Displaying publications 1 - 20 of 115 in total

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  1. Ridzwan BH, Jais AM, Waton NG
    Gen. Pharmacol., 1988;19(4):631-6.
    PMID: 3410287
    1. 30 mg kg-1 chlorpromazine (CPZ) depleted more than half of the tissue histamine from lungs, stomach, ileum and skin of the normal guinea-pigs. However, the drug increased the tissue histamine content in scorbutic animals. 2. In contrast, reserpine depleted histamine from the four tested tissues in both normal and scorbutic animals, except those in the lungs of the control animals. 3. Ascorbic acid only depleted histamine from the stomach and ileum. 4. A 24 hr period was the time limit for CPZ to deplete the histamine in all the four tested tissues. 5. Histamine partially or completely recovered in the tissues after the next 24 hr.
    Matched MeSH terms: Drug Synergism
  2. Idris N, Leong KH, Wong EH, Abdul Rahim N
    J Antibiot (Tokyo), 2023 Dec;76(12):711-719.
    PMID: 37821539 DOI: 10.1038/s41429-023-00659-2
    Polymyxins are last-line antibiotics against multidrug-resistant Klebsiella pneumoniae but using polymyxins alone may not be effective due to emerging resistance. A previous study found that combining polymyxin B with chloramphenicol effectively kills MDR K. pneumoniae, although the bone marrow toxicity of chloramphenicol is concerning. The aim of this study is to assess the antibacterial efficacy and cytotoxicity of polymyxin B when combined with chloramphenicol and its derivatives, namely thiamphenicol and florfenicol (reported to have lesser toxicity compared to chloramphenicol). The antibacterial activity was evaluated with antimicrobial susceptibility testing using broth microdilution and time-kill assays, while the cytotoxic effect on normal bone marrow cell line, HS-5 was evaluated using the MTT assay. All bacterial isolates tested were found to be susceptible to polymyxin B, but resistant to chloramphenicol, thiamphenicol, and florfenicol when used alone. The use of polymyxin B alone showed bacterial regrowth for all isolates at 24 h. The combination of polymyxin B and florfenicol demonstrated additive and synergistic effects against all isolates (≥ 2 log10 cfu ml-1 reduction) at 4 and 24 h, respectively, while the combination of polymyxin B and thiamphenicol resulted in synergistic killing at 24 h against ATCC BAA-2146. Furthermore, the combination of polymyxin B with florfenicol had the lowest cytotoxic effect on the HS-5 cells compared to polymyxin B combination with chloramphenicol and thiamphenicol. Overall, the combination of polymyxin B with florfenicol enhanced bacterial killing against MDR K. pneumoniae and exerted minimal cytotoxic effect on HS-5 cell line.
    Matched MeSH terms: Drug Synergism
  3. Hussain MA, Ahmed D, Anwar A, Perveen S, Ahmed S, Anis I, et al.
    Int Microbiol, 2019 Jun;22(2):239-246.
    PMID: 30810990 DOI: 10.1007/s10123-018-00043-3
    Silver nanoparticles (SN) have been recently developed as a new class of antimicrobial agents against numerous pathogenic microorganisms. SN have also been used as efficient drug delivery systems and have been linked with increasing drug potency. Here, we demonstrated the enhanced antifungal efficacy of nystatin (NYT) and fluconazole (FLU) after conjugation with SN. The antifungal bioactivity of NYT- and FLU-coated SN was evaluated against Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404 by the agar tube dilution method. The aim of this study was to determine and compare the antifungal efficacy of NYT and FLU with their SN and, finally, the combination of both nanoparticles as NYT-SN + FLU-SN against pathogenic fungi. The results indicated that all test samples showed a dose-dependent response against tested fungi. SN significantly enhanced the antifungal effects of NYT and FLU as compared to drugs alone. We observed a remarkable increase in the percent inhibition of both fungi (90-100%) when treated with a combination of both nanoparticles NYT-SN + FLU-SN at 200 μg/mL only. Furthermore, the morphological modifications occurred at the surface of fungal species were also analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). While tested against primary human cell line, all SN showed negligible cytotoxicity. Hence, these results suggest that the combination of SN with NYT and FLU may have clinical implications in the treatment of fungal infections. However, in vivo studies are needed before recommending the use of these nanoparticles safely in clinical situations.
    Matched MeSH terms: Drug Synergism*
  4. Dassanayake MK, Khoo TJ, An J
    Ann Clin Microbiol Antimicrob, 2021 Dec 02;20(1):79.
    PMID: 34856999 DOI: 10.1186/s12941-021-00485-0
    BACKGROUND AND OBJECTIVES: The chemotherapeutic management of infections has become challenging due to the global emergence of antibiotic resistant pathogenic bacteria. The recent expansion of studies on plant-derived natural products has lead to the discovery of a plethora of phytochemicals with the potential to combat bacterial drug resistance via various mechanisms of action. This review paper summarizes the primary antibiotic resistance mechanisms of bacteria and also discusses the antibiotic-potentiating ability of phytoextracts and various classes of isolated phytochemicals in reversing antibiotic resistance in anthrax agent Bacillus anthracis and emerging superbug bacteria.

    METHODS: Growth inhibitory indices and fractional inhibitory concentration index were applied to evaluate the in vitro synergistic activity of phytoextract-antibiotic combinations in general.

    FINDINGS: A number of studies have indicated that plant-derived natural compounds are capable of significantly reducing the minimum inhibitory concentration of standard antibiotics by altering drug-resistance mechanisms of B. anthracis and other superbug infection causing bacteria. Phytochemical compounds allicin, oleanolic acid, epigallocatechin gallate and curcumin and Jatropha curcas extracts were exceptional synergistic potentiators of various standard antibiotics.

    CONCLUSION: Considering these facts, phytochemicals represents a valuable and novel source of bioactive compounds with potent antibiotic synergism to modulate bacterial drug-resistance.

    Matched MeSH terms: Drug Synergism*
  5. Santiago C, Pang EL, Lim KH, Loh HS, Ting KN
    Biomed Res Int, 2014;2014:965348.
    PMID: 25101303 DOI: 10.1155/2014/965348
    The inhibitory activity of a semipure fraction from the plant, Acalypha wilkesiana assigned as 9EA-FC-B, alone and in combination with ampicillin, was studied against methicillin-resistant Staphylococcus aureus (MRSA). In addition, effects of the combination treatment on PBP2a expression were investigated. Microdilution assay was used to determine the minimal inhibitory concentrations (MIC). Synergistic effects of 9EA-FC-B with ampicillin were determined using the fractional inhibitory concentration (FIC) index and kinetic growth curve assay. Western blot experiments were carried out to study the PBP2a expression in treated MRSA cultures. The results showed a synergistic effect between ampicillin and 9EA-FC-B treatment with the lowest FIC index of 0.19 (synergism ≤ 0.5). The presence of 9EA-FC-B reduced the MIC of ampicillin from 50 to 1.56 μg mL(-1). When ampicillin and 9EA-FC-B were combined at subinhibitory level, the kinetic growth curves were suppressed. The antibacterial effect of 9EA-FC-B and ampicillin was shown to be synergistic. The synergism is due the ability of 9EA-FC-B to suppress the activity of PBP2a, thus restoring the susceptibility of MRSA to ampicillin. Corilagin was postulated to be the constituent responsible for the synergistic activity showed by 9EA-FC-B.
    Matched MeSH terms: Drug Synergism*
  6. Mori IC, Arias-Barreiro CR, Koutsaftis A, Ogo A, Kawano T, Yoshizuka K, et al.
    Chemosphere, 2015 Feb;120:299-304.
    PMID: 25151133 DOI: 10.1016/j.chemosphere.2014.07.011
    The aquatic ecotoxicity of chemicals involved in the manufacturing process of thin film transistor liquid crystal displays was assessed with a battery of four selected acute toxicity bioassays. We focused on tetramethylammonium hydroxide (TMAH, CAS No. 75-59-2), a widely utilized etchant. The toxicity of TMAH was low when tested in the 72 h-algal growth inhibition test (Pseudokirchneriellia subcapitata, EC50=360 mg L(-1)) and the Microtox® test (Vibrio fischeri, IC50=6.4 g L(-1)). In contrast, the 24h-microcrustacean immobilization and the 96 h-fish mortality tests showed relatively higher toxicity (Daphnia magna, EC50=32 mg L(-1) and Oryzias latipes, LC50=154 mg L(-1)). Isobologram and mixture toxicity index analyses revealed apparent synergism of the mixture of TMAH and potassium iodide when examined with the D. magna immobilization test. The synergistic action was unique to iodide over other halide salts i.e. fluoride, chloride and bromide. Quaternary ammonium ions with longer alkyl chains such as tetraethylammonium and tetrabutylammonium were more toxic than TMAH in the D. magna immobilization test.
    Matched MeSH terms: Drug Synergism
  7. Lai PL, Naidu M, Sabaratnam V, Wong KH, David RP, Kuppusamy UR, et al.
    Int J Med Mushrooms, 2013;15(6):539-54.
    PMID: 24266378
    Neurotrophic factors are important in promoting the growth and differentiation of neurons. Nerve growth factor (NGF) is essential for the maintenance of the basal forebrain cholinergic system. Hericenones and erinacines isolated from the medicinal mushroom Hericium erinaceus can induce NGF synthesis in nerve cells. In this study, we evaluated the synergistic interaction between H. erinaceus aqueous extract and exogenous NGF on the neurite outgrowth stimulation of neuroblastoma-glioma cell NG108-15. The neuroprotective effect of the mushroom extract toward oxidative stress was also studied. Aqueous extract of H. erinaceus was shown to be non-cytotoxic to human lung fibroblast MRC-5 and NG108-15 cells. The combination of 10 ng/mL NGF with 1 μg/mL mushroom extract yielded the highest percentage increase of 60.6% neurite outgrowth. The extract contained neuroactive compounds that induced the secretion of extracellular NGF in NG108-15 cells, thereby promoting neurite outgrowth activity. However, the H. erinaceus extract failed to protect NG108-15 cells subjected to oxidative stress when applied in pre-treatment and co-treatment modes. In conclusion, the aqueous extract of H. erinaceus contained neuroactive compounds which induced NGF-synthesis and promoted neurite outgrowth in NG108-15 cells. The extract also enhanced the neurite outgrowth stimulation activity of NGF when applied in combination. The aqueous preparation of H. erinaceus had neurotrophic but not neuroprotective activities.
    Matched MeSH terms: Drug Synergism
  8. Yunos NM, Mutalip SS, Jauri MH, Yu JQ, Huq F
    Anticancer Res, 2013 Oct;33(10):4365-71.
    PMID: 24123004
    Andrographolide (Andro) is a diterpenoid that is isolated from Andrographis paniculata and reported to be active against several cancer cell lines. However, few in-depth studies have been carried out on its effects on ovarian cancer cell lines alone or in combination with cisplatin (Cis), which is commonly used to treat ovarian cancer. The aim of this study was to determine the anti-proliferative and apoptotic effects of Andro administered alone and in combination with Cis in the ovarian A2780 and A2780(cisR) cancer cell lines using five different sequences of administration (Cis/Andro h): 0/0h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. The results were evaluated in terms of medium-effect dose (Dm) and combination indices (CI) using the CalcuSyn software. Unlike Cis, whose activity was lower in the resistant A2780(cisR) cell line than in the parent A2780 cell line, Andro was found to be three times more active in the A2780(cisR) cell line as compared to that in A2780 cell line. Synergism was observed when Cis and Andro were administered using the sequences 0/4 h and 4/0 h. The percentage of apoptotic cell death was found to be greater for the 0/4 h combination of Andro and Cis as compared to those values from single-drug treatments. The results may be clinically significant if confirmed in vivo.
    Matched MeSH terms: Drug Synergism
  9. Yap PS, Lim SH, Hu CP, Yiap BC
    Phytomedicine, 2013 Jun 15;20(8-9):710-3.
    PMID: 23537749 DOI: 10.1016/j.phymed.2013.02.013
    In this study we investigated the relationship between several selected commercially available essential oils and beta-lactam antibiotics on their antibacterial effect against multidrug resistant bacteria. The antibacterial activity of essential oils and antibiotics was assessed using broth microdilution. The combined effects between essential oils of cinnamon bark, lavender, marjoram, tea tree, peppermint and ampicillin, piperacillin, cefazolin, cefuroxime, carbenicillin, ceftazidime, meropenem, were evaluated by means of the checkerboard method against beta-lactamase-producing Escherichia coli. In the latter assays, fractional inhibitory concentration (FIC) values were calculated to characterize interaction between the combinations. Substantial susceptibility of the bacteria toward natural antibiotics and a considerable reduction in the minimum inhibitory concentrations (MIC) of the antibiotics were noted in some paired combinations of antibiotics and essential oils. Out of 35 antibiotic-essential oil pairs tested, four of them showed synergistic effect (FIC≤0.5) and 31 pairs showed no interaction (FIC>0.5-4.0). The preliminary results obtained highlighted the occurrence of a pronounced synergistic relationship between piperacillin/cinnamon bark oil, piperacillin/lavender oil, piperacillin/peppermint oil as well as meropenem/peppermint oil against two of the three bacteria under study with a FIC index in the range 0.26-0.5. The finding highlighted the potential of peppermint, cinnamon bark and lavender essential oils being as antibiotic resistance modifying agent. Reduced usage of antibiotics could be employed as a treatment strategy to decrease the adverse effects and possibly to reverse the beta-lactam antibiotic resistance.
    Matched MeSH terms: Drug Synergism
  10. Din WM, Jin KT, Ramli R, Khaithir TM, Wiart C
    Phytother Res, 2013 Sep;27(9):1313-20.
    PMID: 23109276 DOI: 10.1002/ptr.4876
    The present study served to gain further insight into the bactericidal effects of ellagitannins from Acalypha wilkesiana var. macafeana hort. against pathogenic bacteria. Ellagitannins from the aerial parts of A. wilkesiana var. macafeana hort. (EAW) inhibited the growth of Bacillus cereus (ATCC 11778), Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 11632) and Methicillin-resistant Staphylococcus aureus (MRSA) clinical strain with inhibition zones equal to 11.01 ± 1.53 mm, 16.63 ± 0.11 mm, 11.40 ± 1.10 mm and 8.22 ± 0.19 mm, respectively. The minimal inhibition concentration and the minimal bactericidal concentration of ellagitannins from A. wilkesiana var. macafeana hort. (EAW) against MRSA were 750 µg/mL and 3000 µg/mL, respectively. We then examined the synergistic effect of EAW with three antibiotics, i.e. ampicillin, streptomycin and tetracycline, via the checkerboard assay and time-kill assay and observed that EAW is synergistic with ampicillin against S. aureus (ATCC 11632). Environmental electron scanning microscopy analysis showed cell lysis against S. aureus (ATCC 11632) upon treatment with the ellagitannin fraction. The ellagitannin fraction from A. wilkesiana var. macafeana hort. is bactericidal against gram-positive bacteria tested and works synergistically with ampicillin against S. aureus. Morphology analysis of the cell suggests that the bactericidal property of the ellagitannin fraction mechanism involves lysis of the cell wall. In summary, our studies demonstrate that A. wilkesiana var. macafeana hort. produces bactericidal ellagitannins of clinical and/or cosmetological value.
    Matched MeSH terms: Drug Synergism
  11. Bakar NS, Zin NM, Basri DF
    Pak J Pharm Sci, 2012 Jul;25(3):633-8.
    PMID: 22713953
    This study evaluated in vitro activity of 9 flavonoids in combination with vancomycin or oxacillin against vancomycin-intermediate Staphylococcus aureus (VISA) ATCC 700699 by employing the checkerboard method to obtain Minimal inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) index. Six flavonoids namely hesperitin, rutin, naringenin, flavones, naringin and 3, 7-dihyroxyflavone which exhibited notable inhibitory activity (MIC values < 3200 μg/ml) were further evaluated for combination assay with antibiotics. The combinations of vancomycin+flavone and oxacillin+flavone were found synergistic with the FIC index value 0.094 and 0.126, respectively. Other combinations showed an additive interaction (FIC index = 1.063) but no antagonistic reaction (FIC index > 4) were observed. In time kill studies, oxacillin-flavone combination at synergistic concentration demonstrated bactericidal effect at 24 h period with concentration-dependent manner on the VISA strain. Following 1 h exposure, the combination also produced persistent effect on the bacteria growth for 2.9 hrs at 1x sub-MIC and more than 24 h at 5x of sub-MIC and there was a significant difference between both concentrations (p<0.05). Vancomycin-flavone combination, however, showed no concentration-dependent effect and lower PAE values (1.159 h and 2.322 h at 1x and 5x sub-MIC, respectively) on the VISA strain. In conclusion, flavone markedly intensifies the susceptibility of oxacillin against VISA and the combination can be implicated for further interaction studies at molecular level.
    Matched MeSH terms: Drug Synergism
  12. Chung PY, Navaratnam P, Chung LY
    PMID: 21658242 DOI: 10.1186/1476-0711-10-25
    There has been considerable effort to discover plant-derived antibacterials against methicillin-resistant strains of Staphylococcus aureus (MRSA) which have developed resistance to most existing antibiotics, including the last line of defence, vancomycin. Pentacyclic triterpenoid, a biologically diverse plant-derived natural product, has been reported to show anti-staphylococcal activities. The objective of this study is to evaluate the interaction between three pentacyclic triterpenoid and standard antibiotics (methicillin and vancomycin) against reference strains of Staphylococcus aureus.
    Matched MeSH terms: Drug Synergism
  13. Khodavandi A, Alizadeh F, Aala F, Sekawi Z, Chong PP
    Mycopathologia, 2010 Apr;169(4):287-95.
    PMID: 19924565 DOI: 10.1007/s11046-009-9251-3
    Candidiasis is a term describing infections by yeasts from the genus Candida, and the type of infection encompassed by candidiasis ranges from superficial to systemic. Treatment of such infections often requires antifungals such as the azoles, but increased use of these drugs has led to selection of yeasts with increased resistance to these drugs. In this study, we used allicin, an allyl sulfur derivative of garlic, to demonstrate both its intrinsic antifungal activity and its synergy with the azoles, in the treatment of these yeasts in vitro. In this study, the MIC(50) and MIC(90) of allicin alone against six Candida spp. ranged from 0.05 to 25 microg/ml. However, when allicin was used in combination with fluconazole or ketoconazole, the MICs were decreased in some isolates. Our results demonstrated the existing synergistic effect between allicin and azoles in some of the Candida spp. such as C. albicans, C. glabrata and C. tropicalis, but synergy was not demonstrated in the majority of Candida spp. tested. Nonetheless, In vivo testing needs to be performed to support these findings.
    Matched MeSH terms: Drug Synergism
  14. Min TH, Khairul MF, Low JH, Che Nasriyyah CH, A'shikin AN, Norazmi MN, et al.
    Exp Parasitol, 2007 Apr;115(4):387-92.
    PMID: 17118354
    Chloroquine (CQ) and mefloquine (MQ) are no longer potent antimalarial drugs due to the emergence of resistant Plasmodium falciparum. Combination therapy has become the standard for many regimes in overcoming drug resistance. Roxithromycin (ROM), a known p-glycoprotein inhibitor, is reported to have antimalarial activity and it is hoped it will potentiate the effects of both CQ/MQ and reverse CQ/MQ-resistance. We assayed the effects of CQ and MQ individually and in combination with ROM on synchronized P. falciparum (Dd2 strain) cultures. The IC(50) values of CQ and MQ were 60.0+/-5.0 and 16.0+/-3.0 ng/ml; these were decreased substantially when combined with ROM. Isobolograms indicate that CQ-ROM combinations were relatively more synergistic (mean FICI 0.70) than MQ-ROM (mean FICI 0.85) with their synergistic effect at par with CQ-verapamil (VRP) (mean FICI 0.64) and MQ-VRP (mean FICI 0.60) combinations. We conclude that ROM potentiates the CQ/MQ response on multidrug-resistant P. falciparum.
    Matched MeSH terms: Drug Synergism
  15. Thoo YY, Abas F, Lai OM, Ho CW, Yin J, Hedegaard RV, et al.
    Food Chem, 2013 Jun 1;138(2-3):1215-9.
    PMID: 23411234 DOI: 10.1016/j.foodchem.2012.11.013
    The synergistic antioxidant effects of ethanolic extracts of Centella asiatica (CE), and α-tocopherol have been studied. The types of interactions exhibited by CE and α-tocopherol combined at different ratios were measured using three assays: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) radical-scavenging capacity, the β-carotene bleaching system and liposome peroxidation assays. Fixed-fraction isobolographic analysis was used to detect any inducement of the antioxidant activity compared with the individual activities of CE and α-tocopherol. Of all synergistic combinations of CE and α-tocopherol, only fraction 2/3 showed the synergistic combination that fits well in three different assays and can be explained by the regeneration of α-tocopherol by CE despite the interaction effect of β-carotene present in the analytical assay. This phenomenon involved complex interactions between CE and α-tocopherol to exhibit different degrees of interactions that eventually increased antioxidant activity.
    Matched MeSH terms: Drug Synergism
  16. Hassan Y, Awaisu A, Aziz NA, Ismail O
    Pharm World Sci, 2005 Feb;27(1):16-9.
    PMID: 15861930
    Phenytoin has been reported to have major interactions with warfarin. Phenytoin induces warfarin's metabolism. However, there are many case reports which provide conflicting conclusions. Here, we report a case of a 65-year-old man with mechanical heart valve on chronic warfarin therapy who experienced persistent fluctuations of INR and bleeding secondary to probable warfarin-phenytoin interactions. The patient's anticoagulation clinic visits prior to hospitalization were thoroughly evaluated and we continued to follow-up the case for 3 months post-hospitalization. The reported interaction could be reasonably explained from the chronology of events and the pattern of INR fluctuations whenever phenytoin was either added or discontinued from his drug regimen.
    Matched MeSH terms: Drug Synergism
  17. Esmaeili C, Abdi MM, Mathew AP, Jonoobi M, Oksman K, Rezayi M
    Sensors (Basel), 2015;15(10):24681-97.
    PMID: 26404269 DOI: 10.3390/s151024681
    Integrating polypyrrole-cellulose nanocrystal-based composites with glucose oxidase (GOx) as a new sensing regime was investigated. Polypyrrole-cellulose nanocrystal (PPy-CNC)-based composite as a novel immobilization membrane with unique physicochemical properties was found to enhance biosensor performance. Field emission scanning electron microscopy (FESEM) images showed that fibers were nanosized and porous, which is appropriate for accommodating enzymes and increasing electron transfer kinetics. The voltammetric results showed that the native structure and biocatalytic activity of GOx immobilized on the PPy-CNC nanocomposite remained and exhibited a high sensitivity (ca. 0.73 μA·mM(-1)), with a high dynamic response ranging from 1.0 to 20 mM glucose. The modified glucose biosensor exhibits a limit of detection (LOD) of (50 ± 10) µM and also excludes interfering species, such as ascorbic acid, uric acid, and cholesterol, which makes this sensor suitable for glucose determination in real samples. This sensor displays an acceptable reproducibility and stability over time. The current response was maintained over 95% of the initial value after 17 days, and the current difference measurement obtained using different electrodes provided a relative standard deviation (RSD) of 4.47%.
    Matched MeSH terms: Drug Synergism
  18. Akbar A, Sharma JN, Yusof AP, Gan EK
    Int J Tissue React, 1998;20(3):95-100.
    PMID: 9894182
    We studied the effect of indomethacin, a cyclooxygenase inhibitor, on bradykinin-induced responses in the intact and denuded epithelium of the isolated tracheal smooth muscle in guinea pigs. Epithelium removal alone did not alter the responsiveness to bradykinin. Indomethacin (2.8 microM) enhanced the sensitivity to bradykinin of both intact and denuded preparations. This finding suggests that the tracheal epithelial may have no protective effect on the contractile responses induced by bradykinin. This may be due to the presence of high amounts of bradykinin-inactivating enzymes in the tracheal smooth muscle. Indomethacin-medicated potentiation caused by bradykinin in epithelium intact and denuded preparations may be an indication of removal of the bronchodilator prostaglandin biosynthesis. The significance of these findings is discussed.
    Matched MeSH terms: Drug Synergism
  19. Cercek B, Lew AS, Hod H, Yano J, Lewis B, Reddy KN, et al.
    Thromb Res, 1987 Aug 15;47(4):417-26.
    PMID: 3660351
    Since thrombi continue to incorporate fibrin during lysis we tested the effect of pretreatment with ancrod, a defibrinating agent from Malaysian pit viper venom, on thrombolysis with urokinase and streptokinase. Thrombi were induced by copper-coils in the carotid arteries of the dogs, weighed after 1 hour and inserted into the femoral arteries of the same animals. They were then exposed for 15 min to iv boluses of streptokinase 10,000 U/kg, urokinase 10,000 U/kg and urokinase 25,000 U/kg with or without pretreatment with ancrod. Ancrod depleted fibrinogen within 5 min and enhanced the lytic effect of streptokinase from 25 +/- 8% to 59 +/- 13% (p less than .05), urokinase 10,000 U/kg from 16 +/- 11% to 66 +/- 18% (p less than .01) and urokinase 25,000 U/kg from 27 +/- 17% to 85 +/- 8% (p less than .001) of the initial thrombus weight. Ancrod itself did not activate plasminogen to plasmin. We conclude that ancrod enhances thrombolysis probably by depleting fibrinogen and preventing new fibrin incorporation into the thrombus during lysis.
    Matched MeSH terms: Drug Synergism
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