Displaying publications 41 - 60 of 120 in total

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  1. Ghosh AK, Rahaman AA, Singh R
    Int J Sport Nutr Exerc Metab, 2010 Jun;20(3):216-23.
    PMID: 20601739
    The purpose of the study was to investigate whether a combination of sago and soy protein ingested during moderate-intensity cycling exercise can improve subsequent high-intensity endurance capacity compared with a carbohydrate in the form of sago and with a placebo. The participants were 8 male recreational cyclists with age, weight, and VO2max of 21.5 +/- 1.1 yr, 63.3 +/- 2.4 kg, and 39.9 +/- 1.1 ml . kg(-1) . min(-1), respectively. The design of the study was a randomized, double-blind placebo-controlled crossover comprising 60 min of exercise on a cycle ergometer at 60% VO2max followed by a time-to-exhaustion ride at 90% VO2max. The sago feeding provided 60 g of carbohydrate, and the sago-soy combination provided 52.5 g of carbohydrate and 15 g of protein, both at 20-min intervals during exercise. Times to exhaustion for the placebo, sago, and sago-soy supplementations were 4.09 +/- 1.28, 5.49 +/- 1.20, and 7.53 +/- 2.02 min, respectively. Sago-soy supplementation increased endurance by 84% (44-140%; p < .001) and by 37% (15-63%; p < .05) relative to placebo and sago, respectively. The plasma insulin response was elevated above that with placebo during sago and sago-soy supplementations. The authors conclude that a combination of sago and soy protein can delay fatigue during high-intensity cycling.
    Matched MeSH terms: Drug Synergism
  2. Ullah A, Ashraf M, Javeed A, Anjum AA, Attiq A, Ali S
    Environ Toxicol Pharmacol, 2016 Jul;45:227-34.
    PMID: 27327526 DOI: 10.1016/j.etap.2016.05.017
    Pathophysiological changes in diabetes like hyperglycemia, oxidative stress, insulin resistance and compensatory hyperinsulinemia predispose cells to malignant transformation and damage DNA repair mechanism. This study was designed to explore the potential synergistic toxic effects of anti-diabetic drug (Metformin), and an analgesic drug (Celecoxib) at cellular level. MTT assay run on Vero cell line revealed that the combinations of Metformin and Celecoxib augment the anti-proliferative effects, whereas Single cell gel electrophoresis spotlighted that Metformin produce non-significant DNA damage with the threshold concentration of 400μg/ml in peripheral blood mononuclear cells (lymphocytes and monocytes), while Celecoxib produced significant (P<0.05) DNA damage (class III comets) above the concentration of 75μg/ml, however the DNA damage or DNA tail protrusions by combinations of both drugs were less than what was observed with Celecoxib alone. Metformin or Celecoxib did not appear mutagenic against any mutant strains (TA 100 and TA 98) but their combination exhibited slight mutagenicity at much higher concentration. The results obtained at concentrations higher than the therapeutic level of drugs and reflect that Metformin in combination with Celecoxib synergistically inhibits the cell proliferation in a concentration dependent pattern. Since, this increase in cytotoxicity did not confer an increase in DNA damage; this combination could be adopted to inhibit the growth of malignant cell without producing any genotoxic or mutagenic effects at cellular level.
    Matched MeSH terms: Drug Synergism
  3. Talik Sisin NN, Abdul Razak K, Zainal Abidin S, Che Mat NF, Abdullah R, Ab Rashid R, et al.
    Int J Nanomedicine, 2020;15:7805-7823.
    PMID: 33116502 DOI: 10.2147/IJN.S269214
    Purpose: This study aimed to quantify synergetic effects induced by bismuth oxide nanoparticles (BiONPs), cisplatin (Cis) and baicalein-rich fraction (BRF) natural-based agent on the reactive oxygen species (ROS) generation and radiosensitization effects under irradiation of clinical radiotherapy beams of photon, electron and HDR-brachytherapy. The combined therapeutic responses of each compound and clinical radiotherapy beam were evaluated on breast cancer and normal fibroblast cell line.

    Methods: In this study, individual BiONPs, Cis, and BRF, as well as combinations of BiONPs-Cis (BC), BiONPs-BRF (BB) and BiONPs-Cis-BRF (BCB) were treated to the cells before irradiation using HDR brachytherapy with 0.38 MeV iridium-192 source, 6 MV photon beam and 6 MeV electron beam. The individual or synergetic effects from the application of the treatment components during the radiotherapy were elucidated by quantifying the ROS generation and radiosensitization effects on MCF-7 and MDA-MB-231 breast cancer cell lines as well as NIH/3T3 normal cell line.

    Results: The ROS generated in the presence of Cis stimulated the most substantial amount of ROS compared to the BiONPs and BRF. Meanwhile, the combination of the components had induced the higher ROS levels for photon beam than the brachytherapy and electron beam. The highest ROS enhancement relative to the control is attributable to the presence of BC combination in MDA-MB-231 cells, in comparison to the BB and BCB combinations. The radiosensitization effects which were quantified using the sensitization enhancement ratio (SER) indicate the highest value by BC in MCF-7 cells, followed by BCB and BB treatment. The radiosensitization effects are found to be more prominent for brachytherapy in comparison to photon and electron beam.

    Conclusion: The BiONPs, Cis and BRF are the potential radiosensitizers that could improve the efficiency of radiotherapy to eradicate the cancer cells. The combination of these potent radiosensitizers might produce multiple effects when applied in radiotherapy. The BC combination is found to have the highest SER, followed by the BCB combination. This study is also the first to investigate the effect of BRF in combination with BiONPs (BB) and BC (BCB) treatments.

    Matched MeSH terms: Drug Synergism
  4. Arya A, Al-Obaidi MM, Shahid N, Bin Noordin MI, Looi CY, Wong WF, et al.
    Food Chem Toxicol, 2014 Sep;71:183-96.
    PMID: 24953551 DOI: 10.1016/j.fct.2014.06.010
    The aim of this study was to investigate the synergistic effects of quercetin (QE) and quinic acid (QA) on a STZ-induced diabetic rat model to determine their potential role in alleviating diabetes and its associated complications. In our study design, diabetic rats were treated with single and combined doses of QE and QA for 45days to analyse their effects on liver, kidney and pancreas tissues. The study result showed that QE and QA treated groups down-regulated hyperglycaemia and oxidative stress by up-regulating insulin and C-peptide levels. Moreover, histological observations of the liver, kidney and pancreas of diabetic rats treated with single and combined doses of QE and QA showed a significant improvement in the structural degeneration. Interestingly, the combination dose of QE and QA (50 mg/kg) exhibited maximum inhibition of the pro-apoptotic protein Bax expression and demonstrate enhancement of the anti-apoptotic protein Bcl-2 expression in the kidney tissues, suggesting a protective role in the kidneys of diabetic rats. Taken together, these results indicates the synergistic effects of QE and QA in ameliorating hyperglycaemia, hyperlipidemia and insulin resistance in diabetic rats and therefore, open a new window of research on the combinatorial therapy of flavonoids.
    Matched MeSH terms: Drug Synergism
  5. Khairul MF, Min TH, Low JH, Nasriyyah CH, A'shikin AN, Norazmi MN, et al.
    Jpn J Infect Dis, 2006 Oct;59(5):329-31.
    PMID: 17060702
    Fluoxetine (FLX), a P-glycoprotein inhibitor with antimalarial activity, is promising candidate for reversing chloroquine/mefloquine (CQ/MQ) resistance. The Dd2 strain of CQ- and MQ-resistant Plasmodium falciparum was synchronized and assayed with various concentrations of CQ/MQ individually and in combination with FLX or verapamil (VPL). Our results indicated the 50% inhibitory concentration values of CQ and MQ were greatly lowered when FLX was used simultaneously. Isobolograms indicated that CQ-FLX combinations are more synergistic (mean fractional inhibitory concentration [FIC] index 0.55) than MQ-FLX (mean FIC index 0.64), and their synergistic effect was better than or at par with CQ-VPL (mean FIC index 0.88) and MQ-VPL (mean FIC index 0.60) combinations. We conclude that the FLX potentiates the CQ and MQ response on multidrug-resistant P. falciparum at clinically achievable concentrations.
    Matched MeSH terms: Drug Synergism
  6. Low SY, Tan BS, Choo HL, Tiong KH, Khoo AS, Leong CO
    Cancer Lett, 2012 Jan 28;314(2):166-75.
    PMID: 22033244 DOI: 10.1016/j.canlet.2011.09.025
    The efficacy of cisplatin for treating nasopharyngeal carcinoma (NPC) is limited by the dose-related toxicities and the development of resistance to cisplatin. Recent studies have shown that B cell lymphoma-2 (BCL-2) is overexpressed and confers chemoresistance in NPC. Thus, targeted therapy against BCL-2 may enhance the antitumour effects of chemotherapy by sensitizing the tumor cells to undergo apoptosis. This study evaluated the combined effects of BCL-2 inhibition and cisplatin in NPC cells. Our results demonstrate that inhibition of BCL-2 by small-hairpin RNA (shRNA) or the BCL-2 inhibitor YC137, synergizes cisplatin sensitivity in NPC cells that overexpress BCL-2. We also show that YC137 enhance cisplatin-induced apoptosis in HK1 and CNE1 cells through suppression of BCL-2 protein expression, induction of mitochondrial depolarization and activation of caspase 9 and caspase 3/7. These findings suggest that the combination of BCL-2 inhibition and cisplatin represents a promising strategy for treating NPC.
    Matched MeSH terms: Drug Synergism
  7. Su Wei Poh M, Voon Chen Yong P, Viseswaran N, Chia YY
    PLoS One, 2015;10(3):e0121382.
    PMID: 25816349 DOI: 10.1371/journal.pone.0121382
    Glabridin is an isoflavan from licorice root, which is a common component of herbal remedies used for treatment of menopausal symptoms. Past studies have shown that glabridin resulted in favorable outcome similar to 17β-estradiol (17β-E2), suggesting a possible role as an estrogen replacement therapy (ERT). This study aims to evaluate the estrogenic effect of glabridin in an in-vitro endometrial cell line -Ishikawa cells via alkaline phosphatase (ALP) assay and ER-α-SRC-1-co-activator assay. Its effect on cell proliferation was also evaluated using Thiazoyl blue tetrazolium bromide (MTT) assay. The results showed that glabridin activated the ER-α-SRC-1-co-activator complex and displayed a dose-dependent increase in estrogenic activity supporting its use as an ERT. However, glabridin also induced an increase in cell proliferation. When glabridin was treated together with 17β-E2, synergistic estrogenic effect was observed with a slight decrease in cell proliferation as compared to treatment by 17β-E2 alone. This suggest that the combination might be better suited for providing high estrogenic effects with lower incidences of endometrial cancer that is associated with 17β-E2.
    Matched MeSH terms: Drug Synergism
  8. Nik Mohamed Kamal NNS, Abdul Aziz FA, Tan WN, Fauzi AN, Lim V
    Molecules, 2021 Jun 09;26(12).
    PMID: 34207699 DOI: 10.3390/molecules26123518
    Pancreatic cancer is an aggressive disease that progresses in a relatively symptom-free manner; thus, is difficult to detect and treat. Essential oil is reported to exhibit pharmacological properties, besides its common and well-known function as aromatherapy. Therefore, this study herein aimed to investigate the anti-proliferative effect of essential oil extracted from leaves of Garcinia atroviridis (EO-L) against PANC-1 human pancreatic cancer cell line. The cell growth inhibitory concentration at 50% (IC50) and selective index (SI) values of EO-L analyses were determined as 78 µg/mL and 1.23, respectively. Combination index (CI) analysis revealed moderate synergism (CI values of 0.36 to 0.75) between EO-L and 2 deoxy-d-glucose (2-DG) treatments. The treatments of PANC-1 cells with EO-L, 2-DG and EOL+2DG showed evidence of depolarization of mitochondrial membrane potential, cell growth arrest and apoptosis. The molecular mechanism causing the anti-proliferative effect between EO-L and 2-DG is potentially through pronounced up-regulation of P53 (4.40-fold), HIF1α (1.92-fold), HK2 (2.88-fold) and down-regulation of CYP3A5 (0.11-fold), as supported by quantitative mRNA expression analysis. Collectively, the current data suggest that the combination of two anti-proliferative agents, EO-L and 2-DG, can potentially be explored as therapeutic treatments and as potentiating agents to conventional therapy against human pancreatic cancer.
    Matched MeSH terms: Drug Synergism
  9. Lin YW, Abdul Rahim N, Zhao J, Han ML, Yu HH, Wickremasinghe H, et al.
    PMID: 30670431 DOI: 10.1128/AAC.02176-18
    Polymyxins are used as a last-line therapy against multidrug-resistant (MDR) New Delhi metallo-β-lactamase (NDM)-producing Klebsiella pneumoniae However, polymyxin resistance can emerge with monotherapy; therefore, novel strategies are urgently needed to minimize the resistance and maintain their clinical utility. This study aimed to investigate the pharmacodynamics of polymyxin B in combination with the antiretroviral drug zidovudine against K. pneumoniae Three isolates were evaluated in static time-kill studies (0 to 64 mg/liter) over 48 h. An in vitro one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model (IVM) was used to simulate humanized dosage regimens of polymyxin B (4 mg/liter as continuous infusion) and zidovudine (as bolus dose thrice daily to achieve maximum concentration of drug in broth [Cmax] of 6 mg/liter) against K. pneumoniae BM1 over 72 h. The antimicrobial synergy of the combination was further evaluated in a murine thigh infection model against K. pneumoniae 02. In the static time-kill studies, polymyxin B monotherapy produced rapid and extensive killing against all three isolates followed by extensive regrowth, whereas zidovudine produced modest killing followed by significant regrowth at 24 h. Polymyxin B in combination with zidovudine significantly enhanced the antimicrobial activity (≥4 log10 CFU/ml) and minimized bacterial regrowth. In the IVM, the combination was synergistic and the total bacterial loads were below the limit of detection for up to 72 h. In the murine thigh infection model, the bacterial burden at 24 h in the combination group was ≥3 log10 CFU/thigh lower than each monotherapy against K. pneumoniae 02. Overall, the polymyxin B-zidovudine combination demonstrates superior antimicrobial efficacy and minimized emergence of resistance to polymyxins.
    Matched MeSH terms: Drug Synergism
  10. Lee WX, Basri DF, Ghazali AR
    Molecules, 2017 Mar 17;22(3).
    PMID: 28304328 DOI: 10.3390/molecules22030463
    The antibacterial activity of pterostilbene in combination with gentamicin against six strains of Gram-positive and Gram-negative bacteria were investigated. The minimum inhibitory concentration and minimum bactericidal concentration of pterostilbene were determined using microdilution technique whereas the synergistic antibacterial activities of pterostilbene in combination with gentamicin were assessed using checkerboard assay and time-kill kinetic study. Results of the present study showed that the combination effects of pterostilbene with gentamicin were synergistic (FIC index < 0.5) against three susceptible bacteria strains: Staphylococcus aureus ATCC 25923, Escherichia coli O157 and Pseudomonas aeruginosa 15442. However, the time-kill study showed that the interaction was indifference which did not significantly differ from the gentamicin treatment. Furthermore, time-kill study showed that the growth of the tested bacteria was completely attenuated with 2 to 8 h treatment with 0.5 × MIC of pterostilbene and gentamicin. The identified combinations could be of effective therapeutic value against bacterial infections. These findings have potential implications in delaying the development of bacterial resistance as the antibacterial effect was achieved with the lower concentrations of antibacterial agents.
    Matched MeSH terms: Drug Synergism
  11. Abu-Serie MM, Habashy NH, Attia WE
    BMC Complement Altern Med, 2018 May 10;18(1):154.
    PMID: 29747629 DOI: 10.1186/s12906-018-2218-5
    BACKGROUND: Since oxidative stress and inflammation are two linked factors in the pathogenesis of several human diseases. Thus identification of effective treatment is of great importance. Edible mushroom and microalgae are rich in the effective antioxidant phytochemicals. Hence, their beneficial effects on oxidative stress-associated inflammation are extremely required to be investigated.

    METHODS: This study evaluated the functional constituents, antioxidant and anti-inflammatory activities of Malaysian Ganoderma lucidum aqueous extract (GLE) and Egyptian Chlorella vulgaris ethanolic extract (CVE). Also, the synergistic, addictive or antagonistic activities of the combination between the two extracts (GLE-CVE) were studied. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor-kappa B, as well as levels of nitric oxide, tumor necrosis factor (TNF)-α, lipid peroxidation, reduced glutathione and antioxidant enzymes were determined using in vitro model of lipopolysaccharide-stimulated white blood cells.

    Matched MeSH terms: Drug Synergism
  12. Dorasamy MS, Ab A, Nellore K, Wong PF
    Biomed Pharmacother, 2019 Feb;110:29-36.
    PMID: 30458345 DOI: 10.1016/j.biopha.2018.11.010
    Malignant melanoma continues to be a fatal disease for which novel and long-term curative breakthroughs are desired. One such innovative idea would be to assess combination therapeutic treatments - by way of combining two potentially effective and very different therapy. Previously, we have shown that DHODH inhibitors, A771726 and Brequinar sodium (BQR) induced cell growth impairment in melanoma cells. Similar results were seen with DHODH RNA interference (shRNA). In the present study, we showed that combination of BQR with doxorubicin resulted in synergistic and additive cell growth inhibition in these cells. In addition, in vivo studies with this combination of drugs demonstrated an almost 90% tumor regression in nude mice bearing melanoma tumors. Cell cycle regulatory proteins, cyclin B1 and its binding partner pcdc-2 and p21 were significantly downregulated and upregulated respectively following the combined treatment. Given that we have observed synergistic effects with BQR and doxorubicin, both in vitro and in vivo, these drugs potentially represent a new combination in the targeted therapy of melanoma.
    Matched MeSH terms: Drug Synergism
  13. Yap JKY, Tan SYY, Tang SQ, Thien VK, Chan EWL
    Microb Drug Resist, 2021 Feb;27(2):234-240.
    PMID: 32589487 DOI: 10.1089/mdr.2020.0178
    Aims: Currently, limited antibiotics are available to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. One approach is the use of adjuvants in antibiotic therapy. 1,4-Naphthoquinones are naturally occurring alkaloids shown to have antibacterial properties. The objective of this study is to investigate the synergy between 1,4-naphthoquinone and selected β-lactam antibiotics and to evaluate the potential use of 1,4-naphthoquinone as an adjuvant in antibiotic treatment against MRSA infections. Methods: The antibacterial activity of 1,4-naphthoquinone and plumbagin was tested against nine pathogenic bacterial strains using the microdilution broth method. The interactions between 1,4-naphthoquinone and three antibiotics (cefuroxime, cefotaxime, and imipenem) were estimated by calculating the fractional inhibitory concentration of the combination. Results: The compounds 1,4-naphthoquinone and plumbagin exhibited a broad range of bacteriostatic and bactericidal effects against both Gram-positive and Gram-negative bacteria. The interaction between 1,4-naphthoquinone and imipenem, cefuroxime, and cefotaxime was synergistic against methicillin-sensitive Staphylococcus aureus and MRSA clinical strains. Against ATCC-cultured MRSA, a synergistic effect was observed between 1,4-naphthoquinone and cefotaxime. However, combination with imipenem only produced an additive effect, and an antagonistic action was observed between 1,4-naphthoquinone and cefuroxime. Conclusions: Although individually less potent than common antibiotics, 1,4-naphthoquinone acts synergistically with imipenem, cefuroxime, and cefotaxime against MRSA clinical strains and could potentially be used in adjuvant-antibiotic therapy against multidrug resistant bacteria.
    Matched MeSH terms: Drug Synergism
  14. Mohd Sazlly Lim S, Heffernan AJ, Roberts JA, Sime FB
    Microb Drug Resist, 2021 Apr;27(4):546-552.
    PMID: 32898467 DOI: 10.1089/mdr.2020.0197
    Background and Objective: Combination therapy may be a treatment option against carbapenem-resistant Acinetobacter baumannii (CR-AB) infections. In this study, we explored the utility of fosfomycin in combination with meropenem (FOS/MEM) against CR-AB isolates. Materials and Methods: Screening of synergistic activity of FOS/MEM was performed using the checkerboard assay. A pharmacokinetic/pharmacodynamic analysis was performed for various FOS/MEM regimens using Monte Carlo simulations. Results: The minimum inhibitory concentration (MIC) required to inhibit the growth of 50% of the isolates (MIC50) and MIC required to inhibit the growth of 90% of the isolates (MIC90) of FOS and MEM were reduced fourfold and twofold, respectively. The combination was synergistic against 14/50 isolates. No antagonism was observed. Sixteen out of fifty isolates had MEM MICs of ≤8 mg/L when subjected to combination therapy, compared to none with monotherapy. Forty-one out of 50 isolates had FOS MICs of ≤128 mg/L when subjected to combination therapy, compared to 17/50 isolates with monotherapy. The cumulative fraction response for MEM and FOS improved from 0% to 40% and 40% to 80%, with combination therapy, respectively. Conclusions: Addition of MEM improved the in vitro activity of FOS against the CR-AB isolates. FOS/MEM could be a plausible option to treat CR-AB for a small fraction of isolates.
    Matched MeSH terms: Drug Synergism
  15. Teow SY, Ali SA
    Pak J Pharm Sci, 2015 Nov;28(6):2109-14.
    PMID: 26639480
    This study evaluated the synergistic antibacterial activity of Curcumin with 8 different antibiotic groups. Two reference, one clinical and ten environmental strains of Staphylococcus aureus (S. aureus) were tested. Disc diffusion assay with 25 μg/mL Curcumin demonstrated synergism in combination with a majority of tested antibiotics against S. aureus. However, checkerboard micro dilution assay only showed synergism, fractional inhibitory concentration index (FICI) <0.5 in three antibiotics i.e. Gentamicin, Amikacin, and Ciprofloxacin. Other antibiotics showed indifferent interactions but no antagonism was observed. In time-kill curve, appreciable reduction of bacterial cells was also observed in combination therapy (Curcumin + antibiotics) compared to monotherapy (Curcumin or antibiotic(s) alone). The antibiotics with higher synergistic interaction with Curcumin are arranged in a decreasing order: Amikacin > Gentamicin > Ciprofloxacin.
    Matched MeSH terms: Drug Synergism
  16. Bandyopadhyay A, Ping FW, Keong CC
    J Hum Ergol (Tokyo), 2011 Dec;40(1-2):63-72.
    PMID: 25665208 DOI: 10.11183/jhe.40.63
    Acute supplementation of Panax ginseng (PG) is known not to impose any significant effect on endurance performance of recreational Malaysian runners, while caffeine augments the ergogenic property of some herbs. The present study was aimed to examine the effects of acute supplementation of caffeine and PG on endurance running performance in a hot and humid condition. Nine heat adapted Malaysian recreational runners (age : 25.4 ± 6.9 years, body mass : 57.6 ± 8.4 kg; body height : 168.3 ± 7.6 cm) ingested either placebo or combined dose of 5 mg x kg(-1) of body weight of caffeine and 200 mg of PG one hour before the running on treadmill at 70% of VO2(max) in this placebo-controlled double blind randomised study in a laboratory environment of 31 degrees C and 70% relative humidity. They drank 3 ml x kg(-1) of body weight of cool water every 20 minutes during the exercise to prevent dehydration. Blood samples were withdrawn and oxygen uptake was recorded every 20 minutes while heart rate, core body temperature, skin temperature and ratings of perceived exertion (RPE) were recorded every 10 minutes during the trials. Endurance time was significantly different (P < 0.05) between experimental and placebo trials. Heart rate, skin temperature, core body temperature, oxygen uptake, RPE, plasma insulin, glucose, free fatty acid and lactate levels during the endurance exercise did not show any significant difference between the trials. Thus, we conclude that combined and acute supplementation of caffeine and PG in the said doses improved the endurance running performance of the heat-adapted male recreational runners.
    Matched MeSH terms: Drug Synergism
  17. Mohd Sazlly Lim S, Heffernan AJ, Zowawi HM, Roberts JA, Sime FB
    Eur J Clin Microbiol Infect Dis, 2021 Sep;40(9):1943-1952.
    PMID: 33884516 DOI: 10.1007/s10096-021-04252-z
    Due to limited treatment options for carbapenem-resistant Acinetobacter baumannii (CR-AB) infections, antibiotic combinations are commonly used. In this study, we explored the potential efficacy of meropenem-sulbactam combination (MEM/SUL) against CR-AB. The checkerboard method was used to screen for synergistic activity of MEM/SUL against 50 clinical CR-AB isolates. Subsequently, time-kill studies against two CR-AB isolates were performed. Time-kill data were described using a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Subsequently, Monte Carlo simulations were performed to estimate the probability of 2-log kill, 1-log kill or stasis at 24-h following combination therapy. The MEM/SUL demonstrated synergy against 28/50 isolates. No antagonism was observed. The MIC50 and MIC90 of MEM/SUL were decreased fourfold, compared to the monotherapy MIC. In the time-kill studies, the combination displayed synergistic killing against both isolates at the highest clinically achievable concentrations. At concentrations equal to the fractional inhibitory concentration, synergism was observed against one isolate. The PK/PD model adequately delineated the data and the interaction between meropenem and sulbactam. The effect of the combination was driven by sulbactam, with meropenem acting as a potentiator. The simulations of various dosing regimens revealed no activity for the monotherapies. At best, the MEM/SUL regimen of 2 g/4 g every 8 h demonstrated a probability of target attainment of 2-log10 kill at 24 h of 34%. The reduction in the MIC values and the achievement of a moderate PTA of a 2-log10 reduction in bacterial burden demonstrated that MEM/SUL may potentially be effective against some CR-AB infections.
    Matched MeSH terms: Drug Synergism
  18. Yang SK, Yusoff K, Mai CW, Lim WM, Yap WS, Lim SE, et al.
    Molecules, 2017 Nov 04;22(11).
    PMID: 29113046 DOI: 10.3390/molecules22111733
    Combinatory therapies have been commonly applied in the clinical setting to tackle multi-drug resistant bacterial infections and these have frequently proven to be effective. Specifically, combinatory therapies resulting in synergistic interactions between antibiotics and adjuvant have been the main focus due to their effectiveness, sidelining the effects of additivity, which also lowers the minimal effective dosage of either antimicrobial agent. Thus, this study was undertaken to look at the effects of additivity between essential oils and antibiotic, via the use of cinnamon bark essential oil (CBO) and meropenem as a model for additivity. Comparisons between synergistic and additive interaction of CBO were performed in terms of the ability of CBO to disrupt bacterial membrane, via zeta potential measurement, outer membrane permeability assay and scanning electron microscopy. It has been found that the additivity interaction between CBO and meropenem showed similar membrane disruption ability when compared to those synergistic combinations which was previously reported. Hence, results based on our studies strongly suggest that additive interaction acts on a par with synergistic interaction. Therefore, further investigation in additive interaction between antibiotics and adjuvant should be performed for a more in depth understanding of the mechanism and the impacts of such interaction.
    Matched MeSH terms: Drug Synergism
  19. Yahya MFZR, Alias Z, Karsani SA
    Folia Microbiol (Praha), 2018 Jan;63(1):23-30.
    PMID: 28540585 DOI: 10.1007/s12223-017-0532-9
    Biofilms are complex microbial communities that tend to attach to either biotic or abiotic surface. Enclosed in a self-produced extracellular polymeric substance (EPS) matrix, the biofilms often cause persistent infections. The objective of this study was to investigate the antibiofilm activity of dimethyl sulfoxide (DMSO) and afatinib against Gram-negative pathogens. Test microorganisms used in this study were Escherichia coli ATCC 1299, Pseudomonas aeruginosa ATCC 10145, and Salmonella typhimurium ATCC 14028. Biofilms were developed in 96-well microplate at 37°C for 24 h. Following removal of non-adherent cells, analysis of biofilm viability, biofilm biomass, and extracellular polymeric substances (EPS) matrix were performed using resazurin assay, crystal violet assay, and attenuated total reflectance fourier transform infrared (ATR-FTIR) spectroscopy, respectively. Bradford protein assay was conducted to determine the total amount of EPS proteins. The results demonstrated that both 32% DMSO alone and its combination with 3.2 μg/mL afatinib were effective in killing biofilm cells and reducing biofilm biomass. IR spectral variations of EPS matrix of biofilms in the range between 1700 and 900 cm-1 were also observed. Reduction in EPS proteins verified the chemical modifications of EPS matrix. In conclusion, 32% DMSO alone and its combination with 3.2 μg/mL afatinib showed remarkable antibiofilm activities against Gram-negative pathogens. It was suggested that the biofilm inhibition was mediated by the chemical modification of EPS matrix.
    Matched MeSH terms: Drug Synergism
  20. Aljaafari MN, AlAli AO, Baqais L, Alqubaisy M, AlAli M, Molouki A, et al.
    Molecules, 2021 Jan 26;26(3).
    PMID: 33530290 DOI: 10.3390/molecules26030628
    The emergence of antimicrobial resistance (AMR) has urged researchers to explore therapeutic alternatives, one of which includes the use of natural plant products such as essential oils (EO). In fact, EO obtained from clove, oregano, thymus, cinnamon bark, rosemary, eucalyptus, and lavender have been shown to present significant inhibitory effects on bacteria, fungi, and viruses; many studies have been done to measure EO efficacy against microorganisms. The strategy of combinatory effects via conventional and non-conventional methods revealed that the combined effects of EO-EO or EO-antibiotic exhibit enhanced efficacy. This paper aims to review the antimicrobial effects of EO, modes of EO action (membrane disruption, efflux inhibition, increase membrane permeability, and decrease in intracellular ATP), and their compounds' potential as effective agents against bacteria, fungi, and viruses. It is hoped that the integration of EO applications in this work can be used to consider EO for future clinical applications.
    Matched MeSH terms: Drug Synergism
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