Lipid preparations of amphotericin B, commonly used to treat fungal infections, have been demonstrated to have reduced nephrotoxicity compared to conventional amphotericin B. However, to our knowledge, a comprehensive comparison of nephrotoxicity induced by different lipid preparations of amphotericin B has not been performed. We conducted a meta-analysis to evaluate nephrotoxicity associated with amphotericin B lipid complex (ABLC) and liposomal amphotericin B (L-AmB). We searched the PubMed MEDLINE database and abstracts presented at key scientific meetings, and identified 11 studies reported between 1995 and 2008 that compared nephrotoxicity resulting from the use of these agents. Eight of the 11 studies were included in the meta-analysis. The Cochran-Mantel-Haenszel test was used to determine odds ratio (OR) and relative risk (RR), and the Breslow-Day test was used to analyze homogeneity of ORs across different studies. Analysis of all 8 studies (n = 1160) included in the meta-analysis showed an increased probability of nephrotoxicity in patients treated with ABLC versus L-AmB (OR, 1.75; RR, 1.55), but there was a significant lack of homogeneity across these studies (p < 0.001). After excluding the study by Wingard et al, the probability of experiencing nephrotoxicity was more similar between the 2 AmB lipid preparations (OR, 1.31; RR, 1.24; n = 916), particularly when the analysis included only the salvage patient population reported by Hachem et al (OR, 1.12; RR, 1.09; n = 839); the 7 remaining studies were more homogenous by Breslow-Day test (p = 0.054). Our results suggest that nephrotoxicity is generally similar for ABLC and L-AmB in patients receiving antifungal therapy and prophylaxis.
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Available from: Dr. Sushilkumar Janardhan Wankhade
"Amphotericin B is generally considered primary line of defence to tackle infections by Candida species and is often given in combination with more efficacious and less toxic systemic azole antifungal drugs such as fluconazole, miconazole, ketoconazole etc. However, amphotericin B overdose can be nephro and hepatotoxic (Safdar et al. 2010) and indiscriminate use of azole drug such as fluconazole can result in its intrinsic tolerance among C. albicans and non-albicans Candida species (Sanglard et al. 2003). Therefore, resistance to the azole antifungal drugs against Candida species has become predictable over a period of time which can be attributed to its fungistatic rather than the fungicidal nature in general (Vandenbosch et al. 2010). "
[Show abstract][Hide abstract]ABSTRACT: Patil S, Maknikar P, Wankhade S, Ukesh C, Rai M. 2015. Antifungal effect of cumin essential oil alone and in combination with antifungal drugs. Nusantara Bioscience 7: 55-59. We report evaluation of antifungal activity of cumin seed oil and its pharmacological interactions when used in combination with some of the widely used conventional antifungal drugs using CLSI broth microdilution, agar disc diffusion and checkerboard microtitre assay against Candida. The essential oil was obtained from cumin seeds using hydrodistillation technique and was later evaluated for the presence of major chemical constituents present in it using gas chromatography and mass spectrometry (GC-MS) assay. The GC-MS assay revealed the abundance of γ-terpinene (35.42%) followed by p-cymene (30.72%). The agar disc diffusion assay demonstrated highly potent antifungal effect against Candida species. Moreover, the combination of cumin essential oil (CEO) with conventional antifungal drugs was found to reduce the individual MIC of antifungal drug suggesting the occurrence of synergistic interactions. Therefore, the therapy involving combinations of CEO and conventional antifungal drugs can be used for reducing the toxicity induced by antifungal drugs and at the same time enhancing their antifungal efficacy in controlling the infections caused due to Candida species.
"The results showed that the percentage of lycopene entrapment efficacy was 78.5% ± 2. Table 1 shows mean particle size, zeta-potential, and polydispersity index of empty and lycopene-loaded nanospheres. Size homogeneity of empty and loaded nanospheres suggested that lycopene was entrapped into nanoparticle core, according to previous studies. In this work, the results from vesicle size distribution showed a monomodal pattern. "
[Show abstract][Hide abstract]ABSTRACT: Background:
Lycopene, a plant carotenoid, has potent effects against the various types of cancer cells. To date, the effect of lycopene in the free and encapsulated forms on the telomerase activity in human leukemia cell line K562 have not been investigated. The aim of the present study was to prepare a novel lycopene-loaded nanosphere and compare its anti-telomearse activity in K562 cell line with those of free lycopene.
Materials and Methods:
The lycopene-loaded nanospheres were prepared by nanoprecipitation method. The lycopene entrapment efficacy was measured by high-performance liquid chromatography (HPLC) method. The anti-proliferation effect of the lycopene in the free and encapsulated forms in the different times (0-72 h) and the different doses (0-100 μg/ml) on K562 cell line was studied using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The changes of telomerase activity, following treatment with the lycopene in the free and encapsulated forms, were detected using the telomeric repeat amplification protocol-enzyme-linked immunosorbent assay.
The entrapment efficacy of lycopene was 78.5% ± 2. Treatment of the K562 cell line with lycopene, in particular in encapsulated form, resulted in a significant inhibition of the cell growth and increasing of percentage of apoptotic cells. It has also been observed that the telomerase activity in the lycopene-loaded nanospheres-treated cells was significantly inhibited in a dose and time-dependent manner.
Our data suggest a novel mechanism in the anti-cancer activity of the lycopene, in particular in encapsulated form, and could be provided a basis for the future development of anti-telomerase therapies.
No preview · Article · Mar 2014 · Pharmacognosy Magazine
"Due to the probability that the pattern of nephrotoxicity of AmB lipid-based formulations is transitory , the time point of assessing nephrotoxicity (for example, 1 vs. 6 weeks) is a critical factor in determining the rate of nephrotoxicity. In conclusion, these authors suggest that ABLC or L-AmB can be given to immunocompromised patients for the treatment or prophylaxis of invasive fungal infections with comparable efficacy and safety . Martino believed that the differences identified in the Wingard et al. trial can be attributed to the different pharmacokinetic and pharmacodynamic profiles of ABLC and L-AmB  . "
[Show abstract][Hide abstract]ABSTRACT: Purpose:
To collect available clinical data to define the role of diuretics and lipid formulations in the prevention of amphotericin B (AmB)-induced nephrotoxicity (AIN) in human populations.
A literature search was performed in the following databases: Scopus, Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews.
Results and conclusion:
Co-administration of mannitol failed to show any clinically significant benefit in preventing AIN. Potassium-sparing diuretics, such as amiloride and spironolactone, have been shown to have beneficial effects as an alternative or adjunct to oral/parenteral potassium supplements in preventing hypokalemia due to AmB. Lipid-based formulations of AmB are clinically effective and safe in preventing AIN. However, due to their high cost and limited accessibility, these formulations are generally used as second-line antifungal therapy in cases of conventional AmB refractoriness and/or intolerance or pre-existing renal dysfunction. The potential effects of other nephroprotective agents, such as N-acetylcysteine, AIN merit further considerations and investigations.
Full-text · Article · Jan 2013 · European Journal of Clinical Pharmacology