scholarly journals In Vitro Combination Effect of Topical and Oral Anti-Onychomycosis Drugs on Trichophyton rubrum and Trichophyton interdigitale

2021 ◽  
Vol 7 (3) ◽  
pp. 208
Author(s):  
Keita Sugiura ◽  
Akane Masumoto ◽  
Haruki Tachibana ◽  
Yoshiyuki Tatsumi
Keyword(s):  
Synergistic Effect ◽  
Drug Combination ◽  
Trichophyton Rubrum ◽  
Oral Drug ◽  
Combination Effect ◽  
Oral Drugs ◽  
Minimum Inhibitory Concentrations ◽  
Trichophyton Interdigitale ◽  
Oral Itraconazole

To evaluate the combination effects of anti-onychomycosis drugs, the minimum inhibitory concentrations of topical (efinaconazole, luliconazole, and tavaborole) and oral (itraconazole and terbinafine) drugs for Trichophyton rubrum and Trichophyton interdigitale (8 each, with a total of 16 strains) were determined using the microdilution checkerboard technique based on the Clinical and Laboratory Standard Institute guidelines. No antagonism was observed between the topical and oral drugs against all the tested strains. Efinaconazole with terbinafine exerted a synergistic effect on 43.8% of the strains tested (7/16 strains) and efinaconazole with itraconazole on 12.5% (2/16 strains). Conversely, luliconazole showed no synergistic effect with terbinafine but was synergistically effective with itraconazole against 31.3% of the strains (5/16 strains). Tavaborole showed no synergistic effect with terbinafine and was synergistically effective with itraconazole against 18.8% of the strains (3/16 strains). The results suggest that a combination of topical and oral drugs could be a potential clinical option for onychomycosis treatment, and overall, the efinaconazole and oral drug combination would be the most advantageous among the tested combinations.

In Vitro Antifungal Activity of Green Synthesized Silver Nanoparticles in Comparison to Conventional Antifungal Drugs Against Trichophyton Interdigitale, Trichophyton Rubrum and Epidermophyton Floccosum

2020 ◽  
Vol 20 ◽  
Author(s):  
Shahram Mahmoudi ◽  
Mahmoud Vahidi ◽  
Ebadollah Shiri Malekabad ◽  
Alireza Izadi ◽  
Mehrdad Khatami ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Antifungal Activity ◽  
Trichophyton Rubrum ◽  
Geometric Mean ◽  
Antifungal Drugs ◽  
Epidermophyton Floccosum ◽  
Minimum Inhibitory Concentrations ◽  
Trichophyton Interdigitale ◽  
Green Synthesized Silver Nanoparticles

Background: Dermatophytosis is a globally distributed fungal infection. Treatment failure and relapse is common in this disease. Silver nanoparticle are known for their promising antimicrobial activity. The aim of this study was to determine the antifungal activity of these nanoparticles against common dermatophyte species. Methods: A set of 30 molecularly identified dermatophytes including Trichophyton interdigitale (n=10), Trichophyton rubrum (n=10), and Epidermophyton floccosum (n=10) were used in this study. Green synthesized silver nanoparticles using chicory (Cichorium intybus) were tested for their antifungal activity in comparison to fluconazole, itraconazole and terbinafine. Interspecies differences in minimum inhibitory concentrations of antifungal drugs and silver nanoparticles were tested using Kruskal–Wallis test in SPSS software version 21. Results: The highest minimum inhibitory concentrations (MICs) among antifungal drugs were observed for fluconazole [range: 4–64 µg/mL, geometric mean (GM) =17.959 µg/mL], followed by itraconazole (range: 0.008–0.5, GM= 0.066) and terbinafine (range: 0.004– 0.25 µg/mL, GM=0.027 µg/mL). Silver nanoparticles showed potent antifungal activity against all dermatophyte isolates with MICs (range: 0.25–32 µg/mL, GM=4.812 µg/mL) higher than those of itraconazole and terbinafine, but lower than fluconazole. MIC values of silver nanoparticles demonstrated significant differences between species (P=0.044), with E. floccosum having the highest MICs (GM=9.849 µg/mL) compared to T. interdigitale (GM=3.732 µg/mL) and T. rubrum (GM=3.031 µg/mL). Conclusion: Silver nanoparticles demonstrated promising anti-dermatophyte activity against the studied dermatophytes. Due to their widespectrum activity against other fungal and bacterial pathogens, they could be a potential choice, at least in the case of cutaneous and superficial infections.

scholarly journals Clomipramine and Benznidazole Act Synergistically and Ameliorate the Outcome of Experimental Chagas Disease

2016 ◽  
Vol 60 (6) ◽  
pp. 3700-3708 ◽  
Author(s):  
Mónica Cristina García ◽  
Nicolás Eric Ponce ◽  
Liliana Maria Sanmarco ◽  
Rubén Hilario Manzo ◽  
Alvaro Federico Jimenez-Kairuz ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Chagas Disease ◽  
Drug Combination ◽  
Specific Inhibitor ◽  
Chronic Phase ◽  
Control Group ◽  
Histopathological Analysis ◽  
Synergistic Activity ◽  
Content Type

Chagas disease is an important public health problem in Latin America, and its treatment by chemotherapy with benznidazole (BZ) or nifurtimox remains unsatisfactory. In order to design new alternative strategies to improve the current etiological treatments, in the present work, we comprehensively evaluated thein vitroandin vivoanti-Trypanosoma cruzieffects of clomipramine (CMP) (a parasite-trypanothione reductase-specific inhibitor) combined with BZ.In vitrostudies, carried out using a checkerboard technique on trypomastigotes (T. cruzistrain Tulahuen), revealed a combination index (CI) of 0.375, indicative of a synergistic effect of the drug combination. This result was correlated with the data obtained in infected BALB/c mice. We observed that during the acute phase (15 days postinfection [dpi]), BZ at 25 mg/kg of body weight/day alone decreased the levels of parasitemia compared with those of the control group, but when BZ was administered with CMP, the drug combination completely suppressed the parasitemia due to the observed synergistic effect. Furthermore, in the chronic phase (90 dpi), mice treated with both drugs showed less heart damage as assessed by the histopathological analysis, index of myocardial inflammation, and levels of heart injury biochemical markers than mice treated with BZ alone at the reference dose (100 mg/kg/day). Collectively, these data support the notion that CMP combined with low doses of BZ diminishes cardiac damage and inflammation during the chronic phase of cardiomyopathy. The synergistic activity of BZ-CMP clearly suggests a potential drug combination for Chagas disease treatment, which would allow a reduction of the effective dose of BZ and an increase in therapeutic safety.

scholarly journals Tigecycline and homoharringtonine synergistically target myeloid leukemia cells by inhibiting mitochondrial translation through mTOR/4EBP1 pathway

2020 ◽  
Author(s):  
Haiyang Yang ◽  
Chen Mei ◽  
Li Ye ◽  
Yanling Ren ◽  
Hua Zhang ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Drug Combination ◽  
Myeloid Leukemia ◽  
Drug Combinations ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Leukemia Cells ◽  
Mitochondrial Translation

Abstract BackgroundTigecycline (TIG) is a tetracycline derivative antibiotic. Successive studies have shown that TIG is efficacious for the treatment of some solid tumors and hematological malignant diseases both in vivo and in vitro, and drug combinations appear to provide better inhibition. To explore new drug combinations for myeloid leukemia, we compared the differential combination efficacy of TIG with several anti-leukemia drugs, and explored the mechanisms of the combination of TIG and homoharringtonine (HHT) in myeloid leukemia cells both in vitro and in vivo.MethodsCell proliferation was assessed using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyph-enyl)-2-(4-sulfophenyl)-2H-tetrazolium) and CFU-GM (colony forming unit-granulocyte and macrophage) assays. Apoptosis was detected by flow cytometry. The combination of effects was confirmed in myeloid leukemia cells and tumor-bearing mouse model. The regulation of the AKT/mTOR (mammalian target of rapamycin)/4EBP1 (eukaryotic translation initiation factor 4E binding protein 1) pathway was assessed using a Western blot and immunohistochemistry.ResultsThe combination of TIG and HHT had a strong synergistic effect in myeloid leukemia cells. The use of the drug combination in vivo also effectively delayed myeloid tumor development in mice. The synergistic effect of this drug combination is likely to be achieved by inhibiting mitochondrial translation and down-regulating the AKT/mTOR/4EBP1 signaling pathway. Conclusion: The combination of TIG and HHT can synergistically enhance an anti-leukemia effect through downregulating anti-apoptotic proteins. Inhibiting mitochondrial translation through the AKT/mTOR/4EBP1 pathway might be an important mechanism.

scholarly journals In Vitro Antifungal Activity of Novel Triazole Efinaconazole and Five Comparators against Dermatophyte Isolates

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Ali Rezaei-Matehkolaei ◽  
Sadegh Khodavaisy ◽  
Mohamad Mahdi Alshahni ◽  
Takashi Tamura ◽  
Kazuo Satoh ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Trichophyton Rubrum ◽  
Geometric Mean ◽  
Clinical Isolates ◽  
The Novel ◽  
Large Collection ◽  
Content Type ◽  
Trichophyton Interdigitale ◽  
In Vitro Antifungal Activity

ABSTRACT The objective of this study was to assess the in vitro activity of the novel triazole antifungal drug, efinaconazole, and five comparators (luliconazole, lanoconazole, terbinafine, itraconazole, and fluconazole) against a large collection of Trichophyton interdigitale and Trichophyton rubrum clinical isolates. The geometric mean MICs were the lowest for luliconazole (0.0005 μg/ml), followed by lanoconazole (0.002 μg/ml), efinaconazole (0.007 μg/ml), terbinafine (0.011 μg/ml), itraconazole (0.095 μg/ml), and fluconazole (12.77 μg/ml). It appears that efinaconazole, lanoconazole, and luliconazole are promising candidates for the treatment of dermatophytosis due to T. interdigitale and T. rubrum .

Dipyridamole Inhibits Platelet Aggregation in Whole Blood

1983 ◽  
Vol 50 (04) ◽  
pp. 852-856 ◽  
Author(s):  
P Gresele ◽  
C Zoja ◽  
H Deckmyn ◽  
J Arnout ◽  
J Vermylen ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Significant Negative Correlation ◽  
Significant Inhibition ◽  
Oral Drug ◽  
Human Blood Samples ◽  
Induced Aggregation

SummaryDipyridamole possesses antithrombotic properties in the animal and in man but it does not inhibit platelet aggregation in plasma. We evaluated the effect of dipyridamole ex vivo and in vitro on platelet aggregation induced by collagen and adenosine- 5’-diphosphate (ADP) in human whole blood with an impedance aggregometer. Two hundred mg dipyridamole induced a significant inhibition of both ADP- and collagen-induced aggregation in human blood samples taken 2 hr after oral drug intake. Administration of the drug for four days, 400 mg/day, further increased the antiplatelet effect. A significant negative correlation was found between collagen-induced platelet aggregation in whole blood and dipyridamole levels in plasma (p <0.001). A statistically significant inhibition of both collagen (p <0.0025) and ADP-induced (p <0.005) platelet aggregation was also obtained by incubating whole blood in vitro for 2 min at 37° C with dipyridamole (3.9 μM). No such effects were seen in platelet-rich plasma, even after enrichment with leukocytes. Low-dose adenosine enhanced in vitro inhibition in whole blood.Our results demonstrate that dipyridamole impedes platelet aggregation in whole blood by an interaction with red blood cells, probably involving adenosine.

Benzisothiazolone Derivatives Exhibit Cytotoxicity in Hodgkin’s Lymphoma Cells through NF-κB Inhibition and are Synergistic with Doxorubicin and Etoposide

2020 ◽  
Vol 20 (6) ◽  
pp. 715-723
Author(s):  
Natarajan Nandakumar ◽  
Pushparathinam Gopinath ◽  
Jacob Gopas ◽  
Kannoth M. Muraleedharan
Keyword(s):  
Synergistic Effect ◽  
Hodgkin’S Lymphoma ◽  
A549 Cells ◽  
Hodgkin's Lymphoma ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Lymphoma Cells ◽  
Nuclear Extracts ◽  
Gene Assay

Background: The authors investigated the NF-κB inhibitory role of three Benzisothiazolone (BIT) derivatives (1, 2 and 3) in Hodgkin’s Lymphoma cells (L428) which constitutively express activated NF-κB. All three compounds showed dose-dependent NF-κB inhibition (78.3, 70.7 and 34.6%) in the luciferase reporter gene assay and were found cytotoxic at IC50 values of 3.3μg/ml, 4.35μg/ml and 13.8μg/ml, respectively by the XTT assay. BIT 1and BIT 2 (but not BIT 3) suppressed both NF-κB subunits p50 and p65 in cytoplasmic and nuclear extracts in a concentration-dependent manner. Furthermore, BIT 1 showed a moderate synergistic effect with the standard chemotherapy drugs etoposide and doxorubicin, whereas BIT 2 and 3 showed a moderate additive effect to antagonistic effect. Cisplatin exhibited an antagonist effect on all the compounds tested under various concentrations, except in the case of 1.56μg/ml of BIT 3 with 0.156μg/ml of cisplatin. The compounds also inhibited the migration of adherent human lung adenocarcinoma cells (A549) in vitro. We conclude that especially BIT 1 and BIT 2 have in vitro anti-inflammatory and anti-cancer activities, which can be further investigated for future potential therapeutic use. Methods: Inspired by the electrophilic sulfur in Nuphar alkaloids, monomeric and dimeric benzisothiazolones were synthesized from dithiodibenzoic acid and their NF-κB inhibitory role was explored. NF-κB inhibition and cytotoxicity of the synthesized derivatives were studied using luciferase reporter gene assay and XTTassay. Immunocytochemistry studies were performed using L428 cells. Cell migration assay was conducted using the A549 cell line. L428 cells were used to conduct combination studies and the results were plotted using CompuSyn software. Results: Benzisothiazolone derivatives exhibited cytotoxicity in Hodgkin’s Lymphoma cells through NF-κB inhibition. Potent compounds showed suppression of both NF-κB subunits p50 and p65 in a concentrationdependent manner, both in cytoplasmic and nuclear extracts. Combination studies suggest that benzisothiazolone derivatives possess a synergistic effect with etoposide and doxorubicin. Furthermore, the compounds also inhibited the migration of A549 cells. Conclusion: Benzisothiazolones bearing one or two electrophilic sulfur atoms as part of the heterocyclic framework exhibited cytotoxicity in Hodgkin’s Lymphoma cells through NF-κB inhibition. In addition, these derivatives also exhibited a synergistic effect with etoposide and doxorubicin along with the ability to inhibit the migration of A549 cells. Our study suggests that BIT-based new chemical entities could lead to potential anticancer agents.

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