culture and antibiotic susceptibility testing. Definitive antibiotic therapy is initiated based on the above culture and testing. Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria infections appears to be superior to monotherapy in mortality with the risk of increasing antibiotic resistance rates. The never-ending war between bacterial resistance and new antibiotics is continuing. This article reviews prevention, diagnosis, and treatment of infection in pain medicine.