scholarly journals Copper Acyl Salicylate Has Potential as an Anti-CryptococcusAntifungal Agent

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Adepemi O. Ogundeji ◽  
Boitumelo F. Porotloane ◽  
Carolina H. Pohl ◽  
Pravin S. Kendrekar ◽  
Olihile M. Sebolai
Keyword(s):  
Antifungal Activity ◽  
Metal Complex ◽  
Growth Inhibition ◽  
Metabolic Activity ◽  
Immune Cells ◽  
Dependent Manner ◽  
Content Type ◽  
Therapeutic Outcomes ◽  
Dose Dependent

ABSTRACTThein vitroantifungal activity of aspirin against cryptococcal cells has been reported. However, the unwanted effects of aspirin may limit its clinical application. Conceivably, a derivative of aspirin could overcome this challenge. Toward this end, this study considered the usage of an aspirinate-metal complex, namely, copper acyl salicylate (CAS), as an anti-Cryptococcusantifungal agent. Additionally, the study examined the effects of this compound on macrophage function. Thein vitrosusceptibility results revealed that cryptococcal cells were vulnerable (in a dose-dependent manner) to CAS, which might have effected growth inhibition by damaging cryptococcal cell membranes. Interestingly, when CAS was used in combination with fluconazole or amphotericin B, synergism was observed. Furthermore, CAS did not negatively affect the growth or metabolic activity of macrophages; rather, it sensitized those immune cells to produce interferon gamma and interleukin 6, which, in turn, might have aided in the phagocytosis of cryptococcal cells. Compared to our aspirin data, CAS was noted to be more effective in killing cryptococcal cells (based on susceptibility results) and less toxic toward macrophages (based on growth inhibition results). Taking these findings together, it is reasonable to conclude that CAS may be a better anti-Cryptococcusdrug that could deliver better therapeutic outcomes, compared to aspirin.

scholarly journals In VitroAnalyses of the Effects of Heparin and Parabens on Candida albicans Biofilms and Planktonic Cells

2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
High Dose ◽  
Dependent Manner ◽  
Planktonic Cells ◽  
Content Type ◽  
Heparin Sodium ◽  
The Individual

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.

scholarly journals Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benjamin N. Nelson ◽  
Savannah G. Beakley ◽  
Sierra Posey ◽  
Brittney Conn ◽  
Emma Maritz ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Cryptococcus Neoformans ◽  
Mammalian Cells ◽  
Cysteine Proteases ◽  
Dependent Manner ◽  
Life Threatening ◽  
Opportunistic Fungal Pathogen ◽  
Dose Dependent ◽  
Lysosomal Proteins

AbstractCryptococcal meningitis is a life-threatening disease among immune compromised individuals that is caused by the opportunistic fungal pathogen Cryptococcus neoformans. Previous studies have shown that the fungus is phagocytosed by dendritic cells (DCs) and trafficked to the lysosome where it is killed by both oxidative and non-oxidative mechanisms. While certain molecules from the lysosome are known to kill or inhibit the growth of C. neoformans, the lysosome is an organelle containing many different proteins and enzymes that are designed to degrade phagocytosed material. We hypothesized that multiple lysosomal components, including cysteine proteases and antimicrobial peptides, could inhibit the growth of C. neoformans. Our study identified the contents of the DC lysosome and examined the anti-cryptococcal properties of different proteins found within the lysosome. Results showed several DC lysosomal proteins affected the growth of C. neoformans in vitro. The proteins that killed or inhibited the fungus did so in a dose-dependent manner. Furthermore, the concentration of protein needed for cryptococcal inhibition was found to be non-cytotoxic to mammalian cells. These data show that many DC lysosomal proteins have antifungal activity and have potential as immune-based therapeutics.

scholarly journals Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis

2015 ◽  
Vol 60 (2) ◽  
pp. 1035-1039 ◽  
Author(s):  
Yuji Tabata ◽  
Naomi Takei-Masuda ◽  
Natsuki Kubota ◽  
Sho Takahata ◽  
Makoto Ohyama ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agent ◽  
Fungal Growth ◽  
Trichophyton Mentagrophytes ◽  
Dependent Manner ◽  
Content Type ◽  
Etiologic Agents ◽  
Prevalent Disease ◽  
Penetration Ability

ABSTRACTFungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate thein vitroantifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity againstTrichophyton rubrumandTrichophyton mentagrophytes(the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50and MIC90of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition ofTrichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation.

In vitro anti-diabetic activity of Tribulus terrestrisL. fruits extracts

2019 ◽  
Vol 50 (4) ◽  
pp. 631-640
Author(s):  
Kholowd AlKhaldi ◽  
Manal Daghestani ◽  
Thanaa Al-Haddad
Keyword(s):  
Acetone Extract ◽  
Hexane Extract ◽  
Tribulus Terrestris ◽  
Dependent Manner ◽  
Inhibition Activity ◽  
Content Type ◽  
Significant Difference ◽  
Ethanol Extracts ◽  
Dose Dependent

Purpose The purpose of this paper is to evaluate the inhibition activity of Tribulus terrestris L. (T. terrestris) fruits extracts with solvents of increasing polarity against α-glucosidase and α-amylase, and to determine the inhibition mode of the most effective extract against both enzymes. Design/methodology/approach Hexane, acetone, ethanol and aqueous extracts of T. terrestris fruits were prepared using ultrasonic sequential extraction and analyzed for their α-amylase and α-glucosidase inhibitory activities by specific assay for each enzyme. The modes of inhibitions were detected using Lineweaver–Burk plots. Findings T. terrestris fruits extracts showed inhibition activity against α-glucosidase and α-amylase which was in the dose-dependent manner. Hexane extract had the highest α-glucosidase inhibition activity (IC50 = 27.28 μg/ml, p = 0.003), followed by acetone and ethanol extracts (IC50 = 60.58 μg/ml and IC50 = 84.21 μg/ml, respectively). The inhibition mode of hexane extract was noncompetitive. While acetone extract showed the highest inhibition activity against α-amylase (IC50 = 6.18 mg/ml, p = 0.002), hexane and ethanol extracts showed no significant difference (IC50 = 13.04 mg/ml and IC50 = 14.20 mg/ml, respectively, p = 0.09). The inhibition mode of acetone extract was competitive. Originality/value T. terrestris fruits extracts had strong inhibition activity against α-glucosidase and α-amylase, and they can be used as a promising anti-diabetic agent.

scholarly journals Strong Antifungal Activity of SS750, a New Triazole Derivative, Is Based on Its Selective Binding Affinity to Cytochrome P450 of Fungi

2002 ◽  
Vol 46 (2) ◽  
pp. 308-314 ◽  
Author(s):  
Masaru Matsumoto ◽  
Kazuya Ishida ◽  
Akihiro Konagai ◽  
Kazunori Maebashi ◽  
Takemitsu Asaoka
Keyword(s):  
Cytochrome P450 ◽  
Antifungal Activity ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Strong Affinity ◽  
Dose Dependent ◽  
Potent Inhibitory Activity ◽  
In Vitro Antifungal Activity

ABSTRACT SS750 [(R)-(−)-2-(2,4-difluorophenyl)-1-(ethylsulfonyl)-1,1-difluoro-3-(1H-1,2,4-triazol-1-yl)-2-propanol] is a new triazole, and its potential as an antifungal agent was evaluated by in vitro and in vivo studies. In a comparison of the MICs at which 50% of isolates are inhibited (MIC50s) for all strains of Candida species and Cryptococcus neoformans tested, SS750 was four times or more active than fluconazole and had activity comparable to that of itraconazole. The most important advantage of SS750 was that, when the MIC90s were compared, SS750 had 64 and 32 times greater antifungal activities than fluconazole against Candida krusei and Candida glabrata, respectively, which are intrinsically less susceptible to fluconazole. In cyclophosphamide-immunosuppressed mouse models of systemic and pulmonary candidiasis caused by C. albicans, oral SS750 prolonged the number of days of survival of infected animals in a dose-dependent manner and was 4 and ≥64 times more potent than fluconazole and itraconazole, respectively. In a safety profile, SS750, like fluconazole, had less of an affinity for binding to mammalian cytochrome P450 compared with that of ketoconazole, despite its strong affinity for binding to fungal cytochrome P450. The mechanism for the increased in vitro antifungal activity of SS750 against C. krusei is partially due to the potent inhibitory activity (3.7 times versus that of fluconazole) of C. krusei cytochrome P450 sterol 14α-demethylase; SS750 showed a strong affinity for binding to cytochrome P450 of C. krusei, indicating that SS750 acts by inhibiting the cytochrome P450 sterol 14α-demethylase of fungal cells.

Carfilzomib, An Irreversible Proteasome Inhibitor, Induces Long-Term Growth Inhibition of Mantle Cell Lymphoma In Vivo,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3740-3740
Author(s):  
Liang Zhang ◽  
Jianfei Qian ◽  
Zhishuo Ou ◽  
Luhong Sun ◽  
Kejie Zhang ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Proteasome Inhibitor ◽  
Cell Lymphoma ◽  
Proteasome Inhibitors ◽  
Dependent Manner ◽  
Mantle Cell ◽  
Induced Apoptosis ◽  
Dose Dependent

Abstract Abstract 3740 Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with poor clinical outcome, thus, novel therapeutic agents are urgently needed. The proteasome inhibitors are small molecular agents which show significant anti-tumor effect in patients with relapsed/refractory MCL. Carfilzomib, an irreversible proteasome inhibitor with selectivity for the chymotrypsin-like active site, inhibits the proliferation of MCL cells in vitro, as well as the reversible proteasome inhibitor bortezomib. Unlike bortezomib, carfilzomib is good-tolerated and does not induce severe neuropathy in patients. Therefore, carfilzomib can be used in higher dose than bortezomib in vivo. Our study was undertaken to evaluate the therapeutic efficacy of carfilzomib on MCL cells both in vitro and in vivo compared with bortezomib. Four human MCL cell lines, MINO, Jeko-1, MAVER, and NCEB-1, freshly isolated primary MCL cells from the patients with relapsed/refractory MCL, were treated with carfilzomib or bortezomib. A 3H-thymidine incorporation assay showed that both carfilzomib and bortezomib displayed the same dose-dependent manner in inducing growth inhibition of the MCL cells. Similarly, flow cytometry analysis with fluorescence-labeled Annexin V and propidium iodide showed that carfilzomib induced apoptosis of MCL cells in the same dose-dependent manner with bortezomib. However, under the tolerable dose of each of the two proteasome inhibitors, they had different therapeutic effect in a MCL-bearing mouse model established in severe combined immunodeficient (SCID) mice. MINO cells (5 × 106) were inoculated subcutaneously into the right flank of SCID mice. Three weeks later, after palpable tumors developed, mice were treated intravenously with carfilzomib (5 mg/kg) on day 1 and day2, for 5 cycles, or treated intraperitoneally with bortezomib (1 mg/kg) on days 1, 4, 7 and 10, per 21 days. Tumor growth was almost abrogated after treatment with carfilzomib compared with bortezomib, and the survival time of tumor-bearing mice was significantly prolonged in the carfilzomib-treated mice versus bortezomib-treated mice. Notably, Increasing the frequency or dose of bortezomib treatment was unable because the mice were too suffered in toxicity to tolerate the treatment. Western blot analysis showed that carfilzomib induced apoptosis in caspase-dependent manner as well as bortezomib. Carfilzomib inhibited the phosphorylation of IκB, STAT3, and AKT and irreversibly blocked the release of NFκB to nuclei. In conclusion, carfilzomib displays the same anti-tumor effect and mechanism with bortezomib on MCL cells in vitro. However, carfilzomib but not bortezomib is well tolerated without severe side effect in vivo. Carfilzomib significantly inhibits tumor growth and prolongs survival indicating that carfilzomib is a potential agent in MCL chemotherapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Docosahexaenoyl ethanolamide mitigates IgE-mediated allergic reactions by inhibiting mast cell degranulation and regulating allergy-related immune cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kosuke Nishi ◽  
Yoshiki Kanayama ◽  
In-Hae Kim ◽  
Akihiro Nakata ◽  
Hisashi Nishiwaki ◽  
...  
Keyword(s):  
Mast Cell ◽  
Immune Cells ◽  
Mast Cell Degranulation ◽  
Allergic Symptom ◽  
Chain Polyunsaturated Fatty Acid ◽  
Dependent Manner ◽  
Ige Mediated ◽  
Dose Dependent

Abstract Docosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid mainly found in fish oil. Although several studies have suggested that it can alleviate allergy symptoms, its mechanism of action remains to be elucidated. In the present study, we found that docosahexaenoyl ethanolamide (DHEA), a metabolite of DHA produced in the human body, exerts the anti-allergic activity in vitro and in vivo. DHEA suppressed degranulation of rat basophilic leukemia RBL-2H3 cells and bone marrow-derived mast cells in a dose-dependent manner without cytotoxicity. This occurred due to a decrease in Ca2+ influx, which is critical for mast cell degranulation. DHEA also suppressed IgE-mediated passive cutaneous anaphylaxis reaction in mice. In addition, DHEA was demonstrated to lessen an allergic symptom in a mouse model of pollinosis and to alter the production of IgE and cytokines secreted by splenocytes collected from the pollinosis mice. Taken together, this study indicates that DHEA is a promising anti-allergic agent as it inhibits mast cell degranulation and modulates other immune cells.

scholarly journals Pharmacokinetics and Pharmacodynamics of Anidulafungin for Experimental Candida Endophthalmitis: Insights into the Utility of Echinocandins for Treatment of a Potentially Sight-Threatening Infection

2012 ◽  
Vol 57 (1) ◽  
pp. 281-288 ◽  
Author(s):  
J. L. Livermore ◽  
T. W. Felton ◽  
J. Abbott ◽  
A. Sharp ◽  
J. Goodwin ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
High Performance ◽  
Vitreous Humor ◽  
Dependent Manner ◽  
Time Curve ◽  
Content Type ◽  
Disseminated Candidiasis ◽  
Exposure Response ◽  
Average Patient ◽  
Dose Dependent

ABSTRACTCandidachorioretinitis and endophthalmitis are relatively common manifestations of disseminated candidiasis. Anidulafungin is increasingly used for the treatment of disseminated candidiasis, but its efficacy forCandidaendophthalmitis is not known. A nonneutropenic model of hematogenousCandidaendophthalmitis was used. Anidulafungin at 5, 10, and 20 mg/kg was initiated at 48 h postinoculation. The fungal densities in the kidney and vitreous humor were determined. Anidulafungin concentrations in the plasma and vitreous humor were measured using high-performance liquid chromatography (HPLC). A pharmacokinetic-pharmacodynamic model was used to link anidulafungin concentrations with the observed antifungal effect. The area under the concentration-time curve (AUC) associated with stasis was determined in the both the kidney and the vitreous humor. The results were bridged to humans to identify likely dosages that are associated with significant antifungal activity within the eye. Inoculation ofCandida albicansresulted in logarithmic growth in both the vitreous humor and the kidney. The pharmacokinetics of anidulafungin were linear. There was dose-dependent penetration of the anidulafungin into the vitreous humor. The exposure-response relationships in the kidney and vitreous were completely discordant. AUCs of 270 and 100 were required for stasis in the eye and kidney, respectively. The currently licensed regimen results in an AUC for an average patient that is associated with stasis in the kidney but minimal antifungal activity in the eye. We conclude that anidulafungin penetrates the eye in a dose-dependent manner and that dosages higher than those currently licensed are required to achieve significant antifungal activity in the eye.

scholarly journals Phytochemicals derived from soya bean husk exert hypoglycemic and anti-adipogenic properties in cell culture models

2019 ◽  
Vol 49 (6) ◽  
pp. 1219-1231 ◽  
Author(s):  
Seok-Tyug Tan ◽  
Amin Ismail ◽  
Muhajir Hamid ◽  
Pei-Pei Chong ◽  
Jian Sun ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Inhibitory Activity ◽  
Lipid Accumulation ◽  
Soya Bean ◽  
Dependent Manner ◽  
Content Type ◽  
Gpdh Activity ◽  
Triglyceride Content ◽  
Dose Dependent

Purpose Literature has shown that phenolic acids and flavonoids are bearing with hypoglycemic and anti-adipogenic properties. Therefore, this study aims to evaluate the possibility of phenolic-rich soya bean husk powder extract (SHPE) in combating diabetes and obesity using in vitro models. Design/methodology/approach The hypoglycemic properties were evaluated by determining the ability of SHPE (25-100 µg/mL) in inhibiting a-amylase and a-glucosidase enzymes and in triggering insulin secretion in BRIN-BD11 cells. Murine 3T3-L1 adipocytes were used for evaluating the anti-adipogenic properties of SHPE through the determination of relative lipid accumulation, triglyceride content and glycerol-3-phosphate dehydrogenase (GPDH) activity. Findings The hypoglycemic properties of SHPE was in the dose-dependent manner, where 100 µg SHPE/mL exhibited a significant higher (p < 0.05) a-amylase inhibitory activity (56.8 ± 0.11 per cent) and insulin secretion activity (0.73 ± 0.02 µg/l) against other concentrations. In contrast to the aforementioned findings, a significant lower a-glucosidase inhibitory activity (52.0 ± 0.44 per cent) was also observed in 100 µg SHPE/mL. Nevertheless, findings revealed that all the SHPE were able to inhibit the activity of a-amylase and a-glucosidase and stimulated the insulin secretion in BRIN-BD11 cells. On the other hand, the anti-adipogenic properties of SHPE were in the reverse dose-dependent manner, where 100 µg SHPE/mL demonstrated a significant lower (p < 0.05) relative lipid accumulation (48.5 ± 0.03 per cent), intracellular triglyceride content (5.7 ± 0.07 mg/dL) and GPDH activity (1.0 ± 0.01 mU/mL). These findings reflected that 100 µg SHPE/mL was a potent anti-adipogenic agent when compared with other concentrations. In conclusion, soya husk could emerge as a potential hypoglycemic and anti-adipogenic agents in in vitro models. Originality/value This was the first study to explore the effectiveness of phytochemicals derived from soya bean husk in ameliorating hyperglycemia and adipogenesis. Promising findings that derived from the present study could enable the scientists to re-evaluate the potential use of agricultural wastes, especially in the formulation of nutraceuticals.

Oxygenation of 18-hydroxycorticosterone as the final reaction for aldosterone biosynthesis

1984 ◽  
Vol 107 (3) ◽  
pp. 395-400 ◽  
Author(s):  
Itaru Kojima ◽  
Etsuro Ogata ◽  
Hiroshi Inano ◽  
Bun-ichi Tamaoki
Keyword(s):  
Carbon Monoxide ◽  
Hydroxysteroid Dehydrogenase ◽  
Dependent Manner ◽  
In Vitro Production ◽  
Mitochondrial Preparation ◽  
Final Reaction ◽  
Vitro Production ◽  
Dose Dependent ◽  
Cytochrome P 450

Abstract. Incubation of 18-hydroxycorticosterone with the sonicated mitochondrial preparation of bovine adrenal glomerulosa tissue leads to the production of aldosterone, as measured by radioimmunoassay. The in vitro production of aldosterone from 18-hydroxycorticosterone requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide. Cytochrome P-450 inhibitors such as metyrapone, SU 8000. SU 10603, SKF 525A, amphenone B and spironolactone decrease the biosynthesis of aldosterone from 18-hydroxycorticosterone. These results support the conclusion that the final reaction in aldosterone synthesis from 18-hydroxycorticosterone is catalyzed by an oxygenase, but not by 18-hydroxysteroid dehydrogenase. By the same preparation, the production of [3H]aldosterone but not [3H]18-hydroxycorticosterone from [1,2-3H ]corticosterone is decreased in a dose-dependent manner by addition of non-radioactive 18-hydroxycorticosterone.

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